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Pathophysiological Conditions (pathophysiological + condition)
Selected AbstractsNitrogen isotopic composition in hair protein is different in liver cirrhotic patientsRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 19 2006Klaus J. Petzke The stable-isotopic composition of nitrogen (,15N) or carbon (,13C) of body tissues depends on the isotopic composition of food sources and on shifts due to isotopic fractionation during metabolism. As little is known about the effects of pathophysiological conditions we measured ,15N and ,13C values in hair and hair amino acids of patients with cirrhosis (n,=,21) and compared the results with those of healthy subjects (n,=,100) randomly selected from the 1987,1988 VERA German nutrition survey population. Cirrhosis was reflected in lower hair 15N abundances (6.7 vs. 9.9, ,15N; P <0.001) whereas hair 13C abundances did not differ from healthy subjects (,19.4 vs. ,19.6, ,13C). Distinct patterns of ,15N and ,13C values were measured in hair amino acids. The ,15N values of phenylalanine were significantly higher in cirrhotics (P,<,0.001). With the exception of isoleucine, threonine, and proline all other measured amino acids showed lower ,15N values than healthy subjects (P,<,0.001). Lower hair ,15N values were associated with cirrhotic liver disease which suggests that under this condition the altered liver amino acid metabolism affects the nitrogen isotopic composition of the amino acids used for hair protein synthesis. It remains to be determined in controlled studies whether the altered nitrogen isotopic composition directly reflects the pathophysiological condition or is related to differences in dietary protein intake from plant or animal food sources. Copyright © 2006 John Wiley & Sons, Ltd. [source] Can we use diffusion MRI as a bio-marker of neurodegenerative processes?BIOESSAYS, Issue 11-12 2008Yaniv Assaf Magnetic resonance imaging (MRI) is an imaging technique with a rapidly expanding application range. This methodology, which relies on quantum physics and substance magnetic properties, is now being routinely used in the clinics and medical research. With the advent of measuring functional brain activity with MRI (functional MRI), this methodology has reached a larger section of the neuroscience community (e.g. psychologists, neurobiologists). In the past, the use of MRI as a biomarker or as an assay to probe tissue pathophysiological condition was limited. However, with the new applications of MRI: molecular imaging, contrast-enhanced imaging and diffusion imaging, MRI is turning into a powerful tool for in vivo characterization of tissue pathophysiology. This review focuses on the diffusion MRI. Although it only measures the averaged Brownian translational motion of water molecules, using different analysis schemes, one can extract a wide range of quantitative indices that represent tissue morphology and compartmentalization. Statistical and visualization routines help to relate these indices to biologically relevant measures such as cell density, water content and size distribution. The aim of this review is to shed light on the potential of this methodology to be used in biological research. To that end, this review is intended for the non-MRI specialists who wish to pursue biological research with this methodology. We will overview the current applications of diffusion MRI and its relation to cellular biology of brain tissue. BioEssays 30:1235,1245, 2008. © 2008 Wiley Periodicals, Inc. [source] Control of muscle blood flow during exercise: local factors and integrative mechanismsACTA PHYSIOLOGICA, Issue 4 2010I. Sarelius Abstract Understanding the control mechanisms of blood flow within the vasculature of skeletal muscle is clearly fascinating from a theoretical point of view due to the extremely tight coupling of tissue oxygen demands and blood flow. It also has practical implications as impairment of muscle blood flow and its prevention/reversal by exercise training has a major impact on widespread diseases such as hypertension and diabetes. Here we analyse the role of mediators generated by skeletal muscle activity on smooth muscle relaxation in resistance vessels in vitro and in vivo. We summarize their cellular mechanisms of action and their relative roles in exercise hyperaemia with regard to early and late responses. We also discuss the consequences of interactions among mediators with regard to identifying their functional significance. We focus on (potential) mechanisms integrating the action of the mediators and their effects among the cells of the intact arteriolar wall. This integration occurs both locally, partly due to myoendothelial communication, and axially along the vascular tree, thus enabling the local responses to be manifest along an entire functional vessel path. Though the concept of signal integration is intriguing, its specific role on the control of exercise hyperaemia and the consequences of its modulation under physiological and pathophysiological conditions still await additional analysis. [source] The birth and postnatal development of purinergic signallingACTA PHYSIOLOGICA, Issue 2 2010G. Burnstock Abstract The purinergic signalling system is one of the most ancient and arguably the most widespread intercellular signalling system in living tissues. In this review we present a detailed account of the early developments and current status of purinergic signalling. We summarize the current knowledge on purinoceptors, their distribution and role in signal transduction in various tissues in physiological and pathophysiological conditions. [source] Role of the astrocytic ETB receptor in the regulation of extracellular endothelin-1 during hypoxiaGLIA, Issue 1 2001Martin Hasselblatt Abstract Astrocytes are known to possess an effective endothelin (ET) eliminatory system which involves astrocytic ETA and ETB receptors and may become particularly relevant under pathophysiological conditions. The present study has therefore been designed to explore the effect of standardized hypoxia on extracellular concentrations of endothelin-1 (ET-1) and on endothelin-converting enzyme (ECE) activity in primary rat astrocytes genetically (sl/sl) or experimentally (dexamethasone) deficient in ETB receptors. The results revealed (1) a hypoxia-mediated decrease of extracellular ET-1 in wildtype astrocytes (+/+) that was not observed in ETB -deficient (sl/sl) cultures; (2) an ET receptor antagonist-induced increase in ET-1 in the media of both genotypes with further elevation upon hypoxia in +/+ cultures only; (3) augmentation of the dexamethasone-induced increase in extracellular ET-1 by hypoxia in +/+, but not in sl/sl cultures; (4) synergistic reduction of ETB gene transcription by hypoxia and dexamethasone; and (5) significant increases in endothelin-converting enzyme activity in the presence of hypoxia. To conclude, hypoxia stimulates astrocytic release of mature ET-1. This stimulation is (over)compensated for by increased ET-1 binding to functional ETB receptors. ETB deficiency, whether genetic or experimentally induced, impairs elimination of extracellular ET-1. GLIA 34:18,26, 2001. © 2001 Wiley-Liss, Inc. [source] The Endocannabinoid System and Energy MetabolismJOURNAL OF NEUROENDOCRINOLOGY, Issue 6 2008L. Bellocchio Many different regulatory actions have been attributed to endocannabinoids, and their involvement in several pathophysiological conditions is under intense scrutiny. Cannabinoid receptors [cannabinoid receptor type 1 (CB1) and CB2] participate in the physiological modulation of many central and peripheral functions. The ability of the endocannabinoid system to control appetite, food intake and energy balance has recently received considerable attention, particularly in the light of the different modes of action underlying these functions. The endocannabinoid system modulates rewarding properties of food by acting at specific mesolimbic areas in the brain. In the hypothalamus, CB1 receptors and endocannabinoids are integrated components of the networks controlling appetite and food intake. Interestingly, the endocannabinoid system was recently shown to control several metabolic functions by acting on peripheral tissues such as adipocytes, hepatocytes, the gastrointestinal tract, the skeletal muscles and the endocrine pancreas. The relevance of the system is further strengthened by the notion that visceral obesity seems to be a condition in which an overactivation of the endocannabinoid system occurs, and therefore drugs interfering with this overactivation by blocking CB1 receptors are considered as potentially valuable candidates for the treatment of obesity and related cardiometabolic risk factors. [source] Effects of altered plasma ,-1-acid glycoprotein levels on pharmacokinetics of some basic antibiotics in pigs: simulation analysisJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2001M. Kuroha Effects of altered plasma , -1-acid glycoprotein (AGP) levels on pharmacokinetic parameters of basic antimicrobials, erythromycin (EM), lincomycin (LM) and clindamycin (CM) were evaluated in pigs by simulation analysis. Intravenous (i.v.) injections of EM, LM and CM were performed to obtain pharmacokinetic parameters in healthy conditions. Binding parameters were obtained from an in vitro study using ultrafiltration. Simulation studies indicated that an increase of plasma AGP levels resulted in a decrease of both volume of distribution at steady state (Vdss) and total body clearance (Cltot) for all the drugs. Elimination rate constant for LM was almost unchanged by an increase of plasma AGP levels, whereas those for EM and CM were increased. Plasma concentration,time profiles at a high AGP level (often observed in pathophysiological conditions) were also simulated. All of the total plasma concentration,time profiles were different from those at normal AGP level. The differences were characterized by a higher initial concentration with faster or similar elimination. Unbound plasma concentration,time profile of LM was unaffected by AGP levels, whereas EM and CM were eliminated from plasma more rapidly at high AGP level. These results suggested that adjustment of dosage regimen of EM and CM is required in pathophysiological conditions, but that of LM is not required. [source] 4-Hydroxynonenal: A membrane lipid oxidation product of medicinal interestMEDICINAL RESEARCH REVIEWS, Issue 4 2008G. Poli Abstract A comprehensive focus on 4-hydroxynonenal (HNE) as candidate molecule in a variety of pathophysiological conditions occurring in humans is here provided. Despite an active, now well characterized, metabolism in most cells and tissues, HNE can be easily detected and quantified by means of several methods, although with different sensitivity. Measurements of HNE and/or stable metabolites in biological fluids are already applied as lipid peroxidation/oxidative stress markers in a huge number of human disease processes, often sustained by inflammatory reactions. A primary involvement of this aldehydic product of membrane lipid oxidation in inflammation-related events, as well as in regulation of cell proliferation and growth, in necrotic or apoptotic cell death, appears supported by its marked ability to modulate several major pathways of cell signaling and, consequently, gene expression. The actual knowledge of HNE reactivity, metabolism, signaling and modulatory effect in the various human organs should provide a solid background to the investigation of the aldehyde's contribution to the pathogenesis of human major chronic diseases and would likely promote advanced and oriented applications not only in diagnosis and prevention but also in molecular treatment of human diseases. © 2007 Wiley Periodicals, Inc. Med Res Rev, 28, No. 4, 569,631, 2008 [source] Cysteinyl-leukotrienes and their receptors in asthma and other inflammatory diseases: Critical update and emerging trendsMEDICINAL RESEARCH REVIEWS, Issue 4 2007Valérie Capra Abstract Cysteinyl-leukotrienes (cysteinyl-LTs), that is, LTC4, LTD4, and LTE4, trigger contractile and inflammatory responses through the specific interaction with G protein-coupled receptors (GPCRs) belonging to the purine receptor cluster of the rhodopsin family, and identified as CysLT receptors (CysLTRs). Cysteinyl-LTs have a clear role in pathophysiological conditions such as asthma and allergic rhinitis (AR), and have been implicated in other inflammatory conditions including cardiovascular diseases, cancer, atopic dermatitis, and urticaria. Molecular cloning of human CysLT1R and CysLT2R subtypes has confirmed most of the previous pharmacological characterization and identified distinct expression patterns only partially overlapping. Interestingly, recent data provide evidence for the immunomodulation of CysLTR expression, the existence of additional receptor subtypes, and of an intracellular pool of CysLTRs that may have roles different from those of plasma membrane receptors. Furthermore, genetic variants have been identified for the CysLTRs that may interact to confer risk for atopy. Finally, a crosstalk between the cysteinyl-LT and the purine systems is being delineated. This review will summarize and attempt to integrate recent data derived from studies on the molecular pharmacology and pharmacogenetics of CysLTRs, and will consider the therapeutic opportunities arising from the new roles suggested for cysteinyl-LTs and their receptors. © 2006 Wiley Periodicals, Inc. Med Res Rev, 27, No. 4, 469,527, 2007 [source] Nitrogen isotopic composition in hair protein is different in liver cirrhotic patientsRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 19 2006Klaus J. Petzke The stable-isotopic composition of nitrogen (,15N) or carbon (,13C) of body tissues depends on the isotopic composition of food sources and on shifts due to isotopic fractionation during metabolism. As little is known about the effects of pathophysiological conditions we measured ,15N and ,13C values in hair and hair amino acids of patients with cirrhosis (n,=,21) and compared the results with those of healthy subjects (n,=,100) randomly selected from the 1987,1988 VERA German nutrition survey population. Cirrhosis was reflected in lower hair 15N abundances (6.7 vs. 9.9, ,15N; P <0.001) whereas hair 13C abundances did not differ from healthy subjects (,19.4 vs. ,19.6, ,13C). Distinct patterns of ,15N and ,13C values were measured in hair amino acids. The ,15N values of phenylalanine were significantly higher in cirrhotics (P,<,0.001). With the exception of isoleucine, threonine, and proline all other measured amino acids showed lower ,15N values than healthy subjects (P,<,0.001). Lower hair ,15N values were associated with cirrhotic liver disease which suggests that under this condition the altered liver amino acid metabolism affects the nitrogen isotopic composition of the amino acids used for hair protein synthesis. It remains to be determined in controlled studies whether the altered nitrogen isotopic composition directly reflects the pathophysiological condition or is related to differences in dietary protein intake from plant or animal food sources. Copyright © 2006 John Wiley & Sons, Ltd. [source] IL-6, but not IL-4, stimulates chemokinesis and TNF stimulates chemotaxis of tissue mast cells: involvement of both mitogen-activated protein kinases and phosphatidylinositol 3-kinase signalling pathwaysAPMIS, Issue 8 2009ANNA MISIAK-T, OCZEK Misiak-T,oczek A, Brzezi,ska-B,aszczyk E. IL-6, but not IL-4, stimulates chemokinesis and TNF stimulates chemotaxis of tissue mast cells: Involvement of both mitogen-activated protein kinases and phosphatidylinositol 3-kinase signalling pathways. APMIS 2009; 117: 558,67. An increase in the number of mast cells within tissues is observed in many pathophysiological conditions. Current data indicate that migration of mature mast cells might be one of the key mechanisms responsible for rapid local accumulation of these cells. Considering that interleukin (IL)-6 and IL-4, as well as tumour necrosis factor (TNF), influence mast cell activity in various ways, the purpose of the current study was to examine whether these cytokines function as rat peritoneal mast cell chemoattractants. We showed that IL-4, in the concentration range from 10,6 to 10,3 ng/ml, did not induce a mast cell migratory response, even in the presence of laminin and fibronectin. Under the same experimental conditions, mast cells were shown to migrate in response to IL-6 stimulation in the presence of laminin. The optimal concentration of IL-6 for maximal migration of mast cells was 10,4 ng/ml (i.e. ,5 nM). In comparison, the optimal concentration of TNF for maximal migration of mast cells was 5 × 10,5 ng/ml (i.e. ,3 fM). IL-6-stimulated mast cell migration was the result of chemokinesis, whereas TNF-induced migration was the result of chemotaxis. Mast cell migratory responses to IL-6 and TNF were entirely blocked by specific anti-IL-6R and anti-TNFR1 antibodies. We also documented that the migration response of mast cells to stimulation with IL-6 and TNF was mediated through signal transduction pathways involving mitogen-activated protein kinases and phosphatidylinositol 3-kinase. Taken together, our results indicate that IL-6, as well as TNF, induces tissue mast cell migration. Thus, these proinflammatory cytokines can be responsible for mast cell accumulation at the site of diverse conditions accompanied by inflammation. [source] A Novel Subcutaneous Counterpulsation Device: Acute Hemodynamic Efficacy During Pharmacologically Induced Hypertension, Hypotension, and Heart FailureARTIFICIAL ORGANS, Issue 7 2010Carlo R. Bartoli Abstract The miniaturization of mechanical assist devices and less invasive implantation techniques may lead to earlier intervention in patients with heart failure. As such, we evaluated the effectiveness of a novel, minimally invasive, implantable counterpulsation device (CPD) in augmenting cardiac function during impaired hemodynamics. We compared the efficacy of a 32-mL stroke volume CPD with a standard 40-mL intra-aortic balloon pump (IABP) over a range of clinically relevant pathophysiological conditions. Male calves were instrumented via thoracotomy, the CPD was anastomosed to the left carotid artery, and the IABP was positioned in the descending aorta. Hemodynamic conditions of hypertension, hypotension, and heart failure were pharmacologically simulated and data were recorded during CPD and IABP support (off, 1:2, 1:1 modes) for each condition. In all three pathophysiological conditions, the CPD and IABP produced similar and statistically significant (P < 0.05) increases in coronary artery blood flow normalized to the left ventricular (LV) workload. During hypotension and heart failure conditions, however, the CPD produced significantly greater reductions in LV workload and myocardial oxygen consumption as compared with the IABP. A novel 32-mL CPD connected to a peripheral artery produced equivalent or greater hemodynamic benefits than a standard 40-mL IABP during pharmacologically induced hypertension, hypotension, and heart failure conditions. [source] Evaluation of GSH adducts of adrenaline in biological samplesBIOMEDICAL CHROMATOGRAPHY, Issue 7 2007Renata Silva Abstract The sustained high release of catecholamines to circulation is a deleterious condition that may induce toxicity, which seems to be partially related to the products formed by oxidation of catecholamines that can be further conjugated with glutathione (GSH). The aim of the present study was to develop a method for the determination of GSH adducts of adrenaline in biological samples. Two position isomers of the glutathion-S-yl-adrenaline were synthesized and characterized by HPLC using diode array, coulometric and mass detectors. A method for the extraction of these adducts from human plasma was also developed, based on adsorption to activated alumina, which showed adequate recoveries and proved to be crucial in removing interferences from plasma. The selectivity, precision and linearity of the method were all within the accepted values for these parameters. Furthermore, the sensitivity of this method allows the detection of adduct amounts that are within the range of the expected concentrations for these adducts under certain pathophysiological conditions and/or drug treatments. In conclusion, the development of this method allows the direct analysis of GSH adducts of adrenaline in human plasma, providing a valuable tool for the study of the catecholamine oxidation process and its related toxicity. Copyright © 2007 John Wiley & Sons, Ltd. [source] From 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] On the Way to Selective PARP-2 Inhibitors.CHEMMEDCHEM, Issue 6 2008Design, Preliminary Evaluation of a Series of Isoquinolinone Derivatives, Synthesis Abstract PARP-1 and PARP-2 are members of the family of poly(ADP-ribose)polymerases, which are involved in the maintenance of genomic integrity under conditions of genotoxic stimuli. The different roles of the two isoforms under pathophysiological conditions have not yet been fully clarified, and this is partially due to the lack of selective inhibitors. We report herein the synthesis and preliminary pharmacological evaluation of a large series of isoquinolinone derivatives as PARP-1/PARP-2 inhibitors. Among them, we identified the 5-benzoyloxyisoquinolin-1(2,H)-one derivative as the most selective PARP-2 inhibitor reported so far, with a PARP-2/PARP-1 selectivity index greater than 60. [source] THE ,BODY FLUID PRESSURE CONTROL SYSTEM' RELIES ON THE RENIN,ANGIOTENSIN,ALDOSTERONE SYSTEM: BALANCE STUDIES IN FREELY MOVING DOGSCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 5-6 2005Erdmann Seeliger SUMMARY 1.,The physiological role of the ,renal body fluid pressure control system', including the intrarenal mechanism of ,pressure natriuresis', is uncertain. 2.,Balance studies in freely moving dogs address the following questions: (i) what is the physiological contribution of pressure natriuresis to the control of total body sodium (TBS); (ii) to what extent is long-term mean arterial blood pressure (MABP) determined by TBS and total body water (TBW); and (iii) during Na accumulation, is Na stored in an osmotically inactive form? 3.,Diurnal time-courses of Na excretion (UNaV) and MABP reveal no correlation. Spontaneous MABP changes do not affect UNaV. The long-term 20% reduction of renal perfusion pressure (RPP) results in Na retention via pressure-dependent stimulation of the renin,angiotensin,aldosterone system (RAAS), not via a pressure natriuresis mechanism. Prevention of pressure natriuresis does not result in ongoing Na retention when the RAAS is operative. The long-term 20% elevation of RPP induced by sustained TBS elevation facilitates Na excretion via pressure natriuresis, but does not restore TBS to normal. 4.,Changes in TBW correlate well with changes in TBS (r2 = 0.79). This correlation is even closer when concomitant changes in total body potassium are also considered (r2 = 0.91). 5.,With normal or elevated TBW, long-term MABP changes correlate well with TBW changes (r2 = 0.69). At lowered TBW, no correlation is found. 6.,In conclusion, the physiological role of pressure natriuresis is limited. Pressure natriuresis does not appear to be operative when RPP is changed from ,20 to +10% and neurohumoral control of UNaV is unimpeded. Within this range, pressure-dependent changes in the RAAS mediate the effects of changes in RPP on UNaV. Pressure natriuresis may constitute a compensating mechanism under pathophysiological conditions of substantial elevation of RPP. A large portion of the long-term changes in MABP are attributable to changes in TBW. The notion of osmotically inactive Na storage during Na accumulation appears to be invalid. [source] Functional Roles Of KATP Channels In Vascular Smooth MuscleCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 4 2002Joseph E Brayden SUMMARY 1. ATP-sensitive potassium channels (KATP) are present in vascular smooth muscle cells and play important roles in the vascular responses to a variety of pharmacological and endogenous vasodilators. 2. The KATP channels are composed of four inwardly rectifying K+ channel subunits and four regulatory sulphonylurea receptors. The KATP channels are inhibited by intracellular ATP and by sulphonylurea agents. 3. Pharmacological vasodilators such as cromakalim, pinacidil and diazoxide directly activate KATP channels. The associated membrane hyperpolarization closes voltage-dependent Ca2+ channels, which leads to a reduction in intracellular Ca2+ and vasodilation. 4. Endogenous vasodilators such as calcitonin gene-related peptide, vasoactive intestinal polypeptide, prostacylin and adenosine activate KATP by stimulating the formation of cAMP and increasing the activity of protein kinase A. Part of the mechanism of contraction of endogenous vasoconstrictors is due to inhibition of KATP channels. 5. The KATP channels appear to be tonically active in some vascular beds and contribute to the physiological regulation of vascular tone and blood flow. These channels also are activated under pathophysiological conditions, such as hypoxia, ischaemia, acidosis and septic shock, and, in these disease states, may play an important role in the regulation of tissue perfusion. [source] | ||||||||||||||||