Comparison of endothelin-1 and -3 on models of inflammation.
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Animals↗
Biomedical subjects
A R Moore
Publications and source records attributed to A R Moore.
The protective effects of cell-free fluid exudate on cartilage degradation in vitro.
In a short-term culture system, polymorphonuclear neutrophils (PMNs) were shown to cause significant loss of glycosaminoglycan (GAG) from cartilage. In addition, a lysate of these cells, and in particular cells stimulated with a phorbol ester, greatly enhanced this loss of GAG. This loss could be partially or completely inhibited by the addition of cell-free fluid exudate to the system. In other long-term culture experiments, IL-1a was shown to enhance fibroblast-induced GAG loss from cartilage. In this system too the breakdown was inhibited by cell-free fluid exudate. Initial characterization of the protective agent or agents shows them to be heat-stable at 56 degrees C and to be non-dialysable. It is proposed that in the chronic inflammatory joint disease, rheumatoid arthritis, the fluid phase of an inflammatory response may have a protective effect against the underlying pathological processes.
Animals↗
The effect of indomethacin on cartilage breakdown.
The effects of recombinant interleukin-1 alpha (rIL-1 alpha) and indomethacin on the glycosaminoglycan (GAG) content of rat femoral head cartilage (FHC) were studied in vitro. Net GAG loss was observed from cartilage cultured in the presence of indomethacin plus rIL-1 alpha. Indomethacin and rIL-1 alpha alone caused no net loss of GAG from cartilage unless the cartilage was cultured in the presence of fibroblasts.
Animals↗
Anti-inflammatory effects of endothelin-1.
Endothelin-1 (ET-1), when injected intradermally in rats concurrently with FMLP, did not suppress cell accumulation 6 h later. In view of the fact that ET-1 can antagonize mediators of increased vascular permeability, it is proposed that this is further evidence that fluid and cell accumulation at an inflammatory site are separate processes.
Animals↗
The effects of heparin and cortisone on an experimental model of pannus.
The effects of heparin and cortisone were investigated in a model of experimental pannus-mediated cartilage degradation. Rat femoral head cartilages were implanted bilaterally (sc.) into female mice either non-wrapped or wrapped in cotton. Animals were treated with tap water (p.o.), heparin 1000 Units (p.o.), cortisone 2 mg/kg (s.c) and heparin-cortisone combined. After 14 days, the implants were removed and analysed for exudate volume, granulation-tissue dry weight and cartilage glycosamino-glycan (GAG) content. In the heparin-treated animals there was a significant (p less than 0.001) increase in the granulation-tissue dry weight, whilst combined treatment significantly (p less than 0.001) reduced both exudate volume and cartilage degradation. It is possible that the effects on angiogenesis may indicate novel treatment for the growth of pannus and cartilage breakdown.
Animals↗
The chemotactic properties of cartilage glycosaminoglycans for polymorphonuclear neutrophils.
Cartilage breakdown products have been tested for their effects on the locomotion of rat polymorphonuclear neutrophils in vitro. Chondroitin sulphate, keratan sulphate and hyaluronic acid were used in checkerboard migration assays to differentiate chemotaxis from chemokinesis. All test substances showed both chemokinetic and chemotactic activities. The same substances were then injected intradermally to determine their effects on vascular permeability and leukocyte accumulation in vivo. There was no significant effect on vascular permeability 30 minutes after injection as measured by a dye-leakage method. Histological examination of skin sections taken 6 hours after injection showed modest accumulations of polymorphonuclear neutrophils. It is suggested that cartilage breakdown products may account for the persistence of polymorphonuclear neutrophils in some chronic inflammatory joint diseases.
Animals↗
Myofibroblasts in cotton-induced granulation tissue and the bovine adrenal capsule: morphological aspects.
Ultrastructural studies of one week old cotton-induced granulation tissue revealed the presence of polymorphonuclear neutrophils (PMN), macrophages and mast cells, whilst the granulation tissue from two week old cotton implants contained fibroblasts, myofibroblasts and abundant collagen fibres. Similarly, the bovine adrenal capsule contained both fibroblasts and myofibroblasts. It is proposed that the bovine adrenal capsule and two week cotton-induced granulation tissue could be utilized as in-vitro models to study the mechanism(s) involved in myofibroblast contraction.
Adrenal Glands↗
Cellular interaction in cartilage degradation.
Rat femoral head cartilages (FHCs) in culture for six days retained their glycosaminoglycan (GAG) content and were not affected by recombinant human interleukin-la (IL-1), conditioned media from concanavalin-A stimulation of sensitized lymphocytes (lymphocyte media), or conditioned media from lymphokine-stimulated macrophages (macrophage media). Similarly FHCs cultured with macrophages in the presence of IL-1, lymphocyte medium or macrophage medium did not suffer a loss of GAG. However, FHCs cultured with fibroblasts showed a substantial loss of GAG. This fibroblast-mediated cartilage degradation was significantly increased by IL-1 and macrophage media respectively. Stimulation of fibroblasts by lymphocyte media failed to increase the loss of GAG. It is proposed that cartilage degradation in inflammatory joint disease is brought about by a sequential cell-to-cell interaction via cytokines leading ultimately to stimulation of fibroblast-mediated cartilage degradation.
Animals↗
A cytochemical study of the adjuvant inflamed air pouch in the rat.
The oxidative biochemistry of the adjuvant-inflamed rat air pouch has been studied using the techniques of quantitative cytochemistry. Highly significant increases in the maximal activities of glucose-6-phosphate dehydrogenase, lactate dehydrogenase and glyceraldehyde-3-phosphate dehydrogenase were observed. These changes are similar to those that have been reported by others in both human rheumatoid synovial tissue and the synovial tissue of rabbits with allergic arthritis. It is suggested that modulation of these changes by putative therapeutic agents may form the basis for a readily quantifiable drug screening programme.
Adjuvants, Pharmaceutic↗
Indomethacin and cartilage breakdown.
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Administration, Oral↗
The local modulation of vascular permeability by endothelial cell derived products.
Endothelin has been shown to suppress increased vascular permeability in the rat at doses of 0.01 pmol. The agonists used were nitric oxide and nitroprusside, which have the same activity as endothelial-derived relaxing factor. Histamine, 5-hydroxytryptamine, platelet activating factor and carrageenan were the other agonists used. It is proposed that endothelin and EDRF act as local hormones produced by endothelial cells to control local vascular permeability.
Animals↗
Adjuvant polyarthritis and the pseudosynovitis.
The cavity lining of a six day old subcutaneous air pouch in rats resembles normal synovium in morphology and responds in a comparable manner during development of polyarthritis. The ability of newly formed pouches (one and two days old) to respond similarly to polyarthritogen was examined here. Positive macro and microscopic changes similar to those seen in the six day old pouch were observed in rats previously inoculated with adjuvant. The intensity of some of these changes varied between pouches. The results of this study indicate that the adjuvant induced air pouch reaction does not depend on the presence of synovial-like lining for its production.
Air↗
A time course study of the changes that occur to the subcutaneous model of synovium following polyarthritogen.
The synovial-like structure lining the cavity of a subcutaneous air pouch in rats was examined macroscopically and microscopically for changes during the induction and progression of adjuvant polyarthritis. The earliest event observed was the infiltration of the lining by inflammatory cells which occurred about 6 days after inoculation with adjuvant. Deposition of fibrin and proliferation of blood vessels and connective tissue soon followed, associated with an even greater infiltration by inflammatory cells and the formation of oedema in the hyperplastic fibrous tissue. These changes resulted in a substantial thickening of the pouch wall (and consequently in air pouch skin thickness) that was most marked on day 9, when few rats had visible signs of joint swelling. As arthritis developed and became established (day 12-14), pouch wall thickness declined to below pre-adjuvant thickness. Histological changes were still evident but at a much reduced intensity. Challenge of pouches with tuberculin at various times showed reactivity of the delayed type, beginning not earlier than day 5 post-adjuvant inoculation. Pouches however failed to respond to tuberculin or to the non-specific irritant carrageenan as arthritis developed.
Animals↗
Cartilage damage by a granulomatous reaction in a murine species.
The encapsulation of intact rat femoral head cartilage or discs of bovine nasal cartilage with cotton-gauze before implantation in the subcutaneous tissues of mice, results in an accelerated loss of cartilage proteoglycan. Loss of proteoglycan from bovine nasal cartilage occurred later than rat femoral head cartilage, but eventually brought about complete dissolution of the cartilage. Freeze-thaw killing of bovine nasal cartilage did not alter the amount of proteoglycan lost. Destruction of both femoral and nasal cartilage was related to the mass of cotton implanted and to the growth of connective tissue within the implanted cotton. Mice previously implanted with femoral head cartilage were able to show enhanced degradation to new implants; this was even greater if the original implants were encapsulated with cotton. Presoaking of cotton-cartilage implants with the non-specific irritant, carrageenan inhibited the breakdown of cartilage. Autoradiographs of 35sulphate pulsed femoral cartilage following implantation with cotton showed reduced incorporation of radiolabel by chondrocytes.
Animals↗
Effectiveness of SMS 201-995, a synthetic, long-acting somatostatin analogue, in treatment of quinine-induced hyperinsulinaemia.
SMS 201-995, a new long-acting, synthetic somatostatin analogue, dose 50 micrograms/h, given as a continuous intravenous infusion, completely abolished quinine-induced insulin release in 9 healthy Thai volunteers. Hyperinsulinaemia, which caused sustained hypoglycaemia in a 32-year-old post-partum Thai patient who was receiving intravenous quinine for falciparum malaria, was suppressed within 30 min of starting SMS 201-995, and the patient became fully conscious. This octapeptide antagonises the stimulatory effect of quinine on the pancreatic beta cell and is a specific therapy for life-threatening hyperinsulinaemic hypoglycaemia complicating falciparum malaria.
Adult↗
Connective tissue abnormalities in MRL/1 mice.
Pathological changes in the connective tissue of the limbs of MRL/1 mice are described. Focal infiltrates of polymorphs or large mononuclear cells, or both, were seen both in synovial lining and subcutaneous tissue. Infiltrates were associated with vasculitis in some cases. Deposits of amorphous material were seen in and around joints and in foot pads. The material was more particulate and refractile than typical 'fibrinoid' and showed a positive Feulgen reaction. It was not surrounded by palisading cells and when seen in synovial tissue was not usually associated with changes in synovial lining cells. No obvious difference was seen between intra-articular and extra-articular lesions. Lesions in subcutaneous tissue occurred exclusively in the foot pads. Lymphocyte infiltration was not prominent at any site and no follicle formation was seen. Of two colonies studied, only one showed a significant increase in lining cell numbers in synovial tissue. Exercised animals had a similar distribution and severity of disease to those of matched controls. All lesions described were distinguishable from non-specific inflammatory lesions in normal control mice and MRL/++ mice on assessment of unmarked sections. The relation between these connective tissue lesions and the changes found in human chronic synovitis is discussed.
Animals↗
Significance of connective tissue proliferation in the breakdown of cartilage: a novel in vivo model.
The implantation of homologous femoral head cartilage in subcutaneous tissues of random bred Wistar rats results in both subchondral and articular surfaces becoming overlaid by an adherent granulation tissue comprising predominantly fibroblast-like cells. The response of the tissue to cartilage encapsulated with cotton fibres was also similar but erosions, mainly subchondral, were more evident and proteoglycan loss markedly greater. The connective tissue response to cotton was the progressive formation of a foreign body granuloma comprising mononuclear cells, multinucleated giant cells, and fibroblasts with very few polymorphonuclear leucocytes.
Animals↗
Adjuvant polyarthritis and the response of air pouch lining cells.
The influence of adjuvant polyarthritis on subcutaneous air pouches in rats was examined in the light of reports of the resemblance of their cavity lining to normal synovium. Marked macroscopic and microscopic changes were observed. These included thickening of air-pouch wall, hyperplasia of lining cells, infiltration of inflammatory cells, fibrosis, and the production of an effusion in the cavity; such changes are comparable to the proliferative synovitis reported in arthritic joints of diseased animals. However, whereas talus and patella cartilage were affected by the disease, these and femoral-head cartilage seemed to be relatively spared when implanted in air pouches of adjuvant-diseased rats even after a massive inflammatory response was elicited in the cavity following challenge with tuberculin. In conclusion, the present study demonstrates the generalized nature of adjuvant disease and confirms the lack of association between inflammation and cartilage destruction.
Air↗