Inhibition of P-glycoprotein activity and reversal of cancer multidrug resistance by <Emphasis Type="Italic">Momordica charantia</Emphasis> extract

Purpose Multidrug resistance (MDR) is known as a problem limiting the success of therapy in patients treated long term with chemotherapeutic drugs. The drug resistance is mainly due to the overexpression of the 170 kDa P-glycoprotein (Pgp), which causes a reduction in drug accumulation in the cancer cells. In this study, novel chemical modulator(s) from bitter melon (Momordica charantia L.) extracts obtained from leaves, fruits and tendrils were tested for their abilities to modulate the function of Pgp and the MDR phenotype in the multidrug-resistant human cervical carcinoma KB-V1 cells (high Pgp expression) in comparison with wildtype drug-sensitive KB-3-1 cells (lacking Pgp).Methods The KB-V1 and KB-3-1 cells were exposed to bitter melon extracts in the presence of various concentrations of vinblastine, and cytotoxicity was assessed by means of the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay. Relative resistance was calculated as the ratio of the IC₅₀ value of the KB-V1 cells to the IC₅₀ value of the KB-3-1 cells. Accumulation and efflux of vinblastine in KB-V1 and KB-3-1 cells were measured using a [³H]-vinblastine incorporation assay.Results The leaf extracts increased the intracellular accumulation of [³H]-vinblastine in KB-V1 cells in a dose-dependent manner, but extracts from the fruits and tendrils had no effect. By modulating Pgp-mediated vinblastine efflux, the leaf extracts decreased the [³H]-vinblastine efflux in KB-V1 cells in a dose-dependent manner, but not in KB-3-1 cells. Treatment of drug-resistant KB-V1 cells with bitter melon leaf extracts increased their sensitivity to vinblastine, but similar treatment of KB-3-1 cells showed no modulating effect. The fruit and tendril extracts did not affect the MDR phenotype in either cell line.Conclusion The leaf extracts from bitter melon were able to reverse the MDR phenotype, which is consistent with an increase in intracellular accumulation of the drug. The exact nature of the active components of bitter melon leaf extracts remains to be identified.     

Nutritional status of mentally retarded children in northwest spain: II. Biochemical indicators

AIM: To evaluate the nutritional status of mentally retarded children in the region of Galicia, northwest Spain, on the basis of serum biochemistry variables. METHODS: The following serum biochemistry variables were determined in a sample of 128 mentally retarded children (81 boys and 47 girls): albumin, prealbumin, retinol-binding protein, transferrin, ferritin, ceruloplasmin, iron, calcium, phosphorus, copper, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, alkaline phosphatase, transaminases and carnitine. A preliminary statistical analysis indicated that most information content could be maintained taking into consideration only five of these variables. A factor analysis of the resulting 5 x 128 variables-by-subjects data matrix was then performed, identifying three factors (FB1, FB2 and FB3) that together explained 74% of total variance. Taking these factors as indicators of nutritional status, the data were then analysed for possible effects of age, gender, socioeconomic and family environment, IQ, presence/absence of cerebral palsy, quality of diet, appetite and use of antiepileptics. RESULTS: The analysis suggests that most subjects were in the normal nutritional range, but that about 37% showed either borderline or definite malnutrition. The FB1 score showed a significant, positive correlation with age, while FB2 score was negatively correlated with age. The FB1 score showed a significant positive correlation with socioeconomic class, and was significantly higher among children from inland-rural areas than among children from coastal or urban areas. The FB1 score was also positively correlated with parents' mean age. Finally, the results suggest that antiepileptic treatment with phenobarbital or diphenylhydantoin led to reductions in serum levels of calcium and phosphorus. CONCLUSION: Malnutrition as revealed by biochemical variables is highly prevalent among mentally retarded children, and the prevalence is affected by socioeconomic and family environment variables.     

Tamm-Horsfall protein excretion to predict the onset of renal insufficiency

OBJECTIVE: Immunosuppressive therapy after liver transplantation may be a risk for kidney dysfunction. This work was designed to determine whether Tamm-Horsfall Protein (THP) could be considered as a marker for nephrotoxicity. DESIGN AND METHODS: THP was determined by an ELISA method in serial 24-h urine from liver transplant patients. Fourteen patients suffered renal insufficiency (LTr(1)) and 20 showed no acute renal damage (LTr(2)) after liver transplantation. RESULTS: No clear association could be seen between daily THP excretion and plasma creatinine levels by comparing serial samples collected at the same time. Nevertheless, significant differences were observed in pretransplant THP excretion between both groups of patients. The results (Median/Interquartile Range) were: Controls: 113.2/84.9 to 146.8 mg/24 h (n = 30); LTr(1): 36.9/18.3 to 54.5 mg/24 h (p<0.001 with respect to C and LTr(2)); LTr(2): 90.8/61.5 to 139.7 mg/24 h. CONCLUSIONS: The higher pretransplant synthesis and/or secretion of THP seem to have a protective role on the kidney during and after liver transplantation.     

Potent inhibition of human folylpolyglutamate synthetase by a phosphinic acid mimic of the tetrahedral reaction intermediate

A phosphorous-containing pseudopeptide folate analog (Valiaeva et al., J Org Chem 2001;66:5146-54) was designed to mimic the tetrahedral intermediate formed in the ATP-dependent reaction catalyzed by folylpolyglutamate synthetase (FPGS). This analog, methotrexate-phosphinate (MTX-phosphinate; 4-amino-4-deoxy-10-methylpteroyl-L-Glu-gamma-[psi(P(O)(OH)-CH(2))]glutarate), is a highly potent (K(is), 3.1+/-0.5 nM), competitive inhibitor of recombinant human cytosolic FPGS. Within experimental limits, FPGS inhibition was not time-dependent, and preincubation of FPGS, inhibitor, and ATP did not potentiate the inhibition. These results suggest that slow phosphorylation to produce a more potent inhibitor form is not involved. MTX-phosphinate was not growth inhibitory to human CCRF-CEM leukemia cells at 1 microM (70-fold above the concentration of MTX giving 50% growth inhibition), probably because of poor transport. Because of its exceedingly high potency as an FPGS inhibitor, MTX-phosphinate represents a lead structure from which cell-permeable analogs may be developed to test the hypothesis that FPGS inhibition is therapeutically efficacious.     

血清生化指标对胆源性胰腺炎的诊断意义

目的探讨血清生化指标的改变对诊断胆源性胰腺炎的临床意义。方法将107例急性胰腺炎患者分为胆源性及非胆源性胰腺炎两组,并对其血清生化指标TBIL、DBIL、ALT、AST、ALP、r-GT的改变进行回顾性分析。结果胆源性胰腺炎组生化指标异常升高的改变显著高于非胆源性胰腺炎组（P〈0.01）。结论血清TBIL、DBIL、ALT、AST、ALP、r-GT的异常升高对急性胆源性胰腺炎诊断有重要的参考意义。     

茶多酚对硝酸羟胺染毒小鼠血常规和血清生化值的影响

目的　观察绿茶提取物茶多酚对硝酸羟胺染毒小鼠血常规、血清生化值的影响。方法　采用腹腔注射硝酸羟胺建立中毒模型。雄性ICR小鼠随机分为正常组、硝酸羟胺染毒组、茶多酚预防组、茶多酚治疗组 ,常规测量各组外周血细胞和生化指标。结果　经过统计学分析 ,茶多酚可明显促进硝酸羟胺中毒导致的小鼠血常规的WBC、RBC、HGB、PLT计数改变的恢复 ,部分血清生化值AST/ALT、ChE、ALB、LDH、UA、Fe病理性改变的恢复。结论　茶多酚灌胃给药对硝酸羟胺中毒引起的氧化损伤具有一定的保护作用     

Evaluation of antihepatotoxic potential of Solanum xanthocarpum fruit extract against antitubercular drugs induced hepatopathy in experimental rodents

Objective

To assess the hepatoprotective effect of Solanum xanthocarpum (S. xanthocarpum) fruit extract against antitubercular drug-induced liver toxicity in experimental animals.

Methods

Ethanolic (50%) fruit extract of S. xanthocarpum (100, 200 and 400 mg/kg bw) was administered daily for 35 days in experimental animals. Liver toxicity was induced by combination of three antitubercular drugs [isoniazid (I) 7.5 mg/kg, rifampicin (R) 10 mg/kg and pyrazinamide (P) 35 mg/kg] given orally as suspension for 35 days in rats. The hepatoprotective activity was assessed using various biochemical parameters like aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatise (ALP), total bilirubin (TBL), albumin (ALB), total protein (TP), lactate dehydroginase (LDH), and serum cholesterol (CHL). Meanwhile, in vivo antioxidant activities as lipid peroxidation (LPO), reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) were measured in rat liver homogenate. The biochemical observations were supplemented by histopathological examination.

Results

The results demonstrated that treatment with S. xanthocarpum significantly (P<0.05-P<0.001) and dose-dependently prevented drug induced increase in serum levels of hepatic enzymes. Furthermore, S. xanthocarpum significantly (up to P<0.001) reduced the LPO in the liver tissue and restored activities of defence antioxidant enzymes GSH, SOD and CAT towards normal levels. Histopathology of the liver tissue showed that S. xanthocarpum attenuated the hepatocellular necrosis and led to reduction in inflammatory cells infiltration.

Conclusions

The results of this study strongly indicate the protective effect of S. xanthocarpum against liver injury which may be attributed to its hepatoprotective activity, and thereby scientifically support its traditional use.     

Biochemical characters and antibiotic susceptibility of Staphylococcus aureus isolates

Objective

To observe the biochemical characters and antibiotic susceptibility of isolated Staphylococcus aureus (S. auerus) strains against some conventional and traditional antibiotics.

Methods

Thirty post operative pathogenic isolated S. aureus strains were used in this study. Bacterial culture was done in Mueller-Hinton broth at 37 °C. Characters of these strains were determined by traditional biochemical tests such as hydrolysis test of gelatin, urea, galactose, starch and protein, and fermentation of lactose and sucrose. Antibiotic susceptibility were carried out by minimum inhibitory concentration test, minium bactericidal concentration test, disc agar diffusion test and brain heart infusion oxacillin screening agar.

Results

From this study, it was observed that 100% S. aureus isolates showed positive results in gelatin, urea and galactose hydrolysis test, 50% isolates were positive in starch hydrolysis test, 35% in protein hydrolysis test, 100% isolates in lactose fermenting test, but no isolate was positive in sucrose fermenting test. Antibiotic susceptibility testing suggested that 20% of isolates were resistant to kanamycin and 46.67% were resistant to oxacillin.

Conclusions

These findings show that all these isolates have gelatin, urea, galactose hydrolysis and lactose fermenting activity. 20% of these isolates were resistant to kanamycin and 46.67% were resistant to oxacillin.     

First trimester obstetric outcome of frozen thawed embryo transfer: does the stage of embryo make any difference?

BackgroundThe direction of management and outcome of frozen thawed embryo transfer (FET) is becoming different day by day with the invention of newer technologies and application of it as a treatment modality in modern medicine. It also contributes to around 25% of births because of Assisted Reproductive Technology (ART) procedures worldwide today.MethodsA prospective longitudinal study was conducted at ART Center of tertiary care hospital. Couples with infertility planned to undergo FET were included in the study. Following FET, all positive cases were followed up till 14 weeks period of gestation. Data were collected and analyzed with appropriate statistical test using Epitable, 6.04 version, and SPSS, version 18, software.ResultsDuring the study period, a total of 470 FET cycles were carried out, and 1108 cryopreserved embryos were subjected to thawing procedure. Overall survival rate of 93.86% was noted. Among various stages of embryos thawed, the lowest survival rate (64.62%) was found in blastocyst group. Biochemical pregnancy rate, clinical pregnancy rate, and ongoing pregnancy rate were also analyzed in different subgroup of transferred embryos. The blastocyst group showed best implantation and clinical pregnancy rate but lowest survival rate among all subgroup of embryos.ConclusionThe blastocyst transfer during FET cycle showed best clinical and ongoing pregnancy rate. So if clinical situations were favorable for blastocyst stage transfer, the same should be preferred for FET cycle.     

骨转换生化标志物昼夜节律的研究进展

骨转换生化标志物可对骨吸收和骨形成的过程提供快速、灵敏、且无创的监测.然而,它们的分泌水平呈现出夜晚或清晨高峰而午后或傍晚低谷的昼夜节律,引起学者们的关注.笔者综述了近20年骨转换生化标志物昼夜节律的研究进展.这一节律性波动,不仅对采样时间和治疗评估有临床意义,而且体现了骨代谢的一个重要的特性.