The aim of this study was to provide a basis for examining the molecular mechanism for the pharmacological action of ethanol. We studied di?myristoyl?phosphatidylethanol (DMPEt)’s effects on specific locations of n-(...The aim of this study was to provide a basis for examining the molecular mechanism for the pharmacological action of ethanol. We studied di?myristoyl?phosphatidylethanol (DMPEt)’s effects on specific locations of n-(9-anthroyloxy) palmitic acid or stearic acid (n-AS) within phos?pholipids of synaptosomal plasma membrane vesicles isolated from bovine cerebral cortex (SPMV) and liposomes of total lipids (SPMVTL) and phospholipids (SPMVPL) extracted from SPMV. DMPEt increased rotational mobility (increased disordering) of hydrocarbon interior, but it decreased mobility (increased ordering) of membrane interface, in native and model membranes. The degree of rotational mobility in accordance with the carbon atom numbers of phospholipids comprising neuronal membranes was in the order at the 16, 12, 9, 6 and 2 position of aliphatic chain present in phospholipids. The sensitivity of increasing or decreasing effect of rotational mobility of hydrocarbon interior or surface region by DMPEt differed depending on the neuronal and model membranes in the descending order of SPMV, SPMVPL and SPMVTL.展开更多
BACKGROUND Steroids remain the primary treatment for severe alcohol-associated hepatitis(AAH),though there is little available tools to predict patient response to steroids.It was hypothesized that phosphatidylethanol...BACKGROUND Steroids remain the primary treatment for severe alcohol-associated hepatitis(AAH),though there is little available tools to predict patient response to steroids.It was hypothesized that phosphatidylethanol(PEth)value will inversely corre-late with response to steroid therapy based on Lille score in AAH.AIM To assess the relationship of patient factors,focusing on pre-steroid therapy PEth value,to steroid therapy response in AAH.METHODS A retrospective case control study was performed on patients who received≥4 days of steroid therapy for AAH at our hospital between July 1,2019 and June 30,2022.A total of 2087 patients were screened for AAH and those treated with steroids were included for statistical analysis utilizing independent sample t-test and for categorical variables using the χ^(2) test.RESULTS No correlation was found between PEth value,pre-steroids abstinence length,or number of drinks per week pre-steroids and response to steroids.Non-responder status significantly correlated with older age(P=0.024),lower albumin(P=0.003),and higher bilirubin(P=0.010)pre-steroids.Our study suggests that age,pre-steroid albumin,and pre-steroid bilirubin levels may predict nonresponse to steroid therapy.Non-responders have increased incidence of death and higher medical costs.CONCLUSION Identifying non-responders through these identified factors should prompt early referral for liver transplantation.Future prospective studies with larger population size are needed to assess the efficacy of combined pre-steroid age,albumin,bilirubin and other biochemical markers as predictors of steroid response.展开更多
Acute alcohol-associated hepatitis(AAH)is a life-threatening condition with high mortality,and steroid therapy remains the mainstay of treatment despite variable efficacy.The study by Sabatose et al explores patient f...Acute alcohol-associated hepatitis(AAH)is a life-threatening condition with high mortality,and steroid therapy remains the mainstay of treatment despite variable efficacy.The study by Sabatose et al explores patient factors distinguishing responders and non-responders to steroid therapy for AAH,focusing on phosphatidylethanol(PEth)-a biomarker of alcohol consumption-and other clinical variables.Their findings indicate that PEth,abstinence duration,and pretreatment alcohol intake do not predict steroid response,while older age,lower pre-steroid albumin,and higher pre-steroid bilirubin are associated with nonresponse.Non-responders exhibit higher mortality and healthcare costs,underscoring the need for early identification to guide liver transplantation referrals.This commentary evaluates the implications of these findings-specifically,how prioritizing pre-steroid albumin,bilirubin,and age over alcohol biomarkers can improve clinical decision-making by reducing unnecessary steroid exposure and expediting transplantation referrals for high-risk non-responders-contextualizes them within existing literature,and highlights directions for future research to optimize AAH management.展开更多
In utero exposure to ethanol continues to be a significant public health issue and neonatal healthcare professionals are in need of objective means to identify exposed newborns. The aim of this study was to fully vali...In utero exposure to ethanol continues to be a significant public health issue and neonatal healthcare professionals are in need of objective means to identify exposed newborns. The aim of this study was to fully validate two methods for the detection of two direct alcohol biomarkers, 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanol (POPE) and ethyl glucuronide (EtG), in umbilical cord and apply the assays to a group of authentic specimens. The limits of detections were 2 and 1 ng/g for POPE and ETG and the limits of quantitation were 4 and 3 ng/g, respectively. Inter and intra-day precision and accuracy measurements were within 15%. The assays were applied to 308 authentic specimens where we detected POPE in five (1.6%) specimens and EtG in twelve (3.9%) specimens. The mean concentrations were 11.4 ng/g ± 9.4 ng/g and 127.2 ± 227.7 ng/g for POPE and EtG, respectively. This study suggested that umbilical cord was a suitable specimen type for the identification of newborns exposed to ethanol in the womb and the prevalence of POPE and EtG detected in umbilical cord were consistent with the prevalence of self-reported binge drinking reported by the National Birth Defect Prevention Study (NBDPS) and Behavioral Risk Factor Surveillance System (BRFSS). Further studies are required to fully describe the association between the observed concentrations of POPE and EtG in umbilical cord to the level of maternal consumption of ethanol.展开更多
文摘The aim of this study was to provide a basis for examining the molecular mechanism for the pharmacological action of ethanol. We studied di?myristoyl?phosphatidylethanol (DMPEt)’s effects on specific locations of n-(9-anthroyloxy) palmitic acid or stearic acid (n-AS) within phos?pholipids of synaptosomal plasma membrane vesicles isolated from bovine cerebral cortex (SPMV) and liposomes of total lipids (SPMVTL) and phospholipids (SPMVPL) extracted from SPMV. DMPEt increased rotational mobility (increased disordering) of hydrocarbon interior, but it decreased mobility (increased ordering) of membrane interface, in native and model membranes. The degree of rotational mobility in accordance with the carbon atom numbers of phospholipids comprising neuronal membranes was in the order at the 16, 12, 9, 6 and 2 position of aliphatic chain present in phospholipids. The sensitivity of increasing or decreasing effect of rotational mobility of hydrocarbon interior or surface region by DMPEt differed depending on the neuronal and model membranes in the descending order of SPMV, SPMVPL and SPMVTL.
文摘BACKGROUND Steroids remain the primary treatment for severe alcohol-associated hepatitis(AAH),though there is little available tools to predict patient response to steroids.It was hypothesized that phosphatidylethanol(PEth)value will inversely corre-late with response to steroid therapy based on Lille score in AAH.AIM To assess the relationship of patient factors,focusing on pre-steroid therapy PEth value,to steroid therapy response in AAH.METHODS A retrospective case control study was performed on patients who received≥4 days of steroid therapy for AAH at our hospital between July 1,2019 and June 30,2022.A total of 2087 patients were screened for AAH and those treated with steroids were included for statistical analysis utilizing independent sample t-test and for categorical variables using the χ^(2) test.RESULTS No correlation was found between PEth value,pre-steroids abstinence length,or number of drinks per week pre-steroids and response to steroids.Non-responder status significantly correlated with older age(P=0.024),lower albumin(P=0.003),and higher bilirubin(P=0.010)pre-steroids.Our study suggests that age,pre-steroid albumin,and pre-steroid bilirubin levels may predict nonresponse to steroid therapy.Non-responders have increased incidence of death and higher medical costs.CONCLUSION Identifying non-responders through these identified factors should prompt early referral for liver transplantation.Future prospective studies with larger population size are needed to assess the efficacy of combined pre-steroid age,albumin,bilirubin and other biochemical markers as predictors of steroid response.
基金Supported by National Natural Science Foundation of China,No.82170406 and No.81970238.
文摘Acute alcohol-associated hepatitis(AAH)is a life-threatening condition with high mortality,and steroid therapy remains the mainstay of treatment despite variable efficacy.The study by Sabatose et al explores patient factors distinguishing responders and non-responders to steroid therapy for AAH,focusing on phosphatidylethanol(PEth)-a biomarker of alcohol consumption-and other clinical variables.Their findings indicate that PEth,abstinence duration,and pretreatment alcohol intake do not predict steroid response,while older age,lower pre-steroid albumin,and higher pre-steroid bilirubin are associated with nonresponse.Non-responders exhibit higher mortality and healthcare costs,underscoring the need for early identification to guide liver transplantation referrals.This commentary evaluates the implications of these findings-specifically,how prioritizing pre-steroid albumin,bilirubin,and age over alcohol biomarkers can improve clinical decision-making by reducing unnecessary steroid exposure and expediting transplantation referrals for high-risk non-responders-contextualizes them within existing literature,and highlights directions for future research to optimize AAH management.
文摘In utero exposure to ethanol continues to be a significant public health issue and neonatal healthcare professionals are in need of objective means to identify exposed newborns. The aim of this study was to fully validate two methods for the detection of two direct alcohol biomarkers, 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanol (POPE) and ethyl glucuronide (EtG), in umbilical cord and apply the assays to a group of authentic specimens. The limits of detections were 2 and 1 ng/g for POPE and ETG and the limits of quantitation were 4 and 3 ng/g, respectively. Inter and intra-day precision and accuracy measurements were within 15%. The assays were applied to 308 authentic specimens where we detected POPE in five (1.6%) specimens and EtG in twelve (3.9%) specimens. The mean concentrations were 11.4 ng/g ± 9.4 ng/g and 127.2 ± 227.7 ng/g for POPE and EtG, respectively. This study suggested that umbilical cord was a suitable specimen type for the identification of newborns exposed to ethanol in the womb and the prevalence of POPE and EtG detected in umbilical cord were consistent with the prevalence of self-reported binge drinking reported by the National Birth Defect Prevention Study (NBDPS) and Behavioral Risk Factor Surveillance System (BRFSS). Further studies are required to fully describe the association between the observed concentrations of POPE and EtG in umbilical cord to the level of maternal consumption of ethanol.
