Physiological signals such as peptide hormones and neurotransmitters are recognized on the surface of their target cell membranes and they bind to specific receptors on it. These interactions then initiate biochemical alterations in membranes which in turn allow stimulated cells to exert their various specific functions. It is now well documented that one of the earliest and crucial membrane changes in the stimulus-response compling is the rapid turnover of phosphoinositides. Compelling experimental evidence indicates that the calcium ion mobilizing receptors affect intracellular calcium levels via hydrolysis of phosphatidylinositol 4, 5-bisphosphate (PIP2) into inositol trisphosphate (IP3) and diacylglycerol (DG), which serves as intracellular second messengers. The former acts as an effective releaser of calcium ion from intracellular stores and the latter messenger is a potent activator of protein kinase C. Recently, it is known that guanine nucleotide-binding protein (s) is involved in the coupling of calcium ion mobilizing receptors of PIP2 hydrolysis and calcium ion mobilization. This review will focus on the signal transduction mechanism in the receptor activation of human platelets.
Structure and function of human serum lipoprotein are described as follows : 1. The formation of lipoprotein is based on the hydrophobic interaction between apoprotein and lipid constituent. 2-a. Chylomicron is synthesized in the intestine cell and secreted into the blood through lymph. It is degradated by lipoprotein lipase (LPL) resulting with chylomicron remnant, which is incorporated into the liver by E receptor. 2-b. Very low density lipoprotein (VLDL) is synthesized in the liver and secreted into the blood stream. It is digested by LPL to form VLDL remnant. A part of VLDL remnant is changed to low density lipoprotein (LDL) by LPL and other part of remnant is incorporated into the liver. Resulting LDL enters partially into extrahepatic tissues by B, E receptor. 2-c. High density lipoprotein (HDL) is formed by the surface of chylomicron or VLDL. HDL is also synthesized in the liver. HDL transports cholesterol ester to VLDL or LDL after free cholesterol is transferred from cell surface of tissue to HDL, in which free cholesterol is subjected to esterification of lecithin-cholesterol acyl transferase (LCAT) of HDL. 3. High performance liquid chromatography (HPLC) analysis of serum lipoprotein has been recently performed by us. This analysis uses gel-permeation column and determination of lipid constituents in post column effluent.
The reaction of 1, 7-phenanthroline (1) with various acyl chlorides and trimethyl phosphite in the presence of sodium iodide gave the corresponding α (8)-phosphonates (2) and γ (10)-phosphonates (3) as observed in the reaction of benzo [f] quinoline, while in Reissert reaction γ-type's compound was not obtained. In the similar reaction to 4, 7-phenanthroline (4), the corresponding α, α'-diphosphonates (5) and α, γ'-diphosphonates (6) were obtained. Furthermore cis-(5b2 and 5c2) and trans-(5b1 and 5c1) isomers were separated by silicagel column chromatography from α, α'-diphosphonates (5b and 5c). α-Phosphonates (2, 5) and γ-phosphonates (3, 6) were identified by comparison of 13C-nuclear magnetic resonance and ultraviolet spectra with those of phosphonates obtained from quinoline and benzo [f] quinoline. 1, 10-Phenanthroline (7) was recovered in the similar reaction. The reaction of acridine (8) with trimethyl phosphite gave 9-phosphonates (9).
From the leaves and the barks of Melicope triphylla MERR., three new flavonoids (6-8) were isolated, together with 4'-hydroxy-3, 3', 5, 7-tetramethoxyflavone (1), 3, 5, 7-trimethoxy-3', 4'-methylenedioxyflavone (2), 4'-hydroxy-3, 3', 5, 7, 8-pentamethoxyflavone (3), 3, 5-dimethoxy-3', 4' : 6, 7-bismethylenedioxyflavone (4) and 3, 5, 8-trimethoxy-3', 4' : 6, 7-bismethylenedioxyflavone (5). The structures of 6, 7 and 8 were established as 4'-hydroxy-7-isopentenyloxy-3, 3', 5-trimethoxyflavone, 7-isopentenyloxy-3, 3', 4', 5, 8-pentamethoxyflavone and 7-isopentenyloxy-3, 5, 8-trimethoxy-3', 4'-methylenedioxyflavone by their respective chemical and spectral data.
The seasonal variations in the essential oil of Schizonepeta tenuifolia BRIQ. (Labiatae, Japanese name, "Keigai") was studied. During the growing season, (-)-pulegone content decreased from 77.3 to 21.2%, (+)-menthone concentration varied from 11.1 to 61.5%. These changes of contents in the oils are similar to those of Mentha, namely toward the climax stage of vegetation, pulegone was gradually reduced to menthone. The essential oils of leaves, spikes, and stems were analyzed by using gas chromatography-mass spectrometry, and 43 constituents were positively identified, including 26 newly identified ones.
For studies on the metabolism of 17β-hydroxyestra-1, 3, 5 (10)-triene (3-deoxyestradiol) sulfate, authentic compounds as potential metabolites were prepared. The synthetic procedures of 2-, 3-, 4-, 6α-, and 6β-hydroxylated products of 3-deoxyestradiol 17-sulfate are described.
Rhodophyllus rhodopolius has so far been known as a poisonous mushroom, but its toxic principle has not been proved clearly yet. The aqueous extract of this mushroom showed the toxicity causing diarrhea and death to mice, while the methanol extract does not. Bile storage in the duodenal, and intestinal edema were observed by autopsy of the intoxicated mice. Fractionation of the aqueous extract by ultrafiltration, ion exchange column chromatography and gel filtration afforded protein fractions as a toxic component with molecular weight of about 40000. Furthermore, several kinds of assay related to diarrhea were examined in order to find a suitable method adaptable for fractionation of the toxic principle. As a result, the toxic fraction causing diarrhea and intestinal hemorhharge to suckling mice was also found to exhibit hemolytic activity. Accordingly, the examination of hemolytic activity in vitro is possibly employed for screening as an assay method instead of diarrhea.
Although colicin E1 type plasmids (colE1 and pKY-1) can not transform Escherichia coli recB recC sbcB, pBR322, a derivative of a colicin E1 type plasmid, can transform it. The analysis by using the derivatives of pKY-1 gave the following conclusions concerning their inability. 1) E. coli recB recC sbcB was not transformed with the plasmid carrying cea gene of colicin E1 which was transcribed by constitutive promoter. 2) Transcription of the first 250 bases of the cea gene was sufficient to inhibit the transformation. 3) The inhibition of transformation with the plasmid is expressed by transcription of its own cea gene (cis-acting). 4) When the replication origin of pKY-1 was changed to pKYM, the transformation was not inhibited. The transcript inhibits only the transformation with the plasmid carrying the replication origin derived from colicin E1 or its relative. 5) Transcription of the cea gene inhibited multiplication of the host cells carrying the plasmid. The synthesis of plasmid deoxyribonucleic acid (DNA) continued in the host cells but the DNA was not isolated from the cytoplasm as a closed circular form.
The influence of coadministration of phenobarbital (PB) on the disposition of carbamazepine (CBZ) and its active metabolite, CBZ-10, 11-epoxide (EPO), were investigated by use of rabbits. The disposition of CBZ or EPO after intravenous injection is well described by a one-component model, and the formation and elimination of EPO after the administration of CBZ followed linear first-order kinetics at doses below 20 mg/kg. The total plasma clearance (CL), volume of distribution (Vd), and half-life (T1/2) of CBZ were 1.219±0.470 (mean±S.D.) l/h/kg, 1.086±0.287 l/kg, and 0.648±0.134 h, respectively. The values for CL, Vd, and T1/2 of EPO were 0.340±0.210 l/h/kg, 1.025±0.138 l/kg, and 2.569±1.041 h, respectively. The epoxidation rate constant (kf) and fraction (fm) of CBZ biotransformed to EPO were 0.167±0.075 h-1 and 0.152±0.055, respectively, and the area under the plasma concentration (AUC) ratio of EPO to CBZ after intravenous injection of CBZ was 0.575±0.197 for control rabbits. The single intravenous injection of PB (50 mg/kg) at 30 min prior to the administration of CBZ or EPO has no significant effect on any of these pharmacokinetic parameters of CBZ or EPO. However, repeated PB treatment (intraperitoneal injection of 50 mg/kg/d of PB for 7d) caused an increase in CL of CBZ and EPO (2.620±0.345 and 0.588±0.188 l/h/kg), a decrease in T1/2 of CBZ and EPO (0.350±0.078 and 1.189±0.418 h), and no change in Vd of CBZ and EPO (1.328±0.371 and 0.928±0.161 l/kg) compared to those of control rabbits. Although repeated PB treatment increased significantly in kf (0.213±0.069 h-1), there was no singificant change in the AUC ratio of EPO to CBZ (0.568±0.149). This result was well explained by the facts that there was no change of fm values (0.110±0.039) and that the degree in enzyme-inducing effects for CBZ and EPO between repeated PB treatment and control rabbits was the same.
By comparison of the choleretic effects of several kinds drugs, it was recognized that there exists a significant positive correlation between doses and the choleretic effects of sodium dehydrocholate and 1-phenylpropanol. Moreover, small differences in the amount of excretion of bile acid from bile were detected by use of these two drugs. It was also recognized to be suited in screening to utilize the rate of variation in the amount of bile acid to the values just before 120 min after the administration of drugs for the determination of their choleretic effects. As a result of screening in 17 out of 47 kinds of crude drugs high choleretic effects were detected. These drugs were classified into the following two groupes ; Hyperici erecti Herba, Forsythiae Fructus, Gardeniae Fructus, Gentianae Scabrae Radix, Atractylodis Rhizoma, Aurantii Percicarpium, Swertiae Herba, Plantaginis Semen and Desmodii Herba with a biliary bile acid increase and Ganoderma, Sophorae Radix, Valerianae Radix, Myricae Cortex, Acer nikoense, Scutellariae Radix, Curcumae Rhizoma and Patriniae Radix without a biliary bile acid increase.
The flavonoids, eight quercetin-3-O-glycosides, two kaempferol-3-O-glycosides, myricetin-3-O-glucoside, quercetin, kaempferol and gallic acid in twenty-two native Polygonum species in Japan were identified by the comparison of mass spectroscopy and the several thin layer chromatography techniques. It has been evident that flavonol glycoside, especially, quercetin glycoside was widely distributed in Polygonum species and that the plantlet of P. nodosum contained flavonol-3-O-glycoside-2"-gallate as a main component.
The dissolution behaviour of phenylbutazone (PBZ) polymorphs, pure α, β, and δ forms prepared by the method described in our previous paper, was investigated kinetically by the rotating disk method. The dissolution activation energies obtained by the measurement of the initial dissolution rate at various temperatures were different among three polymorphs, and those of α, β, and δ forms were 7.90, 8.93, and 4.52 kcal/mol, respectively. This result indicated the participation of interfacial chemical reaction in the dissolution of PBZ. Furthermore, it is suggested that both interfacial chemical reaction and transport process were concerned in the dissolution of PBZ as judged by the values of the dissolution activation energy.