Chemical and biological properties of metabolically activated species of carcinogenic N-nitrosodialkylamines are reviewed. α-Hydroxy nitrosamines and their derivatives ; α-acetoxy nitrosamines, α-hydroperoxy nitrosamines, α-phosphonooxy nitrosamines and alkanediazotates are included. Metabolic deactivation through denitrosation and metabolic activation through β-oxidation are also mentioned.
Tu-er-feng ( ?? ?? ?? ) is one of famous Chinese folk medicines in Sichuan prov. ( ?? ?? ?? ) for common cold with cough, rheumatism, etc. Its sources are said to be either whole plants of some Gerbera or Ainsliaea species of family Compositae. In the recent markets, two types of Tu-er-feng are surely available. In this paper, Tu-er-feng derived from Gerbera species are studied to clarify the botanical origin ; comparing mainly with the internal morphologies of the leaves and roots of G. piloselloides, G. delavayi, G. nivea, G. anandria (=Leibnitzia anandria) and G. jamesonii. As the result, G. piloselloides is determined as the botanical origin of Tu-er-feng obtained from the recent 16 markets.
In the previous paper, Tu-er-feng ( ?? ?? ?? ), one of Chinese folk medicines used locally in Sichuan prov. ( ?? ?? ?? ), derived from the whole plants of Gerbera piloselloides of family Compositae, was pharmacognostically reported. In the recent markets, besides this known material, Tu-er-feng made of different components are found. In this paper, the Ainsliaea derivatives are studied to clarify the botanical origins ; comparing anatomically with leaves and petioles of thirteen Ainsliaea species growing wildly in Sichuan prov. The result shows that A. glabra and A. rubrinervis are the ingredients.
Concerning the decomposition of a novel semisynthetic penicillin, aspoxicillin (ASPC) in aqueous solution, several labile products were isolated and their structures elucidated. The stepwise rearrangements of the penam ring were recognized and they were similar to the known decomposition system about the practical penicillins, in spite of the unique 6-acyl side chain of ASPC.
Intermolecular condensation of a novel semisynthetic penicillin, aspoxicillin (ASPC) was studied. Several products with small amounts on standing in an aqueous solution at room temperature were detected by the amide-bond formation between a primary amine at the side chain and a lactam carbonyl of another molecule. Their structures were estimated to be a dimer, epi-isomer of dimer, a trimer, and their analogues of the β-lactam ring opening. This polymerization reaction is known to occur in penicillins such as ampicillin and amoxicillin with the primary amine group at the benzylic position.
In order to elucidate anti-inflammatory action of Sho-saiko-to, its components were analyzed and purified by thin layer chromatography (TLC) and high performance liquid chromatography (HPLC), and their effects on lipid peroxidation were compared with those of Sho-saiko-to in guinea pig neutrophils, rat liver mitochondria and microsomes. The results obtained were as follows : 1) Sho-saiko-to gave no effect on arachidonate- and PMA (phorbol 13-myristate 12-acetate)-induced NADPH-O2 generation in neutrophils though it gave a weak LPS-like effect on the cells. No inhibition of reduced nicotinamido adenine dinucleotide phosphate (NADPH) oxidation was shown in liver microsomes. However, it markedly inhibited iron-induced lipid peroxidation in microsomes and mitochondria. 2) The active components to suppress lipid peroxidation could be concentrated in a lipid-soluble fraction from the Sho-saiko-to solution. The ED50 values to give 50% inhibition of the mitochondrial lipid peroxidation were 160 ng/mg prot, and 50μg/mg prot, for the lipid-soluble fraction and Sho-saiko-to, respectively. 3) The components in the lipid-soluble fraction were further separated by TLC and HPLC, and their inhibitory effects on the lipid peroxidation were examined. The active components were baicalein, ginsenoside Rf and baicalin, of which ED50 values were 0.2, 0.2 and 1 nmol/mg prot, respectively. Glycyrrhizin and its derivatives, ginsenoside (except ginsenoside Rf), and saikosaponins gave no effect in the concentration examined. 4) From these results anti-inflammatory action of Sho-saiko-to was discussed.
The mechanisms of resistance of Serratia marcescens and Pseudomonas cepacia to chlorhexidine were studied. Leakage of the cellular component such as protein was observed in a chlorhexidine sensitive strain (S1) of S. marcescens when S1 was treated with chlorhexidine at 40μg/ml concentration, while this phenomenon was not observed in a resistant strain (R1). The following observations were made concerning about cell surface structure in the chlorhexidine sensitive and resistant strains of S. marcescens by chemical analyses of membrane components and electron microscopical studies of the thin sections of the cells. (1) When the S1 strains was treated with chlorhexidine, the outer membrane of the cells formed a wrinkled surface with irregular blebs, and some of which broke out to form various sizes of granules. The R1 strain did not undergo such morphological changes under the same conditions used in the sensitive strain. (2) A prominent protein with apparent molecular weight of 45 K was found exclusively in the R1 strain of S. marcescens as major outer membrane protein, while it was not found in S1 strain. (3) There were no differences in the composition of phospholipids and the amount of 3-hydroxytetradecanoic acid between S1 and R1 strains of S. marcescens. In Pseudomonas cepacia PCJ1 which is resistant to chlorhexidine, 50 K protein was also observed as a major protein of outer membrane of the cells. In contrast to the strain, a mutant of the strain, #102 which was obtained from PCJ1 strain by the treatment with methanesulfonic acid ethylester, did not possese the 50 K protein in its outer membrane. These data suggested that outer membrane components of bacteria were related importantly in resistant mechanism.
Bioavailabilities of morphine after rectal administration of three different morphine·HCl suppositories (5 mg/kg) were evaluated in rats. The suppositories were prepared with three fatty bases (Witepsol H-15, Witepsol W-35, Suppocire AT) by the fusion method. The plasma and brain concentrations of morphine and its metabolites, morphine-3-glucuronide and morphine-6-glucuronide, were determined by high-performance liquid chromatography. The bioavailabilities of morphine after rectal administration were compared with those after intravenous and oral administration of morphine·HCl solution (5 mg/kg). The plasma levels of morphine after rectal administration of morphine·HCl solution were higher than those after oral administration, whereas the plasma levels of metabolite, morphine-3-glucuronide was lower than those after oral administration. Morphine after rectal administration of Witepsol H-15 suppository released more easily than other suppositories. The inter-animal variation in the plasma levels of morphine after rectal administration of Witepsol H-15 suppository was smaller than those of other suppositories. Results obtained in this study indicate that morphine·HCl suppository prepared with Witepsol H-15 is a promising material as preparation of suppositories.
Bioavailabilities of morphine after rectal administration of three different morphine·HCl suppositories were evaluated in dogs, whose rectum was lavaged or non-lavaged. The suppositories were prepared with three fatty bases (Witepsol H-15, Witepsol W-35, Suppocire AT) by the fusion method. The release of morphine from the suppositories was examined after stored for two weeks at 30°C. The plasma concentrations of morphine and its metabolites, morphine-3-glucuronide and morphine-6-glucuronide, were determined by high-performance liquid chromatography. The bioavailabilities of morphine after rectal administration were compared with those after intravenous and oral administration of morphine·HCl solution. In the case of rectal lavaged dogs, the plasma levels of morphine after rectal administration of morphine·HCl solution were higher than those after oral administration of morphine·HCl solution. The release of morphine from Witepsol H-15 suppository was more rapid than those from other suppositories. Morphine after rectal administration of Witepsol H-15 suppository was rapidly absorbed in the rectum, and the inter-animal variation of its plasma levels was smaller than those of other suppositories. In rectal non-lavaged dogs, the bioavailabilities of morphine after rectal administration of morphine·HCl solution and suppositories decreased more than those of rectal lavaged dogs. Although the bioavailability of morphine after rectal administration of morphine·HCl was decreased by the influence of contents in the rectum, morphine from Witepsol H-15 suppository was more rapidly absorbed in the rectum, and the inter-animal variation of its plasma levels was smaller. These results indicate that, among their suppositories, Witepsol H-15 suppository is available for the terminal care of malignant disease.
Chitosan films with or without chemicals of interest were prepared and degradation properties of chitosan films of themselves by lysozyme and releases of the loaded chemicals from the films were investigated. Enzymatic degradation rate of the films was dependent on the degree of deacetylation of chitosan used and decreased with an increase in its deacetylation. The acidic conditions accelerated the degradation compared to the neutral pH. Most of the water-soluble chemicals used in the present experiments except Coomassie Brilliant Blue with a strong acidic group and pullulan with a high molecular weight (5.8×104-38.0×104), were rapidly released from the films within 1 h. The two chemicals described above were released only in the presence of lysozyme, and their release rates were controlled by the degradation rate of the films.
The Friedel-Crafts reactions of N-alkyl-2(1H)-pyridone and its derivatives with acid anhydride were carried out. In the cases of N-benzyl-2(1H)-pyridone(1a) and N-benzyl-2(1H)-pyridone(1b), reaction with benzoic anhydride (2a) gave 5-benzoyl compounds (3a, b) and 3, 5-dibenzoyl compounds (4a, b), respectively, in good yields. Reactions of 1a, b with acetic anhydride (2b) gave only 5-acetyl compounds (5a, b). Reactions of dimethyl-2(1H)-pyridone(6a-d) bearing the methyl group on the pyridone ring with 2a were carried out. Only 6a gave 5-benzoyl-1, 3-dimethyl compound (7) and 6b-d gave no benzoyl compound. Reactions of 6a, b and 6d with 2b gave 5-acetyl compounds (8a, b, d), but reaction of 6c with 2b gave no acetyl compound. The result that reactions of 6b and 6d with 2a gave no benzoyl compound may be attributed to the steric hindrance between one methyl group on the pyridone ring and the reagent. Reactions of thiolactam compounds (thiopyridone, thioquinolone) with 2a gave 5-benzoylpyridone (3c) and 6-benzoylquinolone (11) in poor yields, respectively.
The methods for the chemical identification of Forsythiae Fructus and Plantaginis Herba are respectively discussed. On Forsythia Fructus, a color reaction with 4-aminoantipyrine due to phenylethanoid glycosides, namely, forsythiaside and acteoside, is distinctive by showing red. Moreover, a color reaction with hydroxyamine and ferric chloride due to lignan, arctigenin, is distinctive by showing reddish purple, and a color reaction with sulfuric acid due to lignan, phillyrin, is distinctive by showing red. The three origins of Forsythiae Fructus recorded in the Japanese Pharmacopeia XI, are distinguishable from each other by difference of color reactions due to lignans. On Plantaginis Herba, a color reaction with 4-aminoantipyrine due to plantamajoside is remarkable and its identification is also applicable by thin-layer chromatography.
This paper describes the preparation of pyrene-1-carbonyl azide (PCA) which is applicable for the labeling of primary and secondary alcohols for high performance liquid chromatography (HPLC) with fluorescence detection and the optimum conditions for precolumn derivatization reaction. Alcohols were derivatized quantitatively into the corresponding fluorescent urethanes by treating with PCA at 60°C for 5 min. The derivatives were subjected to HPLC on a TSKgel ODS-120A (250×4.6 mm i.d., 5μm) column with acetonitrile-ethanol-water (70 : 29 : 1, v/v/v) as the mobile phase and monitored with an excitation wavelength of 342 nm and an emission wavelength of 389 nm. The detection limits for the alcohols were in the range 25-125 fmol per injection with a signal-to-noise ratio of 3.