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1.
Iran J Med Sci ; 47(5): 468-476, 2022 Sep.
Article in English | MEDLINE | ID: mdl-36117576

ABSTRACT

Background: Alcohol consumption in pregnancy is associated with an increased risk of cardiovascular abnormalities, but the mechanisms are unknown. This study evaluated the impact of ethanol exposure on the offspring's aorta structural, functional, and molecular alterations on postnatal (PN) both on days 21 and 90. Methods: This experimental study was conducted at Urmia University of Medical Sciences (Urmia, Iran) in 2019. Twenty Pregnant Wistar rats on the seventh day of Gestation Day (GD) were randomly divided into two groups: control and ethanol-treated groups (n=10 per group). From the seventh day of GD throughout lactation, rats in the ethanol group were fed binge alcohol (4.5 g/Kg body weight) once daily. Systemic hemodynamic variables in the offspring were analyzed using waveform contour analysis 90 days after birth. On postnatal days (PN) 21 and 90, aorta wall histological alterations and the level of inflammatory factors were assessed in the aorta of male offspring. The statistical differences were examined via an independent samples t test. P<0.05 was considered to be statistically significant. Results: The results revealed that offspring in the ethanol group had higher systolic, diastolic, mean arterial pressure, and dicrotic pressure than the control group (P<0.001). The level of aorta tissue tumor necrosis factor (TNF)-α, intercellular adhesion molecule (ICAM)-1, nuclear factor (NF)-κ, and endothelin-1 were significantly higher in the ethanol offspring group than in the control group (P<0.001). Histopathological changes such as total aorta thickness, tunica media, tunica adventitia, elastin fiber thickness, fiber interval, and elastin/media ratio significantly increased in the aorta of the offspring of the ethanol group compared to the control group 21 and 90 days after birth. Conclusion: Our findings suggest that prenatal and early postnatal ethanol exposure-induced cardiovascular abnormalities are, in part, due to predisposing the aorta to atherosclerosis, which was mediated through the aorta wall remodeling and inflammation process.


Subject(s)
Elastin , Endothelin-1 , Animals , Aorta , Cell Adhesion Molecules , Ethanol/adverse effects , Female , Follow-Up Studies , Hemodynamics , Male , Pregnancy , Rats , Rats, Wistar , Tumor Necrosis Factors
2.
Oxid Med Cell Longev ; 2022: 5025237, 2022.
Article in English | MEDLINE | ID: mdl-36052161

ABSTRACT

Alcoholic liver disease (ALD) is a major public health problem worldwide, which needs to be effective prevention. Ginsenoside Rg1 (GRg1), a bioactive ingredient extracted from ginseng, has benefit effects on health. In this study, 11 potential targets of GRg1 against ALD were firstly obtained by network pharmacology. KEGG pathway enrichment showed that GRg1-target-ALD was closely related to Toll-like receptor (TLR) and nuclear factor-kappa B (NF-κB) signaling pathways. In addition, GRg1 decreased antioxidant levels and increased oxidative levels in alcohol-treated mice, which alleviated oxidative stress-induced hepatic damage. GRg1 enhanced intestinal barrier function via upregulating the levels of tight junction protein and immunoglobulin A. GRg1 also reduced alcohol-induced inflammation by suppressing TLR4/NF-κB pathway, which was consistent with the prediction of network targets. Moreover, GRg1 altered GM population, and Verrucomicrobia, Bacteroidetes, Akkermansia, Bacteroides, Lachnospiraceae_NK4A136_group, and Alloprevotella played positive association with intestinal barrier indicators and negative correlation with hepatic inflammation biomarkers. The results suggest that GRg1 administration might be a promising strategy for protection of alcohol-induced liver damage.


Subject(s)
Gastrointestinal Microbiome , Liver Diseases, Alcoholic , Animals , Ethanol/adverse effects , Ginsenosides , Inflammation/metabolism , Liver/metabolism , Liver Diseases, Alcoholic/drug therapy , Liver Diseases, Alcoholic/metabolism , Mice , NF-kappa B/metabolism , Network Pharmacology
3.
J Agric Food Chem ; 70(36): 11236-11244, 2022 Sep 14.
Article in English | MEDLINE | ID: mdl-36063077

ABSTRACT

Alcoholic beverages are widely consumed all over the world, but continuous ethanol exposure leads to hepatic steatosis that, without proper treatment, will later develop into severe liver disorders. In this study, we investigated the potential protective effect of tangeretin, a flavonoid derived from citrus peel, against alcoholic fatty liver. The in vivo effects of tangeretin were analyzed by oral intake in a chronic-binge alcohol feeding C57BL/6j mouse model, while the underlying mechanism was explored by in vitro studies performed on ethanol-treated hepatic AML-12 cells. Ethanol feeding increased the serum alanine aminotransferase and aspartate aminotransferase levels, the liver weight, and the serum and liver triacylglycerol contents, whereas 20 and 40 mg/kg tangeretin treatment promoted a dose-dependent suppression of these effects. Interestingly, tangeretin prevented increases in the liver oxidative stress level and protected the hepatocyte mitochondria from ethanol-induced morphologic abnormalities. A mechanistic study showed that 20 µM tangeretin treatment activated mitophagy through an AMP-activated protein kinase (AMPK)-uncoordinated 51-like kinase 1 (Ulk1) pathway, thereby restoring mitochondria respiratory function and suppressing steatosis. By contrast, blocking the AMPK-Ulk1 pathway with compound C reversed the hepatoprotective effect of tangeretin. Overall, tangeretin activated mitophagy and protected against ethanol-induced hepatic steatosis through an AMPK-Ulk1-dependent mechanism.


Subject(s)
Fatty Liver, Alcoholic , Fatty Liver , AMP-Activated Protein Kinases/genetics , AMP-Activated Protein Kinases/metabolism , Animals , Ethanol/adverse effects , Ethanol/metabolism , Fatty Liver/chemically induced , Fatty Liver/drug therapy , Fatty Liver/genetics , Fatty Liver, Alcoholic/drug therapy , Fatty Liver, Alcoholic/genetics , Fatty Liver, Alcoholic/prevention & control , Flavones , Liver/metabolism , Mice , Mice, Inbred C57BL , Mitophagy
4.
Alcohol Clin Exp Res ; 46(8): 1515-1524, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35989585

ABSTRACT

BACKGROUND: Although recent literature provides promising support for the analgesic properties of alcohol, potential differences in alcohol analgesia as a function of chronic pain status are not well understood. Thus, this study examined chronic pain status as a potential moderator of alcohol analgesia and distinguished between multiple aspects of pain experience and sensitivity: pain threshold, pain intensity, pain unpleasantness, and perceived relief. METHODS: Social drinkers with (N = 19) and without (N = 29) chronic jaw pain completed two testing sessions in a counterbalanced order: alcohol (target BrAC = 0.08 g/dl) and placebo. In each, pressure algometry was performed at the insertion of the masseter. Alcohol analgesia was assessed by examining the main and interactive effects of beverage condition, pressure level (4, 5, or 6 pound-feet [lbf]), and chronic jaw pain status (chronic pain vs. pain-free control) on quantitative sensory testing measures and pain relief ratings following noxious stimuli. RESULTS: Analyses indicated significant increases in pain threshold and pain relief and reductions in pain unpleasantness and pain intensity, under the alcohol condition. Chronic pain participants demonstrated lower pain thresholds and greater pain intensity and pain unpleasantness ratings than controls. There were no interactive effects of alcohol and pain conditions on any pain measure. CONCLUSIONS: Findings provide experimental evidence of alcohol's analgesic and pain-relieving effects and suggest that these effects do not significantly differ by chronic pain status. Individuals, who self-medicate pain via alcohol consumption, irrespective of pain status, may be at increased risk to engage in hazardous drinking patterns and thus experience adverse alcohol-related consequences.


Subject(s)
Chronic Pain , Adult , Alcohol Drinking , Analgesics/pharmacology , Analgesics/therapeutic use , Chronic Pain/diagnosis , Chronic Pain/drug therapy , Ethanol/adverse effects , Humans , Pain Measurement , Pain Threshold
5.
Food Funct ; 13(18): 9285-9298, 2022 Sep 22.
Article in English | MEDLINE | ID: mdl-35968694

ABSTRACT

Chronic consumption of excess ethanol is one of the major risk factors for colorectal cancer (CRC), and the pathogenesis of ethanol-related CRC (ER-CRC) involves ethanol-induced oxidative-stress and inflammation in the colon and rectum, as well as gut leakiness. In this study, we hypothesised that oral administration of sesaminol, a sesame lignan, lowers the risk of ER-CRC because we found that it is a strong antioxidant with very low prooxidant activity. This hypothesis was examined using a mouse model, in which 2.0% v/v ethanol was administered ad libitum for 2 weeks with or without oral gavage with sesaminol (2.5 mg per day). Oral sesaminol administration suppressed the ethanol-induced colonic lesions and the ethanol-induced elevation of the colonic levels of oxidative stress markers (8-hydroxy-2'-deoxyguanosine, malondialdehyde, and 4-hydroxyalkenals). It consistently suppressed the chronic ethanol-induced expressions of cytochrome P450-2E1 and inducible nitric oxide synthase and upregulated heme oxygenase-1 expression, probably via the nuclear factor erythroid-derived 2-like 2 pathway in the mouse colon. Oral sesaminol administration also suppressed the chronic ethanol-induced elevation of colonic inflammation marker levels, such as those of tumour necrosis factor-α, interleukin-6, and monocyte chemoattractant protein-1, probably via the nuclear factor-kappa B pathway. Moreover, it prevented the chronic ethanol-induced gut leakiness by restoring tight junction proteins, giving rise to lower plasma endotoxin levels compared with those of ethanol-administered mice. All of these results suggest that dietary supplementation of sesaminol may lower the risk of ER-CRC by suppressing each of the above-mentioned steps in ER-CRC pathogenesis.


Subject(s)
Colitis , Lignans , 8-Hydroxy-2'-Deoxyguanosine , Administration, Oral , Antioxidants/metabolism , Chemokine CCL2/metabolism , Colitis/chemically induced , Colitis/drug therapy , Colitis/metabolism , Cytochrome P-450 CYP2E1/metabolism , Dioxoles , Endotoxins , Ethanol/adverse effects , Furans , Heme Oxygenase-1/metabolism , Humans , Inflammation/metabolism , Interleukin-6/genetics , Interleukin-6/metabolism , Malondialdehyde , Nitric Oxide Synthase Type II/genetics , Nitric Oxide Synthase Type II/metabolism , Oxidative Stress , Tight Junction Proteins/metabolism , Tumor Necrosis Factor-alpha/metabolism
6.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 47(7): 872-880, 2022 Jul 28.
Article in English, Chinese | MEDLINE | ID: mdl-36039583

ABSTRACT

OBJECTIVES: Osteonecrosis of the femoral head (ONFH), also known as vascular necrosis of the femoral head, is combined with lipid metabolism disorders in most patients. This study aims to explore the lipid metabolism profiles in different subtypes of ONFH. METHODS: The subjects were divided into an alcohol-induced osteonecrosis of the femoral head (AONFH) group, a steroid-induced osteonecrosis of the femoral head (SONFH) group, and a normal control (NC) group (n=16, 29, and 32, respectively). Ultra-performance liquid chromatography-mass spectrometry/mass spectrometry (UPLC-MS/MS) was used to detect the lipidomics analysis in the peripheral blood samples of subjects and identify the underlying biomarkers. The samples were preprocessed, the partial least squares discriminant analysis (PLS-DA) was adopted, and the variable importance for the projection (VIP) values were calculated to measure the expression pattern of each lipid metabolite and observe the influence and explanatory power of the expression pattern of each lipid metabolite on the classification and discrimination between the different groups. The lipid metabolites with fold change (FC)>2, P<0.05 and VIP>1 in the different groups were screened as differential lipids. Among them, the differential lipids co-existing in the AONFH group and the SONFH group were regarded as common differential lipids for ONFH, and the differential lipids that exist separately were regarded as specific differential lipids in the AONFH group or the SONFH group. Binary logistic regression was used to evaluate the diagnostic value of differential lipid metabolites on the basis of the receiver operator characteristic (ROC) curve analysis. Based on the disease stage information, the correlation between the differential lipids and the disease stage was analyzed in the AONFH group and the SONFH group. RESULTS: In this study, 1 358 lipid metabolites were detected in each plasma sample. Compared with the NC group, there were significant difference in the expression patterns of lipid metabolism profiles in the AONFH group and the SONFH group. A total of 62 and 64 differential lipid metabolites were screened in the AONFH and SONFH patients (FC>2, P<0.05, VIP>1) respectively, and these differential lipids were mainly up-regulated in the disease samples. Nine differential lipid metabolites were further identified, which were shared by the AONFH group and the SONFH group; the area under the curve (AUC) in 6 kinds of lipid components was greater than 0.7, including 1-myristoyl-2-docosahexaenoyl-sn-glycero-3-phosphocholine, hypoxanthin, serotonin, PE (19:0/22:5), PE (19:0/22:5), and cholest-5-en-3-yl beta-D-glucopyranosiduronic acid. Fifty-three specific differential lipid metabolites were identified in the AONFH group, and 55 specific differential lipid metabolites were identified in the SONFH group. The AUC in 6 kinds of lipid components was greater than 0.9, including 1D-myo-Inositol 1,2-cyclic phosphate, L-pyroglutamic acid, DL-carnitine, 8-amino-7-oxononanoic acid, Clobetasol, and presqualene diphosphate. In the AONFH group, there were 9 differential lipid metabolites related to the disease stages, including LPG 18:1, serotonin, PC (22:4e/23:0), PC (19:2/18:5), hypoxanthin, PE (18:1/20:3), LPE 18:1, 1-stearoyl-2-arachidonoyl-sn-glycerol, and PE (16:0/18:1); with AONFH disease progresses from I/II stages to III/IV stages, the relative content of these 9 differential lipid metabolites was increased. In the SONFH group, 8 differential lipid metabolites were found to be related to the stage of the disease, including TM6076000, 4-(1,1-dimethylpropyl)phenol, D-617, asarone, phenylac-gln-OH, creatine, leu-pro, and 8-amino-7-oxononanoic acid; and with the SONFH progressed from stage I/II to stage III/IV, the content of these 8 differential lipid metabolites were gradually increased. CONCLUSIONS: This study analyzes the characteristics of the plasma lipid metabolism profile in the AONFH and SONFH patients, and which identifies the differential lipid metabolites related to disease diagnosis and evaluation. These results provide evidence for exploring lipid metabolism alterations and the mining of novel lipid biomarkers for the ONFH.


Subject(s)
Femur Head Necrosis , Femur Head , Biomarkers , Chromatography, Liquid , Ethanol/adverse effects , Ethanol/metabolism , Femur Head/metabolism , Femur Head Necrosis/chemically induced , Humans , Lipid Metabolism , Lipids/adverse effects , Serotonin , Steroids/adverse effects , Steroids/metabolism , Tandem Mass Spectrometry
7.
Biomed Khim ; 68(4): 279-287, 2022 Aug.
Article in Russian | MEDLINE | ID: mdl-36005846

ABSTRACT

Nucleus accumbens (NAc) is the ventral part of the striatum of the brain; it is an important part of the mesolimbic pathway involved in the reward system that mediates the formation of various forms of addiction, in particular alcohol addiction. Neuroimaging data and in vitro studies indicate the development of a pronounced neurodegenerative process in the NAc, with long-term alcohol use, but the key mechanisms mediating this process remain unknown. In recent years, the attention of researchers has been focused on studying the system of Toll-like receptors (TLRs), the increased activity of which is clearly shown in the cerebral cortex and hippocampus during prolonged alcohol exposure, but there is a need to study the role of this system in other brain structures. In this study, we have shown that prolonged alcohol exposure (2 months) with moderate doses of ethanol (2 g/kg) promotes a pronounced increase in the expression of the Tlr4 gene and its endogenous ligand Hmgb1 in NAc during the period of alcohol withdrawal in rats. Injections of rifampicin (100 mg/kg) reduced the elevated expression level of Hmgb1, Tlr4, as well as pro-inflammatory cytokine genes (IL1ß, IL6), while the administration of the drug increased the reduced level of mRNA of anti-inflammatory cytokines (IL10, IL11).


Subject(s)
Alcoholism , HMGB1 Protein , Substance Withdrawal Syndrome , Alcoholism/drug therapy , Alcoholism/genetics , Animals , Brain , Ethanol/adverse effects , HMGB1 Protein/metabolism , Nucleus Accumbens/metabolism , Rats , Rifampin/pharmacology , Toll-Like Receptor 4/genetics
8.
Nutrients ; 14(14)2022 Jul 13.
Article in English | MEDLINE | ID: mdl-35889826

ABSTRACT

Prenatal alcohol exposure can disrupt the development of numerous systems, including the immune system. Indeed, alterations in cytokine levels may contribute to the neuropathological, behavioral, and cognitive problems, and other adverse outcomes observed in individuals with fetal alcohol spectrum disorders. Importantly, supplementation with the essential nutrient choline can improve performance in hippocampal-dependent behaviors; thus, the present study examined the effects of choline on plasma and hippocampal cytokines in adult rats exposed to ethanol in early development. From postnatal day (PD) 4-9 (third trimester equivalent), pups received ethanol (5.25 g/kg/day) or Sham intubations. Subjects were treated with choline chloride (100 mg/kg/day) or saline from PD10-30. On PD60, plasma and hippocampal tissue was collected before and after an immune challenge (lipopolysaccharide (LPS); 50 ug/kg). Prior to the immune challenge, ethanol-exposed subjects showed an overall increase in hippocampal pro-inflammatory cytokines, an effect mitigated by choline supplementation. In contrast, in the plasma, choline reduced LPS-related increases in pro-inflammatory markers, particularly in ethanol-exposed subjects. Thus, early choline supplementation may modify both brain and peripheral inflammation. These results suggest that early choline can mitigate some long-term effects of ethanol exposure on hippocampal inflammation, which may contribute to improved hippocampal function, and could also influence peripheral immune responses that may impact overall health.


Subject(s)
Choline , Ethanol , Prenatal Exposure Delayed Effects , Animals , Animals, Newborn , Choline/pharmacology , Cytokines , Dietary Supplements , Ethanol/adverse effects , Female , Hippocampus , Immunity , Inflammation , Lipopolysaccharides , Pregnancy , Rats
9.
J Clin Invest ; 132(14)2022 07 15.
Article in English | MEDLINE | ID: mdl-35838051

ABSTRACT

Intrahepatic neutrophil infiltration has been implicated in severe alcoholic hepatitis (SAH) pathogenesis; however, the mechanism underlying neutrophil-induced injury in SAH remains obscure. This translational study aims to describe the patterns of intrahepatic neutrophil infiltration and its involvement in SAH pathogenesis. Immunohistochemistry analyses of explanted livers identified two SAH phenotypes despite a similar clinical presentation, one with high intrahepatic neutrophils (Neuhi), but low levels of CD8+ T cells, and vice versa. RNA-Seq analyses demonstrated that neutrophil cytosolic factor 1 (NCF1), a key factor in controlling neutrophilic ROS production, was upregulated and correlated with hepatic inflammation and disease progression. To study specifically the mechanisms related to Neuhi in AH patients and liver injury, we used the mouse model of chronic-plus-binge ethanol feeding and found that myeloid-specific deletion of the Ncf1 gene abolished ethanol-induced hepatic inflammation and steatosis. RNA-Seq analysis and the data from experimental models revealed that neutrophilic NCF1-dependent ROS promoted alcoholic hepatitis (AH) by inhibiting AMP-activated protein kinase (a key regulator of lipid metabolism) and microRNA-223 (a key antiinflammatory and antifibrotic microRNA). In conclusion, two distinct histopathological phenotypes based on liver immune phenotyping are observed in SAH patients, suggesting a separate mechanism driving liver injury and/or failure in these patients.


Subject(s)
Hepatitis, Alcoholic , Liver Diseases, Alcoholic , Animals , Ethanol/adverse effects , Hepatitis, Alcoholic/genetics , Hepatitis, Alcoholic/metabolism , Inflammation/pathology , Liver/metabolism , Liver Diseases, Alcoholic/genetics , Liver Diseases, Alcoholic/metabolism , Mice , Mice, Inbred C57BL , Phenotype , Reactive Oxygen Species/metabolism
10.
Aten. prim. (Barc., Ed. impr.) ; 54(7): 102349, Jul 2022. tab
Article in Spanish | IBECS | ID: ibc-205882

ABSTRACT

La morbilidad asociada al consumo de alcohol incluye patología digestiva, psiquiátrica, neurológica, infecciosa, cáncer de diversos tipos, enfermedades cardiovasculares, lesiones intencionales, no intencionales, patología social y problemas familiares. Las evidencias más recientes no indican que el consumo «moderado» sea beneficioso para la salud. Por lo tanto, debe enfatizarse más bien la idea de evitar los consumos de riego y transmitir a los pacientes que lo más beneficioso para la salud sería no consumir alcohol o hacerlo en dosis de bajo riesgo. El instrumento más adecuado de cribado es el AUDIT-C. Las bases de la intervención breve consisten en estrategias cognitivo-conductuales y motivacionales. Hay que dar una información positiva sobre los beneficios de la moderación e informar sobre el peligro de la ingesta de alcohol. En fases precoces de la dependencia se contempla la oferta de tratamiento farmacológico de desintoxicación, deshabituación y seguimiento. Los casos más graves requieren coordinación con los servicios de adicciones. En España se ha podido comprobar que la intervención breve es efectiva y que disminuye el consumo 100 gramos de alcohol a la semana. Las estrategias comunitarias son el marco normativo adecuado para lograr los mejores resultados de la intervención breve. Estas deberán ir encaminadas a reducir la oferta y la disponibilidad para el consumo, mediante la adopción de medidas legislativas, de manera que se limite tanto la accesibilidad económica como la física. Por otra parte, habrá que implementar medidas para disminuir la demanda del alcohol mediante la educación para la salud a determinados grupos de riesgo.(AU)


Morbidity associated with alcohol consumption includes digestive, psychiatric, neurological, infectious disease, cancers of various types, cardiovascular disease, intentional injuries, unintentional injuries, social pathology, and family problems. The most recent evidence does not indicate that “moderate” consumption is beneficial to health. The most recent evidence indicates that “moderate” consumption is not beneficial to health. Therefore, the emphasis should be placed on avoiding risky drinking and advising patients that it would be in their best health interest to avoid alcohol or to drink alcohol at low-risk doses. The AUDIT-C is the most appropriate screening instrument. Cognitive-behavioural and motivational strategies form the basis of brief intervention. Positive information about the benefits of moderation and information about the dangers of alcohol intake should be given. In early stages of dependence, pharmacological treatment for detoxification, withdrawal and follow-up is considered. More serious cases require coordination with addiction services. In Spain, BI has proven effective and to reduce alcohol consumption by 100g/week. Community strategies are the appropriate policy framework to achieve the best results from brief intervention. They should aim to reduce the supply and availability for consumption by adopting legislative measures to limit both economic and physical accessibility. Furthermore, measures should be implemented to reduce the demand for alcohol through health education for specific risk groups.(AU)


Subject(s)
Mass Screening , Alcohol Drinking , Morbidity , Alcoholism/complications , Alcoholism/prevention & control , Ethanol/adverse effects , Spain , Primary Health Care
11.
Birth Defects Res ; 114(12): 611-630, 2022 07 15.
Article in English | MEDLINE | ID: mdl-35775613

ABSTRACT

BACKGROUND: Gestation alcohol consumption produces fetal growth restriction and malformations by affecting the embryo-fetal development. Recently a relationship between abnormal placentation and fetal malformation and intrauterine growth retardation has been suggested. However, the effects of perigestational alcohol ingestion up to early pregnancy on the placenta at term and its association with fetal abnormalities are little known. METHODS: In female mice, ethanol 10% in water was administered for 15 days previous and up to days 4 (D4), 8 (D8), or 10 (D10) of gestation (TF), and gestation continues without ethanol exposure. Control females (CF) received ethanol-free water. At day 18, feto-placental units and implantation sites were studied. RESULTS: TF had increased resorptions and only fetuses from D8-TF and D10-TF had significantly increased weights versus CF. D4 and D10-TF-placentas had significantly reduced weights. All TF had increased junctional zone (JZ) and reduced labyrinth (Lab) areas (PAS-histology and morphometry) compared with CF. Fetuses with mainly with craniofacial abnormalities and skeletal defects (Alizarin red staining), significantly increase; while the fetal bone density (alizarin color intensity, ImageJ) was reduced in D4, D8 and D10-TF versus CF. Although all TF-placentas were histo-structural affected, TF-abnormal fetuses had the most severe placental anomalies, with junctional abundant glycogenic cells into the labyrinth, disorganized labyrinthine vascularization with signs of leukocyte infiltrates and feto-maternal blood mix. CONCLUSIONS: Perigestational alcohol consumption up to early gestation induces at term fetal growth alterations, dysmorphology and defective skeleton, linked to deficient growth and abnormal morphogenesis of placenta, highlighting insight into the prenatal etiology of FASD.


Subject(s)
Placenta , Placentation , Alcohol Drinking/adverse effects , Animals , Ethanol/adverse effects , Female , Fetal Development , Fetal Growth Retardation/etiology , Humans , Mice , Placenta/pathology , Pregnancy , Water
12.
J Med Case Rep ; 16(1): 269, 2022 Jul 07.
Article in English | MEDLINE | ID: mdl-35799217

ABSTRACT

BACKGROUND: Ethanol dependence is associated with a discontinuation withdrawal delirium. Chlordiazepoxide is frequently successfully used in its treatment. CASE PRESENTATION: A 27-year-old, Caucasian female with ethanol dependence who had objective symptoms of withdrawal experienced worsening of her delirium after administration of chlordiazepoxide, but improved with lorazepam and cleared with discontinuation of benzodiazepine administration. CONCLUSIONS: Worsening of delirium appears to be related to the specific use of chlordiazepoxide, but the mechanism of this effect is not clear. While this case does not alter the standard care of ethanol dependence, it does alert clinicians that our treatment approach may not be fully benign.


Subject(s)
Alcoholism , Delirium , Substance Withdrawal Syndrome , Adult , Alcoholism/complications , Chlordiazepoxide , Delirium/chemically induced , Delirium/complications , Ethanol/adverse effects , Female , Humans , Substance Withdrawal Syndrome/drug therapy
13.
Front Immunol ; 13: 911951, 2022.
Article in English | MEDLINE | ID: mdl-35844518

ABSTRACT

Drinking alcohol, even in moderation, can affect the immune system. Studies have shown disproportionate effects of alcohol on circulating and tissue-resident myeloid cells (granulocytes, monocytes, macrophages, dendritic cells). These cells orchestrate the body's first line of defense against microbial challenges as well as maintain tissue homeostasis and repair. Alcohol's effects on these cells are dependent on exposure pattern, with acute drinking dampening but chronic drinking enhancing production of inflammatory mediators. Although chronic drinking is associated with heightened systemic inflammation, studies on tissue resident macrophage populations in several organs including the spleen, liver, brain, and lung have also shown compromised functional and metabolic capacities of these cells. Many of these effects are thought to be mediated by oxidative stress caused by alcohol and its metabolites which can directly impact the cellular epigenetic landscapes. In addition, since myeloid cells are relatively short-lived in circulation and are under constant repopulation from the bone marrow compartment, alcohol's effects on bone marrow progenitors and hematopoiesis are important for understanding the impact of alcohol systemically on these myeloid populations. Alcohol-induced disruption of progenitor, circulating, and tissue resident myeloid populations contribute to the increased susceptibility of patients with alcohol use disorders to viral and bacterial infections. In this review, we provide an overview of the impact of chronic alcohol consumption on the function of monocytes and macrophages in host defense, tissue repair and inflammation. We then summarize our current understanding of the mechanisms underlying alcohol-induced disruption and examine changes in transcriptome and epigenome of monocytes and mcrophages. Overall, chronic alcohol consumption leads to hyper-inflammation concomitant with decreased microbial and wound healing responses by monocytes/macrophages due to a rewiring of the epigentic and transcriptional landscape. However, in advanced alcoholic liver disease, myeloid cells become immunosuppressed as a response to the surrounding hyper-inflammatory milieu. Therefore, the effect of chronic alcohol on the inflammatory response depends on disease state and the immune cell population.


Subject(s)
Alcoholism , Graft vs Host Disease , Alcohol Drinking/adverse effects , Alcoholism/metabolism , Epigenesis, Genetic , Ethanol/adverse effects , Graft vs Host Disease/metabolism , Humans , Inflammation , Macrophages , Monocytes
14.
Sci Rep ; 12(1): 12569, 2022 Jul 22.
Article in English | MEDLINE | ID: mdl-35869160

ABSTRACT

The alcohol flushing response is experienced by 36-45% of East Asians after they consume a small amount of alcohol. Because individuals with this response are unable to metabolize the toxic acetaldehyde derived from alcohol effectively, the response offers a potential indicator of the health risks associated with alcohol intake. Depression is a major health problem linked to alcohol consumption; it might also be associated with the alcohol flushing response. Therefore, we examined the association between the alcohol flushing response and the risk of depression in the general population of South Korea. Our analysis included 139,380 participants and used data from the 2019 Korean Community Health Survey. Only current drinkers were considered in the analysis. The relationship between the alcohol flushing response and depression was evaluated by logistic regression analysis using SAS 9.4. Of the participants, more than one-third were current flushers; compared to never flushers, current flushers had a significantly greater risk of depression (adjusted odds ratio [AOR] 1.23, 95% confidence interval [CI] 1.12-1.34, P < 0.001). Former flushers did not exhibit a risk of depression. The risk of depression was significantly greater among alcohol flushers who drank < 15 g alcohol/day (< 5 g alcohol/day: AOR 1.20, 95% CI 1.07-1.35, P = 0.002; 5-14.9 g alcohol/day: AOR 1.39, 95% CI 1.13-1.70, P = 0.002). In conclusion, a large number of South Koreans experience the alcohol flushing response; compared with never flushers, current flushers are more likely to develop depression with a small dose of alcohol (< 15 g alcohol/day).


Subject(s)
Alcohol-Related Disorders , Depression , Alcohol Drinking/adverse effects , Alcohol Drinking/epidemiology , Alcohol-Related Disorders/complications , Depression/epidemiology , Ethanol/adverse effects , Flushing/chemically induced , Humans
15.
Biomed Pharmacother ; 152: 113278, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35709655

ABSTRACT

Colitis-associated cancer (CAC) is the colorectal cancer (CRC) subtype that is difficult to treat, and shows high mortality. The consumption of flavonoid-rich fructus aurantii extracts (FAE) has been associated with multiple beneficial effects including anti-inflammatory and anti-cancer properties, but the potential effects on the colitis-associated carcinogenesis have not been thoroughly investigated. Recent clinical data show that, as yet, few agents clearly inhibited CRC development in long-standing inflammatory bowel diseases. Here, we identified that FAE showed significant efficiency to inhibit HT-29 cell proliferation. The potential of FAE in vivo was further evaluated in an AOM/DSS-induced CAC mouse model. Intriguingly, FAE diminished the number of polyps in mice. Furthermore, FAE inhibited CAC by regulating the gene expression of Notch/ NF-κB/IL-1 signaling pathways. Collectively, these results were indicative of FAE has great potential in CAC prevention and treatment.


Subject(s)
Colitis , NF-kappa B , Animals , Carcinogenesis , Colitis/chemically induced , Colitis/complications , Colitis/drug therapy , Dextran Sulfate/toxicity , Disease Models, Animal , Ethanol/adverse effects , Interleukin-1 , Mice , Mice, Inbred C57BL , NF-kappa B/metabolism , Plant Extracts/adverse effects , Signal Transduction
16.
Ann Hepatol ; 27(5): 100729, 2022.
Article in English | MEDLINE | ID: mdl-35700935

ABSTRACT

INTRODUCTION: Radiofrequency ablation and percutaneous ethanol injection are important treatment modalities for hepatocellular carcinoma patients; Whether a combination treatment yields, additional benefit still remains controversial. METHODS: A systematic review and meta-analysis was concluded. Randomized controlled trials published before January 1, 2022, from PubMed, EMBASE, Scopus, and CNKI were searched. Studies were excluded when patients received different ablative treatment or had serious liver dysfunction. The risk of bias assessment was evaluated using the Cochrane Collaboration's tool. RESULTS: Ten studies, encompassing 854 patients, with histologically proven HCC were finally analyzed. The results demonstrated that patients who received RFA-PEI had slightly improvements in 1-year overall survival (OS) [risk ratio (RR): 1.11; 95% confidence interval (CI): 1.03, 1.19, I2 = 10%], 2-year OS (RR: 1.25; 95% CI: 1.12, 1.40, I2 = 0%), 3-year OS (RR: 1.42; 95% CI: 1.11, 1.83, I2 = 38%), 1-year local recurrence-free (LRF) proportion (RR: 1.2; 95% CI: 1.01, 1.42, I2 = 61%), and complete tumor necrosis (CTN) (RR: 1.32; 95% CI: 1.14, 1.53, I2 = 45%). Nevertheless, common complications, such as fever, were found to be significant (RR: 1.78, 95% CI: 1.13, 2.80). CONCLUSION: Despite RFA-PEI appearing to be superior for HCC patients with a compensated liver in terms of OS, current evidence contained moderate to significant heterogeneity, and it was difficult to draw a definite conclusion regarding the therapeutic management in terms of LRF and CTN.


Subject(s)
Carcinoma, Hepatocellular , Catheter Ablation , Liver Neoplasms , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/surgery , Catheter Ablation/adverse effects , Ethanol/adverse effects , Humans , Liver Neoplasms/drug therapy , Liver Neoplasms/surgery , Odds Ratio , Treatment Outcome
17.
J Mol Med (Berl) ; 100(7): 1071-1085, 2022 07.
Article in English | MEDLINE | ID: mdl-35708745

ABSTRACT

Myeloid differentiation primary response gene 88 (MyD88), an adaptor protein in the Toll-like receptors (TLRs) signalling pathway, is expressed in various liver cells including hepatocytes, Kupffer cells and hepatic stellate cells (HSCs). And yet, the functional role of MyD88 in HSCs is poorly elucidated in alcoholic fatty liver (AFL). Here, to study the functional role of MyD88 in HSCs and the molecular mechanism related to the development of AFL, chronic-binge ethanol mouse models were established in mice with specific MyD88 knockout in quiescent (MyD88GFAP-KO) and activated HSCs (MyD88SMA-KO), respectively. Our results clearly showed an elevated expression of MyD88 in liver tissues of ethanol treated mouse model which harbours the wild type. Intriguingly, ethanol treatment profoundly inhibited inflammation in both MyD88GFAP-KO and MyD88SMA-KO mice, but the suppression of lipogenesis was only observed in MyD88GFAP-KO mice. Molecularly, our study indicated that MyD88 induced osteopontin (OPN) secretion in HSCs, which consequently resulted in activation of AKT signalling pathway and accumulation of fat in hepatocytes. Additionally, our data also suggested that OPN promoted inflammation by activating p-STAT1. Thus, targeting MyD88 may be a potentially represent a promising strategy for the prevention and treatment of AFL. KEY MESSAGES: The expression of MyD88 in HSCs was significantly increased in ethanol-induced liver tissues of wild-type mice. MyD88 deficiency in quiescent HSCs inhibited inflammation and lipogenesis under the ethanol feeding condition. MyD88 deficiency in activated HSCs only inhibited inflammation under the ethanol feeding condition. MyD88 promoted the OPN secretion of HSCs, which further activated the AKT signalling pathway of hepatocytes and upregulated lipogenic gene expression to promote fat accumulation. OPN also promotes inflammation by activating p-STAT1.


Subject(s)
Fatty Liver, Alcoholic , Hepatic Stellate Cells , Animals , Disease Models, Animal , Ethanol/adverse effects , Fatty Liver, Alcoholic/genetics , Fatty Liver, Alcoholic/metabolism , Hepatic Stellate Cells/metabolism , Inflammation/metabolism , Liver/metabolism , Liver Cirrhosis/metabolism , Mice , Mice, Inbred C57BL , Mice, Knockout , Myeloid Differentiation Factor 88/genetics , Primary Immunodeficiency Diseases , Proto-Oncogene Proteins c-akt/metabolism
18.
J Cardiovasc Electrophysiol ; 33(8): 1897-1900, 2022 08.
Article in English | MEDLINE | ID: mdl-35695797

ABSTRACT

An 80-year-old man underwent catheter ablation for atrial tachycardia (AT), which developed after catheter ablation for atrial fibrillation. The AT was diagnosed as dual-loop tachycardia, which included peri-mitral and roof-dependent ATs. An ethanol infusion into the vein of Marshall resulted in left phrenic nerve paralysis. During the procedure, the phrenic nerve paralysis was completely relieved.


Subject(s)
Atrial Fibrillation , Catheter Ablation , Pulmonary Veins , Tachycardia, Supraventricular , Aged, 80 and over , Atrial Fibrillation/diagnosis , Atrial Fibrillation/surgery , Catheter Ablation/adverse effects , Catheter Ablation/methods , Ethanol/adverse effects , Humans , Male , Paralysis/chemically induced , Paralysis/diagnosis , Phrenic Nerve , Pulmonary Veins/surgery , Tachycardia/surgery
19.
J Med Toxicol ; 18(3): 198-204, 2022 07.
Article in English | MEDLINE | ID: mdl-35668289

ABSTRACT

INTRODUCTION: Phenobarbital is frequently used to manage severe alcohol withdrawal. The purpose of this study was to compare the incidence of mechanical ventilation in patients with benzodiazepine-resistant alcohol withdrawal between front-loaded and low-intermittent phenobarbital dosing strategies. METHODS: In this retrospective before-after study, we analyzed patients that received phenobarbital for severe alcohol withdrawal syndrome in a tertiary medical ICU. Patients received low-intermittent phenobarbital doses (260 mg intravenous push × 1 followed by 130 mg intravenous push every 15 min as needed) from January  2013 to July 2015, and front-loaded phenobarbital doses (10 mg/kg intravenous infusion over 30 min) from July 2015 to January 2017. RESULTS: In total, 87 patients met inclusion criteria for this study: 41 received low-intermittent phenobarbital and 46 received front-loaded phenobarbital). The incidence of mechanical ventilation was 13 (28%) in the front-loaded dosing group vs. 26 (63%) in the low-intermittent dosing group (odds ratio 4.4 [95% CI 1.8-10.9]). The cumulative dose of phenobarbital administered and serum phenobarbital levels were similar between both groups, although the front-loaded group had significantly lower benzodiazepine requirements than the low-intermittent group (median 86 mg [IQR 24-197] vs. 228 mg [115-298], P < 0.01) and reduced need for any continuous sedative infusion (OR 7.7 [95% CI 1.6-27], P < 0.01). There was no difference in respiratory failure or hypotension. CONCLUSIONS: Front-loaded phenobarbital dosing, when compared to low-intermittent phenobarbital dosing, for benzodiazepine-resistant alcohol withdrawal was associated with significantly lower mechanical ventilation incidence and continuous sedative use.


Subject(s)
Alcohol Withdrawal Delirium , Alcoholism , Substance Withdrawal Syndrome , Alcohol Withdrawal Delirium/diagnosis , Alcohol Withdrawal Delirium/drug therapy , Alcoholism/drug therapy , Benzodiazepines/adverse effects , Ethanol/adverse effects , Humans , Hypnotics and Sedatives/adverse effects , Length of Stay , Phenobarbital/adverse effects , Retrospective Studies , Substance Withdrawal Syndrome/drug therapy
20.
J Pediatr Gastroenterol Nutr ; 75(3): 304-307, 2022 Sep 01.
Article in English | MEDLINE | ID: mdl-35675704

ABSTRACT

This was a retrospective study that compared outcomes in pediatric intestinal failure (IF) patients that were switched from ethanol lock therapy (ELT) to sodium bicarbonate lock therapy (SBLT). The primary outcome was rate of catheter-related blood stream infections (CRBSI). The secondary outcomes were number of hospitalizations, emergency room (ER) visits, central venous catheter (CVC)-related complications. In 4 patients, median rates of CRBSI were 2.77 (interquartile range [IQR] 0.6-5.6) on ELT versus 0 on SBLT per 1000 catheter days ( P = 0.17). The median rates of hospitalizations and ER visits for CVC-related complications were 6.1 (IQR 3.2-10.2) on ELT versus 0 on SBLT (IQR 0-0; P = 0.11) and 2.8 (IQR 2-3.6) on ELT versus 1.8 (IQR 0-3.7) on SBLT per 1000 catheter days ( P = 0.50), respectively. Rates of CVC-related complications were similar. No adverse events were reported. SBLT may be safe and effective for pediatric IF.


Subject(s)
Bacteremia , Catheter-Related Infections , Catheterization, Central Venous , Central Venous Catheters , Intestinal Failure , Bacteremia/chemically induced , Catheter-Related Infections/prevention & control , Catheterization, Central Venous/adverse effects , Child , Ethanol/adverse effects , Humans , Pilot Projects , Retrospective Studies , Sodium Bicarbonate/therapeutic use
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