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Application of interspecies scaling to the bispyridinium oxime HI-6
1994
Baggot, J.D.
Disposition kinetic variables of HI-6, a bispyridinium oxime, have been determined in mice, rats, rabbits, Rhesus monkeys, Beagles, sheep, and human beings. The drug has a short half-life, small apparent volume of distribution and high body clearance in these species, and is eliminated mainly by renal excretion. Using regression analysis and double logarithmic plots of the pharmacokinetic variables vs body weight of the various species, it was observed that body (systemic) clearance is the pharmacokinetic variable to use for interspecies comparison of elimination of the drug. The allometric exponent denoting the proportionality of body clearance of HI-6 to body weight of the 7 species studied was 0.76, which may be related to the renal excretion process for the drug. The apparent volume of distribution was similar (260 to 304 ml/kg of body weight) in the various species. The results indicate that volume of distribution, body clearance, and with less confidence, half-life might be used for interspecies scaling and for predicting these variables in other mammalian species. On the basis of the pharmacokinetic variables in selected species (rats and mice excluded), IV administration of III-6 at a dosing rate of 20 to 25 mg/kg at 4-hour intervals should provide an average steady-state plasma concentration of 16 to 20 micrograms/ml in domestic animals. The short half-life of III-6 precludes increasing the dosage interval.
Show more [+] Less [-]Determination of calcium, phosphorus, and magnesium values in rib bones from clinically normal cattle
1994
Beighle, D.E. | Boyazoglu, P.A. | Hemken, R.W. | Serumaga-Zake, P.A.
Mean phosphorus (P) content in bovine rib bone was 102.9, 108.3, and 182.7 mg/g of bone on fresh, dry, and ash weight bases, respectively. Values for calcium (Ca) were 194.3, 203.7, and 344.6 mg/g, respectively, and for magnesium (Mg) were 5.3, 5.5, and 9.4 mg/g, respectively. Mean percentage of ash in rib bone was 59.12%. Expected concentrations of Ca, P, and Mg were determined on fresh, dry, and ash weight bases and for 3 age groups, 3 breeds, and bulls, females, and steers. On an ash weight basis, cattle 6 to 18 months old had 185.74 mg of P/g, 372.52 mg of Ca/g, and 12.37 mg of Mg/g. Those 19 to 36 months old had 182.02 mg of P/g, 322.35 mg of P/g, and 8.09 mg of Mg/g. Those > 36 months old had 174.80 mg of P/g, 340.36 mg of Ca/g, and 6.62 mg of Mg/g. Steers had 183.93 mg of P/g, 352.73 mg of Ca/g, and 10.15 mg of Mg/g. Females had 178.47 mg of P/g, 320.28 mg of Ca/g, and 6.5 mg of Mg/g. Males had 176.15 mg of P/g, aH on an ash weight basis. Dairy breeds were found to have 186.08 mg of P/g, 351.25 mg of Ca/g, and 10.47 mg of Mg/g. Cattle of mixed breeding had 177.42 mg of P/g, 341.28 mg of Ca/g, and 6.54 mg of Mg/g. The Africander breed of beef cattle had 167.07 mg of P/g, all on an ash weight basis.
Show more [+] Less [-]Neutrophil function and pathologic findings in Holstein calves with leukocyte adhesion deficiency
1994
Nagahata, H. | Kehrli, M.E. Jr | Murata, H. | Okada, H. | Noda, H. | Kociba, G.J.
Leukocyte adhesion deficiency was diagnosed in 4 Holstein calves from 1 to 4 months old. Calves had severe ulcers on oral mucous membranes, gingivitis, severe periodontitis, chronic pneumonia, and stunted growth associated with severe neutrophilia. Neutrophils from affected calves had function defect, characterized by severely decreased adherence, chemotactic movements, phagocytosis, luminol-dependent chemiluminescent response, and O2(-1)-producing activities. Deficient CD18 expression (0.1 to 1.7%) on neutrophils was clearly detected by use of flow cytometric analysis. These affected calves were linked to a common ancestral sire that has been documented to be a carrier. Clinical features, leukocyte functional abnormalities, deficient expression of CD18, and mode of inheritance indicated that affected calves had leukocyte adhesion deficiency. In vitro leukocyte functional abnormalities were associated with deficiency in the expression of CD11/CD18. Pathologic findings indicated possible increased susceptibility to infection associated with this disease.
Show more [+] Less [-]Effect of succinylcholine, diazepam, and dantrolene on the urethral pressure profile of anesthetized, healthy, sexually intact male cats
1994
Straeter-Knowlen, I.M. | Marks, S.L. | Speth, R.C. | Wirth, W. | Knowlen, G.G.
Effects of the neuromuscular blocking agent succinylcholine (n = 9), the centrally acting skeletal muscle relaxant diazepam (n = 11), and the direct-acting skeletal muscle relaxant dantrolene sodium (n = 8) on the urethral pressure profile were evaluated in anesthetized, healthy, sexually intact, adult male cats. Intravenous administration of succinylcholine (0.075 mg/kg of body weight) significantly decreased mean absolute pressure in the prostatic and post-prostatic/penile intraurethral segments by -9.5 and -6.5 mm of Hg, respectively (P = 0.0002 and P = 0.0006, respectively). Dantrolene (1.0 mg/kg, IV) significantly decreased mean prostatic and postprostatic/ penile intraurethral segmental pressures by -3.5 and -2.8 mm of Hg, respectively (P = 0.005 and P = 0.0181, respectively). Diazepam (0.8 mg/kg, IV) did not significantly alter mean intraurethral segmental pressures. None of the drugs caused a change in segmental lengths of the urethra. These results indicate that skeletal muscle makes a substantial contribution to intraurethral tone in anesthetized, healthy, sexually intact male cats and that skeletal muscle relaxation may be successful in reducing prostatic and post-prostatic/penile urethral segmental tone in male cats. These results also suggest that dantrolene sodium may be valuable for the pharmacologic management of urethral disorders in male cats.
Show more [+] Less [-]Secretagogue-induced [14C]aminopyrine uptake in isolated equine parietal cells
1994
Campbell-Thompson, M.
Equine oxyntic mucosal cells were obtained by sequential exposure to pronase and collagenase. Acid production by parietal cells was assessed by uptake of [14C]aminopyrine (AP), a weak base that accumulates in intracellular acidic spaces. Incubation for various times revealed a maximal AP uptake at 10 minutes for histamine and carbachol. Similar secretagogue responses were observed for parietal cells from the mucosal cell preparation or after enrichment by elutriation. Histamine and isobutyl-methylxanthine (IBMX) stimulated AP uptake with a dose-dependent response and maximal effective concentration of 100 micromolar. Carbachol, 1 to 100 micromolar, and pentagastrin (PG), 1 to 1,000 nM, were ineffective stimulants of AP uptake. The AP uptake values for 100 micromolar IBMX, 1 micromolar carbachol, or 100 nM PG were 77 +/- 6%, 50 +/- 3.2%, and 40 +/- 4.5%, respectively, of that observed with maximal stimulation by 100 micromolar histamine (mean SEM, n = 4 to 14). Uptake of AP by nonstimulated control cells was 36 +/- 3.6% of maximal histamine stimulation. The AP accumulations during control conditions and after stimulation with 100 micromolar histamine and IBMX, 1 micromolar carbachol, or 100 nM PG were 1.18 +/- 0.39, 2.81 +/- 0.85, 1.93 +/- 0.48, 1.44 +/- 0.36, and 1.23 +/- 0.33 pmol of AP/10(5) parietal cells, respectively. Individual histamine dose-response curves were shifted to the right by increasing ranitidine and cimetidine concentrations (0.1 to 50 micromolar). These results indicate that isolated equine parietal cells are maximally stimulated by histamine and minimally stimulated by carbachol and PG.
Show more [+] Less [-]Morphometric analysis of the foramen magnum in Pekingese dogs
1994
Simoens, P. | Poels, P. | Lauwers, H.
The size and shape of the foramen magnum were studied in skulls from 75 adult and 5 juvenile Pekingese dogs. After maceration of the skulls, the height, width, and area of each foramen magnum were measured, and various skull indices were determined. The shape of the foramen varied from ovoid to rectangular and had a dorsal notch in aU but 2 skulls. Prolapse of cerebellum or brain stem through the enlarged opening was prevented by a fibrous membrane covering he dorsal notch. Mean +/- SD area of the foramen was 138.1 +/- 26.1 mm(2); its mean total height was 15.0 +/- 2.9 mm, and its mean maximal width was 13.3 +/- 1.1 mm. Statistically, variability in the area of the foramen was mainly correlated with total height of the foramen, including the dorsal notch. Total height of the foramen was not correlated with age or gender. The degree of dysplasia, notch index, and occipital index of each foramen magnum were determined. To allow a more accurate evaluation of the morphology of the foramen, the foramen magnum index, defined as the ratio between the maximal width and the total height of the foramen, was also computed. Mean +/- SD foramen magnum index was 91.8 +/- 17.1 in the adult Pekingese dogs. Foramen magnum index was not significantly correlated with age, but was significantly larger in male than in female dogs. The large variability in the shape and size of the foramen magnum and the absence of any neurologic problems in dogs of this study indicate that the dorsal notch of the foramen magnum in brachycephalic dogs is a normal morphologic variation, rather than a pathologic condition.
Show more [+] Less [-]Characterization of a murine monoclonal antibody generated against Neospora caninum tachyzoites by use of western blot analysis and immunoelectron microscopy
1994
Cole, R.A. | Lindsay, D.S. | Dubey, J.P. | Toivio-Kinnucan, M.A. | Blagburn, B.L.
A murine monoclonal antibody (MAB) 6G7 generated against tachyzoites of Neospora caninum recognized 8 major and several minor antigens, as observed by western blot analysis. Relative rate of migration of the 8 major antigens ranged from 31 to 97.4 kd. In addition, MAB 6G7 recognized a Toxoplasma gondii tachyzoite antigen with a relative rate of migration of 107 kd. Immunogold labeling of N caninum tachyzoites grown in human foreskin fibroblast cells indicated that MAB 6G7 binds to micronemes, dense granules, basal portions of rhoptries, and intravacuolar tubules within the parasitophorous vacuole. Monoclonal antibody 6G7 also bound to micronemes and basal portions of rhoptries within tachyzoites of T gondii. Monoclonal antibody 6G7 did not significantly inhibit development of tachyzoites in vitro.
Show more [+] Less [-]Comparison of peritoneal fluid analysis before and after exploratory celiotomy and omentopexy in cattle
1994
Anderson, D.E. | Cornwell, D. | St-Jean, G. | Desrochers, A. | Anderson, L.S.
The effect of right paralumbar fossa exploratory celiotomy and omentopexy on peritoneal fluid constituents was studied in 22 adult dairy cows. Six cows were eliminated on the basis of physical examination findings (n = 2), surgical findings (n = 2), or inability to obtain a sufficient volume of peritoneal fluid (n = 2). Sixteen cattle had normal results of Csc and serum biochemical analysis, and a minimum of 1 ml of peritoneal fluid was obtained by abdominocentesis. Abdominocentesis was repeated on days 1, 2, and 6 after surgery. Statistical analysis for repeated measures was performed, using a significance level of P < 0.05. Stage of gestation was evaluated for interaction with time. Mean total nucleated cell count was 3,200 cells/1 before surgery, was significantly increased 2 days after surgery (16,336 cells/microliter), and continued to increase through day 6 (20,542 cells/microliter). Mean polymorphonuclear cell count was 1,312 cells/microliter before surgery and was significantly higher at 2 (11,043 cells/microliter) and 6 (10,619 cells/microliter) days after surgery. Mean lymphocyte count was 254 cells/microliter before surgery and was significantly increased 2 days (1,911 cells/microliter) after surgery. By day 6, lymphocyte numbers were similar to preoperative values. Mean mononuclear cell count was 770 cells/microliter before surgery and was significantly increased on days 1 (3,084 cells/microliter), 2 (3,285 cells/microliter and 6 (2,349 cells/microliter) after surgery. Mean eosinophil numbers were 1,388 cells/microliter before surgery and were significantly increased on day 6 (6,347 cells/microliter) only. Interaction between time and stage of gestation was found only for specific gravity and total protein concentration. In general, specific gravity and total protein concentration increased after surgery (mean before surgery, 1.016 and 3.6 g/dl; mean after surgery, 1.021 and 5.6 g/dl). Left paralumbar fossa celiotomy performed 7 days after surgery did not reveal complications of repeated abdominocentesis, and pregnancy status was unchanged. Peritoneal fluid constituents are highly variable after exploratory celiotomy and omentopexy in cattle. However, results of this study may provide a reference for interpretation of postoperative peritoneal fluid sample findings in cattle.
Show more [+] Less [-]Seroepidemiologic survey of Borrelia burgdorferi exposure of dairy cattle in Wisconsin
1994
Ji, B. | Collins, M.T.
An ELISA, using purified flagellin of Borrelia burgdorferi as the solid-phase antigen, was used to measure antibody concentrations to B burgdorferi in dairy cattle in Wisconsin. Serum obtained from 5,060 cows in 160 randomly selected herds in the state were tested. Serum from an additional 2,600 cattle in Barron County, Wis, a county with a high annual incidence of B burgdorferi infections in human beings, was also tested. Only 7% of the cows that were tested, but 66% of the herds that were tested, were seropositive for B burgdorferi. Sixteen percent of the herds had a prevalence of 15% seropositive cows, whereas 50% of the herds had a prevalence of 1 to 14% seropositive cows. Seropositive herds were concentrated in the west-central part of Wisconsin. An association existed between the geographic location of seropositive herds and counties in which B burgdorferi infection of human beings was acquired (P < 0.05) as well as the geographic location of seropositive herds and the geographic distribution of Ixodes scapularis (P < 0.05). Barron County, in which B burgdorferi infection is endemic, had a significantly (P < 0.05) higher percentage of seropositive cows (17%) than did the state of Wisconsin (7%).
Show more [+] Less [-]Radiographic geometric variation of equine long bones
1994
Hanson, P.D. | Markel, M.D.
As more sophisticated research is performed to refine fracture fixation techniques for horses, it is important that normal values for the geometric properties of the bones of the appendicular skeleton be determined and that suitable controls be available. We evaluated the geometric properties of total bone width, cortical bone width, and medullary canal/trabecular bone width measured from 2 radiographic projections of equine long bones (humerus, radius, third metacarpal bone, femur, tibia, and third metatarsal bone) obtained from a general population of horses. Measurements were performed on slices separated by intervals equal to 5% of the bone's length. Slices were then grouped into 5 regions: proximal epiphysis, proximal part of the metaphysis, diaphysis, distal part of the metaphysis, and distal epiphysis. Results validated use of the contralateral bone as a control for assessing experimental models or clinical cases. Of 858 homotypic slice comparisons between left and right bones, significant (P less than or equal to 0.05) differences were detected in 31 (3.6%) of the comparisons. Of 168 homotypic region comparisons, significant differences were observed in 3 (1.8%) of the comparisons. The greatest variation between left and right bones was observed in metaphyseal regions, areas with bony protuberances, and regions with prominent bone superimposition. At a power of 0.8 for the statistical tests performed in this study, the mean homotypic variation of bones in each region is < 5.8% for the proximal epiphysis, 11.3% for the proximal part of the metaphysis, 6.8% for the diaphysis, 12.2% for the distal part of the metaphysis, and 5.2% for the distal epiphysis.
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