Models for the Prediction of Receptor Tyrosine Kinase Inhibitory Activity of Substituted 3-Aminoindazole Analogues

The inhibition of tumor angiogenesis has become a compelling approach in the development of anticancer drugs. In the present study, topological models were developed through decision tree and moving average analysis using a data set comprising 42 analogues of 3-aminoindazoles. A total of 22 descriptors (distance based, adjacency based, pendenticity and distance-cum-adjacency based) were used. The values of all 22 topological indices for each analogue in the dataset were computed using an in-house computer program. A decision tree was constructed for the receptor tyrosine kinase KDR (kinase insert domain receptor) inhibitory activity to determine the importance of topological indices. The decision tree learned the information from the input data with an accuracy of 88%. Three independent topological models were also developed for prediction of receptor tyrosine kinase inhibitory (KDR) activity using moving average analysis. The models developed were also found to be sensitive towards the prediction of other receptor tyrosine kinases i.e. FLT3 (fms-like tyrosine kinase-3) and cKIT inhibitory activity. The accuracy of classification of single index based models using moving average analysis was found to be 88%. The performance of models was assessed by calculating precision, sensitivity, overall accuracy and Mathew’s correlation coefficient (MCC). The significance of the models was also assessed by intercorrelation analysis

Biochemical responses of cucumber to Tetranychus urticae Koch (Acari: Tetranychidae) mediated biotic stress

The effect of two spotted spider mite (Tetranychus urticae Koch) feeding on leaf level physiological characteristics of cucumber (Cucumis sativus Linnaeus) was investigated. Young cucumber plants were artificially infested with different densities of T. urticae (5, 10, 15 and 20 mites/ grown up leaf) while uninfested plants acted as control. Post infestation, the plants differed in their support to mite density in accordance with initial infestation density and observation period. Highly significant negative correlation of -0.92, -0.93, -0.95 and -0.92 for total chlorophyll, chlorophyll a, chlorophyll b and carotenoids, respectively, at the highest infestation level) was recorded between mite density and photosynthetic pigments in infested leaves as compared to uninfested ones. There was a significant decrease (P= 0.05) in the level of (a progressive decline from 2.82, 0.36 and 2.17% dry weight in control to the maximum of 2.09, 0.26 and 1.87% dry weight for N, P and K, respectively, at highest infestation level) in the infested leaves in response to mite infestation. Interaction between initial infestation level and observation period also suggested a significant impact of T. urticae infestation on the leaf phytochemicals of cucumber (P= 0.05)

Efficacy and safety of oral mifepristone for cervical priming and induction of labor in term pregnancy

Background: The objectives of the study was to assess the efficacy of mifepristone in priming the cervix/inducing labor over next 96 hrs in term pregnancy.Methods: In this single blind randomized controlled trial 200 women with term pregnancy beyond 39 weeks and Bishop’ score <6 were randomly allocated into two groups. Tab Mifepristone 400 mg orally was given to women in study group (n=100) and no intervention in control group (n=100). On follow up one case was lost in control group. All women were observed for change in the bishop’s score or onset of labor in next 96 hrs. If Bishop’s score was <6, the choice of induction was left on the clinician/patient.Results: Mean induction to delivery interval, duration of active phase and improved Bishop score were 79.35±53.43 hr, 2.47±1.23 hr, 6.68±1.69 for study group versus 148±65.66 hr, 3.09±1.45 hr, 5.8±2.15  for control group (p value is <0.001) respectively.  Seventy one (71%) women in study group and 39 (39.3%) women in control group delivered vaginally within 96 hrs without any need of augmentation. There were 9 (9%) caesareans in study group and 24 (24.2%) caesareans in control group but no instrumental delivery in both groups. There was no statistically difference in perinatal outcomes between two groups.Conclusions: Mifepristone is an effective drug for cervical ripening and initiation of labor when given in term pregnancy beyond 39 weeks with poor Bishop’s score (<6) and appearing to reduce need for other agent for augmentation of labor

Effect of Different Edible Coatings on Postharvest Quality of Mandarin Orange (Citrus reticulata Blanco)

Although Nepal produces a large amount of mandarin it faces huge postharvest losses due to improper postharvest practices. Treating fruits with different edible coatings can minimize postharvest losses. The experiment was carried out in the horticulture lab of Prithu Technical College, Dang, Nepal to evaluate the effects of different edible coating materials on the postharvest quality of mandarin. The experiment was laid in Complete Randomized Design (CRD) with three replications and seven treatments  in each replication. Mandarins were coated with different edible coating materials i.e. paraffin wax (100%, 75% and 50%), mustard oil, Aloe vera, turmeric paste and control (non-coated). After coating with different edible materials, mandarins were kept at ambient room conditions (18±2℃ and 52.41±14.35%). The lowest physiological loss in weight at 7, 14and 21 days was recorded in mandarin coated with 75% paraffin wax which was 3.10%, 4.83% and 10.33%, respectively. The highest titratable acidity (0.68%), juice content (46.33%) and marketable fruit percentage (81.73%) were recorded in 75% paraffin wax. The highest total soluble solid (14.00 ˚Brix) was recorded in control. Based on the result obtained from our research, it is suggested to use 75% paraffin wax for the storage of mandarin at ambient room conditions (18±2℃ and 52.41±14.35% RH) as it gives a high percentage of marketable fruits and juice content and also minimizes the physiological loss in weight

Maternal and perinatal outcome in eclampsia at a tertiary care center

Background: Preeclampsia is the occurrence of hypertension in combination with proteinuria, developing after 20 weeks gestation in a previously normotensive non-proteinuric patient. The objective of this study was to study the prevalance of eclampsia at PGIMS, Rohtak. To study the clinical profile, maternal and perinatal outcome in eclamptic patients.Methods: This is a retrospective study and case records of all eclampsia cases were analysed from the study period of January 2018 to December 2018.Results: There were 113 cases of eclampsia out of 11,661 deliveries and prevalence of eclampsia was calculated to be 0.96%. Majority of the patients were not registered 95.57%. 58% of patients were Primigravidas. 56% of the patient in the age group of 21-25 years. Antepartum, intrapartum and postpartum eclampsia were 71%, 1.7% and 27% respectively. Caesarean section was the preferred mode of delivery and was performed in 57% cases. ICU admission was required in 25% and remaining cases were managed in general/eclampsia ward. All patients received MgSO4 by Zuspan regimen. 12% patient developed HELLP syndrome and pulmonary oedema developed in 6% patient. There were a total of 3.5% maternal deaths during the study period. Total percentage of perinatal deaths due to eclampsia was 23%.Conclusions: Eclampsia continues to be one of the prime etiological factors for maternal and perinatal morbidity and mortality. This is due to lack of proper antenatal care, low socioeconomic condition and lack of education. Regular antenatal checkup, early recognition and proper management are vital to tackle this challenge. MgSo4 is the anticonvulsant of choice and Zuspan regimen of MgSO4 is effective in the management of eclampsia

Tuberous sclerosis in pregnancy: a rare genetic disease requiring multidisciplinary approach in pregnancy

Tuberous sclerosis complex (TSC) is a multisystemic, autosomal dominant genetic disorder with complete penetrance, that can evolve with hamartomas in multiple organs, such as skin, central nervous system, kidney and lung. Penetrance in genetics is the proportion of individuals carrying a particular variant (or allele) of a gene (the genotype) that also express an associated trait (the phenotype). Due to the wide phenotypic variability in TSC, the disease is often not recognized. The diagnostic criteria for tuberous sclerosis were reviewed in 2012, at the second International tuberous sclerosis complex consensus conference. The diagnosis is based on genetic criteria, by the identification of inactivating pathogenic mutation of tumour suppressor genes TSC1 and TSC2, and clinical criteria, including cutaneous, renal, pulmonary, cardiac and neurological manifestations. Authors present with a rare case report of a patient with TSC presenting at term

Toll-Like Receptor-2 Mediates Diet and/or Pathogen Associated Atherosclerosis: Proteomic Findings

BACKGROUND. Accumulating evidence implicates a fundamental link between the immune system and atherosclerosis. Toll-like receptors are principal sensors of the innate immune system. Here we report an assessment of the role of the TLR2 pathway in atherosclerosis associated with a high-fat diet and/or bacteria in ApoE+/- mice. METHODS AND RESULTS. To explore the role of TLR2 in inflammation- and infection-associated atherosclerosis, 10 week-old ApoE+/--TLR2+/+, ApoE+/--TLR2+/- and ApoE+/--TLR2-/- mice were fed either a high fat diet or a regular chow diet. All mice were inoculated intravenously, once per week for 24 consecutive weeks, with 50 μl live Porphyromonas gingivalis (P.g) (107 CFU) or vehicle (normal saline). Animals were euthanized 24 weeks after the first inoculation. ApoE+/--TLR2+/+ mice showed a significant increase in atheromatous lesions in proximal aorta and aortic tree compared to ApoE+/--TLR2+/- and ApoE+/--TLR2-/- mice for all diet conditions. They also displayed profound changes in plaque composition, as evidenced by increased macrophage infiltration and apoptosis, increased lipid content, and decreased smooth muscle cell mass, all reflecting an unstable plaque phenotype. SAA levels from ApoE+/--TLR2+/+ mice were significantly higher than from ApoE+/--TLR2+/- and ApoE+/--TLR2-/- mice. Serum cytokine analysis revealed increased levels of pro-inflammatory cytokines in ApoE+/--TLR2+/+ mice compared to ApoE+/--TLR2+/- and TLR2-/- mice, irrespective of diet or bacterial challenge. ApoE+/--TLR2+/+ mice injected weekly for 24 weeks with FSL-1 (a TLR2 agonist) also demonstrated significant increases in atherosclerotic lesions, SAA and serum cytokine levels compared to ApoE+/--TLR2-/- mice under same treatment condition. Finally, mass-spectrometry (MALDI-TOF-MS) of aortic samples analyzed by 2-dimentional gel electrophoresis differential display, identified 6 proteins upregulated greater than 2-fold in ApoE+/--TLR2+/+ mice fed the high fat diet and inoculated with P.g compared to any other group. CONCLUSION. Genetic deficiency of TLR2 reduces diet- and/or pathogen-associated atherosclerosis in ApoE+/- mice, along with differences in plaque composition suggesting greater structural stability while TLR-2 ligand-specific activation triggers atherosclerosis. The present data offers new insights into the pathophysiological pathways involved in atherosclerosis and paves the way for new pharmacological interventions aimed at reducing atherosclerosis.National Heart, Lung, and Blood Institute (R01 HL076801