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  • Author or Editor: Walter E. Hoffmann x
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Abstract

Objective—To determine the effect of glucocorticoids on the induction of alkaline phosphatase (ALP) isoenzymes in the liver, kidneys, and intestinal mucosa, 3 tissues that are principally responsible for ALP synthesis in dogs.

Sample Population—Tissues from the liver, kidneys, and intestinal mucosa of 6 dogs treated with 1 mg of prednisone/kg/d for 32 days and 6 untreated control dogs.

Procedure—Using canine-specific primers for the ALP isoenzymes, a reverse transcription-polymerase chain reaction assay was designed to measure liver ALP (LALP) and intestinal ALP (IALP) mRNA and heterogeneous nuclear RNA (hnRNA) expression in tissues from the liver and kidneys and intestinal mucosa of glucocorticoid-treated and control dogs. Tissue ALP isoenzyme activities were compared between the groups.

Results—The LALP activity and mRNA concentrations increased in tissues of the liver and kidneys in dogs treated with prednisone, whereas LALP hnRNA increased only in liver tissues. The IALP activity and mRNA expression increased in intestinal mucosa and liver tissues in prednisone-treated dogs. We did not detect an increase in IALP hnRNA expression in these tissues.

Conclusions and Clinical Relevance—Synthesis of ALP is increased in the liver, kidneys, and intestinal mucosa of dogs in response to prednisone treatment. This response appears to be regulated at the transcriptional level, but mechanisms may differ between LALP and IALP. (Am J Vet Res 2002;63:1083–1088)

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in American Journal of Veterinary Research

Abstract

Objective—To clone segments of the canine liver alkaline phosphatase (LALP) and corticosteroidinduced alkaline phosphatase (CIALP) genes and use those clones to determine the tissue source of CIALP, the kinetics of LALP and CIALP mRNA expression for glucocorticoid-treated dogs, and the correlation between LALP and CIALP transcript concentrations and isoenzyme activities.

Sample Population—Tissues obtained from 7 dogs treated with prednisone (1 mg/kg, SC, q 24 h) for up to 32 days and 1 untreated (control) dog.

Procedure—Gene segments of LALP and CIALP were obtained by reverse transcription-polymerase chain reaction (RT-PCR) assay. The tissue source of CIALP and IALP mRNA was determined by northern blot analysis of tissues from 1 of the glucocorticoidtreated dogs. Hepatic tissues and serum samples were obtained from the 6 remaining glucocorticoidtreated dogs on days 0, 2, 5, 10, and 32 of prednisone treatment, and relative expression of LALP and CIALP mRNA was correlated with LALP and CIALP activity.

Results—A 2,246-base pair (bp) segment of canine LALP and a 1,338-bp segment of CIALP were cloned. Northern blot analysis revealed CIALP mRNA expression in hepatic tissues only after glucocorticoid treatment. Kinetics of LALP and CIALP mRNA expression in the liver of glucocorticoid-treated dogs paralleled liver and serum activities of LALP and CIALP.

Conclusions and Clinical Relevance—The liver is the most likely source for CIALP in dogs. Analysis of kinetics of serum and hepatic LALP and CIALP mRNA suggests that after glucocorticoid treatment, both are regulated by modification of mRNA transcript concentrations, possibly through differing mechanisms. (Am J Vet Res 2002;63:1089–1095)

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in American Journal of Veterinary Research

Abstract

Objective—To evaluate the usefulness of carboxyterminal cross-linked telopeptide of type I collagen (ICTP) concentrations for screening dogs for the presence of osteosarcoma.

Sample Population—32 client-owned dogs with osteosarcoma (27 dogs with osteosarcoma of the appendicular skeleton and 5 dogs with osteosarcoma of the axial skeleton) and 44 non–tumor-bearing control dogs.

Procedures—Serum was obtained from blood samples collected from dogs with osteosarcoma and from clinically normal dogs. The serum ICTP concentration was determined by use of a commercially available radioimmunoassay for ICTP.

Results—Mean ± SD serum ICTP concentration in the tumor-bearing dogs was 7.32 ± 2.88 ng/mL, and in clinically normal dogs, it was 6.77 ± 2.31 ng/mL; values did not differ significantly. Mean serum ICTP concentration in dogs with appendicular osteosarcoma, compared with that of clinically normal dogs, was not significantly different. Mean serum ICTP concentration in dogs with axial skeletal tumor location was 10.82 ± 2.31 ng/mL, compared with a value of 6.73 ± 2.28 ng/mL in dogs with appendicular osteosarcoma.

Conclusions and Clinical Relevance—On the basis of the results of this study, serum ICTP concentrations are not a clinically useful screening tool for the detection of appendicular osteosarcoma in dogs. Despite the observation that serum ICTP concentration was higher in dogs with axial osteosarcoma than in clinically normal dogs, serum ICTP concentration determination is not a suitable screening test for osteosarcoma.

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in American Journal of Veterinary Research

Abstract

Objective—To evaluate the influence of a 1,4- butanedisulfonate stable salt of S-adenosylmethionine (SAMe) administered orally on clinicopathologic and hepatic effects induced by long-term administration of prednisolone in dogs.

Animals—12 healthy dogs.

Procedure—Following a pilot study (4 dogs), 2 groups of 4 dogs received prednisolone (2.2 mg/kg) orally once daily (84-day trial). One group received SAMe (20 mg/kg/d divided in 2 doses) for 42 days and then a placebo for 42 days; the other group received treatments in the reverse order. Before and during the trial, numerous variables were monitored, including serum total alkaline phosphatase (ALP) and glucocorticoid- induced ALP (G-ALP) activities, serum haptoglobin concentration, and total and oxidized glutathione (TGSH and GSSG) and thiobarbiturate-reacting substances (TBARS) concentrations in erythrocytes and liver tissue (days 0, 42, and 84). Hepatic specimens also were examined microscopically.

Results—The stable salt of SAMe was biologically available; plasma concentrations of SAMe or prednisolone were not affected by coadministration. Compared with baseline values, serum ALP and GALP activities and haptoglobin concentrations increased and erythrocyte GSSG and TBARS concentrations decreased with both treatments. Erythrocyte TGSH concentration decreased with the prednisolone- placebo treatment. Administration of SAMe appeared to conserve erythrocyte TGSH values and did not inhibit hepatocyte glycogen vacuolation but increased hepatic TGSH concentration and improved the hepatic tissue GSSG:TGSH ratio.

Conclusions and Clinical Relevance—In dogs, administration of 20 mg of SAMe/kg/d may mitigate the apparent pro-oxidant influences of prednisolone but did not block development of classic clinicopathologic or histologic features of vacuolar hepatopathy. (Am J Vet Res 2005;66:330–341)

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in American Journal of Veterinary Research

Abstract

Objective—To determine causes of hyperphosphatasemia (high serum alkaline phosphatase [ALP] activity) in apparently healthy Scottish Terriers.

Design—Prospective case-controlled study.

Animals—34 apparently healthy adult Scottish Terriers (17 with and 17 without hyperphosphatasemia).

Procedures—Serum activities for 3 isoforms (bone, liver, and corticosteroid) of ALP were measured. Concentrations of cortisol, progesterone, 17-hydroxyprogesterone, androstenedione, estradiol, and aldosterone were measured before and after cosyntropin administration (ie, ACTH; 5 μg/kg [2.27 μg/lb], IM). Liver biopsy specimens from 16 dogs (11 with and 5 without hyperphosphatasemia) were evaluated histologically.

Results—In dogs with hyperphosphatasemia, the corticosteroid ALP isoform comprised a significantly higher percentage of total ALP activity, compared with the percentage in dogs without hyperphosphatasemia (mean ± SE, 69 ± 5.0% and 17 ± 3.8%, respectively). In 6 dogs with hyperphosphatasemia, but none without, serum cortisol concentrations exceeded reference intervals after ACTH stimulation. Six dogs with and 15 without hyperphosphatasemia had increased concentrations of ≥ 1 noncortisol steroid hormone after ACTH stimulation. Serum ALP activity was correlated with cortisol and androstenedione concentrations (r = 0.337 and 0.496, respectively) measured after ACTH stimulation. All dogs with and most without hyperphosphatasemia had abnormal hepatocellular reticulation typical of vacuolar hepatopathy. Subjectively, hepatocellular reticulation was more severe and widespread in hyperphosphatasemic dogs, compared with that in nonhyperphosphatasemic dogs.

Conclusions and Clinical Relevance—Hyperphosphatasemia in apparently healthy Scottish Terriers was most likely attributable to hyperadrenocorticism on the basis of exaggerated serum biochemical responses to ACTH administration and histologic hepatic changes, but none of the dogs had clinical signs of hyperadrenocorticism.

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in Journal of the American Veterinary Medical Association