Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.5 (thrombin)
 33,306 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recently, it has been reported that both thrombin-sensitive protease-activated receptor 1 (PAR-1) and platelet-derived growth factor (PDGF) are present not only in platelets, but also in the CNS, which indicates that they have various physiological functions. In this study, we evaluated whether PAR-1/PDGF in the spinal cord could contribute to the development of a neuropathic pain-like state in mice. Thermal hyperalgesia and tactile allodynia induced by sciatic nerve ligation were significantly suppressed by repeated intrathecal injection of hirudin, which is characterized as a specific and potent thrombin inhibitor. Furthermore, a single intrathecal injection of thrombin produced long-lasting hyperalgesia and allodynia, and these effects were also inhibited by hirudin in normal mice. In nerveligated mice, the increase in the binding of [35S]GTPgammaS to membranes of the spinal cord induced by thrombin and PAR-1-like immunoreactivity (IR) in the spinal cord were each greater than those in sham-operated mice. Thermal hyperalgesia and tactile allodynia induced by sciatic nerve ligation were also suppressed by repeated intrathecal injection of either the PDGF alpha receptor (PDGFRalpha)/Fc chimera protein or the PDGFR-dependent tyrosine kinase inhibitor AG17 [(3,5-di-tert-butyl-4-hydroxybenzylidene)-malononitrile]. Moreover, thermal hyperalgesia and tactile allodynia induced by thrombin in normal mice were virtually eliminated by intrathecal pretreatment with PDGFRalpha/Fc. In immunohistochemical studies, PAR-1-like IR-positive cells in the spinal dorsal horn were mostly colocated on PDGF-like IR-positive neuronal cells. These data provide novel evidence that PAR-1 and PDGF-A-mediated signaling pathway within spinal cord neurons may be directly implicated in neuropathic pain after nerve injury in mice.
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PMID:Protease-activated receptor-1 and platelet-derived growth factor in spinal cord neurons are implicated in neuropathic pain after nerve injury. 1625 48

Symptomatic prehospital therapy of patients suffering from an ST elevation myocardial infarction basically does not differ from in-hospital care regarding pain relief, beta-blockers, antiplatelets, and thrombin antagonists as well as therapy of elevated blood pressure and acute heart failure. Precondition of a targeted and adequate treatment, however, is the twelve-lead ECG whose reliability does not differ from the ECG in the hospital. Biomarkers have no role in the prehospital setting. Out-of-hospital thrombolysis, which has been proven to be superior to later in-hospital initiation, can be used as a safe strategy for reperfusion. Only the prehospital phase offers a chance to treat the majority of patients within the first 2 h after symptom onset, a time window where thrombolysis results in equal or even better outcomes with respect to mortality, if compared to percutaneous intervention. Therefore, prehospital thrombolysis should be routinely applied in areas with a weak infrastructure and few and less experienced facilities for intervention but should also be considered a principal way for earliest start of reperfusion therapy. There is increasing evidence supporting the "rescue PCI" concept in patients in whom thrombolysis has failed. By contrast, the role of "facilitated PCI" still has to be defined.
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PMID:[Prehospital care of patients with acute ST elevation myocardial infarction]. 1633 63

Despite being widely reported in patients with neoplasms, vena cava superior (VCS) syndrome linked to thrombosis is a major catheter complication that can be encountered during the use of the hemodialysis catheter. Antithrombin III (AT-III), responsible for a large part of thrombin inactivation capacity in plasma, is the most powerful inhibitor of the thrombosis process. This report describes a case of VCS syndrome developing two weeks following the extraction of a right-sided subclavian catheter in a patient transferred from peritoneal dialysis to hemodialysis for one week due to leakage. The patient presented complaining of swelling and pain in the right arm. At Doppler examination, total thrombosis was observed in the subclavian and internal jugular vein. At advanced examinations due to lack of response to heparin and clinical worsening, VCS and AT-III deficiency were determined. Following thrombolytic therapy with streptokinase, AT-III levels were raised by the administration of plasma, and clinical and radiological stabilization was established by continuing heparin and continuous oral anticoagulant therapy.
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PMID:Vena cava superior syndrome developing in a dialysis patient with antithrombin III deficiency following temporary catheterization. 1642 47

Four months after a diagnostic coronary angiography followed by application of a vascular closure device, a female patient presented with an acute femoral pulsing tumor with strong pain in the groin area. There was no prior trauma. Color duplex sonography showed a large pseudoaneurysm of the right femoral artery. In addition, signs of an old hematoma were documented. Due to the large tumor affecting the arterial perfusion of distal arteries, the pseudoaneurysm was treated immediately by thrombin injection. After this procedure, arterial perfusion in the tumor was not detectable anymore and local symptoms decreased rapidly. This is a rare case of late pseudoaneurysm after femoral artery puncture.
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PMID:Large femoral aneurysm as a late complication after vessel closure device application. 1659 90

Pseudoaneurysm of the superficial temporal artery is rare in children and is frequently a result of direct facial trauma. Conventional management has included surgical ligation and resection and more recently endovascular embolization to prevent complications including local pain, headache, facial disfigurement and bleeding. We report a unique case of a US-guided percutaneous thrombin injection for the treatment of a post-traumatic superficial temporal artery pseudoaneurysm in a child.
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PMID:Percutaneous thrombin embolization of a post-traumatic superficial temporal artery pseudoaneurysm. 1740 24

Cholecystitis is one of the most common gastrointestinal diseases. Inflammation induces the activation of proteases that can signal to cells by cleaving protease-activated receptors (PARs) to induce hemostasis, inflammation, pain, and repair. However, the distribution of PARs in the gallbladder is unknown, and their effects on gallbladder function have not been fully investigated. We localized immunoreactive PAR(1) and PAR(2) to the epithelium, muscle, and serosa of mouse gallbladder. mRNA transcripts corresponding to PAR(1) and PAR(2), but not PAR(4), were detected by RT-PCR and sequencing. Addition of thrombin and a PAR(1)-selective activating peptide (TFLLRN-NH(2)) to the serosal surface of mouse gallbladder mounted in an Ussing chamber stimulated an increase in short-circuit current in wild-type but not PAR(1) knockout mice. Similarly, serosally applied trypsin and PAR(2) activating peptide (SLIGRL-NH(2)) increased short-circuit current in wild-type but not PAR(2) knockout mice. Proteases and activating peptides strongly inhibited electrogenic responses to subsequent stimulation with the same agonist, indicating homologous desensitization. Removal of HCO(3)(-) ions from the serosal buffer reduced responses to thrombin and trypsin by >80%. Agonists of PAR(1) and PAR(2) increase intracellular Ca(2+) concentration in isolated and cultured gallbladder epithelial cells. The COX-2 inhibitor meloxicam and an inhibitor of CFTR prevented the stimulatory effect of PAR(1) but not PAR(2). Thus PAR(1) and PAR(2) are expressed in the epithelium of the mouse gallbladder, and serosally applied proteases cause a HCO(3)(-) secretion. The effects of PAR(1) but not PAR(2) depend on generation of prostaglandins and activation of CFTR. These mechanisms may markedly influence fluid and electrolyte secretion of the inflamed gallbladder when multiple proteases are generated.
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PMID:Agonists of protease-activated receptors 1 and 2 stimulate electrolyte secretion from mouse gallbladder. 1743 Dec 14

Stimulating the body's natural healing at the cellular level can be achieved through the application of growth factors located within platelets. Once combined with a mixture of calcium and thrombin, this substance, now referred to as autologous platelet gel (APG), can be applied to surgical wound sites for patients undergoing cardiac surgery. The purpose of this study was to examine the effects of APG on surgical site infection, post-operative pain, blood loss, and bruising. After 30 mL platelet-rich plasma (PRP) was processed, 10 mL PRP was distributed on the sternum after re-approximation and 7 mL PRP before skin closure. Ten milliliters PRP was used on the endoscopic leg harvest (EVH) site. The remaining 3 mL was sent to the laboratory for hematologic testing. Both the control (CTR) and treatment (TRT) groups were well matched, with the exception of ejection fraction and pre-operative platelet count, which was significantly higher in the TRT group. Average platelet count yield was 4.2 +/- 0.5 x 103/mcL, white blood count (WBC) yielded 1.9 +/- 0.7 x 103/mcL, and fibrinogen yielded 1.2 +/- 0.2 mg/dL above baseline. There were no deep or superficial sternal infections. However, one patient from each group did experience a leg infection at the EVH site, which occurred after hospital discharge. More patients in the TRT group experienced less pain on postoperative day (POD) 1 and at the post-operative office follow-up. Blood loss and bruising was less in the TRT group on POD 2; however, there was no statistical significance. The application of APG seems to confer beneficial effects on pain, blood loss, and bruising. However, further studies with a greater sample size are needed to power significant differences.
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PMID:Autologous platelet gel in coronary artery bypass grafting: effects on surgical wound healing. 1748 71

Snake venom is a complex mixture containing diverse protein components with different structures and functions that are used for prey immobilization and death. Snake venoms from the family Viperidae cause pronounced local and systemic effects, such as pain, edema, hemorrhage and necrosis. Here, we investigated the enzymatic and biological activities of venoms from two Amazonian snakes, Bothriopsis bilineata and Bothriopsis taeniata. Both venoms presented high enzymatic activities for proteases kallikrein, thrombin and plasmin, low levels of trypsin, cathepsin C and leucine aminopeptidase activities, while lacked acetylcholinesterase activity. B. taeniata and B. bilineata crude venoms caused inflammation inducing neutrophil recruitment into peritoneal cavity of mice 4h after injection. Neutrophil recruitment induced by B. taeniata venom was accompanied by hemorrhage. EDTA treatment profoundly impaired neutrophil recruitment, suggesting the involvement of a metalloproteinase on venoms-induced neutrophil recruitment. Pretreatment with dexamethasone and zileuton, a 5-lipoxygenase inhibitor, significantly reduced neutrophil migration, but indomethacin and montelukast, a cysteinyl leukotriene receptor antagonist, had no effect, suggesting the involvement of lipoxygenase-derived metabolites, probably LTB(4). Together, these results show that B. bilineata and B. taeniata venoms induce a marked inflammatory reaction, with leukocyte recruitment, and hemorrhage, which parallels to a high proteolytic activity found in these venoms.
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PMID:Biochemical and biological characterization of the venoms of Bothriopsis bilineata and Bothriopsis taeniata (Serpentes: Viperidae). 1753 75

The roles of serine proteases and protease activated receptors have been extensively studied in coagulation, wound healing, inflammation, and neurodegeneration. More recently, serine proteases have been suggested to influence synaptic plasticity. In this context, we examined the role of protease activated receptor 1 (PAR1), which is activated following proteolytic cleavage by thrombin and plasmin, in emotionally motivated learning. We were particularly interested in PAR1 because its activation enhances the function of NMDA receptors, which are required for some forms of synaptic plasticity. We examined several baseline behavioral measures, including locomotor activity, expression of anxiety-like behavior, motor task acquisition, nociceptive responses, and startle responses in C57Bl/6 mice in which the PAR1 receptor has been genetically deleted. In addition, we evaluated learning and memory in these mice using two memory tasks, passive avoidance and cued fear-conditioning. Whereas locomotion, pain response, startle, and measures of baseline anxiety were largely unaffected by PAR1 removal, PAR1-/- animals showed significant deficits in a passive avoidance task and in cued fear conditioning. These data suggest that PAR1 may play an important role in emotionally motivated learning.
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PMID:Learning and memory deficits in mice lacking protease activated receptor-1. 1754 3

It has been almost a decade since the molecular cloning of all four members of the proteinase-activated receptor (PAR) family was completed. This unique family of G protein-coupled receptors (GPCRs) mediates specific cellular actions of various endogenous proteinases including thrombin, trypsin, tryptase, etc. and also certain exogenous enzymes. Increasing evidence has been clarifying the emerging roles played by PARs in health and disease. PARs, particularly PAR1 and PAR2, are distributed throughout the gastrointestinal (GI) tract, modulating various GI functions. One of the most important GI functions of PARs is regulation of exocrine secretion in the salivary glands, pancreas and GI mucosal epithelium. PARs also modulate motility of GI smooth muscle, involving multiple mechanisms. PAR2 appears to play dual roles in pancreatitis and related pain, being pro-inflammatory/pro-nociceptive and anti-inflammatory/anti-nociceptive. Similarly, dual roles for PAR1 and PAR2 have been demonstrated in mucosal inflammation/damage throughout the GI tract. There is also fundamental and clinical evidence for involvement of PAR2 in colonic pain. PARs are thus considered key molecules in regulation of GI functions and targets for development of drugs for treatment of various GI diseases.
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PMID:Gastrointestinal roles for proteinase-activated receptors in health and disease. 1799 14


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