MSH2 118T>C and MSH6 159C>T promoter polymorphisms and the risk of colorectal cancer

The most important indicator of colorectal cancer (CRC) risk is the presence of family history of the disease. Inherited genetic changes, such as single nucleotide polymorphisms, in key candidate genes may contribute to CRC risk. We investigated whether promoter polymorphisms in DNA mismatch repair (MMR) genes MSH2 and MSH6 are associated with the risk of CRC. We genotyped 929 CRC patients and 1098 control subjects from Ontario, and 467 patients and 344 controls from Newfoundland and Labrador, for two promoter polymorphisms in the MMR genes MSH2 and MSH6 using the fluorogenic 5' nuclease assay. We used unconditional logistic regression to evaluate the association between each polymorphism and CRC after adjusting for age and sex. The associations between polymorphisms and tumor clinicopathological features were evaluated with a Pearson's chi-squared test or Fisher's exact test. All statistical tests were two sided. We observed strong associations between the MSH2 -118T>C polymorphism and family history of CRC based on the Amsterdam criteria I (P = 0.005) and Amsterdam criteria I and II (P = 0.036) among cases from Ontario. This association was especially evident among female CRC patients in Ontario (for Amsterdam criteria I, and I and II combined, P = 0.003 and P = 0.0001, respectively). The MSH2 -118T>C polymorphism was associated with strong family history of CRC in Ontario patients.     

HPTLC method for the estimation of alkaloids of Cinchona officinalis stem bark and its marketed formulations

We report a sensitive method for the estimation of quinine (Qn), cinchonine (Cn), and cinchonidine (Cnd) and a new method based on fluorescence enhancement and detection and quantification of quinidine (Qnd) from Cinchona stem bark and its formulations, using HPTLC. Standard solutions of Qn, Qnd, Cn, and Cnd were applied on precoated HPTLC plates and developed with chloroform/diethylamine (9.6:1.4 v/v). The plates were scanned and quantified at 226 nm for Qn, Cn, Cnd and for Qnd at 366 nm in fluorescence and reflectance mode ([symbol: see text] K400 filter). The method was validated for precision, accuracy and repeatability. Further, the stem bark of Cinchona officinalis and some herbal and homeopathic formulations were evaluated for their individual alkaloid content applying the developed method.     

A biostatistical approach to ayurveda: quantifying the tridosha

OBJECTIVE: To compute quantitative estimates of the tridosha--the qualitative characterization that constitutes the core of diagnosis and treatment in Ayurveda--to provide a basis for biostatistical analysis of this ancient Indian science, which is a promising field of alternative medicine. SUBJECTS: The data sources were 280 persons from among the residents and visitors/training students at the Brahmvarchas Research Centre and Shantikuj, Hardwar, India. DESIGN/METHODOLOGY: A quantitative measure of the tridosha level (for vata, pitta, and kapha) is obtained by applying an algorithmic heuristic approach to the exhaustive list of qualitative features/factors that are commonly used by Ayurvedic doctors. A knowledge-based concept of worth coefficients and fuzzy multiattribute decision functions are used here for regression modeling. VALIDATION AND APPLICATIONS: Statistical validation on a large sample shows the accuracy of this study's estimates with statistical confidence level above 90%. The estimates are also suited for diagnostic and prognostic applications and systematic drug-response analysis of Ayurvedic (herbal and rasayanam) medicines. An application with regard to the former is elucidated, extensions of which might also be of use in investigating the role of nadis in Ayurvedic healing vis-a-vis acupuncture and acupressure techniques. The importance and scope of this novel approach are discussed. CONCLUSIONS: This pioneering study shows that the concept of tridosha has a sound empirical basis that could be used for the scientific establishment of Ayurveda in a new light.     

Tyrosine-derived novel antimicrobial hydantoin polymers: synthesis and evaluation of anti-bacterial activities

A new approach for the design and synthesis of cyclic N-halamine polymers having anti-bacterial activity based on a vinyl derivative of tyrosine-derived hydantoin is reported. The synthesis of N-halamine polymers generally involves the chemical modification of 5,5′-disubstituted hydantoin to introduce polymerizable vinyl moieties thereby restricting the halogen capture only on the amide nitrogen. Here we show the possibility of synthesizing vinyl monomers of N-halamine from α-amino acids wherein both the amide and imide nitrogens are available for halogen capture. Thus, a hydantoin monomer was synthesized from L-tyrosine and copolymerized with methyl methacrylate and 2-(hydroxyethyl)methacrylate, to obtain random co-polymers. The monomer and its co-polymers were characterized using NMR, IR, HRMS, GPC, DSC, EDAX and TGA analysis. Films of the co-polymers cast from 10% acetone solutions were exposed to sodium hypochlorite solution to activate the hydantoin moieties. The oxidative chlorine content of the films ranged from 0.6 to 0.9%. The activated films were exposed to both Gram positive (S. aureus) and Gram negative (E. coli) bacteria using standard protocols. Polymers having chlorine content as little as 0.6% exhibited 6 log reduction in the bacterial growth within 30 min of exposure. The method allows the halogenation of both amide and imide nitrogens and could be applied to the preparation of a number of vinyl hydantoins from many amino acids.     

Pune low birth weight study — Birth to adulthood — Cognitive development

Objective

To assess the cognitive development of non-handicapped low birth weight (LBW) infants at 18 years.

Design

Prospective cohort study.

Setting

Infants born between 1987–1989 with birth weight less than 2000g and discharged from a neonatal special care unit were followed up till the age of 18 years.

Methods

The intelligence quotient (IQ) was determined by Raven’s progressive matrices. Assessment of adjustment and aptitude was done.

Results

The cohort of 161 LBW infants was divided into three groups according to their gestation — preterm SGA (n=61), full term SGA (n=30) and preterm AGA (n=70). 71 full term AGA infants served as controls. The IQ of the study group (Percentile 39.3) was significantly lower than that of controls (Percentile 54.9) (P=0.002). Preterm SGA subjects had the lowest IQ (Percentile 35.5), though just within normal limits. Males from the study group had significantly lower IQ than male controls (P=0.03). The IQ of PTSGA subjects of college educated mothers (P=0.004) and belonging to higher socio-economic class (P=0.04) was significantly higher. On the differential aptitude test, PTSGA subjects were poor in speed and mechanical reasoning. The 18 year IQ could be best predicted by IQ at 6 and 12 years.

Conclusion

Preterm SGA children have the lowest IQ at 18 years, males have lower IQ. Maternal education and socioeconomic status have great impact on cognitive development. Good prediction of the 18 year IQ can be done by the 6 and 12 year IQ.     

Prognostic indicators of changes in bone density measures in adolescent girls with anorexia nervosa-II

INTRODUCTION: Adolescents with anorexia nervosa (AN) have low bone mineral density (BMD). Baseline predictors of temporal BMD changes (DeltaBMD) in AN, including 1) gastrointestinal peptides regulating food intake and appetite that have been related to bone metabolism and 2) bone turnover markers, have not been well characterized. We hypothesized that baseline levels of nutritionally regulated hormones and of bone turnover markers would predict DeltaBMD overall. METHODS: In a prospective observational study, lumbar and whole-body BMD was measured at 0, 6, and 12 months in 34 AN girls aged 12-18 yr and 33 controls. Baseline body mass index, lean mass, nutritionally regulated hormones [IGF-I, cortisol, ghrelin, leptin, and peptide YY (PYY)], bone formation, and resorption markers were examined to determine nutritional and hormonal predictors of bone density changes. RESULTS: In a regression model, baseline ghrelin and PYY predicted changes in spine bone measures; and baseline ghrelin, cortisol, and PYY predicted changes in whole-body bone measures independent of baseline nutritional status. CONCLUSIONS: Neuroendocrine gastrointestinal-derived peptides regulating food intake are independent predictors of changes in bone mass in AN.