The present article describes functional development of monoaminergic synapses in the brain. Our recent findings on developmental changes of regional content, uptake, release of noradrenaline, dopamine, serotonin, specific binding of monoamines-related drugs and behavioral effects of these drugs were shown with aspect to the regulation mechanism in synaptic transmission.
New 7α-methoxycephalosporins, 7β-[α-(4-ethyl-2, 3-dioxo-1-piperazinecarboxamido)-α-substituted acetamido]-7α-methoxycephalosporanic acids (Ia-p) were prepared. They showed a broad antibacterial spectrum, especially a strong antibacterial activity against gram-negative bacilli such as Pseudomonas aeruginosa and Serratia marcescens. In these compounds, 7β-[D (-)-α-(4-ethyl-2, 3-dioxo-1-piperazinecarboxamido)-α-phenylacetamido]-7α-methoxy-3-[(1-methyl-1H-tetrazol-5-yl) thiomethyl]-3-cephem-4-carboxylic acid (Ic), 7β-[D-(-)-α-(4-ethyl-2, 3-dioxo-1-piperazinecarboxamido)-α-(4-hydroxyphenyl) acetamido]-7α-methoxy-3-[(1-methyl-1H-tetrazol-5-yl) thiomethyl]-3-cephem-4-carboxylic acid (Id) and 7β-[D (-)-α-(4-ethyl-2, 3-dioxo-1-piperazinecarboxamido)-α-(2-thienyl) acetamido]-7α-methoxy-3-[(1-methyl-1H-tetrazol-5-yl) thiomethyl]-3-cephem-4-carboxylic acid (Ig) were selected and evaluated for antibacterial activity, stability against β-lactamase, protective effects on experimental infections.
7β-[α-(4-Alkyl-2, 3-dioxo-1-piperazinecarboxamido)-α-substituted acetamido]-7α-methoxycephalosporanic acids (Ia-q) were prepared and tested for antibacterial activity. Ia-q showed potent activities to gram-negative bacilli, particularly to Escherichia coli, Klebsiella pneumoniae and Serratia marcescens. Three of these compounds, 7β-[D-(-)-α-(4-ethyl-2, 3-dioxo-1-piperazinecarboxamido)-propanamido]-7α-methoxy-3-[(1-methyl-1H-tetrazol-5-yl) thiomethyl]-3-cephem-4-carboxylic acid (Ia), 7β-[D (+)-α-(4-ethyl-2, 3-dioxo-1-piperazinecarboxamido)-β-[(S)-hydroxy]-butanamido]-7α-methoxy-3-[(1-methyl-1H-tetrazol-5-yl) thiomethyl]-3-cephem-4-carboxylic acid (Ic) and 7β-[D (+)-α-(4-ethyl-2, 3-dioxo-1-piperazinecarboxamido)-β-[(S)-methoxy]butanamido]-7α-methoxy-3-[(1-methyl-1H-tetrazol-5-yl) thiomethyl]-3-cephem-4-carboxylic acid (II) were selected and evaluated for antibacterial activity against clinical isolates, stability against β-lactamases, acute toxity, serum level, urinary and biliary excretions and protective effect against experimental infection compared with cefmetazole (CMZ). These evaluations suggest that Ic will be a useful antibiotic for clinical applications.
Studies were made on the intermolecular interaction of ten 9-diethylaminobenzo [α]-phenoxazonium salts (BPZ) and calf-thymus deoxyribonucleic acid (DNA) and antibacterial activities for Staphylococcus aureus 209P of BPZ. (1) The interaction system of BPZ and DNA was found to show a flow dichroism in the visible region. A value of the ΔE in the equation ΔE=E11-E&bottom; is found to be negative, and flow dichroism studies indicate that BPZ intercalates in the same plane as DNA base pairs. (2) The flow dichroism's ratio in the visible region produced by the interaction of BPZ with DNA paralleled in minimum inhibitory concentration (MIC) of BPZ for Staphylococcus aureus 209P.
A sensitive method for menaquinone-4 (vitamin K2 (20), MQ-4) in the plasma by mass fragmentography was developed. In this method, micro-quantitative reductive acetylation was studied for the conversion of MQ-4 to volatile derivative. Then the concentration of MQ-4 in the plasma after the single administration of MQ-4 dosage forms (30-120 mg/man) to healthy male adult volunteers and the bioavailabilities of the dosage forms were examined. MQ-4 and phylloquinone (vitamin K1, PQ) were extracted from the plasma to which PQ was added as an internal standard (IS). The extracts were dissolved in acetylating reagent (acetic anhydride-acetic acid-sodium acetate) and zinc dust was added, then refluxed for 1 h at 170°C in a sealed glass tube. MQ-4 and PQ were converted to dihydromenaquinone-4 diacetate and dihydrophylloquinone diacetate, respectively and measured by mass fragmentography. The determination limit was 3 ng/ml plasma. MQ-4 given in syrup was absorbed more rapidly than that in capsule. The maximum plasma concentration (Cmax) for the intramuscular administration of injection was lower than that for syrup, but then the concentration decreased very slowly. The plasma concentration after the intravenous administration of injection decreased apparently in a linear 3-compartment model. The area under concentration-time curve (AUC) after the oral administration of syrup or capsule was observed to be in proportion to the dose. The bioavailabilities of syrup and capsule were 38% and 29%, respectively.
A method for the simultaneous determination of glutathione and D-penicillamine in the human blood was developed by use of a high-performance liquid chromatography with a voltammetric detector. The glutathione and D-penicillamine values in the blood of patients with rheumatoid arthritis treated with D-penicillamine (100-300 mg/d) were studied. It was found that the glutathione values in the blood of responders to D-penicillamine (10 patients) were 25% higher than that of non-responders (10 patients) (p<0.01), and that D-penicillamine values in the blood were little in both groups. The measurement of glutathione could be used both as a parameter of disease activity and as a tool for distinguishing responders from non-responders to D-penicillamine.
It was found that high sugar diets induced an elevation in serum levels of triglyceride and insulin in rats by the oral administration for 2 months. When black substances isolated from crude black sugar were orally administered to rats with the high sugar diets, such elevation was not observed. In addition to these effects, black substances were found to reduce serum lipid peroxide. Black substances were found to inhibit absorption of glucose in the rat small intenstine. Therefore, it was suggested that the effect of black substances on hyperlipemia in rats fed with the high sugar diets might be partly attributable to an inhibition of glucose absorption in the small intenstine.
Tissue homogenate could react with thiobarbituric acid (TBA) and gave the maximum coloration at around pH 2.5, even if the peroxidation of the tissue is accelerated by aging, CCl4- or hexachlorobenzene (HCB)-intoxication. Isolated methyl linoleate hydroperoxide (MLHPO) showed the optimum pH at 3.0-4.0 when reacted with TBA in the presence of an inorganic- or heme-iron catalyst, whereas the optimum pH shifted to 2.5 or so when the reaction was catalyzed by defatted homogenate or iron with albumin. Addition of sodium dodecyl sulfate (SDS), which is sometimes employed as a stimulator of TBA reaction, brought about rather diverse effects in the coloration of MLHPO and tissue homogenate. The TBA value of isolated MLHPO was enhanced by the addition of SDS and the optimum pH was 3.5 irrespective of the catalysts. By the addition of SDS into tissue homogenate the maximum coloration could be obtained at pH 1.0 in all cases (young, aging, CCl4- and HCB-intoxication). Moreover, the difference of TBA value due to aging or intoxicating became insignificant.
The equations were derived for the dissolution of polydisperse powders under sink and nonsink conditions. These were applied to hypothetical powders of log-normally and rosin-rammlerly distributed powders, and practical powders of alkylparabens. To study the dissolution rates of the powders influenced by particle distribution, nonsink condition, solubility and crystal shape, these phenomena were simulated.
Nine Strychnos alkaloids were isolated from the trunk without bark of Kaju Ular, a folk medicine in Timor island, whose original plant is assumed to be Strychnos ligustrina : strychnine, brucine, β-colubrine, ψ-strychnine, ψ-brucine, ψ-β-colubrine, strychnine N-oxide, brucine N-oxide and β-colubrine N-oxide. They were identified by direct comparison with authentic samples. This is the first report of isolation of ψ-strychnine, ψ-β-colubrine, and β-colubrine N-oxide from the trunk of S. ligustrina. Reassignment of 13C-nuclear magnetic resonance spectra of those alkaloids were made by use of the additivity rule and by considerating the effects caused by the introduction of oxygenated function at C-16 and at N-19. The result supported the previous assignment by Wenkert et al.
The characteristics of the cell harvester (LM-101, Labo Mash, Labo Science Co.) were developed for separation of bound and free labeled antigens or haptens (B/F separation) in radioimmunoassay to determine cyclic AMP. Sensitivity and accuracy of the Labo Mash filtration method were similar to those of the Millipore filtration method or the double antibody method. The filtration method by use of the cell harvester is effective for B/F separation in radioimmunoassay, since this procedure is very quick and simple.
The relationships between adherence of zymosan and phagocytosis by macrophages with the release of 6-keto-prostaglandin F1α (6KF1α) and thromboxane B2 (TXB2), the stable endometabolites PGI2 and TXA2 respectively, from macrophages were investigated with mouse peritoneal macrophages. Zymosan-induced release of 6KF1α and TXB2 was inhibited by indomethacin, an inhibitor of cyclo-oxygenase, and by hydrocortisone, an inducer of the inhibitor of phospholipase A2. Although release of 6KF1α and TXB2 was significantly enhanced by the interaction of attachment of zymosan particles to cell membranes, the interaction was inhibited by hydrocortisone, not by indomethacin. From these results it is suggested that phospholipase A2 participates in the interaction of zymosan particles with cell membranes for the release of 6KF1α and TXB2.