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2.
Mayo Clin Proc ; 96(7): 1758-1769, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34218856

RESUMO

OBJECTIVE: To investigate the joint associations of amounts of alcohol consumed and drinking habits with the risks of all-cause mortality and cause-specific mortality. PATIENTS AND METHODS: A total of 316,627 healthy current drinkers, with baseline measurements between March 13, 2006, and October 1, 2010, were included in this study. We newly created a drinking habit score (DHS) according to regular drinking (frequency of alcohol intake ≥3 times/wk) and whether consuming alcohol with meals (yes). RESULTS: During a median follow-up of 8.9 years, we documented 8652 incident cases of all-cause death, including 1702 cases of cardiovascular disease death, 4960 cases of cancer death, and 1990 cases of other-cause death. After adjustment confounders and amount of alcohol consumed, higher DHS was significantly associated with a lower risk of all-cause mortality, cardiovascular disease mortality, cancer mortality, or other-cause mortality (Ptrend<.001, Ptrend=.03, Ptrend<.001, and Ptrend<.001, respectively). We observed that the amount of alcohol consumed have different relationships with the risks of all-cause mortality and cause-specific mortality among participants with distinct drinking habits, grouped by DHS. For example, in the joint analyses, a J-shaped association between the amount of alcohol consumed and all-cause mortality was observed in participants with unfavorable DHS (Pquadratictrend=.02) while the association appeared to be U-shaped in participants with favorable DHS (Pquadratictrend=.003), with lower risks in those consuming greater than or equal to 50 g/wk and less than 300 g/wk. CONCLUSION: Our results indicate that alcohol consumption levels have different relationships with the risk of mortality among current drinkers, depending on their drinking habits.


Assuntos
Consumo de Bebidas Alcoólicas , Doenças Cardiovasculares/mortalidade , Etanol , Neoplasias/mortalidade , Medição de Risco , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/epidemiologia , Consumo de Bebidas Alcoólicas/fisiopatologia , Causas de Morte , Depressores do Sistema Nervoso Central/metabolismo , Depressores do Sistema Nervoso Central/farmacologia , Correlação de Dados , Etanol/metabolismo , Etanol/farmacologia , Feminino , Seguimentos , Hormese , Humanos , Masculino , Refeições , Pessoa de Meia-Idade , Mortalidade , Fatores de Proteção , Fatores de Risco , Estados Unidos/epidemiologia
3.
J Chem Phys ; 154(24): 245101, 2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34241335

RESUMO

Ethanol is highly effective against various enveloped viruses and can disable the virus by disintegrating the protective envelope surrounding it. The interactions between the coronavirus envelope (E) protein and its membrane environment play key roles in the stability and function of the viral envelope. By using molecular dynamics simulation, we explore the underlying mechanism of ethanol-induced disruption of a model coronavirus membrane and, in detail, interactions of the E-protein and lipids. We model the membrane bilayer as N-palmitoyl-sphingomyelin and 1-palmitoyl-2-oleoylphosphatidylcholine lipids and the coronavirus E-protein. The study reveals that ethanol causes an increase in the lateral area of the bilayer along with thinning of the bilayer membrane and orientational disordering of lipid tails. Ethanol resides at the head-tail region of the membrane and enhances bilayer permeability. We found an envelope-protein-mediated increase in the ordering of lipid tails. Our simulations also provide important insights into the orientation of the envelope protein in a model membrane environment. At ∼25 mol. % of ethanol in the surrounding ethanol-water phase, we observe disintegration of the lipid bilayer and dislocation of the E-protein from the membrane environment.


Assuntos
Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Coronavirus/metabolismo , Desinfetantes/farmacologia , Etanol/farmacologia , Proteínas do Envelope Viral/metabolismo , Coronavirus/fisiologia , Bicamadas Lipídicas/metabolismo , Conformação Molecular , Simulação de Dinâmica Molecular , Permeabilidade
4.
Int J Mol Sci ; 22(10)2021 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-34067897

RESUMO

Alcohol binge drinking (BD) and poor nutritional habits are two frequent behaviors among many adolescents that alter gut microbiota in a pro-inflammatory direction. Dysbiotic changes in the gut microbiome are observed after alcohol and high-fat diet (HFD) consumption, even before obesity onset. In this study, we investigate the neuroinflammatory response of adolescent BD when combined with a continuous or intermittent HFD and its effects on adult ethanol consumption by using a self-administration (SA) paradigm in mice. The inflammatory biomarkers IL-6 and CX3CL1 were measured in the striatum 24 h after BD, 3 weeks later and after the ethanol (EtOH) SA. Adolescent BD increased alcohol consumption in the oral SA and caused a greater motivation to seek the substance. Likewise, mice with intermittent access to HFD exhibited higher EtOH consumption, while the opposite effect was found in mice with continuous HFD access. Biochemical analyses showed that after BD and three weeks later, striatal levels of IL-6 and CX3CL1 were increased. In addition, in saline-treated mice, CX3CL1 was increased after continuous access to HFD. After oral SA procedure, striatal IL-6 was increased only in animals exposed to BD and HFD. In addition, striatal CX3CL1 levels were increased in all BD- and HFD-exposed groups. Overall, our findings show that adolescent BD and intermittent HFD increase adult alcohol intake and point to neuroinflammation as an important mechanism modulating this interaction.


Assuntos
Consumo de Bebidas Alcoólicas/metabolismo , Consumo Excessivo de Bebidas Alcoólicas/fisiopatologia , Fatores Etários , Consumo de Bebidas Alcoólicas/imunologia , Consumo de Bebidas Alcoólicas/prevenção & controle , Animais , Animais não Endogâmicos , Consumo Excessivo de Bebidas Alcoólicas/metabolismo , Quimiocina CXCL1/metabolismo , Dieta Hiperlipídica , Etanol/farmacologia , Inflamação/metabolismo , Interleucina-6/metabolismo , Masculino , Camundongos , Obesidade , Autoadministração/métodos
5.
Future Microbiol ; 16(11): 797-800, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34165328

RESUMO

Aim: Ethanol is highly effective at inactivating enveloped viruses, including SARS-CoV-2. The aim of this study is to evaluate the virucidal activity of Amuchina Gel Xgerm (74% ethanol) against SARS-CoV-2, according to the European Standard EN14476:2013+A2:2019. Materials & methods: Virucidal activity of the study product was evaluated against SARS-CoV-2 strain USAWA1/2020 in suspension, in the presence of 0.3 g/l of bovine serum albumin. Results: The log10 reduction of SARS-CoV-2 in the presence of bovine serum albumin was ≥4.11 ± 0.12 after 30 s of exposure to the study product (80% dilution). Cytotoxicity was observed in the 100 dilution, affecting the detection limit by 1 log10. Conclusion: Virucidal activity against SARS-CoV-2 supports the effectiveness of this alcohol-based formulation as a prevention measure for COVID-19 illness.


Assuntos
COVID-19/prevenção & controle , Etanol/farmacologia , Higienizadores de Mão/farmacologia , SARS-CoV-2/efeitos dos fármacos , Antivirais/farmacologia , COVID-19/virologia , Higiene das Mãos/métodos , Humanos
6.
Molecules ; 26(9)2021 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-34065080

RESUMO

The crude ethanol extract of the whole plant of Alternanthera philoxeroides (Mart.) Griseb was investigated for its potential as antidementia, induced by estrogen deprivation, based on in vitro antioxidant activity, ß-amyloid aggregation inhibition and cholinesterase inhibitory activity, as well as in vivo Morris water maze task (MWMT), novel object recognition task (NORT), and Y-maze task. To better understand the effect of the extract, oxidative stress-induced brain membrane damage through lipid peroxidation in the whole brain was also investigated. Additionally, expressions of neuroinflammatory cytokines (IL-1ß, IL-6 and TNF-α) and estrogen receptor-mediated facilitation genes such as PI3K and AKT mRNA in the hippocampus and frontal cortex were also evaluated. These effects were confirmed by the determination of its serum metabolites by NMR metabolomic analysis. Both the crude extract of A. philoxeroides and its flavone constituents were found to inhibit ß-amyloid (Aß) aggregation.


Assuntos
Demência/tratamento farmacológico , Espectroscopia de Ressonância Magnética , Metabolômica , Extratos Vegetais/farmacologia , Amaranthaceae/química , Peptídeos beta-Amiloides/química , Animais , Cognição/efeitos dos fármacos , Demência/prevenção & controle , Etanol/química , Etanol/farmacologia , Feminino , Flavonas/química , Sequestradores de Radicais Livres/metabolismo , Lobo Frontal/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Inflamação/tratamento farmacológico , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Aprendizagem em Labirinto/efeitos dos fármacos , Medicina Tradicional do Leste Asiático , Metaboloma , Camundongos , Camundongos Endogâmicos ICR , Ovariectomia , Análise de Componente Principal , Fator de Necrose Tumoral alfa/metabolismo
7.
Photochem Photobiol Sci ; 20(7): 955-965, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34118013

RESUMO

The pandemic created by SARS-CoV-2 has caused a shortage in the supplies of N95 filtering facepiece respirators (FFRs), disposable respirators with at least 95% efficiency to remove non-oily airborne particles, due to increasing cases all over the world. The current article reviewed various possible decontamination methods for FFR reuse including ultraviolet germicidal irradiation (UVGI), hydrogen peroxide vapor (HPV), microwave-generated steam (MGS), hydrogen peroxide gas plasma (HPGP), and 70% or higher ethanol solution. HPV decontamination was effective against bacterial spores (6 log10 reduction of Geobacillus stearothermophilus spores) on FFRs and viruses (> 4 log10 reduction of various types of viruses) on inanimate surfaces, and no degradation of respirator materials and fit has been reported. 70% or higher ethanol decontamination showed high efficacy in inactivation of coronaviruses on inanimate surfaces (> 3.9 log10 reduction) but it was lower on FFRs which filtration efficiency was also decreased. UVGI method had good biocidal efficacy on FFRs (> 3 log10 reduction of H1N1 virus) combined with inexpensive, readily available equipment; however, it was more time-consuming to ensure sufficient reduction in SARS-CoV-2. MGS treatment also provided good viral decontamination on FFRs (> 4 log10 reduction of H1N1 virus) along with less time-intensive process and readily available equipment while inconsistent disinfection on the treated surfaces and deterioration of nose cushion of FFRs were observed. HPGP was a good virucidal system (> 6 log10 reduction of Vesicular stomatitis virus) but filtration efficiency after decontamination was inconsistent. Overall, HPV appeared to be one of the most promising methods based on the high biocidal efficacy on FFRs, preservation of respirator performance after multiple cycles, and no residual chemical toxicity. Nonetheless, equipment cost and time of the HPV process and a suitable operating room need to be considered.


Assuntos
COVID-19 , Descontaminação/métodos , Respiradores N95/microbiologia , Respiradores N95/virologia , Bactérias/efeitos dos fármacos , Bactérias/isolamento & purificação , Bactérias/efeitos da radiação , COVID-19/epidemiologia , Desinfecção/métodos , Etanol/farmacologia , Humanos , Peróxido de Hidrogênio/farmacologia , Micro-Ondas , Raios Ultravioleta , Vírus/efeitos dos fármacos , Vírus/isolamento & purificação , Vírus/efeitos da radiação
8.
Int J Mol Sci ; 22(9)2021 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-34066632

RESUMO

Ethanol has been shown to exhibit therapeutic properties as an ablative agent alone and in combination with thermal ablation. Ethanol may also increase sensitivity of cancer cells to certain physical and chemical antitumoral agents. The aim of our study was to assess the potential influence of nontoxic concentrations of ethanol on hyperthermia therapy, an antitumoral modality that is continuously growing and that can be combined with classical chemotherapy and radiotherapy to improve their efficiency. Human leukemia cells were included as a model in the study. The results indicated that ethanol augments the cytotoxicity of hyperthermia against U937 and HL60 cells. The therapeutic benefit of the hyperthermia/ethanol combination was associated with an increase in the percentage of apoptotic cells and activation of caspases-3, -8 and -9. Apoptosis triggered either by hyperthermia or hyperthermia/ethanol was almost completely abolished by a caspase-8 specific inhibitor, indicating that this caspase plays a main role in both conditions. The role of caspase-9 in hyperthermia treated cells acquired significance whether ethanol was present during hyperthermia since the alcohol enhanced Bid cleavage, translocation of Bax from cytosol to mitochondria, release of mitochondrial apoptogenic factors, and decreased of the levels of the anti-apoptotic factor myeloid cell leukemia-1 (Mcl-1). The enhancement effect of ethanol on hyperthermia-activated cell death was associated with a reduction in the expression of HSP70, a protein known to interfere in the activation of apoptosis at different stages. Collectively, our findings suggest that ethanol could be useful as an adjuvant in hyperthermia therapy for cancer.


Assuntos
Etanol/farmacologia , Hipertermia Induzida , Leucemia Mieloide/patologia , Apoptose/efeitos dos fármacos , Caspases/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Proteínas de Choque Térmico HSP70/metabolismo , Humanos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Modelos Biológicos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Células U937
9.
Neuropsychopharmacology ; 46(8): 1442-1450, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33947965

RESUMO

Poor inhibitory control and heightened feelings of stimulation after alcohol are two well-established risk factors for alcohol use disorder (AUD). Although these risk factors have traditionally been viewed as orthogonal, recent evidence suggests that the two are related and may share common neurobiological mechanisms. Here we examined the degree to which neural activity during inhibition was associated with subjective reports of stimulation following alcohol. To assess neural changes during inhibition, moderate alcohol drinkers performed a stop signal task during fMRI without drug. To assess subjective responses to alcohol they ingested alcohol (0.8 g/kg) or placebo beverages under double-blind conditions and provided subjective reports of stimulation and sedation. Feelings of stimulation following alcohol were inversely associated with activity in the supplementary motor area, insula, and middle frontal gyrus during inhibition (successful stop trials compared to go trials). Feelings of sedation did not correlate with brain activation. These results extend previous findings suggesting that poor inhibitory control is associated with more positive subjective responses to alcohol. These interrelated risk factors may contribute to susceptibility to future excessive alcohol use, and ultimately lead to neurobiological targets to prevent or treat AUD.


Assuntos
Alcoolismo , Estimulantes do Sistema Nervoso Central , Consumo de Bebidas Alcoólicas , Mapeamento Encefálico , Etanol/farmacologia , Humanos , Inibição Psicológica , Imageamento por Ressonância Magnética
10.
Clin Microbiol Infect ; 27(7): 1042.e1-1042.e4, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33901670

RESUMO

OBJECTIVES: Disinfection effectiveness against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on human skin remains unclear because of the hazards of viral exposure. An evaluation model, which has been previously generated using human skin obtained from forensic autopsy samples, accurately mimics in vivo skin conditions for evaluating the effectiveness of disinfection against the virus. Using this model, we evaluated disinfection effectiveness against viruses on human skin. METHODS: Ethanol (EA), isopropanol (IPA), chlorhexidine gluconate (CHG) and benzalkonium chloride (BAC) were used as target disinfectants. First, disinfectant effectiveness against SARS-CoV-2 and influenza A virus (IAV) was evaluated in vitro. Disinfectant effectiveness against SARS-CoV-2 and IAV on human skin was then evaluated by titrating viruses present on the skin after applying each disinfectant on the skin for 5-60 seconds. RESULTS: Both, SARS-CoV-2 and IAV on human skin were completely inactivated within 5 seconds by 40%-80% EA and 70% IPA (log reduction values (LRVs) were >4). However, SARS-CoV-2 and IAV were barely inactivated by 20% EA (LRVs were <1). In vitro evaluation showed that, compared with EA and IPA, CHG and BAC were significantly inferior in terms of disinfection effectiveness. Conversely, the disinfection effectiveness of CHG and BAC against SARS-CoV-2 was higher on human skin than in vitro, and increased with increases in their concentration and reaction time (LRVs of 0.2% CHG/0.05% BAC were >2, and LRVs of 1.0% CHG/0.2% BAC were >2.5). CONCLUSIONS: Proper hand hygiene practices using alcohol-based disinfectants such as EA/IPA effectively inactivate SARS-CoV-2 and IAV on human skin.


Assuntos
COVID-19/prevenção & controle , Desinfetantes/farmacologia , Vírus da Influenza A/efeitos dos fármacos , Influenza Humana/prevenção & controle , SARS-CoV-2/efeitos dos fármacos , 2-Propanol/farmacologia , Anti-Infecciosos Locais/farmacologia , Compostos de Benzalcônio/farmacologia , COVID-19/virologia , Clorexidina/análogos & derivados , Clorexidina/farmacologia , Etanol/farmacologia , Higiene das Mãos/métodos , Humanos , Modelos Biológicos , Pele/virologia
11.
Nutrients ; 13(4)2021 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-33923766

RESUMO

Benefits and harms of different components of human diet have been known for hundreds of years. Alcohol is one the highest consumed, abused, and addictive substances worldwide. Consequences of alcohol abuse are increased risks for diseases of the cardiovascular system, liver, and nervous system, as well as reduced immune system function. Paradoxically, alcohol has also been a consistent protective factor against the development of autoimmune diseases such as type 1 diabetes, multiple sclerosis, systemic lupus erythematosus, and rheumatoid arthritis (RA). Here, we focused on summarizing current findings on the effects of alcohol, as well as of its metabolites, acetaldehyde and acetate, on the immune system and RA. Heavy or moderate alcohol consumption can affect intestinal barrier integrity, as well as the microbiome, possibly contributing to RA. Additionally, systemic increase in acetate negatively affects humoral immune response, diminishing TFH cell as well as professional antigen-presenting cell (APC) function. Hence, alcohol consumption has profound effects on the efficacy of vaccinations, but also elicits protection against autoimmune diseases. The mechanism of alcohol's negative effects on the immune system is multivariate. Future studies addressing alcohol and its metabolite acetate's effect on individual components of the immune system remains crucial for our understanding and development of novel therapeutic pathways.


Assuntos
Consumo de Bebidas Alcoólicas/imunologia , Artrite Reumatoide/imunologia , Etanol/farmacologia , Sistema Imunitário/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Acetaldeído/imunologia , Acetaldeído/farmacologia , Acetatos/imunologia , Acetatos/farmacologia , Etanol/imunologia , Humanos
12.
J Zoo Wildl Med ; 52(1): 117-125, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33827168

RESUMO

The objective of this pilot study was to examine the histologic effects associated with three known sclerosing agents and their ability to induce fibrosis in the subcutaneous space between the cervicocephalic air sac and skin. In the future, these drugs may prove useful in treating birds experiencing cervicocephalic diverticula rupture. The agents used were 1% polidocanol, absolute ethanol, and doxycycline hyclate. Twelve healthy adult chickens (Gallus gallus domesticus) were used in this study. The chickens were randomly allocated into three groups denoting day of euthanasia (day 4, 7, or 14). On day 0, all agents were injected (0.2 ml) subcutaneously, in a four-point grid fashion, in both the cervical and pectoral region of each bird. After euthanasia, the skin and subcutaneous tissues corresponding to the injection sites were harvested for histologic assessment. Tissue sections were assessed for fibrosis and lymphocytic and histiocytic inflammation. A scoring system was established to rank sclerosing agents by fibrosing and inflammatory ability. In the cervical region of chickens, 1% polidocanol induced the greatest inflammatory changes by day 7. Data suggest that doxycycline hyclate may produce the greatest cutaneous and subcutaneous fibrosis overall among all groups of birds. No adverse reactions were associated with any injection. Sterile saline produced the least amount of inflammation when assessed with the scoring system. Further investigation is needed to determine the safety of injections of larger volume with these chemicals and whether these findings can be extrapolated to birds with disease.


Assuntos
Sacos Aéreos/patologia , Galinhas , Doxiciclina/farmacologia , Etanol/farmacologia , Polidocanol/farmacologia , Animais , Doxiciclina/administração & dosagem , Quimioterapia Combinada , Etanol/administração & dosagem , Fibrose/induzido quimicamente , Fibrose/veterinária , Histiócitos , Inflamação/induzido quimicamente , Inflamação/veterinária , Linfócitos , Projetos Piloto , Polidocanol/administração & dosagem , Doenças das Aves Domésticas/terapia , Ruptura/terapia , Ruptura/veterinária , Soluções Esclerosantes/administração & dosagem , Soluções Esclerosantes/uso terapêutico , Pele/efeitos dos fármacos , Pele/patologia
13.
Mol Biol Rep ; 48(4): 3871-3876, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33880672

RESUMO

Microtubules (MTs) are structural units in the cytoskeleton. In brain cells they are responsible for axonal transport, information processing, and signaling mechanisms. Proper function of these processes is critical for healthy brain functions. Alcohol and substance use disorders (AUD/SUDs) affects the function and organization of MTs in the brain, making them a potential neuroimaging marker to study the resulting impairment of overall neurobehavioral and cognitive processes. Our lab reported the first brain-penetrant MT-tracking Positron Emission Tomography (PET) ligand [11C]MPC-6827 and demonstrated its in vivo utility in rodents and non-human primates. To further explore the in vivo imaging potential of [11C]MPC-6827, we need to investigate its mechanism of action. Here, we report preliminary in vitro binding results in SH-SY5Y neuroblastoma cells exposed to ethanol (EtOH) or cocaine in combination with multiple agents that alter MT stability. EtOH and cocaine treatments increased MT stability and decreased free tubulin monomers. Our initial cell-binding assay demonstrated that [11C]MPC-6827 may have high affinity to free/unbound tubulin units. Consistent with this mechanism of action, we observed lower [11C]MPC-6827 uptake in SH-SY5Y cells after EtOH and cocaine treatments (e.g., fewer free tubulin units). We are currently performing in vivo PET imaging and ex vivo biodistribution studies in rodent and nonhuman primate models of AUD and SUDs and Alzheimer's disease.


Assuntos
Cocaína/farmacologia , Etanol/farmacologia , Quinazolinas/farmacologia , Compostos Radiofarmacêuticos/farmacologia , Radioisótopos de Carbono , Linhagem Celular Tumoral , Fármacos do Sistema Nervoso Central/farmacologia , Humanos , Microtúbulos/efeitos dos fármacos , Microtúbulos/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Ligação Proteica , Tubulina (Proteína)/metabolismo , Moduladores de Tubulina/farmacologia
14.
Psychopharmacology (Berl) ; 238(6): 1593-1607, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33660080

RESUMO

RATIONALE: Inhibition is a core executive function and refers to the ability to deliberately suppress attention, behavior, thoughts, and/or emotions and instead act in a specific manner. While acute alcohol exposure has been shown to impair response inhibition in the stop-signal and Go/NoGo tasks, reported alcohol effects on attentional inhibition in the Stroop task are inconsistent. Notably, studies have operationalized attentional inhibition variably and there has been intra- and inter-individual variability in alcohol exposure. OBJECTIVE: This study aimed to examine the acute effects of alcohol on attentional inhibition, considering previous limitations. METHODS: In a single-blind, cross-over design, 40 non-dependent participants with a medium-to-high risk drinking behavior performed a Counting Stroop task (CST) under a baseline and an arterial blood alcohol concentration (aBAC) clamp at 80 mg%. Attentional inhibition was assessed as the alteration of reaction times (RT), error rates (ER), and inverse efficiency scores (IES) between incongruent and congruent trials (interference score). Stroop performance was also assessed regardless of trial-type. RESULTS: Compared to saline, acute alcohol exposure via an aBAC clamp did not affect CST interference scores but increased RTs and IES in both incongruent and congruent trials. CONCLUSIONS: Attentional inhibition (Stroop interference score) was not impaired by clamped moderate alcohol exposure. Acute alcohol impaired Stroop performance evidenced by a general increase in response times. Our findings suggest that response and attentional inhibition do not share the same neurocognitive mechanisms and are affected differently by alcohol. Results could also be explained by automated behaviors known to be relatively unaffected by acute alcohol.


Assuntos
Consumo de Bebidas Alcoólicas/psicologia , Etanol/farmacologia , Inibição Psicológica , Adulto , Atenção/fisiologia , Concentração Alcoólica no Sangue , Estudos Cross-Over , Função Executiva/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tempo de Reação/efeitos dos fármacos , Método Simples-Cego , Teste de Stroop
15.
Psychopharmacology (Berl) ; 238(6): 1713-1728, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33660081

RESUMO

RATIONALE: The relationship between age, ethanol intake, and the hedonic value of ethanol is key to understanding the motivation to consume ethanol. OBJECTIVE: It is uncertain whether ethanol drinking during adolescence changes ethanol's hedonic value into adulthood. METHODS: The current study compared voluntary intermittent ethanol consumption (IAE; 2-bottle choice; 20%v/v) among adolescent and adult Long-Evans rats to examine the effects of age and IAE on taste reactivity in adulthood. For taste reactivity, orally infused fluids included water, ethanol (5, 20, and 40%v/v), and sucrose (0.01, 0.1, 1M). RESULTS: IAE results indicate that adolescents drank more ethanol during IAE but had a lower rate of change in ethanol consumption across time than adults due to initially high adolescent drinking. During taste reactivity testing for ethanol, IAE rats had greater hedonic responding, less aversive responding, and a more positive relationship between hedonic responses and ethanol concentration than water-receiving control rats. Hedonic responses had positive, while aversive responses had negative relationships with ethanol concentration and total ethanol consumed during IAE. Adolescent+IAE rats displayed less hedonic and more aversive responses to ethanol than Adult+IAE rats. Sucrose responding was unrelated to ethanol consumption. CONCLUSIONS: These results suggest that ethanol consumption influences the future hedonic and aversive value of ethanol in a way that makes ethanol more palatable with greater prior consumption. However, it appears that those drinking ethanol as adolescents may be more resistant to this palatability shift than those first drinking as adults, suggesting different mechanisms of vulnerability to consumption escalation for adolescents and adults.


Assuntos
Consumo de Bebidas Alcoólicas , Etanol/farmacologia , Paladar/efeitos dos fármacos , Animais , Masculino , Motivação , Ratos , Ratos Long-Evans , Sacarose/farmacologia
16.
Biochem Biophys Res Commun ; 550: 197-203, 2021 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-33713857

RESUMO

Alcoholic fatty liver disease (AFLD) is induced by alcohol consumption and may progress to more severe liver diseases such as alcoholic steatohepatitis, fibrosis and cirrhosis, and even hepatocellular carcinoma. Mesencephalic astrocyte-derived neurotrophic factor (MANF) participates in maintaining lipid homeostasis. However, the role of MANF in the pathogenesis of AFLD remains unclear. We established an AFLD mouse model following the US National Institute on Alcohol Abuse and Alcoholism procedure. Both mRNA and protein levels of MANF were significantly increased in the chronic binge alcohol feeding model. Liver-specific knockout of MANF aggravated hepatic lipid accumulation. Similarly, liver-specific overexpression of MANF alleviated AFLD in mouse livers. MANF affected hepatic lipid metabolism by modulating autophagy. The levels of LC3-II and Atg5-Atg12 were decreased in mouse livers with MANF liver-specific knockout and increased with MANF liver-specific overexpression. Furthermore, MANF changed the phosphorylation of Stat3 and its nuclear localization. MANF may have a protective role in the development of AFLD.


Assuntos
Autofagia , Fígado Gorduroso Alcoólico/metabolismo , Fatores de Crescimento Neural/metabolismo , Fator de Transcrição STAT3/metabolismo , Animais , Autofagia/efeitos dos fármacos , Consumo Excessivo de Bebidas Alcoólicas , Etanol/farmacologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fatores de Crescimento Neural/deficiência , Fosforilação
19.
Int Heart J ; 62(2): 329-336, 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33731518

RESUMO

The reasons of residual left ventricular outflow tract (LVOT) obstruction following alcohol septal ablation (ASA) remain unclear, and outcomes of myectomy following failed ASA remain underreported.Thirteen symptomatic patients (10 women, a median age of 60.0 years) who underwent septal myectomy following failed ASA were reviewed. The patients were followed up for a median of 6 months. The clinical characteristics and outcomes of these patients were analyzed and were compared with those of 178 patients who underwent isolated myectomy without previous ASA at our institution during the same period.In the first ASA procedure, the median number of septal perforator arteries injected was 1.0 with the median value of peak creatine kinase following ablation of 978.5 U/L.Uncontrollable extent and location of infarcted myocardium caused by ablation and mitral subvalvular anomalies were found in four (30.8%) and seven (53.8%) patients, respectively. No operative or follow-up deaths occurred. The median maximum LVOT gradients fell from preoperative 112.0 to 8.5 mmHg at follow-up (P < 0.001). Compared with controls, patients with failed ASA had a higher proportion of mitral subvalvular anomalies (53.8% versus 13.5%, P = 0.001) and developed a higher incidence of complete atrioventricular block following myectomy (15.4% versus 1.7%, P = 0.038).Low institutional or operator experience with ablation, uncontrollable extent and location of infarcted myocardium caused by ablation, and mitral subvalvular anomalies may be reasons for failed ASA. Surgical myectomy for the treatment of residual LVOT obstruction after unsuccessful ASA may be associated with favorable results.


Assuntos
Técnicas de Ablação/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/métodos , Etanol/farmacologia , Septos Cardíacos/cirurgia , Obstrução do Fluxo Ventricular Externo/terapia , Adulto , Idoso , Feminino , Seguimentos , Frequência Cardíaca/fisiologia , Septos Cardíacos/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Falha de Tratamento , Obstrução do Fluxo Ventricular Externo/diagnóstico , Obstrução do Fluxo Ventricular Externo/fisiopatologia
20.
Eur J Pharmacol ; 899: 174039, 2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-33737011

RESUMO

The orexigenic peptide ghrelin increases the release of dopamine in the nucleus accumbens (NAc) shell via central ghrelin receptors, especially those located in the ventral tegmental area (VTA). The activity of the VTA dopamine neurons projecting to NAc shell, involves somatodendritic dopamine release within the VTA. However, the effects of ghrelin on the concomitant dopamine release in the VTA and NAc shell is unknown. It is further unknown whether addictive drugs, such as alcohol and amphetamine, enhance the dopamine levels in both these areas via ghrelin receptor dependent mechanisms. Thus, the effects of a ghrelin receptor antagonist, JMV2959, on the ability of i) central ghrelin ii) systemic alcohol or iii) systemic amphetamine to increase the dopamine release in the VTA and in the NAc shell in rats by using in vivo microdialysis was explored. We showed that systemic administration of JMV2959 blocks the ability of central ghrelin to increases dopamine release in the VTA and the NAc shell, and reduces the alcohol- and amphetamine-induced dopamine release in both these areas. Locomotor activity studies was then conducted in an attempt to correlate the ghrelin-induced dopamine release in the VTA to a behavioural outcome. These revealed that local infusion of a dopamine D1 receptor antagonist into the VTA blocks the ability of central ghrelin to cause a locomotor stimulation in mice. Collectively, this study adds to the growing body of evidence indicating that ghrelin signalling modulates the ability of ghrelin, and addictive drugs, to activate the mesoaccumbal dopamine pathway.


Assuntos
Anfetamina/farmacologia , Dopamina/metabolismo , Etanol/farmacologia , Grelina/farmacologia , Glicina/análogos & derivados , Antagonistas de Hormônios/farmacologia , Núcleo Accumbens/efeitos dos fármacos , Receptores de Grelina/antagonistas & inibidores , Triazóis/farmacologia , Área Tegmentar Ventral/efeitos dos fármacos , Animais , Comportamento Animal/efeitos dos fármacos , Glicina/farmacologia , Locomoção/efeitos dos fármacos , Masculino , Camundongos , Núcleo Accumbens/metabolismo , Ratos Wistar , Receptores de Dopamina D1/metabolismo , Receptores de Grelina/metabolismo , Recompensa , Área Tegmentar Ventral/metabolismo
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