Changes in expression of BDNF and its receptors TrkB and p75NTR in the hippocampus of a dog model of chronic alcoholism and abstinence

Chronic ethanol consumption can produce learning and memory deficits. Brain-derived neurotrophic factor (BDNF) and its receptors affect the pathogenesis of alcoholism. In this study, we examined the expression of BDNF, tropomyosin receptor kinase B (TrkB) and p75 neurotrophin receptor (p75NTR) in the hippocampus of a dog model of chronic alcoholism and abstinence. Twenty domestic dogs (9-10 months old, 15-20 kg; 10 males and 10 females) were obtained from Harbin Medical University. A stable alcoholism model was established through ad libitum feeding, and anti-alcohol drug treatment (Zhong Yao Jie Jiu Ling, the main ingredient was the stems of watermelon; developed in our laboratory), at low- and high-doses, was carried out. The Zhong Yao Jie Jiu Ling was effective for the alcoholism in dogs. The morphology of hippocampal neurons was evaluated using hematoxylin-eosin staining. The number and morphological features of BDNF, TrkB and p75NTR-positive neurons in the dentate gyrus (DG), and the CA1, CA3 and CA4 regions of the hippocampus were observed using immunohistochemistry. One-way ANOVA was used to determine differences in BDNF, TrkB and p75NTR expression. BDNF, TrkB and p75NTR-positive cells were mainly localized in the granular cell layer of the DG and in the pyramidal cell layer of the CA1, CA3 and CA4 regions (DG>CA1>CA3>CA4). Expression levels of both BDNF and TrkB were decreased in chronic alcoholism, and increased after abstinence. The CA4 region appeared to show the greatest differences. Changes in p75NTR expression were the opposite of those of BDNF and TrkB, with the greatest differences observed in the DG and CA4 regions.

Implicaçöes do alcoolismo e da doença hepática crônica sobre o metabolismo de micronutrientes / The impact of alcohol and chronic liver disease of micronutrients metabolism

Liver disease, alcohol and malnutrition are combinations usually associated with micronutrient impairment. Chronic liver disease courses with lower storage and activation of vitamin-coenzymes related to their malabsorption. Alcohol worsens the picture by reducing food intake, ncreasing micronutrients utilization and decreasing their absorption secondary to either intestinal or pancreatic injuries. Other concurrent causes would be drug treatments, urinary losses, protein deficiency and oxidative stress. As consequences the clinical signs are anemia, liver steatosis, oxidative stress and immunosuppression

Etanol e o trato gastrointestinal / Ethanol and the gastrointestinal tract

É apresentada revisao da literatura sobre efeitos do etanol na boca e faringe, esôfago e duodeno, esfincter de Oddi, intestino delgado, colo e reto. Vários estudos possibilitaram demonstrar que há maior incidência de câncer de boca e de orofaringe em alccólatras, relacionada à açao do etanol e, provavelmente, também de outras substâncias contidas em bebidas alccólicas. O álcool pode desencadear a doença do refluxo gastroesofágico, pois diminui a pressao do esfíncter inferior do esôfago, a amplitude da peristalse primária e a pressao do esfíncter superior do esôfago. Com relaçao ao câncer do esôfago, verificou-se em várias pesquisas evidente associaçao com o consumo excessivo de bebidas alcoólicas. O risco para o desenvolvimento desse tumor aumenta significantemente se o etilista for também fumante. O alcoolismo é condiçao predisponente para o aparecimento da síndrome de Mallory-Weiss e também, provavelmente, de sangramento das varizes de esôfago. O etanol pode alterar a secreçao, motilidade e permeabilidade gástricas. Algumas drogas, atuando sobre a álcool desidrogenase gástrica podem alterar a absorçao, de etanol no estômago. A erradiaçao do Helicobacter pylori aumenta a atividade da álcool desidrogenase antral. Os efeitos do álcool na mucosa gástrica podem ser classificadas em: dano cáustico, retrodifusao de ions H+ e citoproteçao. Essa substância pode ocasionar gastrite aguda, nao sendo responsável, provavelmente, por gastrite crônica. Nao se sabe se o álcool representa fator de risco para a úlcera. Em alguns trabalhos verificou-se que houve maior incidência de câncer de estômago, relacionada com o consumo de cerveja, vinho e vodka. Alguns autores relatam diminuiçao e outros aumento da pressao do esfíncter de Oddi, com a administraçao de etanol. O consumo agudo e crônico deste pode alterar a estrutura e a absorçao de nutrientes no instestino delgado. Quanto ao câncer colorretal houve, em vários estudos, correlaçao significante com o consumo crônico de etanol.

Ritanserin pharmacokinetics in abstnent chronic alcoholics

La ritanserina es un agente timosténico que, en voluntarios sanos, se metaboliza principalmente en el hígado y presenta una prolongada vida media de eliminación. Ha sido usada en alcohólicos crónicos en abstinencia mostrando interesantes resultados. La farmacocinética de la ritanserina ha sido evaluada únicamente en estudios a dosis única en voluntarios sanos, si bien se considera que la medicación debe ser usada en forma crónica por pacientes alcoholistas para la deshabituación. Por lo tanto, el objetivo del presente estudio fue evaluar la cinética de acumulación del antagonista serotoninérgico durante la administración crónica. Se incluyeron 10 pacientes alcohólicos en abstinencia en un estudio abierto. El fármaco se adminsitró a una dosis diaria de 10 mg durante 28 días y la fase activa fue precedida por un período de 7 días de "lavado" con placebo. Las muestras de sangre se tomaron el día 1 y 28 del tratamiento, 24 horas luego de haber tomado la medicación. Se recogieron muestras de orina durante la noche en forma previa a la segunda y vigesimoctava dosis. Las concentraciones de ritanserina en plasma y orina se midieron por cromatografía líquida de alta performance. Se encontró una gran variación en las concentraciones plasmáticas tanto iniciales como correspondientes al estado de equilibrio (CV = 65 y 52 por ciento respectivamente), lo que se refleja en la variabilidad de los parámetros farmacocinéticos calculados. El factor de acumulación (R) fue 6,9 + or - 8,3 X + or - SEM. Dos pacientes que mostraron acumulación extensa presentaron una prolognada vida media de eliminación (433 y 289 horas), lo que en su mayor parte se explicaría por una expansión del volumen de distribución y, en menor grado, por una disminución del clearance

Endogenous nitrogen excretion in alcoholic patients on an enteral diet

1. Obligatory nitrogen losses were evaluated in a group of 9 chronic alcoholic adult males of low socioeconomic status, with an intake of approximately 1 liter/day of a Brazilian beverage (45% ethanol by weight) for at least 5 years. 2. The patients were fed a nitrofen-free diet orally or by tube for 7 days. Since endogenous nitrogen excretion was statistically similar for all subjects, the data wee pooled for overall analysis. 3. a stable rate of urinary nitrogen output of 28.42 ñ 11.93mg N Kg-1 day-1 was reached in about 3 days both after oral and tube feeding. The obligatory fecal losses for days 4 to 7 were 17.20 ñ 8.86 mg NKg-1 day-1. 4. Based on the factorial approach, considering the skin and other minor nitrogen losses to be 10 mg NKg-1 day-1, the total endogenous obligatory nitrogen loss for this group of alcoholic patients was 55.62 ñ 18.57 mg NKg-1 day-1. 5. The present results are discussed on the basis of the controversy about the nitrogen requirement of alcoholic patients. The endogenous nitrogen excretion demonstrated does not suggest the need for increased nitrogen intake, but the protein malnutrition of the patients points to the need for more protein