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Summary

Administration of thiazide diuretics has been recommended to prevent calcium oxalate urolith development in dogs. To evaluate the effects of thiazide diuretics in dogs, 24-hour urine excretion of calcium was measured in 6 clinically normal Beagles after administration of chlorothiazide (ctz) for 2 weeks, administration of ctz for 10 weeks, and administration of calcium carbonate and ctz for 2 weeks. Compared with baseline values, 24-hour urine calcium excretion did not decrease after ctz administration. When ctz was given at a high dosage (130 mg/ kg of body weight), urinary calcium excretion was significantly (P < 0.04) higher than baseline values. Based on these observations, we do not recommend ctz for treatment or prevention of canine calcium oxalate urolithiasis.

Free access
in American Journal of Veterinary Research

Abstract

Objective

To determine whether supplemental IV calcium administration would attenuate or prevent gentamicin-induced acute renal failure, defined as an increase in serum creatinine concentration ≥ 50% above baseline.

Animals

10 healthy pony mares.

Procedure

Pony mares were randomly assigned to receive calcium at a dosage of 20 mg/kg of body weight or saline solution IV, twice daily for 14 days. All pony mares received gentamicin at a dosage of 20 mg/kg IV every 8 hours for 14 days. Gentamicin pharmacokinetic, serum biochemical, and urinalysis data were measured every other day for the 14-day study period. Renal histologic examination was performed, and results were scored at the end of the 14-day period.

Results

4 of 5 mares not receiving calcium supplementation developed acute renal failure. Only 1 of the 5 mares receiving calcium supplementation developed acute renal failure. Over the course of the study, pony mares receiving calcium supplementation had significantly fewer changes in urinalysis variables, and significantly less microscopic renal damage.

Conclusion

Daily IV administration of calcium attenuated gentamicin-induced acute renal failure.

Clinical Relevance

Calcium supplementation may help diminish the risk of acute renal failure associated with aminoglycoside antibiotics. (Am J Vet Res 1998;59:1055–1062)

Free access
in American Journal of Veterinary Research

Abstract

Objective

To evaluate coagulation variables in 2 groups of dogs after tromethamine administration.

Animals

13 Beagles.

Procedures

Both groups of dogs received a 30-minute IV infusion of 10 ml of 0.3M tromethamine/kg of body weight. In unsedated dogs (group 1, n = 8), prothrombin time, activated partial thromboplastin time, normalized ionized calcium concentration, platelet numbers, and platelet function were measured prior to treatment, at the end of the infusion, and 1 hour after the infusion. In xylazine-sedated dogs (group 2, n = 5), buccal mucosal bleeding time and plasma percentage of von Willebrand factor antigen were measured before and 1 hour after infusion, and fibrin degradation products concentration was measured 1 hour after infusion. Platelet function was assessed by determining platelet aggregation and by measuring ATP release from the aggregating platelets over 6 minutes, using a whole blood aggregometer, with 20, 10, and 5 μM ADP and 5 and 10 μg of collagen/ml as platelet activation agonists.

Results

There was no significant change in any of the variables measured in either group of dogs, compared with baseline values.

Conclusions and Clinical Relevance

When administered to healthy dogs, tromethamine does not change the coagulation indices measured. (Am J Vet Res 1997;58:777–780)

Free access
in American Journal of Veterinary Research

Abstract

Objective

To examine whether impaired aggregation of platelets from Japanese Black cattle with Chediak-Higashi syndrome (CHS) was attributable to mobilization of cytosolic Ca2+.

Animals

4 healthy Japanese Black cattle and 3 Japanese Black cattle with CHS.

Procedure

Aggregation and mobilization of cytosolic Ca2+ in response to various receptor agonists was measured in platelets from healthy cattle and cattle with CHS. Involvement of endogenous ADP and arachidonic acid in collagen-induced responses was examined. Cytosolic Ca2+ concentration was measured after platelets were loaded with the Ca2+ indicator fura-PE3. Platelet aggregation was measured with an aggregometer.

Results

Collagen (3 to 15 μg/ml)-induced increases in cytosolic Ca2+ concentration and aggregation were markedly impaired for platelets from cattle with CHS, compared with values for platelets from healthy cattle. Although aggregation and the sustained phase of the cytosolic Ca2+ response to ADP were also decreased in platelets from cattle with CHS, these decreases were small, compared with those in response to collagen. A cyclooxygenase inhibitor and a phospholipase A2 inhibitor did not have any effect on peak cytosolic Ca2+ concentration or collagen-induced aggregation of platelets from healthy cattle. Responses to a P2T-purinoceptor antagonist suggested that decreased release of endogenous ADP was only partially involved in the impaired response to collagen among platelets from cattle with CHS.

Conclusions and Clinical Relevance

Marked inhibition of collagen-induced Ca2+ mobilization, rather than decreased release of endogenous substances, appeared to be the major cause of impaired platelet response to collagen and the hemorrhagic tendency in cattle with CHS. (Am J Vet Res 1998;59:744-749)

Free access
in American Journal of Veterinary Research

Abstract

Objective

To determine the effects of cisapride on feline colonic smooth muscle function.

Design

In vitro smooth muscle mechanical measurements.

Animals

Intact colon was obtained from healthy 2- or 3-year-old cats.

Procedure

Longitudinal smooth muscle strips from proximal and distal portions of feline colon were suspended in physiologic buffer solution (37 C, 100% O2, pH 7.4), attached to isometric force transducers, and stretched to optimal muscle length. Control responses were obtained at each muscle site with acetylcholine (10−8 to 10−4 M), cholecystokinin (10−11 to 10−7 M), substance P (10−11 to 10−7 M), or neurotensin (10−11 to 10−7 M). Muscles were then stimulated with cumulative (10−9 to 10−6 M) or bolus (10−6 M) doses of cisapride in the absence or presence of tetrodotoxin (10−6 M) and atropine (10−6 M), nifedipine (10−6 M), or calcium-free buffer solution.

Results

Cisapride stimulated contractions of longitudinal smooth muscle from proximal and distal portions of feline colon that were similar in magnitude to contractions induced by substance P and neurotensin. Cisapride contractions were only partially inhibited by tetrodotoxin (10−6 M) and atropine (10−6 M). suggesting that cisapride responses are only partially dependent on enteric cholinergic nerves. Nifedipine (10−6 M) inhibited the maximal contraction to cisapride (10−6 M) by approximately 80%. Removal of extracellular calcium did not inhibit cisapride contractions to a greater extent than did inhibition by nifedipine, indicating that calcium influx through voltage dependent calcium channels was predominantly responsible for the dependence of the cisapride contraction on extracellular calcium.

Conclusions

Cisapride-induced contractions of feline colonic smooth muscle are largely smooth muscle-mediated and dependent on calcium influx, and are only partially dependent on enteric cholinergic nerves.

Clinical Relevance

Cisapride may be useful in the treatment of feline colonic motility disorders. (Am J Vet Res 1996;57:541–546)

Free access
in American Journal of Veterinary Research

Abstract

Objective

To determine the response of equine articular cartilage cells to heat and calcium stresses.

Design

Analysis of newly synthesized, [35S]methionine-labeled proteins after treatment of isolated primary equine chondrocytes.

Procedure

Primary cultures of equine articular chondrocytes were incubated at temperatures ranging from 37 to 42 C for heat stress experiments or incubated in the presence or absence of the intracellular calcium pump inhibitor, thapsigargin, for calcium stress experiments. Patterns of new protein synthesis were determined by incubating with [35S]methionine followed by separation of proteins by use of one- or two-dimensional gel electrophoresis and visualization of labeled proteins by use of fluorography.

Results

Equine chondrocytes cultured at temperature of 42 C had increased synthesis of specific proteins, compared with the profile of protein synthesis in control chondrocytes cultured at 37 C. These changes were characteristic of the heat shock stress response described in a number of other mammalian cell-types. Equine chondrocytes cultured in the presence of thapsigargin also had increased synthesis of specific proteins. Two-dimensional gel electrophoresis of these newly synthesized proteins revealed the changes to be consistent with the induction of the glucose-regulated protein family of stress proteins.

Conclusions

Changes in the pattern of new protein synthesis can be induced in differentiated equine articular chondrocytes by heat shock or calcium stress. These responses are characteristic of a widely described mammalian stress response that has been postulated to be involved in cellular protective mechanisms. The ability of equine chondrocytes to mount a robust stress response may be important in the processes of tissue damage and recovery in articular joints of horses. (Am J Vet Res 1996;57:860–865)

Free access
in American Journal of Veterinary Research

Abstract

Objective

Because of the implication of histamine in canine atopic dermatitis, H1-antihistamines may provide a valid alternative to glucocorticoid therapy. In vitro study of these drugs prior to clinical testing can allow the most promising compounds to be selected for trials and render trials with drugs of doubtful efficacy unnecessary.

Sample Population

Isolated canine cutaneous mast cells.

Procedure

Cells were preincubated with antihistamines at increasing concentrations and incubated with concanavalin A (1,000 µg/ml), calcium ionophore A23187 (1 µM), and substance P (100 µM). Compound 48/80 was not used because it proved to be cytotoxic.

Results

Generally, significant prodegranulating effect was not observed for most of the studied agents. Only terfenadine increased spontaneous histamine release at concentrations > 30 µM. Cetirizine did not block histamine release at any of the studied concentrations. Ketotifen had a low inhibitory effect only at the highest concentration (100 µM) after concanavalin A- (23.6 ± 2.8%) and calcium ionophore A23187- (29.8 ± 3.0%) induced release. Terfenadine caused a concentration-dependent inhibitory effect after ionophore A23187- (48.1 ± 2.2%) and concanavalin A- (28.9 ± 2.3%) activation, but was inactive against substance P-induced release. In contrast, loratadine had potent dose-dependent inhibition of concanavalin A- and ionophore A23187-induced histamine release, with maximal effect of 85.6 ± 3.1 % and 62.6 ± 4.7%, respectively, at 100 µM concentration. After substance P activation, histamine release was only slightly inhibited by loratadine (14.8 ± 1.1%).

Conclusions

This study documents the behavior of isolated canine cutaneous mast cells in the presence of nonimmunologic stimulation. Using this in vitro method, we were able to determine that loratadine is the only antihistamine that has potent inhibition of histamine release from dog cutaneous mast cells without a substantial prodegranulating effect. Loratadine is, therefore, a good candidate for clinical testing. (Am J Vet Res 1997;58:293–297)

Free access
in American Journal of Veterinary Research

SUMMARY

A series of studies was conducted to identify a practical measure for preventing dental calculus formation in dogs. The studies involved a colony of 27 Beagles that received an initial dental prophylaxis. The dogs were then stratified on the basis of their normal rate of calculus formation and randomly assigned to parallel groups within each strata. During 4-week test periods, a variety of experimental regimens were instituted, followed by clinical assessments of calculus. Major observations were that a crystal growth inhibitor, soluble pyrophosphate, incorporated into a dry dog food modestly reduced calculus formation when used at high concentrations; anticalculus effects attributable to this agent were significant (P < 0.05) only when it was used as a surface coating; the coating of dry dog chow or plain biscuits with a calcium sequestrant, sodium hexametaphosphate (hmp), provided the greatest benefit and resulted in significant (P < 0.05) reductions in calculus formation of about 60 to 80%, depending on the dosage regimen; and the feeding of a single daily snack of 2 hmp-coated plain biscuits (0.6% hmp) decreased calculus formation by nearly 80%. We concluded that the coating of dry dog chow or plain dog biscuits with hmp is an effective means of reducing calculus formation in dogs.

Free access
in American Journal of Veterinary Research

Abstract

Objective

To evaluate buffering capacity and side effects of equivalent doses of tromethamine (THAM) and sodium bicarbonate (BIC).

Animals

18 purebred dogs.

Procedure

Acidosis was induced by having dogs breathe a hypoxic gas mixture (FIO2 = 0.10) until arterial base balance ≤ −7.5 mEq/L was reached. Dogs then received a 30-minute infusion of 5% BIC (n = 6) or 0.3M THAM (n = 8), and Fio2 increased to 0.30. Drug doses were calculated to correct base balance to zero.

Results

During hypoxia, for BIC- and THAM-treated groups, median (interquartile range [Q1, Q3]) pHa and arterial base balance decreased to 7.16 (7.07, 7.38) and 7.19 (7.11, 7.31), −14 (−16, 9) and −12 (−16, −11) mEq/L, respectively, and mixed venous lactate concentration increased to 7 (2, 15) and 6 (3, 13) mmol/L, respectively. Immediately after each infusion, acid-base and cardiopulmonary variables returned toward baseline. For respective BIC- and THAM-treated groups, pHa increased to 7.37 (7.26, 7.44) and 7.40 (7.33, 7.49) and base balance increased to 0 (−4, 7) and 0 (−4, 2) mEq/L. Lactate concentration decreased only slightly to 5 (2, 6) and 5 (2, 9) mmol/L, but continued to decrease throughout the study. The only significant (P ≤ 0.05) difference between groups was hypernatremia after BIC administration that persisted for 60 minutes. The PaCO2 in BIC-treated dogs increased immediately after infusion, compared with values during hypoxia. Standardized ionized calcium values initially decreased in both groups, but returned to baseline by 60 minutes.

Conclusion

The buffering capacity of THAM is equal to that of BIC, although THAM does not cause the transient hypernatremia or hypercapnia observed after BIC administration. Hypocalcemia may be transient after administration of either solution. Thus, THAM is an acceptable alternative to BIC for treatment of metabolic acidosis in selected anesthetized dogs. (Am J Vet Res 1997;58:771–776)

Free access
in American Journal of Veterinary Research

SUMMARY

Clorazepate dipotassium was administered orally to 8 healthy dogs at a dosage of 2 mg/kg of body weight, q 12 h, for 21 days. Serum disposition of nordiazepam, the principle metabolite of clorazepate, was determined after the first and last dose of clorazepate. Disposition variables were analyzed by use of model-independent pharmacokinetics by the predictive equations method and the trapezoidal rule method. Complete blood counts, serum chemical analyses, and urinalyses were performed before administration of clorazepate and at 10 and 21 days after administration of clorazepate.

Maximal nordiazepam concentrations ranged from 446 to 1,542 ng/ml (814 ± 334 ng/ml), at 59 to 180 minutes (97.9 ± 42.0 minutes) after a single oral dose of clorazepate. Maximal nordiazepam concentrations ranged from 927 to 1,460 ng/ml (1,308 ± 187.6 ng/ml), at 120 to 239 minutes (153 ± 57.9 minutes) after multiple oral doses of clorazepate. Serum disposition was significantly altered after multiple doses of clorazepate. Using data determined by the predictive equations method, the mean residence time after multiple doses (712 ± 214 minutes) was longer (P < 0.05) than after a single dose (527 ± 95.8 minutes). Oral volume of distribution after multiple doses of clorazepate (1.76 ± 0.647 L/kg) was smaller (P < 0.02) than after a single dose (3.18 ± 1.52 L/kg). Oral clearance after multiple doses of clorazepate (3.09 ± 0.726 ml/min/kg) was less (P < 0.001) than after a single dose (6.54 ± 2.15 ml/min/kg). Absorption half-life after multiple doses (72 minutes) was longer (P < 0.01) than after a single dose (33 minutes). The elimination half-life after a single dose (284 minutes) was not significantly different after multiple doses (355 minutes).

Significant changes (P < 0.05) in serum chemical values after multiple doses of clorazepate included decreased concentrations of albumin, total protein, and calcium and increased concentrations of urea nitrogen and glucose. Serum activities of alkaline phosphatase and alanine transaminase increased after multiple doses of clorazepate. Significant changes (P < 0.05) in the hemogram included increased total wbc count, segmented neutrophils, lymphocytes, and eosinophils. Urine pH after multiple doses (5.88 ± 0.641) was lower (P < 0.01) than after a single dose (7.44 ± 1.29). All changes in laboratory values remained within our reference ranges.

Mild sedation and ataxia developed in only 1 dog after the first dose of clorazepate. These effects were transient and did not redevelop with additional dosing.

An oral clorazepate dosage of 2 mg/kg, q 12 h, maintains serum nordiazepam concentrations considered to be therapeutic in human beings (500 to 1,900 ng/ml).

Free access
in American Journal of Veterinary Research