The neutralization effect of montelukast on SARS-CoV-2 is shown by multiscale in silico simulations and combined in vitro studies

Small molecule inhibitors have previously been investigated in different studies as possible therapeutics in the treatment of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). In the current drug repurposing study, we identified the leukotriene (D4) receptor antagonist montelukast as a novel agent that simultaneously targets two important drug targets of SARS-CoV-2. We initially demonstrated the dual inhibition profile of montelukast through multiscale molecular modeling studies. Next, we characterized its effect on both targets by different in vitro experiments including the enzyme (main protease) inhibition-based assay, surface plasmon resonance (SPR) spectroscopy, pseudovirus neutralization on HEK293T/hACE2+TMPRSS2, and virus neutralization assay using xCELLigence MP real-time cell analyzer. Our integrated in silico and in vitro results confirmed the dual potential effect of montelukast both on the main protease enzyme inhibition and virus entry into the host cell (spike/ACE2). The virus neutralization assay results showed that SARS-CoV-2 virus activity was delayed with montelukast for 20 h on the infected cells. The rapid use of new small molecules in the pandemic is very important today. Montelukast, whose pharmacokinetic and pharmacodynamic properties are very well characterized and has been widely used in the treatment of asthma since 1998, should urgently be completed in clinical phase studies and, if its effect is proved in clinical phase studies, it should be used against coronavirus disease 2019 (COVID-19).     

End-to-end microvascular anastomosis in the rat carotid artery using continuous horizontal mattress sutures

This paper reports a continuous horizontal mattress suture technique with advantages such as decreased time for anastomosis, minimized anastomotic leakage, eversion around the vessel edges, and other advantages which the continuous anastomosis technique has. This technique was compared with the classical interrupted and classical continuous suture techniques on a total of 59 Sprague-Dawley rat common carotid arteries: Group 1 (n = 19), interrupted suture technique; Group 2 (n = 20), standard continuous technique, and Group 3 (n = 20), continuous horizontal mattress technique. Early (30 min) and late (21 days) patency rates, anastomosis time, leakage on clamp release, oozing duration, additional sutures needed, and total number of sutures placed were statistically compared between groups. Specimens were taken at the 21st day randomly, and light microscopy (LM), scanning electron microscopy (SEM), and angiographic studies were performed. Results revealed that the continuous mattress suture technique has the advantages of providing a water-tight anastomosis with less suture materials in a shorter time, and minimal intraluminal suture material which can incite thrombosis. On the other hand, a tendency to anastomotic stricture was found to be the sole disadvantage of this technique.     

The effect of pentoxifylline on the healing of intestinal anastomosis in rats with experimental obstructive jaundice

The aims of this study were (1) to investigate the effect of experimental obstructive jaundice on the healing of intestinal anastomosis, and (2) to investigate the effect of pentoxifylline on the healing of intestinal anastomosis in rats with obstructive jaundice. Obstructive jaundice was induced in rats by the ligation and division of the common bile duct. Four days after this operation, either pentoxifylline or isotonic saline solution was administered intraperitoneally to these jaundiced rats and controls, and then intestinal anastomosis was performed. The concentrations of serum tumor necrosis factor α (TNF-α) and serum triglyceride of jaundiced and nonjaundiced rats were measured, and the quality of healing was evaluated by measuring the bursting preasure and hydroxyproline content of the anastomoses on the fifth and tenth days of anastomotic healing. Obstructive jaundice resulted in an impaired wound healing of the intestinal anastomosis in the rats. The administration of pentoxifylline to the jaundiced rats resulted in better anastomotic wound healing. The beneficial effects of pentoxifylline on anastomotic healing in rats with obstructive jaundice was attributed to its inhibitor effect on the endotoxin-induced TNF-α release from macrophages and monocytes, and the stabilizing effect on the neutrophils. Received: March 29, 1999 / Accepted: March 24, 2000     

Liver Transplantation Following Life-threatening Abdominal Trauma: A Case Series of 5 Patients at a Single Institution

Managing traumatic liver injury (TLI) is always challenging and demands precise clinical judgment. Currently, treatment of TLI in most circumstances is non-operative; however, surgical therapy might be required for severe TLI, particularly those that result in extensive blood loss. In the current institutional study carried out from June 1995 to April 2017, we describe our experience with 5 patients who received an orthotopic liver transplant for severe TLI. One patient passed away postoperatively from cerebral edema; 1 patient died of renal failure 4 years after the liver transplantation, and 3 patients are still alive. Based on our experience, we conclude that in patients with TLI, especially those with uncontrollable bleeding or those who develop liver failure, liver transplantation should be taken into consideration.     

High-thoracic ultrasound-guided erector spinae plane block for acute herpes zoster pain management in emergency department

Herpes zoster is a painful, eruptive, viral condition occurring with reactivation in immunosuppressed individuals. The selection of an effective analgesic method in the acute phase of herpes zoster can decrease the incidence of postherpetic neuralgia by reducing neural sensitization. The erector spinae plane block has been reported to provide diffuse and effective analgesia in the cervical, thoracic, and lumbar regions. We report an effective decrease in pain with the application of the high-thoracic erector spinae plane block in the emergency department in a patient with herpes zoster pain in the cervicothoracic and shoulder region.