The Relationship between Type 1 Diabetes Mellitus, TNF-α, and IL-10 Gene Expression.

Type 1 diabetes mellitus (T1DM) is one of the major chronic diseases in children worldwide. This study aimed to investigate interleukin-10 (IL-10) gene expression and tumor necrosis factor-alpha (TNF-α) in T1DM. A total of 107 patients were included, 15 were T1DM in ketoacidosis, 30 patients had T1DM and HbA1c ≥ 8%; 32 patients had T1DM and presented HbA1c < 8%; and 30 were controls. The expression of peripheral blood mononuclear cells was performed using the reverse transcriptase-polymerase chain reaction in real time. The cytokines gene expression was higher in patients with T1DM. The IL-10 gene expression increased substantially in patients with ketoacidosis, and there was a positive correlation with HbA1c. A negative correlation was found for IL-10 expression and the age of patients with diabetes, and the time of diagnosis of the disease. There was a positive correlation between TNF-α expression with age. The expression of IL-10 and TNF-α genes showed a significant increase in DM1 patients. Once current T1DM treatment is based on exogenous insulin, there is a need for other therapies, and inflammatory biomarkers could bring new possibilities to the therapeutic approach of the patients.

Level of physical activity and gene expression of IL-10 and TNF-α in children and adolescents with Type 1 diabetes.

AIMS: The gene expressions of IL-10 and TNF-α have been identified as important factors of the clinical condition in type I diabetes mellitus (DM1). However, the effect of physical exercise on the expression of these markers is poorly understood. Our objective was to evaluate the relationship between the level of physical activity (LPA) and the gene expressions of IL-10 and TNF-α, as the relationship with glycemic control and insulin reserve in children and adolescents with DM1. METHODS: 108 participants (1-23 years), were divided into 4 groups: DM1 with ketoacidosis (KETO) (n = 15); Decompensated DM1 (DM1d) (n = 32); Compensated DM1 (DM1c) (n = 30); and healthy control (C) (n = 30). The level of physical activity (LPA) was classified as low active, active, and very active. So evaluated Fasting blood glucose, HbA1c, C-peptide, and gene expressions of IL-10 and TNF-α. RESULTS: The increase in the level of physical activity significantly affected the expression of TNF-α in the DMd and C groups. The increase in LPA from low to active reduced the gene expression of IL-10; however, the increase in NAF from active to very active was associated with an increase in IL-10 gene expression. A very active LPA contributes to reducing HbA1c and an increase in C-peptide in the KETO group. CONCLUSION: The increase in LPA demonstrated a significant effect on the improvement of IL-10 and TNF-α gene expression in the KETO and DMd groups; however, in the KETO group, improvements were also observed in the percentage of HbA1C and C-peptide.

Xenotransplantation of human dental pulp stem cells in platelet-rich plasma for the treatment of full-thickness articular cartilage defects in a rabbit model.

Stem cells in platelet-rich plasma (PRP) scaffolds may be a promising treatment for cartilage repair. Human dental pulp stem cell (hDPSC) subpopulations have been identified to have substantial angiogenic, neurogenic and regenerative potential when compared with other stem cell sources. The present study evaluated the potential of hDPSCs in a PRP scaffold to regenerate full-thickness cartilage defects in rabbits. Full-thickness articular cartilage defects were created in the patellar groove of the femur of 30 rabbits allocated into three experimental groups: Those with an untreated critical defect (CTL), those treated with PRP (PRP) and those treated with stem cells in a PRP scaffold (PRP+SC). The patellar grooves of the femurs from the experimental groups were evaluated macroscopically and histologically at 6 and 12 weeks post-surgery. The synovial membranes were also collected and evaluated for histopathological analysis. The synovial lining cell layer was enlarged in the CTL group compared with the PRP group at 6 weeks (P=0.037) but not with the PRP+SC group. All groups exhibited low-grade synovitis at 6 weeks and no synovitis at 12 weeks. Notably, macroscopic grades for the area of articular cartilage repair for the PRP+SC group were significantly improved compared with those in the CTL (P=0.001) and PRP (P=0.049) groups at 12 weeks. Furthermore, histological scores (modified O'Driscoll scoring system) of the patellar groove articular cartilage in the PRP+SC and PRP groups, in which the articular cartilage was primarily hyaline-like, were significantly higher compared with those in the CTL group at 12 weeks (P=0.002 and P=0.007, respectively). The present results support the therapeutic use of hDPSCs for the treatment of full-thickness articular cartilage defects.

Prostanoids counterbalance the synergism between endothelin-1 and angiotensin II in mesenteric veins of trained rats.

Exercise-induced adaptations of the modulating mechanisms that influence the angiotensin (Ang II) responses assume different features depending on the venous bed. In femoral veins, exercise mobilizes vasodilator prostanoids to cooperate with NO in order to maintain reduced Ang II responses. On the other hand, exercise's influence on the Ang II responses in veins that drain blood from the mesenteric region has been poorly described. Therefore, the present study aimed to identify the effects of a single bout of exercise, as well as exercise training, on the Ang II responses in mesenteric veins. The present study also aimed to investigate the involvement of prostanoids, NO and ET-1 in eventual exercise-induced modifications in these veins. To this end, mesenteric veins taken from resting-sedentary, exercised-sedentary, resting-trained and exercised-trained animals were studied in organ baths. In addition, the mRNA expression of prepro-endothelin-1 (ppET-1), as well as that of the ETA and ETB receptors, were quantified by real-time PCR in these veins. The results show that, either in absence or in presence of L-NAME, the Ang II responses were not different between groups. In the presence of indomethacin, higher Ang II responses were observed in the resting-trained animals than in the resting-sedentary animals. This difference, however, disappeared when L-NAME, BQ-123 or BQ-788 were added during incubation. In addition, no differences in ppET-1, ETA or ETB mRNA expression were observed between groups. Furthermore, in the presence of PD123,319, the Ang II responses in the exercised-sedentary animals were higher than those in the resting-sedentary animals. In conclusion, exercise training mobilizes endothelin-1 (ET-1) to reinforce the Ang II-induced responses mainly through ETA activation. On the other hand, vasodilator prostanoids are mobilized to act in parallel with NO in order to counterbalance the Ang II responses that have been potentiated by ET-1 in these trained animals.

Association among H. pylori virulence markers dupA, cagA and vacA in Brazilian patients.

BACKGROUND: Only a few Helicobacter pylori-infected individuals develop severe gastric diseases and virulence factors of H. pylori appear to be involved in such clinical outcomes. Duodenal ulcer promoting gene A (dupA) is a novel virulence factor of Helicobacter pylori that is associated with duodenal ulcer development and reduced risk for gastric carcinoma in some populations. The aims of the present study were to determine the presence of dupA gene and evaluate the association among dupA and other virulence factors including cagA and vacA in Brazilian patients. Gastric biopsies were obtained from 205 dyspeptic patients (100 children and 105 adults). DNA was extracted and analyzed for the presence of H. pylori and its virulence factors using the polymerase chain reaction method. RESULTS: Patients with gastritis tested positive for H. pylori more frequently. The dupA gene was detected in 41.5% of them (85/205); cagA gene was found in 98 isolates (47.8%) and vacA genotype s1/m1 in 50.2%, s1/m2 in 8.3%, s2/m2 in 36.6%, s2/m1 in 0.5% and s1/s2/m1/m2 in 4.4%. We also verified a significant association between cagA and dupA genes [p = 0.0003, relative risk (RR) 1.73 and confidence interval [CI] = 1.3-2.3]. The genotypes s1/m1 were also associated with dupA gene (p = 0.0001, RR: 1.72 and CI: 1.3-2.2). The same associations were found when analyzing pediatric and adult groups of patients individually. CONCLUSION: Ours results suggest that dupA is highly frequent in Brazilian patients and is associated with cagA gene and vacA s1/m1 genotype, and it may be considered an important virulence factor in the development of gastric diseases in adults or children.

Exercise reduces angiotensin II responses in rat femoral veins.

The control of blood flow during exercise involves different mechanisms, one of which is the activation of the renin-angiotensin system, which contributes to exercise-induced blood flow redistribution. Moreover, although angiotensin II (Ang II) is considered a potent venoconstrictor agonist, little is known about its effects on the venous bed during exercise. Therefore, the present study aimed to assess the Ang II responses in the femoral vein taken from sedentary and trained rats at rest or subjected to a single bout of exercise immediately before organ bath experiments. Isolated preparations of femoral veins taken from resting-sedentary, exercised-sedentary, resting-trained and exercised-trained animals were studied in an organ bath. In parallel, the mRNA expression of prepro-endothelin-1 (ppET-1), as well as the ETA and ETB receptors, was quantified by real-time PCR in this tissue. The results show that, in the presence of L-NAME, Ang II responses in resting-sedentary animals were higher compared to the other groups. However, this difference disappeared after co-treatment with indomethacin, BQ-123 or BQ-788. Moreover, exercise reduced ppET-1 mRNA expression. These reductions in mRNA expression were more evident in resting-trained animals. In conclusion, either acute or repeated exercise adapts the rat femoral veins, thereby reducing the Ang II responses. This adaptation is masked by the action of locally produced nitric oxide and involves, at least partially, the ETB- mediated release of vasodilator prostanoids. Reductions in endothelin-1 production may also be involved in these exercise-induced modifications of Ang II responses in the femoral vein.

Association analysis between K and -116A variants of butyrylcholinesterase and Alzheimer's disease in a Brazilian population.

In Alzheimer's disease (AD) a reduction in acetylcholinesterase (AChE) and an increase in butyrylcholinesterase (BChE) activity are observed. K variant (539T) is the most common variant of the BCHE gene and, although controversial, several studies reported association between K variant and AD. Previous results showed that the K variant alone is not capable of diminishing BChE activity, depending on the presence of the -116A variant. Considering that, we conducted a case-control association study using a clinically well defined group of AD patients (n = 82) and age and sex matched control subjects (EC; n = 78) in order to test the association with these variations of BCHE gene in a Brazilian population. The allele, genotype and haplotype frequencies of the K and the -116A variants of BCHE gene were not significantly different between cases and controls. Although not reaching statistical significance, the results suggested that the presence of -116A variant may have a protective effect against AD. The association of the K variant with AD in a controversial manner in different surveys is probably caused by its linkage disequilibrium with -116A that, by reducing BChE activity, potentially increases cholinergic transmission in comparison with usual genotypes.

Association of interleukin 1ß polymorphisms and haplotypes with Alzheimer's disease.

Our study aimed to associate IL-1ß and IL-1RN polymorphisms with AD disease in comparison with elderly control group from São Paulo - Brazil. We genotyped 199 Alzheimer's disease (AD) patients, 165 elderly control and 122 young control samples, concerning VNTR (IL-1RN) and -511C>T and -31T>C (IL-1ß) polymorphisms. Our findings revealed that -511C/-31T/2-repetitions VNTR haplotype had a protective effect for AD when compared to EC (p=0.005), whereas -511C/-31C/1-repetition VNTR haplotype was associated as a risk factor for AD (p=0.021). Taken together, we may suggest that there is a relevant role of IL-1 genes cluster in AD pathogenesis in this Brazilian population.