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)

Suramin, a polysulfonated naphtylurea compound that has been used in the past for treatment of trypanosomiasis and onchocerciasis, is also an effective antitumor agent. Its marked antiproliferative potential probably resides in the ability of the drug to interfere with various growth factor signaling mechanisms. We were interested in whether suramin could also interact with signal transduction in bone cells, leading to osteoclast proliferation and, consequently, bone resorption. Utilizing organ-cultured neonatal mouse calvaria, we studied the effect of suramin on bone resorption induced by, for example, parathyroid hormone, 1,25-dihydroxycholecalciferol, epidermal growth factor or thrombin. In the 1 to 100 microM concentration range, in which no toxic effect on bone cells was observed, suramin effectively suppressed bone resorption regardless of whether it was mediated by endogenous prostaglandin production or induced by parathyroid hormone (Ki = 70 microM), 1,25-dihydroxycholecalciferol (Ki = 70 microM), epidermal growth factor (Ki = 5 microM) or thrombin (Ki = 5 microM). The profound inhibitory effect of suramin on various bone resorptive processes around 100 microM, which is regarded as the minimally effective concentration for successful anticancer treatment, could be exploited for the treatment particularly of tumors associated with hypercalcemia.
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PMID:Suramin is a potent inhibitor of calcemic hormone- and growth factor-induced bone resorption in vitro. 838 76

When blood-feeding, black flies introduce secretions into the feeding lesion that act in a coordinated manner on the 3 arms of the vertebrate hemostatic system (platelet aggregation, coagulation, and vasoconstriction). Apyrase activity inhibits platelet aggregation and is ubiquitous in the saliva of black flies, although activity per gland varies by species and has a positive association with anthropophagy. Anticoagulants target components in the final common pathway of the coagulation cascade, including factors V, Xa, and II (thrombin). The antithrombin salivary protein may exert a redundant effect by inhibiting the role of thrombin in platelet aggregation. Antithrombin presence and activity also varies among black fly species, and exhibits a positive correlation with zoophagy. Vasodilation of capillaries to increase blood supply to the feeding wound appears to be an important requirement for Simulium spp., because substantial erythema-inducing activity, has been demonstrated in salivary glands of all New World species examined. Salivary glands of Simulium ochraceum (Walker), a highly anthropophilic vector of Onchocerca volvulus (Leuckhart), contain greater vasodilator activity than several other species, including S. metallicum Bellardi, a secondary zoophagic vector of human onchocerciasis. Simulium vittatum Zetterstedt saliva affects immune cell responses and cytokine production. The ability of the saliva to modulate components of the host immune system provides an opportunity for enhancing transmission of pathogens during bloodfeeding. Thus, the likely possibility that effective pathogen transmission relies on vector saliva may complement present efforts aimed at target epitopes of O. volvulus or identify additional molecules to be investigated as part of a "river blindness" vaccine cocktail. Components in saliva also may enhance the transmission of other microbial agents either by a cofeeding process similar to that observed in ixodid ticks or through rupture of the labrum during escape of Onchocerca infective stage larvae. In a few instances, saliva of some Simulium spp. also has been associated with extensive tissue and organ pathology, including hemorrhagic shock and death. Pathologic signs associated with this syndrome indicate an enhanced antihemostatic activity in saliva.
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PMID:Black fly (Diptera:Simuliidae) salivary secretions: importance in vector competence and disease. 910 50

In this study, anticoagulant activity was detected in salivary gland homogenates (SGHs) of Thyrsopelma guianense (Diptera: Simuliidae). The SGH yielded 1.07 microg +/- 0.03 (n = 15) of total soluble protein per pair of glands. In addition, following SDS-PAGE (12.5% gel) and silver nitrate staining, 12 polypeptides with molecular weights ranging from 14-69 kDa were detected in all physiological ages analyzed (12 h, 24 h, 48 h and 72 h following emergence). Coagulation bioassays showed that the SGHs had activities that interacted at all levels of coagulation (the intrinsic, extrinsic and common pathways), by extending the plasma recalcification time, prothrombin time, thrombin time. This is the first report on the activity of salivary gland proteins from the main vector of onchocerciasis in Brazil. We also suggest detailed studies on the morphology and function of the salivary glands in order to understand the role of these proteins in host/vector interactions.
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PMID:Anticoagulant activity in salivary gland homogenates of Thyrsopelma guianense (Diptera: Simuliidae), the primary vector of onchocerciasis in the Brazilian Amazon. 2042 77