Vitamin D receptor (VDR) gene polymorphisms and expression profile influence upon the immunological imbalance in Turner syndrome.

PURPOSE: Turner syndrome (TS) patients display considerable immune misregulation, and it is hypothesized that Vitamin D (VTD) activity may fluctuate according to Vitamin D receptor (VDR) polymorphisms and/or expression profile. To uncover a possible relationship between VDR genotype and clinical conditions in TS patients, we investigated two functional VDR variants (Cdx-2 and FokI) for allele and genotype frequencies, as well as expression profile in TS individuals versus healthy controls (HC). METHODS: We performed a genetic association study including 100 TS patients and 116 HC. Genotyping for VDR Cdx-2 G > A (rs11568820) and FokI C > T (rs2228570) was performed using Taqman Genotyping Assays. VDR gene expression was also evaluated in 15 TS and 15 HC, using fluorogenic probes by qPCR. Statistical analyses were performed using nonparametric Mann-Whitney test, with a 5% significance level (p < 0.05) to uncover differences between groups. In addition, we investigated whether shifted VDR mRNA levels were associated with Cdx-2 and FokI variants in TS patients. RESULTS: We detected a significantly higher frequency of T allele (p = 0.006) as well as T/T genotype (p = 0.01) for FokI in TS patients when compared to HC. When assessing VDR expression, we identified a downregulation in TS woman (- 2.84 FC) versus HC (p < 0.001). Furthermore, C/T (11.24 FC; p = 0.01) and T/T (9.20 FC; p = 0.01) FokI genotypes were upregulated when compared to C/C reference genotype. CONCLUSION: TS patients show different distribution of FokI polymorphism. Downregulation of VDR gene expression may contribute to immunological imbalance in TS.

αCaMKII controls the establishment of cocaine's reinforcing effects in mice and humans.

Although addiction develops in a considerable number of regular cocaine users, molecular risk factors for cocaine dependence are still unknown. It was proposed that establishing drug use and memory formation might share molecular and anatomical pathways. Alpha-Ca(2+)/calmodulin-dependent protein kinase-II (αCaMKII) is a key mediator of learning and memory also involved in drug-related plasticity. The autophosphorylation of αCaMKII was shown to accelerate learning. Thus, we investigated the role of αCaMKII autophosphorylation in the time course of establishing cocaine use-related behavior in mice. We found that αCaMKII autophosphorylation-deficient αCaMKII(T286A) mice show delayed establishment of conditioned place preference, but no changes in acute behavioral activation, sensitization or conditioned hyperlocomotion to cocaine (20 mg kg(-1), intraperitoneal). In vivo microdialysis revealed that αCaMKII(T286A) mice have blunted dopamine (DA) and blocked serotonin (5-HT) responses in the nucleus accumbens (NAcc) and prefrontal cortex after acute cocaine administration (20 mg kg(-1), intraperitoneal), whereas noradrenaline responses were preserved. Under cocaine, the attenuated DA and 5-HT activation in αCaMKII(T286A) mice was followed by impaired c-Fos activation in the NAcc. To translate the rodent findings to human conditions, several CAMK2A gene polymorphisms were tested regarding their risk for a fast establishment of cocaine dependence in two independent samples of regular cocaine users from Brazil (n=688) and Switzerland (n=141). A meta-analysis across both samples confirmed that CAMK2A rs3776823 TT-allele carriers display a faster transition to severe cocaine use than C-allele carriers. Together, these data suggest that αCaMKII controls the speed for the establishment of cocaine's reinforcing effects.

Tobacco use among the elderly: The first Brazilian National Survey (BNAS).

OBJECTIVE: This study describes the prevalence and pattern of tobacco use among the elderly in Brazil and establishes its association with socio-demographic characteristics, other substance use and depression. METHOD: The analyses were performed in 400 individuals aged 60 years and over who participated in the first Brazilian national alcohol survey (BNAS) in 2000. RESULTS: Nearly 60% of the sample had ever smoked, of them one in three were still smoking at the time of the interview. Most (94.3%) of the tobacco users were smoking everyday and 34.3% consuming more than 20 cigarettes a day. Only 1% of the former smokers had received support to quit. Over half of the current users (65%) would use free treatment to quit if it existed in Brazil, and just under half of them (47.4%) would consider quitting if cigarettes' price were higher. Currently, tobacco users were more likely to be men and alcohol abusers. Prevalence of depression was high regardless participant smoking status (33.0% among non-smokers, 34.7% among current smokers and 39.3% among former smokers). There was no significant association between smoking and depression. CONCLUSION: This study found a disturbingly high proportion of tobacco users among the elderly in Brazil. According to the Global Burden of Disease project, tobacco has the highest mortality risk of all substance use categories, especially for the elderly. This study shows there is an urgent need to develop smoking cessation interventions targeted specifically to the elderly.

Underreporting of cocaine and marijuana during the thrid trimester of gestation among pregnant adolescents

Objetive: The aim of this study is to check the validity of the self-report of drug use by pregnant adolescents, by comparing their responses to a structured interview about their use of cocaine and marijuana during the pregnancy with an analysis of their hair. Results: Hair analysis detected the use of cocaine and/or marijuana, 17 (1,7%) used only cocaine, and 3 (0,3%) used both drugs. None of the patients had reported the use of these substances in their interview with healthcare profissionals. Conclusion: Althougth the prevalence of the use of drugs during pregnancy is significant despite consistent evidence about the compromise of the neurobehavioral development of the newborns that are exposed to drugs during the prenatal period, drugs use is frequently not reported. Therefore, more sensitive methods of detection should be used so that appropriate medical and psychosocial interventions com be implemented for the mothers as well as for their children. (AU)

Correlates of substance use during adolescent pregnancy in São Paulo, Brazil

Objetive: To investigate the association of cocaina and marijuana use during adolescent pregnancy in são paulo-sp, brazil with psychiatric disorders, social status and sexual history. method: one thousand pregnancy adolescents were assessed by using the composite international diagnostic interview, and sociodemographic and socio-economic questionnaire at the obstetric center of a public hospital in são paulo. Hair samples were collected for analysis. Results: the following data were associated with cocaine and/or marijuana use during the third trimester of the pregnancy: being younger than 14 year of agge, having a history of more than 3 sexual partners, and having psychiatric disorders, specifically, bipolar disordes, post-traumatic stress disorder, and somatoform disorder. Conclusion: in earlt adolescence pregnancy, having 3 or more sexual partners in the life for this population os significantly associated with the use of cocaine or marijuana during gestation. This association suggests that specific intervention programs should target these young women.(au) - en

Alcohol consumption in late-life--the first Brazilian National Alcohol Survey (BNAS).

To investigate the alcohol consumption in later life in Brazil and its association with socio-demographic characteristics. This study was a cross-sectional analysis of nationally representative survey data. A multistage cluster sampling procedure was used to select 3007 individuals of 14 years of age and older from the Brazilian household population. In this study we analyzed data from all 400 participants who were over 60 years old. Alcohol Abuse and Dependence Syndrome was established according to DSM-IV and Risky Drinking was defined in two ways: heavy drinkers (>7 drinks/week) and as binge drinkers (>3 drinks/one occasion). Twelve percent of participants reported heavy drinking behavior while 10.4% and 2.9% were binge drinkers and alcohol dependent respectively. In the adjusted logistic regression only gender was associated with heavy drinking behavior. Males, the youngest and the wealthiest were more likely to report binge drinking behaviors. In conclusion, alcohol related-problems are common but under recognized among older adults. Health professionals should be aware that common definitions of alcohol abuse and dependence may not apply as readily to older people, who have had biological changes for alcohol tolerance and its effects on the Central Nervous System.

Gravidez na adolescência: perfil sócio-demográfico e comportamental de uma população da periferia de São Paulo / Teenage pregnancy: socio-demographic and behavioral profile of a population on the outskirts of Sao Paulo

Com objetivo de identificar o perfil sócio-demográfico e comportamental de gestantes adolescentes, foram entrevistadas mil adolescentes, admitidas entre 24 de julho de 2001 e 27 de novembro de 2002, em um hospital municipal de são paulo, brasil, correspondendo a 24,3% das internações para resolução da gestação. setenta (7%) adolescentes foram admitidas para curetagem pós-abortamento e 930 (93%), para parturição, com idade média de 17+/- 1,5 anos. a maioria (72,4%) residia próximo ao hospital e 93% pertenciam às classes econômicas c, d e e. na época da parturição , 627 (67,3%) adolescentes não estudavam. apenas 23,7% das adolescentes faziam uso de método contraceptivo, 81,2% não tinham planejado a gestação e 80,1% eram primigestas. dos partos, 67,4% foram vaginais. dos bebês, 13,3% foram pré-termo e 15,9%, baixo peso. durante a gestação, o consumo referido de tabaco, de álcool e de drogas ilícitas foi, respectivamente de 17,3%, 2,8% e 1,7%. conclui-se que gravidez na adolescência é um fenômeno complexo, associado a fatores econômicos, educacionais e comportamentais, preciptando problemas decorrentes da maternidade precoce. o presente estudo fornece subsídios para políticas públicas de saúde, visando a prevenir a gravidez na adolescência

Crack cocaine: a five-year follow-up study of treated patients.

OBJECTIVES: To follow-up a group of 131 crack cocaine users and examine drug use, treatment experience, employment status, involvement in crime and mortality at 2 and 5 years. METHODS: Consecutive crack-dependent patients who were admitted to a detoxification unit in São Paulo between 1992 and 1994 were re-interviewed on two occasions: 1995-1996 and 1998-1999. RESULTS: 5 years after treatment information was obtained on 124 (95%) of the original cohort. 39.7% (n = 52) of the patients reported having been abstinent from cocaine for at least the last year, and 21.4% (n = 28) had used the drug. Of those subjects not using cocaine at 2 years, 19 (62%) were still abstinent at 5 years. Twenty-three (17.6%) patients had died by the 5-year follow-up with homicide, due to firearms or other weapons, being the commonest cause (n = 13). The annual adjusted mortality rate for the sample was 24.92 deaths/1,000 individuals, the excess mortality rate was of 21.64 deaths/1,000 individuals, and the standardized mortality ratio was 7.60. A history of injecting drug use, unemployment at the time of the index admission and administrative discharge at the index admission were factors that contributed to the risk of dying over the next 5 years. CONCLUSIONS: There was a progressive movement towards abstinence over the follow-up period, and there was evidence that once abstinence had been achieved it was maintained. On the other hand, the mortality rate was extremely high and was higher among those who were still using crack at 2 years.

Teenage pregnancy: use of drugs in the third trimester and prevalence of psyquiatric disorders

Objetivo: Determinar, em adolescentes de baixa renda, a prevalência de transtornos psiquiátricos durante a gravidez, a prevalência de uso de cocaína e maconha no terceiro trimestre de gestação e descrever suas características sociodemográficas. Método: Mil adolescentes grávidas foram avaliadas por meio do Composite International Diagnostic Interview e de um questionário sociodemográfico e socioeconômico no centro obstétrico de um hospital público de São Paulo. Dessas, foi colhida amostra para análise de fios de cabelo. Resultados: Das mil pacientes entrevistadas, 53,6% tem baixa renda , 60,2% abandonaram a escola, 90,4% estão desempregadas e 92,5% são financeiramente dependentes, 6% usaram drogas durante o terceiro trimestre da gravidez (maconha: 4%, cocáina1,7%, ambos: 0,3%) e 27,6% tiveram ao menos um transtorno psiquiátrico. Os diagnósticos mais frequentes foram: depressão(12,9%), transtornos de estresse pós-traumático(10,0%) e ansiedade (5,6%). Discussão: Famílias desestruturadas, evasão escolar, desemprego e baixa capacitação profissional são fatores que contribuem para a manutenção desta situação socioeconômica desfavorável, cenário no qual são elementos importantes a alta prevalência de uso de cocaína e maconha no 3º trimestre de gravidez e de transtornos psiquiátricos.(AU)

Motivation for change in alcohol dependent outpatients from Brazil.

The general aim of this study was to investigate the reliability and factor structure of the stages of change readiness and treatment eagerness scale (SOCRATES) in 326 outpatients with alcohol dependence. The questionnaire was translated and cross-culturally adapted into Portuguese and back-translated to English. The confirmatory factor analysis showed that two correlated factors provided the best fit for the data.

Does multisite sampling improve patient heterogeneity in drug misuse research?

The aim of this study was to investigate whether multisite sampling increased heterogeneity among a sample of cocaine users from São Paulo, Brazil. Six hundred and fourteen cocaine users were interviewed at 23 fixed sites plus an out-of-treatment sample. The sites were then regrouped into six main types: university outpatient clinics, public outpatient clinics, public inpatient units, private inpatient units, HIV services and non-treatment. Marked differences were found between users recruited at these sites, especially in relation to age, gender, employment status, criminal history, history of prostitution, previous drug misuse treatment, duration of cocaine use and lifetime use of intravenous cocaine. These results suggest that multisite sampling is a valid method for increasing patient heterogeneity, but whether it improves representativeness and thus the generalisability of drug misuse research is debatable.

Drinking and driving: pre-driving attitudes and perceptions among Brazilian youth.

The aim of this study was to investigate driving under the influence of alcohol (DUI) risk profiles and predictors in a sample of pre-driving Brazilian youth, in the context of Brazil's new Traffic Code. Data were obtained in the Traffic Department in São Paulo from a sample of 2166 individuals. Subjects displayed a low level of knowledge about the laws and few believed the penalties would actually be enforced for those engaging in DUI. Findings suggest that changes in DUI laws in Brazil and elsewhere should be accompanied by enforcement and education in order to enhance levels of knowledge and credibility of the sanctions.

High dose cocaine use in São Paulo: a comparison of treatment and community samples.

This cross-sectional study investigates patterns of drug use and associated problems among 332 cocaine users from treatment and community samples in São Paulo, Brazil. Data were collected using a structured questionnaire and the Severity of Dependence Scale (SDS). The majority were regular users of high doses of smoked cocaine. After controlling for severity of cocaine use, users in the community were found to be more involved in illegal activities, more likely to report adverse effects of cocaine, to be involved in prostitution, and to have lived on the streets. Better methods are required to provide interventions to tackle the problems and risk behaviors of these cocaine users.

Crack cocaine--a two-year follow-up of treated patients.

OBJECTIVES: To investigate the 2-year outcome of the first 131 crack cocaine users who had been admitted for a period of inpatient treatment. DESIGN: Follow-up study of consecutive patients admitted between 1992 and 1994. SETTING: Inpatient detoxification unit of a public general hospital in São Paulo City, Brazil. PARTICIPANTS: 131 consecutive crack cocaine users. MEASURES: Reported crack use during last 12 months, incarceration and death. FINDINGS: After 2 years, 50 patients reported crack use in the last 12 months, 29 said that they had not used it during this period, 9 were in prison, 13 had died, 2 had disappeared and no information was available on 28. CONCLUSIONS: Crack cocaine use seems to be associated with a high mortality rate and criminal involvement but about one-third of patients give up using the drug within 2 years of inpatient treatment.

HIV-risk behaviour among non-heroin using cocaine injectors and non-injectors in São Paulo, Brazil.

The aim of this study was to investigate HIV-risk behaviour among cocaine users in relation to preferred route of administration and to relate this to reported HIV serostatus. Two hundred and ninety-four patients were interviewed in 15 different services that offer treatment, assistance or counselling to drug users and/or HIV-positive patients using a structured questionnaire that had been developed and piloted in Brazil. At the time of interview, lifetime use of snorted cocaine was 94%, of smoked crack 82% and of injected cocaine 32%. Twenty-eight per cent described themselves as HIV-positive, 32% as negative and 40% were unaware of their status. Non-injectors tended to be younger, had used fewer substances, had spent less time using cocaine, were less likely to have had sex with other drug users or to have been tested for HIV. Non-injectors had high levels of contact with injectors. Those reporting a positive HIV result were older, had used more classes of drugs, had used cocaine for longer and were more likely to have injected and participated in at-risk behaviours. The findings are discussed in terms of policy changes that may be necessary to reduce the high level of risk behaviour among Brazilian cocaine users.

The frequency of smoking and problem drinking among general hospital inpatients in Brazil - using the AUDIT and Fagerström questionnaires.

CONTEXT: Although the CAGE questionnaire is one of the most widely used alcohol screening instruments, it has been criticized for not identifying people who are drinking heavily or who have alcohol related problems but do not as yet show symptoms of alcohol dependence. The AUDIT (Alcohol Use Disorder Identification Test) questionnaire was developed by WHO as a screening instrument specifically designed to identify problem drinkers, as well as those who were already dependent on alcohol. OBJECTIVE: The aim of this study was to use the AUDIT and Fagerström questionnaires in a general hospital inpatient population to measure the frequency of problem drinking and nicotine dependence, and to see if levels varied between medical speciality. DESIGN: Retrospective cross-sectional study. SETTING: Federally funded public teaching hospital. SAMPLE: 275 inpatients from both genders. MAIN MEASUREMENTS: Socio-demographic data, AUDIT (Alcohol Use Disorders Identification Test) and Fagerström Test for Nicotine Dependence. RESULTS: We interviewed 275 inpatients, 49% of whom were men and 51% women. Thirty-four patients were identified as "cases" by the Audit questionnaire; 22% of the male patients and 3% of the females. Just over 21% of inpatients were current smokers. The gastroenterology (26%) and general medicine (16%) inpatient units had the largest number of individual cases. CONCLUSIONS: Only by knowing the prevalence of alcohol abuse/dependence and nicotine dependence in a general hospital can we evaluate the need for a specialized liaison service to identify and treat these patients.

Environmental tobacco smoke exposure among non-smoking waiters: measurement of expired carbon monoxide levels.

CONTEXT: Exposure to environmental tobacco smoke is a health risk that is of concern to patrons and of particular concern to employees of restaurants and bars. OBJECTIVE: To assess environmental tobacco smoke exposure (using expired carbon monoxide levels) in non-smoking waiters before and after a normal day's shift and to compare pre-exposure levels with non-smoking medical students. DESIGN: An observational study. SETTING: Restaurants with more than 50 tables or 100 places in São Paulo. SUBJECTS: 100 non-smoking restaurant waiters and 100 non-smoking medical students in São Paulo, Brazil. MAIN MEASUREMENTS: Levels of expired carbon monoxide, measured with a Smokerlyser (Bedfont EC 50 Scientific), before and after a normal day's work. RESULTS: Waiters' pre-exposure expired carbon monoxide levels were similar to those of medical students, but after a mean of 9 hours exposure in the workplace, median levels more than doubled (2.0 ppm vs. 5.0 ppm, P <0.001). Post-exposure carbon monoxide levels were correlated with the number of tables available for smokers (Kendall's tau = 0.2, P <0.0001). CONCLUSIONS: Exposure to environmental tobacco smoke is the most likely explanation for the increase in carbon monoxide levels among these non-smoking waiters. These findings can be used to inform the ongoing public health debate on passive smoking.