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Pathological Conditions (pathological + condition)
Kinds of Pathological Conditions Selected AbstractsFrom the Background to the Spotlight: TASK Channels in Pathological ConditionsBRAIN PATHOLOGY, Issue 6 2010Stefan Bittner Abstract TWIK-related acid-sensitive potassium channels (TASK1,3) belong to the family of two-pore domain (K2P) potassium channels. Emerging knowledge about an involvement of TASK channels in cancer development, inflammation, ischemia and epilepsy puts the spotlight on a leading role of TASK channels under these conditions. TASK3 has been especially linked to cancer development. The pro-oncogenic potential of TASK3 could be shown in cell lines and in various tumor entities. Pathophysiological hallmarks in solid tumors (e.g. low pH and oxygen deprivation) regulate TASK3 channels. These conditions can also be found in (autoimmune) inflammation. Inhibition of TASK1,2,3 leads to a reduction of T cell effector function. It could be demonstrated that TASK1,/, mice are protected from experimental autoimmune inflammation while the same animals display increased infarct volumes after cerebral ischemia. Furthermore, TASK channels have both an anti-epileptic as well as a pro-epileptic potential. The relative contribution of these opposing influences depends on their cell type-specific expression and the conditions of the cellular environment. This indicates that TASK channels are per se neither protective nor detrimental but their functional impact depends on the "pathophysiological" scenario. Based on these findings TASK channels have evolved from "mere background" channels to key modulators in pathophysiological conditions. [source] Cardiac hypertrophy and failure: lessons learned from genetically engineered miceACTA PHYSIOLOGICA, Issue 1 2001Y. Takeishi Congestive heart failure is a major and growing public health problem. Because of improved survival of myocardial infarction patients produced by thrombolytic therapy or per-cutaneous revascularization it represents the only form of cardiovascular disease with significantly increased incidence and prevalence. Clinicians view this clinical syndrome as the final common pathway of diverse pathologies such as myocardial infarction and haemodynamic overload. Insights into mechanisms for heart failure historically derived from physiological and biochemical studies which identified compensatory adaptations for the haemodynamic burden associated with the pathological condition including utilization of the Frank Starling mechanism, augmentation of muscle mass, and neurohormonal activation to increase contractility. Therapy has largely been phenomenological and designed to prevent or limit the deleterious effects of these compensatory processes. More recently insights from molecular and cell biology have contributed to a more mechanistic understanding of potential causes of cardiac hypertrophy and failure. Many different analytical approaches have been employed for this purpose. These include the use of conventional animal models which permit serial observation of the onset and progression of heart failure and a sequential analysis of underlying biochemical and molecular events. Neonatal murine cardiomyocytes have been a powerful tool to examine in vitro subcellular mechanisms devoid of the confounding functional effects of multicellular preparations and heterogeneity of cell type. Finally, significant progress has been made by utilizing tissue from human cardiomyopathic hearts explanted at the time of orthotopic transplantation. Each of these methods has significant advantages and disadvantages. Arguably the greatest advance in our understanding of cardiac hypertrophy and failure over the past decade has been the exploitation of genetically engineered mice as biological reagents to study in vivo the effects of alterations in the murine genome. The power of this approach, in principle, derives from the ability to precisely overexpress or ablate a gene of interest and examine the phenotypic consequences in a cardiac specific post-natal manner. In contrast to conventional animal models of human disease which employ some form of environmental stress, genetic engineering involves a signal known molecular perturbation which produces the phenotype. [source] Endometrial glandular and stromal breakdown, part 1: Cytomorphological appearanceDIAGNOSTIC CYTOPATHOLOGY, Issue 9 2006C.M.I.A.C., Keiko Shimizu C.T. Abstract Endometrial carcinoma is the most common invasive neoplasm of the female reproductive tract. Early detection and accurate diagnosis of these lesions and its precursor by endometrial cytology is now accepted in Japan and regarded as an effective primary method of evaluating endometrial pathology (atypical hyperplasia or carcinoma). Careful cytomorphologic evaluation of the abnormal endometrial lesions has made possible an accurate and reproducible microscopic assessment. The current study was conducted to determine the significance of endometrial cytology on disordered endometrium associated with anovulation when compared with endometrial hyperplasia. From January 1998 through April 2004, 144 cases on which histopathological diagnoses were obtained by endometrial curettage after taken direct endometrial sample by Endocyte. The materials comprise 49 cases of normal proliferative endometrium, and 63 cases of endometrial hyperplasia without atypia were prepared as control cases. The cytomorphology was examined involving so-called endometrial glandular and stromal breakdown (EGBD). EGBD cases evidenced significant numbers of stromal cells condensed and formed compact nests with hyperchromatic nuclei and little or no cytoplasm. They were often associated with fragmented clusters of endometrial glands with condensed cluster of stromal cells. Both the fragmented cluster of endometrial glands and condensed cluster of stromal cells are a characteristic cytologic feature of EGBD endometrium on the cyto-architectural diagnosis. The combination of these cellular patterns is highly specific to this abnormal pathological condition in EGBD endometrium. To improve the accuracy of the cytodiagnosis, it is important that the cytology of the EGBD endometrium should be diagnosed negative; as a result, we can achieve successful endometrial cytology with cyto-architectural criteria for the endometrial pathology. Diagn. Cytopathol. 2006;34:609,613. © 2006 Wiley,Liss, Inc. [source] CHARACTERISTIC INTRADUCTAL ULTRASONOGRAPHIC FEATURES OF PORTAL BILIOPATHYDIGESTIVE ENDOSCOPY, Issue 4 2008Tsukasa Ikeura The term ,portal biliopathy' is used to describe cholangiographic abnormalities seen in patients with extrahepatic portal vein obstruction. Portal biliopathy is mainly composed of extrinsic compression of the bile duct caused by enlarged venous collaterals. Herein we report a case of asymptomatic portal biliopathy caused by idiopathic extrahepatic portal vein obstruction. In the present case, intraductal ultrasonography showed normal anatomic layers of the distal common bile duct wall, surrounded by numerous tubular structures which were suspected to be collateral vessels. We suggest that intraductal ultrasonography may be a helpful imaging procedure for detection of this pathological condition. [source] Antioxidant Activity of Degradable Polymer Poly(trolox ester) to Suppress Oxidative Stress Injury in the CellsADVANCED FUNCTIONAL MATERIALS, Issue 1 2010Paritosh P. Wattamwar Abstract Oxidative stress is a pathological condition that has been implicated as a central player in a variety of diseases, including vascular and neurodegenerative diseases. More recently, oxidative stress has also been shown to be involved in the biological incompatibility of many materials, especially at the nanoscale. As such, there is a critical need for new biomaterials that can inhibit this response, improving the compatibility of medical devices. In this work, trolox, a synthetic antioxidant and water-soluble analogue of Vitamin E, is polymerized to form an oxidation active polymer as a new class of biomaterial. Synthesized poly(trolox ester) polymers were formulated into nanoparticles using a single emulsion technique, and their size was controlled by changing the polymer concentration in the organic solvent. Nanoparticle cytotoxicity, protective effects against cellular oxidative stress, and degradation kinetics were all evaluated. Poly(trolox ester) nanoparticles were found to have little to no cytotoxicity and were capable of suppressing cellular oxidative stress induced by cobalt nanoparticles. In vitro degradation studies of poly(trolox ester) nanoparticles indicate that the antioxidant activity of nanoparticles was derived from its enzymatic degradation to release active antioxidants. [source] Hyperostosis Frontalis Interna and sex identification of two skeletons from the Early Middle Ages necropolis of Vicenne-Campochiaro (Molise, Italy)INTERNATIONAL JOURNAL OF OSTEOARCHAEOLOGY, Issue 6 2006M. G. Belcastro Abstract Lesions attributable to Hyperostosis Frontalis Interna (HFI) were examined in two skulls (from graves 100 and 113) from the Early Middle Ages necropolis of Vicenne-Campochiaro (Molise, Italy). Both skeletons were of older individuals and it was difficult to sex them using standard anthropological methods. We discuss the sex identification of the skeletons in relation to the presence of HFI, as well as the usefulness of this pathological condition as a sex marker, underlining the importance of the relationship between palaeopathological and clinical-forensic studies. Our study is a further contribution to the case history of HFI in osteoarchaeological material. Copyright © 2006 John Wiley & Sons, Ltd. [source] Frequencies of Morphological Characteristics in Two Contemporary Forensic Collections: Implications for Identification,JOURNAL OF FORENSIC SCIENCES, Issue 5 2006Debra Komar Ph.D. ABSTRACT: Positive identification relies on comparison of antemortem and postmortem data. Some identifications are based on morphological features such as fracture, pathological condition, and surgical hardware, despite little literature indicating the frequencies of such traits. This study examines whether such features are sufficiently rare as to be deemed individualizing. Data were collected on two modern North American skeletal collections (N=482 individuals). Presence/absence of features was scored by skeletal element and side. Results indicate that frequencies vary by geographic region (higher frequency of fractures and pathological conditions in New Mexico while individuals in Tennessee were more likely to have surgical interventions), many features such as fractures are remarkably common and that even suites of traits may not be individualizing. Caution is warranted when using written data rather than radiographic comparisons as the primary source of identification. The implications of these findings to missing person databases are also discussed. [source] Clinical approach to renal neoplasia in budgerigars (Melopsittacus undulatus)JOURNAL OF SMALL ANIMAL PRACTICE, Issue 9 2006S. Simova-Curd Renal neoplasia in budgerigars (Melopsittacus undulatus) is seen regularly in general practice and is of interest to many practicing veterinary surgeons. This review article provides an overview of the current knowledge and the most recent reports in avian literature regarding renal tumours in budgerigars, with the emphasis on clinical diagnosis and treatment. The high prevalence of renal neoplasia in budgerigar is discussed, with notes on the most commonly diagnosed tumours, possibility of metastases, sex and age predisposition. The possibility of ultrasonography and radiography in the diagnosis of this pathological condition are compared as well as the possible role of blood and urine analyses. Two studies are described, both of which investigate the possible involvement of a retrovirus as the aetiological agent. [source] Modified expression of cytoplasmic isocitrate dehydrogenase electrophoretic isoforms in seminal plasma of men with sertoli-cell-only syndrome and seminomaMOLECULAR CARCINOGENESIS, Issue 6 2008Mireille Starita-Geribaldi Abstract Two isoforms of human cytoplasmic isocitrate dehydrogenase (IDPc) of close molecular weights and different isoelectric points were identified in human seminal plasma (SP) by two-dimensional gel electrophoresis (2-DE) followed by mass spectrometry (MS). These two isoforms were detected in the normospermic men SP and their expressions were markedly altered in patients with testicular seminoma, the most frequent testicular germ cell cancer (TGCC): increase of the more acidic spot and decrease of the more basic one. Since oligospermia has been considered as a high risk pathological condition for developing a testicular cancer, the two IDPc isoforms were analyzed in SP of a group of secretory azoospermic patients. In this group the two spots displayed similar variations of expression to those observed in testicular seminoma. These results propose IDPc as a promising SP biomarker of testicular seminoma. Whether IDPc alteration in secretory azoospermia is predictive of testicular seminoma remains to be elucidated. © 2007 Wiley-Liss, Inc. [source] Five years of Homo floresiensisAMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY, Issue 2 2010Leslie C. Aiello Abstract Since Homo floresiensis was first described in October 2004 there has been a lively debate over its status. Is it a late surviving species of early Homo or merely a modern individual afflicted with disordered growth and one of the many syndromes resulting in microchephaly? Recently the discovery team has published a series of articles providing detailed descriptions of the hominin material, its geomorphological context, and the associated archaeology and faunal material (Morwood and Jungers: J Hum Evol 57 (2009) 437-648). In addition, other researchers have put forward new hypotheses for possible pathologies including Laron's Syndrome and Myxoedematous Endemic (ME) Cretinism. Here I review this new information and conclude that the evidence supports the hypothesis that Homo floresiensis is a late-surviving species of early Homo with its closest morphological affinities to early African pre- erectus/ergaster hominins. Although this hypothesis requires fundamental paradigm changes in our understanding of human evolution, it provides a more economical explanation for H. floresiensis than do the alternatives. None of the current explanations for microcephaly and disordered growth account for the range of features observed in H. floresiensis. Neither do they provide explanations for why a pathological condition in modern humans would mimic so closely the morphology observed in earlier hominins. This conclusion is based on the current evidence for H. floresiensis and on the particular pathological explanations that have appeared in the literature. There is no doubt that controversy over H. floresiensis will continue until new and conclusive evidence is available to settle the debate one way or another. Am J Phys Anthropol, 2010. © 2010 Wiley-Liss, Inc. [source] When parsimony backfires: Neglecting DNA repair may doom neurons in Alzheimer's diseaseBIOESSAYS, Issue 2 2003Thierry Nouspikel Taking advantage of the fact that they need not replicate their DNA, terminally differentiated neurons only repair their expressed genes and largely dispense with the burden of removing damage from most of their genome. However, they may pay a heavy price for this laxity if unforeseen circumstances, such as a pathological condition like Alzheimer's disease, cause them to re-enter the cell cycle. The lifetime accumulation of unrepaired lesions in the silent genes of neurons is likely to be significant and may result in aborting the mitotic process and triggering cell death if the cells attempt to express these dormant genes and resume DNA replication. BioEssays 25:168,173, 2003. © 2003 Wiley Periodicals, Inc. [source] 3221: Pathophysiology of dry eye syndromeACTA OPHTHALMOLOGICA, Issue 2010J HORWATH-WINTER Dry eye or dysfunctional tear syndrome is a highly prevalent disease worldwide. It is related to a pathological condition of anyone of the parts of the "ocular surface system" that involves the cornea, conjunctiva, lacrimal gland, accessory lacrimal glands, nasolacrimal duct and the lids with the meibomian glands. These are linked as a functional system by innervation, the endocrine and immune system. Endogenous or exogenous caused alterations in one or several components of the ocular surface system or its secretions result in changes of the tear film or ocular surface provoking inflammation. With time, inflammatory reactions may lead to corneal neuropathy compromising the reflex response of the lacrimal glands. Additionally a self-perpetuating vicious circle with loss of function and damage can be initiated also by an immune-modulated inflammation. [source] Neuroprotein s-100B , a useful parameter in paediatric patients with mild traumatic brain injury?ACTA PAEDIATRICA, Issue 10 2009C Castellani Abstract Aims:, To examine the correlation of S-100B to cranial computerized tomography (CCT) scan results in children after mild traumatic brain injury (MTBI). Methods:, One hundred and nine paediatric patients (0,18 years) with MTBI were included in this prospective single-centre study. Serum was collected within 6 h of trauma for determination of serum S-100B. The upper reference of S-100B was set to 0.16 ,g/L. A CCT scan was performed in all patients and the results were correlated to the S-100B values. Results:, Computerized tomography was abnormal in 36 patients showing intracerebral haemorrhages and/or skull fractures. Serum S-100B level was significantly higher in patients with a pathological condition as shown in CT scan results (p = 0.003). There were no false negative, but 42 false positive test results for S-100B. This resulted in a sensitivity of 1.00, specificity of 0.42, positive predictive value of 0.46 and negative predictive value of 1.00. An area under the receiver operating curve of 0.68 was calculated. Conclusion:, S-100B is a valuable tool to rule out patients with pathological CCT findings in a collective of paediatric patients with MTBI. Elevations of S-100B do not necessarily lead to a pathological finding in the CT scan, but values below the cut-off safely rule out the evidence of intracranial lesions. [source] FLUID FLOW IN DISTENSIBLE VESSELSCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 2 2009CD Bertram SUMMARY 1Flow in single vascular conduits is reviewed, divided into distended and deflated vessels. 2In distended vessels with pulsatile flow, wave propagation and reflection dominate the spatial and temporal distribution of pressure, determining the shape, size and relative timing of measured pressure waveforms, as well as the instantaneous pressure gradient everywhere. Considerable research has been devoted to accessing the information on pathological vascular malformations contained in reflected waves. Slow waves of contraction of vessel wall muscle, responsible for transport of oesophageal, ureteral and gut contents, have also been modelled. 3The pressure gradient in a vessel drives the flow. Flow rate can be predicted both analytically and numerically, but analytical theory is limited to idealized geometry. The complex geometry of biological system conduits necessitates computation instead. Initially limited to rigid boundaries, numerical methods now include fluid,structure interaction and can simultaneously model solute transport, thus predicting accurately the environment of the mechanosensors and chemosensors at vessel surfaces. 4Deflated vessels display all phenomena found in distended vessels, but have additional unique behaviours, especially flow rate limitation and flow-induced oscillation. Flow rate limitation is widespread in the human body and has particular diagnostic importance in respiratory investigation. Because of their liquid lining, the pulmonary airways are also characterized by important two-phase flows, where surface tension phenomena create flows and determine the patency and state of collapse of conduits. 5Apart from the vital example of phonation, sustained self-excited oscillation is largely avoided in the human body. Where it occurs in snoring, it is implicated in the pathological condition of sleep apnoea. [source] Skeletal muscle fibre diversity and the underlying mechanismsACTA PHYSIOLOGICA, Issue 4 2010M. Canepari Abstract The review first briefly summarizes how myosin isoforms have been identified as the major determinant of the functional variability among skeletal muscle fibres. The latter feature is a major characteristic of muscle fibres and a major basis of skeletal muscle heterogeneity and plasticity in vivo. Then, evidence is reported, which indicates that the properties of muscle fibres can vary with no change in the myosin isoform they express. Moreover, the physiological and pathological conditions (ageing, disuse, exercise training, muscular dystrophy) in which such myosin isoform independent change in functional properties occurs and the possible underlying mechanisms are considered. Finally, the known molecular bases of the functional differences among slow and fast isoforms are briefly dealt with. [source] Cardiac basal metabolism: energetic cost of calcium withdrawal in the adult rat heartACTA PHYSIOLOGICA, Issue 3 2010P. Bonazzola Abstract Aim:, Cardiac basal metabolism upon extracellular calcium removal and its relationship with intracellular sodium and calcium homeostasis was evaluated. Methods:, A mechano-calorimetric technique was used that allowed the simultaneous and continuous measurement of both heat rate and resting pressure in arterially perfused quiescent adult rat hearts. Using pharmacological tools, the possible underlying mechanisms related to sodium and calcium movements were investigated. Results:, Resting heat rate (expressed in mW g,1dry wt) increased upon calcium withdrawal (+4.4 ± 0.2). This response was: (1) unaffected by the presence of tetrodotoxin (+4.3 ± 0.6), (2) fully blocked by both, the decrease in extracellular sodium concentration and the increase in extracellular magnesium concentration, (3) partially blocked by the presence of either nifedipine (+2.8 ± 0.4), KB-R7943 (KBR; +2.5 ± 0.2), clonazepam (CLO; +3.1 ± 0.3) or EGTA (+1.9 ± 0.3). The steady heat rate under Ca2+ -free conditions was partially reduced by the addition of Ru360 (,1.1 ± 0.2) but not CLO in the presence of EGTA, KBR or Ru360. Conclusion:, Energy expenditure for resting state maintenance upon calcium withdrawal depends on the intracellular rise in both sodium and calcium. Our data are consistent with a mitochondrial Ca2+ cycling, not detectable under normal calcium diastolic levels. The experimental condition here analysed, partially simulates findings reported under certain pathological situations including heart failure in which mildly increased levels of both diastolic sodium and calcium have also been found. Therefore, under such pathological conditions, hearts should distract chemical energy to fuel processes associated with sodium and calcium handling, making more expensive the maintenance of their functions. [source] Non-apoptotic cell death in Caenorhabditis elegansDEVELOPMENTAL DYNAMICS, Issue 5 2010Manolis Vlachos Abstract The simple nematode worm Caenorhabditis elegans has been instrumental in deciphering the molecular mechanisms underlying apoptosis. Beyond apoptosis, several paradigms of non-apoptotic cell death, either genetically or extrinsically triggered, have also been described in C. elegans. Remarkably, non-apoptotic cell death in worms and pathological cell death in humans share numerous key features and mechanistic aspects. Such commonalities suggest that similarly to apoptosis, non-apoptotic cell death mechanisms are also conserved, and render the worm a useful organism, in which to model and dissect human pathologies. Indeed, the genetic malleability and the sophisticated molecular tools available for C. elegans have contributed decisively to advance our understanding of non-apoptotic cell death. Here, we review the literature on the various types of non-apoptotic cell death in C. elegans and discuss the implications, relevant to pathological conditions in humans. Developmental Dynamics 239:1337,1351, 2010. © 2010 Wiley-Liss, Inc. [source] Development of the corticospinal system and hand motor function: central conduction times and motor performance testsDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 4 2000U M Fietzek Maturation of the corticospinal (CS) tract and hand motor function provide paradigms for central nervous system development. In this study, involving 112 participants (aged from 0.2 to 30 years), we evaluated central motor conduction times (CMCT) obtained with transcranial magnetic stimulation (TMS) during preinnervation conditions of facilitation and relaxation. Auditory reaction time, velocity of a ballistic movement of the arm, finger tapping, diadochokinesis, and fine motor visuomanual tracking were also examined. The maturation profiles for every parameter were calculated. CMCTs for the different preinnervation conditions reached adult values at different times and this could be explained by maturation of excitability at the cortical and spinal level. A stable phase for CMCTs and reaction time was reached during childhood. Parameters which measured motor speed and skill indicated that the development of these continued into adulthood. The maturation of the fast CS tract seems to be completed before the acquisition of the related motor performance has been accomplished. In conclusion, we could demonstrate that data from several neurophysiological methods can be combined and used to study the maturation of the function of the nervous system. This approach could allow appraisal of pathological conditions that show parallels with omissions or lack of developmental progress. [source] Therapeutic aspects of growth hormone and insulin-like growth factor-I treatment on visceral fat and insulin sensitivity in adultsDIABETES OBESITY & METABOLISM, Issue 1 2007K. C. J. Yuen Growth hormone (GH) is generally considered to exert anti-insulin actions, whereas insulin-like growth factor I (IGF-I) has insulin-like properties. Paradoxically, GH deficient adults and those with acromegaly are both predisposed to insulin resistance, but one cannot extrapolate from these pathological conditions to determine the normal metabolic roles of GH and IGF-I on glucose homeostasis. High doses of GH treatment have major effects on lipolysis, which plays a crucial role in promoting its anti-insulin effects, whereas IGF-I acts as an insulin sensitizer that does not exert any direct effect on lipolysis or lipogenesis. Under physiological conditions, the insulin-sensitizing effect of IGF-I is only evident after feeding when the bioavailability of circulating IGF-I is increased. In contrast, many studies in GH deficient adults have consistently shown that GH replacement improves the body composition profile although these studies differ considerably in terms of age, the presence or absence of multiple pituitary hormone deficiency, and whether GH deficiency was childhood or adult-onset. However, the improvement in body composition does not necessarily translate into improvements in insulin sensitivity presumably due to the anti-insulin effects of high doses of GH therapy. More recently, we have found that a very low dose GH therapy (0.1 mg/day) improved insulin sensitivity without affecting body composition in GH-deficient adults and in subjects with metabolic syndrome, and we postulate that these effects are mediated by its ability to increase free ,bioavailable' IGF-I without the induction of lipolysis. These results raise the possibility that this low GH dose may play a role in preventing the decline of ,-cell function and the development of type 2 diabetes in these "high risk" subjects. [source] Adrenomedullin and diabetes mellitusDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 5 2001Eva Ruzicska Abstract Adrenomedullin (AM) is a novel 52 amino acid peptide hormone, originally isolated from human pheochromocytoma. AM acts as a local autocrine and/or paracrine vasoactive hormone and has vasodilator and blood pressure lowering properties. AM as a vasodilative molecule protects the vascular wall but its exact role is still uncertain. AM is considered to play an important endocrine role in various tissues in maintaining electrolyte and fluid homeostasis. Its plasma concentration in healthy conditions is low. In hypertension, chronic renal failure and congestive heart failure its plasma concentration increases in a parallel manner with the severity of the disease. It is assumed that this peptide plays an important role in physiological and pathological conditions compensating the effects of vasoconstrictive molecules. Investigations have proven that in diabetic angiopathies the levels and production of vasoconstrictive factors and AM are increased, while other relaxing substances such as nitric oxide (NO) are decreased. It is still uncertain whether the increased release of AM is a compensatory mechanism or a coincidental event. Although the precise role of AM in the pathogenesis of diabetic complications is still to be elucidated, the altered concentration of AM in diabetes could indicate a certain interaction between AM induction and vascular function. Hence, the induction of vascular AM can be a new target of therapeutic approach to diabetic complications. Copyright © 2001 John Wiley & Sons, Ltd. [source] Effects of diabetes on plasma nitrotyrosine levelsDIABETIC MEDICINE, Issue 6 2004X. L. Wang Abstract Background Oxidative stress plays a major role in disease processes such as atherosclerosis and diabetes. Peroxynitrite is a reaction product of nitric oxide (NO) and superoxide and a potent oxidant. The peroxynitrite-mediated tyrosine nitration, which forms nitrotyrosine (NT), is associated with several pathological conditions. Methods We measured plasma NT levels using the HPLC method in 40 Mexican Americans with diabetes, but not taking medications, and 40 age- and sex-matched euglycaemic controls. Results Plasma-free NT levels were not different between subjects with diabetes (11.0 ± 1.7 nmol/l, n = 40) and with non-diabetes (10.4 ± 1.5 nmol/l, n = 40). There was also no association with levels of fasting glucose (r = ,0.049, P = 0.663) or 2-h glucose (r = ,0.099, P = 0.390). However, females had significantly lower free NT level (7.6 ± 1.4 nmol/l, n = 40) than males (13.8 ± 1.7 nmol/l, n = 40, P = 0.005), which were not affected by age, smoking status, BMI and glucose levels. Conclusions In contrast to some earlier reports, our study shows that diabetes has no effect on plasma NT levels in Mexican Americans. We have also demonstrated lower free NT levels in females than males, which may partly explain the lower risk profile to vascular disease in women. [source] Expanding field of purinergic signalingDRUG DEVELOPMENT RESEARCH, Issue 1-2 2001Geoffrey Burnstock Abstract This article attempts to paint a broad picture of the extraordinary explosive recent developments in the purinergic signaling field. After a brief historical review and update of purinoceptor subtypes, the focus is on the physiological roles of purines and pyrimidines. These are considered both in terms of short-term signaling in neurotransmission, secretion, and vasodilatation and in long-term (trophic) signaling in development, regeneration, proliferation, and cell death. Examples of trophic signaling include cartilage development in limb buds, glial cell proliferation, development of skeletal muscle, changes in receptor expression in smooth-muscle phenotypes, maturation of testicular spermatids, and bone remodeling. Plasticity of purinoceptor expression in pathological conditions is described, including the increase in the purinergic component of parasympathetic nervous control of the human bladder in interstitial cystitis and outflow obstruction and in sympathetic cotransmitter control of blood vessels in hypertensive rats, the appearance of P2X7 receptors in the glomeruli of the kidney from diabetic and transgenic hypertensive animal models, and up-regulation of P2X1 and P2Y2 receptor mRNA in hearts of rats with congestive heart failure. The role of P2X3 receptors in nociception is considered, and a new hypothesis about purinergic mechanosensory transduction in the gut is explored. A personal view of some of the areas ripe for future development concludes this article, including a discussion of different strategies that could lead to the development of purinergic therapeutic agents. Drug Dev. Res. 52:1,10, 2001. © 2001 Wiley-Liss, Inc. [source] Centrosome structure and function under normal and pathological conditionsENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 8 2009Dan L. Sackett No abstract is available for this article. [source] Activated complement is more extensively present in diseased aortic valves than naturally occurring complement inhibitors: a sign of ongoing inflammationEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 1 2010M. Ter Weeme Eur J Clin Invest 2010; 40 (1): 4,10 Abstract Background, Recent studies indicate a role for complement in the pathogenesis of aortic valve disease. However, the role of naturally occurring anti-complement mediators in this context is unknown. In this study, we have analysed this in three different pathological conditions of the aortic valve: degeneration, atherosclerosis and bacterial endocarditis. Materials and methods, Human aortic valves were obtained at autopsy (n = 30): 5 control valves, 10 aortic valves with atherosclerotic changes, 10 aortic valves with degenerative changes and 5 degenerative changed aortic valves with bacterial infection. These valves were analysed immunohistochemically for the presence of activated complement (C3d and C5b9) and the complement inhibitors C1-inh and clusterin. Areas of positivity were then quantified. Results, C3d, C5b9 and the complement inhibitors C1-inh and clusterin depositions were mainly found in the endothelium and extracellular matrix in aortic valves. All these mediators were already present in control valves, but the area of positivity increased significantly in response to the different diseases, with the highest increase in response to bacterial endocarditis. Interestingly, in all three aortic diseases, the depositions of complement were significantly more widespread than that of their inhibitors. Conclusions, Our study indicates that anti-complement mediators (C1-inh and clusterin) are deposited in diseased aortic valves together with activated complement, indicating an existing counter response against complement locally in the valve. However, deposition of activated complement is significantly more widespread than that of its inhibitors, which could explain ongoing inflammation in those diseased aortic valves. [source] Osteopontin is produced by mast cells and affects IgE-mediated degranulation and migration of mast cellsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 2 2008Akiko Nagasaka Abstract Osteopontin (OPN), originally discovered in bone as an extracellular matrix protein, was identified in many cell types in the immune system, presumably being involved in many aspects of pathogenesis of inflammatory and immune diseases. Mast cells are also involved in such pathological aspects by secreting multiple mediators. However, it has not been determined whether mast cells produce OPN and whether it affects their function. To test this, we used murine fetal skin-derived cultured mast cells (FSMC) and bone marrow-derived cultured mast cells. We found that OPN was spontaneously produced by FSMC and inducible by ionomycin and Fc,RI aggregation in bone marrow-derived cultured mast cells. In the presence of mast cell growth factors, FSMC were similarly generated from both OPN-deficient (OPN,/,) and -sufficient (OPN+/+) mice without significant differences in yield, purity, granularity, and viability. Using OPN,/, FSMC, we found that recombinant OPN augmented IgE-mediated degranulation and induced FSMC chemotaxis. Both effects were mediated by OPN receptors (i.e. CD44 and integrin,,v). IgE-mediated passive cutaneous anaphylaxis was significantly reduced in OPN,/, mice compared with OPN+/+ mice, indicating physiological relevance of OPN. These results indicate that OPN is a mast cell mediator, enhances mast cell responses to antigen, and thus may influence mast cell-related pathological conditions. See accompanying commentary at http://dx.doi.org/10.1002/eji200738131 [source] Comparative analysis of NK cell subset distribution in normal and lymphoproliferative disease of granular lymphocyte conditionsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 10 2004Véronique Pascal Abstract We have characterized the heterogeneity of human blood NK cell subsets defined by expression of KIR, lectin like receptors and NK cell differentiation markers within a cohort of 51 healthy Caucasian individuals. High inter-individual variability in cell surface expression of most NK cell markers is observed. Range values defining NK cell subsets in healthy donors were further used as references to characterize 14 patients with NK-type lymphoproliferative disease of granular lymphocytes (NK-LDGL). Alterations of the KIR repertoire were noted in all NK-LDGL patients. NK cell expansions were classified as oligoclonal KIR+ or as non-detectable KIR (ndKIR) using anti-KIR2DL1/2DS1, anti-KIR2DL2/2DL3/2DS2, anti-KIR3DL1 and anti-KIR2DS4 monoclonal antibodies. A major reduction in the size of the CD56bright NK cell subset was a constant feature of NK-LDGL. Altered distribution of CD94+, CD161+, and CD162R+ NK cell subsets was also observed in NK-LDGL patients. Considering the potential role of NK cells in eliminating tumors or virus-infected cells, the reference values defined in this study should be valuable to characterize both quantitative and qualitative alterations of the NK cell repertoire in pathological conditions and to monitor NK cell reconstitution following hematopoietic transplantation. [source] Effects of agrin on the expression and distribution of the water channel protein aquaporin-4 and volume regulation in cultured astrocytesEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 8 2007Susan Noell Abstract Agrin is a heparan sulfate proteoglycan of the extracellular matrix and is known for organizing the postsynaptic differentiation of the neuromuscular junction. Increasing evidence also suggests roles for agrin in the developing CNS, including the formation and maintenance of the blood,brain barrier. Here we describe effects of agrin on the expression and distribution of the water channel protein aquaporin-4 (AQP4) and on the swelling capacity of cultured astrocytes of newborn mice. If astrocytes were cultured on a substrate containing poly dl -ornithine, anti-AQP4 immunoreactivity was evenly and diffusely distributed. If, however, astrocytes were cultured in the presence of agrin-conditioned medium, we observed an increase in the intensity of AQP4-specific membrane-associated staining. Freeze-fracture studies revealed a clustering of orthogonal arrays of particles, representing a structural equivalent of AQP4, when exogenous agrin was present in the astrocyte cultures. Neuronal and non-neuronal agrin isoforms (agrin A0B0 and agrin A4B8, respectively) were able to induce membrane-associated AQP4 staining. Water transport capacity as well as the density of orthogonal arrays of intramembranous particles was increased in astrocytes cultured with the neuronal agrin isoform A4B8, but not with the endothelial and meningeal isoform A0B0. RT-PCR demonstrated that agrin A4B8 increased the level of the M23 splice variant of AQP4 and decreased the level of the M1 splice variant of AQP4. Implications for the regulation and maintenance of the blood,brain barrier including oedema formation under pathological conditions are discussed. [source] Doublecortin expression levels in adult brain reflect neurogenesisEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2005Sebastien Couillard-Despres Abstract Progress in the field of neurogenesis is currently limited by the lack of tools enabling fast and quantitative analysis of neurogenesis in the adult brain. Doublecortin (DCX) has recently been used as a marker for neurogenesis. However, it was not clear whether DCX could be used to assess modulations occurring in the rate of neurogenesis in the adult mammalian central nervous system following lesioning or stimulatory factors. Using two paradigms increasing neurogenesis levels (physical activity and epileptic seizures), we demonstrate that quantification of DCX-expressing cells allows for an accurate measurement of modulations in the rate of adult neurogenesis. Importantly, we excluded induction of DCX expression during physiological or reactive gliogenesis and excluded also DCX re-expression during regenerative axonal growth. Our data validate DCX as a reliable and specific marker that reflects levels of adult neurogenesis and its modulation. We demonstrate that DCX is a valuable alternative to techniques currently used to measure the levels of neurogenesis. Importantly, in contrast to conventional techniques, analysis of neurogenesis through the detection of DCX does not require in vivo labelling of proliferating cells, thereby opening new avenues for the study of human neurogenesis under normal and pathological conditions. [source] Synaptic localization of GABAA receptor subunits in the substantia nigra of the rat: effects of quinolinic acid lesions of the striatumEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2002Fumino Fujiyama Abstract The inhibitory amino acid, ,-aminobutyric acid (GABA), plays a critical role in the substantia nigra (SN) in health and disease. GABA transmission is controlled in part by the type(s) of GABA receptor expressed, their subunit composition and their location in relation to GABA release sites. In order to define the subcellular localization of GABAA receptors in the SN in normal and pathological conditions, sections of SN from control rats and rats that had received quinolinic acid lesions of the striatum were immunolabelled using the postembedding immunogold technique with antibodies against subunits of the GABAA receptor. Immunolabelling for ,1, ,2/3 and ,2 subunits was primarily located at symmetrical synapses. Double-labelling revealed that ,2/3 subunit-positive synapses were formed by terminals that were enriched in GABA. Colocalization of ,1, ,2/3 and ,2 subunits occurred at individual symmetrical synapses, some of which were identified as degenerating terminals derived from the striatum. In the SN ipsilateral to the striatal lesion there was a significant elevation of immunolabelling for ,2/3 subunits of the GABAA receptor at symmetrical synapses, but not of GluR2/3 subunits of the AMPA receptor at asymmetrical synapses. It was concluded that fast GABAA -mediated transmission occurs primarily at symmetrical synapses within the SN, that different receptor subunits coexist at individual synapses and that the upregulation of GABAA receptors following striatal lesions is expressed as increased receptor density at synapses. The upregulation of GABAA receptors in Huntington's disease and its models is thus likely to lead to an increased efficiency of transmission at intact GABAergic synapses in the SN and may partly underlie the motor abnormalities of this disorder. [source] Cloning, distribution and functional analysis of the type III sodium channel from human brainEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2000Yu Hua Chen Abstract The type III voltage-gated sodium channel was cloned from human brain. The full-length cDNA has 89% identity with rat type III, and the predicted protein (1951 amino acids) has 55 differences. The expression pattern of human type III mRNA was determined in adult brain tissue and, in contrast to rat, was detected in many regions, including caudate nucleus, cerebellum, hippocampus and frontal lobe. The human type III channel was stably expressed in Chinese hamster ovary (CHO) cells and its biophysical properties compared to the human type II channel using identical conditions. The voltage dependence and kinetics of activation were found to be similar to that of type II. The kinetics of inactivation of the two human subtypes were also similar. However, type III channels inactivated at more hyperpolarized potentials and were slower to recover from inactivation than type II. When expressed in human embryonic kidney (HEK293T) cells, type III channels produced currents with a prominent persistent component, which were similar to those reported for rat type II [Ma et al. (1997) Neuron, 19, 443,452]. However, unlike type II, this was prominent even in the absence of coexpressed G-proteins, suggesting type III may adopt this gating mode more readily. The distinct properties of the channel, together with its wide distribution in adult brain, suggest that in humans, type III may have important physiological roles under normal, and perhaps also pathological conditions. [source] | |||||||||||||||||||||||||||||||||||||||||||