Testosterone increases GLUT4-dependent glucose uptake in cardiomyocytes.

Testosterone exerts important effects in the heart. Cardiomyocytes are target cells for androgens, and testosterone induces rapid effects via Ca(2+) release and protein kinase activation and long-term effects via cardiomyocyte differentiation and hypertrophy. Furthermore, it stimulates metabolic effects such as increasing glucose uptake in different tissues. Cardiomyocytes preferentially consume fatty acids for ATP production, but under particular circumstances, glucose uptake is increased to optimize energy production. We studied the effects of testosterone on glucose uptake in cardiomyocytes. We found that testosterone increased uptake of the fluorescent glucose analog 2-(N-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl)amino)-2-deoxyglucose and [(3) H]2-deoxyglucose, which was blocked by the glucose transporter 4 (GLUT4) inhibitor indinavir. Testosterone stimulation in the presence of cyproterone or albumin-bound testosterone-induced glucose uptake, which suggests an effect that is independent of the intracellular androgen receptor. To determine the degree of GLUT4 cell surface exposure, cardiomyocytes were transfected with the plasmid GLUT4myc-eGFP. Subsequently, testosterone increased GLUT4myc-GFP exposure at the plasma membrane. Inhibition of Akt by the Akt-inhibitor-VIII had no effect. However, inhibition of Ca(2+) /calmodulin protein kinase (CaMKII) (KN-93 and autocamtide-2 related inhibitory peptide II) and AMP-activated protein kinase (AMPK) (compound C and siRNA for AMPK) prevented glucose uptake induced by testosterone. Moreover, GLUT4myc-eGFP exposure at the cell surface caused by testosterone was also abolished after CaMKII and AMPK inhibition. These results suggest that testosterone increases GLUT4-dependent glucose uptake, which is mediated by CaMKII and AMPK in cultured cardiomyocytes. Glucose uptake could represent a mechanism by which testosterone increases energy production and protein synthesis in cardiomyocytes.

Histological comparison of DBBM and platelet rich fibrin for guided bone regeneration in a rabbit model.

PURPOSE: To histologically evaluate the use of bovine derived deproteinized xenograft (DBBM), leukocyte and platelet rich fibrin (L-PRF) and the combination of both in Guided Bone Regeneration (GBR) performed in non-critical size defects in rabbit. METHODS: A prospective experimental study was performed. Four bone defects in the tibiae of 12 rabbits were made and each of them was filled with DBBM, L-PRF, a combination of DBBM + L-PRF or was left to heal as control site. All defects were covered with a collagen membrane. Rabbits were randomly distributed in three groups and euthanatized at 3, 6 or 9 weeks. Samples were obtained and histologically analyzed to determine vital bone, connective tissue and remaining graft particles percentage. Analysis of variance, Kruskal Wallis and non-paired t-test where used to evaluate the significance of the results. RESULTS: At 3 weeks of healing, DBBM showed significantly more vital bone percentage than L-PRF (p = 0,05) and DBBM + L-PRF showed significantly less connective tissue than control (p < 0,05). All other groups showed no statistical difference between them. At 6 weeks of healing, DBBM showed significantly more vital bone percentage than L-PRF (p < 0,05), DBBM + L-PRF (p < 0,05) and control (p < 0,05) and there wasn't any other significant difference regarding to connective tissue or remaining particle percentage between groups. At t 9 weeks healing period, there weren't any significant differences between groups. CONCLUSIONS: DBBM seems to enhance vital bone formation at early healing stages. The use of L-PRF alone or combined with DBBM, didn't show any histological improvement regarding to vital bone formation. The use of DBBM, alone or in conjunction with L-PRF showed a trend to reduce connective tissue percentage. The use of L-PRF combined with DBBM didn't affect the remaining particle percentage.

Sarcopenia and Androgens: A Link between Pathology and Treatment.

Sarcopenia, the age-related loss of skeletal muscle mass and function, is becoming more prevalent as the lifespan continues to increase in most populations. As sarcopenia is highly disabling, being associated with increased risk of dependence, falls, fractures, weakness, disability, and death, development of approaches to its prevention and treatment are required. Androgens are the main physiologic anabolic steroid hormones and normal testosterone levels are necessary for a range of developmental and biological processes, including maintenance of muscle mass. Testosterone concentrations decline as age increase, suggesting that low plasma testosterone levels can cause or accelerate muscle- and age-related diseases, as sarcopenia. Currently, there is increasing interest on the anabolic properties of testosterone for therapeutic use in muscle diseases including sarcopenia. However, the pathophysiological mechanisms underlying this muscle syndrome and its relationship with plasma level of androgens are not completely understood. This review discusses the recent findings regarding sarcopenia, the intrinsic, and extrinsic mechanisms involved in the onset and progression of this disease and the treatment approaches that have been developed based on testosterone deficiency and their implications.

First report on the diagnosis and treatment of encephalic and urinary paracoccidioidomycosis in a cat.

A male Persian cat was presented with persistent fever, anorexia, weakness, hypopyon, nystagmus, and intention tremors. The hemogram showed severe neutropenia and laboratory analysis on cerebrospinal fluid (CSF) smears revealed abundant yeast cells compatible with Paracoccidioides brasiliensis. Urinalysis demonstrated persistent funguria and an increased urine protein-to-creatinine ratio (UPC) in addition to mild azotemia. Long-term therapy with oral fluconazole was effective in controlling the nervous system signs. Funguria was resolved with subcutaneous administration of diluted amphotericin B in a large volume of saline solution for a period of 12 weeks during the second year after initial diagnosis. Throughout 5 years of treatment, no adverse effects were observed and tolerance to the drugs was normal. Due to development of progressive uremic syndrome the animal was euthanased. To the best of our knowledge, this report is the first clinical case described of a nervous and urinary system infection caused by the P brasiliensis in a cat.