Alcohol use patterns and disorders among individuals with personality disorders in the Sao Paulo Metropolitan Area.

INTRODUCTION: Alcohol Use Disorders are frequently comorbid with personality disorders. However, the heterogeneity of the prevalence estimates is high, and most data come from high income countries. Our aim is to estimate the prevalence and association between alcohol use outcomes and the three DSM-5 clusters of personality disorders in a representative sample of the São Paulo Metropolitan Area. MATERIALS AND METHODS: A representative household sample of 2,942 adults was interviewed using the WHO Composite International Diagnostic Interview and the International Personality Disorder Examination Screening Questionnaire. Lifetime PD diagnoses were multiply imputed, and AUD diagnoses were obtained using DSM-5 criteria. We conducted cross-tabulations and logistic regression to estimate the associations between AUDs and PDs. RESULTS AND DISCUSSION: Our study did not find significant associations of PDs with heavy drinking patterns or mild AUD. Cluster B PD respondents tended to show the highest conditional prevalence estimates of most alcohol use patterns and AUD, including its severity subtypes. When alcohol outcomes were regressed on all PD Clusters simultaneously, with adjustment for sex and age, only cluster B was significantly associated with past-year alcohol use (OR 3.0), regular drinking (OR 3.2), and AUDs (OR 8.5), especially moderate and severe cases of alcohol use disorders (OR 9.7 and 16.6, respectively). These associations between Cluster B PDs and these alcohol outcomes were shown to be independent of other PD Clusters and individuals´ sex and age. CONCLUSION: The main finding of our study is that AUDs are highly comorbid with PDs. The presence of Cluster B PDs significantly increases the odds of alcohol consumption and disorders and of more severe forms of AUDs. Considering the local context of poor treatment provision, more specific prevention and intervention strategies should be directed to this population.

Experimentation with tobacco during adolescence as a factor influencing treatment of smoking in adulthood. A retrospective cohort.

BACKGROUND: There are still few studies on predictors of smoking cessation in Brazilian samples. Experimentation with tobacco during adolescence (ETA) may be one of the important predictors. OBJECTIVE: This study aimed, within the context of a treatment-seeking group of subjects, to test the hypothesis that ETA negatively affects the outcome of smoking cessation during adulthood. DESIGN AND SETTING: Retrospective (historic) cohort study conducted at a psychosocial care center in São Paulo, Brazil, between 2007 and 2010. METHODS: Data on sociodemographics, smoking and medical profiles were obtained through self-report questionnaires that were completed at the baseline and at any follow-up appointment. Logistic regression models were constructed to describe factors associated with the outcome of smoking cessation, measured according to the self-reported four-week success rate among 367 outpatient smokers. RESULTS: ETA was found to be associated with not quitting smoking through the treatment (odds ratio = 0.57; 95% confidence interval = 0.33-0.96; P < 0.05), even after adjustment for dependence level, sociodemographics, nicotine patch use and number of years of smoking. CONCLUSIONS: Early exposure to nicotine may lead to higher risk of continuing smoking after treatment, in adulthood.

Estimating Service Needs for Alcohol and Other Drug Users According to a Tiered Framework: The Case of the São Paulo, Brazil, Metropolitan Area.

OBJECTIVE: The purpose of this study was to estimate the need for population-level services for alcohol and other drug abuse in support of local planning. METHOD: Data were drawn from a subsample of 2,942 interviewees from the São Paulo Megacity Study, which evaluated mental health in the general population (18 years and older) of residents in the São Paulo metropolitan area. This population was classified into five hierarchical categories of severity, making it possible to obtain estimates of need for services, combining evaluation criteria regarding drug and alcohol use and general and mental health comorbidities over the last 12 months. For the at-risk groups in this population, estimates from the Potential Demand for the Use of Services survey interviews over the last year were generated. RESULTS: Concerning the need for services, 86.5% of the population (Tier 1) had no problems related to drug and alcohol use, 8.9% (Tier 2) used heavily, 3.5% (Tiers 3, 4, and 5) met criteria for substance abuse disorders, among whom 1.3% (Tiers 4 and 5) require more specialized and intensive treatment and support. The following estimates for the Potential Demand for the Use of Services were found: 25.5% (Tier 3) and 51.1% (Tier 4), indicating that a significant number of individuals met criteria for substance abuse disorders but did not perceive any need for professional help or neglected the help available. CONCLUSIONS: In São Paulo there exists a large sector of the population that requires prevention strategies regarding the risks and harm resulting from alcohol and drug use, followed by a group requiring more specialized care. But a large number of substance users requiring specialized support did not use services and did not believe that they needed professional help.

Dual burden of chronic physical diseases and anxiety/mood disorders among São Paulo Megacity Mental Health Survey Sample, Brazil.

BACKGROUND: We assessed comorbid associations of 12-month DSM-IV mood/any anxiety disorders with chronic physical conditions within the São Paulo (SP) Megacity Mental Health cross-sectional survey of 5037 participants and explored whether strength of comorbid associations were modified when controlling for demographics. METHODS: Chi-square tests and logistic regressions were used to examine comorbid associations of DSM-IV mood/anxiety disorders as measured by the WHO Composite International Diagnostic Interview (CIDI 3.0), and self-reported chronic physical conditions among adults from the SP Megacity Mental Health Survey. RESULTS: Among those with any mood or anxiety disorder, chronic pain disorder was the most common physical condition (48.9% and 44.9%, respectively). Significant unadjusted odds ratios (OR) of comorbidity were found between diagnosis of two or more physical conditions and any mood disorders (3.08, 95% CI: 2.27-4.17), and any anxiety disorders (2.49, 95% CI: 1.95-3.17). Comorbidities remained significant when stratified by gender and controlling for marital status, household income, and education (latter two only included within anxiety models). LIMITATIONS: These results cannot be generalized to other cities or rural populations. Homeless and institutionalized populations were not surveyed. Due to cross-sectional study design, the direction of association between chronic disease/chronic disease risk factors and mood disorders is unclear. CONCLUSIONS: Dual burden of chronic physical conditions and mood/anxiety disorders is a notable problem among the São Paulo Megacity Survey population, with enhanced comorbidity experienced by community members with multiple physical conditions. Clinicians should consider these findings in understanding healthcare delivery for individuals suffering from both psychiatric disorders and chronic physical conditions.

Use of psychotropic medications in São Paulo Metropolitan Area, Brazil: pattern of healthcare provision to general population.

PURPOSE: We estimate the proportion of psychotropic medication use (PMU) among adults in São Paulo Metropolitan Area, Brazil. We investigated whether socio-demographic factors, comorbidity, and disease severity influence PMU among individuals with psychiatric disorders. METHODS: Data are from the São Paulo Megacity Mental Health Survey, a cross-sectional, population-based study, the Brazilian branch of the World Mental Health Survey Initiative. Trained lay interviewers face-to-face assessed psychiatric disorders and PMU through the Composite International Diagnostic Interview. Respondents were asked about use of healthcare service and prescribed medications for mental disorders in the previous year. Information on PMU was collected for 2935 adult residents in the area and among those with disorders who received treatment. RESULTS: Around 6% of respondents reported PMU in the past year: hypnotics or sedatives were used by 3.7% and antidepressants by 3.5%. Among individuals with 12-month disorders, only 14% reported past year PMU. Gender, age, education, income, occupational status, comorbidity, and severity were significant predictors for PMU. Among those with 12-month DSM-IV disorders who obtained treatment in healthcare settings, almost 40% received medication only. Among those treated in specialty mental health service, around 23% received combination of medication and psychotherapy. CONCLUSION: Our study has pointed out that the recent trend of access to mental healthcare in Brazil depicts unmet needs, characterized by a low prevalence of PMU among individuals with psychiatric disorders. Policies that improve appropriate access to prescribed drugs for those most in need are urgent public health priority.

Investigating dimensionality and measurement bias of DSM-5 alcohol use disorder in a representative sample of the largest metropolitan area in South America.

BACKGROUND: Given the recent launch of a new diagnostic classification (DSM-5) for alcohol use disorders (AUD), we aimed to investigate its dimensionality and possible measurement bias in a non-U.S. METHODS: The current analyses were restricted to 948 subjects who endorsed drinking at least one drink per week in the past year from a sample of 5037 individuals. Data came from São Paulo Megacity Project (which is part of World Mental Health Surveys) collected between 2005 and 2007. First, exploratory factor analysis (EFA) was carried out to test for the best dimensional structure for DSM-5-AUD criteria. Then, item response theory (IRT) was used to investigate the severity and discrimination properties of each criterion of DSM-5-AUD. Finally, differential criterion functioning (DCF) were investigated by socio-demographics (income, gender, age, employment status, marital status and education). All analyses were performed in Mplus software taking into account complex survey design features. RESULTS: The best EFA model was a one-dimensional model. IRT results showed that the criteria "Time Spent" and "Given Up" have the highest discrimination and severity properties, while the criterion "Larger/Longer" had the lowest value of severity, but an average value of discrimination. Only female gender had DCF both at criterion- and factor-level, rendering measurement bias. CONCLUSION: This study reinforces the existence of a DSM-5-AUD continuum in the largest metropolitan area of South America, including subgroups that had previously higher rates of alcohol use (lower educational/income levels). Lower DSM-5-AUD scores were found in women.

Drinking patterns and alcohol use disorders in São Paulo, Brazil: the role of neighborhood social deprivation and socioeconomic status.

BACKGROUND: Research conducted in high-income countries has investigated influences of socioeconomic inequalities on drinking outcomes such as alcohol use disorders (AUD), however, associations between area-level neighborhood social deprivation (NSD) and individual socioeconomic status with these outcomes have not been explored in Brazil. Thus, we investigated the role of these factors on drink-related outcomes in a Brazilian population, attending to male-female variations. METHODS: A multi-stage area probability sample of adult household residents in the São Paulo Metropolitan Area was assessed using the WHO Composite International Diagnostic Interview (WMH-CIDI) (n = 5,037). Estimation focused on prevalence and correlates of past-year alcohol disturbances [heavy drinking of lower frequency (HDLF), heavy drinking of higher frequency (HDHF), abuse, dependence, and DMS-5 AUD] among regular users (RU); odds ratio (OR) were obtained. RESULTS: Higher NSD, measured as an area-level variable with individual level variables held constant, showed an excess odds for most alcohol disturbances analyzed. Prevalence estimates for HDLF and HDHF among RU were 9% and 20%, respectively, with excess odds in higher NSD areas; schooling (inverse association) and low income were associated with male HDLF. The only individual-level association with female HDLF involved employment status. Prevalence estimates for abuse, dependence, and DSM-5 AUD among RU were 8%, 4%, and 8%, respectively, with excess odds of: dependence in higher NSD areas for males; abuse and AUD for females. Among RU, AUD was associated with unemployment, and low education with dependence and AUD. CONCLUSIONS: Regular alcohol users with alcohol-related disturbances are more likely to be found where area-level neighborhood characteristics reflect social disadvantage. Although we cannot draw inferences about causal influence, the associations are strong enough to warrant future longitudinal alcohol studies to explore causal mechanisms related to the heterogeneous patterns of association and male-female variations observed herein. Hopefully, these findings may help guide future directions for public health.

DSM-5 latent classes of alcohol users in a population-based sample: results from the São Paulo Megacity Mental Health Survey, Brazil.

BACKGROUND: We aimed to identify different categorical phenotypes based upon the DSM-V criteria of alcohol use disorders (AUD) among alcohol users who had at least one drink per week in the past year (n=948). METHODS: Data are from the São Paulo Megacity Mental Health Survey collected in 2005-2007, as part of the World Mental Health Survey Initiative. A latent class analysis of the 11 DSM-5-AUD criteria was performed using Mplus, taking into account complex survey design features. Weighted logistic regression models were used to examine demographic correlates of the DSM-5-AUD latent classes. RESULTS: The best latent-class model was a three-class model. We found a "non-symptomatic class" (69.7%), a "use in larger amounts class" (23.2%), defined by high probability (>70%) of the "use in larger amounts" criterion only, and a "high-moderate symptomatic class" (7.1%), defined by high-moderate probability of all the 11 AUD criteria. Compared to those in the non-symptomatic class, individuals in the "high-moderate symptomatic class" were more likely to have been married, have lower educational attainment and to be unemployed or in non-regular/informal employment. Those on the "use in larger amounts class" were more likely to have been married or never married. CONCLUSION: The two symptomatic classes clearly represented the dimensionality of the new proposed AUD criteria, and could be more specifically targeted by different prevention or treatment strategies. DSM-5-AUD has the advantage of shedding light on risky drinkers included in the "use in larger amounts class", allowing for preventive interventions, which will reach a large number of individuals.

Days out-of-role due to common physical and mental health problems: results from the São Paulo Megacity Mental Health Survey, Brazil.

OBJECTIVES: To investigate the relative importance of common physical and mental disorders with regard to the number of days out-of-role (DOR; number of days for which a person is completely unable to work or carry out normal activities because of health problems) in a population-based sample of adults in the São Paulo Metropolitan Area, Brazil. METHODS: The São Paulo Megacity Mental Health Survey was administered during face-to-face interviews with 2,942 adult household residents. The presence of 8 chronic physical disorders and 3 classes of mental disorders (mood, anxiety, and substance use disorders) was assessed for the previous year along with the number of days in the previous month for which each respondent was completely unable to work or carry out normal daily activities due to health problems. Using multiple regression analysis, we examined the associations of the disorders and their comorbidities with the number of days out-of-role while controlling for socio-demographic variables. Both individual-level and population-level associations were assessed. RESULTS: A total of 13.1% of the respondents reported 1 or more days out-of-role in the previous month, with an annual median of 41.4 days out-of-role. The disorders considered in this study accounted for 71.7% of all DOR; the disorders that caused the greatest number of DOR at the individual-level were digestive (22.6), mood (19.9), substance use (15.0), chronic pain (16.5), and anxiety (14.0) disorders. The disorders associated with the highest population-attributable DOR were chronic pain (35.2%), mood (16.5%), and anxiety (15.0%) disorders. CONCLUSIONS: Because pain, anxiety, and mood disorders have high effects at both the individual and societal levels, targeted interventions to reduce the impairments associated with these disorders have the highest potential to reduce the societal burdens of chronic illness in the São Paulo Metropolitan Area.

Days out-of-role due to common physical and mental health problems: Results from the Sao Paulo Megacity Mental Health Survey, Brazil

OBJECTIVES: To investigate the relative importance of common physical and mental disorders with regard to the number of days out-of-role (DOR; number of days for which a person is completely unable to work or carry out normal activities because of health problems) in a population-based sample of adults in the São Paulo Metropolitan Area, Brazil. METHODS: The São Paulo Megacity Mental Health Survey was administered during face-to-face interviews with 2,942 adult household residents. The presence of 8 chronic physical disorders and 3 classes of mental disorders (mood, anxiety, and substance use disorders) was assessed for the previous year along with the number of days in the previous month for which each respondent was completely unable to work or carry out normal daily activities due to health problems. Using multiple regression analysis, we examined the associations of the disorders and their comorbidities with the number of days out-of-role while controlling for socio-demographic variables. Both individual-level and population-level associations were assessed. RESULTS: A total of 13.1% of the respondents reported 1 or more days out-of-role in the previous month, with an annual median of 41.4 days out-of-role. The disorders considered in this study accounted for 71.7% of all DOR; the disorders that caused the greatest number of DOR at the individual-level were digestive (22.6), mood (19.9), substance use (15.0), chronic pain (16.5), and anxiety (14.0) disorders. The disorders associated with the highest population-attributable DOR were chronic pain (35.2%), mood (16.5%), and anxiety (15.0%) disorders. CONCLUSIONS: Because pain, anxiety, and mood disorders have high effects at both the individual and societal levels, targeted interventions to reduce the impairments associated with these disorders have the highest potential to reduce the societal burdens of chronic illness in the São Paulo Metropolitan Area. .

Dependência química: álcool

Texto que compõe a unidade 2 ­ parte I do módulo 3 "Álcool e outras drogas" do Curso de Capacitação em Dependência Química, produzido pela UNA-SUS/UFMA. Aborda os aspectos neurobiológicos e farmacocinéticos da dependência química, os transtornos e comorbidades relacionados ao uso do álcool, bem como o apoio da família do dependente na superação de dificuldades no modo de vida sem o uso de álcool.

Tratamento para dependência química de álcool e outras drogas

Texto que compõe a unidade 4 do módulo 3 "Álcool e outras drogas" do Curso de Capacitação em Dependência Química, produzido pela UNA-SUS/UFMA. Aborda os tipos de tratamento: medicamentoso, psicológico e a atividade física e ocupacional destinado a usuários de álcool e drogas.

Gender differences in drinking patterns and alcohol-related problems in a community sample in São Paulo, Brazil.

OBJECTIVE: To investigate drinking patterns and gender differences in alcohol-related problems in a Brazilian population, with an emphasis on the frequency of heavy drinking. METHODS: A cross-sectional study was conducted with a probability adult household sample (n = 1,464) in the city of São Paulo, Brazil. Alcohol intake and ICD-10 psychopathology diagnoses were assessed with the Composite International Diagnostic Interview 1.1. The analyses focused on the prevalence and determinants of 12-month non-heavy drinking, heavy episodic drinking (4-5 drinks per occasion), and heavy and frequent drinking (heavy drinking at least 3 times/week), as well as associated alcohol-related problems according to drinking patterns and gender. RESULTS: Nearly 22% (32.4% women, 8.7% men) of the subjects were lifetime abstainers, 60.3% were non-heavy drinkers, and 17.5% reported heavy drinking in a 12-month period (26.3% men, 10.9% women). Subjects with the highest frequency of heavy drinking reported the most problems. Among subjects who did not engage in heavy drinking, men reported more problems than did women. A gender convergence in the amount of problems was observed when considering heavy drinking patterns. Heavy and frequent drinkers were twice as likely as abstainers to present lifetime depressive disorders. Lifetime nicotine dependence was associated with all drinking patterns. Heavy and frequent drinking was not restricted to young ages. CONCLUSIONS: Heavy and frequent episodic drinking was strongly associated with problems in a community sample from the largest city in Latin America. Prevention policies should target this drinking pattern, independent of age or gender. These findings warrant continued research on risky drinking behavior, particularly among persistent heavy drinkers at the non-dependent level.

Mental disorders in megacities: findings from the São Paulo megacity mental health survey, Brazil.

BACKGROUND: World population growth is projected to be concentrated in megacities, with increases in social inequality and urbanization-associated stress. São Paulo Metropolitan Area (SPMA) provides a forewarning of the burden of mental disorders in urban settings in developing world. The aim of this study is to estimate prevalence, severity, and treatment of recently active DSM-IV mental disorders. We examined socio-demographic correlates, aspects of urban living such as internal migration, exposure to violence, and neighborhood-level social deprivation with 12-month mental disorders. METHODS AND RESULTS: A representative cross-sectional household sample of 5,037 adults was interviewed face-to-face using the WHO Composite International Diagnostic Interview (CIDI), to generate diagnoses of DSM-IV mental disorders within 12 months of interview, disorder severity, and treatment. Administrative data on neighborhood social deprivation were gathered. Multiple logistic regression was used to evaluate individual and contextual correlates of disorders, severity, and treatment. Around thirty percent of respondents reported a 12-month disorder, with an even distribution across severity levels. Anxiety disorders were the most common disorders (affecting 19.9%), followed by mood (11%), impulse-control (4.3%), and substance use (3.6%) disorders. Exposure to crime was associated with all four types of disorder. Migrants had low prevalence of all four types compared to stable residents. High urbanicity was associated with impulse-control disorders and high social deprivation with substance use disorders. Vulnerable subgroups were observed: women and migrant men living in most deprived areas. Only one-third of serious cases had received treatment in the previous year. DISCUSSION: Adults living in São Paulo megacity had prevalence of mental disorders at greater levels than similar surveys conducted in other areas of the world. Integration of mental health promotion and care into the rapidly expanding Brazilian primary health system should be strengthened. This strategy might become a model for poorly resourced and highly populated developing countries.

Gender differences in drinking patterns and alcohol-related problems in a community sample in São Paulo, Brazil

OBJECTIVE: To investigate drinking patterns and gender differences in alcohol-related problems in a Brazilian population, with an emphasis on the frequency of heavy drinking. METHODS: A cross-sectional study was conducted with a probability adult household sample (n = 1,464) in the city of São Paulo, Brazil. Alcohol intake and ICD-10 psychopathology diagnoses were assessed with the Composite International Diagnostic Interview 1.1. The analyses focused on the prevalence and determinants of 12-month nonheavy drinking, heavy episodic drinking (4-5 drinks per occasion), and heavy and frequent drinking (heavy drinking at least 3 times/week), as well as associated alcohol-related problems according to drinking patterns and gender. RESULTS: Nearly 22% (32.4% women, 8.7% men) of the subjects were lifetime abstainers, 60.3% were non-heavy drinkers, and 17.5% reported heavy drinking in a 12-month period (26.3% men, 10.9% women). Subjects with the highest frequency of heavy drinking reported the most problems. Among subjects who did not engage in heavy drinking, men reported more problems than did women. A gender convergence in the amount of problems was observed when considering heavy drinking patterns. Heavy and frequent drinkers were twice as likely as abstainers to present lifetime depressive disorders. Lifetime nicotine dependence was associated with all drinking patterns. Heavy and frequent drinking was not restricted to young ages. CONCLUSIONS: Heavy and frequent episodic drinking was strongly associated with problems in a community sample from the largest city in Latin America. Prevention policies should target this drinking pattern, independent of age or gender. These findings warrant continued research on risky drinking behavior, particularly among persistent heavy drinkers at the non-dependent level.

Estrogen receptors mediate rapid activation of phospholipase C pathway in the rat endometrium.

The aim of the present study was to investigate the activation of rapid signaling events by 17ß-estradiol in the rat uterus. 17ß-Estradiol induced a rapid increase of total [3H]-inositol phosphate accumulation in the whole uterus and endometrium, but not in the myometrium. The effect of 17ß-estradiol in the endometrium was blocked by phospholipase C (PLC) inhibitor (U73122), estrogen receptors antagonist (ICI 182,780), exportin CRM1 inhibitor (leptomycin B) and selective inhibitor of the SRC family of protein tyrosine kinases (PP2). Furthermore, a selective agonist of ESR1 (PPT) and a selective agonist of GPER (G-1) also induced a rapid increase of total [(3)H]-inositol phosphate accumulation in the endometrium. The G-1 effects were blocked by GPER antagonist (G-15). 17ß-Estradiol and G-1 promoted an additive effect on total [3H]-inositol phosphate accumulation. In conclusion, the present results indicate that a rapid activation of the PLC-mediated phosphoinositide hydrolysis occurred in the rat endometrium after 17ß-estradiol stimulation, and this effect was mediated by ESR1 that underwent nuclear export after hormone stimulation, and that GPER activation may play an additive role for this response. These rapid actions might be one of the key steps that mediate the estrogen-dependent activation of cellular events in the endometrium.

Estrogen receptors mediate rapid activation of phospholipase C pathwayin the rat endometrium

The aim of the present study was to investigate the activation of rapid signaling events by 17b-estradiolin the rat uterus. 17b-Estradiol induced a rapid increase of total [3H]-inositol phosphate accumulation inthe whole uterus and endometrium, but not in the myometrium. The effect of 17b-estradiol in the endometriumwas blocked by phospholipase C (PLC) inhibitor (U73122), estrogen receptors antagonist (ICI 182,780), exportin CRM1 inhibitor (leptomycin B) and selective inhibitor of the SRC family of protein tyrosine kinases (PP2). Furthermore, a selective agonist of ESR1 (PPT) and a selective agonist of GPER (G-1) also induced a rapid increase of total [3H]-inositol phosphate accumulation in the endometrium.The G-1 effects were blocked by GPER antagonist (G-15). 17b-Estradiol and G-1 promoted an additive effect on total [3H]-inositol phosphate accumulation. In conclusion, the present results indicate that a rapid activation of the PLC-mediated phosphoinositide hydrolysis occurred in the rat endometrium after 17b-estradiol stimulation, and this effect was mediated by ESR1 that underwent nuclear export after hormonestimulation, and that GPER activation may play an additive role for this response. These rapid actions might be one of the key steps that mediate the estrogen-dependent activation of cellular events in the endometrium.

Environmental toxicants and male reproductive function.

Environmental toxicants, such as cadmium and bisphenol A (BPA) are endocrine disruptors. In utero, perinatal or neonatal exposure of BPA to rats affect the male reproductive function, such as the blood-testis barrier (BTB) integrity. This effect of BPA on BTB integrity in immature rats is likely mediated via a loss of gap junction function at the BTB, failing to coordinate tight junction and anchoring junction function at the site to maintain the immunological barrier integrity. This in turn activates the extracellular signal-regulated kinases 1/2 (Erk1/2) downstream and an increase in protein endocytosis, destabilizing the BTB. The cadmium-induced disruption of testicular dysfunction is mediated initially via its effects on the occludin/ZO-1/focal adhesion kinase (FAK) complex at the BTB, causing redistribution of proteins at the Sertoli-Sertoli cell interface, leading to the BTB disruption. The damaging effects of these toxicants to testicular function are mediated by mitogen-activated protein kinases (MAPK) downstream, which in turn perturbs the actin bundling and accelerates the actin-branching activity, causing disruption of the Sertoli cell tight junction (TJ)-barrier function at the BTB and perturbing spermatid adhesion at the apical ectoplasmic specialization (apical ES, a testis-specific anchoring junction type) that leads to premature release of germ cells from the testis. However, the use of specific inhibitors against MAPK was shown to block or delay the cadmium-induced testicular injury, such as BTB disruption and germ cell loss. These findings suggest that there may be a common downstream p38 and/or Erk1/2 MAPK-based signaling pathway involving polarity proteins and actin regulators that is shared between different toxicants that induce male reproductive dysfunction. As such, the use of inhibitors and/or antagonists against specific MAPKs can possibly be used to "manage" the illnesses caused by these toxicants and/or "protect" industrial workers being exposed to high levels of these toxicants in their work environment.

Sociodemographic correlates of transitions from alcohol use to disorders and remission in the São Paulo megacity mental health survey, Brazil.

AIMS: To evaluate sociodemographic correlates associated with transitions from alcohol use to disorders and remission in a Brazilian population. METHODS: Data are from a probabilistic, multi-stage clustered sample of adult household residents in the São Paulo Metropolitan Area. Alcohol use, regular use (at least 12 drinks/year), DSM-IV abuse and dependence and remission from alcohol use disorders (AUDs) were assessed with the World Mental Health version of the Composite International Diagnostic Interview. Age of onset (AOO) distributions of the cumulative lifetime probability of each alcohol use stage were prepared with data obtained from 5037 subjects. Correlates of transitions were obtained from a subsample of 2942 respondents, whose time-dependent sociodemographic data were available. RESULTS: Lifetime prevalences were 85.8% for alcohol use, 56.2% for regular use, 10.6% for abuse and 3.6% for dependence; 73.4 and 58.8% of respondents with lifetime abuse and dependence, respectively, had remitted. The number of sociodemographic correlates decreased from alcohol use to disorders. All transitions across alcohol use stages up to abuse were consistently associated with male gender, younger cohorts and lower education. Importantly, low education was a correlate for developing AUD and not remitting from dependence. Early AOO of first alcohol use was associated with the transition of regular use to abuse. CONCLUSION: The present study demonstrates that specific correlates differently contribute throughout alcohol use trajectory in a Brazilian population. It also reinforces the need of preventive programs focused on early initiation of alcohol use and high-risk individuals, in order to minimize the progression to dependence and improve remission from AUD.

In vivo treatments with fulvestrant and anastrozole differentially affect gene expression in the rat efferent ductules.

Estrogen plays a key role in maintaining the morphology and function of the efferent ductules. We previously demonstrated that the antiestrogen fulvestrant markedly affected gene expression in the rat efferent ductules. The mechanism of fulvestrant action to modulate gene expression may involve not only the blockade of ESR1 and ESR2 estrogen receptors, but also the activation of ESR1 and ESR2 when the receptors are tethered to AP-1 or SP1 transcription factors, or the activation of the G protein-coupled estrogen receptor 1. We therefore compared the effects of two strategies to interfere with estrogen action in the rat efferent ductules: treatment with fulvestrant or with the aromatase inhibitor anastrozole. Whereas fulvestrant markedly increased Mmp7 and Spp1, and reduced Nptx1 mRNA levels, no changes were observed with anastrozole. Fulvestrant caused changes in epithelial morphology that were not seen with anastrozole. Fulvestrant shifted MMP7 immunolocalization in the epithelial cells from the supranuclear to the apical region; this effect was less pronounced with anastrozole. In vitro studies of (35)S-methionine incorporation showed that protein release was increased, whereas tissue protein content in the efferent ductules of fulvestrant-treated rats was decreased. Although fulvestrant markedly affected gene expression, no changes were observed on AP-1 and SP1 DNA-binding activity. The blockade of ESRs seems to be the major reason explaining the differences between both treatments. At least some of the effects of fulvestrant appear to result from compensatory mechanisms activated by the dramatic changes caused by ESR1 blockade.