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

Venous Thrombosis could be Gender Specific, Women Beware!

Venous thrombosis (VT) is the third major cause of mortality in the world after heart attack and stroke. Its two major clinical manifestations are deep vein thrombosis (DVT) and pulmonary embolism (PE) which are serious medical conditions but often remain under-diagnosed. Although rate of occurrence of venous thrombosis in men is slightly higher, a number of studies have pointed out that woman poses higher risk of venous thromboembolism (VTE) compared to men at various stages of life. Risk of VTE increases in women’s life particularly with use of oral contraceptives, during pregnancy and with exogenous administration of hormones like in post-menopausal hormone therapy. Various reports show that these factors increase risk of DVT and PE by several folds. DVT is considered as an important cause of maternal death in western countries. It is often asymptomatic and its signs and symptoms are similar to those of normal pregnancy. The hormonal changes at various stages of life and less physical activity increase the risk of VTE by blood flow stasis. It is extremely important for women to know the stages of life when they are prone to develop VTE, about its prevention and treatment. Detailed studies on differences in clinical manifestations of VTE between men and women are lacking. This review focusses on assessing the increased risk of VTE and its prognosis in women based on available literature

Wildlife Collisions to Aircraft in India

Wildlife strikes (mainly birds, but also includes bats and other mammals on the ground) with aircraft isa serious economic and safety concern in the aviation industry. The solution to the problem can be evolved byidentifying the species involved in the incidents/ accidents. In the Indian context, such an attempt was started in1980. In the recent past, the Indian Air Force adopted the DNA Bar-coding technology to identify the species involved. The extent of the problems faced by the country and involvement of different species in various time blocks has been compared with the objective of analyzing changes over different periods to gauge the changes and assess the future requirements. The data indicates that over the years, the number of strikes has increased manifold in the civil aviation sector. The number of species involved in strikes has almost doubled. The serious strikes due to Vultures have nearly disappeared and their place has been mainly taken over by Black Kites. In the recent past, Black Kites are the cause of the highest damages and also have the highest probability of causing damages (61.17%) when struck. Adoption of DNA Barcoding technology has helped to identify the species in incidents where minimal bird remnants were found. Although the number of accidents has decreased, the economical losses continue to rise due to the high cost of modern aircraft

Gut Microbiome and COVID 19 Role of Probiotics on Gut Lung Axis

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has caused the greatest worldwide pandemic called Coronavirus-2019 (COVID-19) disease. The SARS-CoV-2 virus primarily attacks the respiratory tract, but it also disturbs the gastrointestinal system (GIT). The presence of the angiotensin-converting enzyme-2 (ACE-2) receptor in the intestinal epithelial cells, suggest the transmission of SARS-CoV-2 viruses from lungs to gut through systemic circulation. The virus detected in fecal samples of COVID-19 patients causes several gastrointestinal maladies including vomiting, diarrhea, and pain in abdomen. The gastrointestinal symptoms are associated with alterations in gut microbial composition, an increase in inflammatory cytokines and delayed virus clearance. Several studies demonstrated a decreased abundance of beneficial microbial species and increased opportunistic pathogens in the fecal samples of COVID-19 patients. The gut and lungs, share a bi-directional relationship called the “gut-lung axis” which is modulated by imbalanced gut microbiota. Since the gut microbes are suggested to play a vital role in health and disease by maintaining homeostasis of the immune system, therefore targeting the intestinal dysbiosis with beneficial microbial species, seems plausible to eventually diminish the effects of pulmonary infections and diseases. In this review, we have summarized studies demonstrating the gut-lung axis in association with gut dysbiosis in COVID-19 patients. In addition, the review also highlights the studies showing the potential role of probiotic supplementation in the amelioration of various respiratory infections and diseases. Data demonstrate that the restoration of gut microbial communities by probiotic supplementation can enhance lung capacity to combat respiratory viral infections including SARS-CoV-2

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

Advances in Rapid Detection and Antimicrobial Susceptibility Tests: A Review

The rise of antibiotic resistance is an emerging problem of the millennium. Clinical microbiology plays an important role in combating the problem by facilitating diagnostics and therapeutics thus managing infection in patients. Diagnostic failures are a major limiting factor during bacterial infection that causes inappropriate use of antibiotics, delay in start up of treatment and decrease in the survival rate during septic conditions. Thus rapid and reliable detection is highly relevant during such bacterial infections and also at the time of disease outbreak as many such pathogens can be used as biothreat agents or bioweapons affecting human health and posing risk to national security. This review highlights the importance of various methods for fast pathogen detection and antimicrobial susceptibility determination. These methods have the potential to provide very precise and rapid ways for bacterial screening and identifying the correct antibiotics to cure infectio

Yoga Intervention as a Potential Countermeasure for Polar T3 Syndrome

Polar T3 syndrome is a common ailment for polar sojourners. It is characterised by abnormal fluctuations of thyroid hormones during extended polar winter. A randomised controlled study was conducted on 14 winter expedition members of Indian Scientific Expedition (2016) to Antarctica by introducing customised yoga module. Blood samples were collected during January to October, 2016 at different intervals for the estimation of total thyroxine (TT4), total triiodothyronine (TT3), thyroid stimulating hormone and noradrenaline (NA) by ELISA. In October yoga group showed significant (p = 0.04) higher TT3 values (2.1 ng/ml ± 0.9; mean ± SD) as compared to the control (0.7 ng/ml ± 0.6). In October a significant difference (p=0.0085) was observed between yoga and control group for NA values (47.0 pg/ml ± 22.0 and 107 pg/ml ± 46.0). Thyroid response of control group at the end of the study revealed presence of polar T3 syndrome in control group. Results indicate that regular yoga practice helped mitigating polar T3 syndrom

Heat Induced Oxidative Stress and Aberrations in Liver Function Leading to Hepatic Injury in Rats

Exposure to heat stress (HS) elicits systemic and cellular response in experimental animals and humans. The current study was undertaken to determine the effect of HS on liver microstructure and function in rats. A heat simulation chamber with ambient temperature (Ta) 45 ± 0.5 °C and relative humidity (RH) 30 ± 5 per cent was used to expose animals to HS. Rats were categorised as moderately heat stressed (MHS, Tc = 40 °C) and severely heat stressed (SHS, Tc = 42 °C) group. We observed that with rise in core temperature (Tc) alanine aminotransferase(ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) levels were increased but glucose level was decreased in both plasma and liver tissue. Significantly elevated levels of reactive oxygen species (ROS) and nitric oxide (NO) were detected in liver of MHS and SHS animals. Additionally, glutathione disulfide and glutathione (GSSG and GSH) ratio was found to be increased with rise in Tc which suggested saturation in antioxidant capacity of tissue. Furthermore, levels of heat shock proteins (HSPs) and caspases were upregulated upon HS. Results of histological examination indicated extensive loss of cells in liver parenchyma leading to disorganisation of lobular structure. Thus, biochemical and histological studies in experimental animals demonstrates that HS may severely altered structural and biochemical functions of liver

Induction of stress proteins in response to hypoxia

344-349Hypoxia is a severe stress factor to which man and most other mammalian species are capable of adapting. However, the cellular mechanism which enable cells to adapt are still unknown. Effect of hypoxia was studied on the synthesis of hypoxia induced proteins in rat kidney and in vero clell line (monkey kidney). These were exposed to hypoxia at 240 mmHg pressure for 1 hr. The induction of stress protein was determined by probing with monoclonal antibodies against 65kDa heat shock protein (hsp65). The induction of a 65kDa protein was 3.6 fold higher to the total cellular protein, both in cell lines and kidney of rats. In vivo response was predominantly observed in renal cortical region particularly in glomeruli. The induction of stress proteins during hypoxia suggests their importance in the maintenance of cellular integrity under hypoxia

Role of altered proteostasis network in chronic hypobaric hypoxia induced skeletal muscle atrophy.

BACKGROUND:High altitude associated hypobaric hypoxia is one of the cellular and environmental perturbation that alters proteostasis network and push the healthy cell towards loss of muscle mass. The present study has elucidated the robust proteostasis network and signaling mechanism for skeletal muscle atrophy under chronic hypobaric hypoxia (CHH). METHODS:Male Sprague Dawley rats were exposed to simulated hypoxia equivalent to a pressure of 282 torr for different durations (1, 3, 7 and 14 days). After CHH exposure, skeletal muscle tissue was excised from the hind limb of rats for biochemical analysis. RESULTS:Chronic hypobaric hypoxia caused a substantial increase in protein oxidation and exhibited a greater activation of ER chaperones, glucose-regulated protein-78 (GRP-78) and protein disulphide isomerase (PDI) till 14d of CHH. Presence of oxidized proteins triggered the proteolytic systems, 20S proteasome and calpain pathway which were accompanied by a marked increase in [Ca2+]. Upregulated Akt pathway was observed upto 07d of CHH which was also linked with enhanced glycogen synthase kinase-3β (GSk-3β) expression, a negative regulator of Akt. Muscle-derived cytokines, tumor necrosis factor-α (TNF-α), interferon-ϒ (IFN-©) and interleukin-1β (IL-1β) levels significantly increased from 07d onwards. CHH exposure also upregulated the expression of nuclear factor kappa-B (NF-κB) and E3 ligase, muscle atrophy F-box-1 (Mafbx-1/Atrogin-1) and MuRF-1 (muscle ring finger-1) on 07d and 14d. Further, severe hypoxia also lead to increase expression of ER-associated degradation (ERAD) CHOP/ GADD153, Ub-proteasome and apoptosis pathway. CONCLUSIONS:The disrupted proteostasis network was tightly coupled to degradative pathways, altered anabolic signaling, inflammation, and apoptosis under chronic hypoxia. Severe and prolonged hypoxia exposure affected the protein homeostasis which overwhelms the muscular system and tends towards skeletal muscle atrophy