Search PubMed⌕ Search

Biomedical subjects

W Ho

Publications and source records attributed to W Ho.

At least 127 records · Page 7Linked to original sources
PubMed1988

Disposition of detirelix, a potent luteinizing hormone-releasing hormone antagonist, in rats and monkeys.

The disposition of detirelix, a potent luteinizing hormone-releasing hormone (LHRH) antagonist, was studied in rats and monkeys. After a single 300-microgram/kg intravenous dose in rats, the plasma elimination t1/2 was 1.6 hr and the plasma clearance was 3.3 ml/min/kg. In the monkey, the mean t1/2 and plasma clearance were 7.1 hr and 1.3 ml/min/kg, respectively, after an 80-microgram/kg intravenous dose. Long plasma t1/2 values of 18.7 and 31.6 hr were observed after single 0.2- and 1.0-mg/kg subcutaneous doses in the monkey, suggesting the possibility of subcutaneous depot formation at the injection site. Biliary excretion was the predominant route of elimination of detirelix in both species. Less than 10% of the detirelix was excreted renally. A major metabolite, isolated from the rat bile, was the 1-4 tetrapeptide fragment of detirelix. This metabolite was formed by enzymatic hydrolysis of the Ser4-Tyr5 bond, one of the only two peptide bonds in detirelix not containing a D-amino acid.

Animals↗
PubMed1988

The mechanism of reducing thiopentone dose in elderly patients undergoing surgery.

The dose of thiopentone required to induce anesthesia in adults decreasing with age is not due to pharmacodynamic change. The change of pharmacokinetic properties of thiopentone with age in undergoing surgery patient's arterial blood was investigated in seven elderly (67-82 yr) and six young (21-33 yr) patients of both sexes. Thiopentone (3 mg kg-1) was administered intravenously and arterial blood samples were obtained immediately after the injection to measure plasma and red blood cell thiopentone concentrations by an HPLC method. Plasma protein binding was studied using ultracentrifuge method. The disappearance of thiopentone from the arterial blood was described by a two-compartment open model. The distribution rate constant (alpha) was significantly larger in the young patients (p less than 0.001). The distribution half-life was longer in the elderly (p less than 0.05). Both the input microscopic rate constant, K21, and the exit microscopic rate constant, K12, with the central compartment were significantly larger in the young patients. (p less than 0.02 and p less than 0.001, respectively). The difference between the exit and input microscopic rate constant, K12-K21, was much larger in the young patients (p less than 0.001). The plasma protein binding was significantly reduced in the elderly (p less than 0.05). The apparent overall volume of distribution, Vd was not significantly different between young and elder patients. However, the volume of distribution of the central compartment was smaller in the young patients (p less than 0.05). This was probably due to the difficulty of estimation of initial thiopentone plasma concentration post-equilibrium in the central compartment after administration of thiopentone.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Plasma exchange improves the glomerulonephritis of systemic lupus erythematosus in selected pediatric patients.

The effects of short-course plasma exchange (PE) followed by tapering dose prednisone therapy was assessed in six children with systemic lupus erythematosus (SLE) and severe glomerulonephritis. All patients received pulse methylprednisolone therapy and three patients were treated with cytotoxic drugs prior to PE, but none had exhibited a good response. PE resulted in a rapid and sustained (greater than 1 year) remission of renal failure in the three patients with renal failure and severe glomerulonephritis. All six patients had severe nephrotic syndrome and five of six experienced a complete and sustained (greater than 1 year) remission post-PE (the sixth patient has greater than 4 month remission at the time of writing). Of interest was the high frequency of membranous [World Health Organization (WHO) Type V] and mixed membranous and diffuse proliferative SLE nephritis (WHO Type IV) on renal biopsy (4/6 patients). In addition, the severe anemia and leukopenia seen in most patients responded favorably to PE. Five of the six patients are currently managed on low-dose prednisone (0.25-0.5 mg/kg) every other day. One patient progressed to renal failure and dialysis more than 1 year post-PE. One patient required cytotoxic drug therapy post-PE (6 weeks). No significant complications were encountered; in fact, all patients eventually received their PE treatments as outpatients. We conclude that PE may provide a safe and effective therapeutic option for the treatment of severe progressive SLE nephritis in selected children who are unresponsive to steroid or cytotoxic drug therapy.

Adolescent↗
PubMed1987

Resolution of (+/-)-2-tetradecyloxiranecarboxylic acid. Absolute configuration and chiral synthesis of the hypoglycemic R enantiomer and biological activity of enantiomers.

The resolution of the hypoglycemic agent (+/-)-2-tetradecyloxiranecarboxylic acid (3) as its d- and l-ephedrine salts is presented. The active enantiomer (R)-(+)-3 was also synthesized by the Sharpless chiral epoxidation procedure and its methyl ester (R)-(+)-4 was shown to be identical with the corresponding ester from the resolved acid. Single-crystal X-ray structure analysis of the diastereomeric salt of (+)-3 and (-)-ephedrine allowed assignment of (+)-3 as the R configuration. The effects on fatty acid oxidation and glucose tolerance of the racemic and enantiomeric forms of 3, 4, and the CoA ester of 3 are presented. A postulated mechanism of action for the active enantiomer as an enantioselective, active-site-directed, irreversible inhibitor of carnitine palmitoyl transferase is suggested.

Animals↗
PubMed1986

Alkylglycidic acids: potential new hypoglycemic agents.

A series of alkylglycidic acid analogues and derivatives were synthesized and tested for their ability to inhibit long-chain fatty acid oxidation in vitro and to lower blood sugar in rats. The extent of inhibition of carnitine acyl transferase, the enzyme at the mitochondrial membrane necessary to transport long-chain fatty acids into the mitochondria for subsequent beta-oxidation, was determined for the series. Structure-activity relationships using in vitro inhibition of [1-14C]palmitic acid oxidation in rat hemidiaphragm muscle indicate that potent activity resides mainly in 2-alkyl (C12-C16) glycidates. Replacement of the oxirane ring with cyclopropyl, thiirane, or other rings diminishes activity, as does substitution of the glycidate ring at the 3-position. In vivo potency in the rat glucose tolerance test roughly parallels the hemidiaphragm results. The lead compound, methyl 2-tetradecylglycidate (8), is a potent hypoglycemic agent following oral administration to several animal species. The hypoglycemic analogues interfere with fatty acid oxidation by specific and irreversible inhibition of mitochondrial carnitine palmitoyl transferase-A.

Animals↗