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1.
Int J Mol Sci ; 22(9)2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-34067023

RESUMO

Classical inflammation in response to bacterial, parasitic, or viral infections such as HIV includes local recruitment of neutrophils and macrophages and the production of proinflammatory cytokines and chemokines. Proposed biomarkers of organ integrity in Alcohol Use Disorders (AUD) include elevations in peripheral plasma levels of proinflammatory proteins. In testing this proposal, previous work included a group of human immunodeficiency virus (HIV)-infected individuals as positive controls and identified elevations in the soluble proteins TNFα and IP10; these cytokines were only elevated in AUD individuals seropositive for hepatitis C infection (HCV). The current observational, cross-sectional study evaluated whether higher levels of these proinflammatory cytokines would be associated with compromised brain integrity. Soluble protein levels were quantified in 86 healthy controls, 132 individuals with AUD, 54 individuals seropositive for HIV, and 49 individuals with AUD and HIV. Among the patient groups, HCV was present in 24 of the individuals with AUD, 13 individuals with HIV, and 20 of the individuals in the comorbid AUD and HIV group. Soluble protein levels were correlated to regional brain volumes as quantified with structural magnetic resonance imaging (MRI). In addition to higher levels of TNFα and IP10 in the 2 HIV groups and the HCV-seropositive AUD group, this study identified lower levels of IL1ß in the 3 patient groups relative to the control group. Only TNFα, however, showed a relationship with brain integrity: in HCV or HIV infection, higher peripheral levels of TNFα correlated with smaller subcortical white matter volume. These preliminary results highlight the privileged status of TNFα on brain integrity in the context of infection.


Assuntos
Alcoolismo/sangue , Infecções por HIV/sangue , Hepatite C/sangue , Fator de Necrose Tumoral alfa/sangue , Substância Branca/patologia , Alcoolismo/complicações , Comorbidade , Feminino , Infecções por HIV/complicações , Hepatite C/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Análise de Componente Principal , Solubilidade
2.
J Postgrad Med ; 67(1): 12-17, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33565472

RESUMO

Background: Craving plays an important role in maintenance of alcohol dependence. Earlier studies have analyzed the role of ghrelin in craving and their results have been heterogenous. Acyl ghrelin is its more active form as it crosses the blood brain barrier. Hence we aimed to examine the relationship between plasma acyl ghrelin and craving in Indian patients having alcohol dependence syndrome. Methods: The present study was a hospital-based prospective study. A total of 60 drug-naive patients of alcohol dependence and 30 healthy controls were included. After taking informed consent fasting blood samples were collected from them on day 1 and tested for plasma acyl ghrelin level. Fasting blood samples were repeated in all cases on day 14. During this time, we also assessed the patients' cravings by obsessive compulsive drinking scale, and alcohol craving questionnaire; and withdrawal by clinical institute withdrawal assessment for alcohol scale. These scales were repeated on day 14. Data analysis was done by SPSS version 25.0. Results: Plasma concentrations of acyl ghrelin increased significantly during early abstinence in patients from day 1 to day 14 (P < 0.0001). Pearson correlation test revealed a trend of positive correlation between plasma concentration of acyl ghrelin on day 14 and severity of craving on day 1. Conclusion: Our results suggest the plasma concentration of acyl ghrelin may be a predictor of severity of alcohol craving during early abstinence. Anti-craving drugs acting on acyl ghrelin level in brain may open an innovative avenue for optimum treatment of alcohol dependence.


Assuntos
Consumo de Bebidas Alcoólicas/epidemiologia , Alcoolismo/sangue , Fissura , Grelina/sangue , Adulto , Consumo de Bebidas Alcoólicas/sangue , Alcoolismo/epidemiologia , Alcoolismo/psicologia , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Humanos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Inquéritos e Questionários , Adulto Jovem
3.
Medicine (Baltimore) ; 100(4): e24467, 2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33530257

RESUMO

ABSTRACT: Although recent gathered evidence indicates that obtaining the diagnostic value of serum carbohydrate-deficient transferrin might be more useful for identifying alcohol abuse than other widely available biochemical tests; however, its precise value as an indicator of chronic alcoholism is unclear. The main objective is to investigate the diagnostic significance of carbohydrate-deficient transferrin in chronic alcoholism in the Chinese population.In this study, we enrolled (1) 52 physically healthy subjects, (2) 20 patients with nonalcoholic liver disease, and (3) 70 alcoholics. Patients with liver injuries and a history of liver surgery were excluded. Serum gamma-glutamyltransferase, aspartate aminotransferase, alanine aminotransferase, and mean corpuscular volume were determined by standard biochemical assays, and serum carbohydrate-deficient transferrin was estimated in each group using capillary electrophoresis. Subsequently, the diagnostic value of carbohydrate-deficient transferrin (CDT) in chronic alcoholism was determined based on differences between each indicator among the three groups.The CDT level in the alcoholic group was significantly higher than that of the non-alcoholic liver disease and healthy control groups (P < .05). The area under the curve for alcoholism diagnosis was the highest for CDT, at 0.922, whereas those for gamma-glutamyltransferase, aspartate aminotransferase, alanine aminotransferase, and mean corpuscular volume were 0.860, 0.744, 0.615, and 0.754, respectively. When the cutoff value of CDT was set at 1.25%, the sensitivity and specificity were 85.5% and 89.6%, respectively. However, the correlation between CDT and daily alcohol consumption was weak (r = 0.175; P = .16).Compared with the other parameters evaluated, CDT was a better indicator of alcoholism. It should, therefore, be actively promoted in clinical practice. However, the correlation between CDT and daily alcohol consumption needs further evaluation.


Assuntos
Alcoolismo/sangue , Transferrina/análogos & derivados , Adulto , Alcoolismo/diagnóstico , Grupo com Ancestrais do Continente Asiático , Biomarcadores/sangue , Estudos de Casos e Controles , China , Eletroforese Capilar , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Transferrina/análise
4.
Psychopharmacology (Berl) ; 238(3): 833-844, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33410985

RESUMO

RATIONALE: After alcohol ingestion, the brain partly switches from consumption of glucose to consumption of the alcohol metabolite acetate. In heavy drinkers, the switch persists after abrupt abstinence, leading to the hypothesis that the resting brain may be "starved" when acetate levels suddenly drop during abstinence, despite normal blood glucose, contributing to withdrawal symptoms. We hypothesized that ketone bodies, like acetate, could act as alternative fuels in the brain and alleviate withdrawal symptoms. OBJECTIVES: We previously reported that a ketogenic diet during alcohol exposure reduced acute withdrawal symptoms in rats. Here, our goals were to test whether (1) we could reproduce our findings, in mice and with longer alcohol exposure; (2) ketone bodies alone are sufficient to reduce withdrawal symptoms (clarifying mechanism); (3) introduction of ketogenic diets at abstinence (a clinically more practical implementation) would also be effective. METHODS: Male C57BL/6NTac mice had intermittent alcohol exposure for 3 weeks using liquid diet. Somatic alcohol withdrawal symptoms were measured as handling-induced convulsions; anxiety-like behavior was measured using the light-dark transition test. We tested a ketogenic diet, and a ketone monoester supplement with a regular carbohydrate-containing diet. RESULTS: The regular diet with ketone monoester was sufficient to reduce handling-induced convulsions and anxiety-like behaviors in early withdrawal. Only the ketone monoester reduced handling-induced convulsions when given during abstinence, consistent with faster elevation of blood ketones, relative to ketogenic diet. CONCLUSIONS: These findings support the potential utility of therapeutic ketosis as an adjunctive treatment in early detoxification in alcohol-dependent patients seeking to become abstinent. TRIAL REGISTRATION: clinicaltrials.gov NCT03878225, NCT03255031.


Assuntos
Alcoolismo/metabolismo , Dieta Cetogênica , Corpos Cetônicos/metabolismo , Cetonas/uso terapêutico , Síndrome de Abstinência a Substâncias/prevenção & controle , Alcoolismo/sangue , Animais , Ansiedade/tratamento farmacológico , Encéfalo/metabolismo , Ensaios Clínicos como Assunto , Suplementos Nutricionais , Etanol/administração & dosagem , Etanol/efeitos adversos , Etanol/sangue , Glucose , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ratos , Síndrome de Abstinência a Substâncias/metabolismo , Síndrome de Abstinência a Substâncias/psicologia
5.
J Surg Res ; 257: 92-100, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32818790

RESUMO

BACKGROUND: Alcohol use remains abundant in patients with traumatic injury. Previous studies have suggested that serum carbohydrate-deficient transferrin (%dCDT) levels, relative to blood alcohol levels (BALs), may better differentiate episodic binge drinkers from sustained heavy consumers in admitted patients with traumatic injury. We characterized %dCDT levels and BAL levels to differentiate binge drinkers from sustained heavy consumers in admitted trauma patients and their associations with outcomes. METHODS: This prospective, cross-sectional, observational study assessed %dCDT and BAL levels in admitted male and female patients with traumatic injury (≥18 y) at an American College of Surgeons Committee on Trauma level-1 center from July 2014 to June 2016. We designated patients with %dCDT levels ≥1.7% (CDT+) as chronic alcohol users and dichotomized acutely intoxicated patients using three different BAL-level thresholds. Primary outcomes included in-hospital complications, along with prolonged ventilation and intensive care unit length of stay, both defined as the top decile. Secondary outcomes included rates of drug or alcohol withdrawal and all-cause mortality. Analyses were adjusted for clinical factors. RESULTS: We studied 715 patients (77.5% men, 60.6% ≤ 40 y of age, median Injury Severity Score: 14, 41.7% motor vehicle crashes, 17.9% gunshot wounds, 11.1% falls). While 31.0% were CDT+, 48.7% were BAL>0. After adjusting for CDT levels, BAL levels >0, >100, or >200 were not associated with adverse outcomes. However, CDT+ relative to patients with CDT were associated with complications (adjusted odds ratio: 1.96 [1.24-3.09]), prolonged ventilation days (3.23 [1.08-9.65]), and prolonged intensive care unit stays (2.83 [1.20-6.68]). CONCLUSIONS: In this 2-year prospective, cross-sectional, and observational study, we found that %dCDT levels, relative to BAL levels, may better stratify admitted patients with traumatic injury into acute versus chronic alcohol users, identifying those at higher risk for in-hospital complications.


Assuntos
Transtornos Relacionados ao Uso de Álcool/sangue , Transtornos Relacionados ao Uso de Álcool/epidemiologia , Concentração Alcoólica no Sangue , Transferrina/análogos & derivados , Ferimentos e Lesões/sangue , Acidentes de Trânsito , Adolescente , Adulto , Alcoolismo/sangue , Alcoolismo/epidemiologia , Consumo Excessivo de Bebidas Alcoólicas/sangue , Consumo Excessivo de Bebidas Alcoólicas/epidemiologia , Estudos Transversais , Diagnóstico Diferencial , Feminino , Humanos , Escala de Gravidade do Ferimento , Unidades de Terapia Intensiva , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Transferrina/análise , Resultado do Tratamento , Ferimentos e Lesões/epidemiologia , Ferimentos e Lesões/terapia , Ferimentos por Arma de Fogo/sangue , Adulto Jovem
6.
Medicine (Baltimore) ; 99(17): e19938, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32332675

RESUMO

The pathophysiology of alcohol use disorder (AUD) is not totally clear. The aim of this study was to investigate the serum levels of brain-derived neurotrophic factor (BDNF) and oxidative stress markers in AUD patients during alcohol detoxification. Evaluation of changes in BDNF, glutathione peroxidase (GPX), catalase, superoxide dismutase, thiobarbituric acid reactive substances, 8-hydroxy 2'-deoxyguanosine, PCC and S100B were carried out.14 AUD inpatients and 20 healthy control subjects were recruited for this study. The serum BDNF, S100B and oxidative stress markers were measured with assay kits.Serum levels of catalase, GPX, PCC and 8-hydroxy 2'-deoxyguanosine were significantly higher in the AUD group subjects than in the controls (P < .05). However, BDNF levels were lower in the AUD group than in the controls (P < .05). After alcohol detoxification treatment, the GPX levels in the AUD group dropped (P < .05) and the BDNF levels rose (P < .05).The results suggest that serum BDNF and GPX levels might be state biomarkers for AUD patients undergoing alcohol detoxification.


Assuntos
Alcoolismo/sangue , Alcoolismo/tratamento farmacológico , Fator Neurotrófico Derivado do Encéfalo/análise , Glutationa Peroxidase/análise , Inativação Metabólica/fisiologia , Adulto , Alcoolismo/fisiopatologia , Biomarcadores/análise , Biomarcadores/sangue , Fator Neurotrófico Derivado do Encéfalo/sangue , Feminino , Glutationa Peroxidase/sangue , Humanos , Inativação Metabólica/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade
7.
J Immunoassay Immunochem ; 41(2): 184-194, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31842683

RESUMO

Lymphocyte-related parameters in Alcohol Use Disorder (AUD) have recently been investigated. However, knowledge of platelet to lymphocyte ratio (PLR) in AUD is limited. In this study, we compared complete blood count values of 31 AUD male patients and 31 healthy male controls. There was no significant difference between the two groups in terms of PLR (p = .123). When the age was controlled, there was a negative correlation between the duration of alcohol use and PLR (r = -0.567; p = .005). The significance of the parameters in the AUD group was found to be related to the duration of alcohol use.


Assuntos
Alcoolismo/sangue , Alcoolismo/diagnóstico , Plaquetas , Linfócitos , Adulto , Biomarcadores/análise , Plaquetas/química , Estudos de Coortes , Humanos , Contagem de Linfócitos , Linfócitos/química , Masculino , Contagem de Plaquetas , Estudos Retrospectivos
8.
Biol Trace Elem Res ; 193(1): 7-13, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30805875

RESUMO

Alcohol abuse is a well-known cause of imbalance in trace element levels and oxidant/antioxidant status of individuals with long time consumption. However, the levels of these parameters in the patients on the early stages of alcohol dependence without liver damage differ on various studies. The aim of our study was to measure the levels of trace elements in the serum and oxidative/antioxidative system members in the red blood cells (RBC) of early-stage alcoholic individuals and compare with control subjects. Our study included 21 male patients recently hospitalized for alcohol abuse and 25 healthy non-abusing male controls. Levels of Fe, Zn, and Cu in the serum and MDA, SOD, CAT, and GSH in the red blood cells (RBC) of the subjects were measured. Fe, Zn, and Cu levels were lower in the study group when compared to the controls. Levels of lipid peroxidation marker MDA was high, whereas the activities of antioxidant enzymes SOD and CAT were decreased in our study group. However, levels of GSH, an antioxidant compound were higher in the alcohol abuse group. RBC SOD levels were positively correlated with Fe, Cu, Zn, and CAT. There was a positive correlation between Fe-Cu, Zn-Fe, Zn-Cu, CAT-Zn, and CAT-SOD. MDA was negatively correlated with Fe, Zn, SOD, and CAT. The results obtained from present study indicate that high levels of alcohol intake are related with increased oxidative damage and decreased levels of antioxidant enzymes and trace elements. Additionally, antioxidant compensation mechanisms are still on process in the early stages of chronic alcohol exposure.


Assuntos
Alcoolismo/sangue , Antioxidantes/metabolismo , Oxidantes/sangue , Oligoelementos/sangue , Adulto , Catalase/sangue , Glutationa/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Superóxido Dismutase/sangue
9.
Int J Neuropsychopharmacol ; 23(1): 1-11, 2020 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-31722379

RESUMO

BACKGROUND: Preclinical studies suggest that decreased levels of brain-derived neurotrophic factor in the amygdala play a role in anxiety and alcohol use disorder. The association between brain-derived neurotrophic factor levels and amygdala function in humans with alcohol use disorder is still unclear, although neuroimaging studies have also implicated the amygdala in alcohol use disorder and suggest that alcohol use disorder is associated with disrupted functional connectivity between the amygdala and prefrontal cortex during aversive states. METHODS: The current study investigated whether plasma brain-derived neurotrophic factor levels in individuals with and without alcohol use disorder (n = 57) were associated with individual differences in amygdala reactivity and amygdala-prefrontal cortex functional connectivity during 2 forms of aversive responding captured via functional magnetic resonance imaging: anxiety elicited by unpredictable threat of shock and fear elicited by predictable threat of shock. We also examined whether brain-derived neurotrophic factor and brain function were associated with binge drinking episodes and alcohol use disorder age of onset. RESULTS: During anxiety, but not fear, lower levels of plasma brain-derived neurotrophic factor were associated with less connectivity between the left amygdala and the medial prefrontal cortex and the inferior frontal gyrus. In addition, within individuals with alcohol use disorder (only), lower levels of brain-derived neurotrophic factor and amygdala-medial prefrontal cortex functional connectivity during anxiety were associated with more binge episodes within the past 60 days and a lower age of alcohol use disorder onset. There were no associations between brain-derived neurotrophic factor levels and focal amygdala task reactivity. CONCLUSIONS: Together, the results indicate that plasma brain-derived neurotrophic factor levels are related to amygdala circuit functioning in humans, particularly during anxiety, and these individual differences may relate to drinking behaviors.


Assuntos
Alcoolismo , Tonsila do Cerebelo/fisiopatologia , Ansiedade , Consumo Excessivo de Bebidas Alcoólicas , Fator Neurotrófico Derivado do Encéfalo/sangue , Conectoma , Córtex Pré-Frontal/fisiopatologia , Adulto , Idade de Início , Alcoolismo/sangue , Alcoolismo/epidemiologia , Alcoolismo/fisiopatologia , Tonsila do Cerebelo/diagnóstico por imagem , Ansiedade/sangue , Ansiedade/epidemiologia , Ansiedade/fisiopatologia , Aprendizagem da Esquiva/fisiologia , Consumo Excessivo de Bebidas Alcoólicas/sangue , Consumo Excessivo de Bebidas Alcoólicas/epidemiologia , Consumo Excessivo de Bebidas Alcoólicas/fisiopatologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Córtex Pré-Frontal/diagnóstico por imagem , Adulto Jovem
11.
Ann Biol Clin (Paris) ; 77(6): 638-644, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31859640

RESUMO

This article aims to place the phosphatidylethanol (PEth) blood test in the detection area of ethanol consumption causing alcohol-related disorders, to present the current methods of analysis, data on interpretation, some practical applications and the prospects of use of this biomarker. PEth is a minor metabolite of ethanol. Among nearly 50 PEth counterparts, PEth 16:0/18:1 is the most abundant. The interest that PEth brings compared to other biomarkers is the extended window of detection of ethanol consumptions. Indeed, it has a blood elimination half-life of approximately 5 days, which offers estimated alcohol consumption for a 21 to 28 days period. Thus, the detection of alcohol use disorders and withdrawal monitoring (systematically combined with urinary ethylglucuronide) in addictology and in liver pre- and post-transplantation are today its main routine applications. Nevertheless, additional data are still necessary to improve the interpretation of measured concentrations and to reach a consensus on interpretation cut-offs of blood PEth concentrations.


Assuntos
Consumo de Bebidas Alcoólicas/sangue , Alcoolismo/diagnóstico , Análise Química do Sangue/métodos , Glicerofosfolipídeos/sangue , Alcoolismo/sangue , Biomarcadores/sangue , Cromatografia Líquida , Etanol/análise , Etanol/sangue , Glucuronatos/urina , Glicerofosfolipídeos/análise , Meia-Vida , Humanos , Espectrometria de Massas em Tandem , Urinálise/métodos
12.
Arq Neuropsiquiatr ; 77(10): 689-695, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31664344

RESUMO

OBJECTIVE: This study aimed to analyze the cerebellum of rats submitted to an experimental focal cerebral ischemia, by middle cerebral artery occlusion for 90 minutes, followed by reperfusion for 48 hours, associated with an alcoholism model. METHODS: Fifty adult Wistar rats were used, subdivided into five experimental groups: control group (C): animals submitted to anesthesia only; sham group (S): animals submitted to complete simulation of the surgical procedure; ischemic group (I): animals submitted to focal cerebral ischemia for 90 minutes followed by reperfusion for 48 hours; alcoholic group (A): animals that received daily absolute ethanol diluted 20% in water for four weeks; and, ischemic and alcoholic group (I + A): animals receiving the same treatment as group A and, after four weeks, submitted to focal cerebral ischemia for 90 minutes, followed by reperfusion for 48 hours. The cerebellum samples were collected and immunohistochemical analysis of Caspase-9 protein and serum analysis by RT-PCR of microRNAs miR-21, miR-126 and miR155 were performed. RESULTS: The expression of Caspase-9 was higher in groups I, A and I + A. In the microRNAs analyses, miR-126 was higher in groups A and I + A, miR-155 was higher in groups I and I + A. CONCLUSIONS: We conclude that apoptosis occurs in the cerebellar cortex, even if it is distant from the ischemic focus, and that microRNAs 126 and 155 show a correlation with cellular apoptosis in ischemic rats and those submitted to the chronic alcohol model.


Assuntos
Alcoolismo/patologia , Apoptose , Isquemia Encefálica/patologia , Caspase 9/análise , Cerebelo/patologia , MicroRNAs/sangue , Alcoolismo/sangue , Animais , Isquemia Encefálica/sangue , Cerebelo/química , Imuno-Histoquímica , Infarto da Artéria Cerebral Média , Masculino , Distribuição Aleatória , Ratos Wistar , Reação em Cadeia da Polimerase em Tempo Real , Traumatismo por Reperfusão/patologia , Fatores de Tempo
13.
Drug Alcohol Depend ; 204: 107588, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31590131

RESUMO

BACKGROUND: The aim was to estimate the prevalence of harmful alcohol use in relation to socio-demographic characteristics among acutely ill medical patients, and examine identification measures of alcohol use, including the alcohol biomarker phosphatidylethanol 16:0/18:1 (PEth). METHODS: A cross-sectional study, lasting one year at one hospital in Oslo, Norway and one in Moscow, Russia recruiting acute medically ill patients (≥ 18 years), able to give informed consent. Self-reported data on socio-demographics, mental distress (Symptom Check List-5), alcohol use (Alcohol Use Disorder Identification Test-4 (AUDIT-4) and alcohol consumption past 24 h were collected. PEth and alcohol concentration were measured in whole blood. RESULTS: Of 5883 participating patients, 19.2% in Moscow and 21.1% in Oslo were harmful alcohol users, measured by AUDIT-4, while the prevalence of PEth-positive patients was lower: 11.4% in Oslo, 14.3% in Moscow. Men in Moscow were more likely to be harmful users by AUDIT-4 and PEth compared to men in Oslo, except of those being ≥ 71 years. Women in Oslo were more likely to be harmful users compared to those in Moscow by AUDIT-4, but not by PEth for those aged < 61 years. CONCLUSIONS: The prevalence of harmful alcohol use was high at both study sites. The prevalence of harmful alcohol use was lower when assessed by PEth compared to AUDIT-4. Thus, self-reporting was the most sensitive measure in revealing harmful alcohol use among all groups except for women in Moscow. Hence, screening and identification with objective biomarkers and self-reporting might be a method for early intervention.


Assuntos
Alcoolismo/sangue , Alcoolismo/epidemiologia , Glicerofosfolipídeos/sangue , Hospitalização/tendências , Adolescente , Adulto , Idoso , Consumo de Bebidas Alcoólicas/sangue , Consumo de Bebidas Alcoólicas/epidemiologia , Alcoolismo/diagnóstico , Biomarcadores/sangue , Estudos Transversais , Intervenção Educacional Precoce/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Moscou/epidemiologia , Noruega/epidemiologia , Autorrelato , Adulto Jovem
14.
Arq. neuropsiquiatr ; 77(10): 689-695, Oct. 2019. graf
Artigo em Inglês | LILACS | ID: biblio-1038728

RESUMO

ABSTRACT This study aimed to analyze the cerebellum of rats submitted to an experimental focal cerebral ischemia, by middle cerebral artery occlusion for 90 minutes, followed by reperfusion for 48 hours, associated with an alcoholism model. Methods Fifty adult Wistar rats were used, subdivided into five experimental groups: control group (C): animals submitted to anesthesia only; sham group (S): animals submitted to complete simulation of the surgical procedure; ischemic group (I): animals submitted to focal cerebral ischemia for 90 minutes followed by reperfusion for 48 hours; alcoholic group (A): animals that received daily absolute ethanol diluted 20% in water for four weeks; and, ischemic and alcoholic group (I + A): animals receiving the same treatment as group A and, after four weeks, submitted to focal cerebral ischemia for 90 minutes, followed by reperfusion for 48 hours. The cerebellum samples were collected and immunohistochemical analysis of Caspase-9 protein and serum analysis by RT-PCR of microRNAs miR-21, miR-126 and miR155 were performed. Results The expression of Caspase-9 was higher in groups I, A and I + A. In the microRNAs analyses, miR-126 was higher in groups A and I + A, miR-155 was higher in groups I and I + A. Conclusions We conclude that apoptosis occurs in the cerebellar cortex, even if it is distant from the ischemic focus, and that microRNAs 126 and 155 show a correlation with cellular apoptosis in ischemic rats and those submitted to the chronic alcohol model.


RESUMO O objetivo deste estudo foi analisar o cerebelo de ratos submetidos à isquemia cerebral focal experimental, por oclusão da artéria cerebral média por 90 minutos, seguida de reperfusão por 48 horas, associada a um modelo de alcoolismo. Métodos Foram utilizados 50 ratos Wistar adultos, subdivididos em cinco grupos experimentais: grupo controle (C): animais submetidos apenas à anestesia; grupo sham (S): animais submetidos à simulação completa do procedimento cirúrgico; grupo isquêmico (I): animais submetidos à isquemia cerebral focal por 90 minutos, seguidos de reperfusão por 48 horas; grupo alcoólico (A): animais que receberam etanol absoluto diário diluído em 20% em água por quatro semanas; e grupo isquêmico e alcoólico (I + A): animais que recebem o mesmo tratamento do grupo A e, após quatro semanas, submetidos à isquemia cerebral focal por 90 minutos, seguidos de reperfusão por 48 horas. As amostras de cerebelo foram coletadas e a análise imuno-histoquímica da proteína Caspase-9 e a análise sérica por RT-PCR dos microRNAs miR-21, miR-126 e miR155 foram realizadas. Resultados A expressão de Caspase-9 foi maior nos grupos I, A e I + A. Nas análises de microRNAs, o miR-126 foi maior nos grupos A e I + A, o miR-155 foi maior nos grupos I e I + A. Conclusões Concluímos que a apoptose ocorre no córtex cerebelar, mesmo distante do foco isquêmico, e que os microRNAs 126 e 155 mostram uma correlação com a apoptose celular em ratos isquêmicos e submetidos ao modelo crônico de álcool.


Assuntos
Animais , Masculino , Cerebelo/patologia , Isquemia Encefálica/patologia , Apoptose , MicroRNAs/sangue , Alcoolismo/patologia , Caspase 9/análise , Fatores de Tempo , Imuno-Histoquímica , Traumatismo por Reperfusão/patologia , Distribuição Aleatória , Cerebelo/química , Isquemia Encefálica/sangue , Ratos Wistar , Infarto da Artéria Cerebral Média , Alcoolismo/sangue , Reação em Cadeia da Polimerase em Tempo Real
15.
Alcohol Alcohol ; 54(6): 567-573, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31529064

RESUMO

AIM: Measurement of whole-blood phosphatidylethanol (PEth) offers high sensitivity and specificity as alcohol biomarker. A remaining issue of importance for the routine application is to better establish the relationship between PEth concentration and amount and duration of drinking. METHODS: The study included 36 subjects (32-83 years) voluntarily attending outpatient treatment for reduced drinking. At ~ 3- to 4-week intervals, they provided a diary on their daily alcohol intake and gave blood samples for measurement of PEth and carbohydrate-deficient transferrin (CDT). Whole-blood PEth 16:0/18:1 was measured by liquid chromatography-tandem mass spectrometry and serum CDT (%disialotransferrin) by high-performance liquid chromatography. RESULTS: At start, the self-reported past 2-week alcohol intake ranged 0-1260 (median 330) g ethanol, the PEth 16:0/18:1 concentration ranged 0.05-1.20 (median 0.23) µmol/L, and the CDT value ranged 0.7-13.0% (median 1.5%). At the final sampling after 5-20 (median 12) weeks, neither reported alcohol intake nor PEth and CDT levels differed significantly from the starting values. The PEth concentration showed best association with past 2-week drinking, followed by for intake in the next last week. The changes in PEth concentration vs past 2-week alcohol intake between two successive tests revealed that an increased ethanol intake by ~ 20 g/day elevated the PEth concentration by on average ~ 0.10 µmol/L, and vice versa for decreased drinking. CONCLUSIONS: The PEth concentration correlated well with past weeks alcohol intake, albeit with a large inter-individual scatter. This indicates that it is possible to make only approximate estimates of drinking based on a single PEth value, implying risk for misclassification between moderate and heavy drinking.


Assuntos
Consumo de Bebidas Alcoólicas/sangue , Alcoolismo/sangue , Glicerofosfolipídeos/sangue , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Cromatografia Líquida de Alta Pressão , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Autorrelato , Sensibilidade e Especificidade , Espectrometria de Massas em Tandem , Transferrina/análogos & derivados , Transferrina/análise
16.
Alcohol Clin Exp Res ; 43(11): 2374-2383, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31483873

RESUMO

BACKGROUND: HIV infection is now largely a chronic condition as a result of the success of antiretroviral therapy. However, several comorbidities have emerged in people living with HIV (PLWH), including alcohol use disorders and musculoskeletal disorders. Alcohol use has been associated with lower bone mineral density, alterations to circulating bone turnover markers, and hypocalcemia. The pathophysiological basis of bone loss in the PLWH population is unclear but has been suggested to be linked to oxidative stress and inflammation. To test the hypothesis that PLWH consuming excessive alcohol have altered markers of bone turnover and/or calcium homeostasis in association with oxidative stress, we correlated measurements of alcohol consumption with markers of oxidative stress and inflammation, serum calcium concentrations, and measurements of bone turnover, including c-terminal telopeptide cross-links (CTX-1) and osteocalcin. METHODS: Data were drawn from cross-sectional baseline data from the ongoing New Orleans Alcohol Use in HIV (NOAH) study, comprised of 365 in care PLWH. Alcohol consumption measures (Alcohol Use Disorders Test, 30-day timeline follow-back calendar, and phosphatidylethanol [PEth]) were measured in a subcohort of 40 subjects selected based on highest and lowest PEth measurements. Multivariate linear regression was performed to test the relationships between alcohol consumption and systemic oxidative stress (4-hydroxynonenal; 4-HNE) and inflammation (c-reactive protein; CRP). RESULTS: Serum calcium and CTX-1 did not differ significantly between the high and low-PEth groups. Individuals in the high-PEth group had significantly lower serum osteocalcin (median low-PEth group: 13.42 ng/ml, inter-quartile range [IQR] 9.26 to 14.99 ng/ml; median high-PEth group 7.39 ng/ml, IQR 5.02 to 11.25 ng/ml; p = 0.0005, Wilcoxon rank-sum test). Osteocalcin negatively correlated with PEth (Spearman r = -0.45, p = 0.05) and self-reported measures after adjusting for covariates. Alcohol consumption showed mild, but significant, positive associations with serum 4-HNE, but not with CRP. Osteocalcin did not correlate with either 4-HNE or CRP. CONCLUSIONS: In this subcohort of PLWH, we detected significant associations between at-risk alcohol use and osteocalcin, and at-risk alcohol use and serum 4-HNE, suggesting suppression of bone formation independent of increased systemic oxidative stress with increasing alcohol consumption.


Assuntos
Alcoolismo/complicações , Infecções por HIV/complicações , Inflamação/complicações , Osteocalcina/deficiência , Estresse Oxidativo , Alcoolismo/sangue , Alcoolismo/metabolismo , Cálcio/sangue , Cálcio/metabolismo , Estudos Transversais , Feminino , Glicerofosfolipídeos/sangue , Infecções por HIV/sangue , Infecções por HIV/metabolismo , Humanos , Inflamação/sangue , Inflamação/metabolismo , Masculino , Nova Orleans , Osteocalcina/sangue , Estresse Oxidativo/efeitos dos fármacos
17.
Cells ; 8(9)2019 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-31470644

RESUMO

Background: The current diagnosis of early-stage liver fibrosis often relies on a serological or imaging-based evaluation of the stage of fibrosis, sometimes followed by an invasive liver biopsy procedure. Novel non-invasive experimental diagnostic tools are often based on markers of hepatocyte damage, or changes in liver stiffness and architecture, which are late-stage characteristics of fibrosis progression, making them unsuitable for the diagnosis of early-stage liver fibrosis. miRNAs control hepatic stellate cell (HSC) activation and are proposed as relevant diagnostic markers. Methods: We investigated the possibility of circulating miRNAs, which we found to be dysregulated upon HSC activation, to mark the presence of significant liver fibrosis (F ≥ 2) in patients with chronic alcohol abuse, chronic viral infection (HBV/HCV), and non-alcoholic fatty liver disease (NAFLD). Results: miRNA-profiling identified miRNA-451a, miRNA-142-5p, Let-7f-5p, and miRNA-378a-3p to be significantly dysregulated upon in vitro HSC activation, and to be highly enriched in their extracellular vesicles, suggesting their potential use as biomarkers. Analysis of the plasma of patients with significant liver fibrosis (F ≥ 2) and no or mild fibrosis (F = 0-1), using miRNA-122-5p and miRNA-29a-3p as positive control, found miRNA-451a, miRNA-142-5p, and Let-7f-5p, but not miRNA-378a-3p, able to distinguish between the two patient populations. Using logistic regression analysis, combining all five dysregulated circulating miRNAs, we created the miRFIB-score with a predictive value superior to the clinical scores Fibrosis-4 (Fib-4), aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio, and AST to platelet ratio index (APRI). The combination of the miRFIB-score with circulating PDGFRß-levels further increased the predictive capacity for the diagnosis of significant liver fibrosis. Conclusions: The miRFIB- and miRFIBp-scores are accurate tools for the diagnosis of significant liver fibrosis in a heterogeneous patient population.


Assuntos
Biomarcadores/sangue , Cirrose Hepática , Fígado/metabolismo , MicroRNAs/sangue , Adulto , Idoso , Alcoolismo/sangue , Animais , Feminino , Hepatite B Crônica/sangue , Hepatite C Crônica/sangue , Humanos , Biópsia Líquida , Fígado/patologia , Cirrose Hepática/sangue , Cirrose Hepática/diagnóstico , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/sangue
18.
Drug Alcohol Depend ; 204: 107553, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31541874

RESUMO

BACKGROUND: Inflammatory pathways are known to be negatively affected in patients with alcohol use disorder (AUD). Cognitive bias modification (CBM), an emerging behavioral treatment that involves the 're-training' of cognitive biases using computerized tasks, has been reported to reduce alcohol craving and relapse rates. The aim of this study was to compare peripheral concentrations of the proinflammatory biomarkers IL-18, IL-6, IL-1ß, TNF-α and CRP in AUD patients versus controls and to identify whether CBM treatment affected these biomarkers in AUD patients. METHODS: This 3-week double-blind randomized controlled study tested 36 male abstinent AUD patients receiving CBM or placebo-training, who were also compared to 18 male healthy controls. The approach avoidance task (AAT) was used to test the AUD patients before and after training. CBM training took place over 6 sessions, using a joystick-based approach-avoidance task. Blood samples were collected after the pre- and post-AAT test sessions for the AUD groups, and during an outpatient appointment with the controls. RESULTS: AUD patients, versus controls, presented with significantly higher plasma levels of TNF- α (P < 0.0001) and CRP (P = 0.0031). No changes in the CBM versus placebo groups were noted in IL-18, TNF-α and CRP concentrations following pre-post change or within group pretest- posttest analysis. IL-6 and IL-1ß levels fell under the lower detection limit, thus were not included in the final analyses. CONCLUSIONS: This study confirms that the inflammatory system is altered in AUD. This was the first study that investigated whether CBM training affected proinflammatory markers in AUD patients.


Assuntos
Alcoolismo/sangue , Alcoolismo/terapia , Terapia Cognitivo-Comportamental/métodos , Mediadores da Inflamação/sangue , Regulação para Cima/fisiologia , Adulto , Alcoolismo/psicologia , Biomarcadores/sangue , Cognição/fisiologia , Fissura/fisiologia , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva
19.
Alcohol Alcohol ; 54(5): 510-515, 2019 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31294769

RESUMO

AIMS: Carbohydrate-deficient transferrin (CDT) is a marker of chronic alcohol abuse. Uninterpretable (atypical) CDT patterns have been detected by both capillary electrophoresis (CE) and HPLC. The aim of this study was to evaluate the performance of HPLC as a second-line test for the interpretation of most frequent atypical CDT profiles detected by CE. METHODS: CDT was analyzed by CE (Capillarys 2, Sebia) on 9120 consecutive samples in a routine laboratory setting during a 2-year period. A commercial method (ClinRep CDT kit, Recipe) was employed to retest 123 (1.4%) samples with atypical CDT patterns on a Prominence LC-20AT HPLC (Shimadzu). RESULTS: CE-uninterpretable samples were categorized as having low transferrin (Tf) concentration (LT; n = 42, 0.5%), di-trisialotransferrin bridging (D-TB; n = 63, 0.7%) or atypical peak profile (APP; n = 18, 0.2%). CDT was detectable by HPLC in 58 of 123 (47%) samples including 21of 42 (50%) with LT, 27 of 63 (43%) with D-TB and 10 of 18 (56%) with APP. CONCLUSIONS: Second-line HPLC testing reduced uninterpretable samples by 47%, with similar rates of improvement regardless of the type of CDT pattern. The usefulness of HPLC as a second-line test for CDT should be evaluated according to cost-benefit considerations in the context of each laboratory.


Assuntos
Alcoolismo/sangue , Alcoolismo/diagnóstico , Eletroforese Capilar/métodos , Transferrina/análogos & derivados , Biomarcadores/análise , Biomarcadores/sangue , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Líquida de Alta Pressão/normas , Eletroforese Capilar/normas , Humanos , Transferrina/análise , Transferrina/metabolismo
20.
Neuropharmacology ; 158: 107711, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31310775

RESUMO

Increasing evidence supports the role of appetite-regulating hormones, including ghrelin, in alcohol use disorder (AUD). Effects of ghrelin administration on cortisol and aldosterone, two hormones known to influence the development and maintenance of AUD, have been observed in ghrelin-exposed tissues or cells, as well as rodents and healthy volunteers, however whether these effects replicate in individuals with AUD is unknown. Here, we tested the hypothesis that intravenous administration of ghrelin leads to increase in endogenous serum cortisol and aldosterone concentrations in alcohol-dependent, heavy drinking individuals, and that these changes may predict ghrelin-induced alcohol craving. This was a double-blind, placebo-controlled human laboratory study in non-treatment-seeking, heavy-drinking, alcohol-dependent individuals randomized to receive either placebo, 1 mcg/kg or 3 mcg/kg of intravenous ghrelin. Then, participants underwent a cue-reactivity procedure in a bar-like setting, which included exposure to both neutral (juice) and alcohol cues. Repeated blood samples were collected and used to measure endogenous cortisol and aldosterone serum concentrations, in response to exogenous ghrelin administration. Furthermore, cortisol and aldosterone serum concentrations were used to develop a model to predict the effect of exogenous ghrelin administration on alcohol craving. Intravenous ghrelin administration increased endogenous cortisol and aldosterone serum concentrations. While the effects on cortisol were greater than those on aldosterone, only the ghrelin-induced changes in aldosterone serum concentrations predicted craving. These findings provide initial evidence of ghrelin effects on glucocorticoids and mineralocorticoids in individuals with AUD, thereby providing additional information on the potential mechanisms by which the ghrelin system may play a role in alcohol craving and seeking in AUD.


Assuntos
Alcoolismo/sangue , Aldosterona/sangue , Grelina/farmacologia , Hidrocortisona/sangue , Administração Intravenosa , Alcoolismo/fisiopatologia , Alcoolismo/psicologia , Fissura , Sinais (Psicologia) , Método Duplo-Cego , Humanos , Distribuição Aleatória
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