The pharmacokinetics of indomethacin (7 mg/kg) was determined in six adult sheep after intraruminal administration. The plasma concentration-time curves showed different patterns for each sheep, depending on the physiological state of the gastrointestinal tract, where absorption took place, and possible enterohepatic and saliva recycling.Indomethacin was irregularly and poorly absorbed from the rumen after intraruminal administration to sheep. Plasma concentrations barely rose to the lower therapeutic margin and mean bioavailability was 38.25 +/- 15.98%. The elimination phase was slow (beta = 0.015 +/- 0.010 h(-1)) and the half-life was long (t(1/2 beta) = 56.52 +/- 31.21 h). The mean residence time was 20.01 +/- 6.92 h.
The aim of this study was to evaluate the effects of permanent tracheostomy on baseline breathing, reflex responses to lung hyperinflation (1.5 kPa) and right atrial capsaicin injection (5 micrograms/kg) before and at 3 and 5 weeks after tracheostomy in sevoflurane-anaesthetized spontaneously breathing dogs (n = 6). In all observation periods, apnoeic responses, represented by an increase in expiration time after lung inflation and right atrial capsaicin injection, were consistently observed to be a result of the Hering-Breuer inflation reflex and the pulmonary C-fibre chemoreflex. Investigation at 3 and 5 weeks after tracheostomy revealed no significant evidence of changing baseline breathing pattern or reflex responses to lung inflation and capsaicin in any ventilatory variable (inspiration time, expiration time, tidal volume, expired ventilation, and end-tidal PCO2) from levels recorded before surgery. These results indicate that permanent tracheostomy, at least up to 5 weeks, does not affect the baseline breathing pattern, the Hering-Breuer inflation reflex or the pulmonary C-fibre chemoreflex. Further, our investigation provides a useful canine model in respiratory physiology.
Behavioural patterns and plasma adrenaline, noradrenaline and cortisol responses were studied in domestic pigs with different dominance status during 10-h social confrontation tests with a familiar and an unfamiliar group. Eight trials were carried out, where in each trial two groups of nine growing pigs (12 weeks old) were randomly formed. The pigs with the highest (HR) and lowest (LR) rank from each group were selected as test animals, provided with surgically implanted catheters and kept in single housing for 2 to 3 weeks. After this period, each test animal was introduced once into the familiar and once into the unfamiliar group for 10 h. Introduction of the test animals into the groups caused frequent agonistic interactions during the first 30 min and significantly more agonistic interactions during the confrontation with the unfamiliar group. The agonistic behaviour was accompanied by a rapid increase of plasma catecholamines and cortisol. HR pigs showed significantly higher plasma catecholamine concentrations and more agonistic interactions during the first 30 min compared with the LR pigs. During confrontation with the unfamiliar group, HR pigs experienced more defeats and showed a higher increase of plasma cortisol levels than during the confrontation with the familiar group. No influences of rank or familiarity were found on the other behavioural patterns examined. The results show that agonistic behaviour and activation of the sympatho-adrenomedullary and the hypothalamic-pituitary-adrenal system in pigs during a social confrontation test are determined by the former dominance rank of the animals and the familiarity of the group.
The depletion rates of sulphadimethoxine (SDM) and its metabolite N4-acetylsulphadimethoxine (N4-AcSDM) were estimated in blood and various tissues of laying hens. The tissue contents (ppm) of SDM and N4-AcSDM after the withdrawal of SDM, which was fed to hens at 400 ppm diet for 5 successive days, were determined by HPLC. The elimination half-life (t1/2) of N4-AcSDM in the liver, ovary and muscle was estimated to be 4.3 h with a 95% confidence interval from 3.6 to 5.3 h. No significant difference between t1/2 of N4-AcSDM in the tissues and that of SDM (4.4 h) in the blood, kidney, muscle, ovary and adipose tissue was observed. On the other hand, the t1/2 of N4-AcSDM in the kidney (8.1 h) was significantly longer than that in the above 3 tissues.
The effect of acetylcholine on the isolated, non-precontracted, porcine internal mammary artery (IMA) was investigated. Acetylcholine induced concentration-dependent contractions of non-precontracted IMA rings with denuded endothelium (pEC50 = 5.80 +/- 0.04) and was without effect on arterial segments with intact endothelium. The muscarinic receptor antagonists atropine, pirenzepine, methoctramine and p-fluoro-hexahydro-sila-diphenidol (pFHHSiD) antagonized the response to acetylcholine. The constrained pA2 values were 10.14, 7.74, 7.34 and 10.5, respectively. It is concluded that acetylcholine induces concentration-dependent contractions of porcine internal mammary artery rings on basal tone and that this contractile effect is probably due to direct cholinergic stimulation of smooth muscle cells, maybe including activation of muscarinic M1 receptors.
Two cases of urinary retention in male dromedaries due to silica uroliths are presented. The animals were urethrostomized and one dromedary was euthanized 7 months later due to urethrostomy obstruction. The estimated daily intake of silica was 84.44 g. Silica, calcium, phosphorus and pH in urine were determined in healthy animals from the same farms, and the following values were obtained: 174.78 ± 3.46 mg/l (silica), 41.48 ± 4.82 mg/l (calcium), 20.4 ± 3.6 mg/l (phosphorus) and pH 8.2, respectively. Possible causes of urolithiasis were the early castration of the animals and the fact that salt was not added to the diet. To our knowledge, this is the first description of silica urolithiasis in the dromedary camel.
Narcolepsy associated with localized brain lesions is described in a 10-month-old Argentine Dogo. Neurological examination and MRI study suggested an inflammatory lesion of the left frontal lobe. Postmortem examination revealed diffuse encephalitis in the forebrain and marked necrotic lesions in the ventral pontine area. Immunohistochemistry for distemper virus antigen showed positive staining of the cytoplasm of many neurones of the pons and cerebral cortex. The pathological pattern was suggestive of post-vaccinal distemper encephalitis and the localization of the lesions was consistent with the neurological syndrome shown by the animal. At any event, the possibility of coincidental findings of distemper encephalitis and idiopathic narcolepsy must be accounted for.
Spiramycin (SP), oxytetracycline (OTC) or sulphamonomethoxine (SMM) was fed to laying hens at a dietary level of 400 p.p.m. for 7 successive days. After 7 days of medicated feed, the concentrations of SP, OTC and SMM were determined in the blood, liver, ovary, oviducts (magnum and isthmus plus shell gland) and eggs (albumen and yolk) by high-performance liquid chromatography. Of the three drugs, OTC showed the lowest content in the above tissues and eggs, while the reverse was true for SMM. Low concentrations of SP were measured in the blood, whereas contents in the liver and the oviducts were relatively much higher.
In order to study the influence of portal lipid loading on the extraction rate of bile salts by the liver, four cholecystectomized calves (mean body weight 103 kg) were fitted with permanent cannulae to the common bile duct, duodenum and portal vein. A venflon catheter was also set up in the jugular vein to collect blood for analysis of fatty acids (FA) and bile salts (PBS) in plasma. The experiments were divided into two parts. In the first part sodium taurocholate (TCHNa) was infused for at least 2 h at a rate of 25 mumol/min into the duodenum to stabilize the bile flow and bile salt output in bile and the concentration in plasma. In the second part, as well as TCHNa, Intralipid (Itlp) (infusible 10% of lipid compounds) was also infused into the portal vein. Itlp was infused for 40 min, starting at a rate of 3 ml/min at the beginning of the 3rd hour of TCHNa infusion followed by a rate of 6 ml/min at the beginning of the 4th hour of TCHNa infusion. During TCHNa infusion the plasma bile salt concentrations were in the range 15.69-20.21 mumol/l, similar to that of the pre-infusion period. Introduction of Itlp to the infusion of TCHNa resulted in a significant (P < 0.05) increase of PBS, about 2 times higher at an Itlp infusion rate of 3 ml/min, and 3 times higher (62.82 +/- 16.42 mumol/l) at 6 ml/min. Under Itlp infusion, all common plasma FA increased, but the largest increases were in levels of linolenic, palmitic and oleic acids. During TCHNa infusion, the bile flow and the content of bile salts in bile did not change. The infusion of TCHNa with Itlp at the rate of 6 ml/min caused a 2-fold decrease both of the bile flow and of the output of bile salts from 18.58 +/- 3.04 microliters/min/kg and from 0.58 +/- 0.07 mumol/min/kg observed at the beginning of both infusions to 9.51 +/- 2.95 microliters/min/kg and 0.28 +/- 0.05 mumol/min/kg, respectively, at the end of the collecting period. When only TCHNa was infused, almost all of it was secreted to the bile, while with the additional infusion of Itlp only about half of the infused TCHNa was secreted to the bile. These results indicate that the extraction rate of PBS by the liver is decreased by loading of the portal blood by lipids, allowing more bile salts to escape into the systemic circulation, and thus reducing bile production.
The aim of this study was to clarify the triggering mechanism of lipolysis in adipose tissue during feed withdrawal in pigs. Evaluation of blood samples drawn via an intravenous catheter from 10 growing pigs fasted for 60 h demonstrated, in addition to a haemodilution, a significant rise in plasma levels of non-esterified fatty acids (250 +/- 37 to 1427 +/- 144 mu mol/l) and free glycerol (98 +/- 27 to 232 +/- 41 mu mol/l) within 48 h of feed restriction, and thereafter the concentrations levelled off. The pigs also showed a significant decrease in plasma levels of glucose (6.01 +/- 0.20 to 4.62 +/- 0.12 mmol/l) within 48 h of fasting, followed by repeated increase until the end of the experimental period. A significant decrease in plasma insulin-like growth factor I (84 +/- 13 to 65 +/- 7 ng/ml) was observed after 16 h, which continued during the whole period of feed withdrawal However, no significant changes in plasma levels of adrenaline and noradrenaline during the period of increased lipolysis were detected. Therefore, the observed stimulation of lipolysis in growing swine during fasting is not the result of an increase in plasma concentration of catecholamines.
A panel of specific antibodies against CD3, CD4, CD5, CD8, MHC I and II was used in single and two colour flow cytometry to define T cell subpopulations in bronchoalveolar lavage fluid of horses affected with chronic obstructive pulmonary disease and of healthy controls. According to the results of the clinical examination including bronchoscopy and cytology of the tracheal aspirate the horses were divided into four groups (healthy, subclinically to mildly affected; moderately affected, and severely affected). All groups of horses had a similar percentage of CD3+ cells in the BALF. Compared to controls, severely affected horses had a significantly increased number of CD4+ cells in the BALF, but a similar percentage of CD4+ cells whereas mildly and moderately affected horses had a decreased percentage. The percentage and number of CD8+ cells and the percentage of CD8+/MHCII+ cells in the BALF was found to be higher than normal and varied according to the disease state. This novel finding raises the possibility that not only the CD4+ cells but also the CD8+ cells are involved in the pathogenesis of COPD. The percentage and the number of CD8+ cells in BALF might be of diagnostic value to detect subclinical to mild cases of COPD.
The in vitro effects of the ketone bodies beta-OH-butyrate (2.4 or 4.8 mmol/l) and acetoacetate (2.4 or 4.8 mmol/l) on the uptake of latex particles (1.09 microns) and chemotaxis were investigated in ovine neutrophils. Because the acetoacetate used was a lithium salt, the effect of 2.4 or 4.8 mmol/l lithium chloride was also tested. Neutrophils from eight non-lactating, non-pregnant ewes were studied. The uptake of latex particles, as measured by a spectrophotometric method, showed wide individual variation. The phagocytotic activity was unaffected by 2.4 mmol/l ketone bodies and LiCl, but it was significantly inhibited by 4.8 mmol/l beta-OH-butyrate and activated by 4.8 mmol/l LiCl. The latter result could be masking an inhibitory effect of acetoacetate. Chemotactic movements of neutrophils, as evaluated in a modified Boyden chamber using homologous zymosan-activated serum (ZAS) as a chemoattractant, were slightly but significantly reduced by a 2.4 mmolar concentration of the ketone bodies, administered singly or simultaneously, and by LiCl. We conclude therefore that the inhibitory effect of lithium-acetoacetate could be due to its lithium component. The 4.8 mmol/l dose of acetoacetate and beta-OH butyrate significantly decreased chemotaxis only when both compounds were added simultaneously. No effect of 4.8 mmol/l LiCl was observed. These results suggest that ketone bodies, in particular beta-OH butyrate, could directly influence particle uptake and chemotaxis in neutrophils. Although other factors could decrease the efficiency of the immune system in ketotic ruminants, the effects of the ketone bodies on neutrophils functions may explain the high frequency of infectious disease during 'ketotic syndrome'. The immunomodulatory effect of lithium needs to be evaluated further and it should be considered when testing lithium compounds.
Sixteen dairy cows were studied to assess the status of the natural antioxidant vitamin E and lipid peroxidation in their livers. Cows with liver failure (n = 7) showed clinical signs of a hepatic encephalopathy and had the following values of selected blood indices: AST > 80 U/l and GLDH > 15 U/l in serum, and venous plasma ammonia > 35 mmol/l. The control group (n = 9) consisted of dairy cows which were recovering from surgery (omentopexy) and were free of any health complications. Blood was analysed for alpha-tocopherol, aspartate aminotransferase, glutamate dehydrogenase, gamma-glutamyl transferase, total bilirubin, ammonia, cholesterol, albumin, free fatty acids, glucose, and beta-hydroxybutyrate. Alpha-tocopherol, triglyceride and malondialdehyde were measured in wet liver tissue. The cows with hepatic failure were clearly low in alpha-tocopherol and had significantly lower (P < 0.01) plasma alpha-tocopherol than the controls. Both liver triglycerides and MDA were higher (P < 0.05) in the cows with fatty livers. It is concluded that the cows with liver failure had an increase in the intensity of hepatic lipoperoxidative processes and a low antioxidative status, which should be taken into consideration in cases where treatment of the disease is proposed.
Perinatal death is one of the major causes of calf mortality in Japanese Black beef herds. A series of experiments were carried out to determine causes of perinatal calf mortality in a region of northern Japan. An aetiological survey revealed that the incidence of perinatal mortality in 6475 calves was 4.5% and the majority of neonatal deaths were caused by weak calf syndrome. The weak calves delivered after a normal gestation period had a significantly lower body weight at birth than normal calves (P < 0.01), indicating growth retardation in the uterus during pregnancy. Haematological and histopathological examinations showed that the weak calves had anaemia characterized by a significant decrease of blood cell values and bone marrow hypofunction. The anaemia due to bone marrow hypofunction presumably caused intrauterine growth retardation of the foetus. Dams delivering the weak calves showed significantly lower serum concentrations of estrone sulphate during late pregnancy than those with normal calves (P < 0.01), indicating foeto-placental dysfunction as a possible cause of growth retardation. Effects of sires as well as the maternal family on the incidence of neonatal death and on the rate of weak calves in dead neonates were found in the survey. Intrauterine growth retardation associated with anaemia may be the most important cause of weak calf syndrome in Japanese Black beef calves. The bull and maternal family may also have an influence on the incidence of neonatal death.
The accuracy of ageing mini-Shetland ponies and donkeys was assessed by correlating the appearance of specific dental features with the known ages of 106 mini-Shetland ponies and 63 donkeys. The ages of the animals ranged between 2 days and 26 years. In both species the eruption of the deciduous and permanent incisors occurred later than in horses. On the other hand, the appearance of the dental stars on the permanent incisors of mini-Shetlands and donkeys was seen at a younger age than in horses. As in most horse breeds, the disappearance of the cups, the clinical crown lengths, the presence of hooks on the upper corner and the presence of a Galvayne's groove are unreliable features for dental age determination in the pony and the donkey. Specific dental characteristics of both the mini-Shetland pony and the donkey are discussed.
A dot-blot assay for the detection of IgM antibodies (ABs) against canine distemper virus (CDV) in canine serum is described. The diagnostic potential of this technique was evaluated by analysing sera from three test groups: (i) specific pathogen-free (SPF) beagle dogs experimentally infected with virulent CDV; (ii) SPF dogs immunized with a combined vaccine containing CDV, and (iii) SPF dogs immunized with a CDV-free vaccine. As antigen for the dot-blot assay we used the recombinant nucleocapsid protein (N protein) of the virulent A75/17 CDV strain. All 12 dogs of group 1, infected with virulent CDV, showed detectable CDV-specific IgM levels in their serum. All dogs of group 2 were also positive for anti-CDV IgM after the first immunization with the CDV-containing vaccine. The four dogs immunized with a CDV-free vaccine (group iii) remained negative throughout the course of the experiment. From these results, we conclude that the IgM detection test, which requires only a single serum sample, is a useful method for diagnosing current or recent CDV infection in CDV-infected or CDV-immunized dogs under experimental conditions.
The enzymatic fundamentals of lipid metabolism of equine have not been thoroughly investigated at this point in time. It is still unclear why ponies in contrast to horses may become hyperlipaemic when coming negative energy balance. In this study, the activities of the triglyceride-cleaving key enzymes of ponies are large bred horses were investigated in order to obtain insight into the aetiology of the syndrome. The objective of the study was to measure the activities of hormone-sensitive lipase (HSL), lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) in ponies and horses in ex vivo in vitro assays. Norepinephrine (NE) stimulated pony adipocytes to release FFA in a linear fashion (4.57 +/- 2.09 nmol FFA.10(5) cells-1.min-1). This was not observed in horses. Lipolysis was significantly higher in fat cells of ponies than in horses when adenosine deaminase (ADA) and NE were added (12.71 +/- 3.12 vs. 1.96 +/- 1.22 nmol FFA.10(5) cells-1.min-1). Relative inhibition of lipolysis by the action of insulin was comparable in adipocytes of horses and ponies. However, absolute FFA release in pony fat cells was as high as the maximal NE and ADA stimulated lipolysis in horse adipocytes. Postheparin plasma lipase activities in ponies and horses did not differ between the sub-species. This finding was supported by the results obtained from measurement of LPL activity in adipose and muscle tissue showing only a tendency of increased activities in pony explants when compared to horse tissue incubations. This study further supports the hypothesis that differences in regulation of TG release from fat stores rather than clearance of TG from plasma is causative for the development of hyperlipaemia in ponies. Abbreviations used: ADA, adenosine deaminase; BW, body weight; FFA, free fatty acid; HSL, hormone-sensitive lipase; HTGL, hepatic triglyceride lipase; LPL, lipoprotein lipase; NE, norepinephrine; SDS, sodium dodecyl sulfate; TG, triglyceride; VLDL, very low density lipoprotein.
After 14C-labelled cortisol infusion in ponies and pigs, faecal samples were collected. Extraction of 0.5 g faeces with 5 ml 80-90% methanol yielded the highest radioactivity in the supernatant. Most of the metabolites were ether soluble. After high performance liquid chromatography (HPLC), the presence of immunoreactive metabolites was demonstrated by measuring each HPLC fraction using enzyme immunoassays for cortisol, corticosterone and 11-oxoaetiocholanolone. Only the assay for 11-oxoaetiocholanolone revealed peaks with co-eluting radioactivity. For biological validation of the test system, adrenocorticotrophic hormone (ACTH) and dexamethasone were injected intravenously successively in both species (n = 6). Cortisol concentration in blood and the 11-oxoaetiocholanolone immunoreactive substances in faeces were determined. In horse faeces, basal values of 2.3-35.2 nmol/kg were measured. After ACTH administration, an increase (more than 200% above basal values) of these metabolites was seen about 1 day after ACTH administration. After dexamethasone injection the levels decreased, reaching minimum concentrations 2 days after administration. In pigs, an increase in these metabolites was measured in only three animals after ACTH; dexamethasone did not cause a decrease. The stability of the samples after defecation was tested by storing samples from cows, horses and pigs at room temperature. It was shown that there was a significant increase in the concentration of measured cortisol metabolites in bovine, equine and porcine faeces after storage for 1 h, 4 h and 24 h, respectively. In frozen samples this effect was diminished after thawing samples at 40 degrees C; thawing the samples at 95 degrees C prevented an increase in immunoreactive substances.
The pathological alterations caused by Anoplocephala perfoliata in the ileocaecal junction of 28 equids slaughtered in an abattoir in Madrid (Central Spain) are described. The lesions were scored in grades based on the intensity of the damage and were related to the tapeworm number observed. The first grade (grade I) of alterations consisted of a slight enteritis associated with focal erosions observed in 43% of parasitized animals with low parasitic burden (1-26 tapeworms). The second grade (grade II) was a focal pseudomembranous enteritis, present in the ileocaecal junctions of 36% infected animals with moderate to high burden (23-188 tapeworms), and the third grade (grade III) was a regional necrotizing enteritis, present in the animals (21%) with the highest burden (72-248 tapeworms). The possible role of the lesions caused by this parasite in the aetiology of colic is discussed.
The effects of subarachnoid administration of the alpha 2-agonists xylazine and medetomidine on haemodynamic parameters in six adult goats were evaluated. Xylazine (0.05 mg/kg body wt) or medetomidine (0.01 mg/kg body wt) was administrated in the lumbosacral subarachnoid space. Mean arterial blood pressure and central venous pressure and electrocardiograms were monitored up to 120 min post-injection. Xylazine and medetomidine produced significant and comparable decreases in mean arterial blood pressure in the post-injection period. However, mean central venous pressure increased during this period. The ECG changes produced by these drugs were bradycardia and increased PR and QT intervals. The study suggested that both alpha 2-agonists depress haemodynamic parameters and produce comparable effects after subarachnoid administration.
