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K Nishide

Publications and source records attributed to K Nishide.

At least 37 records · Page 2Linked to original sources
PubMed1986

Age-related change of cefazolin binding to rat serum proteins and its relation to the molar ratio of free fatty acid to serum albumin.

The binding of cefazolin to rat sera has been studied as a function of age. A significant difference was observed in the cefazolin binding to serum protein among 1-, 2-, 3-, 5-, 7-, 50- and 100-week-old rats. There was a good correlation between the dissociation constants of cefazolin binding and the molar ratio of free fatty acid to albumin concentration in sera. This suggests that both changes of concentration of albumin and free fatty acid, which could be a major endogenous inhibitor of cefazolin binding, play an important role in the age-related changes of the serum protein binding. Removal of free fatty acid in 1- and 2-week-old rat sera showed marked increases of the cefazolin binding. On the contrary, addition of oleic acid to 7-week-old rat serum produced significant reduction of cefazolin binding to rat serum protein. Accordingly, free fatty acid could effectively inhibit the cefazolin binding in the physiological concentration range with increasing age, and the age-related changes of cefazolin binding to rat serum protein appear to be due to the fluctuation of the molar ratios of free fatty acid to albumin concentration in sera.

Aging↗
PubMed1985

Effect of extracellular water volume on the distribution kinetics of beta-lactam antibiotics as a function of age.

The distribution kinetics of cefazolin in rats has been examined at four different ages (1, 7, 50 and 100 weeks). The steady state distribution volume of cefazolin, estimated from the plasma time course after i.v. injection of 20 mg/kg, varied between 136 ml/kg (50-week-old rats) and 297 ml/kg (1-week-old rats). The extracellular fluid volume, obtained from the steady state distribution volume of inulin, varied between 126 ml/kg (50-week-old rats) and 370 ml/kg (1-week-old rats). There was a good correlation between the steady state distribution volume of cefazolin and extracellular fluid volume (r = 0.977). The influence of changes on the value of the plasma unbound fraction and extracellular fluid volume on the tissue-to-plasma partition coefficient of beta-lactam antibiotics was simulated by using a physiological pharmacokinetic model. The results of the simulation showed that extracellular fluid volume is an important factor affecting the distribution volume of beta-lactam antibiotics and that plasma binding plays a minor role on it. The experimental and simulation results suggested that the change in the interstitial fluid volume is a determinant factor in the age-related changes in the distribution volume of beta-lactam antibiotics.

Aging↗
PubMed1984

Delayed neurotoxicity produced by an organophosphorus compound (Sumithion). A case report.

A case of late-onset manifestation of organophosphorous insecticide poisoning is described. The patient was a 70-year-old female who ingested 40 ml Sumithion emulsion (50% fenitrothion). At first, no toxic symptoms were apparent. However, 48 h after ingestion certain signs became apparent. An impediment in consciousness was observed. Fasciculation and muscular weakness were noted, while plasma and urinary 4-nitro-3-methylphenol (NMC), the degradation product of Sumithion, reached a maximum. Neither atropine sulfate nor PAM (pyridine 2-aldoxime methiodine) were effective. For 3 weeks the patient required ventilatory support, and consequently her muscle strength and neurological status gradually recovered with falling NMC levels.

Aged↗
PubMed1984

[Right-sided traumatic diaphragmatic hernia following blunt trauma].

The mechanism of right-sided traumatic diaphragmatic hernia following blunt trauma was examined. In 13 cases of Traumatic diaphragmatic hernia admitted to the Department of Traumatology Osaka University Hospital, 3 cases were on the right. All cases were associated with severe injuries in the chest, abdomen and pelvis. Rib fractures, hemothorax, and liver injury were seen in the same site of the ruptured diaphragm. So it seemed that there were some differences in the force itself caused diaphragmatic rupture between right-sided and left. We reviewed 40 cases of right-sided traumatic diaphragmatic hernia reported in Japan. The following results were obtained. Main force which caused right-sided diaphragmatic rupture was the blunt impact to the right thoracic wall. In the right-sided diaphragmatic hernia, the most frequently herniated organ was the right lobe of the liver and there was high-frequency of G-I tract herniation in delayed types. Herniation of the abdominal organs seemed to be varied as the time passed.

Abdominal Injuries↗
PubMed1983

Physiologically based pharmacokinetic model for beta-lactam antibiotics I: Tissue distribution and elimination in rats.

The disposition characteristics of beta-lactam antibiotics in rats were investigated, and a physiologically based pharmacokinetic model capable of predicting the tissue distribution and elimination kinetics of these drugs was developed. Protein-binding parameters in rat serum were determined by equilibrium dialysis. Linear binding was found for penicillin G, methicillin, dicloxacillin, and ampicillin; however, nonlinear binding was observed for penicillin V and cefazolin. After intravenous bolus dosing, cefazolin was recovered almost completely in urine and bile, while for the penicillins, penicilloic acid was found to be the major metabolite. Biliary excretion of cefazolin followed Michaelis-Menten kinetics, and no significant inhibition of urinary secretion was observed after probenecid administration. The renal clearance of unbound drug was 0.82 ml/min with a reabsorption ratio (R) of 0.22. Tubular secretion was inhibited for the penicillins by probenecid plasma concentrations of 50 micrograms/ml, resulting in an R-value of 0.32. Erythrocyte uptake, serum protein binding, and tissue-to-plasma partition coefficient (Kp) were measured. Theoretical Kp values were calculated and found to be in good agreement with the Kp values for three of the antibiotics. Plasma and tissue concentrations (lung, heart, muscle, skin, gut, bone, liver, and kidney) were measured as a function of time at various doses for inulin and cefazolin in rats after an intravenous bolus dose, and were found to be in reasonable agreement with concentrations predicted by the model. These correlations demonstrate that the proposed model can accurately describe the plasma and tissue contributions of inulin and cefazolin in the rat and suggest that this model could have utility in predicting drug distribution in humans.

Animals↗
PubMed1981

Degradation kinetics and mechanism of aminocephalosporins in aqueous solution: cefadroxil.

The degradation kinetics and mechanism of a new, orally effective cephalosporin derivative, cefadroxil, in aqueous solution were investigated at pH 2.51-11.5 at 35 degrees and ionic strength 0.5. The degradation rates were determined by high=pressure liquid chromatography. At constant pH and temperature, the degradation followed first-order kinetics and a log k-pH profile was presented. The shape of the rate-pH profile resembled that for cephalexin or cephradine under the same conditions. Citrate and phosphate buffers enhanced general acid and base catalysis of the degradation. In aqueous solution, cefadroxil was shown to degrade by three parallel reactions: (a) intramolecular aminolysis by the C-7 side-chain amino group on the beta-lactam moiety, (b) water-catalyzed or spontaneous hydrolysis, and (c) beta-lactam cleavage by the nucleophilic attack of hydroxide ion. In neutral and weak alkaline solutions, the main degradation products were two piperazine-2, 5-diones and 3-hydroxy-4-methyl-2(5H)-thiophenone, the former being formed from Reaction a, while the latter arose via the degradation pathways of Reaction b and/or c.

Buffers↗