Prefrontal cortical and striatal activity to happy and fear faces in bipolar disorder is associated with comorbid substance abuse and eating disorder

Background: The spectrum approach was used to examine contributions of comorbid symptom dimensions of substance abuse and eating disorder to abnormal prefrontal-cortical and subcortical-striatal activity to happy and fear faces previously demonstrated in bipolar disorder (BD). Method: Fourteen remitted BD-type I and sixteen healthy individuals viewed neutral, mild and intense happy and fear faces in two event-related fMRI experiments. All individuals completed Substance-Use and Eating-Disorder Spectrum measures. Region-of-Interest analyses for bilateral prefrontal and subcortical-striatal regions were performed. Results: BD individuals scored significantly higher on these spectrum measures than healthy individuals (p<0.05), and were distinguished by activity in prefrontal and subcortical-striatal regions. BD relative to healthy individuals showed reduced dorsal prefrontal-cortical activity to all faces. Only BD individuals showed greater subcortical-striatal activity to happy and neutral faces. In BD individuals, negative correlations were shown between substance use severity and right PFC activity to intense happy faces (p<0.04), and between substance use severity and right caudate nucleus activity to neutral faces (p<0.03). Positive correlations were shown between eating disorder and right ventral putamen activity to intense happy (p<0.02) and neutral faces (p<0.03). Exploratory analyses revealed few significant relationships between illness variables and medication upon neural activity in BID individuals. Limitations: Small sample size of predominantly medicated BD individuals. Conclusion: This study is the first to report relationships between comorbid symptom dimensions of substance abuse and eating disorder and prefrontal-cortical and subcortical-striatal activity to facial expressions in BD. Our findings suggest that these comorbid features may contribute to observed patterns of functional abnormalities in neural systems underlying mood regulation in BD. (C) 2009 Elsevier B.V. All rights reserved.

Stigmatization of alcohol and other drug users by primary care providers in Southeast Brazil

This study reports on the views of Primary Health Care (PHC) providers in Southeast Brazil on the use of alcohol and other drugs which reflect stigma, moralization, or negative judgment. Six hundred nine PHC professionals from the Brazilian states of Sao Paulo and Minas Gerais took part in the study. The majority (86.5%) of these professionals were female. Attitudes toward the use of alcohol and other drugs were evaluated in comparison to Hansen`s disease, obesity, depression, schizophrenia. HIV/AIDS, and tobacco use. The use of tobacco, marijuana/cocaine, and alcohol were the most negatively judged behaviors (p < 0.05). Nursing assistants and community health care workers demonstrated the severest judgment of alcohol use. In addition, marijuana/cocaine addicts and alcoholics suffered the highest rate of rejection by professionals. The hypothesis that the use of alcohol and other drugs is a behavior stigmatized by health professionals being confirmed, it is important to develop strategies for changing provider attitudes in order to provide a higher quality of service to these patients. This study is important as a first study among PHC professionals about social stigma of alcohol and other drugs users. (C) 2009 Elsevier Ltd. All rights reserved.

Ethanol and gene expression in brain

This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were Izuru Matusmoto and Peter A. Wilce. The presentations were (1) GABA receptor subunit expression in the human alcoholic brain, by Tracey Buckley and Peter Dodd; (2) NMDAR gene expression during ethanol addiction, by Jorg Puzke, Rainer Spanagel, Walther Zieglgansberger, and Gerald Wolf; (3) Differentially expressed gene in the nucleus accumbens from ethanol-administered rat, by Shuangying Leng; (4) Expression of a novel gene in the alcoholic brain, by Peter A. Wilce; and (5) Investigations of haplotypes of the dopamine Da-receptor gene in alcoholics, by Hans Rommelspacher, Ulrich Finckh, and Lutz G. Schmidt.

Application of DNA microarrays to study human alcoholism

An emerging idea is that long-term alcohol abuse results in changes in gene expression in the brain and that these changes are responsible at least partly for alcohol tolerance, dependence and neurotoxicity, The overall goal of our research is to identify genes which are differentia[ly expressed in the brains of well-characterized human alcoholics as compared with non-alcoholics. This should identify as-yet-unknown alcohol-responsive genes, and may well confirm changes in the expression of genes which have been delineated in animal models of alcohol abuse. Cases were carefully selected and samples pooled on the basis of relevant criteria; differential expression was monitored by microarray hybridization. The inherent diversity of human alcoholics can be exploited to identify genes associated with specific pathological processes, as well as to assess the effects of concomitant disease, severity of brain damage, drinking behavior, and factors such as gender and smoking history. initial results show selective changes in gene expression in alcoholics; of particular importance is a coordinated reduction in genes coding for myelin components, Copyright (C) 2001 National Science Council, ROC and S. Karger AG, Basel.

Molecular cloning and characterization of hNP22: a gene up-regulated in human alcoholic brain

An improved differential display technique was used to search for changes in gene expression in the superior frontal cortex of alcoholics, A cDNA fragment was retrieved and cloned. Further sequence of the cDNA was determined from 5' RACE and screening of a human brain cDNA library. The gene was named hNP22 (human neuronal protein 22). The deduced protein sequence of hNP22 has an estimated molecular mass of 22.4 kDa with a putative calcium-binding site, and phosphorylation sites for casein kinase II and protein kinase C. The deduced amino acid sequence of hNP22 shares homology (from 67% to 42%) with four other proteins, SM22 alpha, calponin, myophilin and mp20. Sequence homology suggests a potential interaction of hNP22 with cytoskeletal elements. hNP22 mRNA was expressed in various brain regions but in alcoholics, greater mRNA expression occurred in the superior frontal cortex, but not in the primary motor cortex or cerebellum. The results suggest that hNP22 may have a role in alcohol-related adaptations and may mediate regulatory signal transduction pathways in neurones.

Excited to death: different ways to lose your neurones

The selective loss of neurones in a range of neurodegenerative diseases is widely thought to involve the process of excitotoxicity, in which glutamate-mediated neuronal killing is elaborated through the excessive stimulation of cell-surface receptors. Every such disease exhibits a distinct regional and subregional pattern of neuronal loss. so processes must be locally triggered to different extents to account for this. We have studied several mechanisms which could lead to excitotoxic glutamate pathophysiology and compared them in different diseases. Our data suggest that glutamate can reach toxic extracellular levels in Alzheimer disease by malfunctions in cellular transporters, and that the toxicity may be exacerbated by continued glutamate release from presynaptic neurones acting on hypersensitive postsynaptic receptors. Thus the excitotoxicity is direct. In contrast, alcoholic brain damage arises in regions where GABA-mediated inhibition is deficient, and fails properly to dampen trans-synaptic excitation, Thus the excitotoxicity is indirect. A variety of such mechanisms is possible, which may combine in different ways.

Free radicals in alcoholic myopathy: Indices of damage and preventive studies

Chronic alcoholic myopathy affects up to two-thirds of all alcohol misusers and is characterized by selective atrophy of Type If (glycolytic, fast-twitch, anaerobic) fibers. In contrast, the Type I fibers (oxidative, slow-twitch, aerobic) are relatively protected. Alcohol increases the concentration of cholesterol hydroperoxides and malondialdehyde-protein adducts, though protein-carbonyl concentration levels do not appear to be overtly increased and may actually decrease in some studies. In alcoholics, plasma concentrations of a-tocopherol may be reduced in myopathic patients. However, a-tocopherol supplementation has failed to prevent either the loss of skeletal muscle protein or the reductions in protein synthesis in alcohol-dosed animals. The evidence for increased oxidative stress in alcohol-exposed skeletal muscle is thus inconsistent. Further work into the role of ROS in alcoholic myopathy is clearly warranted. (C) 2002 Elsevier Science Inc.

Community-acquired Klebsiella pneumoniae bacteremia: Global differences in clinical patterns

We initiated a worldwide collaborative study, including 455 episodes of bacteremia, to elucidate the clinical patterns of Klebsiella pneumoniae. Historically, community-acquired pneumonia has been consistently associated with K. pneumoniae. Only four cases of community-acquired bacteremic K. pneumoniae pneumonia were seen in the 2-year study period in the United States, Argentina, Europe, or Australia; none were in alcoholics. In contrast, 53 cases of bacteremic K. pneumoniae pneumonia were observed in South Africa and Taiwan, where an association with alcoholism persisted (p=0.007). Twenty-five cases of a distinctive syndrome consisting of K. pneumoniae bacteremia in conjunction with community-acquired liver abscess, meningitis, or endophthalmitis were observed. A distinctive form of K. pneumoniae infection, often causing liver abscess, was identified, almost exclusively in Taiwan.

Couple communication and female problem drinking: A behavioral observation study

Couples with alcohol and relationship problems often report poor communication, yet little is known about the communication of maritally distressed couples in which the woman abuses alcohol (MDWA couples). Compared with maritally distressed couples without alcohol problems (MDNA) and couples with neither problem (NDNA), MDWA couples showed a distinctive pattern of negative communication. Similar to MDNA men, MDWA men spoke negatively to their partners but listened positively to their partners much like NDNA men. MDWA women listened negatively, much as MDNA women did, but spoke positively, like NDNA women did. The interactions of MDWA couples can be characterized as a male-demand-female-withdraw pattern, which is a gender reversal of the female-demand-male-withdraw pattern often observed in MDNA couples.

Increased TUNEL positive cells in human alcoholic brains

Alcohol-sensitive neuronal cell loss, which has been reported in the superior frontal cortex and hippocampus, may underlie the pathogenesis of subsequent cognitive deficits. In the present study, we have used the TUNEL labeling to detect the DNA damage in human alcoholic brains. Seven out of eleven alcoholics exhibited TUNEL-positive cells in both superior frontal cortex and hippocampus, which were co-localized with GFAP immunoreactivity. In contrast, almost no positive cells were detected in the non-alcoholic controls. None of the TUNEL-positive cells showed any typical morphological features of apoptosis or necrosis. TUNEL-positive cells observed in the present study may indicate DNA damage induced by ethanol-related overproduction of reactive oxygen species. (C) 2003 Elsevier Ireland Ltd. All rights reserved.

Generation of aldehyde-derived protein modifications in ethanol-exposed heart

Background: Although excessive ethanol consumption is known to lead to a variety of adverse effects in the heart, the molecular mechanisms of such effects have remained poorly defined. We hypothesized that posttranslational covalent binding of reactive molecular species to proteins occurs in the heart in response to acute ethanol exposure. Methods: The generation of protein adducts with several aldehydic species was examined by using monospecific antibodies against adducts with malondialdehyde (MDA), acetaldehyde (AA), MDA-AA hybrids, and hydroxyethyl radicals. Specimens of heart tissue were obtained from rats after intraperitoneal injections with alcohol (75 mmol/kg body weight) with or without pretreatment with cyanamide (0.05 mmol/kg body weight), an aldehyde dehydrogenase inhibitor. Results: The amounts of MDA and unreduced AA adducts were found to be significantly increased in the heart of the rats treated with ethanol, cyanamide, or both, whereas no other adducts were detected in statistically significant quantities. Immunohistochemical studies for characterization of adduct distribution revealed sarcolemmal adducts of both MDA and AA in the rats treated with ethanol and cyanamide in addition to intracellular adducts, which were also present in the group treated with ethanol alone. Conclusions: These findings support the role of enhanced lipid peroxidation and the generation of protein-aldehyde condensates in vivo as a result of excessive ethanol intake. These findings may have implications in the molecular mechanisms of cardiac dysfunction in alcoholics.

A trajetória de um serviço público em álcool e outras drogas no município de Vitória : o caso do CPTT

Comunicação oral apresentada na 18th World Conference of Social Work realizada em 2006 em Munique, Alemanha.

Tuberculose na população privada de liberdade: características clínicas e epidemiológicas relacionadas à doença

Introdução: Há cerca de duas décadas, a tuberculose (TB) foi considerada pela Organização Mundial de Saúde (OMS) como uma doença em estado de emergência em todo o mundo. Atualmente, apesar de todas as ações de controle da doença, ainda trata-se de um importante problema de saúde pública, apresentando forte relação com questões socioeconômicas, o que acarreta no maior adoecimento em grupos específicos, tais como a população privada de liberdade. Os dados de tuberculose em populações vulneráveis podem atingir índices ainda mais altos e por isso preocupante. Objetivos: Analisar as características clínicas e epidemiológicas associadas com os desfechos do tratamento da tuberculose na população privada de liberdade do Brasil, registrado no Sistema de Informação de Agravos de Notificação (SINAN), de 2007 a 2011; conhecer a taxa de incidência e de mortalidade por tuberculose na população privada de liberdade do Espírito Santo, de julho de 2009 a julho de 2010; e identificar as características clínicas e epidemiológicas dos casos diagnosticados de tuberculose na população privada de liberdade do Espírito Santo, de julho de 2009 a julho de 2010. Métodos: A população do estudo consistiu em presos diagnosticados com tuberculose identificados através do SINAN, entre janeiro de 2007 e dezembro de 2011 e dos casos diagnosticados de tuberculose na população prisional do Espírito Santo no período de 1º de julho de 2009 a 30 de junho de 2010. O teste de qui-quadrado de Pearson e o modelo de regressão polinomial foram utilizados na analise, além de estatística descritiva, por meio de tabelas e gráficos. Resultados: Em relação pacientes com TB na população privada de liberdade do Brasil, nota-se que os presos que abandonaram o tratamento eram mais jovens (P <0,001), com menor escolaridade (P <0,001) e maior probabilidade de alcoolismo (P < 0,001), eram mais propensos a ter TB recorrente ou recidiva (P < 0,001) e eles não estavam sob tratamento diretamente observado (TDO) (P < 0,001), comparados com aqueles que completaram o tratamento da tuberculose. Aqueles que morreram de tuberculose tendem a ter idade ⩾ 43 anos (P < 0,001) e alcoolistas (P < 0,001), também eram mais propensos a tipo de tratamento desconhecido (P <0,001) e apresentar tuberculose pulmonar e tuberculose extrapulmonar (TBEP). Presos que desenvolveram tuberculose multidroga resistente (TB-MDR) foram mais propensos a 9 experiência de recorrência de TB, retorno após abandono e transferência de local de tratamento. Além disso, observou-se 167 casos de tuberculose (taxa de incidência de 1962,6 por 100 mil presos) no Espírito Santo. O sexo masculino apresentou maior número de pacientes, assim como a faixa etária de 25 a 36 anos e a forma clínica pulmonar. Destaca-se que 109 (65,3%) pacientes tiveram alta por cura, ocorrendo dois óbitos durante o período, sendo a taxa de mortalidade por tuberculose de 11,7 por 100 mil presos. A maior incidência da tuberculose foi em pacientes localizados nas unidades prisionais da Região Metropolitana e um pequeno número de casos ocorreu em outros locais externos às unidades prisionais. Conclusão: Nossos resultados destacam a necessidade de melhorar as políticas de controle da TB nas penitenciárias, bem como os desfechos do tratamento de presos a fim de impedir a transmissão para outros presos, seus familiares e profissionais de saúde.

Determination of human cytomegalovirus genetic diversity in different patient populations in Costa Rica

Seroprevalence of HCMV in Costa Rica is greater than 95% in adults; primary infections occur early in life and is the most frequent congenital infection in newborns. The objectives of this study were to determine the genetic variability and genotypes of HCMV gB gene in Costa Rica. Samples were collected from alcoholics, pregnant women, blood donors, AIDS patients, hematology-oncology (HO) children and HCMV isolates from neonates with cytomegalic inclusion disease. A semi-nested PCR system was used to obtain a product of 293-296 bp of the gB gene to be analyzed by Single Stranded Conformational Polymorphism (SSCP) and sequencing to determine the genetic polymorphic pattern and genotypes, respectively. AIDS patients showed the highest polymorphic diversity with 14 different patterns while fifty-six percent of HO children samples showed the same polymorphic pattern, suggesting in this group a possible nosocomial infection. In neonates three genotypes (gB1, gB2 and gB3), were determined while AIDS patients and blood donors only showed one (gB2). Of all samples analyzed only genotypes gB1, 2 and 3 were determined, genotype gB2 was the most frequent (73%) and mixed infections were not detected. The results of the study indicate that SSCP could be an important tool to detect HCMV intra-hospital infections and suggests a need to include additional study populations to better determine the genotype diversity and prevalence.

Prevalence of intestinal nematodes in alcoholic patients

We report the results of a retrospective study on the frequency of intestinal nematodes among 198 alcoholic and 440 nonalcoholic patients at the University Hospital Cassiano Antonio Moraes in Vitória, ES, Brazil. The control sample included 194 nonalcoholic patients matched according to age, sex and neighborhood and a random sample of 296 adults admitted at the same hospital. Stool examination by sedimentation method (three samples) was performed in all patients. There was a significantly higher frequency of intestinal nematodes in alcoholics than in controls (35.3% and 19.2%, respectively), due to a higher frequency of Strongyloides stercoralis (21.7% and 4.1%, respectively). Disregarding this parasite, the frequency of the other nematodes was similar in both groups. The higher frequency of S. stercoralis infection in alcoholics could be explained by immune modulation and/or by some alteration in corticosteroid metabolism induced by chronic ethanol ingestion. Corticosteroid metabolites would mimic the worm ecdisteroids, that would in turn increase the fecundity of females in duodenum and survival of larvae. Consequently, the higher frequency of Strongyloides larvae in stool of alcoholics does not necessarily reflect an increased frequency of infection rate, but only an increased chance to present a positive stool examination using sedimentation methods.