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

During the past decade, efforts to limit the extent of myocardium exhibiting infarction once ischemia has been initiated have focused on manipulation of myocardial oxygen supply and demand as well as the process of injury itself. Interventions of promise range from the conventional, moderate increase in inspired oxygen content, to administration of hyaluronidase or intracoronary thrombolysis to augment oxygen supply; use of beta-adrenergic blocking drugs and nitroglycerin to diminish demand; and administration of calcium antagonists and prostaglandin synthesis inhibitors to limit the injury process. The ultimate effects on infarct size and long-term mortality have yet to be established unequivocally for any of these approaches in the clinical setting of acute myocardial infarction, but significant preservation of ischemic myocardium with hypothermia and with administration of nifedipine during coronary-artery bypass surgery have been documented. Several prospective, large-scale, blinded, and random sample selection clinical trials are currently in progress. Their results should definitively elucidate the clinical utility of specific interventions under defined conditions and should help to further improve the management of patients with ischemic heart disease.
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PMID:Pharmacological salvage of myocardium. 612 93

There is now evidence that infarct size in man can be reduced by early treatment and that some cases of threatened infarction can be aborted. Beta blockade, given intravenously within about 6-8 hours after the onset of pain can reduce infarct size and abort some infarctions. So far we have no conclusive data on mortality. Beta blockers may act by a number of mechanisms, namely reduction of cardiac contractility, heart rate and blood pressure thus reducing cardiac work and oxygen requirement, prevention of cardiac rupture by the same mechanism, and by an early effect on R on T ectopic beats and hence serious ventricular arrhythmia. Early myocardial revascularization either by coronary graft, percutaneous angioplasty or intracoronary streptokinase are all promising but so far unproven by adequate clinical trial. Randomized trials suggest that intravenous streptokinase may be effective and hyaluronidase appears promising, possibly by promotion of collateral vessel flow. Calcium channel blockade may also be helpful and there are some early studies which support this. Lowering work by sodium nitroprusside also reduces infarct size. Heparin may have a place in the treatment of threatened infarction. After recovery it now appears established that beta 1-blockade will lower mortality. We do not know how long this effect persists. Other agents are less well established perhaps because the trials have been too small. Anticoagulants may have a place but their use is not widespread. Anti-platelet agents are also controversial. Studies of dipyridamole and sulphinpyrazone have been suggestive but not conclusive; the studies of aspirin are moderately encouraging, when all trials are pooled. Anti-arrhythmic therapy after infarction has been disappointing, with the exception of beta blockade. Perhaps more emphasis should also be put upon changes in lifestyle, notably stopping smoking, reduction of fat intake and encouraging regular exercise.
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PMID:Interventions during and after acute myocardial infarction. 613 2

A procedure for dissociation of the nasal salt glands of the domestic duck, Anas platyrhynchos, into suspensions of individual cells has been developed. This technique employs enzymatic digestion with collagenase, hyaluronidase, and chymotrypsin; divalent cation chelation with EDTA; and gentle mechanical dispersion. Average cellular yields of 39 and 26% based on DNA recovered were obtained from the glands of freshwater- and saline-adapted ducks, respectively. Epithelial secretory cells comprised 60-80% of the cell suspensions with the remainder of the populations consisting of endothelial cells, fibroblasts, and blood cells. The dissociated cells were viable as judged by trypan blue exclusion (80-100%, maintenance of ultrastructural integrity, and retention of responsiveness to secretagogues and metabolic inhibitors. Methacholine chloride (0.5 mM) stimulated oxygen consumption by suspensions of both freshwater- and saline-adapted cells, whereas ouabain (0.05 mM) abolished the methacholine-stimulated respiratory response. These cell suspensions provide a promising system for the in vitro study of secretory mechanisms in the avian salt gland.
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PMID:Dissociation of avian salt gland: separation procedures and characterization of dissociated cells. 624 10

A homogeneous population of single cells from the thick ascending limb of Henle's loop (TALH) has been isolated from the rabbit kidney medulla. A total medullary cell suspension was prepared by a series of collagenase, hyaluronidase, and trypsin digestions and separated on a Ficoll gradient (2.6-30.7% wt/wt). Morphologically, the cells isolated from the TALH were homogeneous and showed polarity within their plasma membrane structure, with a few blunt microvilli on their apical surface and deep infoldings of the basal-lateral membrane. Biochemically, the TALH cells were highly enriched in calcitonin-sensitive adenylate cyclase and Na, K-ATPase. Alkaline phosphatase and arginine vasopressin-sensitive adenylate cyclase, highly concentrated in proximal tubule and collecting duct, were present only in low concentrations in the TALH cells. Additionally, furosemide, a diuretic inhibiting sodium chloride transport in the TALH in vivo, inhibited oxygen consumption of the TALH cells in a dose-dependent manner. The TALH cells were viable, as judged by morphological appearance, trypan blue exclusion, the response of oxygen consumption to 2,4-dinitrophenol, succinate and ouabain, and the cellular Na, K and ATP levels.
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PMID:Separation of renal medullary cells: isolation of cells from the thick ascending limb of Henle's loop. 625 27

We measured lung hyaluronidase activity in rats during postnatal life and during the repair of oxygen-induced lung injury. Hyaluronidase activity increased rapidly after birth and peaked at 16-fold the initial value at 8 days. The peak preceded decreased cell proliferation and the onset of differentiation; this is consistent with current concepts of the role of hyaluronidase. During the repair of lung injury, hyaluronidase activity increased to 2.5-fold the control value at 1 day post-injury, but had decreased by 3 days. This early peak is probably related to simultaneous cell proliferation and differentiation. We postulate that changes in hyaluronidase can influence lung growth and repair and that the system may be amenable to manipulation.
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PMID:Changes in lung hyaluronidase activity associated with lung growth, injury and repair. 666 Dec 31

The 1H-n.m.r. spectra of solutions in [2H6]dimethyl sulphoxide of the sodium salts of tetra-, hexa- and octa-saccharides prepared from hyaluronate by testicular-hyaluronidase digestion were examined at 300 and 500 MHz. The signals from hydroxy groups at positions 2 and 3 in the glucuronic acid moiety were assigned. Their chemical shifts and associated temperature-dependencies, as well as their coupling constants, depended on whether or not the uronic acid was at the non-reducing end. Deviations from the 'normal' pattern of hydroxy-group proton n.m.r. behaviour were attributable to participation in hydrogen bonds, either to the acetamido carbonyl oxygen atom or the pyranose ring oxygen atom of neighbouring N-acetylhexosamine moieties. A secondary structure, containing four different hydrogen bonds per trisaccharide unit of glucuronsyl-hexosaminyl-glucuronic acid, was demonstrated. This is the first complete and detailed secondary structure to be established for hyaluronate in any solvent. Hyaluronate is compared with chondroitin sulphate, dermatan sulphate, heparan sulphate and keratan sulphate in their potential to form secondary structures with features in common. The significance of the details of the structure to its overall stability, and the probability of their persistence into aqueous environments, are discussed. The presence of all or most of the secondary structure in glycosaminoglycuronans is correlated with a space-filling function in the tissue, and with a high carbohydrate content in the parent proteoglycan in the case of the chondroitin sulphates.
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PMID:Secondary structure of hyaluronate in solution. A 1H-n.m.r. investigation at 300 and 500 MHz in [2H6]dimethyl sulphoxide solution. 674 60

Chondroitin sulfate lyase (EC 4.2.2.4) was present constitutively at low levels (0.06 to 0.08 U/mg of protein) in cells of Bacteroides thetaiotaomicron which were growing on glucose or other monosaccharides. When these uninduced bacteria were incubated with chondroitin sulfate A (5 mg/ml), chondroitin sulfate lyase specific activity increased more than 10-fold within 90 min. Synthesis of ribonucleic acid and of protein was required for induction, and induction was sensitive to oxygen. The disaccharides which resulted from chondroitinase action did not act as inducers, nor did tetrasaccharides or hexasaccharides obtained by digestion of chondroitin sulfate with bovine testicular hyaluronidase. None of these substances was taken up by uninduced cells; they may not have been able to penetrate the outer membrane. The smallest oligomer capable of acting as an inducer was the outer membrane. The smallest oligomer capable of acting as an inducer was the octassacharide. Oligomers larger than the octassacharide induced chondroitin lyase activity nearly as well as intact chondroitin sulfate.
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PMID:Induction of chondroitin sulfate lyase activity in Bacteroides thetaiotaomicron. 678 77

The value of three agents in reducing the area of myocardial ischemia in rabbit hearts perfused with crystalloid solution was examined. Ten hearts received crystalloid solution with methylprednisolone (M), 0.25 mg/ml; 18 with hyaluronidase (H), 4 U/ml; and 10 with propranolol (P), 1 microgram/ml. Thirty-six hearts served as controls. The mitral valves were excised, the hearts were paced at 240 beats/min and a coronary artery was ligated. The ischemic area was evaluated by nicotinamide adenine dinucleotide autofluorescence photography, an intrinsic, high-resolution display of anoxic tissue. The ischemic area was determined by computer from standardized photographs. Myocardial oxygen consumption (MVO2) was determined and photographs were taken before and at 10-minute intervals after ligation. At 60 minutes, each heart was perfused with rhodamine dye and quick-frozen. In hearts treated with M and H, coronary blood flow increased by 151% (51.7 +/- 3 to 77.9 +/- 3 ml/min) and 150% (48.3 +/- 2 to 72.3 +/- 2 ml/min), respectively (p less than 0.001), whereas in hearts treated with U and P, coronary flow decreased at 60 minutes. In the control hearts, the ischemic area did not change between 5 and 40 minutes of ischemia. The ischemic area of H-treated hearts decreased from 136 +/- 4 mm2 to 110 +/- 9 mm2 between the postligation control and the end of the experiment (p less than 0.01). The ischemic area of M-treated hearts decreased from 131 +/- 5 mm2 to 113 +/- 5 mm2 (p less than 0.05). P produced no change in ischemic area (p greater than 0.4). There was no change in the oxygen-diffusion zone of P-treated or control hearts (439 +/- 13 vs 383 +/- 12 mu, p greater than 0.1). The oxygen-diffusion zone between perfused and anoxic tissue in the M and H hearts increased from 383 +/- 12 mu to 861 +/- 76 mu and 681 +/- 62 mu, respectively (p less than 0.001). We conclude that significant volumes of myocardium remain normoxic within nonperfused areas of M-, P- and H-treated hearts.
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PMID:Pharmacologic modification of myocardial ischemia. 709 66

The influence of hyaluronidase (H) on subacute experimental myocardial ischemia was studied in isolated perfused rabbit hearts. Changes in ischemic area were assessed by epicardial nicotinamide adenine dinucleotide (NADH) fluorescence photography, an intrinsic high-resolution display of myocardial ischemia. Computerized determination of ischemic area was made from standardized photographs. Hyaluronidase was begun 20 minutes after coronary artery occlusion at 4 units/ml perfusate. NADH fluorophotographs were taken at 10-minute intervals up to 60 minutes of ischemia. Coronary sinus oxygen tension (PcsO2), myocardial oxygen consumption (MVO2), and coronary flow were determined. After 70 minutes, the hearts were perfused with rhodamine solution to identify areas of myocardial perfusion. In 13 H-treated hearts 54.3% +/- 3.7% (mean +/- SEM) of the nonperfused area (rhodamine stained) was ischemic (NADH fluorescent). In 14 untreated hearts 79.8% +/- 3.2% of the nonperfused area was ischemic (p less than 0.0001) and the ischemic areas were uniform. The distance between perfused and ischemic tissue was 952 +/- 78 micrometers in the H hearts and 504 +/- 35 micrometers in the untreated heart (p less than 0.0001). In the H hearts PcsO2 increased to 155% of the post-ligation control while it decreased to 79% in the untreated hearts (p less than 0.0001). MVO2 decreased in the H-treated hearts to 62%; the untreated hearts had no further change. In the H-treated hearts, coronary flow increased to 146% of the post-ligation control while it fell to 91% in the untreated group (p less than 0.0001). We conclude that H increases coronary flow while decreasing MVO2 during subacute ischemia. In H-treated hearts, significant amounts of myocardium remain normoxic within the nonperfused areas, and may potentially be salvaged after prolonged myocardial ischemia.
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PMID:Mechanism of action of hyaluronidase in decreasing myocardial ischemia post coronary occlusion in the isolated perfused rabbit heart. 711 92

The mechanism for reduced myocardial ischaemic injury by hyaluronidase was studied in open chest anaesthetized dogs. Repeated coronary artery occlusions were performed and the effect of hyaluronidase (225 NF units per kg) was studied during infusion of noradrenaline 0.125 mg/kg . min. Ischaemic injury was measured as the sum of ST-segment elevations (sigma ST) at 10-15 sites. Regional myocardial blood flow was determined by tracer microspheres. Blood for metabolic studies was sampled from a local coronary vein draining ischaemic tissue and from the coronary sinus draining predominantly non-ischaemic tissue. Hyaluronidase reduced sigma ST and increased subepicardial and transmural blood flow in ischaemic myocardium, but flow was not significantly changed in the ischaemic subendocardium or in non-ischaemic myocardium. Hyaluronidase had no significant effect on arterio-local venous differences of oxygen, glucose, lactate or free fatty acids across the ischaemic myocardium. In conclusion, reduction of myocardial ischaemic injury by hyaluronidase can be explained by increased collateral blood flow and not by an effect on fluxes of substrates across the ischaemic myocardium.
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PMID:Effect of hyaluronidase on substrate exchange and blood flow in the ischaemic myocardium of the dog. 720 7


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