Hepatic serine and alanine metabolism during endotoxin-induced fever in sheep.

Time course changes in plasma amino acid concentrations and the hepatic metabolism of serine and alanine were measured in six mature wethers during endotoxin-induced fever. In separate trials, the animals' responses to injections of saline and endotoxin were measured. The endotoxin was from Escherichia coli serotype 055:B5 and was injected intravenously (4 micrograms/kg body weight). Liver biopsies were obtained from the sheep at 6 h postinjection during both endotoxin and saline injection trials. Rectal temperature in the endotoxin treated animals was increased (P less than 0.05, above that in control animals from 4.25 h to 9 h postinjection, with a maximum rise of 2.43 degrees C at 5.5 h postinjection. Glucose concentration in jugular plasma decreased (P less than 0.05) by 3 h postinjection and remained depressed throughout the 24 h postinjection sampling period. Plasma serine concentration was decreased (P less than 0.05) by 3 h postinjection. Plasma alanine concentration was decreased significantly (P less than 0.05) only at 24 h postinjection. Endotoxin injection increased (P less than 0.05) hepatic oxidation of 14C-serine (162%) and the net incorporation of 14C-serine carbon into hepatic protein (173%) and glycogen (275%). The net incorporation of 14C-alanine carbon into hepatic protein (172%) and glycogen (323%) were increased (P less than 0.05) by endotoxin injection, while alanine oxidation was not affected by endotoxin treatment (P greater than 0.05). The increased hepatic use of serine may explain, in part, the dramatic decrease in plasma concentrations of this amino acid following endotoxin injection into sheep.     

Cell-mediated Hypersensitivity to Pasteurella hemolytica in Normal and Cold-stressed Mice

Mice infected with Pasteurella hemolytica developed cell-mediated hypersensitivity manifested by inhibition of macrophage migration but not by delayed skin reactions, to two antigen preparations from this organism. Relative to migration by the cells of uninfected animals, migration by cells from infected animals was inhibited to the same degree whether or not the animals were chilled. However, the cells from infected chilled animals were not able to migrate as far as the cells from normal mice even in the absence of antigen.     

Time course changes in blood metabolites during endotoxin fever in sheep.

Time course changes in the concentration of plasma amino acids, glucose, insulin, and creatinine were measured in seven mature sheep during fever induced by Escherichia coli (serotype 055:B5) endotoxin. Rectal temperature was increased above that recorded in control animals from 0.75 to 6.25 h postinjection with a maximum rise of 2.3 degrees C. Total amino acid concentrations decreased (P less than 0.05) 4.5 h postinjection and remained depressed (P less than 0.05) until 19 h postinjection. The plasma concentration of each individual amino acid decreased (P less than 0.05) at some point during the experiment with the exception of tryptophan and tyrosine. Glucose concentration decreased (P less than 0.05) and remained depressed until at least 55 h postinjection. Plasma insulin concentration was elevated (P less than 0.05) from 4.5 to 13 h postinjection. Plasma creatinine concentration increased during fever (P less than 0.05) and returned to normal by 31 h postinjection.     

Pharmacokinetics of antipyrine and trimethoprim in pigs with endotoxin-induced fever

Oral administration of antipyrine or trimethoprim to normal and endotoxin-pretreated, febrile pigs resulted in pharmacokinetic parameters which were different in the two groups of pigs. The one-compartment model with first order absorption rate constant can be used to describe the pharmacokinetics of antipyrine and trimethoprim in normal pigs but cannot satisfactorily describe the plasma concentration versus time data in the febrile pigs. The absorption rate and the elimination rate of antipyrine and trimethoprim are reduced in the febrile pigs whereas the volume of distribution is increased.     

The role of prostanoids and nitric oxide in endotoxin-induced hyporesponsiveness of equine digital blood vessels.

Endotoxin has been implicated in the pathophysiology of acute laminitis. The aim of this study was to examine the direct effects of endotoxin on isolated equine digital blood vessels. Equine digital veins (EDV), incubated in Krebs-Henseleit solution containing lipopolysaccharide (LPS) (1 microg/ml) became hyporesponsive to 5-HT after 16 h. Cycloheximide and ibuprofen blocked this effect of LPS and increased the maximum response obtained to 5-HT when compared to control vessels. L-nitroarginine methyl ester (L-NAME) reversed the hyporesponsiveness caused by LPS. Vessels maintained in culture medium containing LPS also became hyporesponsive to 5-HT, an effect which was completely prevented by ibuprofen but only partially reversed by L-NAME. Measurements were made of 6-keto PGF1alpha and nitrite production by segments of equine digital artery and vein in culture medium alone or co-cultured with peripheral blood leucocytes. LPS did not stimulate nitrite production from vessel segments but increased nitrite release from leucocytes, an effect which was inhibited by cycloheximide and L-NAME. Lipopolysaccharide increased 6-keto PGF1alpha production by blood vessels, an effect which was inhibited by cycloheximide and ibuprofen but not L-NAME. No synergistic effect on release of nitrite or 6-keto PGF1alpha was noted in co-cultures of blood vessels and leucocytes. These data suggest that induction of cyclo-oxygenase by LPS was a major cause of hyporesponsiveness of digital blood vessels to 5-HT. Release of nitric oxide was not detectable in LPS-stimulated blood vessels maintained in culture even in the presence of activated leucocytes yet L-NAME did protect against LPS-induced hyporesponsiveness indicating nitric oxide synthase induction may play some role in the effect of LPS. These findings are important in furthering our understanding of the pathophysiological mechanisms underlying the vascular changes which occur in acute laminitis.     

The Effect of Edema, Hydrocortisone Acetate, Concurrent Viral Infection and Immunization on the Clearance of Pasteurella hemolytica from the Bovine Lung

The influence of pulmonary edema, hydrocortisone, immunization against Pasteurella hemolytica and concurrent infection with parainfluenza-3 virus upon pulmonary clearance of aerosolized P. hemolytica was studied in 31 calves. Following the various treatments calves were challenged with an aerosol of P. hemolytica. One control calf was killed immediately after the aerosol and the numbers of bacteria in the lung taken as 100%. Two calves were killed four hours after challenge and the numbers of bacteria in the lungs were compared to the 100% of the control calf. The result was the percentage clearance of bacteria at four hours.

Pulmonary edema was induced by three different methods: by an aerosol of histamine, by intravenous injection of endotoxin and by intravenous injection of croton oil emulsion. The edema impaired the clearance of P. hemolytica, which was reflected in high numbers of P. hemolytica present in the lungs at four hours after challenge: 260% after histamine, 300% and 400% after endotoxin and 92% after croton oil.

Six days of treatment of four calves with high doses of hydrocortisone acetate produced inconsistent results: two calves treated with a higher daily dose (36 mg/kg) had normal clearance whereas two calves treated with a lower dose had pulmonary edema and displayed lowered clearance with 111% and 31% respectively of P. hemolytica retained in the lungs four hours after challenge.

Immunization of calves by three different methods, a subcutaneously injected bacterin of P. hemolytica (2 calves), single aerosol (2 calves) and four aerosols (4 calves) of live P. hemolytica was reflected in an accelerated pulmonary clearance of P. hemolytica (with a mean of 1.55% of bacteria retained at four hours).

Concurrent infection with parainfluenza-3 virus did not lower the clearance of P. hemolytica in the lungs of 12 calves over 15 days except on the first day following the exposure to parainfluenza-3 virus. These calves had hemagglutinating antibodies against P. hemolytica before exposure.

     

Partitioning of propofol between blood cells, plasma and deproteinised plasma in sheep

The partitioning of propofol within the blood, when administered in its usual emulsion carrier, has been determined in vitro in sheep. The blood:plasma ratio was found to be 1.13 and the blood-cell:plasma ratio 1.42. When oxalate was used as the anticoagulant, the plasma protein binding was calculated to be 92.6% - slightly lower than reported for dog, rat, rabbit and man. However, when heparin was the anticoagulant, the binding was significantly less, 83.0%. Differences from some results in the literature may be attributable to other workers using propofol without the lipid emulsion carrier. From the results of this study it is argued that anaemia and plasma levels of protein and lipid may affect propofol requirements.     

Assessment of serotonin in serum,plasma, and platelets of aggressive dogs

Canine aggression is the most common reason for the referral of dogs to behavior practices. In addition, dog bites represent an important problem for public health and animal welfare. The serotonergic system is believed to play an important role in modulating aggression. The aim of the present study was (1) to assess the suitability of different types of blood samples for measuring circulating serotonin in canine clinical studies, and (2) to investigate the relationship between the serotonergic system and canine aggression. The assessment of serotonin was simultaneously carried out in serum, plasma, and platelets of 28 aggressive and 10 nonaggressive dogs with an enzyme immunoassay technique. The mean serotonin concentration in aggressive dogs was significantly lower than in nonaggressive dogs in all the assayed samples. These findings suggest an inverse relationship between the activity of the serotonergic system and canine aggression. Considering the simplicity of the methodology, the authors propose sampling serum as the most suitable method for measuring circulating serotonin in dogs.     

Influence of Escherichia coli endotoxin-induced fever on pharmacokinetics of imidocarb in dogs and goats

The pharmacokinetics of imidocarb, administered as an IV bolus dose (4 mg/kg), was studied in normal and Escherichia coli endotoxin-induced febrile dogs and goats. In the febrile group, the drug was administered 1 hour after injection of the endotoxin. The plasma and urine concentrations of imidocarb were measured by spectrophotometry. The decline in plasma drug concentrations in both species was analyzed, using a 2-compartment open model. With the exception of the coefficient A and the volume of central compartment, E coli endotoxin-induced fever produced the same changes in kinetic determinants in both species. Fever significantly decreased the distribution rate constant in both dogs (P less than 0.05) and goats (P less than 0.01). The elimination rate constant and, in turn, the half-life were not altered by the endotoxin-induced fever in either species. The volume of distribution at steady-state was significantly lower (P less than 0.01) in the febrile dogs and goats. The body clearance of imidocarb was also significantly lower in the febrile dogs (P less than 0.05) and goats (P less than 0.01). The decreased apparent volume of distribution and lower body clearance of imidocarb could explain the higher plasma values of the drug in the febrile, compared with normal, animals.     

Effects of dipyrone on endotoxininduced fever, central nervous depression and hypoglycaemia in sheep

Sixteen sheep were divided into four groups and were given saline, Escherichia coli endotoxin at 35 micrograms/kg0.75, dipyrone at 88 mg/kg0.75, or endotoxin and dipyrone intravenously. Plasma glucose concentrations, rectal temperature and depression of central nervous function were assessed at hourly intervals for 10 h and again at 24 h. Dipyrone had no effect on normal sheep but in sheep given endotoxin, it blocked the febrile response and partially blocked the depression effect upon the central nervous system without affecting the hypoglycaemic response.     

Differential haematological effects of tick-borne fever in sheep and goats

Tick-borne fever (TBF) is a rickettsial disease of domestic and wild ruminants in temperate climates. It is characterized by high fever and severe leukopenia. In the present study, the possible difference in the severity of disease in sheep and goats was investigated by inoculating one group of eight goats and one group of eight sheep with the Old Sourhope (OS) strain of Ehrlichia (Cytoecetes) phagocytophila. All sheep and goats experimentally infected with E. phagocytophila reacted with fever and rickettsiaemia, but there were significant differences between goats and sheep in the severity of clinical disease, the duration and magnitude of fever, the magnitude of rickettsiaemia and the patterns of reduction in the number of total leucocytes. Sheep reacted with fever significantly earlier than goats and the febrile period lasted for a significantly longer period. In contrast, the magnitude of rickettsiaemia was significantly higher in goats than in sheep. Infection with TBF was characterized by a transient increase in the number of neutrophils, which was quickly followed by an acute reduction in the number of lymphocytes and a prolonged reduction in the number of neutrophils in both sheep and goats. In both groups of animals, infection with TBF was also characterized by significant reductions in the total number of red blood cells (RBCs), thrombocytes and packed cell volume (PCV) and the concentration of haemoglobin (Hb). However, the mean corpuscular volume (MCV) and mean corpuscular Hb (MCH) were significantly increased in sheep only.     

甘加藏羊发情周期腺垂体和血浆中GTH含量动态变化

为了探讨甘加藏羊发情周期腺垂体和血浆中FSH和LH含量动态变化规律及排卵的关系。选取2.5~5岁,健康未孕雌性甘加藏羊30只,采集发情周期各阶段和乏情期腺垂体和血浆,采用酶联免疫吸附试验(ELISA)测定发情前期、发情期、发情后期、间情期及乏情期腺垂体和血浆中FSH和LH的含量。结果表明,甘加藏羊发情周期内腺垂体FSH浓度在发情期(6.873IU/L)和发情后期(6.863IU/L)较低,与间情期最大(8.228IU/L)差异显著(P<0.05),发情前期又降低(8.096IU/L);腺垂体LH浓度发情期(9.39IU/L)和发情后期(9.585IU/L)较低,间情期最大(10.629IU/L),发情前期(9.7325IU/L)降低,各时期差异不显著(P>0.05);发情周期内血浆中FSH浓度在发情前期(2.599IU/L)达到峰值,其他时期均较低,发情前期与其他时期差异显著(P<0.05);血浆LH浓度在发情期(3.866IU/L)达到峰值,发情后期(3.179IU/L)和间情期(3.292IU/L)降低,各时期差异不显著(P>0.05);并且FSH和LH在发情周期内均出现4个波峰:乏情期腺垂体和血浆中FSH和LH的浓度均低于发情周期内FSH和LH各自的基础值。FSH和LH含量在垂体和血浆的这些差异性应该是两者协同调控藏羊发情和排卵的主要原因。     

Diurnal changes in plasma melatonin and the timing of reproductive onset in anestrous sheep fed melatonin.

Seasonally anestrous Suffolk ewes (n = 28) were randomly divided into 5 groups and treated with varying doses of melatonin as follows; Groups C (n = 4), M1 (n = 6), M2 (n = 6), M3 (n = 6), M4 (n = 6) of ewes were fed pellets containing 0, 1, 2, 3 and 4 mg melatonin, respectively, daily for 60 days from May 17 (Day 0). Following feeding of the pellets at 13.00 hr plasma levels of melatonin rapidly increased reaching the peak values within 30 min, which ranged from 92.0 to 292.7 pg/ml and were highly correlated with the dose of melatonin administered (r = 0.986, P less than 0.01). Maximum dose of melatonin (4 mg) produced an increase of plasma melatonin similar in magnitude to nocturnal peaks of endogenous secretion. The onset of ovulatory cyclicity, assessed from plasma progesterone profiles, was advanced by melatonin administration. The mean +/- SEM intervals from the commencement of melatonin treatment until the onset of ovulatory cyclicity were 53.0 +/- 5.8, 53.6 +/- 2.5, 42.0 +/- 5.6 and 44.3 +/- 4.3 days for the Groups M1, M2, M3 and M4, respectively, which were shorter (M1, P less than 0.05; M2, M3 & M4, P less than 0.01) than that for the Group C (72.5 +/- 1.4 days). The melatonin treatment also suppressed, in a dose related manner, the rise in plasma prolactin under the lengthening photoperiod. We conclude that the dose-related efficacy of melatonin could be ascribed to the difference in the diurnal profiles of circulating melatonin.