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C T Van Duin

Publications and source records attributed to C T Van Duin.

17 recordsLinked to original sources

Pentoxifylline pretreatment fails to block the acute-phase response to Escherichia 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 to E. 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 of E. coli endotoxin (LPS: 0.1 microgram/kg) were determined. This endotoxin induced fever, tachycardia, inhibition of rumen motility, and decreases in plasma zinc and iron concentrations. Three weeks later, the effect of E. 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 of E. coli LPS.

Acute-Phase Reaction↗

Effects of flurbiprofen on recombinant human IL-1 alpha-induced fever and associated clinical, haematological and blood biochemical changes in the dwarf goat.

Flurbiprofen, a potent NSAID, was given as an intravenous infusion (1 mg/kg) to dwarf goats. After drug administration, no significant changes were observed in heart rate and rumen motility, whereas rectal temperature increased slightly; mean plasma glucose and creatinine concentrations gradually increased during the observation period. Plasma iron concentration and the number of circulating lymphocytes were significantly lower after flurbiprofen infusion. Intravenous injection of recombinant human interleukin-1 alpha (r. HuIL-1 alpha: 0.5 microgram/kg) caused shivering, fever, inhibition of rumen contractions, tachycardia, hypoferraemia, hypozincaemia, hyperglycaemia followed by hypoglycaemia, changes in plasma urea and creatinine values, lymphopaenia and neutropaenia followed by neutrophilic leukocytosis. Pretreatment with flurbiprofen partly antagonized the febrile reactions to r.HuIL-1 alpha. The r.HuIL-1 alpha-induced tachycardia and inhibition of rumen contractions were only delayed. The drug prevented the initial hyperglycaemia but did not abolish the secondary hypoglycaemia. Furthermore, flurbiprofen delayed the decline in plasma zinc and iron concentrations, whereas plasma creatinine values were significantly lower. Finally, after drug pretreatment the changes in circulating neutrophils were more pronounced. These data demonstrate that most of the haematological, blood biochemical, and clinical effects of r.HuIL-1 alpha cannot be blocked by flurbiprofen, suggesting that an increased synthesis of prostaglandins is not involved in these r.HuIL-1 alpha-induced effects.

Animals↗

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

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 micrograms or 2.5 micrograms/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 micrograms/kg body wt/min during 15 min), levodopa (i.v. 40 micrograms/kg body weight during 10 min), apomorphine (i.v. 2 micrograms/kg body wt/min during 10 min) and lisuride (i.v. 0.2 microgram/kg body wt/min during 15 min and 0.5 microgram/kg body wt during 10 min) failed to modify food intake. Given in association with benserazide, a decarboxylase inhibitor (i.v. 20 micrograms/kg body wt/min during 10 min), levodopa was still inactive as an anorectic agent. Levodopa, 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.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The regulation of oxidative drug metabolism by growth hormone in the dwarf goat: differences from and similarities to the mechanisms in rats.

The effects of bovine GH (BST), administered in different dose patterns, on in-vivo oxidative drug metabolism, were studied in female dwarf goats. Animals received recombinantly derived methionyl BST at a dose of 500 micrograms/kg body weight per 24 h for 6 days. It was administered to one group of goats as one s.c. injection per day, another group received a similar 24-h dose divided into three s.c. injections given at 8-h intervals, and the third group received 50 micrograms BST/kg body weight every 2.5 h by a pulsative i.v. infusion. Oxidative metabolic capacity was assessed by determining plasma sulphadimidine (SDD) elimination and urinary metabolite excretion. SDD shows a marked sex-dependent plasma elimination in dwarf goats, with male goats having a lower plasma clearance than female goats. When BST was given by daily injection, no clear effects on SDD plasma clearance or urinary metabolite excretion were observed. However, when the total dose was divided into three injections given at 8-h intervals, the plasma SDD elimination rate decreased. This was associated with a decrease in urinary excretion of the two main hydroxy SDD metabolites. When BST was given by discontinuous i.v. infusion, simulating the male endogenous plasma GH pattern, a marked decrease in SDD plasma clearance was observed. In addition, the excretion of the two urinary hydroxy metabolites was considerably reduced. These results suggest that GH can affect drug oxidation in dwarf goats via mechanisms similar to those suggested for rats. However, in the dwarf goat, the sex differences in drug metabolism are opposite to those in rats.

Animals↗

Food intake and rumen motility in dwarf goats. Effects of some serotonin receptor agonists and antagonists.

The serotonergic regulation of feeding behaviour has not so far been studied in ruminants. Therefore, the effects of some serotonin (5-HT) receptor agonists and antagonists on food intake and forestomach motility were studied in dwarf goats. Goats ate less food when treated intravenously (IV) with the 5-HT precursor 5-HTP (25 micrograms, 50 micrograms or 100 micrograms kg-1 min-1 over 15 min) than when they were treated with 5-HT (which does not pass the blood-brain barrier) or with saline. Accordingly, IV dexfenfluramine infusions (50 micrograms or 100 micrograms kg-1 min-1 over 15 min), which induces release of brain 5-HT, also led to dose-related reductions in food intake. In contrast, no anorectic effects were observed after IV infusions with the selective 5-HT reuptake inhibitor fluoxetine (100 micrograms kg-1 min-1 over 15 min), the selective 5-HT1A agonist 8-OH-DPAT (0.5 micrograms kg-1 min-1 over 15 min), or eltoprazine (4 or 8 micrograms kg-1 min-1 over 15 min), a mixed 5-HT1A/5HT1B receptor agonist. None of the 5-HT antagonists tested gave any increase in food consumption in this model. Interestingly, the non-selective 5-HT receptor antagonist methysergide (360 micrograms/kg IV) reduced food intake. This effect was most noticeable at 3 h after injection. The 5-HT3 receptor antagonist ondansetron (IV 10 micrograms kg-1 min-1 over 15 min) and the peripheral 5-HT2 receptor antagonist xylamidine (IV 100 micrograms kg-1 min-1 over 10 min) failed to modify food intake. These results provide evidence for central serotonergic involvement in the control of feeding. However, this control system differs markedly in goats and rodents. Dexfenfluramine, 5-HTP and eltoprazine administered at similar dose rates to those used in the food intake experiments induced some clinical signs including inhibition of forestomach contractions. These results, together with our earlier in vivo and in vitro observations, suggest that the inhibitory effects of serotonin receptor agonists on forestomach contractions are due to interactions with both peripheral and central serotonergic receptors. The change in smooth muscle tension, which leads to a change in the signals transmitted via vagal afferents to the central nervous system, appears not to modify feeding behaviour in dwarf goats.

Animals↗

Fever and changes in plasma zinc and iron concentrations in the goat. The effects of interferon inducers and recombinant IFN-alpha 2a.

Inflammation or invasion by pathogenic micro-organisms induces systemic changes, collectively known as the acute phase response. Among the varied alterations that together produce this response are fever, hypoferraemia and hypozincaemia. It is likely that these responses are mediated, in part, by production and release of cytokines such as interleukin-1 (Il-1), interferons (IFN-alpha) and tumour necrosis factor (TNF). The present report describes a comparative study in dwarf goats on recombinant human IFN-alpha 2a (0.5 x 10(5) IU per kg intravenously (i.v.) and 0.5 x 10(6) IU per kg intramuscularly (i.m.], Poly I:Poly C (an interferon inducer; 30 micrograms per kg i.v.), Newcastle disease virus La Sota strain (an interferon inducer; 0.5 ml per kg i.v.) and Escherichia coli endotoxin (an Il-1 and TNF inducer; 0.1 microgram per kg i.v.). The i.v. injection of recombinant IFN-alpha 2a caused characteristic monophasic febrile reactions, but no significant changes in plasma zinc and iron concentrations. The temperature responses were not due to endotoxin contamination because polymyxin B, which blocks endotoxin, had no inhibitory effect on the pyrogenicity of IFN-alpha 2a. In contrast, the IFN-alpha 2a-induced fever was completely prevented by flurbiprofen pretreatment (1 mg per kg i.v.). In contrast to the i.v. administration, i.m. injection of IFN-alpha 2a caused fever, hypoferraemia and hypozincaemia. Similar results were obtained after E. coli endotoxin, NCD La Sota strain and Poly I:Poly C injection. However, the shapes of the temperature curves and the changes in trace metal concentrations were markedly different. These data support the theory that fever and the changes in plasma zinc and iron concentrations are regulated by different mechanisms.

Animals↗

Oral chloramphenicol in dwarf goats--influence of vasopressin on its absorption and effect of diet on its biodegradation in ruminal fluid samples.

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.

Absorption↗

Influence of gestation on the pharmacokinetics of four sulphonamides in goats.

The influence of gestation on the pharmacokinetics of four sulphonamides was studied in goats before, during and after pregnancy. Similar doses were given as intravenous boluses of 50 mg kg-1 each. Results were compared with those of non-pregnant goats to eliminate seasonal effects. With sulphadimidine elimination was mainly apparently first-order. In gestating goats the mean residence times decreased and mean plasma clearance rates increased with sulphadimidine during pregnancy, but this effect was continued after kidding at least until the end of May. The same happened with sulphadimethoxine, but sulphisomidine was not affected. In contrast to the other sulphonamides the mean residence time of sulphadoxine showed a maximum in February in gestating goats, while mean plasma clearance remained constant during and after pregnancy, at a lower level than in September. The mean plasma clearance of sulphadoxine decreased significantly from September to February in the non-pregnant control goats. In May five of six control goats and two of six goats which had kidded showed capacity-limited elimination against only two control goats in the foregoing experiments. With sulphadoxine one animal in the gestation group, but not the same one in each experiment, showed capacity-limited elimination against one, four and three in the control group in December, February and May, respectively. Distribution volumes increased significantly during and after pregnancy with sulphisomidine and sulphadimethoxine. A decrease in distribution volumes was seen in control goats with sulphadimidine, sulphisomidine and sulphadoxine, but was only significant for sulphadoxine. The pregnant uterus could not be recognised as an extra compartment, either in distribution volume nor in the pharmacokinetic model.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Appetite-modulating drugs in dwarf goats, with special emphasis on benzodiazepine-induced hyperphagia and its antagonism by flumazenil and RO 15-3505.

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.

Animals↗

Has bovine somatotropin (BST) an effect upon drug disposition? Comparative studies in goats and cattle with sulphadimidine and antipyrine after parenteral administration of BST, zeranol and proligestone.

Daily subcutaneous BST injection in lactating cows, bulls and castrated male dwarf goats did not induce significant changes in the pharmacokinetic parameters of antipyrine (AP) and sulphadimidine (SDD). Similarly, no changes were obtained after injection of slow-release BST formulations in lactating cows and non-lactating female goats. In contrast to androgenic hormones, both zeranol and proligestone had no effect upon the disposition of AP and SDD, although both synthetic hormones did induce enhanced plasma somatotropin concentrations. In goats, metabolic effects induced by zeranol and BST included significant reductions in plasma urea values, whereas plasma creatinine levels were somewhat lower after daily BST administration.

Animals↗

Fever and changes in plasma zinc and iron concentrations in the goat: the role of leukocytic pyrogen.

In goats with trypanosomiasis (T. vivax or T. congolense) no marked fall in plasma zinc concentration was seen despite high temperature peaks, whereas plasma concentrations of iron tended to undergo some decline. In goats infected with Ehrlichia phagocytophila, there was a marked decline in plasma zinc and iron to low values on the 3rd and 4th day, respectively. Circulating endogenous pyrogen (EP) or leukocytic endogenous mediator (LEM) could not be detected in plasma from febrile goats with tick-borne fever. The intravenous injection of leukocytic pyrogen (LP) in kids caused characteristic monophasic febrile reactions, whereas no significant changes in plasma trace metals were found. So, previous evidence purporting to show that LP is similar to or may be identical with LEM is demonstrably inconclusive. Intravenous injection of E. coli lipopolysaccharide (LPS) or staphylococcal enterotoxin B (SEB) induced fever and lowering of plasma zinc and iron concentrations. The decrease in those trace metal values was more persistent in goats given SEB than in those given E. coli LPS. After intramammary infusion of SEB or E. coli LPS, fever and significant decreases in plasma zinc and iron concentrations were observed but no clear relationship was found between the temperature responses and the alterations in plasma trace metal concentrations. Furthermore, the decrease in plasma iron concentration developed more rapidly in goats given SEB than in those given E. coli LPS, whereas the decrease in plasma zinc concentrations in the former was more delayed. These data support the theory that the concentrations of zinc and iron in plasma are regulated by different mechanisms, whereas febrile reactions are mediated by another type of endogenous protein.

Animals↗

Comparative observations of fever and associated clinical hematological and blood biochemical changes after intravenous administration of staphylococcal enterotoxins B and F (toxic shock syndrome toxin-1) in goats.

The present investigation was undertaken to examine the characteristics of purified toxic shock syndrome toxin-1 (staphylococcal enterotoxin F) given intravenously to dwarf goats (dose, 0.02 to 20 micrograms kg-1). Rectal temperature, heart rate, rumen motility, plasma zinc and iron concentrations, and certain other blood biochemical and hematological values were studied and compared with the changes seen after intravenous administration of staphylococcal enterotoxin B (dose, 0.02 to 0.5 micrograms kg-1). Similar changes such as fever, tachycardia, inhibition of rumen contractions, drop in plasma zinc and iron concentrations, lymphopenia, and a decrease in serum alkaline phosphatase activity were observed. In contrast to the effects of toxic shock syndrome toxin-1, staphylococcal enterotoxin B induced colic, watery diarrhea with pseudomembranes, hemoconcentration, and a more pronounced increase in blood urea nitrogen. The results obtained demonstrate that (i) in the goat staphylococcal enterotoxin B is much more potent than toxic shock syndrome toxin-1 and (ii) the goat is a useful model to study the gastro-intestinal effects caused by staphylococcal enterotoxin B. The present finding that no clear relationship could be found between the temperature response and the alterations in zinc and iron levels in plasma support the theory that the febrile reactions and the changes in plasma trace metals are mediated by different polypeptides released by activated macrophages.

Animals↗

Effect of intracerebroventricular injection of PGE2 and 5HT on body temperature, heart rate and rumen motility of conscious goats.

Changes in rumen motility and heart rate following injection of 5-HT and PGE2 into the third cerebral ventricle were investigated in conscious goats. The doses used were known to produce predictable changes in thermoregulation in goats. The changes in body temperature, ear temperature (PGE2, 5-HT) and shivering (PGE2) were as reported by others. The i.c.v. injection of PGE2 and 5-HT inhibited rumen motility and slightly decreased the heart rate, probably due to a central action.

Animals↗

The antipyretic effect of flurbiprofen.

Flurbiprofen, like its predecessor ibuprofen, possesses antipyretic properties in the endotoxin-fevered rabbit. Comparison of flurbiprofen and ibuprofen at varying dosages, reveals that flurbiprofen is at least 15 times more potent in this species. In goats, flurbiprofen is more potent than in rabbits. Flurbiprofen inhibited the pyrogenic effect of intravenously administered leucocytic pyrogen, but it did not alter the release of leucocytic pyrogen from peritoneal exudate cells in vitro. Moreover, flurbiprofen did not inhibit endotoxin-induced release of endogenous pyrogen in vivo. Incubation of leucocytic pyrogen with flurbiprofen did not alter its pyrogenic poteny. These results suggest that the antipyretic activity of flurbiprofen is due neither to interference with endogenous pyrogen synthesis and release, nor to inactivation of circulating endogenous pyrogen.

Analgesics↗