Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 3.317
Filtrar
1.
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
2.
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
3.
Trials ; 20(1): 402, 2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31277683

RESUMO

BACKGROUND: Alcohol use disorder (AUD) leads to a significant individual and societal burden. To achieve higher therapy success rates, therapeutic interventions still need to be improved. Most current neuroscientific conceptualizations of AUD focus on the imbalance between an enhanced automatic reaction to alcohol cues and impaired inhibition. Complementary to traditional relapse prevention strategies, novel computerized training interventions aim to directly alter these processes. This study tests a computerized alcohol-specific inhibition training in a large clinical sample and investigates its effects on behavioral, experimental and neurophysiological outcomes. It also analyzes whether variations in inhibition difficulty and/or endogenous cortisol levels during training impact these effects. METHODS: This is a double-blind, randomized controlled trial (RCT) with 246 inpatients with AUD participating. After baseline assessment, participants are randomly assigned to one of three computerized Go-NoGo-based inhibition training interventions (two alcohol-specific versions with different Go/NoGo ratios, or neutral control training) and one of two intervention times (morning/afternoon), resulting in six study arms. All patients perform six training sessions within 2 weeks. Endogenous cortisol is measured in 80 patients before and after the first training session. Inhibitory control and implicit associations towards alcohol are assessed pre and post training, at which point electroencephalography (EEG) is additionally measured in 60 patients. Patients' alcohol consumption and relevant psychological constructs (e.g., craving, self-efficacy, treatment motivation) are measured at discharge and at 3-, 6- and 12-month follow-ups. Fifty healthy participants are assessed (20 with EEG) at one time point as a healthy control group. DISCUSSION: This study investigates the effects of a computerized, alcohol-specific inhibition training for the first time in patients with AUD. Results should give insight into the effectiveness of this potential add-on to standard AUD treatment, including proximal and distal measures and effects on behavioral, experimental and neurophysiological measures. Information about working mechanisms and potential optimizations of this training are gathered through variations regarding difficulty of inhibition training and training time. This study may thus contribute to a deepened understanding of AUD and the improvement of its evidence-based treatment. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02968537 . Registered on 18 November 2016.


Assuntos
Abstinência de Álcool/psicologia , Consumo de Bebidas Alcoólicas/prevenção & controle , Alcoólicos/psicologia , Alcoolismo/terapia , Aprendizagem , Motivação , Adolescente , Adulto , Consumo de Bebidas Alcoólicas/sangue , Consumo de Bebidas Alcoólicas/fisiopatologia , Consumo de Bebidas Alcoólicas/psicologia , Alcoolismo/sangue , Alcoolismo/fisiopatologia , Alcoolismo/psicologia , Biomarcadores/sangue , Encéfalo/fisiopatologia , Método Duplo-Cego , Feminino , Humanos , Hidrocortisona/sangue , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Suíça , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
4.
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
5.
Rev Med Suisse ; 15(654): 1173-1176, 2019 Jun 05.
Artigo em Francês | MEDLINE | ID: mdl-31166667

RESUMO

Estimating alcohol consumption using biomarkers raises interpretation problems. The biomarkers currently used in clinical settings have limited performances to identify unhealthy alcohol use (e.g. CDT, AST, ALT). New direct biomarkers, ethylglucuronide (EtG) and phosphatydilethanol (PEth) are available and offer better sensitivity and specificity compared to indirect biomarkers. In forensic medicine, EtG and PEth are replacing indirect biomarkers. However, in clinical routine practice these markers are usually not considered. Still, for specific purposes such in pre-liver transplant evaluations, direct markers may help specialists in the decision process.


Assuntos
Alcoolismo , Biomarcadores , Consumo de Bebidas Alcoólicas , Alcoolismo/sangue , Humanos , Sensibilidade e Especificidade
6.
Biomed Res Int ; 2019: 3646975, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31192254

RESUMO

The aim of this study was to evaluate the diagnostic values of noninvasive indirect markers of liver fibrosis: APRI, GAPRI, Forns, FIB-4, Age-Platelet, and Hepascore in alcoholics. Blood samples were collected from a randomized group of 142 alcohol-dependent patients. The diagnosis of dependency was made according to the ICD-10 WHO criteria. The values of noninvasive markers were calculated with specific algorithms. The fibrosis stage was evaluated on the basis of FibroTest. The values of APRI, Forns, FIB-4, GAPRI, AP, and Hepascore differ between various stages of liver fibrosis. Patients with fibrosis stage F0 present lower values of APRI, Forns, FIB-4, GAPRI, and Hepascore in comparison to the patients with stages F1 and F0-F1. Patients with fibrosis stages < F2 have lower values of all noninvasive markers than patients with stages ≥F2. Patients with fibrosis stages ≥F2 but

Assuntos
Alcoolismo/sangue , Cirrose Hepática Alcoólica/sangue , Adulto , Alcoolismo/patologia , Biomarcadores/sangue , Feminino , Humanos , Cirrose Hepática Alcoólica/patologia , Masculino , Pessoa de Meia-Idade
7.
Alcohol Alcohol ; 54(5): 472-476, 2019 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31188414

RESUMO

INTRODUCTION: Transforming growth factor beta-1 (TGF-ß1) is a pleiotropic cytokine. Its relationship with atherosclerosis is debatable, protective or deleterious effects have been described. Alcoholics are at increased vascular risk. Although TGF-ß1 is increased in alcoholics, its role on vascular risk factors has not been analyzed. This is the objective of this study. PATIENTS AND METHODS: 79 heavy alcoholics and 34 controls were included. Calcium deposition in the aortic arch was assessed in the plain thorax X-ray film. Ankle-brachial index was recorded in 48 patients. All the patients underwent complete laboratory evaluation, including serum levels of TGF-ß1, tumor necrosis factor (TNF)-α, interleukin (IL)-4, IL-6, and interferon-γ (IFN-γ).We analyzed the relationships between TGF-ß1 and vascular risk factors by both univariate (parametric or non parametric tests), or multivariate analysis to discern on which variables TGF-ß1 levels depend. RESULTS: Serum TGF-ß1 levels were higher among patients (t = 2.73; P = 0.008), but no differences exist among cirrhotics (17246 ± 11,021 pg/mL) and non-cirrhotics (21,340 ± 12,442 pg/mL). TGF-ß1 showed significant correlations with total cholesterol (r = 0.28; P = 0.017) and HDL- cholesterol (r = 0.25; P = 0.042), and inverse correlations with body mass index (BMI; ρ = -0.37; P = 0.004), IL-4 (ρ = -0.31; P = 0.009), INF-γ (ρ = -0.28; P = 0.001), and IL-6 (ρ = -0.38; P = 0.001). By multivariate analysis, only BMI, IL-6 and HDL-cholesterol showed independent relationships with TGF-ß1. No relationships were observed with ankle-brachial index or calcium in the aortic arch, hypertension, diabetes, left ventricular hypertrophy or atrial fibrillation. CONCLUSION: TGF-ß1 levels are increased in alcoholics, but are unrelated to vessel wall calcification or arterial stiffness.


Assuntos
Alcoólicos , Alcoolismo/sangue , Fator de Crescimento Transformador beta1/sangue , Calcificação Vascular/sangue , Rigidez Vascular/fisiologia , Idoso , Alcoolismo/diagnóstico , Alcoolismo/epidemiologia , Aorta Torácica/metabolismo , Aorta Torácica/patologia , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Calcificação Vascular/diagnóstico , Calcificação Vascular/epidemiologia
8.
Dig Dis Sci ; 64(7): 1878-1892, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31076986

RESUMO

BACKGROUND: Alcohol-related liver disease is one of the most prevalent chronic liver diseases worldwide. Mechanisms involved in the pathogenesis of alcohol-related liver disease are not well understood. Oxylipins play a crucial role in numerous biological processes and pathological conditions. Nevertheless, oxylipins are not well studied in alcohol-related liver disease. AIMS: (1) To characterize the patterns of bioactive ω-3 and ω-6 polyunsaturated fatty acid metabolites in alcohol use disorder and alcoholic hepatitis patients and (2) to identify associations of serum oxylipins with clinical parameters in patients with alcohol-related liver disease. METHODS: We performed a comprehensive liquid chromatography with tandem mass spectrometry (LC-MS/MS) analysis of serum and fecal oxylipins derived from ω-6 arachidonic acid, ω-3 eicosapentaenoic acid, and docosahexaenoic acid in a patient cohort with alcohol-related liver disease. RESULTS: Our results show profound alterations in the serum oxylipin profile of patients with alcohol use disorder and alcoholic hepatitis compared to nonalcoholic controls. Spearman correlation of the oxylipins with clinical parameters shows a link between different serum oxylipins and intestinal permeability, aspartate aminotransferase, bilirubin, albumin, international normalized ratio, platelet count, steatosis, fibrosis and model for end-stage liver disease score. Especially, higher level of serum 20-HETE was significantly associated with decreased albumin, increased hepatic steatosis, polymorphonuclear infiltration, and 90-day mortality. CONCLUSIONS: Patients with alcohol-related liver disease have different oxylipin profiles. Future studies are required to confirm oxylipins as disease biomarker or to connect oxylipins to disease pathogenesis.


Assuntos
Alcoolismo/sangue , Ácidos Graxos Ômega-3/sangue , Ácidos Graxos Ômega-6/sangue , Fezes/química , Hepatite Alcoólica/sangue , Oxilipinas/sangue , Adulto , Idoso , Alcoolismo/diagnóstico , Biomarcadores/sangue , Cromatografia Líquida de Alta Pressão , Cromatografia de Fase Reversa , Feminino , Hepatite Alcoólica/diagnóstico , Humanos , Masculino , Metabolômica/métodos , Pessoa de Meia-Idade , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas em Tandem
9.
Molecules ; 24(7)2019 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-30959950

RESUMO

The aim of this paper was to review recent literature (from 2000 onwards) and summarize the newest findings on fluctuations in the concentration of some essential macro- and microelements in those patients with a history of chronic alcohol abuse. The focus was mainly on four elements which the authors found of particular interest: Iron, magnesium, copper, and manganese. After independently reviewing over 50 articles, the results were consistent with regard to iron and magnesium. On the other hand, data were limited, and in some cases contradictory, as far as copper and manganese were concerned. Iron overload and magnesium deficiency are two common results of an excessive and prolonged consumption of alcohol. An increase in the levels of iron can be seen both in the serum and within the cells, hepatocytes in particular. This is due to a number of factors: Increased ferritin levels, lower hepcidin levels, as well as some fluctuations in the concentration of the TfR receptor for transferrin, among others. Hypomagnesemia is universally observed among those suffering from alcoholism. Again, the causes for this are numerous and include malnutrition, drug abuse, respiratory alkalosis, and gastrointestinal problems, apart from the direct influence of excessive alcohol intake. Unfortunately, studies regarding the levels of both copper and manganese in the case of (alcoholic) liver disease are scarce and often contradictory. Still, the authors have attempted to summarize and give a thorough insight into the literature available, bearing in mind the difficulties involved in the studies. Frequent comorbidities and mutual relationships between the elements in question are just some of the complications in the study of this topic.


Assuntos
Alcoolismo/sangue , Cobre/sangue , Ferro/sangue , Magnésio/sangue , Manganês/sangue , Alcoolismo/metabolismo , Biomarcadores , Encéfalo/metabolismo , Suscetibilidade a Doenças , Metabolismo Energético , Humanos , Fígado/metabolismo , Especificidade de Órgãos
10.
Gut Microbes ; 10(6): 663-675, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30894059

RESUMO

Excessive alcohol intake can alter the gut microbiota, which may underlie the pathophysiology of alcohol-related diseases. We examined gut microbiota composition and functions in patients with alcohol overconsumption for >10 years, compared to a control group of patients with a history of no or low alcohol intake. Faecal microbiota composition was assessed by 16S rRNA sequencing. Gut microbiota functions were evaluated by quantification of short-chain fatty acids (SCFAs) and predictive metagenome profiling (PICRUSt). Twenty-four patients, mean age 64.8 years (19 males), with alcohol overconsumption, and 18 control patients, mean age 58.2 years (14 males) were included. The two groups were comparable regarding basic clinical variables. Nutritional assessment revealed lower total score on the screening tool Mini Nutritional Assessment, lower muscle mass as assessed by handgrip strength, and lower plasma vitamin C levels in the alcohol overconsumption group. Bacteria from phylum Proteobacteria were found in higher relative abundance, while bacteria from genus Faecalibacterium were found in lower relative abundance in the group of alcohol overconsumers. The group also had higher levels of the genera Sutterella, Holdemania and Clostridium, and lower concentration and percentage of butyric acid. When applying PICRUSt to predict the metagenomic composition, we found that genes related to invasion of epithelial cells were more common in the group of alcohol overconsumers. We conclude that gut microbiota composition and functions in patients with alcohol overconsumption differ from patients with low consumption of alcohol, and seem to be skewed into a putative pro-inflammatory direction.


Assuntos
Alcoolismo/microbiologia , Microbioma Gastrointestinal/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Alcoolismo/sangue , Alcoolismo/fisiopatologia , Ácido Ascórbico/sangue , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Proteínas de Bactérias/genética , Ácidos Graxos Voláteis/análise , Fezes/química , Fezes/microbiologia , Feminino , Microbioma Gastrointestinal/genética , Força da Mão , Humanos , Masculino , Metagenômica , Pessoa de Meia-Idade , Avaliação Nutricional , RNA Ribossômico 16S/genética , Vitaminas/sangue
12.
Drug Alcohol Depend ; 197: 183-190, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30840924

RESUMO

BACKGROUND: Sex-related differences in the susceptibility, progression, and treatment response in alcohol-dependent subjects have been repeatedly reported. In this study, we aimed to investigate the associations of the sex-related hormone/protein levels with alcohol dependence (AD) and alcohol craving in male and female subjects. METHODS: Plasma sex-related hormones (estradiol, estrone, total testosterone, progesterone, follicle stimulated hormone [FSH], luteinizing hormone), and sex hormone binding globulin were measured by mass spectrometry or automated immunoassays from 44 recently-abstained subjects (29 males and 15 females; mean age = 45.9 ± 15.6) meeting DSM-IV-TR criteria for AD and 44 age-, sex- and race-matched non-AD controls. Conditional logistic regression was conducted to examine the association of sex-related hormone and protein levels with AD risk, accounting for matching variables. Their associations with alcohol craving scales (Penn Alcohol Craving Scale and Inventory of Drug-Taking Situations) were assessed in AD subjects. RESULTS: Plasma FSH level was significantly higher in AD males (10.3 ± 9.8 IU/L) than control males (8.0 ± 15.9 IU/L; p = 0.005, pcorrected = 0.035). We also found a significant inverse correlation of FSH level with propensity to drink in negative emotional situations (Spearman's rho=-.540; p = 0.021) and positive correlations between progesterone level and craving intensity (Spearman's rho=.464; p = 0.020) and between total testosterone level and propensity to drink under temptations (adjusted for no-drinking days; ß=6.496; p = 0.041) in AD males. CONCLUSIONS: These results suggest that FSH, progesterone, and testosterone levels may be associated with AD and alcohol craving in AD males. Future research is needed to replicate these findings and investigate the underlying biological mechanisms.


Assuntos
Consumo de Bebidas Alcoólicas/sangue , Consumo de Bebidas Alcoólicas/psicologia , Alcoolismo/sangue , Alcoolismo/psicologia , Fissura/fisiologia , Hormônios Esteroides Gonadais/sangue , Adulto , Alcoolismo/epidemiologia , Biomarcadores/sangue , Emoções/fisiologia , Estradiol/sangue , Feminino , Hormônio Foliculoestimulante/sangue , Humanos , Hormônio Luteinizante/sangue , Masculino , Pessoa de Meia-Idade , Progesterona/sangue , Autorrelato , Testosterona/sangue
13.
Artigo em Inglês | MEDLINE | ID: mdl-30826461

RESUMO

BACKGROUND: High-dose baclofen could prove beneficial in patients with unhealthy alcohol use in intensive care units (ICU). However, the pharmacokinetic properties of baclofen are unknown in this population. Our objectives were to investigate the pharmacokinetics of baclofen and the relationship between baclofen exposure and its toxicity in the ICU. MATERIALS AND METHODS: As part of a healthcare quality improvement project, we conducted a prospective, single-center study in a surgical intensive care unit at Nantes University Hospital in order to assess our local protocol of sedation in patients with consumption of alcohol above the recommended limits by the National Institute on Alcohol Abuse and Alcoholism (NIAAA). Baclofen pharmacokinetics were investigated by a non-compartment analysis and a population approach in 20 patients under mechanical ventilation. After a baclofen loading dose on day 1, daily doses were divided into 3 intakes adapted to glomerular filtration rate (GFR) and blood samples were withdrawn on day 3 for pharmacokinetic analysis. Baclofen was administered until extubation or tracheostomy and agitation-related events as well as the potential side effects of baclofen were noted. RESULTS: In this population, pharmacokinetic parameters [absorption latency time = 0.37 h, absorption constant rate = 2.2 h-1, apparent volume of distribution = 105 L, apparent clearance (l/h) = 13.5 × (GFR/103)0.839] were characterized by modified absorption and the influence of renal function: renal failure significantly increased baclofen exposure (p = .007) and significantly decreased baclofen clearance (p = .007) compared with patients without renal failure. When comparing patients with or without possible signs of baclofen toxicity, no difference was found regarding baclofen exposure (p = .34) and plasma peak concentration (p = .26). CONCLUSIONS: The a priori planned algorithm for dose adaptation according to renal clearance appeared to be suitable in our population. Daily administration of 150 mg of baclofen in ICU patients with preserved renal function did not lead to toxic concentrations in the plasma. A dose reduction of approximately 40%, 60% and 70% in patients with mild, moderate and severe renal failure could be suggested.


Assuntos
Alcoolismo/sangue , Baclofeno/efeitos adversos , Baclofeno/farmacocinética , Cuidados Críticos/métodos , Unidades de Terapia Intensiva , Alcoolismo/complicações , Alcoolismo/fisiopatologia , Baclofeno/administração & dosagem , Baclofeno/sangue , Taxa de Filtração Glomerular/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Dinâmica não Linear , Insuficiência Renal/sangue , Insuficiência Renal/complicações
14.
PLoS One ; 14(3): e0213791, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30870525

RESUMO

Major depressive disorder (MDD) is the most prevalent comorbid mental disorder among people with substance use disorders. The MDD can be both primary and substance-induced and its accurate diagnosis represents a challenge for clinical practice and treatment response. Recent studies reported alterations in the circulating expression of inflammatory mediators in patients with psychiatric disorders, including those related to substance use. The aim of the study was to explore TNF-α, IL-1ß, CXCL12, CCL2, CCL11 (eotaxin-1) and CX3CL1 (fractalkine) as potential biomarkers to identify comorbid MDD and to distinguish primary MDD from substance-induced MDD in patients with substance disorders. Patients diagnosed with cocaine (CUD, n = 64) or alcohol (AUD, n = 65) use disorders with/without MDD were recruited from outpatient treatment programs [CUD/non-MDD (n = 31); CUD/primary MDD (n = 18); CUD/cocaine-induced MDD (N = 15); AUD/non-MDD (n = 27); AUD/primary MDD (n = 16) and AUD/alcohol-induced MDD (n = 22)]. Sixty-two healthy subjects were also recruited as control group. Substance and mental disorders were assessed according to "Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision" (DSM-IV-TR) and a blood sample was collected for determinations in the plasma. The cocaine group showed lower TNF-α (p<0.05) and CCL11 (p<0.05), and higher IL-1ß (p<0.01) concentrations than the control group. In contrast, the alcohol group showed higher IL-1ß (p<0.01) and lower CXCL12 (p<0.01) concentrations than the control group. Regarding MDD, we only observed alterations in the cocaine group. Thus, CUD/MDD patients showed lower IL-1ß (p<0.05), CXCL12 (p<0.05) and CCL11 (p<0.05), and higher CXC3CL1 (p<0.05) concentrations than CUD/non-MDD patients. Moreover, while CUD/primary MDD patients showed higher CCL11 (p<0.01) concentrations than both CUD/non-MDD and CUD/cocaine-induced MDD patients, CUD/cocaine-induced MDD patients showed lower CXCL12 (p<0.05) concentrations than CUD/non-MDD patients. Finally, a logistic regression model in the cocaine group identified CXCL12, CCL11 and sex to distinguish primary MDD from cocaine-induced MDD providing a high discriminatory power. The present data suggest an association between changes in inflammatory mediators and the diagnosis of primary and substance-induced MDD, namely in CUD patients.


Assuntos
Alcoolismo/diagnóstico , Biomarcadores/sangue , Transtornos Relacionados ao Uso de Cocaína/diagnóstico , Transtorno Depressivo Maior/diagnóstico , Mediadores da Inflamação/sangue , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Adulto , Alcoolismo/sangue , Alcoolismo/epidemiologia , Estudos de Casos e Controles , Transtornos Relacionados ao Uso de Cocaína/sangue , Transtornos Relacionados ao Uso de Cocaína/epidemiologia , Transtorno Depressivo Maior/sangue , Transtorno Depressivo Maior/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Espanha/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/sangue , Transtornos Relacionados ao Uso de Substâncias/epidemiologia
15.
Artigo em Inglês | MEDLINE | ID: mdl-30677468

RESUMO

OBJECTIVE: Alcohol use disorders inflict a great individual and societal burden. Although sex hormone effects have been implicated in alcohol dependence, research has mostly neglected estrogen activities and female alcohol-dependent patients. Here, we investigated associations of estrogen receptor 1 (ESR1) genetics and serum estradiol activities with aspects of alcohol dependence. METHOD: Serum estradiol activities of early-abstinent alcohol-dependent in-patients (n[♂] = 113, n[♀] = 87) were followed for at median 5 days and compared with healthy controls (n[♂] = 133, n[♀] = 107). All participants were genotyped for five ESR1 single nucleotide polymorphisms (rs6902771, rs11155819, rs6557171, rs2982683, rs2982712). RESULTS: Bioavailable estradiol levels decreased during withdrawal treatment (P[♂] < .001, P[♀] = .011). Male patients with an increase of bioavailable estradiol during withdrawal showed fewer days to (P = .033) and more alcohol-related readmissions (P < .05) during the 12-month follow-up. Higher estradiol and estradiol-to-testosterone activities were significantly related to liver, muscle, and cell count damage in male patients. Estradiol-to-testosterone activities in female patients were lower compared to female controls (total P = .013, bioavailable P = .009). Moreover, the ESR1 genotypes jointly separated alcohol-dependent patients from controls (P = .037). CONCLUSION: Our findings support the role of ESR1 genetics in alcohol dependence and show for the first time that estradiol activities may sex-specifically predict alcohol-related sequelae and outcome following in-patient withdrawal treatment.


Assuntos
Alcoolismo/genética , Estradiol/sangue , Receptor alfa de Estrogênio/genética , Adulto , Alcoolismo/sangue , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , Pacientes Internados , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Caracteres Sexuais , Síndrome de Abstinência a Substâncias/sangue , Testosterona/sangue
16.
Drug Test Anal ; 11(6): 859-869, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30618164

RESUMO

Direct and indirect biomarkers are widely applied for the determination of alcohol consumption. They help to assess past or present alcohol consumption. Depending on the window of detection and sensitivity of the investigated marker, punctual alcohol consumption may remain undetected. In this study, different sampling strategies for the intermediary long-term marker phosphatidylethanol (PEth) are evaluated and compared to the determination of the short-term markers ethyl glucuronide (EtG) and ethyl sulfate (EtS) in urine. Samples from 19 patients undergoing alcohol use disorder treatment were collected during the withdrawal treatment and successive rehabilitation (33 ± 26 days (range: 3-74 days)). With liquid chromatography-tandem mass spectrometry (LC-MS/MS) EtG and EtS in urine, PEth in blood, PEth in dried blood spot (DBS) from venous blood, and PEth in DBS from capillary blood were quantified and compared. The use of volumetric capillary DBS, prepared from 20 µL of blood, provided the same results as the use of venous DBS (95% ± 10%, R2 0.9899 for PEth 16:0/18:1). Capillary DBS sampling has the advantage that it can be performed without venipuncture. The use of PEth in DBS proved to prevent post-sampling degradation, providing a longer detection in comparison to PEth in liquid blood, which only showed 67% ± 24% of the PEth DBS 16:0/18:1 concentration. When compared with EtG and EtS in urine, PEth monitoring proved to be advantageous for the detection of relapse situations, as the accumulation of PEth in blood prolongs the detectability. In conclusion, volumetric capillary DBS sampling for PEth is a simple and useful tool for compliance monitoring, and avoids hematocrit issues.


Assuntos
Alcoolismo/sangue , Alcoolismo/urina , Glucuronatos/urina , Glicerofosfolipídeos/sangue , Ésteres do Ácido Sulfúrico/urina , Adulto , Idoso , Alcoolismo/reabilitação , Alcoolismo/terapia , Biomarcadores/sangue , Biomarcadores/urina , Cromatografia Líquida/métodos , Teste em Amostras de Sangue Seco/métodos , Feminino , Humanos , Limite de Detecção , Masculino , Pessoa de Meia-Idade , Espectrometria de Massas em Tandem/métodos , Adulto Jovem
17.
J Chromatogr A ; 1589: 1-9, 2019 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-30598290

RESUMO

BACKGROUND: Phosphatidylethanols (PEths) are currently under investigation as highly sensitive and specific direct biomarkers of long-term alcohol abuse. PEths belong to a group of aberrant phospholipids formed in erythrocyte membranes in presence of ethanol by the catalytic action of the enzyme phospholipase D on phosphatidylcholine. Compared to other alcohol biomarkers, a higher sensitivity (94.5-100%) and specificity (100%) characterizes PEth species. METHOD: Prior to detection, an important practical aspect in the work-flow of PEths analysis is the sample preparation step. To date, traditional techniques such as liquid-liquid extraction (LLE) and solid phase extraction (SPE) require multiple steps to remove blood interferences. Due to the simplicity of use and the possibility of automation, sample filtration is also a widespread technique in biomedical laboratories. In this work, a reliable sample preparation method based on an automated filtration with Phree™ Phospholipid Removal Plates (Phenomenex, California, USA) was developed to extract PEths from human whole blood. Surface characteristics of Phospholipids Removal material allow phospholipids retention on the filter and a suitable PEths recovery after elution. The blood samples were added with internal standard (IS) and purified in acetonitrile (1 mL). After centrifugation, supernatants were applied to the Phospholipids Removal Plates in an automated workstation. After washing, the phospholipids retained on the filter were eluted with 1-mL 2-propanol 1% ammonia. PEth 16:0/18:1, PEth 16:0/16:0 and PEth 18:1/18:1 were extracted using the proposed method and detected by LC-MS/MS operated in electron spray ionization (ESI). The detection of all compounds was based on multiple reaction monitoring (MRM) transitions. This method was validated for the quantitative profiling of PEth molecular species in human blood collected from heavy and social drinkers. RESULTS: The method was validated according to Food and Drug Administration (FDA) guidelines. Linearity was observed in the 25-1250 (PEth 16:0/18:1) and 5-250 (PEth 16:0/16:0 and PEth 18:1/18:1) ng/mL range with a correlation coefficient (r²) between 0.997 and 0.999 for all three compounds. Moreover, the nominal concentrations of non-zero calibrators were ±15%. Variation coefficient (%CV) was < 10% for all the analytes, while lowest limit of quantitation (LLOQ) was found to be 1.25 ng/mL for PEth 16:0/18:1, 0.50 ng/mL for PEth 16:0/16:0 and 0.50 ng/mL for PEth 18:1/18:1. Intra- and inter-day precision and accuracy were always lower than 14% and 11%, respectively. Analytical recovery was higher than 68.8% for all analytes. Sample stability at 4 °C and -20 °C showed a concentration drop lower than 20% up to 4 weeks. Extracts were stable for 7 days in the autosampler and 30 days at -20 °C and 4 °C in a closed vial. The procedure was successfully applied to blood samples collected from heavy drinkers (n = 8), social drinkers (n = 5), and teetotalers (n = 7). CONCLUSIONS: Due to the simplicity of application and the possibility of automation, sample filtration is well suited for a clinical and forensic laboratory. To monitor alcohol consumption, an analytical method based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) with novel and automated sample preparation was developed and validated for the simultaneous quantification of PEth 16:0/18:1, PEth 16:0/16:0 and PEth 18:1/18:1 in whole blood samples, characterized by a fast sample preparation and lower pre-analysis costs than other extraction procedures.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Etanol/análise , Glicerofosfolipídeos/sangue , Espectrometria de Massas em Tandem/métodos , Adulto , Consumo de Bebidas Alcoólicas , Alcoolismo/sangue , Automação , Biomarcadores/sangue , Calibragem , California , Estudos de Casos e Controles , Etanol/normas , Feminino , Glicerofosfolipídeos/química , Humanos , Limite de Detecção , Masculino , Pessoa de Meia-Idade , Padrões de Referência , Espectrometria de Massas por Ionização por Electrospray
18.
Psychiatry Res ; 272: 431-437, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30611960

RESUMO

The orexigenic hormone ghrelin is involved in the regulation of food intake and energy balance. Previous findings suggest its involvement in the modulation of mesolimbic reward pathways, thus potentially being relevant in the pathophysiology of substance use disorders such as alcohol dependence. In the present study, we assessed plasma levels of total and acylated ghrelin within the BACLAD trial, where alcohol-dependent patients received individually titrated high-dose baclofen (30-270 mg/d) within a randomized, placebo-controlled design. Plasma levels of total ghrelin and acylated ghrelin were measured at baseline, during treatment with individually titrated high-dose baclofen and after termination of the study medication within a timeframe of up to 20 weeks. Multivariate longitudinal non-parametric analysis revealed that plasma levels of total ghrelin significantly decreased in the group of abstinent patients receiving high-dose baclofen. In addition, plasma levels of total ghrelin correlated negatively with days of abstinence during treatment with high-dose baclofen. Plasma levels of acylated ghrelin increased during the study in the group of relapsed patients under baclofen and placebo treatment. These findings suggest that the long-term response to baclofen treatment in alcohol use disorder (AUD) might be monitored by assessing total and acylated ghrelin plasma levels.


Assuntos
Alcoolismo/sangue , Alcoolismo/tratamento farmacológico , Baclofeno/administração & dosagem , Agonistas dos Receptores de GABA-B/administração & dosagem , Grelina/sangue , Acilação/fisiologia , Adulto , Alcoolismo/diagnóstico , Biomarcadores/sangue , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo
19.
Biomarkers ; 24(4): 317-324, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30512980

RESUMO

Context: Pesticide poisoning and related deaths are a global concern, but there is little information about its effect on the occupationally exposed tea garden workers of North Bengal. Objective: This study investigates the level of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) in the blood of the tea garden workers at risk of exposure to a mixture of pesticides. Materials and methods: The study sample consisted of pesticide exposed workers, non-exposed (control), smokers and alcoholics. AChE and BuChE activity was measured and tested for significance. Results: Results showed that AChE activity was half in the pesticide exposed individuals than controls (p≤ 0.001). BuChE activity was also significantly decreased in the pesticide exposed individuals than controls (p≤ 0.001), while AChE and BuChE activity in smokers and alcoholics were not different from that of controls. However, significantly decreased AChE and BuChE activities were recorded in pesticide exposed workers compared to smokers and alcoholics. Conclusions: The results indicated that the decrease in enzyme activities in tea garden workers was due to mixed pesticides (containing organophosphates) exposure. Age was not found to influence the enzyme activities. However, the gender had little effect on the enzyme activities but the effect was not so prominent.


Assuntos
Acetilcolinesterase/sangue , Butirilcolinesterase/sangue , Inibidores da Colinesterase/envenenamento , Fazendeiros , Exposição Ocupacional/efeitos adversos , Praguicidas/envenenamento , Adulto , Agricultura/métodos , Alcoolismo/sangue , Alcoolismo/fisiopatologia , Estudos de Casos e Controles , Feminino , Jardins , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Fumar/sangue , Fumar/fisiopatologia , Chá
20.
Alcohol Alcohol ; 54(1): 51-55, 2019 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-30260366

RESUMO

Aims: Aim of this study was to associate concentration of naltrexone and its major active metabolite 6ß-naltrexol in blood with therapeutic outcome during treatment with naltrexone in subjects with alcohol dependence. Treatment with the µ-opiate receptor antagonist naltrexone has been shown to reduce craving for alcohol and alcohol intake in patients suffering from alcohol dependence. Short summary: This article shows the use of therapeutic drug monitoring in alcohol dependent patients, who are treated with naltrexone. The plasma concentrations of naltrexone and 6ß-naltrexol showed high inter-individual variability. They were predictive for treatment response, as they correlated significantly with the reduction of alcohol craving. Methods: Naltrexone and 6ß-naltrexol were analysed by high performance liquid chromatography with column switching and spectrophotometric detection. Alcohol craving was assessed with the Obsessive-Compulsive Drinking Scale (OCDS). Results and conclusions: The study included 43 patients who were treated with naltrexone with a dose of 50 mg/day. Blood was taken for drug analysis 8 h after the last dose of the day at Week 4, 8 and 12. The plasma concentrations of naltrexone and 6ß-naltrexol showed high inter-individual variability. They were predictive for treatment response, as they correlated significantly with the reduction of alcohol craving. Defining patients with OCDS reduction of 70% or higher as responders, the mean±SD concentration of naltrexone plus naltrexol was 22 ± 13 ng/ml compared to 15 ± 8 ng/ml in patients with score reductions of 1-69%. Further analyses indicated that concentrations of 17-50 ng/ml at 8 h and 7-20 ng/ml at 24 h after drug intake were required for treatment response. Conclusions: Since plasma concentration of naltrexone plus 6ß-naltrexol was found to be predictive for reduction of alcohol craving, it is concluded that therapeutic drug monitoring has the potential to enhance naltrexone's moderate therapeutic efficiency in patients with alcohol dependence.


Assuntos
Alcoolismo/sangue , Alcoolismo/tratamento farmacológico , Fissura/efeitos dos fármacos , Monitoramento de Medicamentos/métodos , Naltrexona/administração & dosagem , Naltrexona/sangue , Acamprosato/administração & dosagem , Acamprosato/sangue , Adulto , Dissuasores de Álcool/administração & dosagem , Dissuasores de Álcool/sangue , Fissura/fisiologia , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Naltrexona/análogos & derivados , Antagonistas de Entorpecentes/administração & dosagem , Antagonistas de Entorpecentes/sangue , Valores de Referência , Resultado do Tratamento
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA