Complement C3 F and BF S allotypes are risk factors for Chagas disease cardiomyopathy.

The heterogeneity in the clinical expression of Chagas disease gives strong evidences for the involvement of genetic factors on its pathogenesis. Several studies have indicated different markers of genetic susceptibility to Chagas cardiomyopathy. In the present study, we present evidence of association between complement C3 and BF allotypes, and the susceptibility to Chagas disease and the development of cardiomyopathy. C3, BF, C4A, C4B and C2 polymorphism were determined in 100 seropositive Chagasic patients [cardiomyopathic (CARD), n = 57; asymptomatic indetermined (IND), n = 43] and in 100 non-related seronegative healthy controls. Patients and controls were matched according to their ethnic and geographical origin. A significantly increased frequency of C3F was observed in patients with the CARD form (8/57 14.03%), when compared with those presenting the IND form (0/43, 0%; RR 7.0) and with the healthy controls (5/100, 5%; RR 3.1). A negative association of the BF S allotype was observed in the CARD patients (19/57 33.33%) and in the Chagas total (38/100 38.0%), when compared with the controls (55/100, 55.0%; RR 0.4). All other C3, BF, C4A, C4B and C2 alleles showed no significant differences. These results suggest the allele C3F as a susceptible marker for the progression of the CARD form. On the other hand, BF S may represent a protective role against severe CARD disease. These results corroborate the importance of the alternative pathway in Trypanosoma cruzi infection and indicate possible genetic markers of Chagas cardiomyopathy.

[Multicenter comparative study of felodipine-ER and nifedipine-OROS in the treatment of mild-to-moderate arterial hypertension]. / Estudo multicêntrico comparativo da felodipina-ER e nifedipina-OROS no tratamento da hipertensão arterial leve e moderada.

PURPOSE: To compare the efficacy and tolerance of felodipine-ER and nifedipine OROS, both once daily, in the treatment of mild-to-moderate uncomplicated arterial hypertension (AH). METHODS: This was a multicentric, opened, randomized, paralled trial, that selected 121 patients with uncomplicated, mild to moderate essential AH (diastolic blood pressure (DBP) > or = 95 and < or = 110 mmHg; not under anti-hypertensive medication. All patients received placebo for two weeks. After that period, they would take either 5mg/day of felodipine, or 30mg/day of nifedipine OROS, both once daily, in a randomized fashion. Patients underwent laboratory tests and electrocardiogram (ECG) at the begining and at the end of the study, and heart rate and blood pressure (BP) measurements, nearly 24 hours after the last active drug dose. RESULTS: Completed the study 111 patients, 60 in the felodipine group and 51 in the nifedipine group. Compared to baseline, the average of systolic BP and DBP decreased from 162.5 +/- 14.3mmHg and from 102.2 +/- 5.1mmHg to 143.3 +/- 14.6 and 87.9 +/- 7.2mmHg, respectively, at the end of the treatment in the felodipine group; and from 160.5 +/- 16.3mmHg and 102.5 +/- 6.2mmHg to 136.1 +/- 14.2 and 86.7 +/- 7.0mmHg, respectively in nifedipine group (p < 0.0001 for all diferences). Adequate BP response to the treatment (DBP normalization or reduction > 10mmHg from baseline) occured in 47/60 (78.3%) patients in the felodipine group and in 38/51 (74.5%) in the nifedipine group (NS). Side effects, occured in approximately 15% of the cases, and were similar in both groups. These were usually moderate and transient, but were responsible for the withdrawal from the study of two cases in the felodipine group and of three cases in the nifedipine group. CONCLUSION: Felodipine-ER and nifedipine OROS, are similarly effective and generally well tolerated in patients with mild-to-moderate essential hypertension.