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Biomedical subjects

G F Grauer

Publications and source records attributed to G F Grauer.

7 recordsLinked to original sources
PubMed1992

Effects of a thromboxane synthetase inhibitor on established immune complex glomerulonephritis in dogs.

Twelve Beagles were inoculated with concanavalin A, and after a mean ninefold increase in antibody titer, 1 mg of concanavalin A was infused into each renal artery of each dog to induce in situ immune complex glomerulonephritis. Starting 4 weeks after renal arterial infusion, 6 dogs were treated orally 3 times daily with 30 mg of 3-methyl-2 (3 pyridyl)-1-indolectanoic acid (CGS 12970)/kg of body weight, a thromboxane synthetase inhibitor, and 6 dogs (control group) received a gelatin capsule 3 times daily. Endogenous creatinine clearance and 24-hour urinary excretion of protein and thromboxane B2 were determined for each dog prior to renal arterial infusion, at the initiation of treatment and at 2, 4, 6, and 8 weeks after initiation of treatment. In addition, methyoxy-3H inulin clearance was determined at initiation of treatment and 4 and 8 weeks later. Renal specimens were examined histologically at the initiation of treatment and 4 and 8 weeks later. Glomerular mononuclear profiles/microns 3 were determined from at least 10 equatorially sectioned glomeruli from each dog. Paired t tests were used to compare mean values at the various time points to the respective mean baseline value and 2-sample t tests were used to evaluate differences between treatment groups. At the start of treatment (4 weeks after renal arterial infusion of concanavalin A), histologic evaluation of renal specimens revealed glomerular epithelial crescent formation, mononuclear cell proliferation, and infiltration of neutrophils. Mononuclear cell profiles and urinary excretion of protein and thromboxane B2 were significantly increased, but endogenous creatinine clearance values were unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Effects of low-dose aspirin and specific thromboxane synthetase inhibition on whole blood platelet aggregation and adenosine triphosphate secretion in healthy dogs.

Platelet aggregation and adenosine triphosphate (ATP) secretion in response to arachidonic acid (10 microM) or collagen (5 micrograms/ml) were compared in healthy, adult female Beagles treated with low-dosage aspirin (3.5 mg/kg of body weight, PO, q 12 h for 7 treatments) or with CGS 12970, a specific thromboxane synthetase inhibitor (10 mg/kg, PO, q 8 h for 10 treatments). Platelet aggregation was assessed in whole blood by use of an electrical impedance method. Baseline values obtained prior to treatment served as controls. Addition of arachidonic acid to blood from nontreated dogs resulted in significantly (P less than 0.001) increased impedance, but had no effect in blood from dogs treated with either aspirin or CGS 12970. Treatment with CGS 12970 or aspirin significantly (P less than 0.001) decreased platelet ATP secretion in response to arachidonic acid, compared with baseline values; however ATP secretion in aspirin-treated dogs was significantly (P less than 0.01) less than ATP secretion in CGS 12970-treated dogs. Differences in platelet aggregation were not observed between control dogs and aspirin- or CGS 12970-treated dogs in response to collagen as an aggregant, however, collagen-induced platelet ATP secretion was significantly (P less than 0.001) decreased in dogs treated with aspirin, compared with control values and values from dogs treated with CGS 12970. In dogs treated orally with 0.1, 0.2, 1.0, or 10 mg of CGS 12970/kg, dose-dependent inhibition of arachidonic acid-induced platelet aggregation was observed, with impedance changes not observed at the 10-mg/kg dosage and normal platelet aggregation associated with the 0.1-mg/kg dosage.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1991

Effects of thromboxane synthetase inhibition on immune complex glomerulonephritis.

To determine the role of thromboxane A2 in the pathogenesis of experimentally induced immune complex glomerulonephritis, 12 concanavalin A-immunized Beagles were infused with 1 mg of concanavalin A via each renal artery and treated twice daily for 8 days with either 30 mg of CGS 12970/kg, PO, a specific thromboxane synthetase inhibitor, or placebo. The effect of treatment was assessed by measuring endogenous creatinine clearance and urine protein and eicosanoid excretion, and by evaluating changes in glomerular morphometric characteristics. On postinfusion day 8, urine protein, thromboxane B2, and 11-dehydro-thromboxane B2 excretion, glomerular epithelial crescent formation, and glomerular cell proliferation in the CGS 12970-treated dogs were significantly decreased when compared with values in the placebo-treated group. Differences were not observed in endogenous creatinine clearance, urine prostaglandin E2 and 6-keto-prostaglandin F1 alpha excretion, or glomerular polymorphonuclear leukocyte infiltration between groups in this study. These findings suggest thromboxane A2 has a role in the development of immune complex glomerulonephritis and that thromboxane synthetase inhibition may be beneficial in attenuating some of the functional and histological changes associated with immune complex glomerulonephritis.

6-Ketoprostaglandin F1 alpha↗
PubMed1990

Effects of a specific thromboxane synthetase inhibitor on thromboxane generation and excretion in healthy dogs.

A specific thromboxane synthetase inhibitor, 3-methyl-2 (3-pyridyl)-1-indoleoctanoic acid (CGS 12970) was administered orally to 6 healthy adult Beagles at a dosage of 30 mg/kg of body weight. Blood generation of thromboxane B2 and urinary excretion of thromboxane B2 were measured before and after administration of CGS 12970. Although 97 +/- 0.4% inhibition of thromboxane B2 generation was observed within 2 hours after a single dose of CGS 12970 was administered orally, an effect on urinary excretion of thromboxane B2 was not observed. Additionally, oral administration of 30 mg/kg every 12 hours resulted in 80 +/- 14% inhibition of thromboxane B2 generation but had no effect on urinary thromboxane B2 excretion.

Administration, Oral↗
PubMedDate not supplied

Plasma histamine and gastrin concentrations in 17 dogs with mast cell tumors.

Dogs with mast cell tumors (MCT) are often affected with paraneoplastic syndromes such as gastrointestinal ulceration. The mechanism of ulceration is believed to be related to hyperhistaminemia. To test this hypothesis, plasma histamine and gastrin concentrations were measured in 17 dogs with MCT. Plasma histamine concentrations in dogs with MCT were significantly higher than those in normal dogs. Conversely, plasma gastrin concentrations in dogs with MCT were significantly lower than gastrin concentrations in normal dogs. Additionally, plasma gastrin concentrations were inversely related to plasma histamine concentrations, which provided indirect evidence for the presence of hyperacidity secondary to hyperhistaminemia (r2 = 57.7). Plasma histamine and plasma gastrin concentrations were not related to clinical stage of disease, tumor histologic grade, or tumor size. Median survival time was 245 days, with a range of 90 to 1315 days. Because the degree of hyperhistaminemia could not be predicted in this study from the clinical stage, histologic grade, or tumor size, these data suggest that hyperhistaminemia may occur in any dog with MCT.

Animals↗
PubMedDate not supplied

Treatment of membranoproliferative glomerulonephritis and nephrotic syndrome in a dog with a thromboxane synthetase inhibitor.

A 2-year-old spayed female Whippet with membranoproliferative glomerulonephritis and nephrotic syndrome was treated with a specific thromboxane synthetase inhibitor (3-methyl-2[3-pyridyl]-1-indoleoctanoic acid), resulting in decreased proteinuria and resolution of ascites and edema. Glomerular histology, however, appeared unaffected by treatment. Discontinuation of treatment for 10 weeks resulted in increased proteinuria and decreased serum albumin concentrations that were again attenuated when treatment was reinitiated. Thromboxane synthetase inhibitors have been used successfully to treat experimentally induced glomerulonephritis in several species and this treatment appears to hold promise for naturally occurring glomerulonephritis in dogs.

Animals↗