MICROWAVE-ASSISTED SYNTHESIS OF AGNP USING AQUEOUS LEAVES EXTRACT OF VINCA ROSEA AND ITS THERAPEUTIC APPLICATION

Objective: Green synthesis of silver nanoparticles was attempted with the help of aqueous Vinca rosea leaf extract. The aim of the study was to combine the therapeutic activity of Vinca rosea and the deep tissue penetration capabilities of the silver nanoparticles.Methods: This study focuses on the green synthesis of silver nanoparticles (AgNPs) using an aqueous extract of Vinca rosea leaves, its characterization, and evaluation of its antibacterial and anticancer activity by diffusion method and MTT assay using human lung carcinoma cell line A549 respectively. The nanoparticles were synthesised by exposing the reaction mixture containing silver nitrate and Vinca leaf aqueous extract to microwave radiation.Results: The characterization of synthesised nanoparticles was carried out by observing the peaks on scanning from 250 to 800 nm using UV spectroscopy, the end point for the complete formation of nanoparticles marked by a colour change to reddish brown. Dynamic Light Scattering (DLS) which evaluated particle size uniformity and Scanning Electron Microscopy (SEM) which determines the particle size revealed that the nanoparticles were spherical in shape and measured an average of 50.75 nm. 170µg/ml of AgNPs of Vinca leaf aqueous extract should potent anti-bacterial activity tested by agar well diffusion method as well as the cytotoxic activity which was evaluated by MTT assay.Conclusion: The synthesised nanoparticles were found to be potentially cytotoxic against A549 cell line and also demonstrated anti-bacterial activity. The activity may be attributed to the fact that silver ions are known to impair macromolecules containing sulphur and phosphorus like protein and DNA owing to their small size and high penetration power.Â

Imaging of Knee Joint Pathologies: A Comparative Study of Ultrasound and Magnetic Resonance Imaging

Background: Magnetic resonance imaging (MRI) has been accepted as the best non-invasive imaging modality for the evaluation of knee joint pathology but the advantages of ultrasound (US) over magnetic resonance imaging (MRI) are that the ultrasound is readily available, cheap and offers real-time imaging. Aim: To assess the accuracy of ultrasound in diagnosing knee joint pathologies using MRI as a reference. Materials And Methods: 50 patients were evaluated prospectively over a period of 1.5 years by USG followed by MRI of the affected knee. Accuracy of USG was calculated with MRI as reference. Results: In our study, the majority of patients were in age group 21-30 years. Perfect agreement was noted between ultrasound and MRI for detecting Baker’s cyst. Near perfect agreement was noted between ultrasound and MRI for detecting joint effusion, soft tissue edema and osteophytes. Substantial agreement was noted between ultrasound and MRI for Collateral ligaments tear and Meniscal injuries. Moderate agreement was noted between ultrasound and MRI for PCL tear. Fair agreement was noted between ultrasound and MRI for ACL tear. Conclusion: Knee USG has high accuracy in diagnosing pathologies like knee joint effusion, synovitis, popliteal/baker’s cysts, soft tissue edema/cellulitis, arthritic changes, collateral ligament and meniscal tears. Keywords: Knee joint pathologies, Ultrasound, MRI, Ligament

Bisphosphonate-based molecules as potential new antiparasitic drugs

Neglected tropical diseases such as Chagas disease and leishmaniasis affect millions of people around the world. Both diseases affect various parts of the globe and drugs traditionally used in therapy against these diseases have limitations, especially with regard to low efficacy and high toxicity. In this context, the class of bisphosphonate-based compounds has made significant advances regarding the chemical synthesis process as well as the pharmacological properties attributed to these compounds. Among this spectrum of pharmacological activity, bisphosphonate compounds with antiparasitic activity stand out, especially in the treatment of Chagas disease and leishmaniasis caused by Trypanosoma cruzi and Leishmania spp., respectively. Some bisphosphonate compounds can inhibit the mevalonate pathway, an essential metabolic pathway, by interfering with the synthesis of ergosterol, a sterol responsible for the growth and viability of these parasites. Therefore, this review aims to present the information about the importance of these compounds as antiparasitic agents and as potential new drugs to treat Chagas disease and leishmaniasis.publishersversionpublishe

The Role of Major Phenolics in Apple to Total Antioxidant Capacity

The naturally occurring phenolic compounds have received major attention in recent years as huge amounts of phenolic compounds can be extracted from fruits, vegetables and beverages that have substantial health benefits. From a physiological and metabolic aspect, phenolic compounds are vital in defence responses, such as anti-ageing, anti-inflammatory, anti-oxidant and anti-proliferative, anti-bacterial, anti-hyperlipidemic, anti-cancer, anti-diabetic, neuroprotective, cardioprotective activities. Among the fruits having a higher content of phenolic compounds, the apple (Malus Domestica) is the most widely consumed fruit in the world. Apples have a high nutritional value as it is a rich source of ascorbic acid, polyphenols and pectin. Apple peel forms a small percentage (6–8%) of the total fruit weight and contains the highest content of phenolic compounds, particularly chlorogenic acid. There are five major groups of polyphenolic compounds found in apples namely flavanols (Catechin, Epicatechin and Pyrocyanidins), phenolic compounds, phenolic acids (mainly Chlorogenic acids), dihydrochalcones (Phloretin glycosides), flavonols (Quercetin glycosides) and anthocyanins (Cyanidin). This chapter reviews the chemical properties, mode of action, types, extraction of phenolics in apples and the contribution and role of major phenolics in apples to the total antioxidant capacity

May Measurement Month 2018: a pragmatic global screening campaign to raise awareness of blood pressure by the International Society of Hypertension

Aims Raised blood pressure (BP) is the biggest contributor to mortality and disease burden worldwide and fewer than half of those with hypertension are aware of it. May Measurement Month (MMM) is a global campaign set up in 2017, to raise awareness of high BP and as a pragmatic solution to a lack of formal screening worldwide. The 2018 campaign was expanded, aiming to include more participants and countries. Methods and results Eighty-nine countries participated in MMM 2018. Volunteers (≥18 years) were recruited through opportunistic sampling at a variety of screening sites. Each participant had three BP measurements and completed a questionnaire on demographic, lifestyle, and environmental factors. Hypertension was defined as a systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg, or taking antihypertensive medication. In total, 74.9% of screenees provided three BP readings. Multiple imputation using chained equations was used to impute missing readings. 1 504 963 individuals (mean age 45.3 years; 52.4% female) were screened. After multiple imputation, 502 079 (33.4%) individuals had hypertension, of whom 59.5% were aware of their diagnosis and 55.3% were taking antihypertensive medication. Of those on medication, 60.0% were controlled and of all hypertensives, 33.2% were controlled. We detected 224 285 individuals with untreated hypertension and 111 214 individuals with inadequately treated (systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg) hypertension. Conclusion May Measurement Month expanded significantly compared with 2017, including more participants in more countries. The campaign identified over 335 000 adults with untreated or inadequately treated hypertension. In the absence of systematic screening programmes, MMM was effective at raising awareness at least among these individuals at risk

Biochemical and cellular characterization of key enzymes of Plasmodium falciparum phospholipid metabolism

Le développement du parasite Plasmodium falciparum, responsable du paludisme, nécessite la synthèse de phospholipides et plus particulièrement de phosphatidylcholine (PC) et phosphaditylethanolamine (PE) qui représentent environ 85% de la totalité des phospholidipes du parasite. Leur synthèse s'effectue principalement par les voies métaboliques de novo, voies de Kennedy, en trois étapes enzymatiques. Les enzymes CTP: phosphoethanolamine cytidylyltransferase (ECT) et CTP: phosphocholine cytidylyltransferase (CCT) catalysent les étapes limitantes des deux voies de biosynthèse de la PE et de la PC, respectivement. Ces deux enzymes sont essentielles à la survie du parasite murin, P. berghei et représentent ainsi des cibles thérapeutiques potentielles. La PfCCT est constituée de deux domaines cytidylyltranférases (CT) répétés alors que l'enzyme homologue chez l'homme est composée d'un seul domaine. En revanche, pour la ECT, la présence de deux domaines CT est retrouvée chez toutes les espèces mais les analyses de séquences et de structures ont montré que des résidus importants du site catalytique liant le substrat n'étaient pas conservés dans le domaine CT C-terminal de la PfECT. Ce travail a eu pour but de déterminer les propriétés enzymatiques et les caractéristiques cellulaires de la PfECT et de la PfCCT. Les paramètres cinétiques de ces enzymes ont été quantifiés in vitro à l'aide protéines recombinantes ainsi que sur les enzymes endogènes à l'aide d'extraits parasitaires. Grâce à l'utilisation de protéines recombinantes ponctuellement mutées, nous avons montré que seul le domaine CT N-terminal de la PfECT est catalytiquement actif. Chez P. falciparum, la PfECT et la PfCCT sont exprimées tout au long du cycle intra-érythrocytaire du parasite. La PfECT est présente dans la fraction soluble du parasite alors que la PfCCT apparait aussi bien dans la fraction soluble qu'insoluble. Des expériences d'immunofluorescence ont montré que la PfECT est cytosolique. L'ensemble des résultats présentés apportent un éclairage important sur les fonctions et les propriétés de ces deux cibles potentielles et constituent les premières étapes indispensables à l'élaboration d'une approche thérapeutique.Phospholipids are essential for the growth and development of Plasmodium falciparum malaria parasite. Phosphatidylcholine (PC) and phosphatidylethanolamine (PE) are its major structural phospholipids. This study focused on CTP: phosphoethanolamine cytidylyltransferase (ECT) and CTP: phosphocholine cytidylyltransferase (CCT) that catalyzes the rate-limiting steps of the de novo Kennedy pathways for PE and PC biosynthesis respectively. Both ECT and CCT are essential in the rodent malaria parasite P. berghei and constitute potential chemotherapeutic targets to fight against malaria. PfCCT consists of two very similar cytidylyltransferase (CT) domains whereas the human enzyme consists of only one CT domain. The presence of two CT domains in ECT seems to be widespread in all the organisms. Sequence and structural analysis showed that the C-terminal CT domain of ECT lacks key residues in the substrate binding motif. This study aimed at unravelling the enzymatic properties and cellular characteristics of PfECT and PfCCT enzymes. In addition, these studies addressed the key question if C-terminal CT domain of PfECT is catalytically active. Kinetic parameters of the enzymes were evaluated in vitro on native proteins as well as on recombinant proteins, the latter being produced in bacterial system. Cellular characterisation studies using polyclonal antisera showed that PfECT and PfCCT are expressed throughout the intra-erythrocytic life cycle of the parasite. PfECT is found mainly in soluble form in the parasite while PfCCT is present in soluble as well as insoluble forms in the parasite. Furthermore, immunofluorescence studies for PfECT revealed that it is mainly cytosolic. To assess the contribution of each CT domain to overall PfECT enzyme activity, recombinant PfECT mutants were generated by site-directed mutagenesis. Kinetic studies on these mutants indicated that the N-terminal CT domain was the only active domain of PfECT. Collectively, these results bring new insights into the kinetic and cellular properties of the enzymes and will pave the way in developing a future pharmacological approach

Caractérisation biochimique et cellulaire des enzymes clés du métabolisme des phospholipides chez Plasmodium falciparum

Le développement du parasite Plasmodium falciparum, responsable du paludisme, nécessite la synthèse de phospholipides et plus particulièrement de phosphatidylcholine (PC) et phosphaditylethanolamine (PE) qui représentent environ 85% de la totalité des phospholidipes du parasite. Leur synthèse s'effectue principalement par les voies métaboliques de novo, voies de Kennedy, en trois étapes enzymatiques. Les enzymes CTP: phosphoethanolamine cytidylyltransferase (ECT) et CTP: phosphocholine cytidylyltransferase (CCT) catalysent les étapes limitantes des deux voies de biosynthèse de la PE et de la PC, respectivement. Ces deux enzymes sont essentielles à la survie du parasite murin, P. berghei et représentent ainsi des cibles thérapeutiques potentielles. La PfCCT est constituée de deux domaines cytidylyltranférases (CT) répétés alors que l'enzyme homologue chez l'homme est composée d'un seul domaine. En revanche, pour la ECT, la présence de deux domaines CT est retrouvée chez toutes les espèces mais les analyses de séquences et de structures ont montré que des résidus importants du site catalytique liant le substrat n'étaient pas conservés dans le domaine CT C-terminal de la PfECT. Ce travail a eu pour but de déterminer les propriétés enzymatiques et les caractéristiques cellulaires de la PfECT et de la PfCCT. Les paramètres cinétiques de ces enzymes ont été quantifiés in vitro à l'aide protéines recombinantes ainsi que sur les enzymes endogènes à l'aide d'extraits parasitaires. Grâce à l'utilisation de protéines recombinantes ponctuellement mutées, nous avons montré que seul le domaine CT N-terminal de la PfECT est catalytiquement actif. Chez P. falciparum, la PfECT et la PfCCT sont exprimées tout au long du cycle intra-érythrocytaire du parasite. La PfECT est présente dans la fraction soluble du parasite alors que la PfCCT apparait aussi bien dans la fraction soluble qu'insoluble. Des expériences d'immunofluorescence ont montré que la PfECT est cytosolique. L'ensemble des résultats présentés apportent un éclairage important sur les fonctions et les propriétés de ces deux cibles potentielles et constituent les premières étapes indispensables à l'élaboration d'une approche thérapeutique.Phospholipids are essential for the growth and development of Plasmodium falciparum malaria parasite. Phosphatidylcholine (PC) and phosphatidylethanolamine (PE) are its major structural phospholipids. This study focused on CTP: phosphoethanolamine cytidylyltransferase (ECT) and CTP: phosphocholine cytidylyltransferase (CCT) that catalyzes the rate-limiting steps of the de novo Kennedy pathways for PE and PC biosynthesis respectively. Both ECT and CCT are essential in the rodent malaria parasite P. berghei and constitute potential chemotherapeutic targets to fight against malaria. PfCCT consists of two very similar cytidylyltransferase (CT) domains whereas the human enzyme consists of only one CT domain. The presence of two CT domains in ECT seems to be widespread in all the organisms. Sequence and structural analysis showed that the C-terminal CT domain of ECT lacks key residues in the substrate binding motif. This study aimed at unravelling the enzymatic properties and cellular characteristics of PfECT and PfCCT enzymes. In addition, these studies addressed the key question if C-terminal CT domain of PfECT is catalytically active. Kinetic parameters of the enzymes were evaluated in vitro on native proteins as well as on recombinant proteins, the latter being produced in bacterial system. Cellular characterisation studies using polyclonal antisera showed that PfECT and PfCCT are expressed throughout the intra-erythrocytic life cycle of the parasite. PfECT is found mainly in soluble form in the parasite while PfCCT is present in soluble as well as insoluble forms in the parasite. Furthermore, immunofluorescence studies for PfECT revealed that it is mainly cytosolic. To assess the contribution of each CT domain to overall PfECT enzyme activity, recombinant PfECT mutants were generated by site-directed mutagenesis. Kinetic studies on these mutants indicated that the N-terminal CT domain was the only active domain of PfECT. Collectively, these results bring new insights into the kinetic and cellular properties of the enzymes and will pave the way in developing a future pharmacological approach.MONTPELLIER-BU Sciences (341722106) / SudocSudocFranceF

Guidelines for physical activity in children with heart disease

Justification : In recent years, there has been increasing recognition of children with heart disease in our country. These children belong to different age groups and have untreated, partially treated, or completely treated heart disease. The role of physical activity for optimal physical, emotional, and psychosocial well-being for children is well understood. There is a challenge for the parents and the medical professionals to take a decision regarding the type of physical activity safe for the child as heart disease may affect the hemodynamic demands. Most of the existing international guidelines focus on competitive sports in operated heart disease children. This may be of limited use when we have a mixed population of children with heart disease, different types of sports in our country and where a larger subset is looking for recommendations to leisure time activities. Process : The Pediatric Cardiac Society of India decided to formulate recommendations for physical activity in children with heart diseases. A committee of experts, who were well-versed with the subject of physical activity in children with heart disease, volunteered to take up the task of writing the guidelines. The recommendations emerged following deliberations of the committee members, on the virtual platform as well as mails. The final version of manuscript was approved by all committee members and all members are co-authors of this manuscript. The different types of physical activities were defined including leisure sports and competitive sports. The exercise was classified based on the mechanical action of muscles involved into dynamic and static components. Each type of exercise was then classified based on the intensity into low, medium, and high. Recommendations for the type of physical activity for individual heart lesions were decided based on the rationale available. Objectives : The recommendations here are made with an intention to provide general guidelines for physical activity in children with operated and unoperated heart diseases, not excluding a need for individualizing a plan, serial assessment, and comprehensive checkup in special situations. Recommendations : We hope the recommendations mentioned below would provide basic clarity in planning physical activity in children with heart disease. This is with the hope to encourage physically active life, at the same time ensuring a safety net

Quantitative prioritization of potentially critical glacial Lakes in the Indus River basin using satellite derived parameters

Glacial Lake Outburst Floods (GLOFs) in a deglaciating environment, representing significant threat to downstream people and infrastructure, increasing the necessity of prioritization and assessment of potentially critical glacial lakes (PCGLs). In this current study, a comprehensive updated inventory of glacial lakes for the Indus River basin has been prepared, resulting in 5335 lakes (≥ 0.0025 ± 0.0006 km2), covering a total area of 173.95 ± 10.13 km2. Parameters have been derived using satellite data for two purposes, ‘preliminary screening’ and ‘quantitative assessment’. Using 4 parameters, 367 lakes were preliminary screened-in for further analysis, and 6 quantitative parameters were analysed using Equal Weights (EW) and Unequal Weights methods (UEW). These both methods were applied for two scenarios, scenario-1 which considers 73 lakes (≥ 0.1 km2), and scenario-2 which considers all 367 preliminary screened-in lakes (≥ 0.02 km2). UEW outperformed EW analysis and identified 20 and 48 high potential lakes for scenario-1 and scenario-2 respectively, where all 20 lakes of scenario-1 have been found in common with those of scenario-2, with a difference in their rank. But only 10 of them have storage volume ≥ 10 MCM and has been flagged as high-risk lakes, of which 6 are end-moraine dammed lakes and have been considered as PCGLs, due to their high bursting potential and self-destructive nature. Rest 4 high risk lakes along with remaining 38 lakes with volume < 10 MCM, are considered as critical lakes in case of dynamic mode of failure, caused due to mass movement of avalanche, landslide, heavy precipitation, etc. Highlights 152 historic GLOF events has been reported from 28 sites that occurred in Indus River basin Updated glacial lake inventory of Indus River basin using high resolution IRS satellite data Total of 5335 GL’s were mapped, and 48 of them are identified as high potential lakes UEW outperformed EW method to evaluate weighted integrated index for potentiality assessment 6 lakes are found to be as potentially critical glacial lakes (PCGLs) in the Indus River basi

Biochemical characterization of Plasmodium falciparum CTP:phosphoethanolamine cytidylyltransferase shows that only one of the two cytidylyltransferase domains is active

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