Metabolism of afloqualone, a new centrally acting muscle relaxant, in the rat.
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Biomedical subjects
Publications and source records attributed to K Kotera.
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During the period from May through July 1981, a comparative study was carried out on the antibacterial activities of cefotaxime (CTX) and ceftizoxime (CZX), cefoperazone (CPZ), latamoxef (LMOX), cefotiam (CTM), cefmetazole (CMZ) and cefazolin (CEZ). CTX and these other cephem antibiotics were tested against fresh clinical isolates which had been obtained from clinical materials by the laboratories of 14 participating medical institutions. 1. The clinical isolates were obtained from various clinical materials in the following decreasing order: urine, sputum and pus/discharge; 85.7% of the isolates came from these materials. 2. Concerning the sources of each species of clinical isolates, it was found that P. aeruginosa was isolated from the greatest number -9- of different clinical materials. This was followed by E. coli and E. cloacae, each isolated from 8 different clinical materials, and C. freundii and E. aerogenes, each found in 7 different clinical materials. 3. In relation to S. pyogenes, S. agalactiae and S. pneumoniae, CTX showed the best antibacterial activity; the second most potent antibiotic was CZX. CMZ and LMOX were found to show relatively high MIC values for those species. Against S. aureus, CEZ showed the best antibacterial activity, but 3 resistant strains had MICs of greater than 100 micrograms/ml. 4. With regard to Gram-negative bacteria, CTX and CZX showed the best antibacterial activities for all of the species, except for P. aeruginosa. These were followed, in order, by LMOX and CPZ. Compared with these 4 antibiotics, CTM, CMZ and CEZ were found to have inferior antibacterial activities against these bacteria. In relation to P. aeruginosa, the peak of the MIC distribution for CPZ was 6.25 micrograms/ml, and this was the best antibacterial activity detected with the various antibiotics tested. This was followed by CTX (25 micrograms/ml) LMOX (25 micrograms/ml) and CZX (50 micrograms/ml). CTM had an MIC of 100 micrograms/ml for 1 strain, and MICs of greater than 100 micrograms/ml for all of the other strains of P. aeruginosa, indicating them to be resistant to this antibiotic. All of the strains were resistant to CMZ and CEZ, showing MICs of greater than 100 micrograms/ml. 5. For each of the tested antibiotics, no correlation was found between the MIC and the serogroup for either P. aeruginosa or S. marcescens.
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We found that human sera can be divided into five types depending on the gas chromatography/electron capture detector (GC/ECD) chromatogram pattern. A preliminary GC/MS study on one of the GC/ECD peaks has suggested the presence of a hitherto unknown iodine-containing substance of probably endogenous origin.
Effects of extracellular diffusible ions, such as K+, Cl- and HCO3- (pH), on the peritubular membrane potential (EM) and intracellular activities of K+, (K)i, or Cl-, (Cl)i, were studied in the perfused proximal tubule of bullfrog kidneys with K+ or Cl- -selective microelectrodes. In steady-state conditions, in which both the peritubular and luminal sides were perfused with control Ringer solutions, the K+ equilibrium potential (EK) always exceeded the EM by approximately 19 mV and correlated well with the EM (correlation coefficient r = 0.78), whereas no correlation was recognized between the equilibrium potential of Cl-(ECl) and the EM. In the quick peritubular perfusion experiments, in which the extracellular diffusible ions were changed, the (K)i and (Cl)i were maintained relatively stable. The following facts were observed: (1) At constant EK, decreasing the peritubular chloride (Cl)e produced a small degree of hyperpolarization of the EM instead of depolarization. (2) At constant ECl, increasing the (K)e depolarized the EM. (3) At constant PCO2, the EM was depolarized with low HCO3- (acid) perfusions, while it was hyperpolarized with high HCO3- (alkaline) perfusions. These results are in agreement with the views that, 1) intracellular K+ in the proximal tubule is maintained by an uphill uptake mechanism on the peritubular cell membrane, (2) the ionic conductance of peritubular membrane is relatively high to K+, but low to Cl-, and (3) the pH gradient across the peritubular membrane can modulate the passive permeability to Na+ or K+.
A double-barreled Na+-selective microelectrode was constructed with monensin as a liquid ion exchanger. The HCl-treated monensin was dissolved in a solvent (Corning 477317) at 10% (weight/weight). Internal reference solution of its ionic barrel was mixture of 0.49 M NaCl and 0.01 M KCl, the pH being adjusted to 3 with 0.1 M citrate-HCl buffer, whereas that of the PD barrel was 0.5 M KCl. Average slope and selectivity ratio (Na+/K+) tested on 10 different microelectrodes were -57.5 +/- 1.87 mV/P(Na) (SEM) and 6.7 +/- 0.44, respectively. The electrical resistance was an order of 10(10) ohm and the response time was less than 10 sec. Using this microelectrode, a free flow micropuncture experiment was carried out in the bullfrog kidney and the intracellular Na+ activity as well as the membrane PD was determined on the proximal tubular cell. Average value (+/- SEM, n = 15) for the intracellular Na+ and K+ was 20.7 +/- 1.56 mEq/L and 61.2 +/- 1.16 mEq/L, respectively, and -68.7 +/- 0.88 mV for the peritubular membrane PD. There was a significant negative correlation between Na+ and K+ activities within the cell, i.e., the lower the ionic activity of cellular Na+ was, the higher the cellular K+, and vice versa, the sum of these two being kept nearly constant. The above finding may be somehow related to the isosmosis in the reabsorptive process across the proximal tubular epithelium.
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Micropuncture study was performed in the proximal segment of bullfrog nephrons with double-barreled ion-sensitive microelectrodes to determine the electrochemical profile of K and Cl across the individual borders of tubular epithelium. The mean peritubular potential obtained was -68.4 mV, and the K activity in the plasma and the cell interior was 2.64 and 61.6 mEq/liter, respectively. The calculated equilibrium potential for K was 79.3 mV. Therefore, the cell K must be maintained by some K uptake mechanism against an electrochemical gradient of 11 mV. Further, the K activity of the tubular fluid was 2.92 mEq/liter and the actually measured PD across the brush border membrane was -55.7 mV. Since the calculated Nernst K potential is 76.8 mV, the K entry from lumen to cell must be done against an electrochemical gradient of 21.1 mV in the net. These facts might suggest a possibility of bilateral existence of K uptake mechanism in both the peritubular and brush border membranes of proximal tubular cells. In contrast, the Cl activity was measured to be 9.30, 78.0, and 72.5 mEq/liter for the cell, tubular fluid, and plasma, respectively. The Nernst Cl potentials calculated were 53.6 and 51.7 mV for the brush border and the peritubular membrane, the data being less than the actually determined values, 55.7 and 68.4 mV, respectively. Thus, the Cl ion seemed to distribute passively throughout its reabsorptive process in the bullfrog proximal tubule.
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