Prevalence,outcome and risk factor associated with vancomycin-resistant Enterococcus faecalis and Enterococcus faecium at a Tertiary Care Hospital in Northern India

Purpose: To determine the prevalence, genotype, risk factors and mortality in patients having vancomycin-resistant Enterococcus faecalis (VR E. faecalis) and Enterococcus faecium (VR E. faecium) infection or colonisation. Materials and Methods: A total of 1488 clinical isolates of E. faecalis and E. faecium were tested for vancomycin resistance by phenotypic (disk diffusion, E-test and broth micro-dilution test) and genotypic polymerase chain reaction methods. Records of all 1488 patients who had E. faecalis or E. faecium infection or colonisation were reviewed for the identification of host, hospital and medication related risk factors associated with VR E. faecalis and VR E. faecium. Results: Of 1488 isolates, 118 (7.9%) were vancomycin-resistant and their distributions were as follows: E. faecalis =72 (61%) and E. faecium =46 (39%). All 118 vancomycin-resistant isolates were vanA genotype (minimum inhibitory concentration [MIC] to vancomycin ≥64 μg/ml and MIC to teicoplanin ≥32 μg/ml) and none of the isolates was vanB genotype. Multivariate logistic regression analysis identified ventilator support and hospital stay for ≥48 h as independent risk factors associated with VR E. faecalis and VR E. faecium infection or colonisation. Hospital stay ≥48 h was the only independent risk factor for mortality in patients infected with vancomycin-resistant enterococci. Conclusions: Strategies to limit the nosocomial infection especially in patients on ventilator support can reduce VRE incidence and related mortality.     

黄芩苷、二甲双胍和氨基胍对D-半乳糖诱导大鼠体内蛋白非酶糖基化-氧化应激、醛糖还原酶活性及胰岛素抵抗作用

目的：观察黄芩苷、二甲双胍和氨基胍对D-半乳糖诱导大鼠体内蛋白非酶糖基化-氧化应激、醛糖还原酶活性及胰岛素抵抗作用。方法：清洁级健康SD大鼠90只,完全随机分为6组正常对照组、模型对照组、氨基胍组、二甲双胍组、黄芩苷高剂量和黄芩苷低剂量组,每组各15只。除空白对照组外,其余组大鼠均采用腹腔注射D-gal,灌胃;结束时观察各组大鼠晚期糖基化终末产物、糖化血红蛋白、胰岛素等,并计算胰岛素敏感指数,醛糖还原酶和超氧化物歧化酶的活性。结果：D-gal处理大鼠出现血糖升高、糖耐量减退、糖基化产物及胰岛素含量增高,SOD活性降低及红细胞内AR活性增强;Met,AG以及Bai高和低剂量均能改善D-gal诱导大鼠IGT和降低糖基化产物和胰岛素含量。结论：D-gal诱导能使大鼠体内糖基化反应、胰岛素抵抗和醛糖还原酶活性增强;Bai,Met和AG能抑制蛋白非酶糖基化反应和醛糖还原酶活性,改善高胰岛素血症。     

Protective effect of Clerodendron glandulosum extract against experimentally induced metabolic syndrome in rats

Context: Metabolic syndrome (MetS) has become one of the major health burdens worldwide. To date, no single pharmacological agent has been developed to correct metabolic abnormalities associated with MetS. Use of indigenous medicinal plants as alternative medicines against MetS could be beneficial due to multiple therapeutic usage, easy availability, and relatively few side effects.

Objective: To investigate the protective effect of Clerodendron glandulosum Coleb. (Verbenaceae) aqueous leaf extract (CgE) against experimentally induced MetS in rats.

Methods: Changes in body weight, food and fluid intake, plasma glucose, insulin, fasting insulin resistance index (FIRI), plasma total lipid profile, free fatty acids (FFA), oral glucose tolerance test (OGTT), blood pressure and vascular reactivity have been investigated in various experimental groups.

Results: Fructose+CgE groups recorded significant decrement (P <0.05) in plasma glucose, insulin, FIRI, total cholesterol, triglycerides, LDL, VLDL and FFA, whereas plasma HDL level was significantly increased (P <0.05) along with an efficient clearance of glucose during OGTT and lowered area under curve values. FRU+CgE groups also showed significantly decreased (P <0.05) mean arterial blood pressure along with decreased vasoconstriction and increased vasorelaxation in response to administration of various pharmacological agents. These results were comparable with metformin treated rats.

Discussion: C. glandulosum leaf extract ameliorates experimentally induced MetS by improving dyslipidemia and insulin resistance.

Conclusion: This study provides the first pharmacological evidence for the protective role of C. glandulosum leaves against experimentally induced MetS. Thus, therapeutic use of C. glandulosum in controlling MetS is indicated.     

Antibody-based fusion proteins to target death receptors in cancer

Ideally, an immunotoxin should be inactive ‘en route’, acquire activity only after tumor cell surface binding and have no off-target effects towards normal cells. In this respect, antibody-based fusion proteins that exploit the tumor-selective pro-apoptotic death ligands sFasL and sTRAIL appear promising. Soluble FasL largely lacks receptor-activating potential, whereas sTRAIL is inactive towards normal cells. Fusion proteins in which an anti-tumor antibody fragment (scFv) is fused to sFasL or sTRAIL prove to be essentially inactive when soluble, while gaining potent anti-tumor activity after selective binding to a predefined tumor-associated cell surface antigen. Importantly, off-target binding by scFv:sTRAIL to normal cells showed no signs of toxicity. In this review, we highlight the rationale and perspectives of scFv:TRAIL/scFv:sFasL based fusion proteins for cancer therapy.     

Radioimmunoassay for rat galanin: immunochemical and chromatographic characterization of immunoreactivity in tissue extracts

Galanin is a regulatory peptide with wide distribution in the central and peripheral nervous system and with numerous biological effects. Several radioimmunoassays based on antisera raised against porcine galanin have been used to measure immunoreactivity in rat tissues. However, considerable lack of parallelism has been observed between the porcine standard and rat tissue extracts, which may decrease the reliability of the quantitative data. The purpose of the present study was therefore to raise antibodies against rat galanin and establish a competitive radioimmunoassay for rat galanin. Two antisera, RatGal4 and RatGal5, were characterized in detail. The homogeneity of the immunoreactive material from several tissues was also investigated with column chromatography. At reverse-phase high-pressure liquid chromatography more than 95% of the immunoreactive material from rat CNS eluted as a single peak in the position of synthetic rat galanin, whereas almost half of the immunoreactive material from the intestine eluted in positions different from the synthetic peptide. Extracts of rat brains as well as jejunum diluted in parallel with the standard curve for both antisera. We conclude that measurements of rat galanin based on these antisera are therefore more reliable than those based on antisera raised against porcine galanin.     

Halofantrine in the treatment of acute malaria: A multi-centre study in 268 patients

Summary

The clinical efficacy and tolerability of halofantrine, a new antimalarial schizontocide, was studied in a multi-centre trial involving 268 patients ranging in age from 6 months to 58 years. The patients were suffering from acute uncomplicated malaria due to either P.vivax or P. falciparum. Patients were treated orally with 3 doses of halofantrine hydrochloride, 500?mg/6-hourly in adults or 8?mg/kg body weight 6-hourly in children. The overall cure rate was 96.9%. The mean fever clearance time for different species was as follows: P. vivax — 39.1 hours, P. falciparum — 43.2 hours, mixed infection — 60.0 hours, and the mean parasitaemia clearance times were 47.7, 55.1 and 72.0 hours, respectively. Recrudescence was reported in 11 (4.1%) patients, although all of them were parasite-free on Day 7 post-treatment. No haematological or biochemical abnormalities were noted. The drug was very well tolerated and no significant side-effects were reported. Halofantrine was found to be highly effective in acute malaria and offers an important alternative to existing medications.     

High Prevalence of Activated Protein C Resistance Due to Factor V Leiden Mutation in Cases of Intrauterine Fetal Death

Objective: To test a possible association between activated protein C resistance and intrauterine fetal death.

Methods: The activated protein C anticoagulant activity and factor V R506Q mutation were assessed in 14 nonpregnant women with a history of intrauterine fetal death and 14 healthy controls.

Results: Four women in the study group were heterozygotes for the factor V mutation and none of the controls. The mean activated protein C activity of the study group was statistically significantly lower than that of the controls (P = 0.013).

Conclusion: Resistance to activated protein C activity may be of etiologic importance in some cases of intrauterine fetal death.