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Biomedical subjects

K Nakatsu

Publications and source records attributed to K Nakatsu.

At least 109 records · Page 6Linked to original sources
PubMed1983

Determination of disopyramide and mono-N-desisopropyl-disopyramide in serum by gas-liquid chromatography with nitrogen-selective detection.

A rapid, reliable assay is described for the quantitation of disopyramide (DP) and its metabolite, mono-N-desisopropyl-disopyramide (MNDP), in serum using p-chloro-disopyramide as the internal standard and aqueous standards for calibration. The procedure involves extraction of the serum sample with diethyl ether, derivatization of MNDP with acetic anhydride, and gas-liquid chromatographic analysis with nitrogen-selective detection. The accuracy of the procedure is 97.8 +/- 10.3 (SD)% for DP over the concentration range, 0.25-10.00 micrograms/ml (n = 37), and 99.6 +/- 10.2 (SD)% for MNDP over the concentration range, 0.50-5.00 micrograms/ml (n = 18). The within-day coefficient of variation is less than 8% for DP and 12% for MNDP. The lower limit of quantitative sensitivity is 0.25 micrograms/ml for DP and 0.50 micrograms/ml for MNDP, and the lower limit of detection is 0.6 ng and 1.6 ng, respectively, for DP and MNDP. This assay has been used to determine the time-course of DP and MNDP and the protein binding of DP (without requiring an in vitro protein binding curve) in the serum obtained from patients and laboratory animals during DP administration.

Chromatography, Gas↗
PubMed1983

Diacetylmorphine (heroin) hydrolases in human blood.

Human blood esterases responsible for diacetylmorphine (DAM, heroin) metabolism were examined by means of an HPLC assay system for DAM, 6-monoacetylmorphine (MAM), and morphine. Four kinetically distinct enzymes capable of hydrolyzing DAM to MAM were observed in the plasma, erythrocyte (RBC) cytosol, and RBC membrane fractions of human blood. Under physiological conditions (pH 7.4, 37 degrees C), the Km (micromolar) and Vmax (micromolar per minute) values, respectively, for these enzymes were as follows: plasma, 200 and 210; RBC cytosol, 710 and 815; RBC membranes, 2000 and 748, and 38 and 80. For DAM blood concentrations less than or equal to 100 ng/mL, RBC associated esterases are responsible for the majority (76%) of DAM hydrolysis in blood.

Adult↗
PubMed1983

Gas-liquid chromatographic determination of the distribution of 3,3',4,4'-tetrachlorobiphenyl in the adult female rat following short-term oral administration.

A gas-liquid chromatographic assay using electron-capture detection was developed for the quantitation of 3,3',4,4'-tetrachlorobiphenyl (TCBP) in the serum, urine, brain, liver, adipose tissue, and feces of the rat. The sample preparation involves extraction of 3,3',4,4'-TCBP with hexane under neutral or alkaline conditions (and washing with concentrated acid for feces only). Aqueous standards are used for calibration of the assay, except for adipose tissue. The lower limit of quantitative sensitivity of the assay for 3,3',4,4'-TCBP is 25 ng/mL for serum and urine and 125 ng/g for brain, liver, adipose tissue, and feces, which can be extended to 5 ng/mL and 25 ng/g, respectively, by analyzing a larger aliquot of the hexane extract. The overall accuracy is greater than 95% for serum, urine, brain and feces and 86% for liver, and the within-day coefficient of variation does not exceed 8.6%. 3,3',4,4'-TCBP was administered orally to adult, female, Sprague-Dawley rats in the dosage regimens: 0.2, 0.5 and 2 mg X kg-1 X day-1 for 10 days and 5 mg X kg-1 X day-1 for 4 days. 3,3',4,4'-TCBP distributed preferentially into adipose tissue and liver, where the xenobiotic concentration was greater in adipose tissue. The adipose tissue and hepatic 3,3',4,4'-TCBP concentrations were dependent on both the absolute dose and dosing schedule of the xenobiotic. Only trace concentrations, usually below the lower limit of quantitation, were detected in the serum, brain and kidney. Fecal excretion of 3,3',4,4'-TCBP was greater than urinary excretion for the 5 mg X kg-1 X day-1 X 4-day regimen.

Administration, Oral↗
PubMed1981

Dose-dependency of theophylline clearance and protein binding.

Dose-dependency in theophylline pharmacokinetics and protein binding characteristics was examined in 10 healthy male volunteers. Theophylline disposition was determined after an intravenous infusion of both 1 mg/kg and 6 mg/kg aminophylline in a randomised crossover study. There was considerable intrasubject variability in theophylline clearance but no significant dose-dependency. Theophylline protein binding was assessed by equilibrium dialysis at varying theophylline concentrations. The percentage of free non-protein bound theophylline was significantly increased at high theophylline concentrations. This increase in free theophylline would lead to a non-linear increase in the risk of toxicity with increasing drug concentration.

Adult↗
PubMed1980

Action of coenzyme A on adenine derivative receptors in isolated tissues.

The action of Coenzyme A (CoA) was investigated on the mechanical activity of four isolated tissues known to possess adenine derivative (AD) receptors that are sensitive, or resistant to blockade by theophylline. CoA produced a dose-related inhibition of the electrically stimulated myenteric plexus longitudinal muscle of the guinea pig ileum, and of the spontaneously contracting rabbit ileum. This effect was competitively antagonized by theophylline in both tissues. CoA caused a dose-related relaxation of the rat ileum. Low doses of CoA were not antagonized by theophylline but higher doses were antagonized by this drug. The rabbit detrusor, which was contracted by ATP and ADP, was not affected by CoA. Differences in the action of CoA at AD receptors in these four tissues, and in its antagonism by theophylline reflect a heterogeneity of these receptors. It is suggested that the simple sub-division of adenine derivative receptors into two types may be inappropriate.

Adenine↗
PubMed1980

A microprocessor-based animal monitoring system.

The construction of a system for continuous, automatic monitoring of the activity of many animals is described. The system uses a microprocessor to control sampling of each animal box, accumulate activity scores, keep time, and control printout. For the detection units, infrared light-emitting diodes and infrared-sensitive phototransistors were used. With limited technical advice the system can be constructed by a novice of electronics. A system to monitor 40 animals would take approximately 3 wk to build and would cost about $700.

Animals↗
PubMed1980

Drug-specific antibodies in human serum?

In view of the fact that all drugs possess the potential to stimulate an immunological response when administered to man, it was proposed that certain individuals in the general population may have developed high antibody titres to certain commonly used drugs. Human serum samples were incubated with radioactively-labelled drugs and the amount of IgG antibody present was determined by coprecipitation. Using the method outlined, we were unable to detect any antibodies specific for acetylsalicylic acid, ampicillin, erythromycin, lidocaine, penicillin, procainamide or tetracycline, and conclude that drug-specific immunoglobulins are not one of the major factors involved in the equilibrium between the free and bound drug forms.

Anti-Bacterial Agents↗
PubMed1979

Theophylline-7-acetic acid: lack of absorption and therapeutic effectiveness.

A double-blind cross-over trial was conducted to evaluate the effectiveness of oral theophylline-7-acetic acid (T7AA) in 13 asthmatic patients. Pulmonary function tests showed no difference between T7AA and placebo. No T7AA or theophylline was found in the sera of these patients or of healthy volunteers who took T7AA tablets or syrup.

Adult↗
PubMed1979

Uptake of liposome-entrapped mannitol by diaphragm.

Tissue uptake of liposome-entrapped radioactive mannitol was examined in rats and mice after both intravenous and intraperitoneal injection. In accord with results from other laboratories, liver and spleen effectively accumulated liposomes. Diaphragm also took up significant amounts of label. In nearly all cases the radioactive content of perfused tissues was less than tissues which were not perfused but this was statistically significant in only a few comparisons.

Animals↗
PubMed1979

Evidence for two adenine derivative receptors in rat ileum which are not involved in the nonadrenergic, noncholinergic response.

The receptors mediating inhibition of the rat ileum by adenosine and adenine nucleotides were studied. ATP and ADP were more potent than AMP or adeonsine. Theophylline antagonized the effects of adenosine and AMP but not those of ATP or ADP. Preparations desensitized to ATP or ADP were still inhibited by adenosine and vice versa. The nonadrenergic, noncholinergic inhibition produced by field stimulation or nicotine was not attenuated by the presence of theophylline or desensitization to ATP. These data indicate that more than one adenine derivative receptor is present in rat ileum and that ATP and adenosine are unlikely candidates for the unknown transmitter.

Adenine↗