DENSITOMETRIC VALIDATION OF LAPACHOL IN TECOMELLA UNDULATA SEEM BARK BY HIGH-PERFORMANCE THIN-LAYER CHROMATOGRAPHY

Objective: To develop a validated high-performance thin layer chromatography (HPTLC) method for the quantitative estimation of Lapachol in a Soxhlet extracted bark of Tecomella undulata seem (T. undulata). Methods: The bark of T. undulata was extracted with chloroform by Soxhlet apparatus. The separation was achieved on a silica-gel 60 F254 HPTLC plate using toluene-ethyl acetate–glacial acetic acid (8.5:1.5:0.02 v/v/v) as a mobile phase. Densitometric analysis of Lapachol was carried out in absorbance mode at 254 nm.Results: The proposed method was accurate for the separation and resolution between peaks of the standard and Lapachol (5.04µg) with Rf value 0.77. Calibration curves were found to be linear over the concentration range (10-130µg) for Lapachol and correlation coefficient over (R2= 0.9973), indicating an excellent correlation between peak areas and concentrations of the marker compound. The experimentally derived LOD and LOQ for Lapachol were determined to be 0.028 µg and 0.086 µg respectively and the developed HPTLC-UV method showed lower %RSD and SEM, value indicating the method to be precise, accurate and robust.Conclusion: The study concludes that HPTLC-UV validation method can be very efï¬cient and promising technique for the identiï¬cation and quantitative analysis of Lapachol from T. undulata bark. The statistical analysis of data indicates that the developed method is reproducible and specific

Primary arthroplasty as an option for surgical treatment of unstable intertrochanteric fracture femur in elderly patients: a retrospective study

Background: An unstable intertrochanteric fracture in osteoporotic elderly patients presents a very challenging problem to the surgeons. This category of patients if kept in bed for long tends to have many complications like deep vein thrombosis, pneumonia, bed sores, etc. Surgeon’s worldwide face difficulty in getting a good anatomical reduction and do not allow early mobility to these patients because of risk of loss of reduction and implant cut out. The purpose of our study is to study the usefulness of arthroplasty in these patients in terms of better functional outcomes and no increase in complication rates.Methods: It was a retrospective study involving 25 patients (17 females, 8 males) with mean age of 76±2.3 years having intertrochanteric femur fractures (AO type A 2.2 and above) with osteoporosis operated upon with bipolar hemiarthroplasty at IQ City Medical College and NM Hospital between January 2015 and January 2017.Results: All the patients were followed up for a period of 1 year. We had a mean operative time of 75 min (range 55-125 min) with an average blood loss of 450 ml. 4 of our patients required postoperative blood transfusion. All patients walked on 2nd postoperative day. We had a mean Harris hip score of 82 and mean VAS of 1 at the end of 1 year.Conclusions: Hemiarthroplasty done in cases of unstable intertrochanteric femur fractures in elderly patients with osteoporotic bones allows early weight bearing thus improves the final functional outcomes. Further randomized trials are required before deriving any conclusions

Dengue virus-specific suppressor T cells: current perspectives

Dengue virus was the first microorganism that was shown to induce generation of antigen-specific suppressor T (TS) cells in mice. The cascade of the three generations of TS cells (TS1, TS2, TS3) and their secretary products, the suppressor factors (SF1, SF2), was delineated. The TS pathway was proposed to be protective through inhibition of the production of enhancing antibody, which may enhance the severity of dengue disease. The currently second most favoured mechanism of severe dengue disease is the 'cytokine tsunami'. During the last decade, suppressor/regulatory T cells have been studied in greater detail using modern techniques in various diseases, including viral infections. This brief review discusses the role of dengue-specific suppressor T cells in protection and/or induction of severe dengue disease in view of our current understanding of suppressor/regulatory T cells

Pattern of adverse drug reactions with chemotherapeutic drugs in a tertiary care hospital of North India: a retrospective study

Background: Adverse drug reactions are important causes of mortality and morbidity in the patients. Early detection, evaluation and monitoring of ADRs is essential to improve public health. Methods: This was an observational, non-interventional and retrospective study conducted at the ADR monitoring centre of a tertiary care hospital of North India. Suspected ADR forms reported over a period of 4 years involving at least one chemotherapeutic drug with at least one dose were analyzed. Results: A total of 261 chemotherapeutic drugs associated ADRs were analyzed. Out of these, maximum numbers of ADRs were reported by males (54%). Maximum reporting was done by Skin and VD department (37.93%). Causality assessment was probable in maximum number of cases (54%). Most common ADRs were skin rashes (21.46%), followed by jaundice, urticaria and fixed drug eruptions. Maximum ADRs were suspected to be caused by Anti tubercular drugs (31.42%) followed by anticancer drugs (14.56%). Conclusions: ADRs due to antibiotics and anticancer drugs is a significant health problem

Recent Trends in In-silico Drug Discovery

A Drug designing is a process in which new leads (potential drugs) are discovered which have therapeutic benefits in diseased condition. With development of various computational tools and availability of databases (having information about 3D structure of various molecules) discovery of drugs became comparatively, a faster process. The two major drug development methods are structure based drug designing and ligand based drug designing. Structure based methods try to make predictions based on three dimensional structure of the target molecules. The major approach of structure based drug designing is Molecular docking, a method based on several sampling algorithms and scoring functions. Docking can be performed in several ways depending upon whether ligand and receptors are rigid or flexible. Hotspot grafting, is another method of drug designing. It is preferred when the structure of a native binding protein and target protein complex is available and the hotspots on the interface are known. In absence of information of three Dimensional structure of target molecule, Ligand based methods are used. Two common methods used in ligand based drug designing are Pharmacophore modelling and QSAR. Pharmacophore modelling explains only essential features of an active ligand whereas QSAR model determines effect of certain property on activity of ligand. Fragment based drug designing is a de novo approach of building new lead compounds using fragments within the active site of the protein. All the candidate leads obtained by various drug designing method need to satisfy ADMET properties for its development as a drug. In-silico ADMET prediction tools have made ADMET profiling an easier and faster process. In this review, various softwares available for drug designing and ADMET property predictions have also been listed

Effect of high day and night temperature regimes on tomato (Solanum lycopersicum) genotypes

Five tomato (Solanum lycopersicum L.) genotypes, including heat tolerant (Pusa Sadabahar, Booster, Pusa Sheetal), one F1 combination (Pusa Sheetal × Pusa Sadabahar ) and one susceptible genotype (Pusa Rohini) were grown under phytotron under four temperature regimes, i.e. 20/24, 22/26, 24/32, 27/37°C night (11 hours)/day (13 hours) temperature, respectively. Pusa Sadabahar and Booster recorded high value of relative water content (RWC) and low value of membrane injury index (MII) both at normal and high temperature conditions. High value of chlorophyll a and chlorophyll b ratio was recorded in Pusa Sadabahar and Pusa Sheetal×Pusa Sadabahar under all the temperature regimes showed their tolerance to high temperature. Normal (more than 80 percent) flowering and fruiting was recorded in all the genotypes at 20/24°C & 22/26°C. However at 24/32°C Pusa Sadabahar recorded 65 per cent fruit set and other genotypes 25 to 49 percent fruit setting only. None of the genotypes could record fruit set at 27/37°C, except Pusa Sadabahar which could set few small fruits (19%). Pollen germination was maximum (ranging from 21.8 - 62.9%) in Pusa Sadabahar under all temperature regimes. The susceptible genotype, Pusa Rohini recorded exerted stigma in 100% flowers at 27/37°C temperature whereas it was 75% in tolerant genotype Pusa Sadabahar. Night/day temperature 22/26°C was optimum for fruit set, pollen viability and normal stigma development in tomato. High night temperature (³ 26°C ± 2°C) at flowering was the major factor in reducing fruit set in tomato than the day temperature. The study showed that day temperature of ³ 35°C and night temperature of ³ 26oC may be used for screening tomato against high temperature tolerance

Exploring potential of pearl millet germplasm association panel for association mapping of drought tolerance traits

A pearl millet inbred germplasm association panel (PMiGAP) comprising 250 inbred lines, representative of cultivated germplasm from Africa and Asia, elite improved open-pollinated cultivars, hybrid parental inbreds and inbred mapping population parents, was recently established. This study presents the first report of genetic diversity in PMiGAP and its exploitation for association mapping of drought tolerance traits. For diversity and genetic structure analysis, PMiGAP was genotyped with 37 SSR and CISP markers representing all seven linkage groups. For association analysis, it was phenotyped for yield and yield components and morpho-physiological traits under both well-watered and drought conditions, and genotyped with SNPs and InDels from seventeen genes underlying a major validated drought tolerance (DT) QTL. The average gene diversity in PMiGAP was 0.54. The STRUCTURE analysis revealed six subpopulations within PMiGAP. Significant associations were obtained for 22 SNPs and 3 InDels from 13 genes under different treatments. Seven SNPs associations from 5 genes were common under irrigated and one of the drought stress treatments. Most significantly, an important SNP in putative acetyl CoA carboxylase gene showed constitutive association with grain yield, grain harvest index and panicle yield under all treatments. An InDel in putative chlorophyll a/b binding protein gene was significantly associated with both stay-green and grain yield traits under drought stress. This can be used as a functional marker for selecting high yielding genotypes with 'stay green' phenotype under drought stress. The present study identified useful marker-trait associations of important agronomics traits under irrigated and drought stress conditions with genes underlying a major validated DT-QTL in pearl millet. Results suggest that PMiGAP is a useful panel for association mapping. Expression patterns of genes also shed light on some physiological mechanisms underlying pearl millet drought tolerance

Outcomes and Recommendations of an Indian Expert Panel for Improved Practice in Controlled Ovarian Stimulation for Assisted Reproductive Technology

. Purpose. To improve success of in vitro fertilization (IVF), assisted reproductive technology (ART) experts addressed four questions. What is optimum oocytes number leading to highest live birth rate (LBR)? Are cohort size and embryo quality correlated? Does gonadotropin type affect oocyte yield? Should "freeze-all" policy be adopted in cycles with progesterone >1.5 ng/mL on day of human chorionic gonadotropin (hCG) administration? Methods. Electronic database search included ten studies on which panel gave opinions for improving current practice in controlled ovarian stimulation for ART. Results. Strong association existed between retrieved oocytes number (RON) and LBRs. RON impacted likelihood of ovarian hyperstimulation syndrome (OHSS). Embryo euploidy decreased with age, not with cohort size. Progesterone > 1.5 ng/dL did not impair cycle outcomes in patients with high cohorts and showed disparate results on day of hCG administration. Conclusions. Ovarian stimulation should be designed to retrieve 10-15 oocytes/treatment. Accurate dosage, gonadotropin type, should be selected as per prediction markers of ovarian response. Gonadotropin-releasing hormone (GnRH) antagonist based protocols are advised to avoid OHSS. Cumulative pregnancy rate was most relevant pregnancy endpoint in ART. Cycles with serum progesterone ≥1.5 ng/dL on day of hCG administration should not adopt "freeze-all" policy. Further research is needed due to lack of data availability on progesterone threshold or index

Integration of Sequence Data from a Consanguineous Family with Genetic Data from an Outbred Population Identifies PLB1 as a Candidate Rheumatoid Arthritis Risk Gene

Integrating genetic data from families with highly penetrant forms of disease together with genetic data from outbred populations represents a promising strategy to uncover the complete frequency spectrum of risk alleles for complex traits such as rheumatoid arthritis (RA). Here, we demonstrate that rare, low-frequency and common alleles at one gene locus, phospholipase B1 (PLB1), might contribute to risk of RA in a 4-generation consanguineous pedigree (Middle Eastern ancestry) and also in unrelated individuals from the general population (European ancestry). Through identity-by-descent (IBD) mapping and whole-exome sequencing, we identified a non-synonymous c.2263G>C (p.G755R) mutation at the PLB1 gene on 2q23, which significantly co-segregated with RA in family members with a dominant mode of inheritance (P = 0.009). We further evaluated PLB1 variants and risk of RA using a GWAS meta-analysis of 8,875 RA cases and 29,367 controls of European ancestry. We identified significant contributions of two independent non-coding variants near PLB1 with risk of RA (rs116018341 [MAF = 0.042] and rs116541814 [MAF = 0.021], combined P = 3.2×10−6). Finally, we performed deep exon sequencing of PLB1 in 1,088 RA cases and 1,088 controls (European ancestry), and identified suggestive dispersion of rare protein-coding variant frequencies between cases and controls (P = 0.049 for C-alpha test and P = 0.055 for SKAT). Together, these data suggest that PLB1 is a candidate risk gene for RA. Future studies to characterize the full spectrum of genetic risk in the PLB1 genetic locus are warranted

Integration of sequence data from a consanguineous family with genetic data from an outbred population identifies PLB1 as a candidate rheumatoid arthritis risk gene

Integrating genetic data from families with highly penetrant forms of disease together with genetic data from outbred populations represents a promising strategy to uncover the complete frequency spectrum of risk alleles for complex traits such as rheumatoid arthritis (RA). Here, we demonstrate that rare, low-frequency and common alleles at one gene locus, phospholipase B1 (PLB1), might contribute to risk of RA in a 4-generation consanguineous pedigree (Middle Eastern ancestry) and also in unrelated individuals from the general population (European ancestry). Through identity-by-descent (IBD) mapping and whole-exome sequencing, we identified a non-synonymous c.2263G>C (p.G755R) mutation at the PLB1 gene on 2q23, which significantly co-segregated with RA in family members with a dominant mode of inheritance (P = 0.009). We further evaluated PLB1 variants and risk of RA using a GWAS meta-analysis of 8,875 RA cases and 29,367 controls of European ancestry. We identified significant contributions of two independent non-coding variants near PLB1 with risk of RA (rs116018341 [MAF = 0.042] and rs116541814 [MAF = 0.021], combined P = 3.2×10-6). Finally, we performed deep exon sequencing of PLB1 in 1,088 RA cases and 1,088 controls (European ancestry), and identified suggestive dispersion of rare protein-coding variant frequencies between cases and controls (P = 0.049 for C-alpha test and P = 0.055 for SKAT). Together, these data suggest that PLB1 is a candidate risk gene for RA. Future studies to characterize the full spectrum of genetic risk in the PLB1 genetic locus are warranted. © 2014 Plenge et al