Lysosome suspensions were prepared from both polymorphonuclear leucocytes and liver of rats. The incubation of the lysosomes with or without hydrogen peroxide caused the release of enzymes (acid phosphatase, aryl sulfatase), which was inhibited by 2-(5H--benzopyrano [2, 3-b] pyridin-7-yl) propionic acid (Y-8004), nonsteroidal anti-inflammatory drugs such as phenylbutazone, and steroidal anti-inflammatory drugs such as prednisolone. Hydrogen peroxide not only released enzymes but also caused lipid peroxidation of the lysosome suspension. The above anti-inflammatory agents inhibited the release of enzymes more strongly than lipid peroxidation in experiments using leucocyte lysosomes. The inhibitory activity of Y-8004 and nonsteroidal anti-inflammatory drugs on the release of enzymes decreased by the addition of albumin to the incubation mixture. However, in this case, steroidal anti-inflammatory drugs retained their potent activities, and strongly inhibited the release of enzymes induced by phospholipase C. Based on these evidences, discussion was extended on the stabilizing action of Y-8004 and anti-inflammatory drugs on lysosome membranes, and on their possible mechanisms.
In the course of a study on the isoquinoline synthesis in which halosulfonic acid was employed as a cyclizing agent, 3, 4-dimethoxybenzylideneaminoacetal (4) was treated with chlorosulfonic acid at -5°, followed by standing at a room temperature for 72 hr to afford two bases, 3-chloro-6, 7-dimethoxyisoquinoline (7), mp 134-135° (hydrochloride, mp 158-162° (decomp.)) in 53% yield and a very small amount of 6, 7-dimethoxyiso-quinoline (12). The former is a new compound whose structure was determined from various spectral data and by degradative evidence including its reduction to 6, 7-dimethoxy-1, 2, 3, 4-tetrahydroisoquinoline hydrochloride (8) and its oxidation to a new acid, 6-chlorocinchomeronic acid (10), mp 191-193°. Formation of 12 was recognized by means of thin-layer chromatography (TLC) and gas-liquid chromatography (GLC) identical with those of an authentic sample.
In order to clarify the mechanism of the so-called "nonspecific supersensitization" induced by cocaine, effect of cocaine on dose-response curves of various agonists was examined with isolated vas deferens of a guinea pig. Cocaine increased the sensitivity but did not change the maximum response of vas deferens to norepinephrine, epinephrine, and acetylcholine. Increase in the degree of supersensitivity to acetylcholine was dose-dependent up to 3×10-5M, while that to norepinephrine and epinephrine decreased at the concentration of 3×10-5M of cocaine. Cocaine did not change the affinity of norepinephrine and acetylcholine receptors to phentolamine and atropine, respectively. Higher concentration of cocaine was required to induce rhythmic contraction and supersensitivity to acetylcholine of vas deferens from older guinea pigs. Cocaine induced slight increases in the sensitivity and maximum response of vas deferens to histamine. These results suggest that cocaine-induced supersensitivity to acetylcholine is elicited through post-junctional beyond-receptor mechanism and does not contribute to the potentiation of contractile response to catecholamines and histamine by cocaine.
A Schiff base (4'-dimethylamino-5, 5'-dioxo-1, 1'-diphenyl-2, 2', 3-trimethyl-N-(3'-pyrazolin-3'-ylmethylidene)-3-pyrazolin-4-ylamine) was found in the urine of rats and rabbits, and in the bile of rats as a new metabolite of aminopyrine. This Schiff base was produced by reacting 4-aminoantipyrine (AA) with 4-dimethylamino-3-formyl-2-methyl-1-phenyl-3-pyrazolin-5-one (AmCHO) in aqueous solution and in the serum of rats. When AA and AmCHO were intravenonsly administered to rats, the Schiff base was found in various tissues, urine, and bile. Therefore, it may be suggested that this metabolite (Schiff base) was excreted after being produced chemically in vivo without the enzymic reaction. When this Schiff base was orally administered to rats, it was distributed in various tissues and excreted in the bile more than in the urine.
The mass spectrometric fragmentation pattern of 21 kinds of fumariline alkaloids of the spirobenzylisoquinoline type was studied. All of the compounds examined were classified into three groups according to the alkoxy substituent pattern on the ring-C, the first group consists of the compounds having alkoxy groups in 9- and 10-positions, the second one at 11- and 12-positions, and the third one at 10- and 11-positions. The compounds of the first and third groups exclusively exhibited the base peak of (M-29), while the second group compounds showed the base peak at (M-59). The fragmentation mechanism has been proposed from the evidence that the mass spectra of appropriate aporphine alkaloids were closely related with those of fumariline-type alkaloids, and the mechanism was suported by the accompanying metastable ions.
In order to clarify the properties of wet powders which gave maximum granulating pressure in the preparation of ganules, compaction behavior, flow property, and plasticity of wet powders kneaded with various amounts of binder were investigated. It has become apparent that several characteristics curves indicating the properties of wet powder have a maximum or a flexion point at about the same amount of the hinder, and that the amount of a binder giving these points corresponds to that for maximum granulating pressure. Therefore, it can be presumed that the wet powder giving a maximum granulating pressure is in the plastic limit.
3-(α, α-Bismethylthiomethylene) indolenium methyl sulfate (IV), which was prepared by the reaction of methyl indole-3-dithiocarboxylates with dimethyl sulfate, reacted with active methylene compounds to form 3-(methylthio) vinylindole derivatives (VIa, b, c, d) in good yields. Similary, substitution reactions of methylthio or amino groups in 3-(α-amino-α-methylthio) methyleneindolenium iodides (VIIIa, b), which were synthesized by the reaction of thioamide derivatives with methyl iodide, with active methylene or amines gave the corresponding substituted compounds.
N-Oxidation of 3, 2'-diquinolyl (4) was examined under various conditions to give the 1-oxide (5) and 1, 1'-dioxide (6). The 1-oxide group in 5 and 6 was easily deoxygenated by heating with carbon disulfide in N, N-dimethylformamide (DMF); the 1'-oxide group resisted this deoxygenation. This indicates that 1-oxide function has a slight nitrone-like property, and this was supported by the fact that nitation of 5 did not give γ- or α-nitro compound.
Protolyofoligenic acid (III) was correlated with cycloartenol by converting both to the same substance, 3α-hydroxy-24(R), 25-isopropylidenedioxy-9, 19-cyclolanostane (V). Based on the present and previous evidence, the structure of lyofolic acid has been elucidated as 24(R), 25-dihydroxy-3(R)[6'-O-acetyl-D-β-glucopyranosyloxy]-9, 19-cyclolanostan-32-oic acid (I).
Condensation of aminopyrazines with diethyl ethoxymethylenemalonate readily gave diethyl N-(6- and 5, 6-di-substituted 2-pyrazinyl) aminomethylenemalonates (V), which was subjected to thermal cyclization to afford ethyl 8-hydroxypyrido [2, 3-b] pyrazine-7-carboxylates (VII) and ethyl 4H-4-oxopyrazino [1, 2-a] pyrimidine-3-carboxylates. (VI). Ethyl 3-(substituted amino)-8-hydroxypyrido [2, 3-b] pyrazine-7-carboxylates (VIIe-VIIh) were obtained by the reaction of 3-chloro compound (VIId) with appropriate amines. A series of 3- and 2, 3-di-substituted 5-ethyl-5, 8-dihydro-8-oxopyrido [2, 3-b] pyrazine-7-carboxylic acids (IX) were prepared from VII and assayed for their antibacterial activity.
In order to investigate the fragrant components, the essential oil of the flowers of Viburnum dilatatum. THUNB. was examined and as the main fragrant substances phenethyl alcohol, cis-3-hexen-1-ol, α-terpineol, benzyl alcohol, l-linalool, and methyl salicylate were isolated. The acidic oil contained 12 kinds of volatile acids. It is very characteristic that isovaleric acid forms over 90% of the volatile acid oil. Quercetin, kaempferol, apigenin, luteolin, ursolic acid, and several paraffins were obtained from the steam distillation residue, and identified.
The droplet countercurrent chromatographic separation of the quaternary bases has been examined. From the quaternary base fraction of Corydalis pallida var.tenuis YATABE, palmatine chloride, dehydrocapaurine chloride, dehydrocorydalmine chloride, dehydrocapaurimine chloride, and choline chloride were isolated.
The mechanisms of bactericidal action of hydrogen peroxide on E.coli were studied. It was found that incorporation of take up of 14C-glutamic acid, 3H-uracil, glucose, and galactose by E.coli was inhibited by H2O2 treatment and the inhibitory effect increased with the amount of hydrogen peroxide on cellular nitrogen. Membrane fragility of H2O2-treated cells of E.coli increased with increasing amount of H2O2 and this increase was assumed to be due to changes in the cell membrane. When the H2O2-injured cells (H2O2/N mg>50) were placed in bouillon and incubated at 37° with shaking, the injury and the growth rate were recovered gradually.
From the fruits of Lindera erythrocarpa MAKINO ("Kanakuginoki" in Japanese) (Lauraceae), used as a folk medicine, linderone, methyllinderone, lucidone, methyllucidone, kanakugiol, kanakugin and trans-cinnamic acid were isolated. Kanakugiol and kanakugin were found to be 2'-hydroxy-3', 4', 5', 6'-tetramethoxychalcone and 5, 6, 7, 8-tetramethoxyflavanone, respectively.
The effect of calcium on the fluoride-treated blood was studied. The blood level of glucose increased rapidly, and the plasma level of total calcium decreased after administration of sodium fluoride to buccal mucosa. Morphological changes in the rabbit erythrocyte membrane induced by sodium fluoride in vivo was observed by scanning electron microscopy. These activities of fluoride were significantly depressed in the rabbit pretreated with calcium chloride.
From the aqueous extract of Puerariae radix, anticholinergic substances like daidzein, daidzin, and puerarin were removed as much as possible to make a syrup material which has a constant cholinergic activity. This syrup material was termed MTF-101. From MTF-101, two cholinergic substances and five other compounds were isolated; choline chloride (ca. 1.0%), acetylcholine chloride (ca. 0.1%), allantoin (ca. 3%), D-mannitol (ca. 15%), D-(+)-pinitol (ca. 8%), succinic acid (ca. 10%), and L-(+)-Mg lactate (ca. 15%).
The difference of stability was compared between the aqueous extract of Puerariae radix (MTF-101), which contains about 0.1% acetylcholine, and the commercial acetylcholine chloride against cholinesterase, high temperature, and the rat gastric juice. Effect of MTF-101 and acetylcholine on the intestinal movement and the intestinal internal pressure in the anesthetized guinia pig was also investigated, and it was proved that MTF-101 (1×10-4 g/ml) is much more stable against cholinesterase and high temperature, and more effective on the intestinal movement and intestinal internal pressure than acetylcholine chloride.(1×10-4 g/ml).