Diminazene aceturate is one of a limited number of drugs currently being used in animals to treat the tsetse fly-transmitted protozoal disease, African trypanosomiasis. Efficacy of the drug at the recommended single IM administered doses of 3.5 and 7.0 mg/kg of body weight is widely acknowledged. However, resistance to the drug at these dosages has been reported. Although the mechanisms of resistance to diminazene are poorly understood, field and experimental data indicate that it may develop naturally through administration of subcurative doses, or as a result of cross-resistance. Evidence from other experimental studies indicates that there are additional mechanisms by which trypanosomes may develop resistance to diminazene aceturate. For instance, some populations ot Trypanosoma brucei and T. vivax are refractory to treatment because of their ability to invade the CNS, a site that is believed to be poorly accessible to diminazene. Furthermore, in recent studies carried out in goats, it has been documented that the ability of T. Congolense IL 3274 to survive treatment with diminazene depends on the stage of infection when treatment is administered; populations of the parasite reappeared in animals that were treated on day 19 after tsetse fly challenge, whereas all goats were cured when treated on day 1 of infection. Because trypanosomes are confined to the skin on day 1 after infection, but thereafter invade the blood circulation, it is possible that the efficacy of the treatment on day 1 is attributable to exposure of the small number of parasites, relative to later stages of infection, to higher concentrations of drug than those attained in blood. The objective of the study reported here was to determine whether diminazene's pharmacokinetics differ between plasma and lymph draining the skin of goats and therefore account for the variation in therapeutic activity of the drug at different stages of a tsetse fly-transmitted infection. Peripheral lymph was used for this work because it appears to be identical in composition to tissue interstitial fluid, into which trypanosomes are inoculated by infected tsetse flies when feeding.

Four intrauterine treatment strategies were evaluated for effectiveness in mares that were confirmed to be susceptible to chronic uterine infection. Pretreatment samples were obtained at detection of estrus, and a genital strain of Streptococcus zooepidemicus was infused into the uterus when a preovulatory (> 35 mm) follicle was detected. At 12 hours after inoculation, mares were assigned to 1 of 4 selected treatment groups: autologous plasma, 100 ml (n = 5); potassium penicillin, 5 million U in 100 ml of phosphate-buffered saline solution (PBSS; n = 5); 10 mg of prostaglandin F2alpha in 100 ml of PBSS (n = 5); and large-volume lavage with normal saline solution (1,000 ml increments). A fifth group, treated with vehicle alone (100 ml of PBSS), served as a negative control (n = 7). All treatments were administered into the uterus. To assess the effectiveness of the treatment, samples for culture and cytologic examination were collected at 96 hours after bacterial inoculation. An effect of treatment was observed on the number of uterine neutrophils (P = 0.02) and growth of S zooepidemicus (P < 0.01). Intrauterine treatment with potassium penicillin, prostaglandin F2alpha, and large-volume uterine lavage significantly reduced the growth of S zooepidemicus (P < 0.01) as well as the number of neutrophils (P < 0.02). Autologous plasma reduced the number of neutrophils (P < 0.05), but not growth of S zooepidemicus. There was significant correlation between the number of uterine neutrophils and growth of S zooepidemicus for each treatment group (r = 0.57; P < 0.05).

Objective--To study whether end products of 2 pathways of anaerobic energy metabolism, lactate and purines, that accumulate in the blood after intense exercise indicate any relation to exercise performance. Design--Venous blood samples were taken within 1 and 15 minutes after a trotting race of 2,100 m. Animals--16 Clinically healthy Standardbred trotters. Procedure--Blood and plasma lactate concentrations were measured by enzymatic analyzer, and purines, uric acid and allantoin, were determined by high-performance liquid chromatography. The concentrations of metabolites were then correlated to racing time and individual performance indexes that are annually calculated from the percentage of winnings, placings, and starts rejected, average earnings per start, and the racing record. Results--Blood lactate concentration immediately and calculated cell lactate concentration immediately and 15 minutes after the race correlated positively (P < 0.05 to P < 0.01 ) with the individual performance indexes. Plasma lactate concentration was not correlated to the individual performance indexes. Uric acid concentration, immediately and 15 minutes after the race, was negatively correlated (P < 0.05) to the individual performance indexes, and a positive relation (P < 0.05) was found between the highest concentration of uric acid and the racing time. Concentration of allantoin immediately or 15 minutes after the race did not have any significant correlation to the individual performance indexes. Conclusions--Accumulation of lactate in the blood, which was greater in the superior performing horses, may prove to be an useful predictor of anaerobic capacity. The results also indicate that the loss of purine nucleotides was less in the superior performing horses, although further studies are needed to confirm this.

Plasma insulin concentration of many species has a characteristic early or acute-phase response in the minutes after IV administration of glucose, However, the plasma insulin response of horses soon after the Iv administration of glucose has not been examined, whereas the more prolonged response has been evaluated. We examined the plasma insulin and glucose concentration responses of adult mares during the 30 minutes after rapid Iv administration of glucose (0.33 g/kg of body weight). Plasma glucose concentration peaked at 664 +/- 54 mg/dl within I minute of cessation of glucose administration, whereas insulin concentration peaked at 326 +/- 24 pmol/L at 2 minutes after the end of glucose administration. Thus, these mares had an acute insulin response, consistent with that observed in other species, including dogs, human beings, and cattle.

Duration and magnitude of hypothalamic-pituitary-adrenal axis suppression caused by daily oral administration of a glucocorticoid was investigated, using an anti-inflammatory dose of prednisone. Twelve healthy adult male dogs were given prednisone orally for 35 days (0.55 mg/kg of body weight, q 12 h), and a control group of 6 dogs was given gelatin capsule vehicle. Plasma cortisol (baseline and 2-hour post-ACTH administration) and plasma ACTH and cortisol (baseline and 30-minutes post corticotropin-releasing hormone [CRH] administration) concentrations were monitored biweekly during and after the 35-day treatment period. Baseline plasma ACTH and cortisol and post-ACTH plasma cortisol concentrations were significantly (P < 0.05) reduced in treated vs control dogs after 14 days of oral prednisone administration. By day 28, baseline ACTH and cortisol concentrations remained significantly (P < 0.05) reduced and reserve function was markedly (P < 0.0001) reduced as evidenced by mean post-CRH ACTH, post-CRH cortisol, and post-ACTH cortisol concentrations in treated vs control dogs. Two weeks after termination of daily prednisone administration, significant difference between group means was not evident in baseline ACTH or cortisol values, post-CRH ACTH or cortisol values, or post-ACTH cortisol values, compared with values in controls. Results indicate complete hypothalamic-pituitary-adrenal axis recovery 2 weeks after oral administration of an anti-inflammatory regimen of prednisone given daily for 5 weeks.

Plasma elimination rates of sulfamethazine (100 mg/kg of body weight, IV), trimethoprim (20 mg/kg, IV), and antipyrine (35 mg/kg, IV) were studied in adult female dwarf goats (n = 5) before and after implantation with trenbolone acetate (5 mg/kg). Pretreatment with trenbolone caused a significant decrease in the elimination rate of the drugs tested: for sulfamethazine, 5 times; for antipyrine, 3 times; and for trimethoprim, 2 times. After treatment with testosterone (1 mg/kg, SC, twice weekly for 2.5 weeks), female goats (n = 5) had a similar decrease in the elimination rate of sulfamethazine. Other induced effects included a change in social behavior, a lower voice, and the development of a typical billy goat-like odor. Plasma creatinine concentrations after androgen administration were significantly higher than those before androgen administration; changes were not observed in plasma urea values. Because of the differences observed, we believe that more attention should be paid to the effects of androgenic agents on drug kinetic properties, with particular reference to studies on clinical efficacy, side effects, and drug residues in food products.

Twenty-four horses were randomly allocated to 3 groups. Horses were anesthetized, subjected to a ventral midline celiotomy, and the large colon was exteriorized and instrumented. Group-1 horses served as sham-operated controls. Group-2 horses were subjected to 6 hours of low-flow colonic arterial ischemia, and group-3 horses were subjected to 3 hours of ischemia and 3 hours of reperfusion. Baseline (BL) samples were collected, then low-flow ischemia was induced by reducing ventral colonic arterial blood flow to 20% of BL. All horses were monitored for 6 hours after BL data were collected. Blood samples were collected from the colonic vein and main pulmonary artery (systemic venous (SV) for measurement of plasma endotoxin, 6-keto prostaglandin F1alpha (6-kPG), thromboxane B2 (TXB2), and prostaglandin E2 (PGE2) concentrations. Tumor necrosis factor and interleukin-6 activities were measured in colonic venous (CV) serum samples. Data were analyzed, using two-was ANOVA, and post-hoc comparisons were made, using Dunnett's and Tukey's tests. Statistical significance was set at P < 0.05 Endotoxin was not detected in CV or SV plasma at any time. There was no detectable tumor necrosis factor or interleukin-6 activity in CV samples at any time. There were no differences at BL among groups for CV or SV 6-kPG, PGE2, or TXB2 concentrations, nor were there any changes across time in group-1 horses. Colonic venous 6-kPG concentration increased during ischemia in horses of groups 2 and 3; CV 6-kPG concentration peaked at 3 hours in group-3 horses, then decreased during reperfusion, but remained increased through 6 hours in group-2 horses. Systemic venous 6-kPG concentration increased during reperfusion in group-3 horses, but there were no changes in group-2 horses. Colonic venous PGE2 concentration increased during ischemia in horses of groups 2 and 3, and remained increased for the first hour of reperfusion in group-3 horses and for the 6-hour duration of ischemia in group-2 hors.

Renal clearance procedures were performed on adult mixed-breed dogs with a wide range of renal function. Endogenous creatinine clearance was computed after analyzing plasma and urine for creatinine by use of 2 methods, PAP and kinetic Jaffe. For 20-minute clearance procedures, [14C]inulin clearance was measured simultaneously with endogenous creatinine clearance. For 111 twenty-minute clearance procedures performed on 24 dogs, [14C]inulin clearance was highly correlated with creatinine clearance for both methods of creatinine analysis (R2 = 0.979 for [14C]inulin-PAP; R2 = 0.943 for [14C]inulin-Jaffe). The absolute values for PAP and [14C]inulin clearance were nearly the same (PAP-to-[14C]inulin clearance ratio = 1.03 +/- 0.08), but those for Jaffe clearance were substantially less than those for [14C] inulin clearance Jaffe-to-[14C]inulin clearance ratio = 0.88 +/- 0.10). The Jaffe-to-[14C] inulin clearance ratio was inversely correlated with degree of renal function (R2 = 0.464), whereas the PAP-to-[14C]inulin clearance ratio was not correlated with degree of renal function (R2 = 0.060). Thus, Jaffe-determined creatinine clearance varied, in relation to [14C] inulin clearance, depending on degree of renal function. In 4 clinically normal dogs, 20-minute and 24-hour sample collections analyzed by use of the PAP method gave clearance values significantly greater, for both periods, than did Jaffe analyses. The PAP-determined creatinine clearance values were less than, but not significantly different from 20-minute exogenous creatinine clearance values determined 10 days after 24-hour collections. For 20-minute and 24-hour collections, the difference in clearance values between the PAP and Jaffe methods was attributable mostly to lower plasma creatinine values for the PAP method (mean +/- SEM, plasma PAP-to-Jaffe ratio = 0.798 +/- 0.053). However, urine creatinine values also were less by use of the PAP method.

Keratan sulfate (KS) is a glycosaminoglycan, distribution of which is confined mostly to hyaline cartilage. As such, it is a putative marker of hyaline cartilage catabolism. In experiment 1, a focal osteochondral defect was made arthroscopically in 1 radial carpal bone of 2 ponies, and in 2 other ponies, chymopapain was injected into the radiocarpal joint to induce cartilage catabolism. Sequential and concurrent plasma and synovial fluid concentrations of KS were measured, up to 13 months after induction of cartilage injury, to determine whether changes in KS concentrations reflected cartilage catabolism. In experiment 2, a large, bilateral osteochondral defect was made in the radial carpal bones of 18 ponies, which were subsequently given postoperative exercise and/or injected intra-articularly with 250 mg of polysulfated glycosaminoglycan (PSGAG). Medication was given at surgery, then weekly for 4 weeks. Blood samples were collected and synovial fluid was aspirated before surgery, when medication was given, and at postmortem examination (postoperative week 17). The KS concentration was measured in these fluids to determine whether changes in KS concentration indicated an effect of joint treatment. In experiment 1, the concentration of KS in synovial fluid was highest 1 day after joint injury, and the concentration in plasma peaked 2 days after joint injury. For ponies receiving chymopapain intra-articularly (generalized cartilage catabolism), a fivefold increase over baseline was observed in the concentration of KS in plasma (peak mean, 1.2 microgram/ml), and a tenfold increase over baseline in synovial fluid (peak mean, 2.0 mg/ml) was observed. On average, these maxima were threefold higher than values in fluids of ponies with osteochondral defects (focal cartilage disease). In experiment 2, nonexercised ponies had lower KS concentration (as a percentage of the preoperative concentration) in synovial fluid than did exercised ponies at all postoperative times, and.

Epidemiologic relations were evaluated between plasma concentrations of nutrients and cardiovascular diseases. A total of 220 cats were assessed: 144 cats with noninduced acquired heart disease and 76 clinically normal cats. Plasma was assayed for taurine, alpha-tocopherol, selenium, retinol, and total cholesterol and triglycerides concentrations. Cardiovascular disease groups included dilated cardiomyopathy (n = 53), left ventricular hypertrophy (n = 28), hyperthyroidism (n = 11), and uncertain classification (n = 52). In cats with dilated cardiomyopathy, mean plasma taurine concentration was the lowest of that in cats of any group, being only 38% of the value in healthy cats; females had less than half the mean value of males. Tocopherol concentration was 20% lower than normal, and retinol concentration was 40% higher than normal. Total cholesterol concentration was 36% lower than normal. Triglycerides concentration was higher in these cats than in any other group-twice the value recorded in healthy cats and 67% higher than that in hyperthyroid cats. In cats with hypertrophic cardiomyopathy, almost 15% had mean plasma taurine concentration < 30 micromol/L. Retinol concentration was 15% higher, and triglycerides concentration was 54% higher than normal. Approximately 27% of hyperthyroid cats had mildly decreased plasma taurine concentration. Hyperthyroid cats had the lowest tocopherol and cholesterol values; both were at least 30% lower than normal. Retinol concentration was 30% higher than Approximately 14% of cats with uncertain classification had mildly decreased plasma taurine concentration. Plasma retinol and triglycerides concentrations were higher than normal in 25 and 38% of these cats, respectively. Plasma selenium concentration, compared between healthy cats and cats with cardiac disease, was not significantly different. This observation may not be meaningful, however, in light of the limited number of cats in which selenium was assessed.