Disturbed energy metabolism after lung and heart transplantation

Overweight, in combination with other cardiovascular risk factors, reduces survival after transplantation. The aim of this prospective study was to observe leptin, adiponectin, and energy intake as predictors of body mass index (BMI) and body composition and as risk factors associated with metabolic syndrome after lung and heart transplantation. After pre-operative baseline investigations, 35 lung and 59 heart recipients were followed and re-investigated two, six, and 12 months after transplantation. Linear regressions were performed to predict BMI and body composition. The lung recipients had a substantial weight gain after transplantation. Leptin increased, especially in the lung recipients and positively predicted BMI. Energy intake predicted BMI before and at two months after transplantation, but not after 12 months. Percentage trunk fat increased and lean mass decreased. Before transplantation, the dominant determinant of lean mass was adiponectin (positively associated), while after it was leptin (negatively associated), controlled for possible confounding variables (including prednisolone). Metabolic syndrome 12 months after transplantation was associated with higher leptin, greater weight gain without increased energy intake. After transplantation, a disturbed energy metabolism is indicated, where adiponectin and especially leptin are involved and a disadvantageous body composition is favored with increased body fat and decreased lean mass.     

Alginates induce differentiation and expression of CXCR7 and CXCL12/SDF-1 in human keratinocytes-The role of calcium

Alginates from seaweed are used in chronic wound management, though the molecular and cellular effects of various alginate dressings are not well documented. We have developed ultrapure sodium-alginates from Pseudomonas fluorescens with different content and distribution of single guluronic acid (G) residues (0-45% G), and tested their biological activities on human primary keratinocytes (KCs). The alginates inhibited KC migration and induced expression of differentiation markers. The potency of the alginates correlated with the increasing percentage of single G residues. These findings were explained by different binding and release of ionic calcium (Ca++) from the alginates which subsequently triggered differentiation. Ca-free alginates had no effect on KC migration and differentiation, but the chemokine receptor CXCR7 was upregulated. Q-PCR revealed that also CXCL12/SDF-1, one of two known CXCR7-ligands, was induced by the alginates. Both CXCR7 and CXCL12-induction was dependent on the alginate G-content, and highest upregulation was induced by an alginate with 19% single G residues. In the epidermis, CXCR7 expression was restricted to the basal layer. This study defines two biological effects of ultrapure alginates on KCs, both being dependent on the alginate structure, and being either dependent or independent of Ca. ? 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A 100A:2803-2812, 2012.     

Post-embryonic remodelling of neurocranial elements: a comparative study of normal versus abnormal eye migration in a flatfish, the Atlantic halibut

The process of eye migration in bilaterally symmetrical flatfish larvae starts with asymmetrical growth of the dorsomedial parts of the ethmoid plate together with the frontal bones, structures initially found in a symmetrical position between the eyes. The movement of these structures in the future ocular direction exerts a stretch on the fibroblasts in the connective tissue found between the moving structures and the eye that is to migrate. Secondarily, a dense cell population of fibroblasts ventral to the eye starts to proliferate, possibly cued by the pulling forces exerted by the eye. The increased growth ventral to the eye pushes the eye dorsally. Osteoblasts are deposited in the dense cell layer, forming the dermal part of the lateral ethmoid, and at full eye migration this will cover the area vacated by the migrated eye. When the migrating eye catches up with the previous migrated dermal bones, the frontals, these bones will be remodelled to accommodate the eye. Our findings suggest that a combination of extremely localized signals and more distant factors may impinge upon the outcome of the tissue remodelling. Early normal asymmetry of signalling factors may cascade on a series of events.     

The 14-3-3 σ gene promoter is methylated in both human melanocytes and melanoma

Background  

Recent evidence demonstrates that 14-3-3σ acts as a tumor suppressor gene inactivated by methylation of its 5' CpG islands in epithelial tumor cells, while remaining un-methylated in normal human epithelia. The methylation analysis of 14-3-3σ has been largely overlooked in melanoma.     

Sodium-calcium balance in coronary angiography and experimental experience with iodixanol

The present short review describes the physiological effects of rapid transient changes in cardiac extracellular ions (electrolytes) caused by the bolus of x-ray contrast medium (CM) during coronary angiography. The underlying hypothesis is that as the molecular and osmolal toxicities of modern CM is low, cardiac side-effects result mainly from secondary and biphasic ionic changes which occur during the initial washout phase and during the later re-introduction of blood. In particular the washout pattern for sodium (Na) and calcium (Ca) has great influence on cardiac function. Thus the Na-Ca exchange system of the cardiac cell membrane plays a pivotal role in controlling intracellular Ca and contractility during very brief coronary bolus injections of both nonionic and ionic CM. The nonionic dimer iodixanol is hyposmolal without an additive. Animal experiments demonstrate the value of taking myocarcardial Na-Ca relationships into careful consideration when adding ions to iodixanol and formulating an isotonic CM like Visipaque     

The NMDA antagonist MK-801 improved metabolic recovery after 10 minutes global cerebral ischaemia in rats measured with 31 phosphorous magnetic resonance spectroscopy

Summary The blockade of postsynaptic receptors for excitatory amino acids is a promising new field for the possible treatment of cerebral ischaemia. The most important receptor seems to be the N-methyl-D-aspartate (NMDA) subtype of the glutamate receptors and MK-801 is a potent non-competitive antagonist to the NMDA receptor.31P NMR Spectroscopy was used to measure the recovery of intracellular pH and the high energy phosphates Phosphocreatine (PCr) and ATP after ten minutes of temporary global cerebral ischaemia in the rat. Cerebral ischaemia was obtained by combining bilateral carotid ligation and systemic hypotension (2 vessel occlusion model).Two intervention groups with intravenous injection of MK-801 in doses of 0.25mg/kg and 0.5mg/kg 15 minutes before onset of ischaemia were compared to a control group. Both intervention groups showed a more rapid recovery of PCr and ATP than the control group, but there were no significant differences for intracellular pH.     

Reversibility of mild to moderate ischemic injuries in the isolated rat heart. A characterization by 31P-NMR and by physiological and ultrastructural indices.

We have studied cardiac function, metabolism, and ultrastructure during reperfusion after global ischemia of short duration (6 and 12 minutes) in isolated rat hearts. Our aim was to obtain more detailed information on the reversibility of changes following presumedly mild and moderate ischemic injuries by use of multiple time-based indices. In a modified Langendorff perfusion system, hearts were subjected to 24 minutes of control perfusion and 6 or 12 minutes of ischemia followed by 1.5 or 24 minutes of reperfusion. During the experiments we monitored left ventricular developed pressure (LVDP), heart rate, and coronary flow rate, and intracellular phosphocreatine (PCr), inorganic phosphate (P(i)), pH, and ATP by 31P nuclear magnetic resonance spectroscopy. The number of cells with sarcolemmal and nuclear injuries was counted. Our main findings during 24 minutes of reperfusion following 6 and 12 minutes of ischemia were 80% versus 53% recovery of LVDP at the end of reperfusion, an increased PCr, 80% versus 65% recovery of ATP, and a rapid versus slower recovery of pH. Ultrastructural examination revealed sarcolemmal and unclear abnormalities at the end of ischemia, these alterations being fully (rapidly versus more slowly) reversible during reperfusion. According to these findings, there was a dissociation between an essentially normal ultrastructure, and a depressed recovery of LVDP, reduced ATP, and an overshoot of PCr upon 24 minutes of reperfusion after 12 minutes of ischemia. This may indicate a postischemic dysfunction closely related to stunning.