Metabolism, excretion, pharmacokinetics and tissue residues of phenylbutazone in the horse

The pharmacokinetics, metabolism, excretion and tissue residues of phenylbutazone (PBZ) in the horse were studied following both intravenous and oral administration of the drug at a dose rate of 4.4 mg/kg. A 72-hour blood sampling schedule failed to demonstrate a third exponential phase; the plasma disposition following intravenous injection being described by a two compartment open model, with the following elimination phase parameters: beta = 0.13h-1, t1/2 beta = 5.46h, Vdarea = 0.141 1/kg and C1B = 17.9 ml/kg/h. The hydroxylated metabolites oxyphenbutazone (OPBZ) and gamma-hydroxyphenylbutazone (OHPBZ) were present in detectable concentrations in plasma for 72 and 24 h, respectively. After 36 h OPBZ concentrations exceeded plasma PBZ concentrations. In urine the principal metabolites were OPBZ and OHPBZ but smaller concentrations of another compound, probably gamma-hydroxyoxyphenbutazone (OHOPBZ), were also detected. The percentages of the administered dose recovered from urine were 30.7, 39.0 and 40.3 after 24, 48 and 72 h from the time of injection. Recovery of PBZ and its metabolites from urine was significantly reduced in the first 24 h after oral dosing when the horses had free access to hay, probably as a result of markedly delayed absorption, but this did not occur in animals deprived of food for a few hours before and after dosing. Determination of approximate values of urine/plasma (U/P) concentration ratios for PBZ and its metabolites relative to endogenous creatinine U/P concentration ratio suggested that PBZ was filtered in small amounts only because of the high degree of plasma protein binding and then excreted by diffusion trapping in the alkaline urine. Much higher U/P ratios were obtained for the hydroxylated derivatives, and one at least (OHPBZ) was secreted into urine.     

Clinical pathologic alterations in horses during a water deprivation test

A 72-hour water deprivation test was performed in 12 horses to determine clinical pathologic changes. Reference values for electrolyte (X) clearance, expressed as a percentage of creatinine clearance (CLCR; %CLCRX), were also determined. A comparison was made between urine concentration measurement techniques. Results of %CLCRX determination in 12 horses before water deprivation were 0.034 +/- 0.095 %CLCRNa, 42.4 +/- 9.8 %CLCRK, 0.352 +/- 0.190 %CLCRCl, and 0.710 +/- 0.250 %CLCRP. During water deprivation, there was individual variation for electrolyte clearances, but Na excretion increased significantly (P less than 0.01) at 24 and 48 hours. After 48 hours' water deprivation, %CLCRNa decreased significantly, but was still greater than the initial clearance. Plasma protein was a better indicator of water deprivation (dehydration) in the horse than was PCV. Electrolyte concentrations in serum and urine were determined. Little significant (P less than 0.01) change in acid-base values was noticed after 72 hours' water deprivation. Urine osmolality (as determined by osmometry) was compared with sp gr (determined by refractometry) in determining urine concentration. Initially, sp gr correlated well with urine osmolality determinations, but this correlation decreased after 48 hours.     

Evaluation of urine and serum metabolites in miniature schnauzers with calcium oxalate urolithiasis.

To evaluate underlying causes of calcium oxalate urolithiasis, 24-hour excretion of urine metabolites was measured in 6 Miniature Schnauzers that formed calcium oxalate (CaOx) uroliths during periods when they were fed a standard diet and during periods when food was withheld. Serum concentrations of parathyroid hormone and 1,25-dihydroxyvitamin D also were evaluated. Serum calcium concentrations were normal in all 6 affected Miniature Schnauzers; however, during diet consumption, mean 24-hour urinary excretion of calcium was significantly (P = 0.025) higher than calcium excretion when food was withheld. In 1 dog, urinary calcium excretion was lower during the period of food consumption, compared with the period when food was withheld. Compared with clinically normal Beagles, Miniature Schnauzers that formed CaOx uroliths excreted significantly greater quantities of calcium when food was consumed (P = 0.0004) and when food was withheld (P = 0.001). Miniature Schnauzers that formed CaOx uroliths excreted significantly less oxalate than clinically normal Beagles during fed (P = 0.028) and nonfed (P = 0.004) conditions. Affected Miniature Schnauzers also excreted abnormally high quantities of uric acid. Excretion of citrate was not different between Miniature Schnauzers with CaOx urolithiasis and clinically normal Beagles. In 5 of 6 Miniature Schnauzers with CaOx urolithiasis, concentrations of serum parathyroid hormone were similar to values from age- and gender-matched Miniature Schnauzers without uroliths. The concentration of serum parathyroid hormone in 1 dog was greater than 4 times the mean concentration of clinically normal Miniature Schnauzers. Mean serum concentrations of 1,25-dihydroxyvitamin D in Miniature Schnauzers with calcium oxalate urolithiasis were similar to concentrations of clinically normal Miniature Schnauzers.     

Urine metabolite values in fed and nonfed clinically normal beagles.

Twenty-four-hour excretion of urine metabolites was determined in 33 clinically normal Beagles during periods of consumption of a standard diet and when food was withheld. The goal was to determine normal canine values for urine analytes incriminated in the genesis of calcium oxalate uroliths. During periods when dogs consumed food, dairy urinary excretion of calcium, uric acid, sodium, potassium, magnesium, ammonium, and hydrogen ions were significantly (P = 0.0004, 0.0038, 0.001, 0.0001, 0.0004, 0.0001, and 0.024, respectively) higher than when food was withheld. Urinary excretion of phosphorus, oxalate, and citrate were not significantly different between samples obtained during periods of food consumption and when food was withheld. Male dogs excreted significantly higher quantities of urine oxalate than females during fed (P = 0.003) and nonfed (P = 0.003) conditions. When food was withheld, urinary uric acid excretion was significantly higher in males than females (P = 0.01). Females excreted significantly more urine calcium than males when food was withheld (P = 0.003). Our results indicated that dietary conditions influence the quantity of sodium, potassium, calcium, magnesium, and uric acid excreted in the urine of clinically normal dogs; therefore, dietary conditions should be considered when measuring the concentration of these analytes in urine.     

Disposition, elimination, and bioavailability of phenytoin and its major metabolite in horses

OBJECTIVE: To determine pharmacokinetics and excretion of phenytoin in horses. ANIMALS: 6 adult horses. PROCEDURE: Using a crossover design, phenytoin was administered (8.8 mg/kg of body weight, IV and PO) to 6 horses to determine bioavailability (F). Phenytoin also was administered orally twice daily for 5 days to those same 6 horses to determine steady-state concentrations and excretion patterns. Blood and urine samples were collected for analysis. RESULTS: Mean (+/- SD) elimination half-life following a single IV or PO administration was 12.6+/-2.8 and 13.9+/-6.3 hours, respectively, and was 11.2+/-4.0 hours following twice-daily administration for 5 days. Values for F ranged from 14.5 to 84.7%. Mean peak plasma concentration (Cmax) following single oral administration was 1.8+/-0.68 microg/ml. Steady-state plasma concentrations following twice-daily administration for 5 days was 4.0+/-1.8 microg/ml. Of the 12.0+/-5.4% of the drug excreted during the 36-hour collection period, 0.78+/-0.39% was the parent drug phenytoin, and 11.2+/-5.3% was 5-(phydroxyphenyl)-5-phenylhydantoin (p-HPPH). Following twice-daily administration for 5 days, phenytoin was quantified in plasma and urine for up to 72 and 96 hours, respectively, and p-HPPH was quantified in urine for up to 144 hours after administration. This excretion pattern was not consistent in all horses. CONCLUSIONS AND CLINICAL RELEVANCE: Variability in F, terminal elimination-phase half-life, and Cmax following single or multiple oral administration of phenytoin was considerable. This variability makes it difficult to predict plasma concentrations in horses after phenytoin administration.     

Quantitation of intestinal D-xylose absorption in normal and reovirus-inoculated turkeys

A micromethod was modified to quantitate intestinal D-xylose absorption in young and extremely small birds. This test was performed in control and cloned-reovirus-inoculated turkey poults to investigate intestinal absorptive function. Absorption peaks and curves for control poults closely resembled those observed in normal humans. Poult groups absorbed significantly less D-xylose at 24 and 72 hours (P less than 0.0001 and P less than 0.0008, respectively) but not at 120 hours (P = 0.3178) after receiving a single oral dose of cloned reovirus. The modified D-xylose absorption test is suitable for experimental and clinical determination of absorptive function of the small intestine in the fowl.     

Renal clearance and fractional excretion of electrolytes over four 6-hour periods in cattle

Four consecutive 6-hour urine sample collections were performed on 7 healthy adult Holstein cows fed a diet of coastal Bermuda hay with ad libitum water consumption. Urine (via indwelling urinary catheter) and venous blood samples were collected at 6, 12, 18, and 24 hours. Total 24-hour urine production for the 7 cows ranged from 4,515 to 7,130 ml/d (mean +/- SD, 5,633 +/- 946 ml/d) or 0.02 to 0.04 ml/kg of body weight/d (mean +/- SD, 0.03 +/- 0.007 ml/kg/d). Renal clearance (C) of creatinine (Cr), sodium (Na), calcium (Ca), and magnesium (Mg) varied significantly (P less than 0.05) among individuals, but did not vary significantly among the four 6-hour collection periods. Clearance of chloride (Cl) and phosphorous (P) did not vary significantly either among individuals or among the four 6-hour periods. Clearance of potassium (K) varied significantly (P less than 0.05) among individuals and among the four-6-hour periods. Creatinine clearance was significantly (P less than 0.01) correlated with C(Cl), C(Ca), C(P), and C(Mg) when all data were considered. Significant (P less than 0.05) correlations were also found between C(Cl) and C(K), C(Ca), C(P), and C(Mg); between C(Ca) and C(P) and C(Mg); and between C(P) and C(Mg). Fractional excretion (FE) of Na, K, Cl, Ca, P, and Mg did not vary significantly among the four 6-hour periods. Fractional excretion of Na, Ca, and Mg (P less than 0.01) and K and P (P less than 0.05) varied significantly within individuals among the 6-hour periods.(ABSTRACT TRUNCATED AT 250 WORDS)     

Renal Clearance, Urinary Excretion of Endogenous Substances, and Urinary Diagnostic Indices in Healthy Neonatal Foals

Urine (U) and serum (S) were obtained every 2 hours during a 12- or 24-hour period from eight healthy 96-hour-old pony or horse foals. Dams' milk samples were obtained concurrently. Urine volume was measured during this 12- or 24-hour period. The mean amount of urine produced was 148 +/- 20 ml/kg/day. Baseline urinalyses were evaluated on all foals at two days of age, before any manipulation. Urine generally was dilute (less than 1.008) but the specific gravity was as high as 1.027 in one normal foal. Continuous (12 or 24 hour) urinary catheterization resulted in bacteriuria but not white blood cells in the urine. Prolonged catheterization did not cause foals to become febrile or exhibit clinical signs of cystitis or other illness. Urinary electrolyte excretion, urinary electrolyte clearances, and fractional electrolyte excretions (FE) were measured. When compared with normal values reported in adult horses, excretion, clearance, and FE were similar for sodium (Na) but higher for potassium (K), phosphorus (P), and calcium (Ca). There were no significant differences between data collected during different time periods, and it was concluded that the use of single sample urine/serum estimates of fractional excretion in the neonatal foal was an appropriate indicator of the renal handling of electrolytes, and when viewed in conjunction with urinalysis and other serum parameters, a valuable aid to evaluating renal function.     

Disposition and excretion of flunixin meglumine in horses

The disposition of flunixin meglumine administered IV at a dosage of 1.1 mg/kg was described by a 2-compartment model; the alpha and beta half-lives (t1/2) were 0.61 and 1.5 hours, respectively. When administered IV at a rate of 2.2 mg/kg, the disposition was best described by a 3-compartment model, and the alpha, beta, and lambda t1/2 were 0.16, 1.52, and 6.00 hours, respectively. The zero-time plasma concentrations after flunixin meglumine was administered at 1.1 and 2.2 mg/kg were 9.3 +/- 0.76 and 21.5 +/- 7.4 mg/L, respectively. The bioavailability after oral administration of 1.1 mg/kg was 85.8%. The absorption t1/2 was 0.57 hours, with a peak concentration of 2.50 +/- 1.25 mg/L. The cumulative urinary recoveries for IV and oral administrations were 61.0% and 63.3%, respectively, of the dose for the 12-hour collection period. The final asymptotic points of urine excretion after IV and oral administrations were 406.4 +/- 65.5 and 357.7 +/- 53.5 mg, respectively, which represented 75.5 and 77.5% of the drug accounted for between 30 and 35 hours after administration. Flunixin meglumine was rapidly excreted in urine over a 2- to 4-hour period after drug administration and was highly bound to protein in plasma.     

Reliability of taurine concentrations measured in single urine samples obtained from dogs eight hours after eating

OBJECTIVE: To evaluate the reliability of taurine concentrations measured in a single urine sample obtained from dogs 8 hours after eating, compared with taurine concentrations measured in 24-hour urine samples. ANIMALS: 18 healthy Beagles. PROCEDURE: After emptying the urinary bladder by transurethral catheterization, dogs were fed a canned maintenance diet. Approximately 8 hours later, urine, plasma, and serum samples were obtained for determination of fractional urinary excretion of taurine and urine taurine-to-creatinine concentration ratios (Utaur:Ucr). Results were compared with 24-hour urinary taurine excretion rate. RESULTS: Unbound and total fractional urinary taurine excretion correlated well with unbound and total 24-hour urinary taurine excretion. However, bound fractional urinary taurine excretion correlated poorly with bound 24-hour urinary taurine excretion. Unbound and total Utaur:Ucr correlated well with unbound and total 24-hour urinary taurine excretion. However, bound Utaur:Ucr correlated poorly with bound 24-hour urinary taurine excretion. CONCLUSION AND CLINICAL RELEVANCE: Fractional urinary excretion of unbound and total taurine, and unbound and total Utaur:Ucr are reliable indicators of 24-hour urinary unbound and total taurine excretion in healthy dogs. However, determination of 24-hour urinary taurine excretion is recommended for evaluating urinary bound taurine concentrations of dogs.     

Effect of collection time and exercise restriction on the prediction of urine protein excretion, using urine protein/creatinine ratio in dogs

Nonproteinuric and proteinuric dogs were studied to determine whether the urine protein/creatinine ratio from a 24-hour urine sample could be used to predict urine protein excretion. Urine protein/creatinine ratios estimated from urine produced during daylight hours and from that produced during nighttime hours were compared to determine whether time of sample collection influenced the prediction of the urine protein excretion value. Urine protein/creatinine ratios in urine from male dogs were compared with those from female dogs to determine whether sex had an influence on the value. Hospitalized and nonhospitalized dogs were used to determine the effect of exercise restriction. The urine protein/creatinine ratio varied significantly between healthy and proteinuric dogs (P = 0.0001). It was not influenced by collection period or sex. Animals not confined to hospital cages had a significantly lower urine protein/creatinine ratio than did hospitalized animals confined to a cage (P = 0.003).     

Water deprivation test in the dog: maximal normal values.

Studies were undertaken to determine maximal urine osmolality and urine specific gravity following water deprivation for 20 dogs with normal renal function. In addition, the reliability of body weight, skin pliability, total plasma protein concentration, and packed cell volume as indices of negative water balance was assessed. Following water deprivation for periods sufficient to induce dehydration, the mean maximal urine osmolality was 2,289 mOsm/kg. The corresponding mean maximal urine specific gravity was 1.062 and ranged from 1.050 to 1.076. The ratio of mean maximal urine osmolality to mean serum osmolality at the time of peak urine concentration was 7.3. There was no detectable difference in urine concentration indices between males and females. Changes in skin pliability and packed cell volume proved unreliable as estimates of dehydration. Weight loss and increases in total plasma protein concentration proved to be more consistent indicators of hydration status. Abnormal increases in serum urea nitrogen and serum creatinine concentrations occurred rarely, even though some dogs had water withheld for periods of up to 96 hours.     

Effects of collection time and food consumption on the urine protein/creatinine ratio in the dog

Effects of collection time and food consumption on the variability of the urine protein/creatinine ratio were determined in 10 healthy dogs. In trial 1, dogs were fasted for 12 hours, and urine specimens were obtained by bladder catheterization every 2 hours over an 8-hour collection period during the day. After a 1-week rest, the dogs were entered into trial 2. Dogs were fed at least 60 kcal of a high protein meal/kg of body weight, and urine specimens were obtained every 2 hours over an 8-hour period during the day. Urine total protein and urine creatinine concentrations and the urine protein/creatinine ratio were determined for each urine specimen obtained. Friedman's 2-way analysis by ranks was used to determine the constancy of this ratio over the 4 periods in the 2 trials (fasted and fed). There was no significant variability (P greater than 0.05) in ratios over the 8-hour collection periods in the fasted or fed trial. Feeding did not significantly alter this ratio, because there was no significant difference (P greater than 0.05) in the urine protein/creatinine ratios of the dogs when they were fasted, compared with those of the dogs when they were fed. Seemingly, urine specimens obtained anytime during the day from dogs in both trials (fasted and fed) reflected the urine protein/creatinine ratio.     

Introduction and reisolation of selected gram-positive bacteria from fermented edible wastes

A fermentation process using Lactobacillus acidophilus added to edible food wastes was evaluated for its bactericidal action on selected gram-positive organisms. The Lactobacillus fermentation converts food wastes into an animal feed ingredient. In this study, 5 gram-positive bacteria of zoonotic importance were individually tested. These organisms were: Group E Streptococcus, Erysipelothrix rhusiopathiae, Clostridium perfringens, Corynebacterium pseudotuberculosis, and Listeria monocytogenes. For each experiment, Lactobacillus was first mixed into ground waste; one of the test organisms was then inoculated and mixed. This mixture was divided among eight 5.5-L containers and incubated (duplicates) at 5 C, 10 C, 20 C, and 30 C for 96 hours. Internal waste temperature, reduction-oxidation, and pH were monitored. Waste samples were taken initially and at subsequent 24-hour periods. Qualitative and quantitative recoveries of the test bacteria were attempted for each sample. Group E Streptococcus was reisolated in increasing numbers at all temperatures throughout the fermentation period. Erysipelothrix rhusiopathiae was recovered throughout the 96-hour period at 5 C; at 10 C it was recovered at 24 hours but not at 48 hours. Erysipelothrix rhusiopathiae was killed by 24 hours at 20 C and 30 C fermentation temperatures. Clostridium perfringens survived the entire test period at 5 C, 10 C, and 20 C; it was killed by 72 hours at 30 C. Neither Corynebacterium pseudotuberculosis nor Listeria monocytogenes was reisolated at any temperature at any time.     

The effect of vitamin C supplementation on plasma concentration and urinary excretion of vitamin C in cattle

We investigated the plasma concentration and urinary excretion of vitamin C in cows supplemented with vitamin C. Five cows (mean BW = 597 kg) were allocated to a 5 x 5 Latin square design and supplemented with a vitamin C preparation coated with hydrogenated soybean oil at 0, 10, 20, 40, or 60 mg of vitamin C per kg of BW per day for 9 d. Plasma and urine samples were collected for measuring vitamin C concentration. Urinary excretion of vitamin C was expressed as the ratio of vitamin C to creatinine. Plasma vitamin C concentration and urinary vitamin C excretion increased quadratically as dietary vitamin C increased (P < 0.001); that is, the lowest dose affected neither plasma vitamin C concentration nor urinary vitamin C excretion but the plasma vitamin C concentration and urinary vitamin C excretion increased (P < 0.05) with increasing supplementation of vitamin C at greater doses. This suggests that plasma vitamin C concentration affects urinary excretion of vitamin C in cattle and that plasma vitamin C concentration exceeded the renal threshold for vitamin C in the cows receiving vitamin C at 20 mg/kg of BW per day. Furthermore, increased urinary excretion of vitamin C appears to limit plasma vitamin C concentration in response to vitamin C intake. The daily excretion of vitamin C was estimated by the reported value of daily creatinine excretion, indicating that the daily amount of vitamin C excreted into urine was more than half of supplied vitamin C. Therefore, a large part of supplied vitamin C probably escapes ruminal degradation and is absorbed but excreted into urine.     

Evaluation of urinary carnitine and taurine excretion in 5 cystinuric dogs with carnitine and taurine deficiency

Five client owned dogs with cystinuria were diagnosed with carnitine and taurine deficiency while participating in a clinical trial that used dietary management of their urolithiasis. Stored 24-hour urine samples collected from the cystinuric dogs before enrollment in the clinical diet trial were quantitatively evaluated for carnitine and taurine. These results were compared to those obtained from 18 healthy Beagles. Both groups of dogs were fed the same maintenance diet for a minimum of 2 weeks before 24-hour urine collection. The protocol used for 24-hour urine collections was the same for cystinuric dogs and healthy Beagles except that cystinuric dogs were catheterized at baseline, 8 hours, 12 hours, and at the end of the collection, whereas Beagles were catheterized at baseline, 8 hours, and at the end of the collection. Three of 5 dogs with cystinuria had increased renal excretion of carnitine. None of the cystinuric dogs had increased renal excretion of taurine, but cystinuric dogs excreted significantly less (P < .05) taurine in their urine than the healthy Beagles. Carnitinuria has not been recognized previously in either humans or dogs with cystinuria, and it may be 1 risk factor for developing carnitine deficiency. Cystinuric dogs in this study were not taurinuric; however, cystine is a precursor amino acid for taurine synthesis. Therefore, cystinuria may be 1 risk factor for developing taurine deficiency in dogs. We suggest that dogs with cystinuria be monitored for carnitine and taurine deficiency or supplemented with carnitine and taurine.     

Dehydration in stressed ruminants may be the result of a cortisol-induced diuresis

The effect on water and electrolyte balance of stress, simulated by intravenous infusion of cortisol, was studied using 24 18-mo-old Merino wethers (37.0 +/- 0.94 kg mean body weight [BW]) over 72 h. The sheep were allocated to one of four groups: 1) no water/no cortisol (n = 6); 2) water/no cortisol (n = 4); 3) no water/cortisol (n = 6); and 4) water/cortisol (n = 4). Animals allocated to the two cortisol groups were given 0.1 mg x kg BW(-1) x h(-1) of hydrocortisone suspended in isotonic saline to simulate stress for the duration of the experiment. Total body water, plasma cortisol, osmolality and electrolytes, and urine electrolytes were determined at 24-h intervals for 72 h. In the presence of cortisol, total body water was maintained in the face of a water deprivation insult for 72 h. Water deprivation alone did not induce elevated plasma concentrations of cortisol, in spite of a 13% loss of total body water between 48 and 72 h. Infusion of cortisol was found to increase urine output (P = 0.003) and decrease total urinary sodium output (P = 0.032), but had no effect on plasma electrolyte levels or water intake. Water deprivation was found to increase plasma sodium concentrations (P = 0.037). These results indicate that sheep given cortisol to simulate stress suffer from a loss of body water in excess of that associated with a loss of electrolytes, and support the hypothesis that elevated physiological concentrations of cortisol induce a diuresis in ruminants that contributes to dehydration.     

Excess cortisol interferes with a principal mechanism of resistance to dehydration in Bos indicus steers

This study investigated the effects of excess cortisol on physiological mechanisms that resist dehydration in Bos indicus steers (n = 31, 2 yr of age, 193 +/- 21.47 kg mean BW) during a 90-h period. Steers were assigned randomly to one of four groups: 1) no water/no cortisol (n = 8), 2) water/no cortisol (n = 8), 3) no water/cortisol (n = 8), and 4) water/cortisol (n = 7). Animals allocated to cortisol treatment groups were given 0.1 mg x kg BW(-1) x h(-1) of hydrocortisone suspended in isotonic saline for the duration of the study. Total body water, osmolality, hematocrit, urine output, feed and water intake, and plasma concentrations of arginine vasopressin (AVP), angiotensin II (AII), electrolytes, total protein, and albumin were determined at 24-h intervals for 90 h. In the presence of excess plasma cortisol, total body water was maintained in the presence of a water deprivation insult for 90 h, whereas hydration indices, such as total plasma protein and albumin, did not change, supporting the body water data. However, plasma osmolality increased for the water-deprived groups from 24 h (P = 0.008). Hematocrit did not reflect dehydration in any group. Water deprivation induced an increase in endogenous plasma cortisol concentrations after 60 h of the study (P = 0.028). Plasma concentrations of AVP increased with water deprivation (P = 0.006). Excess cortisol decreased the plasma concentration of AVP at 72 h only (P = 0.027) and suppressed plasma concentrations of AII at 24 and 72 h (P < 0.001 and P = 0.036, respectively). Animals treated with excess cortisol maintained urinary output for 48 h before decreasing at 72 h (P = 0.057), although there was no effect on water or feed intake. Water deprivation increased plasma sodium concentrations (P < 0.05) until 72 h, whereas potassium decreased under the influence of excess plasma cortisol (P = 0.001) at 24 h. Water deprivation increased plasma chloride concentration at 72 and 90 h (P = 0.051 and P = 0.026, respectively). Plasma phosphorus decreased at 24 h (P = 0.001) and remained at lesser concentrations for the duration of the study (P = 0.05). These results highlight the complexity of endocrine interactions associated with water balance in Bos indicus steers. We accept our hypothesis that, in the presence of excess cortisol, the renin-angiotensin-aldosterone axis is suppressed; however, homeostasis is achieved through other physiological systems.     

Serum and urine inorganic fluoride concentrations and urine oxalate concentrations following methoxyflurane anesthesia in the dog.

Plasma fluoride, urine fluoride and urine oxalate concentrations were measured before administering an anesthetic to 8 dogs, and at 0, 3, 9, 24, 48, and 72 hours following 1.5 hours of anesthesia with 1% methoxyflurane. Plasma and urine osmolalities were measured and compared with fluoride and oxalate values. Fluoride concentration increased in both plasma and urine following anesthesia when compared with the preanesthetic concentrations. Maximum mean plasma inorganic fluoride was 106.71 mumoles per liter (+/- 25.44 SE) at 9 hours after exposure to methoxyflurane was completed. By 72 hours after exposure to methoxyflurane the plasma fluoride concentration was 23.47 microM/L (+/- 5.74 SE). Mean urine inorganic fluoride concentration was highest at 9 hours after exposure to methoxyflurane and reached 6047.03 microM/L (+/- 1378.46 SE) as compared to the mean preanesthetic base-line concentration of 542.68 microM/L (+/- 132.93 SE), and the 72 hour mean urine fluoride concentration which was 1593.78 microM/L (+/- 579.46 SE). Urine oxalate concentrations, when compared with urine osmolality (mg/mOsm), increased throughout the study. The 72-hour concentration after exposure to methoxyflurane was 2.5 times the preanesthetic (mg/mOsm) oxalate concentration. Plasma osmolality did not change markedly during the study. Urine osmolalities varied between animals and collection times, but a consistent pattern did not occur. Clinical and laboratory signs of renal dysfunction were not observed in any animal during the study.     

Role of mixed-function oxidase in 3-methylindole-induced acute pulmonary edema in goats

The relationship between the pulmonary toxicity of 3- methylindole (3MI, skatole) and the mixed-function oxidase (MFO) system was investigated. Nine goats assigned to three groups were given a jugular infusion of [14C]3MI (0.02 to 0.03 g of 3MI/kg of body weight containing 0.5 muCi/kg of body weight) for 1.5 hours to induce acute pulmonary edema. Two groups of three goats each were treated with phenobarbital (PB) or piperonyl butoxide (BT) prior to 3MI infusion to induce or to inhibit the MFO system. Three goats were used as 3MI controls. During a 72-hour test period, blood was collected for determination of plasma 3MI concentration and radioactivity. Urine was collected and was fractionated by column chromatography. The severity of pulmonary lesions was evaluated by gross and microscopic examination. Pretreatment with BT prevented the onset of acute pulmonary edema. Goats pretreated with PB had more severe lung lesions than did 3MI controls. Plasma of goats pretreated with BT had a longer half-life (2.1 hours) of radioactivity, whereas plasma of goats pretreated with PB had a shorter half-life (1.0 hour) when compared with plasma of 3MI control goats (1.5 hours) given the same dosage of [14C]3MI (P less than 0.025). The plasma half-life of 3MI was longer (P less than 0.025) in BT-pretreated goats (0.45 hour) than that in PB-pretreated goats (0.26 hour). At 72 hours, 70% to 98% of the infused radioactivity had been excreted in the urine. The pattern of urinary metabolites of 3MI was altered in BT-pretreated goats compared with patterns in control and PB-pretreated goats. Results indicate that the MFO system is one of the pathways involved in the metabolism of 3MI and that pulmonary toxicosis results from metabolism of 3MI by this enzyme system.