Nausea, vomiting, and renal injury are the common adverse effects associated with cisplatin.Cisplatin is excreted via the multidrug and toxin release (MATE) transporter, and the involvement of the MATE transporter in cisplatin-induced kidney injury has been reported. The MATE transporter is also involved in the excretion of ondansetron, but the effects of 5-HT 3 receptor antagonists used clinically for cisplatin-induced renal injury have not been elucidated. Therefore, the aim of this study was to investigate the effects of 5-HT 3 receptor antagonists in a mouse model of cisplatin-induced kidney injury and to validate the results using medical big data analysis of more than 1.4 million reports and a survey of 3,000 hospital medical records. The concomitant use of a first-generation 5-HT 3 receptor antagonist (ondansetron, granisetron, or ramosetron) significantly increased cisplatin accumulation in the kidney and worsened renal damage.Conversely, the concomitant use of palonosetron had no effect on renal function compared with the use of cisplatin alone. Furthermore, an analysis of data from the US Food and Drug Administration Adverse Event Reporting System and retrospective medical records revealed that the combination treatment of cisplatin and a first-generation 5-HT 3 receptor antagonist significantly increased the number of reported renal adverse events compared with the combination treatment of cisplatin and a second-generation 5-HT 3 receptor antagonist. These results suggest that compared with the first-generation antagonists, second-generation 5-HT 3 receptor antagonists do not worsen cisplatin-induced acute kidney injury. The findings should be validated in a prospective controlled trial before implementation in clinical practice.

Adipose tissues poorly produce adiponectin in the population with increased body fat mass and diabetes mellitus. It was investigated whether hypoadiponectinemia is associated with obesity and insulin resistance in patients with chronically medicated schizophrenia. A cross-sectional study was designed for 73 non-diabetic Japanese patients with schizophrenia. The patients aged < 70 years with body mass index (BMI) ≥ 18.5 were selected. Anthropometrics and blood parameters including fat-derived cytokines were measured, and then the BMI and homeostasis model assessmentinsulin resistance (HOMA-IR) was calculated. The variables were compared between the nonobesity (BMI, 18.5-24.9) and obesity ( ≥ 25.0) groups, and between genders. Plasma adiponectin negatively correlated with BMI ( r = -0.554, P < 0.0003) and HOMA-IR ( r = -0.380, P = 0.007) in men, but not in women. The obesity group in men, as compared with the non-obesity group, showed significantly lower plasma adiponectin ( P = 0.008) and higher HOMA-IR ( P < 0.05), but not in women. Plasma leptin showed a significant positive correlation with BMI ( r = 0.604, P < 0.0001 in men; r = 0.763, P < 0.0001 in women) and HOMA-IR ( r = 0.618, P < 0.0001 in men; r = 0.679, P < 0.0001 in women). The mean plasma leptin in the obesity group was significantly higher than that in the non-obesity group ( P < 0.01 in men; P < 0.01 in women). In contrast to plasma leptin, plasma adiponectin showed gender difference in relation to BMI and HOMA-IR.

Background There is a growing concern about the association between the combined use of daptomycin (DAP) and statins and the occurrence of musculoskeletal adverse events (MAEs), but this remains controversial. This study aimed to clarify the association between statin use and DAP-related MAEs. Methods We used a mixed approach that combines two methodologies. First, we conducted a meta-analysis to examine the effects of statin use on DAP-related MAEs. Second, we conducted a disproportionality analysis using the FDA Adverse Events Reporting System (FAERS) to further confirm the results of the meta-analysis and to examine the effect of each type of statin on DAP-related MAEs in a large population. Results In the meta-analysis, statin use significantly increased the incidence of DAP-related rhabdomyolysis (odds ratio [OR]: 3.83, 95% confidence interval [CI]: 1.43–10.26) but not DAP-related myopathy (OR: 1.72, 95% CI: 0.95–3.12). In the disproportionality analysis using the FAERS, the use of statin significantly increased the reporting OR (ROR) for DAP-related myopathy (ROR: 5.69, 95% CI: 4.31–7.51) and rhabdomyolysis (ROR: 5.77, 95% CI: 4.33–7.68). Atorvastatin, rosuvastatin, and simvastatin all increased the incidence of DAP-related myopathy and rhabdomyolysis. Conclusion The mixed approach combining a meta-analysis and disproportionality analysis showed that statin use was associated with the occurrence of DAP-related rhabdomyolysis. The appropriate use of statins and DAP should be performed with careful consideration of its safety.

Objective : This study was conducted to address the question of whether the 3-adrenergic receptor gene mutation (Trp64Arg) is associated with metabolic disease in Japanese patients with schizophrenia. Methods : In a cross-sectional study, 89 participants were grouped into three genotypes. The 64 Arg allelic frequency in patients with or without metabolic disease was analyzed. Anthropometrics variables and biochemical parameters were compared among the genotypes. Results : The64Arg allele, which had a frequency of 0.22, was not associated with obesity, type2 diabetes mellitus, dyslipidemias, or hypertension. No significant differences among the genotypes were found in current age, age at diagnosis with schizophrenia, body mass index, waist-hip ratio, plasma glucose, plasma insulin, triglycerides, free fatty acids. Patients with the 64 Arg allele had greater 24-h excretion of norepinephrine than those lacking the variant (p=0.019). Conclusion : The 64 Arg allelic mutation is not associated with obesity, type2 diabetes mellitus, lipid metabolism dysfunction, or hypertension in Japanese patients with schizophrenia.