Objective: This study investigated the effect of interval training on blood biochemistry and immune parameters in type 1 diabetic rats. Materials and methods: Male Wistar rats were divided into four groups: sedentary (SE, n = 15), interval training (IT, n = 17), diabetic sedentary (DSE, n = 17), diabetic interval training (DIT, n = 17). Diabetes was induced by i.v. injection of streptozotocin (60 mg/kg). Swimming Interval Training consisted of 30-s exercise with 30-s rest, for 30 minutes, during 6 weeks, four times a week, with an overload of 15% of body mass. Plasma glucose, lactate, triacylglycerol and total cholesterol concentrations, phagocytic capacity, cationic vesicle content, and superoxide anion and hydrogen peroxide production by blood neutrophils and peritoneal macrophages were evaluated. Proliferation of mesenteric lymphocytes was also estimated. Results: Interval training resulted in attenuation of the resting hyperglycemic state and decreased blood lipids in the DIT group. Diabetes increased the functionality of blood neutrophils and peritoneal macrophages in the DSE group. Interval training increased all functionality parameters of peritoneal macrophages in the IT group. Interval training also led to a twofold increase in the proliferation of mesenteric lymphocytes after 6 weeks of exercise in the DIT group. Conclusion: Low-volume high-intensity physical exercise attenuates hyperglycemia and dislipidemia induced by type 1 diabetes, and induces changes in the functionality of innate and acquired immunity. Arq Bras Endocrinol Metab. 2013;57(8):594-602 Keywords Interval training; diabetes mellitus; immune system; hyperglycemia RESUMO Objetivo: Este estudo investigou os efeitos do treinamento intervalado sobre parâmetros bioquí-micos e imunológicos em ratos diabéticos do tipo 1. Materiais e métodos: Ratos Wistar machos foram divididos em quatro grupos: sedentário (SE, n = 15), treinamento intervalado (TI, n = 17), sedentário diabético (SED, n = 17) e treinamento intervalado diabético (TID, n = 17). O diabetes foi induzido por uma injeção intravenosa de estreptozotocina (60 mg/kg). O treinamento intervalado de natação consistiu de 30s de exercício com 30s de recuperação, 30 minutos, durante 6 semanas, 4 vezes por semana, com sobrecarga de 15% da massa corporal. Foram avaliados glicemia, lactato sanguíneo, concentração de triacilglicerol e colesterol total, capacidade fagocítica, conteúdo de vesí-culas catiô nicas, produção de ânion superóxido e peróxido de hidrogênio por neutrófilos sanguíneos e macrófagos peritoneais. A proliferação de linfócitos mesentéricos também foi avaliada. Resultados: O treinamento intervalado resultou em atenuação do estado hiperglicêmico e diminuiu os lipídeos sanguíneos no grupo TID. O diabetes aumentou a funcionalidade dos neutrófilos sanguíneos e macrófagos peritoneais do grupo SED. O treinamento intervalado aumentou todos os parâmetros funcionais dos macrófagos peritoneais do grupo TI. O treinamento intervalado também aumentou duas vezes a proliferação dos linfóci...

Fabry disease (FD) clinical manifestations often start in childhood. Among the FD complications, renal failure causes significant morbidity and mortality. Early diagnosis and treatment of FD nephropathy in children may be critical to preserve renal function. In proteinuric progressive nephropathies it has been described that pro-fibrotic miR-21, miR-192, and miR-433 families are activated and that anti-fibrotic miR-29 and miR-200 families are inhibited. Objective: Analyze urinary excretion of microRNAs related to renal fibrosis in FD patients with mild or absent nephropathy. Patients with confirmed diagnosis of FD under 18 years of age were compared with healthy subjects. Patients were classified into two groups: 1) Patients with urinary excretion profile of microRNAs indicative of renal fibrosis; and 2) Patients with urinary excretion profile of microRNAs not indicative of renal fibrosis. Results: 9 healthy subjects were enrolled in the study (18.66 ± 13.43 years), 4 males and 5 females. All of them presented normal eFGR without pathological albuminuria. FD population: 12 patients (10.33 ± 3.93 years) were studied, 5 males and 7 females. Patients presented 2 different genotypes: L415P (6 patients) and E398X (6 patients). The urinary excretion profile of microRNAs indicative of renal fibrosis was present in 4 patients (2 with L415P genotype and 2 with E398X genotype), all of them with a decreased of miR-29 and/or miR-200. No patient presented increased miR-21, miR-192 and/or miR-433. Decreased α-galA activity was the only variable associated with statistical significance (p ≤ 0.01) to urinary excretion profile of microRNA indicative of

Damage in fish activates retina repair that restores sight. The purinergic signalling system serves multiple homeostatic functions and has been implicated in cell cycle control of progenitor cells in the developing retina. We examined whether changes in the expression of purinergic molecules were instrumental in the proliferative phase after injury of adult zebrafish retinas with ouabain. P2RY messenger RNA (mRNA) increased early after injury and showed maximal levels at the time of peak progenitor cell proliferation. Extracellular nucleotides, mainly ADP, regulate P2RY transcriptional and protein expression. The injury-induced upregulation of P2RY is mediated by an autoregulated mechanism. After injury, the transcriptional expression of ecto-nucleotidases and ecto-ATPases also increased and ecto-ATPase activity inhibitors decreased Müller glia-derived progenitor cell amplification. Inhibition of P2RY endogenous activation prevented progenitor cell proliferation at two intervals after injury: one in which progenitor Müller glia mitotically activates and the second one in which Müller glia-derived progenitor cells amplify. ADPβS induced the expression of lin28a and ascl1a genes in mature regions of uninjured retinas. The expression of these genes, which regulate multipotent Müller glia reprogramming, was significantly inhibited by blocking the endogenous activation of P2RY early after injury. We consistently observed that the number of glial fibrillary acidic protein-BrdU-positive Müller cells after injury was larger in the absence than in the presence of the P2RY antagonist. Ecto-ATPase activity inhibitors or P2RY-specific antagonists did not modify apoptotic cell death at the time of peak progenitor cell proliferation. The results suggested that ouabain injury upregulates specific purinergic signals which stimulates multipotent progenitor cell response.

Further characterization of an aspartyl protease from Mucor bacilliformis with milk-clotting activity was performed. An extinction coefficient, epsilon 278 cm = 1.61 mL/mg/cm, a molecular mass of 35,400 Da and a pI of 5.2 were determined. Proteolytic activity and kinetic parameters were evaluated by using the hexapeptide Leu-Ser-pNO2-Phe-Nle-Ala-Leu-OMe as the substrate. The effect of pH and temperature on peptide cleavage, as well as protease heat stability, was determined. Such properties, taken as a whole, indicate that the M. bacilliformis protease can be considered a potential substitute for bovine chymosin in cheese manufacture.

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Introduction. In advanced Fabry nephropathy stages, enzyme replacement theraphy (ERT) efficacy decreases, due to its impossibility to reverse renal fibrosis. Therefore, the finding of early kidney fibrosis biomarkers in affected patients is of interest. During renal fibrosis miR-21, miR-192 and miR-433 (fibrosis promotors) are activated by transforming growth factor-β (TGF-β), and miR-29 and miR-200 family (fibrosis supressors) are inhibited by TGF-β. The aim of this study is to analyze the probability that Fabry disease (FD) patients with some clinical variables can present an urinary microRNAs excretion profile indicative of renal fibrosis through a logistic regression analysis. Results. A population of 34 participants was included: 24 FD patients and 10 controls. 16/24 (66.66%) FD patients presented microRNAs urinary excretion profile indicative of renal fibrosis. This profile was observed by decrease of fibrosis suppresors miR-29 and miR-200 and not by increase of fibrosis promotors miR-21, miR192, and miR-433. Hypohidrosis, angiokeratomas, neuropathic pain, hearing loss, cardiac involvement, male gender, reduced αGalA activity, and renin-angiotensin-aldosterone system inhibitors treatment are associated with the appearance of amicroRNAs urinary excretion profile indicative of renal fibrosis. A probable beneficial effect on urinary microRNAs excretion profile was observed in patients receiving ERT with agalsidase beta. The correlation between parameters of renal function with each family of microRNAs was studied. The only association with statistical significance was found between miR-21 and urine albumin-creatinine ratio (p =0.021). Conclusions. A probable microRNAs regulation not mediated by TGF-β should be considered or TGF-β has a different effect in FD than in other nephropathies on microRNAs regulation. Typical clinical manifestations of classic FD are associated with appearance of urinary microRNAs profile indicative of renal fibrosis. FD patients express renal fibrosis biomarkers in urine prior to onset of pathological albuminuria. A direct correlation between urinary miR-21 and degree of albuminuria was observed.

Renal involvement is associated with a greater morbidity and mortality in Fabry disease. Pathological albuminuria, the first Fabry nephropathy clinical manifestation, can occur from early childhood, although histological lesions such as tubulo-interstitial fibrosis and glomerulosclerosis are present or may precede the onset of pathological albuminuria. In renal cells, exposure to Lyso-Gb3 is correlated with increased expression of Transforming Growth Factor-βeta (TGF-β). miR-21, miR-192, and miR-433 that promote fibrosis are activated by TGF-β, and miR-29 and miR-200 that suppress fibrosis are inhibited by TGF-β. A 23-year-old male was diagnosed with FD. αGalA decreased enzyme activity: 0.1 nmol/hour/liter; genotype: [c.317T>G (p.L106R)]; GFR: 104.4 mL/min/m2; urinary albumin excretion: 6.00 mg/day; plasma Lyso-Gb3: 124.5 nmol/L. A decrease urinary excretion of miR-29 and miR-200 was found (p <0.005) compared to controls. In addition to its usefulness as a phenotype marker, Lyso-Gb3 has been proposed as an indicator of therapeutic response. We detect an association of high Lyso-Gb3 plasma values with decreased urinary excretion of miRNAs with known antifibrotic effect (miR-29 and miR-200). Although the present work is a case report, it could be hypothesized that one of the harmful Lyso-Gb3 effects could be the miRNAs regulation through changes in TGF-β expression.