Comportamento materno e câncer de bexiga urinária: implicações da modulação de eixos hormonais e receptores de esteroides na fisiopatologia de lesões neoplásicas

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Adrenal function in 23 children with paracoccidioidomycosis

Adrenal involvement by Paracoccidioides brasiliensis was described at necropsies and in many clinical studies, but only in adults. Therefore, the aim of this study was to evaluate adrenal function in children with paracoccidioidomycosis. Twenty-three children with the systemic form of paracoccidioidomycosis were evaluated and divided in two Groups: Group A (n = 8) included children before treatment and Group B (n = 15) children after the end of treatment. Plasma cortisol (basal and after ACTH test), ACTH, renin activity, aldosterone, sodium and potassium were measured. They were within normal range in all cases, except for renin activity and aldosterone, which were elevated in some cases. Group A patients showed basal and post-ACTH cortisol levels significantly greater than Group B patients. The results showed that adrenal function was not compromised in these children with paracoccidioidomycosis.

Identification of Paracoccidioides brasiliensis in adrenal glands biopsies of two patients with paracoccidioidomycosis and adrenal insufficiency

The authors report two cases of adrenal insufficiency secondary to infiltration of the adrenal glands by Paracoccidioides brasiliensis. The first patient had been treated for a chronic multifocal form of paracoccidiodomycosis 11 years ago. The diagnosis of the mycosis was done simultaneous with that of the adrenal insufficiency in the second patient. In both patients the diagnosis was done by direct visualization of fungus in adrenal biopsies. They were treated with hormonal supplements and itraconazol by 12 and six months, without relapses during the follow-up period.

DISSEMINATED FUNGAL INFECTION WITH ADRENAL INVOLVEMENT: REPORT OF TWO HIV NEGATIVE BRAZILIAN PATIENTS

Paracoccidioidomycosis and histoplasmosis are systemic fungal infections endemic in Brazil. Disseminated clinical forms are uncommon in immunocompetent individuals. We describe two HIV-negative patients with disseminated fungal infections, paracoccidioidomycosis and histoplasmosis, who were diagnosed by biopsies of suprarenal lesions. Both were treated for a prolonged period with oral antifungal agents, and both showed favorable outcomes.

Personality, Brain Asymmetry, and Neuroendocrine Reactivity in Two Immune-Mediated Disorders: a Preliminary Report

Development of some immune-mediated disorders may depend on dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. To explore neuropsychologic mechanisms in relation to the abnormal endocrine reactivity in patients with systemic lupus erythematosus (SLE) and chronic hepatitis C (CHC) we used the corticotropin releasing hormone (CRH) test, the Minnesota Multiphasic Personality Inventory (MMPI), and the Edinburgh Inventory of Manual Preference Inventory (EIMP). Compared to controls, the adrenocorticotrophic hormone (ACTH) response to CRH was reduced in CHC, while SLE presented reduced baseline dehydroepiandrosterone sulfate levels; higher neurotic scores were found in SLE and higher behavior deviant scores in CHC. Peak ACTH levels were a significant factor for the MMPI profile variability, while the manual preference score was a significant factor for the ACTH response. Personality and manual preference contribute to neuroendocrine abnormalities. Different behavioral and neuroimmunoendocrine models emerge for these disorders.

Molecular tools to dissect the role of Dmrt2a and Dmrt2b in the left-right axis formation in zebrafish

Dissertação para obtenção do Grau de Mestre em Genética Molecular e Biomedicina

Bilateral adrenal histoplasmosis in an immunocompetent man

Histoplasmosis is a fungal disease that is endemic in Brazil. It may present as chronic pulmonary infection or in disseminated form. Disseminated histoplasmosis frequently affects the adrenal gland; however, unilateral involvement in immunosuppressed patients is the usual presentation. We report a case of an elderly immunocompetent male with history of weight loss, fever and bilateral adrenal mass who was successfully treated with itraconazole.

Ectopic schistosomiasis: description of five cases involving skin, one ovarian case and one adrenal case

Seven cases of patients with ectopic schistosomiasis from the State of Sergipe, Brazil, are presented (five involving skin, one ovarian and one adrenal). Data were collected from surveying the clinical records and anatomopathological reports in the files of the dermatology and pathology clinics of the University Hospital of the Federal University of Sergipe, from 1995 to 2005. The patients' mean age at diagnosis was 21.1 years. In the dermatological cases, full cures were achieved after treatment with oxamniquine. In the ovarian case, there was an association with embryonic carcinoma: this patient underwent surgery with adjuvant chemotherapy and praziquantel treatment, with satisfactory evolution. The adrenal case was associated with adenoma.

Avaliação do funcionamento do eixo HPA em deprimidos por meio de medidas basais: revisão sistemática da literatura e análise das metodologias utilizadas

Objetivo Realizar revisão sistemática da literatura para conhecer a atividade do eixo hipotálamo-pituitária-adrenal (HPA) em deprimidos considerando-se as medidas basais dos hormônios e analisar criticamente as metodologias utilizadas. Métodos Foi realizada busca de artigos nas bases de dados PubMed e SciELO. Na primeira base de dados, introduziram-se as palavras-chave “depressive disorder” e “HPA axis”, e na segunda utilizaram-se os termos “depression” ou “depressão” e “HHA” ou “HPA axis”. Optou-se por pesquisa realizada em humanos adultos, em inglês e português, do ano 2000 até 2011. Resultados Dos 27 artigos selecionados, obtiveram-se como resposta do eixo HPA tanto hiperatividade como atividade desregulada, hipoatividade ou não alteração. Tais resultados dependem das variáveis e dos hormônios estudados, do fluido coletado – plasma, urina, saliva, líquido cefalorraquidiano – do horário de coleta, do número de coletas, da análise estatística utilizada, do subtipo de doença depressiva, entre outros. Conclusão: Os resultados não apresentam consenso em relação à atividade do eixo HPA. Considerando as variáveis estudadas, o eixo HPA, na maioria das vezes, apresenta-se disfuncional na presença da depressão.

Methylation at the CpG island shore region upregulates Nr3c1 promoter activity after early-life stress

Early-life stress (ELS) induces long-lasting changes in gene expression conferring an increased risk for the development of stress-related mental disorders. Glucocorticoid receptors (GR) mediate the negative feedback actions of glucocorticoids (GC) in the paraventricular nucleus (PVN) of the hypothalamus and anterior pituitary and therefore play a key role in the regulation of the hypothalamic-pituitary-adrenal (HPA) axis and the endocrine response to stress. We here show that ELS programs the expression of the GR gene (Nr3c1) by site-specific hypermethylation at the CpG island (CGI) shore in hypothalamic neurons that produce corticotropin-releasing hormone (Crh), thus preventing Crh upregulation under conditions of chronic stress. CpGs mapping to the Nr3c1 CGI shore region are dynamically regulated by ELS and underpin methylation-sensitive control of this region's insulation-like function via Ying Yang 1 (YY1) binding. Our results provide new insight into how a genomic element integrates experience-dependent epigenetic programming of the composite proximal Nr3c1 promoter, and assigns an insulating role to the CGI shore.

Malignant hypertension and hypertensive encephalopathy in primary aldosteronism caused by adrenal adenoma

Two cases are reported as follows: 1) 1 female patient with accelerated-malignant hypertension secondary to an aldosterone-producing adrenal adenoma; and 2) 1 female patient with adrenal adenoma, severe hypertension, and hypertensive encephalopathy. This association is a rare clinical finding, and malignant hypertension may modify the hormonal characteristic of primary aldosteronism, making its diagnosis more difficult. The diagnosis of primary aldosteronism should be considered in patients with malignant hypertension or hypertensive encephalopathy if persistent hypokalemia occurs. Identification of primary aldosteronism is of paramount importance for the patient's evolution, because the surgical treatment makes the prognosis more favorable.

Hipertensão arterial secundária a tumor raro da glândula adrenal

O ganglioneuroma é um tumor do sistema nervoso simpático, podendo estar associado à hipersecreção de substâncias vasoativas responsáveis por sintomas e sinais variados, como a hipertensão arterial. Os autores apresentam um caso de ganglioneuroma e uma revisão da literatura, focando os aspectos mais importantes do diagnóstico e da terapêutica. A paciente apresentava crises hipertensivas sintomáticas recorrentes, tendo realizado estudo imaginológico que detectou uma imagem nodular na adrenal direita. Sendo os tumores neuroblásticos indistinguíveis radiologicamente, procedeu-se à excisão, confirmando-se o diagnóstico pela análise anatomopatológica. Este caso demonstra a variabilidade clínica dos ganglioneuromas, a utilidade da imaginologia e a importância do estudo histológico.

Excesso de Hormônio Tireoidiano em Curto Prazo Afeta o Coração, mas não Afeta a Atividade Adrenal em Ratos

Fundamento: O hipertireoidismo (Hi) exerce um amplo leque de influências em diversos parâmetros fisiológicos. Seu efeito perturbador sobre o sistema cardiovascular é um de seus impactos mais importantes. Além disso, o Hi foi clinicamente associado com o estresse induzido pela hiperativação do eixo hipotalâmico-pituitário-adrenal. Objetivo: Avaliar o impacto do Hi de curto prazo sobre o desempenho cardíaco e a atividade adrenal de ratos. Métodos: A indução de Hi em ratos Wistar através de injeções de T3 (150 μg/kg) por 10 dias (grupo com hipertireoidismo - GH) ou veículo (grupo controle). O desempenho cardiovascular foi avaliado por: ecocardiograma (ECO); razão peso do coração/peso corporal (mg/gr); contratilidade de músculos papilares isolados (MPI) e mensuração direta da pressão arterial. A atividade adrenal foi avaliada pela razão peso adrenal/ peso corporal (mg/gr) e níveis de 24 horas de corticosterona fecal (CF) no 1º, 5º e 10º dias de tratamento com T3. Resultados: No GH, o ECO mostrou redução dos Volumes Finais Sistólico e Diastólico, Tempos de Ejeção, Relaxamento Isovolumétrico e Diastólico Total, Áreas Sistólicas e Diastólica e razão E/A. Aumentaram a frequência cardíaca, a fração de ejeção e o débito cardíaco. A razão peso corporal/peso do coração foi maior. Da mesma forma, nos MPI, a taxa máxima de degradação da força durante o relaxamento foi maior em todas as concentrações extracelulares de cálcio. Os níveis de pressão arterial sistólica (PAS) foram maiores. (p ≤ 0,05). Por outro lado, não houve diferença na razão peso das adrenais/peso corporal ou níveis de 24 horas de CF. Conclusões: O Hi induz efeitos inotrópicos, cronotrópicos e lusitrópicos positivos no coração através de efeito direto do T3, e aumenta a PAS. Essas alterações não estão correlacionadas com as alterações na atividade adrenal.

Neuroendocrine, metabolic, and immune functions during the acute phase response of inflammatory stress in monosodium L-glutamate-damaged, hyperadipose male rat.

In rats, neonatal treatment with monosodium L-glutamate (MSG) induces several metabolic and neuroendocrine abnormalities, which result in hyperadiposity. No data exist, however, regarding neuroendocrine, immune and metabolic responses to acute endotoxemia in the MSG-damaged rat. We studied the consequences of MSG treatment during the acute phase response of inflammatory stress. Neonatal male rats were treated with MSG or vehicle (controls, CTR) and studied at age 90 days. Pituitary, adrenal, adipo-insular axis, immune, metabolic and gonadal functions were explored before and up to 5 h after single sub-lethal i.p. injection of bacterial lipopolysaccharide (LPS; 150 microg/kg). Our results showed that, during the acute phase response of inflammatory stress in MSG rats: (1) the corticotrope-adrenal, leptin, insulin and triglyceride responses were higher than in CTR rats, (2) pro-inflammatory (TNFalpha) cytokine response was impaired and anti-inflammatory (IL-10) cytokine response was normal, and (3) changes in peripheral estradiol and testosterone levels after LPS varied as in CTR rats. These data indicate that metabolic and neroendocrine-immune functions are altered in MSG-damaged rats. Our study also suggests that the enhanced corticotrope-corticoadrenal activity in MSG animals could be responsible, at least in part, for the immune and metabolic derangements characterizing hypothalamic obesity.