COVID-19 patients in myasthenic crisis managed successfully with noninvasive positive pressure ventilation: a case series.

The management of respiratory failure during the present pandemic has been a challenging issue for the intensivists. There have been few case series and case reports on myasthenic crisis precipitated by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. The combination of coronavirus disease-19 (COVID-19) pneumonia and myasthenic crisis can result in increased morbidity and mortality if not managed efficiently. The choice of ventilation ranges from non-invasive to invasive. However a lack of proper understanding of pathophysiology of myasthenia gravis and also the COVID-19 could make the decision of selecting the modality of ventilation a real difficult one. Although invasive ventilation is traditionally indicated when the myasthenia gravis patient presents in myasthenic crisis, there is emerging evidence for use of non-invasive ventilation with BiPAP mode in these patients. We present two cases of myasthenic crisis precipitated by SARS-CoV-2 which were successfully managed on non-invasive ventilation, thereby avoiding intubation and complications of invasive mechanical ventilation

UTILITY OF BLIND PLEURAL BIOPSY IN UNDIAGNOSED PLEURAL EFFUSION USING ABRAMS NEEDLE

BACKGROUND As many as one-fifth of all the exudative pleural effusions remain non-diagnostic, despite all the routine biochemical and cytological examinations of pleural fluid. The aim of the study is to examine the role of closed pleural biopsy using Abrams needle in such cases of pleural effusion in a tertiary care hospital of central India. MATERIALS AND METHODS All the patients with initial non-diagnostic pleural fluid thoracentesis from January 2017 to October 2017 were included in the study and subjected to closed Abrams pleural biopsy. Biopsy sample was sent for histopathological examination, culture and CBNAAT (cartridge based nucleic acid amplification test) for tuberculosis. The patients who still remained nondiagnostic, further underwent other procedures as per the physician’s decision. Statistical analysis was then done on the data collected. RESULTS Closed percutaneous pleural biopsy was performed in 60 patients. It yielded granulomatous inflammation suggestive of tuberculosis in 17 (28.33%), out of them, 15 cases were also detected by the CBNAAT. All of them were rifampicin sensitive. Malignancy was detected in 12 (20%) patients, mixed inflammatory pattern with pus cells in 9 (15%) patients. Almost, 22 samples (36.66%) were declared nondiagnostic. CONCLUSION Our age old closed biopsy technique was diagnostic in almost 64% cases of non-diagnostic pleural fluid exudates on thoracentesis. This study supports the use of Abrams needle for investigation purpose of pleural fluid in economically constrained countries

Molecular dynamics and quantum chemistry-based approaches to identify isoform selective HDAC2 inhibitor – a novel target to prevent Alzheimer’s disease

<p>Histone deacetylase 2 (HDAC2) is an emerging target of Alzheimer’s disease. Four featured pharmacophore model (ADRR) with one H-bond acceptor (A), one H-bond donor (D), and two aromatic rings (R) was generated using experimentally reported compounds, ((E-5[3-benzenesulfonamido) phenyl]-N-hydroxypent-2-en-4-ynamide)) and (N’-hydroxy-N-phenyloctanediamide) with IC₅₀ values of 0.16 ± 0.11 nM and 62 ± 0.15 nM, respectively. Quantum Polarized Ligand Docking and Binding Free Energy calculation was performed for the top three identified leads RH01652, JFD02573, and HTS00800 from HitFinder database. RH01652 (methyl 2-[({5-[(benzoylamino) methyl]-2-thienyl} sulfonyl) amino]-3-(1H-indol-3-yl) propanoate) with docking score (−12.62 kcal/mol) and binding free energy (−75.27 kcal/mol), shows good binding affinity. RH01652 interacts with Gly154, His183, Glu208, and Phe210 with four H-bonds and stabilized by π–π interactions with His146, Tyr209, and Phe210. DFT studies at B3LYP level with 6-31G* basis set for the lead RH01652 reveals low band gap/Δ<i>E</i> (<i>E</i>_HOMO–<i>E</i>_LUMO) of −0.16 eV, which illustrates good reactivity of the lead. MD simulation studies (40 ns) was performed to confirm the stability of lead binding. Comparative molecular docking studies of the lead RH01652 with class I HDACs (HDAC1, HDAC2, HDAC3, and HDAC8) shows higher binding affinity towards HDAC2. Thus, lead RH01652 could serve as template to design novel and potent inhibitor of HDAC2.</p

Antimalarial drugs inhibiting hemozoin (β-hematin) formation: a mechanistic update

Digestion of hemoglobin in the food vacuole of the malaria parasite produces very high quantities of redox active toxic free heme. Hemozoin (β-hematin) formation is a unique process adopted by Plasmodium sp. to detoxify free heme. Hemozoin formation is a validated target for most of the well-known existing antimalarial drugs and considered to be a suitable target to develop new antimalarials. Here we discuss the possible mechanisms of free heme detoxification in the malaria parasite and the mechanistic details of compounds, which offer antimalarial activity by inhibiting hemozoin formation. The chemical nature of new antimalarial compounds showing antimalarial activity through the inhibition of hemozoin formation has also been incorporated, which may help to design future antimalarials with therapeutic potential against multi-drug resistant malaria

Apoptosis in liver during malaria: role of oxidative stress and implication of mitochondrial pathway

Hepatic dysfunction is a common clinical complication in malaria, although its pathogenesis remains largely unknown. Using a variety of in vivo and ex vivo approaches, we have shown for the first time that malarial infection induces hepatic apoptosis through augmentation of oxidative stress. Apoptosis in hepatocyte has been confirmed by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin-nick-end labeling assay (TUNEL) and caspase-3 activation. Gene expression analysis using RT-PCR indicates the significant down-regulation of Bcl-2 and up-regulation of Bax expression in liver of malaria infected mice suggesting the involvement of mitochondrial pathway of apoptosis. The levels of Fas expression and caspase-8 activity in infected liver were same as that of uninfected control mice indicating death receptor (Fas) pathway did not contribute to liver apoptosis during malarial infection. Moreover, evidence has been presented by confocal microscopy to show the translocation of Bax from cytosol to mitochondria in apoptotic hepatocyte, resulting in opening of permeability transition pores, which in turn decreases mitochondrial membrane potential and induces cytochrome c release into cytosol. Malarial infection induces the generation of hydroxyl radical (·OH) in liver, which may be responsible for the induction of oxidative stress and apoptosis as administration of ·OH specific antioxidant as well as spin trap, alpha-phenyl-tert-butyl-nitrone in malaria-infected mice significantly inhibits the development of oxidative stress as well as induction of apoptosis. Thus, results suggest the implication of oxidative stress induced-mitochondrial pathway of apoptosis in the pathophysiology of hepatic dysfunction in malaria.—Guha, M., Kumar, S., Choubey, V., Maity, P., Bandyopadhyay, U. Apoptosis in liver during malaria: Role of oxidative stress and implication of mitochondrial pathway

Successful prolonged use of non-invasive ventilation in severe COVID-19 patients: a case series.

BACKGROUND: The Coronavirus disease-19 (COVID-19) primarily affects respiratory system leading to acute hypoxemic respiratory failure. Invasive mechanical ventilation has been a gold standard in the respiratory therapy of patients with acute respiratory distress syndrome (ARDS). It requires advanced ventilators, qualified intensivists and trained intensive care unit (ICU) staff to manage, which is not readily available and of which there has been a perpetual shortage during the current pandemic. Non-invasive ventilation (NIV) is one of the bridging non-invasive respiratory supports to avoid invasive intubation intended to improve oxygenation and ventilation in severe COVID-19 patients where conventional oxygen therapy fails. CASE: The authors report a series of four cases where prolonged NIV was used under expert supervision in patients with severe COVID-19 disease. CONCLUSIONS: This case series showed that NIV can be prolonged successfully under supervision in severe COVID-19 patients that can avoid intubation and its complications

A comparison between nitroprusside and nitroglycerine for hypotensive anesthesia in ear, nose, and throat surgeries: A double-blind randomized study

Context: Blood obscures the operative field and makes precise technique difficult, and to the anesthetist, when the volume of blood lost is large. Practice of induced hypotension in the otolaryngology is a common practice owing to its benefits in providing a better visibility and preventing blood loss. Aims: The aim was to compare controlled induced hypotension for facilitating surgical exposure, and reducing intraoperative blood loss using sodium nitroprusside and nitroglycerin in ear, nose, and throat surgeries under general anesthesia. Settings and Design: A prospective, randomized, double-blind study. Materials and Methods: The study was carried out in 60 adults, American Society of Anesthesiologists grade I and II patients, allocated randomly in to three groups: group A was control group, group B patients received nitroprusside (0.5-10 μg/kg/min) and group C patients received nitroglycerine (1-10 μg/kg/min). Mean arterial pressure was maintained in the range of 50-60 mmHg. Statistical Analysis Used: Statistical Package for Social Sciences version 17.0 (ANOVA) followed by independent samples t-test and Chi-square test. Results: The results of the present study indicate that the use of controlled hypotension provides a better surgical field and reduces the blood loss. Of the two modalities under question, use of sodium nitroprusside gives the desired results in a significantly, shorter time as compared to nitroglycerin; however, the use of sodium nitroprusside must be carried out with caution as it has toxic effects. Conclusions: (1) The achievement of target level was quicker in sodium nitroprusside group as compared to nitroglycerin group. (2) Reflex tachycardia was the main side effect of the nitroglycerin group. (3) Rebound hypertension was the associated side effect of the sodium nitroprusside group