The plasma membrane in mammalian cells posesses unique permeability properties serving as a selective permeability barrier as well as transporters for nutrients and ions in maintaining cellular homeostasis. External ATP modulates the permeability barrier in transformed cells. The characteristics and possible mechanism for this permeability change are summarized. Application of this membrane change for cancer chemotherapy was also examined in both in vitro and in vivo. The uptake of D-glucose by mammalian cells was carried out by a facilitated diffusion through a specific transporter protein in the membrane. The control mechanism for glucose transport by growth factors based on the changes in the glucose transporter levels is summarized. Modulation of glycosylation in the transporter protein and its possible role are discussed.
Recent studies on the synthesis of highly modified nucleosides, especially carbocyclic nucleosides, aiming at creating anti-HIV agents have been reviewed. The review includes new methods for the synthesis of carbocyclic C-nucleosides and carbocyclic N-nucleosides including carbocyclic oxetanocin and its analogues developed in our laboratory. Among the carbocyclic nucleosides synthesized, 9-(c-4, t-5-bishydroxymethylcyclopent-2-en-r-1-yl)-9H-adenine (BCA) showed significant anti-HIV activity.
As a continuing study on the evaluation of various Zingiberis Rhizoma and the chemical characterization of the processing, a quantitative method by high performance liquid chromatography (HPLC) for 6, 8, 10-gingerol (1, 2, 3), 6, 8-shogaol (4, 5), 6-dehydrogingerdione (6), and galanolactone (7) has been developed. By the use of this HPLC method, the contents of these compound in twenty kinds of Zingiberis Rhizoma [originating in China, Taiwan, Vietnam, and Japan (Shizuoka Prefecture)] and fresh ginger root cultivated in Shizuoka Prefecture were examined. It was found that Japanese Zingiberis Rhizoma and fresh ginger root contained 6-gingerol (1), 6-dehydrogingerdione (6), and galanolactone (7) as major constituents, whereas 7 was not detected in imported Zingiberis Rhizoma and 6 was detected in Vietnamese Zingiberis Rhizoma. Furthermore, the contents of 1 and 7 in fresh ginger root decreased remarkably during the processing procedure for Zingiberis Rhizoma. In addition, anti-ulcer sesquiterpene constituents in seven kinds of Zingiberis Rhizoma were analyzed by means of gas liquid chromatography (GLC).
A method of the quantitative analysis was established for the determination of deacylgymnemic acid (DAGA) in the alkaline hydrolysate of the sample containing gymnemic acids which are ingredients of Gymnema sylvestre R.BR. leaves, by means of high-performance liquid chromatography. This method was used for comparing the contents of gymnemic acids in various samples. The amount of gymnemic acids analyzed as DAGA in 70% ethanol extract of dry leaves was about twice that in hot water extract. The commercial health-supplemental foods of five companies were investigated for the contents of gymnemic acids as DAGA and there were large differences from 38 to 251 mg in the dosage per day recommended by each company.
In order to obtain a basic knowledge for developing the rectal dosage form of salbutamol (SB), a comparison of the bioavailability was made between oral and rectal administrations. After the intravenous, oral and rectal dosing of SB solution in rabbits, SB and its glucuronide (SBG) in plasma and urine were determined. The bioavailability estimated by the area under the blood concentration-time curve (AUC) of SB from 0 to 9 h after oral and rectal administrations were 1.1±0.5% and 7.8±2.2% (mean±S.E., n=5), respectively. Percent of dose excreted in urine as total SB (SB+SBG) 10 h after oral and rectal administrations were 77.3±3.82% and 9.80±0.15% (mean±S.E., n=3), respectively, which indicating relatively good oral and poor rectal SB absorption. A partial avoidance of first-pass-effects might contribute to higher bioavailability after the rectal administration.
Anti-inflammatory activities of quercitrin (Qu) were studied using various experimental models in mice, rats and guinea pigs. Qu (50, 100 and 200 mg/kg, p.o.) inhibited the rat hind paw edema induced by various phlogistics (carrageenin, dextran, histamine, serotonin and bradykinin) in a dosedependent manner, and 200 mg/kg of this compound also inhibited the scald edema induced by hot water (54°C). Qu did not show any significant inhibition of the ultraviolet light-induced erythema in guinea-pigs and of the increase of vascular permeability induced by acetic acid in mice. Qu did not affect the granuloma formation in a cotton pellet and the development of adjuvant arthritis in rats. These results indicate that Qu might have an inhibitory effect on acute inflammation.
The present research was an attempt to determine the pharmacological actions as for anti-fatigue, antiobesity and hypoglycemia of small peptide isolated from soybean in mice. Small peptide administration prevented the decrease in sporting movement induced by concussion stress for 3 h in mice. In addition, it should be noted that the recovery rate of fatigue in 60 min after small peptide administration was over one hundred percentage in comparison with that after pretreatment, while the equivalent dose administration of amino acid mixture with the same small peptide amino acid composition did not prevent the decrease in sporting movement. In goldthioglucose (500 mg/kg (i.p.))-induced obese mouse body weight gain, liver weight and body lipid level around uterine were significantly reduced by the chronicoral administration of small peptide (200, 1000 mg/kg). Administration in 1000 mg per kg of small peptide significantly lowerd hyperglycemia in 30 and 120 min after glucose (3 g/kg (p.o.)) administration, whereas the equivalent amino acid mixture showed no effect. In conclusion, it suggested that small peptide isolated from soybean might have some pharmacological effects of anti-fatigue, antiobesity, and hypoglycemia.