Celastrol inhibits aminoglycoside-induced ototoxicity via heat shock protein 32

Hearing loss is often caused by death of the mechanosensory hair cells of the inner ear. Hair cells are susceptible to death caused by aging, noise trauma, and ototoxic drugs, including the aminoglycoside antibiotics and the antineoplastic agent cisplatin. Ototoxic drugs result in permanent hearing loss for over 500 000 Americans annually. We showed previously that induction of heat shock proteins (HSPs) inhibits both aminoglycoside- and cisplatin-induced hair cell death in whole-organ cultures of utricles from adult mice. In order to begin to translate these findings into a clinical therapy aimed at inhibiting ototoxic drug-induced hearing loss, we have now examined a pharmacological HSP inducer, celastrol. Celastrol induced upregulation of HSPs in utricles, and it provided significant protection against aminoglycoside-induced hair cell death in vitro and in vivo. Moreover, celastrol inhibited hearing loss in mice receiving systemic aminoglycoside treatment. Our data indicate that the major heat shock transcription factor HSF-1 is not required for celastrol-mediated protection. HSP32 (also called heme oxygenase-1, HO-1) is the primary mediator of the protective effect of celastrol. HSP32/HO-1 inhibits pro-apoptotic c-Jun N-terminal kinase (JNK) activation and hair cell death. Taken together, our data indicate that celastrol inhibits aminoglycoside ototoxicity via HSP32/HO-1 induction

Serum leptin levels in children with acute viral hepatitis A

Conclusion: Leptin levels are not altered in children with A VH-A. In the convalescence period, leptin increased parallel to BMI. It is suggested that expected increment in leptin due to inflammation might be balanced with the decrease due to loss of appetite during acute illness or it might be entirely due to loss of production

Are hypertension and diabetes mellitus risk factors for pelvic organ prolapse?

Objectives Pelvic organ prolapse (POP) is an important problem for women with multifactorial etiology. This study aims to determine the role of hypertension (HT) and diabetes mellitus (DM) in POP. Study design The study included 586 women admitted to Bulent Ecevit University Hospital between September 2013 and April 2015 for hysterectomy, comprising 186 patients with POP and 400 patients without. The demographic characteristics, age, body mass index (BMI), obstetrical history, type of delivery, associated medical diseases, and benign gynecological diseases were recorded. HT, DM, or both together were particularly considered as coexisting medical diseases. Results Median gravida, parity, and live birth numbers were significantly higher in POP patients (4 vs. 3, 3 vs. 2, and 3 vs. 2 respectively, p 0.05). There was a significant difference between groups regarding comorbid diseases (p < 0.001). Logistic regression analysis for risk factors of POP revealed age, BMI, vaginal parturition, and co-morbidity with HT + DM together significantly increased POP risk (p < 0.05). HT + DM together significantly increased risks with OR of 1.9 (1.1-3.16). Conclusions In addition to multiple factors increasing POP risk, comorbidities as HT + DM together should be considered as risk factors. Patients with these comorbidities should be encouraged to change their lifestyles to prevent POP. © 2015 Elsevier Ireland Ltd