Objective To explore the predictive value of baseline HBs Ag level and early response for HBs Ag loss in patients with HBe Ag-positive chronic hepatitis B during pegylated interferon alpha-2a treatment. Methods A tota...Objective To explore the predictive value of baseline HBs Ag level and early response for HBs Ag loss in patients with HBe Ag-positive chronic hepatitis B during pegylated interferon alpha-2a treatment. Methods A total of 121 patients with HBe Ag-positive chronic hepatitis B who achieved HBs Ag loss were enrolled; all patients were treated with PEG-IFNα-2a 180 μg/week. Serum HBV DNA and serological indicators （HBs Ag, anti-HBs, HBe Ag, and anti-HBe） were determined before and every 3 months during treatment. Results The median treatment time for HBs Ag loss was 84 weeks （7-273 weeks）, and 74.38% （90 cases） of the patients needed extended treatment （〉 48 weeks）. The correlation between baseline HBs Ag levels and the treatment time of HBs Ag loss was significant （B = 14.465, t = 2.342, P = 0.021）. Baseline HBs Ag levels together with the decline range of HBs Ag at 24 weeks significantly correlated with the treatment time of HBs Ag loss （B = 29.862, t = 4.890, P = 0.000 and B = 27.993, t = 27.993, P = 0.005）. Conclusion Baseline HBs Ag levels and extended therapy are critical steps toward HBs Ag loss. Baseline HBs Ag levels together with early response determined the treatment time of HBs Ag loss in patients with HBe Ag-positive chronic hepatitis B during pegylated interferon alpha-2a treatment.展开更多
Radiation is an important modality in cancer treatment, and eighty percent of cancer patients need radiotherapy at some point during their clinical management. However, radiation-induced damage to normal tissues restr...Radiation is an important modality in cancer treatment, and eighty percent of cancer patients need radiotherapy at some point during their clinical management. However, radiation-induced damage to normal tissues restricts the therapeutic doses of radiation that can be delivered to tumours and thereby limits the effectiveness of the treatment. The use of radioprotectors represents an obvious strategy to obtain better tumour control using a higher dose in radiotherapy. However, most of the synthetic radioprotective compounds studied have shown inadequate clinical efficacy owing to their inherent toxicity and high cost. Hence, the development of radioprotective agents with lower toxicity and an extended window of protection has attracted a great deal of attention, and the identification of alternative agents that are less toxic and highly effective is an absolute necessity. Recent studies have shown that alpha-2-macroglobulin（α2M） possesses radioprotective effects. α2M is a tetrameric, disulfide-rich plasma glycoprotein that functions as a nonselective inhibitor of different types of non-specific proteases and as a carrier of cytokines, growth factors, and hormones. α2M induces protein factors whose interplay underlies radioprotection, which supports the idea that α2M is the central effector of natural radioprotection in the rat. Pretreatment with α2M has also induced a significant reduction of irradiation-induced DNA damage and the complete restoration of liver and body weight. Mihailovi？ et al. concluded that the radioprotection provided by α2M was in part mediated through cytoprotection of new blood cells produced in the bone marrow; these authors also indicated that an important aspect of the radioprotective effect of amifostine was the result of the induction of the endogenous cytoprotective capability of α2M. The radioprotective effects of α2M are possibly due to antioxidant, antifibrosis, and anti-inflammatory functions, as well as the maintenance of homeostasis, and enhancement of the DNA repair and cell recovery processes. This review is the first to summarise the observations and elucidate the possible mechanisms responsible for the beneficial effects of α2M. The lacunae in the existing knowledge and directions for future research are also addressed.展开更多
Currently available monotherapies of oral nucleoside/nucleotide analogs or interferon are unable to achieve a sustained and effective response in most of patients with chronic hepatitis B（CHB）. The objective of the ...Currently available monotherapies of oral nucleoside/nucleotide analogs or interferon are unable to achieve a sustained and effective response in most of patients with chronic hepatitis B（CHB）. The objective of the present study was to compare the efficacy and safety of pegylated interferon（Peg-IFN） alpha-2b plus adefovir dipivoxil combination therapy versus Peg-IFN alpha-2b alone. Sixty-one HBeAg-positive chronic hepatitis B patients were randomized to receive Peg-IFN alpha-2b alone（1.5 μg/kg once weekly） or Peg-IFN alpha-2b plus adefovir（10 mg daily） for up to 52 weeks. Efficacy and safety analyses were performed on all participants who received at least one dose of study medication. The rate of HBeAg seroconversion and undetectable HBV-DNA were evaluated after 52 weeks of therapy. At the end of treatment, 11 of 30（36.7%） patients receiving combination therapy achieved HBeAg seroconversion versus 8 of 31（25.8%） in the monotherapy group（P=0.36）. In contrast, the percentage of patients with undetectable serum HBV DNA was significantly higher in the combination group than in the monotherapy group（76.7% vs. 29.0%, P〈0.001）. Thyroid dysfunction was more frequent in the combination group than in the monotherapy group（P〈0.05）. In HBeAg-positive CHB, combination of Peg-IFN alpha-2b and adefovir for 52 weeks resulted, at the end of treatment, in a higher virological response but without significant impact on the rate of HBeAg seroconversion and possibly an adverse effect on thyroid function.展开更多
Background: Viral hepatitis C (HCV) is common in Benin. Untreated, it can be complicated by cirrhosis and hepatocarcinoma, which are sources of death. The objectives of this work were twofold: 1) to evaluate the effec...Background: Viral hepatitis C (HCV) is common in Benin. Untreated, it can be complicated by cirrhosis and hepatocarcinoma, which are sources of death. The objectives of this work were twofold: 1) to evaluate the effectiveness and safety of treatment with classic dual interferon pegylated alpha-2a (IFN) and ribavirin therapy in Benin, and 2) to present problems related to financial accessibility to this treatment. Methods: This was a cross-sectional, descriptive and analytical study, with a retrospective collection of data from November 1, 2010 to December 31, 2015 and prospective collection from January 1, 2016 to July 31, 2016 (7 months). We included all patients treated with IFN + ribavirin for hepatitis C at CNHU/HKM. Sustained virological response (SVR) was defined as undetectable viral load C 6 months after stopping treatment. Safety was appreciated by the search for clinical and hematological adverse effects. Results: One hundred and six patients were followed for HCV, of whom 58 (54.7%) undergoing treatment (26 under standard dual therapy and 32 under direct-acting antivirals). Of the 26 patients under-conventional dual therapy, 12 (46.1%) were genotype 1, 13 (50%) genotype 2 and one (3.9%) genotype 4. In conventional dual therapy, SVR was achieved in 15 (57.7%) patients, including the genotype 4 patient, 4 out of 12 (33.3%) genotype 1 patients, and 10 out of 13 (76.9%) for genotype 2 patients. The most common side effects with this treatment were severe asthenia (23 cases), flu-like symptoms (22 cases), weight loss (21 cases) and neutropenia (22 cases), anemia and thrombocytopenia (20 of 26 cases). The overall cost of treatment per patient was 11,800,624 FCFA for genotypes 1 and 4;and 7,835,048 FCFA for genotype 2. Conclusion: The treatment of HCV with IFN + ribavirin in Benin is effective for genotype 2. But its adverse effects are manifold and its cost is high. The switch to direct-acting antivirals (more effective, better tolerated and less expensive) was therefore necessary.展开更多
Aroma touch therapy is widely used in clinical fields for alleviating pain-related symptoms;however, few studies have reported the pain-relief mechanisms. The present study aimed to elucidate the analgesic effects of ...Aroma touch therapy is widely used in clinical fields for alleviating pain-related symptoms;however, few studies have reported the pain-relief mechanisms. The present study aimed to elucidate the analgesic effects of aroma touch therapy with Citrus junos oil based on the quantitative evaluation of deep brain network (DBN) activity using electroencephalogram (EEG) occipital alpha-2 rhythm (10-13 Hz) powers. Experimental investigations were performed with 13 healthy volunteers using the cold pressor task for simulating chronic pain in three different sessions: a baseline session with no therapies, a control session with a touch therapy, and an aroma touch therapy. We have found for the first time that the interviewed pain ratings represented by Numeric Rating Scale (NRS) scores were strongly correlated with a DBN activity index, which was derived from the slow fluctuation components of occipital EEG alpha-2 rhythm powers. The correlation was characterized by a V-shaped curve in the DBN activity index versus the pain rating, i.e., the NRS score, which provided the complete analgesic states (NRS = 0) for some subjects under aroma touch therapy at an appropriate DBN activity index. Such analgesic states were not so strongly correlated with emotional valence. In conclusion, aroma touch therapy may directly modulate DBN activity so that pain-induced outcomes are minimized.展开更多
BACKGROUND It has been suggested that serum leucine-richα-2 glycoprotein(LRG)could be a novel monitoring biomarker for the assessment of disease activity in inflammatory bowel disease.In particular,the relationship b...BACKGROUND It has been suggested that serum leucine-richα-2 glycoprotein(LRG)could be a novel monitoring biomarker for the assessment of disease activity in inflammatory bowel disease.In particular,the relationship between LRG levels and the endoscopically assessed activity of ulcerative colitis(UC)has become a matter of interest.AIM To clarify appropriate LRG cut-off values for the prediction of endoscopic and histologic remission in Japanese patients with UC.METHODS This was a cross-sectional,single-center,observational study of Japanese patients with UC.Among 213 patients with UC,in whom LRG was measured from September 2020 to February 2022,we recruited 30 patients for whom a total colonoscopy and measurements of LRG and C-reactive protein(CRP)were performed on the same day.We retrospectively analyzed correlations between the LRG and CRP levels and endoscopic indices,including the Mayo endoscopic subscore and UC endoscopic index of severity.RESULTS Correlations between the LRG values and the Mayo endoscopic subscore or UC endoscopic index of severity were significant(r=0.754,P<0.0001;r=0.778,P<0.0001,respectively).There were also significant correlations between CRP levels and Mayo endoscopic subscore or UC endoscopic index of severity(r=0.599,P=0.0005;r=0.563,P=0.0012,respectively),although the correlation coefficients were higher for LRG.The LRG cutoff value for predicting endoscopic remission was 13.4μg/mL for a Mayo endoscopic subscore of 0[area under the curve(AUC):0.871;95%confidence interval(CI):0.744-0.998],and 13.4μg/mL for an UC endoscopic index of severity of 0 or 1(AUC:0.904;95%CI:0.792-1.000).CONCLUSION LRG may be a surrogate marker for endoscopic activity in UC,with a cut-off value of around 13.4μg/mL for endoscopically inactive disease.展开更多
AIM: To study the differential protein profile in serum of hepatitis B patients.METHODS: Serum samples were obtained from patients with chronic hepatitis B who were receiving peginterferon alfa-2b.The serum samples we...AIM: To study the differential protein profile in serum of hepatitis B patients.METHODS: Serum samples were obtained from patients with chronic hepatitis B who were receiving peginterferon alfa-2b.The serum samples were subjected to albumin depletion and analyzed by two-dimensional gel electrophoresis(2-DE).Differentially expressed protein spots were identified by electrospray ionizationquadrupole time-of-flight mass spectrometry.Alpha2-HS-glycoprotein,complement component C3c and CD5 antigen were further analyzed by an enzymelinked immunosorbent assay and immunonephelometry.RESULTS: Nineteen patients with HBeAg-positive chronic hepatitis B(CHB) were studied.These patients were followed for at least 1 year after treatment and were classified according to their treatment response: responders(n = 9) and non-responders(n = 10).2-DE and MS/MS analysis were performed to compare the serum proteins before initiating peginterferon alfa2b.From the quantitative analysis of the 2-D gel,7 proteins were detected between the two groups at different levels before treatment.Among these potential candidates,serum levels of alpha-2-HS-glycoprotein,complement component C3c and CD5 antigen-like precursor were further analyzed.In the validation phase,23 subjects,9 sustained responders and 14 nonresponders,were recruited.Interestingly,the levels of alpha-2-HS-glycoprotein and complement component C3c were elevated in the serum of the non-responders compared to the responders.CONCLUSION: Serum alpha-2-HS-glycoprotein and complement component C3c may be potential serum biomarkers in predicting the treatment response of peginterferon alfa-2b in patients with CHB prior to treatment.展开更多
AIM To report on the efficacy, safety and tolerability of interferon alfa-2a combined with a "low dose" of ribavirin for relapsers and non responders to alpha interferon monotherapy.METHODS Thirty-four chron...AIM To report on the efficacy, safety and tolerability of interferon alfa-2a combined with a "low dose" of ribavirin for relapsers and non responders to alpha interferon monotherapy.METHODS Thirty-four chronic hepatitis C virus-infected non-responders to interferon alfa2a monotherapy (a course of at least 3 months treatment) and 13 relapsers to interferon alfa 2a monotherapy (a dose of 3 to 6 million units three times per week for at least 20 weeks but not more than 18 months) were treated with the same dose of interferon alfa-2a used before (3 to 6 million units three times per week) and ribavirin (10 mg/ kg daily) for 6 months. In complete responders, interferon alfa-2a was administered for further 6 months at the same dose used before as monotherapy.RESULTS Seven (20.6%) of 34 non-responders stopped the combined therapy due to adverse events, including two patients with histological and clinical Child A cirrhosis. In 17/27 (63%)non-responders, the combined therapy was stopped after three months because of non-response. Ten of the 27 non-responders completed the 1;2-month treatment course. At a mean follow up of 28 months (16- 37 months)after the treatment, 4/10 (15%) previous non-responders still remained complete responders,All 13 previous relapsers completed the 12-month treatment course. At a mean follow up of 22months (9 - 36 months) after treatment, 6/13(46%) the previous relapsers were stillsustained complete responders.CONCLUSION Our treatment schedule of the combined therapy for 6 months of interferon alfa2a with a low dose of ribavirin (10 mg/kg/day)followed by 6 months of interferon alfa-2amonotherapy is able to induce a sustainedcomplete response rate in 15% of non-responders and 46% of relapsers with chronic hepatitis C virus-related liver diseases comparable to those obtained with the standarddoses of ribavirin 1000 - 1200 mg/day.Randomized prospective controlled trials using lower total amounts of ribavirin in combination with interferon should be performed.展开更多
α 2-macroglobulin (α2M) could stimulate the regeneration of thymic and bone marrow cells in rats received γ-irradiation, but there was very few reports concerning its mechanism. Wistar rats were irradiated by 16Co ...α 2-macroglobulin (α2M) could stimulate the regeneration of thymic and bone marrow cells in rats received γ-irradiation, but there was very few reports concerning its mechanism. Wistar rats were irradiated by 16Co at 7 Gy, 8.5 Gy, 15 Gy total body doses. Blood plasma and some tissue’s extracts were collected α 2M level. a M activity and cathepsin D activity, malonaldehyde level were determined by radioimmunoassay, modified Schidlow’s method, Barrett’s method and Ohkawa’s method respectively.展开更多
基金supported by Beijing Science and Technology Commission(No.D121100003912001)Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding,Support(No.ZY201402)
文摘Objective To explore the predictive value of baseline HBs Ag level and early response for HBs Ag loss in patients with HBe Ag-positive chronic hepatitis B during pegylated interferon alpha-2a treatment. Methods A total of 121 patients with HBe Ag-positive chronic hepatitis B who achieved HBs Ag loss were enrolled; all patients were treated with PEG-IFNα-2a 180 μg/week. Serum HBV DNA and serological indicators （HBs Ag, anti-HBs, HBe Ag, and anti-HBe） were determined before and every 3 months during treatment. Results The median treatment time for HBs Ag loss was 84 weeks （7-273 weeks）, and 74.38% （90 cases） of the patients needed extended treatment （〉 48 weeks）. The correlation between baseline HBs Ag levels and the treatment time of HBs Ag loss was significant （B = 14.465, t = 2.342, P = 0.021）. Baseline HBs Ag levels together with the decline range of HBs Ag at 24 weeks significantly correlated with the treatment time of HBs Ag loss （B = 29.862, t = 4.890, P = 0.000 and B = 27.993, t = 27.993, P = 0.005）. Conclusion Baseline HBs Ag levels and extended therapy are critical steps toward HBs Ag loss. Baseline HBs Ag levels together with early response determined the treatment time of HBs Ag loss in patients with HBe Ag-positive chronic hepatitis B during pegylated interferon alpha-2a treatment.
基金supported by grant of the Science and Technology Planning Project of Guangdong Province (2010B060900052 and 2009B030801186)the Fundamental Research Funds for the Central Universities (the Young Teacher Training Project of Sun Yat-sen University 09ykpy12)the Medical Scientific Research Project of Zhuhai City (2012003)
文摘Radiation is an important modality in cancer treatment, and eighty percent of cancer patients need radiotherapy at some point during their clinical management. However, radiation-induced damage to normal tissues restricts the therapeutic doses of radiation that can be delivered to tumours and thereby limits the effectiveness of the treatment. The use of radioprotectors represents an obvious strategy to obtain better tumour control using a higher dose in radiotherapy. However, most of the synthetic radioprotective compounds studied have shown inadequate clinical efficacy owing to their inherent toxicity and high cost. Hence, the development of radioprotective agents with lower toxicity and an extended window of protection has attracted a great deal of attention, and the identification of alternative agents that are less toxic and highly effective is an absolute necessity. Recent studies have shown that alpha-2-macroglobulin（α2M） possesses radioprotective effects. α2M is a tetrameric, disulfide-rich plasma glycoprotein that functions as a nonselective inhibitor of different types of non-specific proteases and as a carrier of cytokines, growth factors, and hormones. α2M induces protein factors whose interplay underlies radioprotection, which supports the idea that α2M is the central effector of natural radioprotection in the rat. Pretreatment with α2M has also induced a significant reduction of irradiation-induced DNA damage and the complete restoration of liver and body weight. Mihailovi？ et al. concluded that the radioprotection provided by α2M was in part mediated through cytoprotection of new blood cells produced in the bone marrow; these authors also indicated that an important aspect of the radioprotective effect of amifostine was the result of the induction of the endogenous cytoprotective capability of α2M. The radioprotective effects of α2M are possibly due to antioxidant, antifibrosis, and anti-inflammatory functions, as well as the maintenance of homeostasis, and enhancement of the DNA repair and cell recovery processes. This review is the first to summarise the observations and elucidate the possible mechanisms responsible for the beneficial effects of α2M. The lacunae in the existing knowledge and directions for future research are also addressed.
文摘Currently available monotherapies of oral nucleoside/nucleotide analogs or interferon are unable to achieve a sustained and effective response in most of patients with chronic hepatitis B（CHB）. The objective of the present study was to compare the efficacy and safety of pegylated interferon（Peg-IFN） alpha-2b plus adefovir dipivoxil combination therapy versus Peg-IFN alpha-2b alone. Sixty-one HBeAg-positive chronic hepatitis B patients were randomized to receive Peg-IFN alpha-2b alone（1.5 μg/kg once weekly） or Peg-IFN alpha-2b plus adefovir（10 mg daily） for up to 52 weeks. Efficacy and safety analyses were performed on all participants who received at least one dose of study medication. The rate of HBeAg seroconversion and undetectable HBV-DNA were evaluated after 52 weeks of therapy. At the end of treatment, 11 of 30（36.7%） patients receiving combination therapy achieved HBeAg seroconversion versus 8 of 31（25.8%） in the monotherapy group（P=0.36）. In contrast, the percentage of patients with undetectable serum HBV DNA was significantly higher in the combination group than in the monotherapy group（76.7% vs. 29.0%, P〈0.001）. Thyroid dysfunction was more frequent in the combination group than in the monotherapy group（P〈0.05）. In HBeAg-positive CHB, combination of Peg-IFN alpha-2b and adefovir for 52 weeks resulted, at the end of treatment, in a higher virological response but without significant impact on the rate of HBeAg seroconversion and possibly an adverse effect on thyroid function.
文摘Background: Viral hepatitis C (HCV) is common in Benin. Untreated, it can be complicated by cirrhosis and hepatocarcinoma, which are sources of death. The objectives of this work were twofold: 1) to evaluate the effectiveness and safety of treatment with classic dual interferon pegylated alpha-2a (IFN) and ribavirin therapy in Benin, and 2) to present problems related to financial accessibility to this treatment. Methods: This was a cross-sectional, descriptive and analytical study, with a retrospective collection of data from November 1, 2010 to December 31, 2015 and prospective collection from January 1, 2016 to July 31, 2016 (7 months). We included all patients treated with IFN + ribavirin for hepatitis C at CNHU/HKM. Sustained virological response (SVR) was defined as undetectable viral load C 6 months after stopping treatment. Safety was appreciated by the search for clinical and hematological adverse effects. Results: One hundred and six patients were followed for HCV, of whom 58 (54.7%) undergoing treatment (26 under standard dual therapy and 32 under direct-acting antivirals). Of the 26 patients under-conventional dual therapy, 12 (46.1%) were genotype 1, 13 (50%) genotype 2 and one (3.9%) genotype 4. In conventional dual therapy, SVR was achieved in 15 (57.7%) patients, including the genotype 4 patient, 4 out of 12 (33.3%) genotype 1 patients, and 10 out of 13 (76.9%) for genotype 2 patients. The most common side effects with this treatment were severe asthenia (23 cases), flu-like symptoms (22 cases), weight loss (21 cases) and neutropenia (22 cases), anemia and thrombocytopenia (20 of 26 cases). The overall cost of treatment per patient was 11,800,624 FCFA for genotypes 1 and 4;and 7,835,048 FCFA for genotype 2. Conclusion: The treatment of HCV with IFN + ribavirin in Benin is effective for genotype 2. But its adverse effects are manifold and its cost is high. The switch to direct-acting antivirals (more effective, better tolerated and less expensive) was therefore necessary.
文摘Aroma touch therapy is widely used in clinical fields for alleviating pain-related symptoms;however, few studies have reported the pain-relief mechanisms. The present study aimed to elucidate the analgesic effects of aroma touch therapy with Citrus junos oil based on the quantitative evaluation of deep brain network (DBN) activity using electroencephalogram (EEG) occipital alpha-2 rhythm (10-13 Hz) powers. Experimental investigations were performed with 13 healthy volunteers using the cold pressor task for simulating chronic pain in three different sessions: a baseline session with no therapies, a control session with a touch therapy, and an aroma touch therapy. We have found for the first time that the interviewed pain ratings represented by Numeric Rating Scale (NRS) scores were strongly correlated with a DBN activity index, which was derived from the slow fluctuation components of occipital EEG alpha-2 rhythm powers. The correlation was characterized by a V-shaped curve in the DBN activity index versus the pain rating, i.e., the NRS score, which provided the complete analgesic states (NRS = 0) for some subjects under aroma touch therapy at an appropriate DBN activity index. Such analgesic states were not so strongly correlated with emotional valence. In conclusion, aroma touch therapy may directly modulate DBN activity so that pain-induced outcomes are minimized.
文摘BACKGROUND It has been suggested that serum leucine-richα-2 glycoprotein(LRG)could be a novel monitoring biomarker for the assessment of disease activity in inflammatory bowel disease.In particular,the relationship between LRG levels and the endoscopically assessed activity of ulcerative colitis(UC)has become a matter of interest.AIM To clarify appropriate LRG cut-off values for the prediction of endoscopic and histologic remission in Japanese patients with UC.METHODS This was a cross-sectional,single-center,observational study of Japanese patients with UC.Among 213 patients with UC,in whom LRG was measured from September 2020 to February 2022,we recruited 30 patients for whom a total colonoscopy and measurements of LRG and C-reactive protein(CRP)were performed on the same day.We retrospectively analyzed correlations between the LRG and CRP levels and endoscopic indices,including the Mayo endoscopic subscore and UC endoscopic index of severity.RESULTS Correlations between the LRG values and the Mayo endoscopic subscore or UC endoscopic index of severity were significant(r=0.754,P<0.0001;r=0.778,P<0.0001,respectively).There were also significant correlations between CRP levels and Mayo endoscopic subscore or UC endoscopic index of severity(r=0.599,P=0.0005;r=0.563,P=0.0012,respectively),although the correlation coefficients were higher for LRG.The LRG cutoff value for predicting endoscopic remission was 13.4μg/mL for a Mayo endoscopic subscore of 0[area under the curve(AUC):0.871;95%confidence interval(CI):0.744-0.998],and 13.4μg/mL for an UC endoscopic index of severity of 0 or 1(AUC:0.904;95%CI:0.792-1.000).CONCLUSION LRG may be a surrogate marker for endoscopic activity in UC,with a cut-off value of around 13.4μg/mL for endoscopically inactive disease.
基金Supported by The 90th Anniversary of Chulalongkorn University Fund(Ratchadaphiseksomphot Endowment Fund)The Thailand Research Fund,No.RMU5180051+2 种基金The Thailand Research Fund Senior Research Scholarship,No.RTA5380005The Higher Education Research Promotion and National Research University Project of Thailand,Office of the Higher Education Commission,No.HR1163AIntegrated Innovation Academic Center,Chulalongkorn University Centenary Academic Development Project,No.CU56-HR05,The Liver Research Unit,Chulalongkorn University
文摘AIM: To study the differential protein profile in serum of hepatitis B patients.METHODS: Serum samples were obtained from patients with chronic hepatitis B who were receiving peginterferon alfa-2b.The serum samples were subjected to albumin depletion and analyzed by two-dimensional gel electrophoresis(2-DE).Differentially expressed protein spots were identified by electrospray ionizationquadrupole time-of-flight mass spectrometry.Alpha2-HS-glycoprotein,complement component C3c and CD5 antigen were further analyzed by an enzymelinked immunosorbent assay and immunonephelometry.RESULTS: Nineteen patients with HBeAg-positive chronic hepatitis B(CHB) were studied.These patients were followed for at least 1 year after treatment and were classified according to their treatment response: responders(n = 9) and non-responders(n = 10).2-DE and MS/MS analysis were performed to compare the serum proteins before initiating peginterferon alfa2b.From the quantitative analysis of the 2-D gel,7 proteins were detected between the two groups at different levels before treatment.Among these potential candidates,serum levels of alpha-2-HS-glycoprotein,complement component C3c and CD5 antigen-like precursor were further analyzed.In the validation phase,23 subjects,9 sustained responders and 14 nonresponders,were recruited.Interestingly,the levels of alpha-2-HS-glycoprotein and complement component C3c were elevated in the serum of the non-responders compared to the responders.CONCLUSION: Serum alpha-2-HS-glycoprotein and complement component C3c may be potential serum biomarkers in predicting the treatment response of peginterferon alfa-2b in patients with CHB prior to treatment.
文摘AIM To report on the efficacy, safety and tolerability of interferon alfa-2a combined with a "low dose" of ribavirin for relapsers and non responders to alpha interferon monotherapy.METHODS Thirty-four chronic hepatitis C virus-infected non-responders to interferon alfa2a monotherapy (a course of at least 3 months treatment) and 13 relapsers to interferon alfa 2a monotherapy (a dose of 3 to 6 million units three times per week for at least 20 weeks but not more than 18 months) were treated with the same dose of interferon alfa-2a used before (3 to 6 million units three times per week) and ribavirin (10 mg/ kg daily) for 6 months. In complete responders, interferon alfa-2a was administered for further 6 months at the same dose used before as monotherapy.RESULTS Seven (20.6%) of 34 non-responders stopped the combined therapy due to adverse events, including two patients with histological and clinical Child A cirrhosis. In 17/27 (63%)non-responders, the combined therapy was stopped after three months because of non-response. Ten of the 27 non-responders completed the 1;2-month treatment course. At a mean follow up of 28 months (16- 37 months)after the treatment, 4/10 (15%) previous non-responders still remained complete responders,All 13 previous relapsers completed the 12-month treatment course. At a mean follow up of 22months (9 - 36 months) after treatment, 6/13(46%) the previous relapsers were stillsustained complete responders.CONCLUSION Our treatment schedule of the combined therapy for 6 months of interferon alfa2a with a low dose of ribavirin (10 mg/kg/day)followed by 6 months of interferon alfa-2amonotherapy is able to induce a sustainedcomplete response rate in 15% of non-responders and 46% of relapsers with chronic hepatitis C virus-related liver diseases comparable to those obtained with the standarddoses of ribavirin 1000 - 1200 mg/day.Randomized prospective controlled trials using lower total amounts of ribavirin in combination with interferon should be performed.
基金The Project Supported by National Natural Science Foundation of China
文摘α 2-macroglobulin (α2M) could stimulate the regeneration of thymic and bone marrow cells in rats received γ-irradiation, but there was very few reports concerning its mechanism. Wistar rats were irradiated by 16Co at 7 Gy, 8.5 Gy, 15 Gy total body doses. Blood plasma and some tissue’s extracts were collected α 2M level. a M activity and cathepsin D activity, malonaldehyde level were determined by radioimmunoassay, modified Schidlow’s method, Barrett’s method and Ohkawa’s method respectively.
