Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 8.913
Filtrar
1.
Drug Alcohol Depend ; 245: 109830, 2023 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-36907121

RESUMO

RATIONALE: Alcohol effects on social cognition have been studied by measuring facial emotion recognition, empathy, Theory of Mind (ToM) and other forms of information processing. OBJECTIVES: Using the PRISMA guidelines, we reviewed experimental studies that examined acute effects of alcohol on social cognition. METHODS: Scopus, PsycInfo, PubMed, and Embase were searched between July 2020 - January 2023. The PICO strategy was used for identifying participants, interventions, comparators, and outcomes. Participants (N = 2330) were adult social alcohol users. Interventions consisted of acute alcohol administration. Comparators included placebo or the lowest alcohol dose. Outcome variables were grouped into three themes: facial processing, empathy and ToM, and perceptions of inappropriate sexual behavior. RESULTS: A total of 32 studies were reviewed. Studies measuring facial processing (67%) often found no effects of alcohol on the recognition of specific emotions, facilitated emotion recognition at lower doses and worsened emotion recognition at higher doses. In studies measuring empathy or ToM (24%), lower doses were more likely to lead to improvements while higher doses were generally impairing. Within the third group of studies (9%), moderate to high alcohol doses made it more difficult to perceive sexual aggression accurately. CONCLUSIONS: Lower alcohol doses might sometimes help facilitate social cognition, but most data were in line with the idea that alcohol tends to worsen social cognition, particularly at higher doses. Future studies might focus on examining other moderators of the effects of alcohol on social cognition, particularly interpersonal characteristics such as trait emotional empathy, and participant and target gender.


Assuntos
Cognição Social , Teoria da Mente , Adulto , Humanos , Emoções , Empatia , Cognição , Etanol/efeitos adversos
2.
J Wound Care ; 32(3): i-xiii, 2023 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-36930190

RESUMO

Objective: The aim of this study was to examine the in vivo wound healing potential of Salvia huberi Hedge (endemic to Turkey) on excision and incision wound models in diabetic rats. Method: Male Wistar albino rats, 3-4 months old and weighing 180-240g were used. The animals were randomly divided into five groups including Control, Vehicle and Fito reference, and two different concentrations (0.5% and 1% weight/weight (w/w)) of ethanol extract of Salvia huberi were investigated in both wound models on streptozocin-induced diabetic rats using macroscopic, biomechanical, biochemical, histopathological, genotoxic and gene expression methods over both seven and 14 days. Fito cream (Tripharma Drug Industry and Trade Inc., Turkey) was used as the reference drug. Results: A total of 60 rats were used in this study. Salvia huberi ointments at 0.5% and 1% (w/w) concentrations and Fito cream showed 99.3%, 99.4% and 99.1% contraction for excision wounds, and 99.9%, 97.0% and 99% contraction for incision wounds, respectively. In Salvia huberi ointments and Fito cream groups, re-epithelialisation increased dramatically by both day 7 and day 14 (p<0.05). By day 14, low hydroxyproline and malondialdehyde (MDA) levels, and high glutathione (GSH) levels were observed in the Salvia huberi ointment groups. After two application periods, damaged cell percent and genetic damage index values and micronucleus frequency of Salvia huberi ointment treatment groups were lower than Control and Vehicle groups (p<0.001). A growth factor expression reached a high level by day 7 in the Control group; in Salvia huberi-treated groups it was decreased. Conclusion: The study showed that application of Salvia huberi ointments ameliorated the healing process in diabetic rats with excisional and incisional wounds and may serve as a potent healing agent.


Assuntos
Diabetes Mellitus Experimental , Salvia , Ferida Cirúrgica , Masculino , Animais , Ratos , Estreptozocina/efeitos adversos , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/induzido quimicamente , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Pomadas/uso terapêutico , Ratos Wistar , Cicatrização , Etanol/efeitos adversos , Ferida Cirúrgica/tratamento farmacológico
3.
J Wound Care ; 32(Sup3a): i-xiii, 2023 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-36930535

RESUMO

Objective: The aim of this study was to examine the in vivo wound healing potential of Salvia huberi Hedge (endemic to Turkey) on excision and incision wound models in diabetic rats. Method: Male Wistar albino rats, 3-4 months old and weighing 180-240g were used. The animals were randomly divided into five groups including Control, Vehicle and Fito reference, and two different concentrations (0.5% and 1% weight/weight (w/w)) of ethanol extract of Salvia huberi were investigated in both wound models on streptozocin-induced diabetic rats using macroscopic, biomechanical, biochemical, histopathological, genotoxic and gene expression methods over both seven and 14 days. Fito cream (Tripharma Drug Industry and Trade Inc., Turkey) was used as the reference drug. Results: A total of 60 rats were used in this study. Salvia huberi ointments at 0.5% and 1% (w/w) concentrations and Fito cream showed 99.3%, 99.4% and 99.1% contraction for excision wounds, and 99.9%, 97.0% and 99% contraction for incision wounds, respectively. In Salvia huberi ointments and Fito cream groups, re-epithelialisation increased dramatically by both day 7 and day 14 (p<0.05). By day 14, low hydroxyproline and malondialdehyde (MDA) levels, and high glutathione (GSH) levels were observed in the Salvia huberi ointment groups. After two application periods, damaged cell percent and genetic damage index values and micronucleus frequency of Salvia huberi ointment treatment groups were lower than Control and Vehicle groups (p<0.001). A growth factor expression reached a high level by day 7 in the Control group; in Salvia huberi-treated groups it was decreased. Conclusion: The study showed that application of Salvia huberi ointments ameliorated the healing process in diabetic rats with excisional and incisional wounds and may serve as a potent healing agent.


Assuntos
Diabetes Mellitus Experimental , Salvia , Ferida Cirúrgica , Masculino , Animais , Ratos , Estreptozocina/efeitos adversos , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/induzido quimicamente , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Pomadas/uso terapêutico , Ratos Wistar , Cicatrização , Etanol/efeitos adversos , Ferida Cirúrgica/tratamento farmacológico
4.
Biomaterials ; 295: 122049, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36827892

RESUMO

Alcohol-associated liver disease (ALD) and its complications are significant health problems worldwide. Several pathways in ALD are influenced by alcohol that drives inflammation, fatty acid metabolism, and fibrosis. Although miR-96 has become a key regulator in several liver diseases, its function in ALD remains unclear. In contrast, sonic hedgehog (SHH) signaling has a well-defined role in liver disease through influencing the activation of hepatic stellate cells (HSCs) and the inducement of liver fibrosis. In this study, we investigated the expression patterns of miR-96 and Hh molecules in mouse and human liver samples. We showed that miR-96 and Shh were upregulated in ethanol-fed mice. Furthermore, alcoholic hepatitis (AH) patient specimens also showed upregulated FOXO3a, TGF-ß1, SHH, and GLI2 proteins. We then examined the effects of Hh inhibitor MDB5 and anti-miR-96 on inflammatory and extracellular matrix (ECM)-related genes. We identified FOXO3 and SMAD7 as direct target genes of miR-96. Inhibition of miR-96 decreased the expression of these genes in vitro in AML12 cells, HSC-T6 cells, and in vivo in ALD mice. Furthermore, MDB5 decreased HSCs activation and the expression of ECM-related genes, such as Gli1, Tgf-ß1, and collagen. Lipid nanoparticles (LNPs) loaded with the combination of MDB5, and anti-miR-96 ameliorated ALD in mice. Our study demonstrated that this combination therapy could serve as a new therapeutic target for ALD.


Assuntos
MicroRNAs , Fator de Crescimento Transformador beta1 , Animais , Humanos , Camundongos , Antagomirs/farmacologia , Etanol/efeitos adversos , Proteínas Hedgehog/metabolismo , Fígado/patologia , Cirrose Hepática/tratamento farmacológico , MicroRNAs/genética , MicroRNAs/metabolismo , Fator de Crescimento Transformador beta1/metabolismo
5.
Food Funct ; 14(3): 1750-1760, 2023 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-36727425

RESUMO

Various studies have reported that Noni shows various health effects. This study aimed to assess the ability of Noni fruit extract to serve as a single active functional ingredient for the alleviation of hangover symptoms in Sprague Dawley rats and healthy subjects in a single-dose, randomized, double-blind, crossover, placebo-controlled study. The rats were orally administered Noni fruit extract at 50 or 100 mg per kg body weight (B.W.) and HOVENIA. The blood ethanol (EtOH) and acetaldehyde concentrations were significantly lower in the 100 mg per kg B.W. group than in the EtOH group. Alcohol dehydrogenase and aldehyde dehydrogenase activity tended to increase in the 100 mg kg-1 B.W. group. In the human study, 30 subjects received either a placebo or Noni fruit extract (1 g). The Noni fruit extract group showed significantly faster time point at which the maximum concentration (Tmax) of alcohol than in the placebo group. In addition, blood acetaldehyde levels and diarrhea at 40 and 720 min after alcohol intake and the area under the curve between 40 and 60 min of acetaldehyde were significantly decreased in the Noni fruit extract group compared to the placebo group. According to the QUalitative INteraction Trees, subjects who were ≤36 years old who consumed more alcohol (>15 drinks per week) and had a higher total hangover score (>27.5 and 33) presented significantly lower blood acetaldehyde levels and less severe hangover symptoms. These results indicate that Noni fruit extract has the potential to improve hangover symptoms by decreasing alcohol and acetaldehyde levels.


Assuntos
Intoxicação Alcoólica , Morinda , Extratos Vegetais , Adulto , Animais , Humanos , Ratos , Acetaldeído , Intoxicação Alcoólica/tratamento farmacológico , Etanol/efeitos adversos , Frutas , Ratos Sprague-Dawley , Extratos Vegetais/uso terapêutico
6.
Pharmacol Rev ; 75(2): 380-396, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36781218

RESUMO

Studies universally find early age of drinking onset is linked to lifelong risks of alcohol problems and alcohol use disorder (AUD). Assessment of the lasting effect of drinking during adolescent development in humans is confounded by the diversity of environmental and genetic factors that affect adolescent development, including emerging personality disorders and progressive increases in drinking trajectories into adulthood. Preclinical studies using an adolescent intermittent ethanol (AIE) exposure rat model of underage binge drinking avoid the human confounds and support lifelong changes that increase risks. AIE increases adult alcohol drinking, risky decision-making, reward-seeking, and anxiety as well as reductions in executive function that all increase risks for the development of an AUD. AIE causes persistent increases in brain neuroimmune signaling high-mobility group box 1 (HMGB1), Toll-like receptor, receptor for advanced glycation end products, and innate immune genes that are also found to be increased in human AUD brain. HMGB1 is released from cells by ethanol, both free and within extracellular vesicles, that act on neurons and glia, shifting transcription and cellular phenotype. AIE-induced decreases in adult hippocampal neurogenesis and loss of basal forebrain cholinergic neurons are reviewed as examples of persistent AIE-induced pathology. Both are prevented and reversed by anti-inflammatory and epigenetic drugs. Findings suggest AIE-increased HMGB1 signaling induces the RE-1 silencing transcript blunting cholinergic gene expression, shifting neuronal phenotype. Inhibition of HMGB1 neuroimmune signaling, histone methylation enzymes, and galantamine, the cholinesterase inhibitor, both prevent and reverse AIE pathology. These findings provide new targets that may reverse AUD neuropathology as well as other brain diseases linked to neuroimmune signaling. SIGNIFICANCE STATEMENT: Adolescent underage binge drinking studies find that earlier adolescent drinking is associated with lifelong alcohol problems including high levels of lifetime alcohol use disorder (AUD). Preclinical studies find the underage binge drinking adolescent intermittent ethanol (AIE) model causes lasting changes in adults that increase risks of developing adult alcohol problems. Loss of hippocampal neurogenesis and loss of basal forebrain cholinergic neurons provide examples of how AIE-induced epigenetic and neuroimmune signaling provide novel therapeutic targets for adult AUD.


Assuntos
Alcoolismo , Consumo Excessivo de Bebidas Alcoólicas , Proteína HMGB1 , Consumo de Álcool por Menores , Adolescente , Animais , Humanos , Ratos , Consumo de Bebidas Alcoólicas , Alcoolismo/tratamento farmacológico , Alcoolismo/genética , Alcoolismo/patologia , Consumo Excessivo de Bebidas Alcoólicas/genética , Consumo Excessivo de Bebidas Alcoólicas/metabolismo , Consumo Excessivo de Bebidas Alcoólicas/patologia , Epigênese Genética , Etanol/efeitos adversos , Proteína HMGB1/genética , Proteína HMGB1/metabolismo
7.
Mol Hum Reprod ; 29(2)2023 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-36637195

RESUMO

Increasingly, couples struggling with fertility turn to assisted reproductive techniques, including IVF, to have children. Despite the demonstrated influence of periconception male health and lifestyle choices on offspring development, studies examining IVF success rates and child health outcomes remain exclusively focused on maternal factors. Using a physiologically relevant mouse model, we tested the hypothesis that chronic paternal preconception alcohol intake adversely affects IVF success and negatively impacts IVF offspring fetoplacental growth. Using a voluntary, binge-like mouse model, we exposed sexually mature C57BL/6J males to three preconception treatments (0% (Control), 6% EtOH or 10% EtOH) for 6 weeks, isolated and cryopreserved caudal sperm from treated males, and then used these samples to fertilize oocytes before assessing IVF embryo developmental outcomes. We found that preconception paternal alcohol use reduced IVF embryo survival and pregnancy success rates in a dose-dependent manner, with the pregnancy success rate of the 10% EtOH treatment falling to half those of the Controls. Mechanistically, we found that preconception paternal alcohol exposure disrupts embryonic gene expression, including Fgf4 and Egfr, two critical regulators of trophectoderm stem cell growth and placental patterning, with lasting impacts on the histological organization of the late-term placenta. The changes in placental histoarchitecture were accompanied by altered regulation of pathways controlling mitochondrial function, oxidative phosphorylation and some imprinted genes. Our studies indicate that male alcohol use may significantly impede IVF success rates, increasing the couple's financial burden and emotional stress, and highlights the need to expand prepregnancy messaging to emphasize the reproductive dangers of alcohol use by both parents.


Assuntos
Etanol , Fertilização In Vitro , Exposição Paterna , Taxa de Gravidez , Animais , Feminino , Masculino , Camundongos , Gravidez , Camundongos Endogâmicos C57BL , Placenta , Sêmen , Etanol/efeitos adversos
8.
Artigo em Inglês | MEDLINE | ID: mdl-36690322

RESUMO

Alcohol abuse and its related diseases are the major risk factors for human health. Alcohol-related liver disease (ALD) is a leading cause of morbidity and mortality worldwide. Although the mechanism of ALD has been widely investigated, liver metabolites associated with long-term alcohol intake-induced hepatic steatosis have not been well explored. In this study, we aimed to investigate the role and mechanisms of 1-methylnicotinamide (1-MNA), a metabolite during nicotinamide adenine dinucleotide (NAD+) metabolism, in the pathogenesis of ALD. C57BL/6 wild-type mice were subjected to chronic alcohol feeding with or without 1-MNA (50 mg/kg/day). Our data showed that 1-MNA administration significantly enhanced chronic alcohol consumption-induced hepatic steatosis. Mechanistic studies revealed that alcohol-increased hepatic protein levels of sterol regulatory element-binding transcription factor (SREBP-1c), a key enzyme that regulates lipid lipogenesis, were enhanced in mice administered with 1-MNA, regardless of alcohol feeding. Consistently, alcohol-increased mRNA and protein levels of hepatic diacylglycerol o-acyltransferase 2 (DGAT2) and very low-density lipoprotein receptor (VLDLR) were also exacerbated by 1-MNA administration. Alcohol-induced hepatic endoplasmic reticulum (ER) stress was enhanced by 1-MNA administration, which was evidenced by increased protein levels of binding immunoglobulin protein (BIP), phosphorylated- protein kinase r-like ER kinase (PERK), activating transcription factor 4 (ATF4), and C/EBP-homologous protein (CHOP) in the mouse liver. Overall, this study demonstrated that 1-MNA serves as a pathogenic factor in the development of ALD. Targeting liver 1-MNA levels may serve as a promising therapeutic approach for improving hepatic steatosis in ALD.


Assuntos
Fígado Gorduroso Alcoólico , Fígado Gorduroso , Animais , Camundongos , Doença Crônica , Etanol/efeitos adversos , Fígado Gorduroso/induzido quimicamente , Fígado Gorduroso Alcoólico/genética , Camundongos Endogâmicos C57BL , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo
9.
Hepatol Commun ; 7(2): e0029, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36706195

RESUMO

Chronic alcohol consumption is associated with intestinal fungal dysbiosis, yet we understand little about how alterations of intestinal fungi (mycobiota) contribute to the pathogenesis of alcohol-associated liver disease. By reanalyzing internal transcribed spacer 2 amplicon sequencing of fecal samples from a cohort of 66 patients with alcohol use disorder for presence (as opposed to relative abundance) of fungal species, we observed that the presence of Malassezia restricta was associated with increased markers of liver injury. M. restricta exacerbates ethanol-induced liver injury both in acute binge and chronic ethanol-feeding models in mice. Using bone marrow chimeric mice, we found that the disease exacerbating effect by M. restricta was mediated by C-type lectin domain family 4, member N on bone marrow-derived cells. M. restricta induces inflammatory cytokines and chemokines in Kupffer cells through C-type lectin domain family 4, member N signaling. Targeting fungal pathobionts might be a therapeutic strategy for alcohol-associated liver disease.


Assuntos
Doença Hepática Crônica Induzida por Substâncias e Drogas , Hepatopatias Alcoólicas , Animais , Camundongos , Etanol/efeitos adversos , Hepatopatias Alcoólicas/microbiologia , Lectinas Tipo C/genética
10.
Int J Mol Sci ; 24(2)2023 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-36675170

RESUMO

Binge Drinking (BD) corresponds to episodes of ingestion of large amounts of ethanol in a short time, typically ≤2 h. BD occurs across all populations, but young and sports-related people are especially vulnerable. However, the short- and long-term effects of episodic BD on skeletal muscle function have been poorly explored. Young rats were randomized into two groups: control and episodic Binge-Like ethanol protocol (BEP) (ethanol 3 g/kg IP, 4 episodes of 2-days ON-2-days OFF paradigm). Muscle function was evaluated two weeks after the last BEP episode. We found that rats exposed to BEP presented decreased muscle strength and increased fatigability, compared with control animals. Furthermore, we observed that skeletal muscle from rats exposed to BEP presented muscle atrophy, evidenced by reduced fiber size and increased expression of atrophic genes. We also observed that BEP induced fibrotic and inflammation markers, accompanied by mislocalization of nNOSµ and high levels of protein nitration. Our findings suggest that episodic binge-like ethanol exposure alters contractile capacity and increases fatigue by mechanisms involving atrophy, fibrosis, and inflammation, which remain for at least two weeks after ethanol clearance. These pathological features are common to several neuromuscular diseases and might affect muscle performance and health in the long term.


Assuntos
Consumo Excessivo de Bebidas Alcoólicas , Etanol , Ratos , Animais , Etanol/efeitos adversos , Etanol/metabolismo , Músculo Esquelético/metabolismo , Inflamação/metabolismo , Atrofia Muscular/metabolismo , Força Muscular , Fibrose , Consumo Excessivo de Bebidas Alcoólicas/metabolismo
11.
Drug Alcohol Depend ; 242: 109736, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36516550

RESUMO

BACKGROUND: Prenatal cocaine exposure (PCE) has been associated with child and adolescent externalizing behaviors and early substance use, yet few studies investigated its association with substance use disorder (SUD) in emerging adults. The present study examined the association of PCE with SUD in emerging adulthood, and whether childhood externalizing behaviors and adolescent substance use mediated the relationship. METHODS: Participants were 367 (187 PCE; 53% female) adults at age 21, primarily urban African American who were recruited at birth. PCE and exposure to alcohol, tobacco, and marijuana were determined using biologic assays for drug metabolites and/or maternal self-report at birth. Offspring externalizing problems were assessed using the Youth Self-Report at age 12, substance use and substance use-related problems via biologic assays and/or self-report at age 15, and SUD determined using DSM-5 diagnostic criteria at age 21. RESULTS: About 32.3% of the emerging adults were determined to have marijuana use disorder, 30.3% tobacco use disorder, and 15.5% alcohol use disorder. PCE was related to greater externalizing behaviors at age 12 (ß = 0.12, p = .042), which in turn was related to SUD (ß = 0.22, p = .008). PCE was also related to substance use, mainly marijuana, at age 15 (ß = 0.22, p = .011), which was related to SUD (ß = 0.51, p < .001). Total indirect effects including these two pathways were significant (ß = 0.19, p = .002). CONCLUSIONS: PCE may increase risk for SUD in emerging adulthood through childhood externalizing behaviors and adolescent substance use.


Assuntos
Efeitos Tardios da Exposição Pré-Natal , Transtornos Relacionados ao Uso de Substâncias , Feminino , Humanos , Masculino , Gravidez , Adulto Jovem , Consumo de Bebidas Alcoólicas/epidemiologia , Cannabis/efeitos adversos , Cocaína/efeitos adversos , Etanol/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/epidemiologia
12.
Europace ; 25(2): 441-449, 2023 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-36504017

RESUMO

OBJECTIVE: This study sought to assess the effect of ethanol infusion into the vein of Marshall (EIVOM) on the acute success of left pulmonary vein (LPV) isolation in persistent atrial fibrillation (PeAF). METHODS AND RESULTS: A total of 313 patients with drug-resistant PeAF were enrolled (135 in Group 1 and 178 in Group 2). In Group 1, EIVOM was firstly performed, followed by radiofrequency ablation (RFA) including bilateral pulmonary vein isolation (PVI) and linear ablation at roofline, cavotricuspid isthmus, and mitral isthmus (MI). In Group 2, PVI and linear ablations were completed with RFA. First-pass isolation of the LPV was achieved in 119 (88.1%) and 132 (74.2%) patients in Groups 1 and 2, respectively (P = 0.002). The rate of acute pulmonary vein reconnection (PVR) was significantly lower in Group 1 (9.6% vs. 22.5%, P = 0.003). About half of acute PVR occurred in the carina with or without EIVOM. CONCLUSION: EIVOM is effective in achieving a higher first-pass isolation and a lower acute PVR of LPV in PeAF.


Assuntos
Fibrilação Atrial , Ablação por Cateter , Veias Pulmonares , Ablação por Radiofrequência , Humanos , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Veias Pulmonares/cirurgia , Etanol/efeitos adversos , Ablação por Cateter/efeitos adversos , Ablação por Cateter/métodos , Resultado do Tratamento , Recidiva
13.
Alcohol Clin Exp Res ; 47(2): 219-239, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36529893

RESUMO

BACKGROUND: People with alcohol use disorder (AUD) may be at higher risk for COVID-19. Angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) are required for cellular entry by SARS-CoV-2, but information on their expression in specific brain regions after alcohol exposure is limited. We sought to clarify how chronic alcohol exposure affects ACE2 expression in monoaminergic brainstem circuits and other putative SARS-CoV-2 entry points. METHODS: Brains were examined for ACE2 using immunofluorescence after 4 weeks of chronic intermittent ethanol (CIE) vapor inhalation. We also examined TMPRSS2, Cathepsin L, and ADAM17 by Western blot and RAS pathway mediators and pro-inflammatory markers via RT-qPCR. RESULTS: ACE2 was increased in most brain regions following CIE including the olfactory bulb (OB), hypothalamus (HT), raphe magnus (RMG), raphe obscurus (ROB), locus coeruleus (LC), and periaqueductal gray (PAG). We also observed increased colocalization of ACE2 with monoaminergic neurons in brainstem nuclei. Moreover, soluble ACE2 (sACE2) was elevated in OB, HT, and LC. The increase in sACE2 in OB and HT was accompanied by upregulation of ADAM17, an ACE2 sheddase, while TMPRSS2 increased in HT and LC. Cathepsin L, an endosomal receptor involved in viral entry, was also increased in OB. Alcohol can increase Angiotensin II, which triggers a pro-inflammatory response that may upregulate ACE2 via activation of RAS pathway receptors AT1R/AT2R. ACE2 then metabolizes Angiotensin II to Angiotensin (1-7) and provokes an anti-inflammatory response via MAS1. Accordingly, we report that AT1R/AT2R mRNA decreased in OB and increased in the LC, while MAS1 mRNA increased in both OB and LC. Other mRNAs for pro-inflammatory markers were also dysregulated in OB, HT, raphe, and LC. CONCLUSIONS: Our results suggest that alcohol triggers a compensatory upregulation of ACE2 in the brain due to disturbed RAS and may increase the risk or severity of SARS-CoV-2 infection.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Angiotensina II/metabolismo , Enzima de Conversão de Angiotensina 2/metabolismo , Encéfalo/metabolismo , Catepsina L/metabolismo , Etanol/efeitos adversos , Peptidil Dipeptidase A/genética , Peptidil Dipeptidase A/metabolismo , RNA Mensageiro , SARS-CoV-2/genética , SARS-CoV-2/metabolismo
14.
Behav Brain Res ; 438: 114156, 2023 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-36243244

RESUMO

There are growing evidence indicating that the adolescent brain is persistently affected by the use of psychostimulant agents. In this regard, alcohol drinking has become rather common among the adolescents in many societies during the last decade. It is currently well known that long-term ethanol exposure deteriorates various cognitive functions such as learning and memory. Mechanistically, these adverse effects have been shown to be mediated by oxidative damage to central nervous system. On the other hand, Vit-B12 is known to improve cognitive performance by suppression of oxidative parameters. Thus, in the present study we aimed to test whether treatment by Vit-B12 could prevent ethanol-induced complications in mice using behavioral and biochemical methods. Different groups of male Syrian mice received ethanol, ethanol+Vit-B12, Vit-B12 alone, or saline during adolescence and then learning and memory functions were assessed by Morris water maze (MWM) and Passive Avoidance (PA) tests. Finally, mice were sacrificed for measurement of biochemical factors. Results indicated that, adolescent ethanol intake impairs learning and memory function through exacerbation of oxidative stress and Vit-B12 treatment improves these complications by re-establishment of oxidant/anti-oxidant balance in CNS. Moreover, we found that Vit-B12 prevents ethanol-induced reduction of BDNF and enhancement of GFAP and acetylcholinesterase (AChE) activity. In conclusion, it seems that Vit-B12 supplementation could be used as an effective therapeutic strategy to prevent learning and memory defects induced by chronic alcohol intake during adolescence.


Assuntos
Antioxidantes , Fator Neurotrófico Derivado do Encéfalo , Proteína Glial Fibrilar Ácida , Transtornos da Memória , Animais , Masculino , Camundongos , Acetilcolinesterase , Encéfalo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Etanol/efeitos adversos , Aprendizagem em Labirinto , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/tratamento farmacológico , Transtornos da Memória/prevenção & controle , Oxidantes , Estresse Oxidativo , Vitamina B 12/farmacologia , Vitamina B 12/uso terapêutico , Proteína Glial Fibrilar Ácida/metabolismo
15.
Alcohol Clin Exp Res ; 47(2): 211-218, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36543333

RESUMO

BACKGROUND: Alcohol withdrawal syndrome (AWS) results from the sudden cessation of chronic alcohol use and is associated with high morbidity and mortality. Alcohol withdrawal-induced central nervous system (CNS) hyperexcitability results from complex, compensatory changes in synaptic efficacy and intrinsic excitability. These changes in excitability counteract the depressing effects of chronic ethanol on neural transmission and underlie symptoms of AWS, which range from mild anxiety to seizures and death. The development of targeted pharmacotherapies for treating AWS has been slow, due in part to the lack of available animal models that capture the key features of human AWS. Using a unique optogenetic method of probing network excitability, we examined electrophysiologic correlates of hyperexcitability sensitive to early changes in CNS excitability. This method is sensitive to pharmacologic treatments that reduce excitability and may represent a platform for AWS drug development. METHODS: We applied a newly developed method, the optogenetic population discharge threshold (oPDT), which uses light intensity response curves to measure network excitability in chronically implanted mice. Excitability was tracked using the oPDT before, during, and after the chronic intermittent exposure (CIE) model of alcohol withdrawal (WD). RESULTS: Alcohol withdrawal produced a dose-dependent leftward shift in the oPDT curve (denoting increased excitability), which was detectable in as few as three exposure cycles. This shift in excitability mirrored an increase in the number of spontaneous interictal spikes during withdrawal. In addition, Withdrawal lowered seizure thresholds and increased seizure severity in optogenetically kindled mice. CONCLUSION: We demonstrate that the oPDT provides a sensitive measure of alcohol withdrawal-induced hyperexcitability. The ability to actively probe the progression of excitability without eliciting potentially confounding seizures promises to be a useful tool in the preclinical development of next-generation pharmacotherapies for AWS.


Assuntos
Convulsões por Abstinência de Álcool , Alcoolismo , Síndrome de Abstinência a Substâncias , Humanos , Camundongos , Animais , Síndrome de Abstinência a Substâncias/complicações , Alcoolismo/complicações , Alta do Paciente , Etanol/efeitos adversos , Convulsões/induzido quimicamente , Convulsões por Abstinência de Álcool/complicações
16.
J Vasc Interv Radiol ; 33(1): 42-48.e4, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34547475

RESUMO

PURPOSE: To evaluate the safety and efficacy of ethanol embolization of lip arteriovenous malformations (AVMs). MATERIALS AND METHODS: Seventy-six patients with lip AVMs were treated with 173 ethanol embolization procedures. Lip AVMs were treated with direct puncture alone in 21 patients (35 procedures, 20.2%), transarterial embolization alone in 13 patients (18 procedures, 10.4 %), and a combination of both in 60 patients (120 procedures, 69.3%). Adjunctive surgical resection was performed after embolization for cosmetic purposes based on the patient's request, including patient preference, functional impairment, and skin necrosis. The mean duration of follow-up was 30.9 months ± 27.6. The follow-up included clinic visits and telephonic questionnaires to evaluate the clinical signs and symptoms of AVMs as well as quality of life measures. RESULTS: Of 76 patients, 51 showed 100% devascularization of AVMs, as determined using arteriography, followed by 23 with 76%-99% devascularization and 2 with 50%-75% devascularization. Of the 76 patients, 40 achieved complete symptom relief and 25 achieved major improvements in cosmetic deformity after embolization. Additionally, 54 patients achieved satisfactory function and aesthetic improvement with ethanol embolotherapy alone, whereas 22 achieved similar outcomes with a combination of ethanol embolotherapy and surgical intervention. Thirty-three adverse events (including 1 major) were documented. CONCLUSIONS: Ethanol embolization of lip AVMs, as a mainstay, is efficacious in managing these lesions, with acceptable complications. Surgical resection after embolization may improve function and cosmesis in a subset of patients.


Assuntos
Malformações Arteriovenosas , Embolização Terapêutica , Malformações Arteriovenosas/diagnóstico por imagem , Malformações Arteriovenosas/terapia , Embolização Terapêutica/efeitos adversos , Embolização Terapêutica/métodos , Etanol/efeitos adversos , Humanos , Lábio , Qualidade de Vida , Estudos Retrospectivos , Resultado do Tratamento
17.
Front Endocrinol (Lausanne) ; 13: 976165, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36506078

RESUMO

Background: Alcoholic osteonecrosis of the femoral head (ONFH) is a multifaceted illness that seriously disturbs the patients' quality of life. The role of lncRNAs in alcoholic ONFH has attracted widespread attention in recent years. This study mainly explored whether MIR31HG polymorphism affects the risk of ONFH. Methods: There were 733 males (308 alcohol-induced ONFH patients and 425 healthy controls). Seven single nucleotide polymorphisms from MIR31HG were genotyped using the Agena MassARRAY platform. Odds ratio (OR) and 95% confidence intervals (CI) via logistic regression was applied to assess the contribution of MIR31HG variants to alcoholic ONFH susceptibility. Results: We found that rs10965059 was related to a lower risk of alcoholic ONFH in the overall, age, and necrotic sites analysis. Rs10965064 also showed a risk-reducing effect in the occurrence of alcoholic ONFH patients older than 40 years old. Conclusions: We confirmed that MIR31HG variants have a significant correlation with the occurrence of alcoholic ONFH among the Chinese Han male population. our findings may provide new ideas for understanding the effect of MIR31HG on the prevention and diagnosis of alcoholic ONFH.


Assuntos
Necrose da Cabeça do Fêmur , Predisposição Genética para Doença , Adulto , Humanos , Masculino , Estudos de Casos e Controles , População do Leste Asiático , Etanol/efeitos adversos , Cabeça do Fêmur , Necrose da Cabeça do Fêmur/etiologia , Necrose da Cabeça do Fêmur/genética , Qualidade de Vida
18.
Int J Mol Sci ; 23(23)2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36499404

RESUMO

Clinical and animal studies suggest that paternal exposure to adverse environments (bad living habits and chronic stress, etc.) has profound impacts on offspring development; however, the mechanism of paternal disease has not been clarified. In this study, a meta-analysis was first performed to suggest that paternal exposure to nicotine, ethanol, or caffeine is a high-risk factor for adverse pregnancy outcomes. Next, we created a rat model of paternal nicotine/ethanol/caffeine mixed exposure (PME), whereby male Wistar rats were exposed to nicotine (0.1 mg/kg/d), ethanol (0.5 g/kg/d), and caffeine (7.5 mg/kg/d) for 8 weeks continuously, then mated with normal female rats to obtain a fetus (n = 12 for control group, n = 10 for PME group). Then, we analyzed the changes in paternal hypothalamic-pituitary-adrenal (HPA) axis activity, testicular function, pregnancy outcomes, fetal serum metabolic indicators, and multiple organ functions to explore the mechanism from the perspective of chronic stress. Our results demonstrated that PME led to enhanced paternal HPA axis activity, decreased sperm quality, and adverse pregnancy outcomes (stillbirth and absorption, decreased fetal weight and body length, and intrauterine growth retardation), abnormal fetal serum metabolic indicators (corticosterone, glucolipid metabolism, and sex hormones), and fetal multi-organ dysfunction (including hippocampus, adrenal, liver, ossification, and gonads). Furthermore, correlation analysis showed that the increased paternal corticosterone level was closely related to decreased sperm quality, adverse pregnancy outcomes, and abnormal offspring multi-organ function development. Among them, the decreased activity of the glucocorticoid-insulin-like growth factor 1 (GC-IGF1) axis may be the main mechanism of offspring development and multi-organ dysfunction caused by PME. This study explored the impact of common paternal lifestyle in daily life on offspring development, and proposed the GC-IGF1 programming mechanisms of paternal chronic stress-induced offspring dysplasia, which provides a novel insight for exploring the important role of paternal chronic stress in offspring development and guiding a healthy lifestyle for men.


Assuntos
Cafeína , Etanol , Fator de Crescimento Insulin-Like I , Nicotina , Exposição Paterna , Efeitos Tardios da Exposição Pré-Natal , Animais , Feminino , Masculino , Gravidez , Ratos , Cafeína/efeitos adversos , Corticosterona , Etanol/efeitos adversos , Sistema Hipotálamo-Hipofisário/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Insuficiência de Múltiplos Órgãos , Nicotina/efeitos adversos , Sistema Hipófise-Suprarrenal/metabolismo , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Ratos Wistar , Sêmen/metabolismo , Exposição Paterna/efeitos adversos
20.
Int J Mol Sci ; 23(24)2022 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-36555338

RESUMO

Growing evidence supports the pivotal role of the bidirectional interplay between the gut microbiota and the central nervous system during the progression of alcohol use disorder (AUD). In our previous study, supplementation with sodium butyrate (SB) in C57BL/6J mice prevented increased ethanol consumption in a binge-like drinking paradigm (DID) as a result of treatment with a non-absorbable antibiotic cocktail (ABX). In this study, we tested the hypothesis that SB protection against enhanced ABX-induced ethanol consumption in mice is partially due to modulation of neuroinflammatory responses. Pro- and anti-inflammatory cytokines, as well as changes in microglia and astrocytes were analyzed in hippocampus tissues from ABX-, SB-, ABX+SB-treated mice subjected to 4-week DID. We found that ethanol without or with ABX treatment increased mRNA levels of key brain cytokines (MCP-1, TNF-α, IL-1ß, IL-6 and IL-10) while SB supplementation prevented these changes. Additionally, SB supplementation prevented changes in microglia, i.e., increase in Iba-1 positive cell number and morphology, and in astrocytes, i.e., decrease in GFAP-positive cell number, induced by combination of ethanol and ABX treatments. Our results suggest that gut microbiota metabolites can influence drinking behavior by modulation of neuroinflammation, highlighting the potential for microbiome-targeting strategies for treatment or prevention of AUD.


Assuntos
Alcoolismo , Citocinas , Animais , Camundongos , Ácido Butírico/farmacologia , Camundongos Endogâmicos C57BL , Citocinas/metabolismo , Etanol/efeitos adversos , Consumo de Bebidas Alcoólicas , Inflamação/tratamento farmacológico , Alcoolismo/tratamento farmacológico , Modelos Animais de Doenças , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Suplementos Nutricionais
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...