A randomized comparative study between low-dose magnesium sulphate and standard dose regimen for management of eclampsia

Background: Eclampsia is a hypertensive disorder related to pregnancy, in which there is occurrence of one or more generalized convulsions and or coma, in the absence of other neurologic conditions. It is a common obstetric emergency. It contributes significantly to maternal and perinatal morbidity and mortality. Dr. J. A. Pritchard in 1955, introduced magnesium sulphate for control of convulsions in eclampsia and is used worldwide. Considering the low body mass index of Indian women, a low dose magnesium sulphate regime has been introduced by some authors. The Objective was to compare the efficacy of low dose magnesium sulphate regimen with standard Pritchard’s regimen for eclampsia.Methods: A prospective randomized study of fifty eclampsia cases, treated with magnesium sulphate (25 each with low dose regime and Pritchard regime) was carried out from October 2010 to January 2012 at MAMC & LNH, New Delhi, India. Results were analysed using Statistical Package of Social Sciences (SPSS) software 17.0.Results: In the present study, convulsions were controlled in 96% of eclampsia cases with low dose magnesium sulphate regimen. One case i.e. 4% had single episode of recurrence of convulsion, which was controlled by giving additional drugs and shifted to standard dose regimen. There was no maternal mortality.Conclusions: The maternal and perinatal morbidity and mortality in the present study were comparable to those of standard Pritchard’s regimen. The study did not find a single case of magnesium related toxicity with low dose magnesium sulphate regimen. Low dose magnesium sulphate regimen was found to be safe and effective in eclampsia

Dynamics on Multiple Potential Energy Surfaces: Quantitative Studies of Elementary Processes Relevant to Hypersonics

The determination of thermal and vibrational relaxation rates of triatomic systems suitable for application in hypersonic model calculations is discussed. For this, potential energy surfaces for ground and electronically excited state species need to be computed and represented with high accuracy and quasiclassical or quantum nuclear dynamics simulations provide the basis for determining the relevant rates. These include thermal reaction rates, state-to-state cross-sections, or vibrational relaxation rates. For exemplary systems - [NNO], [NOO], and [CNO] - all individual steps are described and a literature overview for them is provided. Finally, as some of these quantities involve considerable computational expense, for the example of state-to-state cross sections the construction of an efficient model based on neural networks is discussed. All such data is required and being used in more coarse-grained computational fluid dynamics simulations.Comment: Review article, 46 pages, 8 figure

Permutationally Invariant, Reproducing Kernel-Based Potential Energy Surfaces for Polyatomic Molecules: From Formaldehyde to Acetone

Constructing accurate, high dimensional molecular potential energy surfaces (PESs) for polyatomic molecules is challenging. Reproducing Kernel Hilbert space (RKHS) interpolation is an efficient way to construct such PESs. However, the scheme is most effective when the input energies are available on a regular grid. Thus the number of reference energies required can become very large even for penta-atomic systems making such an approach computationally prohibitive when using high-level electronic structure calculations. Here an efficient and robust scheme is presented to overcome these limitations and is applied to constructing high dimensional PESs for systems with up to 10 atoms. Using energies as well as gradients reduces the number of input data required and thus keeps the number of coefficients at a manageable size. Correct implementation of permutational symmetry in the kernel products is tested and explicitly demonstrated for the highly symmetric CH$_4$ molecule.Comment: 40 pages, 13 Figure

Influence of Glutathione S-Transferase Polymorphisms on Cognitive Functioning Effects Induced by p,p′-DDT among Preschoolers

5 pages, 4 tables.-- PMID: 19057715 [PubMed].-- PMCID: PMC2592282.-- Printed version published Nov 2008.Background Early-life exposure to p,p′-DDT [2,2-bis(p-chlorophenyl)-1,1,1-trichloroethane] is associated with a decrease in cognitive skills among preschoolers at 4 years of age. We hypothesized that genetic variability in glutathione S-transferase (GST) genes (GSTP1, GSTM1, and GSTT1) could influence the effects of prenatal exposure to p,p′-DDT.Methods We used data from 326 children assessed in a prospective population-based birth cohort at the age of 4 years. In that study, the McCarthy Scales of Children’s Abilities were administrated by psychologists, organochlorine compounds were measured in cord serum, and genotyping was conducted for the coding variant Ile105Val from GSTP1 and for null alleles from GSTM1 and GSTT1. We used linear regression models to measure the association between organochlorines and neurodevelopmental scores by GST polymorphisms.Results p,p′-DDT cord serum concentration was inversely associated with general cognitive, memory, quantitative, and verbal skills, as well as executive function and working memory, in children who had any GSTP1 Val-105 allele. GSTP1 polymorphisms and prenatal p,p′-DDT exposure showed a statistically significant interaction for general cognitive skills (p = 0.05), quantitative skills (p = 0.02), executive function (p = 0.01), and working memory (p = 0.02). There were no significant associations between p,p′-DDT and cognitive functioning at 4 years of age according to GSTM1 and GSTT1 polymorphisms.Conclusions Results indicate that children with GSTP1 Val-105 allele were at higher risk of the adverse cognitive functioning effects of prenatal p,p′-DDT exposure.This study was funded by grants from the Spanish Ministry of Health (FIS-PI041436, FIS-PI041705, FIS-PI051187), Instituto de Salud Carlos III (Red INMA G03/176 and CB06/02/0041), and Ciber en Epidemiología y Salud Pública, the Generalitat de Catalunya-CIRIT (Consejo Interdepartmental de Investigación e Innovación de Cataluña) (1999SGR 00241), and Genome Spain.Peer reviewe

Chiral edge waves in a dance-based human topological insulator

Topological insulators are insulators in the bulk but feature chiral energy propagation along the boundary. This property is topological in nature and therefore robust to disorder. Originally discovered in electronic materials, topologically protected boundary transport has since been observed in many other physical systems. Thus, it is natural to ask whether this phenomenon finds relevance in a broader context. We choreograph a dance in which a group of humans, arranged on a square grid, behave as a topological insulator. The dance features unidirectional flow of movement through dancers on the lattice edge. This effect persists when people are removed from the dance floor. Our work extends the applicability of wave physics to the performance arts

Estrogenic Activity of Coumestrol, DDT, and TCDD in Human Cervical Cancer Cells

Endogenous estrogens have dramatic and differential effects on classical endocrine organ and proliferation. Xenoestrogens are environmental estrogens that have endocrine impact, acting as both estrogen agonists and antagonists, but whose effects are not well characterized. In this investigation we sought to delineate effects of xenoestrogens. Using human cervical cancer cells (HeLa cells) as a model, the effects of representative xenoestrogens (Coumestrol-a phytoestrogen, tetrachlorodioxin (TCDD)-a herbicide and DDT-a pesticide) on proliferation, cell cycle, and apoptosis were examined. These xenoestrogens and estrogen inhibited the proliferation of Hela cells in a dose dependent manner from 20 to 120 nM suggesting, that 17-β-estrtadiol and xenoestrogens induced cytotoxic effects. Coumestrol produced accumulation of HeLa cells in G2/M phase, and subsequently induced apoptosis. Similar effects were observed in estrogen treated cells. These changes were associated with suppressed bcl-2 protein and augmented Cyclins A and D proteins. DDT and TCDD exposure did not induce apoptosis. These preliminary data taken together, suggest that xenoestrogens have direct, compound-specific effects on HeLa cells. This study further enhances our understanding of environmental modulation of cervical cancer

Determining Protease Substrate Selectivity and Inhibition by Label-Free Supramolecular Tandem Enzyme Assays

An analytical method has been developed for the continuous monitoring of protease activity on unlabeled peptides in real time by fluorescence spectroscopy. The assay is enabled by a reporter pair comprising the macrocycle cucurbit[7]uril (CB7) and the fluorescent dye acridine orange (AO). CB7 functions by selectively recognizing N-terminal phenylalanine residues as they are produced during the enzymatic cleavage of enkephalin-type peptides by the metalloendopeptidase thermolysin. The substrate peptides (e.g., Thr-Gly-Ala-Phe-Met-NH2) bind to CB7 with moderately high affinity (K ≈ 104 M–1), while their cleavage products (e.g., Phe-Met-NH2) bind very tightly (K \u3e 106 M–1). AO signals the reaction upon its selective displacement from the macrocycle by the high affinity product of proteolysis. The resulting supramolecular tandem enzyme assay effectively measures the kinetics of thermolysin, including the accurate determination of sequence specificity (Ser and Gly instead of Ala), stereospecificity (d-Ala instead of l-Ala), endo- versus exopeptidase activity (indicated by differences in absolute fluorescence response), and sensitivity to terminal charges (−CONH2 vs −COOH). The capability of the tandem assay to measure protease inhibition constants was demonstrated on phosphoramidon as a known inhibitor to afford an inhibition constant of (17.8 ± 0.4) nM. This robust and label-free approach to the study of protease activity and inhibition should be transferable to other endo- and exopeptidases that afford products with N-terminal aromatic amino acids

Influence of glutathione S-transferase polymorphisms on cognitive functioning effects induced by p,p'-DDT among preschoolers

5 pages, 4 tables.-- PMID: 19057715 [PubMed].-- PMCID: PMC2592282.-- Printed version published Nov 2008.Background Early-life exposure to p,p′-DDT [2,2-bis(p-chlorophenyl)-1,1,1-trichloroethane] is associated with a decrease in cognitive skills among preschoolers at 4 years of age. We hypothesized that genetic variability in glutathione S-transferase (GST) genes (GSTP1, GSTM1, and GSTT1) could influence the effects of prenatal exposure to p,p′-DDT.Methods We used data from 326 children assessed in a prospective population-based birth cohort at the age of 4 years. In that study, the McCarthy Scales of Children’s Abilities were administrated by psychologists, organochlorine compounds were measured in cord serum, and genotyping was conducted for the coding variant Ile105Val from GSTP1 and for null alleles from GSTM1 and GSTT1. We used linear regression models to measure the association between organochlorines and neurodevelopmental scores by GST polymorphisms.Results p,p′-DDT cord serum concentration was inversely associated with general cognitive, memory, quantitative, and verbal skills, as well as executive function and working memory, in children who had any GSTP1 Val-105 allele. GSTP1 polymorphisms and prenatal p,p′-DDT exposure showed a statistically significant interaction for general cognitive skills (p = 0.05), quantitative skills (p = 0.02), executive function (p = 0.01), and working memory (p = 0.02). There were no significant associations between p,p′-DDT and cognitive functioning at 4 years of age according to GSTM1 and GSTT1 polymorphisms.Conclusions Results indicate that children with GSTP1 Val-105 allele were at higher risk of the adverse cognitive functioning effects of prenatal p,p′-DDT exposure.This study was funded by grants from the Spanish Ministry of Health (FIS-PI041436, FIS-PI041705, FIS-PI051187), Instituto de Salud Carlos III (Red INMA G03/176 and CB06/02/0041), and Ciber en Epidemiología y Salud Pública, the Generalitat de Catalunya-CIRIT (Consejo Interdepartmental de Investigación e Innovación de Cataluña) (1999SGR 00241), and Genome Spain.Peer reviewe