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

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

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

Hypertension, cancer and angiogenesis: relevant epidemiological and pharmacological aspects

Hypertension and cancer are two leading diseases in the world. Often they coexist in patients. They share some common predisposing factors e.g., ageing, obesity, alcohol consumption and smoking habit. Abnormal angiogenesis (i.e. the formation of new blood vessels from an existing vasculature) is a common pathological feature, and some pro-angiogenic factors e.g., vascular endothelial growth factor, basic fibroblast growth factor, tumor necrosis factor-alpha and few interleukins are common mediators in both the conditions. Among these, the most important is vascular endothelial growth factor, a specific mitogen for vascular endothelium. It increases vascular permeability and induces proteolytic enzymes that are necessary for vascular remodeling. Monocyte/macrophages also have been shown to play a role in angiogenesis by releasing some of the above mediators. Angiogenesis is essential for the growth and metastasis of solid tumors. The essence of impaired angiogenesis (despite high level of angiogenic factors), probably due to signaling defects in the endothelium in hypertension, is not clearly understood. Some anticancer drugs e.g., taxanes, vinblastine, temozolomide and doxorubicin have antiangiogenic activity. Nevertheless, several classes of specific antiangiogenic agents are being evaluated for their anticancer effects and are emerging as new drugs for cancer treatment. COX-2 inhibitors (e.g., celecoxib and rofecoxib), neovastat, thalidomide analogues and some cytokine inhibitors also inhibit angiogenesis. Although certain antihypertensives are found to have antiangiogenic properties, some show pro-angiogenic activity. Also, a number of epidemiological studies have found an association between the use of antihypertensive drugs and risk of cancer. However, a better understanding of common cell biology and the relationship between hypertension and malignancy may be helpful in elucidating more preventive and therapeutic avenues to manage hypertension and cancer

Comparative Evaluation of Peroxidation of Sesame and Cottonseed Oil Induced by Different Methods of Heating

162-165Flame, induction and microwave are three commonly used methods of heating during cooking. The extent of thermal alteration differs in different oils and depends on several factors. Thermal alteration in cottonseed oil, is not yet fully explored. This study compares peroxidation in cottonseed oil induced by flame, induction and microwave heating with that in sesame oil. Cottonseed oil and sesame oil were heated on the controlled flame of Bunsen burner, induction cooker and microwave oven. Lipid peroxide level from these oils at 0, 5, 10 and 20 minutes of heating was measured from thiobarbituric acid reactivity. Lipid peroxidation in both the oils increased in a time-dependent manner and was the maximum when heated on a controlled flame, followed by induction cooker and then by microwave heating. Fold rise in lipid peroxides were lower in cottonseed oil. It resisted lipid peroxidation significantly in comparison to sesame oil by all three methods of heating. So the use of cottonseed oil and microwave may be promoted and encouraged for cooking in oil

Hepatoprotective activity of six polyherbal formulations in CCl₄-induced liver toxicity in mice

257-263To evaluate pretreatment of six polyherbal liquid formulations (PLFs) commercially available in India, on CCl4-induced liver injury, Swiss albino mice were treated for 7 days with distilled water or PLFs (2.6 and 5.2 ml/kg body weight/day, po) followed by single sc injection of 50% (v/v) CCl4 in arachis oil at a dose of 1ml/kg. The serum biochemical parameters such as alanine transaminases, aspartate transaminases and alkaline phosphatase were estimated. Phenobarbitone-induced sleeping time and liver histopathology were also carried out. CCl4-treated animals showed significant increase in the levels of liver enzymes, phenobarbitone-induced sleeping time and revealed fatty changes and centrizonal necrosis on histological examination of liver indicating hepatic damage. When pretreated with PLFs at a dose of 5.2 ml/kg body weight/day, the CCl4-induced changes were significantly reversed. The pretreatment with PLFs can prevent acute liver damage induced by CCl4 only at a higher dose. Therefore, it is suggested that a dose adjustment of these PLFs may be necessary for their optimal effects in human liver diseases

DataSheet1_A quantification method for trace level of oxytocin in food matrices using LC-MS/MS.docx

Backgrounds: Oxytocin is nowadays used to increase the agricultural products besides its use during the milking of cattle leading to the contamination of agricultural produce and milk with oxytocin. Monitoring of accurate oxytocin contaminations from foodstuffs is sometimes required to maintain the quality standard. The commonly used oxytocin assays in this study were interfered with by the food matrix. There is a need to develop an accurate and confirmed method for monitoring oxytocin contaminations in foodstuffs.Objective: An attempt is made to develop an accurate assay method of oxytocin from milk and agricultural produces.Methods: The acidified methanol was used for the extraction of oxytocin from target food stuff/matrices (agricultural produce and Milk). LC-MS/MS was used for its detection and quantification. In the chromatographic separation, Oxytocin concentration was optimized using selective reaction monitoring (SRM) with heated electrospray ionization (HESI) in positive polarity. The chromatographic separation was performed using a reversed-phase C18 column with gradient elution at a flow rate of 0.4 ml/min. The acidified methanol was used for the extraction of oxytocin in all target food matrices. The method performance was verified as per the SANTE 2021 guideline. After method validation, the method was applied in real food samples analysis for assessing the presence/absence of oxytocin.Results: The calibration curve offered excellent linearity (R2 = 0.999) with less than 15% residuals. The matrix effect was Conclusion: Extraction of oxytocin using acidified methanol followed by assays using LC-MS/MS is a simple, sensitive, accurate, reproducible, and practically suitable method for detection and quantification of oxytocin from milk, fruits, and vegetables.</p

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