MM： To investigate if and to what extent antiviral therapy influenced a broad panel of quantitative testing of liver function （QTLF）. METHODS： Fifty patients with chronic hepatitis C were either treated with inter...MM： To investigate if and to what extent antiviral therapy influenced a broad panel of quantitative testing of liver function （QTLF）. METHODS： Fifty patients with chronic hepatitis C were either treated with interferon （n = 8）, interferon/ribavirin （n = 19） or peg-interferon/ribavirin （n = 23）. Quantitative testing of liver function, including aminopyrine breath test （ABT）, galactose elimination capacity （GEC）, sorbitol clearance （SCI） and indocyanine green clearance （ICG） was performed before and 3 mo after initiation of antiviral therapy. RESULTS： After 3 mo of antiviral treatment, 36 patients showed normal transaminases and were negative for HCVRNA, 14 patients did not respond to therapy. ABT and GEC as parameters of microsomal and cytosolic liver function were reduced in all patients before therapy initiation and returned to normal values in the 36 therapy responders after 3 too. Parameters of liver perfusion （SCl and ICG） were not affected by antiviral therapy. In the 14 non-responders, no changes in QTLF values were observed during the treatment period. CONCLUSION： ICG and SCI remained unaffected in patients with chronic hepatitis C, while ABT and GEC were significantly compromised. ABT and GEC normalized in responders to antiviral therapy. Early determination of ABT and GEC may differentiate responders from non-responders to antiviral treatment in hepatitis C.展开更多
Nonalcoholic fatty liver disease （NAFLD） is highly prevalent and can result in nonalcoholic steatohepatitis （NASH） and progressive liver disease including cirrhosis and hepatocellular carcinoma. A growing body of ...Nonalcoholic fatty liver disease （NAFLD） is highly prevalent and can result in nonalcoholic steatohepatitis （NASH） and progressive liver disease including cirrhosis and hepatocellular carcinoma. A growing body of literature implicates the peroxisome proliferators- activated receptors （PPARs） in the pathogenesis and treatment of NAFLD. These nuclear hormone receptors impact on hepatic triglyceride accumulation and insulin resistance. The aim of this review is to describe the data linking PPARα and PPART to NAFLD/NASH and to discuss the use of PPAR ligands for the treatment of NASH.展开更多
Oxidative stress, generated by chronic ethanol consumption, is a major cause of hepatotoxicity and liver injury. Increased production of oxygen-derived free radicals due to ethanol metabolism by CYP2E1 is principally ...Oxidative stress, generated by chronic ethanol consumption, is a major cause of hepatotoxicity and liver injury. Increased production of oxygen-derived free radicals due to ethanol metabolism by CYP2E1 is principally located in the cytoplasm and in the mitochondria, which does not only injure liver cells, but also other vital organs, such as the heart and the brain. Therefore, there is a need for better treatment to enhance the antioxidant response elements. To date, there is no established treatment to attenuate high levels of oxidative stress in the liver of alcoholic patients. To block this oxidative stress, proteasome inhibitor treatment has been found to significantly enhance the antioxidant response elements of hepatocytes exposed to ethanol. Recent studies have shown in an experimental model of alcoholic liver disease that proteasome inhibitor treatment at low dose has cytoprotective effects against ethanol-induced oxidative stress and liver steatosis. The beneficial effects of proteasome inhibitor treatment against oxidative stress occurred because antioxidant response elements （glutathione peroxidase 2, superoxide dismutase 2, glutathione synthetase, glutathione reductase, and GCLC） were upregulated when rats fed alcohol were treated with a low dose of PS-34Z （Bortezomib, Velcade）. This is an important finding because proteasome inhibitor treatment up-regulated reactive oxygen species removal and glutathione recycling enzymes, while ethanol feeding alone down-regulated these antioxidant elements. For the first time, it was shown that proteasome inhibition by a highly specific and reversible inhibitor is different from the chronic ethanol feeding-induced proteasome inhibition. As previously shown by our group, chronic ethanol feeding causes a complex dysfunction in the ubiquitin proteasome pathway, which affects the proteasome system, as well as the ubiquitination system. The beneficial effects of proteasome inhibitor treatment in alcoholic liver disease are related to proteasome inhibitor reversibility and the rebound of proteasome activity 72 h post PS-341 administration.展开更多
Background： The specialty of allergy developed quickly in western countries because of the rapid increase of allergic diseases, whereas it developed relatively slowly in China. The prevalence of allergen sensitizatio...Background： The specialty of allergy developed quickly in western countries because of the rapid increase of allergic diseases, whereas it developed relatively slowly in China. The prevalence of allergen sensitization and allergic diseases in Zhejiang Province of China is high and improving the medical services for these diseases is critically needed. Objective： To investigate the working status of the diagnosis and treatment of allergic diseases, including doctor resources, diagnostic methods, and allergen-specific immunotherapy in patients of Zhejiang Province, and to provide instructions for the strategic development of subspecialties of allergic diseases. Methods： First we defined the doctors who treat allergic diseases, and designed a comprehensive questionnaire to collect personal and hospital information for these doctors. The questionnaires were distributed to hospitals with different ranks and from different areas in the province. The general condition of doctor＇s resources, carryout of diagnostic methods, and allergen-specific immunotherapy were described and variations in the different specialties, hospitals, and areas were further analyzed. Results： Doctors in their thirties with bachelor＇s degrees were the mainstream for diagnosing and treating allergic diseases. The main specialties of the doctor resources were the specialties of Ear, Nose and Throat（ENT）, Respirology, Pediatrics, and Dermatology. The Pediatrics specialty had a more reasonable infrastructure of doctor resources with more young doctors working in this subspecialty. The development of allergy subspecialty varied within hospitals at different levels or from different areas. The carryout of the skin prick test（SPT）, serum specific Ig E（ss Ig E）, and subcutaneous immunotherapy（SCIT） was best performed in provincial hospitals, while sublingual immunotherapy（SLIT） was prescribed most commonly in municipal hospitals. The performance of SPT and ss Ig E in Hangzhou, Jiaxing, and Wenzhou areas was much better than that in other places. The performance of SCIT and SLIT was best in Wenzhou. Conclusions： Our survey revealed a very initial and unbalanced development for the allergy subspecialty in Zhejiang Province. Doctor resources for allergic diseases were mainly from the specialties of ENT, Respirology, and Pediatrics, and the performance of diagnosis and treatment was mainly focused on provincial and municipal hospitals. Continuous education of allergies could be extended to primary healthcare centers and more efforts should be directed to those areas with poor medical resources.展开更多
文摘MM： To investigate if and to what extent antiviral therapy influenced a broad panel of quantitative testing of liver function （QTLF）. METHODS： Fifty patients with chronic hepatitis C were either treated with interferon （n = 8）, interferon/ribavirin （n = 19） or peg-interferon/ribavirin （n = 23）. Quantitative testing of liver function, including aminopyrine breath test （ABT）, galactose elimination capacity （GEC）, sorbitol clearance （SCI） and indocyanine green clearance （ICG） was performed before and 3 mo after initiation of antiviral therapy. RESULTS： After 3 mo of antiviral treatment, 36 patients showed normal transaminases and were negative for HCVRNA, 14 patients did not respond to therapy. ABT and GEC as parameters of microsomal and cytosolic liver function were reduced in all patients before therapy initiation and returned to normal values in the 36 therapy responders after 3 too. Parameters of liver perfusion （SCl and ICG） were not affected by antiviral therapy. In the 14 non-responders, no changes in QTLF values were observed during the treatment period. CONCLUSION： ICG and SCI remained unaffected in patients with chronic hepatitis C, while ABT and GEC were significantly compromised. ABT and GEC normalized in responders to antiviral therapy. Early determination of ABT and GEC may differentiate responders from non-responders to antiviral treatment in hepatitis C.
文摘Nonalcoholic fatty liver disease （NAFLD） is highly prevalent and can result in nonalcoholic steatohepatitis （NASH） and progressive liver disease including cirrhosis and hepatocellular carcinoma. A growing body of literature implicates the peroxisome proliferators- activated receptors （PPARs） in the pathogenesis and treatment of NAFLD. These nuclear hormone receptors impact on hepatic triglyceride accumulation and insulin resistance. The aim of this review is to describe the data linking PPARα and PPART to NAFLD/NASH and to discuss the use of PPAR ligands for the treatment of NASH.
基金Supported by NIH/NIAAA 8116 and by a Pilot Project Funding from the Alcohol Center Grant on Liver and Pancreas P50-011999
文摘Oxidative stress, generated by chronic ethanol consumption, is a major cause of hepatotoxicity and liver injury. Increased production of oxygen-derived free radicals due to ethanol metabolism by CYP2E1 is principally located in the cytoplasm and in the mitochondria, which does not only injure liver cells, but also other vital organs, such as the heart and the brain. Therefore, there is a need for better treatment to enhance the antioxidant response elements. To date, there is no established treatment to attenuate high levels of oxidative stress in the liver of alcoholic patients. To block this oxidative stress, proteasome inhibitor treatment has been found to significantly enhance the antioxidant response elements of hepatocytes exposed to ethanol. Recent studies have shown in an experimental model of alcoholic liver disease that proteasome inhibitor treatment at low dose has cytoprotective effects against ethanol-induced oxidative stress and liver steatosis. The beneficial effects of proteasome inhibitor treatment against oxidative stress occurred because antioxidant response elements （glutathione peroxidase 2, superoxide dismutase 2, glutathione synthetase, glutathione reductase, and GCLC） were upregulated when rats fed alcohol were treated with a low dose of PS-34Z （Bortezomib, Velcade）. This is an important finding because proteasome inhibitor treatment up-regulated reactive oxygen species removal and glutathione recycling enzymes, while ethanol feeding alone down-regulated these antioxidant elements. For the first time, it was shown that proteasome inhibition by a highly specific and reversible inhibitor is different from the chronic ethanol feeding-induced proteasome inhibition. As previously shown by our group, chronic ethanol feeding causes a complex dysfunction in the ubiquitin proteasome pathway, which affects the proteasome system, as well as the ubiquitination system. The beneficial effects of proteasome inhibitor treatment in alcoholic liver disease are related to proteasome inhibitor reversibility and the rebound of proteasome activity 72 h post PS-341 administration.
基金Project supported by the National Natural Science Foundation of China(No.30600266)the Zhejiang Provincial Science and Technology Project(No.2011C37073)+2 种基金the Zhejiang Provincial Natural Science Foundation(No.LQ12H16012)the National Key Clinical Project of Allergy of Chinathe National Key Clinical Specialist Construction Programs of China
文摘Background： The specialty of allergy developed quickly in western countries because of the rapid increase of allergic diseases, whereas it developed relatively slowly in China. The prevalence of allergen sensitization and allergic diseases in Zhejiang Province of China is high and improving the medical services for these diseases is critically needed. Objective： To investigate the working status of the diagnosis and treatment of allergic diseases, including doctor resources, diagnostic methods, and allergen-specific immunotherapy in patients of Zhejiang Province, and to provide instructions for the strategic development of subspecialties of allergic diseases. Methods： First we defined the doctors who treat allergic diseases, and designed a comprehensive questionnaire to collect personal and hospital information for these doctors. The questionnaires were distributed to hospitals with different ranks and from different areas in the province. The general condition of doctor＇s resources, carryout of diagnostic methods, and allergen-specific immunotherapy were described and variations in the different specialties, hospitals, and areas were further analyzed. Results： Doctors in their thirties with bachelor＇s degrees were the mainstream for diagnosing and treating allergic diseases. The main specialties of the doctor resources were the specialties of Ear, Nose and Throat（ENT）, Respirology, Pediatrics, and Dermatology. The Pediatrics specialty had a more reasonable infrastructure of doctor resources with more young doctors working in this subspecialty. The development of allergy subspecialty varied within hospitals at different levels or from different areas. The carryout of the skin prick test（SPT）, serum specific Ig E（ss Ig E）, and subcutaneous immunotherapy（SCIT） was best performed in provincial hospitals, while sublingual immunotherapy（SLIT） was prescribed most commonly in municipal hospitals. The performance of SPT and ss Ig E in Hangzhou, Jiaxing, and Wenzhou areas was much better than that in other places. The performance of SCIT and SLIT was best in Wenzhou. Conclusions： Our survey revealed a very initial and unbalanced development for the allergy subspecialty in Zhejiang Province. Doctor resources for allergic diseases were mainly from the specialties of ENT, Respirology, and Pediatrics, and the performance of diagnosis and treatment was mainly focused on provincial and municipal hospitals. Continuous education of allergies could be extended to primary healthcare centers and more efforts should be directed to those areas with poor medical resources.
