Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Wear characteristics of hybrid denture teeth, plastic denture teeth which were partially reinforced with metal, was evaluated. The plane specimens were made up with resin and metal. Light curing veneering resin, new metacolor, heat curing veneering resin, Mitel-OM and PMMA (Poly methyl methacrylate) were used for resin parts, while gallium containing filling alloy, silver alloy, palladium alloy and titanium containing chromium cobalt alloy were used for metal parts. The specimens were abraded by the rod specimens of palladium alloy with abrasion test machine. The wear depth and width were measured at 1, 5, 10 and 20 x 10(4) times of abrasion which stroke was 10 mm each. The specimens of heat cured veneering resin reinforced with chromium cobalt alloy showed the least wear loss while the specimens of PMMA reinforced with silver alloy did the most. The difference of wear ratio between light cured and heat cured veneering resin was not statistically significant.
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PMID:[The evaluation of wear resistance of hybrid denture teeth]. 213 14

To evaluate the perioperative outcomes and the immediate increases in size after patch closure, 140 carotid endarterectomies were randomized into one of three groups: direct no-patch closure, saphenous vein patch closure, and polytetrafluoroethylene patch closure. Seven patients (4.4%) experienced signs of cerebral ischemia in the immediate postoperative period. In three cases this was transient and reversible. In the other four reexploration was undertaken and carotid thrombosis was corrected by thrombectomy. The condition of one of these patients deteriorated to a permanent stroke, whereas the other patients made a complete recovery. Neurologic complications were more frequent in the no-patch group, but the differences between the groups were not significant. The incidence of perioperative internal carotid stenosis, aneurysmal dilatation, and other morphologic abnormalities was assessed in 131 intravenous digital subtraction angiograms taken before the patient was discharged from the hospital. Eight (17.0%) of the endarterectomies in the no-patch group were narrowed by 30% to 50% diameter stenosis, whereas none of the patched arteries had more than 30% stenosis. In contrast, dilatation of the common or internal carotid artery to more than twice the measured diameter was absent in non-patched arteries but was present in seven (17.0%) saphenous patch closures and four (9.23%) polytetrafluoroethylene patch closures. We conclude that patch closure after carotid endarterectomy is less likely to cause stenosis in the perioperative period. Poly-tetrafluoroethylene patches resist dilatation better than do saphenous vein patches and are less likely to become aneurysmal.
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PMID:Comparison of saphenous vein patch, polytetrafluoroethylene patch, and direct arteriotomy closure after carotid endarterectomy. Part I. Perioperative results. 270 21

Poly(ADP-ribose) synthetase (PARS) activation, a downstream event of nitric oxide (NO) neurotoxicity has been implicated in cerebral reperfusion injury. The aim of our study was to identify the trigger of PARS activation during stroke. Formation of poly(ADP-ribose) profoundly increased in the early phase of reperfusion. Poly(ADP-ribose) formation was attenuated in mice deficient for neuronal NO synthase (nNOS). We next tested in glioma cells whether NO, or peroxynitrite (a cytotoxic oxidant formed from NO and superoxide) is the actual trigger of PARS activation. Peroxynitrite, but not various NO donors, activated PARS and suppressed cellular viability in a PARS-dependent fashion. Thus, nNOS is responsible for PARS activation in stroke. PARS activation, however, is not a direct result of NO production, but it occurs via peroxynitrite formation.
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PMID:Role of peroxynitrite and neuronal nitric oxide synthase in the activation of poly(ADP-ribose) synthetase in a murine model of cerebral ischemia-reperfusion. 966 59

This overviews recent understanding of the mechanisms of apoptosis on ischemia-induced neuronal cell death. Apoptosis is a prominent feature of the developing nervous system. Several lines of evidence suggest that apoptosis is also an important mechanism of cell death in adult brain in acute or chronic diseases such as stroke and Alzheimer's disease. In animal models of stroke, markers of apoptosis such as cytoplasmic and nuclear condensation and DNA fragmentation appear in neurons. A variety of physiological and pathological stimuli can activate signal-transduction pathways that result in the sequential proteolytic activation of caspase family members. The activation of caspases can be inhibited by several molecules, including peptide aldehydes (caspase-1 and or caspase-3 inhibitors) and crmA that target the active-site cysteine of caspase family members, Bcl-2, IAP (inhibitor of apoptosis protein) and NAIP (neuronal apoptosis inhibitory protein). Once activated, caspase-1 protease can activate the caspase family members and hydrolyze a discrete set of cellular targets. Poly (ADP-ribose)polymerase (PARP), which appears to facilitate apoptosis, was recognized as a substrate of activated caspase-3. These results suggest that caspase family, bcl-2 family, IAP family and substrates such PARP contribute to mechanisms of cell death in ischemic brain injury. Inhibition of the caspase family, particularly by non-peptide inhibitors that cross the blood-brain barrier and easily penetrate neurons and glia, could provide novel treatments for stroke and other forms of brain and spinal cord injury in humans.
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PMID:[Involvement of caspase on apoptosis in ischemia-induced neuronal cell death: usefulness of caspase inhibitors for stroke therapy]. 1020 84

Poly (ADP-ribose) polymerase (PARP) is a nuclear enzyme that is activated by DNA strand breaks to participate in DNA repair. Excessive activation of PARP, however, can deplete tissue stores of nicotinamide adenine dinucleotide (NAD), the PARP substrate which, with the resultant depletion of ATP, leads to cell death. In many cases of CNS damage, for example vascular stroke, nitric oxide release is a key stimulus to DNA damage and PARP activation. In conditions as diverse as focal cerebral ischaemia, myocardial infarction and toxin-induced diabetes, PARP inhibitors and PARP gene deletion afford dramatic protection from tissue damage. Accordingly, PARP inhibitors could provide novel therapeutic approaches in a wide range of clinical disorders.
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PMID:Poly (ADP-ribose) polymerase, nitric oxide and cell death. 1032 3

Poly(ADP-ribose) synthase (PARS), an abundant nuclear protein, has been described as an important candidate for mediation of neurotoxicity by nitric oxide. However, in cerebral ischemia, excessive PARS activation may lead to energy depletion and exacerbation of neuronal damage. We examined the effect of inhibiting PARS on the (a) degree of cerebral injury, (b) process of inflammatory responses, and (c) functional outcomes in a neonatal rat model of focal ischemia. We demonstrate that administration of 3-aminobenzamide, a PARS inhibitor, leads to a significant reduction of infarct volume: 63 +/- 2 (untreated) versus 28 +/- 4 mm(3) (treated). The neuroprotective effects currently observed 48 h postischemia hold up at 7 and 17 days of survival time and attenuate neurological dysfunction. Inhibition of PARS activity, demonstrated by a reduction in poly(ADP-ribose) polymer formation, also reduces neutrophil recruitment and levels of nitrotyrosine, an indicator of peroxynitrite generation. Taken together, our results demonstrate that PARS inhibition reduces ischemic damage and local inflammation associated with reperfusion and may be of interest for the treatment of neonatal stroke.
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PMID:Poly(ADP-ribose) synthase inhibition reduces ischemic injury and inflammation in neonatal rat brain. 1082 Feb 12

Poly(ADP-ribose) polymerases (PARPs) are defined as cell signaling enzymes that catalyze the transfer of ADP-ribose units from NAD(+)to a number of acceptor proteins. PARP-1, the best characterized member of the PARP family, that presently includes six members, is an abundant nuclear enzyme implicated in cellular responses to DNA injury provoked by genotoxic stress (oxygen radicals, ionizing radiations and monofunctional alkylating agents). Due to its involvement either in DNA repair or in cell death, PARP-1 is regarded as a double-edged regulator of cellular functions. In fact, when the DNA damage is moderate, PARP-1 participates in the DNA repair process. Conversely, in the case of massive DNA injury, elevated PARP-1 activation leads to rapid NAD(+)/ATP consumption and cell death by necrosis. Excessive PARP-1 activity has been implicated in the pathogenesis of numerous clinical conditions such as stroke, myocardial infarction, shock, diabetes and neurodegenerative disorders. PARP-1 could therefore be considered as a potential target for the development of pharmacological strategies to enhance the antitumor efficacy of radio- and chemotherapy or to treat a number of clinical conditions characterized by oxidative or NO-induced stress and consequent PARP-1 activation. Moreover, the discovery of novel functions for the multiple members of the PARP family might lead in the future to additional clinical indications for PARP inhibitors.
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PMID:Potential clinical applications of poly(ADP-ribose) polymerase (PARP) inhibitors. 1184 17

Poly(ADP-ribose) polymerase-1 (PARP-1) is a member of the PARP enzyme family consisting of PARP-1 and several recently identified novel poly(ADP-ribosylating) enzymes. PARP-1 is an abundant nuclear protein functioning as a DNA nick-sensor enzyme. Upon binding to DNA breaks, activated PARP cleaves NAD(+) into nicotinamide and ADP-ribose and polymerizes the latter onto nuclear acceptor proteins including histones, transcription factors, and PARP itself. Poly(ADP-ribosylation) contributes to DNA repair and to the maintenance of genomic stability. On the other hand, oxidative stress-induced overactivation of PARP consumes NAD(+) and consequently ATP, culminating in cell dysfunction or necrosis. This cellular suicide mechanism has been implicated in the pathomechanism of stroke, myocardial ischemia, diabetes, diabetes-associated cardiovascular dysfunction, shock, traumatic central nervous system injury, arthritis, colitis, allergic encephalomyelitis, and various other forms of inflammation. PARP has also been shown to associate with and regulate the function of several transcription factors. Of special interest is the enhancement by PARP of nuclear factor kappa B-mediated transcription, which plays a central role in the expression of inflammatory cytokines, chemokines, adhesion molecules, and inflammatory mediators. Herein we review the double-edged sword roles of PARP in DNA damage signaling and cell death and summarize the underlying mechanisms of the anti-inflammatory effects of PARP inhibitors. Moreover, we discuss the potential use of PARP inhibitors as anticancer agents, radiosensitizers, and antiviral agents.
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PMID:The therapeutic potential of poly(ADP-ribose) polymerase inhibitors. 1222 30

Poly(ADP-ribose) polymerase-1 (PARP-1) is the principal member of the PARP enzyme family consisting of PARP-1 and several recently identified novel poly(ADP-ribosyl)ating enzymes. PARP-1 functions as a DNA damage sensor and signalling molecule. Upon binding to DNA breaks, activated PARP cleaves NAD(+) into nicotinamide and ADP-ribose and polymerizes the latter onto nuclear acceptor proteins including histones, transcription factors and PARP itself. This Poly(ADP-ribosyl)ation contributes to inflammatory signal transduction processes. In addition, oxidative stress-induced overactivation of PARP consumes NAD(+) and consequently ATP, culminating in cell dysfunction or necrosis. Activation of PARP has been implicated in the pathogenesis of stroke, myocardial ischemia, diabetes, diabetes-associated cardiovascular dysfunction, shock, traumatic central nervous system injury, arthritis, colitis, allergic encephalomyelitis and various other forms of inflammation. Therefore, inhibition of PARP by pharmacological agents may prove useful for the therapy of these diseases, as has been shown in preclinical animal models. Moreover, PARP inhibitors may have additional, potential utility as anticancer agents, radiosensitizers and antiviral agents. In the present article we overview the structures and pharmacological actions of various pharmacological classes of compounds which inhibit the catalytic activity of PARP.
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PMID:Poly(ADP-ribose) polymerase inhibitors. 1257 Jul 5

Poly (ADP-ribose) polymerase-1 (PARP-1)-deficient mice are protected against septic shock, type I diabetes, stroke and inflammation. It is now accepted that inflammation and related events, such as activation of NF-kappaB, are key components in the initiation and progression of epithelial cancer and in particular in the neoplastic transformation of keratinocytes and skin carcinogenesis. Here, we report that PARP-1-deficient mice display a strikingly reduced susceptibility to skin carcinogenesis. In parp-1(-/-) mice, development of papilloma-like premalignant lesions induced with DMBA and TPA, is strongly delayed and the final number of tumor-bearing mice and total tumor number were significantly reduced. In addition, epidermis of parp-1(-/-) mice did not show increased proliferation rates after treatment with carcinogen. Deregulated NF-kappaB is a hallmark for tumorigenesis together with the concomitant release of early inflammatory mediators. In the absence of PARP-1, NF-kappaB activation and induction kappaB-target genes did not take place during the promotion of tumor development. These results suggest that PARP-1 abolition impairs the promotion of skin carcinogenesis interfering with the activation of NF-kappaB and might have an important implication in targeting PARP-1 as a new antineoplastic therapeutic approach.
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PMID:Crosstalk between PARP-1 and NF-kappaB modulates the promotion of skin neoplasia. 1507 72


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