Inhibition of prolyl hydroxylation and procollagen processing in chick-embryo calvaria by a derivative of pyridine-2,4-dicarboxylate. Characterization of the diethyl ester as a proinhibitor.

The biochemical and morphological consequences of procollagen prolyl 4-hydroxylase inhibition by pyridine-2,4-dicarboxylic acid (2,4-PDCA) and its diethyl ester (diethyl-2,4-PDC) were studied in chick-embryo calvaria, which predominantly synthesize type I collagen. Half-maximal inhibition of tissue hydroxyproline formation required 650 microM-2,4-PDCA, whereas the Ki with respect to chicken prolyl 4-hydroxylase in vitro was 2 microM. In contrast, half-maximal inhibition was caused by 10 microM-diethyl-2,4-PDC in the intact calvaria, although chicken prolyl 4-hydroxylase in vitro was not inhibited even at 1 mM.

Beneficial effects of inhibitors of prolyl 4-hydroxylase in CCl4-induced fibrosis of the liver in rats.

S 0885 and HOE 077 inhibit CCl4-induced liver fibrosis in rats, as shown by significantly reduced hydroxyproline content of the liver and improved liver histology. Mortality of drug-treated animals is significantly diminished. Serum collagen parameters correlate well with the hydroxyproline content of the liver and can be used as noninvasive markers for the fibrotic process.

Chronic intravenous toxicity of the new antibiotic cefpirome in monkeys.

Chronic intravenous toxicity studies in monkeys were carried out with 3-[(2,3-cyclopenteno-1-pyridinium)-methyl]-7-[2-syn-methoximino - 2-(2-aminothiazol-4-yl)-acetamido]-ceph-3-em-4-carboxylate (cefpirome, HR 810; CAS 84957-29-9) a new cephalosporin derivative. In a 90-day study in rhesus monkeys (4 males/4 females per group) dosages of 0, 50, 160 and 500 mg/kg/day were administered. In a 6-month study 5 groups of 6 male and 6 female cynomolgus monkeys received NaCl-solution (0.

Subchronic and chronic toxicity of the new antibiotic cefpirome in rats.

Subchronic and chronic toxicity studies in rats were performed with 3-[(2,3-Cyclopenteno-1-pyridinium)-methyl]- 7-[2-syn-methoximino-2-(2-aminothiazol-4-yl)-acetamido] -ceph-3-em-4- carboxylate (cefpirome, HR 810), a new cephalosporin derivative. In subchronic (14 day) studies cefpirome was intravenously administered in dose levels up to 1500 mg/kg/d with good kidney tolerance. Signs of renal functional impairment were observed (800 and 1500 mg/kg) but histologically no morphological changes could be detected.

Pharmacological studies on androgen suppression in therapy of prostate carcinoma.

In hormone-dependent prostate carcinoma, androgens can be suppressed into the castrate range by LHRH agonists. Testosterone secretion is blocked at two levels: testicular androgens and adrenal androgens. In humans, the contribution of testicular androgens is about 95%, whereas in the rat, the adrenal androgen secretion is negligible.