AIM:To investigate the potential association of circulating zonulin with the stage of liver disease in obese children with biopsy-confirmed nonalcoholic fatty liver disease(NAFLD).METHODS:A case-control study was perf...AIM:To investigate the potential association of circulating zonulin with the stage of liver disease in obese children with biopsy-confirmed nonalcoholic fatty liver disease(NAFLD).METHODS:A case-control study was performed.Cases were 40 obese children with NAFLD.The diagnosis of NAFLD was based on magnetic resonance imaging(MRI)with high hepatic fat fraction(HFF≥5%),and confirmed by liver biopsy with≥5%of hepatocytes containing macrovesicular fat.Controls were selected from obese children with normal levels of aminotransferases,and without MRI evidence of fatty liver as well as of other causes of chronic liver diseases.Controls were matched(1-to 1)with the cases on age,gender,pubertal stage and as closely as possible on body mass index-standard deviation score.All participants underwent clinical examination,laboratory testsincluding zonulin,inflammatory and metabolic parameters,and MRI for measurement of HFF and visceral adipose tissue.RESULTS:Zonulin values were significantly greater in obese subjects with NAFLD than in those without NAFLD[median(interquartile range),4.23(3.18-5.89)vs 3.31(2.05-4.63),P<0.01].In patients with NAFLD,zonulin concentrations increased significantly with the severity of steatosis and the Spearman’s coefficient revealed a positive correlation between zonulin values and steatosis(r=0.372,P<0.05);however,we did not find a significant correlation between zonulin and lobular inflammation(P=0.23),ballooning(P=0.10),fibrosis score(P=0.18),or presence of nonalcoholic steatohepatitis(P=0.17).Within the entire study population,zonulin levels were positively associated with gamma-glutamyl transferase,2-h insulin,HFF,and negatively associated with whole-body insulin sensitivity index(WBISI),after adjustment for age,gender and pubertal status.When the associations were restricted to the group of NAFLD patients,2-h insulin,hepatic fat,and WBISI retained statistical significance.CONCLUSION:Circulating zonulin is increased in children and adolescents with NAFLD and correlates with the severity of steatosis.展开更多
BACKGROUND Increased gut permeability and bacterial translocation play an important role in liver cirrhosis.Zonulin is a recently recognized protein involved in the disintegration of the intestinal barrier.AIM To inve...BACKGROUND Increased gut permeability and bacterial translocation play an important role in liver cirrhosis.Zonulin is a recently recognized protein involved in the disintegration of the intestinal barrier.AIM To investigate possible differences in serum zonulin levels among patients with different cirrhosis stages and their potential prognostic implications.METHODS Consecutive cirrhotic patients who attended our liver clinic were included in the study.Serum zonulin levels,clinical,radiological and biochemical data were collected at baseline.Patients who accepted participation in a regular surveillance program were followed-up for at least 12 mo.RESULTS We enrolled 116 cirrhotics[mean Child-Turcotte-Pugh(CTP)score:6.2±1.6;model for end-stage liver disease score:11±3.9].The causes of cirrhosis were viral hepatitis(39%),alcohol(30%),non-alcoholic fatty liver disease(17%),and other(14%).At baseline,53% had decompensated cirrhosis,48% had ascites,and 32% had history of hepatic encephalopathy.Mean zonulin levels were significantly higher in patients with CTP-B class than CTP-A class(4.2±2.4 ng/dL vs 3.5±0.9 ng/dL,P=0.038),with than without ascites(P=0.006),and with than without history of encephalopathy(P=0.011).Baseline serum zonulin levels were independently associated with the probability of decompensation at 1 year(P=0.039),with an area under the receiving operating characteristic of 0.723 for predicting hepatic decompensation.Higher CTP score(P=0.021)and portal vein diameter(P=0.022)were independent predictors of mortality.CONCLUSION Serum zonulin levels are higher in patients with more advanced chronic liver disease and have significant prognostic value in identifying patients who will develop decompensation.展开更多
AIM To evaluate the measurement of zonulin level and antibodies of zonulin and other tight junction proteins in the blood of controls and celiac disease patients.METHODS This study was conducted to assess the variabil...AIM To evaluate the measurement of zonulin level and antibodies of zonulin and other tight junction proteins in the blood of controls and celiac disease patients.METHODS This study was conducted to assess the variability or stability of zonulin levels vs Ig A and Ig G antibodies against zonulin in blood samples from 18 controls at 0, 6, 24 and 30 h after blood draw. We also measured zonulin level as well as zonulin, occludin, vinculin, aquaporin 4 and glial fibrillary acidic protein antibodies in the sera of 30 patients with celiac disease and 30 controls using enzyme-linked immunosorbent assay methodology. RESULTS The serum zonulin level in 6 out of 18 subjects was low or < 2.8 ng/m L and was very close to the detection limit of the assay. The other 12 subjects had zonulin levels of > 2.8 ng/m L and showed significant fluctuation from sample to sample. Comparatively, zonulin antibody measured in all samples was highly stable and reproducible from sample to sample. Celiac disease patients showed zonulin levels with a mean of 8.5 ng/m L compared to 3.7 ng/m L in controls(P < 0.0001). Elevation of zonulin level at 2SD above the mean was demonstrated in 37% of celiac disease patients, while antibodies against zonulin, occludin and other tight junction proteins was detected in up to 86% of patients with celiac disease. CONCLUSION Due to its fluctuation, a single measurement of zonulin level is not recommended for assessment of intestinal barrier integrity. Measurement of Ig G and Ig A antibodies against zonulin, occludin, and other tight junction proteins is proposed for the evaluation of the loss of intestinal barrier integrity.展开更多
BACKGROUND An important area of effective control of the coronavirus disease 19(COVID-19)pandemic is the study of the pathogenic features of severe acute respiratory syndrome coronavirus 2 infection,including those ba...BACKGROUND An important area of effective control of the coronavirus disease 19(COVID-19)pandemic is the study of the pathogenic features of severe acute respiratory syndrome coronavirus 2 infection,including those based on assessing the state of the intestinal microbiota and permeability.AIM To study the clinical features of the new COVID-19 in patients with mild and moderate severity at the stage of hospitalization,to determine the role of hepatobiliary injury,intestinal permeability disorders,and changes in the qualitative and quantitative composition of the microbiota in the development of systemic inflammation in patients with COVID-19.METHODS The study was performed in 80 patients with COVID-19,with an average age of 45 years,19 of whom had mild disease,and 61 had moderate disease severity.The scope of the examination included traditional clinical,laboratory,biochemical,instrumental,and radiation studies,as well as original methods for studying microbiota and intestinal permeability.RESULTS The clinical course of COVID-19 was studied,and the clinical and biochemical features,manifestations of systemic inflammation,and intestinal microbiome changes in patients with mild and moderate severity were identified.Intestinal permeability characteristics against the background of COVID-19 were evaluated by measuring levels of proinflammatory cytokines,insulin,faecal calprotectin,and zonulin.CONCLUSION This study highlights the role of intestinal permeability and microbiota as the main drivers of gastroenterological manifestations and increased COVID-19 severity.展开更多
Gastrointestinal(GI)symptoms have been described in a conspicuous percentage of coronavirus disease 2019(COVID-19)patients.This clinical evidence is supported by the detection of viral RNA in stool,which also supports...Gastrointestinal(GI)symptoms have been described in a conspicuous percentage of coronavirus disease 2019(COVID-19)patients.This clinical evidence is supported by the detection of viral RNA in stool,which also supports the hypothesis of a possible fecal-oral transmission route.The involvement of GI tract in severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection is corroborated by the theoretical assumption that angiotensin converting enzyme 2,which is a SARS-CoV-2 target receptor,is present along the GI tract.Studies have pointed out that gut dysbiosis may occur in COVID-19 patients,with a possible correlation with disease severity and with complications such as multisystem inflammatory syndrome in children.However,the question to be addressed is whether dysbiosis is a consequence or a contributing cause of SARS-CoV-2 infection.In such a scenario,pharmacological therapies aimed at decreasing GI permeability may be beneficial for COVID-19 patients.Considering the possibility of a fecal-oral transmission route,water and environmental sanitation play a crucial role for COVID-19 containment,especially in developing countries.展开更多
文摘AIM:To investigate the potential association of circulating zonulin with the stage of liver disease in obese children with biopsy-confirmed nonalcoholic fatty liver disease(NAFLD).METHODS:A case-control study was performed.Cases were 40 obese children with NAFLD.The diagnosis of NAFLD was based on magnetic resonance imaging(MRI)with high hepatic fat fraction(HFF≥5%),and confirmed by liver biopsy with≥5%of hepatocytes containing macrovesicular fat.Controls were selected from obese children with normal levels of aminotransferases,and without MRI evidence of fatty liver as well as of other causes of chronic liver diseases.Controls were matched(1-to 1)with the cases on age,gender,pubertal stage and as closely as possible on body mass index-standard deviation score.All participants underwent clinical examination,laboratory testsincluding zonulin,inflammatory and metabolic parameters,and MRI for measurement of HFF and visceral adipose tissue.RESULTS:Zonulin values were significantly greater in obese subjects with NAFLD than in those without NAFLD[median(interquartile range),4.23(3.18-5.89)vs 3.31(2.05-4.63),P<0.01].In patients with NAFLD,zonulin concentrations increased significantly with the severity of steatosis and the Spearman’s coefficient revealed a positive correlation between zonulin values and steatosis(r=0.372,P<0.05);however,we did not find a significant correlation between zonulin and lobular inflammation(P=0.23),ballooning(P=0.10),fibrosis score(P=0.18),or presence of nonalcoholic steatohepatitis(P=0.17).Within the entire study population,zonulin levels were positively associated with gamma-glutamyl transferase,2-h insulin,HFF,and negatively associated with whole-body insulin sensitivity index(WBISI),after adjustment for age,gender and pubertal status.When the associations were restricted to the group of NAFLD patients,2-h insulin,hepatic fat,and WBISI retained statistical significance.CONCLUSION:Circulating zonulin is increased in children and adolescents with NAFLD and correlates with the severity of steatosis.
文摘BACKGROUND Increased gut permeability and bacterial translocation play an important role in liver cirrhosis.Zonulin is a recently recognized protein involved in the disintegration of the intestinal barrier.AIM To investigate possible differences in serum zonulin levels among patients with different cirrhosis stages and their potential prognostic implications.METHODS Consecutive cirrhotic patients who attended our liver clinic were included in the study.Serum zonulin levels,clinical,radiological and biochemical data were collected at baseline.Patients who accepted participation in a regular surveillance program were followed-up for at least 12 mo.RESULTS We enrolled 116 cirrhotics[mean Child-Turcotte-Pugh(CTP)score:6.2±1.6;model for end-stage liver disease score:11±3.9].The causes of cirrhosis were viral hepatitis(39%),alcohol(30%),non-alcoholic fatty liver disease(17%),and other(14%).At baseline,53% had decompensated cirrhosis,48% had ascites,and 32% had history of hepatic encephalopathy.Mean zonulin levels were significantly higher in patients with CTP-B class than CTP-A class(4.2±2.4 ng/dL vs 3.5±0.9 ng/dL,P=0.038),with than without ascites(P=0.006),and with than without history of encephalopathy(P=0.011).Baseline serum zonulin levels were independently associated with the probability of decompensation at 1 year(P=0.039),with an area under the receiving operating characteristic of 0.723 for predicting hepatic decompensation.Higher CTP score(P=0.021)and portal vein diameter(P=0.022)were independent predictors of mortality.CONCLUSION Serum zonulin levels are higher in patients with more advanced chronic liver disease and have significant prognostic value in identifying patients who will develop decompensation.
文摘AIM To evaluate the measurement of zonulin level and antibodies of zonulin and other tight junction proteins in the blood of controls and celiac disease patients.METHODS This study was conducted to assess the variability or stability of zonulin levels vs Ig A and Ig G antibodies against zonulin in blood samples from 18 controls at 0, 6, 24 and 30 h after blood draw. We also measured zonulin level as well as zonulin, occludin, vinculin, aquaporin 4 and glial fibrillary acidic protein antibodies in the sera of 30 patients with celiac disease and 30 controls using enzyme-linked immunosorbent assay methodology. RESULTS The serum zonulin level in 6 out of 18 subjects was low or < 2.8 ng/m L and was very close to the detection limit of the assay. The other 12 subjects had zonulin levels of > 2.8 ng/m L and showed significant fluctuation from sample to sample. Comparatively, zonulin antibody measured in all samples was highly stable and reproducible from sample to sample. Celiac disease patients showed zonulin levels with a mean of 8.5 ng/m L compared to 3.7 ng/m L in controls(P < 0.0001). Elevation of zonulin level at 2SD above the mean was demonstrated in 37% of celiac disease patients, while antibodies against zonulin, occludin and other tight junction proteins was detected in up to 86% of patients with celiac disease. CONCLUSION Due to its fluctuation, a single measurement of zonulin level is not recommended for assessment of intestinal barrier integrity. Measurement of Ig G and Ig A antibodies against zonulin, occludin, and other tight junction proteins is proposed for the evaluation of the loss of intestinal barrier integrity.
基金study was reviewed and approved by the independent ethics committee of the Military Medical Academy named after SM.Kirov,protocol(Approval No.246).
文摘BACKGROUND An important area of effective control of the coronavirus disease 19(COVID-19)pandemic is the study of the pathogenic features of severe acute respiratory syndrome coronavirus 2 infection,including those based on assessing the state of the intestinal microbiota and permeability.AIM To study the clinical features of the new COVID-19 in patients with mild and moderate severity at the stage of hospitalization,to determine the role of hepatobiliary injury,intestinal permeability disorders,and changes in the qualitative and quantitative composition of the microbiota in the development of systemic inflammation in patients with COVID-19.METHODS The study was performed in 80 patients with COVID-19,with an average age of 45 years,19 of whom had mild disease,and 61 had moderate disease severity.The scope of the examination included traditional clinical,laboratory,biochemical,instrumental,and radiation studies,as well as original methods for studying microbiota and intestinal permeability.RESULTS The clinical course of COVID-19 was studied,and the clinical and biochemical features,manifestations of systemic inflammation,and intestinal microbiome changes in patients with mild and moderate severity were identified.Intestinal permeability characteristics against the background of COVID-19 were evaluated by measuring levels of proinflammatory cytokines,insulin,faecal calprotectin,and zonulin.CONCLUSION This study highlights the role of intestinal permeability and microbiota as the main drivers of gastroenterological manifestations and increased COVID-19 severity.
文摘Gastrointestinal(GI)symptoms have been described in a conspicuous percentage of coronavirus disease 2019(COVID-19)patients.This clinical evidence is supported by the detection of viral RNA in stool,which also supports the hypothesis of a possible fecal-oral transmission route.The involvement of GI tract in severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection is corroborated by the theoretical assumption that angiotensin converting enzyme 2,which is a SARS-CoV-2 target receptor,is present along the GI tract.Studies have pointed out that gut dysbiosis may occur in COVID-19 patients,with a possible correlation with disease severity and with complications such as multisystem inflammatory syndrome in children.However,the question to be addressed is whether dysbiosis is a consequence or a contributing cause of SARS-CoV-2 infection.In such a scenario,pharmacological therapies aimed at decreasing GI permeability may be beneficial for COVID-19 patients.Considering the possibility of a fecal-oral transmission route,water and environmental sanitation play a crucial role for COVID-19 containment,especially in developing countries.
