A connection between extracellular matrix and hormonal signals during the development of the human fetal adrenal gland

The human adrenal cortex, involved in adaptive responses to stress, body homeostasis and secondary sexual characters, emerges from a tightly regulated development of a zone-specific secretion pattern during fetal life. Its development during fetal life is critical for the well being of pregnancy, the initiation of delivery, and even for an adequate adaptation to extra-uterine life. As early as from the sixth week of pregnancy, the fetal adrenal gland is characterized by a highly proliferative zone at the periphery, a concentric migration accompanied by cell differentiation (cortisol secretion) and apoptosis in the central androgen-secreting fetal zone. After birth, a strong reorganization occurs in the adrenal gland so that it better fulfills the newborn's needs, with aldosterone production in the external zona glomerulosa, cortisol secretion in the zona fasciculata and androgens in the central zona reticularis. In addition to the major hormonal stimuli provided by angiotensin II and adrenocorticotropin, we have tested for some years the hypotheses that such plasticity may be under the control of the extracellular matrix. A growing number of data have been harvested during the last years, in particular about extracellular matrix expression and its putative role in the development of the human adrenal cortex. Laminin, collagen and fibronectin have been shown to play important roles not only in the plasticity of the adrenal cortex, but also in cell responsiveness to hormones, thus clarifying some of the unexplained observations that used to feed controversies.

Implications of infectious diseases and the adrenal hypothesis for the etiology of childhood acute lymphoblastic leukemia

Acute leukemia is the most frequent cancer in children. Recently, a new hypothesis was proposed for the pathogenesis of childhood acute lymphoblastic leukemia (ALL). The so-called "adrenal hypothesis" emphasized the role of endogenous cortisol in the etiology of B-cell precursor ALL. The incidence peak of ALL in children between 3 to 5 years of age has been well documented and is consistent with this view. The adrenal hypothesis proposes that the risk of childhood B-cell precursor ALL is reduced when early childhood infections induce qualitative and quantitative changes in the hypothalamus-pituitary-adrenal axis. It suggests that the increased plasma cortisol levels would be sufficient to eliminate all clonal leukemic cells originating during fetal life. Because Brazil is a continental and tropical country, the exposure to infections is diversified with endemic viral and regionally non-viral infections, with some characteristics that support the recent adrenal hypothesis. Here we discuss this new hypothesis in terms of data from epidemiological studies and the possible implications of the diversity of infections occurring in Brazilian children.

Psoriasis severity and hypothalamic-pituitary-adrenal axis function: results from the CALIPSO study

Psoriasis is a chronic inflammatory disease that significantly impacts life quality, being associated with stress and mental disorders. We investigated whether the activity of the hypothalamic-pituitary-adrenal (HPA) axis was associated with psoriasis severity, daily life stress and anxiety, and depressive symptoms. In this ancillary study, which was part of the CALIPSO (coronary artery calcium in psoriasis) study, saliva was collected from 102 patients with psoriasis immediately upon awakening, 30, and 60 min after awakening, at 2:00 pm and at bedtime (five time points) to determine salivary cortisol levels. We used Pearson's correlation coefficient to evaluate the association of clinical and psychopathological variables with HPA activity. We found a direct correlation between bedtime cortisol and psoriasis severity evaluated by the psoriasis area severity index (PASI; r=0.39, P<0.001). No correlations between other clinical and psychopathological variables or with other cortisol assessments were observed. The findings indicated that HPA dysfunction may be present in psoriasis, as bedtime cortisol was correlated with psoriasis severity. Our study is limited by the lack of a control group; therefore, we were not able to explore whether these cortisol values were different compared with a concurrent, healthy sample.

POD-1/Tcf21 overexpression reduces endogenous SF-1 and StAR expression in rat adrenal cells

During gonad and adrenal development, the POD-1/capsulin/TCF21transcription factor negatively regulates SF-1/NR5A1expression, with higher SF-1 levels being associated with increased adrenal cell proliferation and tumorigenesis. In adrenocortical tumor cells, POD-1 binds to the SF-1 E-box promoter region, decreasing SF-1 expression. However, the modulation of SF-1 expression by POD-1 has not previously been described in normal adrenal cells. Here, we analyzed the basal expression of Pod-1 and Sf-1 in primary cultures of glomerulosa (G) and fasciculata/reticularis (F/R) cells isolated from male Sprague-Dawley rats, and investigated whether POD-1 overexpression modulates the expression of endogenous Sf-1 and its target genes in these cells. POD-1 overexpression, following the transfection of pCMVMycPod-1, significantly decreased the endogenous levels of Sf-1 mRNA and protein in F/R cells, but not in G cells, and also decreased the expression of the SF-1 target StAR in F/R cells. In G cells overexpressing POD-1, no modulation of the expression of SF-1 targets, StAR and CYP11B2, was observed. Our data showing that G and F/R cells respond differently to ectopic POD-1 expression emphasize the functional differences between the outer and inner zones of the adrenal cortex, and support the hypothesis that SF-1 is regulated by POD-1/Tcf21 in normal adrenocortical cells lacking the alterations in cellular physiology found in tumor cells.

Paracoccidioidomicose pulmonar agressiva, endotraqueíte estenosante e cor-pulmonale subagudo: descrição de um caso

A paracoccidioidomicose (Pbmicose) atinge os pulmões pela via inalatória, onde se estabelece o complexo primário semelhante ao da tuberculose. A traquéia comprometida pela via tubohemolinfática desenvolveria reação inflamatória em processo granulomatoso levando à obstrução estenosante com asíixia. Acompanhou-se um doente, masculino, 32 anos, branco, natural de Sarutaiá (SP), lavrador, que há 8 meses desenvolveu tosse expectorativa branco-amarelada, diária, sem fatores de melhora ou piora e dispnéia inicial discreta. Há 4 meses, anorexia, fraqueza e astenia. Há 1 mês a dispneia se agravou. Perdeu 15 kg. Tabagista e etilista há 16 anos. Exame físico revelou: PA — 10/7 mmHg, FR = 28 bpm, peso 31 kg, hipocratismo digital e hipotrofia muscular Tórax enfisematoso e síndrome obstrutivo aos testes de função pulmonar. Coração: P2 desdobrada e hiperfonética. Hepatesplenomegalia. Desenvolveu cor-pulmonale e insuficiência adrenal à internação, evoluindo após 45 dias para óbito em insuficiência respiratória aguda asfixiante, apesar da terapia antifúngica ter sido completa. A literatura médica revista não mostrou registro de caso semelhante de cor-pulmonale e insuficiência adrenal de evolução subaguda.

Paracoccidioidomicose: estudo radiológico e pulmonar de 58 casos

Provas funcionais respiratórias foram realizadas em 58 pacientes com Paracoccidioidomicose (Pbmicose) pulmonar uni e multifocal em 52; tumoral em 5 e genital feminino interno em 01. A idade oscilou de 20 a 74 anos e a duração da doença variou de 3 a 25 anos. Manifestações respiratórias, tegumentares e linfáticas foram predominantes. Catorze deles desenvolveram Cor pulmonale, função renal alterada em 19, modificações eletrocardiográficas em 8 e atividade hiporeatora adrenal em 13 dos 20 casos estudados. A análise radiológica revelou lesões designadas: leve em 16; moderada em 24 e grave em 18 que à evolução evidenciaram: manutenção e piora, respectivamente, em 35 e em 23 deles. As provas funcionais respiratórias mostraram: espirografia normal em 17; obstrutivo em 32 e misto em 9 doentes. O espaço morto foi superior a 35% em 25 e a ventilação alveolar minuto estava elevada em 54. A diferença alvéolo-arterial de Oxigênio estava aumentada em todos. A análise estatística revelou associação significativa entre radiologia: evolução radiológica e a função pulmonar. A Pbmicose em doentes tabagistas inveterados conduziu ao enfisema, enquanto que as modificações alvéolo-arteriais anoxêmicas propiciaram a disseminação da Doença de Lutz.

Evaluation of the allergenicity of spore and mycelia extracts of Pisolithus tinctorius

The antigenic and allergenic chemical analysis of spore and mycelia extracts of Pisolithus tinctorius was carried out. The spores were collected from basidiocarps in plantations of Eucalyptus spp and the mycelia from culture in MNM medium. With basis on the fungus growth curve, the mycelia masses were obtained after 10, 20, 30, and 40 days of incubation, which correspond, respectively, to the beginning, middle and end of the log phase, and beginning of the decline phase. The mycelia masses, together with the spores, were submitted to the action of three extractors (Coca, Tris-HCl, and ammonium bicarbonate). The contents of carbohydrates and proteins were determined. The SDS-PAGE electrophoretical analysis revealed separate fractions in these extracts, besides common fractions, in function of cultivation time and extraction methods. The selected extracts for the allergic tests were the ones with the highest number of fractions. The prick-tests were conducted in 374 patients – rural workers, eucalyptus plantation works and college students. The positivity to the "prick test" with the antigenic extract of P. tinctorius was, respectively, 3.78%, 28.20% and 6.40%. Most prick-test positive patients (82.75%) also presented symptoms of respiratory allergy (asthma and rhinitis). There was no reactivity difference when the spore and mycelia extracts were employed. The analysis of the positive patients’ sera revealed the presence of IgE specific to the P. tinctorius antigens. Since Pisolithus tinctorius is found as mycorrhyza of Eucalyptus spp, and this plant is used in reforestation in most countries, the importance of that fungus should be regarded as a possible cause of respiratory allergies, especially in occupationally exposed workers

Comparative study of the fecundity and fertility of Biomphalaria glabrata (Say, 1818) and Biomphalaria straminea (Dunker, 1848) in a laboratory through self-fertilization and cross-fertilization

The aim of this study was to compare the fecundity and fertility of B. glabrata and B. straminea by cross- and self-fertilization. To attain this objective, laboratory-raised strains of B. glabrata and B. straminea were used. The former originated from natural breeding grounds in the municipality Paulista, state of Pernambuco, Brazil. The latter originated from irrigation ditches in the municipality of Petrolândia, in the same state. Snail populations of B. glabrata and B. straminea were maintained for 240 days in laboratory. Their fecundity was evaluated by noting the number of egg-masses, eggs and eggs per mass. Their fertility was evaluated by the number of viable eggs and the hatching rate. B. straminea was markedly more fecund than B. glabrata through cross- and self-fertilization, namely: greater egg-mass; higher egg production and more eggs per mass. Regarding fertility, there seemed to be no preferential period for occlusion to occur or a trend in the rhythm of producing viable eggs.

Primary pulmonary AIDS-related lymphoma

Extranodal involvement is common in lymphomas associated with human immunodeficiency virus infection (HIV) and acquired immunodeficiency syndrome (AIDS). However, primary pulmonary AIDS-related non-Hodgkin's lymphoma is very rare and only few reports were published in the medical literature. Clinical presentation is nonspecific, with "B" and respiratory symptoms. Also, patients were with advanced immunodeficiency at the time of diagnosis. Generally, chest radiography showed peripheral nodules or cavitary masses. Primary pulmonary lymphoma associated with AIDS is generally a high-grade B-cell non-Hodgkin lymphoma and Epstein-Barr virus is strongly associated with the pathogenesis of these tumors. We report a patient with AIDS and primary pulmonary lymphoma which clinical presentation was a total atelectasis of the left lung.

Primary liver AIDS-related lympoma

Non-Hodgkin's lymphomas (NHL) are the second most frequent malignancies in AIDS patients. The majority of NHL associated with AIDS involves extranodal sites, especially the digestive tract and the central nervous system. Primary liver lymphoma (PLL) is an uncommon neoplasm among these patients. Ultrasonography and computed tomography scans may be helpful in the diagnosis of focal hepatic lymphoma. Image-guided fine-needle biopsy with histopathology of the liver lesions is the gold standard for the diagnosis of hepatic lymphoma. We report a case of PLL as the initial manifestation of AIDS in a patient without any previous infection by hepatitis C or B virus, presented as multiple and large hepatic masses.

Endobronchial leiomyoma: an unusual non-defining neoplasm in a patient with AIDS

Smooth muscle neoplasms are more frequent in human immunodeficiency infected children than in HIV seropositive adults. Endobronchial leiomyoma is a rare benign tumor in HIV infected adult patients. Epstein-Barr virus (EBV) has been implicated in the pathogenesis of these tumors. Here we describe an adult patient with HIV infection with atelectasis of the left upper pulmonary lobe as the first clinical expression of an intrabronchial leiomyoma. In this case, we can not show the association with EBV. Our report suggests that smooth muscle tumors as leiomyoma should be included in the differential diagnosis of endobronchial masses in AIDS patients.

Human ocular sparganosis in southern Brazil

We report the first case of human ocular sparganosis in the state of Santa Catarina, southern Brazil. A young female patient presented with three periocular moveable inflammatory masses in her right eye, during two years. By surgical excisional biopsy, a helminth larval stage was removed and identified as sparganum. Clinical, laboratory and epidemiological data on this parasite are presented.

PARACOCCIDIOIDOMYCOSIS TREATMENT

SUMMARYConsidered to be an emerging endemic mycosis in Latin America, paracoccidioidomycosis is characterized by a chronic course and involvement of multiple organs in immunocompromised hosts. Infection sequelae are mainly related to pulmonary and adrenal insufficiency. The host-parasite interaction results in different expressions of the immune response depending on parasite pathogenicity, fungal load and genetic characteristics of the host. A few controlled and case series reports have shown that azoles and fast-acting sulfa derivatives are useful treatment alternatives in milder forms of the disease. For moderate/severe cases, more prolonged treatments or even parenteral routes are required especially when there is involvement of the digestive tract mucosa, resulting in poor drug absorption. Although comparative studies have reported that shorter treatment regimens with itraconazole are able to induce cure in chronically-infected patients, there are still treatment challenges such as the need for more controlled studies involving acute cases, the search for new drugs and combinations, and the search for compounds capable of modulating the immune response in severe cases as well as the paradoxical reactions.

Identificação do Trypanosoma cruzi nos tecidos extracardíacos de portadores de miocardite crônica chagásica

Em autópsias realizadas durante 20 anos em portadores de miocardite crônica chagásica parasitologicamente comprovados, foi realizada uma pesquisa exaustiva das formas tissulares do Trypanosoma cruzi nas secções histológicas de vários órgãos. Os parasitos intracelulares foram encontrados nos tecidos extracardíacos em 11 casos (55%), a saber: tubo digestivo (10 vezes), adrenal (6 vezes) e em vários outros órgãos (1 vez cada). A presença dos parasitos se associava com discreta infiltração mononuclear focal, mas, o mais das vezes, não havia qualquer alteração. O estudo mostra que as formas de multiplicação do T. cruzi tendem a se distribuir amplamente na infecção crônica, mas como são escassas, o seu encontro depende de pesquisa minuciosa. Um fato interessante é que somente no miocárdio os parasitos aparecem associados com inflamação crônica, difusa, progressiva e fibrosante.

Acometimento da supra-renal associado à paracoccidioidomicose

A supra-renal foi estudada em 60pacientes com paracoccidioidomicose. Dentre eles, 10(16,7%) apresentavam alterações anatômicas ou funcionais das supra-renais. As lesões glandulares associaram-se à paracoccidioidomicose disseminada, com evolução da doença de pelo menos cinco anos sem tratamento e com hipotensão arterial sistêmica. Não houve associação entre alterações anatomoclínicas supra-renais e alterações raáiolôgicaspulmonares. Esses dados revelam a importância da avaliação sistemática da função supra-renal em portadores de formas disseminadas da paracoccidioidomicose.