METHODOLOGY: A retrospective analysis of a methanol poisoning outbreak in September 2018 was performed, describing patients who presented to a major tertiary referral centre.
RESULT: A total of 31 patients were received over the period of 9 days. Thirty of them were males with a mean age of 32 years old. They were mostly foreigners. From the 31 patients, 19.3% were dead on arrival, 3.2% died in the emergency department and 38.7% survived and discharged. The overall mortality rate was 61.3%. Out of the 12 patients who survived, two patients had toxic optic neuropathy, and one patient had uveitis. The rest of the survivors did not have any long-term complications. Osmolar gap and lactate had strong correlations with patient's mortality. Serum pH, bicarbonate, lactate, potassium, anion gap, osmolar gap and measured serum osmolarity between the alive and dead patients were significant. Post-mortem findings of the brain were unremarkable.
CONCLUSION: The mortality rate was higher, and the morbidity includes permanent visual impairment and severe neurological sequelae. Language barrier, severity of illness, late presentation, unavailability of intravenous ethanol and fomipezole and delayed dialysis may have been the contributing factors. Patient was managed based on clinical presentation. Laboratory parameters showed difference in median between group that survived and succumbed for pH, serum bicarbonate, lactate, potassium and osmolar and anion gap. Management of methanol toxicity outbreak in resource-limited area will benefit from a well-designed guideline that is adaptable to the locality.
METHODS AND RESULTS: The rapid delayed rectifier potassium current (IKr), L-type Ca2+ current (ICa,L) and action potential duration (APD) were measured by whole cell patch-clamp. The expression of KCNH2 and cytotoxicity was determined by real-time PCR and Caspase activity measurements. After significant IKr suppression by Mitragynine (10 µM) was confirmed in hERG-HEK cells, we systematically examined the effects of Mitragynine and other chemical constituents in hiPSC-CMs. Mitragynine, Paynantheine, Speciogynine and Speciociliatine, dosage-dependently (0.1∼100 µM) suppressed IKr in hiPSC-CMs by 67%∼84% with IC50 ranged from 0.91 to 2.47 µM. Moreover, Mitragynine (10 µM) significantly prolonged APD at 50 and 90% repolarization (APD50 and APD90) (439.0±11.6 vs. 585.2±45.5 ms and 536.0±22.6 vs. 705.9±46.1 ms, respectively) and induced arrhythmia, without altering the L-type Ca2+ current. Neither the expression, and intracellular distribution of KCNH2/Kv11.1, nor the Caspase 3 activity were significantly affected by Mitragynine.
CONCLUSIONS: Our study indicates that Mitragynine and its analogues may potentiate Torsade de Pointes through inhibition of IKr in human cardiomyocytes.
PATIENTS & METHODS: DPP4, WFS1 and KCNJ11 gene polymorphisms were genotyped in a cohort study of 662 T2DM patients treated with DPP-4 inhibitors sitagliptin, vildagliptin or linagliptin. Genotyping was performed by Applied Biosystems TaqMan SNP genotyping assay.
RESULTS: Patients with triglyceride levels less than 1.7 mmol/l (odds ratio [OR]: 2.2.; 95% CI: 1.031-4.723), diastolic blood pressure (DBP) less than 90 mmHg (OR: 1.7; 95% CI: 1.009-2.892) and KCNJ11 rs2285676 (genotype CC) (OR: 2.0; 95% CI: 1.025-3.767) were more likely to response to DPP-4 inhibitor treatment compared with other patients, as measured by HbA1c levels.
CONCLUSION: Triglycerides, DBP and KCNJ11 rs2285676 are predictors of the DPP-4 inhibitor treatment response in T2DM patients.
AIM OF THE STUDY: This study is designed to investigate the vasorelaxant effect of Chen pi and to study its pharmacology effects.
MATERIALS AND METHODS: The vasorelaxant effect of water extract of Chen pi (CRW) were evaluated on thoracic aortic rings isolated from Sprague Dawley rats. The fingerprint of Chen pi and the extracts were developed with quantification of hesperidin content by HPTLC.
RESULTS: CRW exhibited the strongest vasorelaxant activity. CRW caused the relaxation of the phenylephrine pre-contracted aortic rings in the presence and absence of endothelium as well as in potassium chloride pre-contracted endothelium-intact aortic ring. The incubation of propranolol (β-adrenergic receptor blocker), atropine (muscarinic receptor blocker), Nω-nitro-L-arginine methyl ester (NO synthase inhibitor), ODQ (sGC inhibitor), indomethacin (COX inhibitor), 4-aminopyridine (KV blocker), barium chloride (Kir blocker), and glibenclamide (KATP blocker) significantly reduced the vasorelaxant effects of CRW. CRW was also found to be active in reducing Ca2+ releases from the sarcoplasmic reticulum and suppressing the voltage-operated calcium channels.
CONCLUSION: The vasorelaxant effect of CRW on rat aorta involves NO/sGC, calcium and potassium channels, muscarinic and β-adrenergic receptors.
METHODS AND STUDY DESIGN: A cross-sectional study was conducted among 184 Malaysian HD patients. Anthropometric measurements and handgrip strength (HGS) were obtained using standardized protocols. Relevant biochemical indicators were retrieved from patients' medical records. Nutritional status was assessed using the dialysis malnutrition score. The sleep quality of patients was determined using the Pittsburgh Sleep Quality Index questionnaire on both dialysis and non-dialysis days.
RESULTS: Slightly more than half of the HD patients were poor sleepers, with approximately two-third of them having a sleep duration of <7 hours per day. Sleep latency (1.5±1.2) had the highest sleep component score, whereas sleep medicine use (0.1±0.6) had the lowest score. Significantly longer sleep latency and shorter sleep duration were observed in the poor sleepers, regardless of whether it was a dialysis day or not (p<0.001). Poor sleep quality was associated with male sex, old age, small triceps skinfold, hypoproteinemia, hyperkalemia, hyperphosphatemia, and poorer nutritional status. In a multivariate analysis model, serum potassium (β=1.41, p=0.010), male sex (β=2.15, p=0.003), and HGS (β=-0.088, p=0.021) were found as independent predictors of sleep quality.
CONCLUSIONS: Poor sleep quality was evident among the HD patients in Malaysia. The sleep quality of the HD patients was associated with nutritional parameters. Routine assessment of sleep quality and nutritional parameters indicated that poor sleepers have a risk of malnutrition and may benefit from appropriate interventions.