A structural and functional analysis of the phosphatidylinositol 3-kinase

Phosphatidylinositol 3-kinase has emerged as an important signal transducing molecule which is activated by diverse receptor and non-receptor protein-tyrosine kinases (PTK) and in some cells may be an important mediator in the events leading to mitogenesis. The affinity purification of PI 3-kinase from bovine brain has shown that this enzyme is a tightly associated heterodimer of 85 kDa and 110 kDa subunits. Structural analysis at the protein and cDNA levels revealed two forms of the 85 kDa subunit, p85 [alpha] which corresponds to the material purified from the bovine brain, and another highly related protein termed p85 [beta]. Both p85 proteins contain an N-terminal SH3 domain, followed by a BCR domain and two SH2 domains separated by a region predicted to adopt a helical conformation. The p85 proteins have been expressed in insect cells using the baculovirus expression system and they are shown to form tight complexes with many PTKs when coexpressed in the same cell. The cloning of the catalytic bovine pi 10 subunit of PI 3-kinase has allowed expression of the p110 subunit in insect cells. This protein was subsequently shown to possess an intrinsic PI 3-kinase activity when expressed alone and to form a stable active complex with p85aand p85?both in vitro and in vivo. The sites of interaction between the two subunits have been mapped to the N-terminal region of pi 10 to a sequence of 35 amino acids in the inter-SH2 domain of p85. The p85[alpha]/p110 and the p85[beta]/p110 complexes bind to activated PTKs in a manner that is more selective than the binding of p85[alpha] or p85 [beta] alone to PTKs. Additional biochemical and mutagenesis studies of the catalytic p110 subunit have demonstrated that this is a novel dual specificity enzyme with an intrinsic protein-serine kinase activity which in turn regulates its PI 3-kinase activity. These studies using the recombinant enzyme have been complemented by the analysis of endogenous PI 3-kinase activation in PDGF-stimulated NIH 3T3 cells

Self medicated Combiflam induced acute dermatological drug reaction

A 30 year old female  took a single tablet of Combiflam (ibuprofen 400mg + paracetamol 325mg) for backache following which she noticed maculopapular rashes with generalized facial and lip swelling with generalized itching. Subsequently patient was treated with antihistaminic and steroids and she responded well. The causality assessment according to Naranjo casualty assessment scale come under “Probable” category of adverse drug reaction. According to World Health Organization-Uppsala Monitoring Centre causality assessment scale it falls under “Probable/Likely” category. According to Hartweig and Siegel severity assessment scale it was level 3 and moderate adverse drug reaction.  This is a rare adverse effect of combiflam with the incidence less than 0.1%. The awareness of the health care personnel to this widely used drug on its rare adverse effect is necessary

Role of antihypertensives drugs on proteinuria in patients with chronic kidney disease and hypertension

Background: Hypertension is the most prevalent cardiovascular disease and the relevant data suggest that the burden, risk factors and co-morbidities associated with the essential hypertension is increasing with every passing day. It is one of the major chronic diseases resulting in high mortality and morbidity in today’s world. Aim: The aim of the study was to compare effects of cilnidipine and amlodipine on the blood pressure (BP), heart rate and proteinuria among patients of hypertension with chronic kidney disease.Methods: 100 patients were included in this study. Patients were randomly assigned into two groups Group A and Group B (50 each). Group A: Patients received Cilnidipine (5-10mg/day). Group B: Patients received amlodipine (5-10mg/day).Results: No significant difference in SBP, DBP, MBP and proteinuria while comparing both the groups of patients taking cilnidipine and amlodipine at baseline i.e. 0 to 12 week, 12 to 24 weeks and 0 to 24 weeks. Cilnidipine caused decrease in HR 0 to 12 week (p value 0.001), 12 to 24 weeks (p value 0.001) and 0 to 24 weeks (p value 0.0001). Amlodipine had increased heart rate from baseline to 12 weeks (p value 0.0001), 12 to 24 weeks (p value 0.051) and 0 to 24 weeks (p value 0.001). No significant difference was seen in any biochemical readings.Conclusions: There was a significant change in all the parameters including BP, heart rate, proteinuria and other biochemical tests when they compared within the group but no significant difference while comparing both the groups

Development of near isogenic lines (NILS) using backcross method of breeding and simultaneous screening against Karnal bunt disease of wheat

Karnal bunt of wheat caused by Tilletia indica can be a hindrance to wheat trade as the fungal disease is known to affect the quality of the grain. As a breeding strategy, a set of eight near isogenics lines (NILs) and backcross derived recombinant inbred lines (micro-RILs) were developed in the background of PBW 343 and WH542 for Karnal bunt resistance over a period of time. The donor stocks resistant to Karnal bunt used in the study were ALDAN ‘ S’ / IAS 58, CMH 77.308, H567.7I, HD29, HP1531, W485 and their derived lines KBRL 22 and KBRL 57. Effective method for screening to Karnal bunt was standardized and used for identification of resistant lines across many seasons. Some of the identified lines evaluated for yield were found to be equivalent to the high yielding parents and the commercially grown check varieties. These developed lines will serve as a basic material for production of Karnal bunt free wheat

Knowledge and attitude towards antimicrobial self medication usage: a cross sectional study among medical and nursing students

Background: Antimicrobial drug resistance is a fast mounting universal crisis. Many factors like self medication, inappropriate use and unregulated sale of medicines and self medication have been attributed to this problem. The objective was to determine extend and causes of antimicrobial self medication and to compare the knowledge attitude of senior and junior medical/nursing students. Methods: We conducted a cross-sectional study on randomly selected 410 students from Baba Farid University of Health Sciences Faridkot, Punjab. A total sample of 220 medical students were enrolled from GGS Medical College, Faridkot (1st year students 50 and 170 above 1st year senior medical students ) and 190 nursing students were enrolled from University College of Nursing, Faridkot. Results: prevalence of antimicrobial self medication came out to be around 74%. The most common cause for seeking antimicrobial (self therapy) was upper respiratory tract infection. A statistical significant knowledge/attitude gap was found between senior and fresher medical/nursing students. Conclusions: High prevalence of antimicrobial self medication among medical/nursing students is a matter of concern and it should be discouraged at appropriate level to safeguard students from preventable adversary exposure.

Association of proton pump inhibitors with renal dysfunction: a cross-sectional study

Background: Proton pump inhibitors are the most frequently prescribed class of medications for prescription and over-the-counter, and the data suggest that comorbidities, polypharmacy, self-medication, no clear indications and duration beyond the recommended guidelines PPIs use are associated with renal dysfunction. Aim was to study the proportion of renal dysfunction among patients using oral PPIs and determine the association between the duration of oral PPIs use and the severity of renal dysfunction. Methods: The data collection of 250 patients was done at the time of contact, which included demographic profiles, complete medical history, physical examination, and laboratory investigation in this study. For analysis, name of oral PPIs used, duration and dosage of oral PPIs therapy, laboratory values of serum blood urea, serum creatinine, eGFR, and serum electrolytes parameters have been considered. Results: Amongst 250 patients with PPIs used for a week, 23 patients showed mildly reduced kidney function (p=0.000), PPIs used for >1 to 2 weeks, 29 patients showed grade 2 kidney function (p=0.001), while PPIs used for >2-3 weeks only two patients showed grade 3 kidney function (p=0.44). Patients aged >50 years in all groups showed grade 2 renal function, regardless of the duration of PPIs use. Increasing age, males, rural, smoking, and alcoholics were the risk factors for renal dysfunction. PPIs use significantly impacts eGFR. Conclusions: Collectively, this study found a significant association between PPIs use and renal dysfunction. PPIs used for >2 weeks in elderly patients have shown a 4−fold increased risk of developing renal dysfunction

Kinetic and mechanistic studies of oxidation of chloramphenicol by sodium metaperiodate using Rh(III)-chloride as homogeneous catalyst

The kinetics of oxidation of an antibiotic drug, chloramphenical(CHP) by NaIO4 in the presence of Rh(III) catalyst has been investigated in alkaline medium at 350C. The reaction shows first order kinetics with respect to [IO4-] and [Rh(III)]. The fractional positive order kinetics in [OH-] and [CHP] throughout their variations were observed. It was found that ionic strength and dielectric constant of the medium had no effects on the rate of reactions. There is no effect of [Cl-] in presence of Rh(III) chloride. The values of rate constants observed at four different temperatures were utilized to calculate various activation parameters. The species [IO4-] and [RhCl3(H2O)2OH]- are assumed as the reactive species of NaIO4 and Rh(III) respectively in alkaline medium. On the basis of kinetic results, spectroscopic information and activation parameters, a suitable mechanism and rate law for the oxidation of CHP has been proposed

Dr. Ritu Bala: A study of errors and misconceptions in mathematics at elementary school stage A study of errors and misconceptions in mathematics at elementary school stage

Abstract: The main purpose of this study was to study the errors and misconceptions in mathematics by the elementary school students. Three-Tier Concept Achievement Test in Mathematics (TTCATM) comprising of 50 items was administered to 1000 sixth-grade students. After the identification of errors and prior to the identification of misconceptions, false negatives and lack of knowledge were observed in between. In addition, the analysis of data showed that location and gender did not have significant effect. Patterns and sources of errors and misconceptions were also identified

Investigation of Bioplastic Properties Developed from Acrylate Epoxidized Soybean Oil Through Ring Opening Polymerization Process

Soybean oil is one of the major vegetable oils containing more than 99% of triglycerides of saturated and unsaturated fatty acids and has become an interesting source to produce bioplastic. This study investigates the synthesis and characterization of bioplastic developed by the acrylate epoxidized soybean oil through ring opening polymerization process. The mechanical properties of the samples were characterized using Fourier Transform Infrared Spectroscopy, Thermo gravimetric analysis and the physio-chemical properties of the bioplastics were studied. In this study, the bioplastic made up from soybean oil with the lowest glycerol concentration showed the best mechanical properties