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)

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

The objective of this phase 3, multicentered, prospective, randomized, evaluator-blinded, clinical study was to compare skin graft adherence utilizing a fibrin sealant containing 4 IU/ml thrombin (FS 4IU VH S/D [FS 4IU VH S/D will be marketed under the trade name ARTISS upon licensure in the United States]) to graft adherence utilizing staples in burn patients requiring wound excision and skin grafting. FS 4IU VH S/D was compared with staples in 138 patients. Patients had burn wounds measuring < or =40% of total body surface area with two comparable test sites measuring between 1 and 4% total body surface area each. Wound closure at day 28 was assessed using test site planimetry and review of day 28 photographs by three independent blinded evaluators (primary endpoint analysis). Secondary efficacy measures included hematoma/seroma on day 1, engraftment on day 5, and wound closure on day 14. Investigator and patient-reported outcomes were also assessed. The proportion of test sites with complete wound closure at day 28 was 70.3% in FS 4IU VH S/D treated sites and 65.8% in stapled sites, as assessed by planimetry. Blinded review of day 28 photographs confirmed that the rate of complete wound closure was similar between the two treatments, although the overall assessed rates of closure were lower than those determined by planimetry: FS 4IU VH S/D (43.3%) and staples (37.0%). The lower limit of the 97.5% confidence interval of the difference between FS 4IU VH S/D and staples was -0.029, which is above the predefined noninferiority margin of -0.1. Therefore, FS 4IU VH S/D is at least as efficacious as staples at the 97.5% one-sided level for complete wound closure by day 28. Hematoma/seroma on day 1 occurred at significantly (P < .0001) fewer FS 4IU VH S/D-treated sites (29.7% [95% CI 22.2-38.1%]) compared with stapled sites (62.3% [95% CI 53.7-70.4%]). Engraftment on day 5 was deemed to be 100% in 62.3% (95% CI 53.7-70.4%) of the FS 4IU VH S/D-treated sites and 55.1% (95% CI 46.4-63.5%) of the stapled sites (P = .0890). Complete wound closure by day 14 occurred in 48.8% (95% CI 39.9-57.8%) of the FS 4IU VH S/D treated sites and 42.6% (95% CI 34.0-51.6%) of the stapled sites (P = .2299). FS 4IU VH S/D scored significantly better than staples for all investigator-assessed outcomes, namely quality of graft adherence (P < .0001), preference for method of fixation (P < .0001), satisfaction with graft fixation (P < .0001), and overall quality of healing (P < .0001). Likewise, FS 4IU VH S/D scored significantly better than staples for all patient-assessed outcomes, namely anxiety about pain (P < .0001) and treatment preference (P <.0001). The safety profile of FS 4IU VH S/D was excellent as indicated by the lack of any related serious adverse experiences. These findings demonstrate that FS 4IU VH S/D is safe and effective for attachment of skin grafts, with outcomes at least as good as or better than staple fixation.
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PMID:Efficacy and safety of a fibrin sealant for adherence of autologous skin grafts to burn wounds: results of a phase 3 clinical study. 1835 85

Proteases, like thrombin, trypsin, cathepsins, or tryptase, can signal to cells by cleaving in a specific manner, a family of G protein-coupled receptors, the protease-activated receptors (PARs). Proteases cleave the extracellular N-terminal domain of PARs to reveal tethered ligand domains that bind to and activate the receptors. Recent evidence has supported the involvement of PARs in inflammation and pain. Activation of PAR(1), PAR(2), and PAR(4) either by proteinases or by selective agonists causes inflammation inducing most of the cardinal signs of inflammation: swelling, redness, and pain. Recent studies suggest a crucial role for the different PARs in innate immune response. The role of PARs in the activation of pain pathways appears to be dual. Subinflammatory doses of PAR(2) agonists induce hyperalgesia and allodynia, and PAR(2) activation has been implicated in the generation of inflammatory hyperalgesia. In contrast, subinflammatory doses of PAR(1) or PAR(4) increase nociceptive threshold, inhibiting inflammatory hyperalgesia, thereby acting as analgesic mediators. PARs have to be considered as an additional subclass of G protein-coupled receptors that are active participants to inflammation and pain responses and that could constitute potential novel therapeutic targets.
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PMID:Protease signaling to G protein-coupled receptors: implications for inflammation and pain. 1843 28

Pseudoaneurysms are not a common complication of the endovascular procedures but can present a serious therapeutic problem. Both, the application of compression therapy and surgical operation can lead to the development of subsequent complications. The aim of this study was analysis of the treatment results of iatrogenic pseudoaneurysms managed with percutaneous thrombin injection. Treated group consisted of 69 patients diagnosed with iatrogenic femoral pseudoaneurysms. The indication for injection technique was ineffective compression therapy as well as necrotic changes or bacterial skin infection in the groin area or a large diameter of pseudoanurysm's chambers. Thrombin was injected percutaneously during 1-3 sessions in the dose of 100-1200 U into the centre of the chamber under ultrasound control. Primary and secondary success rate was 88% and 94% respectively. The following factors significantly decreased effectiveness of the method: complex pseudoaneurysms (with treatment efficacy 82% and 88% respectively vs 90% and 96% for simple pseudoaneurysms), and large chamber volume. Early and late recanalization of the thrombotic changes appeared in 7% and 3% of treated cases. The most frequent complication was appearance of non-elastic tumor (71%) or pain (64%) in the groin area. The most serious complication was acute lower limb ischemia detected in one case (2%) as a result of femoral artery compression by the thrombosed pseudoaneurysm. Percutaneous thrombin injection should be a preferred method of pseudoaneurysms treatment, especially in cases of ineffective compression therapy or its contraindications due to low cost of the therapy, simplicity of the technique and relatively low percentage of the complications.
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PMID:[Application of the percutaneuos thrombin injection in treatment of iatrogenic femoral pseudoaneurysms]. 1863 25

Wound healing impairment in the leg after removal of the saphenous vein within the framework of a coronary artery bypass graft (CABG) operation represents a clinically significant problem. Patients suffer from this complication, and treatment of the wounds is costly in terms of both time and money. No method is known to date that reliably prevents postoperative wound healing disturbances. The effect of autologous platelet gel to stimulate wound healing is known from various medical disciplines. Within a prospective randomized study, we wanted to determine whether intraoperative use of autologous platelet gel on the leg during a CABG operation could reduce the incidence of postoperative wound healing disturbances. The application group (AG) included 35 patients and was compared to a control group (CG) that also had 35 patients. The platelet gel, as well as the thrombin required to activate the platelets, was prepared from autologous patient blood during the operation. Validation of the platelet gel comprised measurement of the growth factors platelet-derived growth factor AB (PDGF AB) and epidermal growth factor (EGF), as well as the thrombocyte and leukocyte counts. Wound healing was photographically documented after surgery, and the patients were contacted by telephone on day 50 after surgery to obtain information on wound healing status. After cell separation, the platelet count was 1616 +/- 845/microL, which is higher than in whole blood by a factor of 7.1 +/- 2.0, with a platelet yield of 47.0% +/- 13.2%. The PDGF AB concentration after activation of the platelets was raised by a median factor of 158 and EGF by a median factor of 64 compared with whole blood. During the primary clinical stay, no statistically significant differences were recorded in the number of hematomas, postoperative leg swelling, or pain level. Large-area hematomas were less frequent in the application group (AG, 29.4% vs. CG, 60%, p = .007). In the follow-up 51 +/- 9 days after surgery, 17.6% (6/34) of the patients from the AG and 31.4% (11/35) of the patients from the CG showed leg wound healing disturbances (p = .184). Using the cell separation system, a biological product that contains high concentrations of platelets, leukocytes, and growth factors can be prepared reproducibly. Despite optimum application of the autologous platelet gel to the wound, no clinically relevant differences were found between the groups, either during the primary clinic stay or in the follow-up period.
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PMID:Autologous platelet gel fails to show beneficial effects on wound healing after saphenectomy in CABG patients. 1885 33

Lamiophlomis rotata (Benth.) Kudo (LR) is a traditional drug used by Chinese minorities such as Tibetans, Mongolians and Na Xi with the beneficial effects of hemostasis and alleviating pain. Flavonoids ingredients (P(1)), iridoid glycosides ingredients (P(2)) and maximus polarity components ingredients (P(3)) were isolated from the aqueous extract of LR (AELR) with polyamide and macroporous adsorptive resins chromatographic columns. The hemostatic activity of these ingredients was estimated by the changes in bleeding time (BT), clotting time (CT) and blood coagulation parameters in mice or rats. RP-HPLC was used to analyze the chemical composition of P(2). As a result, AELR and P(2) significantly shortened BT, CT and thrombin time (TT), and increased fibrinogen (FIB), but P(1) and P(3) showed no hemostatic effect during the experiment. Moreover, P(2) showed satisfactory hemostatic effect with dose-effect relationship and low toxicity in mice. 8-Dehydroxy shanzhiside, phloyoside II, shanzhiside methylester, loganin, and 8-O-acetylshanzhiside methylester were detected as the main iridoid glycosides in P(2) by RP-HPLC. Our results suggest that iridoid glycosides may be the hemostatic activity ingredients of L. rotata and are a potential hemostatic medicine.
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PMID:Isolation and identification of hemostatic ingredients from Lamiophlomis rotata (Benth.) Kudo. 1917 19

A 42-year-old male presented to the emergency department with pain and swelling of his distal right wrist. Bedside ultrasound placed over the swelling revealed a pseudoaneurysm of the radial artery. The patient received percutaneous thrombin injection of the aneurysm sac followed by direct ultrasound compression therapy of the pseudoaneurysm neck, resulting in thrombosis of the sac. The use of bedside ultrasound by the emergency physician led to appropriate care and proper disposition for definitive management.
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PMID:Pseudoaneurysm of the radial artery diagnosed by bedside ultrasound. 1956 25

Serine proteases such as thrombin, trypsin and mast cell tryptase can act on different cell types through protease-activated receptors (PARs). These receptors have been shown to be implicated in several phenomena such as inflammation, platelet activation, immune response and atherosclerosis. Several studies recently reported PARs expression on neurons and some of them demonstrated that these receptors could interfere with nociception. The contribution of PAR(1) to inflammatory pain and the mechanism involved in this phenomenon were investigated. Intraplantar injection of PAR(1) agonist increased withdrawal latency and reduced response frequency to von Frey filaments, thus inhibiting nociceptive response to both mechanical and thermal stimuli in mice. PAR(1) agonist also reduced carrageenan-induced inflammatory hyperalgesia. The anti-nociceptive effects of PAR(1) agonist were mediated by endogenous opioids, as this effect was inhibited by local injection of naloxone methiodide, and because intraplantar injection of PAR(1) agonist increased mRNA expression of the endogenous opioid precursor proenkephalin. However, PAR(1) agonist was not able to inhibit calcium signals in isolated sensory neurons exposed to pro-nociceptive agents. Finally, despite similar inflammatory parameters, PAR(1)-deficient mice showed a strong potentiation of inflammatory hyperalgesia induced by the intraplantar injection of either formalin or carrageenan, or in the chronic model of collagen-induced arthritis, compared to wild-type mice. This study highlights a previously unknown endogenous mechanism of analgesia, showing a central role for the thrombin receptor PAR(1) in the regulation of inflammatory pain and as an activator of opioid pathways.
Pain 2009 Nov
PMID:Thrombin receptor: An endogenous inhibitor of inflammatory pain, activating opioid pathways. 1967 41

Low-grade inflammation, a minor elevation in the baseline concentration of inflammatory markers such as C-reactive protein (CRP), is nowadays recognized as an important underlying condition in many common diseases. Concentrations of CRP under 10 mg/1 are called low-grade inflammation and values above that are considered as clinically significant inflammatory states. Epidemiological studies have revealed demographic and socioeconomic factors that associate with CRP concentration; these include age, sex, birth weight, ethnicity, socioeconomic status, body mass index (BMI), fiber consumption, alcohol intake, and dietary fatty acids. At the molecular level, production of CRP is induced by proinflammatory cytokines IL-1, IL-6, and IL-17 in the liver, although extra hepatic production most likely contributes to systemic concentrations. The cytokines are produced in response to, for example, steroid hormones, thrombin, C5a, bradykinin, other cytokines, UV-light, neuropeptides and bacterial components, such as lipopolysaccharide. Cytokines exert their biological effects on CRP by signaling through their receptors on hepatic cells and activating different kinases and phosphatases leading to translocation of various transcription factors on CRP gene promoter and production of CRP protein. Genetic polymorphisms in the interleukin genes as well as in CRP gene have been associated with minor elevation in CRP. As minor elevation in CRP is associated with both inflammatory and noninflammatory conditions, it should be noticed that the elevation might just reflect distressed or injured cells homeostasis maintenance in everyday life, rather than inflammation with classical symptoms of redness, swelling, heat, and pain.
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PMID:Proinflammatory cytokines in CRP baseline regulation. 1980 17

The authors report the clinical case of a 29 year-old caucasian male, previously healthy, victim of traffic accident with head and chest trauma, resulting in a prolonged stay (around 60 days) in an intensive care unit. After hospital discharge, the patient noticed a slow growing of a left supraclavicular pulsatile mass, associated with pain, both local and irradiating to the left arm. The diagnostic investigation revealed a complex false aneurysm with associated arterio-venous fistulae, dissecting cervical muscle planes and involving the braquial plexus. He was submitted to surgical intervention consisting in the ligation of a scapular afferent artery and ligation of communication to the internal jugular vein, with significant decrease in the intra-luminal blood flow velocity. He was subsequently submitted to percutaneous eco-guided thrombin injection under Valsalva manouver, with complete thrombosis of the false aneurysm. There was a quick resolution of the clinical complaints and a progressive reduction of the mass volume (6 month follow-up). A discussion is made on the main features of this entity, normally its etiopathogeny, surgical management and false aneurysm exclusion by means of eco-guided injection of thrombin.
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PMID:[Complex supraclavicular false aneurysm. Case report]. 1982 8


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