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Biology subjects

Konduri, G. G.

Publications and source records attributed to Konduri, G. G..

2 recordsLinked to original sources

Extracorporeal Placental Support in a Sheep's Gravid Uterus

BACKGROUNDThe placenta is a vital organ in animal development, yet its function is understudied. Existing ex vivo placental support models study the organ in isolation, without the uterus and fetus. We report our early experience with a novel model of extracorporeal placental support by perfusing a sheeps gravid uterus. METHODSA sheep gravid hysterectomy was performed after cannulating the uterine vessels. The isolated uterus was maintained in a warm crystalloid tank. Oxygenation, electrolyte supplementation, and glucose were provided through an extracorporeal life support circuit, while monitoring the fetal heart rate and pressure. Our primary objective was to establish the feasibility of the model, confirm the ability to transition the organ to ex vivo support (fetal survival for >30 minutes after hysterectomy), and measure the duration of fetal survival after uterine explantation. RESULTSA total of 51 surgeries were performed, and 76% were successfully transitioned to extracorporeal support. Growing experience throughout the study period led to technical adaptations and more prolonged survival. Uteri with a singleton fetus had longer mean survival times, when compared to twins (253 minutes vs. 104 minutes, p=.019). Anemia and coagulopathy were frequently encountered, and most of the uteri had significant clot formation around the placentomes at the end of the experiment. CONCLUSIONUsing a model of extracorporeal placental support in sheep, we were able to maintain a live fetus within the uterus for more than 16 hours after hysterectomy. This technique is feasible and could provide an avenue to study fetoplacental physiology in an ex vivo environment.

physiology↗

ProLung™-budesonide Inhibits SARS-CoV-2 Replication and Reduces Lung Inflammation

BackgroundInhaled budesonide benefits patients with COVID-19. ProLung-budesonide enables the sustained, low dose administration of budesonide within a delivery vehicle similar to lung surfactant. ProLung-budesonide may offer anti-inflammatory and protective effects to the lung in COVID-19, yet its effect on SARS-CoV-2 replication is unknown. ObjectiveTo determine the efficacy of ProLung-budesonide against SARS-CoV-2 infection in vitro, evaluate its ability to decrease inflammation, and airway hyperresponsiveness in an animal model of lung inflammation. MethodsSARS-CoV-2-infected Vero 76 cells were treated with ProLung-budesonide ([0.03- 100 g/ml]) for 3 days, and virus yield in the supernatant was measured. Ovalbumin-sensitized C57BL/6 mice received aerosolized (a) ProLung-budesonide weekly, (b) only budesonide, either daily or weekly, or (c) weekly empty ProLung-carrier (without budesonide). All treatment groups were compared to sensitized untreated, or normal mice using histopathologic examination, electron microscopy (EM), airway hyperresponsiveness (AHR) to Methacholine (Mch) challenge, and eosinophil peroxidase activity (EPO) measurements in bronchioalveolar lavage (BAL). ResultsProLung-budesonide showed significant inhibition on viral replication of SARS-CoV-2-infected cells with the selectivity index (SI) value > 24. Weekly ProLung-budesonide and daily budesonide therapy significantly decreased lung inflammation and EPO in BAL. ProLung-budesonide localized in type II pneumocytes, and was the only group to significantly decrease AHR, and EPO in BAL with Mch challenge ConclusionsProLung-budesonide significantly inhibited viral replication in SARS-CoV-2 infected cells. It localized into type II pneumocytes, decreased lung inflammation, AHR and EPO activity with Mch challenge. This novel drug formulation may offer a potential inhalational treatment for COVID-19.

pharmacology and toxicology↗