RESUMO

SUMMARY: The Viperidae venoms are composed of a mixture of constituents with enzymatic and non-enzymatic actions, which act on ultrastructural components of cells and tissues. Here, the number of mitochondria, mitochondrial area and the number of mitochondrial cristae from adrenal glands cortex treated with snake venoms were tested after 3, 6 and 24 hours of venom injections. The mitochondria quantitative changes showed a statistically significant decrease, in the number of mitochondria past 3, 6 and 24 h. There was an increase in the mitochondrial area after 6 h, where Crotalus vegrandis venom did not present significant differences with Crotalus pifanorum or Bothrops venezuelensis venoms. After 24 h, there was an escalation of mitochondrial area in all tested venoms. The number of mitochondrial cristae after 3 h did not present important differences with the control treatment. After 6 h, the number of mitochondrial cristae initiated to decrease under the activities of the 3 venoms action, until 24 h of observation. In the qualitative observations it was possible to witness an intense damage of the mitochondria, with loss and swelling of membranes, disappearance of cristae and the appearance of myelin figures, which started at 3 h after the Crotalus and Bothrops venoms injections. These damages probably were due to cytotoxic effects of phospholipases, metalloproteases and/or other proteolytic activities present in Viperidae snake venoms, being more evident in Crotalus venoms. As far as we know, these results define a novel finding that suggest that Viperidae snake venoms are extremely toxic to mammalian mitochondria.

RESUMEN: Los venenos de Viperidae tienen acciones enzimáticas y no enzimáticas, que actúan sobre la estructura celular. Aquí se probaron, a las 3, 6 y 24 horas de la inyección del veneno, el número de mitocondrias, el área mitocondrial y el número de crestas mitocondriales de la corteza de las glándulas adrenales. Los cambios cuantitativos de las mitocondrias mostraron una disminución en el número de mitocondrias a las 3, 6 y 24 h. Hubo un aumento en el área mitocondrial a las 6 h, donde el veneno de la serpiente Crotalus vegrandis no presentó diferencias significativas con los venenos de Crotalus pifanorum o Bothrops venezuelensis. Después de 24 h, hubo un aumento del área mitocondrial en todos los venenos. El número de crestas mitocondriales a las 3 h no presentó alteraciones o diferencias importantes con el tratamiento de control. Después de 6 h, el número de crestas mitocondriales comenzó a disminuir bajo la acción de los 3 venenos, hasta las 24 h de observación. En las observaciones cualitativas se observó un daño intenso de las mitocondrias, con pérdida y edema de las membranas, desaparición de las cristae y aparición de figuras mielínicas, que comenzó a las 3 h después de las inyecciones de veneno de Crotalus y Bothrops. Estos daños se debieron factiblemente a los efectos citotóxicos de componentes proteolíticos de los venenos. Creemos que estos resultados definen un nuevo y original hallazgo, que sugiere que los venenos de serpiente Viperidae son extremadamente tóxicos para las mitocondrias de mamíferos.

Assuntos

Assuntos

RESUMO

Hipertensão secundária corresponde aproximadamente a 5 a 10% das causas de hipertensão arterial e, entre elas, o hiperaldosteronismo primário apresenta uma incidência variável de 0,05 a 2% em hipertensos, com quadro característico de hipocalemia, produção aumentada de aldosterona, redução ou supressão da renina, relação aldosterona/renina elevada e alcalose metabólica. Descrevemos um caso de paciente com hipertensão arterial primária controlada, que apresentou na sua evolução um adenoma de supra-renal com piora dos níveis tensionais.

Assuntos

Assuntos

RESUMO

When mice were infected with virulent Mycobacterium tuberculosis H37Rv by the intra-tracheal route, there was an early phase of adrenal hyperplasia, histologically resembling the adrenocorticotropic (ACTH)-driven changes seen in Cushing's disease. This was followed at 3 weeks by progressive atrophy until the weight of the adrenals was approximately 50% of that seen in control uninfected mice, in spite of the fact that the adrenals were not infected. All layers of the adrenal cortex were affected, but the medulla was normal. Electron microscope studies revealed apoptosis. The switch from adrenal hyperplasia to adrenal atrophy corresponded to onset of an IgG1 response recognising a wide range of mycobacterial components in Western blots. Delayed type hypersensitivity (DTH) responses were seen throughout, but differed in their sensitivity to TNF alpha. Thus if TNF alpha was injected at 24 h into DTH sites elicited during the phase of adrenal hyperplasia, there was no increment in swelling at 48 h. However similar injections of TNF alpha resulted in a doubling of the swelling in DTH sites elicited during the phase of adrenal atrophy. This may be relevant to the pathogenesis of cytokine-mediated tissue damage in the human disease. If 2 months before mice received the intratracheal infection, they were pre-immunised with 1 x 1097) autoclaved Mycobacterium vaccae, a stimulus previously shown to induce a Th1 pattern of response, the early increase in adrenal weight was attenuated and delayed, and the subsequent atrophy did not occur. In sharp contrast, pre-immunisation with 1 x 10(9) autoclaved M. vaccae, known to prime a mixed pattern of cytokine release (IFN gamma and IL-4), resulted in adrenal atrophy that began within 4 days of infection, and was complete by day 14. These results suggested that the pattern of cytokine release provoked by the infection, modulated the adrenal changes, perhaps in synergy with products derived from the organisms themselves. Since we have already shown that profound adrenal changes also occur in human tuberculosis, we now propose that a change somewhere in the cytokine-hypothalamo-pituitary-adrenal axis may underlie the T cell dysfunction and immunologically-mediated tissue damage in this disease.

Assuntos

RESUMO

In this work we confirm by a metabolic method the existence of at least two enzymes with 11 beta- and 18-hydroxylase activities in rat adrenal mitochondria. The method was based on the ability of cortisol (F), a foreign alternative substrate, to inhibit competitively metabolite productions from various precursors. F inhibited a) aldosterone (ALDO) production from 11-deoxycorticosterone (DOC) without affecting the yields of corticosterone (B) and 18-hydroxy-11-deoxycorticosterone (18-OHDOC); b) 18-hydroxycorticosterone and aldosterone productions from B (Ki = 2.5 +/- 0.5 microM); and c) ALDO production from 18-OHDOC. These results suggest the existence of two categories of enzymes with both 11 beta- and 18-hydroxylase activities, one comprising those that catalyze the conversions of DOC to B and 18-OHDOC (F-insensitive reactions [FIS]) and the other one comprising the enzymes involved in the conversions of B to 18-OHB and ALDO and that of 18-OHDOC to ALDO (F-sensitive reactions [FS]). The cloned enzymes CYP11B1 and CYP11B2 would pertain respectively to the FIS and FS categories.

Assuntos

RESUMO

Corticosterone (B) and 18-hydroxy-11-deoxycorticosterone (18OHDOC) but not 11-deoxycorticosterone (DOC) displaced cortisol (F) specifically bound to rat adrenal mitochondria. F. competitively inhibited aldosterone formation from B, 18OHB and 18OHDOC but did not inhibit conversions of DOC to B or 18OHDOC. High concentrations of DOC increased its conversion to 18OHDOC rather than B.

Assuntos

RESUMO

The implantation of histotypic adrenal gland cultures is described in the present study. The cultures were prepared from mice at birth and were rotary incubated for 10 days. When the cells reached phenotypic maturation, they were implanted in the dermal bed of the auricular pavilion of young adult mice. This location was ideal for implantation because transillumination enabled daily inspection of the progress of implant survival. Twenty days after implantation, the implants and associated tissues were removed to study the degree of maturation and the viability of the implants. Some cultures showed a moderate percentage of steroidal cells, while others demonstrated a high predominance of the chromaffin cells. All the implanted cultures successfully survived a postoperative period of 20 days. Both adrenergic and noradrenergic cells reached their maximum grade of cytological differentiation and neither inflammatory reactions nor adverse immunological effects were observed. On the contrary, the implants were profusely vascularized by the host tissue, particularly in those implants with a higher content of chromaffin cells.

Assuntos

RESUMO

The distributions of tyrosine hydroxylase (TH), protein gene product (PGP) 9.5, calcitonin gene-related peptide (CGRP), and peptide histidine isoleucine (PHI) have been examined immunohistochemically in the adrenal gland of the snake Waglerophis merremii. The morphology of chromaffin cells and the presence of ganglionic neurons in the gland revealed by means of the glutaraldehyde-silver technique and electron microscopy are also described. Two distinct types of TH-immunoreactive (-IR) cells are present in the dorsal noradrenergic ribbon: small chromaffin cells and a larger type identified as ganglionic neurons. Small, mostly round or fusiform cells often displayed long processes. Ganglionic cells, arranged in patches, had long processes entering the cortex of the gland. Chromaffin adrenergic cells, forming small groups of 4-7 cells, were scattered within the interrenal tissue and had a wide variety of shapes with processes that appeared to contact other chromaffin cells. Bundles of PGP 9.5-IR fibers occurred in the subcapsular zone of the adrenal gland with fibers entering the cortex and dorsal noradrenergic ribbon of the gland. Thick and thin TH-IR fibers were seen. Thick TH-IR fibers were nonvaricose and appeared to originate mainly in ganglionic neurons. Thin TH-IR fibers with small varicosities were numerous in the interrenal tissue and were frequently seen between clusters of adrenergic cells in close apposition to cortical cells and vessels. CGRP-IR fibers were present throughout the entire adrenal gland, whereas PHI-IR fibers had a preferential distribution in the interrenal tissue. Both CGRP- and PHI-IR fibers were closely associated with vessels and cortical cells.

Assuntos