Biomedical subjects

I Nakatsuka

Publications and source records attributed to I Nakatsuka.

At least 19 recordsLinked to original sources

PubMed1992

Differences in alpha 2u-globulins increased in male rat kidneys following treatment with several alpha 2u-globulin accumulating agents: cystein protease(s) play(s) an important role in production of kidney-type-alpha 2u-globulin.

Effects of alpha 2u-globulin accumulating agents on alpha 2u-globulins in rat kidneys were examined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting analysis. Treatment of male animals with decalin (150 mg/kg), 2,2,4-trimethylpentane (50 mg/kg), isophorone (150 mg/kg), d-limonene (150 mg/kg) or 1,4-dichlorobenzene (150 mg/kg) by gavage for 14 consecutive days in each case resulted in a marked intensification of a protein band corresponding to kidney-type-alpha 2u-globulin, with a molecular mass calculated to be approximately 16 kDa. However, intraperitoneal treatment with leupeptin and E-64 (two times 0.07 mmol/kg, for each), well known cystein protease inhibitors, while only slightly increasing this kidney-type-alpha 2u-globulin band, caused the intensification of a approximately 19-kDa molecular mass protein band which was revealed to be a native-type-alpha 2u-globulin by SDS-PAGE and immunoblotting. These results indicated that at least two types of alpha 2u-globulin can be increased in male rat kidney by chemical treatment. Moreover, cystein protease(s) appear(s) to play an important role in the degradation of alpha 2u-globulin and particularly in the conversion of native-type-alpha 2u-globulin to kidney-type-alpha 2u-globulin in rat kidneys.

Alpha-Globulins↗

PubMed1992

Preparation of 123I-labeled 2'-iodospiperone and imaging of D2 dopamine receptors in the human brain using SPECT.

[123I]2'-ISP was readily prepared using a radioiodine exchange reaction with a radiochemical yield of approx. 50% after HPLC purification. The radiochemical purity of the product was more than 98% and the specific activity was 5.55-11.1 GBq/mumol. Biodistribution studies performed in mice indicated that injection of [123I]2'-ISP with albumin produced a higher gastric uptake and a lower brain uptake than injection of the radioligand in a weakly acidic solution. In addition, toxicity tests performed in mice demonstrated that acute toxic effects would be very unlikely to be encountered if 2'-ISP was used for diagnostic purposes. A preliminary imaging study with [123I]2'-ISP in a healthy human volunteer showed its specific uptake by the basal ganglia, a region of the brain known to have a high density of D2 dopamine receptors.

Animals↗

PubMed1992

Evaluation of N-alkyl derivatives of radioiodinated spiperone as radioligands for in vivo dopamine D2 receptor studies: effects of lipophilicity and receptor affinity on the in vivo biodistribution.

A series of radioiodinated spiperone (2'-ISP) derivatives bearing amide N-alkyl substituents (N-methyl-2'-ISP, N-ethyl-2'-ISP, and N-propyl-2'-ISP) were synthesized and evaluated as potential singlet photon emission computed tomographic radiopharmaceuticals for visualizing dopaminergic receptors. The lipophilicity of these ligands (i.e., the partition coefficient for octanol-phosphate buffer) increased as the chain length increased. Investigation of blood-brain barrier permeability in rats showed a parabolic relationship between the brain uptake index and the partition coefficient. In vitro competitive binding studies showed that the relative affinity for the dopamine D2 receptor was in the order of N-propyl-2'-ISP greater than 2'-ISP greater than N-methyl-2'-ISP approximately N-ethyl-2'-ISP. In vivo biodistribution studies showed that the initial brain uptake correlated fairly well with the brain uptake index and that the kinetics of the radioactivity specifically bound to the striatum were strongly influenced by the dopamine receptor binding affinity of the compounds. Thus, the in vivo behavior of these N-alkylated 2'-ISP derivatives involved a complex interplay between receptor affinity, lipophilicity, and blood-brain barrier permeability.

Animals↗

PubMed1992

[Usefulness of a disposable nasogastric tube with a pH sensor--comparison with a class pH electrode].

We evaluated a disposable nasogastric tube with a pH sensor in comparison with an external glass pH electrode with aspiration of gastric contents, continuously. The mean pH value determined by pH sensor was 3.01, and 2.99 by glass pH electrode. There was a good correlation between the two methods (r = 0.91). The agreement between the two methods was especially good when pH less than 5.0. There was a wide scattering in the data when pH greater than 5.1. When the glass pH electrode data were above 5.1, the pH sensor tended to show lower pH values than glass pH electrode.

Electrodes↗

PubMed1991

[Blood gas changes after laparoscopy].

Blood gas changes after laparoscopy under general anesthesia were examined. Thirty-six ASA I or II women were allocated to one of the two groups: carbon dioxide was used for pneumoperitoneum in group C and nitrous oxide in group N. Anesthesia was maintained with enflurane, buprenorphine, and supplemental midazolam. Arterial blood gases were measured in patients breathing room air. A significant fall in PaO2 (from 92.8 mmHg to 71.5 mmHg) was observed 5 minutes after extubation in group N as compared with the preoperative level and with group C, but there is no change in PaO2 in group C. PaCO2 showed no significant changes in both groups. In 6 out of 36 patients, PaO2 decreased below 60 mmHg. Possible causes of the difference between the two groups are diffusion hypoxia produced by nitrous oxide, gas embolism, or postoperative hyperventilation in response to hypercarbia during laparoscopy by carbon dioxide insufflation, and the last one is most probable. This may have prevented hypoxia in group C.

Adult↗

PubMed1988

An improved method for 14C-labelling of farnesylacetic acid and its geranyl ester.

Farnesylacetic acid was efficiently labelled with 14C at the 5-position and gefarnate, a potent ulcer inhibitor, was prepared from it in radioactive form for use in metabolic studies. Condensation of [carbonyl-14C]acetyl chloride (5) with t-butyl 2-ethoxymagnesiomalonate (6) followed by acid-catalyzed deprotection and decarboxylation gave ethyl 3-oxo[3-14C]butanoate (8). Alkylation of the keto ester (8) with geranyl bromide (9) afforded the unsaturated keto ester (10), which was hydrolyzed and decarboxylated to give geranyl[2-14C]acetone (11). Grignard reaction of 11 with cyclopropylmagnesium bromide followed by treatment with hydrobromic acid yielded [4-14C]homofarnesyl bromide (13). Cyanation of 13 with potassium cyanide and subsequent hydrolysis gave [5-14C]farnesylacetic acid (1) in 6.1% yield from barium [14C]carbonate (3). Chlorination of 1 followed by esterification with geraniol afforded [5-14C]gefarnate (2) in 88% yield.

Carbon Radioisotopes↗

PubMed1987

In vitro evaluation of radioiodinated butyrophenones as radiotracer for dopamine receptor study.

Radioiodinated butyrophenone compounds are attracting the interest of those working on dopamine receptor studies; structure-activity relationship study has revealed the ortho position of the p-fluorobutyrophenone moiety as a very plausible iodination site. Various synthesized butyrophenones iodinated at the ortho position of p-fluorobutyrophenone moiety, 2'-iodohaloperidol (2'-IHP), 2'-iodotrifluperidol (2'-ITP) and 2'-iodospiperone (2'-ISP) were tested for their abilities to inhibit 3H-spiperone (SP) binding for the dopamine (D-2) receptor, together with reference compounds (SP, haloperidol(HP) and 4-iodospiperone (4-ISP]. The order of binding affinity of the tested compounds was SP greater than 2'-ISP greater than HP greater than 4-ISP greater than 2'-IHP greater than 2'-ITP. Whereas, the serotonin (S-2) receptor binding affinity of SP and its iodinated analogues were in the order of SP much greater than 4-ISP greater than 2'-ISP. Furthermore, in the saturation binding study using the striatal membrane preparations, the 2'-ISP displayed a KD of 0.25 nM with maximum number of binding site Bmax of 210 fmol/mg protein. These data indicated the 2'-ISP as holding high affinity for dopamine receptors and a low affinity for serotonin receptors. Thus, the 125I-2'-ISP was a very potent radioligand for in vitro dopamine (D-2) receptor studies, and 123I-2'-ISP holds very promising characteristics as for in vivo dopamine receptor studies, as well.

Animals↗

PubMed1987

Radioiodinated 2'-iodospiperone: a new radioligand for in vivo dopamine receptor study.

In vivo dopamine receptor binding of the newly synthesized ligand, 125I-2'-iodospiperone (125I-2'-ISP), was studied in mouse brain. The highest accumulation was found in the striatum. Analysis of the striatal homogenate showed the 125I-2'-ISP to be metabolically stable. Furthermore, this striatal binding was saturable and displaced only by dopaminergic drugs. On the other hand, the accumulation in the cortex was as low as that of the cerebellum and uneffected by the administration of serotoninergic drugs and dopaminergic drugs; results assessed by macroautoradiographic studies. Thus, the newly synthesized 125I-2'-ISP presented high affinity for dopamine receptors in vivo and therefore, holds great potential for the in vivo dopamine receptor studies, provided 123I becomes readily available.

Animals↗

PubMed1985

Benzodiazepines and their metabolites: relationship between binding affinity to the benzodiazepine receptor and pharmacological activity.

Experiments were carried out to study the relationship between binding affinity to the benzodiazepine receptor and pharmacological activity, especially anti-anxiety activity, of clinically useful benzodiazepines. In the in vitro experiments, fludiazepam showed the highest affinity to the benzodiazepine receptor with 4 times more potency than that of diazepam, which paralleled the in vivo activity. Diazepam and nimetazepam also bound with high affinities as expected from their in vivo activities. On the contrary, medazepam and cloxazolam showed extremely low affinities and oxazolam showed no affinity, although they showed moderate in vivo activity. However, their metabolites were found to have both high affinity and in vivo activities. These results strongly suggest that in the case of medazepam, cloxazolam and oxazolam, their metabolites may bind to receptor sites in the brain and then elicit pharmacological action. This conclusion was supported by the fact that a good correlation between the binding affinity and the anti-anxiety activity of the tested compounds was observed.

Animals↗

PubMed1985

A method for measuring specific activities of 14C-labelled compounds by gas chromatography-mass spectrometry-computer system.

A method for measuring specific activities of 14C-labelled compounds by gas chromatography-mass spectrometry-computer system (GC-MS-CPU) was developed. This method was proved to provide practically precise and accurate specific activities of various 14C-labelled compounds with such merits as requirement of small amount of samples, being applicable to volatile compounds, and convenience. The C.V. percent obtained for tested compounds was within 3.9 and the reliable sensitivity should be over 37 MBq/mM (1 mCi/mM). This method was also useful for obtaining information on the labelling pattern and the synthetic procedures applied.

Carbon Radioisotopes↗

PubMed1985

Application of gas chromatograph-mass spectrometer-computer system to evaluation of 14C-labelled compounds.

Usefulness of gas chromatograph-mass spectrometer-computer system (GC-MS-CPU) not only for measurement of specific activities of 14C-labelled compounds in a mixture but also for evaluation of 14C-labelled compounds in terms of examining their purities and elucidating chemical structures of the impurities was proved. A sample of methyl 2-(p-chlorophenyl-14Cn)-3-methylbutylate (III) synthesized from p-chlorophenyl-14Cn-acetonitrile (VI) was analyzed by GC-MS-CPU, and it was found that the labelled compound was contaminated with a small amount of the corresponding m-isomer (IV) having a very high specific activity. Further examination suggested that the contaminating m-isomer (IV) originated from m-chlorophenyl-14Cn-acetonitrile (IX) which had already contaminated in the starting material (VI), and also that cyanomethylation of p-dichlorobenzene-14Cn (VIII) by benzene-type reaction resulted in producing a mixture of p- and m-chlorophenyl-14Cn-acetonitriles (VI, IX).

Carbon Radioisotopes↗

PubMed1984

Synthesis and evaluation of (17 alpha,20E)-21-[125I]iodo-19-norpregna-1,3,5(10),20-tetraene-3,17 -diol and (17 alpha,20E)-21-[125I]iodo-11 beta-methoxy-19-norpregna-1,3,5(10),20-tetraene-3,17-diol (17 alpha-(iodovinyl)estradiol derivatives) as high specific activity potential radiopharmaceuticals.

Two 17 alpha-[125I]iodovinyl estradiol derivatives 4b,d possessing high specific activity have been prepared and tested as potential radiopharmaceuticals. The use of the 3-acetyl derivatives 2c,e and the replacement of iodine monochloride with sodium iodide and Chloramine-T in THF/phosphate buffer (pH 7.0) permitted us to synthesize no-carrier-added (17 alpha,20E)-21-[125I]iodo-19-norpregna-1,3,5(10),20-tetraene-3,17-d iol (4b) and (17 alpha,20E)-21-[125I]iodo-11 beta-methoxy-19-norpregna-1,3,5(10),20-tetraene-3,17-diol (4d) with 50% radiochemical yield and high purity. Although the specific activity represents only half of the theoretical value in some cases, this modified approach is a substantial improvement over the previously published method. Our preliminary distribution studies indicate that although both 4b and 4d localize in the tissues known to have a large concentration of estrogen receptors, 4d accumulates in higher amounts in target tissues and provides a high target to nontarget ratio.

Animals↗

PubMed1982