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).     

Evaluation of staining susceptibility of resin artificial teeth and stain removal efficacy of denture cleansers

Objective. To assess the staining susceptibility of four acrylic resin (Ivostar, SR Vivodent PE, Major Dent, Integral) and a nanocomposite resin (Veracia) artificial teeth and to evaluate the stain removal efficacy of denture cleansers. Materials and methods. Sixty maxillary incisors of each brand (total = 300) were divided into three groups according to staining solution as coffee, red wine and tea. Baseline color measurements were performed with a spectrophotometer. Specimens were immersed in staining solutions for 14 h (2 h × 7 days) and then second color measurements were performed. Each group was further divided into four sub-groups according to denture cleanser as Corega tabs, Fittydent, NaOCl (0.5%) and distilled water (control) (n = 5). Specimens were immersed in denture cleansers for 8 h and third color measurements were made. Thus, the weekly simulation period was completed. This cycle was repeated 12 times to simulate a 3-month time period and measurements were performed at the end of the 4th, 8th and 12th cycles. ΔE values were calculated and data were analyzed with 3-way repeated measures ANOVA and Bonferroni tests. Results. Significant color differences were found among the teeth and staining solutions, but all of the color differences were in the clinically acceptable range (ΔE < 5.5). Integral showed the highest ΔE values for all solutions, while Ivostar and Vivodent demonstrated the lowest ΔE values for red wine and tea solutions. There was no significant difference among the denture cleansers in terms of stain removal efficacy. Conclusions. Cross-linked acrylic (Integral) and nanocomposite (Veracia) resin teeth were more susceptible to staining. Denture cleansers were efficient on stain removal from artificial teeth.     

Leukoaraiosis in stroke patients

Pathogenesis of leukoaraiosis (LA) is not clearly understood and its significance in patients with stroke remains undetermined. In the Neurology Department of Ankara Hospital, computed tomography (CT) examination of brain was performed for various reasons in 288 patients. LA was detected in 178 patients by the use of brain CT. Patients with LA had a higher incidence of hypertension history (70.8%) when compared with the non-LA group (57.3%; p <.05). There was no statistically significant difference in terms of sex, mean age, smoking, diabetes mellitus, history of cerebrovascular disease, cardiac failure, ischemic cardiac disease between patients with and without LA. We showed that LA is related to hypertension but not related to age, diabetes mellitus, or cardiac disease in our patient population.     

Sex difference in perceptual-verbal ability in relation to body size

Sex difference in verbal ability was reconsidered in relation to body size. The perceptual-verbal ability (PVA) was assessed using the A's Test. For the raw data, women excelled men, as expected. PVA positively correlated with height and weight of the subjects, but only for women. As a covariate of height, sex difference increased by increasing the women's score; men's score did not change. Tall women had much higher scores than short men. It was concluded that sex difference in PVA is stable despite the smaller body size of females than males, and body height may be predictive for this ability, but only in women.     

Thrombin activatable fibrinolysis inhibitor activity (TAFIa) levels in neonates with meconium-stained amniotic fluid

OBJECTIVE: Meconium-stained amniotic fluid (MSAF) is thought to be a sign of fetal hypoxia, which causes activation of coagulation and inhibition of fibrinolysis. Inflammation is also seen in MSAF. On the other hand, thrombin activatable fibrinolysis inhibitor (TAFI) is an inhibitor of fibrinolysis and a regulator of vascular inflammation. For this reason, in this study we aimed to evaluate the relation between hypoxia, fibrinolysis, and inflammation by determining the levels of TAFI activity (TAFIa) in MSAF where inflammation was also thought to have a role in the pathogenesis. METHODS: The MSAF group consisted of 22 neonates; 20 neonates served as the control group. Plasma TAFIa levels were evaluated in all neonates in the first six hours of life. RESULTS: TAFIa levels were significantly higher in the MSAF group when compared with the control group and the levels correlated negatively with cord blood pH levels. CONCLUSIONS: Increased TAFIa levels in neonates with MSAF might be due to hypoxia. Inflammation observed in MSAF may also play an additional role in increased TAFIa expression. Although no clinical complication that can be attributed to this increase was seen, one should be alert to the complications of depressed fibrinolysis that might be observed in these neonates.     

Asymptomatic pons tuberculoma in an infant with miliary tuberculosis

Miliary tuberculosis is caused by the hematogenous spread of Mycobacterium tuberculosis and consists of 1.5% of all tuberculosis cases. It is seen mostly in infants because of the immature immune system, and central nervous system CNS involvement is not rare. Tuberculomas are rarely seen in the localized form of CNS tuberculosis, and only 4% are localized in the brain stem. We report a 4.5-month-old infant who deteriorated during follow-up with the diagnosis of cytomegalovirus pneumonia, and afterwards received the diagnosis of miliary tuberculosis. Although the baby had no neurologic abnormality and cerebrospinal fluid findings were normal, cranial MRI revealed contrast enhanced nodular lesions in pons, cerebellum, and right parietal region. The case is presented to intensify the importance of CNS investigation even if the patient with miliary tuberculosis has no neurologic finding.     

Antibody titers and immune response to diphtheria-tetanus-pertussis and measles-mumps-rubella vaccination in children treated for acute lymphoblastic leukemia

The objective of this study was to investigate the diphtheria-tetanus-pertussis and/or measles-mumps antibody titers before and after vaccination at various time points of acute lymphoblastic leukemia (ALL) therapy and to suggest an appropriate vaccination approach for ALL patients. The authors studied 37 ALL patients and 14 healthy control subjects, divided into three groups. In group 1 (newly diagnosed patients), baseline anti-diphtheria, anti-tetanus, and anti-pertussis titers were determined. Patients in group 2 (on maintenance chemotherapy) and group 3 (patients not receiving therapy for 3-6 months) were vaccinated with diphtheria-tetanus with or without acellular pertussis; group 3 and control subjects were also given measles-mumps-rubella vaccine. Preimmunization and 1-month postimmunization titers were drawn. Preimmunization anti-diphtheria and anti-tetanus antibody titers between the groups and the controls were statistically similar. The seropositivity rate for anti-measles antibody in group 3 was significantly lower than controls. After vaccination, all of the patients developed protective anti-diphtheria and anti-tetanus antibody titers. The seroconversion rates of group 3 and controls for anti-measles and anti-mumps antibodies were statistically similar. The results showed that patients on maintenance therapy and after cessation of therapy made good antibody responses to diphtheria and tetanus toxoids, but response to measles and mumps vaccines was not as sufficient as toxoid vaccines. Children with ALL can receive the appropriate vaccines during and after maintenance treatment.