Restoring sinus rhythm improves excessive heart rate response to exercise in patients with atrial fibrillation

The aim of this study was to investigate improvement in the cardiovascular response to isometric and isotonic exercises after reverting rhythm to sinus in patients with atrial fibrillation. Twenty seven cases with nonvalvular paroxysmal atrial fibrillation were included in the study. Sinus rhythm could not be restored in two cases so they were excluded. The remaining cases were divided into two groups according to the existence of cardiac diseasc. Group 1 (n:14, mean age. 60.8 +/- 14.9 years) included cases with cardiac diseases (8 of the patients had hypertension in addition to the cardiac disease) and group 2 (n:11, mean age. 64.8 +/- 13.9 years) included those without cardiac disease (patients with hypertension and diabetes mellitus). Isometric and isotonic exercise tests were performed in all of the patients before and 48 hours after the rhythm was reverted to sinus and the values in atrial fibrillation were compared with those in sinus rhythm (following cardioversion). The isotonic exercise period increased significantly in only group 1 patients following cardioversion (P = (0.0061). In both groups, the increase in heart rate during atrial fibrillation was significantly higher compared to those after being reverted to sinus, at all stages of the isotonic exercise (in groups 1 and 2, heart rate in patients with atrial fibrillation increased from 96.5 +/- 19.3 to 173.3 +/- 19.3 beats/min and 96.1 +/- 12.6 to 185.0 +/- 12.1 beats/ min, respectively; and in sinus rhythm, it ranged from 85.1 +/- 11.4 to 164.6 +/- 9.1 beats/min and 81.3 +/- 11.4 to 157.6 +/- 15.1 beats/min, respectively). Systolic arterial pressure increased significantly during atrial fibrillation in group 1, at the 2nd stage of the isotonic exercise test (P = 0.0070). In group 2, systolic arterial pressure increased significantly at the 3rd stage in sinus rhythm and at the 4th stage when in rhythm in atrial fibrillation. Also, diastolic arterial pressure increased significantly during atrial fibrillation only at the 3rd stage of the exercise. As a result, restoring sinus rhythm by cardioversion improves excessive heart rate responses to exercise significantly in patients with atrial fibrillation during both isometric and isotonic exercises. Also, we have revealed that the exercise time increased significantly by restoring sinus rhythm in patients with heart disease.     

Inpatient rehabilitation outcomes in neoplastic spinal cord compression vs. traumatic spinal cord injury

Objective: To compare neurological and functional outcomes, and complications of patients with neoplastic vs traumatic spinal cord injury (SCI) after in-patient rehabilitation.Design: This study is a retrospective analysis.Setting: In-patient rehabilitation unit of a tertiary research hospital.Participants: A total of 252 patients with a SCI were included; 43 with neoplastic SCI (mean age: 60.9 ± 15.7 years, 60.5% were males) and 209 with traumatic SCI (mean age: 43.1 ± 16.8 years, 71.3% were males).Outcome measures: Comparisons were made of demographic characteristics, etiology, American Spinal Injury Association (ASIA) impairment scale, functional independence measurement (FIM) and Functional Ambulation Categories (FAC) scores, length of stay (LOS), bladder independence, medical comorbidities and complications in both groups.Results: Patients with neoplastic SCI were significantly older than those with traumatic SCI (P < 0.01). No difference was present between the groups in terms of sex and lesion level (P > 0.05). Incomplete SCI was significantly higher in the neoplastic group when compared with the traumatic group (P < 0.01). The LOS was significantly shorter in the neoplastic group than traumatic group (34.8 ± 41.03 vs. 60.02 ± 53.1, P < 0.01). There were no differences in the admission FIM scores (69.3 ± 24.7 vs. 58.7 ± 18.9, P > 0.05), discharge FIM scores (82.1 ± 25.1 vs. 74.02 ± 23.3, P > 0.05) and FIM efficiencies (0.43 ± 0.72 vs. 0.36 ± 0.51, P > 0.05) for the neoplastic and traumatic groups, respectively. However, neoplastic SCI patients demonstrated lower FIM gains compared to traumatic patients (12.9 ± 11.9 vs. 15.4 ± 15.2, P < 0.05). During rehabilitation, urinary tract infection (48.4% vs. 69.4%) and decubitus ulcer (11.6% vs. 35.9%) were significantly more common in the traumatic group than the neoplastic group (P < 0.05).Conclusion: Neoplastic SCI patients who commonly present at rehabilitation units exhibit different characteristics from traumatic SCI patients but the rehabilitation results are similar. Similar functional development can be achieved in a shorter period of time with inpatient rehabilitation in the neoplastic SCI group.     

Loss of DPP4 activity is related to a prothrombogenic status of endothelial cells: implications for the coronary microvasculature of myocardial infarction patients

Pro-coagulant and pro-inflammatory intramyocardial (micro)vasculature plays an important role in acute myocardial infarction (AMI). Currently, inhibition of serine protease dipeptidyl peptidase 4 (DPP4) receives a lot of interest as an anti-hyperglycemic therapy in type 2 diabetes patients. However, DPP4 also possesses anti-thrombotic properties and may behave as an immobilized anti-coagulant on endothelial cells. Here, we studied the expression and activity of endothelial DPP4 in human myocardial infarction in relation to a prothrombogenic endothelial phenotype. Using (immuno)histochemistry, DPP4 expression and activity were found on the endothelium of intramyocardial blood vessels in autopsied control hearts (n?=?9). Within the infarction area of AMI patients (n?=?73), this DPP4 expression and activity were significantly decreased, coinciding with an increase in Tissue Factor expression. In primary human umbilical vein endothelial cells (HUVECs), Western blot analysis and digital imaging fluorescence microscopy revealed that DPP4 expression was strongly decreased after metabolic inhibition, also coinciding with Tissue Factor upregulation. Interestingly, inhibition of DPP4 activity with diprotin A also enhanced the amount of Tissue Factor encountered and induced the adherence of platelets under flow conditions. Ischemia induces loss of coronary microvascular endothelial DPP4 expression and increased Tissue Factor expression in AMI as well as in vitro in HUVECs. Our data suggest that the loss of DPP4 activity affects the anti-thrombogenic nature of the endothelium.     

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).     

CYP1A1 gene polymorphism and polycystic ovary syndrome

The aim of this study was to assess the rates of variant alleles of cytochrome P4501A1 (CYP1A1) in patients with polycystic ovary syndrome (PCOS). It was designed as a case-control study in Hacettepe University, Faculty of Medicine, Department of Obstetrics and Gynecology and Genetics. Forty-eight patients with PCOS served as the study group. Ninety-six regularly cycling women with no clinical and biochemical evidence of hyperandrogenism and polycystic ovary appearance served as the controls. The CYP1A1 variant alleles of all patients were determined via polymerase chain reaction. The rate of the CYP1A1 isoleucine (Ile)/valine (Val) allele was significantly higher in patients with PCOS than in the controls (OR: 7.8, 95% CI: 3.45-17.52, P < 0.001). However, there was no statistically significant difference in the distribution of Val/Val genotype (OR: 4.0, 95% CI: 0.60-26.73). The rate of any Val genotype (Ile/Val or Val/Val) was significantly higher in patients with PCOS compared with the control group (OR: 7.4, 95% CI: 3.33-16.46, P < 0.001). In conclusion, the patients with PCOS had a 7.8-fold higher frequency of CYP1A1 Ile/Val genotype and a 7.4-fold higher frequency of CYP1A1 of any Val genotype (Ile/Val or Val/Val).