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Lancet (London, England) May 1972
Topics: Alcohols; Hodgkin Disease; Humans; Pain
PubMed: 4112205
DOI: 10.1016/s0140-6736(72)91248-2 -
International Archives of Allergy and... May 1996Headache can be induced by histamine in wine in patients suffering from histamine intolerance, a disease characterized by impaired histamine degradation based on reduced... (Review)
Review
Headache can be induced by histamine in wine in patients suffering from histamine intolerance, a disease characterized by impaired histamine degradation based on reduced diamine oxidase activity or a lack of the enzyme. Diamine oxidase is localized in the jejunal mucosa and is the most important enzyme metabolising histamine. It is competitively inhibited by alcohol and numerous drugs. In preliminary investigations, assessment of diamine oxidase levels gave decreased activity (0.03 nKat/l) in patients with histamine intolerance compared to healthy controls (0.07 nKat/l). In pregnancy, diamine oxidase levels are known to be about 500-fold elevated, giving mean levels of 25.0 nKat/l. Other biogenic amines such as phenylethylamine or serotonin may be causative for wine/food-induced headache. In experimental models, headache has been induced by histamine infusion as well as red wine provocation. Histamine-induced headache is a vascular headache likely to be caused by nitric oxide which probably represents a key molecule in vascular headaches. A histamine-free diet is the treatment of choice for patients with histamine intolerance and chronic headache. To start treatment, an antihistamine (H1 blocker) for 14 days as well as a histamine-free diet for at least 4 weeks are recommended. Clinical improvement to the diet as well as in vitro tests for plasma histamine and diamine oxidase in the serum as well as vitamin B6 levels have to confirm the diagnosis. As supportive treatment, a vitamin B6 (pyridoxal phosphate) substitution appears useful in histamine-intolerant patients as pyridoxal phosphate seems to be crucial for diamine oxidase activity. Histamine intolerance, based on reduced diamine oxidase activity or a lack in the enzyme is causative for wine/food-induced chronic headache. According to the localization of diamine oxidase in the jejunal mucosa, histamine intolerance is primarily a disease of intestinal origin. A histamine-free diet is the treatment of choice in histamine-intolerant patients suffering from chronic headache. In addition, it is also important to avoid diamine-oxidase-blocking drugs and alcohol which act as inhibitors of diamine oxidase. As avoidance of histamine-rich food is simple, inexpensive and harmless treatment, histamine-containing food such as cheese and alcoholic beverages should be labeled.
Topics: Headache; Histamine; Humans; Wine
PubMed: 8645981
DOI: 10.1159/000237304 -
The Journal of Nervous and Mental... Nov 1987The Oriental flushing reaction is an adverse response to alcohol that appears to be genetically determined. In this study, the Oriental flushing reaction that was... (Clinical Trial)
Clinical Trial
The Oriental flushing reaction is an adverse response to alcohol that appears to be genetically determined. In this study, the Oriental flushing reaction that was produced with ingestion of small amounts of alcohol was antagonized by antihistamine administration. A group of 17 subjects was tested. Each subject received placebo, diphenhydramine 50 mg (H-1 receptor antagonist), and cimetidine 300 mg (H-2 receptor antagonist) singularly and in combination. Alcohol was then administered orally. Most subjects given placebo experienced the typical flushing reaction that included a cutaneous flush, increase in skin temperature, decrease in blood pressure, increase in pulse rate and subjective symptoms such as dizziness, sleepiness, anxiety, headache, generalized weakness, and nausea. The flush, temperature and systolic hypotension were significantly blocked by the combined antihistamine administration. Cimetidine given alone blocked the flush, temperature increase, and systolic hypotension significantly more than diphenhydramine but less than the combined antihistamines. Diphenhydramine was similar to placebo in its effect on the flushing reaction. The role of histamine in the expression of tolerance to alcohol is not known. Antihistamine antagonism of the adverse flushing reaction suggests that histamine receptors may participate in the intolerance to ethanol in Orientals. Histamine may be an important protective factor in the low prevalence of alcoholism in Orientals.
Topics: Adolescent; Adult; Asian People; Blood Pressure; Cimetidine; Diphenhydramine; Drug Synergism; Ethanol; Female; Flushing; Humans; Male; Middle Aged; Receptors, Histamine; Skin Temperature
PubMed: 3681277
DOI: 10.1097/00005053-198711000-00003 -
Acta Pharmacologica Et Toxicologica May 1986According to clinical reports, several therapeutic agents produce ethanol intolerance, which is often referred as disulfiram reaction. The mechanism of this...
According to clinical reports, several therapeutic agents produce ethanol intolerance, which is often referred as disulfiram reaction. The mechanism of this manifestation was investigated in the Wistar rat, by measuring the alcohol and aldehyde dehydrogenases (ADH, ALDH) of the liver and the brain after subacute administration of chloramphenicol (100 mg/kg X 4, intraperitoneally), chlorpropamide (80 mg/kg X 4, intraperitoneally), disulfiram (150 mg/kg X 4, intraperitoneally), griseofulvin (100 mg/kg X 4, intraperitoneally), isoniazid (200 mg/kg X 4, intraperitoneally), metronidazole (200 mg/kg X 4, intraperitoneally), and procarbazine (100 mg/kg X 4, intraperitoneally). All substances tested decrease the activity of the low-Km ALDH in the brain, with the exception of griseofulvin. The hepatic low-Km enzyme is also inhibited, with the exception of griseofulvin and metronidazole. The high-Km ALDH responds in an inconsistent way, while ADH is not affected at all. The results suggest that the so-called "disulfiram-reaction" is mediated mainly, but not exclusively, by inhibition of the low-Km ALDH.
Topics: Alcohol Dehydrogenase; Alcohol Deterrents; Alcohol Oxidoreductases; Aldehyde Dehydrogenase; Animals; Brain; Ethanol; Kinetics; Liver; Male; Rats; Rats, Inbred Strains
PubMed: 2943133
DOI: 10.1111/j.1600-0773.1986.tb00114.x -
Polski Tygodnik Lekarski (Warsaw,... Dec 1966
Review
Topics: Drug Incompatibility; Drug Synergism; Ethanol; Humans
PubMed: 5342684
DOI: No ID Found -
PloS One 2014Perilipin 2 (Plin2) is a lipid droplet protein that has roles in both lipid and glucose homeostasis. An increase in Plin2 in liver is associated with the development of...
BACKGROUND
Perilipin 2 (Plin2) is a lipid droplet protein that has roles in both lipid and glucose homeostasis. An increase in Plin2 in liver is associated with the development of steatosis, glucose intolerance, and ceramide accumulation in alcoholic liver disease. We investigated the role of Plin2 on energy balance and glucose and lipid homeostasis in wildtype and Plin2 knockout (Plin2KO) mice chronically fed a Lieber-DeCarli liquid ethanol or control diet for six weeks.
METHODS
We performed in vivo measurements of energy intake and expenditure; body composition; and glucose tolerance. After sacrifice, liver was dissected for histology and lipid analysis.
RESULTS
We found that neither genotype nor diet had a significant effect on final weight, body composition, or energy intake between WT and Plin2KO mice fed alcohol or control diets. Additionally, alcohol feeding did not affect oxygen consumption or carbon dioxide production in Plin2KO mice. We performed glucose tolerance testing and observed that alcohol feeding failed to impair glucose tolerance in Plin2KO mice. Most notably, absence of Plin2 prevented hepatic steatosis and ceramide accumulation in alcohol-fed mice. These changes were related to downregulation of genes involved in lipogenesis and triglyceride synthesis.
CONCLUSIONS
Plin2KO mice chronically fed alcohol are protected from hepatic steatosis, glucose intolerance, and hepatic ceramide accumulation, suggesting a critical pathogenic role of Plin2 in experimental alcoholic liver disease.
Topics: Animals; Body Composition; Body Weight; Ceramides; Down-Regulation; Ethanol; Fatty Liver; Glucose Intolerance; Glucose Tolerance Test; Homeostasis; Lipid Metabolism; Liver; Liver Diseases, Alcoholic; Male; Membrane Proteins; Mice; Mice, Inbred C57BL; Mice, Knockout; Oxygen Consumption; Perilipin-2; Time Factors; Triglycerides
PubMed: 24831094
DOI: 10.1371/journal.pone.0097118 -
Proceedings of the Royal Society of... Dec 1967
Topics: Breast Neoplasms; Ethanol; Female; Humans; Ovarian Neoplasms; Uterine Cervical Neoplasms; Uterine Neoplasms
PubMed: 6066581
DOI: No ID Found -
The American Journal of Forensic... Dec 2023The PPA2 gene encodes a mitochondrial pyrophosphatase protein. Mutations in the gene are inherited in an autosomal recessive fashion and, when mutated, function to...
The PPA2 gene encodes a mitochondrial pyrophosphatase protein. Mutations in the gene are inherited in an autosomal recessive fashion and, when mutated, function to induce mitochondrial ATP production failure resulting in increased stress on the heart and sudden cardiac death, especially when combined with alcohol. Herein, we describe a case of a 19-year-old female patient with a history of "alcohol intolerance" who was found unexpectedly deceased after consuming a minimal amount of alcohol. Histological examination of her heart revealed widespread fibrosis of the left ventricle and the interventricular septum. Other findings include hypertrophied myocytes, including some with pleomorphic nuclei. Genetic studies were performed on postmortem blood, revealing heterozygous PPA2 gene mutations, the pathogenic variant c.683C>T (p.Pro228Leu), and the other variant c.814C>T (p.His272Tyr), a novel variant of undetermined significance. We propose that the variant of undetermined significance is likely a pathogenic mutation due to the decedent's phenotype.
Topics: Female; Humans; Adolescent; Young Adult; Adult; Mutation; Death, Sudden, Cardiac; Ethanol; Mitochondria; Fibrosis; Mitochondrial Proteins; Inorganic Pyrophosphatase
PubMed: 37249496
DOI: 10.1097/PAF.0000000000000841 -
Molecular Metabolism Dec 2023Alcohol-associated liver disease (ALD) is the leading cause of liver-related mortality worldwide. Current strategies to manage ALD focus largely on advanced stage...
Ceramide synthase 6 (CerS6) is upregulated in alcohol-associated liver disease and exhibits sex-based differences in the regulation of energy homeostasis and lipid droplet accumulation.
OBJECTIVE
Alcohol-associated liver disease (ALD) is the leading cause of liver-related mortality worldwide. Current strategies to manage ALD focus largely on advanced stage disease, however, metabolic changes such as glucose intolerance are apparent at the earliest stage of alcoholic steatosis and increase the risk of disease progression. Ceramides impair insulin signaling and accumulate in ALD, and metabolic pathways involving ceramide synthase 6 (CerS6) are perturbed in ALD during hepatic steatosis. In this study, we aimed to investigate the role of CerS6 in ALD development and the relevance of CerS6 to human ALD.
METHODS
C57BL/6 WT and CerS6 KO mice of both sexes were fed either a Lieber-DeCarli control (CON) or 15% ethanol (EtOH) diet for six weeks. In vivo metabolic tests including glucose and insulin tolerance tests (GTT and ITT) and energy expenditure were performed. The mice were euthanized, and serum and liver lipids and liver histology were examined. For in vitro studies, CerS6 was deleted in human hepatocytes, VL17A and cells were incubated with EtOH and/or C-ceramides. RNAseq analysis was performed in livers from mice and human patients with different stages of ALD and diseased controls.
RESULTS
After six weeks on an EtOH diet, CerS6 KO mice had reduced body weight, food intake, and %fat mass compared to WT mice. Energy expenditure increased in both male and female KO mice, however, was only statistically significant in male mice. In response to EtOH, WT mice developed mild hepatic steatosis, while steatosis was ameliorated in KO mice as determined by H&E and ORO staining. KO mice showed significantly decreased long-chain ceramide species, especially C-ceramides, in the serum and liver tissues compared to WT mice. CerS6 deletion decreased serum TG and NEFA only in male not female mice. CerS6 deletion improved glucose tolerance and insulin resistance in EtOH-fed mice of both sexes. RNAseq analysis revealed that 74 genes are significantly upregulated and 66 genes are downregulated by CerS6 deletion in EtOH-fed male mice, with key network pathways including TG biosynthetic process, positive regulation of lipid localization, and fat cell differentiation. Similar to RNAseq results, absence of CerS6 significantly decreased mRNA expression of lipid droplet associated proteins in EtOH-fed mice. In vitro, EtOH stimulation significantly increased PLIN2 protein expression in VL17A cells while CerS6 deletion inhibited EtOH-mediated PLIN2 upregulation. C-ceramide treatment significantly increased PLIN2 protein expression compared to CON. Notably, progression of ALD in humans was associated with increased hepatic CerS6 expression.
CONCLUSIONS
Our findings demonstrate that CerS6 deletion improves glucose homeostasis in alcohol-fed mice and exhibits sex-based differences in the attenuation of EtOH-induced weight gain and hepatic steatosis. Additionally, we unveil that CerS6 plays a major role as a regulator of lipid droplet biogenesis in alcohol-induced intra-hepatic lipid droplet formation, identifying it as a putative target for early ALD management.
Topics: Animals; Female; Humans; Male; Mice; Ceramides; Ethanol; Fatty Liver; Glucose; Homeostasis; Insulins; Lipid Droplets; Liver Diseases, Alcoholic; Mice, Inbred C57BL; Perilipin-2
PubMed: 37714377
DOI: 10.1016/j.molmet.2023.101804 -
The Cochrane Database of Systematic... Sep 2015Feeding intolerance is a common clinical problem among preterm infants. It may be an early sign of necrotising enterocolitis, sepsis or other serious gastrointestinal... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Feeding intolerance is a common clinical problem among preterm infants. It may be an early sign of necrotising enterocolitis, sepsis or other serious gastrointestinal conditions, or it may result from gut immaturity with delayed passage of meconium. Glycerin laxatives stimulate passage of meconium by acting as an osmotic dehydrating agent and increasing osmotic pressure in the gut; they stimulate rectal contraction, potentially reducing the incidence of feeding intolerance.
OBJECTIVES
To assess the effectiveness and safety of glycerin laxatives (enemas/suppositories) for prevention or treatment of feeding intolerance in very low birth weight (VLBW) infants.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 4), MEDLINE, EMBASE and the Cumulative Index to Nursing and Allied Health Literature (CINAHL). We restricted our search to all randomised controlled trials and applied no language restrictions. We searched the references of identified studies and reviews on this topic and handsearched for additional articles. We searched the database maintained by the US National Institutes of Health (www.clinicaltrials.gov) and European trial registries to identify ongoing trials.
SELECTION CRITERIA
We considered only randomised or quasi-randomised controlled trials that enrolled preterm infants < 32 weeks' gestational age (GA) and/or < 1500 g birth weight. We included trials if they administered glycerin laxatives and measured at least one prespecified clinical outcome.
DATA COLLECTION AND ANALYSIS
We used standard methods of The Cochrane Collaboration and its Neonatal Group to assess methodological quality of trials, to collect data and to perform analyses.
MAIN RESULTS
We identified three trials that evaluated use of prophylactic glycerin laxatives in preterm infants. We identified no trials that evaluated therapeutic use of glycerin laxatives for feeding intolerance. Our review showed that prophylactic administration of glycerin laxatives did not reduce the time required to achieve full enteral feeds and did not influence secondary outcomes, including duration of hospital stay, mortality and weight at discharge. Prophylactic administration of glycerin laxatives resulted in failure of fewer infants to pass stool over the first 48 hours. Included trials reported no adverse events.
AUTHORS' CONCLUSIONS
Our review of available evidence for glycerin laxatives does not support the routine use of prophylactic glycerin laxatives in clinical practice. Additional studies are needed to confirm or refute the effectiveness and safety of glycerin laxatives for prevention or treatment of feeding intolerance in VLBW infants.
Topics: Enema; Enteral Nutrition; Gestational Age; Glycerol; Humans; Infant, Very Low Birth Weight; Laxatives; Meconium; Randomized Controlled Trials as Topic; Suppositories
PubMed: 26421424
DOI: 10.1002/14651858.CD010464.pub2