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1.
Am J Respir Crit Care Med ; 204(7): e61-e87, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34609257

RESUMO

Background: Severe alcohol withdrawal syndrome (SAWS) is highly morbid, costly, and common among hospitalized patients, yet minimal evidence exists to guide inpatient management. Research needs in this field are broad, spanning the translational science spectrum. Goals: This research statement aims to describe what is known about SAWS, identify knowledge gaps, and offer recommendations for research in each domain of the Institute of Medicine T0-T4 continuum to advance the care of hospitalized patients who experience SAWS. Methods: Clinicians and researchers with unique and complementary expertise in basic, clinical, and implementation research related to unhealthy alcohol consumption and alcohol withdrawal were invited to participate in a workshop at the American Thoracic Society 2019 International Conference. The committee was subdivided into four groups on the basis of interest and expertise: T0-T1 (basic science research with translation to humans), T2 (research translating to patients), T3 (research translating to clinical practice), and T4 (research translating to communities). A medical librarian conducted a pragmatic literature search to facilitate this work, and committee members reviewed and supplemented the resulting evidence, identifying key knowledge gaps. Results: The committee identified several investigative opportunities to advance the care of patients with SAWS in each domain of the translational science spectrum. Major themes included 1) the need to investigate non-γ-aminobutyric acid pathways for alcohol withdrawal syndrome treatment; 2) harnessing retrospective and electronic health record data to identify risk factors and create objective severity scoring systems, particularly for acutely ill patients with SAWS; 3) the need for more robust comparative-effectiveness data to identify optimal SAWS treatment strategies; and 4) recommendations to accelerate implementation of effective treatments into practice. Conclusions: The dearth of evidence supporting management decisions for hospitalized patients with SAWS, many of whom require critical care, represents both a call to action and an opportunity for the American Thoracic Society and larger scientific communities to improve care for a vulnerable patient population. This report highlights basic, clinical, and implementation research that diverse experts agree will have the greatest impact on improving care for hospitalized patients with SAWS.


Assuntos
Alcoolismo/terapia , Pesquisa Biomédica , Depressores do Sistema Nervoso Central/efeitos adversos , Etanol/efeitos adversos , Hospitalização , Síndrome de Abstinência a Substâncias/terapia , Alcoolismo/fisiopatologia , Cuidados Críticos/métodos , Cuidados Críticos/normas , Humanos , Determinação de Necessidades de Cuidados de Saúde , Melhoria de Qualidade , Sociedades Médicas , Síndrome de Abstinência a Substâncias/fisiopatologia , Pesquisa Médica Translacional
2.
Nutrients ; 13(10)2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34684453

RESUMO

BACKGROUND: Alcohol is a teratogen and prenatal exposure may adversely impact the developing fetus, increasing risk for negative outcomes, including Fetal Alcohol Spectrum Disorder (FASD). Global trends of increasing alcohol use among women of childbearing age due to economic development, changing gender roles, increased availability of alcohol, peer pressure and social acceptability of women's alcohol use may put an increasing number of pregnancies at risk for prenatal alcohol exposure (PAE). This risk has been exacerbated by the ongoing COVID-19 pandemic in some countries. METHOD: This literature review presents an overview on the epidemiology of alcohol use among childbearing age and pregnant women and FASD by World Health Organization regions; impact of PAE on fetal health, including FASD; associated comorbidities; and social outcomes. RESULTS/CONCLUSION: The impact of alcohol on fetal health and social outcomes later in life is enormous, placing a huge economic burden on countries. Prevention of prenatal alcohol exposure and early identification of affected individuals should be a global public health priority.


Assuntos
Consumo de Bebidas Alcoólicas/epidemiologia , Consumo de Bebidas Alcoólicas/patologia , Etanol/efeitos adversos , Transtornos do Espectro Alcoólico Fetal/epidemiologia , Transtornos do Espectro Alcoólico Fetal/patologia , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/patologia , Causalidade , Feminino , Humanos , Gravidez
3.
Molecules ; 26(19)2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34641616

RESUMO

Several Cissus species have been used and reported to possess medicinal benefits. However, the anti-inflammatory mechanisms of Cissus subtetragona have not been described. In this study, we examined the potential anti-inflammatory effects of C. subtetragona ethanol extract (Cs-EE) in vitro and in vivo, and investigated its molecular mechanism as well as its flavonoid content. Lipopolysaccharide (LPS)-induced macrophage-like RAW264.7 cells and primary macrophages as well as LPS-induced acute lung injury (ALI) and HCl/EtOH-induced acute gastritis mouse models were utilized. Luciferase assays, immunoblotting analyses, overexpression strategies, and cellular thermal shift assay (CETSA) were performed to identify the molecular mechanisms and targets of Cs-EE. Cs-EE concentration-dependently reduced the secretion of NO and PGE2, inhibited the expression of inflammation-related cytokines in LPS-induced RAW264.7 cells, and decreased NF-κB- and AP-1-luciferase activity. Subsequently, we determined that Cs-EE decreased the phosphorylation events of NF-κB and AP-1 pathways. Cs-EE treatment also significantly ameliorated the inflammatory symptoms of HCl/EtOH-induced acute gastritis and LPS-induced ALI mouse models. Overexpression of HA-Src and HA-TAK1 along with CETSA experiments validated that inhibited inflammatory responses are the outcome of attenuation of Src and TAK1 activation. Taken together, these findings suggest that Cs-EE could be utilized as an anti-inflammatory remedy especially targeting against gastritis and acute lung injury by attenuating the activities of Src and TAK1.


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Anti-Inflamatórios/administração & dosagem , Cissus/química , Etanol/efeitos adversos , Gastrite/tratamento farmacológico , Ácido Clorídrico/efeitos adversos , Lipopolissacarídeos/efeitos adversos , Macrófagos/citologia , Polifenóis/administração & dosagem , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/genética , Administração Oral , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Citocinas/genética , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Gastrite/induzido quimicamente , Gastrite/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Células HEK293 , Humanos , MAP Quinase Quinase Quinases/genética , MAP Quinase Quinase Quinases/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Masculino , Camundongos , Extratos Vegetais/química , Polifenóis/química , Células RAW 264.7 , Transdução de Sinais/efeitos dos fármacos , Resultado do Tratamento , Quinases da Família src/genética
4.
Nutrients ; 13(9)2021 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-34579050

RESUMO

Approximately 4% of cancers worldwide are caused by alcohol consumption. Drinking alcohol increases the risk of several cancer types, including cancers of the upper aerodigestive tract, liver, colorectum, and breast. In this review, we summarise the epidemiological evidence on alcohol and cancer risk and the mechanistic evidence of alcohol-mediated carcinogenesis. There are several mechanistic pathways by which the consumption of alcohol, as ethanol, is known to cause cancer, though some are still not fully understood. Ethanol's metabolite acetaldehyde can cause DNA damage and block DNA synthesis and repair, whilst both ethanol and acetaldehyde can disrupt DNA methylation. Ethanol can also induce inflammation and oxidative stress leading to lipid peroxidation and further DNA damage. One-carbon metabolism and folate levels are also impaired by ethanol. Other known mechanisms are discussed. Further understanding of the carcinogenic properties of alcohol and its metabolites will inform future research, but there is already a need for comprehensive alcohol control and cancer prevention strategies to reduce the burden of cancer attributable to alcohol.


Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Transtornos Induzidos por Álcool/metabolismo , Carcinogênese/induzido quimicamente , Etanol/efeitos adversos , Neoplasias/induzido quimicamente , Acetaldeído/efeitos adversos , Dano ao DNA/efeitos dos fármacos , Metilação de DNA/efeitos dos fármacos , Humanos
5.
PLoS One ; 16(9): e0256414, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34473735

RESUMO

OBJECTIVE: To estimate the prevalence and factors associated with the effect of alcohol on crack cocaine use and to analyze experiences related to combined use. Materials and methods: sequential mixed methods (qualitative and quantitative) research, carried out between August 2014 and August 2015 with people who use crack. In the quantitative approach, a cross-sectional study was conducted with 1,062 participants. Factors associated with "alcohol use with the effect of increasing the effect of crack/crack craving" were estimated by multiple regression. In the qualitative approach, 39 interviews were conducted using Bardin's content analysis technique. RESULTS: 871 (82.0%) participants reported consuming alcohol, among them, 668 (76.7%) used alcohol combined with crack: 219 (32.8%) reported feeling an effect of reduction in paranoia and/or crack craving and 384 (57.5%) reported feeling an increase in the effect of crack and in the craving to consume the drug. This relationship was also observed in the narratives of the people who use crack, with the possibility of a cyclic effect of consumption of the two substances. Those who related alcohol use to the effect of increasing crack craving (384) were more likely to use alcohol before crack (OR: 1.81; 95%CI: 1.13-2.89); to consume more than 20 stones daily (OR: 1.48; 95%CI: 1.01-2.16); to remain in abstinence from crack for less than one month (OR: 3.20; 95%CI: 1.91-5.35); to use dependence treatment services (OR: 1.85; 95%CI: 1.26-2.71); and to commit physical violence (OR:1.67; 95%CI:1.08-2.56). CONCLUSION: The findings of this study indicate that the modulation of the effect of alcohol use on crack cocaine depends on the moment when the drugs are consumed, and the use of alcohol before crack consumption is associated with characteristics that suggest a greater vulnerability to patterns of harmful crack use. Even though combined use is referred to as a way of reducing the negative effects of crack, the damage of this association may be greater than its possible benefits.


Assuntos
Consumo de Bebidas Alcoólicas/epidemiologia , Transtornos Relacionados ao Uso de Cocaína/epidemiologia , Cocaína Crack/efeitos adversos , Etanol/efeitos adversos , Adolescente , Adulto , Idoso , Consumo de Bebidas Alcoólicas/fisiopatologia , Consumo de Bebidas Alcoólicas/psicologia , Brasil/epidemiologia , Transtornos Relacionados ao Uso de Cocaína/fisiopatologia , Transtornos Relacionados ao Uso de Cocaína/psicologia , Fissura/fisiologia , Estudos Transversais , Interações Medicamentosas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Inquéritos e Questionários , Violência
6.
Int J Mol Sci ; 22(18)2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34575850

RESUMO

Alcohol is a psychoactive substance that is widely used and, unfortunately, often abused. In addition to acute effects such as intoxication, it may cause many chronic pathological conditions. Some of the effects are very well described and explained, but there are still gaps in the explanation of empirically co-founded dysfunction in many alcohol-related conditions. This work focuses on reviewing actual knowledge about the toxic effects of ethanol and its degradation products.


Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Transtornos Relacionados ao Uso de Álcool/metabolismo , Etanol/efeitos adversos , Etanol/metabolismo , Acetaldeído/metabolismo , Álcool Desidrogenase/genética , Álcool Desidrogenase/metabolismo , Transtornos Relacionados ao Uso de Álcool/etiologia , Etanol/toxicidade , Regulação Enzimológica da Expressão Gênica , Humanos , Redes e Vias Metabólicas , Especificidade de Órgãos , Estresse Oxidativo
7.
J Stud Alcohol Drugs ; 82(5): 553-563, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34546901

RESUMO

OBJECTIVE: Research concerning the combined effects of alcohol and benzodiazepines on driving-related skills is largely inconsistent. Because as many as 88% of benzodiazepine users report the additional consumption of alcohol, this review aims to provide an updated and concise synthesis of the available high-quality research. METHOD: We searched EBSCOhost, PubMed, Scopus, and Web of Science until April 1, 2020, for double-blind, placebo-controlled, repeated-measures intervention trials that examined the effects of alcohol (any dose provided as blood alcohol concentration [BAC]) in combination with oral benzodiazepines on neurocognitive tasks related to driving. RESULTS: We identified evidence of a substance and timing-dependent interaction for measures of reaction time, tracking, divided attention, and visual functioning. Administering alcohol in conjunction with or shortly after a benzodiazepine resulted in a stronger interactive effect than when administration occurred further apart. An additive and/or synergistic effect often occurred when a therapeutic dose of benzodiazepine was combined with alcohol at a BAC below .05%. CONCLUSIONS: Combined alcohol and benzodiazepine use was associated with significant impairments in driving-related neurocognitive skills. There is a clear need for more high-quality research in this area to better elucidate the mechanisms of alcohol and benzodiazepine interactions. Drivers may be unaware of impairments following the combination of these drugs at legal driving limits. Thus, drivers should be warned to take caution when consuming even small amounts of alcohol while under treatment with benzodiazepines.


Assuntos
Condução de Veículo , Benzodiazepinas , Benzodiazepinas/efeitos adversos , Concentração Alcoólica no Sangue , Cognição , Etanol/efeitos adversos , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
8.
Front Cell Infect Microbiol ; 11: 636231, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34336709

RESUMO

Long-term and excessive alcohol consumption are risk factors for osteoporosis. Excessive drinking can reduce bone density and also cause imbalance of gut microbiota. And gut microbiota can affect bone metabolism through various mechanisms, and the regulation of gut microbiota is closely related to age. However, the effects of gut microbiota on alcohol-induced osteoporosis at different ages are unclear. In this study, young and old rats were used to induce osteoporosis by long-term alcohol consumption, and alcohol metabolism, bone morphology, bone absorption and immune activity of rats were analyzed to determine the effects of alcohol on rats of different ages. In addition, changes of gut microbiota in rats were analyzed to explore the role of gut microbiota in alcohol-induced osteoporosis in rats of different ages. The results showed the ability of alcohol metabolism was only associated with age, but not with alcohol consumption. Long-term alcohol consumption resulted in the changes of bone metabolism regulating hormones, bone loss, activation of receptor activator of NF-κB ligand (RANKL) signaling and inflammatory response. And osteoporosis was more severe in old rats than young rats, suggesting that alcohol-induced osteoporosis is age-related. In addition, long-term drinking also affected the composition of gut microbiota in rats, with a significant increase in the proportion of pro-inflammatory microorganisms. Overall, this study found that long-term alcohol consumption induced osteoporosis and affected the composition of gut microbiota. And alcohol can activate T lymphocytes directly or indirectly by regulating the changes of gut microbiota to produce cytokines, and further activate osteoclasts. In addition, the osteoporosis was more severe in the old rats than young rats, which may be due to the higher diversity and stronger regulation ability of gut microbiota in young rats compared with old rats.


Assuntos
Etanol/efeitos adversos , Microbioma Gastrointestinal , Osteoporose , Animais , Densidade Óssea , NF-kappa B , Osteoclastos , Osteoporose/induzido quimicamente , Ratos
9.
Nutrients ; 13(7)2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34371928

RESUMO

The "drunken monkey" hypothesis posits that attraction to ethanol derives from an evolutionary linkage among the sugars of ripe fruit, associated alcoholic fermentation by yeast, and ensuing consumption by human ancestors. First proposed in 2000, this concept has received increasing attention from the fields of animal sensory biology, primate foraging behavior, and molecular evolution. We undertook a review of English language citations subsequent to publication of the original paper and assessed research trends and future directions relative to natural dietary ethanol exposure in primates and other animals. Two major empirical themes emerge: attraction to and consumption of fermenting fruits (and nectar) by numerous vertebrates and invertebrates (e.g., Drosophila flies), and genomic evidence for natural selection consistent with sustained exposure to dietary ethanol in diverse taxa (including hominids and the genus Homo) over tens of millions of years. We also describe our current field studies in Uganda of ethanol content within fruits consumed by free-ranging chimpanzees, which suggest chronic low-level exposure to this psychoactive molecule in our closest living relatives.


Assuntos
Consumo de Bebidas Alcoólicas , Evolução Biológica , Exposição Dietética , Etanol/metabolismo , Fermentação , Frutas/microbiologia , Leveduras/metabolismo , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/metabolismo , Consumo de Bebidas Alcoólicas/psicologia , Alcoolismo/metabolismo , Alcoolismo/psicologia , Animais , Exposição Dietética/efeitos adversos , Etanol/efeitos adversos , Comportamento Alimentar , Frutas/metabolismo , Humanos , Pan troglodytes
10.
Molecules ; 26(16)2021 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-34443679

RESUMO

Alcohol consumption is associated with gut dysbiosis, increased intestinal permeability, endotoxemia, and a cascade that leads to persistent systemic inflammation, alcoholic liver disease, and other ailments. Craving for alcohol and its consequences depends, among other things, on the endocannabinoid system. We have analyzed the relative role of central vs. peripheral cannabinoid CB1 receptors (CB1R) using a "two-bottle" as well as a "drinking in the dark" paradigm in mice. The globally acting CB1R antagonist rimonabant and the non-brain penetrant CB1R antagonist JD5037 inhibited voluntary alcohol intake upon systemic but not upon intracerebroventricular administration in doses that elicited anxiogenic-like behavior and blocked CB1R-induced hypothermia and catalepsy. The peripherally restricted hybrid CB1R antagonist/iNOS inhibitor S-MRI-1867 was also effective in reducing alcohol consumption after oral gavage, while its R enantiomer (CB1R inactive/iNOS inhibitor) was not. The two MRI-1867 enantiomers were equally effective in inhibiting an alcohol-induced increase in portal blood endotoxin concentration that was caused by increased gut permeability. We conclude that (i) activation of peripheral CB1R plays a dominant role in promoting alcohol intake and (ii) the iNOS inhibitory function of MRI-1867 helps in mitigating the alcohol-induced increase in endotoxemia.


Assuntos
Consumo de Bebidas Alcoólicas/patologia , Antagonistas de Receptores de Canabinoides/farmacologia , Endotoxemia/patologia , Etanol/efeitos adversos , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Receptor CB1 de Canabinoide/antagonistas & inibidores , Consumo de Bebidas Alcoólicas/sangue , Animais , Ansiedade/sangue , Ansiedade/complicações , Comportamento Animal/efeitos dos fármacos , Catalepsia/induzido quimicamente , Catalepsia/complicações , Cicloexanóis/administração & dosagem , Teste de Labirinto em Cruz Elevado , Endotoxemia/sangue , Endotoxemia/complicações , Endotoxinas/sangue , Trato Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/metabolismo , Hipotermia Induzida , Camundongos Endogâmicos C57BL , Óxido Nítrico Sintase Tipo II/metabolismo , Pirazóis/administração & dosagem , Receptor CB1 de Canabinoide/metabolismo , Rimonabanto/administração & dosagem , Rimonabanto/farmacologia , Estereoisomerismo , Sulfonamidas/administração & dosagem
11.
Nutrients ; 13(8)2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34444939

RESUMO

Globally, almost four and a half million people died from injury in 2019. Alcohol's contribution to injury-related premature loss of life, disability and ill-health is pervasive, touching individuals, families and societies throughout the world. We conducted a review of research evidence for alcohol's causal role in injury by focusing on previously published systematic reviews, meta-analyses and where indicated, key studies. The review summarises evidence for pharmacological and physiological effects that support postulated causal pathways, highlights findings and knowledge gaps relevant to specific forms of injury (i.e., violence, suicide and self-harm, road injury, falls, burns, workplace injuries) and lays out options for evidence-based prevention.


Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Etanol/efeitos adversos , Ferimentos e Lesões/epidemiologia , Acidentes por Quedas/estatística & dados numéricos , Acidentes de Trânsito/estatística & dados numéricos , Queimaduras/epidemiologia , Feminino , Carga Global da Doença , Saúde Global , Política de Saúde , Humanos , Masculino , Traumatismos Ocupacionais/epidemiologia , Fatores de Risco , Comportamento Autodestrutivo/epidemiologia , Suicídio/estatística & dados numéricos , Violência/estatística & dados numéricos , Local de Trabalho , Ferimentos e Lesões/etiologia , Ferimentos e Lesões/prevenção & controle
13.
Nutrients ; 13(6)2021 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-34204516

RESUMO

Peptic ulcer has a serious impact on people's health around the world, and traditional medicines can cause adverse reactions. This study investigated the protective effects of tilapia collagen oligopeptides (TCOPs) on gastroduodenal injury. Seventy-two specific pathogen-free (SPF) male Sprague Dawley (SD) rats were randomly divided into six groups according to body weight: normal control group, ethanol group, whey protein group (500 mg/kg BW), and three TCOPs dose groups (250, 500, 1000 mg/kg BW). After intragastric administration for 30 days, the acute gastroduodenal injury was induced by anhydrous ethanol (5 mL/kg, intragastrically) in all groups except the normal control group. Biomarkers in gastric and duodenal tissue and serum were measured. Furthermore, western blot was used to detect the expression of apoptosis-related proteins. The results showed that the administration with TCOPs significantly reduced gastric and duodenal ulcer index, increased gastric juice pH, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities, along with the reduction of malondialdehyde (MDA) contents. TCOPs decreased tumor Necrosis Factor-α (TNF-α), interleukin-1ß (IL-1ß), and myeloperoxidase (MPO) levels, while interleukin- 10 (IL-10) levels were increased. Furthermore, pepsinogens 1 (PG1), pepsinogens 2 (PG2), gastrin (GAS), and the pepsinogen ratio (PGR) were decreased, the prostaglandin E2 (PGE2) and NO contents were increased after TCOPs intervention. Moreover, TCOPs up-regulated the expression of Bcl-2 and inhibited the expression of Bax and Caspase-3. In conclusion, TCOPs have protective effects on ethanol-induced gastroduodenal injury through gastrointestinal mucosal microcirculation promotion, antioxidation, anti-inflammation, and anti-apoptosis mechanisms.


Assuntos
Anti-Inflamatórios/farmacologia , Etanol/efeitos adversos , Oligopeptídeos/isolamento & purificação , Oligopeptídeos/farmacologia , Tilápia/metabolismo , Animais , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Biomarcadores , Catalase/metabolismo , Colágeno , Citocinas/metabolismo , Modelos Animais de Doenças , Trato Gastrointestinal/lesões , Interleucina-1beta , Masculino , Malondialdeído/metabolismo , Peroxidase/metabolismo , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
15.
J Immunol ; 207(2): 483-492, 2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-34193599

RESUMO

Alcohol use disorders (AUD) increase susceptibility to respiratory infections by 2- to 4-fold in part because of impaired alveolar macrophage (AM) immune function. Alcohol causes AM oxidative stress, diminishing AM phagocytic capacity and clearance of microbes from the alveolar space. Alcohol increases AM NADPH oxidases (Noxes), primary sources of AM oxidative stress, and reduces peroxisome proliferator-activated receptor γ (PPARγ) expression, a critical regulator of AM immune function. To investigate the underlying mechanisms of these alcohol-induced AM derangements, we hypothesized that alcohol stimulates CCAAT/enhancer-binding protein ß (C/EBPß) to suppress Nox-related microRNAs (miRs), thereby enhancing AM Nox expression, oxidative stress, and phagocytic dysfunction. Furthermore, we postulated that pharmacologic PPARγ activation with pioglitazone would inhibit C/EBPß and attenuate alcohol-induced AM dysfunction. AM isolated from human AUD subjects or otherwise healthy control subjects were examined. Compared with control AM, alcohol activated AM C/EBPß, decreased Nox1-related miR-1264 and Nox2-related miR-107, and increased Nox1, Nox2, and Nox4 expression and activity. These alcohol-induced AM derangements were abrogated by inhibition of C/EBPß, overexpression of miR-1264 or miR-107, or pioglitazone treatment. These findings define novel molecular mechanisms of alcohol-induced AM dysfunction mediated by C/EBPß and Nox-related miRs that are amenable to therapeutic targeting with PPARγ ligands. These results demonstrate that PPARγ ligands provide a novel and rapidly translatable strategy to mitigate susceptibility to respiratory infections and related morbidity in individuals with AUD.


Assuntos
Alcoolismo/tratamento farmacológico , Alcoolismo/metabolismo , Etanol/efeitos adversos , Macrófagos Alveolares/efeitos dos fármacos , Fagócitos/efeitos dos fármacos , Pioglitazona/farmacologia , Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Linhagem Celular , Humanos , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Macrófagos Alveolares/metabolismo , Masculino , NADPH Oxidases/metabolismo , Estresse Oxidativo/efeitos dos fármacos , PPAR gama/metabolismo , Fagócitos/metabolismo
16.
PLoS One ; 16(7): e0255276, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34310648

RESUMO

OBJECTIVE: The risk of alcohol dependence (AD) in Japanese men and women was evaluated according to combinations of alcohol flushing and aldehyde dehydrogenase-2 (ALDH2, rs671) and alcohol dehydrogenase-1B (ADH1B, rs1229984) genotypes, all of which are known to determine AD susceptibility in Asians. Previous studies have focused on men, since women account for a smaller proportion of AD subjects. METHODS: Case control studies were conducted between 3721 male and 335 female AD Japanese and 610 male and 406 female controls who were asked about their current or former tendency to experience facial flushing after drinking a glass of beer and underwent ALDH2 and ADH1B genotyping. The time at which alcohol-induced facial flushing tendencies had disappeared in former-flushing AD subjects was also evaluated. RESULTS: Current alcohol flushing, the inactive ALDH2*1/*2 genotype, and the fast-metabolizing ADH1B*2 allele were less frequently found in the AD groups. Although alcohol flushing was strongly influenced by the ALDH2 and ADH1B genotypes, multiple logistic model showed that never or former flushing and the genotype combinations were independent strong risk factors of AD in men and women. Never or former flushing (vs. current flushing) markedly increased the odds ratios of AD in carriers of each of the ALDH2 and ADH1B genotype combinations. The temporal profiles for drinking and flushing in former-flushing AD subjects revealed that the flushing response disappeared soon after or before the start of habitual drinking during young adulthood, regardless of the ALDH2 genotype. CONCLUSION: Although alcohol flushing is influenced by the ALDH2 and ADH1B genotypes, constitutional or acquired flushing tolerance is an independent susceptibility trait for AD. The combination of the alcohol flushing status and the ALDH2 and ADH1B genotypes can provide a better new strategy for AD risk assessment than the alcohol flushing status alone or the genotypes alone in Asian men and women.


Assuntos
Álcool Desidrogenase/genética , Alcoolismo/genética , Aldeído-Desidrogenase Mitocondrial/genética , Etanol/efeitos adversos , Rubor/etiologia , Adulto , Idoso , Alcoolismo/diagnóstico , Alelos , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , Japão , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Polimorfismo de Nucleotídeo Único , Fatores de Risco
17.
Nutrients ; 13(5)2021 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-34064981

RESUMO

Alcoholic liver disease (ALD) is one type of liver disease, causing a global healthcare problem and mortality. The liver undergoes tissue damage by chronic alcohol consumption because it is the main site for metabolism of ethanol. Chronic alcohol exposure progresses from alcoholic fatty liver (AFL) to alcoholic steatohepatitis (ASH), which further lead to fibrosis, cirrhosis, and even hepatocellular cancer. Therapeutic interventions to combat ALD are very limited such as use of corticosteroids. However, these therapeutic drugs are not effective for long-term usage. Therefore, additional effective and safe therapies to cope with ALD are urgently needed. Previous studies confirmed that edible food plants and their bioactive compounds exert a protective effect against ALD. In this review article, we summarized the hepatoprotective potential of edible food plants and their bioactive compounds. The underlying mechanism for the prevention of ALD by edible food plants was as follows: anti-oxidation, anti-inflammation, lipid regulation, inhibition of apoptosis, gut microbiota composition modulation, and anti-fibrosis.


Assuntos
Hepatopatias Alcoólicas/terapia , Plantas Comestíveis/química , Polifenóis/uso terapêutico , Substâncias Protetoras/uso terapêutico , Consumo de Bebidas Alcoólicas , Animais , Etanol/efeitos adversos , Etanol/metabolismo , Fígado Gorduroso Alcoólico/metabolismo , Fígado Gorduroso Alcoólico/terapia , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Hepatopatias Alcoólicas/metabolismo , Neoplasias Hepáticas , Compostos Fitoquímicos/química , Compostos Fitoquímicos/uso terapêutico , Extratos Vegetais/uso terapêutico , Substâncias Protetoras/química
18.
Nutrients ; 13(6)2021 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-34073981

RESUMO

Diverticulitis and hemorrhoidal proctitis in the population are significant public health problems. We studied the potential association between the intake of certain plant foods and diverticulitis or hemorrhoidal episodes through a case-control study including 410 cases and 401 controls. We used a semiquantitative food frequency questionnaire. The intake was additionally quantified according to a 24 h recall. The plant foods or derived food products were categorized by their main chemical components into ethanol, caffeine/theine/theobromine, capsaicin, alliin, acids, eugenol, and miscellaneous foods such as curcumin. The mean score for overall intake of plant foods under consideration was 6.3 points, and this was significantly higher in cases (8.5) than in controls (4.1). Overall intake was similar in cases presenting with diverticulitis or hemorrhoidal proctitis. Cases had 13 times the odds of being in the upper quartile for overall intake (>7 points), compared to controls. Explanatory logistic regression models showed that the strongest association with diverticulitis and hemorrhoidal proctitis was shown by the chemical food group of capsaicin, followed by ethanol, eugenol, caffeine/theine/theobromine, and acids. Neither alliin nor miscellaneous food groups showed any association. High, frequent consumption of capsaicin, followed by ethanol, eugenol, caffeine/theine/theobromine, and acids increase the risk of diverticulitis and hemorrhoidal proctitis.


Assuntos
Dieta/efeitos adversos , Diverticulite/epidemiologia , Hemorroidas/epidemiologia , Plantas Comestíveis/efeitos adversos , Proctite/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Cafeína/efeitos adversos , Capsaicina/efeitos adversos , Estudos de Casos e Controles , Inquéritos sobre Dietas , Diverticulite/etiologia , Etanol/efeitos adversos , Eugenol/efeitos adversos , Feminino , Hemorroidas/etiologia , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Proctite/etiologia , Fatores de Risco , Adulto Jovem
19.
Ann Agric Environ Med ; 28(2): 220-223, 2021 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-34184501

RESUMO

According to the World Health Organization (WHO), ethyl alcohol occupies the third place among health risks for the general population, causing damage to health as well as social damage. Ethanol is also considered the greatest risk factor in injuries. Both alcohol and its main metabolite, acetaldehyde, are directly toxic to tissues and lead to several systemic pathologies. Alcohol abuse may also lead to mental health disorders. Although one-in-eight adult Poles abstains from drinking alkohol, 10-20% of adult Poles drink alcohol regularly. It is estimated that this group includes about 900,000 addicts, and over 2,000,000 people who drink alcohol at a risky or harmful level. It affects their occurrence and their consequences Drink- driving is one of the problems most often raised, although alcohol is a documented risk factor in pedestrian accidents. It is also an important risk factor for suicidal behaviour with people under the influence of alcohol choosing more radical and effective methods of committing suicide, such as hanging or 'throwing themselves under a moving vehicle.' Only properly selected and consistently taken preventive actions can improve the tragic statistics related to ethanol stimulating risky and auto-aggressive behaviours. It is also necessary to improve the system for reporting such events because only reliable statistics enable proper assessment of the scale of the problem, and the effectiveness of these activities.


Assuntos
Agressão/efeitos dos fármacos , Condução de Veículo/psicologia , Etanol/efeitos adversos , Acidentes de Trânsito , Consumo de Bebidas Alcoólicas/psicologia , Humanos
20.
Lab Invest ; 101(9): 1210-1224, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34112940

RESUMO

Alcoholic liver disease (ALD) is a major cause of chronic liver disease worldwide. Macrophages exhibit different functional states and are classified as classically activated (M1) and alternatively activated (M2) macrophages. However, the mechanisms that govern M1/M2 polarization in chronic ALD remain to be elucidated. Prostacyclin (PGI2) synthase (PTGIS) is an enzyme of the prostaglandin pathway which catalyzes the conversion of Prostaglandin H2 (PGH2) to PGI2. PTGIS has anti-inflammatory properties. However, the function of PTGIS in ALD has not yet been determined. In this study, we demonstrated that PTGIS was downregulated in ALD and forced PTGIS expression in vivo using recombinant adeno-associated viral vector-packed PTGIS overexpression plasmid, which alleviated the inflammatory response and suppressed the macrophage M1 phenotype in mice. Loss- and gain-of function-experiments demonstrated that forced PTGIS expression inhibited the macrophage switch to the M1 phenotype and promoted M2 polarization. Furthermore, we identified the genes regulated by PTGIS through RNA-sequencing (RNA-seq) analysis. Gene ontology and KEGG pathway analyses showed that PTGIS regulates many genes involved in the immune response and is enriched in the Janus kinase/signal transducers and activators of transcription (JAK/STAT) signal transduction pathway, which plays an important role in regulating macrophage polarization. The proteins interacting with JAKs were predicted using the STRING database. The overlap between the RNA-seq and the STRING database was interleukin-6; this indicated that it was involved in macrophage polarization regulated by JAK/STAT signaling. We further explored the microRNAs that could regulate the expression of PTGIS through TargetScan. The results of luciferase assay illustrated that the expression of PTGIS was regulated by miR-140-3p.1. These results imply that PTGIS plays a pivotal role in ALD, partly by influencing macrophage polarization.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Sistema Enzimático do Citocromo P-450 , Oxirredutases Intramoleculares , Ativação de Macrófagos , Macrófagos , Animais , Células Cultivadas , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Sistema Enzimático do Citocromo P-450/farmacologia , Etanol/efeitos adversos , Oxirredutases Intramoleculares/genética , Oxirredutases Intramoleculares/metabolismo , Oxirredutases Intramoleculares/farmacologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Ativação de Macrófagos/efeitos dos fármacos , Ativação de Macrófagos/genética , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Células RAW 264.7 , Transdução de Sinais/efeitos dos fármacos
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