This study was conducted to determine the tolerability and efficacy of valsartan (DIOVAN) compared to perindopril (COVERSYL) in Malaysian patients with mild to moderate hypertension. Two hundred and fifty adult Malaysian patients with a mean sitting diastolic blood pressure of more than 95 mmHg and less than 115 mmHg after a 14 day washout period were randomized to receive either valsartan 80 mg once daily (n=125) or perindopril 4 mg daily (n=125) for eight weeks. The primary end point for efficacy was the change in mean sitting systolic and diastolic blood pressure (SiSBP and SiDBP). The primary criteria for evaluation of tolerability was the incidence of adverse events. There were no significant differences between the two groups with respect to sex, age, weight, baseline sitting and standing systolic and diastolic blood pressure. At 0, 4 and 8 weeks the mean SiDBP in the valsartan group were 101.4, 92.8 and 91.0 mmHg respectively. The corresponding BP for the perindopril treated group was 102.6, 93.8 and 93.2 mmHg. (95% CI -1.39 to +3.27). There were no significant differences in the mean BP measurements between the valsartan and perindopril group at 0, 4 and 8 weeks. In each group there were significant differences between the BP at 4 and 8 weeks compared to baseline. A similar pattern was seen with SiSBP. At 4 weeks 28.7% of the valsartan and 25% of the perindopril group had their BP normalized (SiDBP <90 mmHg) The percentages of patients who responded (SiDBP reduction >10 mmHg but SiDBP >90 mmHg) were 21.3 in the valsartan group and 20.8 in the perindopril group. At 8 weeks, 31.1% of the valsartan group and 30.8% of the perindopril group had their BP normalized. The response rate was 27% and 22.5% for valsartan and perindopril respectively. The major adverse event was cough which occurred in 18 patients (14.4%) in the perindopril and 1 (0.8%) in the valsartan group at 4 weeks. At 8 weeks the figures were 24 (19.2%) and 2 (1.6%) respectively. The results indicate that Valsartan is safe and efficacious in the treatment of mild to moderate hypertension. It is equally efficacious to Perindopril and not associated with any major adverse event. It has a better tolerability profile with respect to dry cough.
High levels of angiotensin receptor antibodies (ATRab) are associated with acute cellular and humoral rejection, vascular occlusion, de novo human leucocyte antigen donor specific antibody (HLA DSA) and poor graft survival in kidney transplant recipients (KTR). Since 2015 we proactively managed patients "at risk" (AR) with ATRab >17 U/ml with perioperative plasma exchange (PLEX) and/or angiotensin receptor blockade (ARB). 44 patients were treated with this protocol. 265 KTR with ATRab ≤17 U/ml deemed "low risk" (LR) were transplanted under standard conditions. PLEX and ARB were not associated with increased risk of: delayed graft function requiring haemodialysis (HDx), hyperkalaemia >5.5 mmol/l requiring HDx, and the combined clinical end-point of severe hypotension, blood transfusion and re-operation for bleeding. Rejection rates were similar at 90 days: 8/44 (18%) in the AR group and 36/265 (14%) in the LR group (p = 0.350). Death censored graft survival was the same between the AR and LR groups with a 94% 48-month graft survival - hazard ratio (log-rank) 1.16 [95% CI 0.2-5.8] p = 0.844. Proactive treatment of ATRab >17 U/ml with PLEX and/or ARB is not associated with increased rates of perioperative complications and comparable rates of rejection and death censored graft survival at 4 years compared to KTR <17 U/ml ATRab.
Various works have been carried out in developing therapeutics against dengue. However, to date, no effective vaccine or anti-dengue agent has yet been discovered. The development of protease inhibitors is considered as a promising option, but most previous works have involved competitive inhibition. In this study, we focused on rational discovery of potential anti-dengue agents based on non-competitive inhibition of DEN-2 NS2B/NS3 protease. A homology model of the DEN-2 NS2B/NS3 protease (using West Nile Virus NS2B/NS3 protease complex, 2FP7, as the template) was used as the target, and pinostrobin, a flavanone, was used as the standard ligand. Virtual screening was performed involving a total of 13 341 small compounds, with the backbone structures of chalcone, flavanone, and flavone, available in the ZINC database. Ranking of the resulting compounds yielded compounds with higher binding affinities compared with the standard ligand. Inhibition assay of the selected top-ranking compounds against DEN-2 NS2B/NS3 proteolytic activity resulted in significantly better inhibition compared with the standard and correlated well with in silico results. In conclusion, via this rational discovery technique, better inhibitors were identified. This method can be used in further work to discover lead compounds for anti-dengue agents.