Nonalcoholic Control Subjects Research Articles

Effect of Oral Administration of Syzygium cumini Seed Powder on the Hepatic Function-related Enzymes of the Alcoholic Transport Laborers

Background: Syzygium cumini (locally known as Kalo Jam) seed powder is being used as folk medicine in various diseases since unknown times in Bangladesh. However, data on the systematic studies in human subjects are rare. Objective: To determine the effect of Syzygium cumini seed powder on the hepatic function-related enzymes of the alcoholic transport laborers. Methods: Here, we investigated the effects of oral administration of Syzygium cumini seed powder on hepaticfunction markers that included activities of Gamma-glutamyl transferase (GGT), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and renal-function markers such as creatinine and urea along with lipid profile, blood pressure and body mass index (BMI) upon chronic alcoholic human volunteers. Results: The levels of serum ALT, AST and GGT levels decreased, respectively, by 15.0, 8.5 and 23.0% after oral administration of the S. cumini powder in the alcoholic subjects. However, the levels of creatinine and urea were not altered significantly. In contrast, the effects of administration of S. cumini on the hepatic ALT, AST and GGT enzymes in the non-alcoholic control subjects were less prominent than those found in the alcoholic subjects. Blood pressure decreased only by 5-4 mmHg, while BMI was not altered in either the alcoholic or the non-alcoholic groups. Furthermore, there were significant reduction in the levels of TC (by 10%) and LDL-C (by >20%) and elevation of HDL-C (by 11%) in the S. cumini-prescribed alcoholic subjects. TC and LDL-C levels also decreased in the non-alcoholic subjects, but the rate was not statistically significant. Conclusions: Our results suggest that S. cumini seed extract ameliorated GGT, ALT and the atherosclerotic lipid parameters TC and LDL-C without having a significant side effect on the kidney functions, as indicated by the unaltered levels of serum creatinine levels in the alcoholic human subjects without any effect on BP and BMI of the same subjects. Thus, alcohol drinkers can be advised to intake S. cumini seed powder to protect against the oxidative hepatic damage. Bangladesh Medical Res Counc Bull 2022; 48: 97-104

SFRP5 hepatic expression is associated with non-alcoholic liver disease in morbidly obese women

Background and aims. Secreted frizzled-related protein 5 (SFRP5) was recently described as a new adipokine protective for hepatic steatosis and other obesity-related complications in the mouse model. To date, SFRP5 expression in non-alcoholic fatty liver disease (NAFLD) has not been fully assessed in humans. We measured circulating SFRP5 levels and its expression in liver and adipose tissue, and evaluated its association with NAFLD in morbidly obese women.Material and methods. Fifty-four morbidly obese women undergoing bariatric surgery were included in the study. Liver biopsies were used for histology and hepatic triglyceride content quantification. Circulating SFRP5 levels were measured through enzyme-linked immunoabsorbent assay, and SFRP5 expression was performed in hepatic and adipose tissue (subcutaneous and visceral).Results. Although circulating SFRP5 levels showed a tendency to decrease with NAFLD progression, no significant differences were observed among non-alcoholic steatosis, steatohepatitis, and control subjects. Hepatic SFRP5 expression showed a negative correlation with hepatic triglyceride content (r = -0.349, P = 0.016 for mRNA and r = -0.291, P = 0.040 for SRFP5 protein) and ALT serum levels (r = -0.437, P = 0.001 for SRFP5 protein). In addition, hepatic SFRP5 protein levels were significantly lower in NASH than in control subjects (P = 0.006). Conclusion. This is the first study reporting an association of hepatic SFRP5 expression with NAFLD in humans.

Altered CB1 receptor coupling to G-proteins in the post-mortem caudate nucleus and cerebellum of alcoholic subjects.

Biochemical, pharmacological and genetic evidence suggests the involvement of the endocannabinoid system in alcohol dependence. The aim of the present study was to evaluate the state of CB1 receptors in post-mortem caudate nucleus, hippocampus and cerebellum of alcoholic subjects.CB1 protein levels were measured by Western blot, CB1 receptor density and affinity by [(3)H]WIN55,212-2 saturation assays and CB1 functionality by [(35)S]GTPγS binding assays. Experiments were performed in samples from 24 subjects classified as non-suicidal alcoholics (n = 6), suicidal alcoholics (n = 6), non-alcoholic suicide victims (n = 6) and control subjects (n = 6).Alcoholic subjects presented hyperfunctional CB1 receptors in the caudate nucleus resulting in a higher maximal effect in both alcoholic groups compared to the non-alcoholic groups (p < 0.001). Conversely, in the cerebellum the non-suicidal alcoholic subjects showed hypofunctional receptors with lower maximal effect and potency (p < 0.001). No changes were found in the CB1 protein expression in either region. In the hippocampus of alcoholic subjects, no changes were observed either in the functionality, density or protein levels.Our data support an association between endocannabinoid system activity and alcoholism. The modifications reported here could be either a consequence of high lifetime ethanol consumption or a vulnerability factor to develop alcohol addiction.

AMPA receptors in post-mortem brains of Cloninger type 1 and 2 alcoholics: A whole-hemisphere autoradiography study

Dysfunction of the brain glutamate system has been associated with alcoholism. Ionotropic glutamatergic alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors (AMPARs) play an important role in both neurotransmission and post-synaptic plasticity. Alterations in AMPAR densities may also play a role in the neurobiological changes associated with alcoholism. In the present study, [3H] AMPA binding density was evaluated in the nucleus accumbens (NAc), frontal cortex, anterior cingulate cortex (ACC), dentate gyrus and hippocampus of Cloninger type 1 (n=9) and 2 (n=8) alcoholics, and compared with non-alcoholic control subjects (n=10) by post-mortem whole-hemisphere autoradiography. The [3H] AMPA binding density was significantly higher in the ACC of early onset type 2 alcoholics when compared with controls (p=0.011). There was also a significant negative correlation between [3H] AMPA binding and previously published results of dopamine transporter (DAT) density in the ACC in these same brain samples (R=−0.95, p=0.001). Although preliminary, and from a relatively small diagnostic group, the present results help to further explain the pathology of alcohol dependence and impulsive behaviour in type 2 alcoholics.

Endogenous cannabinoids in amygdala and hippocampus in post-mortem brains of Cloninger type 1 and 2 alcoholics

Accumulating evidence continues to link certain aspects of the endogenous cannabinoid (EC) system with alcohol dependence, negative-reinforcement learning, and the modulation of stress responses. Specific alterations in brain regions that are related to stress and negative-reinforcement learning have been reported to exist in Cloninger type 1 and type 2 alcoholics. To study possible differences in profiles of EC systems between Cloninger type 1 (n = 9) and type 2 (n = 8) alcoholics and non-alcoholic control subjects (n = 10), we analyzed post-mortem amygdala and hippocampus brain samples for several ECs by quantitative liquid chromatography with triple quadrupole mass-spectrometric detection. A significant difference was found between these 3 groups in terms of EC profiles in the amygdala (p = 0.037). In particular, this difference was prominent for variations in docosahexaenoylethanolamide levels, which were significantly higher in type 1 alcoholics (p = 0.022) when compared to controls. There was also a large negative correlation between anandamide concentration and mGlu1/5 receptor density in the hippocampi of Cloninger type 1 alcoholics (R = −0.88, p = 0.002), which was not seen in Cloninger type 2 alcoholics or in controls. Although preliminary, and from relatively small diagnostic groups, these results suggest that the EC system profile may be altered in the hippocampus and amygdala of Cloninger type 1 alcoholics.

Brain-derived neurotrophic factor Val66Met polymorphism and alcohol-related phenotypes

Alcoholism is a chronic psychiatric disorder affecting neural pathways that regulate motivation, stress, reward and arousal. Brain-derived neurotrophic factor (BDNF) regulates mood, response to stress and interacts with neurotransmitters and stress systems involved in reward pathways and addiction. Aim of the study was to evaluate the association between a single nucleotide polymorphism (BDNF Val66Met or rs6265) and alcohol related phenotypes in Caucasian patients. In ethnically homogenous Caucasian subjects of the Croatian origin, the BDNF Val66Met genotype distribution was determined in 549 male and 126 female patients with alcohol dependence and in 655 male and 259 female healthy non-alcoholic control subjects. Based on the structured clinical interview, additional detailed clinical interview, the Brown-Goodwin Scale, the Hamilton Rating Scale for Depression and the Clinical Global Impression scores, alcoholic patients were subdivided into those with or without comorbid depression, aggression, delirium tremens, withdrawal syndrome, early/late onset of alcohol abuse, prior suicidal attempt during lifetime, current suicidal behavior, and severity of alcohol dependence. The results showed no significant association between BDNF Val66Met variants and alcohol dependence and/or any of the alcohol related phenotypes in either Caucasian women, or men, with alcohol dependence. There are few limitations of the study. The overall study sample size was large (N=1589) but not well-powered to detect differences in BDNF Val66Met genotype distribution between studied groups. Healthy control women were older than female alcoholic patients. Only one BDNF polymorphism (rs6265) was studied. In conclusion, these data do not support the view that BDNF Val66Met polymorphism correlates with the specific alcohol related phenotypes in ethnically homogenous medication-free Caucasian subjects with alcohol dependence.

Study of serum gamma glutamyl transferase as a diagnostic marker in alcoholic hepatitis

Serum gamma glutamyl transferase (GGT or γ-GT) is a microsomal enzyme, catalyzes the transfer of the gamma-glutamyl moiety of glutathione to various peptide acceptors. It is a reliable diagnostic marker of alcohol ingestion which is one of the most sensitive and most commonly employed biochemical marker of alcohol consumption . This study was carried out with 30 alcoholic hepatitis and 30 normal non-alcoholic control subjects. The aim of this study was to establish the role of serum GGT alone in the diagnosis of alcoholic hepatitis. A significant correlation in the level of serum GGT is observed in alcoholics when compared with the normal subjects. The enzyme activity of GGT in serum is increased in average by 527.31% in the patients with alcoholic hepatitis compared to normal control subjects (p<0.05). Measurement of GGT in serum appears to be a sensitive index with low specificity in the diagnosis of alcoholics with hepatitis when correlated clinically.

Brain volumetric measures in alcoholics: a comparison of two segmentation methods

Measures of regional brain volumes, which can be derived from magnetic resonance imaging (MRI) images by dividing a brain into its constituent parts, can be used as structural indicators of many different neuroanatomical diseases and disorders, including alcoholism. Reducing the time and cost required for brain segmentation would greatly facilitate both clinical and research endeavors. In the present study, we compared two segmentation methods to measure brain volumes in alcoholic and nonalcoholic control subjects: 1) an automated system (FreeSurfer) and 2) a semi-automated, supervised system (Cardviews, developed by the Center for Morphometric Analysis [CMA] at Massachusetts General Hospital), which requires extensive staff and oversight. The participants included 32 abstinent alcoholics (19 women) and 37 demographically matched, nonalcoholic controls (17 women). Brain scans were acquired in a 3 Tesla MRI scanner. The FreeSurfer and CMA methods showed good agreement for the lateral ventricles, cerebral white matter, caudate, and thalamus. In general, the larger the brain structure, the closer the agreement between the methods, except for the cerebral cortex, which showed large between-method differences. However, several other discrepancies existed between the FreeSurfer and CMA volume measures of alcoholics’ brains. The CMA volumes, but not FreeSurfer, demonstrated that the thalamus, caudate, and putamen were significantly smaller in male alcoholics as compared with male controls. Additionally, the hippocampus was significantly smaller in alcoholic women compared with women controls. In general, correlation between methods was lowest in male alcoholic subjects, who also showed the greatest abnormalities. These results suggest that although many brain structures can be segmented reliably by CMA and FreeSurfer, low correlations between methods in some regions may be due to morphological changes in the brains of alcoholics.

Occurrence of antibodies against hepatitis C virus (HCV) among alcoholics

Studies have shown that hepatitis C virus (HCV)-infected alcoholics have more severe biochemical and histological evidence of liver disease than anti-HCV-negative patients. One possible mechanism for the increased liver damage is that alcohol may have a stimulatory effect on HCV replication. This study was therefore carried out to investigate the seroprevalence of HCV virus among alcoholics. Two-hundred and seventy (270) alcoholics and fifty (50) control subjects at selected locations in Jos South local government area (LGA), of Plateau State were screened for HCV antibodies using grand rapid diagnostic test strip. Structured questionnaire was employed to obtain demographic data of study subjects. Overall, the prevalence of HCV infection was found to be 45(16.7%) in response to alcoholics while the non-alcoholic (control) subjects recorded 3 (6.0%) positivity, [(x 2 = 3.765); P > 0.05]. Gender consideration showed that females subjects had a higher prevalence of 25 (9.3%) compared to males with 20 (7.4%) among the alcoholic subjects. The 19 – 30 years age group recorded the highest seroprevalence of 14 (5.2%) to the HCV, [(x 2 = 4.757); P > 0.05], while no significant difference was observed among positive subjects screened for serum aminotranferase levels in relation to age and gender. Available evidence from this study indicates that alcoholic consumption is a strong determinant of HCV infection. Drastic measures at creating awareness and the need for routine screening among alcoholics should be given due consideration. However, future HCV studies need to quantify concurrent alcoholic consumption to further our understanding of the total burden of illness from alcohol associated HCV in the community. Keywords: Alcoholics, hepatitis c virus, occurrence

Yes, Simultaneous Damage to Both the Pancreas and Liver Are Associated in Subjects Who Drink Excessive Amounts of Alcohol!

It has generally been accepted that although excessive alcohol intake might lead to liver damage or pancreatic damage, both conditions are rarely associated, and the pathogenesis of the tissue injury is not related. Indeed, many have believed that subjects with alcohol-induced liver damage are somehow not apt to develop pancreatic damage and vice versa. The study by Pace et al 1 in this issue of Clinical Gastroenterology and Hepatology refutes that remarkably well. These authors evaluated the prevalence of simultaneous liver cirrhosis and chronic pancreatitis in subjects who were heavy imbibers. Postmortem autopsy data were evaluated from 620 individuals with a history of excessive alcohol use and 100 nonalcoholic control subjects. The individuals were classified into groups on the basis of macroscopic observations of the pancreas (no injury, acute pancreatitis, fibrosis, and chronic pancreatitis) and liver (no injury, moderate steatosis, severe steatosis, and cirrhosis). The same classification system was used for histologic data that were used to confirm and correlate macroscopic findings. Of 183 subjects with liver cirrhosis, 33 (18%) had chronic pancreatitis, and 93 (51%) had pancreatic fibrosis. Of the 230 subjects with severe steatosis, 37 (16%) had chronic pancreatitis, and 97 (42%) were found to have pancreatic fibrosis. Thirtythree (39%) subjects with chronic pancreatitis also had liver cirrhosis, and 37 (44%) had severe steatosis. Thirty-eight percent of the subjects with pancreatic fibrosis were found to have liver cirrhosis, and in another 40%, severe steatosis occurred. Thirtyfive subjects demonstrated neither liver nor pancreatic damage. In the control group neither chronic pancreatitis nor cirrhosis was detected. Thus, Andrea and associates demonstrated the simultaneous occurrence of liver and pancreatic damage in these individuals who were heavy drinkers. Recent studies indicated that both chronic pancreatitis and cirrhosis have precursor lesions. Chronic pancreatitis develops through fibrosis of the pancreas. 2,3 The precursor form of liver cirrhosis appears to be hepatic steatosis. 4,5 Thus, hepatic and stellate cells are important in the development of fibrosis in both the liver and the pancreas, implying similar molecular mechanisms for the fibrotic changes in both organs. 3,6 The authors were unable to accurately evaluate the effect of nicotine use as a risk factor for liver and/or pancreatic damage because smoking data were only available for 49% of the subjects. Why is it that the consensus opinion was that these lesions in the pancreas and liver did not occur simultaneously? First, the studies in the literature that defended the nonoccurrence of these lesions were usually performed in small numbers of patients. 7 In addition, none of these studies looked systematically into morphologic changes such as pancreatic fibrosis. 8,9 Indeed, the importance of fibrosis as a crucial initial event in chronic pancreatitis has only been emphasized relatively recently. Andrea and associates readily recognized the limitations of their study such as having no quantitative data on exactly how much alcohol was taken by these “heavy drinkers” and the duration of drinking; the semiquantitative analysis of the tissue damage; the inability to evaluate nicotine use as a risk factor for either liver or pancreatic damage; and the lack of data on other potential risk factors such as diabetes, body mass index, and nutrition status. These criticisms notwithstanding, the data obtained in this large number of subjects should convincingly demonstrate, contrary to common belief, that there is a close association between pancreatic and liver injury in patients with heavy alcohol intake. The authors also make a good case for a correlation of organ damage between the pancreas and the liver.

Amygdala serotonin transporters in alcoholics measured by whole hemisphere autoradiography

A dysfunction in brain serotonin turnover is a well-established factor associated with the impulsive and sociopathic behavior in alcoholics. The conjuncted alterations in functioning of serotonin transporter (SERT) may play a role in the regulation of emotional balance, judgement, and the adverse behavioral effects of ethanol misuse. These traits may be related to serotonergic regulation in the amygdala and prefrontal cortex. The binding of [(3)H]citalopram to SERT was evaluated in the amygdala of Cloninger type 1 and 2 alcoholics (n = 17), and nonalcoholic control subjects (n = 10) by postmortem whole-hemisphere autoradiography. The SERT binding was substantially lower in the dorsal amygdala in alcoholic subjects when compared with the controls (-28%, effect size 1.26, P = 0.016). In secondary analysis, this reduction was observed in both alcoholic subgroups (-26% in type 1 alcoholics, and -33% in type 2 alcoholics). In ventral amygdala, no alteration was observed. There were significant correlations between the SERT binding in dorsal amygdala and in previous results from frontal cortical areas in alcoholics, depending on the type of alcoholic. These results suggest that SERT binding in the amygdala, as well as the differential regulation of the SERT in amygdala and frontal cortex in alcoholics may help to explain the dysfunctional regulation of emotions in alcoholics.

Gender Differences in Neurocognitive Functioning Among Alcohol‐Dependent Russian Patients

There are a limited number of studies that have examined gender differences in the neurocognitive test performances of alcohol-dependent individuals. Those that have been conducted reported that compared with men, women's visuospatial skills, psychomotor speed, and working memory are more profoundly affected by chronic alcohol abuse despite a shorter duration of drinking and a lesser quantity of alcohol consumed. The performances of Russian male and female alcoholic and nonalcoholic control subjects were compared on a series of neurocognitive tasks that assess motor speed, visuoperceptual processing, visuospatial processing, decision making, and cognitive flexibility. Group and gender differences emerged on specific components of each task administered. Female compared with male alcoholic subjects exhibited poorer performances on tests of visual working memory, spatial planning and problem solving, and cognitive flexibility. The data support and extend prior research demonstrating a more deleterious impact of alcohol dependence on female alcoholic subjects' cognitive functioning compared with male alcoholic subjects. Several theories are offered to account for gender differences in neurocognitive performance.

Lower serotonin transporter binding in caudate in alcoholics

Dorsal striatum is regulated by the serotonergic system, and it is a brain area with a role in the development of obsessive thought patterns, which may be related to addiction. In this study, possible alterations of [(3)H]citalopram binding to serotonin transporter (SERT) were evaluated in the dorsal striatum of Cloninger type 1 and 2 alcoholics, and nonalcoholic control subjects by postmortem whole-hemisphere autoradiography in humans. The SERT binding was significantly lower (-26%, effect size 1.74) in the caudate body of alcoholics. The SERT binding tended to be lower also in the other parts of the dorsal striatum in alcoholics, but the results did not reach significance. In addition, there was a significant positive correlation, especially in type 1 alcoholics, between the SERT binding in the body of the caudate and in the perigenual anterior cingulate cortex, an area in which the SERT binding has been shown to be lower among alcoholics. These results give preliminary evidence to suggest that the SERT binding in the dorsal striatum may be lower in alcoholics, and that the serotonergic system may be affected in cortical and striatal areas simultaneously. The cortico-striatal-thalamic axis may have an important role in fully developed addictions and the characterization of these correlations within the serotonergic system may lead to a better understanding of the anatomical dynamics underlying the neurochemistry of alcoholism.

Polymorphisms of the dopamine D2 receptor, serotonin transporter, and GABA A receptor β 3 subunit genes and alcoholism in Mexican-Americans

The etiology of alcohol dependence is a complex interaction of psychosocial and biologic factors. To study the impact of genetic factors that play an important role in an individual's vulnerability to alcohol abuse and dependence, we examined the genetic variations of the major neurotransmitter genes, including the dopamine D2 receptor ( DRD2) TaqI A, B, and -141C insertion/deletion ( Ins/Del) polymorphisms, the serotonin transporter–linked polymorphic region ( 5-HTTLPR), and the gamma-aminobutyric acid A (GABA A) receptor β 3 subunit gene ( GABRβ3), for 130 Mexican-American alcoholic men and 251 nonalcoholic control subjects (105 men and 146 women). The genotype frequency for the DRD2 -141C Ins/Del allele was significantly different between alcoholic and control subjects ( P = .007). The frequency of the 5-HTTLPR short ( S) allele was significantly higher in alcoholic individuals (61.5%) than in nonalcoholic control subjects (52.8%; P = .021). When smokers were excluded from both control and alcoholic groups, the association between the DRD2 -141C Ins allele, as well as between the 5-HTTLPR S allele, and alcoholism became significant at both genotypic and allelic levels. No positive association was found between alcoholism and the DRD2 TaqI A or B, or the GABRβ3, genotype. Our findings indicate that the DRD2 -141C Ins allele and the 5-HTTLPR S allele are genetic risk factors for alcoholism in Mexican-Americans, and that smoking modulates the association between genetic risk factors and alcoholism.

Serum hyaluronate correlates with histological progression in alcoholic liver disease.

Chronic alcohol consumption may lead to the development of liver cirrhosis. Serum concentrations of hyaluronate were suggested as a predictor in chronic liver disease, but its power to distinguish between severity of fibrosis and inflammation had not been assessed. In order to evaluate hyaluronate as a marker to detect early stages of alcoholic liver disease and to establish a possible correlation with hepatic histology, serum concentrations were measured by radioimmunoassay in 87 patients with biopsy-proven fatty liver, fatty liver and mild fibrosis, fatty liver and inflammation, severe fibrosis and inflammation, and cirrhosis, and in 12 non-alcoholic control subjects. In addition, serum hyaluronate was determined in 40 non-cirrhotic alcoholic patients with either a normal serum aspartate aminotransferase (AST) or an AST elevated at least two-fold. Serum hyaluronate increased significantly with advanced stages of alcoholic liver disease, while levels in patients with fatty liver were elevated only slightly without reaching significance. Hyaluronate correlated well with histological stage and was highly sensitive for detecting fibrosis in general and perivenular fibrosis as an indicator of progression to cirrhosis. Hyaluronate levels were not influenced by AST levels. Serum hyaluronate is a good predictor of the presence of even moderate hepatic fibrosis in alcoholic liver disease, justifying its clinical use to assess morphological alterations of the liver in alcoholics.

Executive Dysfunction and Clinical Outcome in Chronic Alcoholics

Background The purpose of this study was to investigate which of 12 neuropsychological tests predict alcoholic patients’ alcohol‐specific and/or alcoholic‐nonspecific outcome. Our hypothesis was that the ecologically valid neuropsychological tests that measure executive function are better predictors of alcoholics’ functional outcome.Methods We administered 12 neuropsychological tests to chronic alcoholics. Included in the tests were tasks of Reaction Time, Symbol Digit Modalities, Figure Position, Digit Span, Block Design, Trail Making, and six subtests of a battery called the Behavioral Assessment of the Dysexecutive Syndrome (BADS). Previous investigators have suggested that the BADS has ecological validity. Twenty‐two male alcoholics were compared with 15 nonalcoholic control subjects on these neuropsychological measures 7 weeks after detoxification. Two functional outcome indices, i.e., resumption of drinking and occupation, were evaluated 18 months after discharge.Results The total profile score and the score on three of the six subtests of the BADS were lower in alcoholics than in nonalcoholic controls. Alcoholics’ performance on the BADS predicted alcohol‐nonspecific outcome (occupation) but not alcohol‐specific (drinking) outcome. In contrast, other neuropsychological tests did not predict either of the two outcome indices.Conclusions The BADS total profile score is related to alcohol‐nonspecific outcome but not to alcohol‐specific outcome.

Obesity and female gender increase breath ethanol concentration: potential implications for the pathogenesis of nonalcoholic steatohepatitis

OBJECTIVES: Similarities between histological features of alcoholic hepatitis and obesity-related liver disease suggest a common pathogenic mechanism. Because intestinal bacteria can produce ethanol, it is conceivable that intestinally derived alcohol may contribute to fatty liver disease. An indirect way of measuring endogenous ethanol is to measure the breath ethanol concentration. In a previous study in ob/ob mice, breath ethanol decreased with a course of nonabsorbable antibiotics, suggesting that the ethanol is derived from intestinal bacterial flora. The aims of this study were 1) to determine whether alcohol can be detected in the breath of human subjects, and 2) to assess whether there is any correlation between ethanol and obesity in patients with nonalcoholic steatohepatits (NASH) and control subjects without known liver disease. METHODS: Breath ethanol concentration was determined in 21 patients with biopsy-proven NASH and in 10 control subjects by gas chromatography. An abnormal breath ethanol level was defined as two standard deviations above the mean value of the breath ethanol of lean controls. RESULTS: Minute quantities of ethanol were detected in the breath of human subjects who had not consumed alcohol in the recent past. Patients who were obese were more likely to have higher breath ethanol concentrations. Women also had higher breath alcohol than men. However, there was no difference between patients with NASH and controls. Severity of liver disease, as evidenced by cirrhosis, did not influence the breath ethanol concentration. CONCLUSIONS: Higher breath ethanol concentrations are observed in obese subjects than in leaner ones. It is possible that intestinally derived ethanol may contribute to the pathogenesis of NASH.

Obesity and female gender increase breath ethanol concentration: potential implications for the pathogenesis of nonalcoholic steatohepatitis.

Similarities between histological features of alcoholic hepatitis and obesity-related liver disease suggest a common pathogenic mechanism. Because intestinal bacteria can produce ethanol, it is conceivable that intestinally derived alcohol may contribute to fatty liver disease. An indirect way of measuring endogenous ethanol is to measure the breath ethanol concentration. In a previous study in ob/ob mice, breath ethanol decreased with a course of non-absorbable antibiotics, suggesting that the ethanol is derived from intestinal bacterial flora. The aims of this study were 1) to determine whether alcohol can be detected in the breath of human subjects, and 2) to assess whether there is any correlation between ethanol and obesity in patients with nonalcoholic steatohepatits (NASH) and control subjects without known liver disease. Breath ethanol concentration was determined in 21 patients with biopsy-proven NASH and in 10 control subjects by gas chromatography. An abnormal breath ethanol level was defined as two standard deviations above the mean value of the breath ethanol of lean controls. Minute quantities of ethanol were detected in the breath of human subjects who had not consumed alcohol in the recent past. Patients who were obese were more likely to have higher breath ethanol concentrations. Women also had higher breath alcohol than men. However, there was no difference between patients with NASH and controls. Severity of liver disease, as evidenced by cirrhosis, did not influence the breath ethanol concentration. Higher breath ethanol concentrations are observed in obese subjects than in leaner ones. It is possible that intestinally derived ethanol may contribute to the pathogenesis of NASH.

Sweet liking and family history of alcoholism in hospitalized alcoholic and non-alcoholic patients.

The present study was designed to test the hypothesis that preference for stronger sweet solutions may be associated with the genetic risk for alcoholism. Thirty-two male patients with alcohol dependence admitted for alcoholism in-patient treatment and 25 non-alcoholic control subjects were used in the study. Hedonic response to sweets was evaluated using the sweet preference test. Family history of alcoholism was evaluated using a Russian version of the Michigan Alcoholism Screening Test modified for the assessment of the alcohol-related behaviour of the subject's biological father. Similar to our previous findings, alcoholics were far more likely to prefer the highest offered sucrose concentration (0.83 M), compared to non-alcoholic controls. Such preference was determined by two factors: positive family history of alcoholism and alcoholic status. Statistically, these factors contributed to the likelihood of preferring sweet solutions independently. Therefore, the effects of these factors may enhance each other. These findings support the hypothesis that preference for a stronger sweet solution is associated with a paternal history of alcohol dependence and may reflect a genetic predisposition to alcoholism.

The role of small intestinal bacterial overgrowth, intestinal permeability, endotoxaemia, and tumour necrosis factor α in the pathogenesis of non-alcoholic steatohepatitis

BACKGROUNDSmall intestinal bacterial overgrowth may contribute to the development of non-alcoholic steatohepatitis, perhaps by increasing intestinal permeability and promoting the absorption of endotoxin or other enteric bacterial products.AIMSTo investigate the...