-
World Journal of Hepatology Dec 2020Disorders of esophageal motility have been described in patients with cirrhosis in a small number of studies. In this review, we aim to provide an overview of the... (Review)
Review
Disorders of esophageal motility have been described in patients with cirrhosis in a small number of studies. In this review, we aim to provide an overview of the available evidence on esophageal motility disorders in cirrhosis and their clinical implications. This review delves into the following concepts: (1) Gastroesophageal reflux disease is common in liver cirrhosis due to many mechanisms; however, when symptomatic it is usually nocturnal and has an atypical presentation; (2) Endoscopic band ligation is better than sclerotherapy in terms of its effect on esophageal motility and seems to correct dysmotilities resulting from the mechanical effect of esophageal varices; (3) Chronic alcoholism has no major effects on esophageal motility activity other than lower esophageal sphincter hypertension among those with alcoholic autonomic neuropathy; (4) An association between primary biliary cholangitis and scleroderma can be present and esophageal hypomotility is not uncommon in this scenario; and (5) Cyclosporin-based immunosuppression in liver transplant patients can have a neurotoxic effect on the esophageal myenteric plexus leading to reversible achalasia-like manifestations.
PubMed: 33442445
DOI: 10.4254/wjh.v12.i12.1158 -
Scientific Reports Mar 2023Nonalcoholic fatty liver disease (NAFLD) has become an important risk of type 2 diabetes mellitus (T2DM). Peripheral neuropathy (PN) is regarded as one of the main...
Nonalcoholic fatty liver disease (NAFLD) has become an important risk of type 2 diabetes mellitus (T2DM). Peripheral neuropathy (PN) is regarded as one of the main microvascular complications of diabetes. But the association of NAFLD with PN is still unclear. We aimed to investigate the association between NAFLD and PN in US population by conducting a cross-sectional study. We enrolled 3029 participants aged 40-85 years from National Health and Nutrition Examination Survey (NHANES) 1999-2004. NAFLD was defined as a US Fatty Liver Index (FLI) score ≥ 30, and PN was defined as having one or more insensate areas on either foot. Participants were divided into two groups (with or without PN). We performed multivariate logistic regression models to evaluate the association between NAFLD and PN. Subgroup analyses were used to find out whether the association was stable in different stratified groups. Sensitivity analyses were conducted to assess the robustness of the results. All the analyses were weighted. Among the individuals, 524 (17.3%) had PN and 1250 (41.27%) had NAFLD. In the multivariate logistic regression models, NAFLD was associated with an increased risk of PN (OR 1.44 [1.03 ~ 2.02]) after fully adjusting for covariates. In the subgroup analyses, NAFLD was significantly associated with PN in the age group (40-64 years), compared with those in the age group (65-85 years), (P for interaction: 0.004). The results of association of NAFLD with PN were stable in sensitivity analyses. In this cross-sectional study among US adults aged 40-85 years old, NAFLD was associated with an increased likelihood of prevalent PN.
Topics: Adult; Humans; Middle Aged; Aged; Aged, 80 and over; Non-alcoholic Fatty Liver Disease; Diabetes Mellitus, Type 2; Cross-Sectional Studies; Nutrition Surveys; Peripheral Nervous System Diseases; Risk Factors
PubMed: 37002268
DOI: 10.1038/s41598-023-32115-4 -
Acta Pharmacologica Sinica Aug 2014Alcohol use disorders (AUD) are defined as alcohol abuse and alcohol dependence, which create large problems both for society and for the drinkers themselves. To date,... (Review)
Review
Alcohol use disorders (AUD) are defined as alcohol abuse and alcohol dependence, which create large problems both for society and for the drinkers themselves. To date, no therapeutic can effectively solve these problems. Understanding the underlying mechanisms leading to AUD is critically important for developing effective and safe pharmacological therapies. Benzodiazepines (BZs) are used to reduce the symptoms of alcohol withdrawal syndrome. However, frequent use of BZs causes cross-tolerance, dependence, and cross-addiction to alcohol. The FDA-approved naltrexone and acamprosate have shown mixed results in clinical trials. Naltrexone is effective to treat alcohol dependence (decreased length and frequency of drinking bouts), but its severe side effects, including withdrawal symptoms, are difficult to overcome. Acamprosate showed efficacy for treating alcohol dependence in European trials, but two large US trials have failed to confirm the efficacy. Another FDA-approved medication, disulfiram, does not diminish craving, and it causes a peripheral neuropathy. Kudzu is the only natural medication mentioned by the National Institute on Alcohol Abuse and Alcoholism, but its mechanisms of action are not yet established. It has been recently shown that dihydromyricetin, a flavonoid purified from Hovenia, has unique effects on GABAA receptors and blocks ethanol intoxication and withdrawal in alcoholic animal models. In this article, we review the role of GABAA receptors in the treatment of AUD and currently available and potentially novel pharmacological agents.
Topics: Acamprosate; Alcohol Deterrents; Alcohol Drinking; Alcoholism; Animals; Benzodiazepines; Disulfiram; Ethanol; Fructose; Humans; Naltrexone; Narcotic Antagonists; Neuroprotective Agents; Plant Preparations; Receptors, GABA-A; Taurine; Topiramate
PubMed: 25066321
DOI: 10.1038/aps.2014.50 -
Journal of Neurology, Neurosurgery, and... Jul 1984Ten male alcoholics aged 38-72 years with clear clinical and electroneurographical signs of peripheral neuropathy were re-examined three to five years later. Conduction...
Ten male alcoholics aged 38-72 years with clear clinical and electroneurographical signs of peripheral neuropathy were re-examined three to five years later. Conduction velocities, latencies and nerve action potential amplitudes were measured from median, peroneal and sural nerves on both occasions and the results were compared with age-matched reference values from 80 healthy men. Seven of the alcoholics showed normal or nearly normal scores in electroneurographical and clinical examination and they had all managed to stop drinking alcohol. The results suggest that the prognosis of alcoholic peripheral neuropathy is good and independent of age provided that intake of alcohol is discontinued and other causes of neuropathy (malignancy, diabetes, nerve trauma) are carefully excluded.
Topics: Adult; Aged; Alcoholism; Evoked Potentials; Follow-Up Studies; Humans; Median Nerve; Middle Aged; Motor Neurons; Muscles; Neural Conduction; Peripheral Nervous System Diseases; Peroneal Nerve; Prognosis; Reaction Time; Sural Nerve
PubMed: 6086844
DOI: 10.1136/jnnp.47.7.699 -
Journal of Leukocyte Biology Nov 2016Fetal alcohol spectrum disorder (FASD), which results from ethanol exposure during pregnancy, and alcohol use disorder (AUD), which includes both binge and chronic... (Review)
Review
Fetal alcohol spectrum disorder (FASD), which results from ethanol exposure during pregnancy, and alcohol use disorder (AUD), which includes both binge and chronic alcohol abuse, are strikingly common and costly at personal and societal levels. These disorders are associated with significant pathology, including that observed in the CNS. It is now appreciated in both humans and animal models that ethanol can induce inflammation in the CNS. Neuroinflammation is hypothesized to contribute to the neuropathologic and behavioral consequences in FASD and AUD. In this review, we: 1) summarize the evidence of alcohol-induced CNS inflammation, 2) outline cellular and molecular mechanisms that may underlie alcohol induction of CNS inflammation, and 3) discuss the potential of nuclear receptor agonists for prevention or treatment of neuropathologies associated with FASD and AUD.
Topics: Adolescent; Adult; Age Factors; Alcoholic Neuropathy; Alcoholism; Animals; CX3C Chemokine Receptor 1; Central Nervous System; Chemokine CX3CL1; Child; Cognition Disorders; Disease Models, Animal; Encephalomyelitis; Female; Fetal Alcohol Spectrum Disorders; Humans; Infant, Newborn; Inflammasomes; Male; Mental Disorders; Microglia; Neurons; Pregnancy; Prenatal Exposure Delayed Effects; Receptors, Cytokine; Receptors, HIV; Toll-Like Receptor 4
PubMed: 27462100
DOI: 10.1189/jlb.3MR0416-171R -
Indian Journal of Psychiatry 2021Thiamine is essential for the activity of several enzymes associated with energy metabolism in humans. Chronic alcohol use is associated with deficiency of thiamine... (Review)
Review
Thiamine is essential for the activity of several enzymes associated with energy metabolism in humans. Chronic alcohol use is associated with deficiency of thiamine along with other vitamins through several mechanisms. Several neuropsychiatric syndromes have been associated with thiamine deficiency in the context of alcohol use disorder including Wernicke-Korsakoff syndrome, alcoholic cerebellar syndrome, alcoholic peripheral neuropathy, and possibly, Marchiafava-Bignami syndrome. High-dose thiamine replacement is suggested for these neuropsychiatric syndromes.
PubMed: 34194054
DOI: 10.4103/psychiatry.IndianJPsychiatry_440_20 -
1-Deoxysphingolipids Encountered Exogenously and Made de Novo: Dangerous Mysteries inside an Enigma.The Journal of Biological Chemistry Jun 2015The traditional backbones of mammalian sphingolipids are 2-amino, 1,3-diols made by serine palmitoyltransferase (SPT). Many organisms additionally produce... (Review)
Review
The traditional backbones of mammalian sphingolipids are 2-amino, 1,3-diols made by serine palmitoyltransferase (SPT). Many organisms additionally produce non-traditional, cytotoxic 1-deoxysphingoid bases and, surprisingly, mammalian SPT biosynthesizes some of them, too (e.g. 1-deoxysphinganine from L-alanine). These are rapidly N-acylated to 1-deoxy-"ceramides" with very uncommon biophysical properties. The functions of 1-deoxysphingolipids are not known, but they are certainly dangerous as contributors to sensory and autonomic neuropathies when elevated by inherited SPT mutations, and they are noticeable in diabetes, non-alcoholic steatohepatitis, serine deficiencies, and other diseases. As components of food as well as endogenously produced, these substances are mysteries within an enigma.
Topics: Alanine; Animals; Diabetes Mellitus; Humans; Lipids; Mutation; Non-alcoholic Fatty Liver Disease; Peripheral Nervous System Diseases; Serine C-Palmitoyltransferase; Sphingosine
PubMed: 25947379
DOI: 10.1074/jbc.R115.658823 -
Basic & Clinical Pharmacology &... Jun 2014Chronic pain conditions, such as neuropathic pain, are a common problem that poses a major challenge to health-care providers due to its complex natural history, unclear... (Review)
Review
Chronic pain conditions, such as neuropathic pain, are a common problem that poses a major challenge to health-care providers due to its complex natural history, unclear aetiology and poor response towards therapy. Despite the large number of drugs available, the adherence is limited by the large range of side effects and pharmacological ineffectiveness. Thus, the search for new chemical entities that can act as promising molecules to treat chronic pain conditions has emerged. The natural products remain as the most promising sources of new chemical entities with applicability for the medical approach. Hence, we performed a systematic review analysing pre-clinical studies shown to be promising in a possible applicability in neuropathic pain. The search terms neuropathic pain, phytotherapy and medicinal plants were used to retrieve English language articles in LILACS, PUBMED and EMBASE published until 10 April 2013. From a total of 1529 articles surveyed, 28 met the inclusion and exclusion criteria established. The main chemical compounds studied were flavonoids (28%), terpenes (17%), alkaloids (14%), phenols (10%), carotenoids (10%) and others (21%). The mostly described animal models for the study of neuropathic pain included were chronic constriction injury (CCI - 32%), partial sciatic nerve ligation (PSNL - 28%), streptozotocin - induced diabetic (28%), alcoholic neuropathy (3.5%), sodium monoiodoacetate (MIA - 3.5%) and neuropathic pain induced by paclitaxel (3.5%). The opioids, serotonergic and cannabinoid systems are suggested as the most promising targets for the natural products described. Therefore, the data reviewed here suggest that these compounds are possible candidates for the treatment of chronic painful conditions, such as neuropathic pain.
Topics: Alkaloids; Animals; Biological Products; Disease Models, Animal; Flavonoids; Humans; Neuralgia; Phytotherapy; Terpenes
PubMed: 24252102
DOI: 10.1111/bcpt.12178 -
Journal of Medical Case Reports Mar 2016Neuropathy is a rare adverse side effect of disulfiram therapy and is under-recognized. There have been few case reports documenting this side effect.
BACKGROUND
Neuropathy is a rare adverse side effect of disulfiram therapy and is under-recognized. There have been few case reports documenting this side effect.
CASE PRESENTATION
Two cases of disulfiram peripheral neuropathy are discussed. The first case is that of a 25-year-old Caucasian woman who was exposed to disulfiram therapy for a total of 8 months and developed pain and stiffness that prevented her from walking. The second case is that of a 46-year-old Caucasian woman who developed sudden-onset numbness in her lower extremities with progression to pain. Her symptoms improved over the course of 2 months after cessation of disulfiram therapy. In both cases, symptoms improved after cessation of disulfiram therapy.
CONCLUSIONS
Disulfiram neuropathy occurs in persons with a history of chronic alcohol use. It is under-recognized and often attributed to alcoholic neuropathy given its comorbidity with alcoholic neuropathy. A greater understanding of this side effect may reduce neurologic complications related to disulfiram neuropathy and aid in early withdrawal of this offending agent.
Topics: Adult; Alcohol Deterrents; Alcoholism; Disulfiram; Female; Humans; Hypesthesia; Middle Aged; Neuralgia; Peripheral Nervous System Diseases
PubMed: 27029711
DOI: 10.1186/s13256-016-0865-z -
Journal of Diabetes Investigation Nov 2021Non-alcoholic fatty liver disease and type 2 diabetes mellitus are closely related, and often occur simultaneously in patients. Type 2 diabetes increases the risk of...
AIMS/INTRODUCTION
Non-alcoholic fatty liver disease and type 2 diabetes mellitus are closely related, and often occur simultaneously in patients. Type 2 diabetes increases the risk of diabetic peripheral neuropathy, resulting in intolerable pain and extremity amputation that reduces the quality of life. However, the role of non-alcoholic fatty liver disease in the pathogenesis of diabetic peripheral neuropathy remains unclear. Thus, we evaluated the correlation of liver fibrosis and steatosis, which are representative histological morphologies of non-alcoholic fatty liver disease, with diabetic peripheral neuropathy in type 2 diabetes patients.
MATERIALS AND METHODS
Five hundred twenty individuals with type 2 diabetes were recruited. All the patients were detected nerve conduction study for diabetic peripheral neuropathy and fibro touch for liver steatosis and fibrosis. Correlation of DPN with liver steatosis and fibrosis were analysed with binary logistic analysis.
RESULTS
Among the 520 patients, the prevalence of liver steatosis, fibrosis and diabetic peripheral neuropathy was 63.0% (n = 328), 18.1% (n = 94) and 52.1% (n = 271), respectively. The prevalence of diabetic peripheral neuropathy was significantly elevated in patients with liver steatosis (55.7 vs 44.9%, P = 0.03) and fibrosis (61.5 vs 50%, P = 0.04), and it increased as liver stiffness measurement increased. Additionally, both hepatic steatosis (odds ratio 1.48, 95% confidence interval 1.04-2.11, P = 0.03) and fibrosis (odds ratio 1.60, 95% confidence interval 1.02-2.51, P = 0.04) were correlated with diabetic peripheral neuropathy. After adjusting for age, sex, weight, height, body mass index, waist hip ratio, duration of type 2 diabetes, blood glucose, homeostatic model assessment of insulin resistance, blood pressure, serum lipid, liver enzyme, urea, uric acid, creatinine and inflammatory factors, liver fibrosis remained associated with diabetic peripheral neuropathy (odds ratio 2.24, 95% confidence interval 1.11-4.53, P = 0.02).
CONCLUSIONS
The prevalence of diabetic peripheral neuropathy was elevated in patients with liver steatosis and fibrosis. Liver fibrosis was also independently associated with an increased risk of diabetic peripheral neuropathy.
Topics: Aged; Blood Glucose; Blood Pressure; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Female; Humans; Insulin Resistance; Liver Cirrhosis; Logistic Models; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Prevalence; Risk Factors
PubMed: 33943028
DOI: 10.1111/jdi.13562