Biomedical subjects

I R Garrett

Publications and source records attributed to I R Garrett.

29 records · Page 2Linked to original sources

PubMed1989

Relationship between interleukin-1 and prostaglandins in resorbing neonatal calvaria.

The relationship between the cytokine interleukin-1 and prostaglandins in resorbing bone cultures is very confusing. In some reports, the effects of interleukin-1 are described as prostaglandin dependent, but in some they appear prostaglandin independent. Recent data suggest that events occurring during the preculture period may be important for understanding later effects of any factor on bone resorption in neonatal mouse calvaria. In this study, we examined neonatal mouse calvaria morphologically for indices of resorption to determine the importance of this preculture period to their subsequent response to interleukin-1. Our results show that after a preculture period of 24 h in control media, osteoclast numbers and resorption areas are markedly enhanced. The numbers of osteoclasts fall when the calvaria are transferred to fresh control media for the following 72 h. This increase in osteoclast formation was inhibited by the addition of indomethacin (10(-6) M) during the preincubation period. When interleukin-1 was added to bones after the preincubation period, osteoclast numbers present at this time were maintained and indomethacin had no effect on this response. Furthermore, the inhibitory effect of indomethacin on osteoclast formation during the preculture period could be reversed by adding prostaglandins of the E series in low concentrations together with indomethacin. The effects of interleukin-1 did not appear to be related to osteoclast precursor proliferation, since hydroxyurea (which inhibits DNA synthesis in these cultures) had no effect on the response of calvaria calavaria increases osteoclast to interleukin-1. These results indicate that prostaglandin production by mouse numbers during the preincubation period.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Effects of interleukin-1 on bone turnover in normal mice.

Interleukin-1 (IL-1) is a potent stimulator of osteoclastic bone resorption in vitro and causes hypercalcemia and increased osteoclastic resorption when infused into normal mice for 72 h. However, its longer term or local effects on bone turnover in vivo are unknown. To study these, we injected IL-1 alpha once daily for 3 days into the sc tissue over the calvariae of normal mice and examined its effects on calvarial bone morphology during the subsequent 4 weeks using quantitative histomorphometry. Increased bone resorption inside the calvariae and elevated plasma calcium concentrations were present 24 h after the last IL-1 injection. These early systemic effects were not prevented by indomethacin. During the following 3-4 weeks most of the bone on the injected side of the calvariae was resorbed by osteoclasts and was subsequently replaced by increased amounts of new bone. These longer term local effects on bone turnover were prevented by indomethacin. However, indomethacin did not prevent the formation of new bone inside the calvariae at sites of resorption induced by IL-1 independent of prostaglandin production. These findings indicate that IL-1 stimulates bone turnover systemically, independent of prostaglandin production, and that it has profound long term local effects on bone turnover that are mediated through prostaglandins.

Animals↗

PubMed1988

Effect of gold salt treatment on the receptor binding activity of monocytes and macrophages isolated from rats with adjuvant arthritis.

We investigated the effect of chrysotherapy on the Fc and complement receptor binding activity of peripheral blood (PB) monocytes and peritoneal (PE) macrophages isolated from normal rats and rats with adjuvant induced arthritis. The adjuvant induced severe disease in Dark Agouti (DA) rats and less marked disease in J. C. Lewis (JC) rats. Gold treatment reduced the disease in DA rats but exacerbated the disease in JC rats. PB monocytes generally exhibited increased receptor activity after adjuvant injection. Gold treatment resulted in a simultaneous reduction of the PB monocyte receptor activity and increased the PE macrophage receptor activity. This was considered to be due to a direct effect of gold, since the Fc receptor activity of PE macrophages increased after in vitro gold treatment.

Animals↗

PubMed1988

Do gold drugs inhibit interleukin-1? Evidence from an in vitro lymphocyte activating factor assay.

The ability of some antiarthritic gold (I) compounds to inhibit the in vitro lympho-proliferative activity of human interleukin-1 (IL-1) in the lymphocyte activating factor (LAF) assay was investigated. Marked inhibition was seen at concentrations of auranofin (AF) and gold sodium thiomalate (GSTM) that correspond to gold levels found in the serum of patients receiving these drugs. This inhibition was not due to direct inactivation of the IL-1 molecule. Omitting 2-mercaptoethanol from the LAF assay potentiated the effect of GSTM. The antiproliferative effect of AF occurs almost immediately and probably reflects its direct cytotoxicity to stimulated lymphocytes.

Animals↗

PubMed1987

Production of lymphotoxin, a bone-resorbing cytokine, by cultured human myeloma cells.

Myeloma cells destroy bone by producing an osteoclast-stimulating factor that has chemical and biological characteristics similar to the bone-resorbing activity present in the supernatants of activated leukocyte cultures. Recently, a number of bone-resorbing leukocyte cytokines have been identified, including interleukin-1, lymphotoxin, and tumor necrosis factor. We have examined the products of human myeloma cells for the presence of these bone-resorbing cytokines. In a tumor cell line derived from a patient who had myeloma with osteolytic bone lesions and hypercalcemia, we found that the myeloma cells induced bone-resorbing activity and cytotoxic activity in vitro. Most of the bone-resorbing activity and all cytotoxic activity were suppressed by neutralizing antibodies to lymphotoxin. The myeloma cells expressed both lymphotoxin and tumor necrosis factor mRNA, but no tumor necrosis factor could be detected in the cell-culture medium. Interleukin-1 mRNA was not detected in the myeloma cells, and biologic activity of interleukin-1 was not measurable in the medium harvested from the cultured cells. The bone-resorbing activity induced by recombinant tumor necrosis factor and recombinant interleukin-1 was not affected by treatment with the lymphotoxin antibodies. When lymphotoxin was infused subcutaneously into normal mice (10 micrograms per day for three days), their plasma calcium levels increased. We also evaluated four established cell lines derived from three other patients with myeloma, and found a similar pattern of lymphotoxin expression in each. It appears that production of the bone-resorbing cytokine lymphotoxin is related to osteoclastic bone destruction and hypercalcemia in patients with myeloma.

Animals↗

PubMed1986

Influence of prednisolone and methotrexate on cellular and biochemical aspects of acute and chronic inflammation studied in subcutaneously implanted sponges in rats.

The effects of prednisolone and methotrexate on the histology and the content of collagen and proteoglycans of the inflammatory tissue in polyurethane sponges impregnated with heat killed M. tuberculosis and implanted subcutaneously in hooded Wistar rats for up to 63 days were studied. Drugs were administered during the 6-day period before sponge removal 7, 21, 35, 49 and 63 days after implantation. Our findings indicate that prednisolone and methotrexate have profound effects on the cellular events of acute and chronic inflammation, and influence the synthesis or degradation of connective tissue macromolecules at certain stages of the inflammatory process.

Acute Disease↗

PubMed1985

Biodistribution of 64Cu in inflamed rats following administration of two anti-inflammatory copper complexes.

64Cu was administered in two anti-inflammatory formulations to normal rats and to rats with 2 forms of local inflammation, namely (a) an acute paw oedema (elicited with carrageenan) or (b) a chronic granulomatous response to an implanted irritant (Mycobacterium tuberculosis in a polyurethane sponge). The copper formulations used were (i) a slow release one consisting of Cu(II) salicylate applied dermally with ethanol/DMSO and (ii) short acting hydrophilic complex (Cu(I)Cu(II)-penicillamine)5- given subcutaneously. Three types of changes in copper biodistribution with these forms of inflammation were discerned based on determination of 64Cu and copper content in the following organs: inflammatory locus (foot or sponge implant), kidney, liver, spleen, adrenals, brain, blood, thymus, heart, and skin (site of application). The most evident changes were in the kidneys, liver, spleen, adrenals, thymus and serum from animals with chronic granulomatous inflammation. In contrast, a short term acute inflammatory stress (carrageenan paw oedema) had little effect. While copper D-penicillamine (applied subcutaneously) appeared to move as a bolus through the animals, the results with the percutaneous copper salicylate formulation are consistent with it providing a slow release source of copper(II). Exogenous 64Cu from both formulations was sequestered at inflammatory sites (relative to serum). This may partly explain how applied copper complexes can be anti-inflammatory.

Administration, Topical↗

PubMed1985

Ambivalent properties of gold drugs in adjuvant induced polyarthritis in rats.

We evaluated the antiarthritic activity of gold sodium aurothiomalate (GSTM) and auranofin (AF) against experimental polyarthritis induced in 3 rat strains using 3 different adjuvants. These 2 gold drugs were found to either stimulate, inhibit or have no effect upon the development of arthritis, dependent upon the rat strain and/or the adjuvant used. The ambivalent antiarthritic activities of GSTM and AF did not appear to be associated with any variations in serum gold levels. These results highlight the need for caution in studying gold drugs using the adjuvant polyarthritic model in the rat and, if used, the need to define clearly the strain/adjuvant/gold drug combination. Within these constraints however, our findings support the concept that GSTM and AF have different mechanisms of action.

Animals↗

PubMed1982

Renal malakoplakia. Experimental production and evidence of a link with interstitial megalocytic nephritis.

The intrarenal injection of Boivin antigen is followed by the development of true melakoplakic lesions as characterised by the accumulation of macrophages containing MG bodies. Similarly the injection of diluted antigen is followed by the accumulation of macrophages with a granular PAS-positive cytoplasm but lacking MG bodies. These experimental models are compared with typical human renal malakoplakia and that entity known as megalocytic interstitial nephritis.

Animals↗

PubMed1981

Lanthanide-induced calcergy.

The subcutaneous injection of solutions of chloride salts of the rare earths is followed by calcification of the dorsal fascia in the mouse. The concentration of salt required to produce a constant, predictable response varies from salt to salt. The macroscopic outline of the reaction is generally irregular and therefore a quantitative radiological method has been developed to allow an accurate assessment of the dose/response relationship. This with the majority of salts is best described as a log regression and with three as a linear regression.

Animals↗

PubMedDate not supplied

A novel method for embedding neonatal murine calvaria in methyl methacrylate suitable for visualizing mineralization, cellular and structural detail.

The study of undecalcified bone by histological methods is essential in the field of bone research. Culturing skeletal tissues such as neonatal murine calvaria provides a reliable bridge between assessment of bone formation in vitro and anabolic activity in vivo and contains most of the essential elements of bone for studying bone formation. Neonatal calvarial assay, supported by histological methods, is used to study the anabolic effects of a wide variety of factors and compounds on bone tissue. To optimize visualization and histomorphometric measurements using neonatal calvaria, we developed a method that provides high quality tissue sections suitable for routine and histochemical staining. Undecalcified neonatal mouse calvaria were processed and embedded using a low temperature methyl methacrylate procedure. Various staining methods were performed on deplastisized and floated sections to examine mineralization and to identify cells. The Von Kossa stain counterstained with a modified H & E yielded precise images of unmineralized bone including mineralization sites, and distinct osteoblasts and osteoclasts. Toluidine blue, Ladewig's trichrome, tartrate-resistant acid phosphatase, Goldner, H & E and Villanueva stains also were tested on the undecalcified neonatal calvaria sections.

Animals↗