Biomedical subjects

P De La Cruz

Publications and source records attributed to P De La Cruz.

8 recordsLinked to original sources

PubMed2003

Effects of clopidogrel and ticlopidine on experimental diabetic ischemic retinopathy in rats.

Ticlopidine, a thienopyridine that prevents the progression of diabetic retinopathy in humans, was recently shown to increase nitric oxide (NO) production in human neutrophils. The thienopyridine clopidogrel has been found to be clinically useful in the secondary prevention of thrombotic events. The aim of the present study was to evaluate the effect of clopidogrel on ischemic retinopathy in streptozotocin-diabetic rats and its influence on prostanoids and NO production. We compared nondiabetic rats and rats after 3 months of diabetes that were given three doses (1, 10 or 20 mg/kg per day p.o.) of ticlopidine or clopidogrel from the first day of diabetes. The variables recorded after 3 months of diabetes were platelet aggregation, thromboxane B(2) (TxB(2)) production, 6-keto-prostaglandin F(1)(alpha) (stable metabolite of prostacyclin), aortic NO, plasma nitrites/nitrates, and the percentage of the retinal surface occupied by horseradish peroxidase (HRP)-permeable vessels. In diabetic rats, platelet aggregation and thromboxane concentration were increased, and prostacyclin, NO and area occupied by HRP-permeable vessels were decreased. Ticlopidine and clopidogrel reduced the maximum extent of platelet aggregation in a dose-dependent manner: maximal inhibition with respect to untreated diabetic rats was 48.6% with ticlopidine and 66.6% with clopidogrel. Ticlopidine reduced thromboxane B(2) only at a dose of 20 mg/kg per day p.o. (47.4% inhibition) and clopidogrel at doses of 10 mg/kg per day (51% inhibition) or 20 mg/kg per day (51.7% inhibition). Aortic prostacyclin production did not change after treatment with either thienopyridine. Treatment with ticlopidine reduced the inhibition of NO production in untreated rats (89.6% inhibition) to 0.9%, and clopidogrel reduced inhibition to 30%. Treatment with ticlopidine or clopidogrel reduced the retinal nonperfused area from 86.8% inhibition in untreated rats to 45.6% and 25.3%, respectively. In conclusion, the early administration of thienopyridines in streptozotocin-diabetic rats partly prevented the appearance of diabetic retinal ischemia.

6-Ketoprostaglandin F1 alpha↗

PubMed2001

Effect of aspirin on prostanoids and nitric oxide production in streptozotocin-diabetic rats with ischemic retinopathy.

The importance in experimental diabetic retinopathy of prostacyclin and nitric oxide (NO), as well as the possible effect of acetylsalicylic acid (ASA), are well known. To investigate the effect of two doses of aspirin in the prevention of retinal ischemia in streptozotocin-diabetic rats, we compared nondiabetic rats and diabetic rats after 1, 2 and 3 months of diabetes, and diabetic rats treated with 2 mg or 10 mg ASA/kg per day p.o. from the first day of diabetes. The parameters determined after 1, 2 and 3 months of development were platelet aggregation, thromboxane B(2) (TxB(2)) production, 6-keto-prostaglandin F(1)(alpha) (stable metabolite of prostacyclin), NO, plasma nitrites/nitrates, and percentage retinal surface occupied by horseradish peroxidase (HRP)-permeable vessels. In diabetic rats platelet aggregation and thromboxane concentration were increased, and prostacyclin, NO and area occupied by HRP-permeable vessels were decreased. Acetylsalicylic acid reduced platelet aggregation, and lowered thromboxane production by 82%-99%. Prostacyclin production was inhibited by 92%-95% with 10 mg ASA/kg per day, and by 8%-20% with 2 mg ASA/kg per day. In diabetic rats NO production increased after 2 and 3 months of treatment to levels seen in nondiabetic rats. The reduction in HRP-permeable retinal surface decreased from a maximum of 87% in DR to 51% after treatment with 2 mg ASA/kg per day, and to 62% after 10 mg ASA/kg per day. We conclude that ASA (2 mg/kg per day and 10 mg/kg per day) increased NO production in streptozotocin-diabetic rats and reduced the degree of retinal ischemia.

Administration, Oral↗

PubMed1998

A phase I and pharmacokinetic trial of terephthalamidine (NSC 57155) as a 120-hour continuous infusion.

In this phase I study, terephthalamidine was administered as a 120-hour continuous infusion repeated every 21 days. Thirteen patients received 27 courses of terephthalamidine at four dose levels ( 14, 28, 46, and 70 mg/m2/day). Dose-limiting toxicity consisted of profound and intractable anorexia, weight loss and prostration in all patients. Toxicity was delayed and accompanied by hyponatremia and hypokalemia. No hematologic or other toxicity was documented. One patient with adenocarcinoma of the lung had a 40% decrease in mediastinal lymph nodes and resolution of a pleural effusion lasting 2 months. Pharmacokinetic analysis by HPLC was performed in all patients during their first course. The harmonic mean terminal half-life for terephthalamidine was 23 hours with a plasma clearance of 1.7 1/hr/m2. Both plasma concentrations achieved during infusion (r2 = 0.9) and area under the curve (AUC) (r2 = 0.8) were proportional to increase in dose (p < 0.002). Renal excretion accounted for 64% of the total cumulative dose, with an average renal clearance of 1.16 1/hr/m2. Due to the unacceptable toxicity seen at all doses with this schedule, no further studies are recommended unless the mechanism of toxicity is better understood and can be prevented.

Adult↗

PubMed1997