Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.2.1.36 (hyaluronidase)
 4,606 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to measure the protective effect of interventions following coronary artery occlusions in dogs, the creatine kinase activity of myocardial tissue was assayed after 24 h and related to the myocardial blood flow of that tissue measured with 85Sr labelled microspheres injected 15 min after occlusion. This assay showed normal levels when flow exceeded 50 cm3.min-1.100 g-1. In myocardium with flow reduced to 0 to 15 cm3. min-1.100g-1, creatine kinase activity was 7.6 +/- 0.6 IU.mg-1 protein in control dogs and 13.1 +/- 1.8 IU.mg-1 protein (P less than 0.01) in dogs given 500 NF units.kg-1 of hyaluronidase 20 min after occlusion. Where myocardial blood flow was reduced to 16 to 50 cm3. min-1. 100g-1, creatine kinase activity was increased from 14.1 +/- 1.1 to 20.5 +/- 1.4 IU.mg-1 protein by hyaluronidase. This method therefore assesses ischaemic damage independent of electrophysiological measurements and confirms myocardial preservation by hyaluronidase.
Cardiovasc Res 1978 Jun
PMID:A method for demonstrating the efficacy of interventions designed to limit infarct size following coronary occlusion: beneficial effect of hyaluronidase. 69 85

A study was carried out of a therapy supporting the anaerobic glycolysis and coronary perfusion of ischemic myocardium and preserving its potassium and magnesium contents, which consisted in combined administration of hyaluronidase, glucose, insulin, Tris, methoxamine, and potassium and magnesium aspartate. The drugs were administered to Beagle dogs between 30 minutes and 20 hours after the ligation of the left anterior descending coronary artery. The size of infarction was determined by the Nachlas method, which is based on the detection of activities of dehydrogenases in heart slices. Treated animals showed a reduced infarction size (p less than 0.001). The evidence of the favourable effect of the therapy used was brought also by hemodynamic measurements. The heart rate was slower (p less than 0.02) and the mean arterial blood pressure was higher (p less than 0.001) in treated animals than in control ones (as evaluated at the end of the experimental period). Significant correlation between the infarction size and the heart rate on the one hand and the mean arterial pressure on the other hand was found (r = 0.59, p less than 0.01; r=--0.47, p less than 0.05, respectively).
J Cardiovasc Surg (Torino)
PMID:Suppression of the progress of necrosis after coronary artery ligation in the dog by pharmacologic interventions. 93 74

The effects on the evolution of canine myocardial infarction (MI) of the lymphagogues hyaluronidase (hyaluronate glucanohydrolase) (known to reduce the size of MIs) and calcium dobesilate (calcium, 2,5-dihydroxybenzenesulfonate, CLS 2210) were compared in a coded, placebo-controlled study in 48 dogs, during the first 24 h after coronary occlusion. MI was induced by embolization of the anterior descending branch of the left coronary artery. The animals were given either a placebo, CLS 2210, or hyaluronidase by intravenous infusion begun immediately after embolization and continued for 24h. The volume of myocardial tissue at risk was evaluated at 2 and 24 h by ungated computed tomography (CT), and after necropsy by staining myocardial sections with triphenyl tetrazolium chloride (TTC). Electrocardiography and estimation of serum creatine kinase (CK) activity were also performed. In the 25 animals that survived 24 h, the results of all tests showed that there was less myocardial damage in the animals treated with the two lymphagogues than in those treated with placebo, and less damage with CLS 2210 than with hyaluronidase. The good correlation between the volume of ischemic tissue as assessed by CT in vivo and as assessed by TTC staining after necropsy (r = 0.959) confirms that the CT perfusion phase defect accurately reflects the volume of tissue at risk during the evolution of MI. This study has shown that CLS 2210 is at least as effective as hyaluronidase in reducing myocardial damage due to coronary artery occlusion in dogs.
J Cardiovasc Pharmacol 1990 Aug
PMID:Myocardial infarction treated with two lymphagogues, calcium dobesilate (CLS 2210) and hyaluronidase: a coded, placebo-controlled animal study. 169 85

In this article, data on mortality have been systematically reviewed from the randomized trials of intracoronary and intravenous (i.v.) thrombolytic therapy, hyaluronidase, i.v. nitrates, and calcium channel blockers in acute myocardial infarction (AMI). Such analyses confirm that i.v. streptokinase (SK) reduces short-term mortality by about 20%. Despite a higher incidence of reinfarction in the treated group, this early benefit is maintained long term. The excess reinfarction was observed whether or not SK was followed by anticoagulants or aspirin. The roles of pharmacologic interventions and percutaneous transluminal coronary angioplasty (PTCA) in preventing reinfarction and improving survival further are currently being evaluated. The pooled data from the existing trials of hyaluronidase and i.v. nitrates are consistent with a 20-30% reduction in mortality; ideally, these interventions should also be studied in future large randomized trials. Currently, there is no evidence either from individual studies or the aggregate of all the trials that calcium channel blockers reduce mortality. The collective experience from these trials conducted over the last two decades suggests that most interventions in AMI can at best have only moderate effects (10%, 20%, or at best 30%) on mortality. However, such modest effects produced by the widespread use of these agents could prevent several thousand premature deaths each years. Therefore, current and future trials that assess the effects of new or existing cardiovascular treatments on mortality should aim to randomize at least 10,000 average risk patients or a few thousand high risk patients.
J Cardiovasc Pharmacol 1988
PMID:An overview of the clinical trials of agents (other than beta-blockers) that potentially limit myocardial infarct size. 246 35

Ventricular cells from adult rats were isolated enzymatically and used as a model system for determining what factors affect the release of adenosine triphosphate (ATP) from myocardial cells. The enzyme systems used to isolate cells were trypsin:collagenase; hyaluronidase:collagenase and dispase:collagenase. Adenosine triphosphate was released in greater amounts in response to hypoxia from cells freed by each of the enzymatic procedures. This occurred while the intracellular concentration of ATP remained constant. Experiments were then performed to determine whether the conditions that occur during myocardial ischaemia or hypoxia altered the release of ATP. Cells suspended in either oxygenated or anoxic buffer at a pH of 6.8 released a significantly lower amount of ATP than cells suspended in either condition at pH 7.4. To test the possibility that ATP was released from nucleotide-protein-Ca2+ complexes located in the sarcolemma, artificial disruption of these structures was carried out. Incubation of oxygenated cells with the chelating agent, ethyleneglycol-bis (B-aminoethyl ether)-N, N-tetraacetic acid (EGTA), stimulated the release of ATP in a hyperbolic relationship while incubation of anoxic cells with ethylenediamine tetraacetate (EDTA) stimulated the release of ATP in such a way that the pattern of release followed a sigmoid response with maximal amounts of ATP, 995 +/- 55 pmol.mg-1 protein, occurring in the presence of 0.1 to 2.0 mmol.litre-1 EDTA. By incubating cells with radioactive EDTA, there was no indication that EDTA entered the cells. No release of ATP above control levels occurred when EDTA was chelated with Ca2+ before being applied to isolated cells. These data suggest that the source of ATP found extracellularly may have been nucleotide-protein-Ca2+ complexes located in the sarcolemma, and further support the role of ATP as a coronary vasodilator during hypoxic conditions.
Cardiovasc Res 1983 May
PMID:Possible source of adenosine triphosphate released from rat myocytes in response to hypoxia and acidosis. 641 42

The goals of this investigation were: 1) to examine the pattern of evolution of epicardial R wave voltage during the 24 h after experimental coronary artery occlusion; and 2) to determine whether hyaluronidase, an agent shown previously to reduce myocardial ischaemic injury, alters this evolution. Coronary artery occlusion was performed in 36 dogs. In the control dogs, the average R wave voltage (R) recorded over the ischaemic myocardium increased by 7.6 +/- 0.8 mV (P less than 0.001) from before to 15 min after coronary artery occlusion, then gradually returned to baseline over the ensuing 4 h. Subsequently, R wave voltage continued to fall, and 24 h after occlusion, R was 17.8 +/- 1.8 mV (P less than 0.001) less than before occlusion. In the hyaluronidase-treated dogs (500 NF units . kg-1), R recorded over the ischaemic myocardium increased similarly to the controls before hyaluronidase administration. However, in contrast to the control dogs, the administration of hyaluronidase 20 min after occlusion caused R to return to baseline over the ensuing 40 min and 24 h after occlusion, the treated animals lost significantly less R wave voltage than the controls (P less than 0.001).
Cardiovasc Res 1981 Aug
PMID:Evolution of epicardial R wave voltage following experimental coronary artery occlusion: effects of hyaluronidase. 730 26

Vascular endothelial cell (EC) wound healing was characterized on an EC-synthesized extracellular matrix (ECM) previously treated with enzymes and antibodies specific for ECM components. Using a computer-assisted video-microscope recording system capable of automatic EC recognition, we learned whether components of the EC-synthesized matrix influenced post-injury migration and wound healing in vitro. Localization of actin and its encoded mRNA using isoform-specific antibodies and labeled cDNA probes allowed for a direct correlation of living-cell behavior with cytoskeletal form and distribution. Results of these studies indicate that the computer-assisted EC tracking system allows for an automatic and reproducible analysis of EC behavior following injury in vitro. EC migrate fastest immediately following injury and then achieve a new, slower migration rate that is maintained until EC from one edge of 200- to 300-microns-wide wound zone contact EC from the other wound face. Treatment of EC-synthesized matrices with antibodies against fibronectin and laminin has no effect on EC migration following injury (-0.25 microns/min) or on cytoskeletal array. Similarly, digestion of these matrices with heparinase and hyaluronidase has no effect on wound healing rates. Slowly spreading EC cytoplasm, which borders the intact and antibody-treated EC matrices, is rich in actin but lacks myosin II. Two different preparations of collagenase (bacterial and mammalian) each potentiate EC wound healing in vitro. Bacterial collagenase treatment of the EC-synthesized matrices potentiates EC migration fivefold (1 micron/min) while treatment of EC-matrices with mammalian cell collagenase stimulates EC migration following injury some twofold (0.4 micron/min) over control values. Whereas EC on control matrices migrate in unison as a tissue-like sheet, EC on the collagenase-treated EC matrices migrate as individuals. Concomitant with the increased rates of migration following injury on the collagenase-treated EC-matrices is a two- to fourfold increase in the steady-state levels of beta-actin mRNA. This increase in actin mRNA abundance is observable by its preferential localization (seen by in situ hybridization) in the lamellae bordering the wound edge in association with beta-actin, which is exclusively localized there. Because beta-actin and its encoded mRNA are positioned together in association with the plasma membrane in regions of moving cytoplasm, it seems likely that beta-actin filament assembly is required for motility following endothelial injury.
J Cardiovasc Pharmacol 1993
PMID:Molecular mechanisms regulating the vascular endothelial cell motile response to injury. 752 70

Gene therapy is a therapeutic strategy in treating cardiovascular disease. Vein graft failure, the major limitation on coronary artery bypass surgery, may be amenable to gene approaches. Some studies describe gene therapies using functioning genes to prevent vein graft stenosis. Gene transfer efficiency remains a major issue. In this rabbit vein graft model, we studied gene delivery using a replication-deficit recombinant adenovirus to improve gene transfer efficiency into vein grafts. The adenovirus vector that contains the E.coli lacZ gene encoding beta gal was used because this vector is widely used and thought to be effective. Gene transfer was detected by X-gal staining. We hypothesized that dimethylsulfoxide and hyaluronidase, both drug delivery enhancers, would improve efficiency and that, in transfer to adventitia, direct injection would be more effective than dwelling. We studied 3 gene delivery methods to intima and media (controls, using dimethylsulfoxide and using hyaluronidase before transfection) and 2 delivery methods to adventitia (direct injection and dwelling). We used 6 rabbits per delivery method. X-gal stained positive cell rates were counted using light microscopy. Our findings indicate that (1) dimethylsulfoxide increased the efficiency of transfection to media and intima, (2) hyaluronidase increased intimal transfection efficiency, (3) direct injection to adventitia was more effective than dwelling. These findings suggest that in vein grafting, our methods are feasible for improving gene transfer efficiency.
Jpn J Thorac Cardiovasc Surg 1999 May
PMID:Study of gene delivery in a rabbit vein graft model. Improvement of the efficiency of gene transfer into vein grafts. 1040 67

Vascular integrity or the maintenance of blood vessel continuity is a fundamental process regulated, in part, by the endothelial glycocalyx and cell-cell junctions. Defects in endothelial barrier function are an initiating factor in several disease processes including atherosclerosis, ischemia/reperfusion, tumor angiogenesis, cancer metastasis, diabetes, sepsis and acute lung injury. The glycosaminoglycan, hyaluronan (HA), maintains vascular integrity through endothelial glycocalyx modulation, caveolin-enriched microdomain regulation and interaction with endothelial HA binding proteins. Certain disease states increase hyaluronidase activity and reactive oxygen species (ROS) generation which break down high molecular weight HA to low molecular weight fragments causing damage to the endothelial glycocalyx. Further, these HA fragments can activate specific HA binding proteins upregulated in vascular disease to promote actin cytoskeletal reorganization and inhibition of endothelial cell-cell contacts. This review focuses on the crucial role of HA in vascular integrity and how HA degradation promotes vascular barrier disruption.
Am J Cardiovasc Dis 2011
PMID:Hyaluronan regulation of vascular integrity. 2225 99