Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An acute inflammatory response begins during the reperfusion phase following an ischemic insult in which polymorphonuclear neutrophils (PMNs) play an important role and the release of reactive oxygen species (ROS) causes further damage and a reduction in endogenous antioxidant storage. The ability of butylated hydroxyanisole (BHA) and some phenolic, aliphatic and aromatic BHA derivatives to reduce the human PMN oxidative burst evoked by particulate (Candida albicans and zymosan) or soluble stimulants [N-formyl-methionyl-leucyl-phenylalanine (fMLP) and phorbol myristate acetate (PMA)] was investigated using luminol-amplified chemiluminescence. BHA and the derivative dt-BHA [3,5-di-t-butyl-4-hydroxyanisole] significantly reduced the PMN oxidative burst at concentrations ranging from 5 x 10(-6) to 5 x 10(-5) mol/l for C. albicans stimulation, while for zymosan stimulation, reduction was seen at concentrations ranging from 5 x 10(-6) to 5 x 10(-5) mol/l for BHA, and at concentrations ranging from 5 x 10(-7) to 5 x 10(-5) mol/l for dt-BHA, with dt-BHA being the most active. Another BHA derivative, Bu GAM 1, was active at 5 x 10(-5) mol/l for C. albicans and at 5 x 10(-6) to 5 x 10(-5) mol/l for zymosan. The findings obtained with fMLP and PMA were very similar to those previously reported. ROS release is related to PMN killing activity, but the inhibition of the PMN oxidative burst induced by BHA and BHA derivatives did not significantly modify PMN phagocytosis or killing. It has recently been observed that dt-BHA has a spasmolytic action by inhibiting the influx of Ca(2+) into cells through L-type Ca(2+) channels, which means that a single molecule is capable of counteracting two major steps in the sequence of events triggered by ischemia-reperfusion injury, i.e. free radical release and Ca(2+) overload.
 ...
PMID:Effect of butylated hydroxyanisole and some of its derivatives on human neutrophil oxidative burst: chemiluminescence evaluation. 1266 Apr 74

1. Bradykinin (BK) appears to play an important role in the development and maintenance of inflammation. Here, we assessed the role of the BK B(2) receptor for the injuries that occur after ischemia and reperfusion (I/R) of the territory irrigated by the superior mesenteric artery. 2. Tissue (lung and duodenum) kallikrein activity increased after ischemia with greater enhancement after reperfusion. A selective inhibitor of tissue kallikrein, Phenylacetyl-Phe-Ser-Arg-N-(2,3-dinitrophenyl)-ethylenediamine (TKI, 0.001-10 mg ml(-1)), inhibited kallikrein activity in a concentration-dependent manner in vitro. In vivo, pretreatment with TKI (30 mg kg(-1)) prevented the extravasation of plasma and the recruitment of neutrophils. 3. Similarly, the bradykinin B(2) receptor antagonists, HOE 140 (0.01-1.0 mg kg(-1)) or FR173657 (10.0 mg kg(-1)), inhibited reperfusion-induced increases in vascular permeability and the recruitment of neutrophils in the intestine and lungs. 4. In a model of more severe I/R injury, HOE 140 (1.0 mg kg(-1)) inhibited the increase in vascular permeability, neutrophil recruitment, haemorrhage and tissue pathology. Furthermore, HOE 140 significantly inhibited the elevations of TNF-alpha in tissue and serum and partially prevented lethality. This was associated with an increase in the concentrations of IL-10 in tissue and serum. 5. Thus, our results demonstrate that, following intestinal I/R injury, there is an increase in tissue kallikrein activity and activation of BK B(2) receptors. B(2) receptor activation is essential for the development of inflammatory tissue injury and lethality. These results contrast with those of others showing that BK mostly exerts a protective role during I/R injury.
 ...
PMID:Role of the bradykinin B2 receptor for the local and systemic inflammatory response that follows severe reperfusion injury. 1274 31

Alterations in the composition of the glycocalyx of venular endothelium in postcapillary venules (rat mesentery) were explored in models of inflammation and ischemia-reperfusion injury. Lectins were covalently linked to fluorescently labeled microspheres (0.1-microm diameter) or directly labeled with FITC. Adhesion of lectins specific for glucose and galactose residues of glycosaminoglycans (GAGs) and other components of the endothelial glycocalyx decreased dramatically after superfusion of the mesentery with the chemoattractant N-formylmethionyl-leucyl-phenylalanine and during reperfusion after 60-min ischemia. These reductions were significantly attenuated by superfusion with pertussis toxin (PTX), suggesting that shedding of glycocalyx was mediated by G proteins. Adhesion of microspheres linked with antibody for syndecan-1, a major proteoglycan to which GAGs are bound, revealed increased labeling as GAGs were lost and permitted greater numbers of spheres to adhere to the protein core, which was not shed. Induction of ischemia by occluding proximal microvessels for 60 min resulted in a 40% increase in galactosaminoglycans and a 15% increase in glucosaminoglycans on the endothelium, which was not inhibited by PTX. Reperfusion of vessels led to a rapid loss of GAGs that was inhibited by pretreatment with PTX, with 40% of galactosaminoglycans and 25% of glucosaminoglycans accumulated being removed by G protein-mediated shedding and the remainder freely convected away by fluid shear. We conclude that the composition of the glycocalyx results from a balance of the rate of biosynthesis of GAGs by the endothelial cell and their shedding, which may be mediated by intracellular and/or membrane-bound proteases or lyases released or activated by G protein signaling.
 ...
PMID:Inflammation- and ischemia-induced shedding of venular glycocalyx. 1470 29

Our aim was to examine two aspects of polymorphonuclear leukocyte (PMN) rheology (membrane fluidity and cytosolic Ca2+ content), at baseline and after in vitro activation, in a group of young adults with acute myocardial infarction (AMI) at the initial stage and after 12 months. We enrolled 21 AMI subjects aged < or = 45 years (mean age 41.1 +/- 3.5 years) and evaluated PMN membrane fluidity, labelling intact PMN cells with the fluorescent probe 1,4-(trimethylamino)-phenyl-4-phenylhexatriene and the PMN cytosolic Ca2+ content marking PMN cells with the fluorescent probe Fura 2-AM, at baseline and after in vitro activation with 4-phorbol 12-myristate 13-acetate (PMA) and N-formyl-methionyl-leucyl-phenylalanine (fMLP). During the initial stage PMN membrane fluidity and cytosolic Ca2+ content did not distinguish AMI patients from control subjects; after 12 months, when compared with the initial stage, PMN cytosolic Ca2+ content was significantly increased. In vitro PMN activation with PMA and fMLP caused no variation of the two PMN parameters in control subjects, while in AMI patients membrane fluidity decreased and cytosolic Ca2+ content increased; the same behaviour pattern was observed after 12 months. The constant functional alteration of PMN cells in young AMI patients highlights the role of activated leukocytes as a component of the inflammatory reaction that follows ischemia.
 ...
PMID:Polymorphonuclear leukocyte membrane fluidity and cytosolic Ca(2+) content in young adults with acute myocardial infarction. Evaluation at the initial stage and after 12 months. 1527 52

Hydroxyl radical (.OH) is a reactive oxygen species produced during severe hypoxia, asphyxia, or ischemia that can cause cell death resulting in brain damage. Generation of .OH may occur in the fetal brain during asphyxia in utero. The very short half-life of .OH requires use of trapping agents such as salicylic acid or phenylalanine for detection, but their hydroxylated derivatives are either unstable, produced endogenously, or difficult to measure in the small volume of microdialysis samples. In the present study, we used terephthalic acid (TA), hydroxylation of which yields a stable and highly fluorometric isomer (excitation, 326 nm; emission, 432 nm). In vitro studies using .OH generated by the Fenton reaction showed that hydroxylated TA formed quickly (<10 s), was resistant to bleaching (<5% change in fluorescence), and permitted detection of <0.5 pmol .OH. In vivo studies were performed in fetal sheep using microdialysis probes implanted into the parasagittal cortex. The probe was perfused at 2 mul/min with artificial cerebrospinal fluid containing 5 mM TA, and samples were collected every 30 min. Fluorescence measured in 10 mul of dialysate was significantly greater than in the efflux from probes perfused without TA. High-performance liquid chromotography analysis showed that the fluorescence in dialysis samples was entirely due to hydroxylation of TA. Thus this study shows that it is possible to use TA as a trapping agent for detecting low concentrations of .OH both in vitro and in vivo and that low concentrations of .OH are present in fetal brain tissue and fluctuate with time.
 ...
PMID:Novel method for in vivo hydroxyl radical measurement by microdialysis in fetal sheep brain in utero. 1571 9

Ischemia followed by reperfusion (I/R) in the presence of polymorphonuclear leukocytes (PMNs) results in a marked cardiac contractile dysfunction. A cell-permeable protein kinase C (PKC) betaII peptide inhibitor was used to test the hypothesis that PKC betaII inhibition could attenuate PMN-induced cardiac dysfunction by suppression of superoxide production from PMNs and increase NO release from vascular endothelium. The effects of the PKC betaII peptide inhibitor were examined in isolated ischemic (20 min) and reperfused (45 min) rat hearts with PMNs. The PKC betaII inhibitor (10 microM; n = 7) significantly attenuated PMN-induced cardiac dysfunction compared with I/R hearts (n = 9) receiving PMNs alone in left ventricular developed pressure (LVDP) and the maximal rate of LVDP (+dP/dt(max)) cardiac function indices (p < 0.01). The PKC betaII inhibitor at 10 microM significantly increased endothelial NO release from a basal value of 1.85 +/- 0.18 pmol NO/mg tissue to 3.49 +/- 0.62 pmol NO/mg tissue from rat aorta. It also significantly inhibited superoxide release (i.e., absorbance) from N-formyl-L-methionyl-L-leucyl-L-phenylalanine-stimulated rat PMNs from 0.13 +/- 0.01 to 0.02 +/- 0.004 (p < 0.01) at 10 microM. Histological analysis of the left ventricle of representative rat hearts from each group showed that the PKC betaII peptide inhibitor-treated hearts experienced a marked reduction in PMN vascular adherence and infiltration into the postreperfused cardiac tissue compared with I/R + PMN hearts (p < 0.01). These results suggest that the PKC betaII peptide inhibitor attenuates PMN-induced post-I/R cardiac contractile dysfunction by increasing endothelial NO release and by inhibiting superoxide release from PMNs.
 ...
PMID:Protein kinase C betaII peptide inhibitor exerts cardioprotective effects in rat cardiac ischemia/reperfusion injury. 1587 97

The aim of the current study was to determine whether renal medullary oxygenation is independent of the level of cortical blood flow by testing responses to stimuli that selectively reduce blood flow in either the cortex or medulla. In anesthetized rabbits, renal arterial infusion of [Phe(2),Ile(3),Orn(8)]-vasopressin selectively reduced medullary perfusion and Po(2) (-54 +/- 24 and -50 +/- 10%, respectively) but did not significantly affect cortical perfusion or tissue oxygenation. In contrast, stimulation of the renal nerves resulted in renal cortical ischemia with reductions in total renal blood flow (-76 +/- 3% at 4 Hz), cortical perfusion (-57 +/- 17%), and cortical Po(2) (-44 +/- 12%). Medullary tissue Po(2) was reduced by -70 +/- 5% at 4 Hz, despite medullary perfusion being unaffected and distal tubular sodium reabsorption being reduced (by -83.3 +/- 1.2% from baseline). In anesthetized rats, in which renal perfusion pressure was maintained with an aortic constrictor, intravenous infusion of ANG II (0.5-5 microg. kg(-1).min(-1)) dose dependently reduced cortical perfusion (up to -65 +/- 3%; P < 0.001) and cortical Po(2) (up to -57 +/- 4%; P < 0.05). However, medullary perfusion was only significantly reduced at the highest dose (5 microg. kg(-1).min(-1); by 29 +/- 6%). Medullary perfusion was not reduced by 1 microg. kg(-1).min(-1) ANG II, but medullary Po(2) was significantly reduced (-12 +/- 4%). Thus, although cortical and medullary blood flow may be independently regulated, medullary oxygenation may be compromised during moderate to severe cortical ischemia even when medullary blood flow is maintained.
 ...
PMID:Renal medullary tissue oxygenation is dependent on both cortical and medullary blood flow. 1621 13

We have previously shown that 11 ent-kauranes isolated from the stems of Annona squamosa exhibited immunomodulating effects in leukocytes. In this study, a cellular model using isolated human neutrophils, which are important in the pathogenesis of rheumatoid arthritis, ischemia-reperfusion injury, chronic obstructive pulmonary disease, asthma and other inflammatory diseases, was established in order to elucidate the anti-inflammatory functions of 16beta,17-dihydroxy-ent-kauran-19-oic acid (1). Reactive oxygen species (ROS) and granule proteases produced by neutrophils contribute to the pathogenesis of inflammatory diseases. Compound 1 inhibited the generation of superoxide anion, the formation of ROS, and the release of elastase in formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP)-activated human neutrophils in a concentration-dependent manner with IC (50) values of 3.95 +/- 0.68, 12.20 +/- 2.16, and 12.52 +/- 2.26 microM, respectively. The anti-inflammatory actions were not attributable to cytotoxicity because incubation of the neutrophils with 1 did not result in lactate dehydrogenase release. Compound 1 did not display antioxidant or superoxide anion-scavenging activity. Furthermore, neither subcellular NADPH oxidase activity nor cAMP-dependent pathways were altered by 1. Compound 1 significantly inhibited rapid calcium release from internal calcium stores induced by FMLP but not by thapsigargin. In summary, the presented results indicate that the inhibitory effects of 1 on respiratory burst and degranulation of human neutrophils are through the inhibition of cytosolic calcium mobilization, but not via the cAMP-dependent pathways.
 ...
PMID:An anti-inflammatory ent-kaurane from the stems of Annona squamosa that inhibits various human neutrophil functions. 1625 20

Melanocortin peptides have been shown to produce neuroprotection in experimental ischemic stroke. The aim of the present investigation was to identify the therapeutic treatment window of melanocortins, and to determine whether these neuropeptides chronically protect against damage consequent to brain ischemia. A 10-min period of global cerebral ischemia in gerbils, induced by occluding both common carotid arteries, caused impairment in spatial learning and memory (Morris test: four sessions from 4 to 67 days after the ischemic episode), associated with neuronal death in the hippocampus. Treatment with a nanomolar dose (340 microg/kg i.p., every 12 h for 11 days) of the melanocortin analog [Nle(4), D-Phe(7)]alpha-melanocyte-stimulating hormone (NDP-alpha-MSH), starting 3-18 h after the ischemic episode, reduced hippocampal damage with improvement in subsequent functional recovery. The protective effect was long-lasting (67 days, at least) with all schedules of NDP-alpha-MSH treatment; however, in the latest treated (18 h) gerbils, some spatial memory deficits were detected. Pharmacological blockade of melanocortin MC(4) receptors prevented the protective effects of NDP-alpha-MSH. Our findings indicate that, in conditions of brain ischemia, melanocortins can provide strong and long-lasting protection with a broad therapeutic treatment window, and with involvement of melanocortin MC(4) receptors, 18 h being the approximately time-limit for stroke late treatment to be effective.
 ...
PMID:Broad therapeutic treatment window of [Nle(4), D-Phe(7)]alpha-melanocyte-stimulating hormone for long-lasting protection against ischemic stroke, in Mongolian gerbils. 1664

The impetus for the novel Energy Formula (EF) which combines the niacin-bound chromium (III) (0.45%) (NBC), standardized extract of Withania somnifera extracts (10.71%), caffeine (22.76%), D-ribose (10.71%) and selected amino acids such as phenylalanine, taurine and glutamine (55.37%) was based on the knowledge of the cardioprotective potentials of the Withania somnifera extract, caffeine and D-ribose as well as their abilities to increase energy levels and the abilities of amino acids to increase the muscle mass and energy levels. The effect of oral supplementation of EF on the safety, myocardial energy levels and cardioprotective ability were investigated in an ischemic-reperfused myocardium model in both male and female Sprague-Dawley rats over 90 days trial period. At the completion of 90 days, the EF-treated male and female rats gained 9.4% and 3.1% less body weights, respectively, as compared to their corresponding control groups. No significant difference was found in the levels of lipid peroxidation and activities of hepatic Aspartate transaminase, Alanine transaminase and Alkaline phosphatase in EF treatment when compared with control animals. The male and female rat hearts were subjected to 30 min of global ischemia followed by 2 h of reperfusion at 30 and 90 days of EF treatment. Cardiovascular functions including heart rate, coronary flow, aortic flow, dp/dt(max), left ventricular developed pressure (LVDP) and infarct size were monitored. The levels of myocardial adenosine triphosphate (ATP), creatine phosphate (CP), phospho-adenosine monophosphate kinase (p-AMPK) levels, were analyzed at the end of 30 and 90 days of treatment. Significant improvement was observed in all parameters in the EF treatment groups as compared to their corresponding controls. Thus the niacin-bound chromium (III) based energy formula is safe and effective supplement to boost energy levels and cardioprotection.
 ...
PMID:Enhanced cardiovascular function and energy level by a novel chromium (III)-supplement. 1701 64


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>