Fatores de risco individuais e familiares no desenvolvimento da pré-eclâmpia

Preeclampsia is a spectral disease, with different clinical forms which can evolve with severe multisystemic complications. This present study aimed to determine the risk factors associated with preeclampsia (PE); to validate the existence of aggregation of hypertensive disease in families of women with preeclampsia and verify the existence of association between polymorphisms in the VEGF gene and level of VEGF and its soluble receptor (sFlt1). A case-control study was performed (n = 851). Genotyping of VEGF was performed and serum levels of VEGF and sFlt1 were measured by ELISA. It was observed that 38% of mothers (173, 455) of a case of preeclampsia and 30.8% (78 of 361) of controls had history of hypertension (p <0.0001). Similarly, when examining the history of maternal preeclampsia, we observed that 14.6% (48 of 328) of mothers of women with preeclampsia and 9.6% (12 of 294) of mothers of controls had a history of preeclampsia (p = 0.0001). As for maternal history of preeclampsia, we found that 5.1% (15 of 295) of cases and 3.6% (7 of 314) of controls had a history of preeclampsia (p = 0.0568). Sisters of women with preeclampsia also had a history of hypertensive disease in 9% (41 of 455) versus 6.6% (13 of 361), p = 0.002. Similarly when examining the history of preeclampsia in sisters, it was observed that 22.7% (57 of 251) of a sister of case versus 11.4% (26 of 228) of controls had a history of preeclampsia (P = 0.0011). We observed a decrease in free VEGF in the serum of patients (P <0.05) and increased soluble VEGF receptor. There was no association between polymorphisms in the VEGF gene and preeclampsia. The data obtained in this work validate that hypertensive disease in mothers and sisters with preeclampsia are risk factors for preeclampsia. The risk of illness in the family is higher according to disease severity. High incidence of preeclampsia can be assumed by the high incidence of this disease among the controls. Significant differences between the frequency of preeclampsia in mothers of cases and controls indicate familial factors. Work is being conducted with the to eventually perform genome wide association studies to identify susceptibility loci

Associação do receptor toll-like 2 com o estado pró-inflamatório do diabetes tipo 1

Inflammation has been pointed out as an important factor in development of chronic diseases, as diabetes. Hyperglycemia condition would be responsible by toll-like receptors, TLR2 and TLR4, and, consequently by local and systemic inflammation induction. Thus, the objective of present study was to evaluate type 1 Diabetes mellitus (T1DM) pro-inflammatory state through mRNA expression of TLRs 2 and 4 and proinflammatory cytokines IL-1β, IL-6 and TNF-α correlating to diabetic nephropathy. In order to achieve this objective, 76 T1DM patients and 100 normoglycemic (NG) subjects aged between 6 and 20 years were evaluated. T1DM subjects were evaluated as a total group DM1, and considering glycemic control (good glycemic control DM1G, and poor glycemic control DM1P) and considering time of diagnosis (before achieving 5 years of diagnosis DM1< 5yrs, and after achieving 5 years of diagnosis DM1 <5yrs). Metabolic control was evaluated by glucose and glycated hemoglobin concentrations; to assess renal function serum urea, creatinine, albumin, total protein and urinary albumin-to-creatinine ratio were determined and to evaluate hepatic function, AST and ALT serum activities were measured. Pro-inflammatory status was assessed by mRNA expression of TLRs 2 and 4 and the inflammatory cytokines IL-1β, IL-6 and TNF-α. Except for DM1G group (18.4%), DM1NC patients (81.6%) showed a poor glycemic control, with glycated hemoglobin (11,2%) and serum glucose (225,5 md/dL) concentrations significantly increased in relation to NG group (glucose: 76,5mg/dL and glycated hemoglobin: 6,9%). Significantly enhanced values of urea (20%) and ACR (20,8%) and diminished concentrations of albumin (5,7%) and total protein (13,6%) were found in T1DM patients, mainly associated to a poor glycemic control (DM1P increased values of urea: 20% and ACR:49%, and diminished of albumin: 13,6% and total protein:13,6%) and longer disease duration (DM1 <5yrs - increased values of urea: 20% and ACR:20,8%, and diminished of albumin: 14,3% and total protein:13,6%). As regarding pro-inflammatory status evaluation, significantly increased mRNA expressions were presented for TLR2 (37,5%), IL-1β (43%), IL-6 (44,4%) and TNF-α (15,6%) in T1DM patients in comparison to NG, mainly associated to DM1P (poor glycemic control TLR2: 82%, IL-1β: 36,8% increase) and DM1 <5yrs (longer time of diagnosis TLR2: 85,4%, IL-1β: 46,5% increased) groups. Results support the existence of an inflammatory state mediated by an increased expression of TLR2 and pro-inflammatory cytokines IL-1β, IL-6 and TNF-α in T1DM