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Biomedical subjects

T Higuchi

Publications and source records attributed to T Higuchi.

At least 649 records · Page 36Linked to original sources
PubMed1980

Negative feedback effects of chlormadinone acetate and ethynylestradiol on gonadotropin secretion in patients with prostatic cancer and male rats.

Serum LH and FSH levels were determined before and after LH-RH injection (100 micrograms, i.m.) in patients with prostatic cancer who were chronically treated with either chlormadinone acetate (CMA, 100 mg/day) or ethynylestradiol (EE, 1 mg/day). In patients treated with EE, the levels of serum LH and FSH before and after injection of LH-RH were significantly lower than those in controls. On the other hand in patients treated with CMA, the basal levels of serum gonadotropins did not differ from those in controls, and the increase in gonadotropin after LH-RH injection was comparable to that in controls. To examine the effects of these steroids on the hypothalamo-hypophysial axis in the regulation of gonadotropin secretion, CMA or EE was implanted in castrated male rats. CMA, EE or cholesterol (control) was implanted in the hypothalamic median eminence-arcuate nucleus region through a stainless doublecannula. EE implantation resulted in a 75% decrease in serum LH (p < 0.001) and a 38% decrease in serum FSH (p < 0.05) from the control levels on day 5 of implantation. On the other hand, CMA implantation induced a 33% decrease in serum LH (p < 0.05) from the control level on day 3 of implantation, but no significant change in serum FSH levels. The injection of 2 micrograms/kg of LH-RH on day 7 of implantation induced significant lowering of LH and FSH levels. There was no significant difference between serum levels of the hormones 20 min after LH-RH injection for these two groups and those for the control group. These studies suggest that EE has a potent negative feedback effect on both LH and FSH secretion, and that CMA has a mild negative feedback effect on LH secretion.

Aged↗
PubMed1980

Effect of age on antipyrine metabolism in patients with gastric cancer.

The metabolism of antipyrine was studied in 19 male patients with gastric cancer. Three groups of subjects were chosen for the study: 4 patients 46--51 years of age (group 1), 8 patients 52--61 years old (group 2), and 7 patients 62--75 years old (group 3) matched for sex, smoking, alcohol intake, renal function, and liver function. The mean half-life (t 1/2) of antipyrine in group 3 (15.6 +/- 4.8 hr) was significantly longer than that in group 1 (8.1 +/- 0.9 hr, P < 0.01). Similarly, the mean metabolic clearance rate (MCR) in group 3 (246 +/- 78 ml/hr/kg) was significantly lower than that in group 1 (498 +/- 175 ml/hr/kg, P < 0.02). Significant correlations were observed between age and the t 1/2 of antipyrine (r = 0.592, P < 0.01) and between age and MCR (r = -0.499, P < 0.05). The plasma of 8 patients was tested for testosterone levels. Significant correlations were observed between plasma testosterone levels and both the t 1/2 of antipyrine (4 = -0.783, P < 0.05) and MCR (r = 0.912, P < 0.001). These observations indicate that drug-metabolizing ability might decline with age in cancer patients.

Age Factors↗
PubMed1979

Loss of hydrophobic amine from solution by adsorption onto container surfaces.

The apparent loss of the hydrophobic amine drug alpha-[(dibutylamino)methyl]-6,8-dichloro-2-(3',4'-dichlorophenyl)-4-quinoline-methanol monohydrochloride from solution due to its adsorption onto the surface of its storage container was studied. The drug appeared to be adsorbed only as the free base. Therefore, any perturbations to the solution phase that will help solubilize the drug and thus lower its chemical potential will minimize adsorption. Multilayer drug adsorption to the container surfaces appeared to take place, with some evidence of a highly organized system in the adsorbed phase. Adsorption was minimized when the heterogenous polar functionalities on glass surfaces were covered by a layer of silicone or methacrylate polymer, which yielded less reactive, more hydrophobic surfaces. Loss was also minimized when the environment was kept acidic (pH less than or equal to 4,8), the drug was dissolved in a proton-donating solvent (e.g., chloroform), and an ion-pairing agent (e.g., trichloroacetate) was present to solubilize further the monocationic form of the drug in organic media.

Adsorption↗
PubMed1979

Improved delivery of methoxsalen.

Significant improvement in the effective bioavailability of methoxsalen was achieved when it was administered to rats and dogs in a solution as compared to a suspension. Much earlier and higher peak levels were observed for the solution in both animals. The possible impact of these observations on current use of this agent for psoriasis treatment is discussed.

Administration, Oral↗
PubMed1979

GLC determination of whole blood antimalarial concentrations.

An assay was developed for determining mefloquine (quinolinemethanol) and pyridinemethanol derivative concentrations in whole blood. The method involved ion-pair extraction or usual solvent extraction for drug recovery from whole blood followed by trimethylsilylation. The silylated compounds were then submitted to GLC with electron-capture or flame-ionization detection. Mass spectrometry combined with GLC of the trimethylsilyl derivatives indicated that substitution of one trimethylsilyl group had occurred on the hydroxyl group. A phenyl methyl silicone column with temperature programming separated the drugs from normal blood extracts. The determination limit was 10 ng/ml of whole blood when an electron-capture detector was used with ion-pair extraction. Quantitation was achieved by using one antimalarial as an internal standard for the assay of the other. The utility of the present method was demonstrated by following the whole blood level time course after a single oral 250-mg tablet in beagle dogs.

Animals↗
PubMed1979

Analysis of hydrophobic amine antimalarials in biological fluids with the plastic ion-selective electrode.

Plastic ion-selective electrode analysis of the hydrophobic amine antimalarial mefloquine in blood samples was investigated. The direct electrode response in plasma samples provided poor drug sensitivity due to high mefloquine protein binding. The drug was analyzed in whole blood by initial extraction into ether as its trichloroacetate ion-pair. Mefloquine was monitored in whole blood extracts with the electrode to moderately low levels (to 0.4 microgram/ml). Rapid blood mefloquine level monitoring by this electrode was demonstrated in a bioavailability study. Mefloquine alkylation with various alkyl halides produced derivatives detectable by the electrode at much lower levels (up to two orders of magnitude) than the parent. A kinetic study of this alkylation reaction revealed that an alkyl amine base was necessary to scavenge the acid produced during reaction and to allow the reaction to go to completion. At room temperature, with benzyl bromide as the reagent, reaction was 99% complete in 30 min and mefloquine could be detected to approximately to 10(-8) M, a 100-fold improvement in sensitivity over electrode monitoring of underivatized mefloquine.

Amines↗
PubMed1979

Solubility determination of barely aqueous-soluble organic solids.

Solubility determination of organic molecules having very low solubilities is hampered by such problems as slow equilibration during measurement, influence of impurities, and inherent heterogeneity in the energetic content of the crystalline solid. Three approaches to meeting these problems are presented. The first approach involves enhancing the dissolution rate by the addition of a water-immiscible solvent in which the organic solute is more soluble, thereby increasing the surface area available for dissolution. The second method is a combination of experimental data with a group contribution approach that allows the estimation of extremely insoluble solids. This approach involves measurement of the solubility in an organic solvent and calculation of the aqueous solubility from the estimated partition coefficient and the organic solvent data. The third approach is based on using a large excess of the solid and a highly specific analytical determination of the main component. The first two approaches were explored in detail and tested using norethindrone, norethindrone acetate, methyltestosterone, and methyltestosterone acetate.

Kinetics↗
PubMed1979

Immobilization stress and prolactin secretion in male rats. Possible roles of dopamine and TRH.

Immoblization stress had a biphasic effect on serum prolactin levels: the early short stimulatory phase followed by a long inhibitory phase in male rats. Stress induced the rise in serum prolactin without concomitant increase in serum TSH levels which declined during the immoblization for 300 min. Other stressors, ether inhalation or formalin s.c. injection, or TSH i.v. injection, which were effective in controls failed to elevate serum prolactin after the 300-min immobilization. Serum TSH responded to TRH after the stress as well. Pimozide, dopamine receptor blocker, was effective in increase of serum prolactin in the stressed rats as well as in controls. In pimozide pretreated rats, elevated serum prolactin levels decrease in 10 min by the immobilization and returned to the preimmobilization levels thereafter which were higher than those in stressed animals without pimozide treatment. It is suggested that TRH is not a physiological PRF in the stress-induced prolactin release and that the dopaminergic system may be activated by the immunoblization stress, resulting in decrease of the prolactin-releasing activity of the pituitary.

Animals↗