The Role of the Epicardium in Heart Development

In early embryonic life, the primitive heart tube consists of two layers, the myocardium and the endocardium. Eventually the heart tube loops to form a four-chambered structure providing for a circulation of blood by rhythmic contractions of the myocardium. With the increase in heart size and myocardial work load, a separate vasculature for the free myocardial wall is required. The formation of this coronary system is preceeded by the outgrowth of the epicardium, covering the naked heart tube. Our studies were performed on quail and chicken embryos, because of the high resemblance with human cardiac development. Avian embryos develop in approximately three weeks and were staged according to the Hamburger&Hamilton (HH) stages. In avian embryos the epicardial development starts at stage HH15 which is at three days of embryonic development, and is completed at stage HH25, which is after seven days of incubation. Epicardial cells are derived from the proepicardial organ (PEO), that protrudes as a cauliflower-like structure from the mesothelial lining of the body cavity near the sinus venosus and primitive liver, towards the inner curvature of the heart. The villi of the PEO reach the heart at the posterior atrial side where the sinus venosus myocardium is incorporated and the epicardial cells start to spread over the naked heart tube, until they eventually cover the myocardium completely

Surgical Implications of Coronary Arterial Anatomy in Adults with Congenital Cardiac Disease

In adults with congenital heart disease coronary arterial anatomy, normal as well as anomalous, may have implications in surgical reconstruction of an underlying cardiac structure

Changes in serum proteins after endotoxin administration in healthy and choline-treated calves

Background: This study aimed to investigate the possible serum protein changes after endotoxin administration in healthy and choline-treated calves using proteomics. These results are expected to contribute to the understanding of the pathophysiological mechanisms of endotoxemia and the beneficial effect of choline administration in this clinical situation. Methods: Healthy-calves (n = 20) were divided into 4 groups: Control, Choline treated (C), Lipopolysaccharide administered (LPS), and LPS + C. Control calves received 0.9 % NaCl injection. Calves in C and LPS + C groups received choline chloride (1 mg/kg/iv). Endotoxin (LPS) was injected (2 mu g/kg/iv) to the calves in LPS and LPS + C groups. Serum samples were collected before and after the treatments. Differentially expressed proteins (> 1.5 fold-change relative to controls) were identified by LC-MS/MS. Results: After LPS administration, 14 proteins increased, and 13 proteins decreased within 48 h as compared to controls. In the LPS group, there were significant increases in serum levels of ragulator complex protein (189-fold) and galectin-3-binding protein (10-fold), but transcription factor MafF and corticosteroid binding globulin were down regulated (>= 5 fold). As compared with the LPS group, in LPS + C group, fibrinogen gamma-B-chain and antithrombin were up-regulated, while hemopexin and histone H4 were down-regulated. Choline treatment attenuated actin alpha cardiac muscle-1 overexpression after LPS. Conclusions: LPS administration produces changes in serum proteins associated with lipid metabolism, immune and inflammatory response, protein binding/transport, cell adhesion, venous thrombosis, cardiac contractility and blood coagulation. The administration of choline is associated with changes in proteins which can be related with its beneficial effect in this clinical situation

In situ surface analysis of palladium-platinum alloys in methane oxidation conditions

Palladium and palladium-platinum foils were analysed using temperature-programmed near-ambient pressure x-ray photoelectron spectroscopy (TP-NAP-XPS) under methane oxidation conditions. Oxidation of palladium is inhibited by the presence of water, and in oxygen-poor environments. Pt addition further inhibits oxidation of palladium across all reaction conditions, preserving metallic palladium to higher temperatures. Bimetallic foils underwent significant restructuring under reaction conditions, with platinum preferentially migrating to the bulk under select conditions

Epicardium-derived cells are important for correct development of the Purkinje fibers in the avian heart

During embryonic development, the proepicardial organ (PEO) grows out over the heart surface to form the epicardium. Following epithelial-mesenchymal transformation, epicardium-derived cells (EPDCs) migrate into the heart and contribute to the developing coronary arteries, to the valves, and to the myocardium. The peripheral Purkinje fiber network develops from differentiating cardiomyocytes in the ventricular myocardium. Intrigued by the close spatial relationship between the final destinations of migrating EPDCs and Purkinje fiber differentiation in the avian heart, that is, surrounding the coronary arteries and at subendocardial sites, we investigated whether inhibition of epicardial outgrowth would disturb cardiomyocyte differentiation into Purkinje fibers. To this end, epicardial development was inhibited mechanically with a membrane, or genetically, by suppressing epicardial epithelial-to-mesenchymal transformation with antisense retroviral vectors affecting Ets transcription factor levels (n = 4, HH39-41). In both epicardial inhibition models, we evaluated Purkinje fiber development by EAP-300 immunohistochemistry and found that restraints on EPDC development resulted in morphologically aberrant differentiation of Purkinje fibers. Purkinje fiber hypoplasia was observed both periarterially and at subendocardial positions. Furthermore, the cells were morphologically abnormal and not aligned in orderly Purkinje fibers. We conclude that EPDCs are instrumental in Purkinje fiber differentiation, and we hypothesize that they coo

Dexmedetomidine as a Sedative in the Awake Implantation of a Neuromodulative System

Objective: During implantation of a neuromodulative system, high patient satisfaction is closely associated with the equilibrium between an effective analgesia and sedation regimen, and the possibility for the patient to be awake and cooperative during procedure. This study assessed the efficacy of the sedative dexmedetomidine to achieve this balance, with patient satisfaction as the primary outcome. Methods: Ten patients undergoing implantation of a dorsal column and dorsal root ganglion stimulator received dexmedetomidine (1 mcg/kg over 10 minutes, followed by 0.6 mcg/kg/hour) in combination with remifentanil at a set dose (3 mcg/kg/hour). Sedation was titrated to a Ramsay Sedation Score of 3. Recorded were as follows: patient satisfaction score, patient comfort score, operator comfort score, pain score, rescue medication and number of adjustments of dexmedetomidine intra-operatively, as well as sedation level, hemodynamic (blood pressure and heart rate), and respiratory characteristics (SpO2). Results: Scores were high on patient satisfaction (me

Conscious sedation or local anesthesia during endovascular treatment for acute ischemic stroke

Paroxysmal Cerebral Disorder

Applicability of T1-weighted MRI in the assessment of forensic age based on the epiphyseal closure of the humeral head

This work investigates the value of magnetic resonance imaging analysis of proximal epiphyseal fusion in research examining the growth and development of the humerus and its potential utility in establishing forensic age estimation. In this study, 428 proximal humeral epiphyses (patient age, 12-30years) were evaluated with T1-weighted turbo spin echo (T1 TSE) sequences in coronal oblique orientation on shoulder MRI images. A scoring system was created following a combination of the Schmeling and Kellinghaus methods. Spearman's rank correlation analysis revealed a significant positive relationship between age and ossification stage of the proximal humeral epiphysis (all subjects: rho=0.664, p<0.001; males: 0.631, p<0.001; females: rho=0.651, p<0.001). The intra- and inter-observer reliability assessed using Cohen's kappa statistic was =0.898 and =0.828, respectively. The earliest age of epiphysis closure was 17years for females and 18years for males. MRI of the proximal humeral epiphysis can be considered advantageous for forensic age estimation of living individuals in a variety of situations, ranging from monitoring public health to estimating the age of illegal immigrants/asylum seekers, minors engaged in criminal activities, and illegal participants in competitive sports, without the danger of radiation exposure

Cannulated screw and hexapodal fixator reconstruction for compound upper tibial fractures

OBJECTIVES: The aim of the treatment of tibial plateau fractures is to obtain a pain-free and fully functional knee with closed reduction, percutaneous cannulated screw fixation and hexapodal external fixator reconstruction for high energy compound upper tibial fractures. METHODS: Patients with comminuted tibial plateau fractures underwent closed reduction, percutaneous fixation with cannulated screws, and reconstruction with hexapodal external fixator. The follow-up period was 24 months. RESULTS: The clinical and radiological results were good or excellent. The average knee flexion was 125°. CONCLUSION: Our results are successful in the initial stage, however, it should be pointed out that during the long term follow-up osteoarthritis may develop leading to worsening of the condition. Level of Evidence IV, Case Series

High efficiency of alphaviral gene transfer in combination with 5-fluorouracil in a mouse mammary tumor model

Copyright: Copyright 2014 Elsevier B.V., All rights reserved.Background: The combination of virotherapy and chemotherapy may enable efficient tumor regression that would be unachievable using either therapy alone. In this study, we investigated the efficiency of transgene delivery and the cytotoxic effects of alphaviral vector in combination with 5-fluorouracil (5-FU) in a mouse mammary tumor model (4 T1).Methods: Replication-deficient Semliki Forest virus (SFV) vectors carrying genes encoding fluorescent proteins were used to infect 4 T1 cell cultures treated with different doses of 5-FU. The efficiency of infection was monitored via fluorescence microscopy and quantified by fluorometry. The cytotoxicity of the combined treatment with 5-FU and alphaviral vector was measured using an MTT-based cell viability assay. In vivo experiments were performed in a subcutaneous 4 T1 mouse mammary tumor model with different 5-FU doses and an SFV vector encoding firefly luciferase.Results: Infection of 4 T1 cells with SFV prior to 5-FU treatment did not produce a synergistic anti-proliferative effect. An alternative treatment strategy, in which 5-FU was used prior to virus infection, strongly inhibited SFV expression. Nevertheless, in vivo experiments showed a significant enhancement in SFV-driven transgene (luciferase) expression upon intratumoral and intraperitoneal vector administration in 4 T1 tumor-bearing mice pretreated with 5-FU: here, we observed a positive correlation between 5-FU dose and the level of luciferase expression.Conclusions: Although 5-FU inhibited SFV-mediated transgene expression in 4 T1 cells in vitro, application of the drug in a mouse model revealed a significant enhancement of intratumoral transgene synthesis compared with 5-FU untreated mice. These results may have implications for efficient transgene delivery and the development of potent cancer treatment strategies using alphaviral vectors and 5-FU.publishersversionPeer reviewe