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)

Using the model of knee pain reaction induced by intra-articular injection of endogenous pain substances, especially bradykinin (BK) in rats, the mechanism of the analgesic effect of sodium hyaluronate (SPH) was investigated. The simultaneous administration of prostaglandin E2 with BK or hyaluronidase digestion of endogenous hyaluronic acid (HA) in our experiments brought remarkable hyperalgesia on BK-induced knee pain. These results suggest that higher sensitivity to the pain reaction is induced in a diseased joint (higher prostaglandin content, lower concentration and molecular size of HA in synovial fluid) than in a normal one. SPH definitely decreased BK-induced pain, and its analgesic effect was observed for a longer period, depending on its dose in pre-treatment and the degree of its distribution in synovial tissues. As the analgesic effect of SPH was observed in the hyaluronidase-treated joint as well, it is suggested that the increasing viscosity of synovial fluid caused by increasing HA concentration can decrease the pain even without normalizing molecular size of HA in the joint. HA oligomer and other compounds with similar viscosity or with similar polyanionic character as SPH showed no analgesic effect. From these results, it seems that the characteristic steric configurations of higher molecular HA are needed for the manifestation of the analgesic effect. SPH seems to show its analgesic effect by covering pain receptors in synovial tissues and holding endogenous pain substances in its molecule.
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PMID:[Experimental knee pain model in rats and analgesic effect of sodium hyaluronate (SPH)]. 322 Mar 23

Classical techniques for studying modulations of microvascular permeability have a time resolution of minutes. A newly developed method allows continuous measurement of the electrical resistance of the microvascular membrane in vivo (Olesen & Crone 1983). The technique exploits microelectrodes impaled into the vascular lumen and is based on cable analysis of the vessel. It was applied to venules on the surface of the frog brain to test the effect on microvascular permeability of a wide variety of substances. The following agents increased ionic permeability reversibly within seconds: 5-hydroxytryptamine, bradykinin, ATP, ADP, AMP, phospholipase A2, arachidonic acid, leukotriene C4, oxygen-derived free radicals, ionophore A23187, and unbound Evans blue dye. An irreversible permeability increase was induced by protamine sulphate, neuraminidase, trypsin, melittin, and snake venoms from Crotalus durissus terrificus and Bothrops atrox. The following substances were without effect within an administration period of 5 min: histamine, epinephrine, putrescine, angiotensin II, vasoactive intestinal polypeptide (VIP), substance P, neurotensin, vasopressin, adenosine, PGE2, PGF2 alpha, prostacyclin (PGI2), leukotriene B4, albumin, heparin, plant cytokinins, hyaluronidase, thrombin, wasp venom. Variations in pH between 5.1 and 8.6 did not change permeability. Three conclusions are drawn from the observations: (1) the permeability of cerebral microvessels can be modulated by specific agents, (2) the agents induced changes in the endothelium within a few seconds, and (3) the rapid permeability increase induced by inflammatory mediators was less than two-fold and reversible within minutes.
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PMID:Substances that rapidly augment ionic conductance of endothelium in cerebral venules. 348 16

1 The anti-inflammatory activity of crotalaburnine (=anacrotine) was investigated against increased vascular permeability and oedema produced by formalin, carrageenin, hyaluronidase, 5-hydroxytryptamine, dextran, bradykinin and prostaglandin, and against formation of granulation tissues by cotton-pellet in rats. The effect was compared with the activity of hydrocortisone, phenylbutazone, sodium salicylate and cyproheptadine against different types of inflammation.2 Crotalaburnine (40 mg/kg s.c. x 5 alternate days) had no significant inhibitory effect against formalin-induced arthritis, while hydrocortisone (40 mg/kg s.c. x 10 days) was effective from the fifth day onwards.3 Against carrageenin-induced oedema both crotalaburnine (10 mg/kg s.c.) and phenylbutazone (100 mg/kg oral) produced a similar degree of inhibition. Hydrocortisone (10 mg/kg s.c.) produced slightly greater inhibition.4 In normal rats crotalaburnine (10 mg/kg s.c.), phenylbutazone (100 mg/kg oral) and sodium salicylate (500 mg/kg i.p.) inhibited hyaluronidase-induced oedema. However, in adrenalectomized rats, there was a reduction of the inhibitory effect of sodium salicylate but not of phenylbutazone or crotalaburnine.5 Crotalaburnine (40 mg/kg s.c. and 30 mg/kg i.p., respectively) was ineffective against 5-hydroxytryptamine- and dextran-induced oedema but against bradykinin- and prostaglandin-induced oedema (in a dose of 20 mg/kg i.p.) it was quite effective. In a parallel series cyproheptadine (10 mg/kg oral and i.p., respectively) produced significant inhibition of 5-hydroxytryptamine- and dextran-induced oedema, while phenylbutazone (100 mg/kg i.p.) failed to produce any significant inhibition of prostaglandin-induced oedema.6 Against cotton-pellet granuloma crotalaburnine, in half the dose of hydrocortisone, produced similar inhibition while phenylbutazone produced much greater inhibition in five times the dose of crotalaburnine given orally.7 The possible mode of action of crotalaburnine as an anti-oedema agent is discussed.
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PMID:Inhibitory effect of a pyrrolizidine alkaloid, crotalaburnine, on rat paw oedema and cotton pellet granuloma. 445 64

Contractions of the rat uterus in response to trypsin, kallikrein, bradykinin, angiotensin II, oxytocin and acetylcholine, were abolished when an inside-out preparation was used. Sensitivity to Ba++, however, was preserved. In preparations in which the endometrium was mechanically removed, all above cited agonists elicited contractions. By treating the uterus with both collagenase and hyaluronidase, acetylcholine was able to induce a contraction when applied to the endometrium side of the uterus. The results show that a barrier for protease, peptides and acetylcholine is present in the mucosa of the rat uterus.
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PMID:Pharmacological demonstration of a barrier for protease, peptides and acetylcholine in the endometrium of the rat. 818 17

Human envenomations by Heloderma species are a rare but clinically important medical problem. We report a case of an adult male bitten on the left hand by a 50-cm male, captive specimen of Heloderma suspectum (Gila monster). Immediate signs and symptoms included pain at the bite site radiating into the arm and axilla and swelling of the hand and forearm. Systemic complaints of nausea, diaphoresis, and dizziness (without a decrease in blood pressure) lasted approximately 1 hour, and laboratory studies were normal. The patient's course was uneventful except for persistent hyperesthesia, which eventually abated. Two types of helodermatid bites produce distinct clinical pictures. The chewing bite potentially causes more envenomation than the slashing bite. The venom contains a number of protein and nonprotein components including serotonin, a bradykinin-releasing substance, protease, hyaluronidase, helodermin, and gilatoxin. The clinical presentation of a helodermatid bite can include pain, edema, hypotension, nausea, vomiting, weakness, and diaphoresis. No antivenin is commercially available. Treatment is supportive, and although first aid measures such as suction or compression may impede venom movement, they are unproved. Cryotherapy, tourniquet, and excision are dangerous and should not be used.
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PMID:Report on envenomation by a Gila monster (Heloderma suspectum) with a discussion of venom apparatus, clinical findings, and treatment. 1199 Jan 42

The effects of ethanol (EtOH) administration at a high-dose level on the stimulatory action by bradykinin in vascular permeability were examined in rats, as compared with the effects of histamine and hyaluronidase. Oral administration (7.5 g/kg) and intraperitoneal injection (5 g/kg) of EtOH markedly potentiated the vascular permeability accelerated by bradykinin, but they suppressed in reverse such effects induced by histamine and hyaluronidase. EtOH did not affect the stimulatory action of bradykinin on the vascular permeability when intracutaneous injection was done under the coexistence with bradykinin. The blood pressure was found to descend 30 min later, though there was a transient rise immediately after the oral administration of EtOH (7.5 g/kg). The oral administration of EtOH (7.5 g/kg) caused no change in both enzyme activities of aspartic acid aminotransferase and alanine aminotransferase in blood for 3 h. The intraperitoneal injection of EtOH (5 g/kg) lowered the blood bradykinin level and increased the blood hyaluronidase activity. In vitro, EtOH elicited a concentration-dependent increase in the kallikrein activity, trypsin activity, and bradykinin-decomposed activity in plasma. These results strongly suggest that vascular permeability results from elevation in the bradykinin level, direct action of EtOH on inflamed skin site, and actions of EtOH or its metabolites on bradykinin-regulator, which involves bradykinin receptor and NO and endothelin productions.
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PMID:Effects of ethanol administration at a high-dose level on the stimulatory action by bradykinin in vascular permeability. 1248 17

Unraveling the repertoire of venom toxins of Bothropoides pauloensis was assessed by snake venomics and venom gland transcriptomic surveys. Both approaches yielded converging overall figures, pointing to metalloproteinases (~37%), PLA(2)s (26-32%), and vasoactive (bradykinin-potentiating) peptides (12-17%) as the major toxin classes. The high occurrence of SVMPs, PLA(2) molecules, vasoactive peptides, along with serine proteinases, explains the local and systemic effects observed in envenomations by B. pauloensis. Minor (<3%) C-type lectin, serine proteinase, L-amino acid oxidase, nerve growth factor, and CRISP molecules were also identified in the transcriptome and the proteome. Low abundance (0.3%) EST singletons coding for vascular endothelial growth factor (svVEGF), ohanin, hyaluronidase, and 5' nucleotidase were found only in the venom gland cDNA library. At the molecular level, the transcriptomic and proteomic datasets display low compositional concordance. In particular, although there is good agreement between transcriptome and proteome in the identity of BPPs, PLA(2) molecules and L-amino acid oxidase, both datasets strongly depart in their C-type lectin and SVMP complements. These data support the view that venom composition is influenced by transcriptional and translational mechanisms and emphasize the value of combining proteomic and transcriptomic approaches to acquire a more complete understanding of the toxinological profile and natural history of the snake venom.
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PMID:Combined snake venomics and venom gland transcriptomic analysis of Bothropoides pauloensis. 2248 Sep 9

The venomics of Gloydius intermedius were investigated using expressed sequence tags (ESTs) analyses, 2D gel-electrophoresis combined with MALDI-TOF/TOF, and LC-MS/MS. A total of 1920 ESTs from the venom gland cDNA library were sequenced; 74% of them belonged to toxin-families. The four most abundant families among the toxin transcripts were: serine protease (SP, 36.2%), bradykinin potentiating peptide (25.3%), l-amino acid oxidase (LAAO, 13.1%), and phospholipase A2 (PLA2, 9.9%). Moreover, the full sequences of four PLA2s, eight SPs, cysteine-rich secretory protein (CRISP), C-type-lectin-like-protein (CTLP), hyaluronidase, metalloproteinase, and nerve growth factor were deduced from the cDNA sequences. Excluding the CRISP and hyaluronidase, most of the G. intermedius venom proteins bear 92-99% sequence identities to those of other pitviper venoms. The most abundant components are PLA2s (37%), SPs (20%) and LAAO (6%), while metalloproteinase, CTLP, and other components each account for <3% of the total venom proteins. The abundance of Gintexin (a crotoxin-like neurotoxin) and low levels of hemorrhagic metalloproteases, disintegrins and CTLPs highlight the great venom differences between G. intermedius and other hemorrhagic pitvipers. The bimorphism of hemorrhagic and neurotoxic venoms among Gloydius is confirmed; our results shed more lights on the co-evolution of both neurotoxicity and hypotension in some viperid venoms.
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PMID:Transcriptome and proteome of the highly neurotoxic venom of Gloydius intermedius. 2627 79

Essential hypertension (EH) is a risk factor for some severe diseases. This study aimed to screen out serum special proteins and seek interaction between them, which would provide new therapeutic targets and elucidate the comprehensive pathophysiological mechanism for EH. Patients with EH (Group A, n = 47) and healthy controls (HC) (Group B, n = 47) were recruited in this study. Serums from the two groups were analyzed with isobaric tags for relative and absolute quantitation coupled two-dimensional liquid chromatography followed by electrospray ionization-tandem mass spectrometry technique, while the candidate special proteins were verified with ELISA and western blot. A total of 404 proteins were identified, of which 30 proteins were upregulated (>1.2-fold, p < 0.05) and 81 proteins were downregulated (<0.833-fold, p < 0.05) compared with HC group. With GO, KEGG analysis, and literature retrieval, 4 proteins, cathepsin G, transforming growth factor beta-1, hyaluronidase-1, and kininogen-1, were found jointly involved in the renin-angiotensin-aldosterone system and kallikrein-kinin system. The profiles of these 4 candidate proteins were confirmed with ELISA and western blot. The concentration variation of these 4 proteins could better predict the occurrence and illustrate the pathophysiological mechanism of EH. And their discovery may help pave the way for exploring new therapies of EH.
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PMID:Quantitative Serum Proteomic Analysis of Essential Hypertension Using iTRAQ Technique. 2920 9

The Indian red scorpion (Mesobuthus tamulus), with its life-threatening sting, is the world's most dangerous species of scorpion. The toxinome composition of M. tamulus venom was determined by tandem mass spectrometry (MS) analysis of venom protein bands separated by SDS-PAGE. A total of 110 venom toxins were identified from searching the MS data against the Buthidae family (taxid: 6855) of toxin entries in nonredundant protein databases. The Na+ and K+ ion channel toxins taken together are the most abundant toxins (76.7%) giving rise to the neurotoxic nature of this venom. The other minor toxin classes in the M. tamulus venom proteome are serine protease-like protein (2.9%), serine protease inhibitor (2.2%), antimicrobial peptide (2.3%), hyaluronidase (2.2%), makatoxin (2.1%), lipolysis potentiating peptides (1.2%), neurotoxin affecting Cl- channel (1%), parabutoporin (0.6%), Ca2+ channel toxins (0.8%), bradykinin potentiating peptides (0.2%), HMG CoA reductase inhibitor (0.1%), and other toxins with unknown pharmacological activity (7.7%). Several of these toxins have been shown to be promising drug candidates. M. tamulus venom does not show enzymatic activity (phospholipase A2, l-amino acid oxidase, adenosine tri-, di-, and monophosphatase, hyaluronidase, metalloproteinase, and fibrinogenolytic), in vitro hemolytic activity, interference with blood coagulation, or platelet modulation properties. The clinical manifestations post M. tamulus sting have been described in the literature and are well correlated with its venom proteome composition. An abundance of low molecular mass toxins (3-15 kDa) are responsible for exerting the major pharmacological effects of M. tamulus venom, though they are poorly immune-recognized by commercial scorpion antivenom. This is a major concern for the development of effective antivenom therapy against scorpion stings.
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PMID:Correlation of Venom Toxinome Composition of Indian Red Scorpion (Mesobuthus tamulus) with Clinical Manifestations of Scorpion Stings: Failure of Commercial Antivenom to Immune-Recognize the Abundance of Low Molecular Mass Toxins of This Venom. 3212 69


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