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Biomedical subjects

S Koda

Publications and source records attributed to S Koda.

At least 19 recordsLinked to original sources

Determination of cefixime and its metabolites by high-performance capillary electrophoresis.

Cefixime (CX), an oral cephalosporin antibiotic, and its metabolites in human digestive organs were separated by various modes of high-performance capillary electrophoresis. The zone electrophoresis mode in phosphate buffer (pH 6.8) containing 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulphonate gave the best separation, permitting the complete resolution of CX and all of five metabolites. On the other hand, the plain zone electrophoresis mode in phosphate buffer (pH 6.8) offered a simple procedure for the direct determination of urinary CX concentration using intact urine samples.

Anti-Infective Agents, Urinary

X-ray structural studies and physicochemical characterization of (E)-6-(3,4-dimethoxyphenyl)-1-ethyl-4-mesitylimino-3-methyl- 3,4-dihydro-2(1H)-pyrimidinone polymorphs.

The polymorphism of (E)-6-(3,4-dimethoxyphenyl)-1-ethyl-4-mesitylimino-3-methyl-3,4-di hydro- 2(1 H)-pyrimidinone (FK664; 1) was characterized by using X-ray powder diffractometry, differential scanning calorimetry (DSC), and IR spectroscopy. Structures of two polymorphs (Forms A and B) were determined by X-ray crystallographic analysis. Form A crystallized in the monoclinic space group P2(1)/c, with a = 13.504(2), b = 6.733(1), c = 24.910(8) A, beta = 96.55(4) degrees, z = 4, and dcal = 1.203 g/cm3, while Form B crystallized in the same space group, with a = 8.067(2), b = 15.128(4), c = 18.657(4) A, beta = 102.34(3) degrees, z = 4, and dcal = 1.216 g/cm3. The conformational features of 1 were very similar between the two polymorphs. Compound 1, in both crystal forms, took an energetically reasonable conformation in three rigid planes, such as 2-pyrimidone, trimethylphenyl, and dimethoxyphenyl rings, but the molecules were packed in different ways between the two polymorphs. In the Form B crystal, a short contact was possible, to form pi-pi interactions between two dimethoxyphenyl groups related with the inversion center in the crystal lattice; this interaction seems to contribute to stabilizing the crystal structure of Form B. Both Forms A and B showed only one endothermic peak due to fusion at 115 and 140 degrees C, respectively, on the DSC thermograms; therefore, it is suggested that there are no transition points between the two polymorphs. The heats of fusion obtained from the DSC thermograms were 33.2(2) kJ/mol for Form A and 36.8(1) kJ/mol for Form B.(ABSTRACT TRUNCATED AT 250 WORDS)

Chemical Phenomena

[An epidemiological study on low back pain and occupational risk factors among clinical nurses].

Recently medical services and nursing system are being reformed due to high medical costs and shortage of clinical nurses. The shortage of clinical nurses influences not only their working conditions but also their own health problems. In European countries and the United States, low back pain (LBP) has been reported to be one of the most common and costly health problems among clinical nurses. To estimate the occupational risk factors of LBP among nurses, a questionnaire survey of LBP and occupational risk factors was carried out in 1987 on 947 clinical nurses and as well as on 300 female clerical workers of three local governments. First, to examine the prevalence and the magnitude of the problem, we analyzed several kinds of prevalence rates of LBP and its characteristics among nurses and clerical workers. Second, a case-control study was conducted to investigate the relationship between LBP and occupational risk factors. In analyzing occupational risk factors of LBP, odds ratios, age adjusted odds ratios and 95% confidence intervals were computed. Finally, to estimate simultaneously the effect of multiple risk factors of LBP and to confirm univariate age adjusted odds ratio analyses, several multivariate analyses were performed. Point, period (a month), and lifetime prevalence rates of LBP and prevalence rate of severe LBP among clinical nurses were significantly higher than those of clerical workers (p less than 0.05-0.001, respectively). Demographic and occupational items, such as being an assistant nurse (as opposed to a registered nurse), and working in certain departments (internal medicine, orthopedic surgery, neurosurgery, psychiatry, tuberculosis ward) showed significantly higher odds ratios for LBP (p less than 0.05-0.001, for all). Many items pertaining to working conditions connected with shift work, hospitalized conditions of patients, taking breaks and holidays, working postures, weight of patients and equipment lifting and moving, working environments and so on had significantly elevated age adjusted odds ratios (p less than 0.05-0.001, for all). Intensity of work loads estimated subjectively such as 'caring for patients who are in bed', 'supporting patients when transporting and bathing them', 'preparing drugs and injections, and treating', 'observing and monitoring patients' conditions', 'instructing and explaining procedure to patients and their family' and so on also had significantly elevated age adjusted odds ratios (p less than 0.05-0.001, for all). Moreover, many items on the problems connected with working life and interpersonal relationships showed significantly higher age adjusted odds ratios (p less than 0.05-0.001). In multivariate analyses, independent variables which made a significant contribution to the model were similar to the items which had significantly elevated age adjusted odds ratios.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult

Low-energy collision-induced dissociation of protonated polyamino alcohol derivatives of peptides and N-terminal blocked peptides.

This investigation reports the low-energy collision-induced dissociation of the protonated molecules of polyamino alcohols, formed by chemical reduction of synthetic peptides and N-terminal blocked peptides, in order to evaluate its potential for peptide sequence determination. The --CH2--NH-- cleavage with charge retention on the N-terminus was prominent, and the entire sequence of ions produced in this manner was observed. Some of the sequence ions arising from --CH2--NH-- cleavage accompanied by migration of two hydrogens, and --NH--C alpha H-- cleavage with charge retention on the C-terminus, also occurred prominently. In addition, a great number of internal fragment ions were produced in relatively high abundance; these provided supplementary sequence information and were, in some cases, critical in determining the sequence. The usefulness of this method was exemplified by its application to the sequence determination of bacterial lipopeptides.

Lipoproteins

X-ray crystallographic characterization of two polymorphs of 8-(2-methoxycarbonylamino-6-methylbenzyloxy)-2-methyl-3-(2- propynyl)-imidazo [1,2-a]pyridine.

Structural characterization of two polymorphs (Forms A and B) of 8-(2-methoxycarbonylamino-6-methylbenzyloxy)-2-methyl-3-(2-p ropynyl)-imidazo [1,2-a]pyridine (1) was accomplished by X-ray crystallographic analysis. Form A crystallized in the monoclinic space group C2/c, with a = 42.936 (14), b = 4.356 (1), c = 21.536 (6) A, beta = 109.92 (4) degrees, z = 8, and dcal = 1.275 g/cm3. Form B crystallized in the monoclinic space group P2(1)/c, with a = 4.367 (1), b = 38.214 (3), c = 11.253 (1) A, beta = 95.47 (2) degrees, z = 4, and dcal = 1.292 g/cm3. Some subtle conformational differences between the polymorphs were observed. Although the Form B crystal has a somewhat more compactly packed structure than Form A, this compactness is thought to be disadvantageous to conformational features and to the crystal structure of Form B. The intramolecular hydrogen bonding force between N(1) and NH(22) atoms of Form B is weaker than that of Form A, and the stacking force between the imidazopyridine rings of Form B may also be weaker than that of Form A. Thus, Form A is considered to be a more stable structure than Form B. In DSC analysis, Form B transformed to Form A. Based on these results, phase transformation from Form B to A occurs during a transient fluid state.

Crystallization

Moisture adsorption-desorption effect on the structure of inclusion complex of 6-chloro-2-pyridylmethyl nitrate and beta-cyclodextrin.

A new anti-anginal drug, 6-chloro-2-pyridylmethyl nitrate (FR46171), was found to form a complex with beta-cyclodextrin (beta-CyD), molecular ratio 1:1. The FR46171/beta-CyD complex thus prepared showed a moisture adsorption-desorption hysteresis characteristic of hydrophilic polymers. The moisture adsorption-desorption isotherm and differential scanning calorimetry indicated that the moisture adsorbed FR46171/beta-CyD complex includes 13-15 mol of water while the moisture desorbed complex includes 5 mol of water. X-ray diffraction patterns of these samples confirmed their different structures. The scanning electron photomicrographs and the surface areas (BET) suggested that the moisture adsorption-desorption hysteresis observed in FR46171/beta-CyD complex can be attributed to reversible hydrogen bonding between water molecules and hydroxyl groups.

Adsorption

The clinical significance of iC3b neoantigen expression in plasma from patients with systemic lupus erythematosus.

We studied the expression of an iC3b neoantigen (iC3b-NEO) in plasma from patients with systemic lupus erythematosus (SLE), by using a monoclonal antibody specific for iC3b/C3dg/C3d, to investigate the activation of the third component of complement in SLE. The plasma iC3b-NEO level in 40 untreated patients with active SLE was significantly higher than that in 36 normal subjects (mean +/- SD 31.5 +/- 13.9 micrograms/ml versus 12.3 +/- 3.3 micrograms/ml; P less than 0.001). The plasma iC3b-NEO level was highly correlated with clinical disease activity (tau = 0.62, P less than 0.0001), and it was the parameter most closely correlated with renal histologic activity in lupus nephritis (tau = 0.52, P less than 0.0001). Also, patients with diffuse proliferative lupus nephritis had the highest levels of plasma iC3b-NEO among all World Health Organization classes of lupus nephritis (P less than 0.01). We conclude that the plasma iC3b-NEO level is strongly associated with clinical disease activity and renal histologic activity in patients with SLE, and that plasma iC3b-NEO may be a sensitive and useful measure of complement activation in SLE.

Antibodies, Monoclonal

Nuclear ribonucleoprotein immune complexes in pericardial fluid of a patient with mixed connective tissue disease.

We performed immunopathologic studies of the pericarditis present in a patient with mixed connective tissue disease. A large number of nuclear RNP (nRNP) immune complexes (ICs) were found in the pericardial fluid, but not in the serum. The pericardial small vessels had no deposits of IgG. These results suggest that locally formed nRNP ICs were closely associated with the pathogenesis of pericarditis in this patient.

Adult

Degradation kinetics and mechanisms of a new cephalosporin, cefixime, in aqueous solution.

Hydrolysis of cefixime in buffer solutions (pH 1-9) at 25 degrees C and a constant ionic strength of 0.3 was investigated using ion-pair reversed-phase HPLC. Hydrolysis rates followed pseudo first-order kinetics; the rate of hydrolysis of cefixime was very slow at pH 4-7, slightly faster at lower pH, and quite rapid at higher pH. In the early stages of hydrolysis, six major degradation products were isolated and identified: a beta-lactam ring-opened product and a 7-epimer (basic conditions), three lactones derived from intramolecular cyclization between the 2-carboxyl and 3-vinyl groups (acidic conditions), and an aldehyde derivative involving a 7-acyl moiety (neutral conditions). Principal degradation pathways for cefixime were found to involve initial cleavage of the beta-lactam ring.

Cefixime

Clinical significance of U1-RNP immune complexes in mixed connective tissue disease and systemic lupus erythematosus.

We measured U1-RNP: anti-U1-RNP immune complexes (U1-RNP ICs) in patients with mixed connective tissue disease (MCTD) and systemic lupus erythematosus (SLE) to examine the clinical significance of circulating U1-RNP ICs. The level of U1-RNP ICs in 11 patients with MCTD was significantly higher than that in 22 normal subjects and there was a close correlation between the level of U1-RNP ICs and the clinical disease activity index of MCTD. In contrast, the level of U1-RNP ICs in 31 patients with SLE was not significantly higher than that in normal subjects and that was not correlated with the clinical disease activity index of SLE or the renal histologic activity index of lupus nephritis. We conclude that U1-RNP ICs are present in sera of patients with MCTD and SLE, and that the level of U1-RNP ICs may be closely associated with clinical disease activity in patients with MCTD.

Adult

Antitumour activity of purified arabinogalactan-peptidoglycan complex of the cell wall skeleton of Rhodococcus lentifragmentus.

Antitumour activity of arabinogalactan peptidoglycan (AP) complex (peptidoglycan and arabinogalactan liberated by an acid or alkaline treatment from Rhodococcus lentifragmentus AN-115 cell wall skeleton) was examined in mice and compared with that of the cell wall skeleton. The growth of syngeneic fibrosarcoma Meth A cells after implantation in BALB/c mice was significantly suppressed by AP complex, and also regressed after intratumoral injection of AP complex on days 1, 4 and 7 after tumour implantation. Although the activity of peptidoglycan was less than that of AP complex, peptidoglycan also showed both tumour-suppressive and regressive activities. Arabinogalactan did not show antitumour activity. It is interesting that peptidoglycan has an important role in the effect against tumours.

Animals

[Reproduction study of rokitamycin. Teratological study in rabbits].

A teratological study was performed on rokitamycin (TMS-19-Q), a new macrolide antibiotic, using rabbits. TMS-19-Q, at dose levels of 100, 300 and 600 mg/kg, was orally administered from the day 6 to the day 18 of gestation to dams. Diarrhea and decrease in body weight gain and food consumption were observed in dams at or above 300 mg/kg. Decrease in numbers of live fetuses was observed at dose levels of 300 and 600 mg/kg but there was no teratogenicity at any dose levels. The maximum non-toxic dose level for TMS-19-Q in this study was 100 mg/kg.

Abnormalities, Drug-Induced

A solid-phase radioimmunoassay for the detection of nRNP immune complexes.

We developed a solid-phase radioimmunoassay for complement (C)-fixing nuclear ribonucleoprotein (nRNP):anti-nRNP immune complexes (nRNP ICs). The assay was based on the ability of the C-fixing nRNP ICs to bind strongly to immobilized F(ab')2 anti-C3. The extent of binding was quantified by incubating the C-fixing nRNP ICs bound to anti-C3 with 125I-labeled anti-nRNP-specific IgG. The interaction between anti-C3 and C-fixing nRNP ICs was rapid, time- and concentration-dependent and sensitive over a broad range of nRNP IC concentrations in an antigen-antibody ratio of 8 : 1 (9.8-5000 ng of human aggregated IgG equivalent per ml). We found that the assay also detected an immunoreactive U1-RNP antigen in Sm : anti-Sm immune complexes but did not detect SSA : anti-SSA immune complexes. The assay was preliminary applied for serum samples obtained from patients with mixed connective tissue disease (MCTD), and elevated concentrations of nRNP immune complexes were found in 3 out of 5 patients with MCTD. This assay appears to be applicable to the detection and quantification of circulating nRNP ICs in patients with MCTD.

Adult