Novel aspects of glucocorticoid actions.

Normal hypothalamic-pituitary-adrenal (HPA) axis activity leading to the rhythmic and episodic release of adrenal glucocorticoids (GCs) is essential for body homeostasis and survival during stress. Acting through specific intracellular receptors in the brain and periphery, GCs regulate behaviour, as well as metabolic, cardiovascular, immune and neuroendocrine activities. By contrast to chronic elevated levels, circadian and acute stress-induced increases in GCs are necessary for hippocampal neuronal survival and memory acquisition and consolidation, as a result of the inhibition of apoptosis, the facilitation of glutamatergic neurotransmission and the formation of excitatory synapses, and the induction of immediate early genes and dendritic spine formation. In addition to metabolic actions leading to increased energy availability, GCs have profound effects on feeding behaviour, mainly via the modulation of orexigenic and anorixegenic neuropeptides. Evidence is also emerging that, in addition to the recognised immune suppressive actions of GCs by counteracting adrenergic pro-inflammatory actions, circadian elevations have priming effects in the immune system, potentiating acute defensive responses. In addition, negative-feedback by GCs involves multiple mechanisms leading to limited HPA axis activation and prevention of the deleterious effects of excessive GC production. Adequate GC secretion to meet body demands is tightly regulated by a complex neural circuitry controlling hypothalamic corticotrophin-releasing hormone (CRH) and vasopressin secretion, which are the main regulators of pituitary adrenocorticotrophic hormone (ACTH). Rapid feedback mechanisms, likely involving nongenomic actions of GCs, mediate the immediate inhibition of hypothalamic CRH and ACTH secretion, whereas intermediate and delayed mechanisms mediated by genomic actions involve the modulation of limbic circuitry and peripheral metabolic messengers. Consistent with their key adaptive roles, HPA axis components are evolutionarily conserved, being present in the earliest vertebrates. An understanding of these basic mechanisms may lead to novel approaches for the development of diagnostic and therapeutic tools for disorders related to stress and alterations of GC secretion.

Cannabinoid CB1 receptor mediates glucocorticoid effects on hormone secretion induced by volume and osmotic changes.

The present study provides the first in vivo evidence that the cannabinoid CB(1) receptor mediates the effects of dexamethasone on hormone release induced by changes in circulating volume and osmolality. Male adult rats were administered with the CB(1) receptor antagonist rimonabant (10 mg/Kg, p.o.), followed or not in 1 hour by dexamethasone (1 mg/Kg, i.p.). Extracellular volume expansion (EVE, 2 mL/100 g of body weight, i.v.) was performed 2 hours after dexamethasone or vehicle treatment using either isotonic (I-EVE, 0.15 mol/L) or hypertonic (H-EVE, 0.30 mol/L) NaCl solution. Five minutes after EVE, animals were decapitated and trunk blood was collected for all plasma measurements. Rimonabant potentiated oxytocin (OT) secretion induced by H-EVE and completely reversed the inhibitory effects of dexamethasone in response to the same stimulus. These data suggest that glucocorticoid modulation of OT release is mediated by the CB(1) receptor. Although dexamethasone did not affect vasopressin (AVP) secretion induced by H-EVE, the administration of rimonabant potentiated AVP release in response to the same stimulus, supporting the hypothesis that the CB(1) receptor regulates AVP secretion independently of glucocorticoid-mediated signalling. Dexamethasone alone did not affect atrial natriuretic peptide (ANP) release stimulated by I-EVE or H-EVE. However, pretreatment with rimonabant potentiated ANP secretion induced by H-EVE, suggesting a possible role for the CB(1) receptor in the control of peripheral factors that modulate cardiovascular function. Rimonabant also reversed the inhibitory effects of dexamethasone on H-EVE-induced corticosterone secretion, reinforcing the hypothesis that the CB(1) receptor may be involved in the negative feedback exerted by glucocorticoids on the activity of the hypothalamic-pituitary-adrenal axis. Collectively, the results of the present study indicate that the CB(1) receptor modulates neurohypophyseal hormone secretion and systemic factors, such as corticosterone and ANP, thus participating in homeostatic responses to altered extracellular volume and plasma tonicity.

Hypothalamic cocaine- and amphetamine-regulated transcript and corticotrophin releasing factor neurons are stimulated by extracellular volume and osmotic changes.

Several studies suggest that hypothalamic cocaine- and amphetamine-regulated transcript (CART) may interact with the hypothalamic-pituitary-adrenal (HPA) axis in the control of neuroendocrine function and may also participate in cardiovascular regulation. Therefore, this study aimed to evaluate, in experimental models of isotonic (I-EVE) and hypertonic (H-EVE) extracellular volume expansion and water deprivation (WD), the activation of CART- and corticotrophin releasing factor (CRF)-immunoreactive neurons, as well as the relative expression of CART and CRF mRNAs in the paraventricular (PVN) and supraoptic (SON) nuclei of the hypothalamus. Both H-EVE (0.30M NaCl, 2mL/100g of body weight, in 1 minute) and 24 hours of WD significantly increased plasma sodium concentrations, producing, respectively, either an increase or a decrease in extracellular volume. I-EVE (0.15M NaCl, 2mL/100g of body weight, in 1 minute) evoked a significant increase in the circulating volume accompanied by unaltered plasma concentrations of sodium. CART-expressing neurons of both magnocellular and parvocellular hypothalamic divisions were activated to produce Fos in response to H-EVE but not in response to I-EVE. Furthermore, increased expression of CART mRNA was found in the PVN of H-EVE but not I-EVE rats. These data show for the first time that EVE not only activates hypothalamic CRF neurons but also increases CRF mRNA expression in the PVN. In contrast, WD increases the number of CART-immunoreactive neurons activated to produce Fos in the PVN and SON but does not change the number of neurons double labeled for Fos and CRF or expression of CRF mRNA in the PVN. These findings provided new insights into the participation of CART in diverse processes within the PVN and SON, including its possible involvement in activation of the HPA axis and cardiovascular regulation in response to changes in extracellular volume and osmolality.

CB(1) modulation of hormone secretion, neuronal activation and mRNA expression following extracellular volume expansion.

The endocannabinoid system includes important signaling molecules that are involved in several homeostatic and neuroendocrine functions. In the present study, we evaluated the effects of the type 1 cannabinoid (CB(1)) receptor antagonist, rimonabant (10 mg/kg, p.o.), on hormone secretion, neuronal activation and mRNA expression in the hypothalamus following isotonic (I-) or hypertonic (H-) extracellular volume expansion (EVE). The total nitrate content in the PVN and SON was also assessed under the same experimental conditions. Our results showed that OT and AVP plasma concentrations were increased in response to H-EVE, while decreased AVP levels were found following I-EVE. Accordingly, both I- and H-EVE stimulated oxytocinergic neuronal activation, as evidenced by the increased number of c-Fos/OT double labeled neurons in the hypothalamus. The vasopressinergic cells of the PVN and SON, however, were only activated in response to H-EVE. Furthermore, increased amounts of both AVP and OT mRNAs were found in the hypothalamus following EVE. Pretreatment with rimonabant significantly potentiated hormone secretion and also vasopressinergic and oxytocinergic neuronal activation induced by EVE, although decreased AVP and OT mRNA expression was found in the hypothalami of rimonabant pretreated groups. In addition, the nitrate content in the PVN and SON was not altered in response to EVE or rimonabant pretreatment. Taken together, these results suggest that the CB(1) receptor may modulate several events that contribute to the development of appropriate responses to increased fluid volume and osmolality.

The influence of socio-economic conditions on the prevalence of depressive symptoms and its covariates in an elderly population with slight income differences: the Bambuí Health and Aging Study (BHAS).

BACKGROUND: The influence of socio-economic conditions on covariates of depression has received little attention. AIMS: Examine whether prevalence and covariates of depressive symptoms are affected by socio-economic circumstances. METHODS: Participants were 1,499 (86%) residents in Bambuí city, Brazil, aged ->- 60 years. Depressive symptoms were assessed by the GHQ-12 questionnaire and exploratory variables included demographic characteristics, life events, social support, health conditions and health service use. The analysis was stratified by family income (- US$240.00). RESULTS: The prevalence of depressive symptoms was higher in those with lower income (43.9%) in comparison with the better off (27.7%). Dissatisfaction with relationships, worse self-rated health and insomnia were independently associated with depressive symptoms in both income groups (OR from 2.00 to 4.74; p<0.05). Depressive symptoms were associated with number of chronic diseases, functional disability and hospitalizations among the poorer (OR from 1.73 to 2.37; p<0.05), while old age (OR 2.08) and female gender (OR 2.03) were associated with depressive symptoms among the better off. CONCLUSION: This study provides evidence that the prevalence of depressive symptoms and their covariates are influenced by socio-economic conditions in a population with slight income differences.

The burden of social phobia in a Brazilian community and its relationship with socioeconomic circumstances, health status and use of health services: the Bambuí study.

AIMS: Social phobia in the environment of poverty and major social inequalities, as observed in most developing countries, has received little attention. This population-based study was carried out in a poor community in Brazil (15,000 inhabitants), aiming at determining the prevalence of social phobia and its associated factors. METHOD: The Composite International Diagnostic Interview was applied in a random sample of 1037 residents aged > or = 18 years. RESULTS: The 1-month, 1-year and lifetime prevalence of social phobia were 7.9, 9.1 and 11.8%, respectively. One-month social phobia was independently associated with age (45-64 years), marital status (divorced/separated), worse socioeconomic indicators (family income and education), number of months worked, worse health status and use of health services and medications. CONCLUSION: There was an important burden of social phobia in the study community, due to its high prevalence (similar or superior to those observed in most developed countries), and due to its association with worse health status and use of health services and medications. The strong association between social phobia and socioeconomic circumstance, even in a small and poor community, is certainly a reflex of the major social inequalities in Brazil.

Signos, significados e ações associados à doença de Chagas / Signs, meanings, and actions associated with Chagas disease

A abordagem antropólogica foi empregada para investigar o universo de representações (maneiras de pensar) e comportamentos (maneiras de agir) associados à doença de Chagas, por um grupo de trabalhadores de um serviço público de Belo Horizonte (infectados/não infectados). Procurou-se também avaliar as repercussões deste universo de representações e comportamentos sobre a vida dos indivíduos infectados. A coleta e a análise dos dados, inspirou-se no modelo dos "sistemas de signos, significados e ações", elaborado por Corin et al. (1989, 1992). Foram entrevistados 16 informantes chave, selecionados entre os trabalhadores soro-positivos e 12 entre os trabalhadores soro-negativos, com o objetivo de comparar as maneiras de pensar e agir, predominantes nesses dois grupos. A análise dos dados, permitiu identificar diversos elementos do contexto que vêm maximizar as limitações impostas pela doença de Chagas, e que devem ser levados em conta no planejamento de campanhas educativas e na elaboração de modelos de atenção ao paciente chagásico.

Unexpected high prevalence of 1-month depression in a small Brazilian community: the Bambuí Study.

OBJECTIVE: To determine the prevalence of depression in a community with 15 000 inhabitants in Brazil (Bambuí). METHOD: The Composite International Diagnostic Interview was applied in a random sample of 1041 residents aged 18+ years. RESULTS: The ICD-10 1-month, 1-year and lifetime prevalences of depression were 8.2% (95% CI:6.5-9.8), 10.0% (95% CI:8.2-11.8) and 15.6% (95% CI:13.4-17.8), respectively. Kappa coefficients comparing ICD-10 and DSM-III-R diagnoses were high (0.73-0.79). Female sex (OR=2.4; 95% CI:1.3-4.2), age 45-59 years (OR=3.5; 95% CI:1.7-7.2) and > or =60 years (OR=4.0; 95% CI:1.9-8.5) and being out of work (OR=2.1; 95% CI:1.2-3.6) were independently and positively associated with 1-month depression. CONCLUSION: The 1-month prevalence of depression was higher than that observed in similar studies in developed and developing countries. Depression may be a major unidentified disease of people living in small communities of Brazil and other developing countries, especially among older women.

Ageing with Trypanosoma cruzi infection in a community where the transmission has been interrupted: the Bambuí Health and Ageing Study (BHAS).

BACKGROUND: The prevalence of Chagas' disease is decreasing in Brazil. Due to cohort effect, the disease might remain a public health problem for some time among older individuals. The present burden of Trypanosoma cruzi infection for the elderly living in areas where the transmission has been interrupted has not been studied. METHODS: The prevalence of T. cruzi infection and its association with indicators of health status and health services use were assessed among the elderly living in one of the oldest endemic areas in Brazil (Bambuí, MG). Seropositivity was determined by blood tests (IHA and ELISA) performed in 85.6% of all residents aged 60+ (1496/1742) and in 83.1% of sampled residents aged 5-59 years (1212/1458). RESULTS: Seropositivity showed a cohort effect, with no cases below 20 years and high prevalence among those aged 60+ years (37.7%). After adjustment for confounders, seropositivity was associated with self-rated health reasonable (OR = 1.43; 95% CI : 1.03-1.98) and bad/very bad (OR = 1.89; 95% CI : 1.30-2.75), staying in bed in past 2 weeks (OR = 1.88; 95% CI : 1.21-2.92), hospitalization in past 12 months (OR = 1.41; 95% CI : 1.05-1.89) and use of 5+ prescribed medications in past 3 months (OR = 1.75; 95% CI : 1.15-2.59). IMPLICATIONS: Our results are an example of how survival of individuals with past exposure to infectious disease may lead to a different picture of ageing in the developing world. Policy makers need to consider the extra burden imposed by increasing rates of non-infectious disease among the elderly (as observed in Brazil) including the consequences of T. cruzi infection in areas where the infection was widespread in the past.

The Bambuí Health and Aging Study (BHAS): prevalence of risk factors and use of preventive health care services.

OBJECTIVE: To describe, for the first time in Brazil, the prevalence of risk factors and the use of preventive health care services among adults 60 years and older. METHODS: This population-based study was conducted during 1996-1997 in the state of Minas Gerais, in the town of Bambuí, which is located in the municipality of the same name. In 1996 the town had 14,950 inhabitants. For the study, all the town's residents aged > or = 60 years were selected, along with a comparison sample of persons aged 18-59 years. Data were gathered using interviews and physical examinations. RESULTS: Of the 1,742 inhabitants of the town of Bambuí aged > or = 60 years, 1,606 (92.2%) participated in the interview and 1,495 (85.8%) were examined (blood pressure, anthropometric measurements, and blood tests). Among the 1,020 younger adults selected for the survey, 909 of them (89.1%) participated in the interview, and 820 of them (80.4%) underwent the physical examination. The prevalence of the following risk factors was higher among older adults than among younger adults: physical inactivity (47.7% vs. 28.0%); blood pressure 140-159 mmHg (systolic) or 90-99 mmHg (diastolic) (25.8% vs. 8.7%); blood pressure > or = 160 mmHg (systolic) or > or = 100 mmHg (diastolic) (19.1% vs. 4.1%); total cholesterol > or = 240 mg/dL (40.6% vs. 9.8%); and blood glucose > or = 126 mg/dL (12.4% vs. 2.2%). The daily consumption of fruits and vegetables was similar among the older adults and the younger ones (51.9% and 51.7%), as was also body mass index > or = 25 kg/m2 (51.6% and 56.2%). Smoking was lower among the older adults (18.7%) than among the younger ones (31.1%). The proportion of participants whose blood pressure had been checked in the preceding year was high (86.8% among the older adults and 61.2% among the younger ones), suggesting that the high prevalence of uncontrolled hypertension was not due to limited access to health care. CONCLUSIONS: For a long time it was believed that the kinds of risk factors that we found in the urban section of the municipality of Bambuí were public health problems only in large Brazilian cities. Around 72% of the municipalities in Brazil have < or = 20,000 inhabitants, and these smaller municipalities contain some 19% of the country's entire population. The high prevalence of various risk factors among the older and younger adults in Bambuí indicates a great need for health promotion and disease prevention actions. More research is needed to find out whether our results in Bambuí reflect the reality of other small towns in Brazil.

The Bambuí Health and Aging Study (BHAS): factors associated with hospitalization of the elderly.

This study aimed to identify factors associated with hospital admissions of the elderly. All residents of Bambuí, Minas Gerais State >/= 60 years (n = 1,742) were selected. Some 1,606 of these (92.2%) participated in the study. The dependent variable was the number of hospital admissions (none, one, and two or more) during the previous 12 months. Independent variables were grouped as enabling, predisposing, and need-related factors. The strongest associations with multiple hospital admissions were: living alone; financial constraints to purchase of medication; and various indicators of need (worse self-perceived health, more visits to physician, greater use of prescription medications, and history of coronary heart disease). Such variables could help identify older adults at greatest risk and thus prevent hospitalization.

The control of schistosomiasis in Brazil: an ethnoepidemiological study of the effectiveness of a community mobilization program for health education.

This study combined anthropological and epidemiological approaches to assess the effectiveness of community mobilization for health education, developed as part of the Brazilian program for the control of schistosomiasis. The study was carried out in two villages in the state of Minas Gerais, SE Brazil, exposed to the same established schistosomiaisis control strategies. Residents of one village were also exposed to the community mobilization for health education (study area) while those from the other community were not exposed to this program (control area). Schistosoma mansoni prevalence rates for the study and control villages were compared over time. A population-based survey was carried out in the two villages to obtain information on socio-demographic factors, water contact patterns and knowledge of S. mansoni transmission. Intensive ethnographic interviews with key informants in each locality were employed to determine the knowledge, attitudes and practices of the communities regarding schistosomiasis. Ethnographic data were analysed using the model of systems of signs, meanings and actions. Differences were observed in prevalence trends between the study and control areas but they could not be explained by the existence of the community mobilization program in the former. It was also found that educational actions carried out by the Brazilian Ministry of Health transmitted information on schistosomiasis but were ineffective in transforming the information received into preventive behaviour related to water contact. With regard to disease, the population studied tended to distinguish minor symptoms, which they associated with water contact, from major symptoms, which they attributed to lack of medical treatment. This distinction mediated perceptions of the severity of "xistose" and reduced the importance of avoiding contact with potentially infested waters. The perception of protection conferred by treatment observed in the present study might also apply to other communities where access to treatment is readily available and free. The extent to which this perception exists in endemic areas needs to be determined so that apparent contradictions of this type can be addressed in future educational programs.

The Bambuí health and ageing study (BHAS): methodological approach and preliminary results of a population-based cohort study of the elderly in Brazil.

OBJECTIVE: A cohort study has been designed to identify predictors of adverse health events in the elderly. The methodology of the study and preliminary descriptive results are presented. METHODS: The study population comprises all residents of Bambuí (Minas Gerais, Brazil), aged 60 or more years (n=1.742). From these, 92.2% were interviewed and 85.9% underwent clinical examination, consisting of haematological and biochemical tests, serology for Trypanosoma cruzi, anthropometric and blood pressure measures and electrocardiogram. Aliquots of serum, plasma and DNA were stored for future investigations. The baseline interview included sociodemographic characteristics, self-referred health condition and history of selected diseases, medication use, health service use, source of medical care, physical activities, smoking, drinking and eating habits, reproductive history, physical functioning, life events, social support and mental health. Individuals are being followed up annually. RESULTS: The following characteristics predominated among participants: women (60,0%), married (48.9%) or widowed (35.4%), people living in households with up to 2 residents (73.8%), heads of family (76.7%), people with monthly income between 1.00 and 2.99 Brazilian minimum wages (62.0%) and people with up to 4 years of schooling (89.1%). The median age was 68 years. Among the cohort members, only 1.7% were lost in the first follow-up. CONCLUSIONS: In general, the characteristics of the study population were very similar to those from other epidemiological studies of the elderly based on large Brazilian cities. The small number of losses to follow-up indicates that the choice of Bambuí was adequate, assuring the feasibility of a long term cohort study.

[Death of elderly patients in the Santa Genoveva Clinic in Rio de Janeiro: excess mortality that the public health system could have prevented]. / A morte de idosos na Clínica Santa Genoveva, Rio de Janeiro: um excesso de mortalidade que o sistema público de saúde poderia ter evitado.

From January to May 1996, 156 inpatients died in a clinic for elderly people in Rio de Janeiro, Brazil. The highest mortality rate was observed in May: 143/1,000 inpatients. As a result, the clinic was closed by the Ministry of Health. This study investigated whether the excessive number of deaths observed in the clinic in early 1996 was unexpected or reflected prevailing conditions. The investigation used the Public Health System database (SIH-SUS). The study period was 01/1993 to 05/1996. The investigation was based on: 1) a time-series analysis of the number of deaths and crude mortality rates and 2) comparison of the mortality rates observed in that clinic with those calculated for 15 area hospitals, defined as the reference rates. Risk of death in the clinic was higher than expected in 28 of the 41 months considered in the study. Highest risks were observed in January 1993 (RRcrude = 2.23; 95% CI 1.56-3. 14) and May 1996 (RRadjusted = 2.73; 95% CI 1.88-3.95). The high mortality rates observed in the clinic in 1996 were already present in 1993. Thus, adequate use of the SIH-SUS could have anticipated and avoided the excess mortality identified in early 1996.

[Evaluation of a program for the control of schistosomiasis in municipalities located on the basin of the Sao Francisco River, Minas Gerais, Brazil]. / Avaliação do programa de controle da esquistossomose (pce/pcden) em municípios situados na Bacia do Rio São Francisco, Minas Gerais, Brasil.

An evaluation of the control program on schistosomiasis (PCE/PCDEN) was performed in the region of São Francisco river in MInas Gerais. The study area comprises six municipalities, with 130,000 inhabitants and 916 localities situated in an area with 10,722 km2. The activities initiated in 1983-85 in four municipalities and in 1987 in the other two. The main measures of control were repeated treatment with oxamniquine and use of niclosamide. The prevalence of infection by Schistosoma mansoni in the first four municipalities, that was initially around 18 and 32%, dropped abruptly after the first intervention (1983/85) and remained in levels below the initial ones until the last assessment (1990-94); similar trends were observed for the proportion of infected snails. In these municipalities, the proportion of localities without infection or with prevalence below 5% increased in relation to those with higher prevalence. In the other two municipalities, with initial prevalence below 5%, there were no substantial changes in S. mansoni prevalence or proportion of infected snails; the cost benefit of the program in these municipalities need to be assessed and the priorities redirected to eradicate focal areas and prevent spread to non infected localities. The authors call attention to the difficulties in the long term of a control program based on repeated treatments. Information on factors associated with S. mansoni infection in each locality, or in groups of similar localities, would allow to develop additional measures to treatment that could last longer and be less dependent on the continuous use of chemotherapy.

[Medical anthropology: conceptual and methodological elements for an approach to health and disease]. / Antropologia médica: elementos conceituais e metodológicos para uma abordagem da saúde e da doença.

This paper discusses the relevance, specificity, and potential of the anthropological approach to health and illness. Medical anthropology is shown as complementary to other approaches that currently deal with public health problems. The impact of social and cultural factors on health-related perceptions and behaviors is illustrated and commented. A conceptual and methodological framework is also proposed to systematize the study of representations and practices of communities in the area of public health. The specific contribution of the anthropological approach is discussed in terms of the effectiveness of public health programs.