Oral treatment of avian lead intoxication with meso-2,3-dimercaptosuccinic acid.

The efficacy of meso-dimercaptosuccinic acid (DMSA) (succimer) in treating avian lead intoxication was studied in a retrospective, nonrandomized, longitudinal study. Nineteen birds with moderate to high blood lead concentration and neurologic signs compatible with lead toxicity were treated with DMSA (30 mg/kg p.o., b.i.d.; n = 15) for a minimum of 7 days. In cases with severe neurologic signs, DMSA was supplemented with a single dose of edetate calcium disodium (<50.0 mg/kg of body weight i.m.; n = 4). Blood lead concentrations were measured two or more times (before and after treatment). Median blood lead concentration decreased (87%), neurologic signs were resolved, and there were no apparent adverse secondary effects.     

Effects of induced fescue toxicosis on plasma and tissue catecholamine concentrations in sheep

Sixteen crossbred wethers were distributed among four treatments and fed a control ration based on annual rye-orchardgrass (R-O) for 8 days. Indwelling jugular cannulae were installed and experimental regimes begun the following day (experimental day 1). One-half of the wethers were fed a ration based on endophyte-infected Kentucky-31 fescue while the remainder continued to receive the R-O control diet for 10 days. Spiperone, a dopamine antogonist, was administered to one-half of the wethers receiving each ration on days 8 and 9. Plasma prolactin (PRL), dopamine (DA), norepinephrine (NE) and epinephrine (E) were measured in jugular venous blood on days 1, 3, 5 and 7-10 of the trial. On day 10, the animals were decapitated; and DA, NE, E and 3,4-dihydroxyphenylacetic acid (DOPAC) and monoamine oxidase (MAO) were determined in hypothalamic and pituitary tissue. Plasma DA was elevated (P less than .05) following day 8 in wethers fed infected fescue over those fed (R-O), while plasma PRL was reduced (P = .08). Wethers receiving Spiperone had lowered (P less than .05) plasma DA and elevated (P less than .01) plasma PRL. Plasma DA was negatively correlated (P less than .01) with plasma PRL (r = -0.50) following day 8. Plasma NE and E levels and NE, E, DA and DOPAC tissue concentrations were not affected by Spiperone administration or diet. MAO levels in pituitaries were higher (P less than .01) for Spiperone-treated wethers. Wethers receiving the toxic fescue ration exhibited elevated plasma DA concentrations which was associated with depressed prolactin secretion in wethers.(ABSTRACT TRUNCATED AT 250 WORDS)     

The course of selected bone resorption marker concentrations in response to short-term hypocalcemia experimentally induced with disodium EDTA infusions in dairy cows

The collagen metabolites hydroxyproline (HYP), deoxypyridinoline (DPD), and the carboxyterminal telopeptide of type I collagen (ICTP) are suitable markers for bone resorption in humans and several animal species. The purpose of this study was to describe the course of bone resorption markers during short-term hypocalcemia induced with disodium ethylenediaminetetraacetic acid (Na2EDTA) and to investigate whether bone resorption is increased in dairy cows under these conditions. EDTA infusions have been used as a model for periparturient paresis in dairy cows and to estimate the calcium mobilization rate from body reserves in ruminants. In this study, hypocalcemia was induced by means of a 5% Na2EDTA infusion (0.55 mg/kg/min Na2EDTA for 5 h = total dose of 100.6 g). Two experiments were conducted: (1) Six 4-11 years-old Brown Swiss cows were infused intravenously with EDTA for 5 h. Blood and urine samples were taken repeatedly from 1 day before until 10 days after infusion. (2) Towards the end of the lactation, the experiment was repeated with the same animals after a 14-day-period of feeding a low calcium diet (26 g/animal per day). The EDTA-infusion induced hypocalcemia and hypophosphatemia. The HYP-, DPD- and ICTP-concentration remained mainly unaffected during both infusions. Only DPD showed an increase during infusion and HYP an increase 2 days after the infusion. In conclusion, the EDTA infusion had little effect on the concentrations of the measured bone markers, which may be due to the fact that the serum calcium pool was refilled by increased absorption of Ca via the gastrointestinal tract. From these results, it can be concluded that bone resorption was not influenced by EDTA infusion.     

Serum and tissue concentrations of erythromycin in calves with induced pneumonic pasteurellosis

The effects of pneumonia on the pharmacokinetics of erythromycin administered IM and the tissue concentration changes with time were evaluated in 2-month-old calves. Pneumonia was induced by injection of Pasteurella haemolytica cultures through the thoracic wall into each lung. Six days prior to induction of pneumonia, erythromycin (15 mg/kg) was administered in a single IM dose. Erythromycin was administered again 48, 72, and 96 hours after injection of P haemolytica. On the third day of erythromycin administration (96 hours), the calves were serially euthanatized in groups of 4 calves each at 2, 5, 8, 12, 18, and 24 hours after the final dose was given. Tissue concentrations of erythromycin in kidney, liver, lung, muscle, CSF, and serum were determined. Neither the serum concentrations nor the overall pharmacokinetic values were significantly (P less than or equal to 0.05) changed by pneumonia. The concentrations of erythromycin were maximal at 5 hours for liver, muscle, and serum and at 8 hours for CSF, kidney, and lung. Serum and muscle concentrations were similar, whereas concentrations in CSF were lower than in serum and higher in kidney, liver, and lung. The lung/serum ratios were approximately 2.5 to 3 at 8 through 24 hours after IM administration. The peak concentration in lung was approximately 6 micrograms/g at 8 hours.     

Cardiac isoenzymes in healthy Holstein calves and calves with experimentally induced endotoxemia

This paper describes a controlled study designed to establish normal values for cardiac troponins I and T (cTnI and cTnT) and CK-MB mass in healthy newborn Holstein calves, and to compare values for cTnI, cTnT, CK-MB and total creatine kinase (CK) with age-matched calves experiencing experimentally induced endotoxemia. Nineteen healthy Holstein bull calves, 48 to 72 h of age were used. Baseline cTnI, cTnT, CK-MB and total CK measurements were obtained from control (n = 9) and experimental (n = 10) calves. Controls then received physiological saline and experimental calves received endotoxin (O55:B5 Escherichia coli LPS) intravenously after which cardiac biomarkers and total CK were measured at 3 h, 6 h, 12 h, and 24 h post-initiation of infusion. Measured values were analyzed and compared using analysis of variance (ANOVA) by repeated measure design, with statistical significance set at P < 0.05. The cardiac biomarker cTnT was not detected in any calf at any time point, and CK-MB was only detected in 5 of 95 samples. The cTnI was significantly increased compared to baseline and controls, 3 h post lipopolysaccharide (LPS) infusion. Total CK was significantly increased in LPS administered calves at 18 and 24 h post infusion. The mean, standard deviation, and range for cTnI in healthy controls were 0.023 ng/mL (s = 0.01), and 0.01 to 0.05 ng/mL, respectively. In conclusion, LPS administration was associated with rapid and significant increases in cTnI but CK-MB and cTnT were not detected in the plasma of healthy calves. Total CK values increased significantly following LPS administration. Biochemical evidence of myocardial injury occurs within 3 h following LPS administration to neonatal Holstein calves.     

Use of febantel or ivermectin for treatment of calves with experimentally induced Bunostomum phlebotomum infection

In the first of 2 separate trials, the efficacy of febantel, given at a dosage of 5 mg/kg of body weight, was assessed in calves with 60-day experimentally induced Bunostomum phlebotomum infection. Ten calves were given febantel paste, and 10 were given the vehicle only. All 20 calves were necropsied 7 days after cessation of treatment. Compared with untreated calves, febantel-treated calves harbored 99.4% fewer nematodes. In the second trial, the efficacy of ivermectin, given as a paste formulation at a dosage of 0.2 mg/kg, was assessed in calves with experimentally induced B phlebotomum infection. Ivermectin was given at 18 (n = 6) and 60 (n = 6) days after infection. At each treatment date, 3 additional calves were given vehicle only. At 67 days after infection, all calves were euthanatized. Efficacies of ivermectin against 18- and 60-day infections were 100 and 99.8%, respectively. Both anthelmintic preparations were easily administered, and adverse reactions were not observed.     

Assessment of erythrocyte morphologic abnormalities in mallards with experimentally induced zinc toxicosis

OBJECTIVE: To describe and quantify morphologic abnormalities in RBCs of mallards (Anas platyrhynchos) with experimentally induced zinc toxicosis. ANIMALS: 120 female mallards. PROCEDURE: Farm-raised mallards (6 to 8 months old) were used in the study. On day 0, 60 ducks received shot pellets orally by gavage (mean dose of zinc, 0.97 g); another 60 ducks underwent the same procedure without administration of pellets. On day 15, Romanowsky-stained blood smears were prepared from 53 control and 45 zinc-treated ducks (smears were examined retrospectively). In each smear, 200 RBCs were examined and numbers of erythrocytes with abnormal size, shape, or color were expressed as a percentage. Results were compared with PCV values and zinc dose. RESULTS: Mean PCV value was lower in all zinc-treated ducks, compared with control ducks, and was lower in zinc-treated ducks that died or were euthanatized before day 30 because of severe clinical disease, compared with those that survived. Zinc-treated ducks that survived had a high percentage of polychromatophilic RBCs, and those that that died before day 30 had high percentages of hypochromic RBCs, fusiform RBCs, and RBC nuclear abnormalities. There was no correlation between PCV value or RBC morphologic abnormalities and dose of zinc. CONCLUSIONS AND CLINICAL RELEVANCE: In ducks with severe zinc-induced hemolysis, findings indicated that functional iron deficiency may impair the effectiveness of the erythroid regenerative response and contribute to death. Erythrocyte nuclear abnormalities were consistent with mild dyserythropoiesis. These findings may be applicable to effects of other metal toxicoses and regenerative anemias in birds.     

Effects of experimentally induced Pasteurella haemolytica infection in dairy calves on the pharmacokinetics of flumequine

The effect of experimental Pasteurella haemolytica infection on the intravenous and intramuscular pharmacokinetics of flumequine was studied in dairy calves. The plasma concentration-time curve of flumequine after intravenous injection of 5 mg/kg bodyweight flumequine of a 10% solution before and after experimental infection, was best described by a three-compartment open model. After intramuscular injection of the same dosage rate of a 3% flumequine suspension is was best described by the one-compartment open model with first-order absorption. The experimental infection by intratracheal administration of infectious bovine rhinotracheitis (IBR)-virus and 5 days later intrapulmonary administration of Pasteurella haemolytica produced a clear temperature rise and signs of disease expressed as Average Health Status. Subsequently, plasma Fe and Zn concentration decreased after infection. The distribution volumes Vc, Vd(area) and Vd(ss) after infection (0.07 +/- 0.04, 1.38 +/- 0.36 and 0.50 +/- 0.11 l/kg, respectively) were smaller than those before infection, but the differences were not significant (P less than or equal to 0.1). The intravenous AUC infinity was significantly increased (21.86 +/- 3.51 to 33.85 +/- 2.97 mg.h/l, P less than or equal to 0.01) and the total body clearance (ClB) significantly decreased (0.24 +/- 0.02 to 0.15 +/- 0.01, P less than or equal to 0.01) after infection. After intramuscular injection of flumequine at 5 mg/kg as a 3% suspension, only the bioavailability, F, was significantly decreased after infection (78.5 +/- 14.3 to 59.7 +/- 21.2%, P less than or equal to 0.02). However, this had no consequences for the dosage regimen used. The urine concentration ratio flumequine:7-hydroxy-flumequine:conjugated flumequine changed from 2:1:10 before infection to 6:1:15 after infection, which indicates that hydroxylation and glucuronidation as metabolic pathways for flumequine were decreased after Pasteurella sp. infection.     

Effects of experimentally induced Theileria annulata infection on the pharmacokinetics of oxytetracycline in cross-bred calves

The effects of an experimental Theileria annulata infection on the intravenous (10 mg kg-1) pharmacokinetics of oxytetracycline (OTC) were investigated in crossbred calves. The serum concentration-time curve of oxytetracycline before and after the experimental infection was best described by an open two-compartment model. The experimental infection was induced by a subcutaneous administration of ground-up tick supernate (GUTS) equivalent to 30 Hyalomma anatolicum anatolicum ticks infected with Theileria annulata. It produced a definite temperature rise and symptoms of clinical disease in the calves. The haemoglobin, packed cell volume (PCV), white blood cell (WBC) counts and serum Cu, Fe and Zn concentrations decreased after onset of the infection. The distribution and elimination half-lives (t1/2 alpha and t1/2 beta), volume of the central compartment (Vc), AUC0-infinity, AUMC and mean residence time (MRT), were significantly reduced (P < or = 0.05) and the hybrid rate constants K12, Kel, K12/K21 ratio and total body clearance (ClB) of oxytetracycline were significantly (P < or = 0.05) increased after infection. The infection, however, had no effect on the C0, K21, apparent and steady-state volumes of distribution (Vd(area) and Vdss) of the drug. The above changes may necessitate changes in the dosage regimen of oxytetracycline used to treat Theileria infections in cattle under field conditions.     

Succimer for treatment of lead toxicosis in two cats.

Two cats from a single household were examined because of neurologic abnormalities suggestive of central vestibular disease. The owner had been renovating her 150-year-old house for the preceding 3 months, and renovations included chipping and sanding of old paint from windowsills and stair railings. Lead toxicosis was diagnosed on the basis of history and concentrations of lead in blood and urine. Both cats were treated with succimer. Treatment was not associated with any adverse effects, and both cats recovered completely. Ingestion of old paint from house renovations is the most common source of lead exposure in cats. Owners of cats with gastrointestinal tract or neurologic abnormalities should be questioned specifically about house renovations.     

The effects of experimentally induced bronchopneumonia on the pharmacokinetics and tissue depletion of gentamicin in healthy and pneumonic calves

The effects of a bovine bronchopneumonia model on the pharmacokinetics and tissue residue depletion profiles of gentamicin in calves weighing 90-140 kg was explored. Two groups of heifer calves were used. The first was a normal group, while the second group had bronchopneumonia induced. A scoring system was developed to evaluate the extent of disease in the groups. A bimodal distribution of the serum pharmacokinetic parameters in the pneumonic group was caused by the effects of dehydration. When the severely dehydrated calves were omitted from the analysis, serum clearance of gentamicin was significantly higher in the pneumonic group than in the normal group (P less than 0.05). The pharmacokinetic equations used to fit the tissue concentrations varied from tissue to tissue and between groups. Because the best equation of a particular tissue's concentrations varied between groups, withdrawal periods, which are normally determined in healthy animals, may be inappropriate in diseased animals. Addition of several parameters (serum creatinine, serum urea nitrogen, albumin, fibrinogen, and total protein concentrations, white blood cell counts, central fluid volume, volume of distribution at steady state, area under the serum concentration vs time curve, serum clearance, and elimination rate constant) to these tissue-depletion models using multiple regression improved the prediction of a concentration in a given tissue.     

Effects of treatment with cobra venom factor on experimentally induced feline leukemia

Five- to six-month-old specific-pathogen-free cats were exposed to cobra venom factor (CVF) alone (4 cats), Rickard feline leukemia virus (FeLV; 9 cats), or CVF and FeLV (6 cats). Host-virus relationships were evaluated by monitoring the development of viremia, production of antibody against feline oncornavirus-associated cell membrane antigen, and amount of circulating immune complexes (CIC). Exposure to CVF induced complement depletion, which lasted 8 to 15 days. However, complement depletion did not promote the development of persistent viremia nor alter the production of antibody to feline oncornavirus-associated cell membrane antigen or CIC. Results indicated that the complement system did not protect cats during their initial exposure to FeLV and that an intact complement system was not necessary for the development of antibody against feline oncornavirus-associated antigen or for the formation of CIC.     

Evaluation of edetate and thiamine for treatment of experimentally induced environmental lead poisoning in cattle.

Twenty mature Holstein cows were randomized into 5 treatment groups. Cows of groups 2 to 5 were given 2 mg of elemental Pb/kg of body weight for 28 days. Clinical signs of plumbism were scored, and blood for Pb, progesterone, and hematologic analyses was collected weekly. Cows also were examined weekly for anomalous ovarian cycles. Starting on study day 28, cows in group 3 were treated once daily with 2 mg of thiamine HCl/kg (IM) for 13 days, cows in group 4 were treated twice daily with 62 mg of Na2,Ca-EDTA/kg (IV) for 4 days, and cows in group 5 were given thiamine (dosage regimen the same as for group 3) plus Na2,Ca-EDTA (dosage regimen the same as for group 4). On study days 96 through 139, cows were slaughtered in a commercial abattoir and samples of blood, skeletal muscles, bones, liver, and kidneys were collected and assayed for Pb concentration. Thiamine was not effective in reducing blood Pb concentration, and treatment with Na2,Ca-EDTA and thiamine plus Na2,Ca-EDTA was effective in reducing the concentration of Pb in blood. However, treatment with thiamine was more effective than treatment with Na2,Ca-EDTA or thiamine plus Na2,Ca-EDTA in inducing remission of clinical signs of plumbism. The concentration of Pb in blood was significantly (P less than 0.05) correlated to the concentration of Pb in liver, kidneys, skeletal muscles, and bones. Significant (P less than 0.05) relationship existed between number of days from Pb exposure to slaughter and concentration of Pb in blood, liver, and skeletal muscles. Exposure to Pb did not significantly alter CBC values.(ABSTRACT TRUNCATED AT 250 WORDS)