Nature prefers simplicity. Streptococcal cytoplasmic pH is regulated in a simple biological manner : change in the amount of the adenosinetriphosphatase (H+-ATPase). This enzyme is identical to the F0F1-complex of oxidative phosphorylation, which synthesizes adenosinetriphosphate in mitochondria and most of bacteria, whereas it is used as a regulator of the cytoplasmic pH in streptococci which have no respiratory chain. Eukaryotes use the another type of H+-ATPase to regulate the internal pH. Thus, the evolutional process of H+-ATPase is quite interesting.
Substance P and somatostatin may be transmitters of nociceptive information, which are involved in the transmission of pressure and heat nociceptive information, respectively, in the spinal dorsal horn. Calcitonin gene-related peptide, which is present in the primary sensory neurons having substance P or somatostatin, may function as a pain-promoting substance and be involved in the production of inflammation-induced hyperalgesia. The descending noradrenergic system plays a role in inhibiting nociceptive transmission in the spinal dorsal horn, and inhibits the release of substance P evoked by noxious mechanical stimulation. Persistent noxious stimuli increase the release of Met-enkephalin from the nucleus reticularis gigantocellularis, which promotes the activity of the descending noradrenergic system. Morphine activates the descending noradrenergic system, acting on the nucleus reticularis gigantocellularis. Morphine also activates the descending serotonergic system, which inhibits the release of somatostatin evoked by thermal noxious stimulation.
A new series of 1, 2, 3-trisubstituted-2-propen-1-one derivatives (9a-v, 10a-j, 13a-c, 14a-j) and 3, 4-disubstituted-4-oxo-2-butenoic acids (6a-i, 7a-n) with azole compounds were synthesized. Inhibitory activities against rat passive cutaneous anaphylaxis (PCA) reaction and histamine release from rat mast cells were tested. The ester derivatives (7a-n, 14a-j) exhibited a more potent inhibitory activity against histamine release compared with alkylamine (9a-v), β-hydroxyethoxy (10a-j) and carboxylic acid (6a-i, 13a-c) derivatives, but somewhat weaker in their anti-PCA activity. Structure-activity relationships were discussed.
α-[(Phenoxyethylamino) propyl]-α-(4-methoxyphenyl) acetonitrile derivatives possessing methyl, bromo, nitro, amino or various sulfonamide groups at 3-position on ring A and an alkoxy group on ring B were synthesized. Their α-blocking activities were tested. The activity of 5-[1-cyano-4-[[2-(2-ethoxyphenoxy) ethyl] amino]-1-isopropylbutyl]-2-methoxy-benzenesulfonamide (15a) and 5-[1-cyano-4-[[2-(5-fluoro-2-methoxyphenoxy) ethyl] amino]-1-isopropylbutyl]-2-methoxybenzenesulfonamide (15c) was close to that of prazosin, a typical α-blocker. Structure-activity relationship of these derivatives is also stated.
Radiation protective effects of the methanol extract and its fractions of Cnidii Rhizoma on lethality and skin injury induced by X-irradiation were studied. As a result of these studies, it was observed that significant protective effects exist in both ether and water soluble portions prepared from the above methanol extract, and two of the active principles in the ether and water soluble ones were identified as ferulic acid and adenosine, respectively.
For the purpose of evaluating a Kampo preparation, Hangekouboku-to ( ?? ?? ?? ?? ?? ), the contents of 6-gingerol (Gi), guanosine (Gu) and rosmarinic acid (R) in twelve kinds of ethical extract preparations were compared with the self-made decoctions. Little difference was found in the availability of the three compounds among three decoction methods. A great difference was found in the R content in the ethical extract preparations while no significant difference was found in the Gi and Gu contents, showing that they were not lost in the manufacturing process. These results suggested that Perilla Herb of quite different quality was used as raw materials.
Triethylenetetramine·2·HCl (trientine, TE) is an orphan drug for the treatment of Wilson's disease. There has been no reports regarding the absorption, distribution, metabolism, and excretion in the body. In the current study, the absorption and excretion of TE in rats were examined. The observed mean percentage amount of TE absorbed at the jejunum and ileum with the loop method for 1 h was 42.0% and 22.5%, respectively. Tight junction blocking agent inhibited the absorption of TE from the jejunum loop with 27%, but the absorption of TE from the ileum loop was not affected by this blocking agent. Therefore, the main absorption route for TE might be permeation across the plasma membrane of intestinal epithelial cells. TE and amikacin, a polycationic compound like TE, bound to the brush border membrane (BBM) of rat small intestine in the absence of inorganic ions such as Na+, K+, Ca2+, Mg2+ and Cu2+. But the binding of TE to BBM was inhibited markedly under the physiological concentration of these ions. The bioavailability of TE was below 10% and the plasma levels of TE in non-fasted rats were significantly lower than that observed in fasted rats. The urinary excretion of unchanged TE during 24 h was only 3.5% of the orally administered dose. However, the urinary excretion of total TE including metabolites, though they have not been identified, was 35.7%. These results suggest that low bioavailability of TE might be due to the rapid metabolism in the body after absorption from the gastrointestinal tract.
The ratio of cis/trans isomers (referring to 11b-substituent and 2- or 3-substituent) of benzodiazepinooxazoles was estimated by using the lanthanide shift reagent (Eu (fod)3-d27) for nuclear magnetic resonance (NMR) spectroscopy. The amide carbonyl oxygen at 6-position is considered to coordinate with the reagent, because the largest downfield shifts were observed at the amide carbonyl carbon (C-6) in 13C-NMR and the amide hydrogen (H-7) in 1H-NMR. The ratios depend largely on the substituents at 11b-, 2-, and 3-positions. The cis isomer for compounds having 11b-hydrogen increases with an increase in the bulkiness of the substituents at 2-position. The cis isomer for compounds having 3-methyl group decreases with change from 11b-2'-chlorophenyl group (mexazolam) to 11b-hydrogen.
The essential oils of Torilis japonica (HOUTT.) DC. (Japanese name, Yabujirami) of the family Umbelliferae were prepared from fresh whole herbs and fruits, and investigated by using gas chromatographic and mass spectrometric analyses. The fruits of this plant had been used as a substitute in Japan for a Chinese crude drug Zya-syo-si : Cnidii Monnieri Fructus ( ?? ?? ?? ). Fifty three components were positively identified in the essential oils. The main components of the essential oil were germacrene-D (57.9-71.8% in the oil), α-humulene (2.4-13.2%), bicyclogermacrene (1.9-5.4%), β-caryophyllene (1.5-4.6%), and δ-cadinene (1.0-1.9%).
Twelve purines oxidized with 4, 5-dimethyl-o-phenylenediamine (DMPD) was found to react with N-bromosuccinimide (NBS) to give fluorescent derivatives. In this paper, the identification of oxidation and fluorescent products have been described. In compliance with the substituent on purine skelton, three alloxans were obtained from twelve purines after oxidation by using NBS. The three alloxans reacted with DMPD to form two quinoxalines and an alloxazine, all of which being fluorescent.
One mol perchloric acid-soluble fraction (PASF) obtained from ascitic fluid of a patient (blood group B) with metastatic omentum tumor from ovarian cancer was a glycoprotein fraction containing 35.4% carbohydrate and exhibited A, B and Thomsen-Friedenreich (T) activities. This fraction was separated into three fractions, Frs. 1-3, by a gel filtration with Bio-Gel A-1.5 m column. Among these fractions, Fr. 1 which was obtained in a 5.5% yield to PASF, was a glycoprotein fraction with a high molecular weight, 23.3% carbohydrate and A, B and T activities. Other minor fraction, Fr. 2, and the major fraction, Fr. 3, contained 43.2% and 43.9% carbohydrate, but did not show A, B and T activities, respectively.