Electrolyte permeabilities of the mixed membranes composed of gelatin and chondroitin sulfate-C (ChS) were discussed theoretically by taking the water content as well as the charge density of the membrane into consideration. The membrane constant, f, was found to agree with the theoretical values derived by J.S. Mackie et al. The specific permeabilities were evaluated by the interaction factor, ψ. For the gelatin membranes, the ψ values of various electrolytes were found to be in the following order, ψKSCN>ψKCI>ψCaCl2>ψK2SO4, which is in accordance with the order of the binding property with the gelatin. For the mixed membranes, ψKCI values were found to be independent of the ChS content (ψKCIm1). However, ψCaCl2 values increased with an increase in the ChS content, and the permeabilities of CaCl2 were found to increase in contrast with the expection from the electrstatic effect.
Hemostatic activity of 12 drugs used in Chinese medicine for hemostatics was examined. Tajima's method on mouse was taken for the bioassay. It was found that the following seven drugs have a hemostatic activity. Denhichi, Panax pseudo-ginseng WALL. var. notoginseng (BURKILL) HOO & TSENG. Chiyu, Sanguisorba officinalis L. Kanrenso, Eclipta prostrata L. Seikon, Rubia cordifolia L. Sokuhakuyo, Biota orientalis (L.) ENDL. Renbo, Nulumbo nucifera GAERTN, Gusetsu, Nulumbo nucifera GAERTN.
Chemical constituents of the wood of root of Xanthoxylum inerme KOIDZ. (Fagara boninensis KOIDZ.), (Japanese name "Akou-zansho"), were examined. Two new monomeric phenylpropanoids, methyl boninenalate (16), mp 107-180°, and boninenal (19), mp 95-97.5°, were isolated together with nine known chemical components [Alkaloids : nitidine (1), oxynitidine (6), dictamnine (12). Coumarins : aesculetin dimethyl ether (7), 6, 7, 8-trimethoxycoumarin (9). Amides : N-benzoyltyramine methyl ether (18), (±)-tembamide (21). Lignan : (±)-syringaresinol (10). Others : β-sitosterol (11)].
Cytosol proteins of rat liver were divided into four fractions by gel filtration on Sephadex G-75 column. Neutron activation analysis was carried out to determine 7 elements (Mn, Cu, Cd, Fe, Co, Zn and Se) in each protein. Fe, Mn and Se were mainly combined with large molecular weight proteins, while Cd, Cu and Zn with low molecular weight proteins. It was recognized that Zn quantity in low molecular weight fraction was increased significantly by Cd injection. The behavior of Zn in the fraction was examined by use of 65Zn tracer. Although Zn-thionein was not produced after administration of small amount (0.2 mg) of Zn, it was observed by the injection of 1 mg of Zn. The effect of Cd on Zn elution profile was studied. Cd-thionein was induced by Cd injection, and then Zn content in metallothionein fraction increased. From a result of distribution of Zn among organs, it could be presumed that the increase of Zn was based on renal Zn. Further, metallothionein previously produced by Cd injection was combined with about 28% of Zn incorporated into the liver.
A specific and sensitive method for the determination of cyclazocine and norcyclazocine in the human serum and urine was developed. Trifluoroacetyl (TFA) derivatives of cyclazocine and norcyclazocine were analyzed by mass fragmentography by using pentazocine as an internal standard. Selected ions of TFA derivatives of cyclazocine and norcyclazocine were m/z 352 and 269, respectively. The result of recovery experiments with the urine sample fortified with the known amount of cyclazocine was satisfactory. The radioimmunoassay was also developed for cyclazocine analysis and time course study of serum concentration after intramuscular administration of 300 μg of cyclazocine was performed. Cyclazocine levels in the human urine samples were determined simultaneously by gas chromatography-mass spectrometry and radioimmunoassay. The coefficient of correlation was 0.97. The total excretions of cyclazocine in three human urines for 48 hr were 30.8%, 31.0% and 47.3%.
Isouron (1), one of the urea herbicides was determined colorimetrically by application to diazo coupling with Tsuda reagent. 3-Amino-5-tert-butylisoxazole (2) obtainable by the hydrolysis of 1 was diazotized with HNO2 and the diazonium salt was easily coupled with Tsuda reagent. The diazonium salt was unstable at room temperature different from aniline but stable in cooled water. The calibration curve was linear in a range of 3-15 μg/ml of the standard solution of 1, the coefficient of variation of 0.3-1.3%. 5-Amino-3-tert-butylisoxazole (6) produced by the hydrolysis of the isomer 1-(3-tert-butylisoxazol-5-yl)-3, 3-dimethylurea (5) was not diazotized in the present condition. The effect of major impurity (5) on the determination was removable.
A colorimetric method for the determination of a new type minor tranquilizer, 4-chloro-2-(o-chlorobenzoyl)-N-methyl-Nα-glycylglycinanilide (1), was developed in order to estimate the quality of raw material. Compound 1 was heated in dimethyl sulfoxide with 3, 5-dibromosalicylaldehyde in the presence of piperidine catalyst. The resulting red colored product had absorption maximum at 554 nm. The calibration curve was linear in the range of 0.5-2.0 mg/ml of standard solution of 1 with coefficient of variation less than 1%. Compound 1 was assayed without interference even in the presence of various impurities estimated from synthetic process.
A non-dialysable hot water extract (Tof-CFr) with antitumor activity was isolated from dandelions, Taraxacum officinale. Tof-CFr showed an antitumor effect in the allogeneic tumor system of ddY-Ehrlich, and syngeneic one, C3H/He-MM46 with intraperitoneal injection of 30 or 40 mg/kg in later phase, day 11-20 (every day) or day 2-20 (every other day) if on day 0 tumor cells are inoculated subcutaneously. But it did not inhibit tumor growth with injection in earlier phase (day 1-10) in either system mentioned above. The effectiveness in case of later phase injection was observed with other immunopotentiators with antitumor activity i.e. lentinan, and yeast mannan. Particularly in C3H/He-MM46 syngeneic tumor system, both drugs showed a stronger antitumor activity with injection in later phase (day 11-20) than in earlier phase (day 1-10). And in ddY-Ehrlich allogeneic tumor system, both agents showed almost the same strong antitumor activity, regardless of timing of administration. So no clear difference was observed in antitumor activity due to timing. As to the mechanism of tumor growth inhibiting action, Tof-CFr showed cytolytic activation of macrophages in antibody-dependent macrophage mediated cytolysis and enhancement of antitumor delayed hypersensitivity reaction in C3H/He-MM46 syngeneic and ddY-Ehrlich allogeneic tumor systems. It suggests that Tof-CFr is similar to antitumor polysaccharides such as lentinan in the mechanism of antitumor action.
The kinetic isotope effects in the in vivo metabolism of three kinds of deuterated aminopyrine (AM), i.e., AM-3-CD3, AM-2-CD3 and AM-4-N (CD3)2, were investigated. In order to evaluate the effect of deuterium labeling on the metabolic rate of AM, an equimolar mixture of AM and AM-3-CD8 (AM : AM-3-CD3), AM : AM-2-CD3 or AM : AM-4-N (CD3)2, was orally administered to rats. Urinary metabolites were extracted with chloroform and the extracts were subjected to gas chromatograph-mass spectrometer after trimethylsilylation. AM metabolites were measured by using selected ion monitoring focused on their molecular ions. The kinetic isotope effect was estimated from the ratio of the amount of the metabolite excreted from deuterated AM to that excreted from AM (D/H ratio). After the administration of AM : AM-3-CD3, D/H ratios of 3-hydroxymethyl metabolites were in the range of 0.347 to 0.403. On the contrary, D/H ratios of 4-demethylamino metabolites were in the range of 1.22 to 1.30. These values indicated that the deuterium labeling of AM shifted the initial step of AM metabolism from oxidation of the 3-methyl group to demethylation of the 4-dimethylamino group. This isotope effect is well-known as a "metabolic switching". In the case of AM-4-N (CD3)2, D/H ratio of 4-formylaminoantipyrine indicated the effect on the oxidative formylation by deuterium labeling.
The influence of coadministered fluid volume on pharmacological response, gastrointestinal absorption and gastric emptying of thiopental-Na and aminopyrine after oral administration was examined in mice. When the coadministered fluid volume increased from 4 to 20 ml/kg, the hypnotic effect of thiopental-Na and analgetic effect of aminopyrine increased in proportion to fluid volume. And also the remaining percentages of these drugs in gastrointestine were reduced with an increase in fluid volume. These drugs in the stomach after oral administration were transferred to the small intestine at a relatively fast rate in the initial stage and then gradually evacuated according to exponential process. This fast gastric emptying in the initial stage was accelerated in proportion to fluid volume, however, the gastric emptying rate evacuated expornentially with time was not influenced by the increase of fluid volume. From these results, it was defined that the acceleration of gastric emptying in the initial stage due to the increase of fluid volume enhanced the absorption rate of drugs in the small intestine and that the pharmacological effect. In conclusion, it was shown that a great care should be taken for the fluid volume accompanying the extract of pharmacological response of drug by use of a small animal.
The concentrations of o-ethoxybenzamide (EBA), N-(β-hydroxybutyryl)-p-phenetidine (HBP) and metabolites in the rabbit serum were investigated when EBA was administered orally with HBP and EBA or HBP administered alone. 1) The concentration of EBA in the serum increased when 100 mg/kg of EBA was administered concurrently with 28.5, 33.3 and 62.5 mg/kg of HBP as compared with the administration of 100 mg/kg of EBA alone. The co-administration of EBA and HBP also decreased the concentration of salicylamide (SAM) sulfate in the serum. 2) The concentration of HBP in the serum increased when 28.5, 33.3 and 62.5 mg/kg of HBP and 100 mg/kg of EBA were administered together, while that of N-(β-hydroxybutyryl)-p-aminophenol (HBA) glucuronide was decreased. 3) The deethylation of EBA was inhibited competitively by the addition of HBP, and also the deethylation of HBP inhibited competitively by the addition of EBA in 9000×g supernatant fraction of the rabbit liver. 4) The area under the serum concentration-time curve (AUC, 0-8 hr) of SAM sulfate approached a limiting value when 300 mg/kg of EBA was administered orally, while the AUC values of SAM glucuronide, EBA, SAM total and SAM total plus EBA increased with increasing doses of EBA. 5) The deethylation of HBP approached a limiting value when 300 mg/kg of HBP was administered orally, while the AUC values of HBP and HBA total plus HBP total (HBP plus HBP glucuronide) increased with increasing doses of HBP.
Effects of sugar alcohols on the motility, the fluid movement, the permeability of mesentric blood vessel and the biogenic amines (serotonin (5-HT), histamine (His) and polyamines) in the small intestine of mice were investigated. Diarrhea was induced by oral administration of sugar alcohols (erythritol, arabitol, xylitol, sorbitol, mannitol, maltitol and lactositol) in mice. It is suggested that the acceleration of intestinal motility, the suppression of intestinal fluid movement, the facilitation of mesentric blood vessel permeability and the decrease of substances transport were closely related to the occurrences of diarrhea after ingestion of sugar alcohols. These actions may be mediated by biogenic amines, 5-HT, His and polyamines in the small intestine.
The essential oil of fresh flower of Ligustrum japonicum THUNB. was identified to contain cis-3-hexen-1-ol, benzaldehyde, benzyl alcohol, phenethyl alcohol, linalool, phenol, cresols, guaiacol, eugenol, benzoic acid, phenylacetic acid, fatty acids and n-paraffins. Quercetin, kaempferol, p-hydroxy-β-phenylethyl alcohol, ferulic acid, p-coumaric acid, caffeic acid, ursolic acid, α- and β-amyrins, phytosterols, n-paraffin alcohols, fatty acids, esters and glycerides were isolated from the risidue after steam distillation of its ethereal extract.