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Louis E Remer KA Doherr MG Neumann U Jungi T Schawalder P Spreng D 《Veterinary journal (London, England : 1997)》2006,172(3):466-472
Osteoarthritis due to cranial cruciate ligament (CCL) rupture or hip dysplasia is one of the most important causes of chronic lameness in dogs. This study aimed at comparing nitric oxide (NO) production by the CCL with that of the femoral head ligament (FHL) and the medial collateral ligament (MCL), and investigating the pathway of NO production and the concomitant metalloproteinase (MMP) activity in the presence or absence of an inflammatory stimulus. Ligaments of normal dogs were subjected to different stimuli, and NO and MMP activity from explant culture supernatants were compared. The results showed that in explant cultures of the canine CCL more NO was produced than in those of the other two ligaments. A higher level of NO was produced when CCLs were exposed to the inducible nitric oxide synthase (iNOS)-inducing cocktail TNF/IL-1/LPS, and NO synthesis could be inhibited by both l-NMMA, a general nitric oxide synthase (NOS) inhibitor and l-NIL, a specific iNOS inhibitor. However, a correlation between NO synthesis and iNOS expression levels as determined by immunohistochemistry was not observed. In contrast to CCL, no evidence for iNOS-dependent NO synthesis was observed for MCL and FHL. The CCL produced less MMP than MCL and FHL, and no correlation between MMP and NO could be demonstrated. MMP activity in the CCL increased significantly after 48 h of incubation with the inflammatory stimulus. The results suggest that in canine osteoarthritis NO synthesized by canine CCL plays a more important role in the pathogenesis of osteoarthritis of the stifle than that synthesized by FHL and MCL. 相似文献
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Webb AA Muir GD 《Journal of veterinary internal medicine / American College of Veterinary Internal Medicine》2000,14(4):399-411
The unique microenvironment within the central nervous system (CNS) relies upon the integrity of the blood-brain barrier (BBB). This selectively permeable barrier comprises interendothelial tight junctions located at the capillaries and postcapillary venules. Cells and structures in the local environment are required to maintain normal BBB function. When inflammation is present, the BBB itself plays an integral role in the inflammatory response by either producing or expressing a variety of cytokines, adhesion molecules, metalloproteinases, serine proteases, products of arachidonic acid metabolism, and nitric oxide. Understanding the role of the BBB during inflammation is essential when creating and employing a therapeutic regime for animals with CNS disease. This review focusses on recent discoveries about the BBB and its role in inflammation, and applies this knowledge to our current understanding of inflammatory CNS disease in dogs and cats. 相似文献
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Moore AS Dernell WS Ogilvie GK Kristal O Elmslie R Kitchell B Susaneck S Rosenthal R Klein MK Obradovich J Legendre A Haddad T Hahn K Powers BE Warren D 《Journal of veterinary internal medicine / American College of Veterinary Internal Medicine》2007,21(4):783-790
BACKGROUND: This study was designed to assess the efficacy of a matrix metalloproteinase inhibitor in prolonging posttreatment survival for dogs with appendicular osteosarcoma after treatment with amputation and doxorubicin chemotherapy. HYPOTHESIS: Survival will be prolonged in dogs receiving BAY 12-9566. ANIMALS: The study included 303 dogs with appendicular osteosarcoma. METHODS: Dogs were treated with doxorubicin (30 mg/m2) every 2 weeks for 5 treatments starting 2 weeks after amputation. Dogs were randomly allocated to receive a novel nonpeptidic biphenyl inhibitor of matrix metalloproteinases (MMPs, BAY 12-9566; 4-[4-4-(chlorophenyl)phenyl]-4-oxo-2S-(phenylthiomethyl) butanoic acid) or placebo after doxorubicin chemotherapy. RESULTS: Median survival for all 303 dogs was 8 months; and 1-year, 2-year, and 3-year survival rates were 35%, 17%, and 9%, respectively. Treatment with BAY 12-9566 did not influence survival. Multivariate analysis revealed that increasing age (P = .004), increasing weight (P = .006), high serum alkaline phosphatase (ALP) (P = .012) and high bone ALP (P < .001) were independently associated with shorter median survival times. Additional analyses on available data indicated that as the number of mitotic figures in the biopsy increased (P = .013), and as plasma active MMP-2 concentrations increased (P = .027), the risk of dying increased. CONCLUSIONS AND CLINICAL IMPORTANCE: Doxorubicin is an effective adjuvant to amputation in prolonging survival for dogs with appendicular osteosarcoma. 相似文献
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An Overview of Proteinase Inhibitors 总被引：6，自引：0，他引：6
Kristen Hibbetts Brad Hines David Williams 《Journal of veterinary internal medicine / American College of Veterinary Internal Medicine》1999,13(4):302-308
Proteinase inhibitors are proteins in the body that regulate the catalytic activity of proteinases. They are important in a large variety of physiologic processes including coagulation, digestion, tumor metastasis and immunity. Proteinase inhibitors are categorized as either nonspecific proteinase inhibitors or class-specific proteinase inhibitors. Nonspecific proteinase inhibitors are comprised soley of the alpha macroglobulins, most notably alpha2-macroglobulin. Class-specific proteinase inhibitors are subcategorized as serine proteinase inhibitors, aspartic proteinase inhibitors, metalloproteinase inhibitors, and cysteine proteinase inhibitors. Each subcategory is made up of numerous inhibitors. As the roles of individual proteinase inhibitors are determined, the therapeutic use of natural and synthetic proteinase inhibitors is also being investigated. The purpose of this article is to review the history and classification of proteinase inhibitors and their relevance to veterinary medicine. 相似文献
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Summary A metalloproteinase was found to be the main component of a protease in the extract from an Andosol collected from a tomato field. The protease has a pH optimum of 7 for benzyloxycarbonyl-L-phenylalanyl-L-tyrosyl-L-leucine with tyrosylleucine as the main reaction product. The Km value for the substrate was 0.4 mM. Activity was inhibited by EDTA but not by pepstatin, p-chloromercuribenzoate and phenylmethanesulfonyl fluoride. After the removal of EDTA from the inactivated enzyme by dialysis and the addition of metal ions (Zn2+, Mn2+ and Fe3+), the enzyme activity could be recovered. The apparent isoelectric points of the metalloproteinase components were estimated to be 4.9, 4.5 and 4.1 by isoelectric focusing. A fraction with an apparent isoelectric point of 4.9 was the main component. The apparent molecular weight of the main protease component was estimated to be 4.7 × 104 by gel filtration of Sephadex G-100. The enzyme hydrolyzed a natural polypeptide, angiotensin I (Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu). Main split sites in the peptide were -Tyr7-Ile5- and -Pro7-Phe8-. The former was the most sensitive site to the soil metalloproteinase concerned. 相似文献
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寄生虫金属蛋白酶研究进展 总被引：2，自引：0，他引：2
金属蛋白酶（Metalloproteinase）是虫体活性中心依赖于金属离子的一类蛋白酶，在寄生虫中其分布非常广泛，功能涉及寄生虫营养摄取、细胞分化、对宿主的入侵以及免疫逃避等许多方面，一些金属蛋白酶还具有比较强的免疫原性。寄生虫金属蛋白酶的功能和作用的阐明，将为寄生虫病的免疫诊断和治疗以及新型生物制剂的开发开辟新的思路。本文综述了寄生虫金属蛋白酶的最新研究进展。 相似文献
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