RESUMO
Prenatal adversity or stress can have long-term consequences on developmental trajectories and health outcomes. Although the biological mechanisms underlying these effects are poorly understood, epigenetic modifications, such as DNA methylation, have the potential to link early-life environments to alterations in physiological systems, with long-term functional implications. We investigated the consequences of two prenatal insults, prenatal alcohol exposure (PAE) and food-related stress, on DNA methylation profiles of the rat brain during early development. As these insults can have sex-specific effects on biological outcomes, we analyzed epigenome-wide DNA methylation patterns in prefrontal cortex, a key brain region involved in cognition, executive function, and behavior, of both males and females. We found sex-dependent and sex-concordant influences of these insults on epigenetic patterns. These alterations occurred in genes and pathways related to brain development and immune function, suggesting that PAE and food-related stress may reprogram neurobiological/physiological systems partly through central epigenetic changes, and may do so in a sex-dependent manner. Such epigenetic changes may reflect the sex-specific effects of prenatal insults on long-term functional and health outcomes and have important implications for understanding possible mechanisms underlying fetal alcohol spectrum disorder and other neurodevelopmental disorders.
Assuntos
Álcoois/efeitos adversos , Metilação de DNA/efeitos dos fármacos , Córtex Pré-Frontal/química , Efeitos Tardios da Exposição Pré-Natal/genética , Análise de Sequência de DNA/métodos , Animais , Modelos Animais de Doenças , Epigênese Genética/efeitos dos fármacos , Função Executiva/efeitos dos fármacos , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Masculino , Córtex Pré-Frontal/efeitos dos fármacos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/psicologia , Ratos , Caracteres SexuaisRESUMO
BACKGROUND: Chronic alcohol consumption is more frequently associated with advanced, aggressive hepatocellular carcinoma (HCC) tumors. Alcohol adversely impacts ER/Golgi membrane trafficking and Golgi protein N-glycosylation in hepatocytes; these effects have been attributed (in part) to dysregulated adenosine diphosphate-ribosylation factor (ARF) GTPase signaling. Here, we investigated the role of the ARF GTPase guanine exchange factor PSD4 in HCC progression. METHODS: R-based bioinformatics analysis was performed on publicly available array data. Modulating gene expression was accomplished via lentiviral vectors. Gene expression was analyzed using quantitative real-time PCR and immunoblotting. PSD4 promoter methylation was assessed using quantitative methylation-specific PCR. Phospho-p65(S276)/DNMT1 binding to the PSD4 promoter was analyzed via chromatin immunoprecipitation. We constructed ethanol/DEN-induced and DEN only-induced transgenic murine models of HCC. RESULTS: We identified PSD4 as a hypermethylated, suppressed gene in alcohol-related HCC tumors; however, PSD4 was not dysregulated in all-cause HCC tumors. Certain HCC cell lines also displayed varying degrees of PSD4 downregulation. PSD4 overexpression or knockdown decreased and increased cell migration and invasiveness, respectively. Mechanistically, PSD4 transcription was repressed by TNF-α-induced phospho-p65(S276)'s recruitment of DNA methyltransferase 1 (DNMT1), resulting in PSD4 promoter methylation. PSD4 inhibited pro-EMT CDC42 activity, resulting in downregulation of E-cadherin and upregulation of N-cadherin and vimentin. Hepatocyte-specific PSD4 overexpression reduced ethanol/DEN-induced HCC tumor progression and EMT marker expression in vivo. CONCLUSIONS: PSD4 is a hypermethylated, suppressed gene in alcohol-related HCC tumors that negatively modulated pro-EMT CDC42 activity. Furthermore, we present a novel phospho-NF-κB p65(S276)/DNMT1-mediated promoter methylation mechanism by which TNF-α/NF-κB signaling represses PSD4 transcription in HCC cells.
Assuntos
Álcoois/efeitos adversos , Carcinoma Hepatocelular/genética , Epigênese Genética/genética , Fatores de Troca do Nucleotídeo Guanina/genética , Neoplasias Hepáticas/genética , NF-kappa B/genética , Transcrição Gênica/genética , Fator de Necrose Tumoral alfa/genética , Consumo de Bebidas Alcoólicas/genética , Animais , Caderinas/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , DNA (Citosina-5-)-Metiltransferase 1/genética , Metilação de DNA/genética , Regulação para Baixo/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Células Hep G2 , Hepatócitos/patologia , Humanos , Neoplasias Hepáticas/patologia , Camundongos , Camundongos Transgênicos , Gravidez , Regiões Promotoras Genéticas/genética , Transdução de Sinais/genética , Fator de Transcrição RelA/genéticaRESUMO
Radiotherapy and cisplatin lead to cell killing in head and neck squamous cell carcinoma patients, but adverse events and response to treatment are not the same in patients with similar clinicopathological aspects. The aim of this prospective study was to evaluate the roles of TP53 c.215G > C, FAS c.-671A > G, FAS c.-1378G > A, FASL c.-844 C > T, CASP3 c.-1191A > G, and CASP3 c.-182-247G > T single nucleotide variants in toxicity, response rate, and survival of cisplatin chemoradiation-treated head and neck squamous cell carcinoma patients. Genomic DNA was analyzed by polymerase chain reaction for genotyping. Differences between groups of patients were analyzed by chi-square test or Fisher's exact test, multiple logistic regression analysis, and Cox hazards model. One hundred nine patients with head and neck squamous cell carcinoma were enrolled in study. All patients were smokers and/or alcoholics. Patients with FAS c.-671GG genotype, FAS c.-671AG or GG genotype, and FASL c.-844CC genotype had 5.52 (95% confidence interval (CI): 1.42-21.43), 4.03 (95% CI: 1.51-10.79), and 5.77 (95% CI: 1.23-27.04) more chances of presenting chemoradiation-related anemia of grades 2-4, lymphopenia of grade 3 or 4, and ototoxicity of all grades, respectively, than those with the remaining genotypes. FAS c.-671GG genotype was also seen as an independent predictor of shorter event-free survival (hazard ratio (HR): 2.05; P = 0.007) and overall survival (HR: 1.83; P = 0.02) in our head and neck squamous cell carcinoma patients. These findings present, for the first time, preliminary evidence that inherited abnormalities in apoptosis pathway, related to FAS c.-671A > G and FASL c.-844 C > T single nucleotide variants, can alter toxicity and survival of tobacco- and alcohol-related head and neck squamous cell carcinoma patients homogeneously treated with cisplatin chemoradiation.
Assuntos
Proteína Ligante Fas/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Receptor fas/genética , Adulto , Idoso , Álcoois/efeitos adversos , Quimiorradioterapia/efeitos adversos , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/genética , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Prognóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/induzido quimicamente , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Nicotiana/efeitos adversos , Proteína Supressora de Tumor p53/genéticaRESUMO
This study investigated the protective effects of pu-erh tea extract (PTE) on alcohol-induced microbiomic and metabolomic disorders. In chronic alcohol-exposed mice, PTE ameliorated chronic alcoholic consumption-induced oxidative stress, inflammation, lipid accumulation, and liver and colon damage through modulating microbiomic and metabolomic responses. PTE restored the alcohol-induced fecal microbiota dysbiosis by elevating the relative abundance of potentially beneficial bacteria, for example, Bifidobacterium and Allobaculum, and decreasing the relative abundance of potentially harmful bacteria, for example, Helicobacter and Bacteroides. The alcohol-induced metabolomic disorder was modulated by PTE, which was characterized by regulations of lipid metabolism (sphingolipid, glycerophospholipid, and linoleic acid metabolism), amino acid metabolism (phenylalanine and tryptophan metabolism), and purine metabolism. Besides, the bacterial metabolites of phytochemicals in PTE might contribute to the protective effects of PTE. Overall, PTE could be a functional beverage to treat chronic alcohol consumption-induced microbiomic and metabolomic disorders.
Assuntos
Consumo de Bebidas Alcoólicas/metabolismo , Álcoois/efeitos adversos , Camellia sinensis/metabolismo , Microbioma Gastrointestinal , Metaboloma/efeitos dos fármacos , Chá/metabolismo , Animais , Bactérias/efeitos dos fármacos , Bactérias/genética , Bactérias/isolamento & purificação , Bactérias/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BLRESUMO
The aim of this proof of concept study is to investigate if an electronic nose (eNose) is able to make a distinction between breath profiles of diagnosed epilepsy patients and epilepsy-free control subjects. An eNose is a non-invasive device, with a working mechanism that is based on the presence of volatile organic compounds (VOCs) in exhaled breath. These VOCs interact with the sensors of the eNose, and the eNose has to be trained to distinguish between breath patterns from patients with a specific disease and control subjects without that disease. During the measurement participants were asked to breathe through the eNose for five minutes via a disposable mouthpiece. Seventy-four epilepsy patients and 110 control subjects were measured to train the eNose and create a classification model. To assess the effects of anti-epileptic drugs (AEDs) usage on the classification, additional test groups were measured: seven patients who (temporarily) did not use AEDs and 11 patients without epilepsy who used AEDs. The results show that an eNose is able to make a distinction between epilepsy and control subjects with a sensitivity of 76%, a specificity of 67%, and an accuracy of 71%. The results of the two additional groups of subjects show that the created model classifies one out of seven epilepsy patients without AEDs and six out of 13 patients without epilepsy but with AEDs correctly. In this proof of concept study, the AeonoseTM is able to differentiate between epilepsy patients and control subjects. However, the number of false positives and false negatives is still high, which suggests that this first model is still mainly based on the usage of various AEDs.
Assuntos
Testes Respiratórios/métodos , Epilepsia/diagnóstico , Adulto , Álcoois/efeitos adversos , Anticonvulsivantes/uso terapêutico , Estudos de Casos e Controles , Fumar Cigarros/efeitos adversos , Café/efeitos adversos , Nariz Eletrônico , Epilepsia/tratamento farmacológico , Expiração , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROCRESUMO
Many antibiotics carry caution stickers that warn against alcohol consumption. Data regarding concurrent use are sparse. An awareness of data that address this common clinical scenario is important so health care professionals can make informed clinical decisions and address questions in an evidence-based manner. The purpose of this systematic review was to determine the evidence behind alcohol warnings issued for many common antimicrobials. The search was conducted from inception of each database to 2018 using PubMed, Medline via Ovid, and Embase. It included studies that involved interactions, effects on efficacy, and toxicity/adverse drug reactions (ADR) due to concomitant alcohol consumption and antimicrobials. All interactions were considered in terms of three components: (i) alteration in pharmacokinetics/pharmacodynamics (PK/PD) of antimicrobials and/or alcohol, (ii) change in antimicrobial efficacy, and (iii) development of toxicity/ADR. Available data support that oral penicillins, cefdinir, cefpodoxime, fluoroquinolones, azithromycin, tetracycline, nitrofurantoin, secnidazole, tinidazole, and fluconazole can be safely used with concomitant alcohol consumption. Data are equivocal for trimethoprim-sulfamethoxazole. Erythromycin may have reduced efficacy with alcohol consumption, and doxycycline may have reduced efficacy in chronic alcoholism. Alcohol low in tyramine may be consumed with oxazolidinones. The disulfiram-like reaction, though classically associated with metronidazole, occurs with uncertain frequency and with varied severity. Cephalosporins with a methylthiotetrazole (MTT) side chain or a methylthiodioxotriazine (MTDT) ring, ketoconazole, and griseofulvin have an increased risk of a disulfiram-like reaction. Alcohol and antimicrobial interactions are often lacking evidence. This review questions common beliefs due to poor, often conflicting data and identifies important knowledge gaps.
Assuntos
Álcoois/efeitos adversos , Álcoois/farmacocinética , Antibacterianos/efeitos adversos , Antibacterianos/farmacocinética , Anti-Infecciosos/efeitos adversos , Anti-Infecciosos/farmacocinética , Azitromicina/efeitos adversos , Azitromicina/farmacocinética , Cefalosporinas/efeitos adversos , Cefalosporinas/farmacocinética , Doxiciclina/efeitos adversos , Doxiciclina/farmacocinética , Interações Medicamentosas , Eritromicina/efeitos adversos , Eritromicina/farmacocinética , Fluoroquinolonas/efeitos adversos , Fluoroquinolonas/farmacocinética , Metronidazol/efeitos adversos , Metronidazol/análogos & derivados , Metronidazol/farmacocinética , Penicilinas/efeitos adversos , Penicilinas/farmacocinética , Tetraciclina/efeitos adversos , Tetraciclina/farmacocinéticaRESUMO
BACKGROUND: Alcohol intake predisposes to infections and sepsis. Alcohol and sepsis inhibit the expression of milk fat globule epidermal growth factor-factor VIII (MFG-E8), a glycoprotein essential for optimal efferocytosis, resulting in the release of proinflammatory molecules and increased sepsis severity. We previously reported that recombinant mouse (rm) MFG-E8 attenuates sepsis-induced organ injury in rats with acute alcohol intoxication. In order to develop a therapy that can be safely used in humans, we have produced recombinant human (rh) MFG-E8 and evaluated its efficacy to ameliorate sepsis after acute exposure to alcohol. METHODS: We induced acute alcohol intoxication with a bolus injection of alcohol (1.75 g/kg BW) followed by an intravenous infusion of 300 mg/kg/h alcohol for 10 h. Sepsis was then induced by cecal ligation and puncture (CLP). At -10, 0, and 10 h relative to CLP, rats received MFG-E8 or vehicle (albumin) intravenously. Animals were euthanized at 20 h after CLP for blood and tissue collection. Additional groups of animals were used for a survival study. RESULTS: Compared to vehicle, rhMFG-E8 treatment ameliorated blood levels of proinflammatory cytokines (% improvement: TNF-α 49.8%, IL-6 34.7%) and endotoxin (61.7%), as well as of transaminases (AST 36.2%, ALT 40.1%) and lactate (18.4%). Rats treated with rhMFG-E8 also had a significant histological attenuation of the acute lung injury, as well as a reduction in the number of apoptotic cells in the thymus (43.4%) and cleaved caspase 3 (38.7%) in the spleen. In addition, rhMFG-E8 improved the 10-day sepsis survival rate from 45 to 80% CONCLUSION: rhMFG-E8 significantly ameliorated sepsis in rats with acute alcohol exposure, demonstrating rhMFG-E8's potential to be developed as an effective therapy for sepsis in alcohol abusers.
Assuntos
Álcoois/efeitos adversos , Antígenos de Superfície/farmacologia , Proteínas do Leite/farmacologia , Proteínas Recombinantes/farmacologia , Sepse , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/patologia , Animais , Apoptose/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Citocinas/metabolismo , Modelos Animais de Doenças , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Masculino , Ratos , Ratos Sprague-Dawley , Sepse/induzido quimicamente , Sepse/metabolismo , Sepse/mortalidadeRESUMO
This study investigated the modulatory effects of Decaisnea insignis seed oil (DISO), which was rich in palmitoleic acid (55.25%), palmitic acid (12.25%), and oleic acid (28.74%), on alcohol-induced metabolism disorder in mice. Fifty mice were orally administered with 38% alcohol (0.4 mL/day) and without or with DISO (3, 6, and 12 g/kg) for consecutive 12 weeks. DISO inhibited the alcohol-induced weight loss and liver function abnormality (p < 0.01) and shifted the profiles of cecal microbiome: elevating the abundance of Lactobacillus, Ruminoccoceae_UCG_004 (p < 0.05) and decreasing abundance of Parabacteroides (p < 0.05). This treatment also regulated metabolome response of amino acid and lipid metabolism in cecal content: upregulating 5-hydroxyindole-3-acetic acid (p < 0.05), 6-hydroxynicotinic acid, 5-methoxytryptamine, nicotinamide, and nicotinic acid (p < 0.1) and downregulating androsterone, tryptophan, and indole-3-acetamide (p < 0.05). DISO protected against alcoholic liver injury and gut microbiota dysbiosis by enriching the relative abundance of Lactobacillus, which was positively associated with the improvement of intestinal permeability and tryptophan metabolism.
Assuntos
Álcoois/efeitos adversos , Disbiose/prevenção & controle , Microbioma Gastrointestinal/efeitos dos fármacos , Hepatopatias Alcoólicas/prevenção & controle , Magnoliopsida/química , Óleos de Plantas/administração & dosagem , Consumo de Bebidas Alcoólicas/efeitos adversos , Aminoácidos/metabolismo , Animais , Bactérias/classificação , Bactérias/efeitos dos fármacos , Bactérias/genética , Bactérias/isolamento & purificação , Ceco/efeitos dos fármacos , Ceco/microbiologia , Disbiose/metabolismo , Disbiose/microbiologia , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Hepatopatias Alcoólicas/metabolismo , Hepatopatias Alcoólicas/microbiologia , Masculino , Metaboloma/efeitos dos fármacos , Camundongos , Microbiota/efeitos dos fármacos , Sementes/químicaRESUMO
BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitory peptides were found to alleviate acute hepatitis significantly. In this study, we purified and identified ACE inhibitory peptide from cashew to evaluate its protective role on alcohol-induced acute hepatitis in mice. RESULTS: The ACE inhibitory peptides were purified by using consecutive chromatographic techniques. One of these peptides (FETISFK) exhibited the highest ACE inhibition rate (91.04 ± 0.31%). In vivo, the results showed that ACE inhibitory peptide decreased levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) caused by alcohol exposure. Moreover, it could increase the activities of superoxide dismutase (SOD) and glutathione (GSH), and decrease the level of malondialdehyde (MDA). It was also found to down-regulate markedly the expression of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). It could also decrease the expression of ACE, angiotensin II (AngII) and angiotensin II type 1 receptor (AT1 R). CONCLUSION: These findings support the view that the ACE inhibitory peptide alleviated acute hepatitis by down-regulating the ACE-AngII-AT1 R axis, broadening the research approach to prevent acute hepatitis, and providing experimental data for the development and utilization of cashews. © 2019 Society of Chemical Industry.
Assuntos
Anacardium/química , Inibidores da Enzima Conversora de Angiotensina/química , Hepatite/tratamento farmacológico , Peptídeos/química , Extratos Vegetais/química , Doença Aguda/terapia , Álcoois/efeitos adversos , Angiotensina II/genética , Angiotensina II/metabolismo , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/isolamento & purificação , Animais , Aspartato Aminotransferases/genética , Aspartato Aminotransferases/metabolismo , Hepatite/enzimologia , Hepatite/etiologia , Humanos , Interleucina-6/genética , Interleucina-6/metabolismo , Masculino , Camundongos , Nozes/química , Peptídeos/administração & dosagem , Peptídeos/isolamento & purificação , Peptidil Dipeptidase A/química , Peptidil Dipeptidase A/metabolismo , Extratos Vegetais/administração & dosagem , Extratos Vegetais/isolamento & purificação , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismoRESUMO
BACKGROUND: Chronic consumption of most drugs of abuse leads to brain oxidative stress and neuroinflammation, which inhibit the glutamate transporter GLT-1, proposed to perpetuate drug intake. The present study aimed at inhibiting chronic ethanol and nicotine self-administration and relapse by the non-invasive intranasal administration of antioxidant and anti-inflammatory secretome generated by adipose tissue-derived activated mesenchymal stem cells. The anti-addiction mechanism of stem cell secretome is also addressed. METHODS: Rats bred for their alcohol preference ingested alcohol chronically or were trained to self-administer nicotine. Secretome of human adipose tissue-derived activated mesenchymal stem cells was administered intranasally to animals, both (i) chronically consuming alcohol or nicotine and (ii) during a protracted deprivation before a drug re-access leading to relapse intake. RESULTS: The intranasal administration of secretome derived from activated mesenchymal stem cells inhibited chronic self-administration of ethanol or nicotine by 85% and 75%, respectively. Secretome administration further inhibited by 85-90% the relapse "binge" intake that occurs after a protracted drug deprivation followed by a 60-min drug re-access. Secretome administration fully abolished the oxidative stress induced by chronic ethanol or nicotine self-administration, shown by the normalization of the hippocampal oxidized/reduced glutathione ratio, and the neuroinflammation determined by astrocyte and microglial immunofluorescence. Knockdown of the glutamate transporter GLT-1 by the intracerebral administration of an antisense oligonucleotide fully abolished the inhibitory effect of the secretome on ethanol and nicotine intake. CONCLUSIONS: The non-invasive intranasal administration of secretome generated by human adipose tissue-derived activated mesenchymal stem cells markedly inhibits alcohol and nicotine self-administration, an effect mediated by the glutamate GLT-1 transporter. Translational implications are envisioned.
Assuntos
Transtornos do Sistema Nervoso Induzidos por Álcool/terapia , Inflamação/terapia , Transplante de Células-Tronco Mesenquimais , Tabagismo/terapia , Administração Intranasal , Transtornos do Sistema Nervoso Induzidos por Álcool/patologia , Transtornos do Sistema Nervoso Induzidos por Álcool/prevenção & controle , Álcoois/efeitos adversos , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Humanos , Inflamação/patologia , Inflamação/prevenção & controle , Masculino , Células-Tronco Mesenquimais/metabolismo , Tecido Nervoso/patologia , Tecido Nervoso/transplante , Nicotina/efeitos adversos , Estresse Oxidativo/genética , Ratos , Autoadministração , Tabagismo/patologia , Tabagismo/prevenção & controleAssuntos
Medicina Aeroespacial/história , Medicina Militar/história , Fatores Etários , Álcoois/efeitos adversos , Distinções e Prêmios , Ritmo Circadiano/fisiologia , Sistemas Ecológicos Fechados , História do Século XX , Humanos , Pilotos , Desempenho Psicomotor/efeitos dos fármacos , Desempenho Psicomotor/fisiologiaRESUMO
This study was conducted to investigate the beneficial effects and possible mechanism of action of mangiferin (MF) in alcohol hepatitis (AH) rats. Building on our previous study, the damage-associated molecular patterns (DAMPs), lipid metabolic disorder and mitochondrial dysfunction were investigated. MF effectively regulated the abnormal liver function, the levels of alcohol, FFAs and metal elements in serum. More importantly, MF improved the expression levels of mRNA and protein of PPAR-γ, OPA-1, Cav-1, EB1, NF-κB p65, NLRP3, Cas-1 and IL-1ß, and decreased the positive protein expression rates of HSP90, HMGB1, SYK, CCL20, C-CAS-3, C-PARP and STARD1. Additionally, MF decreased the levels of fumarate, cAMP, xanthurenic acid and d-glucurone-6,3-lactone, and increased the levels of hippuric acid and phenylacetylglycine, and then adjusted the changes of phenylalanine metabolism, TCA cycle and ascorbate and aldarate metabolic pathways. The above results suggested that MF can effectively prevent AH by modulating specific AH-associated genes, potential biomarkers and metabolic pathways in AH rats, etc.
Assuntos
Álcoois/efeitos adversos , Hepatite/tratamento farmacológico , Metabolismo dos Lipídeos/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Xantonas/administração & dosagem , Animais , Glicina/análogos & derivados , Glicina/metabolismo , Hepatite/etiologia , Hepatite/genética , Hepatite/metabolismo , Humanos , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Mitocôndrias/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , PPAR gama/genética , PPAR gama/metabolismo , Ratos , Ratos Sprague-Dawley , Fator de Transcrição RelA/genética , Fator de Transcrição RelA/metabolismo , Xanturenatos/metabolismoRESUMO
Alcohol-attributable mortality in certain countries of Central and Eastern Europe (CEE) remains higher than in their western neighbours. The effect of unrecorded alcohol consumption, including home-made fruit spirits have been suggested as an explanation. Besides ethanol, recorded and unrecorded spirits frequently contain other aliphatic alcohols (OAAs). Our aim was to ascertain whether there is any difference in the amounts of OAAs in recorded and unrecorded spirits, and thus the health risk associated with their consumption. The concentrations of ethanol and OAAs in recorded (nâ¯=â¯119) and unrecorded (nâ¯=â¯87) spirits were determined by gas chromatography and used in a Monte Carlo type probabilistic simulation to assess the risk based on average consumption level, consumption by regular drinkers and chronic heavy drinkers. The concentrations of OAAs in unrecorded spirits were significantly higher [median: 9896.1â¯mg/L, interquartile range (IQR): 7898.3-12 634.6â¯mg/L] than those in their recorded (median: 975.6â¯mg/L, IQR: 136.9-4006.7â¯mg/L) counterparts. Besides ethanol, methanol also posed a health risk at each consumption level. The risk associated with exposure to OAAs was higher only in chronic heavy drinkers consuming unrecorded spirits. These findings reinforce the importance of action to address the risks associated with consumption of recorded and unrecorded spirits.
Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Álcoois/efeitos adversos , Álcoois/análise , Etanol/efeitos adversos , Etanol/análise , Feminino , Humanos , Masculino , Método de Monte Carlo , Medição de Risco , Fatores de RiscoRESUMO
BACKGROUND: The prevalence of lanolin contact allergy in dermatitis patients varies from 1.2% to 6.9%. Different lanolin derivatives are used in patch testing. OBJECTIVES: To determine which combination of lanolin derivatives is most effective in patch testing for the diagnosis of lanolin contact allergy. METHODS: A retrospective analysis of patients patch tested between 2016 and 2017 was performed. Patients were eligible if they had been tested with lanolin alcohol 30% pet., Amerchol L101 50% pet., and a supplementary series containing other lanolin derivatives. Lanolin alcohol and Amerchol L101 were tested in duplicate. RESULTS: Of 594 patients, 28.6% (95% confidence interval [CI]: 25.1%-32.3%) had a positive patch test reaction to at least one lanolin derivative. Reactions to lanolin alcohol (14.7%, 95%CI: 11.3%-18.2%) and Amerchol L101 (15.0%, 95%CI: 11.5%-18.5%) were common in the routinely tested series. Reactions to other test preparations were significantly less frequent (P < 0.05). The addition of Amerchol L101 to lanolin alcohol significantly increased the number of positive cases (odds ratio 1.79, P < 0.001). CONCLUSIONS: The combination of lanolin alcohol and Amerchol L101 is effective in patch testing for the diagnosis of lanolin contact allergy. Routinely testing with other lanolin derivatives may not be worthwhile, as it detects only a few additional patients.
Assuntos
Dermatite Alérgica de Contato/diagnóstico , Lanolina/efeitos adversos , Testes do Emplastro/métodos , Adulto , Álcoois/efeitos adversos , Dermatite Alérgica de Contato/etiologia , Feminino , Humanos , Lanolina/análogos & derivados , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
Antiseptics are chemical substances that when applied topically onto intact skin, mucous membranes or wounds partially or completely reduces the population of living microorganisms in those tissues. Different types of antiseptics are available - those most commonly used in clinical practice being alcohols, iodinated compounds and chlorhexidine. When using an antiseptic, consideration is required of its spectrum of antimicrobial activity, latency, residual effects, possible interferences of the presence of organic material with the activity of the antiseptic, its side effects, compatibility with other antiseptics, and cost. This article is part of a supplement entitled "Antisepsis in the critical patient", which is sponsored by Becton Dickinson.
Assuntos
Álcoois/farmacologia , Anti-Infecciosos Locais/farmacologia , Compostos de Iodo/farmacologia , Álcoois/efeitos adversos , Anti-Infecciosos Locais/efeitos adversos , Anti-Infecciosos Locais/classificação , Cátions/efeitos adversos , Cátions/farmacologia , Clorexidina/efeitos adversos , Clorexidina/farmacologia , Interações Medicamentosas , Etanol/efeitos adversos , Etanol/farmacologia , Humanos , Peróxido de Hidrogênio/efeitos adversos , Peróxido de Hidrogênio/uso terapêutico , Unidades de Terapia Intensiva , Iodo/efeitos adversos , Iodo/farmacologia , Compostos de Iodo/efeitos adversos , Iodóforos/efeitos adversos , Iodóforos/farmacologia , Compostos de Mercúrio/farmacologia , Propranolol/efeitos adversos , Propranolol/farmacologia , Sulfadiazina/efeitos adversos , Sulfadiazina/farmacologia , Triclosan/efeitos adversos , Triclosan/farmacologiaRESUMO
The aim of the study was to determine serum concentrations of afamin and adropin in patients with alcoholic liver cirrhosis and to define their correlation with the stage of disease. The study included 99 patients with alcoholic cirrhosis from the region of Lublin, (Eastern Poland). Liver cirrhosis was diagnosed based on clinical features, history of heavy alcohol consumption, laboratory tests and abdominal ultrasonography. The control group consisted of 20 healthy individuals without liver disease who did not abuse alcohol. The serum afamin and adropin concentrations were determined using ELISA kits. The concentration of afamin was found to be significantly lower in patients with compensated alcoholic liver cirrhosis, i.e. P-Ch B (85.1±40.6 µg/ml) and P-Ch C (56.4±32.3 µg/ml) individuals, compared to the control group (135.9±43.6 µg/ml); p-value was <0.01 and <0.001, respectively. As far as adropin is concerned, a reverse relationship was demonstrated: the highest concentration was found in patients with P-Ch C (11.7±5.7 ng/ml) cirrhosis. Furthermore, the above concentration was significantly higher compared to patients with P-Ch A cirrhosis (7.2±2.8 ng/ml; p<0.05) and controls (7.5±2.6 ng/ml; p<0.05). The concentration of afamin decreases with the severity of alcoholic liver cirrhosis, which most likely results from impaired hepatic synthesis. Otherwise, the higher the stage of disease according to the Child-Pugh score, the higher the concentration of adropin.
Assuntos
Proteínas de Transporte/sangue , Glicoproteínas/sangue , Cirrose Hepática Alcoólica/sangue , Peptídeos/sangue , Adulto , Álcoois/efeitos adversos , Álcoois/metabolismo , Proteínas Sanguíneas/genética , Proteínas de Transporte/genética , Estudos de Casos e Controles , Feminino , Glicoproteínas/genética , Humanos , Peptídeos e Proteínas de Sinalização Intercelular , Cirrose Hepática Alcoólica/diagnóstico por imagem , Cirrose Hepática Alcoólica/etiologia , Cirrose Hepática Alcoólica/genética , Masculino , Pessoa de Meia-Idade , Peptídeos/genética , Polônia , Albumina Sérica Humana/genética , Índice de Gravidade de Doença , Ultrassonografia , Adulto JovemRESUMO
AIMS: The aim of the study was to evaluate the shear bond strength (SBS) of orthodontic brackets after mouth rinsing. MATERIALS AND METHODS: Sixty orthodontically extracted maxillary premolar teeth were used in the present study. Buccal surfaces of all the teeth were bonded with orthodontic bracket. Later, each tooth was embedded into acrylic resin and stored in distilled water. All the teeth were randomly divided into four groups (group I: Artificial saliva, group II: Alcohol mouth rinse- Listerine, group III: Chlorhexidine (CHX) mouth rinse-Hexidine, and group IV: Herbal mouth rinse-Befresh) and stored in each solution for 12 hours. Later, each tooth was subjected to SBS testing using universal testing machine. Brackets and enamel surfaces were examined under a stereomicroscope at 10* magnification for modified adhesive remnant index (ARI). The data were statistically evaluated using IBM Statistical Package for the Social Sciences (SPSS) Statistics for Windows, version 20.0 (IBM Corp., Armonk, New York, USA) and using one-way analysis of variance (ANOVA) and Chi-square test with significance of p < 0.05. RESULTS: Highest mean SBS was observed in artificial saliva control group (14.27 ± 0.52 MPa), followed by herbal Befresh group (11.14 ± 0.72 MPa) and CHX, and least was found in alcohol-Listerine group of 8.48 ± 0.52 MPa (p < 0.001). The ARI score showed highest bond failure for group I (ARI 14) compared to group II (ARI 11) (p < 0.001). CONCLUSION: Alcohol-containing mouth rinses should be avoided in patients during fixed orthodontic treatment because it affects the bond strength. CLINICAL SIGNIFICANCE: Shear bond strength is affected with the use of alcohol-based mouth rinse compared with herbal or CHX mouth rinses.
Assuntos
Álcoois/efeitos adversos , Colagem Dentária , Antissépticos Bucais/efeitos adversos , Antissépticos Bucais/química , Braquetes Ortodônticos , Resistência ao Cisalhamento , Resinas Acrílicas , Dente Pré-Molar , Análise do Estresse Dentário , Humanos , Técnicas In VitroRESUMO
BACKGROUND: Acupuncture has been used as a potential therapy for alcohol withdrawal syndrome (AWS), but evidence for its effects on this condition is limited. OBJECTIVE: To assess the effects and safety of acupuncture for AWS. DATA SOURCES: Central Register of Controlled Trials (CENTRAL), PubMed, Embase, the Cochrane Library, PsycINFO, Chinese Biomedicine Literature (CBM), China National Knowledge Infrastructure (CNKI) and Wan-Fang Database were searched from their inception to August 2016. STUDY ELIGIBILITY CRITERIA: Randomised controlled trials (RCTs) of drug plus acupuncture or acupuncture alone for the treatment of AWS were included. DATA COLLECTION AND ANALYSIS: Continuous data were expressed as mean difference (MD) with 95% confidence intervals (95% CI). Dichotomous data were expressed as risk ratio (RR) with 95% CI. RESULTS: Eleven RCTs with 875 participants were included. In the acute phase, two trials reported no difference between drug plus acupuncture and drug plus sham acupuncture in the reduction of craving for alcohol; however, two positive trials reported that drug plus acupuncture was superior to drug alone in the alleviation of psychological symptoms. In the protracted phase, one trial reported acupuncture was superior to sham acupuncture in reducing the craving for alcohol, one trial reported no difference between acupuncture and drug (disulfiram), and one trial reported acupuncture was superior to sham acupuncture for the alleviation of psychological symptoms. Adverse effects were tolerable and not severe. CONCLUSION: There was nosignificant difference between acupuncture (plus drug) and sham acupuncture (plus drug) with respect to the primary outcome measure of craving for alcohol among participants with AWS, and no difference in completion rates (pooled results). There was limited evidence from individual trials that acupuncture may reduce alcohol craving in the protracted phase and help alleviate psychological symptoms; however, given concerns about the quantity and quality of included studies, further large-scale and well-conducted RCTs are needed. PROTOCOL REGISTRATION: PROSPERO CRD42016039862.
Assuntos
Terapia por Acupuntura , Transtornos Relacionados ao Uso de Álcool/terapia , Álcoois/efeitos adversos , Síndrome de Abstinência a Substâncias/terapia , Humanos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
The aim of this study was to investigate the protective effect and mechanism of selenium-enriched Spirulina platensis (S. platensis) on chronic alcohol-induced liver injury. Selenium incubation raises the nutrition quality of S. platensis by absorption enhancement of functional elements. Our results demonstrated that the effective dose of selenium-enriched S. platensis on HL7702 cells treated with alcohol was 200 µg ml-1, containing 20% selenium. Selenium-enriched S. platensis could raise the cell survival rate by decreasing the expression of p53, Caspase3, LC3, and Caspase1 and by increasing the expression of p70s6k. In vivo experiments, where mice were pretreated with selenium-enriched S. platensis, exhibited obvious inhibition of the liver function index and this pretreatment enhanced the activity of GSH-Px and SOD in alcohol induced mice. In summary, our results indicate that the protective mechanism of selenium-enriched S. platensis on chronic alcoholic liver injury is associated with the activity enhancement of antioxidant enzymes and immunity, the inhibition of DNA damage and apoptosis, accompanied with autophagy and pyroptosis.