Prothrombotic and Inflammatory Effects of Intravenous Administration of Human Immunoglobulin G in Dogs

Background: Intravenous administration of human immunoglobulin G (hIVIgG) has been suggested to potentiate thromboembolism in dogs, but supportive scientific reports are lacking.
Objectives: To determine if hIVIgG therapy promotes hypercoagulability and inflammation in dogs.
Animals: Twelve healthy Beagle dogs.
Methods: Prospective, experimental trial. An hIVIgG/saline solution was infused IV at 1 g/kg BW over 8 hours to 6 dogs, and physiological saline was infused to the other 6 dogs. Blood samples were drawn before, during, and after infusion for serial measurement of indicators of coagulation and inflammation. Data were analyzed by 2-way repeated measures analysis of variance.
Results: Dogs administered hIVIgG developed mildly decreased blood platelet concentrations without thrombocytopenia (median, 200 × 10³/μL; range, 150–302 × 10³/μL; P < .01), leukopenia (median, 3.5 × 10³/μL; range, 20–62 × 10³/μL; P < .001), and mildly increased plasma total protein concentrations (median, 6.3 g/dL; range, 5.6–6.7 g/dL; P < .001). Administration of hIVIgG was also associated with increases in fibrin/fibrinogen degradation products in all dogs (either 5 μg/mL or 10 μg/dL), thrombin-antithrombin III complexes (median, 7.2 ng/mL; range, 4.9–14.2 ng/mL; P < .001), and C-reactive protein concentrations (median, 2.5 mg/dL; range, 0.5–4.3 mg/dL; P < .01).
Conclusion and Clinical Importance: Administration of hIVIgG to dogs promotes hypercoagulability and an inflammatory state. This should be further evaluated and considered when using hIVIgG in dogs with IMHA or other prothrombotic conditions.     

Numbers of nitrate-reducing bacteria in the rumen as estimated by competitive polymerase chain reaction

Cell numbers of known species of nitrate- and nitrite-reducing bacteria, Selenomonas ruminantium, Veillonella parvula and Wollinella succinogenes , in the rumen of goats (25–30 kg) were estimated by competitive polymerase chain reaction (PCR). The number of S. ruminantium was the largest of the three species examined, and tended to be greater in goats fed a high-concentrate diet (5.6 × 10⁷ cells/mL rumen fluid) than in goats fed a high-roughage diet (1.3 × 10⁷ cells/mL). The number of V. parvula tended to be greater when goats were fed a high-roughage diet (6.7 × 10³/mL) than when fed a high-concentrate diet (3.2 × 10³/mL). The number of W. succinogenes was below the detectable level (< 1.0 × 10²/mL) when a high-concentrate diet was fed, but was significantly increased by feeding a high-roughage diet (1.6 × 10³/mL). Addition of potassium nitrate (6 g/day) to the high-concentrate diet tended to increase V. parvula , and significantly increased W. succinogenes , indicating that these two bacteria can be increased by feeding a diet containing nitrate.     

High performance liquid chromatography and pharmacokinetics of the non-steroidal anti-inflammatory drug oxindanac in calves

A high-performance liquid chromatographic method for the determination of the non-steroidal anti-inflammatory drug, oxindanac, in calf plasma is described. Recoveries over the concentration range 0.3 75 to 62.5 μg/ml were 90.2–107.8% with interassay coefficients of variation of 2.1–22.3%. The limit of detection was estimated as 0.10 μg/ml and the limit of quantification calculated to be 0.24 pg/ml in a 1 ml plasma sample. This method was used to establish the pharmacokinetics following intravenous (i.v.), intramuscular (i.m.) and oral (p.o.) administration to calves of oxindanac at a dose rate of 2 mg/kg. The elimination t ¹/₂, was long ( t 1/2 21.2 h after i.v. injection) and absorption was rapid (t¹/_2B 0.072 h) and complete ( F > 100%) following i.m. administration. Bioavailability was incomplete ( F = 66.6%) following p.o. administration to calves that had been fed on milk, and Wagner-Nelson analysis revealed twoabsorption phases ( t ¹/₂'s 0.20 and 1.9 h). Oxindanac produced long-lasting inhibition of serum TxB₂ production, with mean k_max values (% inhibition) of 96.8, 94.1 and 81.3 following i.v., i.m. and p.0. administration, respectively. A single i.v. or i.m. injection of 2 mg/kg oxindanac will probably be active in calves for at least 36–48 h.     

Effect of oral administration of 3,3',4,4',5-pentachlorobiphyenl on the intestinal microbiota of Sprague–Dawley rats

The effect of the endocrine-disrupting chemical 3,3',4,4',5-pentachlorobiphyenl (PCB 126) on intestinal microbiota after oral administration, and the improvement of intestinal microbiota and feces quantity by the subsequent administration of Lactobacillus acidophilus or Lactobacillus reuteri was investigated. All the rats were given 100 μg/kg bodyweight of PCB 126. The changes in bacterial counts were confirmed using a culture method. The administration of PCB 126 tended to decrease the bacterial counts of lactobacilli (10^9.6−10^10.2 to 10^8.8−10^9.2) and bifidobacteria (10^5.3−10^6.1 to 10^3.6−10^4.2), and to increase those of Enterobacteriaceae (10^8.2−10^9.1 to 10^9.4−10^10.3) and staphylococci (10^6.6−10^7.4 to 10^7.2−10^8.4) compared to no PCB 126 administration. After administration of PCB 126, L. acidophilus or L. reuteri orally administered to rats caused Enterobacteriaceae and staphylococci counts to decrease, suggesting that the intestinal microbiota was improved by the lactobacilli. The administration of L. acidophilus and L. reuteri improved the balance of intestinal microbiota, and defecation volume returned to its normal level. L. acidophilus and L. reuteri have a remedial effect on intestinal microbiota affected by PCB 126 and can function to lessen accumulated PCB 126 volume.     

A Single Sample Method for Evaluating 51Chromium-Ethylene Diaminic Tetraacetic Acid Clearance in Normal and Hyperthyroid Cats

Background: Chronic kidney failure is frequently seen in middle-aged and elderly cats. ⁵¹Chromium-ethylene diaminic tetraacetic acid (⁵¹Cr-EDTA) clearance and single blood sample (SBS) method are used in several species to estimate the glomerular filtration rate (GFR).
Hypothesis: The hypothesis of this study was that ⁵¹Cr-EDTA clearance could be determined using an SBS method in normal and hyperthyroid cats.
Animals: Forty-six cats were included in this study, with an average age of 9.5 years. Of these cats, 27 had hyperthyroidism; 19 were healthy.
Methods: After IV injection of ⁵¹Cr-EDTA (average dose: 4.25 MBq), 7 blood samples were obtained between 5 and 240 minutes. Reference clearance was calculated in mL/min and mL/min/kg body weight, using a 2-compartment model. Optimal time for clearance measurement with SBS was then determined by systematically comparing each individual plasma concentration to the reference multisample clearance.
Results: The average reference plasma clearance of ⁵¹Cr-EDTA for all cats was 14.9 mL/min (3.7 mL/min/kg). The clearance in hyperthyroid cats averaged 16.4 mL/min (4.3 mL/min/kg) and in normal cats averaged 10.3 mL/min (2.4 mL/min/kg).
The optimal time for the SBS was 48 minutes after injection of tracer ⁵¹Cr-EDTA ( R ²= 0.9414), giving the following converting equation: clearance = (0.0066 × DV_{48 minutes}) – 0.9277 (in mL/min).
Conclusions and Clinical Importance: In this study, the single sample ⁵¹Cr-EDTA clearance method was used to estimate the global GFR in cats. The method identified differences in clearance between normal and hyperthyroid cats. The optimal time for an SBS was 48 minutes.     

Retinol-Binding Protein in Serum and Urine of Hyperthyroid Cats before and after Treatment with Radioiodine

Background: Retinol-binding protein (RBP) is suggested as a clinically useful marker of renal function in cats.
Hypothesis: Serum and urinary RBP concentrations in hyperthyroid (HT) cats differ from those in healthy (H) cats; radioiodine (¹³¹I) treatment influences serum and urinary RBP concentrations in HT cats.
Animals: Ten HT and 8 H cats.
Methods: RBP concentration was evaluated in feline serum and urine samples from a prospective study.
Results: There was a significant ( P = .003) difference in the urinary RBP/creatinine (uRBP/c) ratios of H (−) and untreated HT (1.4 ± 1.5 × 10⁻² μg/mg) cats. Serum total thyroxine concentration (1.8 ± 1.9 μg/dL, 24 weeks) and uRBP/c (0.6 ± 1.0 × 10⁻² μg/mg, 24 weeks) decreased significantly ( P < .001) in HT cats at all time points after treatment with ¹³¹I, and these variables were significantly correlated with one another ( r = 0.42, P = .007). Serum RBP concentrations from HT cats (199 ± 86 μg/L) did not differ significantly ( P = .98) from those of H cats (174 ± 60) and did not change after treatment with ¹³¹I (182 ± 124 μg/L, P = .80).
Conclusion and Clinical Importance: The presence of urinary RBP in HT cats is a potential marker of tubular dysfunction that is correlated to thyroid status, although it is independent of circulating RBP concentrations. The decreased uRBP/c combined with the absence of changes in serum RBP after treatment suggests that the suspected tubular dysfunction was partly reversible with treatment of ¹³¹I.     

Multiple oral dosing of valacyclovir in horses and ponies

The aim of the current study was to investigate whether multiple oral dosing of valacyclovir could result in plasma concentrations exceeding the EC₅₀-value of acyclovir against equine herpesvirus 1 (EHV1) during the majority of the treatment period. Additionally, we wanted to determine the concentration of acyclovir in nasal mucus and cerebrospinal fluid (CSF). Valacyclovir was administered to four horses and two ponies, three times daily, at a dosage of 40 mg/kg, for four consecutive days. Blood was collected prior to each administration and 1 h after dosing. Nasal mucus samples and CSF were collected once during treatment; 1 h after the last administration. This dosage regimen resulted in plasma concentrations that were higher than the EC₅₀-value of 1.7 μg/mL, i.e. EC₅₀ of an isolate highly susceptible to acyclovir, for 80% of the treatment period; and higher than the EC₅₀-value of 3.0 μg/mL, i.e. EC₅₀ of an isolate less susceptible to acyclovir, for 60% of the treatment period. Concentration in nasal mucus samples and CSF was 0.36–1.17 μg/mL and 0.11–0.23 μg/mL, respectively. This study illustrates that multiple dosing of valacyclovir may result in a therapeutic benefit as plasma concentrations could be maintained above the EC₅₀-value of acyclovir against EHV1 for more than 50% of the treatment period. Acyclovir could be detected in both nasal mucus samples and CSF. However, these concentrations were lower than the EC₅₀.     

Effects of Exogenous Tumour Necrosis Factor-α on the Secretory Function of the Bovine Reproductive Tract Depend on Tumour Necrosis Factor-α Concentrations

The aim of study was to correlate tumour necrosis factor-α (TNF) infused doses used with the TNF concentrations achieved and with the secretory function of both the ovary and the uterus in cows. We evaluated the concentrations of progesterone (P4), prostaglandin (PG)F_2α, PGE₂ nitric oxide (NO) and TNF in the jugular vein and vena cava caudalis as parameters of exogenous TNF action on the female reproductive tract. Aortae abdominalis of cows (n = 18) were infused with saline or two doses of TNF (luteolytic – 1 μg or luteotrophic – 10 μg). In the peripheral blood, 1 μg TNF concentrations achieved within the range of 30–45 pg/ml, and 10 μg TNF provoked a sharp increase in achieved concentrations at a range of 250–450 pg/mL). The TNF concentrations achieved in vena cava caudalis were five to six times higher than that in peripheral blood (p < 0.001). One microgram TNF increased PGF_2α and NO (p < 0.001) and decreased P4 (p < 0.05). The higher TNF dose stimulated P4 and PGE₂ (p < 0.01). TNF infusion at luteolytic dose achieved its concentrations at the physiological range previously observed in cows. Luteotrophic TNF dose achieved the concentrations in vena cava caudalis that are much higher than physiological level and were previously noted in pathological circumstances (i.e. mastitis , metritis ).     

Inhibitory effect of dietary anacardic acid supplementation on cecal lesion formation following chicken coccidial infection

Two experiments were conducted to determine the effects on male chicken performance of anacardic acid and cashew nut shell oil as feed supplements during an experimental coccidial infection. Seven-day-old chicks wer e fed a corn-soybean diet containing anacardic acid at 0, 0.4 or 0.8% (Experiment 1), or cashew nut shell oil at 0, 0.1, 0.2 or 0.4% (Experiment 2) for 10 days. On the third day of each experiment, half of the birds fed each diet were individually inoculated orally with 2 × 10³ or 5 × 10⁴ (Experiment 1) and 1 × 10⁴ or 1 × 10⁵ (Experiment 2) Eimeria tenella oocysts. In Experiment 1, body weight gain and cecal length decreased significantly according to the level of oocyst inoculation, while oocyst production per cecum (log value) and cecal lesion score significantly increased. Dietary anacardic acid supplementation had no effect on these parameters except for that of lesion score, which was improved (i.e. decreased) by anacardic acid supplementation of 0.8% at the inoculation level of 2 × 10³ oocysts, and of 0.4 and 0.8% for the higher inoculation (5 × 10⁴ oocysts). Results of Experiment 2 also showed that cashew nut shell oil affected neither cecal length nor oocyst production per cecum (log value) at either of the inoculation levels, but the lesion score was improved by cashew nut shell oil supplementation at 0.2 and 0.4% in the diet at the inoculation level of 1 × 10⁴ oocysts and at 0.4% for the higher inoculation. The present study provides the first evidence of the reducing effects of anacardic acid and cashew nut shell oil on the severity of cecal lesions in chickens during an experimental coccidial infection.     

Haematological findings in captive dolphins and whales

Objective To examine haematological features in five species of healthy, captive marine mammals.
Animals Twenty bottlenose dolphins ( Tursips truncatus ), seven Pacific white-sided dolphins ( Lagenorhynchus obliquidens ), five Risso dolphins ( Grampus griseus ) and five false killer whales ( Pseudorca crassidens ).
Results and conclusion The red blood cell count was 4.21 × 10¹²/L in bottlenose dolphins, 5.32 × 10¹²/L in Pacific white-sided dolphins, 4.35 × 10¹²/L in Risso dolphins and 4.43 × 10¹²/L in false killer whales. The haemoglobin concentration was 1.51 g/L and packed cell volume 44.7% in bottlenose dolphins; the corresponding values were 1.71 g/L and 48.9% in Pacific white-sided dolphins, 1.72 g/L and 49.4% in Risso dolphins, and 1.52 g/L and 47.8% in false killer whales. The white blood cell count was 7.097 × 10⁹/L in bottlenose dolphins, 5.928 × 10⁹/L in Pacific white-sided dolphins, 5.001 × 10⁹/L in Risso dolphins and 7.921 × 10⁹/L in false killer whales. There were no significant differences in these values among bottlenose dolphins and Pacific white-sided dolphins. The proportion of eosinophils in the differential leukocyte count ranged from 10.3% to 11.5% in bottlenose dolphins, Pacific white-sided dolphins and false killer whales, but was only 0.4% in Risso dolphins. The eosinophilic granules were larger in Risso dolphins and false killer whales than in bottlenose and Pacific white-sided dolphins.     

Pharmacokinetics of a single bolus intravenous, intramuscular and subcutaneous dose of disodium fosfomycin in horses

Pharmacokinetic parameters of fosfomycin were determined in horses after the administration of disodium fosfomycin at 10 mg/kg and 20 mg/kg intravenously (IV), intramuscularly (IM) and subcutaneously (SC) each. Serum concentration at time zero (C_S0) was 112.21 ± 1.27 μg/mL and 201.43 ± 1.56 μg/mL for each dose level. Bioavailability after the SC administration was 84 and 86% for the 10 mg/kg and the 20 mg/kg dose respectively. Considering the documented minimum inhibitory concentration (MIC₉₀) range of sensitive bacteria to fosfomycin, the maximum serum concentration (Cmax) obtained (56.14 ± 2.26 μg/mL with 10 mg/kg SC and 72.14 ± 3.04 μg/mL with 20 mg/kg SC) and that fosfomycin is considered a time-dependant antimicrobial, it can be concluded that clinically effective plasma concentrations might be obtained for up to 10 h administering 20 mg/kg SC. An additional predictor of efficacy for this latter dose and route, and considering a 12 h dosing interval, could be area under the curve AUC_0-12/MIC₉₀ ratio which in this case was calculated as 996 for the 10 mg/kg dose and 1260 for the 20 mg/kg dose if dealing with sensitive bacteria. If a more resistant strain is considered, the AUC_0-12/MIC₉₀ ratio was calculated as 15 for the 10 mg/kg dose and 19 for the 20 mg/kg dose.     

Single and multiple-dose pharmacokinetics of tepoxalin and its active metabolite after oral administration to rabbits (Oryctolagus cuniculus)

The anti-inflammatory agent, tepoxalin, was administered to eight healthy 6-month-old female New Zealand white rabbits once daily at an oral dose of 10 mg/kg. Blood samples were obtained immediately before and at 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 h postadministration on days 1 and 10. Tepoxalin and its active metabolite, RWJ 20142, concentrations were determined in plasma by use of high-performance liquid chromatography with mass spectrometry. C _max of the parent compound was reached between 3 and 8 h of drug administration, with a harmonic mean t _1/2 of 3.6 h. Peak tepoxalin plasma concentrations were 207 ± 49 ng/mL. After oral administration, the metabolite RWJ 20142 achieved C _max in plasma 2–8 h after administration, with a t _1/2 of 1.9–4.8 h (harmonic mean 2.8 h). Peak plasma concentrations of RWJ 20142 on day 1 were 2551 ± 1034 ng/mL.     

Plasma and urine disposition and dose proportionality of ceftiofur and metabolites in dogs after subcutaneous administration of ceftiofur sodium

Nine male dogs (10.3–13.5 kg body weight) were randomly assigned to three groups of three dogs each and administered ceftiofur sodium subcutaneously as a single dose of 0.22, 2.2, or 4.4 mg ceftiofur free acid equivalents/kg body weight. Plasma and urine samples were collected serially for 72 h and assayed for ceftiofur and metabolites (derivatized to desfuroylceftiofur acetamide) using high-performance liquid chromatography. Urine concentrations remained above the MIC ₉₀ for Escherichia coll (4.0 μg/mL) and Proteus mirabilis (1.0 μg/mL) for over 24 h after doses of 2.2 mg/kg (8.1 μg/mL) and 4.4 mg/kg (29.6 μg/mL), the interval between treatments for ceftiofur sodium in dogs, whereas urine concentrations 24 h after dosing at 0.22 mg/kg (0.1 mg/Ib) were below the MIC ₉₀ for E.coli and P. mirabills (0.6 μg/mL). Plasma concentrations were dose-proportional, with peak concentrations of 1.66 ± 0.0990 μg/mL, 8.91 ± 6.42 μg/mL, and 26.7 ± 1.07 μg/mL after doses of 0.22, 2.2, and 4.4 mg/kg, respectively. The area under the plasma concentration versus time curve, when normalized to dose, was similar across all dosage groups.     

Distinct Effects of Boar Seminal Plasma Fractions Exhibiting Different Protein Profiles on the Functionality of Highly Diluted Boar Spermatozoa

The aim of this study was to evaluate how different protein profiles of seminal plasma (SP) fractions affect sperm functionality in vitro. Ejaculates from three boars were separated into six fractions. The fractions differed from each other in their sperm content, in their total SP protein content, and their spermadhesin PSP-I/PSP-II and heparin-binding protein (HBP) concentrations. Spermatozoa were mainly recovered in fraction 2 (sperm-rich fraction, >1800 × 10⁶ spermatozoa/ml), whereas the pre-sperm fraction 1 and the post-sperm fractions 4–6 contained low numbers of spermatozoa (<500 × 10⁶/ml). Except in fraction 2, the total SP protein concentration and the concentration of both, spermadhesin PSP-I/PSP-II and the HBPs increased with fraction order. Distinct time-dependent effects were observed on motility characteristics and membrane integrity of highly diluted boar spermatozoa upon incubation with a 10% dilution of the SP from each fraction. The highest sperm viability was recorded after exposure for 5 h to fraction 2, followed by fractions 1 and 3. The percentages of motile spermatozoa also differed significantly among fractions after 5 h of incubation. Spermatozoa incubated with SP of fractions 1–3 showed the highest percentage motility. We conclude that different SP fractions exert distinct effects on the functionality of highly diluted boar spermatozoa. Fractions 1–3 appear to promote sperm survival, whereas fractions 4–6 seem to be harmful for preserving the physiological functions of highly diluted boar spermatozoa.     

Urinary Corticoid : Creatinine Ratios in Dogs with Pituitary-Dependent Hypercortisolism during Trilostane Treatment

Background: The adrenocorticotropic hormone (ACTH) stimulation test is used to evaluate trilostane treatment in dogs with hypercortisolism.
Hypothesis: The urinary corticoid : creatinine ratio (UCCR) is a good alternative to the ACTH stimulation test to determine optimal trilostane dose.
Animals: Eighteen dogs with pituitary-dependent hypercortisolism.
Methods: In this prospective study, the dose of trilostane was judged to be optimal on the basis of resolution of clinical signs of hypercortisolism and results of an ACTH stimulation test. The owners collected urine for determination of UCCR at 2-week intervals for at least 8 weeks after achieving the optimal trilostane dose.
Results: The UCCRs were significantly higher before treatment (11.5–202.0 × 10⁻⁶; median, 42.0 × 10⁻⁶) than at rechecks 2 months after optimal dosing, but they did not decrease below the upper limit of the reference range in the majority of dogs. The UCCRs of 11 dogs that initially were dosed insufficiently (range, 7.5–79.0 × 10⁻⁶; median, 31.0 × 10⁻⁶) did not differ significantly from UCCRs when the dosage was optimal (8.2–72.0 × 10⁻⁶; median, 33.0 × 10⁻⁶). Post-ACTH cortisol concentrations did not correlate significantly with UCCRs at rechecks during trilostane treatment. Long-term follow-up indicated that the decrease in UCCR below the upper limit of the reference was associated with hypocortisolism.
Conclusion and Clinical Importance: The UCCR cannot be used as an alternative to the ACTH stimulation test to determine the optimal dose of trilostane, but might be helpful in detecting dogs at risk for developing hypocortisolism during trilostane treatment.     

Yohimbine prevents the retrograde flow of spermatozoa into the urinary bladder of dogs induced by xylazine

This study was carried out to determine whether yohimbine antagonizes the retrograde flow of spermatozoa into the urinary bladder of dogs caused by xylazine. Adult dogs were assigned to one of four groups of six dogs each and treated as follows: saline control, xylazine (2.2 mg/kg, i.m.), yohimbine (0.2 mg/kg, im.), yohimbine/xylazine (yohimbine, 0.2 mg/kg, i.m., followed 10 min later by xylazine. 2.2 mg/kg, i.m.). Pre- and post-treatment urine were collected by cystocentesis from all dogs. The mean (± SD) adjusted total number of spermatozoa in the post-treatment urine of xylazine-treated dogs (141.02 ± 136.75 × 10⁶) was 15 times higher ( P < 0.05) than the number in the post-treatment urine of control dogs (9.16 ± 20.26 × 10⁶), 1763 times higher ( P < 0.05) than the number in the urine of yohimbine-treated dogs (0.08 ± 0.20 × 10⁶), and 56 times higher ( P < 0.05) than the total number in the post-treatment urine of yohimbine/xylazine-treated dogs (2.54 ± 4.54 × 10⁶). These results confirm that xylazine induces a significant ( P = 0.007) displacement of spermatozoa into the urinary bladder of dogs and demonstrate that pre-treatment with yohimbine prevents this effect.     

Pharmacokinetics of pradofloxacin and doxycycline in serum, saliva, and tear fluid of cats after oral administration

The pharmacokinetic properties of pradofloxacin and doxycycline were investigated in serum, saliva, and tear fluid of cats. In a crossover study design, six cats were treated orally with a single dose of pradofloxacin (Veraflox^® Oral Suspension 2.5%) and doxycycline (Ronaxan^® 100 mg) at 5 mg/kg body weight. Following administration, samples of serum, saliva, and tear fluid were taken in regular intervals over a period of 24 h and analysed by turbulent flow chromatography/tandem mass spectrometry. All values are given as mean ± SD. Pradofloxacin reached a mean maximum serum concentration ( C _max) of 1.1 ± 0.5 μg/mL after 1.8 ± 1.3 h ( t _max). In saliva and tear fluid, mean C _max was 6.3 ± 7.0 and 13.4 ± 20.9 μg/mL, respectively, and mean t _max was 0.5 ± 0 and 0.8 ± 0.3 h, respectively. Doxycycline reached a mean C _max in serum of 4.0 ± 0.8 μg/mL after 4.3 ± 3.2 h. Whilst only at two time-points doxycycline concentrations close to the limit of quantification were determined in tear fluid, no detectable levels were found in saliva. The high concentrations of pradofloxacin in saliva and tear fluid are promising to apply pradofloxacin for the treatment of conjunctivitis and upper respiratory tract infections in cats. As doxycycline is barely secreted into these fluids after oral application the mechanisms of its clinical efficacy remain unclear.     

Die Verteilung der Spermien im weiblichen Genitale des Schweines nach Insemination von frischem und tiefgefrorenem Sperma

Inhalt: 1. In Versuchen an insgesamt 24 weiblichen Schweinen wurde die Verteilung von Spermien im Uterus und Eileiter 4 bis 6 Stunden und 20 Minuten nach künstlicher Besamung mit 20 × 10⁹ Spermien untersucht. Die Spermien waren normal oder tief-gefroren konserviert und in einem Verdünner von 120 und 100 ml suspendiert.
2. Von den ehemals tiefgefrorenen Samenzellen konnten 4 bis 6 Stunden post inseminationem nur 0,0073 × 10⁶ (weniger als 1%) wiedergefunden werden, während in Vergleichsgruppen mit normal konserviertem Sperma 0,4080 × 10⁶ bzw. 52,4770 × 10⁶ Spermien ermittelt wurden.
20 Minuten nach der Insemination wurden TGN₂-Spermien in ähnlicher Zahl wie normal konservierte gefunden.
Nach Insemination mit abgetöteten Spermien waren im Eileiter keine Samenzellen nachzuweisen.     

Differential inhibition of cyclooxygenase isoenzymes in the cat by the NSAID robenacoxib

Robenacoxib is a new nonsteroidal anti-inflammatory drug (NSAID) developed for use in companion animal medicine. The objectives of this study were: to quantify the inhibitory actions of robenacoxib on cyclooxygenase (COX) isoenzymes in feline whole blood assays; to establish blood concentration–time profiles of robenacoxib after intravenous and subcutaneous dosing in the cat and; to predict the time courses of inhibition of COX isoforms by robenacoxib. COX-1 and COX-2 activities in heparinized feline whole blood samples were induced with calcium ionophore and lipopolysaccharide, respectively. Inhibition of thromboxane B₂ provided a marker of both COX-1 and COX-2 activities and a nonlinear parametric mixed effects modelling approach was used to establish the pharmacodynamic parameters describing this inhibition. Mean values (and prediction intervals) of IC₅₀ were 28.9 (16.4–51.1) μ m (COX-1) and 0.058 (0.010–0.340) μ m (COX-2). These parameters were used to compute several selectivity indices. Selectivity IC ratios (COX-1:COX-2) were 502.3 (IC₅₀/IC₅₀), 451.6 (IC₉₅/IC₉₅) and 17.05 (IC₂₀/IC₈₀). Based on a clinically recommended dosage regimen of 2 mg/kg, it was predicted that the corresponding mean robenacoxib blood concentration over the first 12 h after drug administration corresponded to 5% inhibition of COX-1 and 90% inhibition of COX-2.     

The pharmacokinetics of orbifloxacin in the horse following oral and intravenous administration

The purpose of this study was to determine the pharmacokinetics and physicochemical characteristics of orbifloxacin in the horse. Six healthy adult horses were administered oral and intravenous orbifloxacin at a dose of 2.5 mg/kg. Plasma samples were collected and analyzed by high-pressure liquid chromatography with ultraviolet detection. Plasma protein binding and lipophilicity were determined in vitro . Following i.v. administration, orbifloxacin had a terminal half-life ( t _1/2) of 5.08 h and a volume of distribution (V_d(ss)) of 1.58 L/kg. Following oral administration, the average maximum plasma concentration ( C _max) was 1.25  μ g/mL with a t _1/2 of 3.42 h. Systemic bioavailability was 68.35%. Plasma protein binding was 20.64%. The octanol:water partition coefficient (pH 7.4) was 0.2 ± 0.11. No adverse reactions were noted during this study. Dosage regimens were determined from the pharmacokinetic–pharmacodynamic parameters established for fluoroquinolone antibiotics. For susceptible bacteria, an oral dose of approximately 5 mg/kg once daily will produce plasma concentrations within the suggested range. This dose is suggested for further studies on the clinical efficacy of orbifloxacin for treatment of susceptible bacterial infections in the horse.