Clindamycin phosphate was administered to dogs at dosage of 11 mg/kg of body weight via IV and IM routes. The disposition curve for IV administration was best represented as a 2-compartment open model. Mean elimination half life was 194.6 +/- 24.5 minutes for IV administration and 234.8 +/- 27.3 minutes for IM administration. Bioavailability after IM administration was 87%. Dosage of 11 mg/kg, IV, given every 8 hours, provided serum concentration of clindamycin that exceeded the minimal inhibitory concentration for all Staphylococcus spp, as well as most pathogenic anaerobes, throughout the dosing interval. Intramuscular administration induced signs of pain and cannot be recommended.

Clindamycin phosphate was administered to dogs at dosage of 11 mg/kg of body weight via IV and IM routes. The disposition curve for IV administration was best represented as a 2-compartment open model. Mean elimination half life was 194.6 +/- 24.5 minutes for IV administration and 234.8 +/- 27.3 minutes for IM administration. Bioavailability after IM administration was 87%. Dosage of 11 mg/kg, IV, given every 8 hours, provided serum concentration of clindamycin that exceeded the minimal inhibitory concentration for all Staphylococcus spp, as well as most pathogenic anaerobes, throughout the dosing interval. Intramuscular administration induced signs of pain and cannot be recommended.

We investigated the biochemical composition of blood from Holstein cows, native breed (criollas), and cows descended from fighting bulls (Vacas de lidia) raised at an altitude of 3,000 m (moderately high altitude, MHA), and compared the results with those from Holsteins and cows of similar genetic ancestry as the criollas (scrub cows), both raised at sea level (SL), to determine blood biochemical values characteristic of adaptation to high altitude. Only potassium and calcium concentrations were similar among groups. Glucose concentration was lower in MHA cows, with the exception of Vacas de lidia. Serum bicarbonate concentration was lower in MHA cows; this finding can be explained by hyperventilation in the hypoxic environment. Serum magnesium concentration was lower in SL and MHA Holsteins than in other groups. Serum phosphate concentration was lower in scrub cows, MHA Holsteins, and criollas than in other groups. Cholesterol concentrations were lower in SL Holsteins, whereas triglycerides were higher in scrub cows and MHA Vacas de lidia. Concentration of high-density lipoprotein was significantly greater in Vacas de lidia and less in MHA criollas than in the other groups. Uric acid and total protein were higher in MHA groups. Using radioimmunoassay for human proteins, thyroxine-binding globulin was undetectable. Total and free thyroxine and free triiodothyronine were higher in scrub cows, followed by Vacas de lidia; lower values were detected in SL and MHA Holsteins and MHA criollas.

We investigated the biochemical composition of blood from Holstein cows, native breed (criollas), and cows descended from fighting bulls (Vacas de lidia) raised at an altitude of 3,000 m (moderately high altitude, MHA), and compared the results with those from Holsteins and cows of similar genetic ancestry as the criollas (scrub cows), both raised at sea level (SL), to determine blood biochemical values characteristic of adaptation to high altitude. Only potassium and calcium concentrations were similar among groups. Glucose concentration was lower in MHA cows, with the exception of Vacas de lidia. Serum bicarbonate concentration was lower in MHA cows; this finding can be explained by hyperventilation in the hypoxic environment. Serum magnesium concentration was lower in SL and MHA Holsteins than in other groups. Serum phosphate concentration was lower in scrub cows, MHA Holsteins, and criollas than in other groups. Cholesterol concentrations were lower in SL Holsteins, whereas triglycerides were higher in scrub cows and MHA Vacas de lidia. Concentration of high-density lipoprotein was significantly greater in Vacas de lidia and less in MHA criollas than in the other groups. Uric acid and total protein were higher in MHA groups. Using radioimmunoassay for human proteins, thyroxine-binding globulin was undetectable. Total and free thyroxine and free triiodothyronine were higher in scrub cows, followed by Vacas de lidia; lower values were detected in SL and MHA Holsteins and MHA criollas.

Immunogenicity of the lipid A component of Haemophilus somnus lipooligosaccharide in cattle and mice was examined after purification, detoxification, and covalent conjugation to a protein carrier. After 2 inoculations, a substantial antibody response was induced in most cattle to lipid A and the protein carrier. To determine whether antibodies to lipid A would be protective, 5 X 10(7) colony-forming units of H somnus strain 649 were administered IV to endotoxin-responsive (C3H/HEN) mice. In one study, 8 of 13 C3H/HEN mice aborted when inoculated. In contrast, abortion did not result when mice were inoculated with the same dose of an isolate of H somnus normally found in the prepuce or with the rough mutant Escherichia coli J5. In addition, endotoxin-nonresponsive (C3H/HeJ) mice were significantly (P = 0.03) more resistant to abortion by strain 649 than were C3H/HeN mice, but inoculated C3H/HeN mice were only slightly more resistant to H somnus abortion, compared with control mice. Although a large antibody response to lipid A was detected, there was no significant difference in the immunized group between mice that aborted and mice that delivered normally. Thus, lipooligosaccharide and other properties of virulent H somnus strains may contribute to abortion in mice.

Immunogenicity of the lipid A component of Haemophilus somnus lipooligosaccharide in cattle and mice was examined after purification, detoxification, and covalent conjugation to a protein carrier. After 2 inoculations, a substantial antibody response was induced in most cattle to lipid A and the protein carrier. To determine whether antibodies to lipid A would be protective, 5 X 10(7) colony-forming units of H somnus strain 649 were administered IV to endotoxin-responsive (C3H/HEN) mice. In one study, 8 of 13 C3H/HEN mice aborted when inoculated. In contrast, abortion did not result when mice were inoculated with the same dose of an isolate of H somnus normally found in the prepuce or with the rough mutant Escherichia coli J5. In addition, endotoxin-nonresponsive (C3H/HeJ) mice were significantly (P = 0.03) more resistant to abortion by strain 649 than were C3H/HeN mice, but inoculated C3H/HeN mice were only slightly more resistant to H somnus abortion, compared with control mice. Although a large antibody response to lipid A was detected, there was no significant difference in the immunized group between mice that aborted and mice that delivered normally. Thus, lipooligosaccharide and other properties of virulent H somnus strains may contribute to abortion in mice.

Quantitative computed tomography has been used extensively to measure bone mineral density; particularly in the vertebral column and in the proximal portion of the femur in human beings with osteoporosis. Other potential applications of this technique include evaluation of bone adjacent to metallic endoprostheses and evaluation of fractures as they heal. Unfortunately, metal causes severe image degradation, principally seen as starburst streaking. One method used to decrease these artifacts is by imaging less-attenuating materials, such as titanium alloy. Titanium decreases image degradation sufficiently to allow accurate determination of the geometric properties of cadaveric bone. In our study, the effect of a titanium segmental endoprosthesis on bone mineral density measurement was determined by use of bone specimens from dogs and calibration standards. Titanium decreased the bone mineral density of calibration solutions from 6.8 (500 mg/cm3) to 17.7% (250 mg/cm3), and increased bone mineral density of cortical bone by 5.3%. Titanium did not affect the repeatability of these scans, indicating that the error caused by titanium was systematic and can be corrected. Our data were suggestive that quantitative computed tomography can be used to measure bone mineral density of cortical bone adjacent to titanium endoprostheses, with a predictable increase in density measurement.

Quantitative computed tomography has been used extensively to measure bone mineral density; particularly in the vertebral column and in the proximal portion of the femur in human beings with osteoporosis. Other potential applications of this technique include evaluation of bone adjacent to metallic endoprostheses and evaluation of fractures as they heal. Unfortunately, metal causes severe image degradation, principally seen as starburst streaking. One method used to decrease these artifacts is by imaging less-attenuating materials, such as titanium alloy. Titanium decreases image degradation sufficiently to allow accurate determination of the geometric properties of cadaveric bone. In our study, the effect of a titanium segmental endoprosthesis on bone mineral density measurement was determined by use of bone specimens from dogs and calibration standards. Titanium decreased the bone mineral density of calibration solutions from 6.8 (500 mg/cm3) to 17.7% (250 mg/cm3), and increased bone mineral density of cortical bone by 5.3%. Titanium did not affect the repeatability of these scans, indicating that the error caused by titanium was systematic and can be corrected. Our data were suggestive that quantitative computed tomography can be used to measure bone mineral density of cortical bone adjacent to titanium endoprostheses, with a predictable increase in density measurement.

A murine hybridoma monoclonal antibody (MAB), IBF9, was generated by fusing myeloma cells (P3X63Ag8.653) with spleen cells from a BALB/c mouse immunized with the canine melanoma cell line CML-10c7. Initial screening of hybridoma antibodies was performed by use of an indirect immunoperomidase assay on formalin-fixed CML-10c7 cells. The isotype of MAB IBF9 was IgG1 as determined by radial gel immunodiffusion. The antibody was tested for reactivity against a panel of formalin-fixed, paraffin-embedded normal and neoplastic canine tissues, using immunoperoxidase staining. Immunostaining was observed in melanomas (24 of 38), a few carcinomas, basal cell tumors, and cutaneous lymphosarcomas. Immunostaining was not observed in fibrosarcomas, hemangiosarcomas, hemangiopericytomas, or histiocytomas. Staining of normal adult canine tissues was limited to a few epithehal tissues and a small percentage of lymphocytes. Fetal tissues were not reactive with MAB IBF9. There were statistically significant differences in frequency of reactivity among melanomas with regard to oral vs non-oral, malignant vs benign, and mitotic indices greater than or equal to 1 vs mitotic indices < 1. Differences were not significant when tumors were compared for degree of pigmentation or histologic type. On the basis of these findings, we suggest that MAB IBF9 may be of assistance in diagnosis of nonpigmented melanomas and in assessing the malignant potential of melanomas.

A murine hybridoma monoclonal antibody (MAB), IBF9, was generated by fusing myeloma cells (P3X63Ag8.653) with spleen cells from a BALB/c mouse immunized with the canine melanoma cell line CML-10c7. Initial screening of hybridoma antibodies was performed by use of an indirect immunoperomidase assay on formalin-fixed CML-10c7 cells. The isotype of MAB IBF9 was IgG1 as determined by radial gel immunodiffusion. The antibody was tested for reactivity against a panel of formalin-fixed, paraffin-embedded normal and neoplastic canine tissues, using immunoperoxidase staining. Immunostaining was observed in melanomas (24 of 38), a few carcinomas, basal cell tumors, and cutaneous lymphosarcomas. Immunostaining was not observed in fibrosarcomas, hemangiosarcomas, hemangiopericytomas, or histiocytomas. Staining of normal adult canine tissues was limited to a few epithehal tissues and a small percentage of lymphocytes. Fetal tissues were not reactive with MAB IBF9. There were statistically significant differences in frequency of reactivity among melanomas with regard to oral vs non-oral, malignant vs benign, and mitotic indices greater than or equal to 1 vs mitotic indices < 1. Differences were not significant when tumors were compared for degree of pigmentation or histologic type. On the basis of these findings, we suggest that MAB IBF9 may be of assistance in diagnosis of nonpigmented melanomas and in assessing the malignant potential of melanomas.

Because hepatocyte-stimulating factor/interleukin 6 (IL-6) the principal inducer of acute-phase protein synthesis in the liver, quantification of its activity in blood provides an early and sensitive assessment of the acute-phase response. Circulating IL-6 activity was monitored in 4 adult horses for 72 hours after IV administration of endotoxin. In 4 experiments performed at weekly intervals and in randomized order, each horse was given endotoxin-1,000, 30, 1, and 0 ng/kg of body weight. Plasma IL-6 activity was quantified as the ability to promote growth of the IL-6-dependent B-cell hybridoma, B13.29 clone B9. Interleukin-6 activity (171 +/- 10.2 U/ml) was found in all pretreatment plasma samples and was significantly (P < 0.05) increased above baseline from 2 to 12 hours after 1,000 ng of endotoxin/kg was given and at 3 hours after 30 ng of endotoxin/kg was given. After 1,000- or 30-ng/kg dosage of endotoxin, peak plasma IL-6 activity (10,128 +/- 4,096 and 1,555 +/- 1,326 U/ml, respectively) was observed for 3 hours. The IL-6 response of endotoxin-treated horses began about 1 hour after tumor necrosis factor appeared in the circulation, and its course closely approximated the endotoxin-induced febrile reaction. Significant increase in plasma IL-6 activity was not detected in horses given 1 ng of endotoxin/kg or control buffer.

Because hepatocyte-stimulating factor/interleukin 6 (IL-6) the principal inducer of acute-phase protein synthesis in the liver, quantification of its activity in blood provides an early and sensitive assessment of the acute-phase response. Circulating IL-6 activity was monitored in 4 adult horses for 72 hours after IV administration of endotoxin. In 4 experiments performed at weekly intervals and in randomized order, each horse was given endotoxin-1,000, 30, 1, and 0 ng/kg of body weight. Plasma IL-6 activity was quantified as the ability to promote growth of the IL-6-dependent B-cell hybridoma, B13.29 clone B9. Interleukin-6 activity (171 +/- 10.2 U/ml) was found in all pretreatment plasma samples and was significantly (P < 0.05) increased above baseline from 2 to 12 hours after 1,000 ng of endotoxin/kg was given and at 3 hours after 30 ng of endotoxin/kg was given. After 1,000- or 30-ng/kg dosage of endotoxin, peak plasma IL-6 activity (10,128 +/- 4,096 and 1,555 +/- 1,326 U/ml, respectively) was observed for 3 hours. The IL-6 response of endotoxin-treated horses began about 1 hour after tumor necrosis factor appeared in the circulation, and its course closely approximated the endotoxin-induced febrile reaction. Significant increase in plasma IL-6 activity was not detected in horses given 1 ng of endotoxin/kg or control buffer.

The effects of intra-articular administration of methylprednisolone acetate (MPA) on the healing of full-thickness osteochondral defects and on normal cartilage were evaluated in 8 horses. In group-1 horses (n = 4), a 1-cm-diameter, full-thickness defect was created bilaterally in the articular cartilage on the dorsal distal surface of the radial carpal bone. Cartilage defects were not created in group-2 horses (n = 4). One middle carpal joint was randomly selected in each horse (groups 1 and 2), and treated with an intra-articular injection of 100 mg Of MPA, once a week for 4 treatments. Injections began 1 week after surgery in group-1 horses. The contralateral middle carpal joint received intra-articular injections of an equivalent volume of 0.9% sodium chloride solution (SCS), and served as a control. Horses were evaluated for 16 weeks, then were euthanatized, and the middle carpal joints were examined and photographed. Synovial and articular cartilage specimens were obtained for histologic and histochemical evaluation. Gross morphometric evaluation of the healing defects in group-1 horses revealed that 48.6% of the defect in control joints and 0% of the defect in MPA-treated joints was resurfaced with a smooth, white tissue, histologically confirmed as fibrocartilage. This replacement tissue was a firmly attached fibrocartilage in control joints and a thin fibrous tissue in MPA-treated joints. The articular cartilage in joints treated with MPA had morphologic changes, including chondrocyte cluster formation, loss of palisading architecture, and cellular necrosis in both groups of horses. Histochemical (safranin-0) staining intensity was reduced significantly (P < 0.05) in all layers of articular cartilage in MPA-treated joints in groups 1 and 2. In the replacement tissue, intense safranin-O staining was found only in the chondrocyte clusters deep in the tissue of control joints, confirming fibrocartilage repair. Intra-articular administration of MPA in this dosing regimen thus induced degenerative changes in normal articular cartilage and resulted in histomorphologic changes in the repair of full-thickness articular osteochondral defects in horses.

The effects of intra-articular administration of methylprednisolone acetate (MPA) on the healing of full-thickness osteochondral defects and on normal cartilage were evaluated in 8 horses. In group-1 horses (n = 4), a 1-cm-diameter, full-thickness defect was created bilaterally in the articular cartilage on the dorsal distal surface of the radial carpal bone. Cartilage defects were not created in group-2 horses (n = 4). One middle carpal joint was randomly selected in each horse (groups 1 and 2), and treated with an intra-articular injection of 100 mg Of MPA, once a week for 4 treatments. Injections began 1 week after surgery in group-1 horses. The contralateral middle carpal joint received intra-articular injections of an equivalent volume of 0.9% sodium chloride solution (SCS), and served as a control. Horses were evaluated for 16 weeks, then were euthanatized, and the middle carpal joints were examined and photographed. Synovial and articular cartilage specimens were obtained for histologic and histochemical evaluation. Gross morphometric evaluation of the healing defects in group-1 horses revealed that 48.6% of the defect in control joints and 0% of the defect in MPA-treated joints was resurfaced with a smooth, white tissue, histologically confirmed as fibrocartilage. This replacement tissue was a firmly attached fibrocartilage in control joints and a thin fibrous tissue in MPA-treated joints. The articular cartilage in joints treated with MPA had morphologic changes, including chondrocyte cluster formation, loss of palisading architecture, and cellular necrosis in both groups of horses. Histochemical (safranin-0) staining intensity was reduced significantly (P < 0.05) in all layers of articular cartilage in MPA-treated joints in groups 1 and 2. In the replacement tissue, intense safranin-O staining was found only in the chondrocyte clusters deep in the tissue of control joints, confirming fibrocartilage repair. Intra-articular administration of MPA in this dosing regimen thus induced degenerative changes in normal articular cartilage and resulted in histomorphologic changes in the repair of full-thickness articular osteochondral defects in horses.