The effects of ACTH, prednisolone and Escherichia coli endotoxin on some clinical haematological and blood biochemical parameters in dwarf goats

ACTH (microgram kg-1 i.v.) and prednisolone (1 microgram-1 i.v.) caused a moderate but statistically significant inhibition of rumen contractions, whereas no effects on heart rate and body temperature were observed. Both hormones induced hyperglycaemia and leucocytosis, characterised by moderate lymphopenia and a profound increase in the number of circulating neutrophils. A significant decrease in plasma iron and increase in plasma zinc concentrations were observed. After 3 daily i.m. injections of ACTH (10 micrograms-1 day-1) decreases were seen in both serum Alkaline phosphatase (ALP) activity and plasma trace metal concentrations; heart rate was significantly higher. Intraveneous injection of E. coli endotoxin (0.1 microgram kg-1) caused shivering, fever, inhibition of rumen contractions, changes in heart rate, lymphopenia, neutropenia followed by neutrophilic leucocytosis, hypoferraemia, hypozincaemia, hypoglycaemia and a decline in serum ALP activity. ACTH, given i.m. for 3 days, reduced the febrile responses to E. coli endotoxin, modified the changes in heart rate, intensified the inhibition of rumen contractions, and induced a more marked decrease in the number of circulating neutrophils. ACTH pretreatment did not affect the endotoxin-induced decrease in blood glucose concentrations nor the drop in plasma zinc and iron values. These results suggest that glucocorticosteroids are not primarily involved in the fall in plasma iron and zinc concentrations during E. coli endotoxin-induced fever, the effects of endotoxin released glucocorticosteroids on white blood cells and blood glucose are masked by some other effect(s) of endotoxin, and in dwarf goats, ACTH has antipyretic properties without influencing normal body temperature. This effect is probably not dependent on adrenal cortical activity.     

The effects of ACTH,prednisolone and Escherichia coli endotoxin on some clinical haematological and blood biochemical parameters in dwarf goats

Summary

ACTH (μg kg ^‐1 i.v.) and prednisolone (1 μg^‐1 i.v.) caused a moderate but statistically significant inhibition of rumen contractions, whereas no effects on heart rate and body temperature were observed. Both hormones induced hyperglycaemia and leucocytosis, characterised by moderate lymphopenia and a profound increase in the number of circulating neutrophils. A significant decrease in plasma iron and increase in plasma zinc concentrations were observed.

After 3 daily i.m. injections of ACTH (10 μg ^‐1 day ^‐1) decreases were seen in both serum Alkaline phosphatase (ALP) activity and plasma trace metal concentrations; heart rate was significantly higher. Intraveneous injection of E. coli endotoxin (0.1 μg kg ^‐1) caused shivering, fever, inhibition of rumen contractions, changes in heart rate, lymphopenia, neutropenia followed by neutrophilic leucocytosis, hypoferraemia, hypozincaemia, hypoglycaemia and a decline in serum ALP activity. ACTH, given for 3 days, reduced the febrile responses to E. coli endotoxin, modified the changes in heart rate, intensified the inhibition of rumen contractions, and induced a more marked decrease in the number of circulating neutrophils. ACTH pretreatment did not affect the endotoxin‐induced decrease in blood glucose concentrations nor the drop in plasma zinc and iron values.

These results suggest that (1) glucocorticosteroids are not primarily involved in the fall in plasma iron and zinc concentrations during E. coli endotoxin‐induced fever, (2) the effects of endotoxin released glucocorticosteroids on white blood cells and blood glucose are masked by some other effect(s) of endotoxin, and (3) in dwarf goats, ACTH has antipyretic properties without influencing normal body temperature. This effect is probably not dependent on adrenal cortical activity.     

Endotoxin-induced fever and associated haematological and blood biochemical changes in the goat: the effect of repeated administration and the influence of flurbiprofen

Flurbiprofen, a potent non-steroidal anti-inflammatory and antipyretic agent, was given as an intravenous infusion (2 mg/kg) followed by a bolus injection of 1 mg/kg six hours later. After drug administration body temperature and rumen contractions were slightly depressed, whereas urea values gradually increased; serum sorbitol dehydrogenase (SDH) activity, plasma iron concentration and the number of circulating lymphocytes were significantly lower. Intravenous injection of endotoxin from Escherichia coli O111B4 (0.1 microgram/kg) caused shivering, fever, inhibition of rumen contractions, changes in heart rate, lymphopenia, neutropenia followed by neutrophylic leucocytosis, changes in urea values, hypoferraemia, hypozincaemia and a decline in serum alkaline phosphatase (ALP) activity, whereas gamma-glutamyltranspeptidase, glutamic oxalacetic transaminase, lactic dehydrogenase and SDH values were not significantly altered. Pretreatment with flurbiprofen completely abolished the febrile reactions to endotoxin. The endotoxin-induced inhibition of rumen contractions was only delayed. The drug blocked the initial tachycardia to endotoxin but did not prevent the secondary biphasic increase in heart rate. Flurbiprofen failed to modify the endotoxin-induced decrease in both plasma zinc and serum ALP activity whereas the decline in plasma iron concentration was delayed. After drug pretreatment the changes in circulating white blood cells were more pronounced. These data demonstrate that most of the haematological, blood biochemical and clinical effects of endotoxin cannot be blocked by flurbiprofen, and that these effects are not due to the increase in body temperature alone. Tolerance induced by repetitive daily intravenous administration of endotoxin resulted in an almost complete abolition of all the effects. However, the plasma iron values from tolerant goats were significantly lower than those from non-tolerant animals, which demonstrates that the development of a refractory state can result in modification of this biochemical parameter.     

Effects of pentoxifylline and polymyxin B on the acute-phase-response to Escherichia coli endotoxin in dwarf goats

The purpose of this study was to assess whether polymyxin B together with pentoxifylline, had beneficial effects on the acute-phase-response to E. coli endotoxin in the dwarf goat ( n  = 6). Polymyxin B partly neutralizes E. coli endotoxin by forming inactive polymyxin B-lipopolysaccharide (LPS) complexes; pentoxifylline has been reported to suppress the LPS-induced production of tumour necrosis factor (TNF-α). E. coli LPS (0.0067 μg/kg/min over 30 min) induced fever, tachycardia, inhibition of rumen motility, a decline in WBC, lymphopenia, and decreases in plasma zinc and iron concentrations. Most of the haematological, blood biochemical and clinical effects of E. coli LPS were significantly reduced by polymyxin B pretreatment (0.1 mg/kg/min over 30 min, i.v.). Pentoxifylline (0.3 mg/kg/min over 30 min, i.v.) did not reduce the clinical and blood biochemical effects of E. coli LPS, however, it modulated the number of circulating neutrophils. No synergistic effects were observed after i.v. infusion of polymyxin B with pentoxifylline. The lack of synergy may be due to the production and release of pro-inflammatory cytokines other than TNF-α.     

Anorexia during febrile conditions in dwarf goats. The effect of diazepam,flurbiprofen and naloxone

Summary

The most common sign of febrile diseases is anorexia, which develops at a time when adequate caloric and micronutrient availability may be critical. In order to study the relationship of fever and anorexia, feed intake in dwarf goats was studied under conditions of fever and antipyresis. Furthermore, experiments were done to establish whether a feed intake stimulant would override the anorexia during febrile conditions. Infection with Ehrlichia phagocytophila and i.v. injection of Escherichia coli endotoxin (0₁₁₁B₄, 0.1 μg/kg body weight) both resulted in increased rectal temperatures and significant reductions in feed intake. Administration of the antipyretic drug flurbiprofen (1 mg/kg) to febrile animals inhibited the temperature responses, but food intake was still suppressed. Diazepam (0.06 mg/kg), a feed intake stimulant, did not override the anorexia associated with fever. Blocking the febrile response of E. coli LPS‐injected goats with flurbiprofen plus diazepam or with flurbiprofen plus naloxone (0.1 mg/kg) did not antagonise their reduced feed intake either.

The effects of these drugs and of endotoxin on rumen motility adds an interesting aspect to their activities in the CNS, since the CNS has been shown to regulate various aspects of forestomach motility, which in turn could alter feeding behaviour. Moreover, our findings are consistent with the hypothesis that the suppression of feed intake might depend on the release of interleukin‐1.     

Anorexia during febrile conditions in dwarf goats. The effect of diazepam, flurbiprofen and naloxone

The most common sign of febrile diseases is anorexia, which develops at a time when adequate caloric and micronutrient availability may be critical. In order to study the relationship of fever and anorexia, feed intake in dwarf goats was studied under conditions of fever and antipyresis. Furthermore, experiments were done to establish whether a feed intake stimulant would override the anorexia during febrile conditions. Infection with Ehrlichia phagocytophila and i.v. injection of Escherichia coli endotoxin (0(111) B4, 0.1 microgram/kg body weight) both resulted in increased rectal temperatures and significant reductions in feed intake. Administration of the antipyretic drug flurbiprofen (1 mg/kg) to febrile animals inhibited the temperature responses, but food intake was still suppressed. Diazepam (0.06 mg/kg), a feed intake stimulant, did not override the anorexia associated with fever. Blocking the febrile response of E. coli LPS-injected goats with flurbiprofen plus diazepam or with flurbiprofen plus naloxone (0.1 mg/kg) did not antagonise their reduced feed intake either. The effects of these drugs and of endotoxin on rumen motility adds an interesting aspect to their activities in the CNS, since the CNS has been shown to regulate various aspects of forestomach motility, which in turn could alter feeding behaviour. Moreover, our findings are consistent with the hypothesis that the suppression of feed intake might depend on the release of interleukin-1.     

Pentoxifylline pretreatment fails to block the acute-phase response toEscherichia coli endotoxin in dwarf goats

The purpose of this study was to assess whether pentoxifylline, a drug that can inhibit the production and action of pro-inflammatory cytokines, had beneficial effects on the acute-phase response toE. coli endotoxin in the dwarf goat. First, the effects of 0.5 mg/kg per min pentoxifylline given intravenously over 15 min were examined in five goats. One week later, the clinical changes caused by i.v. injection ofE. coli endotoxin (LPS: 0.1 µg/kg) were determined. This endotoxin induced fever, tachycardia, inhibition of rumen motility, and decreases in plasma zinc and iron concentrations. Three weeks later, the effects ofE. coli LPS were again determined immediately after pentoxifylline infusion in the same group of animals. It was concluded that a pharmacological dose of pentoxifylline has no protective effects on the acute-phase response reactions induced by a pyrogenic dose ofE. coli LPS Abbreviations AMP adenosine phosphate - APR acute-phase response - GMP guanosine phosphate - IL interleukin - i.v. intravenous - LPS lipopolysaccharides - NO nitric oxide - POF pentoxifylline - r recombinant - SEM standard error of mean - TNF tumour necrosis factor     

Effects of intravenous infusion of lipopolysaccharide on plasma micromineral, magnesium, and cytokine concentrations and serum cortisol concentrations in lactating goats

OBJECTIVE: To assess the effects of various doses of lipopolysaccharide (LPS) administered IV on plasma microminerals, magnesium, tumor necrosis factor (TNF)-alpha, and interleukin (IL)-6 concentrations and serum cortisol concentrations in lactating goats. ANIMALS: 6 lactating goats. PROCEDURES: Goats were allotted to 3 LPS-treatment groups: control (0 microg/kg), low LPS (10 microg/kg), and high LPS (50 microg/kg). Rectal temperatures and behaviors of goats were recorded immediately before a 10-minute IV infusion of LPS and at 0.5, 1, 2, 4, 6, 8, and 24 hours after infusion. Blood samples were obtained before IV infusion and at 0.5, 1, 2, 4, 6, 8, and 24 hours after infusion. Plasma zinc, copper, iron, and magnesium concentrations were determined by atomic absorption spectrometry; plasma TNF-alpha and IL-6 concentrations were measured by use of an ELISA; and serum cortisol concentrations were determined by use of a radioimmunoassay. RESULTS: A monophasic fever developed in low-LPS and high-LPS groups. In the low-LPS and high-LPS group, plasma zinc concentrations decreased at 6 hours after infusion; compared with control groups. Plasma iron concentrations were lower at 24 hours after infusion in low-LPS and high-LPS groups than in the control group. Plasma TNF-alpha and IL-6 concentrations were higher in low-LPS and high-LPS groups than in the control group at 1, 2, and 4 hours after infusion. In low-LPS and high-LPS groups, serum cortisol concentrations increased from 0.5 hours onward and peaked at 1 (high-LPS group) and 2 (low-LPS group) hours after infusion. CONCLUSIONS AND CLINICAL RELEVANCE: Following IV infusion of LPS, the immune system is activated, which might affect micromineral homeostatic regulation and, subsequently, the metabolic health of lactating goats.     

Haematological changes in buffalo calves inoculated with Escherichia coli endotoxin and corticosteroids

Haematological studies were conducted on 10 clinically normal water buffalo calves to determine leucocytic responses to Escherichia coli endotoxin, prednisolone and dexamethasone. Intravenous injection of 10 micrograms endotoxin induced minimal decreases in leucocyte numbers, whereas 20, 50 and 100 micrograms produced a marked leucopenia within one hour. Moderate to marked leucopenia, neutropenia and lymphopenia persisted for three to 14 hours. Significant rebound neutrophilia was evident at six to eight hours after inoculation in calves given only 10 and 20 micrograms. Intramuscular injection of prednisolone (100 mg) and dexamethasone (5 mg) produced increases in total leucocyte counts and neutrophil numbers within two hours. Moderate to marked leucocytosis and neutrophilia persisted for eight to 24 hours. Lymphocyte response was unlike that in other species in that lymphopenia was not a consistent feature of the corticosteroid response. A transient monocytosis was seen following administration of prednisolone but not of dexamethasone, while eosinopenia and basopenia developed in both cases. In conclusion, endotoxin and corticosteroid induced changes in total and differential leucocyte counts in water buffalo were largely similar to those seen in cattle.     

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.     

Pharmacokinetics of gentamicin following single dose intravenous administration in normal and febrile goats

A pharmacokinetic study of gentamicin (5 mg/kg intravenous (i.v.)) was conducted first in cinically healthy female goats and then in the same goats after induction of fever by Escherichia coli endotoxin (0.2 μg/kg i.v.). Rectal temperature increased 1 to 1.5°C in febrile goats. Differences in the blood serum concentrations of gentamicin were not observed at any time between febrile and normal goats. The disposition kinetics of gentamicin were described by a biex-ponential expression C_P= Ae^-αt+ Be^-β. Median values for the half-lives of gentamicin were 103.6 min in normal and 136.0 min in febrile goats. The apparent volume of distribution (V_d) was 263.3 ml/kg in the febrile goats which was not different from that in the normal goats (240.6 ml/kg). The volume of the central compartment (V_c) was almost identical in normal and febrile goats. The body clearance (Cl_β) was observed to be 1.7 and 1.6 ml/min-kg in normal and febrile goats, respectively. Dosage regimens for gentamicin were calculated on the basis of median kinetic data.     

Influence of Escherichia coli endotoxin-induced fever on the pharmacokinetic behavior of marbofloxacin after intravenous administration in goats

The pharmacokinetic behavior of marbofloxacin was studied in seven healthy goats and in the same goats with induced fever after single-dose intravenous (i.v.) administration of 2 mg/kg b.w. Fever was induced by the administration of Escherichia coli endotoxin. Drug concentration in plasma was determined by high-performance liquid chromatography (HPLC). Drug distribution was somehow altered by fever as febrile goats showed a volume of distribution at steady-state (Vss = 0.72 +/- 0.15 L/kg) lower than normal goats (Vss = 1.19 +/- 0.33 L/kg). The elimination of the drug was also modified. Total plasma clearance (Cl) decreased from 0.24 +/- 0.12 L/kg/h in healthy animals to 0.13 +/- 0.05 L/kg/h in animals with endotoxin-induced fever, which is related to an increase in the area under the plasma concentration-time curve (AUC). Consequently, mean residence time (MRT) was also slightly increased in sick animals (MRT = 5.28 +/- 00.99 and 6.09 +/- 01.45 h, in healthy and febrile animals, respectively).     

Some pharmacokinetic data of aditoprim and trimethoprim in healthy and tick-borne fever infected dwarf goats

Aditoprim (AP) is a new dihydrofolate reductase inhibitor, which is structurally related to trimethoprim (TMP). The pharmacokinetics of AP (10 mg/kg) and TMP (20 mg/kg) were assessed in healthy dwarf goats. Therapeutic efficacy against rickettsial infections was tested in tick-borne fever (TBF) infected goats. The animals were given TMP (n = 5) or AP (n = 5) by i.v. injection, and subsequently the drugs were administered orally (same groups, similar doses). Finally, both groups were infected with TBF and the i.v. experiment was repeated. Plasma concentration-time curves for both drugs followed first-order two-compartment decay. For TMP, mean t1/2 beta +/- SEM (h) was 0.84 +/- 0.06 (i.v. control) and 0.90 +/- 0.06 (i.v. infected), respectively, whereas for AP values of 8.00 +/- 0.31 (i.v. control) and 10.28 +/- 0.67 (i.v. infected) were obtained (P less than 0.05). Mean Vd beta +/- SEM values (l/kg) were 3.84 +/- 0.27 (i.v. control) and 4.07 +/- 0.85 (i.v. infected) for TMP (NS) and 7.02 +/- 0.63 vs 9.29 +/- 0.21 (P less than 0.05) for AP. After i.v. injection, rumen fluid concentrations of AP were significantly (P less than 0.05) higher and more persistent than those of TMP. For AP, the plasma and rumen fluid concentrations at 3 h were 1.20 +/- 0.06 micrograms/ml and 0.85 +/- 0.17 microgram/ml, respectively. After oral administration of TMP, Cmax in plasma was 0.12 +/- 0.01 microgram/ml and the maximum was reached after 1.2 +/- 0.16 h; systemic bioavailability (F) was 10.3% (relative to AUC i.v.). Oral treatment with AP resulted in a Cmax value of 0.21 +/- 0.02 microgram/ml with Tmax of 22.5 +/- 1.65 h and a F value of 71%. Based on WBC, serum ALP and rectal temperature responses, it was concluded that both TMP and AP were inactive against Ehrlichia phagocytophila.     

Partial prostaglandin-mediated mechanism controlling the release of cortisol in plasma after intravenous administration of endotoxins

In a first series of experiments we studied the influence of E. coli endotoxins or lipopolysaccharides (LPS) administered either intravenously (i.v.) or intramammarily (i.mam.) to lactating goats on plasma cortisol and rectal temperature (RT). Differences in the magnitude of the cortisol release and shape of the fever curve were observed. In both models maximal pyrexia and fever index (FI) were comparable.

In a second series of experiments the influence of LPS on the plasma cortisol and RT was studied after i.v. injection of increasing doses of LPS : low (25 ng/kg), moderate (200 ng/kg) and relatively high (500 ng/kg). Although the cortisol response was dose dependent, the effect was not correlated with FI. The administration of flurbiprofen, a non steroidal anti-inflammatory drug (NSAID), resulted in a complete inhibition of fever at all LPS doses and the cortisol release after administration of low doses LPS. This indicates a prostaglandin mediation. With moderate and high doses LPS the cortisol release was only partially inhibited and delayed suggesting a non prostaglandin mediated mechanism.

In a third series of experiments the influence of flurbiprofen on fever and cortisol release was studied after i.mam. LPS administration. The observed increase of plasma cortisol and RT were completely abolished after flurbiprofen treatment.

It is concluded that: 1) the increase of plasma cortisol after LPS administration in lactating goats is not related to hyperthermia per se, 2) the control of fever and cortisol release may, to some extent, differ according to the LPS dose and method of administration, 3) the cortisol release observed after moderate and high doses of LPS is probably controlled by two phenomena. The first being induced by cyclo-oxygenase metabolites, the second by intermediary mediators other than prostaglandins or by LPS itself. 4) Although an eight-fold higher dose of LPS was given i.mam., a cortisol release comparable to the lowest dose of LPS (25 ng/kg) was observed. These differences in cortisol release can be ascribed to 1) a detoxification of LPS at the level of the mammary gland or 2) a slower resorption of LPS from the mammary gland.     

The effect of induced fever on the biokinetics of norfloxacin and its interaction with probenecid in goats

The kinetic profiles of norfloxacin were evaluated in afebrile, febrile and probenecid pre-treated (70 mg/kg orally) febrile goats after a single intravenous (i.v) dose (5 mg/kg). Fever was induced and maintained for 12 h by injecting Escherichia coli endotoxin (0.2 g/kg, i.v.) and repeating it in half the dose (0.1 g/kg) 5 h later. The plasma pharmacokinetic values for norfloxacin were best represented using a two-compartment open model. The peak norfloxacin plasma level of 90.52±3.18 g/ml attained in the probenecid pre-treated febrile goats was higher than that in the febrile (75.46±0.72 g/ml) or afebrile goats (62.25±1.23 g/ml). Cl_B and K _el values were significantly (p<0.01) decreased in febrile compared with afebrile goats. These values were further reduced in febrile goats after probenecid pre-treatment. However, t _1/2 was not affected by the fever-probenecid interaction. Norfloxacin may be used as an infusion with probenecid in caprine diseases where very high plasma levels are required to combat resistant organisms such as Bacteroides.Abbreviations MIC minimum inhibitory concentration - LPS lipopolysaccharide - i.v. intravenous(ly)     

Effects of dopamine receptor agonists on food intake and rumen motility in dwarf goats

Kaya, F., Van Duin, C.T.M. & Van Miert, A.S.J.P.A.M. Food intake and rumen motility in dwarf goats. Effects of some dopamine receptor agonists. J. vet. PharmacolTherap, 17 , 120–126. In ruminants, the dopaminergic regulation of feeding behaviour has not been investigated. Therefore, the effects of dopamine receptor agonists and antagonists on food intake and forestomach motility were studied in dwarf goats Goats treated i.v. with bromocriptine (1 μg or 2.5 μg/kg body wt/min during 10 min) ate less food than when treated with saline. This inhibitory effect on food intake could not be prevented by the peripheral dopamine receptor antagonist domperidone (0.5 mg/kg body wt i.v.). In contrast, dopamine (i.v. 20 μg/kg body wt/min during 15 min), levodopa (i.v. 40 μg/kg body weight during 10 min), apomorphine (i.v. 2 μg/kg body wt/min during 10 min) and lisuride (i.v. 0.2 μg/kg body wt/min during 15 min and 0.5 μg/kg body wt during 10 min) failed to modify food intake. Given in association with benserazide, a decarboxylase inhibitor (i.v. 20 μg/kg body wt/min during 10 min), levodopa was still inactive as an anorectie agent. Levopoda, bromocriptine and lisuride administered at similar dose rates to those which were used in the food intake experiments, induced some clinical signs including inhibition of forestomach contractions. The inhibition of rumen contractions induced by these drugs was completely antagonized by domperidone pretreatment. These results, together with earlier in vivo and in vitro observations, suggest that the inhibitory effects of dopamine receptor agonists on forestomach contractions are due to interactions with peripheral dopaminergic receptors. The change in smooth muscle tension, which leads to a change in the signals transmitted via vagal afferents to the central nervous system, probably does not modify feeding behaviour in dwarf goats. Furthermore, i.v. infusion of lisuride induced rumination when the inhibition of the forestomach contractions was prevented by domperidone; this effect may involve α₂-adrenoceptor activation.     

Pharmacokinetics of carfentanil and naltrexone in domestic goats (Capra hircus).

Using a crossover study design, the pharmacokinetics of carfentanil and naltrexone after i.v., i.m., and s.c. administration were determined in eight domestic goats (Capra hircus). Serial blood samples were taken up to 120 hr after carfentanil administration, and the plasma drug concentrations were determined using liquid chromatography and mass spectroscopy. All goats were immobilized with 40 microg/kg carfentanil i.m., although the resulting neurologic effects varied considerably. Plasma profiles showed rapid carfentanil absorption and a simple biphasic decline for 12-48 hr. Naltrexone given at 100 mg naltrexone/mg carfentanil 30 min after carfentanil administration produced rapid reversal of immobilization after all routes of administration. Variable fluctuations in the naltrexone plasma concentrations during the first 2.5-3.5 hr were observed, followed by a more consistent biphasic decline. The time to standing was significantly shorter after i.v. compared with s.c. naltrexone, although the time difference (1 min) had little clinical relevance. No statistically significant differences between the naltrexone pharmacokinetic parameters measured for the three routes of naltrexone administration were identified, although the recoveries after i.m. administration were, subjectively, the smoothest. The carfentanil half-life did not differ significantly in the goats given naltrexone by different routes. Although it is currently recommended that the naltrexone dose be divided into s.c. and i.v. portions, this practice does not appear to offer any benefit.     

Effects of Ehrlichia phagocytophila infection on serum thyroid hormone concentrations and on antipyrine clearance and metabolite formation in dwarf goats.

The influence of infection with Ehrlichia phagocytophila (EP) on serum thyroid hormone concentrations and on antipyrine (25 mg/kg of body weight, IV) plasma elimination and urinary metabolite excretion was studied in castrated male dwarf goats. Mean thyroid hormone concentrations moderately decreased in EP-infected goats, with maximal decrease in total and free triiodothyronine and thyroxine serum concentrations of 56, 64, 23, and 19%, respectively. The estimated pharmacokinetic values of antipyrine (AP) in EP-infected goats were similar to those in the goats when healthy. However, glucuronidation of the AP-metabolites 3-hydroxymethyl-AP, 4,4'-dihydroxy-AP, and 4-hydroxy-AP was reduced during the febrile episode of the acute-phase response to EP infection.     

内毒素血症山羊体征变化及氨基胍对其影响

将22只山羊随机分为5组，即对照组、内毒素血症模型组（内毒素LPS1800EU／kg）、内毒素血症氨基胍组（AG25mg／kg）、大剂量内毒素血症模型组（内毒素LPS5400EU／kg）和大剂量内毒素血症氨基胍组。肉眼观察动物精神状态和粪便的变化；用体温计检测直肠体温；用听诊器记录呼吸频率。结果表明：实验后1～9h，大、小剂量的内毒素（LPS）均使山羊表现出不同程度的精神不振、腹泻、食欲废绝。体温显著升高（P〈0．05），24h后体温恢复正常（P〉0．05）；但氨基胍对内毒素血症时体温的变化无调理作用（P〉0．05）。小剂量LPS和氨基胍对呼吸频率无影响（P〉0．05）；大剂量LPS却显著增加了山羊呼吸频率（P〈0．05），同时氨基胍也显著阻止了呼吸频率的升高（P〈0．05）。揭示体温、呼吸与内毒素剂量存在依赖关系；小剂量的氨基胍（25mg／kg）对内毒素血症时体温变化没有影响，但可明显减少呼吸频率。     

Ruminal excretion of sulfadimethoxine and sulfadimethyloxazole in goats and their influence on some enzyme activities and renal clearances

Five clinically health goats were injected with sulfadimethoxine and sulfadimethyloxazole in a single dose of 100 mg/kg b. wt. by intravenous route. Highest concentration levels of sulfadimethoxine and sulfadimethyloxazole in rumen were detected 1 hour following intravenous injection, then the concentration for both compounds declined at 12 and 8 hours post administration, respectively. In addition, both types of sulfonamide completely disappeared in ruminal fluid samples taken after 24 and 12 hours, respectively. The rate of acetylation for sulfadimethoxine and sulfadimethyloxazole were nearly similar and occurred to a high extent in ruminal fluid (22.95 and 23.72%, respectively). On the other hand, both tested drugs increased significantly the ruminal gas production from the first to eight hours after i.v. injection in goats. Changes in the serum enzyme activities (SGOT, SGPT and alkaline phosphatase) observed with sulfadimethoxine and sulfadimethyloxazole, and represented by a significant decrease in the activity of SGOT and SGPT level, alkaline phosphatase 4 hours sulfadimethoxine and in GOT/GPT ratio 24 and 48 hours after i.v. injection, respectively. The creatinine clearance was significantly decreased after 4 hours following the i.v. administration of sulfadimethoxine and sulfadimethyloxazole in goats.