The antipyretic effect of polymyxin B in endotoxin-induced fever

LPSS. typhimurium (0.3 g per kg) injected intravenously into conscious goats induced an inhibition of the extrinsic ruminal contractions in association with pyrexia and changes in heart rate. Pretreatment with polymyxin B (3 mg per kg i.v.) antagonized the endotoxin-induced symptoms in this species. In rabbits, the intravenous administration of LPSE. coli (0.1 g per kg) resulted in a febrile response, which could be markedly reduced by pretreatment with polymyxin B. Unlike endotoxins, the febrile response to leucocytic pyrogen was not inhibited after pretreatment with this antibiotic. Moreover, polymyxin B caused only a minimal decline in the febrile response due to sodium nucleinate from yeast (10 mg per kg). These results strengthen the view that the antipyretic activity of polymyxin B is due to an interaction of this cationic macromolecule with the anionic endotoxin molecule.     

Feed intake and rumen motility in dwarf goats. Effects of some α-adrenergic agonists,prostaglandins and posterior pituitary hormones

The purpose of the present investigation was to test the hypothesis that drug-induced changes in rumen contractions influence feed intake in dwarf goats. Intravenous (i.v.) administration of clonidine (1 g kg^-1 min^-1 for 10 min), xylazine (1 g kg^-1 min^-1 for 10 min), and PGF-2 (10 g kg^-1 min^-1 for 15 min) caused bradycardia and inhibition of rumen contractions. However, no appetite-stimulating effect of these drugs was observed. Other clinical changes induced by the ₂-adrenergic agonists included slight sedation and a decrease in body temperature; all clinical effects of clonidine and xylazine were partly antagonized by tolazoline pretreatment (10 g kg^-1 min^-1 for 30 min). These results suggest that the CNS control of feeding differs in ruminants and monogastric species.In dwarf goats fasted for 2 h, i.v. administration of oxytocin (0.01 IU kg^-1 min^-1 for 15 min), vasopressin (0.01 IU kg^-1 min^-1 for 15 min), octapressin (0.003 IU kg^-1 min^-1 for 15 min) or PGE (0.8 g kg^-1 min^-1 for 15 min) did not change feeding behaviour during the two observation periods (0–30 min and 180–210 min after drug infusion, respectively). In previous studies, similar doses of these drugs induced changes in heart rate and inhibition of rumen contraction in goats. These findings demonstrate that drug-induced changes in forestomach contractions do not simply cause changes in feeding behaviour. The i.v. infusion of the PGF₂ analogues etiproston (10 g kg^-1 min^-1 for 15 min), luprostiol (30 g kg^-1 min^-1 for 15 min), cloprostenol (1 g kg^-1 min^-1 for 15 min) and tiaprost (1 g kg^-1 min^-1 for 15 min) induced hypophagic effects and stimulated intestinal propulsion.     

Pharmacokinetics of Enrofloxacin and Its Metabolite Ciprofloxacin after Intramuscular Administration of Enrofloxacin in Goats

The pharmacokinetics of enrofloxacin and its active metabolite ciprofloxacin were investigated in goats after a single intramuscular administration of enrofloxacin at 2.5 mg/kg body weight. The plasma concentrations of enrofloxacin and ciprofloxacin were determined simultaneously by a HPLC method. The peak concentrations (C _max) of enrofloxacin (1.13 g/ml) and ciprofloxacin (0.24 g/ml) were observed at 0.8 and 1.2 h, respectively. The elimination half-life (t _1/2), volume of distribution (V _d(area)), total body clearance (Cl_B) and mean residence time (MRT) of enrofloxacin were 0.74 h, 1.42 L/kg, 1329 ml/h per kg and 1.54 h, respectively. The t _1/2, area under the plasma concentration–time curve (AUC) and the MRT of ciprofloxacin were 1.38 h, 0.74 g h/ml and 2.73 h, respectively. The metabolic conversion of enrofloxacin to ciprofloxacin was appreciable (36%) and the sum of the plasma concentrations of enrofloxacin and ciprofloxacin was maintained at or above 0.1 g/ml for up to 4 h. Enrofloxacin appears to be useful for the treatment of goat diseases associated with pathogens sensitive to this drug.     

Cholinergic reactivity of the bovine fetal ruminal wall in vitro

Strips of rumen wall from bovine fetuses were incubated in an organ bath with acetylcholine only (0.16 to 5.12 g/ml) or in the presence of neostigmine (0.20 g/ml) or atropine (0.05g/ml). The highest reactivity was observed in the period of 4.0–5.9 months of fetal age. This reactivity could be associated with the starting point of rumen papillary development.     

Endotoxin in the conscious piglet: Its effects on some general and gastrointestinal myoelectrical parameters

The effect of an intravenous bolus injection of endotoxin, 0.1, 1 or 10 g/kg, on rectal temperature, clinical appearance, haematological parameters, and on gastrointestinal electrical activity was examined in 11 conscious piglets of 4–5 weeks of age, with implanted electrodes in the antrum pylori, duodenum, jejunum and ileum. All doses resulted in a significant and dose-dependent increase in rectal temperature, in pronounced clinical signs and in distinct changes in haematological values. These included shivering, depression, respiratory distress, a leukopenia (0.1 g/kg) or a leukocytosis (1 g/kg) with a shift to the left, an accelerated sedimentation rate and a decreased packed cell volume. Doses of 1 and 10 g/kg induced a transient inhibition of gastroduodenal electrical activity. These results suggest that, in the piglet, endotoxin primarily manifests general clinical signs and that the gastrointestinal effects coincide with these.     

Serum Fructosamine Concentrations in Dogs with Hypothyroidism

Serum fructosamine concentrations were measured in 11 untreated hypothyroid dogs with normal serum glucose and serum protein concentrations. The fructosamine level ranged between 276 and 441 mol/L (median 376 mol/L; reference range 207–340 mol/L). Nine of the 11 dogs had fructosamine levels above the reference range. The fructosamine levels decreased significantly during treatment with levothyroxine. It is suggested that serum fructosamine concentrations may be high in hypothyroid dogs because of decelerated protein turnover, independent of the blood glucose concentration.     

Disposition kinetics and distribution of demeclocycline in various biological fluids in female goats

A pharmacokinetic study of demeclocycline was carried out following intravenous administration at 5 mg/kg body weight in lactating goats. Demeclocycline appeared within 5 min in plasma, interstitial fluid (isf) and urine, while it appeared at 1 h in milk. Peak concentrations of 21.70±4.06, 2.67±0.23, 5.65±0.45 and 82.23±10.06 g/ml were attained at 5 min and at 6, 8 and 8 h in plasma, isf, milk and urine respectively. A potentially therapeutic concentration of 0.5 g/ml was maintained from 5 min–36 h, 30 min–30 h, 1–36 h and 5 min–48 h in plasma, isf, milk and urine respectively. The drug was detectable in all the above biological fluids for at least 48 h. A low distribution half life (t_1/2) of 0.44±0.04 h and a high elimination half life (t_1/2) of 19.24±1.22 h denote rapid distribution but very slow elimination of the drug in goats. A high tissue plasma concentration ratio [K₁₂:(K_2I–)] of 5.12±0.97 during the elimination phase and a Vd_area of 1.59±0.18 L/kg indicate uniform distribution of demeclocycline in the tissues and body fluids of goats. The dosage regimen for maintaining minimum plasma concentration (C min = MIC) of 0.5, 1.0 and 1.5 g/ml at selected dosage intervals of 12 and 24 h was also calculated.     

Plasma,Urinary and Biliary Residues in Cattle Following Intramuscular Injection of Nortestosterone Laurate

The synthetic androgen 19-nortestosterone (-NT) has been used illegally as a growth promoter in cattle production in the European Union. Elimination of -NT and its metabolites in plasma, urine and bile was studied in three cattle with cannulated gallbladders following intramuscular injection at a single site of 500 mg of the laurate ester (NTL) containing 300.5 mg -NT. Using enzyme immunoassay quantification, plasma Cmax of free -NT was 0.5±0.15 g/L (mean±SEM). Concentrations of free -NT in plasma were consistently greater than the assay limit of quantification (0.12 g/L) for 32.7±13.42 days. Mean residence time for free -NT in plasma was 68.5±20.75 days. Following sample preparation by immunoaffinity chromatography, high-resolution GC-MS was used to quantify -NT and -NT in urine and bile. -NT was detected irregularly in urine from two of the three animals post injection. The principal metabolite present in the urine, -NT, was detected for 160.3±22.67 days post injection. Cmax for -NT in urine was 13.7±5.14 g/L. Mean urinary AUC0–183 days for -NT was 845.7±400.90 (g h)/L.In bile, -NT was the only metabolite detected for 174.3±8.67 days post treatment. Cmax for -NT in bile was 40.8±12.70 g/L and mean biliary AUC0–183 days for -NT was 1982.6±373.81 (g h)/L. Concentrations of -NT in bile samples were greater than those in urine samples taken at the same time. The mean ratio of biliary:urinary AUC0–183 days was 3.0±0.72. It is concluded that bile is a superior fluid for detection of -NT following injection of NTL, owing to the longer period during which residues may be detected after administration.     

The pharmacokinetics of fenbendazole and oxfendazole in cattle

The pharmacokinetics of fenbendazole and oxfendazole in cattle are described. The pharmacokinetics of oxfendazole were not significantly different when administered orally and by intra-ruminal injection. At a dose rate of 4.5 mg/kg, administered orally, fenbendazole gave rise to mean peak concentrations in plasma of fenbendazole and oxfendazole of 0.11 and 0.13 g/ml respectively. Oral administration of oxfendazole, at 4.5 mg/kg body weight, gave rise to plasma peak concentrations of fenbendazole and oxfendazole of 0.10 and 0.20 g/ml respectively. Following intra-ruminal administration of oxfendazole, the peak concentrations were 0.11 and 0.18 g/ml respectively.     

Clinical Value of Fructosamine Measurements in Non-healthy Dogs

Ninety-three unhealthy dogs (including some with diabetes mellitus or insulinoma) of different ages, sex and breeds were divided into 10 groups according to their pathology. Serum fructosamine concentrations were determined using a commercial colorimetric nitroblue tetrazolium method. Diabetic dogs had the highest fructosamine concentrations (454.85±149.34 mol/L). Dogs with insulinoma had significantly lower fructosamine concentrations (202.80±31.22 mol/L), similar to those with leishmaniosis (202.83±99.83 mol/L). Fructosamine concentrations in non-healthy dogs, except those with diabetes mellitus, insulinoma or leishmaniosis, were within the reference limits previously reported.     

The use of cultured hepatocytes from goats and cattle to investigate xenobiotic oxidative metabolism

The oxidative metabolism of aldicarb (ALD), a carbamate pesticide, and fenbendazole (FBZ), an anthelmintic, was studied using cultured hepatocytes obtained from 4 goats and a bullock and incubated with ALD (50 mol/L) and FBZ (10 mol/L). The parent compounds and the metabolites were measured by HPLC. Both compounds are metabolized at the sulphur atom via two sequential oxidations, first to the sulphoxide (aldicarb sulphoxide and oxfendazole, respectively) and then to the sulphone. Oxfendazole and fenbendazole sulphone from FBZ, and aldicarb sulphoxide from ALD were found in both species. Aldicarb sulphone was not produced by the hepatocyte preparations from the bullock. The good correlation obtained comparing the in vitro results of FBZ metabolism with published in vivo dat obtained on FBZ kinetics in the same species confirmed the usefulness of in vitro models for predictive analysis of in vivo xenobiotic biotransformations.Abbreviations ALD aldicarb - ALDSON aldicarb sulphone - ALDSOX aldicarb sulphoxide - BSA bovine serum albumin - ID internal diameter - EGTA ethylene glycol bis(-aminoethyl ether) N,N,N,N-tetraacetic acid - FBZ fenbendazole - FBZSON fenbendazole sulphone - HBSS Hanks' balanced saline solution - HPLC high-pressure liquid chromatography - LDH lactate dehydrogenase - MFO mixed function oxidase - NCS newborn calf serum - OXF oxfendazole - WME Williams' Medium E     

Central and local actions of opioids upon reticulo-ruminal motility in sheep

The effects of opioids and naloxone on cyclical forestomach motility were determined in anaesthetized and conscious sheep. To assess central or peripheral opioid actions, differential routes of administration were used. Possible dynamic effects along the innervating vagovagal reflex arc were investigated electrophysiologically at the cervical level of the vagus nerve. Further, direct influences on the smooth muscle were evaluatedin vitro on isolated longitudinal reticular strips. Additionally, the effects of some spasmogenic agents were studied for comparative purposes. In anaesthetized sheep, opioids depressed in an identical manner both the amplitude of spontaneous cyclical contractions and contractions evoked by electrical stimulation of the distal end of the cut cervical vagus. In conscious sheep, low doses of normorphine and loperamide inhibited frequency and amplitude centrally (20 g/kg and 4 g/kg via carotid artery respectively), whereas locally higher dose levels (200 g/kg and 10 g/kg via coeliac artery respectively) affected only the amplitude of cyclical contractions. Furthermore the opioid peptides Leu-, Met-enkephalin and [D-Ala²-Met⁵]-enkephalinamide preferentially depressed the amplitude of cyclical motility most efficiently if administrated via the coeliac artery. These results indicate the presence both of a central opioid action depressing frequency and amplitude and of a local opioid action depressing only the amplitude of cyclical reticulo-ruminal motility. Opioids did not alter the resting discharge of afferent tension units and similarly failed to modulate tone of reticular stripsin vitro, suggesting that the opioids act locally on the intramural neuronal plexus, possibly by diminishing the output of excitatory transmitter. Whether substance P could play a role as a vagal excitatory transmitter besides the classically implicated acetylcholine has been discussed. The central opioid mechanism is probably not situated within the gastric centres but elsewhere in the brain. Naloxone ( 100 g/kg, jugular vein) stimulated the frequency of cyclical ruminal motility only in well-defined experimental conditions, probably via a central mechanism.     

Tolerance to the Nephrotoxic Component of Narthecium ossifragum in Sheep: The Effects of Repeated Oral Doses of Plant Extracts

Young adult sheep were dosed with extracts of Narthecium ossifragum plants by the oral or parenteral routes and the resulting nephrotoxicity was assessed from the increases in the concentrations of creatinine and urea in the serum. Following single intraruminal or intraperitoneal doses of extracts derived from 30 g N. ossifragum (wet weight) per kg live weight (kg lw), serum creatinine concentrations increased from about 100 mol/L to between 260 and 510 mol/L. The serum urea concentrations increased from about 5–8 mmol/L to between 11 and 66 mmol/L in individual sheep. Daily intraruminal administration of 5–30 g/kg lw to three sheep over a 10- or 15-day period increased creatinine concentrations from 100 mol/L to 300–760 mol/L, and urea concentrations from 5–8 mmol/L to 35 mmol/L. A single intraperitoneal challenge dose of 30 g/kg lw, delivered 7 or 12 days after the final intraruminal dose, did not lead to increased serum creatinine or urea concentrations, indicating that oral treatment had apparently resulted in an increased tolerance to the nephrotoxic principle(s) in N. ossifragum.     

Efficacy of Chlorhexidine against Some Strains of Cultured and Clinically Isolated Microorganisms

The efficacy of chlorhexidine digluconate was determined against some strains of collected and clinically isolated bacteria and fungi. The efficacy was evaluated either by calculating a minimum inhibitory concentration (MIC) or by efficacy trials according to the guidelines of the European Committee for Standardization. The MIC values of chlorhexidine for Staphylococcus aureus, Microsporum gypseum, Microsporum canis and Trichophyton mentagrophytes were 0.625 g/ml, 12.5 g/ml, 50 g/ml and 6.25 g/ml, respectively. The in vitro efficacy of chlorhexidine was higher against ATCC strains of S. aureus and P. aeruginosa (0.5 mg/ml for 5 min and 0.5 mg/ml for 10 min, respectively) than against clinical isolates (0.5 mg/ml for 15 min and 1 mg/ml for 10 min, respectively). The antiseptic activity of aqueous solutions of chlorhexidine against spores of Bacillus subtilis, Bacillis sfericus and Clostridium perfringens required longer contact times than against the vegetative forms. Nevertheless, 5 mg/ml of chlorhexidine in water–ethanol 20:80 v/v was totally effective against the vegetative forms or spores of these microorganisms.     

Pharmacokinetics and distribution of sulphadimidine in plasma,milk and uterine fluid of female buffaloes

The pharmacokinetics of sulphadimidine after a single dose (200 mg/kg i.v.) was studied in five healthy lactating buffaloes. The study revealed that the drug attained its peak concentration of 314.0±13.0, 242.4±3.0 and 100.2±2.5 g/ml at 15 min, 30 min and 12 h in plasma, milk and uterine fluid, respectively. The pharmacokinetic parameters calculated by a 2-compartment open model gave values for t₁, t₁ and vd_area of 2.10±0.36 h, 12.36±0.57 h and 1.23±0.07 L/Kg, respectively. A high vd_area as well as a value of 0.74±0.08 for K₁₂:K₂₁- (tissue Plasma) indicates better penetration of the drug into the different body fluids and tissues, which is further supported by a high concentration obtained in milk and uterine fluid. The therapeutic concentration (50 g/ml) was maintained for around 24 h in plasma and milk and 12 h in uterine fluid. The results suggest that, apart from its use in systemic infections, the drug can be effectively used by the i.v. route in uterine and mammary gland infections. The dosages for maintaining concentration of 50 g/ml, 100 g/ml and 150 g/ml at convenient dosage intervals of 12 and 24 h were also determined.     

Evaluation of Synchronization of Oestrus Based on Gonadotrophin-releasing Hormone and Its Potential Use for Fixed-Time Breeding in Tuli Beef Cows

The objective of the experiment was to compare the reproductive post-partum performance of beef cows synchronized for oestrus using prostaglandin F₂ (PGF₂) alone or with a gonadotrophin-releasing hormone (GnRH)-based drug. Fifty-five post-partum lactating Tuli cows were randomly allocated to three groups. Two groups were synchronized using either two injections of PGF₂ (500 g Prosolvin per injection) given 11 days apart (group 1), or GnRH (12.5 g Receptal per injection) followed 6 days later by an injection of 500 g PGF₂ (group 2). The cows were bred by artificial insemination 12 h after they were observed in oestrus. Group 3 was synchronized as for group 2, but a second injection of GnRH was given 54 h after the PGF₂ injection, at which time the cows were bred by artificial insemination (AI) without detection of oestrus. Blood samples were taken from the cows in group 3 and analysed for progesterone concentration to establish which cows were cycling and in oestrus before and at the time of breeding. Detection of oestrus and breeding by AI was done over 60 days. There were no significant differences (p>0.05) among the three groups in the first service and total conception rates. The percentage of cows in oestrus within 10 days of the synchronization treatment was not significantly different (p>0.05) between groups 1 and 2. The progesterone concentrations in the cows in group 3 showed that only those that were cycling at the start of the experiment responded to the synchronization treatment and conceived after fixed-time breeding. These results suggest that combinations of PGF₂ and GnRH may be of value in synchronizing oestrus and controlling breeding in Tuli cows. However, the benefit might be greater if only cows that are known to be cycling are bred in this way.     

Preliminary Studies on Hepatic Carnitine Palmitoyltransferase in Dairy Cattle with or without Fatty Liver

The hepatic mitochondrial carnitine palmitoyltransferase (CPT) activity was measured by fluorimetric assay in dairy cows with or without fatty liver. CPT activities in 13 lactating cattle and in 6 non-lactating cows were 304.4±86.6 mol CoA/min per g protein and 169.3±84.8 mol CoA/min per g protein, respectively. This difference was significant (<0.05). CPT activities in early lactation (0–110 days after calving), mid-lactation (111–220 days after calving) and late lactation (over 220 days after calving) were 278.9±68.0, 312.4±124.1 and 320±59.3 mol CoA/min per g protein, respectively. There was no significant difference between the values at different stages of lactation. The CPT activity in 10 lactating cows with fatty liver unrelated to calving was 201.3±80.0 mol CoA/min per g protein. CPT activity in 10 cattle with fatty liver was significantly lower than that in normal lactating cattle. Based on these findings, clinical fatty liver unrelated to calving appears to be associated with a decrease in hepatic CPT activity.     

Failure of 3-methylindole to contract the bovine pulmonary vein or to release mediators of anaphylaxis from the bovine lung in vitro

Strips of smooth muscle from the pulmonary vein, pulmonary artery, trachea and bronchus of calves were incubated in an organ bath with 3-methylindole (3MI) and 3-methyloxindole (3MOI). 3MI and 3MOI (5–640 g/ml) did not cause contraction of any of the isolated smooth muscle preparations. No evidence for the release of mediators of anaphylaxis was obtained when chopped bovine lung preparations were incubated with 3MI (20 g/ml) and 3MOI (25 g/ml). Results of the present work diminish the possibility that the pneumotoxic effect of 3MI is due to a primary hydrodynamic imbalance across the alveolocapillary membrane resulting in excess filtration over reabsorption.     

The influence of clenbuterol on prostaglandin F2α-induced dyspnoea in calves

Pulmonary function tests were performed in six healthy calves. Prostaglandin F₂ causes severe narrowing of both upper and lower airways (total lung resistance increased, dynamic compliance decreased). Clenbuterol administered intravenously fifteen minutes prior to prostaglandin F₂ aerosol, and in increasing doses (0, 0.4, 0.8, 1.2 g/kg), on days 1, 2, 4 and 6 of the experiment, effectively but not entirely suppressed these responses.These data indicate that -adrenergic receptors are present in the bovine airways and that the use of clenbuterol (0.8 g/kg) may be effective in treating clinical respiratory disease such as bronchopneumonia in calves.     

Measurement of Cortisol Metabolites in Faeces of Ruminants

Twenty-one metabolites were detected in faecal samples collected after infusion of (¹⁴C)cortisol into the jugular vein of sheep, using high-performance liquid chromatography/radiometric analysis plus mass spectrometry. One group of metabolites had molecular weights of between 302 and 308, and another group of 350, which indicates that the substances have a C₁₉O₃ or a C₂₁O₄ structure. Therefore, an enzyme immunoassay against 5-androstane-3-o1-11,17-dione-17-CMO:BSA was established. Faecal samples were collected from 10 cows immediately after transport and then during a course in which non-invasive diagnostic procedures were being taught (course 1). For comparison, faeces were sampled from another 5 cows that were being used for teaching invasive procedures (course 2). Six cows from a university farm served as controls. In the animals used in course 1, the highest concentrations of cortisol metabolites were measured immediately after transport to the university (median value: 2.2 mol/kg faeces). During the first 5 days at the university, the concentrations decreased to 0.52 mol/kg (median) and remained at this level during the rest of the course. The median concentration in the samples that were taken during course 2 (collected about 2 months after transport) was 0.48 mol/kg. There was no significant difference in the excretion of cortisol metabolites between these cows and the controls. We conclude from these data that, using the enzyme immunoassay against 5-androstane-3-o1-11,17-dione-17-CMO, we were able to detect transport/novel environment stress but not the potential disturbance that cows experience during diagnostic procedures.