ABSTRACT
We report the synthesis of two new artificial nucleobase scaffolds, 1 and 2, featuring adequate hydrogen bonding donors and acceptors for the molecular recognition of U:A and C:G base pairs, respectively. The tethering of these structures to various amino acids and the assessment of these artificial nucleobase-amino acid conjugates as RNA ligands against a model of HCV IRES IIId domain are also reported. Compound 1e displayed the highest affinity (Kd twice lower than neomycin - control). Moreover, it appears that this interaction is enthalpically and entropically favored.
Subject(s)
5' Untranslated Regions/drug effects , Amino Acids/pharmacology , Antiviral Agents/pharmacology , Hepacivirus/drug effects , Purines/pharmacology , Pyrimidines/pharmacology , RNA, Viral/metabolism , Amino Acids/chemistry , Antiviral Agents/chemistry , Base Pairing/drug effects , Base Sequence , Hepacivirus/chemistry , Hepacivirus/metabolism , Hepatitis C/drug therapy , Hepatitis C/virology , Humans , Ligands , Nucleic Acid Conformation , Purines/chemistry , Pyrimidines/chemistry , RNA, Viral/chemistryABSTRACT
Chronic liver disease is a considerable burden on society, being one of the three main causes of death in certain regions of Africa and Asia. Liver transplant is the only treatment option for cirrhosis, which is the end stage of many chronic liver diseases. This article reviews the preventable causes of cirrhosis and the preventive strategies which could be implemented in order to avoid the catastrophic consequences of cirrhosis. With small variations around the world, 70 to 80 percent of the end stage liver diseases are caused by excessive alcohol consumption and by viral hepatitis, both of which are potentially preventable. Excessive alcohol consumption has important public health consequences because of its involvement not only with cirrhosis, but also with motor vehicle accidents, unemployment, domestic violence etc. Among the viral causes, Hepatitis Virus B and C have the greatest impact on public health. Effective vaccine is available for Hepatitis Virus B and must be put in use. While a vaccine for Hepatitis Virus C is awaited, effective preventive strategies should be undertaken to avoid the preventable cases of end stage liver disease.
As doenças hepáticas crônicas estão entre as três principais causas de morte na Africa e Asia.O transplante de fígado é o único tratamento curativo para esta doença hepática de caráter terminal.O presente artigo tem como objetivo apresentar as causas passíveis de prevenção de cirrose e as estratégias que podem ser utilizadas no sentido de preveni-las. Com pequenas variações ao redor do mundo, 70 a 80 por cento das doenças hepáticas terminais são causadas por consumo excessivo de álcool e por hepatites virais que são doenças passíveis de prevenção.O consumo excessivo de álcool é importante problema de saúde pública, pois envolve violência doméstica, acidentes de trânsito, além da possível evolução para cirrose e suas conseqüências. Entre as causas virais as hepatites pelo vírus B e C têm o maior impacto na saúde pública. Para a hepatite B já há vacinas disponíveis. Enquanto a vacina para a hepatite C é ainda aguardada, estratégias efetivas de prevenção devem ser efetuadas com o objetivo precípuo de se evitar, por conseqüência, casos de hepatopatias crônicas desta natureza.
Subject(s)
Humans , Male , Female , Pregnancy , Adolescent , Alcoholism/complications , Hepatitis B, Chronic/complications , Hepatitis C, Chronic/complications , Liver Transplantation , Liver Cirrhosis/prevention & control , Alcoholism/prevention & control , Hepatitis B, Chronic/prevention & control , Hepatitis C, Chronic/prevention & control , Liver Cirrhosis/etiology , Mass Screening , Risk-Taking , Viral Hepatitis Vaccines/therapeutic useABSTRACT
Chronic liver disease is a considerable burden on society, being one of the three main causes of death in certain regions of Africa and Asia. Liver transplant is the only treatment option for cirrhosis, which is the end stage of many chronic liver diseases. This article reviews the preventable causes of cirrhosis and the preventive strategies which could be implemented in order to avoid the catastrophic consequences of cirrhosis. With small variations around the world, 70 to 80 percent of the end stage liver diseases are caused by excessive alcohol consumption and by viral hepatitis, both of which are potentially preventable. Excessive alcohol consumption has important public health consequences because of its involvement not only with cirrhosis, but also with motor vehicle accidents, unemployment, domestic violence etc. Among the viral causes, Hepatitis Virus B and C have the greatest impact on public health. Effective vaccine is available for Hepatitis Virus B and must be put in use. While a vaccine for Hepatitis Virus C is awaited, effective preventive strategies should be undertaken to avoid the preventable cases of end stage liver disease.(AU)
As doenças hepáticas crônicas estão entre as três principais causas de morte na Africa e Asia.O transplante de fígado é o único tratamento curativo para esta doença hepática de caráter terminal.O presente artigo tem como objetivo apresentar as causas passíveis de prevenção de cirrose e as estratégias que podem ser utilizadas no sentido de preveni-las. Com pequenas variações ao redor do mundo, 70 a 80 por cento das doenças hepáticas terminais são causadas por consumo excessivo de álcool e por hepatites virais que são doenças passíveis de prevenção.O consumo excessivo de álcool é importante problema de saúde pública, pois envolve violência doméstica, acidentes de trânsito, além da possível evolução para cirrose e suas conseqüências. Entre as causas virais as hepatites pelo vírus B e C têm o maior impacto na saúde pública. Para a hepatite B já há vacinas disponíveis. Enquanto a vacina para a hepatite C é ainda aguardada, estratégias efetivas de prevenção devem ser efetuadas com o objetivo precípuo de se evitar, por conseqüência, casos de hepatopatias crônicas desta natureza.(AU)
Subject(s)
Liver Cirrhosis/complications , Liver Cirrhosis/diagnosis , Liver Cirrhosis/epidemiology , Liver Cirrhosis/prevention & control , Liver Transplantation/rehabilitation , Liver Diseases, Alcoholic/epidemiology , Liver Diseases, Alcoholic/prevention & control , Mortality/trendsABSTRACT
El hepatocarcinoma es el tumor primario hepático más frecuente, cuyo pronóstico está ligado a la detección temprana. Su asociación con el daño hepatocelular producido por la infección crónica del virus de hepatitis B y C, obligan a establecer seguimientos estrictos en estos pacientes. Hasta el momento, el tratamiento quirúrgico mediante la resección completa del tumor ha demostrado ser la mejor alternativa con intención curativa para el hepatocarcinoma, sin embargo esta posibilidad está limitada a unos pocos pacientes, debido a la detección tardía de estos tumores, que en su inicio son indolentes y asintomáticos. De igual manera la coexistencia de enfermedad hepática crónica, contraindica en muchos casos la posibilidad de resección por el alto riesgo de falla hepática. En esta revisión se muestra la incidencia de este tumor en nuestro medio, mostrando su distribución, formas de presentación y características clínicas, con el fin de estimular su detección temprana y tratamiento.
The hepatocarcinoma is the most frequent primary hepatic tumor which prognostic is related to the early detection. The association between chronic hepatocellular damage by human hepatitis virus B and C, forces to establish strict follow up in these patients. Until now, the surgical treatment by means of the complete resection of the tumor has demonstrated to be the best alternative with healing intention for the hepatocarcinoma, however this possibility is limited to some few patients, due to the late detection of these tumors that are non-symptomatic in their beginning. In a same way the coexistence of chronic hepatic illness, contraindicates in many cases the resection possibility for the high risk of liver failure. In this revision, the incidence of this tumor is shown in our hospital, as well as its distribution, presentation forms and clinical characteristics, with the purpose of stimulating its early detection and treatment.