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Structural Remodelling (structural + remodelling)
Selected AbstractsImpaired cardiac functional reserve in type 2 diabetic db/db mice is associated with metabolic, but not structural, remodellingACTA PHYSIOLOGICA, Issue 1 2010A. Daniels Abstract Aim:, To identify the initial alterations in myocardial tissue associated with the early signs of diabetic cardiac haemodynamic dysfunction, we monitored changes in cardiac function, structural remodelling and gene expression in hearts of type 2 diabetic db/db mice. Methods:, Cardiac dimensions and function were determined echocardiographically at 8, 12, 16 and 18 weeks of age. Left ventricular pressure characteristics were measured at 18 weeks under baseline conditions and upon dobutamine infusion. Results:, The db/db mice were severely diabetic already at 8 weeks after birth, showing elevated fasting blood glucose levels and albuminuria. Nevertheless, echocardiography revealed no significant changes in cardiac function up to 18 weeks of age. At 18 weeks of age, left ventricular pressure characteristics were not significantly different at baseline between diabetic and control mice. However, dobutamine stress test revealed significantly attenuated cardiac inotropic and lusitropic responses in db/db mice. Post-mortem cardiac tissue analyses showed minor structural remodelling and no significant changes in gene expression levels of the sarcoplasmic reticulum calcium ATPase (SERCA2a) or ,1-adrenoceptor (,1-AR). Moreover, the phosphorylation state of known contractile protein targets of protein kinase A (PKA) was not altered, indicating unaffected cardiac ,-adrenergic signalling activity in diabetic animals. By contrast, the substantially increased expression of uncoupling protein-3 (UCP3) and angiopoietin-like-4 (Angptl4), along with decreased phosphorylation of AMP-activated protein kinase (AMPK) in the diabetic heart, is indicative of marked changes in cardiac metabolism. Conclusion:, db/db mice show impaired cardiac functional reserve capacity during maximal ,-adrenergic stimulation which is associated with unfavourable changes in cardiac energy metabolism. [source] Recruitment of the Sonic hedgehog signalling cascade in electroconvulsive seizure-mediated regulation of adult rat hippocampal neurogenesisEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2005Sunayana B. Banerjee Abstract Electroconvulsive seizure (ECS) induces structural remodelling in the adult mammalian brain, including an increase in adult hippocampal neurogenesis. The molecular mechanisms that underlie this increase in the proliferation of adult hippocampal progenitors are at present not well understood. We hypothesized that ECS may recruit the Sonic hedgehog (Shh) pathway to mediate its effects on adult hippocampal neurogenesis, as Shh is known to enhance the proliferation of neuronal progenitors and is expressed in the adult basal forebrain, a region that sends robust projections to the hippocampus. Here we demonstrate that the ECS-induced increase in proliferation of adult hippocampal progenitors was completely blocked in animals treated with cyclopamine, a pharmacological inhibitor of Shh signalling. Our results suggest that both acute and chronic ECS enhance Shh signalling in the adult hippocampus, as we observed a robust upregulation of Patched (Ptc) mRNA, a component of the Shh receptor complex and a downstream transcriptional target of Shh signalling. This increase was rapid and restricted to the dentate gyrus, where the adult hippocampal progenitors reside. In addition, both acute and chronic ECS decreased Smoothened (Smo) mRNA, the other component of the Shh receptor complex, selectively within the dentate gyrus. However, ECS did not appear to influence Shh expression within the basal forebrain, the site from which it has been suggested to be anterogradely transported to the hippocampus. Together, our findings demonstrate that ECS regulates the Shh signalling cascade and indicate that the Shh pathway may be an important mechanism through which ECS enhances adult hippocampal neurogenesis. [source] Repeated restraint stress suppresses neurogenesis and induces biphasic PSA-NCAM expression in the adult rat dentate gyrusEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2003Kara Pham Abstract Chronic restraint stress has been shown to induce structural remodelling throughout the interconnected dentate gyrus-CA3 fields. To find out how this stressor affects the rate of adult hippocampal neurogenesis, we subjected rats to acute or chronic restraint stress and assessed the proliferation, survival and differentiation of newly born cells in the dentate gyrus. We also examined polysialylated neural cell adhesion molecule expression, a molecule normally expressed in immature neurons and important for morphological plasticity. The results show that acute restraint stress did not change either the proliferation of dentate gyrus precursor cells or the expression of polysialylated neural cell adhesion molecule, whereas 3 weeks of chronic restraint stress suppressed proliferation by 24% and increased polysialylated neural cell adhesion molecule expression by 40%. The study was extended for an additional 3 weeks to trace the survival and development of the cells born after the initial 3 weeks of restraint. Rats subjected to 6 weeks of daily restraint stress exhibited suppressed cell proliferation and attenuated survival of the recently born cells after the extended time course, resulting in a 47% reduction of granule cell neurogenesis. Furthermore, 6 weeks of chronic stress significantly reduced the total number of granule cells by 13% and the granule cell layer volume by 5%. Expression of polysialylated neural cell adhesion molecule followed a biphasic time course, displaying a significant up-regulation after 3 weeks of daily restraint stress that was lost after 6 weeks of stress. These studies may help us understand the basis for hippocampal shrinkage and raise questions about the ultimate reversibility of the effects of chronic stress. [source] Hormonal enhancement of neuronal firing is linked to structural remodelling of excitatory and inhibitory synapsesEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2002A. Parducz Abstract The ovarian hormone estradiol induces morphological changes in the number of synaptic inputs in specific neuronal populations. However, the functional significance of these changes is still unclear. In this study, the effect of estradiol on the number of anatomically identified synaptic inputs has been assessed in the hypothalamic arcuate nucleus. The number of axo-somatic, axodendritic and spine synapses was evaluted using unbiased stereological methods and a parallel electrophysiological study was performed to assess whether synaptic anatomical remodelling has a functional consequence on the activity of the affected neurons. Estradiol administration to ovariectomized rats induced a decrease in the number of inhibitory synaptic inputs, an increase in the number of excitatory synapses and an enhancement of the frequency of neuronal firing. These results indicate that oestrogen modifications in firing frequency in arcuate neurons are temporally linked to anatomical modifications in the numerical balance of inhibitory and excitatory synaptic inputs. [source] Atrial fibrillation: insights from clinical trials and novel treatment optionsJOURNAL OF INTERNAL MEDICINE, Issue 6 2007Y. Blaauw Abstract., Blaauw Y, Crijns HJGM (University Hospital Maastricht, Maastricht, The Netherlands). Atrial fibrillation: insights from clinical trials and novel treatment options (Review). J Intern Med 2007; 262: 593,614. Atrial fibrillation (AF) is the most common encountered sustained arrhythmia in clinical practice. The last decade the result of large ,rate' versus ,rhythm' control trials have been published that have changed the current day practise of AF treatment. It has become clear that rate control is at least equally effective as a rhythm control strategy in ameliorating morbidity as well as mortality. Moreover, in each individual patient the risk of thromboembolic events should be assessed and antithrombotic treatment be initiated. There have also been great advances in understanding the mechanisms of AF. Experimental studies showed that as a result of electrical and structural remodelling of the atria, ,AF begets AF'. Pharmacological prevention of atrial electrical remodelling has been troublesome, but it seems that blockers of the renin angiotensin system, and perhaps statins, may reduce atrial structural remodelling by preventing atrial fibrosis. Clinical studies demonstrated that the pulmonary veins exhibit foci that can act as initiator and perpetuator of the arrhythmia. Isolation of the pulmonary veins using radiofrequency catheter ablation usually abolishes AF. The most promising advances in the pharmacological treatment of AF include atrial specific antiarrhythmic drugs and direct thrombin inhibitors. In the present review we will describe the results of recent experimental studies, discuss the latest clinical trials, and we will focus on novel treatment modalities. [source] Structural and mechanical remodelling of the common bile duct after obstructionNEUROGASTROENTEROLOGY & MOTILITY, Issue 2 2002B. U. DUCH Biliary obstruction in man, most often caused by cholelithiasis, induces remodelling of the bile ducts. Obstruction-induced structural remodelling of the common bile duct (CBD) has been previously described. The mechanical changes that accompany the structural remodelling, however, have not been studied in detail. The aim of this study is to quantify the structural and mechanical changes in the CBD at different time intervals after acute obstruction. The CBD was ligated in the pig, near the duodenum, and studied after 3 h, 12 h, 2 days, 8 days and 32 days (n=5 in each group). One additional animal in each group was sham-operated. At each scheduled time, the CBD was mechanically tested in vitro with a computer-controlled volume infusion system to study the pressure,volume relationship of the CBD segment. A video camera provided simultaneous measurements of the outer dimensions of the CBD at the various pressures. The diameter and wall thickness of the CBD increased about three-fold in the 32-day group compared to the sham group (P < 0.001). The circumferential stress,strain relationship differed between groups (P < 0.001); it was shifted to the right, indicating softening, in the 3-h, 12-h, and 2-day groups and to the left, indicating stiffening, in the 8-day and 32-day group, compared to the sham group. The longitudinal stress,strain curves were all shifted to the left of the circumferential stress,strain curves (P < 0.05). The collagen area increased during obstruction (P < 0.001) but no correlation between the size of the collagen area and the biomechanical parameters was found. A practical implication of the present study serves as a warning to surgeons. A reduction in the wall stiffness in the first several days of obstruction along with an increased duct diameter and a decreased wall thickness suggest that operative procedures such as suturing, anastomosis and procedures related to ERCP must be performed with special care to avoid damage to the CBD. [source] Apoptotic and Anti-Apoptotic Synaptic Signaling MechanismsBRAIN PATHOLOGY, Issue 2 2000Mark P. Mattson Although several prominent morphological features of apoptosis are evident in the cell body (e.g., cell shrinkage, membrane blebbing, and nuclear DNA condensation and fragmentation) the biochemical and molecular cascades that constitute the cell death machinery can be engaged in synaptic terminals and neurites. Initiating events such as oxyradical production and calcium influx, and effector processes such as Par-4 production, mitochondrial alterations and caspase activation, can be induced in synapses and neurites. Several prominent signal transduction pathways in synaptic terminals play important roles in either promoting or preventing neuronal death in physiological and pathological conditions. For example, activation of glutamate receptors in postsynaptic spines can induce neuronal apoptosis, whereas local activation of neurotrophic factor receptors in presynaptic terminals can prevent neuronal death. Factors capable of inducing nuclear chromatin condensation and fragmentation can be produced locally in synaptic terminals and neurites, and may propogate to the cell body. Recent findings suggest that, beyond their roles in inducing or preventing cell death, apoptotic and anti-apoptotic cascades play roles in synaptic plasticity (structural remodelling and long-term functional changes). For example, caspase activation results in proteolysis of glutamate receptor (AMPA) subunits, which results in altered neuronal responsivity to glutamate. Activation of neurotrophic factor receptors in synaptic terminals can result in local changes in energy metabolism and calcium homeostasis, and can induce long-term changes in synaptic transmission. The emerging data therefore suggest that synapses can be considered as autonomous compartments in which both pro- and anti-apoptotic signaling pathways are activated resulting in structural and functional changes in neuronal circuits. A better understanding of such synaptic signaling mechanisms may reveal novel approaches for preventing and treating an array of neurodegenerative conditions that are initiated by perturbed synaptic homeostasis. [source] Large Artery Stiffness: Implications For Exercise Capacity And Cardiovascular RiskCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 3 2002Bronwyn A Kingwell SUMMARY 1. Large artery stiffness, or its inverse, compliance, determines pulse pressure, which, in turn, influences myocardial work capacity and coronary perfusion, both of which impact on exercise capacity and cardiovascular risk. 2. In support of a role for arterial properties in exercise performance, aerobically trained athletes (aged 30,59 years) have lower arterial stiffness than their sedentary counterparts. Furthermore, in healthy older subjects (aged 57,80 years), time to exhaustion on treadmill testing correlated positively with arterial compliance. 3. Arterial stiffness is more closely linked to exercise capacity and myocardial risk in patients with coronary disease where, independently of degree of coronary disease, those with stiffer proximal arteries have a lower exercise-induced ischaemic threshold. 4. Moderate aerobic training elevates resting arterial compliance by approximately 30%, independently of mean pressure reduction, in young healthy individuals but not in isolated systolic hypertensive patients. Rat training studies support a role for exercise training in structural remodelling of the large arteries. 5. High-resistance strength training is associated with stiffer large arteries and higher pulse pressure than matched controls. 6. Large artery stiffness is an important modulator of the myocardial blood supply and demand equation, with significant ramifications for athletic performance and ischaemic threshold in coronary disease patients. Moderate aerobic training, but not high-resistance strength training, reduces large artery stiffness in young individuals whereas older subjects with established isolated systolic hypertension are resistant to such adaptation. [source] | |||||||||||||