Role of Cyclooxygenase Pathway and Risk Associated with Non-Steroidal Anti-inflammatory Drugs Therapy in Cardiovascular Diseases

Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit the cyclooxygenase enzyme activity through differentmechanisms and prevent inflammation. But they all have different risks associated with them. Some are associated withgastrointestinal bleeding and some are strongly allied with the cardiovascular risks. Cyclooxygenase enzyme regulatesprostaglandin synthesis by converting arachidonic acid present at the sn-2 position of membrane phospholipids toprostaglandin H2. Prostaglandin H2 is the precursor of all prostaglandins. There are two isoforms of cyclooxygenaseenzyme, cyclooxygenase-1 and cyclooxygenase-2 which differ in their active site due to an isoleucine to valinesubstitution at amino acid 523 in cyclooxygenase-2. Cyclooxygenase-1 is constitutively expressed in plateletswhere it helps in the formation of thromboxane whereas cyclooxygenase-2 is inductive form and is expressed inthe endothelial cells due to shear stress and forms prostacyclins. Both thromboxanes and prostacyclins maintainthe homeostasis of the vascular wall. During vascular injury prostacyclin production decreases as a result of whichthromboxane synthesis increases in the platelets which leads to platelet aggregation. Although, being stronglyassociated with cardiovascular risks, NSAIDs are still prescribed to the patients to prevent pain according to theircondition. So this review aims to summarise the mechanism of cyclooxygenase pathway, possible mechanism ofaction of NSAIDs and the risks of cardiovascular events associated with the use of NSAIDs

Complete Remission in Newly Diagnosed Type 1 Diabetes Mellitus Patient

Type 1 diabetes mellitus is a chronic disease affects pancreatic beta cells. Usually it has a life long duration, however, in few cases, it can be transient. We reported a 20 year old male patient who visited the diabetic clinic of Lok Nayak Hospital with classical symptoms of type 1 diabetes mellitus. He was diagnosed with type 1 diabetes on the basis of lab parameters. He was found to be positive for ICA512 and GAD antibodies. Measurement of C-peptide was also done by mixed meal tolerance test. Initially, Insulin was advised to control hyperglycemia. After 2 weeks, he was given 14 infusions of Teplizumab injection, one infusion per day and the same has been repeated after six months. As per clinical judgment, it was assumed that he was not on placebo arm and probably received Teplizumab as investigational product. Teplizumab injection drastically reduces the insulin doses and after some time, his insulin was completely waived off. Complete remission was seen in this patient after treatment with Teplizumab injection. During the 4 years follow-up, this remission is still ongoing in this patient. He had normal fasting and home blood glucose concentration with normal HbA1c without insulin therapy from last 4 years. To keep his blood sugar values under control, patient was also advised regular exercise and a diabetic diet

High altitude Provoked Thrombotic Complications

On rapid ascending to high-altitude particularly very high-altitude or extreme high-altitude, there is a risk of developing high-altitude illness and most people may experience acute mountain sickness which may further lead to potentially life-threatening pathologies like high-altitude pulmonary edema, high-altitude cerebral edema, high-altitude-induced thrombosis etc. if not treated on time. Hypercoagulability state associated with high-altitude which lead to the formation of a clot in the blood vessels, a condition called deep vein thrombosis, which may further complicate and lead to pulmonary embolism. Lack of epidemiological data poses a constraint in evaluating the actual incident rate of thromboembolic disorders at high-altitude. In the present scenario, the most commonly used diagnostic marker for thrombosis is the D-dimer test which has low specificity. Various anticoagulants are also available for anticoagulation therapy but they have their own limitation. Under this review, worldwide reported incidents and management strategies related to thrombotic complications are consolidated and presented. It also summarizes diagnostic and anticoagulation therapy regimes against thrombosis existing at present. Accurate diagnosis and therapeutics are a thrust area of further exploration and there is an urgent need to develop quick and advanced methods to reduce the mortality associated with this disorder especially with respect to high-altitude

Panel of Regulatory miRNAs for Blood Coagulation under Normoxic and Hypoxic Conditions

Abnormal blood coagulation may lead to venous thromboembolism (VTE), a complex multifactorial disease. Hypoxia (oxygen deprivation) is a major factor disturbing the blood hemostasis and predisposing the body towards coagulation and VTE. Pathophysiology of VTE can be attributed to post-transcriptional gene regulation by microRNAs (miRNAs). The present study identified regulatory miRNAs involved in causing blood coagulation under normoxic and hypoxic conditions. Meta-analysis was performed, following PRISMA guidelines, for identifying miRNAs involved in blood coagulation pathway. Studies evaluating miRNAs from circulating blood as potential biomarkers of VTE were selected. A total of 16 studies met selection criteria and 8 having complete statistical information were selected for analysis. Study of blood coagulation mechanism under hypoxic conditions involved in-silico search within highly cited databases to identify miRNAs commonly regulating genes of hypoxia-inducible factor (HIF) family and coagulation pathway. Further bio-informatics approaches were employed to identify potential biomarker candidates. Meta-analysis revealed a panel of 12 miRNAs; two members of miR-27 family, hsa-miR-27a and hsa-miR-27b; two members of miR-320 family, hsa-miR-320a and hsa-miR-320b, hsa-miR-1233, hsa-miR-134, hsa-miR-424-5p, hsa-miR-221, hsa-miR-28-3p, hsa-miR-136-5p, hsa-miR-374-5p and hsa-miR-338-5p involved in blood coagulation under normoxic conditions. Besides these, present in-silico analysis identified a set of 5 miRNAs including hsa-miR-4667-5p, hsa-miR-6815-3, hsa-miR-4433a-3p, hsa-miR-6735-5p and hsa-miR-6777-3p which predominantly regulate genes that facilitate both coagulation and response to hypoxic stress. The present study generated a panel of regulatory miRNAs potentially involved in the process of blood coagulation under both normoxic and hypoxic conditions, which may serve as putative epigenetic biomarkers for coagulation

Effect of Multiple Rounds of Mass Drug Administration under Lymphatic Filariasis Elimination Program on Prevalence of Soil-Transmitted Helminthiasis in One of the Co-endemic Districts of India

Both soil-transmitted helminthiasis and lymphatic filariasis are co-endemic in some districts of India. The study was aimed at comparing the prevalence of soil-transmitted helminthiasis (STH) infection before and after mass drug administration (MDA) given for lymphatic filariasis at Alappuzha.We examined stool samples of 219 children aged between 9 and 10 years from nine schools at Alappuzha, Kerala, in June 2015. The current STH situation was compared with that in the year 1999 (before the institution of MDA) in the same age group in the same district. WHO-recommended Kato-Katz technique was used for STH prevalence estimation. Information regarding socio-demographic variables, sanitation, personal hygiene practices was also recorded. Chi-square test was used to study association of risk factors with STH infection.A total of 79 (36.07%) children were found to be positive for STH infection. Out of all samples positive for Ascaris lumbricoides, 4 (5%) were found co-infected with Trichuris trichiura and none with hookworm. Factors like absence of household latrine, lack of hand washing before meals and practice of consumingunwashed fruits were found to be significantly associated with occurrence of STH infection.Over the years, consecutive rounds of MDA for LF have led to a decline in intestinal worm burden but with little effect on the overall prevalence of STH. Thus, STH control activities working synergistically with the Filarial Elimination Strategy can yield better results in the co-endemic areas with optimum resourceutilization

Functional outcome of hybrid external fixator in proximal tibial fractures Schatzker type V and VI with Gustillo grade-II

Background: Management of high energy tibial plateau fractures along with extensive soft tissue damage is still challenging to many orthopaedic surgeons. This study evaluates the purpose of hybrid external fixator intreating high energy tibial plateau fractures with minimal invasion and accurate reduction.Methods: Twenty patients with high energy Schatzker type V and VI tibial plateau fractures with severe soft tissue injury were enrolled into the study in RNT medical college, Udaipur.Results: The results- bony union, range of movements and associated complications were assessed. All fractures united in an average time period of 20 weeks. Ten patients developed knee stiffness, five patients developed delayed union andthreenon-union.15 patients required split skin graft. Final outcome showed excellent score in 53 patients.Conclusions: Hybrid external fixation is a safe option for managing complex high energy tibial plateau fractures by simultaneously providing adequate fracture stabilization and necessary protection to soft tissue healing to achieve bony union

Determination of Nifedipine by Validated RP-HPLC Method in Bulk and Pharmaceutical Dosage Form

The present paper deals with the development and validation of reverse phase HPLC method for the determination of Nifedipine on Nucleosil 100, 5 μm, C8, 250 x 4.0 mm column. A mobile phase consisting of 40 ml 2-propanol: 60 ml phosphoric acid 0.85% was employed in this study. The flow rate was kept at 0.8 ml/min and the injection volume was 10 µl. The separation was performed at 40°C. Eluents were monitored by UV detector set at 237 nm. The developed method was statistically validated for the linearity, precision, robustness, specificity and solution stability. The specificity of the method was ascertained by force degradation studies by acid and alkali hydrolysis, oxidation, heat and photo degradation. The degraded products were well resolved from the analyte peak with significant differences in their retention time values

Evaluating mechanism and inconsistencies in hydraulic conductivity of unsaturated soil using newly proposed biochar conductivity factor

In the past few decades, numerous studies have been conducted to promote the use of biochar as a soil amendment and most recently, for compacted geo-engineered soils. In general, the definite trends of biochar effects on water retention and fertility of soils have been confirmed. However, the biochar effects on hydraulic conductivity, particularly unsaturated hydraulic conductivity of soil-biochar mix remain unclear, making it difficult to understand water seepage in both agricultural and geo-engineered infrastructures in semi-arid regions. This study examines the unsaturated hydraulic conductivity function derived based on the measurements of soil water characteristic curves of soil with biochar contents of 0%, 5% and 10%. A new parameter “biochar conductivity factor (BCF)” is proposed to evaluate the inconsistency in reported biochar effects on soil hydraulic conductivity and to interpret it from various mechanisms (inter- and intra- pore space filling, cracking, aggregation, bio-film formation and piping/internal erosion). The impact of biochar content on unsaturated hydraulic conductivity appears to reduce as the soil becomes drier with minimal effect in residual zone. Qualitative comparison of near-saturated hydraulic conductivity with test results in the literature showed that the BCF is generally higher for smaller ratio of sand to fine content (clay and silt). Moreover, the particle size of biochar may have significant influence on soil permeability. Future scope of research has been highlighted with respect to biochar production for its applications in agriculture and geo-environmental engineering. Long term effects such as root decay and growth, aggregation and nutrient supply need to be considered. Graphical Abstract

Limited Laminectomy and Restorative Spinoplasty in Spinal Canal Stenosis

Study DesignProspective cohort study.PurposeEvaluation of the clinico-radiological outcome and complications of limited laminectomy and restorative spinoplasty in spinal canal stenosis.Overview of LiteratureIt is critical to achieve adequate spinal decompression, while maintaining spinal stability.MethodsForty-four patients with degenerative lumbar canal stenosis underwent limited laminectomy and restorative spinoplasty at our centre from July 2008 to December 2010. Four patients were lost to follow-up leaving a total of 40 patients at an average final follow-up of 32 months (range, 24-41 months). There were 26 females and 14 males. The mean±standard deviation (SD) of the age was 64.7±7.6 years (range, 55-88 years). The final outcome was assessed using the Japanese Orthopaedic Association (JOA) score.ResultsAt the time of the final follow-up, all patients recorded marked improvement in their symptoms, with only 2 patients complaining of occasional mild back pain and 1 patient complaining of occasional mild leg pain. The mean±SD for the preoperative claudication distance was 95.2±62.5 m, which improved to 582±147.7 m after the operation, and the preoperative anterio-posterior canal diameter as measured on the computed tomography scan was 8.3±2.1 mm, which improved to 13.2±1.8 mm postoperatively. The JOA score improved from a mean±SD of 13.3±4.1 to 22.9±4.1 at the time of the final follow-up. As for complications, dural tears occurred in 2 patients, for which repair was performed with no additional treatment needed.ConclusionsLimited laminectomy and restorative spinoplasty is an efficient surgical procedure which relieves neurogenic claudication by achieving sufficient decompression of the cord with maintenance of spinal stability