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Biomedical subjects

R C Renlund

Publications and source records attributed to R C Renlund.

10 recordsLinked to original sources

Partial chondroprotective effect of zoledronate in a rabbit model of inflammatory arthritis.

OBJECTIVE: To test the hypothesis that bisphosphonate treatment has a chondroprotective effect in the carrageenan model of inflammatory arthritis (IA). METHODS: Experimental IA was induced in rabbits by intraarticular injections of carrageenan. One group also received subcutaneous injections of zoledronate, a new bisphosphonate. After 4 weeks, the joints were harvested. Articular cartilage degradation and the degree of synovitis were assessed by light microscope using qualitative grading scores. Articular cartilage and subchondral and cancellous bone were evaluated histomorphometrically. Bone microhardness was measured. RESULTS: Carrageenan injected knees showed changes of inflammatory arthritis with cartilage erosion. Zoledronate treatment partially protected the articular cartilage from degradation. This effect was unlikely due to an antiinflammatory effect of the drug as the carrageenan induced synovitis was unaffected by zoledronate treatment. The treatment preserved subchondral bone thickness and cancellous bone volume and prevented focal breaks in the osteochondral barrier. The subchondral bone hardness was also maintained. CONCLUSION: Zoledronate had a partial effect in a rabbit model of inflammatory arthritis. The chondroprotection may be due to the prevention of bone resorption. By maintaining an intact subchondral bone, normal joint loading may have been maintained and contact between the bone marrow and the articular cartilage averted.

Animals↗

Struvite urolithiasis in a B6C3F1 mouse.

In a 2 year carcinogenicity bioassay using B6C3F1 mice, one male mouse developed clinical signs near termination of the study, comprising skin sores around the prepuce, penile prolapse and urine scalding. The predominant finding at necropsy was a markedly distended urinary bladder filled with numerous crystallized particles. Microscopically, there was subacute cystitis with marked hyperplasia of the transitional epithelium. X-ray diffraction analysis of the crystals showed a diffraction pattern characteristic of struvite (ammonium magnesium phosphate). The implications of the spontaneous occurrence of bladder stones in rodents on long-term toxicology studies are discussed.

Animals↗

Rhesus macaques as an experimental model for degenerative arthritis.

To understand the pathogenesis of degenerative arthritis, an experimental model of the disease in which systemic factors can be investigated is required. This study reviews the evidence that the spontaneous degenerative arthritis in free ranging rhesus macaques at the Caribbean Primate Research Center meets the criteria for such a model. Two forms of degenerative arthritis in rhesus macaques have been identified: osteoarthritis and calcium pyrophosphate dihydrate crystal deposition disease. These diseases resemble spontaneous human arthritis with respect to age, sex, joint histology and cartilage composition. The availability of large numbers of affected primates as well as the availability of age/sex matched controls free of disease are additional factors that make spontaneous degenerative arthritis in rhesus macaques a suitable experimental model for the study of the human disease.

Academies and Institutes↗

Calcium pyrophosphate crystal deposition in hyaline cartilage. Ultrastructural analysis and implications for pathogenesis.

Using transmission electron microscopy, selected area electron diffraction, and micro x-ray diffraction techniques, we studied calcium pyrophosphate dihydrate (CPPD) deposits from 23 patients with chondrocalcinosis affecting the femoral head to delineate the cellular and matrix environment in which CPPD crystals form, to determine the sequence of crystal deposition, and to address the question of coexistent calcium apatite crystal deposition. We found 2 types of CPPD crystal deposits with few transitional forms. First, small collections of crystals were seen at the border of the territorial matrix at the articular and subarticular poles of the chondron. CPPD crystal deposits were unassociated with collagen or matrix vesicles. Second, and more frequently, large collections of randomly arranged crystals (agglomerates) were observed, the smallest replacing the chondrocyte and adjacent pericellular matrix. Chondrocytes adjacent to crystal deposits were intact. Coexistent apatite crystal deposition was demonstrated in only 2 of 23 cartilages ultrastructurally examined, providing evidence that mixed crystal deposits are possible but not common in CPPD crystal arthropathy.

Aged↗

Rhesus monkeys (Macaca mulatta) as a model for calcium pyrophosphate dihydrate crystal deposition disease.

Calcium pyrophosphate dihydrate crystal deposition disease (CPDD) was recognized in 4 of 30 free-ranging rhesus macaques. By means of tissue radiography, focal radiodensities were noted in lumbar intervertebral discs, menisci, and articular cartilage. Crystal deposits were identified as calcium pyrophosphate dihydrate (Ca2P2O7 X 2H2O) by means of X-ray diffraction. The pathogenesis of calcium pyrophosphate dihydrate arthropathy in man remains elusive. However, with the recognition of this arthritis in a well defined population of aged nonhuman primates, a model now exists to facilitate the study of this disease.

Animals↗

Adrenal and hepatic calcium stearate crystal deposits in dogs fed a thiamine-deficient diet.

The nature and histologic environment of birefringent crystals found incidentally at necropsy in the liver and adrenal glands of dogs fed a thiamine-deficient diet were studied. The crystals were identified as calcium stearate by ultrastructural and x-ray microdiffraction techniques. Crystals were observed intracellularly within cytoplasmic vacuoles and extracellularly within sinusoids. Generally, crystals were also observed in pair-fed controls that were given a purified diet (equal in weight to that consumed by the thiamine-deficient animals) plus supplemental thiamine. Crystal deposits were found in trace amounts in a few of the ad libitum-fed controls. Although thiamine deficiency may be involved in promoting crystal deposition in the adrenal cortex, calcium stearate crystal formation within the adrenal glands and the liver appears unrelated to dietary thiamine deficiency per se, but is probably related to deficiency of an unidentified nutrient in the purified thiamine-deficient diet.

Adrenal Glands↗