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At least 847 records · Page 47Linked to original sources
PubMed1997

Outcome assessment in clinical trials involving medical management of osteoarthritis in small animals.

The goal of any clinical trial involving modulation of osteoarthritis is to assess the efficacy of a proposed therapy. This article attempts to provide some insight into assessing the outcome of clinical trials involving the management of osteoarthritis and reviews select key areas within clinical trials that need to be evaluated during critical analysis of any proposed therapeutic product.

Animals↗
PubMed1997

Slow-acting, disease-modifying osteoarthritis agents.

There is evidence to suggest that tetracyclines have benefit beyond their antimicrobial activity. The ability to inhibit metalloproteinase activity may provide a disease-modifying effect in OA, and available data suggest that further investigation is warranted. Controlled, double-blind, prospective clinical studies have not been completed. The canine cruciate ligament transection model studies are frequently cited as the most convincing in vivo evidence of a benefit of oral tetracycline therapy for the treatment of OA. Until more evidence becomes available, the use of tetracyclines as therapeutic agents for OA should be considered investigational.

Administration, Oral↗
PubMed1990

The role of chemical mediators in the pathogenesis of inflammation with emphasis on the kinin system.

In recent years, numerous agents have been recognized as inflammatory mediators. In this review, however, we discuss only those having direct relevance to human inflammatory diseases These mediators are clinically important due to their proinflammatory properties such as vasodilatation, increased vascular permeability, pain and chemotaxis. They may lead to the fifth cardinal sign, loss of function in inflammatory diseases. Agonists and non-specific antagonists are used as pharmacological tools to investigate the inflammatory role of PGs, LTs, PAF, IL-1, histamine, complement, SP, PMN-leukocytes, and kallikrein-kininogen-kinin systems. Unfortunately, no compound is known which concurrently abolishes all actions and interactions of inflammatory mediators. Therefore it would be highly useful to promote efforts in developing selective and competitive antagonists against proinflammatory actions of these chemical mediators. This may help to a better understanding of the pathogenesis of inflammatory reactions, and it may also be useful for the therapy of inflammatory diseases.

Anaphylatoxins↗
PubMed1983

Slow reacting substance in the exudate of allergic air pouch inflammation in rats.

The activity of slow reacting substance was examined in the exudate of the allergic inflammation in rats after partial purification by alkaline decomposition and XAD-8 anion-exchange column chromatography. The guinea-pig ileum contractile substance from the exudate collected at 1 hr after the challenge injection was attributed to leukotriene (LT) C4 and/or D4 since the activity was selectively antagonized by FPL 55712. Participations of histamine, acetylcholine and prostaglandin E2 were ruled out. However, the contraction pattern due to the partially purified substance collected at 24 hr after the challenge injection was different from that at 1 hr. The guinea-pig ileum was contracted much more slowly than by synthetic LT C4 or D4 and this contraction was not antagonized by FPL 55712. It was demonstrated that some unidentified materials exist in the exudate of the allergic air pouch inflammation which contract isolated guinea-pig ileum in a different manner from synthetic LT C4 or D4.

Air↗
PubMed1980

Biomolecular structure determination by mass spectrometry.

Mass spectometry, conventionally used with smallish molecules (less than 1,000 daltons), has suprisingly emerged as a powerful technique for the determination of the amino acid sequences of proteins and the structure of glycopeptides as well as for the characterization of biologically active materials of unusual structure such as the peptidolipids. Further applications to biomedical problems are foreseen.

Amino Acid Sequence↗
PubMed1980

Enzymatic assembly of slow reacting substance.

When basophils or mast cells are stimulated by a specific antigen they release chemical mediators, including a potent bronchoconstrictor, slow reacting substance of anaphylaxis (SRS-A). The structure of SRS from a mouse mastocytoma and rat basophilic leukaemia (RBL-1) cells has been identified as a thioether or arachidonic acid and glutathione [not a thioether of cystene as was originally thought]. SRS has been named leukotriene (LT) C and may be formed by a novel lipoxygenase pathway which also synthesizes 5,6-oxido-7,9,11,14-icosatetraenoic acid (LTA) and 5,12-dihydroxy-6,8,10,14-icosatetraenoic acid (LTB). Homogenates of RBL-1 cells, when incubated with C-arachidonic acid, form 5-hydroxy-icosatetraenoic acid (5-HETE) and 5,12-dihydroxy- and 5,6-dihydroxy-icosatetraenoic acid. The latter is the spontaneous breakdown product of the labile intermediate LTA. Formation of both compounds is stimulated by calcium. We have now produced biologically active SRS in a cell-free system generated from RBL-1 cells. Glutathione was essential for SRS synthesis and calcium stimulated its formation.

Animals↗
PubMed1980

Leukotrienes are potent constrictors of human bronchi.

Slow reacting substance of anaphylaxis (SRS-A) is released by various stimuli, including immunological challenge, and has long been considered an important mediator of immediate hypersensitivity reactions, such as bronchoconstriction in allergic asthma. Recently, slow reacting substances from several tissues have been identified and characterized as members of a newly discovered group of substances, the leukotrienes. Leukotrienes are generated from arachidonic acid and other polyunsaturated fatty acids in a pathway initially involving a lipoxygenase-catalysed oxygenation at C-5 (Fig. 1). This differs from the synthesis of prostaglandins and thromboxanes, where the initial transformation of arachidonic acid is catalysed by a cyclo oxygenase (Fig. 1). Recently, leukotriene C4(LTC4:5(S)-hydroxy,6(R)-S-glutathionyl-7,9-trans, 11,14-cis-eicosatetraenoic acid) and D4(LTD4:5(S)-hydroxy,6(R)-S-cysteinyl-glycyl-7,9-trans,11,14-cis-eicosatetraenoic acid) were found to have biological effects in several bioassay systems, which are strikingly similar to those previously reported for impure extracts of SRS-A. Here we report the remarkable contractile activity of both LTC4 and LTD4 on isolated human bronchi, which further emphasizes the possibility that leukotrienes are potent mediators of bronchoconstriction in man.

Arachidonic Acids↗
PubMed1981

Slow-reacting substances (leukotrienes) contract human airway and pulmonary vascular smooth muscle in vitro.

During a type I allergic reaction histamine, slow-reacting substance of anaphylaxis (SRS-A) and other mediator substances are elaborated from specific tissue sites. In allergic asthma these sites are in the lung and the mediator substances cause airway obstruction by contracting smooth muscle and altering mucociliary function. Unlike histamine, slow-reacting substances (SRSs) have been assessed very little for their roles in obstructive airways disease. This has been partly due to the fact that their chemical nature was unknown until recently and thus pure samples were not available for pharmacological studies. However, SRSs isolated from both immunological and non-immunological reactions have been identified as a combination of two related lipid substances--leukotriene C4 (LTC) and leukotriene D4 (LTD); thus it is now possible to use pure SRSs (leukotrienes) in pharmacological studies of airway smooth muscle. LTC and LTD have been shown to contract guinea pig tracheal and lung parenchymal strips but there is no evidence that these substances produce similar effects on human lung tissue. To clarify this, in vivo pharmacological studies were done to determine the actions of LTC and LTD on smooth muscle strips of human bronchus, pulmonary vein and artery, and lung parenchymal tissue containing smooth muscle components and pleura. As indicated in a preliminary report, all four types of tissues contracted in a dose-dependent fashion to the leukotrienes, although these substances only function as partial agonists.

Airway Resistance↗