Use of plasma clearance of iohexol for estimating glomerular filtration rate in cats

OBJECTIVE: To determine whether plasma clearance of iohexol (PCio) can be used to estimate glomerular filtration rate (GFR) in cats. ANIMALS: 4 renal-intact and 6 partially nephrectomized adult cats. PROCEDURE: Plasma clearance of iohexol was determined after IV administration of iohexol; plasma concentrations of iodine were measured by use of a colorimetric assay. Results for PCio were compared with simultaneously obtained values for urinary clearance of creatinine (CCr). RESULTS: The colorimetric assay used to measure plasma iodine concentrations was extremely precise. Results of PCio for all cats, renal-intact cats, and partially nephrectomized cats were closely associated with results of CCr. Mean difference between CCr and PCio determined for all cats was 0.95 ml/min/kg, which was < 30% of mean CCr for renal-intact cats. Coefficients of variance for PCio (5%) and CCr (8%) in renal-intact cats were similar. CONCLUSIONS AND CLINICAL RELEVANCE: Plasma clearance of iohexol determined by use of a simple colorimetric assay provided an estimation of GFR in cats that was not significantly different from that provided by CCr. Moreover, PCio more reliably estimates renal function than BUN and plasma creatinine concentrations. Because determination of PCio is less labor intensive and invasive, compared with CCr, it may be easier to perform in a clinical setting.     

Bioavailability, distribution and depletion of monensin in chickens

The pharmacokinetics of monensin including apparent volume of distribution, total body clearance, systemic bioavailability, partition coefficients and tissue residues were determined in chickens. The drug was given by intravenous injection in the left wing vein at the dose of 0.46 mg/kg and by intracrop administration at the dose of 4 mg/kg according to a destructive sampling. The pharmacokinetic variables were compared after noncompartmental, naïve averaged, naïve pooled and nonlinear mixed-effects modelling analyses. Partition coefficients and tissue residues were determined after a treatment with feed additives (125 mg/kg of feed) of 33 days. The clearance, volume of distribution and bioavailabilty were approximately 2.2 L/h/kg, approximately 9 L/kg and approximately 30% respectively except with nonlinear mixed effects models that presented values of 1.77 L/h/kg, 14.05 L/kg and 11.36% respectively. Tissue/plasma partition coefficients were estimated to 0.83, 3.39 and 0.51 for liver, fat and thigh muscle respectively. Monensin residues after treatment were not detected 6 h after withdrawal except for fat where monensin was still quantifiable 12 h after. Pharmacokinetic variables seem to be inaccurate when assessed with non linear mixed-effects modelling associated to destructive sampling in chickens. Values varied slightly with noncompartmental, naïve averaged and naïve pooled analyses. The absorption, elimination and partition parameters will be incorporated into a physiologically based pharmacokinetic model and the depletion study will be used to test the ability of this model to describe monensin residues in edible tissues under different dosage regimens.     

Characterization of the renal response to protein ingestion in dogs with experimentally induced renal failure.

Effects of a protein meal (2.7 g of casein/kg of body weight) on glomerular filtration rate (GFR) and renal plasma flow (RPF) were assessed in dogs after 15/16 nephrectomy (n = 10), and were compared with observations in dogs with intact kidneys (n = 5). Increase in GFR and RPF was observed in both groups of dogs between 1.5 and 8 hours after protein ingestion. A maximal value for GFR was observed between 4 and 5 hours after protein ingestion in dogs of both groups. Enhancement of urinary protein excretion was evident in partially nephrectomized dogs after protein ingestion (P less than 0.05), a result that was confirmed by 24-hour total urine collection from partially nephrectomized dogs fed a balanced ration. A qualitatively similar vasodilatory response was observed in partially nephrectomized dogs and in dogs with intact kidneys, and the mean maximal increase of GFR and RPF expressed as a percentage of baseline values in the latter dogs (47.0 +/- 8.1 and 43.6 +/- 10.3%, respectively) exceeded that observed in partially nephrectomized dogs (20.8 +/- 2.2 and 22.7 +/- 6.3%, respectively; P less than 0.01). The incremental response of the kidneys to protein ingestion was directly related to the degree of renal function, as reflected in the linear regression relationship between the incremental increase in GFR and the baseline value for GFR (P less than 0.01, R2 = 0.721).     

Pharmacokinetics of a novel formulation of ivermectin after administration to goats

OBJECTIVE: To evaluate the pharmacokinetics of a novel commercial formulation of ivermectin after administration to goats. ANIMALS: 6 healthy adult goats. PROCEDURE: Ivermectin (200 microg/kg) was initially administered IV to each goat, and plasma samples were obtained for 36 days. After a washout period of 3 weeks, each goat received a novel commercial formulation of ivermectin (200 microg/kg) by SC injection. Plasma samples were then obtained for 42 days. Drug concentrations were quantified by use of high-performance liquid chromatography with fluorescence detection. RESULTS: Pharmacokinetics of ivermectin after IV administration were best described by a 2-compartment open model; values for main compartmental variables included volume of distribution at a steady state (9.94 L/kg), clearance (1.54 L/kg/d), and area under the plasma concentration-time curve (AUC; 143 [ng x d]/mL). Values for the noncompartmental variables included mean residence time (7.37 days), AUC (153 [ng x d]/mL), and clearance (1.43 L/kg/d). After SC administration, noncompartmental pharmacokinetic analysis was conducted. Values of the variables calculated by use of this method included maximum plasma concentration (Cmax; 21.8 ng/mL), time to reach Cmax (3 days), and bioavailability (F; 91.8%). CONCLUSIONS AND CLINICAL RELEVANCE: The commercial formulation used in this study is a good option to consider when administering ivermectin to goats because of the high absorption, which is characterized by high values of F. In addition, the values of Cmax and time to reach Cmax are higher than those reported by other investigators who used other routes of administration.     

Bioavailability, disposition kinetics and dosage of sulfadimethoxine in dogs--a correction.

A reevaluation of the disposition kinetics and extent of absorption of sulfadimethoxine in normal dogs following intravenous and oral dosage has been made. The tissue to plasma level ratio at the peak tissue level (k12/k21) was 0.55, while the tissue to plasma level ratio after distribution equilibrium (k12/k21-beta) was 0.926. The systemic availability of sulfadimethoxine from the oral suspension was 48.8% (24.4-86.2) when corrections for intrasubject variability were made.     

Plasma pharmacokinetics and tissue fluid concentrations of meropenem after intravenous and subcutaneous administration in dogs

OBJECTIVE: To estimate pharmacokinetic variables and measure tissue fluid concentrations of meropenem after IV and SC administration in dogs. ANIMALS: 6 healthy adult dogs. PROCEDURE: Dogs were administered a single dose of meropenem (20 mg/kg) IV and SC in a crossover design. To characterize the distribution of meropenem in dogs and to evaluate a unique tissue fluid collection method, an in vivo ultrafiltration device was used to collect interstitial fluid. Plasma, tissue fluid, and urine samples were analyzed by use of high-performance liquid chromatography. Protein binding was determined by use of an ultrafiltration device. RESULTS: Plasma data were analyzed by compartmental and noncompartmental pharmacokinetic methods. Mean +/- SD values for half-life, volume of distribution, and clearance after IV administration for plasma samples were 0.67 +/- 0.07 hours, 0.372 +/- 0.053 L/kg, and 6.53 +/- 1.51 mL/min/kg, respectively, and half-life for tissue fluid samples was 1.15 +/- 0.57 hours. Half-life after SC administration was 0.98 +/- 0.21 and 1.31 +/- 0.54 hours for plasma and tissue fluid, respectively. Protein binding was 11.87%, and bioavailability after SC administration was 84%. CONCLUSIONS AND CLINICAL RELEVANCE: Analysis of our data revealed that tissue fluid and plasma (unbound fraction) concentrations were similar. Because of the kinetic similarity of meropenem in the extravascular and vascular spaces, tissue fluid concentrations can be predicted from plasma concentrations. We concluded that a dosage of 8 mg/kg, SC, every 12 hours would achieve adequate tissue fluid and urine concentrations for susceptible bacteria with a minimum inhibitory concentration of 0.12 microg/mL.     

Pharmacokinetic variables of mivacurium chloride after intravenous administration in dogs.

OBJECTIVE: To determine pharmacokinetic variables of mivacurium chloride after IV administration in dogs. ANIMALS: 5 healthy Labrador Retrievers. PROCEDURE: Anesthesia was induced with thiopental and maintained with halothane in oxygen. Dogs were ventilated mechanically to an end-tidal P(CO)2 value between 35 and 40 mm Hg. Heart rate, direct blood pressure, and arterial pH were recorded throughout the experiment. Core temperature, end-tidal P(CO)2, and halothane concentration were kept constant throughout the experiment. Paired blood samples for determination of plasma cholinesterase activity were collected prior to administration of a bolus of mivacurium (0.05 mg/kg of body weight), which was administered IV during a 2-second period. Arterial blood samples were obtained for determination of plasma mivacurium concentration 0, 1, 3, 5, 10, 30, 60, 120, 150, and 180 minutes after administration of mivacurium. Blood was collected into tubes containing EDTA and 0.25% echothiophate. Mivacurium concentration was determined, using reversed-phase high-performance liquid chromatography. RESULTS: For the trans-trans isomer, mean +/- SEM volume of distribution was 0.18+/-0.024 L/kg, median half-life was 34.9 minutes (range, 26.7 to 53.5 minutes), and clearance was 12+/-2 ml/min/kg. For the cis-trans isomer, values were 0.31+/-0.05 L/kg, 43.4 minutes (range, 31.5 to 69.3 minutes), and 15+/-2 ml/min/kg, respectively. Values for the cis-cis isomer were not calculated, because it was not detectable in plasma 60 minutes after mivacurium administration in all 5 dogs. CONCLUSIONS AND CLINICAL RELEVANCE: The transtrans and cis-trans isomers of mivacurium have a long half-life and slow clearance in healthy dogs anesthetized with halothane.     

Drug residues in food animals. III. Plasma and tissue kinetics of potassium penicillin G in young cross-bred swine

Twenty-two young cross-bred swine were treated either intravenously or orally with potassium penicillin G. The pharmacokinetics of penicillin G were determined in plasma and tissues. The plasma half-life of penicillin G in swine was found to be 19.45±1.69 min, and the distribution and elimination kinetics were found to fit a classical two-compartment model. The volume of distribution was found to be 0.53±0.12 1/kg, and the body clearance was found to be 19.06±5.06 ml/min/kg which exceeded the effective renal plasma flow of 16.50±2.73 ml/min/kg, suggesting that the drug was eliminated both by tubular excretion and glomerular filtration. The elimination rate constants (Beta) for the major organs were as follows: muscle, 0.00343 min^-1; lung, 0.0310 min^-1; fat, 0.0394 min^-1; and kidney, 0.0213 min^-1, which compared favorably with the elimination rate constant found in plasma (0.0320 min^-1). These values were found to be significantly similar at the level of P < 0.005 in muscle, spleen and fat, and at a level of P < 0.025 in lung tissue. The data indicates that blood plasma would be a satisfactory body fluid for estimating this drug in tissue.     

Disposition and metabolism of the novel macrolide antibiotic CP-163505 in cattle

The plasma pharmacokinetics, lung tissue to plasma concentration ratios, and depletion profiles in edible tissue (liver, muscle, kidney, fat and injection site) for a single subcutaneous dose of a novel macrolide antibiotic, CP-163505 (20-[3-dimethylaminopropyl(L-alanyl)amino]-20-deoxo-repromicin), were investigated in crossbred beef cattle. Mean peak plasma concentration of 2.5 ± 0.4 μg/mL, occurring at 0.5 h, was found for CP-163505 following a 5 mg/kg dose ( n  = 5). The pharmacokinetic profile consisted of a distribution phase, followed by an extended terminal elimination phase (t_1/2 of 19 h). The disposition of CP-163505 was characterized by distribution from the plasma into the tissue resulting in lung to plasma ratios of 103 and 87 at 72 h following a single 5 or 10 mg/kg dose, respectively. The depletion of CP-163505 from edible tissues was determined following administration of tritiated CP-163505 at a dose of 10 mg/kg. On day 42, the liver contained the highest mean concentration of total tritium residues, 5.9 ± 3.4 μg/g. CP-163505 was determined to be a significant component of the total residues in liver with 72% on day 3 and 50% on day 42. Three metabolites of CP-163505 were identified by liquid chromatography with mass spectrometry (LC/MS/MS) in liver samples: loss of alanine, formation of an hydroxyl derivative, and sulfate addition to the lactone ring.     

喹乙醇在动物血浆与组织间残留分布规律研究及相关性分析

试验采用高效液相色谱分析法,对饲喂含有不同浓度喹乙醇饲料(75mg/kg、100mg/kg、125mg/kg)的猪体组织(肝脏、肾脏、肌肉)和血浆中喹乙醇含量进行检测,分析喹乙醇在猪体内的残留分布,探讨喹乙醇在血浆中的含量与猪体内组织的残留含量的相关性。结果表明:饲料中喹乙醇添加量与组织和血浆中残留量均呈线性相关关系;同一浓度的喹乙醇添加量在猪组织和血浆中的残留量分布:肝脏>肾脏>肌肉>血浆;建立的血浆与组织间残留量的回归方程具有较高的可靠性。     

Evaluation of oxidative stress markers for the early diagnosis of allograft rejection in feline renal allotransplant recipients with normal renal function

The purpose of this study was to identify oxidative damage to renal allografts during graft rejection by evaluating changes in oxidative markers and plasma lactate levels in feline renal allotransplant recipients. Heterotopic renal allotransplantations were performed between 8 adult feline cross-matched donors. Following 14 d of immunosuppression, the drugs were discontinued to allow allograft rejection. Baseline and serial postoperative evaluations of serum creatinine, plasma lactate, plasma thiobarbituate reactive substances (TBARS), plasma creatol, urine creatol, and renal sonographic cross-sectional area were performed. When sonographic evaluation revealed the absence of blood flow to the allograft, the rejected kidney was nephrectomized and evaluated histopathologically. Allograft rejection occurred in all cats by day 26. A significant elevation in body temperature occurred during the rejection period. No significant change was observed between any of the time periods for plasma TBARS, creatol, or urine creatol. There was a significant decrease in plasma lactate levels throughout the study. Markers of oxidative stress from venous blood did not reflect renal allograft rejection in cats with a normally functioning native kidney. Renal allograft rejection may be associated with significant increases in body temperature and warrants further investigation.     

Pharmacokinetics and endometrial tissue concentrations of enrofloxacin and the metabolite ciprofloxacin after i.v. administration of enrofloxacin to mares

Enrofloxacin was administered i.v. to five adult mares at a dose of 5 mg/kg. After administration, blood and endometrial biopsy samples were collected at regular intervals for 24 h. The plasma and tissue samples were analyzed for enrofloxacin and the metabolite ciprofloxacin by high-pressure liquid chromatography. In plasma, enrofloxacin had a terminal half-life (t(1/2)), volume of distribution (area method), and systemic clearance of 6.7 +/- 2.9 h, 1.9 +/- 0.4 L/kg, and 3.7 +/- 1.4 mL/kg/min, respectively. Ciprofloxacin had a maximum plasma concentration (Cmax) of 0.28 +/- 0.09 microg/mL. In endometrial tissue, the enrofloxacin Cmax was 1.7 +/- 0.5 microg/g, and the t(1/2) was 7.8 +/- 3.7 h. Ciprofloxacin Cmax in tissues was 0.15 +/- 0.04 microg/g and the t(1/2) was 5.2 +/- 2.0 h. The tissue:plasma enrofloxacin concentration ratios (w/w:w/v) were 0.175 +/- 0.08 and 0.47 +/- 0.06 for Cmax and AUC, respectively. For ciprofloxacin, these values were 0.55 +/- 0.13 and 0.58 +/- 0.31, respectively. We concluded that plasma concentrations achieved after 5 mg/kg i.v. are high enough to meet surrogate markers for antibacterial activity (Cmax:MIC ratio, and AUC:MIC ratio) considered effective for most susceptible gram-negative bacteria. Endometrial tissue concentrations taken from the mares after dosing showed that enrofloxacin and ciprofloxacin both penetrate this tissue adequately after systemic administration and would attain concentrations high enough in the tissue fluids to treat infections of the endometrium caused by susceptible bacteria.     

The Plasma Kinetics and Tissue Distribution of Enrofloxacin and its Metabolite Ciprofloxacin in the Muscovy Duck

Intorre, L., Mengozzi, G., Bertini, S., Bagliacca, M., Luchetti, E. and Soldani, G., 1997. The plasma kinetics and tissue distribution of enrofloxacin and its metabolite ciprofloxacin in the Muscovy duck. Veterinary Research Communications, 21 (2), 127-136The disposition and tissue distribution of enrofloxacin and of its main metabolite ciprofloxacin were investigated in ducks after oral or intramuscular administration of a single dose of 10 mg/kg enrofloxacin. Plasma and tissue concentrations were determined by a HPLC method. The peak concentrations of enrofloxacin after intramuscular administration (1.67 µg/ml at 0.9 h) were higher than after an oral dose (0.99 µg/ml at 1.38 h). The relative bioavailability of enrofloxacin after administration directly into the crop was 68%, while the metabolic conversion of enrofloxacin to ciprofloxacin was quite low (<10%) with both routes of administration. High tissue concentrations and high tissue:plasma concentration ratios were demonstrated for enrofloxacin and ciprofloxacin 24 h after treatment. It was concluded that a dose of 10 mg/kg per day provides serum and tissue concentrations sufficiently high to be effective in the control of many infectious diseases of ducks.     

Use of plasma creatine kinase pharmacokinetics to estimate the amount of excercise-induced muscle damage in Beagles

OBJECTIVE: To assess the effects of moderate exercise on plasma creatine kinase (CK) pharmacokinetics and to estimate exercise-induced muscle damage in dogs. ANIMALS: 6 untrained adult Beagles. PROCEDURE: The study was divided into 3 phases. In phase 1, dogs ran for 1 hour at a speed of 9 km/h, and samples were used to determine the area under the plasma CK activity versus time curve (AUC) induced by exercise. In phases 2 and 3, pharmacokinetics of CK were calculated in dogs during exercise and at rest, respectively. Values for AUC and plasma clearance (CI) were used to estimate muscle damage. RESULTS: At rest, values for Cl, steady-state volume of distribution (Vdss), and mean retention time (MRT) were 0.32+/-0.02 ml/kg of body weight/min, 57+/-173 ml/kg, and 3.0+/-0.57 h, respectively. During exercise, Cl decreased significantly (0.26+/-0.03 ml/kg/min), MRT increased significantly, (4.4+/-0.97 h), and Vdss remained unchanged. Peak of plasma CK activity (151+/-58.8 U/L) was observed 3 hours after completion of exercise. Estimated equivalent amount of muscle corresponding to the quantity of CK released was 41+/-29.3 mg/kg. CONCLUSION AND CLINICAL RELEVANCE: These results revealed that exercise had a minor effect on CK disposition and that the equivalent amount of muscle damaged by moderate exercise was negligible. This study illustrates the relevance for use of the minimally invasive and quantitative pharmacokinetic approach when estimating muscle damage.     

Comparative pharmacokinetics of diminazene in lactating goats and sheep

The pharmacokinetic aspects of diminazene aceturate were studied in lactating goats and sheep after single intravenous and intramuscular administrations of 3.5 mg/kg b.wt. Plasma and milk concentrations were determined by use of reversed phase high-performance liquid chromatography (HPLC) after ion-pair extraction. Following intravenous injection, the disposition of diminazene in goats and sheep conformed to a two-compartment model with rapid distribution and slower elimination phases. Values of (t1/2 beta) were obtained indicating a slower final disappearance of the drug from plasma of sheep (21.17 h) than in goats (16.39 h). Diminazene concentrations were maintained for more than 4 days in the plasma of goats and sheep. In both species of animals, diminazene was rapidly absorbed following intramuscular administration of 3.5 mg/kg b.wt. The peak plasma concentrations (Cmax) were 7.00 and 8.11 micrograms/ml and were attained at (Tmax) 0.92 and 1.12 hours in goats and sheep, respectively. The elimination half-life (t1/2el) of diminazene after intramuscular administration was shorter in goats (16.54 h) than in sheep (18.80 h). Systemic bioavailabilities (F%) of diminazene after intramuscular administration were 94.94% and 82.64% in goats and sheep, respectively. Diminazene could be detected in milk of goats and sheep within 10 min post-injection. Milk concentrations of the drug were lower in goats than in sheep and were detected for 5 and 6 days following both routes of administration, respectively.     

Albendazole sulphoxide enantiomeric ratios in plasma and target tissues after intravenous administration of ricobendazole to cattle

The comparative concentration profiles of the (+) and (-) albendazole sulphoxide (ABZSO) enantiomers obtained in plasma and in selected target tissues/fluids after intravenous (i.v.) administration of a racemic formulation of ricobendazole (RBZ) to cattle were characterised. Fourteen Holstein calves received RBZ (racemic solution, 150 mg/mL) by i.v. administration at 7.5 mg/kg. Jugular blood samples were collected over 48 h post-treatment (plasma kinetic trial) and two animals were sacrificed at either 4, 12, 20, 28 or 32 h post-treatment to obtain samples of abomasal/small intestine mucosal tissue, abomasal/small intestine fluids, bile, liver and lung tissue (tissue distribution study). The (-)ABZSO enantiomer was depleted significantly faster from plasma compared with the (+)ABZSO antipode. The plasma AUC for (+)ABZSO (38.3 microg. h/mL) was significantly higher (P < 0.05) compared with that obtained for (-)ABZSO (20.5 microg. h/mL). The (+)ABZSO enantiomer was the predominant antipode measured in bile, abomasal fluid and abomasal mucosa. For instance, at 12 h post-treatment the (+)/(-) concentration ratios were: 12.9 (plasma), 1.62 (abomasal mucosa), 13.0 (abomasal fluid), 2.92 (intestinal mucosa), 9.87 (intestinal fluid) and 21.5 (bile). No marked differences between the concentration profiles of both enantiomers were observed in the liver tissue. Albendazole (ABZ) was recovered from the liver, lung and gastrointestinal (GI) mucosal tissues of RBZ-treated calves up to 32 h post-treatment, probably produced by a GI microflora-mediated sulphoreduction of RBZ. An enantioselective kinetic behaviour may account both for the faster depletion of the (-) enantiomer and for the higher availabilities of the (+) antipode observed in plasma and in most of the tissues/fluids investigated. The simultaneous evaluation of the plasma kinetics and tissue concentration profiles of both enantiomeric forms reported here, may help to interpret the relationship between chiral behaviour and pharmacological action for sulphoxide derivatives of benzimidazole (BZD) methylcarbamate anthelmintics.     

A physiologically based pharmacokinetic model for valnemulin in rats and extrapolation to pigs

A flow-limited, physiologically based pharmacokinetic (PBPK) model for predicting the plasma and tissue concentrations of valnemulin after a single oral administration to rats was developed, and then the data were extrapolated to pigs so as to predict withdrawal interval in edible tissues. Blood/tissue pharmacokinetic data and blood/tissue partition coefficients for valnemulin in rats and pigs were collected experimentally. Absorption, distribution and elimination of the drug were characterized by a set of mass-balance equations. Model simulations were achieved using a commercially available software program. The rat PBPK model better predicted plasma and tissue concentrations. The correlation coefficients of the predicted and experimentally determined values for plasma, liver, kidney, lung and muscle were 0.96, 0.94, 0.96, 0.91 and 0.91, respectively. The rat model parameters were extrapolated to pigs to estimate valnemulin residue withdrawal interval in edible tissues. Correlation (R(2) ) between predicted and observed liver, kidney and muscle were 0.95, 0.97 and 0.99, respectively. Based on liver tissue residue profiles, the pig model estimated a withdrawal interval of 10 h under a multiple oral dosing schedule (5.0 mg/kg, twice daily for 7.5 days). PBPK models, such as this one, provide evidence of the usefulness in interspecies PK data extrapolation over a range of dosing scenarios and can be used to predict withdrawal interval in pigs.     

Ultrasonographic examination of the adrenal gland and evaluation of the hypophyseal-adrenal axis in 20 cats

The adrenal glands of 20 healthy, non-sedated cats were examined ultrasonographically; visualisation and assessment was possible in all cases. In comparison with the surrounding tissue, the adrenal glands were hypoechoic and two distinct zones could be differentiated in six of the cats. The length and width of the adrenal glands varied from 0.45 to 1.37 cm and 0.29 to 0.53 cm, respectively, and both dimensions could be reliably reproduced. The adrenal glands did not differ between male and female cats, and, in comparison to dogs, those of cats are more easily visualised ultrasonographically. The basal cortisol value ranged from 2.0 to 79 micrograms/litre. Values 30 and 60 minutes after administration of ACTH (0.125 mg/cat intramuscularly) varied from 36 to 126 micrograms/litre. The basal value of aldosterone ranged from 4 to 618 pg/ml. Values 30 and 60 minutes after administration of ACTH varied from 100 to 832 pg/ml. In all cats, suppression of the cortisol value below the level of detection (< 2.0 micrograms/litre) occurred four and eight hours after the administration of dexamethasone (0.1 mg/kg intravenously).     

Clinical evaluation of glomerular function: 24-hour creatinine clearance in dogs.

Methods of renal clearance to measure glomerular filtration rate (GFR) were compared with plasma creatinine concentration in clinically normal and partially nephrectomized dogs. Glomerular filtration rate was measured by use of a simple 24-hour creatinine clearance method in 36 normal female Beagles. Mean values were 57.6 +/- 9.3 ml/minute/m2 of body surface or 3.7 +/- 0.77 ml/minute/kg of body weight. Variability of this measurement was considerable, as determined in 4 dogs studied on 4 consecutive days. Glomerular filtration rate was measured in the same 36 dogs while they were under anesthesia, using short clearance periods to compare inulin and endogenous creatinine clearance. Mean values for inulin were 41.8 +/- 13.9 ml/minute/m2 of body surface. A close agreement with creatinine clearance was found (correlation coefficient, 0.998). Mean plasma creatinine concentration was 0.82 (range, 0.5--1.0) mg/100 ml. The value of GFR measurement compared with plasma creatinine concentration was determined in 10 dogs after 75% nephrectomy. Sixty days after partial nephrectomy, GFR was reduced to 61% of normal. Mean plasma creatinine and blood urea nitrogen were 1.2 +/- 0.14 mg/100 ml and 20.4 +/- 7.1 mg/100 ml, respectively. Thus, the detection of reduced renal function may be uncertain when plasma creatinine or blood urea nitrogen are used as a means of evaluating renal function. It was concluded that a simple method of creatinine clearance is a sensitive and useful measurement to detect early or borderline reduction in glomerular function.     

Relationship between leptin content, metabolic hormones and fat deposition in three beef cattle breeds

The aim of the study was to determine if cattle breeds differing in their carcass characteristics also differ in the profiles of their leptin and metabolic hormones. Three breeds, Belgian Blue (BB) (n = 12), Limousin (L) (n = 12) and Aberdeen Angus (AA) (n = 12) with varying ability to deposit fat and protein were compared. Blood, muscle and subcutaneous (SC) adipose tissue were sampled. Animal performance, carcass and meat characteristics were determined as well as plasma leptin concentration, leptin gene expression in SC adipose tissue, leptin-receptor gene expression in SC adipose tissue and plasma concentration of insulin, tri-iodothyronin (T3), thyroxin (T4) and cortisol. The BB bulls showed the lowest values of leptin gene expression (P < 0.05). Values of plasma leptin concentration and of leptin-receptor gene expression tended to be lower in BB than in the other breeds. For a similar amount of adipose tissue (after normalisation), BB bulls showed a higher ratio of plasma leptin (P < 0.05), whereas normalised leptin gene and leptin-receptor gene expressions did not significantly differ between breeds. Belgian Blue bulls also differed in their metabolic hormone profile, tending to show lower values of insulin, T3 and T4 than the two other breeds. Cortisol levels were significantly lower (P < 0.05) in BB than in L and AA animals.