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Biomedical subjects

R Nakayama

Publications and source records attributed to R Nakayama.

At least 127 records · Page 7Linked to original sources
PubMed1979

Thermodynamic analysis of the nonspecific interaction of sodium dodecyl sulfate with swollen Bio-Gel beads.

In frontal gel chromatography on Bio-Gel P-2, sodium dodecyl sulfate (SDS) at the concentrations below its critical micelle concentration (cmc) showed anomalously high partition coefficients (Kav obs) indicative of strong interactions with the swollen gel phase; further, Kav obs was found to increase with concentration and temperature. This preferential partition of SDS in the Bio-Gel phase was analyzed in terms of the transfer free energy of SDS from the mobile phase (0.1 M NaCl) to the swollen Bio-Gel phase. The results showed that the overall transfer process is primarily governed by hydrophobic free energy arising from the anomalous nature of hydrated water in the gel matrix; that is, in highly hydrated water "iceberg" formation is evidently limited and the hydrophobic free energy is accordingly lowered, resulting in the preferential partition of SDS in the swollen Bio-Gel phase. The increase in the negativity of transfer free energy with concentration, though relatively small, indicated a definite tendency for the formation of SDS clusters in the gel phase. Finally, a model illustrating the states of SDS molecules in the gel matrix is presented, which may also be pertinent to SDS-protein and SDS-amylose complexes.

Chromatography, Gel↗
PubMed1979

Anti-androgen TSAA-291. II. Manifestation of the anti-androgenic action of a steroid ester TSAA-330 (16 beta-ethyl-17 beta-hydroxy-4-oestren-3-one caproate) and elucidation of its long-lasting mechanism using a simple steroid determination technique.

Using a simple steroid determination technique, in situ steroid absorption from a subcutaneously injected sesame oil solution in rats was pursued following the time-course changes in the steroid concentration. Based on the knowledge thus obtained, the anti-androgenic effect of a steroidal compound, TSAA-330, could be manifested in the subcutaneous route. (1) Anti-androgenic steroid TSAA-291 and its esters in the subcutaneously injected sesame oil solution were selectively absorbed into the general circulation at different rates according to their chemical nature and structures, while the oil itself remained at the injected site for a considerably long period. At the injected site where subcutaneous doses of steroids molar equivalent to 50 mg of TSAA-291 were administered in 5 ml/rat of sesame oil, TSAA-291 decreased to the level of 10% of the initial concentration on the 4th day. TSAA-328 decreased slowly to the 50% and 20% levels on the 7th and 21st day, respectively. TSAA-335 decreased more slowly to the 50% level on the 14th day. TSAA-330 decreased most slowly only to the 70% level on the 49th day. (2) A single subcutaneous administration of 200 mg of TSAA-330 suppressed the weight increase of the accessory sex organs caused by a single subcutaneous injection of testosterone caproate (10 mg) in the immature orchiectomized rat. The suppressive effect was obvious from 2 weeks after the administration, and seemed to last for more than two weeks. The levator ani weight was not affected by the administration of TSAA-330. (3) Dose-dependent inhibitions of the accessory sex organs were obtained three weeks after a single subcutaneous administration of 50 to 400 mg of TSAA-330 in the adult male rat. (4) Daily oral administrations of 50 mg of TSAA-291 or TSAA-330 to the adult male rat for 8 days resulted in depression of the accessory sex organs to almost the same extent obtained with either agent. One week after the last administration, however, the weight of the accessory sex organs of the TSAA-291-administered animals recovered to almost the comparable level with the control, whereas a significant after-effect of the inhibition was still evident in the TSAA-330-administered animals.

Absorption↗
PubMed1979

Anti-androgen TSAA-291. III. Hormonal spectra of anti-androgen TSAA-291 (16 beta-ethyl-17 beta-hydroxy-4-oestren-3-one) and its derivatives.

For the purpose of obtaining hormonal spectra of anti-androgen TSAA-291 and its derivatives, a variety of endocrine characteristics were studied. (1) Androgenic and anabolic activity : Subcutaneous administration of anti-androgen TSAA-291 and its acetate, TSAA-328, to the immature orchiectomized rat resulted in significant weight increase of the levator ani but in only a nominal response of seminal vesicles and prostates even at a large daily dose of 9.6 mg. The resultant anabolic/androgenic ratio was estimated to be extremely high. (2) Oestrogenic activity : Uterine weight in response to these anti-androgens were sluggishly dose-dependent, and the maximal plateau response remained considerably lower than that induced by oestradiol-17 beta. The oestrogenic activity of these anti-androgens was estimated to be 1/200 000 or less as that of oestradiol-17 beta. A single subcutaneous dose of 100 mg of TSAA-291 or its caproate, TSAA-330, did not induce the vaginal cornification in the adult ovariectomized rat. (3) Anti-oestrogenic activity : Antagonistic effect of these anti-androgenic compounds on the uterine weight response to oestradiol-17 beta was found in the immature ovariectomized rat. A single subcutaneous dose of 100 mg of TSAA-291 or TSAA-330 also induced the antagonism against the cornification caused by daily treatments with 1 microgram oestrone in the adult ovariectomized rat. (4) Progestational activity : These anti-androgenic compounds proved to be less active than progesterone in the McPhail's test. (5) Anti-inflammatory activity : Daily subcutaneous dose of 20 mg of TSAA-291 for 6 days did not significantly depress the weight of granuloma developed around the cotton-pellet implanted in the young male rat. TSAA-291 did not affect the anti-inflammatory action of 1/6 mg of prednisolone phosphate. Combination of both agents seemed to be effective in enhancing the anti-androgenic action of TSAA-291, whereas prednisolone phosphate alone rather increased the weight of the accessory sex organs. (6) Liver glycogen deposition activity : Daily intramuscular doses up to 38.4 mg of TSAA-291 for 5 days did not increase the liver glycogen level in the adrenalectomized rat.

Androgen Antagonists↗
PubMed1979

Anti-androgen TSAA-291. IV. Effects of the anti-androgen TSAA-291 (16 beta-ethyl-17 beta-hydroxy-4-oestren-3-one) on the secretion of gonadotrophins.

Effects of the anti-androgen TSAA-291 on the gonadotrophin secretion were studied. (1) A single subcutaneous or oral administration of TSAA-291 and its caproate induced the ovulation in the proestrous rat of which the spontaneous ovulation was blocked by the treatment with chlorpromazine. (2) A single subcutaneous administration of TSAA-291 at 2.4 mg/kg to the adult male rat induced only a slight elevation in the serum LH and FSH levels at 30 min after the administration. Successive intramuscular administrations of TSAA-291 to the adult male rat for 2 or 4 weeks resulted in significant decreases in the serum LH and FSH levels at high dose levels. A dose-dependent decrease in the serum LH level but not FSH level was observed in the orchiectomized rat. (3) Successive intramuscular administrations of TSAA-291 at high dose levels to the male rat suppressed the plasma testosterone level in the testicular venous blood and general circulation.

Administration, Oral↗
PubMed1979

Anti-androgen TSAA-291. V. Effects of the anti-androgen TSAA-291 on the androgen-receptor complex formation from [3H]testosterone in rat ventral prostates.

Intramuscular administration of a new steroidal anti-androgen, TSAA-291 (16 beta-ethyl-17 beta-hydroxy-4-oestren-3-one), in doses of 0.05, 0.5 and 5 mg/kg body weight reduced the in vivo uptake of [3H]testosterone by the ventral prostate of castrated rats of 78, 59 and 37% of the control level, respectively. Analysis on subcellular fractions of the prostate by gel-filtration and sucrose density-gradient centrifugation followed by thin layer chromatographic identification of testosterone metabolites revealed that 5 alpha-dihydrotestosterone (5 alpha-DHT) which was found to be largely bound to macromolecules in the cytosol and nucleus was the predominant metabolite even in the presence of the anti-androgen, and radioactivities corresponding to the 5 alpha-DHT-macromolecular complexes were decreased by the anti-androgen. TSAA-291 also inhibited the in vitro formation of the 5 alpha-DHT-macromolecular complexes in both cytosol and nucleus from minced prostates incubated with [3H]testosterone. The importance of the findings is discussed in connection with the mode of anti-androgenic action of TSAA-291 in terms of the interaction with the androgen receptor.

Androgen Antagonists↗
PubMed1979

Anti-androgen TSAA-291. VI. Effects of the anti-androgen TSAA-291 and its related compounds on the in vitro formation of 5 alpha-DHT-receptor complex in the cytosol of rat ventral prostates.

Inhibitory effect of a synthetic steroidal anti-androgen TSAA-291 (16 beta-ethyl-17 beta-hydroxy-4-oestren-3-one) on the in vitro formation of 5 alpha-dihydrotestosterone(5 alpha-DHT)-receptor complex was examined. An aliquot of the cytosol from rat ventral prostates was incubated with [3H]5 alpha-DHT in the presence of various amounts of the anti-androgen. By means of dextran-coated charcoal assay and sucrose density-gradient centrifugation analysis, TSAA-291 was demonstrated to inhibit directly, in a competitive manner, the binding of 5 alpha-DHT to a component analogous in its properties to the cytosol androgen receptor. Further, displacing study using a variety of TSAA-291 analogues was undertaken to examine which of the functional groups of TSAA-291 is important for the affinity to the 5 alpha-DHT binding component, and elucidated that 3-hydroxy or 5 alpha-dihydro derivatives of TSAA-291 and others having axial methyl group at C-10 were less potent competitors for [3H]5 alpha-DHT binding than TSAA-291. Furthermore, using other steroids including androgens and anti-androgens, considerable knowledge was obtained about structural requirements for a steroid molecule to displace the bound [3H]5 alpha-DHT, and this displacing activity of the steroids was discussed in terms of their anti-androgenic activity.

Androgen Antagonists↗
PubMed1979

Anti-androgen TSAA-291. VII. On the mechanism of anti-androgenic action of 16 beta-ethyl-17 beta-hydroxy-4-oestren-3-one (TSAA-291).

The mechanism of anti-androgenic action of a steroidal compound, TSAA-291, was summarized and discussed in reference to its drug-designing and structure-activity relationship. The target of the drug-design was to obtain a substance which is inactive in androgenic activity and is capable of antagonistically competing with androgen for the receptor. With this intention, the androgen molecule was rendered with a steric hindrance influencing upon the functional 17 beta-hydroxy group. Introduction of a bulky group at the steroidal position-13 or -16 led to anti-androgenic properties. Intense steric hindrance by introducing an enormously bulky group or complete elimination of the 17 beta-hydroxy group rather decreased the anti-androgenic activity. Of these anti-androgens thus synthesized, TSAA-291 proved to be the most active in the anti-androgen assay and also antagonistic against the uptake of [3H]testosterone by the rat ventral prostate.

Androgen Antagonists↗
PubMed1979

Anti-androgen TSAA-291. I. Anti-androgenic effects of a new steroid TSAA-291 (16 beta-ethyl-17 beta-hydroxy-4-oestren-3-one) and its derivatives.

Anti-androgenic properties of newly synthesized steroidal compounds, TSAA-291 and its derivatives, were studied in the rat. (1) Subcutaneous administrations of TSAA-291 and TSAA-272 were effective in depressing the weight of seminal vesicles and ventral and dorsal prostates in the adult rat. (2) TSAA-291, TSAA-328 and TSAA-272 were shown to be anti-androgenic by the subcutaneous or oral route in the immature castrated male rat treated with testosterone propionate. The dose-response curves of all the test agents expressed in terms of percentage inhibition were approximately parallel to each other. Cyproterone acetate depressed the weight of levator ani muscle dose-dependently, whereas TSAA-291, TSAA-328 and TSAA-330 did not inhibit the muscle weight in a dose range sufficiently effective in inhibiting the weight of seminal vesicles and ventral and dorsal prostates. (3) TSAA-291 was also anti-androgenic against androstenedione and dehydroepiandrosterone. (4) Local administration of the anti-androgenic compounds into the left seminal vesicle or left testis of the young adult rat depressed the weight of the seminal vesicle or testis on the treated side as compared with the vehicle-injected contra-lateral side.

Androgen Antagonists↗
PubMed1978

An osmotic effect operative in frontal gel chromatography.

The osmotic effect operative in frontal gel chromatography was quantitatively studied. When mixtures of a non-penetrating solute (Kav = 0) and a partially penetrating solute (0 less than Kav less than 1) were subjected to frontal gel chromatography, the latter formed a coextensive concentration gradient across the trailing boundary of the former, leading to the formation of a second plateau where the concentration exceeded that of the original solution plateau. It was shown that this anomaly, which we have previously predicted, was a direct consequence of osmotic perturbation of the bead size of the Sephadex gel and could be satisfactorily described by an equation based solely on the osmotic distention of the gel beads. Finally, the implications of the osmotic effect in the frontal chromatographic analysis of acceptor-ligand interactions is discussed and a method for correcting this effect is presented.

Chromatography, Gel↗
PubMed1977

Noninvasive measurements of digital arterial pressure and compliance in man.

A noninvasive method was developed for measuring the digital arterial pressure and the compliance by using a fingertip pneumoplethysmograph and a pneumatic cuff. The compliance (C) of the digital artery was obtained from the peak amplitude of the volume pulse wave (deltaVp-a) under the effect of the cuff pressure (Po-a) by the equation: C = deltavp-a/(Ps - P-o-a) during the dicrotic phase defined in this study. The normal mean value was 11.37 +/- 0.59 X 10(-5) cm3/mmHg. On lowering of the cuff pressure, the moment when the deltaVp value becomes positive is regarded as the systolic pressure (Ps). At the end of the dicrotic phase, the mean amplitude (deltaVss') of the pulse wave during one pulse cycle (SS') and the ratios (deltaVss'/deltaVsd), where deltaVsd is the mean amplitude of the wave during the systolic period (SD), of successive waves after a particular wave fail to increase at the same rate when the cuff pressure decreased below the diastolic pressure. The cuff pressure corresponding to this particular wave is regarded as the diastolic pressure (Pd). The mean value of the mean digital pressure of normotensive subjects was 80.6 +/- 1.2 mmHg.

Arteries↗
PubMed1977

Pholipomycin, a new member of phosphoglycolipid antibiotics. I. Taxonomy of producing organism and fermentation and isolation of pholipomycin.

Pholipomycin is a new member of the phosphoglycolipid family of antibiotics. Taxonomic studies of the producing organism revealed that it has morphologically characteristic aerial mycelia in which two to three spores are borne usually on short and clavate side branches. The species name, Streptomyces lividoclavatus, has been proposed. Pholipomycin is produced mainly in the solid residue of the fermentation culture broth and is isolated by methanol extraction of the mycelial cake followed by purification on ion-exchange resin and silica gel chromatography.

Anti-Bacterial Agents↗
PubMed1977

Pholipomycin, a new member of phosphoglycolipid antibiotics. II. Physico-chemical properties and comparison with other members of this family of antibiotics.

Physico-chemical characterization of pholipomycin revealed that this antibiotic is a new member of phosphoglycolipid antibiotics. Pholipomycin was differentiated from other members by the products formed on acid hydrolysis as follows: the presence of glucosamine, a 257 nm chromophore and moenocinol-type C25 lipids, but the absence of glucose, 6-deoxyglucosamine and glycine.

Ammonia↗