Bioassay-Guided Fractionation and In Vitro Antiproliferative Effects of Fractions of Artemisia nilagirica on THP-1 cell line

Artemisia nilagirica (Clarke) is a widely used medicinal herb in Indian traditional system of medicine. Therefore, the present study was designed to evaluate the effects of A. nilagirica extracts/fractions on inhibition of proliferation and apoptosis in a human monocytic leukemia (THP-1) cell line. The crude extracts (A. nilagirica ethyl acetate extract [ANE] and A. nilagirica methanolic extract [ANA]) showed cytotoxic activity toward THP-1 cells with the IC₅₀ values of 38.21 ± 7.37 and 132.41 ± 7.19 µg/ml, respectively. However, the cytotoxic activity of active fractions (ANE-B and ANM-9) obtained after column chromatography was found to be much more pronounced than their parent extracts. The IC₅₀ values of ANE-B and ANM-9 were found to be 27.04 ± 2.54 µg/ml and 12.70 ± 4.79 µg/ml, respectively, suggesting greater susceptibility of the malignant cells. Cell cycle analysis and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end-labeling (TUNEL) assay revealed that inhibition of cell growth by A. nilagirica fractions on THP-1 cells was mediated by apoptosis. Active fractions of A. nilagirica increased the expression levels of caspase-3, ?7, and poly-ADP-ribose polymerase (PARP), a critical member of the apoptotic pathway. These results suggested that active fractions of A. nilagirica may play a promising role in growth suppression by inducing apoptosis in human monocytic leukemic cells via mitochondria-dependent and death receptor-dependent apoptotic pathways.     

USEFULNESS OF EVALUATION OF ANTIMEASLES ANTIBODIES IN PRETERM BABIES

As per WHO recommendations, measles vaccine is administered at the age of 9 months which is based on studies demonstrating seroconversion (from positive to negative) at this age. However this contention may not hold good in preterm babies since they may have lower initial levels of passively transferred IgG antimeasles antibodies of maternal origin. To explore this possibility, 50 preterm babies (gestational age less than 37 weeks) were studied for antimeasles antibodies. Serum samples were collected at birth and then at 3 months and 5 months of age in all the cases. Antimeasles antibody assay was done in all the serum samples using ELISA kits. At birth 32% of infants were positive for antimeasles antibodies whereas 60% were weakly positive and 8% were negative. At 3 months of age 50% were sero negative, 2% positive and 40% weakly positive. The sero negativity was found to be 98% at 5 months with only 2% remaining positive. Since seroconversion is seen to occur in this vast majority of preterm infants at the age of 5 months, antimeasles vaccine should be administered at this age to this subset of more vulnerable babies.KEY WORDS: Antimeasles antibodies, Preterm babies, Seroconversion     

Prospective development of an individualised predictive model for treatment coverage using offline cone beam computed tomography surrogate measures in post‐prostatectomy radiotherapy

The aim of this study is to prospectively evaluate and model surrogate explanatory variables (SEVs) of target coverage and rectal dose pertaining to soft tissue anatomy visualised on cone beam computed tomography (CBCT) for incorporation into post‐prostatectomy treatment coverage verification protocols. Twenty post‐prostatectomy patients treated with conformal prostate bed radiotherapy (64–74 Gy) underwent CBCT daily at fractions 1 to 5, and then weekly. Treatment coverage was defined on each CBCT using ‘PTV95’, percentage of the CBCT PTV covered by original treatment fields, and ‘RECTD50’, dose delivered to 50% of CBCT rectal volume by original treatment fields. Three candidate SEVs for treatment coverage were defined for each scan: anterior rectal wall movement, change in bladder length and bladder base movement. Both anterior rectal wall movement and increase in bladder length predicted for the decreased PTV95 (P < 0.001 for each). Anterior movement of the anterior rectal wall predicted for increased RECTD50 (P < 0.001). Predictive models for the PTV95 and RECTD50 that accept the significant SEVs as inputs were developed. We developed simple CBCT‐acquired soft tissue anatomic surrogate measures that signal changes in target coverage and rectal dose during post‐prostatectomy radiotherapy. Conventional bony anatomy patient position verification protocols were inadequate in accounting for soft tissue target and organ variation seen with CBCT.     

Concentration Dependent Effect of (−)‐Epicatechin on Na+/K+‐ATPase and Ca2+‐ATPase Inhibition Induced by Free Radicals in Hypertensive Patients: Comparison with L‐ascorbic Acid

Although the antioxidant properties of flavonoids are well documented, it is still unclear whether these effects are dependent on radical scavenging or iron chelating activities. Oxidative stress, a state of excessive reactive oxygen species (ROS) activity, is associated with vascular disease conditions such as hypertension. Both the anti‐ and pro‐oxidant effects of tea catechins have been implicated in the alterations of cellular functions that determine their chemoprotective and therapeutic potentials in health and diseases. The present study examined the concentration dependent (10^?7 to 10^?4 m ) effects of (?)‐epicatechin and L‐ascorbic acid on Na⁺/K⁺‐ATPase and Ca²⁺‐ATPase activity in hypertensive patients and normal subjects. L‐ascorbic acid has been used as a positive control to compare the effect of (?)‐epicatechin. A significant (p < 0.0001) decrease in the activities of Na⁺/K⁺‐ATPase and Ca²⁺‐ATPase was observed in hypertensive patients compared with normal subjects. We report that (?)‐epicatechin shows a significant (p < 0.001) dose‐dependent protective effect against oxidative stress induced by tert‐butyl hydroperoxide (t‐BHP), which is manisfested as a decrease in the activity of erythrocyte Na⁺/K⁺‐ATPase and Ca²⁺‐ATPase, in hypertensive patients as well as normal subjects. The effect of L‐ascorbic acid was also significant (p < 0.001) and was comparable with that of (?)‐epicatechin. Copyright © 2012 John Wiley & Sons, Ltd.     

Oncogenic extrachromosomal DNA functions as mobile enhancers to globally amplify chromosomal transcription

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Interaction of glutathione-s-transferase genotypes with environmental risk factors in determining susceptibility to head and neck cancer and treatment response and survival outcome

The present case-control study aimed to investigate the role of interaction of glutathione-s-transferase (GST) genotypes with environmental risk factors in determining susceptibility to head and neck squamous cell carcinoma (HNSCC) involving 1,250 cases and equal number of healthy controls. An increase in the risk of HNSCC and its subsites (larynx, pharynx, and oral cavity) was observed among the cases with null genotypes of GSTM1 (odds ratio [OR] = 1.87) or GSTT1 (OR = 1.39) while reduced risk (OR = 0.81) was observed the cases with variant genotype of GSTP1. Tobacco use in the form of smoking or chewing interacted multiplicatively with GSTM1 or GSTT1 to increase the risk several folds (3–10 folds) in HNSCC and its subsites. Alcohol use also increased the risk (2–3 folds) to HNSCC and its subsites in cases with null or variant genotypes of GSTs, though this risk was of lesser magnitude when compared to the tobacco users. A synergistic effect of both, tobacco smoking and alcohol drinking, led to several folds (25-folds) increased risk to HNSCC among the cases with null genotype of GSTM1 and GSTT1 when compared to nonsmokers and nondrinkers with wild genotype of GSTM1 and GSTT1 in controls. Furthermore, cases with variant genotypes of GSTP1 (Val/Val) showed superior treatment response with improved survival rate and lower risk of death when compared to the patients with wild type genotype (Ile/Ile). The data suggest that though polymorphism in GSTs may be a modest risk factor for determining HNSCC risk, gene-environment interactions significantly modify the susceptibility to HNSCC by several folds.     

Glycosylated hemoglobin and diabetic retinopathy

Estimation of glycosylated hemoglobin (HbA1c) levels by modified Fluckinger and Winterhalter's method was done in 25 normal persons, 25 diabetic patients without retinopathy, and 25 diabetic patients with retinopathy. The HbA1c values were significantly higher in diabetic patients with or without retinopathy than in the control group (P less than .001). In diabetic patients with retinopathy, the mean value of HbA1c was higher in proliferative retinopathy than in background retinopathy, but statistical analysis showed this was not significant (P greater than .6).     

常用抗高血压药物对血压的时间生物学特征的影响

目的 :探讨 3类常用抗高血压药物对非杓型的高血压病患者BP的时间生物学特征的影响。方法 :共入选非杓型BP分布的高血压病患者 16 1例 ,将其随机分为 3组 ,分别给予赖诺普利 (10mg·d-1) ,非洛地平 (2 5mg·d-1) ,或氢氯噻嗪 (5 0mg·d-1) ,并于治疗前后行 2 4h动态BP监测。采用余弦拟合方法分析治疗前后患者BP时间生物学特征的改变。结果 :赖诺普利组与非洛地平组治疗后 2 4hBP均值明显降低 ,但其振幅、峰值相位无变化 ;氢氯噻嗪治疗降压效果不甚理想 ,但显著增加了患者BP的夜间降低幅度 ,使患者BP由非杓型转变为杓型分布。结论 :氢氯噻嗪治疗可能使非杓型分布的高血压病患者的BP转变为杓型分布 ,从而有助于降低患者相关并发症的发生率。