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1.
Am J Gastroenterol ; 114(2): 221-232, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30353053

RESUMO

BACKGROUND: Alcoholic liver cirrhosis is preventable and caused by heavy drinking. Few in the general population may be at risk and interventions targeting individuals at high risk may be a more feasible opportunity for prevention than interventions targeting the whole population. METHODS: We conducted a systematic review to identify opportunities to prevent alcoholic liver cirrhosis in high-risk populations. Following MOOSE guidelines, we included observational studies published between 1980 and 2017. Prospective studies of alcohol-problem cohorts were included to investigate whether alcohol-problem cohorts qualify as high-risk populations for alcoholic liver cirrhosis. Studies on the alcohol amount consumed by alcoholic liver cirrhosis patients were included to compare with the amount consumed by the general population. Moreover, studies on alcohol-related healthcare contacts prior to alcoholic liver cirrhosis diagnosis were included to identify opportunities to offer prevention interventions. Of 7198 screened references, 38 studies (N = 120,928) were included. RESULTS: Alcohol-problem cohorts qualified as high-risk populations with an incidence of alcoholic liver cirrhosis ranging from 7 to 16% after 8-12 years. The alcohol amount consumed by alcoholic liver cirrhosis patients was high compared to the general population. For example, 45% (95%CI 34, 56) of alcoholic liver cirrhosis patients were drinking >110 g alcohol/day. Finally, there were opportunities to reach alcoholic liver cirrhosis patients prior to diagnosis; 40-61% of alcoholic liver cirrhosis patients had a previous alcohol-related healthcare contact. CONCLUSIONS: We conclude that alcohol-problem cohorts are high-risk populations for alcoholic liver cirrhosis and there seems to be opportunities to reach later alcoholic liver cirrhosis cases with preventive interventions in healthcare settings.


Assuntos
Cirrose Hepática Alcoólica/prevenção & controle , Alcoolismo/epidemiologia , Redução do Dano , Humanos , Incidência , Cirrose Hepática Alcoólica/epidemiologia
2.
Environ Toxicol Pharmacol ; 45: 170-8, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27314760

RESUMO

The aim of this study was to investigate the effect of betaine (BET) on alcoholic liver fibrosis in rats. Fibrosis was experimentally generated with ethanol plus carbon tetrachloride (ETH+CCl4) treatment. Rats were treated with ETH (5% v/v in drinking water) for 14 weeks. CCl4 was administered intraperitoneally (i.p.) 0.2mL/kg twice a week to rats in the last 6 weeks with/without commercial food containing BET (2% w/w). Serum hepatic damage markers, tumor necrosis factor-α, hepatic triglyceride (TG) and hydroxyproline (HYP) levels, and oxidative stress parameters were measured together with histopathologic observations. In addition, α-smooth muscle-actin (α-SMA), transforming growth factor-ß1 (TGF-ß1) and type I collagen (COL1A1) protein expressions were assayed immunohistochemically to evaluate stellate cell (HSC) activation. mRNA expressions of matrix metalloproteinase-2 (MMP-2) and its inhibitors (TIMP-1 and TIMP-2) were also determined. BET treatment diminished TG and HYP levels; prooxidant status and fibrotic changes; α-SMA, COL1A1 and TGF-ß protein expressions; MMP-2, TIMP-1 and TIMP-2 mRNA expressions in the liver of fibrotic rats. In conclusion, these results indicate that the antifibrotic effect of BET may be related to its suppressive effects on oxidant and inflammatory processes together with HSC activation in alcoholic liver fibrosis.


Assuntos
Betaína/uso terapêutico , Células Estreladas do Fígado/efeitos dos fármacos , Cirrose Hepática Alcoólica/prevenção & controle , Cirrose Hepática Experimental/prevenção & controle , Fígado/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Animais , Antioxidantes/metabolismo , Betaína/administração & dosagem , Biomarcadores/sangue , Peso Corporal/efeitos dos fármacos , Feminino , Células Estreladas do Fígado/imunologia , Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/patologia , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/imunologia , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática Alcoólica/imunologia , Cirrose Hepática Alcoólica/metabolismo , Cirrose Hepática Alcoólica/patologia , Cirrose Hepática Experimental/imunologia , Cirrose Hepática Experimental/metabolismo , Cirrose Hepática Experimental/patologia , Testes de Função Hepática , Tamanho do Órgão/efeitos dos fármacos , Ratos Sprague-Dawley
3.
Indian J Gastroenterol ; 35(3): 167-72, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27146041

RESUMO

BACKGROUND: Alcohol use is increasing in North East India and is important to estimate the influence of these changes in the epidemiology of alcohol related cirrhosis. METHODS: Among 1000 consecutive patients of cirrhosis, diagnosed by a combination of clinical, radiological and/or histopathological features, etiology was established by history of significant alcohol abuse, determining viral and autoimmune markers and by metabolic screening. Patients not confirmed to be cirrhotic were excluded from the study. All cases were studied to determine clinical features, complications, disease prognosis, and mortality. Alcoholic cirrhotics were then compared with nonalcohol etiology. RESULTS: 72.2 % alcoholic cirrhosis were compared with 27.8 % patients of nonalcohol etiology and alcoholic cirrhotics were younger (45 + 9.4 years vs. 47.9 + 12.5 years), predominantly males (M/F ratio 37:1 vs. 1.8:1) with significantly high incidence of jaundice (38.5 % vs. 30.5 %), night blindness (14.4 % vs. 3.6 %), ascites (76.3 % vs. 69.1 %), upper gastrointestinal bleed (46.4 % vs. 34.5 %), and hepatic encephalopathy (24.1 % vs. 10.4 %). Biochemical parameters that were significantly higher in alcoholics were mean bilirubin (4.7 + 8.7 vs. 3.1 + 4.7 mg/dL), AST/ALT ratio (2.03 vs. 1.4), gamma-glutaryl transaminase levels (209.7 + 37.9 vs. 93.9 + 14 IU/mL), and serum ammonia (75.1 + 55.7 vs. 52.1 + 45.4 mg/dL). Mean model for end-stage liver disease, scores, and Child C disease was significantly higher in alcoholics (18.6 + 7.7 vs. 15.6 + 6.4) and (54.1 % vs. 37 %), respectively, representing advanced disease at presentation. Mortality within 1 month was significantly higher among alcoholic cirrhosis (9.8 % vs. 3.2 %). CONCLUSION: Thus, alcoholic cirrhosis is of major concern in North East India as majority patients are in most productive age group and presented with advanced disease. Short-term mortality was high among alcoholic cirrhotics. Proper education and legislation are essential to mitigate the consequences of this disease.


Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/epidemiologia , Cirrose Hepática Alcoólica/epidemiologia , Cirrose Hepática Alcoólica/etiologia , Adolescente , Adulto , Fatores Etários , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Bilirrubina/sangue , Biomarcadores/sangue , Feminino , Educação em Saúde , Humanos , Índia/epidemiologia , Cirrose Hepática Alcoólica/diagnóstico , Cirrose Hepática Alcoólica/prevenção & controle , Masculino , Fatores Sexuais , Adulto Jovem
4.
Can J Physiol Pharmacol ; 94(5): 498-507, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26854595

RESUMO

Hepatic stellate cells (HSCs) activation represents an essential event during alcoholic liver fibrosis (ALF). Previous studies have demonstrated that the rat HSCs could be significantly activated after exposure to 200 µmol/L acetaldehyde for 48 h, and the cAMP/PKA signaling pathways were also dramatically upregulated in activated HSCs isolated from alcoholic fibrotic rat liver. Exchange protein activated by cAMP (EPAC) is a family of guanine nucleotide exchange factors (GEFs) for the small Ras-like GTPases Rap, and is being considered as a vital mediator of cAMP signaling in parallel with the principal cAMP target protein kinase A (PKA). Our data showed that both cAMP/PKA and cAMP/EPAC signaling pathways were involved in acetaldehyde-induced HSCs. Acetaldehyde could reduce the expression of EPAC1 while enhancing the expression of EPAC2. The cAMP analog Me-cAMP, which stimulates the EPAC/Rap1 pathway, could significantly decrease the proliferation and collagen synthesis of acetaldehyde-induced HSCs. Furthermore, depletion of EPAC2, but not EPAC1, prevented the activation of HSC measured as the production of α-SMA and collagen type I and III, indicating that EPAC1 appears to have protective effects on acetaldehyde-induced HSCs. Curiously, activation of PKA or EPAC perhaps has opposite effects on the synthesis of collagen and α-SMA: EPAC activation by Me-cAMP increased the levels of GTP-bound (activated) Rap1 while PKA activation by Phe-cAMP had no significant effects on such binding. These results suggested that EPAC activation could inhibit the activation and proliferation of acetaldehyde-induced HSCs via Rap1.


Assuntos
Fatores de Troca do Nucleotídeo Guanina/agonistas , Células Estreladas do Fígado/efeitos dos fármacos , Cirrose Hepática Alcoólica/metabolismo , Proteínas rap1 de Ligação ao GTP/agonistas , Acetaldeído/antagonistas & inibidores , Acetaldeído/toxicidade , Actinas/agonistas , Actinas/antagonistas & inibidores , Actinas/genética , Actinas/metabolismo , Animais , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Colágeno Tipo I/agonistas , Colágeno Tipo I/antagonistas & inibidores , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Colágeno Tipo II/agonistas , Colágeno Tipo II/antagonistas & inibidores , Colágeno Tipo II/genética , Colágeno Tipo II/metabolismo , AMP Cíclico/agonistas , AMP Cíclico/análogos & derivados , AMP Cíclico/metabolismo , AMP Cíclico/farmacologia , Proteínas Quinases Dependentes de AMP Cíclico/química , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Ativação Enzimática/efeitos dos fármacos , Fatores de Troca do Nucleotídeo Guanina/antagonistas & inibidores , Fatores de Troca do Nucleotídeo Guanina/genética , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/patologia , Cirrose Hepática Alcoólica/patologia , Cirrose Hepática Alcoólica/prevenção & controle , Interferência de RNA , Ratos , Sistemas do Segundo Mensageiro/efeitos dos fármacos , Proteínas rap1 de Ligação ao GTP/antagonistas & inibidores , Proteínas rap1 de Ligação ao GTP/genética , Proteínas rap1 de Ligação ao GTP/metabolismo
5.
Liver Int ; 36(4): 538-46, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26560966

RESUMO

BACKGROUND & AIMS: Cirrhosis because of alcohol could be avoided if drinking behaviour could be altered earlier in the disease course. Our aim was to quantify the burden of morbidities in patients prior to alcoholic cirrhosis diagnosis, as this may inform the earlier identification of people at high risk for targeted interventions. METHODS: We carried out a case-control study using 2479 incident cases of alcoholic cirrhosis and 24 790 controls identified from 357 primary and secondary care centres in England. We assessed the prevalence of morbidities that are partly attributable to alcohol (namely malignant neoplasms, diabetes, epilepsy, injuries, cardiovascular and digestive diseases) prior to alcoholic cirrhosis diagnosis. We compared prevalence in cases to the control population and used logistic regression to derive odds ratios (95% CI). RESULTS: Fifty-eight per cent of cases compared to 29% of controls had had at least one alcohol-attributable condition before cirrhosis diagnosis. The most frequent conditions (proportion in cases vs. controls) were intentional injuries (35.9% vs. 11.9%) and cardiovascular diseases (23.2% vs. 15.6%), followed by diabetes (12.8% vs. 5.3%), digestive diseases (6.1% vs. 1.2%) and epilepsy (5.0% vs. 1.1%). The strongest association with alcoholic cirrhosis was found for digestive diseases [OR 5.4 (4.4-6.7)], epilepsy [OR: 4.4 (3.5-5.5)] and injuries [OR: 4.0 (3.7-4.4)] particularly among those aged 18-44 years. CONCLUSION: These data highlight the high burden of other alcohol-attributable conditions in patients prior to alcoholic cirrhosis diagnosis. Reviewing those consistently presenting with any of these conditions more closely could help practitioners reduce/avoid the long-term consequences of development of alcoholic liver disease.


Assuntos
Abstinência de Álcool , Consumo de Bebidas Alcoólicas/efeitos adversos , Transtornos Relacionados ao Uso de Álcool/terapia , Recursos em Saúde/estatística & dados numéricos , Cirrose Hepática Alcoólica/prevenção & controle , Adolescente , Adulto , Idoso , Consumo de Bebidas Alcoólicas/epidemiologia , Consumo de Bebidas Alcoólicas/prevenção & controle , Transtornos Relacionados ao Uso de Álcool/diagnóstico , Transtornos Relacionados ao Uso de Álcool/epidemiologia , Transtornos Relacionados ao Uso de Álcool/psicologia , Estudos de Casos e Controles , Comorbidade , Diagnóstico Precoce , Inglaterra/epidemiologia , Feminino , Comportamentos Relacionados com a Saúde , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Incidência , Cirrose Hepática Alcoólica/diagnóstico , Cirrose Hepática Alcoólica/epidemiologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Valor Preditivo dos Testes , Prevalência , Estudos Prospectivos , Fatores de Proteção , Medição de Risco , Fatores de Risco , Fatores de Tempo , Adulto Jovem
6.
Claves odontol ; 22(74): 41-46, sept. 2015. tab, graf
Artigo em Espanhol | LILACS | ID: lil-775315

RESUMO

El consumo excesivo de bebidas alcohólicas constituye un serio problema sanitario y social. En los últimos años se han destacado sus propiedades anticancerosas, antioxidantes y protectoras contra la enfermedad cardíaca coronaria, lo que ha generado controversias entre beneficios y perjuicios de su consumo. Los efectos tóxicos sobre el sistema nervioso central lideran el cuadro de la intoxicación aguda, mientras que los efectos del consumo crónico afectan prácticamente todo el organismo, alterando numerosas funciones aún en etapas tempranas de la vida. Los profesionales de las ciencias de la salud tienen un rol clave en la prevención de los daños producidos por este hábito tan difundido.


Assuntos
Humanos , Alcoolismo/complicações , Bebidas Alcoólicas/toxicidade , Saúde Bucal , Bebidas Alcoólicas/efeitos adversos , Cirrose Hepática Alcoólica/prevenção & controle , Doenças da Boca/etiologia , Etanol/metabolismo , Organização Mundial da Saúde
7.
Rev. bras. enferm ; 67(5): 700-707, Sep-Oct/2014. tab, graf
Artigo em Português | LILACS, BDENF - Enfermagem | ID: lil-731203

RESUMO

O artigo descreve a construção de um questionário para avaliação da qualidade do atendimento de um Time de Resposta Rápida, em Hospital Universitário de Londrina-PR, fundamentado no modelo conceitual de Donabedian (estrutura-processoresultado). A coleta de dados ocorreu no mês de março de 2012 e o processo de adequação do questionário foi desenvolvido com a aplicação da Técnica Delphi com a participação de 15 especialistas. Ao término do estudo obteve-se um questionário com 37 enunciados, sendo alcançado índice de concordância final na pesquisa com valores superiores a 80% para todos os conceitos. Espera-se que as contribuições do grupo de especialistas tornem o instrumento confiável e seja aplicado em outros serviços semelhantes. Aplicações futuras deste instrumento poderão trazer subsídios para melhor avaliação da qualidade dos serviços de equipes de Resposta Rápida.


The paper describes the construction of a questionnaire to assess the quality of care of a Rapid Response Team at the University Hospital of Londrina, based on the conceptual model of Donabedian (structure-process-outcome). Data collection occurred in March 2012 and the process of adjusting the questionnaire was developed with the application of the Delphi technique involving 15 experts. At the end of the study the questionnaire contained 37 statements, achieving final compliance level higher than 80% in all concepts. It is hoped that the contributions of the expert group produce a more reliable questionnaire to be applied in other similar services. Future applications of this instrument may provide information to better assess the quality of teams of Rapid Response services.


El artículo describe la construcción de un cuestionario para la evaluación de la calidad de la atención de un Equipo de Respuesta Rápida en un Hospital Universitario de Londrina, Paraná, basado en el modelo conceptual de Donabedian (estructura-procesoresultado). La recolección de datos ocurrió durante el mes de marzo de 2012 y el proceso de ajuste del cuestionario fue desarrollado por medio de la Técnica Delphi con la participación de 15 especialistas. Al término del estudio se obtuvo un cuestionario con 37 enunciados, alcanzándose un índice de concordancia final en la investigación con valores superiores al 80% para todos los conceptos. Se espera que las contribuciones del grupo de especialistas afiancen la confiabilidad del instrumento y que el cuestionario sea utilizado en otros servicios semejantes. Las aplicaciones futuras podrán traer subsidios para evaluar mejor la calidad de los servicios de los equipos de Respuesta Rápida.


Assuntos
Humanos , Animais , Masculino , Ratos , Bebidas Alcoólicas/toxicidade , Hepatócitos/efeitos dos fármacos , Metalotioneína/biossíntese , Divisão Celular/efeitos dos fármacos , Colágeno/biossíntese , Hepatócitos/metabolismo , Hepatócitos/patologia , Cirrose Hepática Alcoólica/etiologia , Cirrose Hepática Alcoólica/prevenção & controle , Ratos Sprague-Dawley
9.
Wei Sheng Yan Jiu ; 43(2): 282-5, 2014 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-24868984

RESUMO

OBJECTIVE: To study the effect of curcumin on antioxidant function in the mice with acute alcoholic liver injury. METHODS: 50 male KM mices were randomly divided into 5 groups according to the weight, i. e. the normal control group, model control group, and curcumin low-dose group, middle-dose group, high-dose group (50, 100 and 200 mg/kg BW). After a 14-day administration, the relative liver weight, the content of MDA, the activity of SOD, GSH-Px, T-AOC in the liver tissue and the content of serum AST, ALT were determined. RESULTS: Compared with the normal control group, all indexes of model control group were significantly different (P < 0.05). The content of serum AST and ALT at high-dose group were significantly decreased compared with model control group (P < 0.05). Meanwhile, the activity of SOD, GSH-Px and T-AOC in the liver tissue were increased significantly (P < 0.05), and the content of MDA decreased significantly (P < 0.05). CONCLUSION: Curcumin can improve the antioxidant activity of the mice with acute alcoholism, and has good protective effects on acute alcoholic liver injury in mice.


Assuntos
Antioxidantes , Curcumina/farmacologia , Cirrose Hepática Alcoólica/prevenção & controle , Animais , Fígado , Masculino , Camundongos
10.
Voen Med Zh ; 334(3): 15-9, 2013 Mar.
Artigo em Russo | MEDLINE | ID: mdl-23808210

RESUMO

Alcohol--is the main causative factor of cirrhosis among the population in Russia. The primary prevention must be focused on exception of consumption of heavy doses of alcohol hepatitis and B vaccination. There are no healthy doses of alcohol. Secondary prevention means the use of the hepatoprotectors. List of hepatoprotectors and also amount of money spent to the purchase of these hepatoprotectors increase constantly. But, unfortunately, alongside with it, increases the mortality from hepatic disorders. Effectiveness of the most hepatoprotectors (such as Essential phospholipids, milk thistle) equals to the effectiveness of placebo.


Assuntos
Cirrose Hepática Alcoólica/prevenção & controle , Prevenção Primária/métodos , Substâncias Protetoras/uso terapêutico , Prevenção Secundária/métodos , Consumo de Bebidas Alcoólicas/efeitos adversos , Ensaios Clínicos como Assunto , Hepatite B/complicações , Humanos , Cirrose Hepática Alcoólica/etiologia , Cirrose Hepática Alcoólica/patologia , Fosfolipídeos/administração & dosagem , Fosfolipídeos/uso terapêutico , Guias de Prática Clínica como Assunto , Substâncias Protetoras/administração & dosagem , Substâncias Protetoras/classificação , S-Adenosilmetionina/administração & dosagem , S-Adenosilmetionina/uso terapêutico , Silimarina/administração & dosagem , Silimarina/uso terapêutico , Resultado do Tratamento , Ácido Ursodesoxicólico/administração & dosagem , Ácido Ursodesoxicólico/uso terapêutico
11.
J Pathol ; 230(4): 365-76, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23839903

RESUMO

The hepatic growth factor hepatopoietin Cn (HPPCn) prevents liver injury induced by carbon tetrachloride in rats. Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid produced by sphingosine kinase (SphK). S1P and S1P receptors (S1PRs) are involved in liver fibrogenesis and oxidative injury. This work sought to understand the mechanism by which SphK/S1P/S1PRs are involved in the protective effects of HPPCn on ethanol-induced liver injury and fibrosis. Transgenic mice with liver-specific overexpression of HPPCn (HPPCn(liver) (+/+)) were generated. Two ethanol feeding protocols were used to assess the protective effect of HPPCn on acute and chronic liver injury in mice. Specific inhibitors of S1PR1, S1PR2 and S1PR3 and siRNA were used to examine the roles of S1PRs in hepatic stellate cell (HSC) activation and hepatocyte apoptosis. Increased HPPCn expression in transgenic mice attenuated fibrosis induced by ethanol and carbon tetrachloride (CCl4). Treatment with recombinant human HPPCn prevented human hepatocyte apoptosis and HSC activation. JTE-013 or S1PR2-siRNA attenuated the effect of HPPCn on HSC activation induced by tumour necrosis factor-α (TNF-α). Consistent with the effect of N,N-dimethylsphingosine (DMS), suramin or S1PR3-siRNA treatment blocked HPPCn-induced Erk1/2 phosphorylation in human hepatocytes. This study demonstrated that HPPCn attenuated oxidative injury and fibrosis induced by ethanol feeding and that the SphK1/S1P/S1PRs signalling pathway contributes to the protective effect of HPPCn on hepatocyte apoptosis and HSC activation.


Assuntos
Etanol , Fator de Crescimento de Hepatócito/metabolismo , Cirrose Hepática Alcoólica/prevenção & controle , Fígado/enzimologia , Proteínas Nucleares/metabolismo , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Receptores de Lisoesfingolipídeo/metabolismo , Animais , Apoptose , Células Cultivadas , Modelos Animais de Doenças , Regulação da Expressão Gênica , Células Estreladas do Fígado/enzimologia , Células Estreladas do Fígado/patologia , Fator de Crescimento de Hepatócito/genética , Humanos , Fígado/efeitos dos fármacos , Fígado/patologia , Cirrose Hepática Alcoólica/enzimologia , Cirrose Hepática Alcoólica/etiologia , Cirrose Hepática Alcoólica/genética , Cirrose Hepática Alcoólica/patologia , Lisofosfolipídeos/metabolismo , Camundongos , Camundongos Transgênicos , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Proteínas Nucleares/genética , Estresse Oxidativo , Fosforilação , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Interferência de RNA , RNA Mensageiro/metabolismo , Receptores de Lisoesfingolipídeo/antagonistas & inibidores , Receptores de Lisoesfingolipídeo/genética , Transdução de Sinais , Esfingosina/análogos & derivados , Esfingosina/metabolismo , Fatores de Tempo , Transfecção , Fator de Necrose Tumoral alfa/metabolismo
12.
Toxicol Lett ; 217(2): 102-10, 2013 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-23274713

RESUMO

This study examined the effect of genistein isolated from Hydrocotyle sibthorpioides on chronic alcohol-induced hepatic injury and fibrosis. Rats underwent intragastric administration of alcohol (5.0-9.5g/kg) once a day for 24 weeks. A subset of rats were also intragastrically treated with genistein (0.5, 1 or 2mg/kg) once a day. Genistein significantly decreased the plasma alcohol concentration, inhibited the activities of alanine and aspartate aminotransferases and decreased levels of inflammatory mediators, including interleukin 6, tumor necrosis factor-α and myeloperoxidase, via down-regulation of nuclear factor-κB. Moreover, genistein effectively inhibited collagen deposition and reduced pathological tissue damage as determined by hepatic fibrosis biomarkers, such as total hyaluronic acid, laminin, and type III collagen. Mechanistically, studies showed that genistein markedly reduced lipid peroxidation, recruited the anti-oxidative defense system, inhibited CYP2El activity, promoted extracellular matrix degradation by modulating the levels of tissue inhibitor of matrix metalloproteinase-1 and matrix metalloproteinase-2, induced HSC apoptosis by down-regulating B-cell lymphoma 2 mRNA, and inhibited the expression of α-smooth muscle actin and transforming growth factor ß(1) proteins. In conclusion, genistein exerts a preventative effect to ameliorate developing liver injury and even liver fibrosis induced by chronic alcohol administration in rats.


Assuntos
Genisteína/farmacologia , Cirrose Hepática Alcoólica/prevenção & controle , Alanina Transaminase/sangue , Alanina Transaminase/metabolismo , Animais , Aspartato Aminotransferases/sangue , Aspartato Aminotransferases/metabolismo , Centella/química , Colágeno Tipo III/metabolismo , Citocromo P-450 CYP2E1/metabolismo , Citocinas/sangue , Citocinas/metabolismo , Etanol/administração & dosagem , Etanol/sangue , Genisteína/isolamento & purificação , Histocitoquímica , Ácido Hialurônico/metabolismo , Inflamação/sangue , Inflamação/induzido quimicamente , Inflamação/enzimologia , Inflamação/metabolismo , Laminina/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática Alcoólica/sangue , Cirrose Hepática Alcoólica/metabolismo , Cirrose Hepática Alcoólica/patologia , Masculino , NF-kappa B/metabolismo , Ratos , Ratos Wistar , Organismos Livres de Patógenos Específicos
13.
Alcohol Clin Exp Res ; 36(7): 1139-47, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22273278

RESUMO

BACKGROUND: Correlative evidence indicates that apoptosis is associated with the progression of alcoholic liver disease. If apoptosis contributes to ethanol (EtOH)-induced steatohepatitis and/or fibrosis, then mice deficient in Bid, a key pro-apoptotic Bcl-2 family member, or mice treated with a pan-caspase inhibitor (VX166) should be resistant to EtOH-induced liver injury. METHODS: This hypothesis was tested in mice using a model of chronic, heavy EtOH-induced liver injury, as well as in a model in which moderate EtOH feeding accelerated the appearance of early markers of hepatic fibrosis in response to acute carbon tetrachloride (CCl(4) ) exposure. RESULTS: Chronic EtOH feeding to mice increased TUNEL- and cytokeratin-18-positive cells in the liver, as well as the expression of receptor-interacting protein kinase 3 (RIP3), a marker of necroptosis. In this model, Bid-/- mice or wild-type mice treated with VX166 were protected from EtOH-induced apoptosis, but not EtOH-induced RIP3 expression. Bid deficiency or inhibition of caspase activity did not protect mice from EtOH-induced increases in plasma alanine and aspartate amino transferase activity, steatosis, or mRNA expression of some inflammatory cytokines. Moderate EtOH feeding to mice enhanced the response of mice to acute CCl(4) exposure, resulting in increased expression of α-smooth muscle actin and accumulation of extracellular matrix protein. VX166-treatment attenuated EtOH-mediated acceleration of these early indicators of CCl(4) -induced hepatic fibrosis, decreasing the expression of α-smooth muscle actin, and the accumulation of extracellular matrix protein. CONCLUSIONS: EtOH-induced apoptosis of hepatocytes was mediated by Bid. Apoptosis played a critical role in the accelerating the appearance of early markers of CCl(4) -induced fibrosis by moderate EtOH but did not contribute to EtOH-induced hepatocyte injury, steatosis, or expression of mRNA for some inflammatory cytokines.


Assuntos
Apoptose/fisiologia , Proteína Agonista de Morte Celular de Domínio Interatuante com BH3/deficiência , Tetracloreto de Carbono/toxicidade , Etanol/toxicidade , Fígado Gorduroso Alcoólico/patologia , Mediadores da Inflamação/toxicidade , Hepatopatias Alcoólicas/metabolismo , Animais , Apoptose/efeitos dos fármacos , Biomarcadores/metabolismo , Fígado Gorduroso Alcoólico/metabolismo , Fígado Gorduroso Alcoólico/prevenção & controle , Feminino , Hepatite Alcoólica/metabolismo , Hepatite Alcoólica/patologia , Hepatite Alcoólica/prevenção & controle , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Hepatócitos/patologia , Cirrose Hepática Alcoólica/metabolismo , Cirrose Hepática Alcoólica/patologia , Cirrose Hepática Alcoólica/prevenção & controle , Hepatopatias Alcoólicas/patologia , Hepatopatias Alcoólicas/prevenção & controle , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout
14.
Int J Epidemiol ; 40(1): 210-8, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20819784

RESUMO

BACKGROUND: A novel approach to derive a threshold dose with respect to alcohol-related harm, the benchmark dose (BMD) methodology, is introduced to provide a basis for evidence-based drinking guidelines. This study is the first to calculate a BMD for alcohol exposure using epidemiological cohort data. With this BMD we will be able to calculate the margin of exposure (MOE) for alcohol consumption, which can be used for comparative risk assessment and applied to setting public health policy. METHODS: Benchmark dose-response modelling of epidemiological data gathered during a recent systematic review and meta-analysis of alcohol consumption as a risk factor for liver cirrhosis morbidity and mortality. RESULTS: For a benchmark response (BMR) of 1.5%, the resulting BMD values were 30.9 g/day for males and 29.7 g/day for females; the corresponding lower one-sided confidence values were 25.7 and 27.2 g/day, respectively. The intake scenario for the Canadian population resulted in an MOE of 1.23. Intake scenarios for individuals as based on the Canadian drinking guidelines led to MOE values between 0.96 and 1.91. Using an uncertainty factor of 10, the acceptable daily intake for alcohol would be 2.6 g/day. CONCLUSIONS: The BMD approach was feasible in developing evidence-based guidelines for low-risk drinking. As our calculated MOEs result around unity (i.e. 1) for moderate drinking, it is evident that the current guidelines correspond very well to low risk on the dose-response curve. The BMD methodology therefore validates current guidelines. The results again highlight the health risk associated with alcohol consumption.


Assuntos
Etanol/toxicidade , Cirrose Hepática Alcoólica/epidemiologia , Medição de Risco , Benchmarking , Canadá/epidemiologia , Estudos de Coortes , Relação Dose-Resposta a Droga , Medicina Baseada em Evidências , Feminino , Humanos , Cirrose Hepática Alcoólica/prevenção & controle , Masculino , Fatores de Risco
15.
Int J Environ Res Public Health ; 7(7): 2881-95, 2010 07.
Artigo em Inglês | MEDLINE | ID: mdl-20717547

RESUMO

This study estimates the avoidable and unavoidable costs of alcohol-related, liver cirrhosis inpatient care, controlling for the lag structure and period of decline in disease risk. Lag structures with different lengths are applied to the exposure to risk from alcohol consumption, which allows for differentiation between avoidable and unavoidable cases due to prior consumption. A lag length of 20 (men) and 23 (women) years (expected remaining life years) gives a total cost of 592 million SEK. Given alcohol consumption is reduced to zero, 72% of cost could potentially be avoided. It is important to account for the length and structure of the risk decline following a consumption change as this substantially affects the estimates.


Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Cirrose Hepática Alcoólica/economia , Feminino , Custos Hospitalares , Humanos , Cirrose Hepática Alcoólica/prevenção & controle , Masculino , Modelos Teóricos , Suécia
16.
Voen Med Zh ; 331(9): 23-30, 2010 Sep.
Artigo em Russo | MEDLINE | ID: mdl-21254525

RESUMO

In the medical institutions of the Ministry of Defence of the Russian Federation was undertook the study with the aim of inclusion of the physicians to the understanding of the danger of alcoholic intoxication through the knowledge provisioning about the influence of the alcohol to the atherogenesis, progression of liver cirrhosis and liver cancer. 2033 patients who had had surgical revascularization were examined. It was found that each of those patients had drunk different doses of alcohol, but it didn't alert the atherogenesis. Also 1283 patients with liver cirrhosis and 126 died of it during 1996-2009 were examined. It was found that alcohol is the most dangerous cause of liver cirrhosis. Anonymous questionnaire of physicians for clearing up their attitude to the alcohol. It was found that only 43% of physicians deny healthful doses of alcohol. According to this fact it is necessary to intensify explanatory work among physicians.


Assuntos
Intoxicação Alcoólica/prevenção & controle , Aterosclerose/prevenção & controle , Cirrose Hepática Alcoólica/prevenção & controle , Adolescente , Adulto , Idoso , Bebidas Alcoólicas/efeitos adversos , Intoxicação Alcoólica/mortalidade , Aterosclerose/mortalidade , Feminino , Humanos , Cirrose Hepática Alcoólica/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
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