Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of dietary n-3 fatty acids (n-3FAs) on the frequency of pain episodes and ex vivo blood tests of thrombosis have been evaluated in patients with sickle cell disease (SCD) utilizing a double-blind, olive oil-controlled clinical trial. Dietary n-3FA therapy (0.1 g/kg/d) was provided as menhaden fish oil (0.25 g/kg/d) containing 12% eicosapentaenoic acid (EPA), and 18% docosahexaenoic acid (DHA). Within 1 month dietary n-3FAs exchanged with n-6FAs in plasma and erythrocyte membrane phospholipids (p <0.01 in all cases). Treatment with dietary n-3FAs for 1 year reduced the frequency of pain episodes requiring presentation to the hospital from 7.8 events during the preceding year to 3.8 events/year (p <0.01; n = 5). By contrast, subjects receiving control dietary olive oil (n = 5) experienced 7.1 pain events/year, compared to 7.6 during the previous year (p >0.4). The reduction in episodes in n-3FA-treated subjects was also significant when compared to control subjects (p <0.01). Dietary n-3FA therapy was not associated with hemorrhagic, gastrointestinal or other adverse effects. Compared to 10 asymptomatic African-American controls, sickle cell subjects demonstrated significantly increased pretreatment: 1) flow cytometric expression of platelet membrane P-selectin (CD62p; p <0.01) and annexin V binding sites (p = 0.02); 2) plasma levels of platelet-specific secretory proteins platelet factor 4 (PF4) and beta-thromboglobulin (betaTG) (p <0.01 in both cases); 3) plasma products of thrombin generation, prothrombin fragment 1.2 (F1.2) and thrombin:antithrombin (TAT) complex (p <0.01 in both cases); and 4) plasma levels of thrombolytic products, D-dimer and plasmin:antiplasmin (PAP) complex (p <0.01 in both cases). Treatment with dietary n-3FAs concurrently decreased plasma levels of F1.2, D-dimer, and PAP (p <0.05, compared to olive oil controls), implying that the reduction in pain events was related to n-3FA-dependent inhibition of thrombosis. We conclude that dietary n-3FAs reduce the frequency of pain episodes perhaps by reducing prothrombotic activity in sickle cell disease.
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PMID:Reduction of pain episodes and prothrombotic activity in sickle cell disease by dietary n-3 fatty acids. 1143 3

We report the result of a randomized, controlled, open trial of anti-thrombin therapy for herpes zoster-associated pain. Fifty-five herpes zoster patients within 8 days after the onset of skin lesion were enrolled in the trial. Patients were treated with an optimal dose of oral acyclovir (4000 mg/day for 7 days) with or without intravenous administration of a specific anti-thrombin agent, argatroban (10 mg/day, three times a week). Administration of argatroban reduced pain intensity at the 4th through 21st day after the initiation of treatment as determined by visual analogue scale (Mann-Whitney U test, p < 0.05). It also shortened the median time to cessation of analgesic use (14 days vs. 24 days, p = 0.02, logrank test), although it did not significantly reduce the median time to cessation of pain (21 days vs. 43 days, p = 0.07, logrank test). None of the enrolled patients showed evidence of adverse effects including hemorrhagic diathesis. The results suggested that relatively low doses of argatroban are effective in reducing herpes zoster-associated pain. Up-regulation of prothrombin expression by the vascular endothelial and sweat gland epithelial cells in the active skin lesion and transient elevation of plasma thrombin-antithrombin III complex levels in a proportion of patients suggest a lesional generation of thrombin in herpes zoster. This may be relevant to the beneficial effects of the anti-thrombin treatment on the resolution of herpes zoster-associated pain.
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PMID:A specific thrombin inhibitor, argatroban, alleviates herpes zoster-associated pain. 1144 71

Fibrin sealant imitates the final phase of the blood coagulation process. Fibrinogen is converted into fibrin on a tissue surface by the action of thrombin, which is then cross-linked by factor XIIIa, creating a mechanically stable fibrin network. This fibrin network is thought to reduce the amount of postoperative bleeding by sealing capillary vessels and allowing raw operative surfaces to adhere. The authors conducted a prospective, double-blind, randomized, controlled trial on the use of fibrin sealant in 20 consecutive patients undergoing bilateral face lifts by the same surgeon. Each patient was randomized for the use of fibrin sealant on either the right or the left side with the contralateral side acting as the control. Total drainage was recorded on each side for 24 hours before drains were removed. The age range of the patients in the trial (all of whom were women) was 44 to 70 years (mean, 55). The side treated with fibrin glue had a median drainage of 10 ml and the control side 30 ml. The Wilcoxon signed rank test shows a significant difference in drainage between sides (p = 0.002). The reduction in postoperative drainage could also reduce pain and bruising, increasing patient satisfaction with this procedure. The need for drains may also be obviated.
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PMID:A prospective, randomized, double-blind trial of the use of fibrin sealant for face lifts. 1236 92

The standard non-invasive treatment of pseudoaneurysms has been ultrasound-guided compression (UGC). Problems with UGC include pain at the site of compression, long compression times and incomplete closure. Each of these difficulties is exacerbated with large pseudoaneurysms. Recently, ultrasound-guided injection of pseudoaneurysms with thrombin has gained popularity. The goal of this study was to report a multicenter registry using this technique and in so doing detail the clinical utility and safety of this emerging procedure. The medical records of all patients diagnosed with pseudoaneurysm in the vascular laboratory who underwent thrombin injection over the past year were reviewed for patient characteristics and clinical outcome. There were 91 patients (55 male) with a mean age of 69 years. Three patients also had an arteriovenous fistula. The majority of patients were receiving one or more antiplatelet agents and/or anticoagulants. All patients underwent pseudoaneurysm injection with bovine thrombin. The mean aneurysm diameter was 3.3 cm, with a range of 1.5-6.3 cm. Successful thrombosis of the pseudoaneurysm was achieved in 89/91 (98%) of cases. Anticoagulation with heparin was used in one of the unsuccessful cases. In two cases, UGC was used to close a small active region that did not completely thrombose after thrombin injection. There were two patients who had recurrence of pseudoaneurysm the day after successful injection and thrombosis of the pseudoaneurysm. There were no local complications after injection; however, one patient suffered a pulmonary embolus that was thought to be unrelated to the procedure. In conclusion, thrombin injection for the treatment of pseudoaneurysms is safe and effective, even in patients receiving anticoagulation. This procedure should be considered as the initial therapeutic approach for peripheral pseudoaneurysms.
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PMID:Therapeutic thrombin injection of pseudoaneurysms: a multicenter experience. 1195 90

Certain extracellular proteases, derived from the circulation and inflammatory cells, can specifically cleave and trigger protease-activated receptors (PARs), a small, but important, sub-group of the G-protein-coupled receptor super-family. Four PARs have been cloned and they all share the same basic mechanism of activation: proteases cleave at a specific site within the extracellular N-terminus to expose a new N-terminal tethered ligand domain, which binds to and thereby activates the cleaved receptor. Thrombin activates PAR1, PAR3 and PAR4, trypsin activates PAR2 and PAR4, and mast cell tryptase activates PAR2 in this manner. Activated PARs couple to signalling cascades that affect cell shape, secretion, integrin activation, metabolic responses, transcriptional responses and cell motility. PARs are 'single-use' receptors: proteolytic activation is irreversible and the cleaved receptors are degraded in lysosomes. Thus, PARs play important roles in 'emergency situations', such as trauma and inflammation. The availability of selective agonists and antagonists of protease inhibitors and of genetic models has generated evidence to suggests that proteases and their receptors play important roles in coagulation, inflammation, pain, healing and protection. Therefore, selective antagonists or agonists of these receptors may be useful therapeutic agents for the treatment of human diseases.
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PMID:Protease-activated receptors: the role of cell-surface proteolysis in signalling. 1246 69

The CNS expresses many components of an extracellular protease signalling system, including the protease-activated receptor-1 (PAR-1) whose tethered ligand is generated by thrombin. Activation of PAR-1 potentiates NMDA receptor activity in hippocampal neurons. Because NMDA activity mediates hyperalgesia, we tested the hypothesis that PAR-1 receptors also regulate pain processing. In contrast to the potentiating effect of thrombin in the hippocampus, NMDA-induced behaviours and the transient mechanical hyperalgesia (von Frey fibres) induced by intrathecally injected NMDA in mice were inhibited by thrombin in a dose-related fashion. This anti-hyperalgesic effect was mimicked by SFLLRN, the natural ligand at PAR-1 binding sites, but not SLIGRL-amide, a PAR-2 agonist. The effects of SFLLRN were less potent and shorter in duration than that of thrombin, consistent with its more transient effect on PAR-1 sites. Both thrombin and SFLLRN inhibited acetic acid-induced abdominal stretch (writhing) behaviours, which were also sensitive to NMDA antagonism, but not hot plate or tail flick latencies, which were insensitive to NMDA antagonists. TFLLR-amide, a selective ligand for PAR-1 sites, mimicked the effects of thrombin while RLLFT-amide, an inactive, reverse peptide sequence, did not. In addition, the effect of TFLLR-amide was prevented by RWJ-56110, a PAR-1 antagonist. Thrombin and TFLLR-amide produced no oedema (Evans Blue extravasation) in the spinal cord that would account for these effects. Based on the reported ability of thrombin to mobilize endothelin-1 from astrocytes, we tested the role of this compound in thrombin's activity. BQ123, an endothelin A receptor antagonist, prevented thrombin's inhibition of writhing and NMDA-induced behaviours while BQ788, an endothelin B receptor antagonist, did not. Thus, activation of PAR-1 sites by thrombin in the CNS appears to inhibit NMDA-mediated nociception by a pathway involving endothelin type A receptors.
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PMID:Thrombin inhibits NMDA-mediated nociceptive activity in the mouse: possible mediation by endothelin. 1271 3

Stapled hemorrhoidectomy (PPH) is a modern approach to the treatment of hemorrhoids removing a circumferential strip of mucosa. In the same way the circumferential resection of the rectal prolapse (STARR) is successfully used for effective treatment of colporectocele and obstructed defecation syndrome. These surgical procedures offer several advantages over conventional techniques including reduced postoperative pain, stenosis and recurrences, an earlier recovery time and return to work. Furthermore, bleeding is one of the most common immediate complication (first week) and one of the possible late complication in these procedures. Our results with this surgery (153 PPH and 37 STARR) confirmed the data of many other Authors regarding the incidence of intra and early post-operative haemorrhages (1.3% in PPH and 2.7% in STARR). With the aim to reduce this complications, which represents the only negative side-effect of these procedures, we employed the FloSeal, a gelatine based haemostatic sealant with thrombin component, to control intraoperative bleeding. The preliminary results obtained in 10 PPH and in 7 STARR confirmed the theoretical usefulness of FloSeal in reducing this hemorrhagic complications.
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PMID:[The use of Floseal in the prevention and treatment of intra- and post-operative hemorrhage in the surgical treatment of hemorrhoids and colporectocele. Preliminary results]. 1472 99

The safety and efficacy of a new hemostatic sealant, based on a gel with collagen derived particles and topical thrombin (FloSeal, Fusion Medical Technologies, Inc. Fremont, CA) were assessed as an alternative to nasal packing for hemostasis in functional endoscopic sinus surgery. In a prospective clinical study of 50 patients undergoing bilateral endoscopic anterior ethmoidectomy, 2 ml FloSeal was used after surgery to stop bleeding. The results were compared to a control group of 50 patients with Merocel packing and showed that intraoperative hemostasis was rapid and equal in both groups. The main advantages of the new hemostatic sealant included a higher degree of comfort during postoperative nasal breathing and absence of complaints due to pressure or pain. There was only one case of postoperative bleeding on the 6th day, which required nasal packing. There were no more cases of stenoses or synechia in the ostiomeatal complex than were found in the Merocel group. No systemic side effects due to FloSeal were observed. This specific hemostatic sealant was shown to be a safe and efficacious alternative method for hemostasis in endoscopic sinus surgery with high patient satisfaction and an easy and fast mode of application.
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PMID:Hemostasis in endoscopic sinus surgery using a specific gelatin-thrombin based agent (FloSeal). 1475 Mar 53

Circulating platelets play a pivotal role in hemostasis. The platelet hemostatic function involves the direct interaction with damaged vessel walls, and circulating coagulation factors, primarily thrombin resulting in platelet activation, aggregation and formation of hemostatic plug. Flow cytometry is a useful technique for the study of platelet activation in circulating blood. Platelet activation markers for ex vivo analysis may include a) activation-dependent epitopes of the membrane glycoprotein (GP) IIb/IIIa (CD41a) receptor, as demonstrated by the binding of activation-specific monoclonal antibodies (MoAbs) PAC1, anti-LIBS1 and anti-RIBS); b) the expression of P-selectin (CD62p), the alpha-granule GP translocated to the platelet surface following release reaction; and c) platelet procoagulant activity, as demonstrated by the binding of i) annexin V protein to the prothrombinase-complex (prothrombin, activated factor X (Xa) and V (Va)) binding sites on the surface of activated platelets, and of ii) MoAbs against activated coagulation factors V and X bound to the surface of activated platelets. Using this method, platelet activation as a marker for in vivo prothrombotic activity can be demonstrated in various clinical conditions including coronary angioplasty, orthostatic challenge in primary depression, sickle cell disease in clinical remission and during pain episode, and in pregnancy-related hypertension with marked increase during preeclampsia. The finding of platelet procoagulant activity is corroborated by increased levels of plasma markers for thrombin generation and fibrinolytic activity.
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PMID:Platelet activation as a marker for in vivo prothrombotic activity: detection by flow cytometry. 1547 Dec 23

We present a case of a lumbar pseudoaneurysm in a 62-year-old patient with myelofibrosis (agnogenic myeloid metaplasia). The patient was submitted to two anesthetic infiltrations for lumbar pain and one biopsy of a suspected hematopoietic site. Subsequently, a 4.5 cm lumbar pseudoaneurysm was diagnosed. The pseudoaneurysm was thrombosed with 1 ml (500 IU) thrombin injection with a successful clinical result. We discuss different treatment options along with several issues related to the most frequent complication of this technique, namely, native artery thrombosis.
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PMID:Paravertebral pseudoaneurysm thrombosed after percutaneous thrombin injection. 1586 76


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