Ultrastructural and proliferative features of the ventral lobe of the prostate in non-obese diabetic mice (NOD) following androgen and estrogen replacement associated to insulin therapy

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Immune modulation induced by tuberculosis DNA vaccine protects non-obese diabetic mice from diabetes progression

We have described previously the prophylactic and therapeutic effect of a DNA vaccine encoding the Mycobacterium leprae 65 kDa heat shock protein (DNA-HSP65) in experimental murine tuberculosis. However, the high homology of this protein to the corresponding mammalian 60 kDa heat shock protein (Hsp60), together with the CpG motifs in the plasmid vector, could trigger or exacerbate the development of autoimmune diseases. The non-obese diabetic (NOD) mouse develops insulin-dependent diabetes mellitus (IDDM) spontaneously as a consequence of an autoimmune process that leads to destruction of the insulin-producing beta cells of the pancreas. IDDM is characterized by increased T helper 1 (Th1) cell responses toward several autoantigens, including Hsp60, glutamic acid decarboxylase and insulin. In the present study, we evaluated the potential of DNA-HSP65 injection to modulate diabetes in NOD mice. Our results show that DNA-HSP65 or DNA empty vector had no diabetogenic effect and actually protected NOD mice against the development of severe diabetes. However, this effect was more pronounced in DNA-HSP65-injected mice. The protective effect of DNA-HSP65 injection was associated with a clear shift in the cellular infiltration pattern in the pancreas. This change included reduction of CD4(+) and CD8(+) T cells infiltration, appearance of CD25(+) cells influx and an increased staining for interleukin (IL)-10 in the islets. These results show that DNA-HSP65 can protect NOD mice against diabetes and can therefore be considered in the development of new immunotherapeutic strategies.

Bacille Calmette-Guérin/DNAhsp65 prime-boost is protective against diabetes in non-obese diabetic mice but not in the streptozotocin model of type 1 diabetes

Type I diabetes is a disease caused by autoimmune destruction of the beta cells in the pancreas that leads to a deficiency in insulin production. The aim of this study was to evaluate the prophylactic potential of a prime-boost strategy involving bacille Calmette-Guérin (BCG) and the pVAXhsp65 vaccine (BCG/DNAhsp65) in diabetes induced by streptozotocin (STZ) in C57BL/6 mice and also in spontaneous type 1 diabetes in non-obese diabetic (NOD) mice. BCG/DNAhsp65 vaccination in NOD mice determined weight gain, protection against hyperglycaemia, decreased islet inflammation, higher levels of cytokine production by the spleen and a reduced number of regulatory T cells in the spleen compared with non-immunized NOD mice. In the STZ model, however, there was no significant difference in the clinical parameters. Although this vaccination strategy did not protect mice in the STZ model, it was very effective in NOD mice. This is the first report demonstrating that a prime-boost strategy could be explored as an immunomodulatory procedure in autoimmune diseases. © 2013 British Society for Immunology.

Central leptin replacement enhances chemorespiratory responses in leptin-deficient mice independent of changes in body weight

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Effect of combined hormonal and insulin therapy on the steroid hormone receptors and growth factors signalling in diabetic mice prostate

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Effects of experimental diabetes on the structure and ultrastructure of the coagulating gland of C57BL/6J and NOD mice

Diabetes mellitus can lead to reproductive disorders that in turn result in weakened fertility brought about by morphofunctional changes in the testes and accessory sex glands. However, doubts persist concerning the basic biology of the secretory epithelial cells and the stroma of the coagulating gland of diabetic mice. Thus, the objective of the present study was to analyze the histological and ultrastructural changes associated with stereology of the coagulating gland of mice with alloxan-induced diabetes, and of spontaneously diabetic mice. Sixteen mice of the C57BL/6J strain, and eight non-obese diabetic (NOD) mice were used. The animals were divided into three groups: 1) control (C), 2) alloxan diabetic (AD), and 3) NOD. Thirty days after the detection of diabetic status in group 2, all of the animals were killed and then perfused with Karnovsky's solution through the left cardiac ventricle. The coagulating gland was then removed and processed for morphometric study by light microscopy and electron microscopy. The results showed thickening of the stroma, atrophy of secretory epithelial cells, and disorganization of the organelles involved in the secretory process in both NOD and alloxan-induced mice. Thus, it may be concluded that the coagulating gland suffered drastic morphological changes, and consequently impaired glandular function, in the presence of diabetes mellitus type I in both NOD and AD mice. (C) 2003 Wiley-Liss, Inc.

Trafficking of phagocytic peritoneal cells in hypoinsulinemic-hyperglycemic mice with systemic candidiasis

Background: Candidemia is a severe fungal infection that primarily affects hospitalized and/or immunocompromised patients. Mononuclear phagocytes have been recognized as pivotal immune cells which act in the recognition of pathogens, phagocytosis, inflammation, polarization of adaptive immune response and tissue repair. Experimental studies have showed that the systemic candidiasis could be controlled by activated peritoneal macrophages. However, the mechanism to explain how these cells act in distant tissue during a systemic fungal infection is still to be elucidated. In the present study we investigate the in vivo trafficking of phagocytic peritoneal cells into infected organs in hypoinsulinemic-hyperglycemic (HH) mice with systemic candidiasis. Methods: The red fluorescent vital dye PKH-26 PCL was injected into the peritoneal cavity of Swiss mice 24 hours before the intravenous inoculation with Candida albicans. After 24 and 48 hours and 7 days of infection, samples of the spleen, liver, kidneys, brain and lungs were submitted to the microbiological evaluation as well as to phagocytic peritoneal cell trafficking analyses by fluorescence microscopy. Results: In the present study, PKH+ cells were observed in the peritoneum, kidney, spleen and liver samples from all groups. In infected mice, we also found PKH+ cells in the lung and brain. The HH condition did not affect this process. Conclusions: In the present study we have observed that peritoneal phagocytes migrate to tissues infected by C. albicans and the HH condition did not interfere in this process. © 2013 Fraga-Silva et al.; licensee BioMed Central Ltd.

Leptin into the ventrolateral medulla facilitates chemorespiratory response in leptin-deficient (ob/ob) mice

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Metabolic profile response to administration of epigallocatechin-3-gallate in high-fat-fed mice

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