Effects of MMP-1 and MMP-3 gene polymorphisms on gene expression and protein level in lumbar disc herniation

The aim of this study was to identify the possible correlation between polymorphisms in matrix metalloproteinase (MMP)-1 and MMP-3 and their corresponding protein levels in disc tissues obtained from patients with lumbar disc herniation (LDH) using biochemical and immunohistochemical analyses. Blood and disc samples were obtained from 100 patients with LDH who underwent a lumbar microdiscectomy. Based on the radiological degeneration, the patients were diagnosed with grade 2, 3, or 4 LDH. MMP-1-1607 1G/2G and MMP-3-1171 5A/6A were analyzed by real-time polymerase chain reaction. The expressions of MMP-1 and MMP-3 were detected by biochemical and immunohistochemical analyses. We found no association between the MMP-1 polymorphism and disc degeneration and MMP-1 expression. However, patients expressing the 6A/6A and 5A/6A alleles of MMP-3-11715A/6A showed higher MMP-3 expression, compared to those expressing the 5A/5A genotype. Additionally, the radiological degeneration grades were correlated with the histological degeneration scoring. Protein levels and immunopositive cell rates of MMP-1 and MMP-3 were associated with disc degeneration grades. Moreover, the MMP-1 and MMP-3 expression and the histological and radiological scores were positively correlated and the MMP-3-11715A/6A polymorphism was associated with MMP-3 expression in herniated disc tissues. This study is the first to investigate polymorphisms in MMP-1 and MMP-3, as well as their corresponding protein expressions. We also quantified an association between the radiological degeneration grades and MMP-1 and MMP-3 expression. Further genomic studies on MMPs could focus on the utilization of MMP-1 and MMP-3 as markers for the prevention and treatment of this disease

Elastic properties of aorta in patients with primary hyperparathyroidism

In this study, we aimed to evaluate whether hyperpara thyroidism affects the elastic properties of aorta, calculated as aortic distensibility and aortic stiffness index

Papain Loaded Poly(epsilon-Caprolactone) Nanoparticles: In-silico and In-Vitro Studies

Papain is a protease enzyme with therapeutic properties that are very valuable for medical applications. Poly(epsilon-caprolactone) (PCL) is an ideal polymeric carrier for controlled drug delivery systems due to its low biodegradability and its high biocompatibility. In this study, the three-dimensional structure and action mechanism of papain were investigated by in vitro and in silico experiments using molecular dynamics (MD) and molecular docking methods to elucidate biological functions. The results showed that the size of papain-loaded PCL nanoparticles (NPs) and the polydispersity index (PDI) of the NPs were 242.9 nm and 0.074, respectively. The encapsulation efficiency and loading efficiency were 80.4 and 27.2%, respectively. Human embryonic kidney cells (HEK-293) were used for determining the cytotoxicity of papain-loaded PCL and PCL nanoparticles. The in vitro cell culture showed that nanoparticles are not toxic at low concentrations, while toxicity slightly increases at high concentrations. In silico studies, which were carried out with MD simulations and ADME analysis showed that the strong hydrogen bonds between the ligand and the papain provide stability and indicate the regions in which the interactions occur

Papain Loaded Poly(epsilon-Caprolactone) Nanoparticles: In-silico and In-Vitro Studies

Papain is a protease enzyme with therapeutic properties that are very valuable for medical applications. Poly(epsilon-caprolactone) (PCL) is an ideal polymeric carrier for controlled drug delivery systems due to its low biodegradability and its high biocompatibility. In this study, the three-dimensional structure and action mechanism of papain were investigated by in vitro and in silico experiments using molecular dynamics (MD) and molecular docking methods to elucidate biological functions. The results showed that the size of papain-loaded PCL nanoparticles (NPs) and the polydispersity index (PDI) of the NPs were 242.9 nm and 0.074, respectively. The encapsulation efficiency and loading efficiency were 80.4 and 27.2%, respectively. Human embryonic kidney cells (HEK-293) were used for determining the cytotoxicity of papain-loaded PCL and PCL nanoparticles. The in vitro cell culture showed that nanoparticles are not toxic at low concentrations, while toxicity slightly increases at high concentrations. In silico studies, which were carried out with MD simulations and ADME analysis showed that the strong hydrogen bonds between the ligand and the papain provide stability and indicate the regions in which the interactions occur

EVALUATION OF ATRIAL CONDUCTION FEATURES IN STABLE CHRONIC OBSTRUCTIVE PULMONARY DISEASE PATIENTS AND ITS RELATIONSHIP WITH NEUTROPHIL TO LYMPHOCYTE RATIO

Aims: Chronic obstructive pulmonary disease (COPD) has been associated with a high frequency of cardiac arrhythmia. While many studies have examined the development of atrial fibrillation (AT) in COPD patients, there is insufficient data about atrial conduction time (ACT) and its relationship with the Neutrophil to Lymphocyte ratio (NLR) in these patients. The aim of the present study was to evaluate atrial conduction features and its relationship with NLR

P6487Sequential combination of different thrombolytic therapy regimens in the management of patients with prosthetic valve thrombosis and stuck valves

Abstract Introduction Prosthetic valve thrombosis (PVT) is serious complication among patients with prosthetic heart valves. Recently, thrombolytic therapy (TT) regimens with low-dose, slow and ultra-slow infusions of tissue type plasminogen activator (tPA) has been widely used as a first-line treatment for PVT. PVT with stuck valves is a special entity which deserves particular management. In our study, we aimed to investigate the effectiveness and safety of sequential combination of different TT regimens in the management of patients with PVT and stuck valves. Methods The study included 52 patients with PVT and stuck valves [female: 34 (65.4%), mean age: 47.5±12.4] who underwent TT with sequential combination of slow (25mg/6 hours) and ultra-slow (25mg/25 hours) infusion of low dose t-PA regimens which was mainly based on the New York Heart Association functional class of the patients according to a previously established algoritm. All patients were evaluated by cinefluoroscopy, transthoracic and transesophageal echocardiography (Figure 1). Results The median number of TT sessions with slow and ultra-slow infusion of tPA were 1 (0–2.75) and 3 (1.25–5) respectively. Total tPA dose was 120 (96–175) mg and TT was successful in 46 (88.4%) patients. There were 3 major complications (cerebrovascular accident: 1, intracranial bleeding: 1, gastrointestinal bleeding requiring transfusion: 1) and 6 minor complications. The in-hospital mortality rate was 1.9%. Increased thrombus area was found to be the only independent predictor of both failed TT and adverse events. Thrombus area above 1.45 cm2 predicted failed TT with a sensitivity of 83% and a specificity of 70% (AUC: 0.871; 95% CI: 0.752–0.991; p=0.003) and predicted adverse events with a sensitivity of 77% and a specificity of 73% (AUC: 0.854; 95% CI: 0.747–0.961; p=0.001). There was a moderate positive correletion between thrombus area and total tPA dose used (r=479; p&lt;0.001). Figure 1 Conclusion This study demostrated that TT with sequential combination of slow and ultra-slow infusion of low dose t-PA regimens may be useful for the treatment of patients with PVT and stuck valves with acceptable success and complications rates. </jats:sec