Pharmacokinetics and distribution of sulphadimidine in plasma,milk and uterine fluid of female buffaloes

The pharmacokinetics of sulphadimidine after a single dose (200 mg/kg i.v.) was studied in five healthy lactating buffaloes. The study revealed that the drug attained its peak concentration of 314.0±13.0, 242.4±3.0 and 100.2±2.5 g/ml at 15 min, 30 min and 12 h in plasma, milk and uterine fluid, respectively. The pharmacokinetic parameters calculated by a 2-compartment open model gave values for t₁, t₁ and vd_area of 2.10±0.36 h, 12.36±0.57 h and 1.23±0.07 L/Kg, respectively. A high vd_area as well as a value of 0.74±0.08 for K₁₂:K₂₁- (tissue Plasma) indicates better penetration of the drug into the different body fluids and tissues, which is further supported by a high concentration obtained in milk and uterine fluid. The therapeutic concentration (50 g/ml) was maintained for around 24 h in plasma and milk and 12 h in uterine fluid. The results suggest that, apart from its use in systemic infections, the drug can be effectively used by the i.v. route in uterine and mammary gland infections. The dosages for maintaining concentration of 50 g/ml, 100 g/ml and 150 g/ml at convenient dosage intervals of 12 and 24 h were also determined.     

The effect of transfer factor treatment on two challenge infections ofHaemonchus contortus in immuno-competent 7-month-old lambs

A number of immuno-competent Blackface lambs were infected with 10,000Haemonchus contortus third stage larvae and were later challenged with a second dose of 10,000H. contortus third stage larvae. One group of lambs was treated with dialysed transfer factor prior to the second challenge dose.Histological changes in the abomasal wall, reductions in abomasal worm burdens at slaughter and faecal egg counts monitored throughout the experiment suggested the presence in some animals of (1) an innate resistance, (2) a self curing effect, (3) an enhancement of this self curing effect in the transfer factor treated group and (4) a response in one transfer factor treated animal comparable to classical self cure.     

Relationship of plasma lactate production to cortisol release following completion of different types of sporting events in horses

Fifty-eight healthy horses were studied during five sporting events of various intensities and durations, namely show-jumping (n=6), cross-country in a three-day event (n=30), trotting races (n=7), galloping reces (n=7) and endurance rides (n=8). Venous blood samples were collected at rest and immediately after exercise and analysed for plasma cortisol (CORT) and lactate (LA) levels. The experimental procedure was the same throughout the investigation so as to permit a reliable comparison between the five types of exercise. The type of event significantly affected both the resting (p0.05) and the postexercise (p0.01) plasma CORT. The degree of exercise-induced hypercortisolaemia was related to both the intensity and the duration of exercise for all five sporting events, but the endurance ride induced the most and show-jumping the least serious post-exercise CORT changes. LA production was much more closely related to the intensity of the exercise than was CORT. It is concluded that simultaneous measurements of plasma CORT and LA levels may be useful to discriminate between different types of exercise, adjust training programmes, and improve our comprehension of the physiology of sport horses at exercise.Abbreviations CORT cortisol - E/R exercise to rest ratio - EDTA ethylenediaminetetraacetic acid - HR heart rate - LA lactate     

Uterine motility of the sow during the oestrous cycle and early pregnancy

With electromyography and strain gauges the uterine motility of the sow during the oestrous cycle and early pregnancy was studied. Special attention was paid to characterization of myometrial activity at the time of intrauterine migration of blastocysts.From recordings of 4 animals (3 became pregnant) 3 types of electrical spiking activity (each could be correlated with an elevation of the strain gauge tension) were discerned. Two of them appeared regularly and were suitable for analysis: High Voltage Slow Acticity (with relative high amplitude and low frequency of spikes) and Low Voltage Fast Activity (with relative low aplitude and high frequency of spikes).The sexual status markedly influenced myometrial activity: during prooestrus and oestrus only one type of electrical activity was present whereas the myoelectrical complex (an episode of this activity and the subsequent interval of inactivity) was shorter than 10 min. During dioestrus the myoelectrical complex was longer than 10 min and High Voltage Slow Activity (solely on the cervix and bifurcation) and Low Voltage Fast Activity occurred simultaneously in episodes which mainly appeared to originate on the bifurcation.The characteristics of uterine activity during pregnancy were similar to those of a cyclic sow until day 12. It was only on day 12 that gestation appeared from an increased frequency of myoelectrical complexes.It is concluded that Low Voltage Fast Activity as it was found on the uterine horn at days 8–9 might be involved in the process of intra-uterine migration of blastocysts. In cyclic and in pregnant animals the patterns of Low Voltage Fast Activity were similar. Therefore, the occurrence of Low Voltage Fast Activity is independent of the actual presence of blastocysts. It seems to be exhibited in dependence on the ovarian hormones.     

Identification of Functional α-Adrenoceptor Subtypes in the Bovine Female Genital Tract During Different Phases of the Oestrous Cycle

The concentration and functionality of the -adrenoceptor (-AR) subtypes in the genital tract of cyclic heifers were investigated. In each tissue sample, a single class of ₁-ARs was observed, whereas two distinct classes of ₂-ARs were discriminated: low-affinity (LA) and high-affinity (HA) ₂-ARs. Statistical analysis showed the presence of significantly (p < 0.05) higher concentrations of all -AR subtypes in the follicle than in the corpus luteum. No significant differences were found in the ovary or myometrium between the luteal and follicular phases. In the ovary, the density of ₁-ARs was significantly (p < 0.05) higher than that of ₂-ARs. By contrast, there were significantly (p < 0.05) more ₂-ARs than ₁-ARs in the myometrium. As far as ₂-ARs are concerned, LA ₂-ARs were significantly (p < 0.05) higher than HA ₂-ARs in all tested tissues. Competition studies suggested that the rank order of potency of antagonists for ₁-ARs was prazosin > phentolamine > yohimbine, whereas for ₂-ARs the order of potency was yohimbine phentolamine > prazosin. Functional assays performed on myometrium showed that noradrenaline, phenylephrine and clonidine elicited concentration-dependent contractions only in dioestrus and pro-oestrus preparations and that clonidine was more effective than phenylephrine as a contractile agent. It appeared that there were no significant modifications in -AR affinity or concentration during the different stages of bovine oestrous cycle, whereas the uterine spontaneous activity and the responsiveness to -adrenergic stimulation was strongly influenced by hormonal levels. The modifications of uterine contractility observed during the oestrous cycle may be related to modifications induced in the transductional mechanisms of -ARs.     

Effect of antisecretory drugs on experimentally induced weanling diarrhoea in piglets

In 45 newly-weaned 3 to 4-week-old piglets, diarrhoea was induced by a combined infection with transmissible gastroenteritis (TGE) virus and enterotoxigenic E. coli (ETEC) strains. In untreated control animals this dual inoculation resulted in profuse diarrhoea, vomiting, hypovolaemic shock and death of 77% of the animals within five days of TGE virus inoculation. Antisecretory drugs were administered intramuscularly for three consecutive days after experimental infection. The neurolepticum chlorpromazine, at 2 mg/kg/24 h, resulted in a significant inhibition of diarrhoea and vomiting, and in an increase in weight gain and survival. Sedation and hypothermia, however, were serious side-effects. The ₂ agonist clonidine, at 80 g/kg/12 h, induced a significant antidiarrhoeal effect and a reduction in mortality. The drug, however, provoked decreased activity of ₂-adrenergic excitation and incoordination. The -adrenergic antagonist propranolol, at 0.33 mg/kg/8 h, and the calcium channel blocker verapamil, at 2 mg/kg/8 h, had no beneficial effect on the experimentally induced diarrhoea.     

The use of cultured hepatocytes from goats and cattle to investigate xenobiotic oxidative metabolism

The oxidative metabolism of aldicarb (ALD), a carbamate pesticide, and fenbendazole (FBZ), an anthelmintic, was studied using cultured hepatocytes obtained from 4 goats and a bullock and incubated with ALD (50 mol/L) and FBZ (10 mol/L). The parent compounds and the metabolites were measured by HPLC. Both compounds are metabolized at the sulphur atom via two sequential oxidations, first to the sulphoxide (aldicarb sulphoxide and oxfendazole, respectively) and then to the sulphone. Oxfendazole and fenbendazole sulphone from FBZ, and aldicarb sulphoxide from ALD were found in both species. Aldicarb sulphone was not produced by the hepatocyte preparations from the bullock. The good correlation obtained comparing the in vitro results of FBZ metabolism with published in vivo dat obtained on FBZ kinetics in the same species confirmed the usefulness of in vitro models for predictive analysis of in vivo xenobiotic biotransformations.Abbreviations ALD aldicarb - ALDSON aldicarb sulphone - ALDSOX aldicarb sulphoxide - BSA bovine serum albumin - ID internal diameter - EGTA ethylene glycol bis(-aminoethyl ether) N,N,N,N-tetraacetic acid - FBZ fenbendazole - FBZSON fenbendazole sulphone - HBSS Hanks' balanced saline solution - HPLC high-pressure liquid chromatography - LDH lactate dehydrogenase - MFO mixed function oxidase - NCS newborn calf serum - OXF oxfendazole - WME Williams' Medium E     

Determination of β-adrenoceptors and cAMP in muscle from normal and splayleg Belgian Landrace pigs

-Adrenoceptors were identified and characterized by [³H]dihydroalprenolol ([³H]DHA) binding experiments in muscle membrane preparations from piglets. The [³H]DHA binding was rapid, reversible and stereoselective. Catecholamines competed for specific binding with a rank order of potency (-)-isopropylnoradrenaline > (-)-epinephrine » (-)-norepinephrine, indicating a -subtype of adrenoceptor. Saturation binding experiments with [³H]DHA showed no significant difference for either the number of binding sites or the equilibrium dissociation constants in normal and splayleg pigs.Adenylate cyclase assays indicated that the basal adenylate cyclase activity and the prostaglandin E₁ (PGE₁)-, (-)-isopropylnoradrenaline (ISO)-, 5-guanylyl-imidodiphosphate (GppNHp)- and sodium fluoride (NaF)-stimulated values were not significantly different in normal and splayleg pigs. In both groups, PGE₁ did not affect basal activity, whereas ISO and GppNHp stimulated adenylate cyclase activity significantly (p<0.001) to about 40% above basal level. NaF induced a significant (p<0.001) increase of cAMP in normal and splayleg pigs amounting to 48% and 61% respectively. Significant correlations between absolute adenylate cyclase responses to ISO (r=0.83^***), NaF (r=0.72^**) and GppNHp (r=0.61^*) and basal activity in the splayleg pigs were the most striking findings. In contrast, these correlations could not be detected in the normal pigs. Whether or not this observation reflects an alteration in the signal transduction system needs to be further investigated.To the best of our knowledge this is the first biochemical study which relates an altered -adrenoceptor function and porcine splayleg.     

Feed intake and rumen motility in dwarf goats. Effects of some α-adrenergic agonists,prostaglandins and posterior pituitary hormones

The purpose of the present investigation was to test the hypothesis that drug-induced changes in rumen contractions influence feed intake in dwarf goats. Intravenous (i.v.) administration of clonidine (1 g kg^-1 min^-1 for 10 min), xylazine (1 g kg^-1 min^-1 for 10 min), and PGF-2 (10 g kg^-1 min^-1 for 15 min) caused bradycardia and inhibition of rumen contractions. However, no appetite-stimulating effect of these drugs was observed. Other clinical changes induced by the ₂-adrenergic agonists included slight sedation and a decrease in body temperature; all clinical effects of clonidine and xylazine were partly antagonized by tolazoline pretreatment (10 g kg^-1 min^-1 for 30 min). These results suggest that the CNS control of feeding differs in ruminants and monogastric species.In dwarf goats fasted for 2 h, i.v. administration of oxytocin (0.01 IU kg^-1 min^-1 for 15 min), vasopressin (0.01 IU kg^-1 min^-1 for 15 min), octapressin (0.003 IU kg^-1 min^-1 for 15 min) or PGE (0.8 g kg^-1 min^-1 for 15 min) did not change feeding behaviour during the two observation periods (0–30 min and 180–210 min after drug infusion, respectively). In previous studies, similar doses of these drugs induced changes in heart rate and inhibition of rumen contraction in goats. These findings demonstrate that drug-induced changes in forestomach contractions do not simply cause changes in feeding behaviour. The i.v. infusion of the PGF₂ analogues etiproston (10 g kg^-1 min^-1 for 15 min), luprostiol (30 g kg^-1 min^-1 for 15 min), cloprostenol (1 g kg^-1 min^-1 for 15 min) and tiaprost (1 g kg^-1 min^-1 for 15 min) induced hypophagic effects and stimulated intestinal propulsion.     

Serum Fructosamine Concentrations in Dogs with Hypothyroidism

Serum fructosamine concentrations were measured in 11 untreated hypothyroid dogs with normal serum glucose and serum protein concentrations. The fructosamine level ranged between 276 and 441 mol/L (median 376 mol/L; reference range 207–340 mol/L). Nine of the 11 dogs had fructosamine levels above the reference range. The fructosamine levels decreased significantly during treatment with levothyroxine. It is suggested that serum fructosamine concentrations may be high in hypothyroid dogs because of decelerated protein turnover, independent of the blood glucose concentration.     

The Effects on Reproductive Performance in the Short and Medium Term of the Combined Use of Exogenous Melatonin and Progestagen Pessaries in Ewes with a Short Seasonal Anoestrous Period

Three hundred and sixty-one adult Rasa Aragonesa ewes were used to evaluate the effect on their reproductive parameters of melatonin implants used in association with the classical synchronization treatment (progestagen plus pregnant mare serum gonadotrophin (PMSG)) in an accelerated breeding system (3 lambings in 2 years). The animals were divided into four groups on the basis of body condition score (H, 2.75; L, 2.5) and treatment (M) or no treatment (C) with a subcutaneous implant containing 18 mg of melatonin on 17 February 1997. Intravaginal pessaries containing 30 mg of fluorogestone acetate were inserted into all the ewes between 3 and 13 March and 500 IU PMSG was injected intramuscularly when the pessaries were withdrawn 14 days later. Fertile rams were introduced on 17 March. The pregnancy rate and litter size were unaffected by either melatonin treatment or body condition. The overall fertility at first plus second oestrus was between 76.4% (HC) and 82.8% (HM), and the litter size was between 1.58 (LM) and 1.82 (HC) lambs born per lambing. However, melatonin did seem to have a positive effect on the reproductive parameters of non-pregnant ewes at the second mating period 2 months later. Finally, no detrimental effect of melatonin implants on fertility and litter size was recorded in the medium term.     

The influence of ageing on muscarinic receptors, β-adrenoceptors and adenylate cyclase activity in the bovine lung

Muscarinic and -adrenoceptors were identified in airway epithelium, smooth muscle and lung parenchyma from Holstein-Friesian calves and cows and were characterized with [³H]quinuclidinyl benzilate and [³H]dihydroalprenolol, respectively. The muscarinic receptor density in the smooth muscle of cows (B _max=4803±245 fmol/mg protein) was 33% greater (p<0.01) than in calves. Low receptor numbers were detected in the epithelium and parenchyma. In both calves and cows, the density of epithelial -adrenoceptors was twice as high as in smooth muscle and parenchyma. The quantity of -adrenoceptors in the tracheal epithelium (B _max=994±83 fmol/mg protein) and smooth muscle (B _max=492±41 fmol/mg protein) in cows was respectively 37% (p<0.001) and 35% (p<0.01) lower than in calves. Adenylate cyclase (AC) assays indicated that the basal and the (–)-isopropylnoradrenaline- (ISO-) stimulated cAMP production were not significantly different between the calves and cows. After stimulation with NaF, significantly higher cAMP production was found in all tissues from cows. Significant correlations were found between absolute AC responses to NaF and -adrenoceptor density in epithelium (r=–0.75,p<0.001) and smooth muscle (r=–0.63,p<0.01). It seems that, in older animals, the production of cAMP is independent of the number of receptors, indicating the presence of fully active compensatory mechanisms.Abbreviations AC adenylate cyclase - cAMP intra-cellular adenosine monophosphate - G-protein GTP binding protein - GTP guanosine 5-triphosphate - ISO isopropylnoradrenaline - M muscarine - QNB quinuclidinyl benzilate     

Acute and Subacute Metabolic and Endocrine Effects of Clenbuterol in Female Pigs

The aim of the study was to assess the relationship between acute and subacute metabolic and endocrine effects after intravenous administration of the ₂-adrenergic agonist clenbuterol in a growth-promoting dose to female pigs. Acute metabolic and endocrine effects were assessed by measuring the blood glucose, serum insulin and nonesterified fatty acid (NEFA) concentrations during 300 min after a single administration of clenbuterol. Significantly higher serum insulin and NEFA concentrations (19.90±2.50 U/ml, p<0.01, and 0.69±0.04 mmol/L, p<0.001, respectively) were measured 30 min after the preprandial administration of clenbuterol in female pigs. Over the same period, the levels of blood glucose (4.42±0.30 mmol/L) showed no difference from those of control pigs. The postprandial serum NEFA concentration decreased moderately during 210 min after feeding. Postprandial blood glucose and insulin concentrations increased and reached maximal levels 120 min after clenbuterol administration (10.91±0.60 mmol/L and 85.22±7.24 U/ml, respectively), and returned to basal levels at 300 min (4.20±0.21 mmol/L and 7.75±1.60 U/ml, respectively) after the administration of clenbuterol. Subacute metabolic and endocrine effects were assessed by measuring the blood glucose, serum insulin and NEFA concentrations for 21 days after the repeated doses of clenbuterol. In addition, the influence of clenbuterol administration on the endocrine regulation of the onset of the next expected oestrus in female pigs was assessed by measuring their serum 17-oestradiol and progesterone concentrations. Blood glucose, serum insulin and NEFA concentrations after the last administration of clenbuterol did not differ significantly from those in control animals. The onset of the next expected oestrus occurred regularly without any significant difference in serum 17-oestradiol or progesterone concentrations between the treated (9.83±2.60 pg/ml and 0.15±0.03 ng/ml) and control pigs (8.52±2.70 pg/ml and 0.25±0.06 ng/ml). The study results suggest the duration of intravenous administration of clenbuterol in a growth-promoting dose necessary to influence the metabolic and endocrine activities in female pigs.     

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)     

The influence of clenbuterol on prostaglandin F2α-induced dyspnoea in calves

Pulmonary function tests were performed in six healthy calves. Prostaglandin F₂ causes severe narrowing of both upper and lower airways (total lung resistance increased, dynamic compliance decreased). Clenbuterol administered intravenously fifteen minutes prior to prostaglandin F₂ aerosol, and in increasing doses (0, 0.4, 0.8, 1.2 g/kg), on days 1, 2, 4 and 6 of the experiment, effectively but not entirely suppressed these responses.These data indicate that -adrenergic receptors are present in the bovine airways and that the use of clenbuterol (0.8 g/kg) may be effective in treating clinical respiratory disease such as bronchopneumonia in calves.     

Haemophilus influenzae and the β-adrenergic system: A review

Haemophilus influenzae is a bacterium that often can be isolated from the deeper respiratory airways of patients with chronic asthmatic bronchitis. In the present study the effects ofH. influenzae vaccination on guinea pig pulmonary -adrenoceptor number and function (in vitro and in vivo) have been evaluated. Functioning of -adrenoceptors is determined by measuring the -mimetic effect of isoprenaline on the inhibition of anaphylactic mediator release and isolated tracheal strip relaxation. The number of -adrenoceptor binding sites was measured by means of a³H-dihydroalprenolol binding assay.Also the mechanism of action underlying the changes in -adrenoceptor functioning was evaluated. Furthermore, it was established that the effect on the -adrenoceptor system was not specific forH. influenzae and that other respiratory pathogens were also biologically active in this respect.     

Comparative In Vitro Activity of 16 Antimicrobial Agents Against Actinobacillus Pleuropneumoniae

Sixteen antimicrobial agents were tested for their activity against 68 isolates of Actinobacillus pleuropneumoniae by determining the minimum inhibitory concentrations (MICs). Ceftiofur and the fluoroquinolones danofloxacin and enrofloxacin were the most active compounds, with a MIC for 90% of the isolates (MIC₉₀) of 0.05 µg/ml. The MIC₉₀ values of benzylpenicillin, amoxicillin and aspoxicillin were 0.78 units/ml, 0.39 µg/ml and 0.05 µg/ml, respectively. Three isolates (4.4%) were resistant to penicillins, but aspoxicillin was as active as ceftiofur against the susceptible isolates, with MICs of 0.05 µg/ml for all isolates. Resistance to oxytetracycline, chloramphenicol and thiamphenicol occurred in 22 (32.4%), 14 (20.6%) and 15 (22.1%) of the isolates, respectively. Doxycycline was more active than oxytetracycline, with a MIC₉₀ of 1.56 µg/ml as against 25 µg/ml. Florfenicol was not only as active as thiamphenicol, with a MIC for 50% of the isolates (MIC₅₀) of 0.39 µg/ml, but also active against thiamphenicol-resistant isolates. All the isolates were susceptible to florfenicol. All the isolates were also susceptible to gentamicin, spectinomycin, tilmicosin, colistin and tiamulin. Of these, spectinomycin was the least active, with a MIC₅₀ of 25 µg/ml, followed by tiamulin, with a MIC₅₀ of 6.25 µg/ml. Of the 68 isolates tested, 49 (72.0%) were of serotype 2; 14 (20.5%) were of serotype 1; 2 each (3.0$) were of serotypes 5 and 6; and one was of serotype 7. Of the isolates, 23 (33.8%) were resistant to one or more of the major antibiotics. Antibiotic resistance was found only infrequently among serotype 2, with 5 (10.2%) of 49 isolates being resistant to chloramphenicol and/or oxytetracycline, while it occurred in 18 (94.7%) of the 19 isolates of other serotypes.     

Pharmacokinetics and distribution of ampicillin in plasma,milk and uterine fluid of female buffaloes

A pharmacokinetic study of ampicillin (6 mg/kg intravenous) revealed that the peak concentrations of 17.81±1.25, 5.64±2.24 and 1.09±0.10 g/ml of the drug were attained at 15 min, 30 min and 2 h in plasma, milk and uterine fluid respectively. A therapeutic concentration of 0.1 g/ml was maintained from 15 min–8 h, 15 min–6 h and 30 min–6 h in plasma, milk and uterine fluid. Hence, the drug may be used effectively in mammary gland and uterine infections apart from its use in other systemic infections.     

Pharmacokinetic data on doxycycline and its distribution in different biological fluids in female goats

A pharmacokinetic study of doxycycline after intravenous administration at 5 mg/kg body weight in goats revealed that a concentration of 0.5 g/ml was maintained for 5 min-2 h, 4–12 h, 2–12 h and 5 min- >48 h in plasma, interstitial fluid, milk and urine respectively. The low t1/2 of 0.73±0.11 h and high t1/2 of 16.63±1.58 h show that the drug is rapidly distributed but slowly eliminated from the body. The tissue:plasma concentration of 4.86±1.06 during the elimination phase [K12/(K21-)] indicates a high expected tissue concentration, which is supported by similarly increased drug concentration in interstitial fluid and milk. The high Vd_area of 9.78±0.86 L/kg observed denotes that, apart from its wide distribution, the drug may be stored in fat depots as it is known to be highly lipophilic. As the drug maintained a therapeutic concentration for a shorter time in plasma, and the calculated dose rate for maintaining a minimal plasma concentration of 0.5–1.5 g/ml is relatively high, it may not be of much use in treating septicaemia in this species. Since the observed tissue:plasma concentration was higher and a therapeutic concentration was maintained in interstitial fluid and milk for longer, the drug can be used for other systemic infections at a lower dose rate than that required for treating septicaemia. As the drug maintained a very high concentration in urine, it may be of particular value in treating urinary tract infections caused by sensitive micro-organisms.     

Pathogenic mechanisms of caprine arthritis-encephalitis virus

Goats infected with caprine arthritis-encephalitis virus (CAEV) show chronic arthritis and cachexia, which are progressive in nature. The immunopathogenic mechanisms responsible for these progressive clinical symptoms have not been fully elucidated. Various haematological and immunological parameters were evaluated in experimentally-infected goats showing typical signs of CAEV-induced disease. Infected goats showed recurrent lymphocytosis that may be due to constant presentation of antigen by infected cells of a monocyte/macrophage lineage. The serum alkaline phosphatase and -glutamyl transferase concentrations were elevated in infected goats, a characteristic of hepatic and bone disorders. All other serum chemistry parameters were similar between infected and control goats. Importantly, the serum tumour necrosis factor- (TNF-) levels were higher in infected goats. The cachexia seen in infected goats may be at least partly due to altered metabolism as a result of prolonged elevation of serum TNF- levels. Depressed natural killer cell activity was observed in infected goats and may contribute towards the establishment of a persistent infection with CAEV.Abbreviations AIDS acquired immunodeficiency syndrome - CAEV caprine arthritis-encephalitis virus - GGT -glutamyl transferase - HBSS Hanks' balanced salt solution - HIV human immunodeficiency virus - NK natural killer - PBMC peripheral blood mononuclear cells - PCR polymerase chain reaction - SAP serum alkaline phosphatase - TNF tumour necrosis factor