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Other patients received incomplete RPEP series. Conclusion Rabies should be suspected in any patient with encephalitis or paralysis who travelled to, or migrated from a rabies-endemic country. Comprehensive information about a rabies risk should be given to travellers to rabies endemic countries, notably migrants visiting friends and relatives.Myotonic dystrophy type 1 (DM1) is a multisystemic disorder characterized by progressive cardiac conduction impairment, arrhythmias and sudden death. Mexiletine is a sodium-channel blocker drug used in such patients for the treatment of myotonia, even if definitive proof of its safety over long-term follow-up is lacking OBJECTIVE To assess the impact of mexiletine for treatment of neurological symptoms on the composite endpoint of significant ECG modification (new onset or worsening of atrioventricular or intraventricular conduction delay) and bradyarrhythmic complications requiring pacemaker implantation (advanced atrioventricular block, symptomatic sinus pause >3 s) METHODS This retrospective longitudinal study included a series of consecutive patients with genetically confirmed DM1 evaluated in our Neurology and Cardiology Clinic from January 1st 2011 to January 1st 2020, who received a 200 mg twice daily (BID) dose of mexiletine. Patients with pacemaker, implantable cardioverter defibrillation, or severe conduction abnormality (PQ interval ≥230ms, complete bundle branch block or atrial fibrillation) at enrollment were excluded RESULTS we included 18 mexiletine-treated patients and 68 mexiletine-free controls. Over a median follow-up of 53 months, the endpoint was reached by 4 (22%) mexiletine-treated patients and 23 (33%) non mexiletine-treated patients (logrank p=0.45). In 3 non mexiletine-treated patients, bradyarrhythmic complications requiring pacemaker implantation were observed. At multivariable univariable analysis, only the presence of mild conduction delay (first-degree AV block with PQ less then 230 ms or left anterior fascicular block) at baseline predicted the endpoint (HR=2.22, CI=1.04-4.76) CONCLUSION Mexiletine, at dosage of 200 mg BID, is safe in patients with DM1 and no severe conduction abnormality.The current study explored the efficacy of piperine in attenuating arsenic induced high fat diet aggravated oxidative stress mediated injury in hepatic and cardiac tissues of male Wistar rats. Oral administration of piperine significantly (p less then 0.05) reduced the levels of organ specific and oxidative stress biomarkers in arsenic and high fat diet treated rat hepatic and cardiac tissues in a dose dependant manner with the dose of 60 mg/kg b.w. exhibiting maximum protection. Arsenic induced high fat diet aggravated oxidative stress mediated damages in liver and heart tissues led to decreased activities of antioxidant enzymes, ROS generation, diminished activities of Krebs' cycle and respiratory chain enzymes, collapsed mitochondrial membrane potential, mitochondrial DNA damage along with altered lipid metabolism and inflammatory cytokine levels. Histochemical and histopathological studies supported the above findings. Piperine efficiently counteracted the arsenic induced high fat diet aggravated oxidative stress mediated damages by modulating antioxidant defense mechanism along with free radical quenching ability. These findings indicate that piperine protected the arsenic induced high fat diet aggravated hepatic and cardiac injuries which underline the importance of piperine in providing a possible therapeutic regime for the amelioration of arsenic-induced high fat diet aggravated oxidative stress mediated organ damages.Di-n-butyl phthalate (DBP) is widely used in consumer products as a plasticizer. Here, we report a natural product taxifolin that can attenuate developmental and reproductive toxicity of DBP. Pregnant rats were daily gavaged with 500 mg/kg DBP alone or together with taxifolin (10 and 20 mg/kg) from gestational day (GD) 12-21. At GD21, sera and testes of male fetus were collected. DBP significantly lowered serum testosterone level at 500 mg/kg and taxifolin can completely reverse its action. selleck chemicals llc DBP caused abnormal aggregation of fetal Leydig cells and taxifolin can reverse it. DBP down-regulated the expression of the genes of cholesterol side-chain cleavage enzyme (Cyp11a1), 17β-hydroxysteroid dehydrogenase 3 (Hsd17b3), and insulin-like 3 (Insl3) and taxifolin can reverse its action. DBP increased malondialdehyde levels and decreased superoxide dismutase and glutathione peroxidase expression and taxifolin can reverse it. DBP increased incidence of multinucleated gonocytes and taxifolin can prevent it. Moreover, DBP lowered sirtuin 1 (SIRT1)/peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α) and phosphorylated AMP-activated protein kinase (pAMPK) signalling and taxifolin antagonized DBP. In conclusion, in utero exposure to DBP caused developmental/reproductive toxicity of male offspring via increasing reactive oxygen species and taxifolin is an effective food component that completely reverses DBP-mediated action.Ethnopharmacological relevance Many prostate cancer (PCa) patients in Mainland China and other Asian countries often use Chinese herbal medicines as an adjuvant treatment while receiving Western medicines. However, concerns have been raised about the potential herb-drug interaction when using herbal medicines containing phytoandrogens. Aim of the study This study aimed to investigate the effects of the selected 21 Chinese herbal medicines on the proliferation and tumor growth using the relevant in vitro and in vivo models of PCa. Materials and methods After treatment of LNCaP and 22Rv1 cells with different concentrations of 70% ethanol extracts of the 21 selected herbal medicines for 48 h, the proliferative activity, the effects on androgen receptor (AR) and prostate specific antigen (PSA) were determined. The anti-tumor effects of the 21 herbs on PCa growth were also investigated on a subcutaneous mouse model of PCa. Results The results showed that Epimedii Folium (EF) and Codonopsis Radix (CNR) could signifexpression of PSA (p less then 0.05 for three herbs) in LNCaP cells, as well as tumor growth (p less then 0.05 for three herbs) and the AR expression (p less then 0.05 for AGR and CXR, p less then 0.001 for BF) in tumor tissues. Conclusion Our results revealed that AGR, CXR and BF suppressed the PCa development via inhibition of AR expression, while EF, CNR and CCH promoted the development and progression of PCa via enhancement of AR expression. The results strongly suggest that caution should be exercised when using androgenic Chinese herbal medicines in PCa patients.
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