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Biomedical subjects

R W Norrdin

Publications and source records attributed to R W Norrdin.

At least 37 records · Page 2Linked to original sources

Trabecular bone remodeling and bone mineral density in the adult cat during chronic dietary acidification with ammonium chloride.

Ammonium chloride (NH4Cl) is used as a urinary acidifier in the treatment and prevention of feline urologic syndrome. It is reported to cause alterations in calcium and bone metabolism in humans, dogs, and rats. Adult cats with normal renal function were fed 1.5% NH4Cl for 6 months to study the effects of chronic dietary acidification on trabecular bone remodeling of the iliac crest and bone mineral density (BMD) of lumbar vertebral trabecular bone and femoral cortex. Histomorphometric analyses of iliac crest biopsies were performed before and after treatment. Static and dynamic parameters of bone resorption and formation were determined. Single-energy quantitative computed tomography (SEQCT) was used to measure lumbar trabecular and femoral cortical BMD. There were no significant treatment effects in iliac crest trabecular bone remodeling or BMD of the vertebrae and femora. Bone remodeling activity decreased with time in both acidotic and control cats. Vertebral BMD increased with time in both groups of cats, whereas no change was seen in the femora. Thus, chronic dietary acidification for 6 months with therapeutic levels of NH4Cl produced no significant changes in trabecular bone remodeling or bone mineral density in adult cats.

Acidosis↗

The role of prostaglandins in bone in vivo.

Prostaglandins of the E series, primarily E2 and E1, have the greatest activity in bone. Following discovery of their potent ability to stimulate bone resorption in vitro, clinical investigations have placed prostaglandins at sites of localized bone resorption associated with inflammatory or space occupying lesions in vivo. These studies have shown that prostaglandin production at such sites may be increased by cytokines such as interleukin-1 but the mechanisms by which prostaglandins stimulate bone resorption are not yet known. Observation of periosteal bone formation in patients given, pharmacological doses of prostaglandin has led to investigation of its bone forming activity. Young, growing rats have increased metaphyseal bone formation and this is accompanied by increased periosteal and endocortical bone formation in older animals. In the mature animals there is a generalized activation of remodelling with increased formation in the remodeling cycle. This is also seen in oophorectomized rats and results in repletion of the lost bone in this model of osteoporosis. In animal models of localized disuse osteopenia, prostaglandins are found to be elevated at the site of bone loss and prostaglandin inhibitors at least partially protect against the exaggerated resorption that occurs. This is also seen in models of orthodontic tooth movement, periodontitis and osteomyelitis. Prostaglandin synthesis inhibitors have been shown to delay healing of bone and this has led to limitations on their use clinically in some situations. Exogenously administered prostaglandins have been found to enhance periosteal callus formation, but healing is not uniformly enhanced. Prostaglandins have also been associated with hypercalcemia in certain animal tumors that model human hypercalcemia of malignancy but are probably most important in this condition as mediators in the localized resorption of bone at tumor sites. These in vivo studies have shown that prostaglandins are involved with increases in both bone formation and bone resorption. In vitro studies have shown that prostaglandins stimulate osteoblasts as well as osteoclastic bone resorption but understanding these effects under in vivo conditions will require further investigation.

Animals↗

Effects of corticosteroids on mechanical strength of intervertebral joints and vertebrae in dogs.

Dogs with hyperadrenocorticism had a higher incidence of intervertebral joint disease, i.e., disc protrusion or spondylosis. In comparing cases of hyperadrenocorticism with age- and breed-matched controls with hypothyroidism, the incidence was significantly greater than expected. This was not seen, however, in beagle dogs in which the incidence was already high and attributed to chondrodystrophoid tendencies in this breed. To investigate the pathogenesis of this association and its possible relationship to steroid-induced osteopenia, adult dogs were given a placebo, prednisone, or prednisone plus calcium for six months. Torque testing of intervertebral joints revealed a consistent trend of lower force to failure in both prednisone-treated groups, but the difference was not statistically significant. In these dogs with mild to moderate hyperadrenocorticism, compression tests of intact vertebral bodies were not significantly different, but blocks of trabecular bone cut from the vertebral bodies failed at significantly lower compressive forces in both prednisone-treated groups compared with controls. Histomorphometric evaluation of lumbar vertebral trabecular bone revealed that the percentage of bone volume was not significantly decreased in the prednisone-treated groups. Nor was there any difference in the thickness or porosity of vertebral end-plates, which might contribute to weakening of intervertebral ligamentous insertions.

Animals↗

Histomorphometric comparison of measurements of trabecular bone remodeling in iliac crest biopsy sites and lumbar vertebrae in cats.

Trabecular bone remodeling values of the right and left iliac crest and lumbar vertebrae in cats were quantitated histomorphometrically and were compared. Healthy cats were given calcein (n = 2) or oxytetracycline (n = 2) twice for double-labeling of bone. Static and dynamic variables of bone resorption and formation were determined. Bone remodeling variables between right and left iliac crest were not significantly different (P less than 0.05). Significant differences (P less than or equal to 0.05) were not detected between values of iliac crest and lumbar vertebrae except in the percentage of osteoid surface. Percentage of osteoid surface was significantly (P less than or equal to 0.05) increased in the iliac crest compared with that in the vertebral body. Although not significantly different, values for bone formation were generally greater in the iliac crest than in the vertebral body. In healthy cats, values of trabecular bone remodeling were comparable between right and left iliac crest, and also were comparable between iliac crests and lumbar vertebrae.

Animals↗

Blindness and sexual dimorphism associated with vitamin A deficiency in feedlot cattle.

Clinical, ophthalmoscopic, and histopathologic findings of vitamin A deficiency in a group of 535 feedlot cattle are described. Liver vitamin A content and results of histologic examination of ocular and osseous (optic canal) tissue confirmed the diagnosis. Blindness was the only clinical sign observed. Even though the steers and heifers in this feedlot were approximately the same age and were fed the same ration for an equal period, none of the heifers had overt clinical signs of hypovitaminosis A. Production of vitamin A by the bovine corpus luteum may account for the sexual dimorphism observed in vitamin A-deficient cattle.

Animals↗

Effects of intramuscular polysulfated glycosaminoglycan on chemical and physical defects in equine articular cartilage.

The effect of intramuscular polysulfated glycosaminoglycan (PSG) on repair of cartilage injury was evaluated in eight horses. In each horse, one middle carpal joint had both a partial-thickness and a full-thickness articular cartilage defect created. In the contralateral middle carpal joint, chemical articular cartilage injury was created by intra-articular injection of 50 mg sodium monoiodoacetate (MIA). Horses were divided into two groups for treatment. Group 1 horses (control) received an intramuscular injection of normal saline every four days for a total of seven injections starting seven days after cartilage injury. Group 2 horses received 500 mg of PSG intramuscularly every four days for seven treatments starting seven days after cartilage injury. Horses were maintained for 12 weeks. Horses were evaluated clinically, and their middle carpal joints were evaluated radiographically and arthroscopically at the end of the study. Joint tissues were also collected and examined microscopically. The only significant difference between groups was slightly greater matrix staining intensity for glycosaminoglycans in the radiate articular cartilage layer in MIA injected and PSG treated joints. Partial-thickness defects had not healed and the predominant repair tissue in full-thickness defects was fibrous tissue. It was concluded that using this joint injury model, 500 mg PSG administered intramuscularly had no effect on the healing of articular cartilage lesions, and minimal chondroprotective effect from chemically induced articular cartilage degeneration.

Animals↗

Characterization of osteosarcoma cells from two sibling large-breed dogs.

Neoplastic cells were isolated from 2 sibling Great Dane/Labrador Retriever mixed-breed dogs in which telangiectatic type osteosarcomas arose concurrently. Cells from various sites in the same osteosarcoma appeared similar in culture, but there were differences between the 2 osteosarcomas in growth characteristics and appearance of cells. Cells from 1 osteosarcoma had a small, but significant (P less than 0.05), cyclic adenosine monophosphate response to parathyroid hormone stimulation, indicating a low order of osteoblastic differentiation. Cells from the other osteosarcoma had no response to parathyroid hormone stimulation. Cells from both osteosarcomas and a concentrated cell-free filtrate from the osteosarcoma with osteoblastic differentiation were injected into nude mice, but osteosarcomas were not induced. Results of ultrastructural examination of osteosarcoma samples for viral particles were negative and supernatant fluids from cultured cells were considered negative for viral reverse transcriptase activity.

Animals↗

Neochondrogenesis in free intra-articular, periosteal, and perichondrial autografts in horses.

Periosteal autografts were obtained from the medial aspect of the proximal portion of the tibia, and perichondrial autografts were obtained from the sternum. Using arthroscopic visualization, each autograft was placed as a loose body into 1 tarsocrural joint in 6 young horses (2 to 4 years old). Horses were hand-walked daily, starting the day after surgery, for a total of 6 h/wk for 8 weeks. Eight weeks after autograft implantation, radiographs were taken of each tarsocrural joint and were interpreted with regard to mineralization in the transplanted autografts. Autografts were then surgically removed, and examined macroscopically and microscopically for viability, size, and production of chondroid tissue. All autografts appeared viable and most had evidence of growth. Longest-by-shortest axis value, cross-sectional area, and perimeter were greater in perichondrial autografts than in their periosteal counterparts in 3 horses, but the difference was not significant. Neochondrogenesis was observed in 5 of 6 periosteal grafts and in 1 of 6 perichondrial grafts. Furthermore, the amount of chondroid tissue produced in periosteal autografts was significantly (P less than 0.05) greater than that produced in the 1 perichondrial graft. The chondroid tissue produced by periosteal autografts had morphologic and matrical staining properties similar to those of hyaline cartilage.

Animals↗

Systemic effects of prostaglandin E2 on vertebral trabecular remodeling in beagles used in a healing study.

Prostaglandin E2 (PGE2) at a dose of 10 mg/kg was administered orally to beagles used in a study of rib fracture and drill hole defect healing. Double fluochrome labels were given prior to surgical manipulation and before necropsy at 30 days. Bone remodeling was evaluated in trabecular bone of the fourth lumbar vertebra. There was a decrease in the number and extent of posttreatment labels (P less than 0.05) in the controls, with decreased mineral apposition rate (P less than 0.05) and decreased active bone formation rate (P less than 0.01). In dogs given PGE2 for 30 days following surgery, the extent of posttreatment labels (P less than 0.05) and bone formation rate (P less than 0.01) were increased. There was no difference found, however, in static morphometric parameters, including osteoid and osteoblast-covered surface, indicating that the stimulation of bone formation may have been transitory and matrix synthesis had declined. In another group of dogs given PGE2 for 5 days prior to surgical manipulation and between the first and second pretreatment labels, the extent of the double-labeled surface was increased (P less than 0.05) indicating an acute PG effect to sustain formation at remodeling sites. These studies show that PGE2 given orally has a systemic effect on bone remodeling in vertebral trabeculae that involves the stimulation of formation activity.

Animals↗

Trabecular bone morphometry in beagles with hyperadrenocorticism and adrenal adenomas.

Trabecular bone morphometry was done on rib samples of beagles with hyperadrenocorticism and adrenal adenomas to evaluate bone loss and the remodeling changes responsible. Beagles diagnosed as having clinical hyperadrenocorticism and those with milder or subclinical hyperadrenocorticism diagnosed on the basis of adrenal and pituitary lesions at necropsy had increased adrenal and pituitary gland weights. In a group of dogs with adrenal cortical adenomas there was atrophy of remaining cortex, and the combined weight of adrenal glands or pituitary weights were not increased. In dogs with clinical hyperadrenocorticism, mean trabecular bone volume was 25% less than controls (P = 0.10). In both clinical and subclinical hyperadrenocorticism groups, the extent of trabecular surface with unmineralized osteoid matrix and osteoblasts was significantly reduced. There were no changes in resorption surfaces or number of osteoclasts present. No bone changes were seen in dogs with adrenal adenomas. In dogs with hyperadrenocorticism it appeared that decreased bone formation was primarily responsible for the relative osteopenia that developed. Although parathyroid glands were moderately enlarged in those dogs for which weights were available, the bone changes were not those of increased remodeling expected in hyperparathyroidism.

Adenoma↗

Humoral hypercalcemia of malignancy in canine lymphosarcoma.

Studies on the pathogenesis of hypercalcemia in canine lymphosarcoma have led to conflicting results. The biochemical and bone histomorphometric findings in canine lymphosarcoma were examined in 19 hypercalcemic and 17 nonhypercalcemic dogs with lymphosarcoma. Compared to the nonhypercalcemic group, the hypercalcemic dogs demonstrated an increase in fasting and 24-h calcium excretion, an increase in fractional phosphorus excretion, and a significant increase in nephrogenous AMP excretion. Plasma 1,25-dihydroxyvitamin D and immunoreactive PTH levels were equivalent in the two groups. Quantitative bone histomorphometry performed on iliac crest biopsies revealed increased parameters of bone resorption in those hypercalcemic dogs with no evidence of tumor at the biopsy site, without a compensatory increase in bone formation. Acid-urea tumor tissue extracts from eight hypercalcemic and six nonhypercalcemic dogs were examined for adenylate cyclase-stimulating activity (ACSA). All tumors from hypercalcemic dogs contained ACSA, whereas none of the tumors from nonhypercalcemic dogs had ACSA. Further purification of one tumor extract yielded an adenylate cyclase-stimulating protein which appeared to interact specifically with the PTH receptor. We conclude that in some cases, hypercalcemia in canine lymphosarcoma is mediated by a tumor-derived circulating bone-resorbing factor which is distinct from PTH. ACSA detected in tumor tissue appears to be a reliable marker for the syndrome in vivo. The role of this activity in the pathogenesis of the syndrome remains to be determined.

Adenylyl Cyclases↗

Sequential study of visceral lesions caused by isolates of an avian osteopetrosis virus (myeloblastosis-associated virus).

Ten-day-old chicken embryos were inoculated with isolates of myeloblastosis-associated virus that induced osteopetrosis of slow or rapid onset. Bursa of Fabricius, thymus, spleen, bone marrow, kidney, liver, and lung were examined at 15, 17, and 19 days in ovo and at 7 and 25 days after hatching by histologic and immunoperoxidase techniques. Tissues from 19-day-old in ovo embryos also were examined by electron microscopy. The lymphoid organs of embryos inoculated with all isolates manifested changes suggesting inhibited development. Virus was most often associated with macrophages, heterophils, and nonlymphoid stromal cells in these organs. Viral particles and antigen were abundant in tissues from embryos inoculated with slow-onset isolates, but cell necrosis was infrequent. The kidney and bursa had especially abundant viral particles and antigen. Conversely, viral particles and antigen were minimal in tissues from embryos inoculated with the rapid-onset isolate, yet intravascular cellular thrombi, substantial cell necrosis, and increased heterophils and hemocytoblasts were found.

Animals↗

Effect of prostaglandin E1 on regional haversian remodeling in beagles with fractured ribs: a histomorphometric study.

A histomorphometric study was carried out on healing defects in the ribs of beagles. A transverse fracture was made surgically in the midshaft of the left 9th and 10th ribs. Ten beagles received injections of either a buffer vehicle (n = 4) or prostaglandin E1 (PGE1) at a dose of 0.4 mg/day locally (n = 6) into the fracture sites for a 10-day period and were killed 30 days after the surgery. Double-pulsed fluorescent labels were given with each of two fluochrome markers, calcein before surgical treatment and oxytetracycline hydrochloride before killing. The objectives were to determine manifestations of the regional acceleratory phenomenon (RAP) as changes in regional remodeling in the haversian envelope induced by fracture, effects of PGE1 on modification of the RAP in the haversian envelope, and systemic effects of PGE1 on remodeling changes of the contralateral matching sites. The differences in haversian remodeling between the injured and uninjured ribs of the experimental dogs indicated an increase in activation frequency, that is, regional acceleratory phenomenon. The significant effect of PGE1 on enhancing fracture-induced acceleration of haversian remodeling was doubtful, because of the preexistent biologic differences found in the two experimental groups. Nevertheless, the two groups shared a similar pattern of remodeling activity. The posttraumatic mineralization that declined at the sampled sites need further investigation.

Alprostadil↗

A sequential study of bone lesions caused by isolates of an avian osteopetrosis virus, MAV-2(0).

The pathogenesis of avian osteopetrosis caused by rapid and slow-onset isolates of myeloblastosis associated virus, MAV-2(0), was studied by inoculation of 10-day-old chick embryos with virus. Femur and calvarium were examined at 15, 17 and 19 days in ovo and 7 and 25 days after hatching by histologic and immunoperoxidase techniques. Femur and calvarium were also examined by electron microscopy at 17 and 19 days in ovo and at 7 days after hatching. Avian osteopetrotic bone lesions were characterized by exuberant periosteal proliferation; the time of onset varied with different virus isolates. In the femur virus was first associated with osteoprogenitor cells, then with osteoblasts and finally with osteocytes as the cells progressed through normal sequences of differentiation. The amount of virus produced by these cells did not correlate with onset of periosteal proliferation. Slow onset isolates provoked early virus production, but proliferative lesions did not develop until later. Conversely, the rapid onset isolate induced little early virus production, although lesions were present. Periosteal proliferation was associated with and preceded by perivascular edema and perivascular cell necrosis within the bone cortex following infection by all isolates. However, the rapid onset isolate caused more severe lesions than other isolates. These lesions included vascular thrombosis, capillary necrosis and focal bone necrosis. The relationship between early vascular lesions and late periosteal proliferation seen with the slow onset isolates is not as clear as with the rapid onset isolate. Calvarial bone, a representative flat bone, was found to have virus present, but at a level less than the femur. Vascular lesions were rarely seen in the calvarium and bone proliferation did not occur at this site.

Animals↗

Effect of PGE2 on regional cortico-endosteal remodeling in beagles with fractured ribs: a histomorphometric study.

A histomorphometric study was done on healing defects in the ribs of Beagles. A transverse fracture was made in the left 9th and 10th ribs. Beagles were given either ethanol vehicle (n = 6) or prostaglandin E2 (PGE2) orally (n = 5) for the 30-day period after surgical manipulation to time of necropsy. Double fluorescent labels were given to measure bone matrix mineralization. Two fluorochrome markers were used: calcein before dogs were surgically manipulated and oxytetracycline HCl before they were killed. The two objectives of the present study were: (1) to determine the effects of fracture on regional cortico-endosteal remodeling 2 cm from a fracture site in the ribs of Beagles; and (2) to determine the effects of orally administered PGE2 on the above condition. The results suggested that the fractured and the non-fractured ribs in either group show a similar static and dynamic remodeling during the first 30 days of healing. The activation frequency in the PGE2 group was increased in both fractured and non-fractured ribs more than in the non-treated group. Therefore, the systemic administration of PGE2 can activate and synchronize remodeling cycles among BMUs.

Animals↗

Comparison of various treatments for experimentally induced equine infectious arthritis.

To evaluate the effects of 5 treatments on clinical responses, synovial fluid analysis, radiographic changes, bacteriologic culture results of the synovial fluid and synovial membrane, microscopic characteristics of the synovial membrane, and articular cartilage histochemistry, Staphylococcus aureus organisms (1.6 X 10(6) colony-forming units) were inoculated into the tarsocrural joints of 12 horses (n = 24 joints; 2 joints/horse). Each horse was given phenylbutazone (2 g) orally, every 24 hours, beginning 24 hours after inoculation. Two horses (ie, 4 joints) were not given other treatment (controls; group 1). All other horses (ie, 20 joints) were given a trimethoprim-sulfadiazine combination orally, once daily (30 mg/kg; 8 joints) or twice daily (30 mg/kg q 12 hr; 12 joints). Each of these 20 joints were assigned to 1 of 5 treatment groups (4 joints/group) in a balanced incomplete block design. Group 2 (4 joints) was given only the antibiotics once daily. Twelve joints were treated by through-and-through joint lavage on day 1 (group 3), days 1 and 3 (group 4), or days 1, 3, and 6 (group 5). Joints in group 6 had an arthrotomy performed on day 1, with subsequent lavage via an indwelling drain every 12 hours for 4 days. In groups 3 through 6, 1 joint in each group was treated with antibiotics once daily, and 3 joints were treated with antibiotics twice daily. All horses were clinically assessed each day. Complete blood count was performed on days 3, 6, 10, and 21. Before inoculation and on days 0, 1, 3, 6, 10, and 21, synovial fluid specimens were collected and analyzed for color, clarity, total protein concentration, WBC count, differential count, and mucin clot-forming ability. Synovial fluid specimens were cultured bacteriologically before inoculation and on days 0 and 21. Horses in group 1 (controls) were euthanatized before day 6. All other horses were euthanatized on day 21. Tarsocrural joints were opened and examined. Synovial membrane specimens were bacteriologically cultured. Synovial membrane specimens were examined histologically (hemotoxylin and eosin stain) and articular cartilage specimens were (safranin O fast green stain) evaluated histochemically. Synovial membrane specimens were histologically graded into 5 categories. Intensity of articular cartilage intercellular staining with safranin 0 was graded for superficial, outer intermediate, inner intermediate, and deep zones. Two-way analysis of variance was performed to evaluate differences among groups and across time for the determinants evaluated.(ABSTRACT TRUNCATED AT 400 WORDS)

Analysis of Variance↗

Povidone-iodine lavage treatment of experimentally induced equine infectious arthritis.

Both tarsocrural joints of 4 horses were inoculated with 1.5 X 10(5) colony-forming units of Staphylococcus aureus. On days 1, 3, and 6, each horse had one tarsocrural joint lavaged with a balanced electrolyte solution and had the contralateral tarsocrural joint lavaged with 0.1% povidone-iodine solution. All horses were orally administered trimethoprim (5 mg/kg)/sufadiazine (25 mg/kg) combination twice daily and phenylbutazone (2 g) once daily for the duration of the study (21 days). On days 0, 1, 3, 6, 9, 14, and 21, synovial fluid specimens were collected and analyzed for color, clarity, total protein concentration, WBC count and differential, and mucin clot-forming ability. Synovial fluid specimens collected on days 1, 3, 6, 9, 14, and 21 were bacteriologically cultured. On day 21, all horses were euthanatized, the tarsocrural joints were opened and examined, synovial membrane specimens were collected, bacteriologically cultured, and histologically evaluated, and articular cartilage specimens were histochemically evaluated. Repeated measures analysis of variance were used to evaluate differences between lavage solutions and among days for objective measurements. A paired t test was used to evaluate differences between solutions for the indices of synovial membrane inflammation and articular cartilage staining intensity with safranin-O-fast green. To be considered significant, the probability of a type-I error was less than 0.05. Significant differences were not found between joints lavaged with electrolyte solution vs povidone-iodine solution for synovial total protein concentration, WBC count, results of synovial fluid and membrane bacteriologic culture, synovial membrane inflammation, or articular cartilage glycosaminoglycan concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

Effect of prostaglandin E1 on the periosteal regional acceleratory phenomenon in fractured ribs: histomorphometric study in beagles.

Transverse fractures were made surgically in the midshaft of the left 9th and 10th ribs in adult Beagles. A buffer vehicle (n = 4) or 0.2 mg of prostaglandin (PG) E1/day (n = 6) was injected into the fracture sites twice a day for 10 days, and dogs were euthanatized on day 30. Double-pulsed fluorescent labels were given with each of 2 fluorochrome markers--calcein before surgical treatment and oxytetracycline HCl before euthanasia. Histomorphometric analysis was carried out on specimens collected in adjacent regions of the healing defects. The surface extent and width of the osteoid on fractured (P less than 0.01, P less than 0.05, respectively) and nonfractured (P less than 0.05) sites in the treated group were greater than those in the nontreated group. The net loss of mineralizing surfaces was noticed on both ribs of both groups. Of 11 samples on the fractured side in the treated group, 4 contained periosteal new bone proliferation. There was increased osteoid formation and decreased mineralizing surfaces in the PGE1-treated group. Seemingly, administration of PGE1 induced bone matrix formation on periosteal envelope adjacent to a fracture site and its contralateral matching site.

Animals↗