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1.
Sci Rep ; 7(1): 13112, 2017 10 13.
Article in English | MEDLINE | ID: mdl-29030642

ABSTRACT

Urea cycle enzyme deficiency (UCED) patients with hyperammonemia are treated with sodium benzoate (SB) and sodium phenylacetate (SPA) to induce alternative pathways of nitrogen excretion. The suggested guidelines supporting their use in the management of hyperammonemia are primarily based on non-analytic studies such as case reports and case series. Canine congenital portosystemic shunting (CPSS) is a naturally occurring model for hyperammonemia. Here, we performed cross-over, randomized, placebo-controlled studies in healthy dogs to assess safety and pharmacokinetics of SB and SPA (phase I). As follow-up safety and efficacy of SB was evaluated in CPSS-dogs with hyperammonemia (phase II). Pharmacokinetics of SB and SPA were comparable to those reported in humans. Treatment with SB and SPA was safe and both nitrogen scavengers were converted into their respective metabolites hippuric acid and phenylacetylglutamine or phenylacetylglycine, with a preference for phenylacetylglycine. In CPSS-dogs, treatment with SB resulted in the same effect on plasma ammonia as the control treatment (i.e. saline infusion) suggesting that the decrease is a result of volume expansion and/or forced diuresis rather than increased production of nitrogenous waste. Consequentially, treatment of hyperammonemia justifies additional/placebo-controlled trials in human medicine.


Subject(s)
Hyperammonemia/drug therapy , Nitrogen/blood , Saline Waters/therapeutic use , Animals , Dogs , Female , Hyperammonemia/blood , Male , Phenylacetates/adverse effects , Phenylacetates/pharmacokinetics , Phenylacetates/therapeutic use , Random Allocation , Sodium Benzoate/adverse effects , Sodium Benzoate/pharmacokinetics , Sodium Benzoate/therapeutic use
2.
Vet Rec ; 173(2): 41, 2013 Jul 13.
Article in English | MEDLINE | ID: mdl-23784060

ABSTRACT

Nineteen dogs with vesico-urethral reflex dyssynergia (VURD) were treated with prazosin or terazosin 0.5 mg/kg twice daily to compare efficacy and side effects. Dogs were referred because of signs of (partial) urethral obstruction. Physical examination, abdominal ultrasonography, urinalysis and a radiographic contrast study of bladder and urethra (urethrocystography) were routinely performed. If no mechanical causes of obstruction or disease of the distal urinary tract were observed, the diagnosis VURD was presumed and the dogs were included in our study. Follow-up information was obtained from owners or referring veterinarians. Significantly more side effects were seen in the dogs treated with terazosin (n=14; 93 per cent) compared with the dogs treated with prazosin (n=5; 20 per cent; P=0.002). Effects of the treatment were comparable between prazosin and terazosin. Labradors and dogs that were castrated surgically had a significant better survival (P<0.01) compared with other breeds and animals that were castrated chemically. There was a moderate to good effect in 60 per cent of the dogs treated with prazosin, and in 64 per cent of the dogs treated with terazosin.


Subject(s)
Adrenergic alpha-1 Receptor Antagonists/therapeutic use , Dog Diseases/drug therapy , Prazosin/analogs & derivatives , Prazosin/therapeutic use , Urinary Retention/veterinary , Adrenergic alpha-1 Receptor Antagonists/adverse effects , Animals , Dogs , Male , Prazosin/adverse effects , Treatment Outcome , Urinary Bladder/pathology , Urinary Retention/drug therapy , Urological Agents/adverse effects , Urological Agents/therapeutic use
3.
J Vet Intern Med ; 23(5): 957-63, 2009.
Article in English | MEDLINE | ID: mdl-19627473

ABSTRACT

BACKGROUND: Copper-associated chronic hepatitis (CACH) recently has been recognized in the Labrador Retriever as an inherited disorder with a late onset of clinical signs. No studies have investigated dietary management for the long-term treatment of this disease or for its potential in delaying the onset of clinical signs in subclinical cases. OBJECTIVES: To investigate the effects of a low-copper diet and zinc gluconate on hepatic copper concentrations in Labrador Retrievers with abnormal hepatic copper concentrations. ANIMALS: Twenty-four client-owned Labradors that were related to patients affected with CACH and that had been diagnosed with increased hepatic copper concentrations. METHODS: Hepatic copper concentrations were assessed before and after an average of 8 and 16 months of treatment. During this time, all dogs were fed exclusively a low-copper diet. In addition, dogs were assigned to 1 of 2 groups in a randomized double-blind manner to receive a supplement of zinc gluconate or placebo. RESULTS: Twenty-one dogs completed the study. Hepatic copper concentrations decreased in both groups at recheck 1 (n = 21; group 1, P < .001; group 2, P= .001) and at recheck 2 (n= 16; group 1, P= .03; group 2, P= .04). No difference in hepatic copper concentrations was found between the 2 groups before treatment (P= .65), at recheck 1 or at recheck 2 (P= .52-.79). CONCLUSIONS AND CLINICAL RELEVANCE: Feeding low-copper diets to Labradors is effective in decreasing hepatic copper concentrations. Adjunctive treatment with zinc does not appear to increase the copper-lowering effects of dietary management.


Subject(s)
Chemical and Drug Induced Liver Injury, Chronic/veterinary , Copper/metabolism , Dog Diseases/diet therapy , Dog Diseases/metabolism , Gluconates/administration & dosage , Hepatitis, Animal/chemically induced , Animals , Biopsy/veterinary , Chemical and Drug Induced Liver Injury, Chronic/diet therapy , Chemical and Drug Induced Liver Injury, Chronic/metabolism , Copper/administration & dosage , Dogs , Double-Blind Method , Female , Genetic Predisposition to Disease , Gluconates/pharmacokinetics , Hepatitis, Animal/diet therapy , Histocytochemistry , Liver/drug effects , Liver/metabolism , Male
7.
Tijdschr Diergeneeskd ; 121(5): 126-30, 1996 Mar 01.
Article in Dutch | MEDLINE | ID: mdl-8685885

ABSTRACT

Before a veterinary drug is licensed for the Dutch market it has to comply to basic pharmaceutical standards. From the results of this study, carried out in the Spring of 1995, it appeared that many amoxicillin-containing tablets marketed in Holland do not fulfil these requirements. Only one third of the preparations complied with all criteria set by us. The preparations investigated originated from eight licence holders. The preparations from two licence holders satisfied our criteria. When choosing a veterinary drug, veterinarians should be aware of the considerable differences in pharmaceutical quality.


Subject(s)
Amoxicillin/standards , Legislation, Drug , Legislation, Veterinary , Tablets/standards , Animals , Netherlands
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