Objective:To explore demographic and metabolic factors associated with increased alanine aminotransferase(ALT)activity in non-diabetic non-alcoholic fatty liver disease(NAFLD)patients.Methods:Overall 372 patients who ...Objective:To explore demographic and metabolic factors associated with increased alanine aminotransferase(ALT)activity in non-diabetic non-alcoholic fatty liver disease(NAFLD)patients.Methods:Overall 372 patients who consecutively attended to Gastroenterology Clinic of Baqiyatallah University of Medical Sciences,Tehran,Iran awere diagnosed as NAFLD entered into analysis.Exclusion criteria were having diabetes mellitus and fasting blood glucose over126 mg/dL,active hepatitis B virus infection,having hepatitis C virus positive serology,and to be under corticosteroid therapy.ALT levels were considered pathologically high when it was over30 IU/L for men and over 19 IU/L for women.Results:Bivariate analyses using t test and chisquare test showed that patients with pathologically augmented ALT levels had significantly higher NAFLD grades in their ultrasonographic evaluations(P=0.003).Moreover,these patients represented significantly higher homeostatic model assessment levels(P=0.003),levels of serum insulin(P=0.002),fasting blood glucose(P<0.001),and uric acid(P=0.02).The prevalence of insulin resistance was also higher in patients with increased serum ALT concentrations.Multifactorial logistic regression models showed that ultrasonographic grading of NAFLD(P=0.027)and insulin resistance(P=0.013)were the only variables significantly associated with abnormal ALT levels.Conclusions:This study shows that the associations of increased ALT serum levels in NAFLD patients are different from what are supposed before.By excluding diabetic patients from our population,we find that increased ALT levels are not associated with dyslipidemias but are independently associated with insulin resistance and NAFLD grading on ultrasonographic evaluations.Further studies are needed to confirm our results.展开更多
Ochratoxin A(OTA),one of the most dangerous mycotoxins for human health,has been subjected to numerous studies for separation and detection in minimal amounts.Aptamers as novel recognition elements have been employed ...Ochratoxin A(OTA),one of the most dangerous mycotoxins for human health,has been subjected to numerous studies for separation and detection in minimal amounts.Aptamers as novel recognition elements have been employed to fabricate ultrasensitive biosensors for the detection of OTA and designing delicate analytical tools.This review attempted to comprehensively examine all reported aptamer-based detection and separation platforms for ochratoxin.The most relevant databases were considered to discover all specific aptamers for dealing with OTA.Aptamer-based detection and separation devices specified for OTA were searched for,analyzed,discussed,and classified based on their specifications.The optical aptasensors have gathered a higher interest than electrochemical aptasensors,which can achieve a lower limit of detections.Moreover,some extraction platforms based on these aptamers were also found.However,aptamer-based devices seem to have some challenges in their application.展开更多
AIM: To investigate the co-incidence of apoptosis, autophagy, and unfolded protein response(UPR) in hepatitis B(HBV) and C(HCV) infected hepatocytes.METHODS: We performed immunofluorescence confocal microscopy on 10 l...AIM: To investigate the co-incidence of apoptosis, autophagy, and unfolded protein response(UPR) in hepatitis B(HBV) and C(HCV) infected hepatocytes.METHODS: We performed immunofluorescence confocal microscopy on 10 liver biopsies from HBV and HCV patients and tissue microarrays of HBV positive liver samples. We used specific antibodies for LC3β, cleaved caspase-3, BIP(GRP78), and XBP1 to detect autophagy, apoptosis and UPR, respectively. AntiHCV NS3 and anti-HBs antibodies were also used to confirm infection. We performed triple blind counting of events to determine the co-incidence of autophagy(LC3β punctuate), apoptosis(cleaved caspase-3), and unfolded protein response(GRP78) with HBV and HCV infection in hepatocytes. All statistical analyses were performed using SPSS software for Windows(Version 16 SPSS Inc, Chicago, IL, United States). P-values < 0.05 were considered statistically significant. Statistical analyses were performed with Mann-Whitney test to compare incidence rates for autophagy, apoptosis, and UPR in HBV- and HCV-infected cells and adjacent noninfected cells.RESULTS: Our results showed that infection of hepatocytes with either HBV and HCV induces significant increase(P < 0.001) in apoptosis(cleavage of caspase-3), autophagy(LC3β punctate), and UPR(increase in GRP78 expression) in the HCV- and HBVinfected cells, as compared to non-infected cells of the same biopsy sections. Our tissue microarray immunohistochemical expression analysis of LC3β in HBV^(Neg) and HBV^(Pos) revealed that majority of HBVinfected hepatocytes display strong positive stainingfor LC3β. Interestingly, although XBP splicing in HBVinfected cells was significantly higher(P < 0.05), our analyses show a slight increase of XBP splicing was in HCV-infected cells(P > 0.05). Furthermore, our evaluation of patients with HBV and HCV infection based on stage and grade of the liver diseases revealed no correlation between these pathological findings and induction of apoptosis, autophagy, and UPR.CONCLUSION: The results of this study indicate that HCV and HBV infection activates apoptosis, autophagy and UPR, but slightly differently by each virus. Further studies are warranted to elucidate the interconnections between these pathways in relation to pathology of HCV and HBV in the liver tissue.展开更多
AIM: To characterize the clinical, serologic and virologic features of hepatitis B virus (HBV) infection in Iranian patients with different stages of liver disease. METHODS: Sixty two patients comprising of 12 inactiv...AIM: To characterize the clinical, serologic and virologic features of hepatitis B virus (HBV) infection in Iranian patients with different stages of liver disease. METHODS: Sixty two patients comprising of 12 inactive carriers, 30 chronic hepatitis patients, 13 patients with liver cirrhosis and 7 patients with hepatocellular carcinoma (HCC) were enrolled in the study. The HBV S, C and basal core promoter (BCP) regions were amplified and sequenced, and the clinical, serologic, phylogenetic and virologic characteristics were investigated. RESULTS: The study group consisted of 16 HBeAg- positive and 46 HBeAg-negative patients. Anti-HBe- positive patients were older and had higher levels of ALT, ASL and bilirubin compared to HBeAg-positivepatients. Phylogenetic analysis revealed that all patients were infected with genotype D (mostly ayw2). The G1896A precore (PC) mutant was detected in 58.1% patients. HBeAg-negative patients showed a higher rate of PC mutant compared to HBeAg-positive patients (χ2 = 9.682, P = 0.003). The majority of patients with HCC were HBeAg-negative and were infected with PC mutant variants. There was no significant difference in the occurrence of BCP mutation between the two groups, while the rate of BCP plus PC mutants was higher in HBeAg-negative patients (χ2 = 4.308, P = 0.04). In the HBV S region, the genetic variability was low, and the marked substitution was P120T/S, with a rate of 9.7% (n = 6). CONCLUSION: In conclusion, HBV/D is the predominant genotype in Iran, and the nucleotide variability in the BCP and PC regions may play a role in HBV disease outcome in HBeAg-negative patients.展开更多
Hepatitis C virus(HCV)infection is highly prevalent among patients on hemodialysis(HD).The prevalence of HCV infection in HD patients varies markedly from country to country.Some factors are especially related to thes...Hepatitis C virus(HCV)infection is highly prevalent among patients on hemodialysis(HD).The prevalence of HCV infection in HD patients varies markedly from country to country.Some factors are especially related to these high prevalence rates,such as blood transfusions and length of dialysis time. Nosocomial routes of transmission including the use of contaminated equipment and patient-to-patient exposure is considered more important.Several prophylactic measures have been suggested to avoid infection by HCV in the HD environment.展开更多
OBJECTIVE: To investigate the use of Aloe vera(A.vera) for the treatment of gastroesophageal reflux disease(GERD) symptoms and compare its effects with those of omeprazole and ranitidine.METHODS: In this pilot, random...OBJECTIVE: To investigate the use of Aloe vera(A.vera) for the treatment of gastroesophageal reflux disease(GERD) symptoms and compare its effects with those of omeprazole and ranitidine.METHODS: In this pilot, randomized controlled trial, 79 subjects were allocated to A. vera syrup(standardized to 5.0 mg polysaccharide per m L of syrup)at a dose of 10 m L/d, omeprazole capsule(20 g/d)or ranitidine tablet(150 mg in a fasted state in the morning and 150 mg 30 min before sleep at night)for a period of 4 weeks. The frequencies of eight main symptoms of GERD(heartburn, food regurgitation, flatulence, belching, dysphagia, nausea,vomiting and acid regurgitation) were assessed at weeks 2 and 4 of the trial.RESULTS: A. vera was safe and well tolerated and reduced the frequencies of all the assessed GERD symptoms, with no adverse events requiring withdrawal.CONCLUSION: A. vera may provide a safe and effective treatment for reducing the symptoms of GERD.展开更多
Treatment of hepatitis C virus(HCV) infection has evolved greatly through the recent decade. The availability of direct-acting antiviral agents(DAAs) targeting the functional proteins of HCV has resulted in the introd...Treatment of hepatitis C virus(HCV) infection has evolved greatly through the recent decade. The availability of direct-acting antiviral agents(DAAs) targeting the functional proteins of HCV has resulted in the introduction of DAA-based combination therapies,providing an optimal rate of treatment success. Among the DAAs,NS5 A inhibitors are used in most of the introduced and approved HCV antiviral regimens. Resistance-associated substitutions(RASs) are amino acid substitutions in HCV protein sequences that result in decreased antiviral efficacy of the HCV DAAs. Among the HCV RASs,the NS5 A RASs were found to effectively modify and decrease treatment response to NS5 A inhibitor-containing regimens. As a baseline predictor of treatment response,NS5 A RAS draws attention for pretreatment testing in targeted patient groups. Given NS5 A RASs are either naturally-occurring or DAA-selected,the application of NS5 A RAS testing can be considered in two settings of NS5 A inhibitor-na?ve patients and NS5 A inhibitor-experienced patients. Less than 5% of NS5 A inhibitor-na?ve patients harbor naturally-occurring NS5 A RAS with high resistance level(> 100 X resistance foldchange). In NS5 A inhibitor-na?ve patients,NS5 A RAS testing accompanied by treatment optimization cannot increase treatment response more than 2%-3%,while in NS5 A inhibitor-experienced patients,> 75% are found to have NS5 A RASs > 100 X and NS5 A RAS testing in this group of patients seems to be reasonable. This editorial will address the debate on the application of NS5 A RAS testing and will discuss if the NS5 A RAS testing has any role in clinical management of hepatitis C.展开更多
基金financially supported by Baqiyatallah University of Medical Sciences
文摘Objective:To explore demographic and metabolic factors associated with increased alanine aminotransferase(ALT)activity in non-diabetic non-alcoholic fatty liver disease(NAFLD)patients.Methods:Overall 372 patients who consecutively attended to Gastroenterology Clinic of Baqiyatallah University of Medical Sciences,Tehran,Iran awere diagnosed as NAFLD entered into analysis.Exclusion criteria were having diabetes mellitus and fasting blood glucose over126 mg/dL,active hepatitis B virus infection,having hepatitis C virus positive serology,and to be under corticosteroid therapy.ALT levels were considered pathologically high when it was over30 IU/L for men and over 19 IU/L for women.Results:Bivariate analyses using t test and chisquare test showed that patients with pathologically augmented ALT levels had significantly higher NAFLD grades in their ultrasonographic evaluations(P=0.003).Moreover,these patients represented significantly higher homeostatic model assessment levels(P=0.003),levels of serum insulin(P=0.002),fasting blood glucose(P<0.001),and uric acid(P=0.02).The prevalence of insulin resistance was also higher in patients with increased serum ALT concentrations.Multifactorial logistic regression models showed that ultrasonographic grading of NAFLD(P=0.027)and insulin resistance(P=0.013)were the only variables significantly associated with abnormal ALT levels.Conclusions:This study shows that the associations of increased ALT serum levels in NAFLD patients are different from what are supposed before.By excluding diabetic patients from our population,we find that increased ALT levels are not associated with dyslipidemias but are independently associated with insulin resistance and NAFLD grading on ultrasonographic evaluations.Further studies are needed to confirm our results.
文摘Ochratoxin A(OTA),one of the most dangerous mycotoxins for human health,has been subjected to numerous studies for separation and detection in minimal amounts.Aptamers as novel recognition elements have been employed to fabricate ultrasensitive biosensors for the detection of OTA and designing delicate analytical tools.This review attempted to comprehensively examine all reported aptamer-based detection and separation platforms for ochratoxin.The most relevant databases were considered to discover all specific aptamers for dealing with OTA.Aptamer-based detection and separation devices specified for OTA were searched for,analyzed,discussed,and classified based on their specifications.The optical aptasensors have gathered a higher interest than electrochemical aptasensors,which can achieve a lower limit of detections.Moreover,some extraction platforms based on these aptamers were also found.However,aptamer-based devices seem to have some challenges in their application.
基金Supported by University of Manitoba Start-up funds and an award from the Manitoba Medical Service Foundation to Ghavami SUniversity of Manitoba Start-up Funds to Alizadeh J
文摘AIM: To investigate the co-incidence of apoptosis, autophagy, and unfolded protein response(UPR) in hepatitis B(HBV) and C(HCV) infected hepatocytes.METHODS: We performed immunofluorescence confocal microscopy on 10 liver biopsies from HBV and HCV patients and tissue microarrays of HBV positive liver samples. We used specific antibodies for LC3β, cleaved caspase-3, BIP(GRP78), and XBP1 to detect autophagy, apoptosis and UPR, respectively. AntiHCV NS3 and anti-HBs antibodies were also used to confirm infection. We performed triple blind counting of events to determine the co-incidence of autophagy(LC3β punctuate), apoptosis(cleaved caspase-3), and unfolded protein response(GRP78) with HBV and HCV infection in hepatocytes. All statistical analyses were performed using SPSS software for Windows(Version 16 SPSS Inc, Chicago, IL, United States). P-values < 0.05 were considered statistically significant. Statistical analyses were performed with Mann-Whitney test to compare incidence rates for autophagy, apoptosis, and UPR in HBV- and HCV-infected cells and adjacent noninfected cells.RESULTS: Our results showed that infection of hepatocytes with either HBV and HCV induces significant increase(P < 0.001) in apoptosis(cleavage of caspase-3), autophagy(LC3β punctate), and UPR(increase in GRP78 expression) in the HCV- and HBVinfected cells, as compared to non-infected cells of the same biopsy sections. Our tissue microarray immunohistochemical expression analysis of LC3β in HBV^(Neg) and HBV^(Pos) revealed that majority of HBVinfected hepatocytes display strong positive stainingfor LC3β. Interestingly, although XBP splicing in HBVinfected cells was significantly higher(P < 0.05), our analyses show a slight increase of XBP splicing was in HCV-infected cells(P > 0.05). Furthermore, our evaluation of patients with HBV and HCV infection based on stage and grade of the liver diseases revealed no correlation between these pathological findings and induction of apoptosis, autophagy, and UPR.CONCLUSION: The results of this study indicate that HCV and HBV infection activates apoptosis, autophagy and UPR, but slightly differently by each virus. Further studies are warranted to elucidate the interconnections between these pathways in relation to pathology of HCV and HBV in the liver tissue.
基金A grant from the Nanotechnology committee of the Ministry of Science, Research and Technology, Iran, No. 31.1895 on 05.03.2004 to Majid Sadeghizadeh
文摘AIM: To characterize the clinical, serologic and virologic features of hepatitis B virus (HBV) infection in Iranian patients with different stages of liver disease. METHODS: Sixty two patients comprising of 12 inactive carriers, 30 chronic hepatitis patients, 13 patients with liver cirrhosis and 7 patients with hepatocellular carcinoma (HCC) were enrolled in the study. The HBV S, C and basal core promoter (BCP) regions were amplified and sequenced, and the clinical, serologic, phylogenetic and virologic characteristics were investigated. RESULTS: The study group consisted of 16 HBeAg- positive and 46 HBeAg-negative patients. Anti-HBe- positive patients were older and had higher levels of ALT, ASL and bilirubin compared to HBeAg-positivepatients. Phylogenetic analysis revealed that all patients were infected with genotype D (mostly ayw2). The G1896A precore (PC) mutant was detected in 58.1% patients. HBeAg-negative patients showed a higher rate of PC mutant compared to HBeAg-positive patients (χ2 = 9.682, P = 0.003). The majority of patients with HCC were HBeAg-negative and were infected with PC mutant variants. There was no significant difference in the occurrence of BCP mutation between the two groups, while the rate of BCP plus PC mutants was higher in HBeAg-negative patients (χ2 = 4.308, P = 0.04). In the HBV S region, the genetic variability was low, and the marked substitution was P120T/S, with a rate of 9.7% (n = 6). CONCLUSION: In conclusion, HBV/D is the predominant genotype in Iran, and the nucleotide variability in the BCP and PC regions may play a role in HBV disease outcome in HBeAg-negative patients.
文摘Hepatitis C virus(HCV)infection is highly prevalent among patients on hemodialysis(HD).The prevalence of HCV infection in HD patients varies markedly from country to country.Some factors are especially related to these high prevalence rates,such as blood transfusions and length of dialysis time. Nosocomial routes of transmission including the use of contaminated equipment and patient-to-patient exposure is considered more important.Several prophylactic measures have been suggested to avoid infection by HCV in the HD environment.
基金Supported by the Clinical Trial Research CenterTehranIran
文摘OBJECTIVE: To investigate the use of Aloe vera(A.vera) for the treatment of gastroesophageal reflux disease(GERD) symptoms and compare its effects with those of omeprazole and ranitidine.METHODS: In this pilot, randomized controlled trial, 79 subjects were allocated to A. vera syrup(standardized to 5.0 mg polysaccharide per m L of syrup)at a dose of 10 m L/d, omeprazole capsule(20 g/d)or ranitidine tablet(150 mg in a fasted state in the morning and 150 mg 30 min before sleep at night)for a period of 4 weeks. The frequencies of eight main symptoms of GERD(heartburn, food regurgitation, flatulence, belching, dysphagia, nausea,vomiting and acid regurgitation) were assessed at weeks 2 and 4 of the trial.RESULTS: A. vera was safe and well tolerated and reduced the frequencies of all the assessed GERD symptoms, with no adverse events requiring withdrawal.CONCLUSION: A. vera may provide a safe and effective treatment for reducing the symptoms of GERD.
文摘Treatment of hepatitis C virus(HCV) infection has evolved greatly through the recent decade. The availability of direct-acting antiviral agents(DAAs) targeting the functional proteins of HCV has resulted in the introduction of DAA-based combination therapies,providing an optimal rate of treatment success. Among the DAAs,NS5 A inhibitors are used in most of the introduced and approved HCV antiviral regimens. Resistance-associated substitutions(RASs) are amino acid substitutions in HCV protein sequences that result in decreased antiviral efficacy of the HCV DAAs. Among the HCV RASs,the NS5 A RASs were found to effectively modify and decrease treatment response to NS5 A inhibitor-containing regimens. As a baseline predictor of treatment response,NS5 A RAS draws attention for pretreatment testing in targeted patient groups. Given NS5 A RASs are either naturally-occurring or DAA-selected,the application of NS5 A RAS testing can be considered in two settings of NS5 A inhibitor-na?ve patients and NS5 A inhibitor-experienced patients. Less than 5% of NS5 A inhibitor-na?ve patients harbor naturally-occurring NS5 A RAS with high resistance level(> 100 X resistance foldchange). In NS5 A inhibitor-na?ve patients,NS5 A RAS testing accompanied by treatment optimization cannot increase treatment response more than 2%-3%,while in NS5 A inhibitor-experienced patients,> 75% are found to have NS5 A RASs > 100 X and NS5 A RAS testing in this group of patients seems to be reasonable. This editorial will address the debate on the application of NS5 A RAS testing and will discuss if the NS5 A RAS testing has any role in clinical management of hepatitis C.