Pharmacokinetics and bioequivalence of parenterally administered doramectin in cattle

Plasma concentrations of doramectin in 40 cattle dosed by subcutaneous (sc) or intramuscular (i.m.) injection (200 μg/kg) were compared to assess the bioequivalence of the two routes of administration. Peak concentration ( C _max), and areas under the concentration curve ( AUC_0– ) were determined from plasma concentrations. Animals treated by the sc route showed a mean AUC_0– of 457 ± 66 ng±day/mL (± SD) and a mean C _max of 27.8 ± 7.9 ng/mL. Results from the i.m. treatment group showed a mean AUC _0– of 475 ± 82 ng-day/mL and a mean C _max of 33.1 ± 9.0 ng/mL Absorption constants ( k _a) determined by modelling were 0.542 ± 0.336 day^-1after sc administration and 0.710 ± 0.357 day^-1after i.m. administration. The 90% confidence limits on the difference between mean AUC _0– values for the sc and i.m. groups fell within 20% of the mean value for the subcutaneous group. C _max was somewhat greater for the i.m. route. The 90% confidence limits on the difference in mean In ( T _max+1) also fell within 20% of the mean sc value. Based on this analysis, bioequivalence of the sc and i.m. formulation has been established.     

Jejunal Intussusception: A Complication of Functional End-to-End Stapled Anastomoses in Two Ponies

Jejunojejunal intussusception occurred after jejunal resection and stapled functional end-to-end anastomosis in two pony mares. In both mares, the lead point of the intussusception was the stapled functional end-to-end (FEE) anastomosis. The stapled free ends of jejunum were oversewn with an inverting suture pattern. A possible explanation for development of the intussusception was the acute angle created in the intestine by the FEE anastomsis. This angulation may have impaired flow of ingesta causing motility changes that predisposed the site to intussusception. Because the oversewn blind intestinal ends acted as the lead point for formation of the intussusception, it may be inadvisable to oversew the stapled anastomotic ends.     

Prolonged-release hydroxypropyl methylcellulose matrix tablets of furosemide for administration to dogs

Furosemide is a problematic drug in a prolonged-release product because its absorption is site specific, taking place mainly in the upper parts of the alimentary tract. The aim of the study reported here was to develop prolonged-release furosemide formulations for dogs. The type of preparation selected was a hydroxypropyl methylcellulose (HPMC) matrix tablet. Evaluation was based on dissolution studies, on in vivo disintegration studies in the canine stomach and on bioavailability studies in Beagle dogs. The variables tested were the viscosity grade of the polymer, the amount of polymer and presence or absence of an alkaline compound (potassium carbonate) in the formulation. When potassium carbonate was included, furosemide was absorbed so slowly that drug administration once daily would give plateau drug plasma concentrations, even though the elimination half-life of furosemide is only about one hour.     

Anal leiomyoma in a Holstein heifer.

A 2-year-old heifer was presented with masses on her anus that were interfering with cervical manipulation during embryo flushing. The masses had broad stalks attached within the anal sphinchter. Recovery was without incident after surgical resection. No recurrence of the masses had occurred 3 months later. Histologic diagnosis was benign leiomyoma.     

Suspected mitochondrial myopathy in a Jack Russell terrier

A Jack Russell terrier with a history of progressive exercise intolerance was examined at the age of four months and again 10 months later. Clinical examination revealed a stunted, thin dog with a stilted gait. The dog had raised lactate levels before and after feeding and a raised lactate/pyruvate ratio after feeding, indicating a metabolic abnormality. Histochemical evaluation of muscle biopsies revealed subsarcolemmal accumulation of oxidative activity when stained with nicotinamide adenine dinucleotide tetrazolium reductase and ragged red fibres when stained with modified Gomori trichrome; all fibre types were involved. Ultrastructural examination of the muscle confirmed the presence of subsarcolemmal accumulations of mitochondria. Histochemical staining for the activity of enzymes of the Krebs cycle, oxidative phosphorylation and other metabolic cytosolic enzymes failed to demonstrate an abnormality. In view of the clinical picture and the biochemical and histological findings, a tentative diagnosis of mitochondrial myopathy was made. The difficulties associated with diagnosing mitochondrial disorders are discussed.     

Changes in taurine levels in response to repeated administration of the β2-agonist salbutamol in lambs

Repeated oral administration of salbutamol to lambs for 28 days was found to decrease levels of taurine significantly in the serum and heart, and the mean excretion of taurine into urine was significantly less than in controls. Serum urea, low density lipoprotein and high density lipoprotein were also significantly reduced. Consistent with these changes, fat content in muscle was reduced, whereas protein content was not significantly changed. Body weight was not significantly changed by salbutamol treatment but heart and kidney weights (relative to body weight) were significantly increased. Salbutamol excretion in urine was relatively constant and residues were detected in certain organs and tissues, notably liver, bile and kidney. Changes in urinary and serum taurine level may reflect subtle changes in protein metabolism not detectable as changes in body weight or gross protein content.     

Determinants and Utility of the Anion Gap in Predicting Hyperlactatemia in Cattle

The objectives of this study were to investigate the determinants of the anion gap (AG) in cattle and to evaluate the utility of AG in detecting hyperlactatemia in sick neonatal calves and adult cattle. The AG was calculated as AG = ([Na+] + [K+]) - ([Cl^-] + [HCO₃]), with all values in mEq/L. The AG of healthy neonatal calves (n = 16) was 29.6 ± 6.2 mEq/L (mean ± SD), and the blood L-lactate concentration ranged from 0.5 to 1.2 mM/L. The AG was significantly (P > .05) correlated with serum phosphate (r = .66) and creatinine (r = .51) concentrations. The AG of neonatal calves with experimentally induced diarrhea (n = 16) was 28.6 ± 5.6 mEq/L, and the blood L-lactate concentration ranged from 1.1 to 2.9 mM/L. The AG was significantly correlated with blood L-lactate concentration (r = .67), serum phosphate concentration (r = .63), creatinine concentration (r = .76), and blood pH (r = -.61). The AG of adult cattle with abomasal volvulus (n = 41) was 20.5 ± 7.8 mEq/L, and the blood L-lactate concentration ranged from 0.6 to 15.6 mM/L. The AG was significantly correlated with blood L-lactate concentration (r = .60), serum phosphate concentration (r = .71), creatinine concentration (r = .65), albumin concentration (r = .47), total protein concentration (r = .54), blood pyruvate concentration (r = .67), and blood pH (r = -.41) but not plasma β-OH butyrate concentration. The results indicate that the AG in cattle is only moderately correlated with blood L-lactate concentration and is similarly correlated with serum phosphate and creatinine concentrations in neonatal calves and adult cattle, as well as with serum albumin and total protein concentrations in adult cattle. Anion gap determination is of limited usefulness in predicting blood L-lactate concentration in sick cattle, whereas the correlation between AG and serum creatinine concentration in sick cattle suggests that an increased AG should alert the clinician to the potential presence of uremic anions.     

A Transtracheal Catheter for Recording the Static Tracheal Pressure in the Exercising Horse

After giving an account of the principles of pressure measurement in flowing air and a review of the literature on tracheal catheters, the authors describe the construction, the introduction and the function of their own transtracheal catheter. This is a teflon catheter with several side–ports which is introduced into the cervical trachea by a guide technique. After introduction, the catheter is stiffened by the insertion of 2 steel wires. The catheter was studied in model experiments concerning: a) the ability to measure the static pressure in flowing air, and b) the dynamic accuracy of a recording system built up around the catheter.The results indicated that the intratracheal pressure sensed in exercising horses well reflected the static pressure, and that the dynamic accuracy of the recording system was good to about 60 Hz. The present technique of recording the intratracheal pressure was used on 122 occasions in 69 exercising horses with only one complication referable to the catheter occurring. The transtracheal route of catheterisation may be superior, as catheters introduced by this route do not appear to influence the function of the pharynx and larynx. In contrast, nasotracheal catheters that traverse the larynx, might interfere with the respiratory function. kw|Keywords|k]upper airway obstruction k]frequency response     

Estimation of genetic correlations between racing times recorded at different racing distances by restricted maximum likelihood in Thoroughbred racehorses

SUMMARY: Genetic correlations between racing times on track type (turf and dirt), and at racing distances on turf (1200 m, 1400 m, 1600 m, 1800 m, and/or 2000 m) and dirt (1000 m, 1200 m, 1400 m, 1600 m, 1700 m, and/or 1800 m) tracks, were estimated in Thoroughbred horses. (Co)variance components were estimated using multiple-trait derivative-free restricted maximum likelihood (MTDFREML). The data used were collected by the Japan Racing Association from 1992 to 1993. The generation 2 pedigree information was preferable for (co)variance estimates. The genetic correlations between racing times on turf and dirt tracks ranged from 0.69 to 0.31 (average 0.51). The genetic correlations between racing distances ranged from 0.68 to 1.00 (average 0.85) and from 0.53 to 1.00 (average 0.88) on turf and dirt tracks, respectively. These results suggest that the racing time per 100 m can be used for horse genetic evaluation within one track type. ZUSAMMENFASSUNG: Sch?tzung genetischer Korrelationen zwischen Rennzeiten von Vollblüternüber verschiednen Distanzen mittels restringierter Genetische Korrelationen zwischen Rennzeiten auf Rasen- und Erdbahnen, Renndistanzen auf Rasen- (1200, 1400, 1600, 1800 und 2000 m) und Erdbahnen (1000, 1200, 1400, 1600, 1700 und 2000 m) wurden für Vollblüter gesch?tzt. (Co)Varianzkomponenten wurden mittels Mehr-Merkmal Ableitungsfreier Restringierter Maximum Likelihood (MTDFREML) gesch?tzt. Die Unterlagen wurden von der Japanischen Renn Vereinigung 1992 und 1993 gesammelt. Generation 2 Abstammungsinformation war für die Co-Varianzsch?tzung günstig. Genetische Korrelationen zwischen Rennzeiten auf Rasen und auf Erdbahnen waren zwischen 0.69 und 0.31 (Durchschnitt 0.51), jene zwischen Distanzen zwischen 0.68 und 1.00 (Durchschnitt 0.85) und zwischen 0.53 und 1.00 (Durchschnitt 0.88) auf Rasen und Erdbahnen. Die Ergebnisse zeigen, da? Rennzeit per 100 m zur Bewertung der Pferde geeignet ist.     

Effects of selection on food intake in the adult mouse

SUMMARY: Replicated lines of mice were selected High and Low for adjusted food intake and contemporaneous control lines were maintained. The selection criterion was food intake between 8 and 10 weeks, adjusted by phenotypic regression on mean body weight at 8 and 10 weeks of age to reduce correlated changes in body weight. Responses are given for the first 23 generations of selection, after which adjusted food intake had diverged by a factor of 1.7-1.95. A small correlated response in body weight occurred and mice from the High line were slightly heavier: at 10 weeks of age body weight had diverged by a factor of 1.09-1.11. The realized within-family heritability varied between the replicates from 0.16-0.27 from which a mean estimated mass selection heritability (h(2) = 0.35±0.05) was derived. Mice from the Low line were fatter, however not significantly, because of a High between replicate variance (p > 0.05). Differences in growth over the selection period may account for around 5% of the divergence and increased maintenance costs associated with the larger lean mass of the high lines may explain a further 5%. Mice from the High lines spilled significantly (p < 0.05) more food which accounted for 23% of the divergence in apparent food intake. The heat increment of feeding, brown adipose tissue activity and locomotor activity all appear to be unchanged. ZUSAMMENFASSUNG: Auswirkungen der Selektion auf Futteraufnahme in der adulten Maus In einem Experiment mit Wiederholungen wurden M?uselinien auf hohe und niedrige korrigierte Futteraufnahme selektiert und korrespondierende Konttrollen gehalten. Das Selektionskriterium war die Futteraufnahme im Alter von 8 bis 10 Wochen, die mittels ph?notypischer Regression korrigiert wurde, um die K?rpermasse m?glichst konstant zu halten. Der direkte Selektionserfolg über die ersten 23 Generationen ist beschrieben. Die Linien divergierten zu diesem Zeitpunkt bezüglich des Selektionsmerkmals um 70 bis 95%. In der K?rpermasse trat ein geringfügiger korrelierter Selektionserfolg auf. Die Tiere der 'high'-Linie waren im Alter von 8 bis Wochen ca. um 6 bis 11% schwerer. Die realisierte Intra-Familien-Heritabilit?t variierte zwischen den Wiederholungen zwischen 0.16 und 0.27, woraus sich eine mittlerer Heritabilit?tskoeffizient von h(2) = 0.35±0.05 für die Massenselektion ergab. M?use der 'low'-Linie hatten mit 10 Wochen 2.4% (P > 0.05) und mit 17 Wochen ca. 7% (P < 0.05%) mehr Fett. Mit Unterschieden im Wachstum lassen sich weniger als 5% der Linienunterschiede in der Futteraufnahme erkl?ren. Der h?here Erhaltungsbedarf, der aus einer h?heren fett-freien K?rpermasse in der 'high'-Linie resultiert, k?nnte weitere 5% erkl?ren. Tiere der 'high'-Linie verstreuten deutlich (P < 0.05) mehr Futter, worauf sich 23% der Divergenz in der scheinbaren Futteraufnahme zurückführen lie?en. Die Aktiv?t des braunen Fettgewebes, die lokomotorische Aktivit?t und die fütterungsbedingte Wàrmeproduktion sind scheinbar unver?ndert.