Anonim
jestem adminem sąsiedniego forum, ale puki mhm nie ruszy dupy strasznie mi się nudzi na necie
to też na szybko skleciłem coś do działu...
Po pierwsze żeby było jasne, nie zachęcam do stosowania nikotyny w żadnej postaci (palenie zabija
), aczkolwiek dodam że siedząc teraz przed kompem mam pod językiem 4mg nikotyny w postaci tabletki i moge śmiało powiedzieć że 'to' działa 
Dodam że nikotyna NIE jest skutecznym środkiem po cyklu, aczkolwiek jako dodatek jest warta rozważenia (po przeczytaniu każdy może wyciągnąć własne wnioski).
Jak wiemy po cyklu największym problemem po cyklu jest wstrzymanie syntezy gonadotropin przez przysadkę i tym samym blokada syntezy męskich hormonów płciowych, problem ten rozwiązuje się najczęściej przez blokade receptorów estrogenowych w przysadce, tym samym stymulując ją do działania... I tu pierwszy pożyteczny efekt nikotyny - w badaniach (1,2,3,4,5) udowodniono że działa jako inhibitor enzymu aromatazy przy udziale którego to powstaje 'blokujący' i odpowiedzialny za niepożądane skutki czyli np. gino estrogen.
Innym problemem związanym z niedoborem hormonów płciowym jest zanik libido i erekcji... I tu znowu pozytywne działanie nikotyny która blokuje enzym odpowiedzialny za metabolizm (przekształcanie go do prohormonu) DHT (silnego androgenu który ma pozytywny wpływ na nastrój i funkcje seksualne). Oczywiście nadmiar DHT może mieć negatywne efekty uboczne w postaci łysienia czy przerostu prostaty, ale po cyklu, przy braku androgenów jest to raczej nierealne (chyba że w/w tkanki zostały zjechane podczas samego cyklu, np przez duze dawki testa czy provironu).
Jedyny problem miedzy nikotyną a układem hormonalnym, jest niejasny wpływ na poziom ACTH i zarazem na poziom sterydów kory nadnerczy, ale po cyklu jak wiadomo ich poziom i tak jest wysoki i najprawdopodobniej nie ma to większego znaczenia.
Tyle o wpływie na układ endokrynny.. Teraz będzie o nerwowym...
Jak wiemy po cyklu z nastrojem nie jest zbyt różowo Dzieje się tak przez przez spadek poziomu neurotansmiterow w mozgu.
Nikotyna łącząc się z receptorami acetylocholinowymi w różnych neuronach, stymuluje neuroprzekaźnictwo na różne sposoby, działając na różne obszary mózgu. Najbardziej 'znanym' bo odpowiedzialnym za uzależnienie od nikotyny efektem jest odziaływanie na układ nagrody w mózgu - wywołanie przyjemności. Pobudza też neurony noradrenergiczne i mimo że jest raczej stymulantem, poprzez wpływ na neurony serotoninergiczne i GABA ergiczne ma uspokajające i tonizujące działanie... Wszystkie te efekty to prawie dokładnie substytut dla 'strat' które mają miejsce po zakończeniu cyklu.
Ważny jest też wpływ na poziom leptyny i neuropeptydu Y - jeżeli idzie o kontrole apetytu (rozregulowanego przez kortykosteroidy) (a także na skutek poburzenia chlolinergicznego przyspieszona perystaltyka i wpływ na wydzielanie w układzie pokarmowym)... ale to efekty bardziej przydatne 'na diecie', bo tam nikotyna ma jeszcze wieksze zastosowanie.
O efektach ubocznych nie pisze bo to każdy zna.
refy co do działania na ukł. endokrynny:
1. Competitive inhibition of human placental aromatase by N-n-octanoylnornicotine and other nornicotine derivatives.
Endocrine Biochemistry Department, Medical Foundation of Buffalo Research Institute, NY 14203.
In a study of the effect of N-n-octanoylnornicotine and other acyl derivatives of nornicotine on the aromatization of androstenedione by human placental microsomal aromatase, we found that N-n-octanoylnornicotine, a component of cigarette smoke, exhibited competitive inhibition with an apparent Ki of 0.65 microM. This is comparable to that of aminoglutethimide, the clinically-used non-steroidal aromatase inhibitor. N-n-Decanoylnornicotine and N-(4-hydroxyundecanoyl)nornicotine exhibited apparent Ki values of 0.86 microM and 0.24 microM, respectively. This study suggests that cigarette smoke components may have a direct effect on estrogen biosynthesis and that these compounds may prove to be useful parent structures for development of active site probes for further elucidation of estrogen biosynthesis and might eventually lead to the development of alternative non-steroidal anti-cancer therapy.
2. Tobacco alkaloid derivatives as inhibitors of breast cancer aromatase.
Endocrine Biochemistry Department, Medical Foundation of Buffalo Research Institute, N.Y. 14203.
The inhibition of estrogen biosynthesis by the use of aromatase inhibitors is emerging as a valuable approach to breast cancer therapy. Because smoking has a profound effect on estrogen-related processes we examined the ability of tobacco constituents to suppress estrogen production by breast cancer aromatase. N-n-octanoylnornicotine and N-(4-hydroxyundecanoyl) anabasine suppressed aromatase activity in culture of two human breast cancer cell lines, MDA-MB-231 (IC50 of 310 and 20 microM, respectively) and SK-BR-3 (IC50 of 450 and approximately 2 microM, respectively). MDA-MB-231 cells induced by 250 nM dexamethasone or 1 mM (Bt)2cAMP were slightly more sensitive to both inhibitors. Kinetic analyses showed that inhibition by N-(4-hydroxyundecanoyl)anabasine is competitive with respect to androstenedione as substrate, with apparent Ki values of 0.2 microM against microsomal aromatase activity derived from both (Bt)2cAMP-induced MDA-MB-231 cells and human breast tumor tissue. The corresponding apparent Ki against human placental microsomal aromatase activity was 0.4 microM. These results indicate that acyl derivatives of nornicotine and anabasine block estrogen formation in breast tumor cells and tissue and could contribute to the decreased intra-tissue estrogen levels in women who smoke.
3. Aromatase inhibitors in cigarette smoke, tobacco leaves and other plants.
Endocrine Biochemistry Department, Medical Foundation of Buffalo Research Institute, NY 14203.
A chance observation that cigarette smoke interferes with the aromatase assay led us to investigate tobacco leaf and smoke extracts for the presence of aromatase inhibitors. The highest inhibitory activity was found in the basic fraction of cigarette smoke. Further purification of this fraction led to the identification of N-n-octanoylnornicotine. Synthesis and testing of a series of acylated nornicotines and anabasines for their ability to inhibit aromatase showed an interesting correlation of activity with the length of the acyl carbon chain, with maximum activity at C-11. The acylated derivatives showed activity which was significantly greater than that of nicotine and anabasine. In vivo studies in rats indicated that administration of this inhibitor delayed the onset of NMU-induced breast carcinoma and altered the estrus cycle. These in vivo studies suggest that tobacco alkaloid derivatives exert their effects by suppression of the aromatase enzyme system. Toxicity studies indicated relatively low toxicity with LD50 for N-n-octanoylnornicotine = 367 mg/kg body weight. When extracts from thirty five varieties of vegetables, plant leaves, and fruits were analyzed, seventeen showed quantitatively significant aromatase inhibition which was comparable to that of green tobacco leaf, suggesting that naturally occurring substances may affect endocrine function through aromatase inhibition.
4. Constituents of cigarette smoke inhibit human granulosa cell aromatase.
Recent epidemiologic studies suggest that women smokers have lower endogenous estrogen levels than nonsmokers. The effects of aqueous extracts of cigarette smoke on aromatase were evaluated in cultures of human granulosa cells. Aqueous extracts of cigarette smoke inhibited the conversion of androstenedione (delta 4A) to estradiol in a dose-dependent manner. Dialysis experiments demonstrated that 90% of the inhibitory activity of aqueous extracts of cigarette smoke was in the less than 1000 mol wt fraction. Removal of the aqueous extract of cigarette smoke from the culture medium resulted in a complete reversal of the inhibition of delta 4A aromatization. Addition of supraphysiologic concentrations of delta 4A (73 microM) to the culture medium blocked the smoke-induced inhibition of aromatization. Two low-molecular-weight components of cigarette smoke, nicotine and anabasine, inhibited granulosa cell aromatase in a dose-dependent manner. These studies suggest that constituents of cigarette smoke inhibit a major steroidogenic pathway.
5. Nicotine, cotinine, and anabasine inhibit aromatase in human trophoblast in vitro.
Epidemiologic studies suggest that women who smoke have lower endogenous estrogen than nonsmokers. To explore the possible link between cigarette smoking and decreased endogenous estrogens, we have examined the effects of constituents of tobacco on estrogen production in human choriocarcinoma cells and term placental microsomes. In choriocarcinoma cell cultures, nicotine, cotinine (a major metabolite of nicotine), and anabasine (a minor component of cigarette tobacco) all inhibited androstenedione conversion to estrogen in a dose-dependent fashion. Removal of nicotine, cotinine, and anabasine from the culture medium resulted in the complete reversal of the inhibition of aromatase. In the choriocarcinoma cell cultures, a supraphysiologic concentration of androstenedione (73 microM) in the culture medium blocked the inhibition of aromatase caused by nicotine, cotinine, and anabasine. In preparations of term placental microsomes, nicotine, cotinine, and anabasine inhibited the conversion of testosterone to estrogen. Kinetic analysis demonstrated the inhibition to be competitive with respect to the substrate. These findings suggest that some nicotinic alkaloids directly inhibit aromatase. This mechanism may explain, in part, the decreased estrogen observed in women who smoke.
6. Nicotine and cotinine effects on 3 alpha hydroxysteroid dehydrogenase in canine prostate.
We have recently observed that cigarette smoking affects plasma androgen concentrations. The effects of nicotine and cotinine, two products of cigarette smoking, on testosterone metabolism were determined. The activity of delta 4 steroid 5 alpha-reductase, which converts testosterone to 5 alpha-dihydrotestosterone (DHT) was measured in isolated dog prostate nuclei using testosterone (0-200 nM) as substrate and NADPH as cofactor. Activity of 3 alpha-hydroxysteroid dehydrogenase (HSD), which converts DHT to 3 alpha-androstanediol (3 alpha-diol) and is a reversible enzyme, was measured in isolated dog prostate microsomes with DHT (0-20 microM) as substrate and NADPH as cofactor. When microsomal fractions were incubated for 1 hour with and without nicotine (0-50 microM) and cotinine (0-100 microM), enzyme activity of HSD was significantly suppressed (p less than 0.001). The Vmax was not affected significantly (p greater than 0.60) and Km increased with increasing concentrations of nicotine and cotinine (p less than 0.05). Both nicotine and cotinine are competitive inhibitors of HSD in dog prostate microsomes with Ki's of 61 and 89 microM, respectively. The apparent 5 alpha-reductase activity was unaffected by nicotine and cotinine. The inhibitors produced a marked effect on activity of HSD when used in concentrations achieved in humans who smoke cigarettes. The results suggest that nicotine and cotinine are competitive inhibitors of the HSD, an important enzyme involved in the metabolism of DHT and produce an accumulation of DHT. These products of cigarette smoking could alter androgen action in tissue such as skin and prostate.
I pozostałe refy... tamte tylko zacytowałem bo sie odnoszą do najważniejszego....
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to też na szybko skleciłem coś do działu...
Po pierwsze żeby było jasne, nie zachęcam do stosowania nikotyny w żadnej postaci
(palenie zabija), aczkolwiek dodam że siedząc teraz przed kompem mam pod językiem 4mg nikotyny w postaci tabletki i moge śmiało powiedzieć że 'to' działa Dodam że nikotyna NIE jest skutecznym środkiem po cyklu, aczkolwiek jako dodatek jest warta rozważenia (po przeczytaniu każdy może wyciągnąć własne wnioski).
Jak wiemy po cyklu największym problemem po cyklu jest wstrzymanie syntezy gonadotropin przez przysadkę i tym samym blokada syntezy męskich hormonów płciowych, problem ten rozwiązuje się najczęściej przez blokade receptorów estrogenowych w przysadce, tym samym stymulując ją do działania... I tu pierwszy pożyteczny efekt nikotyny - w badaniach (1,2,3,4,5) udowodniono że działa jako inhibitor enzymu aromatazy przy udziale którego to powstaje 'blokujący' i odpowiedzialny za niepożądane skutki czyli np. gino estrogen.
Innym problemem związanym z niedoborem hormonów płciowym jest zanik libido i erekcji... I tu znowu pozytywne działanie nikotyny która blokuje enzym odpowiedzialny za metabolizm (przekształcanie go do prohormonu) DHT (silnego androgenu który ma pozytywny wpływ na nastrój i funkcje seksualne
). Oczywiście nadmiar DHT może mieć negatywne efekty uboczne w postaci łysienia czy przerostu prostaty, ale po cyklu, przy braku androgenów jest to raczej nierealne (chyba że w/w tkanki zostały zjechane podczas samego cyklu, np przez duze dawki testa czy provironu).
Jedyny problem miedzy nikotyną a układem hormonalnym, jest niejasny wpływ na poziom ACTH i zarazem na poziom sterydów kory nadnerczy, ale po cyklu jak wiadomo ich poziom i tak jest wysoki i najprawdopodobniej nie ma to większego znaczenia.
Tyle o wpływie na układ endokrynny.. Teraz będzie o nerwowym...
Jak wiemy po cyklu z nastrojem nie jest zbyt różowo
Dzieje się tak przez przez spadek poziomu neurotansmiterow w mozgu.
Nikotyna łącząc się z receptorami acetylocholinowymi w różnych neuronach, stymuluje neuroprzekaźnictwo na różne sposoby, działając na różne obszary mózgu. Najbardziej 'znanym' bo odpowiedzialnym za uzależnienie od nikotyny efektem jest odziaływanie na układ nagrody w mózgu - wywołanie przyjemności. Pobudza też neurony noradrenergiczne i mimo że jest raczej stymulantem, poprzez wpływ na neurony serotoninergiczne i GABA ergiczne ma uspokajające i tonizujące działanie... Wszystkie te efekty to prawie dokładnie substytut dla 'strat' które mają miejsce po zakończeniu cyklu.
Ważny jest też wpływ na poziom leptyny i neuropeptydu Y - jeżeli idzie o kontrole apetytu (rozregulowanego przez kortykosteroidy) (a także na skutek poburzenia chlolinergicznego przyspieszona perystaltyka i wpływ na wydzielanie w układzie pokarmowym)... ale to efekty bardziej przydatne 'na diecie', bo tam nikotyna ma jeszcze wieksze zastosowanie.
O efektach ubocznych nie pisze bo to każdy zna.
refy co do działania na ukł. endokrynny:
1. Competitive inhibition of human placental aromatase by N-n-octanoylnornicotine and other nornicotine derivatives.
Endocrine Biochemistry Department, Medical Foundation of Buffalo Research Institute, NY 14203.
In a study of the effect of N-n-octanoylnornicotine and other acyl derivatives of nornicotine on the aromatization of androstenedione by human placental microsomal aromatase, we found that N-n-octanoylnornicotine, a component of cigarette smoke, exhibited competitive inhibition with an apparent Ki of 0.65 microM. This is comparable to that of aminoglutethimide, the clinically-used non-steroidal aromatase inhibitor. N-n-Decanoylnornicotine and N-(4-hydroxyundecanoyl)nornicotine exhibited apparent Ki values of 0.86 microM and 0.24 microM, respectively. This study suggests that cigarette smoke components may have a direct effect on estrogen biosynthesis and that these compounds may prove to be useful parent structures for development of active site probes for further elucidation of estrogen biosynthesis and might eventually lead to the development of alternative non-steroidal anti-cancer therapy.
2. Tobacco alkaloid derivatives as inhibitors of breast cancer aromatase.
Endocrine Biochemistry Department, Medical Foundation of Buffalo Research Institute, N.Y. 14203.
The inhibition of estrogen biosynthesis by the use of aromatase inhibitors is emerging as a valuable approach to breast cancer therapy. Because smoking has a profound effect on estrogen-related processes we examined the ability of tobacco constituents to suppress estrogen production by breast cancer aromatase. N-n-octanoylnornicotine and N-(4-hydroxyundecanoyl) anabasine suppressed aromatase activity in culture of two human breast cancer cell lines, MDA-MB-231 (IC50 of 310 and 20 microM, respectively) and SK-BR-3 (IC50 of 450 and approximately 2 microM, respectively). MDA-MB-231 cells induced by 250 nM dexamethasone or 1 mM (Bt)2cAMP were slightly more sensitive to both inhibitors. Kinetic analyses showed that inhibition by N-(4-hydroxyundecanoyl)anabasine is competitive with respect to androstenedione as substrate, with apparent Ki values of 0.2 microM against microsomal aromatase activity derived from both (Bt)2cAMP-induced MDA-MB-231 cells and human breast tumor tissue. The corresponding apparent Ki against human placental microsomal aromatase activity was 0.4 microM. These results indicate that acyl derivatives of nornicotine and anabasine block estrogen formation in breast tumor cells and tissue and could contribute to the decreased intra-tissue estrogen levels in women who smoke.
3. Aromatase inhibitors in cigarette smoke, tobacco leaves and other plants.
Endocrine Biochemistry Department, Medical Foundation of Buffalo Research Institute, NY 14203.
A chance observation that cigarette smoke interferes with the aromatase assay led us to investigate tobacco leaf and smoke extracts for the presence of aromatase inhibitors. The highest inhibitory activity was found in the basic fraction of cigarette smoke. Further purification of this fraction led to the identification of N-n-octanoylnornicotine. Synthesis and testing of a series of acylated nornicotines and anabasines for their ability to inhibit aromatase showed an interesting correlation of activity with the length of the acyl carbon chain, with maximum activity at C-11. The acylated derivatives showed activity which was significantly greater than that of nicotine and anabasine. In vivo studies in rats indicated that administration of this inhibitor delayed the onset of NMU-induced breast carcinoma and altered the estrus cycle. These in vivo studies suggest that tobacco alkaloid derivatives exert their effects by suppression of the aromatase enzyme system. Toxicity studies indicated relatively low toxicity with LD50 for N-n-octanoylnornicotine = 367 mg/kg body weight. When extracts from thirty five varieties of vegetables, plant leaves, and fruits were analyzed, seventeen showed quantitatively significant aromatase inhibition which was comparable to that of green tobacco leaf, suggesting that naturally occurring substances may affect endocrine function through aromatase inhibition.
4. Constituents of cigarette smoke inhibit human granulosa cell aromatase.
Recent epidemiologic studies suggest that women smokers have lower endogenous estrogen levels than nonsmokers. The effects of aqueous extracts of cigarette smoke on aromatase were evaluated in cultures of human granulosa cells. Aqueous extracts of cigarette smoke inhibited the conversion of androstenedione (delta 4A) to estradiol in a dose-dependent manner. Dialysis experiments demonstrated that 90% of the inhibitory activity of aqueous extracts of cigarette smoke was in the less than 1000 mol wt fraction. Removal of the aqueous extract of cigarette smoke from the culture medium resulted in a complete reversal of the inhibition of delta 4A aromatization. Addition of supraphysiologic concentrations of delta 4A (73 microM) to the culture medium blocked the smoke-induced inhibition of aromatization. Two low-molecular-weight components of cigarette smoke, nicotine and anabasine, inhibited granulosa cell aromatase in a dose-dependent manner. These studies suggest that constituents of cigarette smoke inhibit a major steroidogenic pathway.
5. Nicotine, cotinine, and anabasine inhibit aromatase in human trophoblast in vitro.
Epidemiologic studies suggest that women who smoke have lower endogenous estrogen than nonsmokers. To explore the possible link between cigarette smoking and decreased endogenous estrogens, we have examined the effects of constituents of tobacco on estrogen production in human choriocarcinoma cells and term placental microsomes. In choriocarcinoma cell cultures, nicotine, cotinine (a major metabolite of nicotine), and anabasine (a minor component of cigarette tobacco) all inhibited androstenedione conversion to estrogen in a dose-dependent fashion. Removal of nicotine, cotinine, and anabasine from the culture medium resulted in the complete reversal of the inhibition of aromatase. In the choriocarcinoma cell cultures, a supraphysiologic concentration of androstenedione (73 microM) in the culture medium blocked the inhibition of aromatase caused by nicotine, cotinine, and anabasine. In preparations of term placental microsomes, nicotine, cotinine, and anabasine inhibited the conversion of testosterone to estrogen. Kinetic analysis demonstrated the inhibition to be competitive with respect to the substrate. These findings suggest that some nicotinic alkaloids directly inhibit aromatase. This mechanism may explain, in part, the decreased estrogen observed in women who smoke.
6. Nicotine and cotinine effects on 3 alpha hydroxysteroid dehydrogenase in canine prostate.
We have recently observed that cigarette smoking affects plasma androgen concentrations. The effects of nicotine and cotinine, two products of cigarette smoking, on testosterone metabolism were determined. The activity of delta 4 steroid 5 alpha-reductase, which converts testosterone to 5 alpha-dihydrotestosterone (DHT) was measured in isolated dog prostate nuclei using testosterone (0-200 nM) as substrate and NADPH as cofactor. Activity of 3 alpha-hydroxysteroid dehydrogenase (HSD), which converts DHT to 3 alpha-androstanediol (3 alpha-diol) and is a reversible enzyme, was measured in isolated dog prostate microsomes with DHT (0-20 microM) as substrate and NADPH as cofactor. When microsomal fractions were incubated for 1 hour with and without nicotine (0-50 microM) and cotinine (0-100 microM), enzyme activity of HSD was significantly suppressed (p less than 0.001). The Vmax was not affected significantly (p greater than 0.60) and Km increased with increasing concentrations of nicotine and cotinine (p less than 0.05). Both nicotine and cotinine are competitive inhibitors of HSD in dog prostate microsomes with Ki's of 61 and 89 microM, respectively. The apparent 5 alpha-reductase activity was unaffected by nicotine and cotinine. The inhibitors produced a marked effect on activity of HSD when used in concentrations achieved in humans who smoke cigarettes. The results suggest that nicotine and cotinine are competitive inhibitors of the HSD, an important enzyme involved in the metabolism of DHT and produce an accumulation of DHT. These products of cigarette smoking could alter androgen action in tissue such as skin and prostate.
I pozostałe refy... tamte tylko zacytowałem bo sie odnoszą do najważniejszego....
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