Polarization correlation in the superfluorescent decay process.

We investigated the polarization properties of superfluorescence (SF) emitted from dense cesium atomic vapor in a cell. The atoms were excited from the 6S ground to the 8P state using a femtosecond laser pulse. The SF fields generated on the cascaded decay, 8P→8S→7P, mediated the nonlinear optical process. We observed 4.2-µm and 456-nm forward directional emissions generated on the 8S→7P and 7P→6S transitions, respectively. The polarizations of the two fields were correlated in each laser shot, and their directions fluctuated from shot to shot, reflecting the noise that initiated the 4.2-µm emission.

Evaluation of enteric coated tablet sensitive to pancreatic lipase. II. In vivo evaluation.

Plain tablets containing a model drug, sulfamethizole (SMZ), were coated with triolein (TO), trilaurin (TL) and ethylcellulose (EC). The biological behavior of the coated tablets (TOTL-Tab), which are pH independent and sensitive to pancreatic lipase, was investigated in humans. Results of the administration of the tablets with or without an antacid, under fasting and non-fasting conditions, and at 0.5 h before and 0.5 h after meals, were examined. A comparison of the in vivo behavior of SMZ after the administration of these tablets was done using the following data: the lag time of urinary excretion (Ulag), the total urinary recovery percentage (X infinity u), and the mean residence time after Ulag (MRTaf). A typical pH-sensitive tablet coated by cellulose acetate phthalate (CAP-Tab) was used as a reference. For the administration of a CAP-Tab alone, the Ulag obtained under both the non-fasting and fasting condition was longer than that of the plain tablet. However, Ulag after the administration of a CAP-Tab with an antacid became considerably shorter. This lag time was about the same as that obtained from the plain tablet, regardless of food ingestion. The obtained CAP-Tab MRTaf and X infinity u values were not significantly different in comparison to the plain tablets. Under the non-fasting condition, Ulag, MRTaf and X infinity u of TOTL-Tab were not affected by the co-administration of an antacid, and these values were virtually the same as those obtained from a CAP-Tab without an antacid. The urinary excretion data obtained after the administration of TOTL-Tab alone under fasting was analogues to the non-fasting case.(ABSTRACT TRUNCATED AT 250 WORDS)

Cytotoxicity of platinum(IV) and platinum(II) complexes containing 1R,2R-cyclohexanediamine as a ligand.

Several Pt(IV) and Pt(II) complexes containing 1R,2R-cyclohexanediamine (1R,2R-dach) as a carrier ligand were synthesized. The cytotoxicities and the uptake of the platinum complexes by leukemia L1210 cells were compared in order to study the correlation between their structures and cytotoxicities. [Pt(II)Cl2(1R,2R-dach)], [(Pt(II)(oxalato)(1R,2R-dach)], and [Pt(II)(malonato)(1R,2R-dach)], which have excellent anticancer properties, exhibited very high cytotoxicities and were easily taken up by leukemia L1210 cells. [Pt(IV)Cl4(1R,2R-dach)], trans(Cl)-[Pt(IV)Cl2(oxalato)(1R,2R-dach)], and trans(Cl)-[Pt(IV)Cl2(malonato)(1R,2R-dach)] also had high cytotoxicities. After a short incubation time, the uptake of [Pt(II)Cl2(1R,2R-dach)], [Pt(II)(oxalato)(1R,2R-dach)], and [Pt(II)(malonato)(1R,2R-dach)] by leukemia L1210 cells were respectively very similar to those of [Pt(IV)Cl4(1R,2R-dach)], trans(Cl)-[Pt(IV)Cl2(oxalato)(1R,2R-dach)], and trans(Cl)-[Pt(IV)Cl2(malonato)(1R,2R-dach)]. In addition, trans(OH)-[Pt(IV)(OH)2Y2(1R,2R-dach)] (Y2: oxalato or malonato) did not exhibit cytotoxicity towards leukemia L1210 cells, whereas trans(Cl)-[Pt(IV)Cl2Y2(1R,2R-dach)] (Y2: oxalato or malonato) were highly cytotoxic. The accumulation of trans(OH)-[Pt(IV)(OH)2Y2(1R,2R-dach)] in leukemia L1210 cells was much lower than that of trans(Cl)-[Pt(IV)Cl2Y2(1R,2R-dach)]. Platinum(IV) complexes, in which leaving groups are replaced by hydroxide groups, have decreased cytotoxic activity, because the hydroxide groups of the platinum(IV) complex reduce the uptake of platinum by the cells. trans(OH),cis(Cl)-[Pt(IV)(OH)2Cl2(1R,2R-dach)], which has hydroxide and chloride groups, was easily incorporated into the cells and exhibited the high cytotoxic activity. This behavior indicates that the chloride group apparently overcomes the ameliorating effect of the hydroxide group.

Nucleophilic aminoalcohol-catalyzed degradation of indomethacin in aqueous solution.

The catalytic effect of ethanolamine and related aminoalcohols on the rate of degradation of indomethacin in alkaline solutions has been shown to be due to a nucleophilic reaction mechanism involving formation of an intermediate ester consisting of p-chlorobenzoic acid and aminoalcohol through the reaction of aminoalcohol hydroxyl group with carbonyl carbon of indomethacin amide group. This ester subsequently undergoes a rapid intramolecular aminolysis to yield a stable p-chlorobenzamide derivative and/or is hydrolyzed to p-chlorobenzoic acid, depending on the chemical structure of aminoalcohols. No catalytic effect was observed with the amines not containing a hydroxyl group.

Kinetics and mechanism of zinc ion-mediated degradation of cephalosporins in tromethamine solution.

Earlier studies of the hydrolysis and aminolysis of penicillin, in the presence of zinc ion and tromethamine (Tris), revealed a very rapid catalysis mediated by a ternary complex in which the metal ion brought the reactants into close proximity in a suitable configuration for reaction. In the present work similar studies with a group of cephalosporins show not only much slower rates of reaction but a different mechanism in which the zinc ion-tromethamine complex functions as a nucleophile in a bimolecular reaction. Evidence for the differences in mechanism includes not only the different dependence of rate upon tromethamine concentration, but comparable rates of reaction of methyl esters of a penicillin and a cephalosporin and the reaction products observed by high-performance liquid chromatography.

Simultaneous determination of imidazoleacetic acid and N tau- and N pi-methylimidazoleacetic acids in human urine by high-performance liquid chromatography with fluorescence detection.

A sensitive method for the simultaneous determination of urinary imidazoleacetic acid and N tau- and N pi-methylimidazoleacetic acids which employs high-performance liquid chromatography with fluorescence detection is described. The compounds were converted into the corresponding fluorescent esters by reaction with 4-bromomethyl-7-methoxycoumarin. These derivatives are separated by liquid chromatography on a Radial-Pak silica column. The detection limits for imidazoleacetic acid and N tau-and N pi-methylimidazoleacetic acids in urine are 15, 10 and 20 pmol/ml, respectively. The 24-h urinary excretion of imidazoleacetic acid and N tau-and N N pi-methylimidazoleacetic acids by healthy persons was 5.7-39.9, 4.3-24.6 and 1.5-19.3 nmol/mg of creatinine, respectively.

Comparison of the effects of sodium salicylate, disodium ethylenediaminetetraacetic acid and polyoxyethylene-23-lauryl ether as adjuvants for the rectal absorption of sodium cefoxitin.

Sodium salicylate, disodium ethylenediaminetetraacetic acid (EDTA) and polyoxyethylene-23-lauryl ether (POE) significantly enhanced the absorption of cefoxitin from the rectum but with the following differences. The effectiveness of salicylate or EDTA was enhanced by sodium chloride, whereas the activity of POE was not. Although the ratios of plasma cefoxitin peak values to cefoxitin dose were constant with POE or EDTA, the peak to dose ratios with salicylate decreased with increasing cefoxitin concentration. Phlorizin and 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) inhibited the effectiveness of salicylate, but did not influence the adjuvant action of either POE or EDTA. Although treatment with salicylate resulted in slightly less protein release than treatment with NaCl, both POE and EDTA increased the release of protein from the rectal mucosa. It appears that the effects of salicylate occur at the protein fraction of the rectal mucosa through a saturable process whereas the adjuvant action of POE and EDTA appears to involve some irreversible disruption of the membrane.

Enhanced rectal absorption of cefmetazole and cefoxitin in the presence of epinephrine metabolites in rats and a high-performance liquid chromatographic assay for cephamycin antibiotics.

4-Hydroxy-3-methoxymandelic acid and 3,4-dihydroxymandelic acid were found to be potent adjuvants for the rectal absorption of water-soluble compounds in rats. Both adjuvants enhanced the absorption of two cephamycin antibiotics, cefmetazole and cefoxitin. Maximum plasma levels of the antibiotics were obtained within 30 min after rectal administration. The bioavailability of both antibiotics appeared to depend on the concentration of the adjuvant in the microenema, the dosage form used in these experiments. Instead of a microbial assay, a new chemical method involving high-performance liquid chromatography with an ion-pairing technique was developed for analyzing the cephamycin antibiotic plasma levels.

Further studies on the catalysis of hydrolysis and aminolysis of benzylpenicillin by metal chelates.

It was suggested previously that the very rapid catalysis of benzylpenicillin hydrolysis and aminolysis by zinc ion and tris(hydroxymethyl)aminomethane (tromethamine) was mediated by a ternary complex in which the metal ion not only held the substrate and tromethamine in close proximity but also lowered the pKa of a bound tromethamine hydroxyl group making it a very powerful nucleophile. In this study the scope of this reaction was explored further by examining the effects of changes in substrate side chain, metal ion, and amino alcohols. All of the penicillins studied showed about the same rate of reaction. Of the other metal ions examined Cu2+ and Ni2+ showed no activity, Mn2+ very slight activity, and Cd2+ and Co2+ somewhat greater activity. The latter was the most effective of this group but was 40 times slower than zinc. The results with a number of amino alcohols provided additional evidence for the ternary complex mechanism. Studies with the methyl ester of benzylpenicillin indicated that the metal ion is bound to the antibiotic at the carboxylate site and that a different mechanism is involved in the slower catalysis observed with the ester. Some comparison is made with a zinc-dependent beta-lactamase.

Quantitative structure-inhibitory activity relationships of phenols and fatty acids for Bacillus subtilis spore germination.

Phenols and fatty acids were found to inhibit L-alanine-initiated germination of Bacillus subtilis spores without altering their heat resistance. Inhibitory effect was defined as the concentration necessary to cause 50% inhibition of the germination rate. The quantitative structure-inhibitory activity relationships for 39 phenols and 7 fatty acids were analyzed. The pH dependency of inhibition showed that the nonionized form of the molecule was responsible for inhibition. Hydrophobicity, which was expressed by the partition coefficient or the distribution coefficient of the compounds, was important for inhibition. In addition to hydrophobicity, the electronic effect, which was expressed by the dissociation constant, played a partial role in phenols. The correlation equation of the fatty acids was similar to those of the alcohols and other hydrophobic compounds, which had been reported earlier. That of the phenols, however, appeared to be different, indicating a different and more complex mechanism of inhibition. The type of inhibition by both compounds was mixed rather than competitive or noncompetitive.