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Pharmacokinetics of caffeine in lactating dairy cows
1995
DeGraves, F.J. | Ruffin, D.C. | Duran, S.H. | Spano, J.S. | Whatley, E.M. | Schumacher, J. | Riddell, M.G.
Because caffeine is metabolized by the hepatic P-450 cytochrome oxidase system, clearance of caffeine is an excellent quantitative test of hepatic function in human beings. It is currently used in much the same way that creatinine clearance is used to assess renal function. Caffeine clearance was measured in lactating dairy cows initially to determine the suitability of caffeine clearance as an indicator of hepatic function in cattle. Pharmacokinetic variables of caffeine were studied in 6 adult lactating dairy cows after IV administration of a single dose of caffeine sodium benzoate (2 mg of caffeine/kg of body weight). Caffeine concentration was analyzed by use of an automated enzyme immunoassay. The lower limit of detection of the assay for caffeine in serum was 0.079 micrograms/ml. Serum caffeine concentration-time curves best fit an open two-compartment pharmacokinetic model. Harmonic mean elimination half-life was 3.8 (range, 2.6 to 6.9) hours, and total clearance was 0.118 (range, 0.090 to 0.197) L/kg/h. Milk caffeine concentration was similar to serum concentration 1.5 to 24 hours after caffeine administration. Adverse effects were not observed in cows given caffeine.
Mostrar más [+] Menos [-]Effects of tumor necrosis factor blockade on interleukin 6, lactate, thromboxane, and prostacyclin responses in Miniature Horses given endotoxin
1995
Cargile, J.L. | MacKay, R.J. | Dankert, J.R. | Skelley, L.
A monoclonal antibody (MAB) against equine tumor necrosis factor-alpha (Eq TNF) was used to investigate the role of TNF in cytokine, eicosanoid, and metabolic responses of Miniature Horses given endotoxin. Plasma concentrations of interleukin 6 (IL-6), lactate, thromboxane A2 metabolite, and prostacyclin metabolite (6-keto-PGF(1 alpha)) were measured in 10 Miniature Horses given 0.25 micrograms of lipopolysaccharide (LPS; Escherichia coli O55:B5)/kg of body weight. Five horses were given Eq TNF MAB and 5 were given isotype-matched MAB as control. All horses were given 1.86 mg of antibody/kg by IV infusion, 5 minutes before LPS was given IV. Blood samples were taken 20 minutes before and at multiple intervals for 24 hours after LPS was given. Interleukin 6 bioactivity in plasma was measured, using IL-6-dependent cell line (B9). Eicosanoid activities were assessed by enzyme immunoassay, and plasma lactate concentration was determined enzymatically. Data were analyzed by ANOVA and Tukey's honest significant difference test for significant (P < 0.05) effect of treatment. Horses given Eq TNF MAB had significantly (P < 0.050) lower peak mean +/- SEM IL-6 (59 +/- 29 U/ml), lactate (16 +/- 2.00 mg/dl), and 6-keto-PGF(1 alpha) (254 +/- 79 pg/ml) values then did horses given control MAB (880 +/- 375 U/ml for IL-6; 26 +/- 0.04 mg/dl for lactate; and 985 +/- 290 pg/ml for 6-keto-PGF(1 alpha)). There was no effect of anti-TNF treatment on LPS-induced thromboxane A2 metabolite production. Tumor necrosis factor mediated IL-6, lactate, and prostacyclin responses, without affecting thromboxane production in horses given LPS.
Mostrar más [+] Menos [-]Eicosanoid concentrations in digital venous blood from horses with chronic laminitis
1995
Owens, J.G. | Kamerling, S.G. | Keowen, M.L.
The eicosanoids are a family of lipid-derived autocoids that are released in response to a variety of physical and hormonal stimuli. In this study, prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) were measured in the digital veins of clinically normal horses and horses with chronic laminitis to determine whether these arachidonic acid metabolites have a role in mediating signs of hoof pain and lesions associated with chronic laminitis. Horses were evaluated at rest and after a brief exercise period, to determine whether eicosanoids are released into the circulation after mild concussion. Digital vein eicosanoid concentrations in horses with signs of hoof pain attributable to chronic laminitis were not different than those in clinically normal horses. There was no difference in resting and postexercise PGE2 or LTB4 concentrations. Mean digital vein PGE2 concentration for the 2 groups was 187.18 pg/ml, whereas mean digital vein LTB4 concentration for the 2 groups was 74.71 pg/ml. These data do not support the hypothesis that PGE2 and LTB4 have a role in mediating the signs of pain and pathologic features of chronic laminitis.
Mostrar más [+] Menos [-]Adrenocortical function in neonatal and weanling Beagle pups
1995
Randolph, J.F. | Center, S.A. | Reimers, T.J. | Scarlett, J.M. | Corbett, J.R.
Adrenocortical function was assessed in 27 Beagle pups at 2, 4, 6, 8, 10, and 12 weeks of age by determination of plasma sodium, potassium, and chloride concentrations; serum aldosterone and cortisol concentrations; and plasma ACTH concentrations. Serum cortisol concentration was measured before and 1 and 2 hours after IM administration of 2.2 IU of ACTH/kg of body weight. Serum progesterone concentration also was determined for all pups at 2, 4, and 6 weeks of age. Mean baseline cortisol concentration was lower for pups 8 weeks old or younger than for mature dogs. Nevertheless, mean serum ACTH-stimulated cortisol concentration in dogs of all age groups increased into the adult reference range after administration of ACTH. For pups 4 weeks old or younger, increase in cortisol concentration was maximal at 2 hours after ACTH administration. However, in pups between 6 and 12 weeks of age, the increase in cortisol concentration was maximal 1 hour after ACTH administration in about a third of the pups, whereas the remaining pups had peak values at 2 hours. Mean plasma sodium, potassium, and chloride concentrations for each age group were within the reference ranges established for mature dogs, with the exception of lower mean plasma sodium and chloride concentrations in pups 4 weeks old or younger. Mean serum aldosterone concentration in pups of each age group was substantially higher than the range of aldosterone concentrations for clinically normal mature dogs. Median progesterone concentration was uniformly less than 0.2 ng/ml for all pups 6 weeks old or younger. The normal endogenous ACTH concentration and adequate cortisol responses to exogenous ACTH seen in our pups would support functional pituitary gland and adrenal cortex for cortisol production. The low baseline cortisol concentration observed in the pups of this study may be related to reduced binding of cortisol to plasma proteins, as exists in human infants. The hyponatremia and increased aldosterone concentration may be explained by reduced renal tubular response to aldosterone, as also evidenced in the human infant kidney.
Mostrar más [+] Menos [-]Lactogenic immunity and milk antibody isotypes to transmissible gastroenteritis virus in sows exposed to porcine respiratory coronavirus during pregnancy
1995
Lanza, I. | Shoup, D.I. | Saif, L.J.
Passive protection provided by sows inoculated with the virulent Miller strain of transmissible gastroenteritis virus (TGEV), or the ISU-1 strain of porcine respiratory coronavirus (PRCV), or both was evaluated in nursing pigs challenge exposed with virulent TGEV. Four sows (group B) were inoculated with PRCV oronasally twice at 4 and 2 weeks before parturition; 1 sow (group C) was inoculated similarly, but in 2 subsequent pregnancies; and 2 sows (group D) were oronasally primed with PRCV at 4 weeks before parturition, and 2 weeks later were administered a booster inoculation of virulent TGEV. Two additional sows (group E) remained uninoculated and served as seronegative controls, and 1 sow (group A) that had been naturally infected with TGEV served as a seropositive control. The degree of passive immunity transferred by these sows to their litters was assessed by challenge exposing the pigs of sows in groups BE (only the second litter of group C) with virulent TGEV at 3 to 5 days of age. After challenge exposure, clinical signs of infection and mortality were noted and fecal and nasal shedding of virus was assessed by ELISA. The IgA, IgG, and IgM antibody titers to TGEV were quantified in colostrum and milk of the sows by use of an isotype-specific monoclonal antibody-capture ELISA, using biotinylated monoclonal antibodies against each porcine isotype as detecting reagents. A plaque-reduction assay was used to quantify neutralizing antibody titers in serum, colostrum, milk, and fractionated whey (IgG and IgA/IgM). In the sow naturally infected with TGEV (group A), there was a pronounced decrease in IgG antibody titers to TGEV in the transition from colostrum to milk, and IgA TGEV antibodies became predominant, with high titers maintained throughout lactation. The 4 group-B sows partially protected their pigs after TGEV challenge exposure; mean mortality was 67%, compared with 100% in pigs suckling the 2 TGEV seronegative control sows (group-E litters). Although IgA TGEV antibodies were detected in colostrum and milk of group-B sows, IgG TGEV antibodies were the most abundant. The sow of group C had a marked increase in IgA TGEV antibody titers in colostrum and milk after reinoculation with PRCV during the second pregnancy, before TGEV challenge exposure of the litter. Its pigs were passively protected to a high degree after TGEV challenge exposure (27% litter mortality). The sows in group D, primed with PRCV and boosted with TGEV, provided the best passive protection after TGEV challenge exposure of their pigs. Not only litter mortality (27%) but also morbidity was reduced, compared with those factors for the other challenge exposed litters, and the sows did not become ill. In these swine, the high degree of passive protection observed could not be associated with the presence of only IgA TGEV antibodies in the milk, but high IgM TGEV antibody titers also were detected in colostrum and milk. Results of this study suggest that PRCV-inoculated sows are able to partially protect their pigs from TGEV challenge exposure and, on the basis of preliminary data, the degree of protection may increase after multiple PRCV exposures or after secondary exposure to TGEV during pregnancy. Also, an IgA respiratory tract-mammary gland link may exist as evident by the low titer of IgA TGEV antibodies in the milk of PRCV-inoculated sows, but may not be as efficient in inducing lactogenic IgA immunity as is the gastrointestinal tract-mammary gland link.
Mostrar más [+] Menos [-]Pharmacokinetics of enrofloxacin in clinically normal dogs and mice and drug pharmacodynamics in neutropenic mice with Escherichia coli and staphylococcal infections
1995
Meinen, J.B. | McClure, J.T. | Rosin, E.
Pharmacodynamic variables of enrofloxacin were investigated in a neutropenic mouse Escherichia coli and staphylococcal thigh infection model. Enrofloxacin pharmacokinetics in clinically normal mice and dogs were compared to confirm that doses evaluated in the mouse model would include enrofloxacin doses appropriate for use in dogs. Mice were made neutropenic by treatment with cyclophosphamide and injected in the thigh muscle with approximately 10(6) colony-forming units of E. coli (n = 2) or a staphylococcal (n = 2) clinical isolate. Enrofloxacin dosages tested ranged from 0.78 to 50 mg/kg of body weight and 6.25 to 200 mg/kg in the E. coli and staphylococcal infection trials, respectively. In each 24-hour dosage trial, enrofloxacin was administered SC as a single dose or in divided doses given every 3, 6, or 12 hours. Comparison of log(10) colony-forming units per thigh muscle in untreated control mice and mice treated with enrofloxacin was used as a measure of efficacy. Two-way ANOVA was used to determine that the enrofloxacin total dose, but not the dose frequency, was significant in determining drug efficacy. Pharmacokinetic values analyzed by use of multivariant stepwise linear regression analysis indicated that the area under the concentration-time curve, but not time above minimum inhibitory concentration, was significant in predicting efficacy of enrofloxacin treatment. We conclude that enrofloxacin killing of E. coli and staphylococci is concentration dependent and not time dependent.
Mostrar más [+] Menos [-]Effect of glucocorticoids on serum osteocalcin concentration in horses
1995
Geor, R. | Hope, E. | Lauper, L. | Piela, S. | Klassen, Jon | King, V. | Murphy, M.
The effects of dexamethasone (0.2 mg/kg of body weight; IV, IM, and PO) and methylprednisolone acetate (120 mg, given intra-articularly) on serum osteocalcin and cortisol concentrations were studied in 6 horses. Serum osteocalcin and cortisol concentrations were serially monitored after each treatment. A significant (P < 0.05) decrease in serum osteocalcin and cortisol concentrations was observed from 12 to 24 and 2 to 48 hours, respectively, after IV and IM administrations of dexamethasone. Serum osteocalcin and cortisol concentrations were significantly decreased from 6 to 48 and 3 to 72 hours, respectively, after oral administration. In contrast, a change in serum osteocalcin concentration was not detected after intra-articular administration of methylprednisolone. Oral, IV, or IM treatment with 0.2 mg of dexamethasone/kg caused a decrease in serum osteocalcin concentration in horses.
Mostrar más [+] Menos [-]Comparative analyses of peritoneal fluid from calves and adult cattle
1995
Anderson, D.E. | Cornwell, D. | Anderson, L.S. | St-Jean, G. | Desrochers, A.
Reference values for hematologic variables change with increasing age in cattle. Therefore, the purpose of the study reported here was to describe the peritoneal fluid constitutents of clinically normal young calves, and to compare cellular concentration and distribution in blood and peritoneal fluid of young calves with those of adult cattle. Eight healthy 8-week-old male Holstein calves and 8 healthy 3- to 8-year-old Holstein cows were studied. Peritoneal fluid was collected from calves along the ventral midline, 4-cm cranial to the umbilicus. Abdominocentesis was performed in the region of the lower right flank in adult cattle. Correlation analysis, using the Pearson's correlation coefficient, and regression analysis were performed for blood and peritoneal fluid data from calves. Data from calves were compared with those of cows, using Wilcoxon's rank sum test. A P value < 0.05 was considered significant for all tests. Calves had significantly lower blood eosinophil count (P < 0.003) and plasma protein concentration (P < 0.001) than did cows. Calves had significantly higher peritoneal fluid nucleated cell (P < 0.05) and mononuclear cell (P < 0.05) counts, but lower peritoneal fluid eosinophil cell count (P < 0.003) than did cows. For calves, nulceated cell and lyhocyte cell counts in the blood had a high, positive correlation with those of peritoneal fluid. However, the prediction equation for nucleated cell count accounted for a modest proportion of variability. A prediction equation for peritoneal fluid lymphocyte cell count was established. On the basis of results of this study, reference ranges established for peritoneal fluid constituents of clinically normal adult cattle may not be appropriate for interpretation of peritoneal fluid analysis of calves.
Mostrar más [+] Menos [-]Effects of age, sex, reproductive status, and hospitalization on serum alpha 1-antitrypsin concentration in dogs
1995
Hughes, D. | Elliott, D.A. | Washabau, R.J. | Kueppers, F.
We performed a study to determine a reference range for serum alpha 1-antitrypsin (alpha 1 AT) in dogs by specific immunoassay; to evaluate whether serum alpha 1 AT concentration varied with age, sex, or reproductive status in healthy dogs; and to investigate whether the serum alpha 1 AT concentration in hospitalized dogs differed from that of healthy, nonhospitalized dogs. Serum alpha 1 AT was quantitated by radial gel immunodiffusion for 60 healthy dogs and 311 hospitalized dogs. In healthy dogs, serum alpha 1 AT concentration was 2.33 +/- 0.41 mg/ml (mean +/- SD), yielding a reference range (mean +/- 2 SD) of 1.51 to 3.15 mg/ml. A correlation was not found between serum alpha 1 AT concentration and age in healthy dogs. The serum alpha 1 AT concentration (mean +/- SEM mg/ml) was significantly higher in healthy, sexually intact females (2.64 +/- 0.1) than in healthy, spayed females (2.22 +/- 0.12; P < 0.004); healthy, sexually intact males (2.14 +/- 0.1; P < 0.0006); and healthy, castrated males (2.25 +/- 0.14; P < 0.02). Hospitalized, sexually intact females had a lower serum alpha 1 AT concentration (1.93 +/- 0.07) than healthy, sexually intact females (2.64 +/- 0.1; P < 0.0002). Likewise, the serum alpha 1 AT concentration in hospitalized, sexually intact males (1.92 +/- 0.04) was less than in healthy, sexually intact males (2.14 +/- 0.1; P < 0.04). A difference in alpha 1 AT concentration was not found between healthy and hospitalized, neutered dogs.
Mostrar más [+] Menos [-]Isolation of thyroid peroxidase and lack of autoantibodies to the enzyme in dogs with autoimmune thyroid disease
1995
Thacker, E.L. | Davis, J.M. | Refsal, K.R. | Bull, R.W.
Fifty serum samples from dogs with clinical signs of hypothyroidism and autoantibodies (AA) to thyroglobulin (Tg), thyroxine, or triiodothyronine were screened for AA to thyroid peroxidase (TPO). Thyroid peroxidase is the antigen against which microsomal AA are formed in human beings with lymphocytic thyroiditis. The TPO was isolated from canine thyroid tissue, using a modification of the procedure for purifying porcine TPO. The enzyme was solubilized from the membrane, using a deoxycholate-trypsin solution, followed by ammonium sulfate precipitation and diethylaminoethyl Sephadex chromatography. Activity of TPO was determined, using an iodide oxidation assay and a guaiacol assay. A monoclonal antibody to canine Tg, coupled to an immunoaffinity column, was used to eliminate the contaminating Tg from the TPO preparation. Using the TPO preparation as an antigen, an ELISA was performed on 10 serum samples and immunoblot assays were performed on 50 canine sera. Autoantibodies to TPO were not found in any of the sera. Assays also were performed, using purified porcine and human TPO and evidence of cross-reactivity with canine TPO was not identified. The absence of AA to TPO in dogs suggests a different pathogenesis for autoimmune thyroid disease in dogs than that hypothesized for lymphocytic thyroiditis in human beings.
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