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11.
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.  相似文献   
12.
Intravenous injection of endotoxin from Escherichia coli (0.01 μg and 0.1 μg per kg body weight), sodium nucleinate from yeast (5 mg and 10 mg per kg body weight) or Poly I: Poly C (15 μg and 30 μg per kg body weight) caused fever, changes in heart rate and stasis of the extrinsic ruminal contractions in conscious goats. It appears that ruminal stasis is associated with clinical and experimental fever. The febrile responses were abolished by the prior intravenous administration of flurbiprofen (2 mg per kg body weight), a potent non-steroidal anti-inflammatory and antipyretic agent. This agent, however, only had a partial antagonistic influence upon pyrogen-induced ruminal stasis. The secondary changes in heart rate were not prevented by the drug. It seems unlikely that the inhibition of the extrinsic ruminal contractions by exogenous pyrogens is due simply to a release of prostaglandins.  相似文献   
13.
Drug disposition, including hepatic drug metabolism, is markedly affected by infection, inflammation and other conditions that invoke the acute phase response. In the present study, an Escherichia coli lipopolysaccharide (LPS)-induced acute phase response model was developed in pigs. This model was used to study the effects of the acute phase response on drug disposition and hepatic drug metabolism in vivo and in microsomal preparations. The results obtained were compared with those from Actinobacillus pleuropneumoniae -infected pigs. Intermittent intravenous administration of LPS induced a mild acute phase response as evidenced by increased rectal body temperatures, anorexia and increased cytokine (TNF-α and IL-6) serum levels within 1-2 h after the first LPS injection. The acute phase response is associated with a pronounced decrease of antipyrine plasma clearance (control 8.5 ± 0.8 vs. LPS 2.2 ± 0.7 mL/min.kg). Furthermore, total cytochrome P450 content and microsomal cytochrome P450-dependent activities were significantly decreased after 24 h. The decrease in cytochrome P450 activities was accompanied by losses of cytochrome P4501A and P4503A apoproteins. The microsomal glucuronidation rate of 1-naphthol was not affected in LPS-treated pigs. Comparing the LPS model with our previous findings in the Actinobacillus pleuropneumoniae model showed a remarkable similarity with regard to the effects on hepatic drug metabolism.  相似文献   
14.
van't Klooster, G.A.E., Blaauboer, B.J., Noordhoek, J. & van Miert, A.S.J.P.A.M. Sulfadimidine metabolism in vitro: II. comparative studies in cultured rat, goat, sheep and cattle hepatocytes. J. vet. Pharmacol. Therap. 16, 454–461.
Hydroxylation and acetylation of sulphadimidine (SDD) and the deacetylation of N4-acetyl SDD was investigated in cultured hepatocytes from male and female rats, from male and female goats and from female sheep and cattle. Significant sex differences were observed for hydroxylation of SDD in hepatocytes from rat and goat. In goat, sheep and cow hepatocytes, the hydroxylation pathway is relatively important, whereas in rat hepatocytes, acetylation is predominant. Hepatocytes of all four species deacetylated N4-acetyl SDD. In ruminant hepatocytes, deacetylating activity was of considerable importance, whereas in rat hepatocytes, it appeared a minor pathway of metabolism. Similar to the in vivo situation, formation of N4-acetyl SDD in cultured hepatocytes results from an equilibrium of acetylation and deacetylation. A good correlation was found between results in isolated hepatocytes and previous findings in vivo , both in levels of species-related activities and in acetylation-hydroxylation ratios. In conclusion, cultured hepatocytes appear a useful in vitro model to study comparative sulfonamide metabolism.  相似文献   
15.
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16.
Goat ruminal strips reacted with an increase in smooth muscle tone after exposure to apomorphine. This rise in tone could be blocked by domperidone, but not by naltrexone. In vivo , both dopamine and apomorphine caused inhibition of extrinsic ruminal contractions. These effects were completely prevented by domperidone pretreatment, whereas naltrexone was not an effective antagonist. These results suggest that apomorphine-induced inhibition of rumen motility is due to DA-receptor activation. The exact location of these DA-receptors remains to be determined.  相似文献   
17.
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18.
In dwarf goats fasted for 2 h, i.v. administration of the benzodiazepine (BZ) agonists diazepam (60 micrograms/kg), brotizolam (2 and 4 micrograms/kg) and climazolam (100 micrograms/kg) induced hyperphagic effects, whereas i.v. injections of the BZ-antagonist flumazenil (R degrees 15-1788; 0.5 mg/kg), the anthelmintic ivermectin (0.1 mg/kg), the 5-HT2 antagonist ritanserine (0.1 mg/kg), ACTH (10 micrograms/kg) and prednisolone (1 mg/kg) were inactive in a 30-min feeding test. Both the BZ-antagonist R degrees 15-3505 (greater than or equal to 0.1 mg/kg) and the opiate receptor antagonist naloxone (0.1 mg/kg) had anorectic effects in dwarf goats given 30 min access to a palatable pelleted concentrate. The hyperphagic effects of climazolam and brotizolam were not antagonized by flumazenil, whereas similar doses of this drug completely reversed muscle incoordination and ataxia induced by much higher doses of these BZ-agonists. In the combination experiments with naloxone and BZ-agonists, naloxone antagonized the hyperphagic effects of both diazepam and brotizolam. Similarly, in the diazepam-R degrees 15-3505 study, there was a significant effect of diazepam and a significant inhibition of this effect by R degrees 15-3505 (50 micrograms/kg). In the diazepam-ivermectin combination experiment no evidence for drug potentiation was found. These results and the mode of action of the above mentioned drugs are discussed in relation to feeding behaviour.  相似文献   
19.
The biodegradation of chloramphenicol was studied by incubating the drug (at concentrations of 72, 48 and 24 micrograms/ml) with ruminal fluid samples from dwarf goats fed two different diets. Biodegradation of the drug was much faster in samples from animals which were fed with hay and concentrate than in those obtained from goats which were fed grass pellets only. Recently, it has been suggested that lysine-vasopressin injected intravenously induces closure of the oesophageal groove in cattle and goats. Therefore, the influence of lysine-vasopressin on the oral absorption of chloramphenicol (50 mg/kg body wt) was studied in dwarf goats, using two formulations of chloramphenicol. The results suggest that vasopressin failed to induce this reflex mechanism. Furthermore, the shapes of the plasma concentration-time curves after oral administration of chloramphenicol palmitate and chloramphenicol dissolved in propylene glycol were markedly different. Possible mechanisms for the observed differences are discussed.  相似文献   
20.
Sulphadimidine (20 mg/kg i.v.) plasma elimination and metabolite formation were studied in intact male, castrated male, and female dwarf goats. Plasma pharmacokinetics and urinary metabolite patterns were first studied in un-treated animals. Afterwards, females and castrates were treated with a combination of testosterone-propionate (1 mg/kg) and 17P-oestradiolbenzoate(0.02 mg/kg) once every 3 days, for a period of 4 weeks. In untreated animals, males showed a considerably lower plasma clearance than females or castrates. This was accompanied by lower partial clearances for the production of two hydroxylated sulphadimidine metabolites. After hormonal treatment of females and castrates, sulphadimidine plasma clearance was significantly reduced, to values corresponding with those observed in control males. Furthermore, hydroxylation was significantly inhibited after treatment. The results indicate that sulphadimidine hydroxylation in the goat is performed by enzymes of the cytochrome P450 complex which are strongly influenced by gonadal hormones. Androgens seem to play a central role in this respect.  相似文献   
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