The frequency of Duchenne muscular dystrophy/Becker muscular dystrophy and Pompe disease in children with isolated transaminase elevation: results from the observational VICTORIA study

IntroductionElevated transaminases and/or creatine phosphokinase can indicate underlying muscle disease. Therefore, this study aims to determine the frequency of Duchenne muscular dystrophy/Becker muscular dystrophy (DMD/BMD) in male children and Pompe disease (PD) in male and female children with isolated hypertransaminasemia.MethodsThis multi-center, prospective study enrolled patients aged 3–216 months with serum alanine transaminase (ALT) and/or aspartate transaminase (AST) levels >2× the upper limit of normal (ULN) for ≥3 months. Patients with a known history of liver or muscle disease or physical examination findings suggestive of liver disease were excluded. Patients were screened for creatinine phosphokinase (CPK) levels, and molecular genetic tests for DMD/BMD in male patients and enzyme analysis for PD in male and female patients with elevated CPK levels were performed. Genetic analyses confirmed PD. Demographic, clinical, and laboratory characteristics of the patients were analyzed.ResultsOverall, 589 patients [66.8% male, mean age of 63.4 months (standard deviation: 60.5)] were included. In total, 251 patients (188 male and 63 female) had CPK levels above the ULN. Of the patients assessed, 47% (85/182) of male patients were diagnosed with DMD/BMD and 1% (3/228) of male and female patients were diagnosed with PD. The median ALT, AST, and CPK levels were statistically significantly higher, and the questioned neurological symptoms and previously unnoticed examination findings were more common in DMD/BMD patients than those without DMD/BMD or PD (p < 0.001).DiscussionQuestioning neurological symptoms, conducting a complete physical examination, and testing for CPK levels in patients with isolated hypertransaminasemia will prevent costly and time-consuming investigations for liver diseases and will lead to the diagnosis of occult neuromuscular diseases. Trial RegistrationClinicaltrials.gov NCT04120168

Uzun süreli biyouyumluluğun geliştirilmesi amacıyla biyomedikal poliüretanların sentezi ve yüzey modifikasyonu çalışmaları.

Thrombus formation and blood coagulation is a major problem associated with blood contacting products such as catheters, vascular grafts and artificial hearts. An intense research is being conducted towards the synthesis of new hemocompatible materials and mdifications of surfaces with biological molecules. In this study, polyurethane (PU) films were synthesized in medical purity from diisocyanate and polyol without using any other ingredients and the chemical, thermal and mechanical properties were characterized by solid state NMR, FTIR, GPC, mechanical tests, DMA and TGA. The surfaces of PU films were modified by covalent immobilization of different molecular weight heparins; low molecular weight heparin (LMWH) and unfractionated heparin (UFH) and these surfaces were examined by ESCA, ATR-FTIR, AFM and contact angle goniometer. Cell adhesion studies were conducted with whole human blood and examined by SEM. The effects of different types of heparins on blood protein adsorption and on platelet adhesion were analyzed by electrophresis and SEM, respectively. The surfaces of the UFH immobilized polyurethane films (PU-UFH) resulted in lesser red blood cell adhesion in comparison to LMWH immobilized polyurethane film surfaces (PU-LMWH). When the PU films were treated with blood plasma, the surfaces modified with two different heparin types showed a clearly different protein adsorption behavior especially in the early stage of blood plasma interaction. PU-LMWH samples showed about three times less protein adsorption compared to PU-UFH samples. The morphologies of platelets adhered on material surfaces demonstrated differences; such as PU-UFH had clusters with some pseudopodia extensions, while PU-LMWH had round shaped platelets with little clustering. PU surfaces modified by immobilization of LMWH and UFH, demonstrated promising results for the improvement of non-thrombogenic devices and surfaces.Ph.D. - Doctoral Progra

Immobilization of heparin on chitosan-grafted polyurethane films to enhance anti-adhesive and antibacterial properties

Infections caused by bacteria adhering to implant surfaces are one of the main reasons for the failure of the implants. In this study, polyurethane (PU), which is the most commonly used polymer in the production of medical devices, was synthesized and surfaces of polyurethane films were modified by chitosan (CH) grafting and heparin (Hep) immobilization in order to enhance anti-adhesiveness and antibacterial properties. Functional groups present on the surface, topographical shapes, and free energies of the polyurethane films were determined. Pristine polyurethane, chitosan-grafted polyurethane (PU-CH), and heparin immobilized polyurethane (PU-CH-Hep) films demonstrated high anti-adhesive efficacy against bacteria in the given order, where PU-CH-Hep was the most effective one. When PU-CH-Hep samples were incubated with different bacteria, complete death was observed for Pseudomonas aeruginosa (Gram negative), Staphylococcus aureus (Gram positive), and Staphylococcus epidermidis (Gram positive). Some living Escherichia coli (Gram negative) were observed after 24h of incubation. Pristine and modified polyurethane samples demonstrated no adverse effect on proliferation of L929 fibroblast cells and were found to be biocompatible according to MTT cytotoxicity tests

Synthesis and surface modification of polyurethanes with chitosan for antibacterial properties

Surface modification and providing antibacterial properties to the materials or devices are getting great attention especially in the last decades. In this study, polyurethane (PU) films were prepared by synthesizing them in medical purity from toluene diisocyanate and polypropylene ethylene glycol without using any other ingredients and then the film surfaces were modified by covalent immobilization of chitosan (CH) which has antibacterial activity. CH immobilized PU films (PU-CH) were found to be more hydrophilic than control PU films. Electron Spectroscopy for Chemical Analysis (ESCA) and Atomic Force Microscopy (AFM) analyses showed higher nitrogen contents and rougher surface topography for PU-CH compared to PU films. Modification with CH significantly increased antibacterial activity against Gram positive (Staphylococcus aureus) and Gram negative (Pseudomonas aeruginosa) bacteria. It was observed that the number of bacteria colonies were less about 10(2)-10(5) CFU/mL and number of attached viable bacteria decreased significantly after CH modification of PU films

Heparin/Chitosan/Alginate Complex Scaffolds as Wound Dressings: Characterization and Antibacterial Study Against Staphylococcus epidermidis

Infected wounds are global healthcare problems since they can lead to dysfunctioning in organs and even result in death in severe cases. In this study, antibacterial wound dressings were prepared to prevent possible infection at the damaged host region. For this purpose, three natural polymers namely heparin, chitosan and alginate were used as anionic, cationic and sulfated polysaccharides, respectively, due to their versatile properties as being nontoxic, biocompatible, biodegradable and antibacterial. Heparin/chitosan/alginate based complex polyelectrolyte scaffolds containing different amounts of heparin were prepared by freeze drying technique. The effects of calcium chloride, which is used as crosslinker for alginate, on the stability of scaffolds were tested. Presence of functional groups and morphological structures of the scaffolds were examined in detail by using FTIR, XPS and SEM. Antibacterial activities against Staphylococcus epidermidis (S. epidermidis) were investigated under in vitro conditions. Presence and the amount of heparin in the scaffolds significantly enhanced the antibacterial activities. The results demonstrated that heparin/chitosan/alginate polyelectrolyte scaffolds have very high potential to be used as therapeutic wound dressings