A novel mutation of dipeptidyl aminopeptidase-like protein-6 in a family with suspicious idiopathic ventricular fibrillation.

BACKGROUND: Sudden cardiac death (SCD) occurs in a broad spectrum of cardiac pathologies and is an important cause of mortality in the general population. Idiopathic ventricular fibrillation (IVF) is a rare but important factor resulting in SCD. It is diagnosed in a resuscitated cardiac arrest victim underlying unknown cause, with documented ventricular fibrillation. Previous studies have demonstrated that mutations in dipeptidyl aminopeptidase-like protein-6 (DPP6) and cardiac sodium channel Nav1.5 (SCN5A) are the most important genetic factors involve in IVF. AIM: By using whole sequencing to identify the genetic lesion of a family with suspicious idiopathic ventricular fibrillation. DESIGN: Prospective genetic study. METHODS: In this study, we employed whole-exome sequencing in combination with arrhythmia-related gene filtering to identify the genetic lesion for a family suffering from suspicious IVF, syncope and SCD. We then generated the plasmids of DPP6-pcDNA3.1+ (WT and c.1578G>C/p.Q526H). Kv4.3-pcDNA3.1+ was co-transfected together with/without DPP6-pcDNA3.1+ (WT and/or c.1578G>C/p.Q526H) into HEK293 cells to perform the patch clamp experiments. RESULTS: A novel missense mutation (c.1578G>C/p.Q526H) of DPP6 was identified and co-segregated with affected patients in this family. Patch clamp experiments suggested that this novel mutation might result in a gain of function and disturb the efflux of potassium ion. CONCLUSION: Our study not only reported the second missense mutation of DPP6 in heart disease and expanded the spectrum of DPP6 mutations, but also contribute to the genetic diagnosis and counseling of families with suspicious IVF, syncope and SCD.

[Clinical comparative trial of co-artemether and benflumetol (two formulations) in the treatment of falciparum malaria].

OBJECTIVE: To observe the efficacy and safety of co-artemether and one of its components benflumetol (two formulations) in the treatment of patients with falciparum malaria. METHODS: Adopting double-blining, randomization and comparative method, all patients were hospitalized and observed for 28 days after treatment. RESULTS: Of 150 patients, 51 patients were treated with co-artemether group(A), 50-patients were treated with benflumetol tablet group(B), 49 patients were freated with benflumetol capsule group(C). The mean fever clearance times for groups A, B and C were 17.1 +/- 8.6, 34.0 +/- 23.2 and 29.4 +/- 24.9 hours, respectively; the mean parasite clearance times were 29.7 +/- 8.9, 51.6 +/- 14.1 and 54.7 +/- 17.4 hours respectively; the cure rates in 28 days for groups A, B and C were 98.2%, 92.0% and 95.8%, respectively. No apparent side-effect was observed. CONCLUSION: Co-artemether and benflumetol (2 formulations) are effective for the treatment of patients with falciparum malaria but co-artemether is more effective than benflumetol (2 formulations) in terms of controlling symptoms and killing parasites.

Schizontocidal effects of oral artesunate on Plasmodium berghei in mice and P knowlesi in monkeys.

AIM: To study the blood schizontocidal effect of oral artesunate on P berghei in mice and P knowlesi in monkey. METHODS: Effects of artesunate and chloroquine were detected with "4-day test" and "28-day test" on P berghei in mice and "7-day test" on P knowlesi in Macaca mudatta. RESULTS: The suppressive efficacy of oral artesunate was inferior to chloroquine on P berghei K173 strain but the time for 50% and 90% reduction and the time of clearance of parasitemia was 10-15 h shorter than that of chloroquine. Its curative effect on RC/K173 line was markedly superior to that of chloroquine. Moreover, artesunate showed no cross-resistance with chloroquine, index of resistance I90 was only 1.4. At 31.6, 10.0, and 3.16 mg.kg-1, artesunate and chloroquine oral administrations cured P knowlesi in all monkeys. Recrudescence did not occur in 105 d. CONCLUSION: The study of effects of oral artesunate in P berghei/mice and P knowlesi/Macaca mulatta model provided a useful index for clinical trial.

[Synthesis and antimalarial activities of fluorenemethanols].

For the purpose of improving the oral antimalarial activities of the fluorenemethanols (reported by us in previous articles) which were less effective by oral than by subcutaneous administration, 24 alpha-(alkylaminomethyl)-2, 7-dichloro-9-substituted benzylidene-4-fluorenemethanols (III) were synthesized. The results of preliminary screenings demonstrated that five compounds (No. 1-4, 8) exhibited significant antimalarial activities against Plasmodium berghei NK65 strain in mice by oral administration, at dose of 6.25 mg.kg-1.d-1 x 3 with suppressive rate of 100%. Further evaluation of these 5 compounds showed that 4 of them (No. 1-4) were superior to chloroquine in parallel tests, their ED50 and ED90 were 1.0, 1.6; 0.6, 0.9; 0.7, 1.5 and 0.8, 1.6 mg.kg-1.d-1 x 3 respectively, while the ED50 and ED90 of chloroquine were 1.9 and 2.9 mg.kg-1. d-1 x 3 respectively; one compound (No 8) was equal to chloroquine, its ED50 and ED90 were 1.5 and 3.2 mg.kg-1.d-1 x 3 respectively. Further assessment of these 4 compounds are in progress.