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Plasma concentrations of immunoreactive proopiomelanocortin peptides and cortisol in clinically normal cats
1994
Peterson, M.E. | Kemppainen, R.J. | Orth, D.N.
We measured immunoreactive (IR) plasma concentrations of the proopiomelanocortin (POMC)-derived. peptides (adrenocorticotropic hormone [ACTH]; beta-endorphin/beta-lipotropin [beta END/beta LPH]; and alpha-melanocyte stimulating hormone [alpha MSH]) and of cortisol in 100 clinically normal cats. Median plasma concentration of IR-ACTH was 2.7 pmol/L (range, less than or equal to 1.1 to 22 pmol/L), of beta END/beta LPH was 28 pmol/L (range, 3.8 to 130 pmol/L), of alpha MSH was 36 pmol/L (range, less than or equal to 3.6 to 200 pmol/L), and of cortisol was 35 nmol/L (range, 5 to 140 nmol/L). Plasma concentrations of IR-ACTH, alpha MSH, and beta END/beta LPH were at or below the assay sensitivity in 34, 3, and 0% of the cats, respectively. We did not detect a correlation between plasma concentrations of IR-ACTH and beta END/beta LPH (r = 0.23) or between plasma concentrations of IR-ACTH and alpha MSH (r = 0.19). However, there was a significant (P < 0.001) correlation between plasma concentrations of IR-beta END/beta LPH and alpha MSH (r = 0.81). There was not a significant correlation between plasma concentration of cortisol and plasma concentration of any of the IR-POMC peptides. High plasma concentrations of IR-alpha MSH and beta END, POMC peptides secreted predominantly by melanotrophs in other species, indicate that clinically normal cats have an actively secreting pars intermedia. Although the beta END/beta LPH assay used in this study measures the pars distalis-derived peptide beta-LPH, as well as beta END itself, over 95% of the IR-beta END/beta LPH activity in feline plasma containing high concentrations of alpha MSH, but low concentrations of IR-ACTH, was found to coelute with human beta END on gel filtration chromatography. In contrast to the high plasma concentrations of IR-alpha MSH and beta END/ beta LPH, many cats had low to undetectable concentrations of IR-ACTH, a peptide secreted predominantly by pars distalis corticotrophs. The pattern of plasma POMC peptide concentrations found in cats is similar to that reported in rats, but is markedly different from that reported in dogs, in which the secretion of pars intermedia POMC peptides is normally low.
显示更多 [+] 显示较少 [-]Pharmacokinetic variables and bioavailability from muscle of creatine kinase in cattle
1994
Lefebvre, H.P. | Toutain, P.L. | Serthelon, J.P. | Lassourd, V. | Gardey, L. | Braun, J.P.
Pharmacokinetic variables of skeletal muscle creatine kinase (CK) activity after IV administration of a muscle extract; CK bioavailability after IM administration of the muscle extract; and effect of IM administration of saline solution, to appreciate the possible release of CK consecutive to muscle puncture, were determined in 6 cows. A general equation for the quantitative estimation of skeletal muscle damage also was derived. Administration of saline solution IM had no effect on plasma CK activity (ANOVA, P > 0.05) in any of the cows. After IV administration of the muscle extract (150 U/kg of body weight), mean volume of the central compartment, plasma half-life, and plasma clearance of CK were 0.027 +/- 0.007 L/kg, 520 +/- 109 minutes, and 6.43 +/- 2.29 ml/kg/h, respectively. After IM administration (150 U/kg), mean bioavailability of CK was 51 +/- 17% and maximal plasma CK activity (500 +/- 97 U/L) was observed at 454 +/- 131 minutes. The rate of CK activity entry into plasma was determined by use of deconvolution analysis. Two peaks were observed; the first appeared before the 30th minute after IM administration, and the second appeared at 3.3 +/- 1.1 hours. Amplitudes were 6.31 +/- 4.45 and 6.57 +/- 3.08 U/kg/h, for the first and the second peaks, respectively. The quantity of CK liberated from control muscle was 0.69 +/- 0.12 U/kg/h, corresponding to a normal daily catabolism of 5.8 +/- 1.0 mg of muscle/kg. From these results, the following equation can be proposed to determine the corresponding mean equivalent of destroyed muscle (Qmuscle, test article) after IM administration of a test article: Qmuscle, test article (g/kg) = 4.41 X 10(-6) AUC (U/h/L), with AUC being the CK plasma activity area under the curve.
显示更多 [+] 显示较少 [-]Effect of in vitro and in vivo migration of bovine neutrophils on binding and expression of Fc receptors for IgG2 and IgM
1994
Worku, M. | Paape, M.J. | Filep, R. | Miller, R.H.
Binding of endogenous and exogenous homologous IgG, and IgM to bovine neutrophils before and after in vitro migration through micropore filters, and in vivo migration through mammary tissues after intramammary injection of endotoxin was evaluated by use of flow cytometry. Immunoglobulin binding to neutrophils at 4 and 37 C was also evaluated. Before and after in vitro migration, neutrophils with endogenously bound IgG, and IgM averaged 1 and 2% and 23 and 7%, respectively. Before and after in vivo migration, IgG2 and IgM binding averaged 1 and 7% and 26 and 15%, respectively. Before and after in vitro migration, binding of purified IgG2 and IgM averaged 75 and 67% and 8 and 24%, respectively. Before and after in vivo migration, percentage of neutrophils binding purified IgG2 and IgM averaged 92 and 98% and 54 and 70%, respectively. When serum was used as a source of exogenous immunoglobulins, binding of total Igg after in vitro migration increased from 5% to 28% and of IgM from 4% to 20%. After in vivo migration, binding increased from 21% to 47% and from 24% to 56%, respectively. Exogenous binding of IgG2 at 4 and 37 C averaged 75 and 84%, and binding of IgM averaged 8% at either temperature. Endogenous IgG2 was unaffected by temperature; however, binding of IgM decreased from 23% at 4 C to 2% at 37 C. These data indicate that endogenous binding was higher for IgM before migration than after migration, in vitro and in vivo. Furthermore, migration in vivo through cellular matrices induced receptor upregulation for IgG and IgM. Source and concentration of ligand and serum components, other than immunoglobulins, appeared to contribute to receptor expression and availability. Neutrophils that were exposed to endotoxin and migrated into milk expressed more receptors than did unstimulated and nonmigrating neutrophils. The association of IgM with its receptor was temperature-dependent.
显示更多 [+] 显示较少 [-]Characterization of the hemodynamic and metabolic alterations in the large colon of horses during low-flow ischemia and reperfusion
1994
Moore, R.M. | Muir, W.W. | Bertone, A.L. | Beard, W.L.
Effects of low-flow ischemia and reperfusion of the large colon on systemic and colonic hemodynamic and metabolic variables were determined in horses. Twenty-four adult horses were randomly allocated to 3 groups: sham-operated (n = 6), 6 hours of ischemia (n = 9), and 3 hours of ischemia and 3 hours of reperfusion (n = 9). Low-flow ischemia was induced in groups 2 and 3 by reducing colonic arterial blood flow to 20% of baseline. Heart rate, arterial blood pressures, cardiac index, pulmonary artery pressure, right atrial pressure, and colonic blood flow were monitored. Arterial, mixed-venous, and colonic venous blood gas and oximetry analyses; PCV; and blood lactate and pyruvate and plasma total protein concentrations were measured. Data were recorded, and blood samples were collected at baseline and at 30-minute intervals for 6 hours; additionally, data were collected at 185, 190, and 195 minutes (corresponding to 5, 10, and 15 minutes of reperfusion in group-3 horses). There were no differences among groups at baseline or across time for any systemic hemodynamic or metabolic variable. Colonic blood flow did not change across time in group-1 horses. Colonic blood flow significantly (P < 0.05) decreased to 20% of baseline at induction of ischemia in horses of groups 2 and 3 and remained significantly decreased throughout the ischemic period in horses of groups 2 (6 hours) and 3 (3 hours). Colonic blood flow significantly (P < 0.05) increased above baseline by 5 minutes of reperfusion in group-3 horses. Colonic oxygen delivery and oxygen consumption, and colonic venous pH, PO2, percentage saturation of hemoglobin, and oxygen content were significantly (P < 0.05) decreased within 30 minutes after induction of ischemia in horses of groups 2 and 3; colonic venous PCO2, colonic oxygen extraction ratio, and lactate and pyruvate concentrations were significantly (P < 0.05) increased by 30 minutes of ischemia. These alterations continued throughout ischemia, but within 5 minutes of reperfusion in group-3 horses, these variables either returned to baseline (pH, PCO2, lactate, pyruvate), significantly (P < 0.05) increased above baseline (PO2, oxygen content, % saturation of hemoglobin), or significantly (P < 0.05) decreased below baseline (colonic oxygen extraction ratio). Colonic oxygen consumption remained decreased during reperfusion in group-3 horses. Colonic mucosal ischemia-reperfusion injury observed in this model of ischemia was associated with local colonic hemodynamic and metabolic alterations in the presence of systemic hemodynamic and metabolic stability. Reactive hyperemia was observed at restoration of colonic blood flow in group-3 horses and persisted during reperfusion. Colonic venous metabolic alterations were corrected at reperfusion, indicating adaptation of the colon to the return of blood flow and oxygen delivery with resultant decrease in anaerobic metabolism. The early alterations in these variables may simply represent a washout of metabolic by-products.
显示更多 [+] 显示较少 [-]Efficacy of 4-methylpyrazole for treatment of ethylene glycol intoxication in dogs
1994
Dial, S.M. | Thrall, M.A.H. | Hamar, D.W.
4-Methylpyrazole (4-MP), an alcohol dehydrogenase inhibitor, was administered to dogs to treat ethylene glycol (EG) intoxication. Eleven dogs were given 10.6 g of EG/kg of body weight; 5 dogs were treated with 4-MP 5 hours after EG ingestion and 6 dogs were treated with 4-MP 8 hours after EG ingestion. 4-Methylpyrazole was administered IV as a 50-mg/dl solution in 50% polyethylene glycol: initial dose, 20 mg/kg; at 12 hours after initial dose, 15 mg/ kg; at 24 hours after initial dose, 10 mg/kg, and at 30 hours after initial dose, 5 mg/kg. Physical, biochemical, hematologic, blood gas, serum and urine EG concentrations, and urinalysis findings were evaluated at 0, 1, 3, 6, 9, 12, 24, 48, 72 hours, and at 1 week and 2 weeks after EG ingestion. Dogs of both groups developed clinicopathologic signs associated with EG intoxication, including CNS depression, hyperosmolality, high anion gap metabolic acidosis, polydipsia, polyuria, calcium oxalate monohydrate and dihydrate crystalluria, and isosthenuria. Fractional excretion of sodium was increased in all dogs between 1 and 9 hours after EG ingestion, but remained increased beyond 24 hours only in the 2 dogs treated at 8 hours after EG ingestion that developed acute renal failure. All dogs treated 5 hours after EG ingestion recovered without morphologic, biochemical, or clinical evidence of renal impairment. Of the 6 dogs treated 8 hours after EG ingestion, 2 developed acute renal failure. One of the dogs treated 8 hours after EG ingestion remained isosthenuric for 2 months, but did not manifest any other signs of renal impairment. Of the dogs treated 8 hours after EG ingestion, 3 recovered without morphologic, biochemical, or clinical evidence of renal impairment. Serum half-life of EG was prolonged in the dogs treated 8 hours after EG ingestion. Percentage of EG excreted unchanged was 84 +/- 2% in the dogs treated 5 hours after EG ingestion, and was 40 +/- 10% in the dogs treated 8 hours after EG ingestion. 4-Methylpyrazole was effective in preventing renal failure in all dogs given 10.6 g of EG/kg when treatment was initiated by 5 hours after EG ingestion, and in 4 of 6 dogs when treatment was initiated by 8 hours after EG ingestion.
显示更多 [+] 显示较少 [-]Blood coagulopathy in dogs with shock induced by injection of heartworm extract
1994
Kitoh, K. | Watoh, K. | Kitagawa, H. | Sasaki, Y.
A crude, whole-body extract of female heartworms was administered IV to 10 dogs with and 13 dogs without heartworm (HW) infection. Shock developed in 8 of 10 infected dogs and 11 of 13 non-infected dogs, and blood coagulopathy was observed in 12 of 19 dogs with shock. Prevalence and severity of blood coagulopathy were proportionate to prevalence and severity of shock. Platelet count decreased in all dogs with shock with or without blood coagulopathy; thus, the decrease in platelet count might be related to shock. In 4 dogs, activated partial thromboplastin time (APTT) was prolonged--192.0 seconds at 30 minutes after HW injection--and prothrombin time (PT) was increased--13.8 seconds at initial collapse. In 8 dogs, APTT was increased--200 seconds for 2 hours after HW injection--and PT was increased--200 seconds at 30 minutes after the injection. The APTT prolongation might have been caused mainly by decreases in activities of factors VIII, IX, XI, and XII of the intrinsic blood coagulation pathway. In dogs with severely prolonged PT, plasma fibrinogen concentration and factor II activity decreased slightly. Prolonged PT was corrected in vitro by addition of normal plasma at high concentration (> 80%), but prolonged APTT could not be corrected in vitro by addition of 80% normal plasma. Serum fibrin degradation products concentration was < 10 microgram/ml, and soluble fibrin monomer complex was negative in all dogs. Thrombi were not found in blood vessels of any organ at necropsy and after histologic study. Therefore, it was suggested that blood coagulopathy resulting from inhibition of coagulation factor activities might develop in shock induced by HW extract.
显示更多 [+] 显示较少 [-]Long-term fate and effects of exercise on sternal cartilage autografts used for repair of large osteochondral defects in horses
1994
Howard, R.D. | McIlwraith, C.W. | Trotter, G.W. | Powers, B.E. | McFadden, P.R. | Harwood, F.L. | Amiel, D.
Bilateral osteochondral defects (10 mm2 X 3 mm deep) were created on the distal articular surface of the radial carpal bone of ten, 2- to 3-year-old horses. One defect of each horse was repaired, using a sternal cartilage autograft (treated), and the other was left untreated (control). The horses were exercised on a high-speed treadmill at incrementally increased speed and duration over the course of 12 months. Horses were evaluated arthroscopically at 6 to 7 weeks, and clinical examinations were conducted weekly at exercise. Twelve months after surgery, carpuses of each horse were radiographed and clinically examined prior to euthanasia. A gross pathologic evaluation of each joint was conducted, and samples were collected for histologic, histochemical, histomorphometric, and biochemical evaluation. Radiographically, the grafted joints had more extensive evidence of arthropathy, and clinically, 8 of the 10 horses were more lame in the grafted limb. On the basis of histomorphometry, the repair tissue of the grafted defects contained a greater median percentage of hyaline cartilage (45%) than that of control defects 4.5%), and the control defects contained a greater percentage of fibrocartilage (82%) than did grafted defects (28.5%). A greater median percentage of repair tissue stained with safranin-O in the grafted defects (24.5%) than in the control defects (3.5%). On gross pathologic and histologic evaluation, repair tissue of the control defects had better continuity and was more firmly attached to the subchondral bone than was repair tissue of the grafted defects. Repair tissue of the grafted defects had extensive fissure and flap formation. Histologically, subchondral bone reactivity and fibroplasia was extensive in grafted joints. Repair tissue of grafted defects had a greater percentage of type II collagen (mean sem, 83.5 +/- 2.95%) than did controls (mean, 79.4 3.87%) that was not statistically significant. Hexosamine content was significantly higher (P < 0.05) in repair tissue of the grafted defect (mean, 28.9 +/- 3.00 mg/g of dry weight) vs control (mean, 20.6 +/- 1.85 mg/g of dry weight). On the basis of this experimental model, sternal cartilage autografts cannot be recommended at this time for repair of osteochondral defects in athletic horses.
显示更多 [+] 显示较少 [-]Ferula communis variety brevifolia intoxication of sheep
1994
Tligui, N. | Ruth, G.R.
Sheep given powdered Ferula communis variety brevifolia at dosage of 2.5 g/kg of body weight/d for 15 days developed classical clinical signs of intoxication: anorexia, somnolence, apparent weakness, and hemorrhage. Marked reduction of vitamin K-dependent coagulation factors and prolongation of prothrombin time and activated partial thromboplastin time were consistent with presence of ferulenol, a toxic coumarinic factor in the plant. Changes induced in the coagulation system developed by the second day of plant administration and were normal within 4 days after dosing was stopped. There was no evidence of primary liver damage or platelet malfunction. Of 6 intoxicated sheep, 2 died with only minimal evidence of hemorrhage.
显示更多 [+] 显示较少 [-]Safety, efficacy, and effects on copper metabolism of intrareticularly placed selenium boluses in beef heifer calves
1994
Maas, J. | Peauroi, J.R. | Weber, D.W. | Adams, F.W.
Intrareticularly placed sustained-release selenium boluses were administered to 1 group of selenium-deficient heifer calves (n = 16), and a second group (n = 16) was left as nontreated controls. Age range for all calves was 83 to 156 days. These boluses release 3 mg of selenium each day, as sodium selenite. Measurements of blood selenium concentration, plasma copper concentration, hepatic copper concentration, and body weight were made over a 188-day day study. The treated group of calves had significantly higher mean blood selenium concentration at posttreatment days 68 (P < .0001), 112 (P < 0.0001), and 188 (P < 0.005) than did the control group. Mean blood selenium concentration in the treated calves was > 0.10 micrograms/ml for 188 days. These boluses were observed to be clinically safe; signs of selenium toxicosis were not detected and untoward effects were not seen in the selenium-treated calves. There were no differences between control and treatment groups with respect to mean hepatic copper concentration or mean plasma copper concentration. There were no observed differences between the control and treatment groups with respect to weight gain during the study.
显示更多 [+] 显示较少 [-]Enhancement of Pasteurella haemolytica leukotoxic activity by bovine serum albumin
1994
Waurzyniak, B.J. | Clinkenbeard, K.D. | Confer, A.W. | Srikumaran, S.
Growth of Pasteurella haemolytica A1 in RPMI 1640 medium containing 0.5% bovine serum albumin (BSA) for 2.5 hours enhanced culture supernatant leukotoxic activity [30,700 +/- 12,900 toxic units/ml, compared with leukotoxic activity of culture supernatants produced in RPMI 1640 medium alone (120 +/- 40 toxic units/ml)]. Gel filtration chromatography of the leukotoxic activity from RPMI 1640 medium supernatants in buffer containing 50 mM NaCl indicated a single leukotoxic activity peak (peak I) eluting near the gel resin molecular mass exclusion limit (estimated molecular mass of approx 8,000 kd). In contrast, culture supernatants produced in RPMI 1640 plus bovine serum albumin medium (RPMI + BSA) had peak I and 2 additional leukotoxic activity peaks (peaks II and III) with estimated molecular mass of approximately 80 and < 30 kd, respectively. All leukotoxic activity peaks were composed of approximately 100-kd molecular mass leukotoxin protomer, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting with a monoclonal antibody against leukotoxin. Subjecting culture supernatant leukotoxic activity produced in RPMI + BSA to gel filtration chromatography in buffer containing 500 mM NaCl or 6M urea resulted in detection of only a single leukotoxic activity peak with estimated approximate molecular mass of 250 and 800 kd, respectively. These findings suggest that P haemolytica exists as a high molecular mass aggregate with low leukotoxic activity which, in the presence of BSA, partially disaggregates to multiple toxin forms with enhanced leukotoxic activity. Some of these leukotoxin forms interact with dextran-based gel resins at low ionic strength.
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