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1.
J Vasc Interv Radiol ; 31(11): 1801-1809, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32951973

RESUMO

PURPOSE: To evaluate treatment outcomes of embolization for peripheral arteriovenous malformations (AVMs) in a tertiary referral center where ethanol is the primary agent of choice. METHODS: A retrospective study was performed of 93 patients (median age, 31 years; range, 2-66 years) with peripheral AVMs treated with embolization (n = 442; median, 2 per patient; range, 1-82) between January 2010 and July 2016. Ethanol was used in most cases (n = 428; 97%). AVMs were classified as type I (n = 3), type II (n = 57), type IIIa (n = 5), type IIIb (n = 15), and type IV (n = 13) according to the Yakes classification system. Effectiveness of embolization was based on AVM devascularization on angiography: 100% (total), 90%-99% (near-total), 70%-90% (substantial), 30%-70% (partial), and 0%-30% (failure). Complications were graded according to the Society of Interventional Radiology classification. RESULTS: In 69% of patients, 70%-100% devascularization was achieved. Total and near-total occlusion of the nidus were more often achieved in AVMs of types I and IIIa (both 100%) than in AVMs of types II, IIIb, and IV (56%, 67%, and 39%, respectively; P = .019). A total of 109 complications were identified: 101 minor (22.9%) and 8 major (1.8%). Major complications included wounds (n = 5), false aneurysm (n = 1), finger contracture (n = 1), and severe pain (n = 1) requiring therapy. The patient complication risk was significantly affected by the number of procedures (relative risk = 2.0; P < .001). Age, AVM location, and angioarchitecture type did not significantly affect complication risk. CONCLUSIONS: AVM embolization resulted in 70%-100% devascularization in 69% of patients, with few major complications. This study indicates that the type of AVM angioarchitecture affects the number of procedures needed and the achievability of AVM devascularization.


Assuntos
Malformações Arteriovenosas/terapia , Embolização Terapêutica , Etanol/administração & dosagem , Adolescente , Adulto , Idoso , Malformações Arteriovenosas/diagnóstico por imagem , Criança , Pré-Escolar , Embolização Terapêutica/efeitos adversos , Etanol/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Adulto Jovem
2.
J Vasc Interv Radiol ; 31(11): 1810-1816, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32958379

RESUMO

PURPOSE: To evaluate endovascular treatment of head and neck arteriovenous malformations (AVMs) based on the Yakes AVM classification and correlate treatment approach with clinical and angiographic outcomes. MATERIALS AND METHODS: A retrospective single-center study was performed in patients who underwent endovascular treatment of head and neck AVMs between January 2005 and December 2017. Clinical and operative records, imaging, and postoperative courses of patients were reviewed. Clinical stage was determined according to the Schobinger classification. AVM architecture and treatment approaches were determined according to the Yakes classification. Primary outcomes were clinical and angiographic treatment success rates and complication rates, with analysis according to the Yakes classification. RESULTS: A total of 29 patients (15 females) were identified, with a mean age of 30.6 years. Downgrading of the Schobinger clinical classification was achieved in all patients. Lesions included 8 Yakes type IIa, 5 type IIb, 1 type IIIa and IIIb, and 14 type IV. Lesions were treated using an intra-arterial, nidal, or transvenous approach, using ethanol and liquid embolic agents. Arteriovenous shunt eradication of >90% was achieved in 22 of 28 patients (79%), including 9 of 13 (69%) of Yakes type IV lesions and 13 of 15 (87%) of the other types. There were 5 significant complications in 79 procedures (6%), including 4 of 50 (8%) in Yakes type IV lesions. CONCLUSIONS: Schobinger stage was downgraded in all patients. Arteriovenous shunt eradication of >90% was achieved in most patients. Yakes type IV lesions required more sessions, and shunt eradication was higher in the Yakes II and III groups.


Assuntos
Malformações Arteriovenosas/terapia , Embolização Terapêutica , Procedimentos Endovasculares , Etanol/administração & dosagem , Cabeça/irrigação sanguínea , Pescoço/irrigação sanguínea , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Malformações Arteriovenosas/classificação , Malformações Arteriovenosas/diagnóstico por imagem , Criança , Pré-Escolar , Embolização Terapêutica/efeitos adversos , Embolização Terapêutica/instrumentação , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/instrumentação , Etanol/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
5.
PLoS One ; 15(8): e0232731, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32817640

RESUMO

This study evaluated the effects of the chronic consumption of different concentrations of alcohol on the experimental periodontitis (EP). 160 rats were divided into 4 groups: (EP-NT) rats with EP and no alcohol exposure; (EP-A14) rats with EP exposed to 14% alcohol; (EP-A25) rats with EP exposed to 25% alcohol; (EP-A36) rats with EP exposed to 36% alcohol. The animals from the EP-A14, EP-A25 and EP-A36 groups were subjected to different concentrations of alcohol 30 days before EP induction. The histological characteristics, percentage of bone in the furcation (PBF) and bone metabolism in the furcation region were evaluated. The PBF and tartrate-resistant acid phosphatase (TRAP) data were subjected to statistical analysis. The EP-A14, EP-A25 and EP-A36 groups had lower PBFs compared with the EP-NT group. A more severe inflammatory process and a greater number of TRAP+ cells were also observed. In the EP-A14, EP-A25 and EP-A36 groups, the inflammatory process became more severe as the ingested alcoholic concentration increased. An increase in RANKL immunolabeling and a significantly higher number of TRAP+ cells were also observed. We conclude that chronic alcohol consumption increases the severity of experimental periodontitis in a dose-dependent manner by increasing the magnitude of local inflammatory responses and stimulating alveolar bone resorption.


Assuntos
Perda do Osso Alveolar/patologia , Etanol/efeitos adversos , Periodontite/patologia , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/fisiopatologia , Animais , Masculino , Ratos , Ratos Wistar , Fosfatase Ácida Resistente a Tartarato/metabolismo
6.
Anticancer Res ; 40(8): 4491-4504, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32727779

RESUMO

BACKGROUND: Peroxiredoxin II (PRDX2) performs unique roles in cells. It can reduce peroxides through cysteine residues, and helps prevent the effects of oxidative stress on cells. It is closely related to the occurrence and development of various diseases, especially alcoholic liver injury and even liver cancer. The metabolism of alcohol in hepatocytes leads to the increase in the levels of reactive oxygen species (ROS), oxidative stress, injury, and apoptosis. Therefore, this study focused on the investigating the protection conferred by PRDX2 against alcohol-induced apoptosis of hepatocytes. MATERIALS AND METHODS: PRDX2 inhibition of alcohol-induced apoptosis in L02 hepatocytes was analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, fluorescence microscopy, flow cytometry, western blotting and hematoxylin and eosin staining. RESULTS: The results showed that the levels of reactive oxygen species, protein kinase B, ß-catenin, B-cell lymphoma-2 (BCL2), BCL-XL, BCL2-associated X, cleaved caspase-3, and cleaved poly (ADP-ribose) polymerase in PRDX2-silenced cells were increased significantly after the treatment of cells with ethanol. Similar results were obtained in an in vivo Prdx2-knockout mouse model of alcoholic liver injury. Therefore, PRDX2 may regulate the phosphorylation of the AKT signal protein by eliminating reactive oxygen species from cells, and it inhibits the downstream mitochondria-dependent apoptosis pathway, and, thereby, the apoptosis of cells. CONCLUSION: Thus, PRDX2 may be a potential molecular target for the prevention and treatment of alcoholic liver injury.


Assuntos
Etanol/efeitos adversos , Hepatócitos/citologia , Peroxirredoxinas/genética , Transdução de Sinais , Apoptose , Linhagem Celular , Regulação da Expressão Gênica/efeitos dos fármacos , Inativação Gênica , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Humanos , Fosforilação/efeitos dos fármacos , Poli(ADP-Ribose) Polimerases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , beta Catenina/metabolismo
7.
J Vasc Interv Radiol ; 31(8): 1216-1220, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32682710

RESUMO

PURPOSE: To retrospectively analyze and compare the incidence of diarrhea in patients who underwent cryoablation of the celiac plexus for intractable abdominal pain versus ethanol therapy over a 5-year period. MATERIALS AND METHODS: From June 2014 to August 2019, 83 patients were identified who underwent neurolysis of the celiac plexus for management of intractable abdominal pain by using either cryoablation (n = 39 [59% female; age range, 36-79 years old [average, 60 ± 11 years old]) or alcohol (n = 44 [48% female; age range, 29-76 years old [average, 60 ± 12 years old]). Pain scores and reports of procedure-related complications or side effects, with special attention to diarrhea and/or other gastrointestinal symptoms, were collected from follow-up visits at 1 week, 1 month, and 3 months post-intervention and were compared between groups. RESULTS: The mean time of follow-up was 17.7 days. Four patients who underwent cryoablation developed gastrointestinal symptoms consisting of 2 cases of nausea and vomiting and 2 cases of diarrhea (5.1%). Twelve patients who underwent ethanol ablation developed gastrointestinal symptoms, including 1 case of nausea, 3 cases of vomiting, and 9 cases of diarrhea (20.5%). There was a significantly higher incidence of both diarrhea (chi-squared likelihood ratio, P = .03) and overall gastrointestinal symptoms (chi-squared likelihood ratio, P = .04) in the ethanol group than in the cryoablation group. CONCLUSIONS: Cryoablation of the celiac plexus may provide a new treatment option for intractable abdominal pain, and it appears to have a lower incidence of diarrhea and fewer gastrointestinal side effects than ablation using ethanol.


Assuntos
Dor Abdominal/cirurgia , Plexo Celíaco/cirurgia , Criocirurgia , Etanol/administração & dosagem , Dor Intratável/cirurgia , Radiografia Intervencionista , Tomografia Computadorizada por Raios X , Dor Abdominal/diagnóstico , Dor Abdominal/epidemiologia , Adulto , Idoso , Plexo Celíaco/diagnóstico por imagem , Plexo Celíaco/fisiopatologia , Criocirurgia/efeitos adversos , Diarreia/epidemiologia , Etanol/efeitos adversos , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Medição da Dor , Dor Intratável/diagnóstico , Dor Intratável/epidemiologia , Radiografia Intervencionista/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Tomografia Computadorizada por Raios X/efeitos adversos , Resultado do Tratamento
8.
Life Sci ; 256: 117908, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32512011

RESUMO

BACKGROUND: Excessive alcohol intake contributes to severe liver damage involving oxidative stress and inflammatory responses, which make them promising therapeutic targets. Previous studies have demonstrated that empagliflozin (EMPA) showed cardiovascular, renal, and cerebral benefits potentially mediated through its antioxidant and anti-inflammatory actions. AIMS: This experiment aimed to evaluate the hepatoprotective effect of EMPA on alcoholic liver disease (ALD) and the possible underlying mechanisms. MATERIALS AND METHODS: Serum biochemical parameters and the liver contents of malondialdehyde (MDA), nitric oxide (NO), reduced glutathione (GSH), and superoxide dismutase (SOD) were measured. Real-time qPCR was conducted to determine the gene expression of peroxisome proliferator-activated receptor gamma (PPAR-γ), nuclear factor erythroid 2-related factor 2 (Nrf-2), and heme oxygenase-1 (Hmox-1). In addition, ELISA was performed to measure tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, IL-6, Nrf-2, and PPAR-γ. Nuclear factor-kappa B (NF-κB) was detected by immunohistochemical staining using an anti-NF-κB p65 antibody. KEY FINDINGS: Our results revealed that the serum levels of alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase were significantly reduced by EMPA. EMPA also decreased the content of MDA and NO and increased the activities of SOD and GSH in liver homogenates. Moreover, EMPA inhibited the release of proinflammatory cytokines, including TNF-α, IL-1ß, and IL-6, via the downregulation of NF-κB. These changes were associated with an improvement in histopathological deterioration. The protective effect of EMPA against oxidative stress and inflammation was associated with the upregulation of PPAR-γ, Nrf-2, and their target gene Hmox-1. SIGNIFICANCE: EMPA showed protective activities against ethanol-induced liver injury by suppressing inflammation and oxidative stress via modulation of the NF-κB/Nrf-2/PPAR-γ axis.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Compostos Benzidrílicos/farmacologia , Doença Hepática Crônica Induzida por Substâncias e Drogas/prevenção & controle , Fator de Transcrição de Proteínas de Ligação GA/metabolismo , Glucosídeos/farmacologia , NF-kappa B/metabolismo , PPAR gama/metabolismo , Alanina Transaminase/metabolismo , Fosfatase Alcalina/metabolismo , Animais , Anti-Inflamatórios/metabolismo , Antioxidantes/metabolismo , Aspartato Aminotransferases/metabolismo , Compostos Benzidrílicos/metabolismo , Doença Hepática Crônica Induzida por Substâncias e Drogas/metabolismo , Descoberta de Drogas , Etanol/efeitos adversos , Regulação da Expressão Gênica/efeitos dos fármacos , Glucosídeos/metabolismo , Glutationa/metabolismo , Heme Oxigenase-1/genética , Heme Oxigenase-1/metabolismo , Interleucinas/metabolismo , Fígado/metabolismo , Masculino , Malondialdeído/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Óxido Nítrico/metabolismo , Estresse Oxidativo/efeitos dos fármacos , PPAR gama/genética , Superóxido Dismutase/metabolismo
9.
J Vis Exp ; (159)2020 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-32478732

RESUMO

Alcohol use disorder (AUD) remains a serious problem in our society. To develop effective interventions for addiction, it is important to understand the underlying neurobiological mechanisms, for which diverse experimental approaches and model systems are needed. The main ingredient of alcoholic beverages is ethanol, which causes adaptive changes in the central nervous system and behavior upon chronic intake. Behavioral sensitization (i.e., escalated responses) in particular represents a key adaptive change underlying addiction. Most ethanol-induced behavioral sensitization studies in animal models have been conducted on the locomotor activating effect of ethanol. A prominent effect of ethanol is behavioral disinhibition. Behavioral sensitization to the disinhibition effect of ethanol, however, is underrepresented. To address this issue, we developed the Flypub assay that allows measuring the escalated increase in disinhibited courtship activities upon recurring ethanol exposure in Drosophila melanogaster. Here, we report the step-by-step Flypub assay including assembly of ethanol exposure chambers, setup of the assay station, criteria for fly care and collection, ethanol delivery, quantification of disinhibited courtship activities, data processing and statistical analysis. Also provided are how to troubleshoot critical steps, overcome limitations and expand its utility to assess additional ethanol-induced behaviors. The Flypub assay in combination with powerful genetic tools in Drosophila melanogaster will facilitate the task of discovering the mechanism underlying ethanol-induced behavioral sensitization.


Assuntos
Alcoolismo/etiologia , Comportamento Animal/efeitos dos fármacos , Etanol/efeitos adversos , Animais , Modelos Animais de Doenças
10.
Chem Biol Interact ; 326: 109113, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32360496

RESUMO

Apple polyphenols (AP) have attracted much attention due to their various bioactivities. In this study, the protective effect of AP against chronic ethanol exposure-induced neural injury as well as the possible mechanisms were investigated. Body weight, daily average food intake and daily average fluid intake were measured and daily average ethanol consumption was calculated. The influences of AP on motor behavior and memory were detected by locomotor activity test, rotarod test, beam walking test, and Y maze test and novel object recognition test, respectively. The changes of blood ethanol concentration and the oxidative stress were also measured. AP improved chronic ethanol exposure-induced the inhibition of body weight and the decrease of daily average food intake, but did not influence the daily average fluid intake and the daily average ethanol intake, indicating that the improve effect of AP did not result from the decrease of ethanol intake. Motor activity and motor coordination were not influenced after chronic ethanol exposure though the blood ethanol concentration was higher than that in control group. AP improved significantly chronic ethanol-induced the memory impairment and the hippocampal CA1 neurons damage. Further studies found that AP decreased the contents of NO and MDA and increased the levels of T-AOC and GSH in the hippocampus of rats. These results suggest that AP exerts a protective effect against chronic ethanol-induced memory impairment through improving the oxidative stress in the hippocampus.


Assuntos
Etanol/efeitos adversos , Neurônios/efeitos dos fármacos , Polifenóis/farmacologia , Substâncias Protetoras/farmacologia , Animais , Glutationa/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , Malus , Aprendizagem em Labirinto/efeitos dos fármacos , Memória/efeitos dos fármacos , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/tratamento farmacológico , Transtornos da Memória/metabolismo , Neurônios/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley
11.
Nutr Metab Cardiovasc Dis ; 30(8): 1249-1259, 2020 07 24.
Artigo em Inglês | MEDLINE | ID: mdl-32446870

RESUMO

BACKGROUND AND AIMS: The alcohol-hypertension relation has been well documented, but whether women have protective effect or race and type of beverage consumed affect the association remain unclear. To quantify the relation between total or beverage-specific alcohol consumption and incident hypertension by considering the effect of sex and race. METHODS AND RESULTS: Articles were identified in PubMed and Embase databases with no restriction on publication date. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated by random effects models. Restricted cubic splines were used to model the dose-response association. This study involved 22 articles (31 studies) and included 414,477 participants. The hypertension risk was different among liquor, wine, and beer at 5.1-10 g/d of ethanol consumption (P-across subgroups = 0.002). The hypertension risk differed between men (RR: 1.14, 95% CI: 1.07, 1.20) and women (RR: 0.98, 95% CI: 0.89, 1.06) at 10 g/d (P-across subgroups = 0.005). We found a linear alcohol-hypertension association among white (P-linearity = 0.017), black people (P-linearity = 0.035), and Asians (P-linearity<0.001). With 10 g/d increment of consumption, the RRs for hypertension were 1.06 (95% CI: 1.04, 1.08), 1.14 (95% CI: 1.01, 1.28), and 1.06 (95% CI: 1.01, 1.10) for Asians, black, and white people, respectively. CONCLUSION: Sex modifies the alcohol-hypertension association at low level of alcohol consumption and we did not find evidence of a protective effect of alcohol consumption among women. Black people may have higher hypertension risk than Asians and white people at the same ethanol consumption.


Assuntos
Grupo com Ancestrais do Continente Africano , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/etnologia , Bebidas Alcoólicas/efeitos adversos , Grupo com Ancestrais do Continente Asiático , Pressão Sanguínea , Grupo com Ancestrais do Continente Europeu , Hipertensão/etnologia , Cerveja/efeitos adversos , Relação Dose-Resposta a Droga , Etanol/efeitos adversos , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/fisiopatologia , Incidência , Masculino , Fatores Raciais , Medição de Risco , Fatores de Risco , Fatores Sexuais , Vinho/efeitos adversos
12.
Chem Biol Interact ; 325: 109132, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32437693

RESUMO

BACKGROUND: Alcohol increases the risk of developing colon cancer (CRC), in part via tissue inflammation and impaired barrier integrity. Circadian dyssynchrony (CD) is an understudied but common lifestyle associated factor that increases the risk of multi-organ tissue injury and number of malignancies including CRC. Our prior studies showed that the shift in light-dark cycle exacerbates barrier dysfunction and colonic inflammation in the setting of alcohol treatment, and increases the risk of CRC. Here we studied the interaction of alcohol with an abnormal eating pattern on markers of CD and colonic barrier integrity. METHOD: Mice were subjected to day (rest-phase = wrong-time WT) or night-time (active-phase = right-time RT) access to food in combination with access to water or 15% alcohol for total duration of 10 weeks. The food and liquid intake was measured. The locomotor activity data was recorded throughout the study, using a beam-break system. Mice were euthanized at two time points (ZT2 and ZT14). Time variation in the expression of the molecular marker of circadian clock (per2 gene) was measured in the central (hypothalamus) and intestinal (colon) tissue. Colonic protein expression of barrier markers (Occludin and Claudin-1) was studied. RESULTS: No significant differences were present in the weight gain and alcohol intake among the groups over the study period. We observed an interaction of WT eating with alcohol on behavioral markers of circadian rhythm. Compared to the RT + Water treated animals ("reference group"), combination of WT eating and alcohol consumption (WT + Alcohol) significantly changed the per2 oscillatory pattern, that was different between the colon and hypothalamus, indicative of worsening circadian dyssynchrony. This was associated with an overall impaired expression of barrier integrity markers in the colon. CONCLUSIONS: Alcohol induces circadian dyssynchrony which is worsened by abnormal food timing, associated with impaired barrier integrity in the colon. Future studies on the interaction of alcohol and food timing could provide further insights into alcohol associated CRC pathophysiology.


Assuntos
Ritmo Circadiano/efeitos dos fármacos , Colo/efeitos dos fármacos , Colo/patologia , Ingestão de Alimentos/fisiologia , Etanol/efeitos adversos , Consumo de Bebidas Alcoólicas/patologia , Consumo de Bebidas Alcoólicas/fisiopatologia , Animais , Biomarcadores/metabolismo , Colo/lesões , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fatores de Tempo
15.
Alcohol Alcohol ; 55(4): 354-356, 2020 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-32400852

RESUMO

AIM: In view of the increase in the use of ethanol-containing hand sanitizers throughout the world due to the current COVID-19 pandemic, we wished to review the possible risks to patients treated with disulfiram, following a case report in which an apparent DER (disulfiram-ethanol reaction) was attributed to the cutaneous absorption of alcohol from hand sanitizers as well as by inhalation of vapour. METHOD: Simple experiments to assess the levels of absorption by each route separately. RESULTS: Our results strongly suggest that while amounts of alcohol sufficient to cause a DER may be inhaled when hand sanitizers are used in confined spaces, absorption can be avoided by dispersal of the fumes, and absorption from the skin alone does not occur in pharmacologically significant quantities. CONCLUSION: Warnings about absorption of alcohol through the skin from hand sanitizers and products such as perfumes, deodorants and after-shave (whose use is often warned against when disulfiram is prescribed) should be modified accordingly.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Dissulfiram/efeitos adversos , Dissulfiram/química , Etanol/química , Etanol/farmacocinética , Higienizadores de Mão/efeitos adversos , Higienizadores de Mão/farmacocinética , Pneumonia Viral/complicações , Administração por Inalação , Testes Respiratórios/métodos , Dissulfiram/farmacocinética , Dissulfiram/uso terapêutico , Etanol/administração & dosagem , Etanol/efeitos adversos , Higienizadores de Mão/administração & dosagem , Higienizadores de Mão/química , Humanos , Pandemias , Absorção Cutânea/efeitos dos fármacos
16.
Nat Commun ; 11(1): 2555, 2020 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-32444624

RESUMO

Fetal alcohol exposure (FAE) is the leading preventable developmental cause of cognitive dysfunction. Even in the absence of binge drinking, alcohol consumption during pregnancy can leave offspring deficient. However, the mechanisms underlying these deficiencies are unknown. Using a mouse model of gestational ethanol exposure (GEE), we show increased instrumental lever-pressing and disruption of efficient habitual actions in adults, indicative of disrupted cognitive function. In vivo electrophysiology reveals disrupted action encoding in dorsolateral striatum (DLS) associated with altered habit learning. GEE mice exhibit decreased GABAergic transmission onto DLS projection neurons, including inputs from parvalbumin interneurons, and increased endocannabinoid tone. Chemogenetic activation of DLS parvalbumin interneurons reduces the elevated lever pressing of GEE mice. Pharmacologically increasing endocannabinoid tone mimics GEE effects on cognition and synaptic transmission. These findings show GEE induces long-lasting deficits in cognitive function that may contribute to human FAE, and identify potential mechanisms for future therapeutic targeting.


Assuntos
Corpo Estriado/fisiopatologia , Etanol/efeitos adversos , Exposição Materna/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal/psicologia , Animais , Cognição/efeitos dos fármacos , Corpo Estriado/metabolismo , Corpo Estriado/fisiologia , Etanol/metabolismo , Feminino , Desenvolvimento Fetal , Humanos , Masculino , Camundongos Endogâmicos C57BL , Linhagem , Gravidez , Efeitos Tardios da Exposição Pré-Natal/etiologia , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia
18.
Subcell Biochem ; 95: 197-225, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32297301

RESUMO

Fetal Alcohol Spectrum Disorder (FASD) is a complex set of developmental malformations, neurobehavioral anomalies and mental disabilities induced by exposing human embryos to alcohol during fetal development. Several experimental models and a series of developmental and biochemical approaches have established a strong link between FASD and reduced retinoic acid (RA) signaling. RA signaling is involved in the regulation of numerous developmental decisions from patterning of the anterior-posterior axis, starting at gastrulation, to the differentiation of specific cell types within developing organs, to adult tissue homeostasis. Being such an important regulatory signal during embryonic development, mutations or environmental perturbations that affect the level, timing or location of the RA signal can induce multiple and severe developmental malformations. The evidence connecting human syndromes to reduced RA signaling is presented here and the resulting phenotypes are compared to FASD. Available data suggest that competition between ethanol clearance and RA biosynthesis is a major etiological component in FASD.


Assuntos
Desenvolvimento Embrionário , Transtornos do Espectro Alcoólico Fetal/metabolismo , Transdução de Sinais , Tretinoína/metabolismo , Desenvolvimento Embrionário/efeitos dos fármacos , Etanol/efeitos adversos , Transtornos do Espectro Alcoólico Fetal/genética , Humanos
19.
Chin J Nat Med ; 18(3): 169-177, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32245586

RESUMO

The objective of this study was to verify the protective effect of Bifidobacterium longum (BL) and the synergistical effect of Selenium and BL on alcohol plus high fat diet (HFD) induced hepatic injury in mice. We also want to explore the mechanism of Selenium-enriched Bifidobacterium longum (SeBL). C57BL/6 mice were treated with alcohol plus HFD with or without different dosage of BL or SeBL for 4 weeks. Serum levels of ALT, AST, TC, TG, LDL-C, HDL-C, FFAs, TNF-α, IL-6 and IL-1ß, hepatic MDA level, SOD activity, the mRNA levels of AMPK, PPAR-α and SREBP1 were invested. SeBL inhibited lipid accumulation in hepatocytes; reduced serum AST and ALT levels; improved dyslipidemia; decreased serum FFAs, TC, TG and LDL-C levels. SeBL also inhibited alcohol plus HFD-induced hepatocyte oxidative stress through decrease in hepatic MDA levels and increase in SOD activity. SeBL also regulated lipid metabolism related genes such as AMPK, PPAR-α and SREBP1. Although BL had similar effect as SeBL, SeBL is more effective than BL. SeBL protected mice from alcohol plus HFD-induced hepatic injury in mice because of its inhibitory effect on hepatocellular oxidative stress, lipogenesis and inflammation. Selenium enhanced the protective effect of BL.


Assuntos
Bifidobacterium longum , Fígado Gorduroso Alcoólico/terapia , Hepatopatia Gordurosa não Alcoólica/terapia , Estresse Oxidativo , Probióticos/uso terapêutico , Selênio/química , Animais , Dieta Hiperlipídica/efeitos adversos , Suplementos Nutricionais , Etanol/efeitos adversos , Metabolismo dos Lipídeos , Fígado/efeitos dos fármacos , Fígado/fisiopatologia , Testes de Função Hepática , Masculino , Camundongos Endogâmicos C57BL
20.
Chin J Nat Med ; 18(3): 186-195, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32245588

RESUMO

Alcoholic liver disease (ALD) has become one of the leading causes of death in the world. Berbamine (BM), a natural product mainly derived from Berberis vulgaris L, possesses multiple bioactivities as a traditional medicine. However, the protective effect of BM on ALD remains unknown. In this study, we investigated the effect of BM on ethanol-induced hepatic injury in mice and its underlying mechanism. It was shown that BM at 0.3125-40 µmol·L-1had no effect on macrophages and hepatocytes proliferation. BM at 5-20 µmol·L-1 significantly inhibited lipopolysaccharide (LPS) or acetate-induced IL-1ß and IL-6 mRNA expression in RAW264.7 cells. Moreover, BM treatment significantly inhibited LPS-induced p65 and STAT3 phosphorylation in RAW264.7 cells. Hepatic histopathology analysis showed that inflammatory cells infiltration and lipid accumulation were suppressed by 25 and 50 mg·kg-1 BM administration in ethanol-induced hepatic injury mouse model. Meanwhile, BM treatment significantly inhibited serum ALT and AST levels in ethanol-fed mice. Oil red O staining results showed that BM administration ameliorated hepatic lipid accumulation in ethanol-fed mice. Preventions of ethanol-induced hepatic injury by BM were reflected by markedly decreased serum and hepatic triglyceride (TG) and total cholesterol (TC) contents. Real-time PCR results showed that BM treatment significantly inhibited pro-inflammatory cytokines mRNA expression in ethanol-fed mouse liver. Remarkably, the mechanism of action of BM was related to the reduction of ethanol-induced NF-κB and STAT3 phosphorylation levels in liver. In addition, BM treatment significantly inhibited ERK phosphorylation but not JNK and p38 of MAPK pathway. Taken together, our results demonstrate a beneficial effect of BM on ethanol-induced liver injury via a mechanism associated with inactivation of NF-κB, STAT3 and ERK pathway, which gives insight into the further evaluation of the therapeutic potential of BM for ALD.


Assuntos
Benzilisoquinolinas/farmacologia , Doença Hepática Crônica Induzida por Substâncias e Drogas/tratamento farmacológico , Inflamação/tratamento farmacológico , Fígado/efeitos dos fármacos , Animais , Colesterol/sangue , Citocinas/metabolismo , Etanol/efeitos adversos , Feminino , Hepatócitos/efeitos dos fármacos , Metabolismo dos Lipídeos , Sistema de Sinalização das MAP Quinases , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Células RAW 264.7 , Fator de Transcrição STAT3/metabolismo , Triglicerídeos/sangue
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