Currently there are no specific treatments available for acute dengue infection. We considered that rupatadine, a platelet-activating factor receptor inhibitor, might modulate dengue-associated vascular leak. The effects of rupatadine were assessed in vitro, and in a dengue model, which showed that rupatadine significantly reduced endothelial permeability by dengue sera in vitro, and significantly inhibited the increased haematocrit in dengue-infected mice with dose-dependency. We conducted a randomised, placebo-controlled trial in 183 adult patients in Sri Lanka with acute dengue, which showed that rupatadine up to 40 mg daily appeared safe and well-tolerated with similar proportions of adverse events with rupatadine and placebo. Although the primary end-point of a significant reduction in fluid leakage (development of pleural effusions or ascites) was not met, post-hoc analyses revealed small but significant differences in several parameters on individual illness days - higher platelet counts and lower aspartate-aminotransferase levels on day 7 in the rupatadine group compared to the placebo group, and smaller effusions on day 8 in the subgroup of patients with pleural effusions. However, due to the small sample size and range of recruitment time, the potential beneficial effects of rupatadine require further evaluation in large studies focused on recruitment during the early febrile phase.
This study investigates the oral hypoglycemic activity of Pleurotus ostreatus (P.o.) and P. cystidiosus (P.c.) mushrooms on normal and alloxan-induced diabetic Wistar rats. Different doses (250, 500, 750, 1000, and 1250 mg/kg/body weight) of suspensions of freeze-dried and powdered (SFDP) P.o. and P.c. were administered to normal rats, and postprandial serum glucose levels were measured. Optimal time of activity was investigated using the dose 500 mg/kg. Hypoglycemic effect of a single dose of SFDP P.o. and P.c. (500 mg/kg) were investigated using diabetic male and female rats at different stages of estrous cycle and compared with metformin and glibenclamide. Chronic hypoglycemic activity of SFDP P.o. and P.c. (500 mg/kg) was studied using serum glucose levels and glycosylated hemoglobin levels. Maximally effective dose of SFDP P.o. and P.c. was 500 mg/kg. The highest reduction in the serum glucose level was observed 120 minutes after administration of mushrooms. A single dose of P.o. and P.c. significantly (P < 0.05) reduced the serum glucose levels of male diabetic rats. The hypoglycemic activity in female rats was highest in proestrous stage. The hypoglycemic effect of P.o. and P.c. is comparable with metformin and glibenclamide. Daily single administrations of P.o. and P.c. to diabetic rats exert apparent control on the homeostasis of blood glucose. SFDP P.o. and P.c. possessed marked and significant oral hypoglycemic activity. This study suggests the consumption of P.o. and P.c. mushrooms might bring health benefits to mankind as it shows hypoglycemic activity in rats.
Background
Rupatadine was previously shown to reduce endothelial dysfunction in vitro, reduced vascular leak in dengue mouse models and to reduce the extent of pleural effusions and thrombocytopenia in patients with acute dengue. Therefore, we sought to determine the efficacy of rupatadine in reducing the incidence of dengue haemorrhagic fever (DHF) in patients with acute dengue.
Methods and findings
A phase 2, randomised, double blind, placebo controlled clinical trial was carried out in patients with acute dengue in Sri Lanka in an outpatient setting. Patients with ≤3 days since the onset of illness were either recruited to the treatment arm of oral rupatadine 40mg for 5 days (n = 123) or the placebo arm (n = 126). Clinical and laboratory features were measured daily to assess development of DHF and other complications. 12 (9.7%) patients developed DHF in the treatment arm compared to 22 (17.5%) who were on the placebo although this was not significant (p = 0.09, relative risk 0.68, 95% CI 0.41 to 1.08). Rupatadine also significantly reduced (p = 0.01) the proportion of patients with platelet counts <50,000 cells/mm3 and significantly reduced (p = 0.04) persisting vomiting, headache and hepatic tenderness (p<0.0001) in patients. However, there was no difference in the duration of illness and in the proportion of individuals who required hospital admission in both treatment arms. Only 2 patients on rupatadine and 3 patients on the placebo developed shock, while bleeding manifestations were seen in 6 patients on rupatadine and 7 patients on the placebo.
Conclusions
Rupatadine appeared to be safe and well tolerated and showed a trend towards a reducing proportion of patients with acute dengue who developed DHF. It usefulness when used in combination with other treatment modalities should be explored.
Trial registration
International Clinical Trials Registration Platform: SLCTR/2017/024.
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