Chronic D1 and D2 dopaminomimetic treatment of MPTP-denervated monkeys: effects on basal ganglia GABA(A)/benzodiazepine receptor complex and GABA content.

The effect of various chronic dopaminergic treatments in 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) monkeys on the brain gamma-aminobutyric acid type A (GABA(A)) /benzodiazepine receptor complex and GABA content was investigated in order to assess the GABAergic involvement in dopaminomimetic-induced dyskinesia. Three MPTP monkeys received for one month pulsatile administrations of the D1 dopamine (DA) receptor agonist SKF 82958 whereas three others received the same dose of SKF 82958 by continuous infusion. A long acting D2 DA receptor agonist, cabergoline, was given to another three animals.

Differential regulation of striatal preproenkephalin and preprotachykinin mRNA levels in MPTP-lesioned monkeys chronically treated with dopamine D1 or D2 receptor agonists.

Studies in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned monkeys and in parkinsonian patients show elevated preproenkephalin (PPE) mRNA levels, unaltered by chronic L-DOPA therapy, whereas preprotachykinin (PPT) mRNA levels are decreased by the lesion and corrected by L-DOPA. The relative contributions of the dopamine D1 and D2 receptors for PPE mRNA regulation were investigated in the present study and compared with those for PPT mRNA. In situ hybridization was used to measure peptide mRNA levels in the striatum of MPTP cynomolgus monkeys after chronic 1-month treatment with the D1 agonist SKF-82958, administered subcutaneously in pulsatile or continuous mode, compared with the long-acting D2 agonist cabergoline.

Validated high-performance liquid chromatographic methods for quantitation of a novel nonsteroidal antiestrogen.

HPLC assays were developed and validated for the quantitation of the novel orally active nonsteroidal antiestrogen EM-800 ¿(S)-(+)-4-[7-(2,2-dimethyl-l-oxopropoxy)-4-methyl-2-[4-[2-(1-pipe ridinyl)- ethoxy]phenyl]-2H-l-benzopyran-3-yl]-phenyl 2,2-dimethylpropanoate¿. The assay involves reversed-phase C18 or C4 columns using different mobile phases with ammonium acetate buffers and UV detection at lambda = 240 nm. The standard curve was linear over the concentration range of 10-1100 micrograms/ml.

Risedronate, a highly effective, short-term oral treatment for Paget's disease: a dose-response study.

Risedronate is a potent pyridinyl bisphosphonate being developed for bone diseases such as Paget's disease and osteoporosis. In this study, we compared the efficacy, safety, and tolerability of three different doses of oral risedronate in 62 patients with severe Paget's disease of bone [serum alkaline phosphatase (AP) >3 times the upper limit of normal]. Patients were treated at six study centers with either 10, 20, or 30 mg oral risedronate daily for 28 days and followed up to day 85.

Simple purification procedure for human prostatic kallikrein hK2 in its active form.

Kallikrein hK2 is a new potential marker of prostate cancer. It is the last member of the human kallikrein gene family to be isolated. We propose a simple purification procedure permitting us to obtain the active form of hK2 starting from human seminal plasma and using commonly available chromatography matrices.

Physiological changes in dehydroepiandrosterone are not reflected by serum levels of active androgens and estrogens but of their metabolites: intracrinology.

This study analyzes in detail the serum concentration of the active androgens and estrogens, as well as a series of free and conjugated forms of their precursors and metabolites, after daily application for 2 weeks of 10 mL 20% dehydroepiandrosterone (DHEA) solution on the skin to avoid first passage through the liver. In men, DHEA administration caused 175%, 90%, 200% and 120% increases in the circulating levels of DHEA and its sulfate (DHEA-S), DHEA-fatty acid esters, and androst-5-ene-3 beta,17 beta-diol, respectively, with a return to basal values 7 days after cessation of the 14-day treatment. Serum androstenedione increased by approximately 80%, whereas serum testosterone and dihydrotestosterone (DHT) remained unchanged.

Marked decline in serum concentrations of adrenal C19 sex steroid precursors and conjugated androgen metabolites during aging.

The present data show a dramatic decline in the circulating levels of dehydroepiandrosterone (DHEA), DHEA-sulfate (DHEA-S), androst-5-ene-3 beta,17 beta-diol (5-diol), 5-diol-sulfate, 5-diol-fatty acid esters, and androstenedione in both men and women between the ages of 20-80 yr. In the 50- to 60-yr-old group, serum DHEA decreased by 74% and 70% from its peak values in 20- to 30-yr-old men and women, respectively. the serum concentrations of the conjugated metabolites of dihydrotestosterone (DHT), namely androsterone (ADT)-G, androstane-3 alpha,17 beta-diol (3 alpha-diol-G), androstane-3 beta,17 beta-diol (3 beta-diol-G), and ADT-sulfate are the most reliable parameters of the total androgen pool in both men and women, whereas serum testosterone and DHT can be used as markers of testicular secretion in men and interstitial ovarian secretion in women.