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Pęcherz nadreaktywny i naglące nietrzymanie moczu - choroba jednostki czy choroba społeczeństwa. Etiologia i leczenie

We are only as sick as our secrets

Niewiele schorzeń budzi u pacjentów uczucie zażenowania w stopniu porównywalnym do nietrzymania moczu, a powyższe motto, będące hasłem przewodnim amerykańskich grup wsparcia, celnie ilustruje ich sytuację. Stosownie do definicji podanej przez International Continence Society (ICS) nietrzymanie moczu to stan, w którym niezależny od woli wyciek moczu jest źródłem istotnych dla chorego problemów higienicznych i socjalnych [1]. Pomimo znacznej dokuczliwości nietrzymania moczu, większość pacjentów godzi się z pogorszeniem jakości życia i ogranicza swą aktywność. Nietrzymanie moczu zyskało miano "choroby przeżywanej w skrytości" (closet disorder), a jedna z jego postaci jest elementem zespołu nadreaktywnego pęcherza (overactive bladder - OAB). W przebiegu OAB zwykle stopniowe nasilenie dolegliwości prowadzi do zmiany stylu życia, pacjenci ograniczają ilość przyjmowanych płynów, starają się nie oddalać od miejsca zamieszkania lub pozostawać w pobliżu toalet [2, 3, 4, 5]. Dwie trzecie pacjentów przyznaje, że jakość ich życia uległa istotnemu pogorszeniu. Wyniki kwestionariuszy oceny jakości życia (quality of life - QoL) pacjentów wykazują, że obniżenie to jest większe niż spadek QoL u chorych z cukrzycą, astmą czy innymi chorobami przewlekłymi [6]. Jedynie objawy choroby zwyrodnieniowej stawów (arthritis) przewyższają częstość objawów nadreaktywności pęcherza [3]. Jest to także jeden z czynników decydujących o przeniesieniu chorych do domów opieki. W USA blisko połowa mieszkańców tych ośrodków ma objawy naglącego nietrzymania moczu [7, 8].

Jak wykazały analizy socjologiczne, nawet w najwyżej rozwiniętych krajach tylko jedna trzecia pacjentów potrafi zwierzyć się z tego problemu lekarzowi, a dwie trzecie szuka pomocy po więcej niż dwu latach trwania dolegliwości. Przyczyną takiego stanu, oprócz niesłusznego uczucia wstydu, jest wiązanie zaburzeń z procesem starzenia oraz mylne przekonanie, że skoro nie dochodzi do uszkodzenia organizmu, leczenie nie jest potrzebne lub jest nieskuteczne [9, 10, 11]. Niestety, pogląd ten spotkać można także wśród części przedstawicieli środowiska medycznego. Tylko 50% pacjentów zwierzających się lekarzowi z trudności w utrzymaniu moczu otrzymuje leczenie farmakologiczne, a jedynie połowa z nich je kontynuuje [2]. Zagadnienie diagnostyki i leczenia różnych postaci nietrzymania moczu będzie narastać, gdyż dotyka znacznego odsetka ludzkości. Szacunkowe dane wskazują, że dotyczy ok. 200 mln ludzi, w tym 7% populacji poniżej 5. r.ż, 1,4% w wieku 15-24 lat i 2,9% w wieku 55-64 lat [12].

Mimowolny wyciek moczu to efekt kilku, często niezwiązanych ze sobą przyczyn i stosownie do nich zostało wyróżnionych pięć głównych postaci tego stanu [12, 13, 14, 15, 16, 17, 18, 19, 20, 21].

1. Wysiłkowe nietrzymanie moczu - do wycieku moczu dochodzi na skutek niewydolności zwieraczy cewki moczowej i/lub osłabienia mięśni dna miednicy stanowiących podporę pęcherza moczowego. W tej sytuacji nawet niewielki wzrost ciśnienia w jamie brzusznej nie jest równoważony przez mechanizm zwieraczowy i prowadzi do niekontrolowanego wycieku moczu.

2. Nietrzymanie moczu z przepełnienia - do wycieku moczu dochodzi w sytuacji, gdy znaczna ilość moczu przekracza maksymalną pojemność pęcherza moczowego i jego ciśnienie powoduje "przelewanie" moczu przez cewkę moczową. Sytuacja ma miejsce, gdy na skutek przeszkody podpęcherzowej (np. przerost stercza) lub zaburzeń neurologicznych (np. pęcherz neurogenny po urazie rdzenia kręgowego) pęcherz moczowy nie opróżnia się całkowicie w trakcie mikcji, wskutek czego pozostaje w nim niedostateczna wolna objętość dla kolejnych napływających porcji moczu. Zmiany wsteczne w ścianie pęcherza, do których dochodzi na skutek przeszkody podpęcherzowej, prowadzą do nadaktywności wypieracza przy spadku podatności jego ścian.

3. Funkcjonalne nietrzymanie moczu - występuje w sytuacji, gdy z przyczyn fizycznych, psychicznych lub socjalnych pacjent nie ma dostępu do toalety, np. jest długotrwale unieruchomiony.

4. Naglące nietrzymanie moczu - wywołane autonomicznymi, niezależnymi od woli skurczami pęcherza na skutek nadmiernej aktywności jego mięśni gładkich (m. wypieracza). Pacjent odczuwa silną i niepohamowaną potrzebę oddania moczu, często niewspółmierną do stopnia wypełnienia pęcherza. Nadaktywność wypieracza może towarzyszyć patologiom pęcherza moczowego (kamica, zakażenia) lub schorzeniom centralnego układu nerwowego. W części przypadków nie można ustalić przyczyn opisywanego objawu. Naglącemu nietrzymaniu moczu może towarzyszyć częste oddawanie moczu w dzień i w nocy oraz stałe uczucie parcia na mocz niezależnie od wypełnienia pęcherza, ujęte przez ICS jako zespół nadreaktywnego pęcherza.

5. Postać mieszana - łącząca w sobie przyczyny i cechy wysiłkowego oraz naglącego nietrzymania moczu.

Oprócz opisanej w pkt. 4 (i częściowo w pkt. 5) postaci nietrzymania moczu, w każdej można ustalić pierwotną przyczynę i w mniejszym lub większym stopniu ją usunąć. Niestety, pomimo postępu neurofizjologiiilepszegopoznaniaanatomiidrógmoczowychnieustalono podłoża naglącego nietrzymania moczu. Pewne światło na istotę choroby rzucają wyniki badań klinicznych. Jej częstość wzrasta z wiekiem, po 75. r.ż. 58% mężczyzn i 68,7% kobiet podaje kłopoty z utrzymaniem moczu [2]. U kobiet 49% przypadków nietrzymania moczu to postać wysiłkowa, 22% postać nagląca, a 29% postać mieszana. Z kolei u mężczyzn 73% przypadków nietrzymania moczu to postać nagląca, 19% mieszana, a tylko 8% wysiłkowa [11, 22]. Objawy pęcherza nadreaktywnego występują w niemal równym stopniu u obu płci, tj. u 15,6% mężczyzn i 17,4% kobiet. Wykazano też, że u 45% pacjentów z naglącym nietrzymaniem moczu dodatkowo występują cechy wysiłkowego nietrzymania moczu [3].

Epidemiologia zespołu pęcherza nadreaktywnego w świetle badań klinicznych

Pomimo rosnącej w ostatnich latach liczby publikacji dotyczących czynnościowych zaburzeń dolnych dróg moczowych, zagadnienie nieprawidłowej i nadmiernej aktywności skurczowej pęcherza nie jest nowe. Już w 1921 roku H. Young i D. Davies opisali objawy odpowiadające dzisiejszemu zespołowi pęcherza nadreaktywnego (overactive bladder - OAB). W późniejszych latach C. Hodgkinson, M. Ayers i B. Drukker nazywali taki stan niestabilnością wypieracza (detrusor instability) i zaproponowali użycie badań urodynamicznych celem jego diagnostyki [23, 24]. Dopiero w roku 1997 P. Abrams i A. Wein zaproponowali obecnie przyjętą przez International Continence Society (ICS) definicję charakterystycznych dolegliwości ze strony dolnych dróg moczowych jako zespół pęcherza nadreaktywnego [23]. Zespół pęcherza nadreaktywnego (OAB) to wzmożone, uporczywe, często nagłe, niewspółmierne do wypełnienia pęcherza odczucie potrzeby oddania moczu (parcie naglące), częste oddawanie moczu w ciągu dnia (frequency) i nocy (nocturia), czasami z towarzyszącym naglącym nietrzymaniem moczu (urge incontinence). Zgodnie z kryteriami ICS częstomocz dzienny to więcej niż 8 mikcji w ciągu doby lub stan, gdy okres pomiędzy poszczególnymi mikcjami jest krótszy niż 2 godziny [23, 25]. Z kolei częstomocz nocny to stan, gdy w ciągu nocy dochodzi do więcej niż 3 mikcji. Objawy te mogą wystąpić wtórnie w przebiegu wielu schorzeń dolnych dróg moczowych, jak kamica, nowotwór, zakażenie, przerost gruczołu krokowego, schorzeń neurologicznych prowadzących do upośledzenia ośrodkowego hamowania kurczliwości mięśnia wypieracza pęcherza (tzw. detrusor hyperreflexia), schorzeń ogólnoustrojowych, jak cukrzyca i zaburzenia hormonalne oraz jako uboczny efekt niektórych leków (preparaty moczopędne, opiaty) [6, 23, 26, 27, 28]. Zgodnie z zaleceniami ICS rozpoznanie samej nadreaktywności wypieracza (czyli reakcji mięśni pęcherza na czynnik zewnętrzny) wymaga potwierdzenia badaniem urodynamicznym, natomiast rozpoznanie zespołu pęcherza nadreaktywnego oparte jest na stwierdzeniu w/w objawów klinicznych po wykluczeniu uchwytnych przyczyn (anatomicznych, metabolicznych) podanej wyżej triady objawów [2, 18, 29, 30]. W zespole pęcherza nadreaktywnego do skurczu pęcherza dochodzi już we wczesnej fazie jego wypełniania.

Skurcze te występują spontanicznie i u części pacjentów prowadzą do wspomnianego naglącego nietrzymania moczu [18, 23]. Naglące nietrzymanie moczu to mimowolny, niemożliwy do zatrzymania jego wypływ występujący krótko po odczuciu parcia w okolicy pęcherza. Wywołane jest nieadekwatnym do stopnia wypełnienia pęcherza skurczem wypieracza. Objawy pęcherza nadreaktywnego (częstomocz, parcia naglące, naglące nietrzymanie moczu) mogą występować łącznie lub w różnych kombinacjach. Częstość ich występowania analizowano w kilku badaniach klinicznych. Jedno z nich, przeprowadzone metodą ankietową, objęło 16 776 kobiet i mężczyzn powyżej 40. r.ż. z Wielkiej Brytanii, Francji, Hiszpanii, Włoch, Niemiec i Szwecji. 16,6% ankietowanych podało przynajmniej jeden z objawów OAB zgodnych z kryteriami ICS i zostało zakwalifikowanych jako chorzy; najczęstszym objawem był częstomocz, zgłaszany przez 85% chorych, parcia naglące podawało 54%, a nietrzymanie moczu 36% chorych. U połowy chorych dolegliwości utrzymywały się dłużej niż 3 lata. Tylko 60% z nich szukało porady lekarskiej, jedynie 27% było leczonych [2]. Pacjenci zgłaszali się do lekarza głównie z powodu naglącego nietrzymania moczu, a przeciętny okres trwania objawów wynosił 8,5 lat. Po 3 miesiącach od rozpoczęcia leczenia liczba używanych podkładek spadła o jedną czwartą, natomiast w tym samym czasie u nie leczonych wzrosła o 135% [2, 31, 32].

Zbliżone dane uzyskano podczas ankietowego badania TheNational Overactive Bladder Evaluation (NOBLE), przeprowadzonego w USA wśród 11 740 osób [29]. Ze względu na niestałą liczbę objawów i różny stopień ich dokuczliwości wyodrębniono dwie postaci OAB: bez nietrzymania moczu oraz z nietrzymaniem moczu ("dry" i "wet" patients). Do pierwszej grupy zaliczono osoby, u których parcia naglące wystąpiły przynajmniej 4-krotnie w ciągu miesiąca, liczba mikcji w ciągu dnia przekroczyła 8, a charakter dolegliwości wymusił zmianę dotychczasowego trybu życia i ograniczenie aktywności. Druga grupa objęła osoby, u których dodatkowo wystąpiły co najmniej 3 epizody wycieku moczu związane z parciem naglącym i u których wykluczono wysiłkowe lub inne typy nietrzymania moczu. Wbrew do niedawna rozpowszechnionemu poglądowi, iż OAB występuje głównie, lub tylko, u kobiet, jak w badaniu poprzednim wykazano, że w równym stopniu dotyka niezależnie od wieku przedstawicieli obu płci, choć naglące nietrzymanie moczu jest częstsze u kobiet. Statystyki wykazują, że pomimo zbliżonej częstości występowania nadreaktywności pęcherza u obu płci, stosunek leczonych z tego powodu kobiet do leczonych mężczyzn wynosi 4:1.

OAB rozpoznano u 16,9% kobiet, z których 55% zakwalifikowano do drugiej grupy. W tym spośród pacjentek w wieku 20-45 lat 11,9% podawało objawy OAB bez nietrzymania moczu, a 15,3% z nietrzymaniem. Częstość naglącego nietrzymania moczu rosła z wiekiem pacjentek, poczynając od 35. roku życia. [8]. Wśród mężczyzn OAB rozpoznano u 16% ankietowanych, z których jedynie 16% zaliczono do grupy z nietrzymaniem moczu; byli to pacjenci po 65. roku życia [3, 23]. Częstsze występowanie postaci "wet" wśród kobiet można tłumaczyć odmienną anatomią oraz zmianami w mięśniach dna miednicy związanymi z wiekiem oraz przebytymi ciążami i porodami. Istotnego udziału czynnika "mięśniowego" dowodzi większy odsetek przypadków naglącego nietrzymania moczu u otyłych pacjentek. W badaniu NOBLE nadaktywność pęcherza z nietrzymaniem moczu występowała ponad dwukrotnie częściej u kobiet z BMI >30 w porównaniu do pacjentek z BMI<24. Inne badania kliniczne potwierdziły te obserwacje. Co więcej, okazało się, że jedynie 23% pacjentów z BMI >30 nie podaje żadnego z objawów nadreaktywności pęcherza [33, 34, 35].

Oba cytowane badania kliniczne dotyczyły dwu odrębnych pod pewnymi względami populacji: "amerykańskiej" i "europejskiej". Zarzut ten nie dotyczy kolejnej analizy. Badanie EPIC objęło 19 000 uczestników w wieku powyżej 18 lat z Kanady, Niemiec, Wielkiej Brytanii, Szwecji Włoch. U 11,8% badanych wykazano objawy OAB i nie stwierdzono różnic w ich występowaniu u obu płci [36]. Wysoki odsetek występowania nadreaktywności pęcherza podany w wyżej cytowanych badaniach może budzić pewne zastrzeżenia. Najmniej wątpliwości budzi z pewnością zgłaszanie przez badane osoby objawów naglącego nietrzymania moczu. Natomiast częstomocz dzienny, na podstawie którego zakwalifikowano największą grupę osób, obarczony jest w dużym stopniu subiektywnością. Trudno w tym przypadku wykluczyć czynniki związane ze zwyczajami danych osób, jak przyjmowanie dużych ilości płynów czy spożycie popularnych napojów zawierających kofeinę. Wśród chorych zgłaszających objawy pęcherza nadreaktywnego znamienny jest wysoki odsetek osób z zaburzeniami depresyjnymi. Jak dowodzi codzienna praktyka, czasami trudno w takich sytuacjach ocenić, które objawy są pierwotne, a które wtórne. Po upływie kilku lat od ogłoszenia wyników wyżej omówionych badań opublikowano rezultaty analiz przeprowadzonych w Finlandii. Jak poprzednio, częstość występowania objawów pęcherza nadreaktywnego analizowano za pomocą ankiet kierowanych do 6000 osób w wieku 18-79 lat. Odpowiedzi uzyskano od 62,4% z nich. Tylko 8% respondentów zakwalifikowano jako osoby z nadreaktywnością pęcherza moczowego. Wśród mężczyzn 6,5% podało objawy nadreaktywności pęcherza moczowego, a po wykluczeniu pacjentów z przerostem gruczołu krokowego odsetek ten zmalał do 5,6%. Z tej grupy 11% zgłaszało naglące nietrzymanie moczu, 23% częstomocz, a 56% nocne oddawanie moczu. Wśród kobiet 9,3% ankietowanych podawało objawy OAB zgodne z kryteriami ICS, z czego naglące nietrzymanie moczu 27%, częstomocz dzienny 38% i 40% częstomocz nocny. Autorzy badania słusznie wskazują, że subiektywność kryteriów oraz ukierunkowany dobór ankietowanych osób (powyżej 40. r.ż.) poprzednich badań wpływały na zawyżenie częstości występowania OAB w populacji [37]. Być może pewne światło na publikowane statystyki rzucą informacje podane w części dotyczącej ekonomicznych uwarunkowań OAB. Czynniki etiologiczne nadreaktywności pęcherza moczowego Przyczyny nadreaktywności pęcherza nie zostały poznane. Pod uwagę brane są zaburzenia neurologiczne związane z centralnym i obwodowym układem nerwowym, zmiany w dolnych drogach moczowych (np. przeszkoda podpęcherzowa, przyczyny mięśniopochodne w wypieraczu), styl życia (siedzący tryb życia, otyłość, dieta - alkohol, kofeina, palenie tytoniu). Podkreślany jest istotny związek czynników psychogennych z nadreaktywnością pęcherza oraz częste współwystępowanie zaburzeń socjologicznych i psychologicznych, zaburzeń snu, lecz trudno ocenić, czy jest to zjawisko wtórne w stosunku do długotrwałych dolegliwości pęcherzowych, czy też mają one wspólne podłoże. Objawy OAB występują 3-krotnie częściej wśród cierpiących na depresję [38, 39, 40, 41, 42, 43, 44]. Wiele badań wykazało, że ryzyko wystąpienia OAB u kobiet otyłych jest 2-krotnie wyższe w porównaniu do kobiet z prawidłową masą ciała, natomiast nie wykazano tej zależności u mężczyzn [3, 46]. Pod uwagę brane są także zmiany neurologiczne analogiczne do objawów pęcherzowych występujących u pacjentów po urazach rdzenia kręgowego lub w przebiegu stwardnienia rozsianego, gdzie dochodzi do nadreaktywności wypieracza przy zmianach powyżej segmentu S2-S4, lub uszkodzeniach mózgu po wylewach, urazach, w chorobie Parkinsona, gdy uszkodzony jest hamujący wpływ ośrodków mózgowych [46, 47, 48, 49]. Najprawdopodobniej, jak w wielu innych schorzeniach, etiologia jest złożona i zespół pęcherza nadreaktywnego jest końcowym wynikiem szeregu odmiennych i nie związanych ze sobą patologii. U podłoża zespołu OAB leżą dwa zjawiska: parcia naglące (wzmożona wrażliwość pęcherza powodująca uczucie potrzeby oddania moczu nawet przy niewielkim wypełnieniu - sensory urgency) oraz nadaktywność wypieracza (skurcze mięśni gładkich wypieracza już podczas wstępnej fazy wypełniania pęcherza) [23]. U pacjentów z nadreaktywnością pęcherza skurcz wypieracza jest niezależny od wypełnienia pęcherza i wymyka się świadomej kontroli - pęcherz staje się nadaktywny. Przyczyny tego zjawiska leżą w mięśniach gładkich pęcherza moczowego (przyczyny miogenne), nieprawidłowościach funkcjonowania włókien nerwowych i ich zakończeń oraz w samym centralnym układzie nerwowym (przyczyny neurogenne). W prawidłowych warunkach opróżnianie pęcherza podlega świadomej kontroli. Przeciętnie, maksymalna objętość pęcherza wynosi 400-600 ml, a odczucie potrzeby mikcji pojawia się dopiero przy wypełnieniu dwóch trzecich tej objętości. W trakcie stopniowego napływu moczu do pęcherza wypieracz ulega zwiotczeniu, a pasma mięśniowe zgrupowane wokół jego szyi oraz cewki moczowej pozostają w stanie stałego skurczu dzięki pobudzeniu przez współczulne włókna nerwowe wychodzące z segmentów Th11-L2 rdzenia kręgowego. Mikcja wymaga koordynacji szeregu zdarzeń zachodzących w obrębie mózgu, rdzenia kręgowego, obwodowego układu nerwowego i dolnych dróg moczowych. W prawidłowych warunkach pęcherz moczowy pozwala na stopniowe gromadzenie moczu bez znacznego wzrostu ciśnienia wewnątrzpęcherzowego. Wypływ moczu (mikcja) jest świadomym aktem zachodzącym pod kontrolą danej osoby - zwieracze cewki moczowej zmniejszają swe napięcie i następuje skurcz wypieracza. Do opróżnienia pęcherza dochodzi dzięki sygnałom z układu przywspółczulnego przekazywanym przez włókna nerwowe z segmentów S2-S4 rdzenia kręgowego, poprzez splot krzyżowy unerwiający dolne drogi moczowe i mięśnie dna miednicy. Powodują one skurcz wypieracza, zwiotczenie szyi pęcherza, zwieraczy cewki moczowej i mięśni dna miednicy. Jednak nawet po maksymalnym wypełnieniu pęcherza skurcz wypieracza może być zahamowany przez zależne od woli sygnały z kory mózgowej. Świadomie zwiększamy także napięcie zewnętrznego zwieracza cewki moczowej. Upośledzenie hamującego wpływu centralnego układu nerwowego zwiększa autonomię mięśni dolnych dróg moczowych, czego wyrazem jest przewaga napięcia nad zwiotczeniem włókien. Dowodzi tego częste występowanie naglącego nietrzymania moczu u kobiet po histerektomii (wiążącej się z uszkodzeniem nerwów miednicznych) [50, 51]. Cukrzyca insulinozależna, której częstym powikłaniem są zmiany zało się, że jedynie 23% pacjentów z BMI >30 nie podaje żadnego z objawów nadreaktywności pęcherza [33, 34, 35].

Oba cytowane badania kliniczne dotyczyły dwu odrębnych pod pewnymi względami populacji: "amerykańskiej" i "europejskiej". Zarzut ten nie dotyczy kolejnej analizy. Badanie EPIC objęło 19 000 uczestników w wieku powyżej 18 lat z Kanady, Niemiec, Wielkiej Brytanii, Szwecji Włoch. U 11,8% badanych wykazano objawy OAB i nie stwierdzono różnic w ich występowaniu u obu płci [36].

Wysoki odsetek występowania nadreaktywności pęcherza podany w wyżej cytowanych badaniach może budzić pewne zastrzeżenia. Najmniej wątpliwości budzi z pewnością zgłaszanie przez badane osoby objawów naglącego nietrzymania moczu. Natomiast częstomocz dzienny, na podstawie którego zakwalifikowano największą grupę osób, obarczony jest w dużym stopniu subiektywnością. Trudno w tym przypadku wykluczyć czynniki związane ze zwyczajami danych osób, jak przyjmowanie dużych ilości płynów czy spożycie popularnych napojów zawierających kofeinę. Wśród chorych zgłaszających objawy pęcherza nadreaktywnego znamienny jest wysoki odsetek osób z zaburzeniami depresyjnymi. Jak dowodzi codzienna praktyka, czasami trudno w takich sytuacjach ocenić, które objawy są pierwotne, a które wtórne.

Po upływie kilku lat od ogłoszenia wyników wyżej omówionych badań opublikowano rezultaty analiz przeprowadzonych w Finlandii. Jak poprzednio, częstość występowania objawów pęcherza nadreaktywnego analizowano za pomocą ankiet kierowanych do 6000 osób w wieku 18-79 lat. Odpowiedzi uzyskano od 62,4% z nich. Tylko 8% respondentów zakwalifikowano jako osoby z nadreaktywnością pęcherza moczowego. Wśród mężczyzn 6,5% podało objawy nadreaktywności pęcherza moczowego, a po wykluczeniu pacjentów z przerostem gruczołu krokowego odsetek ten zmalał do 5,6%. Z tej grupy 11% zgłaszało naglące nietrzymanie moczu, 23% częstomocz, a 56% nocne oddawanie moczu. Wśród kobiet 9,3% ankietowanych podawało objawy OAB zgodne z kryteriami ICS, z czego naglące nietrzymanie moczu 27%, częstomocz dzienny 38% i 40% częstomocz nocny.

Autorzy badania słusznie wskazują, że subiektywność kryteriów oraz ukierunkowany dobór ankietowanych osób (powyżej 40. r.ż.) poprzednich badań wpływały na zawyżenie częstości występowania OAB w populacji [37]. Być może pewne światło na publikowane statystyki rzucą informacje podane w części dotyczącej ekonomicznych uwarunkowań OAB.

Czynniki etiologiczne nadreaktywności pęcherza moczowego

Przyczyny nadreaktywności pęcherza nie zostały poznane. Pod uwagę brane są zaburzenia neurologiczne związane z centralnym i obwodowym układem nerwowym, zmiany w dolnych drogach moczowych (np. przeszkoda podpęcherzowa, przyczyny mięśniopochodne w wypieraczu), styl życia (siedzący tryb życia, otyłość, dieta - alkohol, kofeina, palenie tytoniu). Podkreślany jest istotny związek czynników psychogennych z nadreaktywnością pęcherza oraz częste współwystępowanie zaburzeń socjologicznych i psychologicznych, zaburzeń snu, lecz trudno ocenić, czy jest to zjawisko wtórne w stosunku do długotrwałych dolegliwości pęcherzowych, czy też mają one wspólne podłoże. Objawy OAB występują 3-krotnie częściej wśród cierpiących na depresję [38, 39, 40, 41, 42, 43, 44]. Wiele badań wykazało, że ryzyko wystąpienia OAB u kobiet otyłych jest 2-krotnie wyższe w porównaniu do kobiet z prawidłową masą ciała, natomiast nie wykazano tej zależności u mężczyzn [3, 46]. Pod uwagę brane są także zmiany neurologiczne analogiczne do objawów pęcherzowych występujących u pacjentów po urazach rdzenia kręgowego lub w przebiegu stwardnienia rozsianego, gdzie dochodzi do nadreaktywności wypieracza przy zmianach powyżej segmentu S2-S4, lub uszkodzeniach mózgu po wylewach, urazach, w chorobie Parkinsona, gdy uszkodzony jest hamujący wpływ ośrodków mózgowych [46, 47, 48, 49]. Najprawdopodobniej, jak w wielu innych schorzeniach, etiologia jest złożona i zespół pęcherza nadreaktywnego jest końcowym wynikiem szeregu odmiennych i nie związanych ze sobą patologii.

U podłoża zespołu OAB leżą dwa zjawiska: parcia naglące (wzmożona wrażliwość pęcherza powodująca uczucie potrzeby oddania moczu nawet przy niewielkim wypełnieniu - sensory urgency) oraz nadaktywność wypieracza (skurcze mięśni gładkich wypieracza już podczas wstępnej fazy wypełniania pęcherza) [23].

U pacjentów z nadreaktywnością pęcherza skurcz wypieracza jest niezależny od wypełnienia pęcherza i wymyka się świadomej kontroli - pęcherz staje się nadaktywny. Przyczyny tego zjawiska leżą w mięśniach gładkich pęcherza moczowego (przyczyny miogenne), nieprawidłowościach funkcjonowania włókien nerwowych i ich zakończeń oraz w samym centralnym układzie nerwowym (przyczyny neurogenne).

W prawidłowych warunkach opróżnianie pęcherza podlega świadomej kontroli. Przeciętnie, maksymalna objętość pęcherza wynosi 400-600 ml, a odczucie potrzeby mikcji pojawia się dopiero przy wypełnieniu dwóch trzecich tej objętości. W trakcie stopniowego napływu moczu do pęcherza wypieracz ulega zwiotczeniu, a pasma mięśniowe zgrupowane wokół jego szyi oraz cewki moczowej pozostają w stanie stałego skurczu dzięki pobudzeniu przez współczulne włókna nerwowe wychodzące z segmentów Th11-L2 rdzenia kręgowego. Mikcja wymaga koordynacji szeregu zdarzeń zachodzących w obrębie mózgu, rdzenia kręgowego, obwodowego układu nerwowego i dolnych dróg moczowych. W prawidłowych warunkach pęcherz moczowy pozwala na stopniowe gromadzenie moczu bez znacznego wzrostu ciśnienia wewnątrzpęcherzowego. Wypływ moczu (mikcja) jest świadomym aktem zachodzącym pod kontrolą danej osoby - zwieracze cewki moczowej zmniejszają swe napięcie i następuje skurcz wypieracza. Do opróżnienia pęcherza dochodzi dzięki sygnałom z układu przywspółczulnego przekazywanym przez włókna nerwowe z segmentów S2-S4 rdzenia kręgowego, poprzez splot krzyżowy unerwiający dolne drogi moczowe i mięśnie dna miednicy. Powodują one skurcz wypieracza, zwiotczenie szyi pęcherza, zwieraczy cewki moczowej i mięśni dna miednicy. Jednak nawet po maksymalnym wypełnieniu pęcherza skurcz wypieracza może być zahamowany przez zależne od woli sygnały z kory mózgowej. Świadomie zwiększamy także napięcie zewnętrznego zwieracza cewki moczowej. Upośledzenie hamującego wpływu centralnego układu nerwowego zwiększa autonomię mięśni dolnych dróg moczowych, czego wyrazem jest przewaga napięcia nad zwiotczeniem włókien. Dowodzi tego częste występowanie naglącego nietrzymania moczu u kobiet po histerektomii (wiążącej się z uszkodzeniem nerwów miednicznych) [50, 51]. Cukrzyca insulinozależna, której częstym powikłaniem są zmiany neurologiczne, jest jednym z czynników ryzyka rozwoju zespołu nadreaktywnego pęcherza.

Także na skutek długo trwającej przeszkody podpęcherzowej (np. przerost gruczołu krokowego, zwężenie cewki moczowej, choroba szyi pęcherza) dochodzi do zaburzeń czynności i struktury ściany pęcherza [52]. Przeszkoda taka prowadzi do wzrostu oporu cewkowego i ciśnienia wewnątrzpęcherzowego. Dochodzi do przerostu i przebudowy struktury mięśnia wypieracza, zmian w komórkach mięśniowych gładkich i połączeniach międzykomórkowych. Obniża się próg pobudliwości komórek mięśniowych z jednoczesnym wzrostem szybkości przekazywania sygnałów pomiędzy poszczególnymi włóknami. Nieprawidłowa aktywność komórek mięśniowych prowadzi do nieskoordynowanych i wzmożonych skurczów grup włókien wypieracza (micromotions), wzrostu częstotliwości mimowolnych skurczów wypieracza (bladder instability) i pobudzania receptorów czuciowych zlokalizowanych w ścianie pęcherza (aferentnych typu C). Rezultatem tych zjawisk są odczuwane przez pacjenta mimowolne skurcze wypieracza, parcia naglące oraz bolesność w okolicy pęcherza już we wczesnych fazach wypełniania. Izolowane zmiany w błonie mięśniowej również mogą prowadzić do wystąpienia objawów OAB. Miocyty gładkie wypieracza pobrane od osób chorych cechują się spontaniczną aktywnością skurczową, podwyższoną wrażliwością na mediatory, zmianami funkcjonowania błonowych kanałów wapniowych i potasowych. Wykazano, że średnia grubość ściany pęcherza moczowego u kobiet z nadreaktywnością pęcherza jest większa niż u kobiet z wysiłkowym nietrzymaniem moczu [53].

Do opisanych zaburzeń układu i funkcji włókien mięśniowych gładkich dołączają zmiany związane z wiekiem, wpływające na czynność pęcherza moczowego: wzrost ilości tkanki łącznej, niedokrwienie oraz u kobiet spadek poziomu estrogenów. Istotnej roli zaburzeń mięśni gładkich wypieracza w rozwoju nadreaktywności pęcherza dowodzi poprawa parametrów oddawania moczu oraz złagodzenie objawów związanych z przerostem stercza u pacjentów, u których oprócz standardowego leczenia blokerami receptorów alfa1-adrenergicznych dodatkowo włączono leki antycholinergiczne. Na przykład w wieloośrodkowym randomizowanym badaniu CombAT (Combination of Avodart and Tamsulosin) u pacjentów z przerostem gruczołu krokowego zastosowano dutasteryd oraz tamsulosynę. Po 24 miesiącach terapii łączonej uzyskano istotną statystycznie poprawę, redukcję objawów związanych z nad-reaktywnością wypieracza, objawów podrażnieniowych i spadek objętości moczu zalegającego w porównaniu do pacjentów stosujących monoterapię. Co więcej, w badaniu tym stwierdzono, że monoterapia lekiem antycholinergicznym była równie skuteczna jak monoterapia alfa-blokerem w łagodzeniu objawów związanych z przerostem gruczołu krokowego [54].

Szereg substancji neuroprzekaźnikowych, aktywnych w centralnym układzie nerwowym, wykazuje istotny wpływ na czynność dolnych dróg moczowych. Dominującym przekaźnikiem jest acetylocholina. Uwalniana z zakończeń nerwów przywspółczulnych za pośrednictwem receptorów muskarynowych (M1, M2, M3, M4, M5), powoduje szereg zmian wewnątrz komórek mięśniowych gładkich. Po ich pobudzeniu z magazynów w siateczce endoplazmatycznej zostają uwolnione jony wapnia, czego skutkiem jest skurcz włókien mięśniowych wypieracza. Zaburzenie czynności tych receptorów prowadzi do nadmiernej pobudliwości skurczowej, niewspółmiernej do stopnia stymulacji receptora i w efekcie do nieskoordynowanych skurczów poszczególnych włókien. Najważniejszymi dla czynności pęcherza moczowego rodzajami receptorów muskarynowych są podtypy M2 i M3. W warunkach prawidłowych przeważa podtyp M3, natomiast w nadreaktywności wypieracza stwierdzana jest wzmożona ekspresja receptora M2. Kolejnym istotnym przekaźnikiem jest dopamina, która poprzez oddziaływanie na receptory D1 zmniejsza aktywność wypieracza, a za pośrednictwem receptorów D2 pobudza jego skurcz. Na czynność pęcherza moczowego w większym lub mniejszym stopniu wpływa szereg innych neuroprzekaźników, np. serotonina (powodująca zwiotczenie mięśni) czy kwas glutaminowy (powodujący pobudzenie skurczów). Podkreślana jest też rola tlenku azotu (NO) w utrzymaniu prawidłowego napięcia włókien mięśniowych wypieracza, analogicznie do roli, jaką NO pełni w utrzymaniu prawidłowej czynności ciał jamistych. Oprócz czynników wewnątrzustrojowych na stan i czynność, w tym kurczliwość, ścian pęcherza moczowego wpływa środowisko zewnętrzne. Skład chemiczny moczu, z którym styka się nabłonek pęcherza moczowego, ulega zmianom zależnie od stopnia nawodnienia organizmu czy też przyjmowanych pokarmów. Jak w przypadku śródmiąższowego zapalenia pęcherza moczowego, wysokie stężenie jonów potasowych czy też kwaśny odczyn moczu powodują nasilenie objawów choroby. Prawdopodobną przyczyną tego zjawiska jest uwalnianie acetylocholiny bezpośrednio z nabłonka przejściowego i/lub nadmierna stymulacja zakończeń czuciowych zlokalizowanych w jego bezpośrednim sąsiedztwie. Oprócz tego urothelium uwalnia szereg innych przekaźników, jak ATP, NO [55, 56, 57, 58]. Część objawów ze strony dolnych dróg moczowych (LUTS) pojawiających się w przebiegu przerostu gruczołu krokowego przypomina objawy nadreaktywności pęcherza moczowego. Stan taki występuje u 50-75% pacjentów z przeszkodą podpęcherzową [59]. Chory odczuwa parcia naglące, skarży się na częstomocz dzienny i nocny, częste jest naglące nietrzymanie moczu. Jednak mężczyźni, w przeciwieństwie do kobiet, rzadziej otrzymują odpowiednie leczenie.

Miejsce i rola badania urodynamicznego w diagnostyce pęcherza nadreaktywnego

W nowoczesnej urologii dysponujemy aparaturą do badań urodynamicznych i wideourodynamicznych, umożliwiającą badanie pęcherza moczowego w fazie wypełniania i opróżniania. Badanie urodynamiczne pozwala potwierdzić nadreaktywne skurcze wypieracza. Wówczas objawowe rozpoznanie pęcherza nadreaktywnego (OAB) zmienia się w rozpoznanie nadreaktywności wypieracza (OAD), czyli w obiektywnie stwierdzaną i potwierdzoną badaniem patologię. U 50% pacjentów z rozpoznaniem pęcherza nadreaktywnego obserwuje się później nadreaktywne skurcze wypieracza w badaniu urodynamicznym. Kwestia etapu, na którym badanie powinno być wykonane, nie jest rozstrzygnięta. Brak wytycznych dotyczących niezbędności badania urodynamicznego w procesie diagnostycznym u pacjentów z rozpoznanym pęcherzem nadreaktywnym.

Przed badaniem urodynamicznym należy wykluczyć infekcję dróg moczowych będącą przeciwwskazaniem do jego wykonania. Pacjent powinien być poinformowany o celu badania i ogólnym jego przebiegu, tak by nie budziło w nich strachu, a wynik był obiektywny. Lekarz prowadzący powinien kierować pacjenta do pracowni urodynamicznej z konkretnym pytaniem. Na badanie pacjent zgłasza się bez specjalnego przygotowania. Obowiązkowa jest higiena narządów płciowych i okolicy krocza. Ważne jest dostarczenie przez pacjenta dotychczasowej dokumentacji medycznej oraz informacji o przyjmowanych lekach, gdyż wiele z nich może wpływać na zaburzenia zarówno fazy wypełniania, jak i fazy wydalania. Badanie urodynamiczne powinno rozpoczynać się od spontanicznej urofluometrii, jednak wydaje się, że pominięcie tego etapu na korzyść wcześniejszego wykonania przynajmniej 2-3 badań urofluometrycznych i wybranie spośród nich najlepszego jest znacznie bardziej obiektywne. Podobnie należy postąpić z oceną zalegania moczu po mikcji spontanicznej.

Dobra praktyka urodynamiczna wymaga używania odpowiedniego mianownictwa stosownie do zaleceń ICS. Opis powinien być spójny z urodynamiczną klasyfikacją zaburzeń czynności dolnych dróg moczowych i zawierać odpowiedź na postawione przez lekarza kierującego pytanie oraz sugestię dotyczącą dalszego postępowania.

Badanie w fazie wypełniania (cystometria) pozwala na ocenę czynności wypieracza, czucia pęcherzowego, pojemności czynnościowej, podatności ścian i czynności cewki moczowej. Ten etap badania jest kluczowy dla rozpoznania pęcherza nadreaktywnego i nadreaktywności wypieracza. Jeżeli nie zaobserwowano nadreaktywnych skurczów wypieracza, wówczas mówimy o pęcherzu stabilnym. W przypadku stwierdzenia nadreaktywnych skurczów wypieracza możemy rozróżnić nadreaktywność fazową lub terminalną. Wzrost ciśnienia wypieracza odczuwany przez chorego jako parcie na mocz jest nazywany nadaktywnością wypieracza. Gdy u pacjenta stwierdza się odchylenia w badaniu neurologicznym, mówimy o nadreaktywności neurogennej, w przeciwnym wypadku rozpoznajemy postać idiopatyczną. Nadreaktywne skurcze wypieracza obserwuje się u pacjentów w przebiegu zaawansowanej przeszkody podpęcherzowej.

W drugim etapie badania urodynamicznego ocenie podlega faza wydalania (mikcji), podczas której istotne są panujące ciśnienia, czynność wypieracza, czynność cewki moczowej oraz synergia pomiędzy czynnością zwieracza i wypieracza. Również w tej części badania, zwłaszcza po zakończeniu mikcji, mogą wystąpić nadreaktywne skurcze wypieracza. Poniższe przykłady pochodzą ze zbiorów własnych i przedstawiają przypadki chorych, u których nadaktywność wypieracza potwierdzono badaniem urodynamicznym.

Przykład 1
Nadreaktywne skurcze fazowe w fazie wypełniania pęcherza moczowego u kobiety po urazie kręgosłupa leczonej wcześniej z powodu parć naglących i naglącego nietrzymania moczu.
Przykład 2
Nadreaktywne skurcze fazowe w fazie wypełniania pęcherza moczowego u znacznie otyłego mężczyzny chorującego na cukrzycę, leczonego z powodu mimowolnego nietrzymania moczu.
Przykład 3
Nadreaktywne skurcze fazowe w fazie wypełniania pęcherza moczowego u mężczyzny leczonego z powodu przerostu gruczołu krokowego z potwierdzoną również w tym badaniu przeszkodą podpęcherzową.
Przykład 4
Przykład terminalnej nadreaktywności wypieracza u mężczyzny z zaawansowaną przeszkodą podpęcherzową.
Przykład 5
Przykład terminalnej nadreaktywności wypieracza u mężczyzny z zaawansowaną przeszkodą podpęcherzową. W badaniu widoczna zmniejszona podatność ścian pęcherza moczowego.
Przykład 6
Przykład terminalnej nadreaktywności wypieracza u mężczyzny z nietrzymaniem moczu.
Przykład 7
Nadreaktywny skurcz wypieracza podczas fazy wydalania po zakończeniu mikcji z towarzyszącym nietrzymaniem moczu.

Badanie urodynamiczne pomaga w rozpoznaniu nadreaktywności wypieracza pęcherza moczowego. Jest niezbędne u chorych kwalifikowanych doleczenia operacyjnego, u pacjentów, u których dotychczasowe leczenie nie przyniosło poprawy oraz w przypadku schorzeń neurologicznych.

Możliwości terapii pęcherza nadreaktywnego

Pierwsza wizyta pacjenta cierpiącego na OAB u urologa z reguły ma charakterystyczny przebieg. Chory opisuje kilkuletni okres leczenia dolegliwości u lekarza rodzinnego, ogólnego lub lekarzy innych specjalności, poparty długą listą dotychczas przyjmowanych leków. Częstokroć pacjent "wypróbował" niemal wszystkie dostępne antybiotyki, gdyż, ze względu na objawy, dolegliwości traktowane były jako objaw zakażenia dolnych dróg moczowych. Niestety, także dla urologa leczenie nadreaktywności pęcherza nie jest łatwe i często po początkowym sukcesie następuje nawrót dolegliwości. W terapii OAB stosowane są trzy grupy metod leczenia: metody fizykalne, farmakoterapia przy użyciu różnych typów leków oraz metody chirurgiczne.

Metody fizykalne
Metody fizykalne obejmują tzw. terapię behawioralną, różne formy stymulacji mięśni dna miednicy oraz ćwiczenia fizyczne. W roku 1989 na konferencji poświęconej standardom leczenia nietrzymania moczu Agency for Health Care Policy and Research zaleciła stosowanie terapii behawioralnych jako leczenia pierwszego rzutu [60, 61]. W roku 2004 Third International Consultationon Incontinence podtrzymało tę rekomendację [62]. Metody behawioralne zalecane są w leczeniu pacjentów z miernie nasilonymi objawami. Polegają na wypracowaniu prawidłowych odruchów opróżniania pęcherza i przywróceniu odpowiedniego cyklu mikcji poprzez wymuszanie oddawania moczu w stałym rytmie dobowym (jednakowe odstępy czasu i stałe pory). Obejmują opisane przez Kegla ćwiczenia mięśni dna miednicy oraz naukę reakcji na wystąpienie odczucia parcia poprzez wytworzenie odruchowego rozluźnienia lub odwrócenia uwagi (np. wsteczne odliczanie) i wywołanie wybiórczego skurczu innych grup mięśni. Pacjent dąży do zwiększania pojemności pęcherza za pomocą ćwiczeń polegających na świadomym, stopniowym wydłużaniu czasu pomiędzy kolejnymi mikcjami według wcześniej ustalonego harmonogramu (od 15 minut do 2 godzin).

Jednocześnie chory uczy się świadomej kontroli wypieracza oraz zwieracza cewki. Trening prowadzi do wypracowania mechanizmu, dzięki któremu impulsy korowe pozwalają na hamowanie skurczów wypieracza, stymulują napięcie zwieracza cewki moczowej, modulują dośrodkowe włókna czuciowe [63, 64, 65, 66, 67, 68, 69].

Dodatkowym elementem są zalecenia obejmujące ograniczenie przyjmowania napojów zawierających kofeinę, alkohol oraz zmniejszenie ilości płynów przyjmowanych przed nocnym spoczynkiem [70, 71, 72, 73, 74, 75]. Według części autorów terapia behawioralna znajduje zastosowanie jako leczenie wspomagające farmakoterapię, lecz wyniki badań klinicznych są niejednoznaczne [76)]. W jednym z nich 416 pacjentów nieskutecznie leczonych lekiem antycholiner-gicznym (tolterodyną) uczono zasad terapii behawioralnej (zmiany diety, sposoby ćwiczeń mięśni dna miednicy, regulacji mikcji itp.). W przeprowadzonych po 2 miesiącach ankietach kontrolnych 91% pacjentów potwierdzało poprawę stanu zdrowia i złagodzenie objawów związanych z nadreaktywnością pęcherza [77]. Wyniki innych badań nie wykazały tak dobrych rezultatów. Po dołączeniu terapii behawioralnej do stosowanej dotychczas u kobiet z naglącym nietrzymaniem moczu oksybutyniny i darifenacyny nie uzyskano istotnej poprawy w odniesieniu do monoterapii tymi preparatami [78, 79]. Urinary Incontinence Treatment Network na podstawie analizy uzyskanych danych stwierdziło, że dołączenie terapii behawioralnych nie zezwala na odstawienie leków antycholinergicznych [80].

Biofeedback polega na wyćwiczeniu świadomej kontroli nad czynnością narządów działających dotychczas autonomicznie. W przeciwieństwie do wyżej opisanych metod treningowych pacjent obserwuje reakcje swego organizmu przy użyciu odpowiednich urządzeń monitorujących. W przypadku pęcherza nadreaktywnego pacjent uczy się rozpoznawać sygnały poprzedzające, np. epizod naglącego nietrzymania moczu, kontrolować napięcie mięśni dna miednicy, utrzymywać odpowiedni odstęp czasu pomiędzy mikcjami i korzystać z toalety w określonym czasie (toileting assistance). Ćwiczenia te wspomagane są obserwacją przez ćwiczące pacjentki wskazań manometru dopochwowego lub zapisu z elektromiografu. Publikowane wyniki randomizowanych badań wskazują, że skuteczność prawidłowo prowadzonej terapii biofeedback może być porównywalna do wyników leczenia farmakologicznego [81, 82, 83, 84, 85, 86].

Stymulacja mięśni dna miednicy była pierwotnie stosowana w leczeniu wysiłkowego nietrzymania moczu u kobiet. Odpowiednie elektrody (stymulacja elektryczna) zostają umieszczone dopochwowo, przezskórne lub doodbytniczo, a generowany przez nie impuls pobudza mięśnie dna miednicy do skurczów. Mięśnie stopniowo zwiększają swe napięcie i siłę, podobnie jak każdy mięsień szkieletowy poddany stałym obciążeniom. Generowane impulsy elektryczne wpływają także na czynność nerwów biegnących w miednicy mniejszej, powodując zahamowanie przewodnictwa ("porażenie") włókien ruchowych i czuciowych biegnących w nerwach podbrzusznych i sromowych. Zjawisko to uzasadnia zastosowanie powyższej metody do leczenia zespołu pęcherza nadreaktywnego. Bardziej inwazyjny sposób elektrostymulacji polega na wszczepieniu stymulatorów z elektrodami zakończonymi w okolicach nerwów krzyżowych S2-S4, używanych do leczenia zaburzeń pęcherza neurogennego po urazach rdzenia kręgowego. Inne rozwiązanie to neuromodulacja polegająca na bezpośredniej stymulacji elektrodami włókien nerwowych typu A-d w korzeniach S3-S4 prądem o niskiej amplitudzie wytwarzanym przez wszczepiony stymulator (InterStim firmy Medtronic). Stymulacja taka prowadzi do obniżenia poziomu progu reaktywności ściany pęcherza moczowego i jednocześnie wzrostu napięcia zwieracza cewki moczowej [87]. Dla terapii OAB wykorzystano hamowanie skurczów wypieracza po elektrostymulacji obwodowych włókien eferentnych, jak i zahamowanie przewodnictwa w drogach rdzeniowych w efekcie elektrostymulacji włókien aferentnych. W ostatnich latach do stymulacji mięśni dna miednicy oraz nerwów miednicznych wprowadzane są urządzenia wytwarzające pole magnetyczne (stymulacja magnetyczna). Trudno ocenić użyteczność tych metod, gdyż wyniki publikowanych badań klinicznych są niejednoznaczne [88, 89, 90, 91, 92].

Leczenie farmakologiczne nadreaktywności pęcherza moczowego
Leczenie farmakologiczne OAB nie jest proste i nie zawsze jest skuteczne. Obecnie urolog dysponuje szeregiem grup preparatów o różnym stopniu skuteczności. Szczegółowe omówienia poszczególnych preparatów są łatwo dostępne i nie będą przedmiotem obecnego przeglądu.

Lekami z wyboru są preparaty z grupy leków antycholinergicznych, blokujące receptory muskarynowe. Tą drogą zmniejszają autonomiczne skurcze wypieracza, przynajmniej częściowo łagodząc objawy i zmniejszając liczbę epizodów nietrzymania moczu [93, 94, 95]. Dostępnych jest kilka substancji blokujących receptory muskarynowe (np. darifenacyna, hyoscyamina, oksybutynina, tolterodyna, solifenacyna, trospium), lecz brak preparatów o całkowicie wybiórczym blokowaniu receptorów muskarynowych w ścianie pęcherza. Dlatego ubocznym efektem ich działania jest hamowanie (w różnym stopniu w zależności od rodzaju preparatu) wydzielania śliny, powodujące dokuczliwe uczucie suchości w jamie ustnej, zaburzenia widzenia, zaparcia, uczucie senności. Leki antycholinergiczne mogą nasilać objawy demencji. Stosowane jako monoterapia mogą nasilać zaburzenia oddawania moczu u mężczyzn z przerostem gruczołu krokowego. Przeciwwskazaniem do ich dostosowania jest jaskra z wąskim kątem przesączania. Oksybutynina była pierwszym lekiem z tej grupy wprowadzonym do leczenia nadreaktywności pęcherza. Jednak nie wykazuje wybiórczości działania, a efekt hamujący jest nawet silniej wyrażony w stosunku do tkanek gruczołów ślinowych niż pęcherza. Kolejne wprowadzone na rynek preparaty (m.in. tolterodyna, solifenacyna, darifenacyna) cechuje większa wybiórczość w stosunku do receptorów M3 (najwyższą cechuje się darifenacyna). Dotychczas w żadnym z badań klinicznych nie wykazano wyższej skuteczności żadnego z preparatów nad pozostałymi z tej grupy. Najwyższą wybiórczość w stosunku do receptora M2 wykazuje trospium. Wyjątkowa struktura chemiczna (wielkocząsteczkowa czwartorzędowa amina) powoduje, że w minimalnym stopniu przechodzi przez barierę krew-mózg i może być bezpiecznie stosowana u starszych osób.

Na następnej stronie (tab. 1) przedstawiono dostępne w Polsce preparaty antycholinergiczne, z uwzględnieniem ich charakterystyki farmakologicznej i klinicznej. Zgodnie z wytycznymi ICI (International Consultations on Incontinence) solifenacyna ma najwyższy stopień referencyjności 1A (wg wytycznych oksfordzkich: 1 - w oparciu o przeglądy systematyczne, metaanalizy, dobrej jakości randomizowane badania kliniczne; A - lek najbardziej rekomendowany).

Tabela 1
 

W przypadku solifenacyny nie jest konieczne (tak jak dla oksybutyniny i tolterodyny) opracowywanie form o powolnym uwalnianiu, z uwagi na jej długi okres półtrwania, wynoszący 52 godziny, i czas osiągnięcia maksymalnego stężenia w surowicy krwi wynoszący 3-8 godzin. Wyniki badań klinicznych, zarówno z placebo, jak i z aktywnym komparatorem, wykazują, że solifenacyna jest substancją o wysokim profiluskuteczność/bezpieczeństwo. Roczny okres terapii solifenacyną został ukończony przez 81,4% pacjentów, odsetek pacjentów, którzy zrezygnowali z leczenia z powodu braku skuteczności, wyniósł jedynie 4,8%. Taki sam odsetek pacjentów zrezygnował z leczenia z powodu objawów ubocznych. W indywidualnych ocenach skuteczności leczenia przez pacjentów 74% oceniło ją jako satysfakcjonującą i wyższą, a tylko 1,3% pacjentów oceniło objawy uboczne związane z przyjmowanym lekiem jako nie do zaakceptowania. Kolejne badania kliniczne wykazały, że solifenacyna zmniejsza o 100% liczbę epizodów nietrzymania moczu z parcia, o 60-70% liczbę epizodów parć naglących oraz o 50% liczbę epizodów częstomoczu nocnego. Po leczeniu solifenacyną zupełne ustąpienie objawów nietrzymania moczu było stwierdzane przez 52% pacjentów. Najnowsze badanie kliniczne oceniające solifenacynę w aspekcie wpływu na parcie naglące (jako przyczynę pierwotną wystąpienia innych objawów pęcherza nadreaktywnego) z użyciem 4-stopniowej skali intensywności parcia naglącego PPIUS (Patent Perceptron of Intensity of Urgency Scale), gdzie "0" oznacza brak parcia naglącego, a "4" oznacza nietrzymanie moczu, wykazało, że liczba epizodów parcia naglącego ocenianego na 3 lub 4 po terapii solifenacyną zmniejszyła się średnio o 2,58 punktu, podczas gdy w grupie stosującej placebo tylko o 1,81, co jest wartością znamienną statystycznie (p<0,0001). Wtórną zmienną uwzględnioną w badaniu było postrzeganie choroby jako "problemu", a także miara skrępowania i udręczenia spowodowanego każdym epizodem parcia naglącego. Wykorzystując wzrokową skalę analogową (Visual Analogue Scale), gdzie 0 oznacza "brak niedogodności", a 100 oznacza "najgorszą możliwą niedogodność", po zostosowaniu solifenacyny niedogodności związane parciem naglącym zostały zredukowane o 35 punktów na wspomnianej skali i o 25 w przypadku placebo, co jest wartością znamienną statystycznie (p<0,0001).

Potwierdzono również istniejące dane dotyczące profilu bezpieczeństwa solifenacyny - liczba pacjentów, którzy wycofali się z badania z powodu niepożądanych działań ubocznych wyniosła mniej niż 3%. Częstość występowania suchości ust wynosiła 12,2% dla solifenacyny w dawce 5 mg (15,8% solifenacyna 5 i 10 mg), a zaparcia zgłaszało 5% stosujących tę substancję (6,9% solifenacyna 5 i 10 mg). Nie stwierdzono natomiast istotnej różnicy pomiędzy solifenacyną i placebo w częstości zgłaszanych zaburzeń widzenia. Podane wyniki są zgodne z wcześniejszymi badaniami klinicznymi dotyczącymi solifenacyny. Inne preparaty antycholinergiczne mają znacznie gorszy profilskuteczności i tolerancji w porównaniu z solifenacyną.

Oprócz preparatów antycholinergicznych w terapii OAB znalazło zastosowanie kilka innych grup leków, przeważnie wówczas, gdy nie uzyskano poprawy po dotychczasowych metodach leczenia lub objawy uboczne nie są akceptowane przez pacjentów. Jednymi z nich są trójpierścieniowe leki przeciwdepresyjne, głównie imipramina oraz rzadziej doxepina. Imipramina pierwotnie stosowana była w leczeniu schizofrenii. Ponieważ wpływa na metabolizm wielu neuroprzekaźników, znalazła zastosowanie w leczeniu szeregu innych zaburzeń psychicznych (np. depresji, zaburzeń afektywnych) i fizycznych (jak moczenie nocne, przewlekłe zespoły bólowe). Hamuje wychwyt zwrotny serotoniny, noradrenaliny, dopaminy, blokuje receptory muskarynowe M2, histaminowe H1, zwiększa ekspresję czynnika wzrostu nerwów - neurotrofiny BDNF (Brain Derived Neurotrophic Factor) obecnej m.in. w neuronach motorycznych, śliniankach i dolnych drogach moczowych. Działa także przeciwbólowo, pobudzając receptory opiatowe typu "mi". Ze względu na wyżej opisane właściwości, u chorych z nadreaktywnością pęcherza zmniejsza dolegliwości związane z parciami naglącymi, bólami w okolicy nadłonowej, jednocześnie łagodząc często współistniejące objawy depresyjne [96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112].

W farmakoterapii nadreaktywności pęcherza sięgnięto także po inne preparaty z powodzeniem stosowane w innych gałęziach medycyny: blokery kanału wapniowego (np. nifedypina), blokery receptorów alfa-adrenergicznych (doxazosyna) oraz hormony (estrogeny stosowane doustnie lub dopochwowo) [113, 114, 115, 116, 117, 118, 119]. W różnych fazach badań znajduje się kilkanaście substancji, potencjalnych leków [120]:
1. Antymuskarynowe o większej selektywności w stosunku do receptorów M2 i M3, PSD-506 (Plethora Solutions) i SMP-986 (Dainippon Sumitomo).
2. Substancje agonistyczne w stosunku do receptorów beta-adrenergicznych GW-427353 (GlaxoSmithKline), YM-178 (Astellas) KUC-7483 (Kissei Pharmaceuticals).
3. Antagoniści neurokinin (m.in. substancji P, CGRP): cizolirtine, SSR-240600 (Sanofi-Aventis), TA-5538 (Mitsubishi Tanabe).
4. Substancje otwierające ATP-zależne błonowe kanały potasowe (pinacidil, ZD6169, NS309).
5. Agoniści receptora witaminy D/inhibitory kinaz RhoA/Rho (elocalcitol).

Pomimo wprowadzenia nowych leków, analiza publikowanych badań klinicznych opartych o kwestionariusze pytań i badania urodynamiczne wykazuje, że pomimo leczenia objawy OAB utrzymują się u większości pacjentów, a farmakoterapia, niezależnie od jej rodzaju, pozwala na osiągnięcie jedynie krótko- i średnioterminowej poprawy jakości życia QoL [121, 122]. Coraz szerzej są opisywane w literaturze medycznej i wprowadzane do zastosowań klinicznych nowe metody leczenia wybiórczo nakierowanego na pęcherz moczowy. Ostrzykiwanie ściany pęcherza moczowego (mięśnia wypieracza) neurotoksyną botulinową typu A powoduje okresowe zablokowanie synaps cholinergicznych, zwiotczenie mięśni gładkich wypieracza i z kolei spadek jego nadaktywności. Opisano skuteczność dopęcherzowego podawania kapsaicyny [123, 124, 125].

Leczenie nadreaktywności pęcherza u mężczyzn z przerostem gruczołu krokowego
Najczęściej, bo u 36% mężczyzn z przerostem gruczołu krokowego, farmakoterapia oparta jest na antagonistach receptorów alfa1-adrenergicznych i inhibitorach 5-alfa-reduktazy. Leki te stosowane są łącznie lub jako monoterapia. Tylko 25% mężczyzn z nadreaktywnością pęcherza moczowego i 6% z objawami LUTS w przebiegu przerostu gruczołu krokowego otrzymywało leki antycholinergiczne. Antagoniści receptorów alfa1-adrenergicznych są podstawowymi lekami stosowanymi w terapii przerostu stercza, skutecznie łagodząc objawy przeszkody podpęcherzowej. Wykazano także ich krótkotrwały wpływ na złagodzenie towarzyszących objawów nadreaktywności pęcherza. Sytuację tę mogłoby poprawić dodatkowe włączenie leków antycholinergicznych, jednak osłabienie kurczliwości wypieracza może wiązać się ze wzrostem ryzyka ostrego zatrzymania moczu. Przeprowadzono randomizowane badanie kliniczne 50 mężczyzn z przerostem gruczołu krokowego, porównujące skuteczność monoterapii alfa-blokerem (tamsulosyna) i terapii złożonej (tamsulosyna + tolterodyna). U chorych stwierdzano objawy przeszkody podpęcherzowej oraz nadreaktywności wypieracza.

Obserwacja trwała 3 miesiące. U pacjentów stosujących terapię złożoną stwierdzono poprawę jakości życia oraz wzrost pojemności pęcherza. Nie stwierdzono spadku objętości zalegającego moczu po mikcji w stosunku do pacjentów leczonych tylko alfa1-blokerami. Wyniki te znalazły potwierdzenie w kolejnym badaniu 879 mężczyzn z przerostem stercza i objawami nadreaktywności pęcherza leczonych za pomocą w/w preparatów (badanie TIMES). U tych pacjentów stwierdzono istotną poprawę parametrów IPSS (International Prostate Symptom Score) [126, 127, 128, 129, 130, 131, 132].

W sytuacji, gdy leczenie farmakologiczne jest nieskuteczne lub pojawiają się powikłania przerostu gruczołu krokowego (nawracające, oporne na leczenie infekcje, kamica, znaczne zaleganie moczu, nieakceptowane przez chorego obniżenie jakości życia), należy wdrożyć leczenie chirurgiczne, którym z reguły jest elektroresekcja przezcewkowa (TURP). W efekcie tego leczenia znikają objawy związane z przeszkodą podpęcherzową. Po zabiegu objawy nadreaktywności pęcherza moczowego utrzymują się nadal u ok. 19% pacjentów i odsetek ten wzrasta aż do 63% w ciągu kolejnych lat [133, 134, 135, 136, 137, 138, 139].

Leczenie przyczynowe nadreaktywności pęcherza moczowego

Zgodnie z teorią uszkodzenia neuronalnego w przypadku nadreaktywności może dochodzić do tzw. wyciekania acetylocholiny z zakończeń nerwowych, w czasie gdy włókna cholinergiczne nie są aktywne. Możliwy jest też rozwój nadmiernej impulsacji aferentnej, powodującej na drodze odśrodkowej stymulację wypieracza i powstawanie parcia naglącego.

Te dane stwarzają patofizjologiczne podstawy do zastosowania leków antycholinergicznych, a także do opracowywania nowych metod leczenia ukierunkowanych na wpływanie na poszczególne populacje neuronalne (leki działające na kanały jonowe, neurotoksyny).

Leki wpływające na ośrodkowy układ nerwowy
Obecnie istnieją nieliczne schematy terapeutyczne stosowania leków, których punkt uchwytu znajduje się w ośrodkowym układzie nerwowym, jednak wiedza o neurotransmiterach obecnych w mózgu i rdzeniu kręgowym może być pomocna w doświadczeniach dotyczących poszukiwania nowych leków stosowanych w leczeniu pęcherza nadreaktywnego. Obiecującą grupą leków są substancje wpływające na drogi przewodzenia dopaminergicznego w ośrodkowym układzie nerwowym. Stymulacja receptorów dopaminergicznych D1 powoduje zahamowanie odruchu mikcji, natomiast stymulacja receptorów D2 powoduje inicjację tego odruchu. Wykazano zmniejszenie nasilenia objawów pęcherza nadreaktywnego u małp z chorobą Parkinsona po zastosowaniu substancji SKF 38393 - agonisty receptora D1 [140].

Substancje działające na receptory purynergiczne, których obecność została niedawno wykazana w dolnych drogach moczowych, mogą mieć zastosowanie w leczeniu nadreaktywności pęcherza moczowego. Najbardziej obiecujące wydaje się być stosowanie leków działających na receptory purynergiczne u chorych z neurogennym uszkodzeniem dolnych dróg moczowych oraz u pacjentów w podeszłym wieku. W tych grupach chorych stwierdzono bowiem zwiększoną aktywność transmisji purynergicznej.

Kanabinoidy, czyli pochodne marihuany, wpływają na receptory kanabinoidowe w ośrodkowym układzie nerwowym. Preparat podjęzykowy, składający się z mieszaniny tetrahydrokanabinolu i kanabidilu, był podawany w randomizowanym badaniu z wykorzystaniem placebo pacjentom z nadreaktywnością wypieracza i stwardnieniem rozsianym. Wykazano, że Sativex co prawda nie zmniejszał liczby epizodów nietrzymania moczu, ale zmniejszał liczbę mikcji zarówno w nocy, jak i w dzień oraz poprawiał parametry jakości życia. Lek nie wpływał też na dobową produkcję moczu [141]. Zupełnie inne podejście do problemu pęcherza nadreaktywnego zostało przedstawione przez grupę naukowców z Bristolu. Wychodząc z założenia, że głównym czynnikiem ograniczającym pacjentów z pęcherzem nadreaktywnym i limitującym ich możliwości zawodowe jest częstomocz dzienny, badacze ci zaproponowali stosowanie desmopresyny w dawce 0,2 mg rano, celem zmniejszenia częstotliwości mikcji w dzień. Okazało się, że lek zmniejszał liczbę mikcji o jedną (w porównaniu z placebo) w ciągu 8 godzin od zażycia, ale za to aż 78% pacjentów leczonych desmopresyną nie miało w ogóle epizodów nietrzymania moczu do 8 godzin po zażyciu leku. Zaobserwowano też znamienną poprawę jakości życia u pacjentów przyjmujących desmopresynę. Objawy uboczne miały na ogół nie wielkie nasilenie i dotyczyły bólów głowy oraz biegunki. U żadnego z pacjentów nie zaobserwowano hiponatremii [142].

Neurotoksyny w leczeniu nadreaktywności pęcherza moczowego

Era neurotoksyn w urologii rozpoczęła się od wykazania istnienia tzw. włókien C-reaktywnych, odpowiedzialnych za reorganizację odruchu mikcji po urazie rdzenia kręgowego. To odkrycie dało początek zastosowaniu selektywnej wobec włókien C neurotoksyny - kapsaicyny. Dalsze badania doprowadziły do odkrycia receptora waniloidowego, który ma charakter kanału jonowego. Okazało się, że kapsaicyna, działając za pośrednictwem receptora waniloidowego (VR1), powoduje najpierw pobudzenie aferentnych włókien typu C, co oczywiście nasila parcie naglące oraz wzmaga czucie bólu, a następnie dopiero dochodzi do neurolizy i porażenia czucia [143]. To spowodowało poszukiwania innej neurotoksyny, pozbawionej działania pobudzającego. Resiniferatoksyna, działająca również za pośrednictwem receptora VR1, nie ma pobudzającego działania na komórki nerwowe, wywołuje jedynie ich porażenie. Resiniferatoksyna powoduje ponadto plastyczność neuronalną, polegającą na zmianie fenotypu neuronów. Resiniferatoksyna znalazła zastosowanie w leczeniu neurogennej i nieneurogennej nadreaktywności wypieracza oraz w leczeniu śródmiąższowego zapalenia pęcherza moczowego. Skuteczność resiniferatoksyny wynosi 45-66% w zależności od schorzenia [143].

Kolejną neurotoksyną pochodzenia bakteryjnego, która znalazła szerokie zastosowanie w neurourologii, jest toksyna botulinowa. Toksyna botulinowa (BTX) jest najsilniejszą neurotoksyną występującą w przyrodzie. Jej działanie polega na hamowaniu uwalniania acetylocholiny w obrębie cholinergicznej synapsy nerwowo- mięśniowej. W praktyce urologicznej używana jest toksyna A - (preparaty Dysport i Botox, różniące się dawkami - dawki nie są równoważne, oraz sposobem przygotowania - zamrażanie i liofilizacja).

W największym dostępnym obecnie badaniu klinicznym poddano analizie 200 chorych z neurogenną dysfunkcją pęcherza, którym BTX-A podano w formie iniekcji do ściany pęcherza. W kontroli po 3 i 6 miesiącach stwierdzono statystycznie znamienny wzrost pojemności cystometrycznej pęcherza oraz spadek ciśnień śródpęcherzowych. Toksyna botulinowa może być również stosowana w idiopatycznej nadreaktywności pęcherza moczowego (stosuje się wówczas mniejsze dawki, z uwagi na ryzyko porażenia pęcherza moczowego). Wyniki badań randomizowanych, podwójnie ślepych, kontrolowanych przez placebo wykazały 55% skuteczność BTX w całkowitej eliminacji nadreaktywności wypieracza. W przypadku nadreaktywności na tle idiopatycznym skuteczność wynosi 62,5%, w przeszkodzie podpęcherzowej 85%, a w śródmiąższowym zapaleniu pęcherza 69%. Oprócz zablokowania uwalniania acetylocholiny uważa się, że toksyna botulinowa może wpływać na zakończenia czuciowe zlokalizowane w pęcherzu, co stanowiłoby atrakcyjne wyjaśnienie jej działania w przypadku np. nadreaktywności na tle wzmożonej dośrodkowej impulsacji czuciowej [144, 145].

Leczenie chirurgiczne
Zabiegi chirurgiczne nie znalazły szerszego zastosowania w terapii pęcherza nadreaktywnego. W publikacjach wymieniane są jako opcja leczenia pacjentów, u których inne metody zawiodły, a znaczne nasilenie objawów usprawiedliwia tak radykalny krok. U chorych z nadreaktywnością pęcherza celem jest zwiększenie pojemności pęcherza oraz obniżenie siły i częstotliwości skurczów wypieracza i ciśnienia wewnątrzpęcherzowego. Najczęstszym zabiegiem jest cystoplastyka z wszyciem segmentu jelitowego, pozwalająca na zwiększenie pojemności pęcherza i osłabienie siły skurczów wypieracza dzięki częściowemu rozcięciu. Opisywane są zabiegi polegające na podłużnym rozcięciu pęcherza i ponownym zszyciu (clam plasty), odnerwienie ściany pęcherza, a nawet usunięcie części wypieracza.

Nadreaktywność pęcherza moczowego to problem socjologiczny i ekonomiczny

Zespół nadreaktywnego pęcherza znalazł się w kręgu zainteresowań urologów i ginekologów. Można to wiązać z rozwojem metod diagnostycznych (badań urodynamicznych), postępami neurofizjologii i wyodrębnianiem się nowych dziedzin medycznych (np. uroginekologii). Przyczyną jest także kierowanie się medycyny oraz przemysłu farmaceutycznego na nowe obszary działalności, związane nie tylko z leczeniem chorób zagrażających życiu, lecz także pogarszających jego jakość. Efektem jest opracowanie szeregu nowych leków do terapii dysfunkcji erekcyjnej czy hormonalnej terapii zastępczej u obu płci.

Ze względu na dużą liczbę potencjalnych pacjentów OAB stał się istotnym celem dla firm farmaceutycznych. Tylko wydatki na reklamę stosowanych leków antycholinergicznych wynoszą 127 mln dolarów rocznie, a jest o co walczyć, gdyż roczny wzrost wydatków na te preparaty stanowi 11%.

Jak wiele innych schorzeń, OAB jest problemem społecznym i ekonomicznym, ponieważ w istotny sposób ogranicza aktywność życiową pacjentów, głównie w krajach wysokorozwiniętych. Koszty obejmują wydatki bezpośrednio związane z leczeniem choroby i powikłań oraz pośrednie, związane z wyłączeniem jednostki ze społeczeństwa i ograniczeniem aktywności zawodowej [146, 147, 148]. W roku 2000 w USA wyniosły 12,02 mld dolarów, z czego14% przypadło na utrzymanie chorych w domach opieki, 9% na leczenie, 6% stanowiły powikłania, a jedynie 1% przypadło na badania diagnostyczne. Pozostały odsetek stanowiły wydatki na codzienną opiekę i utrata produktywności pacjenta, ocenione na 841 mln dolarów rocznie [149]. Łączne obciążenia społeczne różnych form nietrzymania moczu w USA przekraczają 26 mld dolarów. Obliczony koszt powikłań nadreaktywności pęcherza moczowego obejmował leczenie zwiększonej ilości infekcji dróg moczowych (1,3 mld dolarów) oraz dwukrotnego wzrostu liczby urazów kości (386 mln dolarów) [150]. Urazy te są związane z upadkami i stanowią 23% wydatków na leczenie powikłań OAB. Pacjenci z naglącym nietrzymaniem moczu ponoszą dodatkowe koszty podkładek higienicznych, wynoszące ok. 135 dolarów rocznie, środków do pielęgnacji i leczenia skóry oraz wydatki na zwiększoną liczbę wizyt lekarskich i hospitalizacji [151, 152, 153, 154, 155, 156, 157, 158].

Podsumowanie

Objawy zespołu pęcherza nadreaktywnego występują z równą częstotliwością wśród obu płci. W istotny sposób wpływają na pogorszenie jakości życia chorych. Dotychczas brak teorii jednoznacznie wyjaśniających etiologię schorzenia. Leczenie obejmujące zmiany stylu życia, terapie behawioralne oraz farmakoterapię jest skuteczne jedynie u części pacjentów. Objawy mają charakter nawrotowy nawet u chorych, u których uzyskano początkowo znaczną poprawę. W odniesieniu do OAB stwierdzenie Bensona "...wolę mówić pacjentom: wierzę, że masz takie objawy, nie wiem, co jest ich przyczyną, ale zrobię wszystko, abyś poczuł się lepiej" nie straciło na aktualności.

dr n. med. Stanisław Wroński
Oddział Urologii, Szpital Uniwersytecki nr 2 im. dr. J. Biziela, Bydgoszcz
ordynator oddziału: dr n. med. Piotr Jarzemski

dr hab. n. med. Piotr Radziszewski
Katedra i Klinika Urologii, Warszawski Uniwersytet Medyczny
kierownik katedry i kliniki: prof. dr hab. n. med. Andrzej Borkowski

lek. med. Daniel Lewczak
Oddział Urologii, Szpital Uniwersytecki nr 2 im. dr. J. Biziela, Bydgoszcz
ordynator oddziału: dr n. med. Piotr Jarzemski

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Hepler <betsy.hepler@gmail.com> poniedziałek, 11 marca 2019, godzina 0439
I have access to a massive network of around 10,000 CBD and Hemp related blogs. I have been using these blogs to rank vape shops and CBD sites on top of the search engines. With this gig, you will receive a guest post on each blog (I will create unique content). These links is literally all that you need to rank at the top of the search engines as far as link building goes. Here are the key features of the links: Insanely strong domain metrics: domain authority from 50 to 80!!! Do Follow and contextual links 100% permanent and indexable with the search engines 100% CBD and hemp niche related. To get started, please send me your website and up to 50 keywords you would like to rank for (one key word per line). https://www.fiverr.com/alecmonopoly/create-backlinks-on-hemp-and-cbd-blogs
Coombes <tony.coombes85@gmail.com> poniedziałek, 11 marca 2019, godzina 0615
Hi again I have tried sending you a message on your site but I got an email saying it was not delivered so here goes again. It would be great if you could let me know if you have received my email and article. I would like to contribute an article to your blog on how cryptocurrencies are reshaping the cannabis and CBD industry. I have used a couple of CBD sites in the UK to buy CBD oil using cryptocurrency. I realised just how much of an impact cryptocurrencies will have on the cannabis industry (which is heavily regulated) and I therefore decided to write this article. Hopefully, your readers will find it useful. I have saved the article in a word document on my G-Drive which you can access from here: https://drive.google.com/drive/folders/1KDnahFgKRGeio0gPiJ61GcftlAyhZvZT?usp=sharing I am very sorry but I did not have the time to collect some images so please feel free to add some of your own. If you like my article, I can write a couple more once I get some free time (it is crazy busy at work right now after the new year). Have an awesome day! Regards Tony
Coombes <tony.coombes85@gmail.com> poniedziałek, 11 marca 2019, godzina 1330
Hi again I have tried sending you a message on your site but I got an email saying it was not delivered so here goes again. It would be great if you could let me know if you have received my email and article. I would like to contribute an article to your blog on how cryptocurrencies are reshaping the cannabis and CBD industry. I have used a couple of CBD sites in the UK to buy CBD oil using cryptocurrency. I realised just how much of an impact cryptocurrencies will have on the cannabis industry (which is heavily regulated) and I therefore decided to write this article. Hopefully, your readers will find it useful. I have saved the article in a word document on my G-Drive which you can access from here: https://drive.google.com/drive/folders/1KDnahFgKRGeio0gPiJ61GcftlAyhZvZT?usp=sharing I am very sorry but I did not have the time to collect some images so please feel free to add some of your own. If you like my article, I can write a couple more once I get some free time (it is crazy busy at work right now after the new year). Have an awesome day! Regards Tony
Coombes <tony.coombes85@gmail.com> środa, 13 marca 2019, godzina 1552
Hi again I have tried sending you a message on your site but I got an email saying it was not delivered so here goes again. It would be great if you could let me know if you have received my email and article. I would like to contribute an article to your blog on how cryptocurrencies are reshaping the cannabis and CBD industry. I have used a couple of CBD sites in the UK to buy CBD oil using cryptocurrency. I realised just how much of an impact cryptocurrencies will have on the cannabis industry (which is heavily regulated) and I therefore decided to write this article. Hopefully, your readers will find it useful. I have saved the article in a word document on my G-Drive which you can access from here: https://drive.google.com/drive/folders/1KDnahFgKRGeio0gPiJ61GcftlAyhZvZT?usp=sharing I am very sorry but I did not have the time to collect some images so please feel free to add some of your own. If you like my article, I can write a couple more once I get some free time (it is crazy busy at work right now after the new year). Have an awesome day! Regards Tony
Demaio <leona.demaio27@outlook.com> czwartek, 14 marca 2019, godzina 1313
Hello I have written a couple of articles on CBD from multiple angles and would love to contribute these articles to your blog. I have saved the articles on my Google drive which you can access from here: https://drive.google.com/drive/folders/1y96hoCPHfKWh52MtfDoRRdjaeBQR37rq?usp=sharing I am sorry but I did not have any time to find some good images so it would be fab if you could add some. Keep up the great work on your site! Regards
Frawley <mozelle.frawley@gmail.com> sobota, 16 marca 2019, godzina 1239
I am currently working with some of the biggest vape wholesalers, MOD makers, e-juice brands and vape shops. I am sure that you have heard of them all or seen them at most vape expos. To put it bluntly, I know what works and what doesn't. I now know the vape industry like the back of my hand. I have taken all the most effective elements of my vape seo equation and lumped them into these incredibly cheap packages, which I would sell for about 10 times the amount I am selling them for here. I have divided the packages on the basis of the amount of competition you are facing. So here is the breakdown of what exactly you will get with each package: Mouse (ideal for small local vape shops located in the suburbs): 100 links inside my vape and ejuice blogs 50 bookmarks and social signals Indexing Cat (mid-sized vape companies) 500 backlinks inside vape blogs 250 social bookmarks promotion on 5,000 forums Around 10,000 mixed blog comment, PBN and other links to increase your domain authority Bear (ideal for companies based in large cities) 1500 vapor blog links 500 social bookmarks Promotion on 10,000 forums 20,000 mixed links Indexing Guest Posts on 5 strong sites Lots of Extras To learn more, please visit https://www.fiverr.com/ghosttownseo/create-a-full-vape-backlinks-package
Coombes <tony.coombes85@gmail.com> poniedziałek, 18 marca 2019, godzina 0056
Hi again I have tried sending you a message on your site but I got an email saying it was not delivered so here goes again. It would be great if you could let me know if you have received my email and article. I would like to contribute an article to your blog on how cryptocurrencies are reshaping the cannabis and CBD industry. I have used a couple of CBD sites in the UK to buy CBD oil using cryptocurrency. I realised just how much of an impact cryptocurrencies will have on the cannabis industry (which is heavily regulated) and I therefore decided to write this article. Hopefully, your readers will find it useful. I have saved the article in a word document on my G-Drive which you can access from here: https://drive.google.com/drive/folders/1KDnahFgKRGeio0gPiJ61GcftlAyhZvZT?usp=sharing I am very sorry but I did not have the time to collect some images so please feel free to add some of your own. If you like my article, I can write a couple more once I get some free time (it is crazy busy at work right now after the new year). Have an awesome day! Regards Tony
Estell <earnest.estell96@gmail.com> poniedziałek, 18 marca 2019, godzina 2203
Hello I have written a couple of articles on CBD from multiple angles and would love to contribute these articles to your blog. I have saved the articles on my Google drive which you can access from here: https://drive.google.com/drive/folders/1y96hoCPHfKWh52MtfDoRRdjaeBQR37rq?usp=sharing I am sorry but I did not have any time to find some good images so it would be fab if you could add some. Keep up the great work on your site! Regards
Coombes <tony.coombes85@gmail.com> poniedziałek, 18 marca 2019, godzina 2204
Hi again I have tried sending you a message on your site but I got an email saying it was not delivered so here goes again. It would be great if you could let me know if you have received my email and article. I would like to contribute an article to your blog on how cryptocurrencies are reshaping the cannabis and CBD industry. I have used a couple of CBD sites in the UK to buy CBD oil using cryptocurrency. I realised just how much of an impact cryptocurrencies will have on the cannabis industry (which is heavily regulated) and I therefore decided to write this article. Hopefully, your readers will find it useful. I have saved the article in a word document on my G-Drive which you can access from here: https://drive.google.com/drive/folders/1KDnahFgKRGeio0gPiJ61GcftlAyhZvZT?usp=sharing I am very sorry but I did not have the time to collect some images so please feel free to add some of your own. If you like my article, I can write a couple more once I get some free time (it is crazy busy at work right now after the new year). Have an awesome day! Regards Tony
Walck <gracie.walck@gmail.com> wtorek, 19 marca 2019, godzina 0219
GLOBAL VAPE SHOP DATABASE AND VAPE STORE EMAIL LIST Do you run an e-liquid company or a vape wholesale or distribution business? Are you tired of hitting the wall with your marketing efforts? Would you like to start exploding your sales with a click of a button? Let us now share with you the secret sauce that has powered some of the biggest e-juice brands from around the world: The Global Vape Shop Email List! Global Vape Shop Database and Vape Store Email List - https://bit.ly/2V3ZKAU WHAT IS THE GLOBAL VAPE SHOP EMAIL LIST AND WHAT DOES IT CONTAIN The Global Vape Shop Email List is an Excel spreadsheet containing vape shop contact details. The spreadsheet comes with many tabs for different countries and each tab contains the vape shop contact details for that respective country. The Global Vape Shop Database contains vape shop names, emails, websites, telephone numbers, locations and store addresses, social media links and much more! Our database has around 15,000 vape shops but this number is approximate because the vape shop numbers fluctuate following updates. Click here to learn more and purchase the database: https://bit.ly/2V3ZKAU
Rhea <dessie.rhea@msn.com> środa, 20 marca 2019, godzina 0807
GLOBAL VAPE COMPANY EMAIL LIST OF VAPE SHOPS AND VAPE WHOLESALERS AND E-LIQUID DISTRIBUTORS Global Vape Company Email List of Vape Shops and Vape Wholesalers and E-Liquid Distributors Did you know that there are over 38,000 vape companies around the world that you can contact today? Whether you run an e-liquid line or a vape wholesale business, these vape company emails can help you to reach practically all vape companies with your message. Are you tired from not making enough B2B sales to vape shops and vape wholesalers? Do you find most of your marketing to be unproductive? Do you want to take your vape business to the next level and start exploding your sales? Here is the secret sauce that has helped over 500 e-liquid brands and wholesalers from around the world since 2012! Some ejuice companies have even tried to buy us out because they felt that the accessibility of this list was putting them against a lot of competition from smaller vape companies and e-liquid brands! This hopefully helps to illustrate just how powerful this vape company email list is! HERE IS WHAT THE VAPE COMPANY EMAIL LIST CONTAINS: Vape Shops (brick-and-mortar and online) Vape Wholesalers and distributors E-Liquid Companies Vape Event Organisers Vape magazines Vape reviewers HERE ARE THE WAYS IN WHICH YOU CAN USE THIS VAPE COMPANY EMAIL LIST Promotional messages Introductory emails Guest post outreach for backlink building Much more Buy and learn more at https://bit.ly/2zcDKeX
Buckner <dominic.buckner@yahoo.com> czwartek, 21 marca 2019, godzina 1043
GLOBAL VAPE COMPANY EMAIL LIST OF VAPE SHOPS AND VAPE WHOLESALERS AND E-LIQUID DISTRIBUTORS Global Vape Company Email List of Vape Shops and Vape Wholesalers and E-Liquid Distributors Did you know that there are over 38,000 vape companies around the world that you can contact today? Whether you run an e-liquid line or a vape wholesale business, these vape company emails can help you to reach practically all vape companies with your message. Are you tired from not making enough B2B sales to vape shops and vape wholesalers? Do you find most of your marketing to be unproductive? Do you want to take your vape business to the next level and start exploding your sales? Here is the secret sauce that has helped over 500 e-liquid brands and wholesalers from around the world since 2012! Some ejuice companies have even tried to buy us out because they felt that the accessibility of this list was putting them against a lot of competition from smaller vape companies and e-liquid brands! This hopefully helps to illustrate just how powerful this vape company email list is! HERE IS WHAT THE VAPE COMPANY EMAIL LIST CONTAINS: Vape Shops (brick-and-mortar and online) Vape Wholesalers and distributors E-Liquid Companies Vape Event Organisers Vape magazines Vape reviewers HERE ARE THE WAYS IN WHICH YOU CAN USE THIS VAPE COMPANY EMAIL LIST Promotional messages Introductory emails Guest post outreach for backlink building Much more Buy and learn more at https://bit.ly/2zcDKeX
McCarron <lizette.mccarron@gmail.com> piątek, 22 marca 2019, godzina 0045
Good morning I am looking to build up my B2B email list for newsletter marketing. I am very keen to get Ivy's B2B Leads Miner - Yellow Pages Scraper Software as it is probably one of the best Yellow Pages scrapers for UK and USA out there. I was just wondering if you have ever used this particular or any other scrapers before? Cheers guys!
Duff <stacie.duff@outlook.com> niedziela, 24 marca 2019, godzina 1021
WHY E-MAIL MARKETING IS CRUCIAL FOR YOUR VAPE BUSINESS? Having operated in the vape industry for over 8 years, we can confidently say that e-mail marketing gets the results. E-mail marketing such as plain introductory e-mails and newsletters help your vape business to get your message across to thousands of vape shops, e-liquid wholesalers and other types of vape businesses. However, in order to make an impact with your newsletter campaign, you have to have quality, verified and cleaned mailing list of vape businesses. A DEFINITIVE AND MOST COMPREHENSIVE E-MAIL LIST OF ALL VAPE SHOPS, E-LIQUID BRANDS, E-LIQUID WHOLESALERS, VAPE DISTRIBUTORS, VAPE EVENT ORGANISERS, ONLINE VAPE SHOPS, BRICK-AND-MORTAR VAPE SHOPS, VAPE MAGAZINES AND VAPE COMMUNITIES IS FINALLY HERE! Following multiple requests from our clients, our e-mail marketing team has worked hard over the past three months to bring you an e-mail list of ALL vape businesses around the world. We have combined all e-mail addresses from our vape shop databases, contacts, business cards from over 50 vape exhibitions, public domain, subscriber lists and other sources. Our entire mailing list has been scrubbed to weed out vape businesses that have gone out of business or changed their domain names to bring you a clean and verified mailing list of vape businesses around the world. Upon payment, the Vape Company E-Mail Mailing List is available as an INSTANT DOWNLOAD in a notepad .txt format that you can simply upload to your subscriber list. Then all you have to do is create a beautiful newsletter campaign and hit the send button. Our Vape Company E-Mail Mailing List has over 38,000 email addresses of brick-and-mortar vape shops, e-liquid wholesalers and distributors, online vape shops, e-liquid brands, vape event organisers, vape communities, vape magazines, vape reviewers and much more! Our team is constantly verifying and updating the Vape Company email list to bring you only the latest vape company leads. DOWNLOAD A SAMPLE OF OUR GLOBAL E-MAIL LIST OF ALL VAPE COMPANIES IN THE WORLD https://theeliquidboutique.co.uk/products/vape-company-e-mail-mailing-list
Chiman <aly1@alychidesigns.com> niedziela, 24 marca 2019, godzina 1250
Hello there, My name is Aly and I would like to know if you would have any interest to have your website here at przeglad-urologiczny.pl promoted as a resource on our blog alychidesign.com ? We are in the midst of updating our broken link resources to include current and up to date resources for our readers. Our resource links are manually approved allowing us to mark a link as a do-follow link as well . If you may be interested please in being included as a resource on our blog, please let me know. Thanks, Aly
Damron <ezra.damron@googlemail.com> poniedziałek, 25 marca 2019, godzina 0418
I am currently working with some of the biggest vape wholesalers, MOD makers, e-juice brands and vape shops. I am sure that you have heard of them all or seen them at most vape expos. To put it bluntly, I know what works and what doesn't. I now know the vape industry like the back of my hand. I have taken all the most effective elements of my vape seo equation and lumped them into these incredibly cheap packages, which I would sell for about 10 times the amount I am selling them for here. I have divided the packages on the basis of the amount of competition you are facing. So here is the breakdown of what exactly you will get with each package: Mouse (ideal for small local vape shops located in the suburbs): 100 links inside my vape and ejuice blogs 50 bookmarks and social signals Indexing Cat (mid-sized vape companies) 500 backlinks inside vape blogs 250 social bookmarks promotion on 5,000 forums Around 10,000 mixed blog comment, PBN and other links to increase your domain authority Bear (ideal for companies based in large cities) 1500 vapor blog links 500 social bookmarks Promotion on 10,000 forums 20,000 mixed links Indexing Guest Posts on 5 strong sites Lots of Extras To learn more, please visit https://www.fiverr.com/ghosttownseo/create-a-full-vape-backlinks-package
Forlong <forlong.orval@gmail.com> piątek, 29 marca 2019, godzina 0024
WHAT IS A VAPE PBN BACKLINK, AND HOW CAN IT HELP YOU MARKET YOUR E-CIGARETTE BUSINESS ONLINE? Backlinks are similar to citations found in non-fiction books. They are references to your website, made by other websites that drive traffic to your online content. The more substantive and qualitative backlinks a website has the better search results your site will receive. However, finding reputable backlinks from e-cigarette sites can be very difficult. Without qualitative references by well-respected websites your online business will suffer. Our E-Cigarette Backlink Package contains substantive, reputable backlinks that can help you improve your websites search-ability. MUST WATCH: COMPLETE GUIDE TO VAPE SEO, VAPE MARKETING & VAPE BACKLINKS https://wowitloveithaveit.com/products/extra-powerful-vape-backlinks-for-shops-seo
Gaddis <williams.gaddis@gmail.com> poniedziałek, 1 kwietnia 2019, godzina 1743
WORLD'S #1 UK VAPE SHOP DATABASE Do you own an e-liquid or a vape brand? Are you looking to sell your product to vape shops directly? Our UK vape store database is the best and most important investment you will make for your vape business. There is simply no point of having a beautiful website and a great brand if nobody has heard of it or will never see it. Our vape shop database will help to connect your brand with vape stores which will equal to brand exposure, higher sales and greater profit. Just over 500 e-liquid and mod brands have purchased our database and have made significant gains. Some of these brands are already so large that you will have heard of them! Our database of UK vape shops will help you to expand your target audience. There are many ways in which you can use the UK vape shop database including vape email marketing campaigns, newsletters, telemarketing, sending of e-liquid samples, vape shop visits and much more! https://theeliquidboutique.co.uk/products/uk-vape-shop-database
Emanuel <mellisa.emanuel67@gmail.com> niedziela, 28 kwietnia 2019, godzina 2241
WORLD'S #1 UK VAPE SHOP DATABASE Do you own an e-liquid or a vape brand? Are you looking to sell your product to vape shops directly? Our UK vape store database is the best and most important investment you will make for your vape business. There is simply no point of having a beautiful website and a great brand if nobody has heard of it or will never see it. Our vape shop database will help to connect your brand with vape stores which will equal to brand exposure, higher sales and greater profit. Just over 500 e-liquid and mod brands have purchased our database and have made significant gains. Some of these brands are already so large that you will have heard of them! Our database of UK vape shops will help you to expand your target audience. There are many ways in which you can use the UK vape shop database including vape email marketing campaigns, newsletters, telemarketing, sending of e-liquid samples, vape shop visits and much more! https://theeliquidboutique.co.uk/products/uk-vape-shop-database
Mullaly <mullaly.conrad@gmail.com> niedziela, 28 kwietnia 2019, godzina 2244
Content marketing is extremely important for increasing your website traffic as well as your SEO rankings. Right now, the major search engines are looking at how long visitors are spending on your site to decide how to rank your site. It is extremely important to have QUALITY blog posts that are interesting to read and add value to your site. As my experience has shown, poor quality spun articles will get you nowhere. I have been involved in the vape market for the past 7 years and know pretty much everything about it, including all the major vape companies, e-juice brands, vape mods, nicotine salts, vape laws and more. With this service, I will write up articles for your blog. I recommend that you keep your article titles relatively broad instead of focusing too much on individual products. Each piece will be conversational, well-researched and fun to read. Simply send me your article titles and leave everything else to me. Frequently Asked Questions I need more than 10 articles. You can order multiple packages or I could send you a custom offer, whichever works best for you. What makes you a good writer? My knowledge of the vape industry is what gives me an unparalleled advantage over other writers who have no experience in this field. Instead of writing the bare basics about the vape market, I can also write very critical and in-depth pieces. Can you help me to come up with the topics? Absolutely. Just send me your site and tell me a bit more about your business and I will put together some prospective titles. How do I choose my blog titles? I would recommend that you do not choose very broad article titles such as what is vaping because it will be very difficult to rank this article on the search engines due to the high keyword competition. Try to stick to more specialised titles such as nicotine salts guide. Why is content important for my blog? Each piece of content or each article translates into more visitors. More quality content equals to more visitors. https://peachesandscreams.co.uk/community/peaches/forums/881-vape-forum-new/topics/5405-i-will-write-10-quality-vape-articles-for-your-blog
Wooley <earnest.wooley82@googlemail.com> niedziela, 28 kwietnia 2019, godzina 2246
A QUICK OVERVIEW OF OUR GLOBAL VAPE SHOP DATABASE Our Global Vape Shop Database contains vape shop contact details including: vape shop names e-mails telephone numbers websites social media links locations/physical addresses Our Global Vape Shop Database comes in an Excel spreadsheet with vape shop details grouped by country in separate worksheets. You will receive the Global Vape Shop Database in a compressed .rar file. Simply extract the document using Windows .rar or an alternative extractor. These can be downloaded online in a click of a button. Our Global Vape Shop Database has been going for the past 5 years! Our team regularly attend vape exhibitions and events. They use this as an opportunity to collect vape shop contact details. Most of the vape shop leads are available online. However, finding, verifying and compiling them is a real administrative burden and we tell you that from our 5 year-long experience in this industry! A QUICK BREAKDOWN OF OUR GLOBAL VAPE SHOP DATABASE Our database covers USA, UK, Europe, Russia and CIS, parts of Asia, Australasia and Africa. Here's a non-exhaustive list of countries covered: Armenia, Australia, Austria, Azerbaijan, Bahrain, Bangladesh, Belgium , Canada, Czech Republic, Denmark, Estonia, Finland, France, Georgia, Germany, Greece , India, Indonesia, Ireland, Italy, Japan, Kazakhstan , Kyrgyzstan, Latvia, Lithuania, Malaysia, Maldives, Moldova, Netherlands, Poland, Romania, Russia, Slovakia, South Africa, Spain, Sweden, Switzerland, Tajikistan, UK , USA, Uzbekistan. DOWNLOAD A SAMPLE OF OUR VAPE SHOP DATABASE https://wowitloveithaveit.com/products/global-vape-shop-database-with-contact-details
Fuller <sherrie.fuller@gmail.com> niedziela, 28 kwietnia 2019, godzina 2305
Content marketing is extremely important for increasing your website traffic as well as your SEO rankings. Right now, the major search engines are looking at how long visitors are spending on your site to decide how to rank your site. It is extremely important to have QUALITY blog posts that are interesting to read and add value to your site. As my experience has shown, poor quality spun articles will get you nowhere. I have been involved in the vape market for the past 7 years and know pretty much everything about it, including all the major vape companies, e-juice brands, vape mods, nicotine salts, vape laws and more. With this service, I will write up articles for your blog. I recommend that you keep your article titles relatively broad instead of focusing too much on individual products. Each piece will be conversational, well-researched and fun to read. Simply send me your article titles and leave everything else to me. Frequently Asked Questions I need more than 10 articles. You can order multiple packages or I could send you a custom offer, whichever works best for you. What makes you a good writer? My knowledge of the vape industry is what gives me an unparalleled advantage over other writers who have no experience in this field. Instead of writing the bare basics about the vape market, I can also write very critical and in-depth pieces. Can you help me to come up with the topics? Absolutely. Just send me your site and tell me a bit more about your business and I will put together some prospective titles. How do I choose my blog titles? I would recommend that you do not choose very broad article titles such as what is vaping because it will be very difficult to rank this article on the search engines due to the high keyword competition. Try to stick to more specialised titles such as nicotine salts guide. Why is content important for my blog? Each piece of content or each article translates into more visitors. More quality content equals to more visitors. https://peachesandscreams.co.uk/community/peaches/forums/881-vape-forum-new/topics/5405-i-will-write-10-quality-vape-articles-for-your-blog
Garay <sadie.garay@msn.com> niedziela, 28 kwietnia 2019, godzina 2313
Download your vape company emails The latest version of the vape company and vape store email list has been released. If you are already subscribed to the service, you should have received your download link. To view the latest changelog, please head over to https://theeliquidboutique.co.uk/products/vape-company-e-mail-mailing-list
Chowne <chowne.ron@gmail.com> niedziela, 28 kwietnia 2019, godzina 2317
After many requests from my clients, I have created this monthly backlinks SEO package for CBD and Hemp businesses. Essentially, the premium package contains everything that you will need to rank higher on the search engines, get more visitors and make more sales. I am working with 50 different CBD and Hemp companies and during my digital marketing journey, I have tried and tested almost every strategy under the sun and picked out the bits that work real magic and chucked them all into a dirt cheap package. Depending on the package that you order, here is what you will receive: Posts and links on CBD and Hemp blog: these will provide you with contextual and extremely powerful links that will tell the search engines that your site is very popular in this niche which will force the search engines to rank you up! Promotion of your brand/site on over 10,000 most popular forums in the world: you will receive links, direct traffic to your site and generate brand awareness. Guest posts: I will post articles on popular sites and add links to your site. Paid promotions on popular sites. Social media signals. Many more extras! https://peachesandscreams.co.uk/community/peaches/forums/881-vape-forum-new/topics/5344-i-will-create-a-tailored-monthly-vape-seo-backlinks-package
Scheffler <maynard.scheffler@gmail.com> niedziela, 28 kwietnia 2019, godzina 2324
GLOBAL VAPE COMPANY EMAIL LIST OF VAPE SHOPS AND VAPE WHOLESALERS AND E-LIQUID DISTRIBUTORS Global Vape Company Email List of Vape Shops and Vape Wholesalers and E-Liquid Distributors Did you know that there are over 38,000 vape companies around the world that you can contact today? Whether you run an e-liquid line or a vape wholesale business, these vape company emails can help you to reach practically all vape companies with your message. Are you tired from not making enough B2B sales to vape shops and vape wholesalers? Do you find most of your marketing to be unproductive? Do you want to take your vape business to the next level and start exploding your sales? Here is the secret sauce that has helped over 500 e-liquid brands and wholesalers from around the world since 2012! Some ejuice companies have even tried to buy us out because they felt that the accessibility of this list was putting them against a lot of competition from smaller vape companies and e-liquid brands! This hopefully helps to illustrate just how powerful this vape company email list is! HERE IS WHAT THE VAPE COMPANY EMAIL LIST CONTAINS: Vape Shops (brick-and-mortar and online) Vape Wholesalers and distributors E-Liquid Companies Vape Event Organisers Vape magazines Vape reviewers HERE ARE THE WAYS IN WHICH YOU CAN USE THIS VAPE COMPANY EMAIL LIST Promotional messages Introductory emails Guest post outreach for backlink building Much more Buy and learn more at https://bit.ly/2zcDKeX
Bryson <ned.bryson@yahoo.com> poniedziałek, 29 kwietnia 2019, godzina 0042
I will create backlinks on my e-liquid and vape blogs built on very high authority domains. Choose the package that most suits your budget and competition you are facing. All extras are highly recommended. These vape backlinks will help to increase your vape shop's domain authority and search engine rankings as well as your sales. Simply send me the keywords you would like to rank for and I will create individual blog posts on each vape blog and add a link to your site with your preferred anchor text. I will embed some vape-related images and video reviews. All work is done manually using content related to your keywords. All of my blogs are hosted on different servers and have different IP addresses. Order now at https://bit.ly/2Vd2FqX
Allwood <rae.allwood@outlook.com> poniedziałek, 29 kwietnia 2019, godzina 0053
The vape industry has grown exponentially since 2012. It all started off with the ego starter kits, then progressed to dripping and subohming and now we seem to have reached the heights of nicotine salts, shortfill e-liquids, CBD and Juul devices. Thousands of brick-and-mortar vape shops have opened all around the world. New online vape shop start-ups are emerging on a daily basis. The competition in the vape industry has become cut throat! Back in 2012, it was a breeze to rank for competitive vape keywords on most search engines whilst today, it is even becoming difficult to rank for local area post codes as every corner of every city seems to have a growing vape shop demographic. We were the first vape SEO company in the world and we know the vape industry inside out. We have ranked some of the biggest e-juice brands since when they were starting out, vape shops that were to become some of the biggest chains in the country, vape wholesalers, event organisers and many other different types of vape sites. Our deep knowledge of the SEO and the vape industries allows us to understand the unique business models of our clients and exactly what it takes to rank a vape shop to the very top of the search engines. WHAT YOU WILL RECEIVE WITH OUR VAPE SEO PACKAGE As we have mentioned above, since working with many vape businesses, we have created a blueprint for ranking a site. We have gone through numerous trial and errors and know what works and what does not work. In the current SEO climate, major search engines are putting a greater emphasis on the overall domain authority and metrics of a site as well as brand and onsite visitor behaviour (browsing, click-throughs and bounces). We are constantly adjusting our package to ensure that all of our practices are closely attuned to the latest SEO best-practices and search engine algorithms. HERE IS WHAT YOU WILL RECEIVE WITH OUR VAPE SEO PACKAGE AND WHY IT IS IMPORTANT FOR YOUR SITE: 1,000 backlinks on vape and e-liquid blogs: all of the links are do follow, permanent and 100% related to the vaping niche. This helps the search engines to classify your site and rank it higher on the basis of the fact that it has a lot of links coming from designated vape blogs. Moreover, each vape blog has a very high domain authority which will pass on a lot of link equity to you site. 5,000+ forum posts: we will post out a unique message about your website or brand on the most popular forums in the world. Not only will this help to generate awareness about your brand but will also give you a lot of backlinks and direct visitors to your site. Guest posts on very powerful sites: we have exclusive access to some very popular and powerful sites on which we can place guests posts with links to your site. Mixed backlinks: in addition to the above work, we will also create some mixed backlinks for some diversity. This would include some blog comments, video comments and more. Indexing: we will index your links with the major searhc engines at a very natural and steady pace to keep the search engine red flags at bay! Learn more and buy at https://wowitloveithaveit.com/products/extra-powerful-vape-backlinks-seo-package-for-shops
Tolentino <tolentino.roseanna@outlook.com> poniedziałek, 29 kwietnia 2019, godzina 0106
Hi! I wanted to ask you if you have heard of this vape seo package (https://wowitloveithaveit.com/products/extra-powerful-vape-backlinks-for-shops-seo)? I was told that many leading companies in the industry are using it with the likes of vapor dna, vape ranger, element eliquids, ie vapor, ejuices.co, marina vape and other big players. I just wanted to check whether you have used them before as I can see that you have a backlink from https://wowitloveithaveit.com so my natural assumption is that you are working with these guys. Would you recommend them? Cheers
Mchenry <caridad.mchenry@gmail.com> poniedziałek, 29 kwietnia 2019, godzina 0256
Are you looking to make your e-liquid or vape brand a global success? Do you want to see your e-liquid or vape brand inside every shop around the world? Our global vape shop database will connect your vape brand with thousands of vape shops around the world and subsequently, increase your revenues and profit. Our global vape shop database has been compiled manually by our internal team over a long period of time through contacts gained at vape exhibitions and publicly available resources. Do you ever wonder, how today's big e-juice brands became big? They did what mattered the most- approached vape stores and established a rapport with vape store owners. We see many excellent e-juice brands that still fail or do not do as well as they should, simply because they do not do what matters- SELL THEIR E-JUICE TO VAPE SHOPS! (this should be the ultimate goal of any vape-related business). Our Global Vape Shop Database connects the dots between e-juice brands and the vape shops! DOWNLOAD A SAMPLE OF OUR VAPE SHOP DATABASE https://theeliquidboutique.co.uk/products/global-vape-shop-database
Montagu <montagu.blaine@outlook.com> poniedziałek, 29 kwietnia 2019, godzina 0440
WORLD'S #1 UK VAPE SHOP DATABASE Do you own an e-liquid or a vape brand? Are you looking to sell your product to vape shops directly? Our UK vape store database is the best and most important investment you will make for your vape business. There is simply no point of having a beautiful website and a great brand if nobody has heard of it or will never see it. Our vape shop database will help to connect your brand with vape stores which will equal to brand exposure, higher sales and greater profit. Just over 500 e-liquid and mod brands have purchased our database and have made significant gains. Some of these brands are already so large that you will have heard of them! Our database of UK vape shops will help you to expand your target audience. There are many ways in which you can use the UK vape shop database including vape email marketing campaigns, newsletters, telemarketing, sending of e-liquid samples, vape shop visits and much more! https://theeliquidboutique.co.uk/products/uk-vape-shop-database
Bernstein <valerie.bernstein@yahoo.com> poniedziałek, 29 kwietnia 2019, godzina 0555
Good morning I am looking to build up my B2B email list for newsletter marketing. I am very keen to get Ivy's B2B Leads Miner - Yellow Pages Scraper Software as it is probably one of the best Yellow Pages scrapers for UK and USA out there. I was just wondering if you have ever used this particular or any other scrapers before? Cheers guys!
Suh <reinaldo.suh@gmail.com> poniedziałek, 29 kwietnia 2019, godzina 0814
Hi I have noticed that your site has a few links from some quality CBD blogs. Are you by any means using this CBD SEO backlinks package? https://wowitloveithaveit.com/products/hemp-and-cbd-seo-backlinks-package I am starting out with my CBD gummies site and need to invest in SEO to rank well on Google but I thought I would check in with you first. I really appreciate your help. Regards
Russell <russell.sherrill@gmail.com> poniedziałek, 29 kwietnia 2019, godzina 1034
A DEFINITIVE AND MOST COMPREHENSIVE E-MAIL LIST OF ALL VAPE SHOPS, E-LIQUID BRANDS, E-LIQUID WHOLESALERS, VAPE DISTRIBUTORS, VAPE EVENT ORGANISERS, ONLINE VAPE SHOPS, BRICK-AND-MORTAR VAPE SHOPS, VAPE MAGAZINES AND VAPE COMMUNITIES IS FINALLY HERE! Following multiple requests from our clients, our e-mail marketing team has worked hard over the past three months to bring you an e-mail list of ALL vape businesses around the world. We have combined all e-mail addresses from our vape shop databases, contacts, business cards from over 50 vape exhibitions, public domain, subscriber lists and other sources. Our entire mailing list has been scrubbed to weed out vape businesses that have gone out of business or changed their domain names to bring you a clean and verified mailing list of vape businesses around the world. Upon payment, the Vape Company E-Mail Mailing List is available as an INSTANT DOWNLOAD in a notepad .txt format that you can simply upload to your subscriber list. Then all you have to do is create a beautiful newsletter campaign and hit the send button. Our Vape Company E-Mail Mailing List has over 38,000 email addresses of brick-and-mortar vape shops, e-liquid wholesalers and distributors, online vape shops, e-liquid brands, vape event organisers, vape communities, vape magazines, vape reviewers and much more! Our team is constantly verifying and updating the Vape Company email list to bring you only the latest vape company leads. DOWNLOAD A SAMPLE OF OUR GLOBAL E-MAIL LIST OF ALL VAPE COMPANIES IN THE WORLD https://theeliquidboutique.co.uk/products/vape-company-e-mail-mailing-list
Jensen <jensen.shelia@hotmail.com> poniedziałek, 29 kwietnia 2019, godzina 1511
After many requests from my clients, I have created this monthly backlinks SEO package for CBD and Hemp businesses. Essentially, the premium package contains everything that you will need to rank higher on the search engines, get more visitors and make more sales. I am working with 50 different CBD and Hemp companies and during my digital marketing journey, I have tried and tested almost every strategy under the sun and picked out the bits that work real magic and chucked them all into a dirt cheap package. Depending on the package that you order, here is what you will receive: Posts and links on CBD and Hemp blog: these will provide you with contextual and extremely powerful links that will tell the search engines that your site is very popular in this niche which will force the search engines to rank you up! Promotion of your brand/site on over 10,000 most popular forums in the world: you will receive links, direct traffic to your site and generate brand awareness. Guest posts: I will post articles on popular sites and add links to your site. Paid promotions on popular sites. Social media signals. Many more extras! https://peachesandscreams.co.uk/community/peaches/forums/881-vape-forum-new/topics/5344-i-will-create-a-tailored-monthly-vape-seo-backlinks-package
Hambleton <shawn.hambleton@gmail.com> poniedziałek, 29 kwietnia 2019, godzina 1728
A QUICK OVERVIEW OF OUR GLOBAL VAPE SHOP DATABASE Our Global Vape Shop Database contains vape shop contact details including: vape shop names e-mails telephone numbers websites social media links locations/physical addresses Our Global Vape Shop Database comes in an Excel spreadsheet with vape shop details grouped by country in separate worksheets. You will receive the Global Vape Shop Database in a compressed .rar file. Simply extract the document using Windows .rar or an alternative extractor. These can be downloaded online in a click of a button. Our Global Vape Shop Database has been going for the past 5 years! Our team regularly attend vape exhibitions and events. They use this as an opportunity to collect vape shop contact details. Most of the vape shop leads are available online. However, finding, verifying and compiling them is a real administrative burden and we tell you that from our 5 year-long experience in this industry! A QUICK BREAKDOWN OF OUR GLOBAL VAPE SHOP DATABASE Our database covers USA, UK, Europe, Russia and CIS, parts of Asia, Australasia and Africa. Here's a non-exhaustive list of countries covered: Armenia, Australia, Austria, Azerbaijan, Bahrain, Bangladesh, Belgium , Canada, Czech Republic, Denmark, Estonia, Finland, France, Georgia, Germany, Greece , India, Indonesia, Ireland, Italy, Japan, Kazakhstan , Kyrgyzstan, Latvia, Lithuania, Malaysia, Maldives, Moldova, Netherlands, Poland, Romania, Russia, Slovakia, South Africa, Spain, Sweden, Switzerland, Tajikistan, UK , USA, Uzbekistan. DOWNLOAD A SAMPLE OF OUR VAPE SHOP DATABASE https://wowitloveithaveit.com/products/global-vape-shop-database-with-contact-details
Morton <morton.omer@yahoo.com> wtorek, 30 kwietnia 2019, godzina 0124
Hi guys I was spoken to someone from your team some time ago about vape marketing. As promised, I am sending you the link to the digital marketing company that helped to rank my online vape shop: https://wowitloveithaveit.com/products/extra-powerful-vape-backlinks-seo-package-for-shops I hope this helps! Have a fab day and see you very soon :)
Miner <miner.trista@gmail.com> wtorek, 30 kwietnia 2019, godzina 0421
Content marketing is extremely important for increasing your website traffic as well as your SEO rankings. Right now, the major search engines are looking at how long visitors are spending on your site to decide how to rank your site. It is extremely important to have QUALITY blog posts that are interesting to read and add value to your site. As my experience has shown, poor quality spun articles will get you nowhere. I have been involved in the vape market for the past 7 years and know pretty much everything about it, including all the major vape companies, e-juice brands, vape mods, nicotine salts, vape laws and more. With this service, I will write up articles for your blog. I recommend that you keep your article titles relatively broad instead of focusing too much on individual products. Each piece will be conversational, well-researched and fun to read. Simply send me your article titles and leave everything else to me. Frequently Asked Questions I need more than 10 articles. You can order multiple packages or I could send you a custom offer, whichever works best for you. What makes you a good writer? My knowledge of the vape industry is what gives me an unparalleled advantage over other writers who have no experience in this field. Instead of writing the bare basics about the vape market, I can also write very critical and in-depth pieces. Can you help me to come up with the topics? Absolutely. Just send me your site and tell me a bit more about your business and I will put together some prospective titles. How do I choose my blog titles? I would recommend that you do not choose very broad article titles such as what is vaping because it will be very difficult to rank this article on the search engines due to the high keyword competition. Try to stick to more specialised titles such as nicotine salts guide. Why is content important for my blog? Each piece of content or each article translates into more visitors. More quality content equals to more visitors. https://peachesandscreams.co.uk/community/peaches/forums/881-vape-forum-new/topics/5405-i-will-write-10-quality-vape-articles-for-your-blog
Pickard <pickard.bess@outlook.com> wtorek, 30 kwietnia 2019, godzina 0524
Are you looking to make your e-liquid or vape brand a global success? Do you want to see your e-liquid or vape brand inside every shop around the world? Our global vape shop database will connect your vape brand with thousands of vape shops around the world and subsequently, increase your revenues and profit. Our global vape shop database has been compiled manually by our internal team over a long period of time through contacts gained at vape exhibitions and publicly available resources. Do you ever wonder, how today's big e-juice brands became big? They did what mattered the most- approached vape stores and established a rapport with vape store owners. We see many excellent e-juice brands that still fail or do not do as well as they should, simply because they do not do what matters- SELL THEIR E-JUICE TO VAPE SHOPS! (this should be the ultimate goal of any vape-related business). Our Global Vape Shop Database connects the dots between e-juice brands and the vape shops! DOWNLOAD A SAMPLE OF OUR VAPE SHOP DATABASE https://theeliquidboutique.co.uk/products/global-vape-shop-database
Bourke <bourke.angeline@gmail.com> wtorek, 30 kwietnia 2019, godzina 0857
A QUICK OVERVIEW OF OUR GLOBAL VAPE SHOP DATABASE Our Global Vape Shop Database contains vape shop contact details including: vape shop names e-mails telephone numbers websites social media links locations/physical addresses Our Global Vape Shop Database comes in an Excel spreadsheet with vape shop details grouped by country in separate worksheets. You will receive the Global Vape Shop Database in a compressed .rar file. Simply extract the document using Windows .rar or an alternative extractor. These can be downloaded online in a click of a button. Our Global Vape Shop Database has been going for the past 5 years! Our team regularly attend vape exhibitions and events. They use this as an opportunity to collect vape shop contact details. Most of the vape shop leads are available online. However, finding, verifying and compiling them is a real administrative burden and we tell you that from our 5 year-long experience in this industry! A QUICK BREAKDOWN OF OUR GLOBAL VAPE SHOP DATABASE Our database covers USA, UK, Europe, Russia and CIS, parts of Asia, Australasia and Africa. Here's a non-exhaustive list of countries covered: Armenia, Australia, Austria, Azerbaijan, Bahrain, Bangladesh, Belgium , Canada, Czech Republic, Denmark, Estonia, Finland, France, Georgia, Germany, Greece , India, Indonesia, Ireland, Italy, Japan, Kazakhstan , Kyrgyzstan, Latvia, Lithuania, Malaysia, Maldives, Moldova, Netherlands, Poland, Romania, Russia, Slovakia, South Africa, Spain, Sweden, Switzerland, Tajikistan, UK , USA, Uzbekistan. DOWNLOAD A SAMPLE OF OUR VAPE SHOP DATABASE https://wowitloveithaveit.com/products/global-vape-shop-database-with-contact-details
Lashley <cleveland.lashley@gmail.com> wtorek, 30 kwietnia 2019, godzina 0943
After many requests from my clients, I have created this monthly backlinks SEO package for CBD and Hemp businesses. Essentially, the premium package contains everything that you will need to rank higher on the search engines, get more visitors and make more sales. I am working with 50 different CBD and Hemp companies and during my digital marketing journey, I have tried and tested almost every strategy under the sun and picked out the bits that work real magic and chucked them all into a dirt cheap package. Depending on the package that you order, here is what you will receive: Posts and links on CBD and Hemp blog: these will provide you with contextual and extremely powerful links that will tell the search engines that your site is very popular in this niche which will force the search engines to rank you up! Promotion of your brand/site on over 10,000 most popular forums in the world: you will receive links, direct traffic to your site and generate brand awareness. Guest posts: I will post articles on popular sites and add links to your site. Paid promotions on popular sites. Social media signals. Many more extras! Please send me your website url and up to 100 keywords you would like to rank for on the search engines. Please do not use any separators between keywords and enter one keyword per line please. I will deliver everything as soon as the work is finished. https://peachesandscreams.co.uk/community/peaches/forums/881-vape-forum-new/topics/5343-i-will-create-a-tailored-hemp-and-cbd-monthly-backlinks-package
Kirkby <victorina.kirkby@yahoo.com> wtorek, 30 kwietnia 2019, godzina 1937
The vape industry has grown exponentially since 2012. It all started off with the ego starter kits, then progressed to dripping and subohming and now we seem to have reached the heights of nicotine salts, shortfill e-liquids, CBD and Juul devices. Thousands of brick-and-mortar vape shops have opened all around the world. New online vape shop start-ups are emerging on a daily basis. The competition in the vape industry has become cut throat! Back in 2012, it was a breeze to rank for competitive vape keywords on most search engines whilst today, it is even becoming difficult to rank for local area post codes as every corner of every city seems to have a growing vape shop demographic. We were the first vape SEO company in the world and we know the vape industry inside out. We have ranked some of the biggest e-juice brands since when they were starting out, vape shops that were to become some of the biggest chains in the country, vape wholesalers, event organisers and many other different types of vape sites. Our deep knowledge of the SEO and the vape industries allows us to understand the unique business models of our clients and exactly what it takes to rank a vape shop to the very top of the search engines. WHAT YOU WILL RECEIVE WITH OUR VAPE SEO PACKAGE As we have mentioned above, since working with many vape businesses, we have created a blueprint for ranking a site. We have gone through numerous trial and errors and know what works and what does not work. In the current SEO climate, major search engines are putting a greater emphasis on the overall domain authority and metrics of a site as well as brand and onsite visitor behaviour (browsing, click-throughs and bounces). We are constantly adjusting our package to ensure that all of our practices are closely attuned to the latest SEO best-practices and search engine algorithms. HERE IS WHAT YOU WILL RECEIVE WITH OUR VAPE SEO PACKAGE AND WHY IT IS IMPORTANT FOR YOUR SITE: 1,000 backlinks on vape and e-liquid blogs: all of the links are do follow, permanent and 100% related to the vaping niche. This helps the search engines to classify your site and rank it higher on the basis of the fact that it has a lot of links coming from designated vape blogs. Moreover, each vape blog has a very high domain authority which will pass on a lot of link equity to you site. 5,000+ forum posts: we will post out a unique message about your website or brand on the most popular forums in the world. Not only will this help to generate awareness about your brand but will also give you a lot of backlinks and direct visitors to your site. Guest posts on very powerful sites: we have exclusive access to some very popular and powerful sites on which we can place guests posts with links to your site. Mixed backlinks: in addition to the above work, we will also create some mixed backlinks for some diversity. This would include some blog comments, video comments and more. Indexing: we will index your links with the major searhc engines at a very natural and steady pace to keep the search engine red flags at bay! Learn more and buy at https://wowitloveithaveit.com/products/extra-powerful-vape-backlinks-seo-package-for-shops
Goward <goward.roberto60@outlook.com> środa, 1 maja 2019, godzina 0105
I will create backlinks on my e-liquid and vape blogs built on very high authority domains. Choose the package that most suits your budget and competition you are facing. All extras are highly recommended. These vape backlinks will help to increase your vape shop's domain authority and search engine rankings as well as your sales. Simply send me the keywords you would like to rank for and I will create individual blog posts on each vape blog and add a link to your site with your preferred anchor text. I will embed some vape-related images and video reviews. All work is done manually using content related to your keywords. All of my blogs are hosted on different servers and have different IP addresses. Order now at https://bit.ly/2Vd2FqX
Wesolowski <wesolowski.dell@gmail.com> środa, 1 maja 2019, godzina 0108
Hi guys I was spoken to someone from your team some time ago about vape marketing. As promised, I am sending you the link to the digital marketing company that helped to rank my online vape shop: https://wowitloveithaveit.com/products/extra-powerful-vape-backlinks-seo-package-for-shops I hope this helps! Have a fab day and see you very soon :)
Ginder <austin.ginder@gmail.com> środa, 1 maja 2019, godzina 0205
The vape industry has grown exponentially since 2012. It all started off with the ego starter kits, then progressed to dripping and subohming and now we seem to have reached the heights of nicotine salts, shortfill e-liquids, CBD and Juul devices. Thousands of brick-and-mortar vape shops have opened all around the world. New online vape shop start-ups are emerging on a daily basis. The competition in the vape industry has become cut throat! Back in 2012, it was a breeze to rank for competitive vape keywords on most search engines whilst today, it is even becoming difficult to rank for local area post codes as every corner of every city seems to have a growing vape shop demographic. We were the first vape SEO company in the world and we know the vape industry inside out. We have ranked some of the biggest e-juice brands since when they were starting out, vape shops that were to become some of the biggest chains in the country, vape wholesalers, event organisers and many other different types of vape sites. Our deep knowledge of the SEO and the vape industries allows us to understand the unique business models of our clients and exactly what it takes to rank a vape shop to the very top of the search engines. WHAT YOU WILL RECEIVE WITH OUR VAPE SEO PACKAGE As we have mentioned above, since working with many vape businesses, we have created a blueprint for ranking a site. We have gone through numerous trial and errors and know what works and what does not work. In the current SEO climate, major search engines are putting a greater emphasis on the overall domain authority and metrics of a site as well as brand and onsite visitor behaviour (browsing, click-throughs and bounces). We are constantly adjusting our package to ensure that all of our practices are closely attuned to the latest SEO best-practices and search engine algorithms. HERE IS WHAT YOU WILL RECEIVE WITH OUR VAPE SEO PACKAGE AND WHY IT IS IMPORTANT FOR YOUR SITE: 1,000 backlinks on vape and e-liquid blogs: all of the links are do follow, permanent and 100% related to the vaping niche. This helps the search engines to classify your site and rank it higher on the basis of the fact that it has a lot of links coming from designated vape blogs. Moreover, each vape blog has a very high domain authority which will pass on a lot of link equity to you site. 5,000+ forum posts: we will post out a unique message about your website or brand on the most popular forums in the world. Not only will this help to generate awareness about your brand but will also give you a lot of backlinks and direct visitors to your site. Guest posts on very powerful sites: we have exclusive access to some very popular and powerful sites on which we can place guests posts with links to your site. Mixed backlinks: in addition to the above work, we will also create some mixed backlinks for some diversity. This would include some blog comments, video comments and more. Indexing: we will index your links with the major searhc engines at a very natural and steady pace to keep the search engine red flags at bay! Learn more and buy at https://wowitloveithaveit.com/products/extra-powerful-vape-backlinks-seo-package-for-shops
Pogue <pogue.tonja@yahoo.com> środa, 1 maja 2019, godzina 0230
After many requests from my clients, I have created this monthly backlinks SEO package for CBD and Hemp businesses. Essentially, the premium package contains everything that you will need to rank higher on the search engines, get more visitors and make more sales. I am working with 50 different CBD and Hemp companies and during my digital marketing journey, I have tried and tested almost every strategy under the sun and picked out the bits that work real magic and chucked them all into a dirt cheap package. Depending on the package that you order, here is what you will receive: Posts and links on CBD and Hemp blog: these will provide you with contextual and extremely powerful links that will tell the search engines that your site is very popular in this niche which will force the search engines to rank you up! Promotion of your brand/site on over 10,000 most popular forums in the world: you will receive links, direct traffic to your site and generate brand awareness. Guest posts: I will post articles on popular sites and add links to your site. Paid promotions on popular sites. Social media signals. Many more extras! https://peachesandscreams.co.uk/community/peaches/forums/881-vape-forum-new/topics/5344-i-will-create-a-tailored-monthly-vape-seo-backlinks-package
Simonds <simonds.maple@hotmail.com> środa, 1 maja 2019, godzina 0425
A QUICK OVERVIEW OF OUR GLOBAL VAPE SHOP DATABASE Our Global Vape Shop Database contains vape shop contact details including: vape shop names e-mails telephone numbers websites social media links locations/physical addresses Our Global Vape Shop Database comes in an Excel spreadsheet with vape shop details grouped by country in separate worksheets. You will receive the Global Vape Shop Database in a compressed .rar file. Simply extract the document using Windows .rar or an alternative extractor. These can be downloaded online in a click of a button. Our Global Vape Shop Database has been going for the past 5 years! Our team regularly attend vape exhibitions and events. They use this as an opportunity to collect vape shop contact details. Most of the vape shop leads are available online. However, finding, verifying and compiling them is a real administrative burden and we tell you that from our 5 year-long experience in this industry! A QUICK BREAKDOWN OF OUR GLOBAL VAPE SHOP DATABASE Our database covers USA, UK, Europe, Russia and CIS, parts of Asia, Australasia and Africa. Here's a non-exhaustive list of countries covered: Armenia, Australia, Austria, Azerbaijan, Bahrain, Bangladesh, Belgium , Canada, Czech Republic, Denmark, Estonia, Finland, France, Georgia, Germany, Greece , India, Indonesia, Ireland, Italy, Japan, Kazakhstan , Kyrgyzstan, Latvia, Lithuania, Malaysia, Maldives, Moldova, Netherlands, Poland, Romania, Russia, Slovakia, South Africa, Spain, Sweden, Switzerland, Tajikistan, UK , USA, Uzbekistan. DOWNLOAD A SAMPLE OF OUR VAPE SHOP DATABASE https://wowitloveithaveit.com/products/global-vape-shop-database-with-contact-details
Pethard <pethard.winifred@hotmail.com> środa, 1 maja 2019, godzina 0532
A DEFINITIVE AND MOST COMPREHENSIVE E-MAIL LIST OF ALL VAPE SHOPS, E-LIQUID BRANDS, E-LIQUID WHOLESALERS, VAPE DISTRIBUTORS, VAPE EVENT ORGANISERS, ONLINE VAPE SHOPS, BRICK-AND-MORTAR VAPE SHOPS, VAPE MAGAZINES AND VAPE COMMUNITIES IS FINALLY HERE! Following multiple requests from our clients, our e-mail marketing team has worked hard over the past three months to bring you an e-mail list of ALL vape businesses around the world. We have combined all e-mail addresses from our vape shop databases, contacts, business cards from over 50 vape exhibitions, public domain, subscriber lists and other sources. Our entire mailing list has been scrubbed to weed out vape businesses that have gone out of business or changed their domain names to bring you a clean and verified mailing list of vape businesses around the world. Upon payment, the Vape Company E-Mail Mailing List is available as an INSTANT DOWNLOAD in a notepad .txt format that you can simply upload to your subscriber list. Then all you have to do is create a beautiful newsletter campaign and hit the send button. Our Vape Company E-Mail Mailing List has over 38,000 email addresses of brick-and-mortar vape shops, e-liquid wholesalers and distributors, online vape shops, e-liquid brands, vape event organisers, vape communities, vape magazines, vape reviewers and much more! Our team is constantly verifying and updating the Vape Company email list to bring you only the latest vape company leads. DOWNLOAD A SAMPLE OF OUR GLOBAL E-MAIL LIST OF ALL VAPE COMPANIES IN THE WORLD https://theeliquidboutique.co.uk/products/vape-company-e-mail-mailing-list
Dunagan <dunagan.jack80@gmail.com> środa, 1 maja 2019, godzina 0711
Good morning I am looking to build up my B2B email list for newsletter marketing. I am very keen to get Ivy's B2B Leads Miner - Yellow Pages Scraper Software as it is probably one of the best Yellow Pages scrapers for UK and USA out there. I was just wondering if you have ever used this particular or any other scrapers before? Cheers guys!
Bible <bible.joni14@gmail.com> środa, 1 maja 2019, godzina 0719
WORLD'S #1 UK VAPE SHOP DATABASE Do you own an e-liquid or a vape brand? Are you looking to sell your product to vape shops directly? Our UK vape store database is the best and most important investment you will make for your vape business. There is simply no point of having a beautiful website and a great brand if nobody has heard of it or will never see it. Our vape shop database will help to connect your brand with vape stores which will equal to brand exposure, higher sales and greater profit. Just over 500 e-liquid and mod brands have purchased our database and have made significant gains. Some of these brands are already so large that you will have heard of them! Our database of UK vape shops will help you to expand your target audience. There are many ways in which you can use the UK vape shop database including vape email marketing campaigns, newsletters, telemarketing, sending of e-liquid samples, vape shop visits and much more! https://theeliquidboutique.co.uk/products/uk-vape-shop-database
Bannerman <finn.bannerman@googlemail.com> środa, 1 maja 2019, godzina 0719
A QUICK OVERVIEW OF OUR GLOBAL VAPE SHOP DATABASE Our Global Vape Shop Database contains vape shop contact details including: vape shop names e-mails telephone numbers websites social media links locations/physical addresses Our Global Vape Shop Database comes in an Excel spreadsheet with vape shop details grouped by country in separate worksheets. You will receive the Global Vape Shop Database in a compressed .rar file. Simply extract the document using Windows .rar or an alternative extractor. These can be downloaded online in a click of a button. Our Global Vape Shop Database has been going for the past 5 years! Our team regularly attend vape exhibitions and events. They use this as an opportunity to collect vape shop contact details. Most of the vape shop leads are available online. However, finding, verifying and compiling them is a real administrative burden and we tell you that from our 5 year-long experience in this industry! A QUICK BREAKDOWN OF OUR GLOBAL VAPE SHOP DATABASE Our database covers USA, UK, Europe, Russia and CIS, parts of Asia, Australasia and Africa. Here's a non-exhaustive list of countries covered: Armenia, Australia, Austria, Azerbaijan, Bahrain, Bangladesh, Belgium , Canada, Czech Republic, Denmark, Estonia, Finland, France, Georgia, Germany, Greece , India, Indonesia, Ireland, Italy, Japan, Kazakhstan , Kyrgyzstan, Latvia, Lithuania, Malaysia, Maldives, Moldova, Netherlands, Poland, Romania, Russia, Slovakia, South Africa, Spain, Sweden, Switzerland, Tajikistan, UK , USA, Uzbekistan. DOWNLOAD A SAMPLE OF OUR VAPE SHOP DATABASE https://wowitloveithaveit.com/products/global-vape-shop-database-with-contact-details
Parkes <parkes.wilford17@gmail.com> środa, 1 maja 2019, godzina 1020
The vape industry has grown exponentially since 2012. It all started off with the ego starter kits, then progressed to dripping and subohming and now we seem to have reached the heights of nicotine salts, shortfill e-liquids, CBD and Juul devices. Thousands of brick-and-mortar vape shops have opened all around the world. New online vape shop start-ups are emerging on a daily basis. The competition in the vape industry has become cut throat! Back in 2012, it was a breeze to rank for competitive vape keywords on most search engines whilst today, it is even becoming difficult to rank for local area post codes as every corner of every city seems to have a growing vape shop demographic. We were the first vape SEO company in the world and we know the vape industry inside out. We have ranked some of the biggest e-juice brands since when they were starting out, vape shops that were to become some of the biggest chains in the country, vape wholesalers, event organisers and many other different types of vape sites. Our deep knowledge of the SEO and the vape industries allows us to understand the unique business models of our clients and exactly what it takes to rank a vape shop to the very top of the search engines. WHAT YOU WILL RECEIVE WITH OUR VAPE SEO PACKAGE As we have mentioned above, since working with many vape businesses, we have created a blueprint for ranking a site. We have gone through numerous trial and errors and know what works and what does not work. In the current SEO climate, major search engines are putting a greater emphasis on the overall domain authority and metrics of a site as well as brand and onsite visitor behaviour (browsing, click-throughs and bounces). We are constantly adjusting our package to ensure that all of our practices are closely attuned to the latest SEO best-practices and search engine algorithms. HERE IS WHAT YOU WILL RECEIVE WITH OUR VAPE SEO PACKAGE AND WHY IT IS IMPORTANT FOR YOUR SITE: 1,000 backlinks on vape and e-liquid blogs: all of the links are do follow, permanent and 100% related to the vaping niche. This helps the search engines to classify your site and rank it higher on the basis of the fact that it has a lot of links coming from designated vape blogs. Moreover, each vape blog has a very high domain authority which will pass on a lot of link equity to you site. 5,000+ forum posts: we will post out a unique message about your website or brand on the most popular forums in the world. Not only will this help to generate awareness about your brand but will also give you a lot of backlinks and direct visitors to your site. Guest posts on very powerful sites: we have exclusive access to some very popular and powerful sites on which we can place guests posts with links to your site. Mixed backlinks: in addition to the above work, we will also create some mixed backlinks for some diversity. This would include some blog comments, video comments and more. Indexing: we will index your links with the major searhc engines at a very natural and steady pace to keep the search engine red flags at bay! Learn more and buy at https://wowitloveithaveit.com/products/extra-powerful-vape-backlinks-seo-package-for-shops
Haverfield <lucile.haverfield@gmail.com> środa, 1 maja 2019, godzina 1147
A DEFINITIVE AND MOST COMPREHENSIVE E-MAIL LIST OF ALL VAPE SHOPS, E-LIQUID BRANDS, E-LIQUID WHOLESALERS, VAPE DISTRIBUTORS, VAPE EVENT ORGANISERS, ONLINE VAPE SHOPS, BRICK-AND-MORTAR VAPE SHOPS, VAPE MAGAZINES AND VAPE COMMUNITIES IS FINALLY HERE! Following multiple requests from our clients, our e-mail marketing team has worked hard over the past three months to bring you an e-mail list of ALL vape businesses around the world. We have combined all e-mail addresses from our vape shop databases, contacts, business cards from over 50 vape exhibitions, public domain, subscriber lists and other sources. Our entire mailing list has been scrubbed to weed out vape businesses that have gone out of business or changed their domain names to bring you a clean and verified mailing list of vape businesses around the world. Upon payment, the Vape Company E-Mail Mailing List is available as an INSTANT DOWNLOAD in a notepad .txt format that you can simply upload to your subscriber list. Then all you have to do is create a beautiful newsletter campaign and hit the send button. Our Vape Company E-Mail Mailing List has over 38,000 email addresses of brick-and-mortar vape shops, e-liquid wholesalers and distributors, online vape shops, e-liquid brands, vape event organisers, vape communities, vape magazines, vape reviewers and much more! Our team is constantly verifying and updating the Vape Company email list to bring you only the latest vape company leads. DOWNLOAD A SAMPLE OF OUR GLOBAL E-MAIL LIST OF ALL VAPE COMPANIES IN THE WORLD https://theeliquidboutique.co.uk/products/vape-company-e-mail-mailing-list
MacGregor <macgregor.novella@gmail.com> środa, 1 maja 2019, godzina 1415
HEMP AND CBD SEO BACKLINKS PACKAGE The hemp and CBD industry has grown exponentially over the last few years. CBD products are now gaining mainstream acceptance all over the world. For example, in the UK, you can now freely purchase CBD eliquid, gummies, creams and oils at Holland and Barrett, one of the most popular health food shops. With this popularity of CBD and hemp products, comes the competition between online businesses. Are you looking to rank higher on the major search engines such as Google and Bing? Do you want to get more visitors and generate more sales? We can certainly help you! Our Hemp and CBD SEO Backlinks Package will help to rank your hemp, cbd or cannabis related site all the way to the top of the search engines. With this SEO package, you will receive a wide variety of backlinks from quality CBD and hemp blogs, forums, guest posts and other quality sites! Boost your visitor counts, sales and online presence! HOW OUR HEMP AND CBD SEO BACKLINKS PACKAGE CAN HELP YOUR BUSINESS Having a great CBD or Hemp site is only a part of the equation. However, you need visitors to see your awesome site. In today's digital marketing landscape, Google and other major search engines have started to rank websites with a high domain authority and solid domain metrics. The best way to increase your domain authority and metrics is by building quality backlinks. WHAT YOU WILL RECEIVE WITH OUR BACKLINKS PACKAGE 1,000 posts on CBD and hemp blogs: this will present you with very powerful and niche-relevant backlinks from very high DA sites ranging from 30 to 70. 10,000 forum posts: we will promote your message on 10,000 most powerful forums in the world. This is an excellent way to start a conversation with people and promote your CBD brand and attract direct visitors to your site! Moreover, this is your opportunity to get backlinks from some of the leading forums in the world! Guest posts on authority sites: we have an arrangement with some of the leading and most powerful sites on which we will be able to publish guest posts with backlinks pointing to your site. 500 social bookmarks: social bookmarks are a great way of sending social signals to your site which is one of the ranking factors. Indexing of all backlinks: we will index all of the links with the major search engines. KEY FEATURES OF OUR HEMP AND CBD SEO BACKLINKS PACKAGE Search Engine Safe: we use the industry's recommended ratio of naked, keyword, branded and LSI anchor texts to keep everything looking natural to the search engines. Link Diversity: we create links on many different CMS platforms, domains and IP addresses to keep all the links as diverse as possible. Drip-Feed Indexing: we will index all the backlinks at a very steady speed to keep everything looking natural to the search engines. SHOW ME SOME EXAMPLES We are currently working with 50 CBD companies on their SEO projects. Here are a few examples of the links we have created for some of our clients. Click here to view the backlinks created for mountainside-medical.com Click here to view the backlinks created for plantandhemp.com PLACING AN ORDER If you like what you see and would like to place an order, here is what you will need to do: Buy the package Prepare a list of 50 keywords you would like to rank for on the search engines and send us your website along with your company details including your name, official email, telephone number, company address and other information that you deem relevant. Please send everything to us via our Facebook page (https://www.facebook.com/wowitloveithaveit/). We are more responsive on our social media pages. We will create all your backlinks and will send you reports in about 30 days as this is a monthly package. https://wowitloveithaveit.com/products/hemp-and-cbd-seo-backlinks-package
Rasch <rasch.wade@gmail.com> środa, 1 maja 2019, godzina 2056
Hi guys I can scrape all the vape shops in your country using my very powerful servers, thousands of dedicated proxies and my custom built software. I will scrape the likes of Google maps, Yellow Pages, Search Engines and other places. Scraping your own leads is by far the best way to get fresh and up-to-date leads than buying pre-made vape shop databases and email lists. If your country is not listed, please order the UK gig if you are based in Europe. For other places, please order the Canada gig. You will receive an Excel spreadsheet with: vape shop names addresses e-mails telephone numbers social media links websites *provided vape shops contain this data. Just to let you know, the software that I will be using is Yoggy's Money Vault Search Engine Scraper and E-Mail Extractor. This is literally the most powerful web scraper in the world that can produce insanely accurate and comprehensive leads! You can learn more and order at https://www.fiverr.com/natalycox/scrape-vape-shop-emails-and-leads-for-you Cheers
Tivey <tivey.miquel@gmail.com> środa, 1 maja 2019, godzina 2227
Hi I have noticed that your site has a few links from some quality CBD blogs. Are you by any means using this CBD SEO backlinks package? https://wowitloveithaveit.com/products/hemp-and-cbd-seo-backlinks-package I am starting out with my CBD gummies site and need to invest in SEO to rank well on Google but I thought I would check in with you first. I really appreciate your help. Regards
Nicolai <nicolai.irish@gmail.com> piątek, 3 maja 2019, godzina 0721
A QUICK OVERVIEW OF OUR GLOBAL VAPE SHOP DATABASE Our Global Vape Shop Database contains vape shop contact details including: vape shop names e-mails telephone numbers websites social media links locations/physical addresses Our Global Vape Shop Database comes in an Excel spreadsheet with vape shop details grouped by country in separate worksheets. You will receive the Global Vape Shop Database in a compressed .rar file. Simply extract the document using Windows .rar or an alternative extractor. These can be downloaded online in a click of a button. Our Global Vape Shop Database has been going for the past 5 years! Our team regularly attend vape exhibitions and events. They use this as an opportunity to collect vape shop contact details. Most of the vape shop leads are available online. However, finding, verifying and compiling them is a real administrative burden and we tell you that from our 5 year-long experience in this industry! A QUICK BREAKDOWN OF OUR GLOBAL VAPE SHOP DATABASE Our database covers USA, UK, Europe, Russia and CIS, parts of Asia, Australasia and Africa. Here's a non-exhaustive list of countries covered: Armenia, Australia, Austria, Azerbaijan, Bahrain, Bangladesh, Belgium , Canada, Czech Republic, Denmark, Estonia, Finland, France, Georgia, Germany, Greece , India, Indonesia, Ireland, Italy, Japan, Kazakhstan , Kyrgyzstan, Latvia, Lithuania, Malaysia, Maldives, Moldova, Netherlands, Poland, Romania, Russia, Slovakia, South Africa, Spain, Sweden, Switzerland, Tajikistan, UK , USA, Uzbekistan. DOWNLOAD A SAMPLE OF OUR VAPE SHOP DATABASE https://wowitloveithaveit.com/products/global-vape-shop-database-with-contact-details
Oshea <lilly.oshea75@gmail.com> sobota, 4 maja 2019, godzina 0446
Hello I wanted to ask for your opinion about the monthly CBD backlink seo package. I can see that you have a backlink from https://wowitloveithaveit.com so I assume that you are working with those guys? I just want to make an informed decision before ordering and thought that there is no better way than to ask some CBD companies in the industry. I think this is the link https://wowitloveithaveit.com/products/hemp-and-cbd-seo-backlinks-package I really appreciate your help! Thank you!
Warby <warby.lenora@outlook.com> niedziela, 5 maja 2019, godzina 0709
I am currently working with some of the biggest vape wholesalers, MOD makers, e-juice brands and vape shops. I am sure that you have heard of them all or seen them at most vape expos. To put it bluntly, I know what works and what doesn't. I now know the vape industry like the back of my hand. I have taken all the most effective elements of my vape seo equation and lumped them into these incredibly cheap packages, which I would sell for about 10 times the amount I am selling them for here. I have divided the packages on the basis of the amount of competition you are facing. So here is the breakdown of what exactly you will get with each package: Mouse (ideal for small local vape shops located in the suburbs): 100 links inside my vape and ejuice blogs 50 bookmarks and social signals Indexing Cat (mid-sized vape companies) 500 backlinks inside vape blogs 250 social bookmarks promotion on 5,000 forums Around 10,000 mixed blog comment, PBN and other links to increase your domain authority Bear (ideal for companies based in large cities) 1500 vapor blog links 500 social bookmarks Promotion on 10,000 forums 20,000 mixed links Indexing Guest Posts on 5 strong sites Lots of Extras To learn more, please visit https://www.fiverr.com/ghosttownseo/create-a-full-vape-backlinks-package
Carney <carney.mikki@yahoo.com> poniedziałek, 6 maja 2019, godzina 2136
Hi! I wanted to ask you if you have heard of this vape seo package (https://wowitloveithaveit.com/products/extra-powerful-vape-backlinks-for-shops-seo)? I was told that many leading companies in the industry are using it with the likes of vapor dna, vape ranger, element eliquids, ie vapor, ejuices.co, marina vape and other big players. I just wanted to check whether you have used them before as I can see that you have a backlink from https://wowitloveithaveit.com so my natural assumption is that you are working with these guys. Would you recommend them? Cheers
Gaytan <ronda.gaytan@googlemail.com> wtorek, 7 maja 2019, godzina 0122
After many requests from my clients, I have created this monthly backlinks SEO package for CBD and Hemp businesses. Essentially, the premium package contains everything that you will need to rank higher on the search engines, get more visitors and make more sales. I am working with 50 different CBD and Hemp companies and during my digital marketing journey, I have tried and tested almost every strategy under the sun and picked out the bits that work real magic and chucked them all into a dirt cheap package. Depending on the package that you order, here is what you will receive: Posts and links on CBD and Hemp blog: these will provide you with contextual and extremely powerful links that will tell the search engines that your site is very popular in this niche which will force the search engines to rank you up! Promotion of your brand/site on over 10,000 most popular forums in the world: you will receive links, direct traffic to your site and generate brand awareness. Guest posts: I will post articles on popular sites and add links to your site. Paid promotions on popular sites. Social media signals. Many more extras! https://peachesandscreams.co.uk/community/peaches/forums/881-vape-forum-new/topics/5344-i-will-create-a-tailored-monthly-vape-seo-backlinks-package
Messenger <von.messenger77@gmail.com> wtorek, 7 maja 2019, godzina 0358
Hi guys I can scrape all the vape shops in your country using my very powerful servers, thousands of dedicated proxies and my custom built software. I will scrape the likes of Google maps, Yellow Pages, Search Engines and other places. Scraping your own leads is by far the best way to get fresh and up-to-date leads than buying pre-made vape shop databases and email lists. If your country is not listed, please order the UK gig if you are based in Europe. For other places, please order the Canada gig. You will receive an Excel spreadsheet with: vape shop names addresses e-mails telephone numbers social media links websites *provided vape shops contain this data. Just to let you know, the software that I will be using is Yoggy's Money Vault Search Engine Scraper and E-Mail Extractor. This is literally the most powerful web scraper in the world that can produce insanely accurate and comprehensive leads! You can learn more and order at https://www.fiverr.com/natalycox/scrape-vape-shop-emails-and-leads-for-you Cheers
Mann <hayley.mann@outlook.com> wtorek, 7 maja 2019, godzina 0610
Are you looking to make your e-liquid or vape brand a global success? Do you want to see your e-liquid or vape brand inside every shop around the world? Our global vape shop database will connect your vape brand with thousands of vape shops around the world and subsequently, increase your revenues and profit. Our global vape shop database has been compiled manually by our internal team over a long period of time through contacts gained at vape exhibitions and publicly available resources. Do you ever wonder, how today's big e-juice brands became big? They did what mattered the most- approached vape stores and established a rapport with vape store owners. We see many excellent e-juice brands that still fail or do not do as well as they should, simply because they do not do what matters- SELL THEIR E-JUICE TO VAPE SHOPS! (this should be the ultimate goal of any vape-related business). Our Global Vape Shop Database connects the dots between e-juice brands and the vape shops! DOWNLOAD A SAMPLE OF OUR VAPE SHOP DATABASE https://theeliquidboutique.co.uk/products/global-vape-shop-database
Tolbert <tolbert.randall@googlemail.com> wtorek, 7 maja 2019, godzina 1003
I am currently working with some of the biggest vape wholesalers, MOD makers, e-juice brands and vape shops. I am sure that you have heard of them all or seen them at most vape expos. To put it bluntly, I know what works and what doesn't. I now know the vape industry like the back of my hand. I have taken all the most effective elements of my vape seo equation and lumped them into these incredibly cheap packages, which I would sell for about 10 times the amount I am selling them for here. I have divided the packages on the basis of the amount of competition you are facing. So here is the breakdown of what exactly you will get with each package: Mouse (ideal for small local vape shops located in the suburbs): 100 links inside my vape and ejuice blogs 50 bookmarks and social signals Indexing Cat (mid-sized vape companies) 500 backlinks inside vape blogs 250 social bookmarks promotion on 5,000 forums Around 10,000 mixed blog comment, PBN and other links to increase your domain authority Bear (ideal for companies based in large cities) 1500 vapor blog links 500 social bookmarks Promotion on 10,000 forums 20,000 mixed links Indexing Guest Posts on 5 strong sites Lots of Extras To learn more, please visit https://www.fiverr.com/ghosttownseo/create-a-full-vape-backlinks-package
Greenfields <vapeshopseo@gmail.com> wtorek, 7 maja 2019, godzina 1129
Good Afternoon I am writing to you to introduce my freelance vape seo services. I specialise in creating quality vape-related links to rank vape-related sites on search engines such as Google. I work with 50 of the leading vape shops, e-juice brands and wholesalers and now I have decided to take the same package that we provide to clients via an agency and offer it ten times cheaper on Fiverr. Please take a look at the package and if it is of interest, please feel free to order it from https://www.fiverr.com/cryptovaper Thank you for your time. Kind regards Sergey
Kelley <lyda.kelley18@gmail.com> czwartek, 9 maja 2019, godzina 0351
After many requests from my clients, I have created this monthly backlinks SEO package for CBD and Hemp businesses. Essentially, the premium package contains everything that you will need to rank higher on the search engines, get more visitors and make more sales. I am working with 50 different CBD and Hemp companies and during my digital marketing journey, I have tried and tested almost every strategy under the sun and picked out the bits that work real magic and chucked them all into a dirt cheap package. Depending on the package that you order, here is what you will receive: Posts and links on CBD and Hemp blog: these will provide you with contextual and extremely powerful links that will tell the search engines that your site is very popular in this niche which will force the search engines to rank you up! Promotion of your brand/site on over 10,000 most popular forums in the world: you will receive links, direct traffic to your site and generate brand awareness. Guest posts: I will post articles on popular sites and add links to your site. Paid promotions on popular sites. Social media signals. Many more extras! https://peachesandscreams.co.uk/community/peaches/forums/881-vape-forum-new/topics/5344-i-will-create-a-tailored-monthly-vape-seo-backlinks-package
Heinig <heinig.carlo@gmail.com> czwartek, 9 maja 2019, godzina 0924
A QUICK OVERVIEW OF OUR GLOBAL VAPE SHOP DATABASE Our Global Vape Shop Database contains vape shop contact details including: vape shop names e-mails telephone numbers websites social media links locations/physical addresses Our Global Vape Shop Database comes in an Excel spreadsheet with vape shop details grouped by country in separate worksheets. You will receive the Global Vape Shop Database in a compressed .rar file. Simply extract the document using Windows .rar or an alternative extractor. These can be downloaded online in a click of a button. Our Global Vape Shop Database has been going for the past 5 years! Our team regularly attend vape exhibitions and events. They use this as an opportunity to collect vape shop contact details. Most of the vape shop leads are available online. However, finding, verifying and compiling them is a real administrative burden and we tell you that from our 5 year-long experience in this industry! A QUICK BREAKDOWN OF OUR GLOBAL VAPE SHOP DATABASE Our database covers USA, UK, Europe, Russia and CIS, parts of Asia, Australasia and Africa. Here's a non-exhaustive list of countries covered: Armenia, Australia, Austria, Azerbaijan, Bahrain, Bangladesh, Belgium , Canada, Czech Republic, Denmark, Estonia, Finland, France, Georgia, Germany, Greece , India, Indonesia, Ireland, Italy, Japan, Kazakhstan , Kyrgyzstan, Latvia, Lithuania, Malaysia, Maldives, Moldova, Netherlands, Poland, Romania, Russia, Slovakia, South Africa, Spain, Sweden, Switzerland, Tajikistan, UK , USA, Uzbekistan. DOWNLOAD A SAMPLE OF OUR VAPE SHOP DATABASE https://wowitloveithaveit.com/products/global-vape-shop-database-with-contact-details
Lienhop <krista.lienhop@googlemail.com> czwartek, 9 maja 2019, godzina 1023
A DEFINITIVE AND MOST COMPREHENSIVE E-MAIL LIST OF ALL VAPE SHOPS, E-LIQUID BRANDS, E-LIQUID WHOLESALERS, VAPE DISTRIBUTORS, VAPE EVENT ORGANISERS, ONLINE VAPE SHOPS, BRICK-AND-MORTAR VAPE SHOPS, VAPE MAGAZINES AND VAPE COMMUNITIES IS FINALLY HERE! Following multiple requests from our clients, our e-mail marketing team has worked hard over the past three months to bring you an e-mail list of ALL vape businesses around the world. We have combined all e-mail addresses from our vape shop databases, contacts, business cards from over 50 vape exhibitions, public domain, subscriber lists and other sources. Our entire mailing list has been scrubbed to weed out vape businesses that have gone out of business or changed their domain names to bring you a clean and verified mailing list of vape businesses around the world. Upon payment, the Vape Company E-Mail Mailing List is available as an INSTANT DOWNLOAD in a notepad .txt format that you can simply upload to your subscriber list. Then all you have to do is create a beautiful newsletter campaign and hit the send button. Our Vape Company E-Mail Mailing List has over 38,000 email addresses of brick-and-mortar vape shops, e-liquid wholesalers and distributors, online vape shops, e-liquid brands, vape event organisers, vape communities, vape magazines, vape reviewers and much more! Our team is constantly verifying and updating the Vape Company email list to bring you only the latest vape company leads. DOWNLOAD A SAMPLE OF OUR GLOBAL E-MAIL LIST OF ALL VAPE COMPANIES IN THE WORLD https://theeliquidboutique.co.uk/products/vape-company-e-mail-mailing-list
Frey <frey.moses@yahoo.com> czwartek, 9 maja 2019, godzina 1059
Hi guys We are excited to let you know that we have now officially launched our CBD and Hemp Backlinks package. Previously, we have worked with some of the biggest CBD companies behind closed doors. However, we have made a decision to make our Hemp and CBD SEO Backlinks package public and accessible to everyone! We would like to invite you to review our package and see how it could benefit your business: https://wowitloveithaveit.com/products/hemp-and-cbd-seo-backlinks-package Our backlinks package has been tried and tested on some of the heaviest hitting CBD companies in the industry and provides an excellent blueprint for ranking almost any type of CBD and hemp site! We have added some example links that we have created for some of our clients for you to get an idea of the links. The package is currently on offer so you can land yourself a pretty good bargain. Do let us know if you have any questions! Thanks :)
Newell <newell.reuben@gmail.com> czwartek, 9 maja 2019, godzina 1345
Content marketing is extremely important for increasing your website traffic as well as your SEO rankings. Right now, the major search engines are looking at how long visitors are spending on your site to decide how to rank your site. It is extremely important to have QUALITY blog posts that are interesting to read and add value to your site. As my experience has shown, poor quality spun articles will get you nowhere. I have been involved in the vape market for the past 7 years and know pretty much everything about it, including all the major vape companies, e-juice brands, vape mods, nicotine salts, vape laws and more. With this service, I will write up articles for your blog. I recommend that you keep your article titles relatively broad instead of focusing too much on individual products. Each piece will be conversational, well-researched and fun to read. Simply send me your article titles and leave everything else to me. Frequently Asked Questions I need more than 10 articles. You can order multiple packages or I could send you a custom offer, whichever works best for you. What makes you a good writer? My knowledge of the vape industry is what gives me an unparalleled advantage over other writers who have no experience in this field. Instead of writing the bare basics about the vape market, I can also write very critical and in-depth pieces. Can you help me to come up with the topics? Absolutely. Just send me your site and tell me a bit more about your business and I will put together some prospective titles. How do I choose my blog titles? I would recommend that you do not choose very broad article titles such as what is vaping because it will be very difficult to rank this article on the search engines due to the high keyword competition. Try to stick to more specialised titles such as nicotine salts guide. Why is content important for my blog? Each piece of content or each article translates into more visitors. More quality content equals to more visitors. https://peachesandscreams.co.uk/community/peaches/forums/881-vape-forum-new/topics/5405-i-will-write-10-quality-vape-articles-for-your-blog
Greenfields <vapeshopseo@gmail.com> czwartek, 9 maja 2019, godzina 1415
Good Afternoon I am writing to you to introduce my freelance vape seo services. I specialise in creating quality vape-related links to rank vape-related sites on search engines such as Google. I work with 50 of the leading vape shops, e-juice brands and wholesalers and now I have decided to take the same package that we provide to clients via an agency and offer it ten times cheaper on Fiverr. Please take a look at the package and if it is of interest, please feel free to order it from https://www.fiverr.com/cryptovaper Thank you for your time. Kind regards Sergey
Eather <eather.jeramy76@gmail.com> czwartek, 9 maja 2019, godzina 1738
Hello I am writing to briefly introduce my CBD and Hemp backlinks packages. I used to work for a London based SEO and digital marketing agency but I have decided to leave and start freelancing instead. I am offering exactly the same package sold by most SEO agencies but ten times cheaper. Having worked for an SEO agency, I know what works and what doesn't insofar as SEO goes. Please take a look at my services here: https://www.fiverr.com/summerinwapping If you are interested, please feel free to place an order or message me for details. Have a great day!
Taul <taul.bessie@outlook.com> czwartek, 9 maja 2019, godzina 2311
After many requests from my clients, I have created this monthly backlinks SEO package for CBD and Hemp businesses. Essentially, the premium package contains everything that you will need to rank higher on the search engines, get more visitors and make more sales. I am working with 50 different CBD and Hemp companies and during my digital marketing journey, I have tried and tested almost every strategy under the sun and picked out the bits that work real magic and chucked them all into a dirt cheap package. Depending on the package that you order, here is what you will receive: Posts and links on CBD and Hemp blog: these will provide you with contextual and extremely powerful links that will tell the search engines that your site is very popular in this niche which will force the search engines to rank you up! Promotion of your brand/site on over 10,000 most popular forums in the world: you will receive links, direct traffic to your site and generate brand awareness. Guest posts: I will post articles on popular sites and add links to your site. Paid promotions on popular sites. Social media signals. Many more extras! https://peachesandscreams.co.uk/community/peaches/forums/881-vape-forum-new/topics/5344-i-will-create-a-tailored-monthly-vape-seo-backlinks-package
Lujan <lujan.kyle@msn.com> piątek, 10 maja 2019, godzina 0029
After many requests from my clients, I have created this monthly backlinks SEO package for CBD and Hemp businesses. Essentially, the premium package contains everything that you will need to rank higher on the search engines, get more visitors and make more sales. I am working with 50 different CBD and Hemp companies and during my digital marketing journey, I have tried and tested almost every strategy under the sun and picked out the bits that work real magic and chucked them all into a dirt cheap package. Depending on the package that you order, here is what you will receive: Posts and links on CBD and Hemp blog: these will provide you with contextual and extremely powerful links that will tell the search engines that your site is very popular in this niche which will force the search engines to rank you up! Promotion of your brand/site on over 10,000 most popular forums in the world: you will receive links, direct traffic to your site and generate brand awareness. Guest posts: I will post articles on popular sites and add links to your site. Paid promotions on popular sites. Social media signals. Many more extras! Please send me your website url and up to 100 keywords you would like to rank for on the search engines. Please do not use any separators between keywords and enter one keyword per line please. I will deliver everything as soon as the work is finished. https://peachesandscreams.co.uk/community/peaches/forums/881-vape-forum-new/topics/5343-i-will-create-a-tailored-hemp-and-cbd-monthly-backlinks-package
Collie <juliet.collie@outlook.com> sobota, 11 maja 2019, godzina 0557
Content marketing is extremely important for increasing your website traffic as well as your SEO rankings. Right now, the major search engines are looking at how long visitors are spending on your site to decide how to rank your site. It is extremely important to have QUALITY blog posts that are interesting to read and add value to your site. As my experience has shown, poor quality spun articles will get you nowhere. I have been involved in the vape market for the past 7 years and know pretty much everything about it, including all the major vape companies, e-juice brands, vape mods, nicotine salts, vape laws and more. With this service, I will write up articles for your blog. I recommend that you keep your article titles relatively broad instead of focusing too much on individual products. Each piece will be conversational, well-researched and fun to read. Simply send me your article titles and leave everything else to me. Frequently Asked Questions I need more than 10 articles. You can order multiple packages or I could send you a custom offer, whichever works best for you. What makes you a good writer? My knowledge of the vape industry is what gives me an unparalleled advantage over other writers who have no experience in this field. Instead of writing the bare basics about the vape market, I can also write very critical and in-depth pieces. Can you help me to come up with the topics? Absolutely. Just send me your site and tell me a bit more about your business and I will put together some prospective titles. How do I choose my blog titles? I would recommend that you do not choose very broad article titles such as what is vaping because it will be very difficult to rank this article on the search engines due to the high keyword competition. Try to stick to more specialised titles such as nicotine salts guide. Why is content important for my blog? Each piece of content or each article translates into more visitors. More quality content equals to more visitors. https://peachesandscreams.co.uk/community/peaches/forums/881-vape-forum-new/topics/5405-i-will-write-10-quality-vape-articles-for-your-blog
Donaghy <donaghy.aundrea@gmail.com> sobota, 11 maja 2019, godzina 1125
After many requests from my clients, I have created this monthly backlinks SEO package for CBD and Hemp businesses. Essentially, the premium package contains everything that you will need to rank higher on the search engines, get more visitors and make more sales. I am working with 50 different CBD and Hemp companies and during my digital marketing journey, I have tried and tested almost every strategy under the sun and picked out the bits that work real magic and chucked them all into a dirt cheap package. Depending on the package that you order, here is what you will receive: Posts and links on CBD and Hemp blog: these will provide you with contextual and extremely powerful links that will tell the search engines that your site is very popular in this niche which will force the search engines to rank you up! Promotion of your brand/site on over 10,000 most popular forums in the world: you will receive links, direct traffic to your site and generate brand awareness. Guest posts: I will post articles on popular sites and add links to your site. Paid promotions on popular sites. Social media signals. Many more extras! https://peachesandscreams.co.uk/community/peaches/forums/881-vape-forum-new/topics/5344-i-will-create-a-tailored-monthly-vape-seo-backlinks-package
Mccurdy <lino.mccurdy14@msn.com> sobota, 11 maja 2019, godzina 1438
GLOBAL VAPE COMPANY EMAIL LIST OF VAPE SHOPS AND VAPE WHOLESALERS AND E-LIQUID DISTRIBUTORS Global Vape Company Email List of Vape Shops and Vape Wholesalers and E-Liquid Distributors Did you know that there are over 38,000 vape companies around the world that you can contact today? Whether you run an e-liquid line or a vape wholesale business, these vape company emails can help you to reach practically all vape companies with your message. Are you tired from not making enough B2B sales to vape shops and vape wholesalers? Do you find most of your marketing to be unproductive? Do you want to take your vape business to the next level and start exploding your sales? Here is the secret sauce that has helped over 500 e-liquid brands and wholesalers from around the world since 2012! Some ejuice companies have even tried to buy us out because they felt that the accessibility of this list was putting them against a lot of competition from smaller vape companies and e-liquid brands! This hopefully helps to illustrate just how powerful this vape company email list is! HERE IS WHAT THE VAPE COMPANY EMAIL LIST CONTAINS: Vape Shops (brick-and-mortar and online) Vape Wholesalers and distributors E-Liquid Companies Vape Event Organisers Vape magazines Vape reviewers HERE ARE THE WAYS IN WHICH YOU CAN USE THIS VAPE COMPANY EMAIL LIST Promotional messages Introductory emails Guest post outreach for backlink building Much more Buy and learn more at https://bit.ly/2zcDKeX
Duck <duck.norberto@msn.com> sobota, 11 maja 2019, godzina 1607
Hey guys! I just wanted to check in with you whether you need any SEO / lead generation services at the moment? I have a pretty good working knowledge of the vape and CBD niches as I have been in this game for 7 years and have helped to rank some of today's leading sites. I can do all sorts of things such as monthly backlink packages, writing blog articles, scraping leads for your business, doing an outreach, promoting you on leading vape and cbd publications and so on! You can buy my links / chat to me here https://www.fiverr.com/ghosttownseo (this is a freelance site). Cheers guys!
Petty <vernita.petty@gmail.com> sobota, 11 maja 2019, godzina 2219
Hello guys! I am dropping you a quick line to introduce you to my services. Unfortunately, due to Brexit, I was laid off by an SEO agency so I decided to freelance instead. I have worked with a lot of CBD and hemp online retailers based in the UK and USA and therefore have a very good understanding of what is needed to rank your site at the top of Google. I am also good at lead gen and have managed to put together a database of all the CBD and hemp stores, manufacturers and wholesalers. I have organised my packages thematically. You can view and order my packages from here: https://www.fiverr.com/canarywharfseo Have a fab day! :) I am back to my CBD gummy bears!
Beg <beg.joycelyn@gmail.com> wtorek, 14 maja 2019, godzina 0248
Hey guys! I just wanted to check in with you whether you need any SEO / lead generation services at the moment? I have a pretty good working knowledge of the vape and CBD niches as I have been in this game for 7 years and have helped to rank some of today's leading sites. I can do all sorts of things such as monthly backlink packages, writing blog articles, scraping leads for your business, doing an outreach, promoting you on leading vape and cbd publications and so on! You can buy my links / chat to me here https://www.fiverr.com/ghosttownseo (this is a freelance site). Cheers guys!
Leworthy <leworthy.maddison@gmail.com> sobota, 18 maja 2019, godzina 1432
A QUICK OVERVIEW OF OUR GLOBAL VAPE SHOP DATABASE Our Global Vape Shop Database contains vape shop contact details including: vape shop names e-mails telephone numbers websites social media links locations/physical addresses Our Global Vape Shop Database comes in an Excel spreadsheet with vape shop details grouped by country in separate worksheets. You will receive the Global Vape Shop Database in a compressed .rar file. Simply extract the document using Windows .rar or an alternative extractor. These can be downloaded online in a click of a button. Our Global Vape Shop Database has been going for the past 5 years! Our team regularly attend vape exhibitions and events. They use this as an opportunity to collect vape shop contact details. Most of the vape shop leads are available online. However, finding, verifying and compiling them is a real administrative burden and we tell you that from our 5 year-long experience in this industry! A QUICK BREAKDOWN OF OUR GLOBAL VAPE SHOP DATABASE Our database covers USA, UK, Europe, Russia and CIS, parts of Asia, Australasia and Africa. Here's a non-exhaustive list of countries covered: Armenia, Australia, Austria, Azerbaijan, Bahrain, Bangladesh, Belgium , Canada, Czech Republic, Denmark, Estonia, Finland, France, Georgia, Germany, Greece , India, Indonesia, Ireland, Italy, Japan, Kazakhstan , Kyrgyzstan, Latvia, Lithuania, Malaysia, Maldives, Moldova, Netherlands, Poland, Romania, Russia, Slovakia, South Africa, Spain, Sweden, Switzerland, Tajikistan, UK , USA, Uzbekistan. DOWNLOAD A SAMPLE OF OUR VAPE SHOP DATABASE https://wowitloveithaveit.com/products/global-vape-shop-database-with-contact-details
Sauls <carmine.sauls@gmail.com> sobota, 18 maja 2019, godzina 1450
A DEFINITIVE AND MOST COMPREHENSIVE E-MAIL LIST OF ALL VAPE SHOPS, E-LIQUID BRANDS, E-LIQUID WHOLESALERS, VAPE DISTRIBUTORS, VAPE EVENT ORGANISERS, ONLINE VAPE SHOPS, BRICK-AND-MORTAR VAPE SHOPS, VAPE MAGAZINES AND VAPE COMMUNITIES IS FINALLY HERE! Following multiple requests from our clients, our e-mail marketing team has worked hard over the past three months to bring you an e-mail list of ALL vape businesses around the world. We have combined all e-mail addresses from our vape shop databases, contacts, business cards from over 50 vape exhibitions, public domain, subscriber lists and other sources. Our entire mailing list has been scrubbed to weed out vape businesses that have gone out of business or changed their domain names to bring you a clean and verified mailing list of vape businesses around the world. Upon payment, the Vape Company E-Mail Mailing List is available as an INSTANT DOWNLOAD in a notepad .txt format that you can simply upload to your subscriber list. Then all you have to do is create a beautiful newsletter campaign and hit the send button. Our Vape Company E-Mail Mailing List has over 38,000 email addresses of brick-and-mortar vape shops, e-liquid wholesalers and distributors, online vape shops, e-liquid brands, vape event organisers, vape communities, vape magazines, vape reviewers and much more! Our team is constantly verifying and updating the Vape Company email list to bring you only the latest vape company leads. DOWNLOAD A SAMPLE OF OUR GLOBAL E-MAIL LIST OF ALL VAPE COMPANIES IN THE WORLD https://theeliquidboutique.co.uk/products/vape-company-e-mail-mailing-list
Jager <jager.jonathon@hotmail.com> sobota, 18 maja 2019, godzina 1752
After many requests from my clients, I have created this monthly backlinks SEO package for CBD and Hemp businesses. Essentially, the premium package contains everything that you will need to rank higher on the search engines, get more visitors and make more sales. I am working with 50 different CBD and Hemp companies and during my digital marketing journey, I have tried and tested almost every strategy under the sun and picked out the bits that work real magic and chucked them all into a dirt cheap package. Depending on the package that you order, here is what you will receive: Posts and links on CBD and Hemp blog: these will provide you with contextual and extremely powerful links that will tell the search engines that your site is very popular in this niche which will force the search engines to rank you up! Promotion of your brand/site on over 10,000 most popular forums in the world: you will receive links, direct traffic to your site and generate brand awareness. Guest posts: I will post articles on popular sites and add links to your site. Paid promotions on popular sites. Social media signals. Many more extras! https://peachesandscreams.co.uk/community/peaches/forums/881-vape-forum-new/topics/5344-i-will-create-a-tailored-monthly-vape-seo-backlinks-package
Coldiron <coldiron.margart@googlemail.com> sobota, 18 maja 2019, godzina 2040
A QUICK OVERVIEW OF OUR GLOBAL VAPE SHOP DATABASE Our Global Vape Shop Database contains vape shop contact details including: vape shop names e-mails telephone numbers websites social media links locations/physical addresses Our Global Vape Shop Database comes in an Excel spreadsheet with vape shop details grouped by country in separate worksheets. You will receive the Global Vape Shop Database in a compressed .rar file. Simply extract the document using Windows .rar or an alternative extractor. These can be downloaded online in a click of a button. Our Global Vape Shop Database has been going for the past 5 years! Our team regularly attend vape exhibitions and events. They use this as an opportunity to collect vape shop contact details. Most of the vape shop leads are available online. However, finding, verifying and compiling them is a real administrative burden and we tell you that from our 5 year-long experience in this industry! A QUICK BREAKDOWN OF OUR GLOBAL VAPE SHOP DATABASE Our database covers USA, UK, Europe, Russia and CIS, parts of Asia, Australasia and Africa. Here's a non-exhaustive list of countries covered: Armenia, Australia, Austria, Azerbaijan, Bahrain, Bangladesh, Belgium , Canada, Czech Republic, Denmark, Estonia, Finland, France, Georgia, Germany, Greece , India, Indonesia, Ireland, Italy, Japan, Kazakhstan , Kyrgyzstan, Latvia, Lithuania, Malaysia, Maldives, Moldova, Netherlands, Poland, Romania, Russia, Slovakia, South Africa, Spain, Sweden, Switzerland, Tajikistan, UK , USA, Uzbekistan. DOWNLOAD A SAMPLE OF OUR VAPE SHOP DATABASE https://wowitloveithaveit.com/products/global-vape-shop-database-with-contact-details
Russo <russo.rodolfo@gmail.com> sobota, 18 maja 2019, godzina 2233
Hey guys I am dropping you a line to quickly introduce my hemp and CBD marketing packages. Whilst doing some research for my existing clients, I came across your site and thought I would write to you to see if you are interested in my CBD and hemp focused packages. My main area of specialisation is sponsored guest posting on vape and cbd blogs as well as business directories. I am currently working with some of the industry leaders. I used to work for a reputable SEO agency but have abandoned the ship since a couple of months ago. With me, you will get a competitively-priced service with a friendly approach. You can view and order my packages from Fiverr https://www.fiverr.com/autumninchelsea For ease of communication, please write to me on Fiverr as I have my auto notifications enabled. I recommend my monthly package with all extras as it literally contains virtually everything you need to rank. I look forward to working with you! Cheers
Morrison <bebe.morrison@gmail.com> sobota, 18 maja 2019, godzina 2233
Content marketing is extremely important for increasing your website traffic as well as your SEO rankings. Right now, the major search engines are looking at how long visitors are spending on your site to decide how to rank your site. It is extremely important to have QUALITY blog posts that are interesting to read and add value to your site. As my experience has shown, poor quality spun articles will get you nowhere. I have been involved in the vape market for the past 7 years and know pretty much everything about it, including all the major vape companies, e-juice brands, vape mods, nicotine salts, vape laws and more. With this service, I will write up articles for your blog. I recommend that you keep your article titles relatively broad instead of focusing too much on individual products. Each piece will be conversational, well-researched and fun to read. Simply send me your article titles and leave everything else to me. Frequently Asked Questions I need more than 10 articles. You can order multiple packages or I could send you a custom offer, whichever works best for you. What makes you a good writer? My knowledge of the vape industry is what gives me an unparalleled advantage over other writers who have no experience in this field. Instead of writing the bare basics about the vape market, I can also write very critical and in-depth pieces. Can you help me to come up with the topics? Absolutely. Just send me your site and tell me a bit more about your business and I will put together some prospective titles. How do I choose my blog titles? I would recommend that you do not choose very broad article titles such as what is vaping because it will be very difficult to rank this article on the search engines due to the high keyword competition. Try to stick to more specialised titles such as nicotine salts guide. Why is content important for my blog? Each piece of content or each article translates into more visitors. More quality content equals to more visitors. https://peachesandscreams.co.uk/community/peaches/forums/881-vape-forum-new/topics/5405-i-will-write-10-quality-vape-articles-for-your-blog
Grimes <grimes.pamala@gmail.com> niedziela, 19 maja 2019, godzina 0618
WORLD'S #1 UK VAPE SHOP DATABASE Do you own an e-liquid or a vape brand? Are you looking to sell your product to vape shops directly? Our UK vape store database is the best and most important investment you will make for your vape business. There is simply no point of having a beautiful website and a great brand if nobody has heard of it or will never see it. Our vape shop database will help to connect your brand with vape stores which will equal to brand exposure, higher sales and greater profit. Just over 500 e-liquid and mod brands have purchased our database and have made significant gains. Some of these brands are already so large that you will have heard of them! Our database of UK vape shops will help you to expand your target audience. There are many ways in which you can use the UK vape shop database including vape email marketing campaigns, newsletters, telemarketing, sending of e-liquid samples, vape shop visits and much more! https://theeliquidboutique.co.uk/products/uk-vape-shop-database
Kingsmill <dorris.kingsmill@yahoo.com> niedziela, 19 maja 2019, godzina 0749
The vape industry has grown exponentially since 2012. It all started off with the ego starter kits, then progressed to dripping and subohming and now we seem to have reached the heights of nicotine salts, shortfill e-liquids, CBD and Juul devices. Thousands of brick-and-mortar vape shops have opened all around the world. New online vape shop start-ups are emerging on a daily basis. The competition in the vape industry has become cut throat! Back in 2012, it was a breeze to rank for competitive vape keywords on most search engines whilst today, it is even becoming difficult to rank for local area post codes as every corner of every city seems to have a growing vape shop demographic. We were the first vape SEO company in the world and we know the vape industry inside out. We have ranked some of the biggest e-juice brands since when they were starting out, vape shops that were to become some of the biggest chains in the country, vape wholesalers, event organisers and many other different types of vape sites. Our deep knowledge of the SEO and the vape industries allows us to understand the unique business models of our clients and exactly what it takes to rank a vape shop to the very top of the search engines. WHAT YOU WILL RECEIVE WITH OUR VAPE SEO PACKAGE As we have mentioned above, since working with many vape businesses, we have created a blueprint for ranking a site. We have gone through numerous trial and errors and know what works and what does not work. In the current SEO climate, major search engines are putting a greater emphasis on the overall domain authority and metrics of a site as well as brand and onsite visitor behaviour (browsing, click-throughs and bounces). We are constantly adjusting our package to ensure that all of our practices are closely attuned to the latest SEO best-practices and search engine algorithms. HERE IS WHAT YOU WILL RECEIVE WITH OUR VAPE SEO PACKAGE AND WHY IT IS IMPORTANT FOR YOUR SITE: 1,000 backlinks on vape and e-liquid blogs: all of the links are do follow, permanent and 100% related to the vaping niche. This helps the search engines to classify your site and rank it higher on the basis of the fact that it has a lot of links coming from designated vape blogs. Moreover, each vape blog has a very high domain authority which will pass on a lot of link equity to you site. 5,000+ forum posts: we will post out a unique message about your website or brand on the most popular forums in the world. Not only will this help to generate awareness about your brand but will also give you a lot of backlinks and direct visitors to your site. Guest posts on very powerful sites: we have exclusive access to some very popular and powerful sites on which we can place guests posts with links to your site. Mixed backlinks: in addition to the above work, we will also create some mixed backlinks for some diversity. This would include some blog comments, video comments and more. Indexing: we will index your links with the major searhc engines at a very natural and steady pace to keep the search engine red flags at bay! Learn more and buy at https://wowitloveithaveit.com/products/extra-powerful-vape-backlinks-seo-package-for-shops
Anna <bryan.anna@outlook.com> niedziela, 19 maja 2019, godzina 0957
A QUICK OVERVIEW OF OUR GLOBAL VAPE SHOP DATABASE Our Global Vape Shop Database contains vape shop contact details including: vape shop names e-mails telephone numbers websites social media links locations/physical addresses Our Global Vape Shop Database comes in an Excel spreadsheet with vape shop details grouped by country in separate worksheets. You will receive the Global Vape Shop Database in a compressed .rar file. Simply extract the document using Windows .rar or an alternative extractor. These can be downloaded online in a click of a button. Our Global Vape Shop Database has been going for the past 5 years! Our team regularly attend vape exhibitions and events. They use this as an opportunity to collect vape shop contact details. Most of the vape shop leads are available online. However, finding, verifying and compiling them is a real administrative burden and we tell you that from our 5 year-long experience in this industry! A QUICK BREAKDOWN OF OUR GLOBAL VAPE SHOP DATABASE Our database covers USA, UK, Europe, Russia and CIS, parts of Asia, Australasia and Africa. Here's a non-exhaustive list of countries covered: Armenia, Australia, Austria, Azerbaijan, Bahrain, Bangladesh, Belgium , Canada, Czech Republic, Denmark, Estonia, Finland, France, Georgia, Germany, Greece , India, Indonesia, Ireland, Italy, Japan, Kazakhstan , Kyrgyzstan, Latvia, Lithuania, Malaysia, Maldives, Moldova, Netherlands, Poland, Romania, Russia, Slovakia, South Africa, Spain, Sweden, Switzerland, Tajikistan, UK , USA, Uzbekistan. DOWNLOAD A SAMPLE OF OUR VAPE SHOP DATABASE https://wowitloveithaveit.com/products/global-vape-shop-database-with-contact-details
Greenfields <vapeshopseo@gmail.com> niedziela, 19 maja 2019, godzina 1003
Good Afternoon I am writing to you to introduce my freelance vape seo services. I specialise in creating quality vape-related links to rank vape-related sites on search engines such as Google. I work with 50 of the leading vape shops, e-juice brands and wholesalers and now I have decided to take the same package that we provide to clients via an agency and offer it ten times cheaper on Fiverr. Please take a look at the package and if it is of interest, please feel free to order it from https://www.fiverr.com/cryptovaper Thank you for your time. Kind regards Sergey
Newman <stormy.newman@gmail.com> poniedziałek, 20 maja 2019, godzina 0533
Hey guys I am dropping you a line to quickly introduce my vape, cbd and hemp marketing packages. Whilst doing some research for my existing clients, I came across your site and thought I would write to you to see if you are interested in my vape, cbd and hemp focused packages. My main area of specialisation is sponsored guest posting on vape and cbd blogs as well as business directories. I am currently working with some of the industry leaders. I used to work for a reputable SEO agency but have abandoned the ship since a couple of months ago. With me, you will get a competitively-priced service with a friendly approach. You can view and order my packages from Fiverr https://www.fiverr.com/autumninchelsea For ease of communication, please write to me on Fiverr as I have my auto notifications enabled. I recommend my monthly package with all extras as it literally contains virtually everything you need to rank. I look forward to working with you! Cheers
Affiliate Program <affiliate-program@woorke.com> sobota, 25 maja 2019, godzina 1910
Dear Partner, This is David Wright from Business Development Department Woorke, A Digital Marketing One Stop Shop We would like to invite you to join our Affiliate Program just refer visitors to Woorke and earn 90% Commission for each Sale! You can moniter the campaign through our Unique Dashboard and can track each records. You will get 150 day's cookie tracking and custom affiliate build available Join our Affiliate Program and we are looking forward to your positive reply. Best Regards David Wright Woorke
Affiliate Program <affiliate-program@woorke.com> piątek, 31 maja 2019, godzina 0203
Dear team, My name is David Wright, and I am the affiliate manager for Woorke, A Digital Marketing One Stop Shop After reviewing your site, I definitely see a lot of potential to work together. I would like to invite you to join our affiliate program at a starting commission rate of 90% on each Sale. If you have any questions about our affiliate program, Please contact Us. Looking forward to working with you. Thanks, David Wright Affiliate Program Manager
Pittman <chauncey.pittman@googlemail.com> piątek, 31 maja 2019, godzina 2246
I am a great fan of CBD and hemp products and I must admit that I know the market inside out. With this very exclusive service, I will try and honestly review your products on the basis of their presentation, quality (taste: if edible), value for money, branding and so on. I can review up to 50 products at most. I am based in the UK, so you would have to ship all the products to my UK address. I would publish the reviews in a CBD and Hemp lifestyle magazine. I can take pictures of your products and add them next to each product (see extra gig). Depending on the number of products involved, I would write up around 1,500 to 3,000 words for the entire review. I would optimise the article for SEO and get it to rank for your brand name. This is by far the most effective way of not only building your brand but also creating goodwill with your prospective clients. Nothing works better than real user reviews free of any corporate bias. It will take me about a month to complete the review. The review would be permanent and feature a link to your site. https://www.fiverr.com/miniksseo/honestly-test-and-review-your-hemp-or-cbd-products
Rader <noreply@buyseotools.org> wtorek, 4 czerwca 2019, godzina 2145
Hello Mate, You are in SEO industry and ofcourse you want SEO Tools for your daily tasks, but buying all tools are very EXPENSIVE. I am now OFFER you all SEO TOP TOOLS in just $27/month. INSTANT access after payment. You can TRIAL the system for one day at just $1. For more detail please visit: https://buyseotools.org Regards,
Selby <tabatha.selby@hotmail.com> piątek, 7 czerwca 2019, godzina 1919
I am a great fan of CBD and hemp products and I must admit that I know the market inside out. With this very exclusive service, I will try and honestly review your products on the basis of their presentation, quality (taste: if edible), value for money, branding and so on. I can review up to 50 products at most. I am based in the UK, so you would have to ship all the products to my UK address. I would publish the reviews in a CBD and Hemp lifestyle magazine. I can take pictures of your products and add them next to each product (see extra gig). Depending on the number of products involved, I would write up around 1,500 to 3,000 words for the entire review. I would optimise the article for SEO and get it to rank for your brand name. This is by far the most effective way of not only building your brand but also creating goodwill with your prospective clients. Nothing works better than real user reviews free of any corporate bias. It will take me about a month to complete the review. The review would be permanent and feature a link to your site. https://www.fiverr.com/miniksseo/honestly-test-and-review-your-hemp-or-cbd-products
Melson <melson.charlie47@hotmail.com> niedziela, 25 sierpnia 2019, godzina 2301
Hi guys I am reaching out to you to see whether you would be interested in our CBD and vape shop databases? At the moment, we have the following databases: Global Vape Shop Database and Vape Store Email List https://creativebeartech.com/product/global-vape-shop-database-and-vape-store-email-list/ Global Hemp and CBD Shops Database with Contact Details https://creativebeartech.com/product/global-hemp-and-cbd-shops-database-with-contact-details/ A lot of ejuice and CBD brands, wholesalers and manufacturers are using our databases for expanding their B2B business. The list includes the likes of The Milkman, Five Pawns, CBD FX, Meet Harmony, Dinner Lady, Marina Vape, Ejuices.co and many others. All of our databases are on promotion for another week. Many thanks for your time and if you have any questions, please feel free to reach out to me!
Negron <alejandro.negron@outlook.com> niedziela, 22 września 2019, godzina 1255
Would you be interested in advertising that costs less than $40 monthly and sends tons of people who are ready to buy directly to your website? Please send me a reply here: lily5885mil@gmail.com and I'll send more details.
Trask <trask.blythe95@gmail.com> środa, 2 października 2019, godzina 0923
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Souza <jacelyn.souza@gmail.com> sobota, 28 grudnia 2019, godzina 0855
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Rickman <gemma.rickman24@gmail.com> piątek, 24 stycznia 2020, godzina 1404
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Chambers <chambers.franklyn@msn.com> sobota, 11 lipca 2020, godzina 1915
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