Branched-chain amino acids promote endothelial dysfunction through increased reactive oxygen species generation and inflammation

Branched‐chain amino acids (BCAA: leucine, isoleucine and valine) are essential amino acids implicated in glucose metabolism and maintenance of correct brain function. Elevated BCAA levels can promote an inflammatory response in peripheral blood mononuclear cells. However, there are no studies analysing the direct effects of BCAA on endothelial cells (ECs) and its possible modulation of vascular function. In vitro and ex vivo studies were performed in human ECs and aorta from male C57BL/6J mice, respectively. In ECs, BCAA (6 mmol/L) increased eNOS expression, reactive oxygen species production by mitochondria and NADPH oxidases, peroxynitrite formation and nitrotyrosine expression. Moreover, BCAA induced pro‐inflammatory responses through the transcription factor NF‐κB that resulted in the release of intracellular adhesion molecule‐1 and E‐selectin conferring endothelial activation and adhesion capacity to inflammatory cells. Pharmacological inhibition of mTORC1 intracellular signalling pathway decreased BCAA-induced pro‐oxidant and pro‐inflammatory effects in ECs. In isolated murine aorta, BCAA elicited vasoconstrictor responses, particularly in pre‐contracted vessels and after NO synthase blockade, and triggered endothelial dysfunction, effects that were inhibited by different antioxidants, further demonstrating the potential of BCAA to induce oxidative stress with functional impact. In summary, we demonstrate that elevated BCAA levels generate inflammation and oxidative stress in ECs, thereby facilitating inflammatory cells adhesion and endothelial dysfunction. This might contribute to the increased cardiovascular risk observed in patients with elevated BCAA blood levels.This study was supported by Ministerio de Economía y Competitividad (MINECO SAF2016‐80305‐P), Instituto de Salud Carlos III (ISCIII) Fondo Europeo de Desarrollo Regional (FEDER) a way to build Europe (PI14/00386, PI14/0041, PIE13/00051, PI13/01488; PI17‐01495, CiberCV, CiberDEM), FP7 grant e‐PREDICE, by the Fundación Renal Iñigo Álvarez de Toledo (FRIAT)/Instituto Reina Sofía de Investigación Nefrológica and from Roche‐IdiPa

Heterochronic faecal transplantation boosts gut germinal centres in aged mice

Ageing is a complex multifactorial process associated with a plethora of disorders, which contribute significantly to morbidity worldwide. One of the organs significantly affected by age is the gut. Age-dependent changes of the gut-associated microbiome have been linked to increased frailty and systemic inflammation. This change in microbial composition with age occurs in parallel with a decline in function of the gut immune system, however it is not clear if there is a causal link between the two. Here we report that the defective germinal centre reaction in Peyer’s patches of aged mice can be rescued by faecal transfers from younger adults into aged mice and by immunisations with cholera toxin, without affecting germinal centre reactions in peripheral lymph nodes. This demonstrates that the poor germinal centre reaction in aged animals is not irreversible, and that it is possible to improve this response in older individuals by providing appropriate stimuli

Kaziranga Wild Life Sanctuary, Assam. a Brief Description and Report on the Census of Large Animals (March 1972)

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IMPACT OF CERTAIN EDUCATIONAL INTERVENTIONS ON ADVERSE DRUG REACTION REPORTING BY NURSING HEALTH PROFESSIONALS AT A TERTIARY CARE HOSPITAL

Objectives: The objectives of the study were to evaluate the impact of certain educational interventions on adverse drug reaction (ADR) reporting by nursing health professionals at a tertiary care hospital. Methods: Knowledge, attitude, and practice (KAP) of the nurses regarding ADR reporting were evaluated before and after interventions using a KAP questionnaire. Educational interventions carried out among the nurses were workshops, booklets, SMSes, personal briefings, and posters. Number and quality of ADR reported by nurses in pre-intervention (3 months), intervention (10 months), and post-intervention (3 months) phase were compared. Results: There was a significant increase in response rate to questionnaires in the post-intervention phase (post-IP) (97.74%) as compared to pre-intervention (91.28%) phase (pre-IP). The knowledge score of the nurses increased significantly in post-IP (11.65 ± 2.14) as compared to the pre-intervention (6.98 ± 2.46) phase. No ADR was reported by nurses in pre-IP. Thirty nurses reported 30 ADRs in the intervention phase and six nurses reported six ADRs in the post-IP. The mean score of completeness of ADR notification forms decreased significantly in post-IP. Maximum ADRs (10) were reported after the workshops. Conclusion: Educational interventions improved the KAP of ADR reporting by nurses, albeit temporary. This suggests the need of continuous educational interventions

Microsphere: a Promising Approach for Drug Delivery

The recent evolution in new drug delivery systems plays a important role in pharmaceutical industries. There are various controlled release products, Microsphere is one among all due to the sustained release and controlled release properties.Microsphere are small spherical shape characteristically free flowing powders, with diameters typically ranging from 1 μm to 1000 μm (1 mm). Microspheres can be produced using several natural and synthetic polymeric materials. Depending on the method, solid or porous microspheres can be obtained for specific intended applications. The variety of methods for the production of microspheres offers numerous opportunities to control the aspects of administration of the API.  It provides the prolonged therapeutic action and reduce the dosing frequency, which improve the patient compliance. To get the desired effect the drug should deliver at the target tissue in an ideal amount in the right period of time with maximum therapeutic effect and minimum side effect. Now a day's microspheres have been used to deliver drugs, vaccines etc. The article is mainly focus on the various aspect of microspheres drug delivery system along with their method of preparation, technique to evaluate its efficiency and pharmaceutical application of microspheres

Yield and Yield Attributing Parameters of Toria (Brassica campestries) under Real Time Rainfall Situation in an Inceptisols of Assam, India

A field experiment was conducted during rabi season of 2018-19 and 2019-20 in Dryland experimental field belong to soil order Inceptisols, Biswanath college of Agriculture, Assam Agricultural University, Biswanath chariali, Assam to study the ‘‘Yield and yield attributing parameters of toria (Brassica campestries) under real time rainfall situation in an Inceptisols of Assam, India’’ under AICRPDA, NICRA. The treatments consisting of 4 different dates of sowing i.e. S1-41th SMW, S2-44th SMW, S3-46th SMW, and S4- 48th SMW, & three variety i.e. V1-JT-90-1(Jeuti), V2-Yellow sarson (Benoy) and V3- TS-38. Growth, yield and yield attributing characters of toria varieties were influenced by different dates of sowing. S1 registered higher plant height (43.2 cm, 92.9 cm and 106.6 cm & 40.2 cm, 89.8 cm and 101.5 cm) and number of branch (3.8, 5.3 and 7.2 & 3.4, 5.1 and 6.9) at 30 DAS, 45 DAS and 60 DAS, respectively, during 2018-19 and 2019-20. Yield attributing characters like number of siliqua, number of seed per siliqua, 1000 seed weight (g) were gradually decreased with advancement of sowing dates. Among the three varieties V1 (Jeuti) recorded highest seed yield (8.9 q ha-1 and 8.1 q ha-1) and stover yield (23.4 q ha-1 and 22.2 q ha-1) in 2018-19 and 2019-20, respectively. Highest HI (28.5% and 25.8%) was recorded in S1 and lowest was recorded in S4 (20.7% and 14.6%)

Liposome: a Carrier for Effective Drug Delivery

Liposomes are the spherical vesicles containing one or more phospholipid bilayer, which was first described in the middle of 60s by Bangham. The bilayer vesicles are considered as an efficient carrier for drug delivery, diagnostic agents, and also an effective tool for vaccine delivery.  Liposome has been used as a potential carrier for several diseases from cardiovascular disease to bacterial infection and also it has the ability to reducing the toxicity of highly potent drugs and simultaneously utilized to improve pharmacokinetics and therapeutic efficacy. A liposome is a formulation which has the capacity to overcome with the limitation of conventional therapies. For the delivery of liposome ocular and inhalation route are some advanced technology. In poorly water soluble substance pulmonary delivery is very much useful. However liposome based vaccines have been demonstrated in clinical trials and further progress in human trails. This review discusses the mechanism of action, Method of preparation, evaluation, application of liposomal drug delivery system along with the recent developments some of the commercially available products