ABSTRACT
Stem and bark of the tree Terminalia arjuna Wight & Arn. (Combretaceae) has been documented to exhibit therapeutic properties like cardiotonic, anticancer, antiviral, antibacterial, antifungal, hypercholesterolemia, hypolipidemic, and anti-coagulant. Our previous studies have shown that, ethanolic extract of T. arjuna bark exhibits radical scavenging anti-oxidant activity and also effectively inhibited catalase activity. In this study, oleanane triterpenoids type compounds viz., oleanolic acid, arjunolic acid, arjunolitin, arjunetin were isolated from ethanolic bark extract as bio-active compound and their structures were elucidated using 1H, 13C NMR, HR-ESIMS, IR. Of the various compounds, Arjunetin showed significant inhibition of catalase activity as compared to the other compounds. Based on the structural similarity between arjunetin and current antiviral drugs, we propose that arjunetin might exhibit antiviral activity. Molecular docking and molecular dynamics studies showed that arjunetin binds to the binds to key targets of SARS-CoV-2 namely, 3CLpro, PLpro, and RdRp) with a higher binding energy values (3CLpro, -8.4 kcal/mol; PLpro, -7.6 kcal/mol and RdRp, -8.1 kcal/mol) as compared with FDA approved protease inhibitor drugs to Lopinavir (3CLpro, -7.2 kcal/mole and PLpro -7.7 kcal/mole) and Remdesivir (RdRp -7.6 kcal/mole). To further investigate this, we performed 200-500 ns molecular dynamics simulation studies. The results transpired that the binding affinity of Arjunetin is higher than Remdesivir in the RNA binding cavity of RdRp. Based on structural similarity between arjunetin and Saikosaponin (a known antiviral agents) and based on our molecular docking and molecular dynamic simulation studies, we propose that arjunetin can be a promising drug candidate against Covid-19.Communicated by Ramaswamy H. Sarma.
ABSTRACT
Introduction: Hematuria is a common condition for which a patient seeks nephrology consultation. The presence of gross hematuria is a frightening experience for patient. The reasons for this gross hematuria can be various like nephrolithiasis, malignancies, glomerular diseases, trauma, urinary tract infections, drugs, hemoglobinuria, etc. To differentiate between the various causes of gross hematuria one must begin by taking good history and clinical examination, followed by urine examination and then other tests. Glomerular hematuria is smoky or cola coloured and is usually accompanied by signs and symptoms of fluid overload, high blood pressure, and proteinuria. However cola coloured urine should not be considered synonymous with glomerular hematuria Methods: We report a case of 22 year old pregnant female who was Gravida-3 (22 weeks gestation) but no live issues. Her previous 2 pregnancies ended up in Intra Uterine Death (IUD) of foetus at 6 months gestation. She was referred to us in view of history of cola coloured urine. History of similar episodes of hematuria in previous 2 pregnancies were also present.The history taking was limited because of the prevailing 2ndpeak of COVID-19 pandemic in India and hence most history taking was done indirectly via phone. Clinically she had mild pedal edema and her BP was 110/70 mm of Hg. Her workup showed that she had severe anaemia. Her Complete Blood Count showed Hb-5.8 gm/dL,TLC-3600/mm3,Plt-1.64lakh/mm3,PBS-Microcytic hypochromic with target cells. Renal function was normal. Liver function showed mild indirect hyperbilirubinemia. Urinalysis showed 3+ protein, 50-60 RBCs, 5-10 Pus cell, No casts. Urine culture was sterile. 24 hour urine protein was 1.29 grams. Ultrasonography-bilateral normal sized kidneys. Her COVID-19 RTPCR was negative Results: Differentials we considered were : Primary Glomerulonephritis;Pregnancy Induced Hypertension (PIH);Anti-Phospholipid Antibody Syndrome (APLA) & Atypical Hemolytic Uremic Syndrome (a-HUS). These were ruled out based on further relevant tests.Kidney biopsy was not offered as there was no nephrotic syndrome. Anti-Nuclear Antigen was negative. Complements were normal. APLA antibodies were negative.BP was always normal making PIH less likely. However LDH was raised (2700 U/L) & serum haptoglobulin was low. So a clear cut evidence of hemolytic anaemia but normal renal function, compelled us to revisit the history by calling the patient in-person despite the pandemic. She admitted that anaemia was present since her childhood days and she had suppressed this history due to social issues. Also the hematuria was episodic with clear urine in between. Hence Flowcytometry for Paroxysmal Nocturnal Hemoglobinuria was done which confirmed the diagnosis as PNH. Conclusions: Our case report highlights the fact that while evaluating cases of hematuria one must keep all possibilities open. Especially when dealing with cola coloured urine it should not be assumed to be glomerular hematuria It also stresses the well established fact that history taking is the key to making any diagnosis. In situations where social factors may lead to suppression of facts,efforts must be made to gain the confidence of patient and provide a conducive environment for complete history. Finally, even after diagnosis of PNH, the definitive treatment is still out of reach for many patients in this part of world. No conflict of interest
ABSTRACT
PURPOSE: To report the incidence, cumulative mortality, and factors influencing the outcomes from a large series of COVID-19-associated mucormycosis (CAM) from western India. METHODS: Consecutive patients with CAM between March 1 and May 10, 2021, with a minimum follow-up of 1 month were included. We recorded the presence of diabetes, use of steroids, and need for non-invasive ventilation (NIV) from the case files. The features of orbital involvement, treatment administered, and outcomes, i.e., death, orbital exenteration, or recovery were noted. Cumulative probability of adverse outcomes, defined as either death or exenteration, was reported using survival analysis. RESULTS: We treated 67 cases of CAM and found an incidence of 13.6 cases per 1,000 patients post-moderate to severe COVID-19. Uncontrolled diabetes (90%) with ketoacidosis (40%) and prior systemic steroids (84%) were the strongest predispositions. The onset of CAM was 15.1 ± 9.5 days (range: 6-42 days) after recovery from COVID-19. The cumulative probability of an adverse outcome was 38% (95% confidence intervals [CI] = 23.7-56.9%) on day 20. The patients who required NIV during COVID-19 were at seven times higher risk of experiencing an adverse outcome (hazard ratios [HR] = 6.92, 95% CI = 2.9-16.2) while those who received amphotericin- -B had a 61% lower risk (HR = 0.39, 95% CI = 0.16-0.97). CONCLUSION: The current outbreak of CAM was seen predominantly in uncontrolled diabetics, especially with ketoacidosis and steroid intake. The cumulative probability of death or orbital exenteration was 38% at day 20 of the infection and those who required NIV and did not receive amphotericin-B were at a high risk of these outcomes.