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1.
Eur J Clin Microbiol Infect Dis ; 38(11): 2171-2176, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31392446

RESUMO

The aim of the study was to determine the effect of chronic alcohol abuse on the course and outcome of bacterial meningitis (BM). We analyzed records of patients with BM who were hospitalized between January 2010 and December 2017 in the largest neuroinfection center in Poland. Out of 340 analyzed patients, 45 (13.2%) were alcoholics. Compared with non-alcoholics, alcoholics were more likely to present with seizures (p < 0.001), scored higher on the Sequential Organ Failure Assessment (SOFA) (p = 0.002) and lower on the Glasgow Coma Scale (GCS) (p < 0.001), and had worse outcome as measured by the Glasgow Outcome Score (GOS) (p < 0.001). Furthermore, alcoholics were less likely to complain of headache (p < 0.001) and nausea/vomiting (p = 0.005) and had lower concentration of glucose in cerebrospinal fluid (CSF) (p = 0.025). In the multiple logistic regression analysis, alcoholism was associated with lower GCS (p = 0.036), presence of seizures (p = 0.041), male gender (p = 0.042), and absence of nausea/vomiting (p = 0.040). Furthermore, alcoholism (p = 0.031), lower GCS score (p = 0.001), and higher blood urea concentration (p = 0.018) were independently associated with worse outcome measured by GOS. Compared with non-alcoholics, chronic alcohol abusers are more likely to present with seizures, altered mental status, and higher SOFA score and have an increased risk of unfavorable outcome. In multivariate analysis, seizures and low GCS were independently associated with alcoholism, while alcoholism was independently associated with worse outcome.


Assuntos
Alcoolismo/epidemiologia , Meningites Bacterianas/epidemiologia , Adulto , Idoso , Alcoolismo/tratamento farmacológico , Alcoolismo/patologia , Alcoolismo/fisiopatologia , Infecções Comunitárias Adquiridas/epidemiologia , Infecções Comunitárias Adquiridas/patologia , Infecções Comunitárias Adquiridas/fisiopatologia , Feminino , Escala de Coma de Glasgow , Humanos , Masculino , Meningites Bacterianas/tratamento farmacológico , Meningites Bacterianas/patologia , Meningites Bacterianas/fisiopatologia , Pessoa de Meia-Idade , Escores de Disfunção Orgânica , Polônia/epidemiologia , Prognóstico , Risco
2.
Dis Markers ; 2019: 4360612, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31191750

RESUMO

A growing interest in the usability of saliva has been observed recently. Using saliva as a diagnostic material is possible because it contains a varied range of composites, organic and inorganic like proteins, carbohydrates, and lipids, which are secreted into saliva. Moreover, this applies to drugs and their metabolites. Saliva collection is noninvasive, and self-collection is possible. There is a lack of risk of injuries related to injection with needle, and it is generally safe. Human saliva has been successfully used, for example, in the diagnosis of many systemic diseases like cancers, autoimmunological diseases, infectious diseases (HIV, hepatitis, and malaria), and endocrinological diseases, as well as diseases of the gastrointestinal tract. Also, it is used in toxicological diagnostics, drug monitoring, and forensic medicine. The usefulness of saliva as a biological marker has also been extended to psychiatry. The specificity of mental illness and patients limits or prevents cooperation and diagnosis. In many cases, the use of saliva as a marker seems to be the most sensible choice.


Assuntos
Alcoolismo/metabolismo , Transtorno do Espectro Autista/metabolismo , Biomarcadores/metabolismo , Doenças do Sistema Endócrino/metabolismo , Saliva/metabolismo , Alcoolismo/patologia , Transtorno do Espectro Autista/patologia , Biomarcadores/análise , Demência , Monitoramento de Medicamentos/métodos , Doenças do Sistema Endócrino/patologia , Humanos , Saliva/química
3.
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
4.
Brain Struct Funct ; 224(6): 2087-2101, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31161472

RESUMO

Despite the common co-occurrence of cognitive impairment and brain structural deficits in alcoholism, demonstration of relations between regional gray matter volumes and cognitive and motor processes have been relatively elusive. In pursuit of identifying brain structural substrates of impairment in alcoholism, we assessed executive functions (EF), episodic memory (MEM), and static postural balance (BAL) and measured regional brain gray matter volumes of cortical, subcortical, and cerebellar structures commonly affected in individuals with alcohol dependence (ALC) compared with healthy controls (CTRL). ALC scored lower than CTRL on all composite scores (EF, MEM, and BAL) and had smaller frontal, cingulate, insular, parietal, and hippocampal volumes. Within the ALC group, poorer EF scores correlated with smaller frontal and temporal volumes; MEM scores correlated with frontal volume; and BAL scores correlated with frontal, caudate, and pontine volumes. Exploratory analyses investigating relations between subregional frontal volumes and composite scores in ALC yielded different patterns of associations, suggesting that different neural substrates underlie these functional deficits. Of note, orbitofrontal volume was a significant predictor of memory scores, accounting for almost 15% of the variance; however, this relation was evident only in ALC with a history of a non-alcohol substance diagnosis and not in ALC without a non-alcohol substance diagnosis. The brain-behavior relations observed provide evidence that the cognitive and motor deficits in alcoholism are likely a result of different neural systems and support the hypothesis that a number of identifiable neural systems rather than a common or diffuse neural pathway underlies cognitive and motor deficits observed in chronic alcoholism.


Assuntos
Alcoolismo , Cognição/fisiologia , Substância Cinzenta/patologia , Córtex Motor/patologia , Vias Neurais/patologia , Adulto , Idoso , Alcoolismo/patologia , Alcoolismo/fisiopatologia , Cerebelo/patologia , Cerebelo/fisiopatologia , Função Executiva/fisiologia , Feminino , Substância Cinzenta/fisiopatologia , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Memória Episódica , Pessoa de Meia-Idade , Córtex Motor/fisiopatologia , Vias Neurais/fisiopatologia
5.
J Clin Neurosci ; 66: 273-275, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31178304

RESUMO

Marchiafava-Bignami disease (MBD) is a rare condition often associated with chronic alcohol abuse. Clinical presentation is diverse. Characteristic magnetic resonance imaging (MRI) changes in the corpus callosum are the mainstay of radiological diagnosis. We present a case of a 54-year-old man with chronic alcoholism and peripherally enhancing lesion in the body of the corpus callosum on MRI Brain. Open biopsy of the lesion showed necrosis and demyelination. He was diagnosed with Marchiafava-Bignami disease based on clinical, radiology and histopathology findings. Our case represents the only case in the literature with antemortem histopathology findings describing MBD.


Assuntos
Corpo Caloso/diagnóstico por imagem , Corpo Caloso/patologia , Imagem por Ressonância Magnética/métodos , Doença de Marchiafava-Bignami/diagnóstico por imagem , Doença de Marchiafava-Bignami/patologia , Alcoolismo/diagnóstico por imagem , Alcoolismo/patologia , Diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade
6.
Toxicol Lett ; 313: 19-29, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31082522

RESUMO

Much efforts have been tried to clarify the molecular mechanism of alcohol-induced brain damage from the perspective of genome and protein; however, the effect of chronic alcohol exposure on global lipid profiling of brain is unclear. In the present study, by using Q-TOF/MS-based lipidomics approach, we investigated the comprehensive lipidome profiling of brain from the rats orally administrated with alcohol daily, continuously for one year. Through systematically analysis of all lipids in prefrontal cortex (PFC) and striatum region, we found that long-term alcohol exposure profoundly modified brain lipidome profiling. Notably, three kinds of lipid classes, glycerophospholipid (GP), glycerolipid (GL) and fatty acyls (FA), were significantly increased in these two brain regions. Interestingly, most of the modified lipids were involved in synthetic pathways of endoplasmic reticulum (ER), which may result in ER stress-related metabolic disruption. Moreover, alcohol-modified lipid species displayed long length of carbon chain with high degree of unsaturation. Taken together, our results firstly present that chronic alcohol exposure markedly modifies brain lipidomic profiling, which may activate ER stress and eventually result in neurotoxicity. These findings provide a new insight into the mechanism of alcohol-related brain damage.


Assuntos
Transtornos do Sistema Nervoso Induzidos por Álcool/metabolismo , Alcoolismo/metabolismo , Corpo Estriado/metabolismo , Metabolismo dos Lipídeos , Metabolômica/métodos , Córtex Pré-Frontal/metabolismo , Espectrometria de Massas por Ionização por Electrospray , Transtornos do Sistema Nervoso Induzidos por Álcool/patologia , Alcoolismo/patologia , Animais , Corpo Estriado/patologia , Modelos Animais de Doenças , Retículo Endoplasmático/metabolismo , Retículo Endoplasmático/patologia , Estresse do Retículo Endoplasmático , Ácidos Graxos/metabolismo , Glicerofosfolipídeos/metabolismo , Córtex Pré-Frontal/patologia , Ratos Wistar , Fatores de Tempo
7.
Artigo em Inglês | MEDLINE | ID: mdl-30982583

RESUMO

The incidence of alcohol use disorder (AUD) in human immunodeficiency virus (HIV) infection is twice that of the rest of the population. This study documents complex radiologically identified, neuroanatomical effects of AUD+HIV comorbidity by identifying structural brain systems that predicted diagnosis on an individual basis. Applying novel machine learning analysis to 549 participants (199 control subjects, 222 with AUD, 68 with HIV, 60 with AUD+HIV), 298 magnetic resonance imaging brain measurements were automatically reduced to small subsets per group. Significance of each diagnostic pattern was inferred from its accuracy in predicting diagnosis and performance on six cognitive measures. While all three diagnostic patterns predicted the learning and memory score, the AUD+HIV pattern was the largest and had the highest predication accuracy (78.1%). Providing a roadmap for analyzing large, multimodal datasets, the machine learning analysis revealed imaging phenotypes that predicted diagnostic membership of magnetic resonance imaging scans of individuals with AUD, HIV, and their comorbidity.


Assuntos
Alcoolismo/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Infecções por HIV/diagnóstico por imagem , Aprendizado de Máquina , Adulto , Alcoolismo/epidemiologia , Alcoolismo/patologia , Encéfalo/patologia , Comorbidade , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/patologia , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade
8.
Int J Mol Sci ; 20(8)2019 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-31022832

RESUMO

Nitrergic enteric neurons are key players of the descending inhibitory reflex of intestinal peristalsis, therefore loss or damage of these neurons can contribute to developing gastrointestinal motility disturbances suffered by patients worldwide. There is accumulating evidence that the vulnerability of nitrergic enteric neurons to neuropathy is strictly region-specific and that the two main enteric plexuses display different nitrergic neuronal damage. Alterations both in the proportion of the nitrergic subpopulation and in the total number of enteric neurons suggest that modification of the neurochemical character or neuronal death occurs in the investigated gut segments. This review aims to summarize the gastrointestinal region and/or plexus-dependent pathological changes in the number of nitric oxide synthase (NOS)-containing neurons, the NO release and the cellular and subcellular expression of different NOS isoforms. Additionally, some of the underlying mechanisms associated with the nitrergic pathway in the background of different diseases, e.g., type 1 diabetes, chronic alcoholism, intestinal inflammation or ischaemia, will be discussed.


Assuntos
Neurônios Nitrérgicos/citologia , Neurônios Nitrérgicos/patologia , Alcoolismo/metabolismo , Alcoolismo/patologia , Animais , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/patologia , Modelos Animais de Doenças , Humanos , Inflamação/metabolismo , Inflamação/patologia , Intestinos/inervação , Intestinos/patologia , Neurônios Nitrérgicos/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase/metabolismo , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia
9.
Oncol Res Treat ; 42(6): 350-353, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30995668

RESUMO

Some chemotherapy formulations contain ethanol as a solvent which can become relevant for medical and nonmedical reasons. Only a few studies have tried to quantify the effects of ethanol in chemotherapy preparations. Furthermore, the alcohol amount highly depends on the specific formulation, with some variation among different manufacturers. Although the actual increase in blood alcohol levels after ethanol-based chemotherapies seems to be limited, the FDA recently released a warning that docetaxel may cause symptoms of alcohol intoxication. Here, we report on a patient with breast cancer who experienced a relapse of alcohol abuse after a single docetaxel infusion. We hypothesize a causal relationship with the ethanol-containing docetaxel infusion. Today, no guidelines exist for the use of ethanol-based chemotherapy, and patient consent forms do not address this matter. We conclude that physicians prescribing chemotherapy and patients should be aware of the potential risks of ethanol-containing infusions and nonethanol-based alternatives should be discussed when needed or desired by the patient. This could be facilitated by revised patient consent forms.


Assuntos
Alcoolismo/patologia , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Docetaxel/uso terapêutico , Composição de Medicamentos , Etanol/efeitos adversos , Abstinência de Álcool , Feminino , Humanos , Perda de Seguimento , Pessoa de Meia-Idade , Pacientes Desistentes do Tratamento , Pacientes/psicologia , Médicos/psicologia , Recidiva , Resultado do Tratamento
10.
eNeuro ; 6(2)2019.
Artigo em Inglês | MEDLINE | ID: mdl-30993181

RESUMO

The transition from adolescence to adulthood is associated with brain remodeling in the final stages of developmental growth. It is also a period when a large proportion of this age group engages in binge alcohol drinking (occasional consumption of four to five drinks leading to intoxication) and heavy alcohol drinking (binge drinking on ≥5 d in a month). Here we report on magnetic resonance imaging of developmental changes in the brain occurring during late adolescence and early adulthood (3.5-7.5 years of age) in a rhesus macaque model of alcohol self-administration. Monkeys were imaged prior to alcohol exposure, and following ∼6 and ∼12 months of daily (22 h/d) access to ethanol and water. The results revealed that the brain volume increases by 1 ml/1.87 years throughout the late adolescence and early adulthood in controls. Heavy alcohol drinking reduced the rate of brain growth by 0.25 ml/year per 1 g/kg daily ethanol. Cortical volume increased throughout this period with no significant effect of alcohol drinking on the cortical growth rate. In subcortical regions, age-dependent increases in the volumes of globus pallidus, thalamus, brainstem, and cerebellum were observed. Heavy drinking attenuated the growth rate of the thalamus. Thus, developmental brain volume changes in the span of late adolescence to young adulthood in macaques is altered by excessive alcohol, an insult that may be linked to the continuation of heavy drinking throughout later adult life.


Assuntos
Alcoolismo , Encéfalo , Depressores do Sistema Nervoso Central/efeitos adversos , Etanol/efeitos adversos , Consumo de Álcool por Menores , Fatores Etários , Alcoolismo/complicações , Alcoolismo/diagnóstico por imagem , Alcoolismo/patologia , Animais , Encéfalo/diagnóstico por imagem , Encéfalo/efeitos dos fármacos , Encéfalo/crescimento & desenvolvimento , Encéfalo/patologia , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/crescimento & desenvolvimento , Córtex Cerebral/patologia , Modelos Animais de Doenças , Feminino , Macaca mulatta , Imagem por Ressonância Magnética , Masculino , Tálamo/diagnóstico por imagem , Tálamo/efeitos dos fármacos , Tálamo/crescimento & desenvolvimento , Tálamo/patologia
11.
Int J Psychiatry Clin Pract ; 23(3): 225-230, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30987473

RESUMO

Background: Previous studies have reported inconsistent findings regarding corticospinal tract (CST) changes in alcohol dependence. Here, we aimed to clarify this issue by examining the micro-structural integrity differences of distinct CST segments between alcohol-dependent patients and healthy controls. Methods: Diffusion tensor imaging was performed in a total of 39 male individuals, including 19 alcohol-dependent patients and 20 age-matched healthy controls. CST was reconstructed using tractography and was divided into inferior and superior segments at the level of the lateral sulcus. Multiple diffusion measures of each segment were compared between two groups. Results: For the bilateral whole CSTs, no diffusion measures showed significant between-group differences. However, compared to healthy controls, alcohol-dependent patients exhibited decreased FA and increased RD in the left-superior segment, increased FA and decreased RD/MD in the left-inferior segment, increased AD/MD in the right-superior segment, decreased RD/MD in the right-inferior segment. Conclusions: These findings suggest that CST impairments may vary with the fibre arrangement patterns of its segments in alcohol dependence. Keypoints We reconstructed the CST using tractography based on DTI data and divided the CST into different segments in order to explore more detailed micro-structural integrity changes in alcoholisms. Alcohol-dependent patients showed decreased RD and MD for the bilateral inferior segments of the CSTs. The left-superior segment exhibited decreased FA and increased RD while the right one exhibited increased AD and MD. These findings suggest that CST impairments may vary with the fiber arrangement patterns of its segments in alcohol dependence. In future work, more elaborate segmentation schemes and lager samples should be used to test the reproducibility of our findings.


Assuntos
Alcoolismo/patologia , Tratos Piramidais/patologia , Adulto , Anisotropia , Estudos de Casos e Controles , Imagem de Tensor de Difusão , Dominância Cerebral , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
12.
Neurochem Int ; 125: 111-116, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30817938

RESUMO

We have analysed post-mortem samples of prefrontal cortex from control and alcoholic human brains by the technique of Western blotting to estimate and compare the expressions of glutamate transporter GLAST (Excitatory Amino Acid Transporter One; EAAT1). Furthermore, using the non-alcoholic prefrontal cortex and custom-made GLAST (EAAT1) antibody we determined GLAST (EAAT1) "interactome" i.e. the set of proteins selectively bound by GLAST (EAAT1). We found that GLAST (EAAT1) was significantly more abundant (about 1.6-fold) in the cortical tissue from alcoholic brains compared to that from non-alcoholic controls. The greatest increase in the level of GLAST (EAAT1) was found in plasma membrane fraction (2.2-fold). Additionally, using the prefrontal cortical tissue from control brains, we identified 38 proteins specifically interacting with GLAST (EAAT1). These can be classified as contributing to the cell structure (6 proteins; 16%), energy and general metabolism (18 proteins; 47%), neurotransmitter metabolism (three proteins; 8%), signalling (6 proteins: 16%), neurotransmitter storage/release at synapses (three proteins; 8%) and calcium buffering (two proteins; 5%). We discuss possible consequences of the increased expression of GLAST (EAAT1) in alcoholic brain tissue and whether or how this could disturb the function of the proteins potentially interacting with GLAST (EAAT1) in vivo. The data represent an extension of our previous proteomic and metabolomic studies of human alcoholism revealing another aspect of the complexity of changes imposed on brain by chronic long-term consumption of ethanol.


Assuntos
Alcoolismo/metabolismo , Transportador 1 de Aminoácido Excitatório/biossíntese , Metabolômica/métodos , Córtex Pré-Frontal/metabolismo , Proteômica/métodos , Adulto , Idoso , Alcoólicos , Alcoolismo/genética , Alcoolismo/patologia , Transportador 1 de Aminoácido Excitatório/genética , Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Córtex Pré-Frontal/patologia
13.
Nat Commun ; 10(1): 1238, 2019 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-30886240

RESUMO

The activation of a neuronal ensemble in the central nucleus of the amygdala (CeA) during alcohol withdrawal has been hypothesized to induce high levels of alcohol drinking in dependent rats. In the present study we describe that the CeA neuronal ensemble that is activated by withdrawal from chronic alcohol exposure contains ~80% corticotropin-releasing factor (CRF) neurons and that the optogenetic inactivation of these CeA CRF+ neurons prevents recruitment of the neuronal ensemble, decreases the escalation of alcohol drinking, and decreases the intensity of somatic signs of withdrawal. Optogenetic dissection of the downstream neuronal pathways demonstrates that the reversal of addiction-like behaviors is observed after the inhibition of CeA CRF projections to the bed nucleus of the stria terminalis (BNST) and that inhibition of the CRFCeA-BNST pathway is mediated by inhibition of the CRF-CRF1 system and inhibition of BNST cell firing. These results suggest that the CRFCeA-BNST pathway could be targeted for the treatment of excessive drinking in alcohol use disorder.


Assuntos
Alcoolismo/fisiopatologia , Comportamento Aditivo/fisiopatologia , Núcleo Central da Amígdala/fisiopatologia , Hormônio Liberador da Corticotropina/metabolismo , Núcleos Septais/fisiopatologia , Alcoolismo/patologia , Animais , Comportamento Animal , Núcleo Central da Amígdala/citologia , Núcleo Central da Amígdala/metabolismo , Núcleo Central da Amígdala/patologia , Hormônio Liberador da Corticotropina/genética , Modelos Animais de Doenças , Humanos , Masculino , Vias Neurais/metabolismo , Vias Neurais/fisiopatologia , Neurônios/metabolismo , Optogenética , Ratos , Núcleos Septais/citologia , Núcleos Septais/metabolismo , Núcleos Septais/patologia , Síndrome de Abstinência a Substâncias/metabolismo , Síndrome de Abstinência a Substâncias/patologia , Síndrome de Abstinência a Substâncias/fisiopatologia , Síndrome de Abstinência a Substâncias/psicologia
14.
Neuroimage Clin ; 22: 101764, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30904825

RESUMO

The profile of brain structural dysmorphology of individuals with Alcohol Use Disorders (AUD) involves disruption of the limbic system. In vivo imaging studies report hippocampal volume loss in AUD relative to controls, but only recently has it been possible to articulate different regions of this complex structure. Volumetric analysis of hippocampal regions rather than total hippocampal volume may augment differentiation of disease processes. For example, damage to hippocampal subfield cornu ammonis 1 (CA1) is often reported in Alzheimer's disease (AD), whereas deficits in CA4/dentate gyrus are described in response to stress and trauma. Two previous studies explored the effects of chronic alcohol use on hippocampal subfields: one reported smaller volume of the CA2+3 in alcohol-dependent subjects relative to controls, associated with years of alcohol consumption; the other, smaller volumes of presubiculum, subiculum, and fimbria in alcohol-dependent relative to control men. The current study, conducted in 24 adults with DSM5-diagnosed AUD (7 women, 53.7 ±â€¯8.8) and 20 controls (7 women, 54.1 ±â€¯9.3), is the first to use FreeSurfer 6.0, which provides state-of-the art hippocampal parcellation, to explore the sensitivity of hippocampal sufields to alcoholism. T1- and T2- images were collected on a GE MR750 system with a 32-channel Nova head coil. FreeSurfer 6.0 hippocampal subfield analysis produced 12 subfields: parasubiculum; presubiculum; subiculum; CA1; CA2+3; CA4; GC-ML-DG (Granule Cell (GC) and Molecular Layer (ML) of the Dentate Gyrus (DG)); molecular layer; hippocampus-amygdala-transition-area (HATA); fimbria; hippocampal tail; hippocampal fissure; and whole volume for left and right hippocampi. A comprehensive battery of neuropsychological tests comprising attention, memory and learning, visuospatial abilities, and executive functions was administered. Multiple regression analyses of raw volumetric data for each subfields by group, age, sex, hemisphere, and supratentorial volume (svol) showed significant effects of svol (p < .04) on nearly all structures (excluding tail and fissure). Volumes corrected for svol showed effects of age (fimbria, fissure) and group (subiculum, CA1, CA4, GC-ML-DG, HATA, fimbria); CA2+3 showed a diagnosis-by-age interaction indicating older AUD individuals had a smaller volume than would be expected for their age. There were no selective relations between hippocampal subfields and performance on neuropsychological tests, likely due to lack of statistical power. The current results concur with the previous study identifying CA2+3 as sensitive to alcoholism, extend them by identifying an alcoholism-age interaction, and suggest an imaging phenotype distinguishing AUD from AD and stress/trauma.


Assuntos
Senilidade Prematura/patologia , Alcoolismo/patologia , Região CA2 Hipocampal/patologia , Região CA3 Hipocampal/patologia , Adulto , Idoso , Senilidade Prematura/diagnóstico por imagem , Senilidade Prematura/etiologia , Alcoolismo/complicações , Alcoolismo/diagnóstico por imagem , Alcoolismo/fisiopatologia , Região CA2 Hipocampal/diagnóstico por imagem , Região CA3 Hipocampal/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
15.
Neuropsychopharmacology ; 44(6): 1076-1083, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30636769

RESUMO

Adolescence is a time of significant neurobiological development, including changes in white matter microstructure. Familial alcoholism and adolescent binge-drinking have both been associated with altered white matter microstructure; however, the temporal nature of these effects, and their interaction, is unclear. Using diffusion-weighted imaging and voxel-wise multilevel modeling, the effects of familial alcoholism and future binge-drinking on white matter microstructural development were assessed in 45 adolescents, who went on to binge-drink (but were alcohol-naive at baseline), and 68 adolescents, who remained largely alcohol-naive, all with varying degrees of familial alcoholism. Both future binge-drinking and familial alcoholism were associated with altered frontostriatal white matter microstructure early in adolescence, prior to alcohol use. While several binge-drinking-related effects persisted throughout adolescence (in the posterior limb of the internal capsule, superior corona radiata, and cerebellar peduncles), the association between familial alcoholism and altered white matter microstructure dissipated across adolescence in all regions. There were no white matter regions identified where future binge-drinking or familial alcoholism were significantly associated with emergent or exacerbated alterations in white matter microstructure. Altogether, these findings suggest that alterations in frontostiatal white matter microstructure, some of which are associated with familial alcoholism, may be used to predict which adolescents are more likely to go on and engage in alcohol use. Meanwhile, a reduction in family history-related associations with altered white matter microstructure by late-adolescence is encouraging for future prevention work targeted at at-risk youth.


Assuntos
Comportamento do Adolescente , Alcoolismo/patologia , Bebedeira/patologia , Corpo Estriado/patologia , Lobo Frontal/patologia , Consumo de Álcool por Menores , Substância Branca/patologia , Adolescente , Adulto , Alcoolismo/diagnóstico por imagem , Alcoolismo/genética , Bebedeira/diagnóstico por imagem , Criança , Corpo Estriado/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética , Feminino , Seguimentos , Lobo Frontal/diagnóstico por imagem , Predisposição Genética para Doença , Humanos , Estudos Longitudinais , Masculino , Análise Multinível , Vias Neurais/diagnóstico por imagem , Vias Neurais/patologia , Substância Branca/diagnóstico por imagem , Adulto Jovem
16.
Bull Exp Biol Med ; 166(3): 317-320, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30627909

RESUMO

The in vitro and in vivo models of ethanol-induced neurodegeneration were used to evaluate the content and functional activity of various types of regeneration-competent cells in subventricular zone of the cerebral hemispheres in C57Bl/6JY mice. In nervous tissue culture, ethanol (65 mM) produced no effect on formation of neurospheres. When administered per os in a daily dose of 3 g/kg for 8 weeks, ethanol produced no effect on the number of neural CFU in situ. In both cases, ethanol reduced proliferative activity of neural CFU. Long-term administration of ethanol in vivo suppressed differentiation of neural stem cells and decreased the number of committed precursors (neural cluster-forming units) in the subventricular zone of cerebral hemispheres. In vitro application of ethanol stimulated secretion of humoral growth factors by the cluster-forming neural glial cells. In contrast, in vivo administration of ethanol suppressed this secretion.


Assuntos
Alcoolismo/patologia , Cérebro/efeitos dos fármacos , Etanol/farmacologia , Ventrículos Laterais/efeitos dos fármacos , Doenças Neurodegenerativas/patologia , Neurônios/efeitos dos fármacos , Alcoolismo/metabolismo , Animais , Contagem de Células , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Cérebro/metabolismo , Cérebro/patologia , Cérebro/fisiopatologia , Modelos Animais de Doenças , Peptídeos e Proteínas de Sinalização Intercelular/agonistas , Peptídeos e Proteínas de Sinalização Intercelular/biossíntese , Ventrículos Laterais/metabolismo , Ventrículos Laterais/patologia , Ventrículos Laterais/fisiopatologia , Camundongos , Camundongos Endogâmicos C57BL , Células-Tronco Neurais/efeitos dos fármacos , Células-Tronco Neurais/patologia , Doenças Neurodegenerativas/metabolismo , Neuroglia/efeitos dos fármacos , Neuroglia/metabolismo , Neuroglia/patologia , Neurônios/patologia , Cultura Primária de Células , Esferoides Celulares/efeitos dos fármacos
17.
PLoS One ; 14(1): e0210546, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30629674

RESUMO

BACKGROUND: The presence of large or multiple esophageal distinct iodine-unstained lesions (DIULs) is a strong predictor of field cancerization in the upper aerodigestive tract. Several risk factors for DIULs, including genetic polymorphisms of alcohol and aldehyde dehydrogenases (ADH1B, rs1229984; ALDH2, rs671), have been demonstrated in Japanese alcohol-dependent men. However, few evaluations of alcohol-dependent women have been conducted in this field. METHODS: Using multiple logistic regression models, we investigated the results of screening using esophageal iodine staining and the identification of determinants for esophageal DIULs in 472 Japanese alcohol-dependent women. RESULTS: DIULs ≥5 mm, multiple DILUs, and both characteristics were observed in 35 (7.4%), 31 (6.6%), and 16 (3.4%) patients, respectively. DIULs ≥5 mm were histologically diagnosed as low-grade intraepithelial neoplasia in 26 patients and superficial squamous cell carcinoma in 9 patients. Although the inactive heterozygous ALDH2*1/*2 genotype was more common (33.3% vs. 11.4%, p = 0.002) in the group with DIULs ≥5 mm than in the group without DIULs ≥5 mm, no significant differences in the results of a questionnaire asking about current and past facial flushing after a glass of beer were seen between the groups with and without DIULs ≥5 mm. When individuals with current or former flushing were assumed to have inactive ALDH2, the sensitivity and specificity of current or former flushing to identify the presence of inactive ALDH2 were 50.0% and 93.5%, respectively; these values were previously reported to be 88% and 92%, respectively, in a Japanese general female population. The low sensitivity in the present study suggests that a lack of alcohol flushing may play a crucial role in the development of alcohol dependence in women with inactive ALDH2. No significant differences in age, usual alcohol consumption, or smoking habits were observed according to ADH1B and ALDH2 genotypes. Multiple logistic regression analyses showed that the slow-metabolizing ADH1B*1/*1 genotype (odds ratio [95% confidence interval], 12.5 [4.82-32.4] and 9.89 [3.50-27.9]), the inactive heterozygous ALDH2*1/*2 genotype (2.94 [1.18-7.38] and 3.79 [1.40-10.3]), a lower body mass index per -1 kg/m2 (1.17 [1.02-1.35] and 1.38 [1.14-1.67]), and a mean corpuscular volume ≥106 fl (3.70 [1.56-8.81] and 3.27 [1.24-8.64]) increased the risk of DIULs ≥5 mm and multiple DIULs, respectively. The combination of ADH1B*1/*1 and ALDH2*1/*2 markedly increased the risk of esophageal DIULs ≥5 mm (39.3 [10.6-146]). CONCLUSIONS: Japanese alcohol-dependent women shared several common risk factors for esophageal squamous cell neoplasia with alcohol-dependent men, but with considerably different magnitudes.


Assuntos
Álcool Desidrogenase/genética , Alcoolismo/complicações , Alcoolismo/genética , Aldeído-Desidrogenase Mitocondrial/genética , Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , Adulto , Idoso , Alcoolismo/patologia , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/etiologia , Carcinoma de Células Escamosas/patologia , Endoscopia Gastrointestinal , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/etiologia , Neoplasias Esofágicas/patologia , Esôfago/metabolismo , Esôfago/patologia , Feminino , Genótipo , Humanos , Iodo/análise , Japão/epidemiologia , Pessoa de Meia-Idade , Polimorfismo Genético , Polimorfismo de Nucleotídeo Único , Prognóstico , Fatores de Risco , Fatores Sexuais , Coloração e Rotulagem
18.
Eur Arch Psychiatry Clin Neurosci ; 269(3): 285-294, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29372325

RESUMO

Although depression and anxiety disorders are common comorbid conditions in alcohol dependence, few structural brain imaging studies have compared alcohol-dependent subjects with and without such comorbidity. In the current study, brain scans of 35 alcohol-dependent with and 40 individuals without diagnosis of a comorbid ICD-10 depressive or anxiety disorder receiving detoxification inpatient treatment were evaluated. Thickness and volumes of automatically segmented neuroanatomical structures were measured in FreeSurfer. Furthermore, associations of brain structure with biological markers and clinical severity markers of alcohol dependence were assessed. Despite comparable addiction severity, the non-comorbid group had evidence of higher cytotoxic effects of alcohol use on hepatic and haematological markers, and showed significantly smaller volumes of total cerebral, and cerebellar grey matter. Similarly, they showed unexpected smaller hippocampal and nucleus accumbens volumes, and thinner frontal, temporal and occipital cortices. Smaller brain volumes correlated with increased markers of hepatic and haematological dysfunction, and with longer duration of alcohol dependence in the non-comorbid group. Evidence of higher biomarkers of alcohol use may be indicative of more severe alcohol dependence or higher vulnerability to ethanol toxicity in this group. Furthermore, psychopathology-related drug treatment, which occurred in 53% of the comorbid group over the recent years, or tissue inflammation may have a moderate effect on the grade of cerebral atrophy in alcohol-dependent patients. Longitudinal studies are needed to investigate this issue more fully.


Assuntos
Alcoolismo/sangue , Alcoolismo/patologia , Alcoolismo/fisiopatologia , Transtornos de Ansiedade , Córtex Cerebral/patologia , Transtorno Depressivo , Substância Cinzenta/patologia , Adulto , Idoso , Alcoolismo/epidemiologia , Transtornos de Ansiedade/epidemiologia , Biomarcadores , Córtex Cerebral/diagnóstico por imagem , Comorbidade , Transtorno Depressivo/epidemiologia , Índices de Eritrócitos/fisiologia , Feminino , Substância Cinzenta/diagnóstico por imagem , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Adulto Jovem , gama-Glutamiltransferase/sangue
19.
Biometrics ; 75(1): 245-255, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30052272

RESUMO

Sufficient dimension reduction (SDR) continues to be an active field of research. When estimating the central subspace (CS), inverse regression based SDR methods involve solving a generalized eigenvalue problem, which can be problematic under the large-p-small-n situation. In recent years, new techniques have emerged in numerical linear algebra, called randomized algorithms or random sketching, for high-dimensional and large scale problems. To overcome the large-p-small-n SDR problem, we combine the idea of statistical inference with random sketching to propose a new SDR method, called integrated random-partition SDR (iRP-SDR). Our method consists of the following three steps: (i) Randomly partition the covariates into subsets to construct an envelope subspace with low dimension. (ii) Obtain a sketch of the CS by applying a conventional SDR method within the constructed envelope subspace. (iii) Repeat the above two steps many times and integrate these multiple sketches to form the final estimate of the CS. After describing the details of these steps, the asymptotic properties of iRP-SDR are established. Unlike existing methods, iRP-SDR does not involve the determination of the structural dimension until the last stage, which makes it more adaptive to a high-dimensional setting. The advantageous performance of iRP-SDR is demonstrated via simulation studies and a practical example analyzing EEG data.


Assuntos
Eletroencefalografia/estatística & dados numéricos , Modelos Teóricos , Alcoolismo/patologia , Algoritmos , Encéfalo/efeitos dos fármacos , Simulação por Computador , Humanos , Aprendizado de Máquina
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