DSC curves of mixtures of synthetic L-phosphatidyl choline and water were measured for samples prepared under various conditions. Various kinds of phase transition were detected and the values for transition temperature and transition enthalpy were obtained from the DSC curves. Between 25°and 140°, there are three lyotropic polymorphs each of which has several thermotropic polymorphs. For phosphatidyl choline with longer hydrocarbon chains, an additional polymorph in crystalline form, was found. On the basis of these experimental results, a phase diagram of phosphatidyl choline-water system was drawn.
Many of the amphipathic drugs tested, which induced shape changes in intact human erythrocytes, produced biphasic effects on hypotonic hemolysis of cells in a similar concentration range, protection at low concentrations and stimulation at higher concentrations. Both the exvaginators and invaginators, which induced shape changes of the membrane exvagination and invagination type, respectively, showed the same type of effect on osmotic resistance. When two drugs of either the exvaginator or invaginator type are present together in a hemolyzing medium, their effects on osmotic resistance appeared to be additive, as was the case with their effects on cell shape. In contrast, when an exvaginator and an invaginator are present together, their effects, both on osmotic resistance and cell shape, seemed to be antagonistic. The present results suggest that these drug effects may be caused, at least partly, by an asymmetric expansion of the membrane lipid bilayer due to asymmetric distribution of the drugs incorporated into the membrane.
The rate of release of prostaglandin F2α (PGF2α) from isolated rat uterus increased markedly from 18 to 21 days of pregnancy. During parturition, it still maintained a high level. When 2-(2-fluoro-4-biphenylyl) propionic acid (flurbiprofen) and indomethacin were orally administered, 0.5 and 2.5 mg/kg twice a day, to pregnant rats from 18th day of gestation to the begining of parturition, the rate of release of PGF2α from the uterus at the time of parturition was reduced by both anti-inflammatory agents. The ability to inhibit the release of PGF2α was more intense in flurbiprofen than in indomethacin in conformity with the results of prolonged pregnancy and delayed spontaneous delivery induced by these drugs. PGF2α level in peripheral plasma increased significantly at the time of parturition. Flurbiprofen and indomethacin were also found to hinder the rise in PGF2α level. 17β-Estradiol in plasma gradually increased in late pregnancy, whereas progesterone in plasma rapidly decreased on 21st day. Neither flurbiprofen nor indomethacin exerted any effect on the action of 17β-estradiol. The drop of progesterone during parturition was hindered relatively little by both drugs. Furthermore, regression of the corpora lutea during parturition was obviously inhibited by both drugs. However, 20α-hydroxysteroid dehydrogenase activity in the corpora lutea was not affected. Δ5-Isomerase activity was enhanced only by flurbiprofen. These results indicated that deficiency of PGF2α release in the uterus might result in the delay of spontaneous derivery, and also concomitant inhibition of luteolysis might be involved in the prolongation of pregnancy induced by treatment with these anti-inflammatory agents.
Effects of neocercosporin (I) on bacteria were determined by the plating broth dilution method using Bacillus subtilis PCI 219, Escherichia coli and others. Gram-positive were more sensitive than gram-negative bacteria which were sensitive with high concentrations of I. I was did not react with CDF1 mouse leukemia P-388.
Nitration of 1-cyanoisoquinoline 2-oxide (1) with potassium nitrate and sulfuric acid gave 5-and 6-nitro derivatives (2 and 3). The reaction was affected by the concentration of sulfuric acid, and 3 was obtained in small yields as the sole product from the reactions in the 85% acid at 70°. Nitration with fuming nitric acid (d=1.50) led to the formation of 3 in fairly good yields together with small amounts of 8-nitro derivative (7). Further, nitration of isoquinoline 2-oxide (9) with fuming nitric acid was found to give 5-, 6- and 8-nitro derivatives (10, 11 and 12). The orienting effect of the N-oxide function is apparently operative in the formation of 11 and 12.
The structures of four hitherto unidentified metabolites of nitrazepam in the rabbit were elucidated using ultra violet (UV), infrared (IR), nuclear magnetic resonance (NMR) and mass spectrometry. They were 2'-benzoyl-2-hydroxy-4'-nitroacetoanilide (M-I), hydroxylated 2-amino-5-nitrobenzophenone (M-II), 7-amino-8-hydroxynitrazepam (M-III) and 2-formamido-5-nitrobenzophenone (M-IV). These metabolites were excreted primarily in conjugated from except for M-IV. Urinary excretion of nitrazepam and its metabolites were studied by preparative thin-layer chromatography (TLC) and characteristic colorimetric methods before and after enzymic hydrolysis of the conjugates. 2-amino-3-hydroxy-5-nitrobenzophenone (3-OH-ANB) was the major metabolite following oral administration. The excretion of 7-amino-nitrazepam and 7-acetamidonitrazepam increased, but that of 3-OH-ANB decreased following intraperitoneal administration. In both types of administration, M-I to IV were minor metabolites (about 1% of the dose), but M-I and M-IV were considered to be intermediates leading to 2-amino-5-nitrobenzophenone. On the basis of these data, the metabolic pathways of nitrazepam in the rabbit were postulated in Chart 1.
Sulfonyl ketenethioacetal derivatives (II) were synthesized by the reaction of sulfonyl carbanions with carbon disulfide in the presence of sodium hydride in tetrahydrofuran, followed by treatment with dimethyl sulfate. The reaction of II with various amines gave the corresponding amine derivatives and heterocyclic compounds (pyrazole, imidazoline, benzimidazoline, oxazoline).
The effects of hog pancreatic kininogenase (Hog Panc. K.) on blood pressure and plasma kininogen level in normal and renal hypertensive rabbits were studied. Intramuscular injection of Hog Panc. K. resulted in a dose-dependent vasodepressor action in normal rabbits, and this action was more pronounced in renal hypertensive rabbits. Intravenous, intramuscular and intraduodenal administration of Hog Panc. K. led to the consumption of plasma kininogen in normal rabbits, however, their total plasma protein levels did not change. Both the vasodepressor response and the consumption of plasma kininogen by Hog. Panc. K. seemed to be dose-dependent in renal hypertensive rabbits. In renal hypertensive rabbits the level of plasma kininogen was 1.7 times higher than in normal rabbits, while the vasodepressor effect of Hog Panc. K. did not appear in spontaneously hypertensive rats. Kinin formation by various kininogenases from plasma kininogen obtained from various animals was also examined. Hog Panc. K. caused a kinin-liberation from the crude kininogen preparations obtained from human, bovine, hog, dog and rabbit plasma, but not from that of guinea pig and rat.
We investigated the effects of oral administration of seven antibiotics and six chemotherapeutic agents on ureolysis in rats by 1) measuring 14CO2 expired in breathing air after oral administration of 14C-urea (in vivo measurement) and by 2) determining urease activity of the ileum-caecum contents of treated rats (in vitro measurement). Urease activity of the ileum-caecum contents was not directly inhibited by these drugs. When antibiotics were administered orally, ureolysis was most strongly depressed by clindamycin, followed by cefazolin, thiophenycol and neomycin, in descending order of depression. The depression percentages of these antibiotics in in vivo and in vitro measurements were 50-76% and 56-96%, respectively."The antibiotics mixture"completely depressed ureolysis in in vivo and in vitro measurements. The antibiotics used inhibited the growth of urease-positive bacteria in the intestinal flora of rats and their depressive effects depended on their antibacterial characteristics. When sulfanilamide- or nitrofuran derivatives were administered, ureolysis in in vivo and in vitro measurements was not depressed but rather, activated. The administration of metronidazole depressed ureolysis in some rats and not in others, possibly due to a difference in the intestinal flora of several urease-positive bacteria. The administration of berberine, lactulose and pectic acid did not affect ureolysis.
The inhibitory effect of gliclazide, a new sulfonylurea, on platelet function was examined in alloxan diabetic rabbits. The blood glucose level in diabetic rabbits was about 3 times higher than in normal rabbits, and the plasma insulin level was below 50% of that of normal rabbits. Platelet adhesiveness to glass beads and platelet aggregation by collagen were markedly enhanced in the diabetic rabbits. 2-4 week daily administration of gliclazide (100 mg/kg, p.o.) to diabetic rabbits effected the reduction of enhanced platelet adhesiveness, and platelet aggregation was also lowered to that of normal rabbits after 4 weeks. Blood glucose and plasma insulin levels, however, were not changed by the treatment. These results suggest that gliclazide exerts an inhibitory action on platelet function via mechanism (s) other than insulin secretion and glucose metabolism.
The difference of degree of peptization in two kinds of ferric hydroxide powders prepared by heat-dry (105°, 6 hr) and freeze-dry methods was investigated in aqueous hydrochloric acid solution. The characteristics of both kinds of powders were estimated by measurements of zero point of charge, particle size distribution and X ray diffraction patterns. Ferric hydroxide was peptized by adding the powder into a hydrochloric acid solution and boiling for 8 hours. The degree of peptization was evaluated by the concentration of ferric hydroxide in the sol thus formed. The concentration was determined by chelatometry after dissolving the colloidal particles into ferric ions. The degree of peptization in freeze-dried was higher than that in heat-dried samples however, peptization was higher in undried samples. The pH values in which 80% of the added amount of ferric hydroxide was peptized were about 2.6, 1.8 and 1.5 for undried, freeze-dried and heat-dried samples, respectively. The efficiency of peptization tended to be higher in lower pH region but it decreased abruptly around pH 1. The mechanism of peptization in these samples was considered from the view point of electrochemical phenomena caused by the adsorption of hydrogen ions on the ferric hydroxide particles and the ionic strength of the systems.
We investigated the effects of crude extracts from 15 varieties of crude drugs on blood urea nitrogen (BUN) and total cholesterol (T. Chol.) concentrations in rat serum at 8 hr after intraperitoneal administration. Concentrations were estimated by an automatic method. We found that the administration of rhei rhizoma, coptidis rhizoma, ephedrae herba, paeoniae radix, and bupleuri radix, resulted in a decrease of BUN and an increase of T. Chol. while administration of asiasari radix and cinnamomi ramulus, resulted in an increase of T. Chol. only. In addition, we found that the most effective doses of rhei rhizoma, coptidis rhizoma, ephedrae herba, and paeoniae radix were 5, 5, 5 and 25 mg/rat on BUN and 5, 5, 2.5 and 25 mg/rat on T. Chol., respectively. In rats treated with 5 mg rhei rhizoma, 5 mg coptidis rhizoma or 25 mg paeoniae radix, BUN was maximally decreased at 6 hr and T. Chol. was maximally increased at 8 hr. In rats administered 5 mg scutellariae radix or 25 mg glycyrrhizae radix BUN was maximally decreased at 4 hr and T. Chol. was maximally increased at 6 hr, although BUN and T. Chol concentrations were not affected at 8 hr after the 5 mg scutellariae radix or 5 mg glycyrrhizae radix.
Various 2-aminoxazoles (I) and 2-acetamidoxazoles (IV) were submitted to catalytic reduction using varying amounts of palladium-carbon or platinum oxide catalyst. In all cases, in which a large amount of catalyst was used, the ring fission occurred preferentially and I was mainly converted to alkylureas (V) via (E)-alkenylureas (II). As the amount of catalyst decreased, the rate of cis-2-amino-2-oxazolines (III) increased, suggesting that the hydrogenolysis reaction pathway of I was determined by the step of the conversion of the half-hydrogenated species to the intermediates (II, III) in terms of the Horiuti-Polanyi mechanism.
Monospecific antiserum to purified human prostatic acid phosphatase was produced in rabbits. Prostatic acid phosphatase treated with neuraminidase retained all enzyme activity before treatment and reacted with the antiserum. The enzyme treated with urea, sodium dodecyl sulfate, 2-mercaptoethanol and guanidine hydrochloride lost all enzyme activity and did not react with the antiserum. We demonstrated that the antibody to the prostatic acid phosphatase can protect the enzyme specifically against heat and pH inactivation. When the prostatic acid phosphatase was coupled with the antibody, enzyme activity was markedly stabilized at pH 4.6-5.8 at 56°. Prostatic acid phosphatase activities in human sera were assayed using the antibody. The activity values were high in sera of patients with prostatic carcinoma and low in sera of patients with prostatic hypertrophy and normal subjects.
Four kinds of normal saturated hydrocarbons, CnH2n+2 (n=19-22), campesterol, stigmasterol, β-sitosterol, α-amyrin, palmitic acid, linoleic acid, stearic acid, behenic acid, and lignoceric acid were detected by gas chromatography-mass spectrometry (GC-MS) from the petals of Chrysanthemum morifolium RAMAT. var. sinense MAKINO forma esculentum MAKINO, one of barnds"Mottenohoka."Eleven kinds of free amino acids were identified by an amino acid analyzer.
Two triterpenoid saponins, hederagenin 3-O-β-D-glucopyranosyl (1→2)-α-L-arabinopyranoside (I) and oleanolic acid 3-O-β-D-glucopyranosyl (1→2)-α-L-arabinopyranoside (III), were obtained from the leaves of Fatsia japonica DECNE. et PLANCH. In addition, the structures of two formerly reported Fatsia saponins, "α-fatsin"and"oleanolic acid 3-O-β-D-glucopyranosyl (1→4)-α-L-arabinopyranoside, were revised as being I and III, respectively.
The essential oil was obtained in 0.070% (I), 0.012% (II) and 0.077% (III) yields by steam distillation from the flowers (I), leaves (II) and roots (III) of Plantago asiatica L., which were collected at Higashiosaka-shi in June 1977. Each essential oil was chemically separated into three parts : i.e. neutral, sodium bicarbonate soluble and sodium hydroxide soluble parts. Each fraction was investigated by gas-liquid chromatography (GLC), instrumental analysis and each compound was identified by comparison with the authentic sample. We found that the major components of the essential oil were (I) carvacrol, (II) : 1-octen-3-ol and (III) : linalool and geranyl acetate, and that it contained terpene compounds, aliphatic alcohols, aromatic compounds, phenol compounds and aliphatic fatty acids. They were α-pinene, camphene, limonene, n-hexanol, 3-hexen-1-ol, camphor, 1-terpinen-4-ol, β-caryophyllene, α-terpinyl acetate, nerolidol, guaiacol, cresols, and miscellaneous.
A rapid determination of arbutin in crude drugs (uva ursi, cowberry, and uva ursi extract) by the use of high-speed liquid chromatography is described. Arbutin is separated by the 25 cm column of Zorbax CN, using liquid chromatograph of Shimadzu-Dupont Model LC-2, with water as the desorption solution, and is completed within 15 min. Arbutin in the crude drugs is extracted with water and the aqueous extract is injected into the column. Precision of determination is ±2% and detection limit is a few nanograms of arbutin.
Unknown compounds, 2, 3, 9-(I) and 1, 2, 9-Trimethoxyoxoaporphine (Ia) were synthesized via Bischler-Napieralski reaction and Pschorr reaction. 1, 2, 10-Trimethoxyoxoaporphine (Ib) was prepared from the corresponding dehydroaporphine by oxidation with peracid. Since the physical properties of the compound are not consistent with the reported data, the structure proposed for a product which was obtained by cleavage reaction with sodium in liquid ammonia of dehydrothalicarpine may be uncorrect.
Stabilization of the rat erythrocyte membrane by neuroleptic butyrophenones such as moperone, haloperidol, trifluperidol, clofluperol, floropipamide, and lenperone was examined. In low concentrations, all drugs used stabilized rat erythrocytes against hypotonic hemolysis, while at higher drug concentrations, the antihemolytic activities decreased along with increasing drug concentration. Clofluperol, the most potent neuroleptic of the drugs used, showed the highest antihemolytic activity and floropipamide, the least potent neuroleptic, showed the lowest. A good correlation was obtained between the partition coefficient (n-octanol/0.15 M phosphate buffer, pH 7.4) and antihemolytic activity of the drugs.