Development and Evaluation of Gastro-retentive Floating Tablet of Rilpivirine Hydrochloride for the Treatment of HIV

Besides enormous improvements in drug delivery, oral route has been highly and effectively utilized route of administration. Floating drug delivery that is also known to be low density system is advancement in the class of gastro-retentive drug delivery system. In the present research work, floating drug delivery of Rilpivirine hydrochloride was developed by overcoming various limitations and troubles associated with the drug including poor absorption in intestinal pH and degradation when comes in contact with higher pH environment. [2] Prepared formulations were evaluated for various parameters like friability, hardness, thickness, drug content analysis, floating properties and in-vitro drug release study. Based on the evaluation, concluded that floating drug delivery system is a non-toxic as well as cost-effective technique for the rationale of enhancing bioavailability and absorption of poorly water soluble drugs. The improvement in gastric residence time is a clear sign. It can be able to use in the future for more acidic soluble drugs to enhance solubility and absorption. Keywords: Floating drug delivery, gastric residence time, Rilpivirine, effervescent, NNRTI

Bilateral internal iliac artery ligation: the procedure of choice in life threatening postpartum haemorrhage

Background: The present study was to assess the indication and study the intraoperative and postoperative complications of bilateral internal iliac artery ligation. Aim of this study was to evaluate the effectiveness of internal iliac artery ligation in arresting postpartum haemorrhage.Methods: This is a retrospective study carried out between January 2015 to December 2018 at Shrimati Kashibai Navale Medical College and General Hospital, Pune. This study included 48 patients with life-threatening PPH. Bilateral internal iliac artery ligation was done by anterior approach in 7 patients and by posterior approach in 41 patients.Results: Intraoperative and postoperative complications were noted in all patients. Of the total patients, 10 required massive blood transfusion and 12 underwent obstetrical hysterectomies (n=12; 25%). Internal iliac vein injury was seen in 1 patient (n=1; 2.08%) and external vein thrombosis was noted in 3 patients (n=3; 6.25%). Maternal mortality was observed in 1 patient due to DIC on day 9 (n=1; 2.08%). The uterine salvage rate was 75%.Conclusions: Internal iliac artery ligation (IIAL) safe, rapid, effective, time tested method of controlling bleeding from genital tract

ADVERSE DRUG REACTION PROFILE OF DRUGS PRESCRIBED IN CORONAVIRUS DISEASE - 19 PATIENTS – A CROSS-SECTIONAL STUDY

Objective: The objective of this study is to assess adverse drug reaction (ADR) profile of the drugs prescribed to treat Coronavirus Disease (COVID-19) positive patients and to determine whether ADRs are associated with any comorbidities. Methods: A cross-sectional study was done with Laboratory confirmed COVID-19 positive patients who experienced ADRs during their admission period at tertiary care center, Rajkot from April 2020 to March 2021. All the necessary information including ADRs information was obtained from patient’s case record file and filled in suspected ADR reporting form. Suspected ADRs were assessed for demographic parameters and causality, preventability, and severity using World Health Organization (WHO) scale and Naranjo algorithm, modified Schumock and Thornton’s criteria, and modified Hartwig’s criteria, respectively. Results: Out of the 100 patients there were 60 males. The mean age of the patients was 52.65±13.95 year. Fourty-six patients had comorbidities. The most common type of ADR was GI disorders. Among the single suspected medication, most common drug was methylprednisolone and among the two drugs, azithromycin was common. According to the WHO and Naranjo scale, Probable ADRs were 70% and 36%, respectively. The percentage for mild, moderate and severe ADRs were 44%, 39%, 17%, respectively. Eighty-six percent ADRs were definitely preventable. Fifty-one patients were recovered from adverse reactions. Conclusions: Seriousness of reactions is mainly associated with co-morbid conditions. This indicates that patients with comorbidity should be closely monitored to avoid harmful consequences. These ADRs monitoring and reporting program will help physicians to choose their therapy sensibly and decrease chances of mortality in this pandemic era

Human Embryonic and Fetal Mesenchymal Stem Cells Differentiate toward Three Different Cardiac Lineages in Contrast to Their Adult Counterparts

Mesenchymal stem cells (MSCs) show unexplained differences in differentiation potential. In this study, differentiation of human (h) MSCs derived from embryonic, fetal and adult sources toward cardiomyocytes, endothelial and smooth muscle cells was investigated. Labeled hMSCs derived from embryonic stem cells (hESC-MSCs), fetal umbilical cord, bone marrow, amniotic membrane and adult bone marrow and adipose tissue were co-cultured with neonatal rat cardiomyocytes (nrCMCs) or cardiac fibroblasts (nrCFBs) for 10 days, and also cultured under angiogenic conditions. Cardiomyogenesis was assessed by human-specific immunocytological analysis, whole-cell current-clamp recordings, human-specific qRT-PCR and optical mapping. After co-culture with nrCMCs, significantly more hESC-MSCs than fetal hMSCs stained positive for α-actinin, whereas adult hMSCs stained negative. Furthermore, functional cardiomyogenic differentiation, based on action potential recordings, was shown to occur, but not in adult hMSCs. Of all sources, hESC-MSCs expressed most cardiac-specific genes. hESC-MSCs and fetal hMSCs contained significantly higher basal levels of connexin43 than adult hMSCs and co-culture with nrCMCs increased expression. After co-culture with nrCFBs, hESC-MSCs and fetal hMSCs did not express α-actinin and connexin43 expression was decreased. Conduction velocity (CV) in co-cultures of nrCMCs and hESC-MSCs was significantly higher than in co-cultures with fetal or adult hMSCs. In angiogenesis bioassays, only hESC-MSCs and fetal hMSCs were able to form capillary-like structures, which stained for smooth muscle and endothelial cell markers.Human embryonic and fetal MSCs differentiate toward three different cardiac lineages, in contrast to adult MSCs. Cardiomyogenesis is determined by stimuli from the cellular microenvironment, where connexin43 may play an important role

Bronchiectasis in India:results from the European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC) and Respiratory Research Network of India Registry

BACKGROUND: Bronchiectasis is a common but neglected chronic lung disease. Most epidemiological data are limited to cohorts from Europe and the USA, with few data from low-income and middle-income countries. We therefore aimed to describe the characteristics, severity of disease, microbiology, and treatment of patients with bronchiectasis in India. METHODS: The Indian bronchiectasis registry is a multicentre, prospective, observational cohort study. Adult patients ( 6518 years) with CT-confirmed bronchiectasis were enrolled from 31 centres across India. Patients with bronchiectasis due to cystic fibrosis or traction bronchiectasis associated with another respiratory disorder were excluded. Data were collected at baseline (recruitment) with follow-up visits taking place once per year. Comprehensive clinical data were collected through the European Multicentre Bronchiectasis Audit and Research Collaboration registry platform. Underlying aetiology of bronchiectasis, as well as treatment and risk factors for bronchiectasis were analysed in the Indian bronchiectasis registry. Comparisons of demographics were made with published European and US registries, and quality of care was benchmarked against the 2017 European Respiratory Society guidelines. FINDINGS: From June 1, 2015, to Sept 1, 2017, 2195 patients were enrolled. Marked differences were observed between India, Europe, and the USA. Patients in India were younger (median age 56 years [IQR 41-66] vs the European and US registries; p<0\ub70001]) and more likely to be men (1249 [56\ub79%] of 2195). Previous tuberculosis (780 [35\ub75%] of 2195) was the most frequent underlying cause of bronchiectasis and Pseudomonas aeruginosa was the most common organism in sputum culture (301 [13\ub77%]) in India. Risk factors for exacerbations included being of the male sex (adjusted incidence rate ratio 1\ub717, 95% CI 1\ub703-1\ub732; p=0\ub7015), P aeruginosa infection (1\ub729, 1\ub710-1\ub750; p=0\ub7001), a history of pulmonary tuberculosis (1\ub720, 1\ub707-1\ub734; p=0\ub7002), modified Medical Research Council Dyspnoea score (1\ub732, 1\ub725-1\ub739; p<0\ub70001), daily sputum production (1\ub716, 1\ub703-1\ub730; p=0\ub7013), and radiological severity of disease (1\ub703, 1\ub701-1\ub704; p<0\ub70001). Low adherence to guideline-recommended care was observed; only 388 patients were tested for allergic bronchopulmonary aspergillosis and 82 patients had been tested for immunoglobulins. INTERPRETATION: Patients with bronchiectasis in India have more severe disease and have distinct characteristics from those reported in other countries. This study provides a benchmark to improve quality of care for patients with bronchiectasis in India. FUNDING: EU/European Federation of Pharmaceutical Industries and Associations Innovative Medicines Initiative inhaled Antibiotics in Bronchiectasis and Cystic Fibrosis Consortium, European Respiratory Society, and the British Lung Foundation

Transcriptomic and metabolomic shifts in rice roots in response to Cr (VI) stress

<p>Abstract</p> <p>Background</p> <p>Widespread use of chromium (Cr) contaminated fields due to careless and inappropriate management practices of effluent discharge, mostly from industries related to metallurgy, electroplating, production of paints and pigments, tanning, and wood preservation elevates its concentration in surface soil and eventually into rice plants and grains. In spite of many previous studies having been conducted on the effects of chromium stress, the precise molecular mechanisms related to both the effects of chromium phytotoxicity, the defense reactions of plants against chromium exposure as well as translocation and accumulation in rice remain poorly understood.</p> <p>Results</p> <p>Detailed analysis of genome-wide transcriptome profiling in rice root is reported here, following Cr-plant interaction. Such studies are important for the identification of genes responsible for tolerance, accumulation and defense response in plants with respect to Cr stress. Rice root metabolome analysis was also carried out to relate differential transcriptome data to biological processes affected by Cr (VI) stress in rice. To check whether the Cr-specific motifs were indeed significantly over represented in the promoter regions of Cr-responsive genes, occurrence of these motifs in whole genome sequence was carried out. In the background of whole genome, the lift value for these 14 and 13 motifs was significantly high in the test dataset. Though no functional role has been assigned to any of the motifs, but all of these are present as promoter motifs in the Database of orthologus promoters.</p> <p>Conclusion</p> <p>These findings clearly suggest that a complex network of regulatory pathways modulates Cr-response of rice. The integrated matrix of both transcriptome and metabolome data after suitable normalization and initial calculations provided us a visual picture of the correlations between components. Predominance of different motifs in the subsets of genes suggests the involvement of motif-specific transcription modulating proteins in Cr stress response of rice.</p

Association of type 1 inositol 1,4,5-trisphosphate receptor (IP₃R1) with protein kinase A and A-kinase Anchoring Protein 9 (AKAP9) in platelets

Cyclic adenosine monophsphoate (cAMP) signalling is thought to regulate inositol-1,4,5 trisphosphate (IP₃)-mediated calcium (Ca²⁺) mobilisation in platelets through protein kinase A (PKA)-mediated phosphorylation, leading to inhibition of inositol-1,4,5 trisphosphate receptors (IP₃Rs). A- kinase Anchoring Proteins (AKAPs) are known to be involved in spatial and temporal regulation of PKA-mediated phosphorylation; however the precise molecular mechanisms regulating the PKA-mediated inhibition of IP₃Rs remain to be fully understood. To further understand this, the presence and functional importance of a novel PKA/IP₃R/AKAP signalling complex in platelets was studied. Protein complexes identified using co-immunoprecipitation and analysed using immunoblotting, while Ca²⁺ measurements were made using spectrofluorometry. We show that platelet stimulation with thrombin evoked a sharp increase in intracellular Ca²⁺ levels, which was blocked by IP₃R1 antagonist, 2-Aminoethoxydiphenyl borate (2-APB). This suggested Ca²⁺ mobilisation through IP₃Rs. Furthermore, activation of cAMP signalling by prostacyclin (PGI2)-treatment restricted Ca²⁺ mobilisation in response to thrombin treatment, suggesting that an involvement of cAMP pathway in regulation of IP₃R channel activity. Furthermore, the presence of all three isoforms of IP₃R in platelets was confirmed by immunoblotting. PGI2-induced phosphorylation of IP₃R1 on Serine1756 (Ser1756) was blocked by pharmacological inhibitors of PKA, and mimicked by direct activators of PKA and adenylyl cyclase. Immunoprecipitates of IP₃R1 also showed an associated PKA activity, owing to the coimmunoprecipitation of PKA with IP₃R1. The functional importance of this association was explored using a cell-permeable peptide PKA-AKAP disruptor peptide; St-Ht31. St-Ht31 inhibited PGI2-induced phosphorylation of IP₃R1 and blunted the ability of PGI2 to inhibit the Ca²⁺ mobilisation. This suggests a role of AKAPs in regulation of Ca²⁺ mobilisation. Numerous AKAPs have been putatively identified in platelets through transcriptomics and proteomics studies. Here, we show the presence of AKAP9 in platelets. Moreover, using coimmunoprecipitation, the association of AKAP9 with PKA/IP₃R1 was also suggested. These data suggest the presence of a novel PKA/IP₃R1/AKAP9 signalling complex in platelets that may modulate intracellular Ca²⁺ mobilisation

Objectifying teachers-and-learners\u27-portfolios as a part of professional development: An action research

Keeping teacher as well as learner’s portfolio has proved to be an effective way for developing subject-based knowledge, technical and professional skills. 21st century skills dictates multiple role from a teacher, keeping a professional portfolio is thus a unique example for the same. The current paper is a part of action-research carried-out in the classroom, Sem-I, on 35 students, of Inter-mediate level, at one of the leading universities of Ahmedabad, Gujarat. The findings presented a gradual development in proficiency of learners learning English as a Second Language(ESL). It also showed teacher’s effectiveness in using or assessing the pre-defined objectives, course plan, along with activities and rubrics. In the process, emphasise has been given on formative assessment and students’ responses were recorded, at the end, on the basis of rubrics and checklists. Teacher’s portfolio reflected some facts about the availability of resources, effectiveness in tackling sessions, students’ involvement and learning process. The tenure of keeping a portfolio was recorded for three-to-four months. It was then presented to the management to give feedback about the classroom planning, methodology, giving an overview about the outcome for keeping portfolio and making it an integral part of course curriculum. Learners’ portfolio too was encouraged where there was a provision of individual feedback given to all. Overall, keeping portfolios showed an effective method of assessing teachers’ performance, professional development and learners’, ESL, development for language proficiency