scholarly journals Longitudinal Mapping of Gyral and Sulcal Patterns of Cortical Thickness and Brain Volume Regain during Early Alcohol Abstinence

2015 ◽  
Vol 22 (2) ◽  
pp. 80-89 ◽  
Author(s):  
Guo-Ying Wang ◽  
Traute Demirakca ◽  
Julia van Eijk ◽  
Ulrich Frischknecht ◽  
Matthias Ruf ◽  
...  
Keyword(s):  
Cortical Thickness ◽  
Brain Volume ◽  
Longitudinal Change ◽  
Partial Recovery ◽  
Excessive Alcohol Consumption ◽  
Brain Volume Loss ◽  
Alcohol Abstinence ◽  
Volume Recovery ◽  
Excessive Alcohol ◽  
Subcortical Volume

We explored brain volume recovery in terms of cortical thickness (CTh; gyral, sulcal pattern) and surface area (SA), as well as subcortical volume recovery in the first 2 weeks of abstinence in 49 alcohol-dependent patients (ADPs). A widespread reduction of CTh in ADPs at day 1 of abstinence compared to healthy controls, with more pronounced differences in sulci relative to gyri was found. After 2 weeks of abstinence, partial recovery to varying degrees of CTh loss in ADPs was observed for several regions. The longitudinal CTh changes were greater in sulci than in gyri of affected regions. No longitudinal change in SAs and subcortical volumes was found. Alterations of CTh contribute to brain volume loss in alcoholism and recovery during early abstinence. Sulci seem to be more vulnerable to excessive alcohol consumption and to drive abstinence-induced volume recovery. During the initial 2 weeks of abstinence no subcortical volume regain was observed. Either the time span was too short or the lower subcortical volume could represent a predisposing trait marker.

scholarly journals Association Between Reduced Brain Glucose Metabolism and Cortical Thickness in Alcoholics: Evidence of Neurotoxicity

2019 ◽  
Vol 22 (9) ◽  
pp. 548-559 ◽  
Author(s):  
Dardo G Tomasi ◽  
Corinde E Wiers ◽  
Ehsan Shokri-Kojori ◽  
Amna Zehra ◽  
Veronica Ramirez ◽  
...  
Keyword(s):  
Cortical Thickness ◽  
Brain Regions ◽  
Excessive Alcohol Consumption ◽  
Mediation Effects ◽  
Cognitive Domains ◽  
Performance Accuracy ◽  
Positron Emission ◽  
Superior Parietal Cortex ◽  
Excessive Alcohol ◽  
Causal Mediation Analysis

Abstract Background Excessive alcohol consumption is associated with reduced cortical thickness (CT) and lower cerebral metabolic rate of glucose (CMRGlu), but the correlation between these 2 measures has not been investigated. Methods We tested the association between CT and cerebral CMRGlu in 19 participants with alcohol use disorder (AUD) and 20 healthy controls. Participants underwent 2-Deoxy-2-[18F]fluoroglucose positron emission tomography to map CMRGlu and magnetic resonance imaging to assess CT. Results Although performance accuracy on a broad range of cognitive domains did not differ significantly between AUD and HC, AUD had widespread decreases in CT and CMRGlu. CMRGlu, normalized to cerebellum (rCMRGlu), showed significant correlation with CT across participants. Although there were large group differences in CMRGlu (>17%) and CT (>6%) in medial orbitofrontal and BA 47, the superior parietal cortex showed large reductions in CMRGlu (~17%) and minimal CT differences (~2.2%). Though total lifetime alcohol (TLA) was associated with CT and rCMRGlu, the causal mediation analysis revealed significant direct effects of TLA on rCMRGlu but not on CT, and there were no significant mediation effects of TLA, CT, and rCMRGlu. Conclusions The significant correlation between decrements in CT and CMRGlu across AUD participants is suggestive of alcohol-induced neurotoxicity, whereas the findings that the most metabolically affected regions in AUD had minimal atrophy and vice versa indicates that changes in CT and CMRGlu reflect distinct responses to alcohol across brain regions.

scholarly journals Acetaldehyde exposure underlies functional defects in monocytes induced by excessive alcohol consumption

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shunsuke Shiba ◽  
Nobuhiro Nakamoto ◽  
Po-Sung Chu ◽  
Keisuke Ojiro ◽  
Nobuhito Taniki ◽  
...  
Keyword(s):  
Alcohol Consumption ◽  
Transgenic Mice ◽  
Inflammatory Cytokines ◽  
Gene Polymorphisms ◽  
Healthy Controls ◽  
Wild Type ◽  
Excessive Alcohol Consumption ◽  
Alcohol Abstinence ◽  
Excessive Alcohol ◽  
Alcohol Dependent

AbstractIncreased intestinal permeability and hepatic macrophage activation by endotoxins are involved in alcohol-induced liver injury pathogenesis. Long-term alcohol exposure conversely induces endotoxin immune tolerance; however, the precise mechanism and reversibility are unclear. Seventy-two alcohol-dependent patients with alcohol dehydrogenase-1B (ADH1B, rs1229984) and aldehyde dehydrogenase-2 (ALDH2, rs671) gene polymorphisms admitted for alcohol abstinence were enrolled. Blood and fecal samples were collected on admission and 4 weeks after alcohol cessation and were sequentially analyzed. Wild-type and ALDH2*2 transgenic mice were used to examine the effect of acetaldehyde exposure on liver immune responses. The productivity of inflammatory cytokines of peripheral CD14+ monocytes in response to LPS stimulation was significantly suppressed in alcohol dependent patients on admission relative to that in healthy controls, which was partially restored by alcohol abstinence with little impact on the gut microbiota composition. Notably, immune suppression was associated with ALDH2/ADH1B gene polymorphisms, and patients with a combination of ALDH2*1/*2 and ADH1B*2 genotypes, the most acetaldehyde-exposed group, demonstrated a deeply suppressed phenotype, suggesting a direct role of acetaldehyde. In vitro LPS and malondialdehyde-acetaldehyde adducted protein stimulation induced direct cytotoxicity on monocytes derived from healthy controls, and a second LPS stimulation suppressed the inflammatory cytokines production. Consistently, hepatic macrophages of ethanol-administered ALDH2*2 transgenic mice exhibited suppressed inflammatory cytokines production in response to LPS compared to that in wild-type mice, reinforcing the contribution of acetaldehyde to liver macrophage function. These results collectively provide new perspectives on the systemic influence of excessive alcohol consumption based on alcohol-metabolizing enzyme genetic polymorphisms.

scholarly journals Alcohol-Related Liver Disease: Basic Mechanisms and Clinical Perspectives

2021 ◽  
Vol 22 (10) ◽  
pp. 5170
Author(s):  
Szu-Yi Liu ◽  
I-Ting Tsai ◽  
Yin-Chou Hsu
Keyword(s):  
Liver Disease ◽  
Liver Steatosis ◽  
Diagnostic Tools ◽  
Therapeutic Approaches ◽  
Excessive Alcohol Consumption ◽  
Non Invasive ◽  
Cell Based Therapy ◽  
Alcohol Abstinence ◽  
Excessive Alcohol ◽  
Related Liver Disease

Alcohol-related liver disease (ALD) refers to the liver damage occurring due to excessive alcohol consumption and involves a broad spectrum of diseases that includes liver steatosis, steatohepatitis, hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). The progression of ALD is mainly associated with the amount and duration of alcohol usage; however, it is also influenced by genetic, epigenetic, and environmental factors. The definite diagnosis of ALD is based on a liver biopsy, although several non-invasive diagnostic tools and serum biomarkers have emerging roles in the early detection of ALD. While alcohol abstinence and nutritional support remain the cornerstone of ALD treatment, growing evidence has revealed that the therapeutic agents that target oxidative stress or gut-liver axis, inflammatory response inhibition, and liver regeneration enhancement also play a role in ALD management. Furthermore, microRNAs modulation and mesenchymal stem cell-based therapy have emerging potential as ALD therapeutic options. This review summarizes the updated understanding of the pathophysiology, diagnosis, and novel therapeutic approaches for ALD.

scholarly journals Regulation of Alcohol and Acetaldehyde Metabolism by a Mixture of Lactobacillus and Bifidobacterium Species in Human

Nutrients ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1875
Author(s):  
Su-Jin Jung ◽  
Ji-Hyun Hwang ◽  
Eun-Ock Park ◽  
Seung-Ok Lee ◽  
Yun-Jo Chung ◽  
...  
Keyword(s):  
Alcohol Dehydrogenase ◽  
Blood Levels ◽  
Double Blind ◽  
Excessive Alcohol Consumption ◽  
Bifidobacterium Species ◽  
Placebo Capsule ◽  
Safety Parameters ◽  
Excessive Alcohol ◽  
Clinically Significant ◽  
Acetaldehyde Metabolism

Excessive alcohol consumption is one of the most significant causes of morbidity and mortality worldwide. Alcohol is oxidized to toxic and carcinogenic acetaldehyde by alcohol dehydrogenase (ADH) and further oxidized to a non-toxic acetate by aldehyde dehydrogenase (ALDH). There are two major ALDH isoforms, cytosolic and mitochondrial, encoded by ALDH1 and ALDH2 genes, respectively. The ALDH2 polymorphism is associated with flushing response to alcohol use. Emerging evidence shows that Lactobacillus and Bifidobacterium species encode alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) mediate alcohol and acetaldehyde metabolism, respectively. A randomized, double-blind, placebo-controlled crossover clinical trial was designed to study the effects of Lactobacillus and Bifidobacterium probiotic mixture in humans and assessed their effects on alcohol and acetaldehyde metabolism. Here, twenty-seven wild types (ALDH2*1/*1) and the same number of heterozygotes (ALDH2*2/*1) were recruited for the study. The enrolled participants were randomly divided into either the probiotic (Duolac ProAP4) or the placebo group. Each group received a probiotic or placebo capsule for 15 days with subsequent crossover. Primary outcomes were measurement of alcohol and acetaldehyde in the blood after the alcohol intake. Blood levels of alcohol and acetaldehyde were significantly downregulated by probiotic supplementation in subjects with ALDH2*2/*1 genotype, but not in those with ALDH2*1/*1 genotype. However, there were no marked improvements in hangover score parameters between test and placebo groups. No clinically significant changes were observed in safety parameters. These results suggest that Duolac ProAP4 has a potential to downregulate the alcohol and acetaldehyde concentrations, and their effects depend on the presence or absence of polymorphism on the ALDH2 gene.

scholarly journals Characterisation of MS phenotypes across the age span using a novel data set integrating 34 clinical trials (NO.MS cohort): Age is a key contributor to presentation

2021 ◽  
pp. 135245852098863
Author(s):  
Frank Dahlke ◽  
Douglas L Arnold ◽  
Piet Aarden ◽  
Habib Ganjgahi ◽  
Dieter A Häring ◽  
...  
Keyword(s):  
Disease Activity ◽  
Brain Volume ◽  
Young Patients ◽  
Clinical Trial Data ◽  
Study Data ◽  
Phase Iii ◽  
Brain Images ◽  
Data Set ◽  
Brain Volume Loss ◽  
Phase Iii Study

Background: The Oxford Big Data Institute, multiple sclerosis (MS) physicians and Novartis aim to address unresolved questions in MS with a novel comprehensive clinical trial data set. Objective: The objective of this study is to describe the Novartis–Oxford MS (NO.MS) data set and to explore the relationships between age, disease activity and disease worsening across MS phenotypes. Methods: We report key characteristics of NO.MS. We modelled MS lesion formation, relapse frequency, brain volume change and disability worsening cross-sectionally, as a function of patients’ baseline age, using phase III study data (≈8000 patients). Results: NO.MS contains data of ≈35,000 patients (>200,000 brain images from ≈10,000 patients), with >10 years follow-up. (1) Focal disease activity is highest in paediatric patients and decreases with age, (2) brain volume loss is similar across age and phenotypes and (3) the youngest patients have the lowest likelihood (<25%) of disability worsening over 2 years while risk is higher (25%–75%) in older, disabled or progressive MS patients. Young patients benefit most from treatment. Conclusion: NO.MS will illuminate questions related to MS characterisation, progression and prognosis. Age modulates relapse frequency and, thus, the phenotypic presentation of MS. Disease worsening across all phenotypes is mediated by age and appears to some extent be independent from new focal inflammatory activity.

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