a1_Vascular repair in response to injury or stress (often referred to as remodeling) is a common complication of many cardiovascular abnormalities including pulmonary hypertension, systemic hypertension, atherosclerosis, vein graft remodeling and restenosis following balloon dilatation of the coronary artery. It is not surprising that repair and remodeling occurs frequently in the vasculature in that exposure of blood vessels to either excessive hemodynamic stress (e.g. hypertension), noxious blood borne agents (e.g. atherogenic lipids), locally released cytokines, or unusual environmental conditions (e.g. hypoxia), requires readily available mechanisms to counteract these adverse stimuli and to preserve structure and function of the vessel wall. The responses, which were presumably evolutionarily developed to repair an injured tissue, often escape self-limiting control and can result, in the case of blood vessels, in lumen narrowing and obstruction to blood flow. Each cell type (i. e. endothelial cells, smooth muscle cells, and fibroblasts) in the vascular wall plays a specific role in the response to injury. However, while the roles of the endothelial cells and smooth muscle cells (SMC) in vascular remodeling have been extensively studied, relatively little attention has been given to the adventitial fibroblasts. Perhaps this is because the fibroblast is a relatively ill-defined cell which, at least compared to the SMC, exhibits few specific cellular markers. Importantly though, it has been well demonstrated that fibroblasts possess the capacity to express several functions such as migration, rapid proliferation, synthesis of connective tissue components, contraction and cytokine production in response to activation or stimulation., a2_The myriad of responses exhibited by the fibroblasts, especially in response to stimulation, suggest that these cells could play a pivotal role in the repair of injury. This fact has been well documented in the setting of wound healing where a hypoxic environment has been demonstrated to be critical in the cellular responses. As such it is not surprising that fibroblasts may play an important role in the vascular response to hypoxia and/or injury. This paper is intended to provide a brief review of the changes that occur in the adventitial fibroblasts in response to vascular stress (especially hypoxia) and the role the activated fibroblasts might play in hypoxia-mediated pulmonary vascular disease., K. R. Stenmark, D. Bouchey, R. Nemonoff, E. C. Dempsey, M. Das., and Obsahuje bibliografii
In our previous studies, IB-MECA, an adenosine A3 receptor agonist, was found to stimulate proliferation of hematopoietic progenitor and precursor cells in mice. This property of IB-MECA was considered to be responsible for its ability to support regeneration of suppressed hematopoiesis after irradiation with sublethal doses of γ-rays when the drug was given in a postirradiation treatment regimen. This study was aimed at assessing the ability of IB-MECA to influence a 30-day survival of lethally irradiated mice. In a series of experiments, IB-MECA was administered following various lethal radiation doses in various numbers of drug doses and various administration routes. Though in some of these experiments a moderate increase in 30-day survival was observed in IB-MECA-treated mice, the differences in comparison with the controls were not significantly different. It can be inferred from these results and those of previous studies assessing the effects of IB-MECA after sublethal radiation doses that IB-MECA can probably influence only a substantially preserved hematopoiesis like that remaining after sublethal irradiation. Future studies should be aimed at evaluation of the abilities of IB-MECA to influence post-irradiation survival when administered as a part of combined treatment regimens., M. Hofer, ... [et al.]., and Obsahuje seznam literatury
This experiment tested the effects of an intracerebroventricular injection of prostaglandin E1 on the sympathetic activation and the thermogenic changes in rats with ibotenate lesions of the ventromedial hypothalamus. Under pentobarbital anesthesia, twelve Sprague-Dawley male rats were lesioned bilaterally in the ventromedial hypothalamus with an injection of ibotenic acid (30 nmol into each side). Sham lesions were carried out in other twelve control rats. After 48 h, all animals were anesthetized with ethyl-urethane. The firing rate of the sympathetic nerves innervating the interscapular brown adipose tissue and the colonic and interscapular brown adipose tissue temperatures were monitored before and after an intracerebroventricular injection of prostaglandin E1 (500 ng) or saline. Prostaglandin E1 induced an increase in the firing rate of sympathetic nerves and the colonic and interscapular brown adipose tissue temperatures. These effects were reduced by the ventromedial hypothalamic lesion. Since ibotenic acid destroys cell bodies, the findings indicate that neurons of the ventromedial hypothalamus play a considerable role in the control of sympathetic activation and the thermogenic changes during prostaglandin E1 hyperthermia., M. Monda, A. Sullo, V. De Luca, A. Viggiano., and Obsahuje bibliografii
Muscle regeneration is regulated through interaction between muscle and immune cells. Studies showed that treatment with supra-physiological doses of Non-Steroidal Anti-Inflammatory Drug (NSAID) abolished inflammatory signaling and impaired muscle recovery. The present study examines the effects of pharmacologically-relevant NSAID treatment on muscle regeneration. C57BL/6 mice were injected in the tibialis anterior (TA) with either PBS or cardiotoxin (CTX). CTX-injected mice received ibuprofen (CTX-IBU) or were untreated (CTX-PLAC). After 2 days, Il-1β and Il-6 expression was upregulated in the TA of CTX-IBU and CTX-PL vs. PBS. However, Cox-2 expression and macrophage infiltration were higher in CTX-PL vs. PBS, but not in CTX-IBU. At the same time, anabolic markers were higher in CTX-IBU vs. PBS, but not in CTX-PL. Nevertheless, ibuprofen did not affect muscle mass or muscle fiber regeneration. In conclusion, mild ibuprofen doses did not worsen muscle regeneration. There were even signs of a transient improvement in anabolic signaling and attenuation of inflammatory signaling., Sebastiaan Dalle, Chiel Poffé, Charlotte Hiroux, Frank Suhr, Louise Deldicque, Katrien Koppo., and Obsahuje bibliografii
Digitonin solubilizes mitochondrial membrane, breaks the integrity of the respiratory chain and releases two mobile redoxactive components: coenzyme Q (CoQ) and cytochrome c (cyt c). In the present study we report the inhibition of glycerol-3- phosphate- and succinate-dependent oxygen consumption rates by digitonin treatment. Our results show that the inhibition of oxygen consumption rates is recovered by the addition of exogenous synthetic analog of CoQ idebenone (hydroxydecylubiquinone; IDB) and cyt c. Glycerol-3-phosphate oxidation rate is recovered to 148 % of control values, whereas succinatedependent oxidation rate only to 68 %. We find a similar effect on the activities of glycerol-3-phosphate and succinate cytochrome c oxidoreductase. Our results also indicate that succinate-dependent oxidation is less sensitive to digitonin treatment and less activated by IDB in comparison with glycerol- 3-phosphate-dependent oxidation. These findings might indicate the different mechanism of the electron transfer from two flavoprotein-dependent dehydrogenases (glycerol-3-phosphate dehydrogenase and succinate dehydrogenase) localized on the outer and inner face of the inner mitochondrial membrane, respectively., H. Rauchová, M. Vokurková, Z. Drahota., and Obsahuje seznam literatury
Spinal deformities such as scoliosis and kyphosis are incurable, and can lead to decreased physical function, pain, and reduced quality of life. Despite much effort, no clear therapies for the treatment of these conditions have been found. Therefore, the development of an animal model for spinal deformity would be extremely valuable to our understanding of vertebral diseases. In this study, we demonstrate that mice deficient in the mitochondrial enzyme isocitrate dehydrogenase 2 (IDH2) develop spinal deformities with aging. We use morphological analysis as well as radiographic and micro-CT imaging of IDH2-deficient mice to characterize these deformities. Histological analysis showed increased abnormalities in IDH2-deficient mice compared to wild type mice. Taken together, the results suggest that IDH2 plays a critical role in maintaining the spinal structure by affecting the homeostatic balance between osteoclasts and osteoblasts. This indicates that IDH2 might be a potent target for the development of therapies for spinal deformities. Our findings also provide a novel animal model for vertebral disease research., U. Chae, N.-R. Park, E. S. Kim, J.-Y. Choi, M. Yim, H.-S. Lee, S.-R. Lee, S. Lee, J.-W. Park, D.-S. Lee., and Obsahuje bibliografii
Celiac disease is a chronic illness of the small bowel caused by gliadin intolerance in genetically predisposed subjects. The aim of this study was to investigate serum levels of IgA and IgG antigliadin antibodies, IgA antiendomysial antibodies, and IgA anti-tissue transglutaminase antibodies in 169 patients with autoimmune thyroid diseases, i.e. chronic thyroiditis and Graves´ disease. Antiendomysial antibodies were positive in 2 out of 169 persons (1.18 %), IgA antigliadin antibodies in 15.98 %, IgG antigliadin antibodies in 51.48 %, and IgA anti-tissue transglutaminase in 14.79 %. The prevalence of positivity was higher compared to the 1312 control blood donors described in our previous study (Vančíková et al. 2002) (p<0.05). Patients with chronic thyroiditis treated with a high replacement dosage of levothyroxin (125-200 μg daily) had higher serum levels of IgA antigliadin antibodies in comparison with patients treated with a lower dosage (50-100 μg daily) (medians: 13.00 vs. 19.69, p=0.033). We found a negative correlation of IgA anti-tissue transglutaminase antibodies and total calcium serum levels (r = -0.480, p=0.0236, n=22). We can conclude that in persons with autoimmune thyropathy there is a high prevalence of positive antigliadin, anti-tissue transglutaminase and antiendomysial antibodies. Latent celiac disease may lead to impaired resorption of therapeutically administered levothyroxine, calcium, or other substances., J. Jiskra, Z. Límanová, Z. Vaníčková, P. Kocna., and Obsahuje bibliografii
Acute lung injury occurs mostly in the very low birth weight and extremely low birth weight infants. The pathological process leading to acute lung injury includes immature and/or diseased lung that experienced oxidative stress, inflammation and mechanical insult with the bronchial, alveolar and capillary injuries and cell death. It may be the first step to the subsequent development of chronic lung disease of prematurity or bronchopulmonary dysplasia. The mechanisms of lung injury are extensively investigated in the experimental models and clinical studies, mostly performed on the adult patients. At present, the explanations of the mechanism(s) leading to lung tissue injury in tiny premature babies are just derived from these studies. Acute lung injury seems to be rather a syndrome than a well-defined nosological unit and is of multifactorial etiology. The purpose of this review is to discuss the main factors contributing to the development of acute lung injury in the very low or extremely low birth weight infants - lung immaturity, mechanical injury, oxidative stress and inflammation. Nevertheless, numerous other factors may influence the status of immature lung after delivery., P. Zoban, M. Černý., and Obsahuje bibliografii
Elevated levels of insulin have been reported to induce both an arterial vasodilation mediated by nitric oxide (NO), and vasoconstriction mediated by endothelin and reactive oxygen radicals. Metformin, used to control blood glucose levels in type 2 diabetes, has also been shown to cause NO-mediated dilation of conduit arteries. It is possible that these contradictory vascular effects are due to a non-direct action on arteries. Therefore, the direct effect of high levels of insulin and metformin infusion on resistance artery diameter was evaluated. Experiments were carried out on the anesthetized pig; blood flow and pressure were measured in the iliac artery. An adjustable snare was applied to the iliac above the pressure and flow measurement site to induce step decreases (3-4 occlusions at 5 min intervals were performed for each infusion) in blood flow, and hence iliac pressure, and the conductance (Δflow / Δpressure) calculated. Saline, insulin (20 and 40 mUSP/l/min), and metformin (1 μg/ml/min) were infused separately downstream of the adjustable snare and their effect on arterial conductance assessed. Insulin at both infusion rates and metformin caused a significant reduction in peripheral vascular conductance. In conclusion, hyperinsulinemia and metformin infusion constrict resistance arterial vessels in vivo., F. Markos, C. M. Shortt, D. Edge, T. Ruane-O'Hora, M. I. M. Noble., and Obsahuje bibliografii
Immunity plays an important role in the reactivity of the organism and, in this context, is an essential factor in the pathogenesis of many diseases. Basically, there is no system or organ in the body, whose dysfunction is not related to immunity consequences. In addition, there are also multisystem diseases simultaneously involving multiple body systems. They are not always caused by weak immunity, but also often by modified immune reactions known as overshooting. The essence of all these diseases is a change in the reactivity of the organism where immunity plays an important role. The immunity as such is then part of the systems of neuroendocrine-immune regulation, which have common mediators and receptors. The establishment of psychoneuroimmunology, a relatively new discipline in neuroscience, contributed to a detailed understanding of these mechanisms between central and peripheral nervous system, the endocrine system and the immune system. This research enabled the uncovering of the nature of stress-diseases and impact of other regulatory disturbances on the function of various body organs and systems of the organism as a whole. The aim of this short review is to show complex interconnections of these relationships to better understand the human health and disease., F. Vožeh., and Seznam literatury