Type 1 diabetes is believed to be a Th1 lymphocyte-mediated disease, and both environmental and genetic factors play a role in its pathogenesis. It was recently found that interleukin (IL)-18 acts as a proinflammatory cytokine and, in synergy with IL-12, promotes development of Th1 lymphocyte response by induction of gamma-interferon production. The aim of our study was to evaluate the frequency of known polymorphisms in the IL-18 promoter in patients with type 1 diabetes in comparison with healthy control subjects, since higher levels of IL-18 were recently reported in the subclinical stage of type 1 diabetes. We studied two recently described single-nucleotide polymorphisms of the promoter of IL-18 gene at the position -137 and -607, which have been suggested to cause differences in transcription factor binding and have an impact on IL-18 gene activity. The genotype distribution differed significantly between patients with type 1 diabetes and control subjects. The difference reflected an increase in the GC genotypes and a decrease in GG genotypes at position -137 in the promoter of IL-18 gene. AA genotype at position -607 was found only in the control group. The results also demonstrated that the contribution of -137GC genotypes to genetic susceptibility to type 1 diabetes differs depending on the combination of IL-18 promotor gene haplotypes. Our study suggests the first evidence of an association between type 1 diabetes and polymorphisms in the promoter of IL-18 gene.
Plasma concentrations of adiponectin, tumor necrosis factor-alpha (TNF-alpha) and its soluble receptors sTNFR-1 and sTNFR-2 were measured in 80 patients with gestational diabetes (GDM) (mean age 29.0 +/- 4.9 years) and 30 pregnant women with normal glucose tolerance (NGT) (mean age 28.2 +/- 6.0 years). We found that GDM patients had significantly lower concentrations of adiponectin (11.28 +/- 5.91 vs. 16.31 +/- 6.04 microg/ml, p = 0.00009) and elevated levels of TNF-alpha (1.71 +/- 0.92 vs. 1.27 +/- 0.42 pg/ml, p = 0.0175) in comparison to NGT women. The differences remained statistically significant after adjusting for BMI. Plasma levels of sTNFR-1 and sTNFR-2 also tended to be higher in GDM patients. In the GDM group TNF-alpha concentrations correlated significantly with sTNFR-1 (r = 0.444, p = 0.00008), sTNFR-2 (r = 0.364, p = 0.0016) and with C-peptide concentrations (r = 0.318, p = 0.016), whereas in women with NGT TNF-alpha correlated only with TG levels (r = 0.50, p = 0.024). Multivariate linear regression analysis revealed that prepregnant BMI was the most predictive indicator of TNF-alpha concentrations in GDM women. TG concentrations as well as BMI before pregnancy and at the time of sampling in pregnant NGT women were significant predictors, explaining 62% of the variance in TNF-alpha concentration. There were also negative correlations between adiponectin concentrations and a pregestational BMI (r = - 0.298, p = 0.009), BMI at the time of sampling (r = - 0.239, p = 0.034) and TG concentrations (r = - 0.379, p = 0.039) in GDM patients, whereas women with NGT showed only a negative correlation between adiponectin and TG concentrations (r = - 0.488, p = 0.025). In a multivariate regression analysis, prepregnancy BMI and TG levels remained significant predictors, explaining 39% of the variation in plasma adiponectin concentration in GDM women. In conclusion, our results suggest that decreased adiponectin concentration in GDM may not simply reflect maternal adiposity and insulin resistant state, but may contribute to the impaired glucose metabolism during pregnancy, with potential implications for screening and prevention of the disease.
The aim of this study was to evaluate lipid peroxidation and scavenging enzyme activity in streptozotocin-induced diabetes, and then to establish whether moderate doses of nonenzymatic antioxidant vitamin E play a role in the antioxidant defence system in diabetic pregnant rats and their offspring. The study group consisted of 30 normal female Wistar rats, which were given a single dose of streptozotocin (40 mg/kg) and were mated 7 days later. Subsequently, the diabetic animals were divided into two matched groups: the first supplemented with vitamin E (30 mg/100 g chow), and the other fed with a standard diet lacking vitamin E. Controls consisted of 15 pregnant rats. On the first day after delivery, the rats were decapitated and homogenates of maternal liver and uterus as well as neonatal lungs and liver were prepared. Then the following parameters were measured: malondialdehyde (MDA) concentrations in the homogenates and blood serum, glutathione (GSH) levels, the activity of CuZn-superoxide dismutase (SOD) and glutathione peroxidase (GPx), and glycaemia. The neonates of diabetic rats were smaller than the healthy ones and serum glucose concentration was markedly higher in the diabetic animals. MDA levels were significantly increased, whereas GSH, SOD and GPx were markedly diminished in the diabetic adult rats and their offspring in comparison to the control group. In the animals supplemented with alpha-tocopherol, MDA concentrations were significantly lower, GSH content and SOD activities were markedly elevated most tissues studied, whereas GPx remained unchanged. We conclude that, by monitoring the activity of selected scavenging enzymes, information on ongoing biological oxidative stress and thereby on the fetus/neonate status may be obtained. Our results suggest that diabetic pregnant rats and their neonates are exposed to an increased oxidative stress and that vitamin E supplementation may reduce its detrimental effects.
Introduction and hypothesisThe aim of this study was to evaluate the results of conservative treatment of urodynamic stress urinary incontinence (SUI) using transvaginal electrical stimulation with surface-electromyography-assisted biofeedback (TVES + sEMG) in women of premenopausal age.MethodsOne hundred and two patients with SUI were divided into two groups: active (n = 68) and placebo (n = 34) TVES + sEMG. The treatment lasted for 8 weeks and consisted of two sessions per day. Women were evaluated before and after the intervention by pad test, voiding diary, urodynamic test, and the Incontinence Quality of Life Questionnaire (I-QOL).ResultsMean urinary leakage on a standard pad test at the end of 8th week was significantly lower in the active than the placebo group (19.5 ± 13.6 vs. 39.8 ± 28.5). Mean urinary leakage on a 24-h pad test was significantly reduced in the active group at the end of 8th and 16th weeks compared with the placebo group (8.2 ± 14.8 vs. 14.6 ± 18.9 and 6.1 ± 11.4 vs. 18.2 ± 20.8, respectively). There was also a significant improvement in muscle strength as measured by the Oxford scale in the active vs the placebo group after 8 and 16 weeks (4.2 vs 2.6 and 4.1 vs 2.7, respectively). No significant difference was found between groups in urodynamic data before and after treatment. At the end of 8th week, the mean I-QOL score in the active vs the placebo group was 78.2 ± 17.9 vs 55.9 ± 14.2, respectively, and at the end of 16th week 80.8 ± 24.1 vs. 50.6 ± 14.9, respectively.ConclusionOur study showed that TVES + sEMG is a trustworthy method of treatment in premenopausal women with SUI; however, its reliability needs to be established.
In the present study, associations between pretreatment interleukin 6 (IL-6), interleukin 8 (IL-8) and C-reactive protein (CRP) serum levels and epithelial ovarian cancer (EOC) were analyzed using commercially available, enzyme-linked immunosorbent assay (ELISA) in 118 patients and 64 control subjects. Values were correlated with clinicopathological characteristics and outcomes. Control variables included age, stage, grade, histological type and residual tumor size. Kaplan-Meier plots and univariate and multivariate Cox proportional hazards models were used to study the associations between IL-6, IL-8 and CRP levels, control variables, overall survival and disease-free survival.The median IL-6, IL-8 and CRP serum levels in EOC were significantly higher than in the normal control group; 11.5 pg/ mL (range, 3.4-62.6) versus 2.9 (1.1-12.3) pg/mL (p<0.001) and 21.8 pg/mL (range, 16.4-105.3) versus 9.3 (4.3-32.4) pg/mL (p<0.001) and 9.51 mg/L (range, 0.3-129.2) versus 1.2 (0.1-11.5) mg/L (p = 0.001), respectively. High levels of IL-6, IL-8 and CRP were associated with reduced overall survival (P = 0.003, P = 0.035, P = 0.046) and disease-free survival (P<0.001, P = 0.026, P = 0.043), respectively. Multivariate analyses showed that IL-6, IL-8 and CRP serum levels independently predicted disease-free survival (P = 0.011, P = 0.001 and P = 0.021), and overall survival (P = 0.004, P = 0.014 and P = 0.016), respectively.EOC is associated with extensive changes in the serum cytokine environment, highlighting the importance of further investigations of relative cytokine level changes. Preoperative serum IL-6, IL-8, and CRP levels seem promising for distinguishing EOC patients from healthy controls; however, their clinical value is still to be confirmed. High levels of IL-6, IL-8, and CRP in EOC patients have been suggested to be a poor prognostic factor for OS and DFS.
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