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Biomedical subjects

M Otsuka

Publications and source records attributed to M Otsuka.

At least 19 recordsLinked to original sources
PubMed1992

The isolated spinal cord-skin preparation of the newborn rat and effects of some algogenic and analgesic substances.

We have developed an isolated spinal cord-skin preparation of the newborn rat. The spinal cord together with a piece of skin connected to the cord by the saphenous nerve was isolated from 1- to 4-day-old rats and separately superfused with artificial cerebrospinal fluid in two neighbouring chambers. Potentials were recorded extracellularly from the third lumbar ventral root. Application of capsaicin (0.5-2 microM) or KCl (60-350 mM) with brief pressure pulses to the perfusion bath of the skin evoked a depolarizing response of 20- to 40-s duration in the ventral root. The response was depressed by [Met5]enkephalin (0.03-3 microM), morphine (0.1-2 microM) and a tachykinin antagonist, [D-Arg1,D-Trp7,9,Leu11] substance P (spantide), (1-10 microM), applied to the spinal cord by superfusion, whereas the response was augmented by centrally administered calcitonin gene-related peptide (0.1-0.2 microM) or bicuculline (0.5-1 microM).

Action Potentials↗
PubMed1992

Simple and sensitive determination of diacetyl and acetoin in biological samples and alcoholic drinks by gas chromatography with electron-capture detection.

Acetoin was quantitatively oxidized into diacetyl by Fe3+ in 1 M perchloric acid. The reaction of diacetyl with 4,5-dichloro-1,2-diaminobenzene afforded 6,7-dichloro-2,3-dimethylquinoxaline (DCDMQ), which was extracted by benzene containing aldrin (25 ng/ml) as an internal standard, and determined by gas chromatography with electron-capture detection. The method is very simple and sensitive. The detection limit of DCDMQ (either diacetyl or acetoin) was 10 fmol/microliters of the benzene extract, and the determination limit of DCDMQ (either diacetyl or acetoin) was 50 fmol/microliters of the extract. Both acetoin and diacetyl could be determined in 0.1 ml of normal human urine or blood, and both were found in rat liver, kidney and brain. The method was also applied to the determination of acetoin and diacetyl in alcoholic drinks.

Acetoin↗
PubMed1992

Self-setting hydroxyapatite cement: a novel skeletal drug-delivery system for antibiotics.

A novel approach using a self-setting hydroxyapatite (HAP) cement as a skeletal drug-delivery system has been proposed to solve the problem of delivering drugs to skeletal tissue at sufficiently high local concentrations for desirable therapeutic effects. HAP cements loaded with antibiotics can be formed in situ and can be used as bonding materials between bone and prostheses, as well as drug-release devices. The cement also possesses sufficient mechanical strength to be a potential bone grafting material. Using cephalexin and norfloxacin as model drugs, we observed continuous in vitro release profiles of these compounds from cement pellets loaded 0.9-4.8% by weight with one of the drugs. This drug-release pattern correlated well with the Higuchi model. This hydroxyapatite cement drug-delivery system can be applied in the treatment of osteomyelitis and infected compound fractures.

Anti-Bacterial Agents↗
PubMed1992

Effect of geometric factors on hydration kinetics of theophylline anhydrate tablets.

The effect of tablet thickness on the hydration kinetics of types I and II theophylline anhydrate tablets at 95% relative humidity and 35 degrees C was studied with various kinetic equations. Samples of 1- and 2-cm-diameter tablets (1 g) were compressed at 1000 kg/cm2. Types I and II tablets expanded by 11-17% in volume during hydration to the monohydrate. The thickness expansion of all tablets exceeded the diameter expansion. After the hygroscopicity test, the final expansion ratio of type I tablets was more than that of type II tablets. The hydration kinetics analysis suggested that the hydration of theophylline anhydrate tablets proceeds as follows: Hydration of the 1-cm-diameter type I tablet followed the two-dimensional phase boundary equation, and that of the 1-cm-diameter type II tablet followed the three-dimensional phase boundary equation, but those of the 2-cm-diameter types I and II tablets followed the equation for two-dimensional growth of nuclei. The hydration kinetics of tablets does not depend on the nature of bulk powder but on geometrical factors (tablet thickness and porosity).

Chemical Phenomena↗
PubMed1992

In vivo effects of doxorubicin on kinase C in cultured cells.

The ability of doxorubicin to inhibit kinase C in vivo in cultured BALB/c 3T3 mouse fibroblasts was determined by the phosphorylation of the myristoylated alanine-rich C kinase substrate (MARCKS) and the induction of c-fos transcription following treatment with 200 nM phorbol 12-myristate 13-acetate. A concentration of 60 microM doxorubicin did not inhibit MARCKS phosphorylation but completely inhibited c-fos expression. The inhibition of c-fos expression was not specifically mediated via kinase C, since both the total RNA synthesis as measured by [3H]-uridine uptake and the fraction of serum-induced c-fos expression that was not attributable to kinase C were inhibited by doxorubicin. The present data do not support the hypothesis that the cytotoxic effect of doxorubicin is attributable to the inhibition of kinase C in vivo.

3T3 Cells↗
PubMed1992

Expressivity of a common fragile site, fra(3)(p14.2), in patients with cancer and other diseases.

A population survey of a common folate-sensitive fragile site, fra(3)(p14.2), has been carried out on PHA-stimulated peripheral lymphocytes of patients with cancer and other diseases, under both culture conditions of folate deprivation and aphidicolin treatment. Overall findings regarding variability of expressivity due to age and sex were very similar to those obtained in a healthy population. The expression of fra(3)(p14.2) by folate deficient condition appeared hardly influenced by such exogenous factors as tobacco smoking habit, past histories of radiotherapy and chemotherapy, while it was associated with the unfavorable prognosis of cancers. Furthermore, proportion of those with higher expression was slightly but significantly larger in both lung and breast cancer patients. These findings suggest that some factors relevant to the expression of fra(3)(p14.2) may be associated with development and progression of certain kinds of cancer.

Adolescent↗
PubMed1992

Regional cerebral glucose metabolism in patients with Parkinson's disease with or without dementia.

By means of positron emission tomography, the cerebral glucose metabolism in 5 patients with Parkinson's disease with dementia was compared with that in 9 patients without dementia, and that in 5 normal volunteers. The metabolic rates for glucose were measured by placing one hundred regions of interest. In the demented patients, cerebral glucose metabolism was diffusely decreased compared with that of the non-demented patients and the normal controls. The most significant decrease in glucose metabolism was observed in the angular gyrus (49.7% of the normal controls). The glucose metabolism in the cingulate, pre- and postcentral, occipital and subcortical regions was relatively spared (62.1 to 85.5% of the normal controls). In the patients without dementia, the glucose metabolism in each region was not significantly different from that in the normal controls. These results suggest that diffuse glucose hypometabolism in the cerebral cortex may correlate with that of patients with Parkinson's disease with dementia.

Aged↗
PubMed1992

Increased striatal 18F-dopa uptake and normal glucose metabolism in idiopathic dystonia syndrome.

Striatal 18F-Dopa uptake and glucose metabolism were studied by positron emission tomography with 6-L-[18F]fluorodopa and [18F]fluorodeoxyglucose, respectively, in 8 patients with idiopathic dystonia. Patients with abnormal findings on the brain CT and MRI were excluded from this study. The clinical diagnosis consisted of torsion dystonia in 3 patients, focal dystonia limited in the arm in 3 and cervical dystonia (spasmodic torticollis) in 2. The 18F-Dopa uptake, corrected by nonspecific retention in the cerebellum, at 120 min post-administration was evaluated, and increased 18F-Dopa uptake in the putamen and in the caudate head was observed in the patients with idiopathic dystonia compared to the normal controls. The striatal glucose metabolism in the patients with idiopathic dystonia showed no difference with the normal controls. These findings suggest that pathogenetic mechanism of idiopathic dystonia involves increased presynaptic activity of the dopaminergic system in the striatum.

Adult↗
PubMed1992

Positron emission tomography (PET) in "pure akinesia".

Positron emission tomography (PET) studies on regional cerebral glucose metabolism and [18F]fluorodopa uptake were performed on 3 patients with "pure akinesia without rigidity and tremors", 3 progressive supranuclear palsy (PSP) patients, and 5 patients with Parkinson's disease. The "pure akinesia" and PSP patients showed a marked decrease in glucose metabolism in the frontal cortex and striatum, and a decreased uptake of [18F]fluorodopa in the striatum. While the Parkinson's disease patients had a decreased uptake of [18F]fluorodopa in the striatum but no abnormality in the glucose metabolism. Magnetic resonance imaging (MRI) showed atrophy of the pretectum and dorsal pons in "pure akinesia" and PSP patients, but there was no such abnormality in the Parkinson's disease patients. As described above, patients with "pure akinesia" and PSP patients revealed similar findings on PET and MRI studies, while Parkinson's disease patients showed substantially different results.

Adult↗
PubMed1992

Enzymatic inactivation of tachykinin neurotransmitters in the isolated spinal cord of the newborn rat.

A mixture of peptidase inhibitors increased the magnitude of the saphenous nerve-evoked slow depolarization of a lumbar ventral root and prolonged the similarly evoked inhibition of monosynaptic reflex (MSR) in the isolated spinal cord of the newborn rat in the presence of naloxone. The saphenous nerve-evoked MSR inhibition was curtailed by a tachykinin antagonist, GR71251, and after the treatment with GR71251, the peptidase inhibitor mixture no more prolonged the MSR inhibition. The present results suggest that enzymatic degradation plays a role in the termination of action of tachykinins released from primary afferents in the newborn rat spinal cord. The results provide a further support for the notion that tachykinins serve as neurotransmitters in the spinal cord of the newborn rat.

Animals↗
PubMed1992

Studies on endogenous formation of N-nitroso compounds in the guinea pig supplemented with proline or thioproline and sodium nitrate.

The endogenous formation of N-nitrosoproline (NPRO) and N-nitrosothioproline (NTPRO, N-nitrosothiazolidine-4-carboxylic acid) was studied by monitoring their excretion in the urine of guinea pigs given oral doses of 10 mg proline or thioproline after supplementation with 34 mg (0.4 mmol) sodium nitrate. In order to estimate the conversion of nitrate to nitrite, the animals were also supplemented with 3.5 mg (0.05 mmol) sodium nitrite instead of sodium nitrate. In animals fed commercial diets, the excretion of NPRO and NTPRO under supplementation with sodium nitrate was 2.0 micrograms and 28.7 micrograms/animal/day, respectively, whereas the excretion under supplementation with sodium nitrite was 0.7 micrograms and 13.3 micrograms/animal/day, respectively. The higher excretion of NTPRO than NPRO in each case shows that thioproline is more effective for nitrite trapping than proline. The animals supplemented with nitrate excreted more than twice the amounts of NPRO or NTPRO than those supplemented with nitrite. It is assumed, therefore, that more than 0.1 mmol nitrate is reduced to nitrite and takes part in the endogenous nitrosation of the guinea pig. When various concentrations of L-ascorbic acid (AsA), known to inhibit the formation of N-nitroso compounds, were also administered orally to animals immediately after supplementation with sodium nitrate, the NPRO excretion decreased with increasing AsA concentration. These data indicate that the guinea pig, which is unable to synthesize AsA as well as humans, may be an appropriate animal model for evaluation of the endogenous nitrosation ability of humans ingesting nitrate.

Animals↗
PubMed1992

Acceleration of late radiation damage of the kidney by unilateral nephrectomy.

Both increased proliferation as measured by labeling index and the appearance of abnormally large nuclei in renal proximal tubule cells, which have been observed in mouse kidneys after irradiation, were enhanced by subsequent unilateral nephrectomy. Nephrectomy alone induced only a transient increase in labeling index, lasting less than 1 month, whereas nephrectomy after irradiation induced an increase above that of the irradiated kidneys without nephrectomy lasting as long as 9 months. The incidence of large nuclei in kidneys from mice unilaterally nephrectomized 1 week after irradiation showed a rapid increase with time, peaking at 4.6% at 6 months, compared to more gradual increases with peaks at about 4.0% at 9 or 12 months in irradiated kidneys without nephrectomy or those in which nephrectomy was done prior to irradiation. This result demonstrates that nephrectomy after irradiation accelerates the appearance of this indicator of radiation damage, rather than enhancing the maximum amount of damage. Unilateral nephrectomy after irradiation also increased kidney damage 9 months later, as indicated by kidney weight loss and increased blood urea nitrogen. These results are consistent with our model for radiation damage of the kidney in which radiation induces cell proliferation and the appearance of reproductively dead, large nuclear cells that are lost at subsequent attempts to divide; the acceleration of radiation damage by unilateral nephrectomy performed after radiation could very well be a result of nephrectomy-induced enhancement in the proliferation of proximal tubule cells.

Animals↗
PubMed1992

Rotating-disk dissolution kinetics of nitrofurantoin anhydrate and monohydrate at various temperatures.

The dissolution behavior of nitrofurantoin anhydrate and monohydrate in JP XI, second fluid (pH 6.8) was investigated at various temperatures using a dispersed-amount method and a rotating-disk method. The initial dissolution process of the monohydrate obtained by the rotating-disk method followed the Noyes-Whitney-Nernst equation, but that of the anhydrate did not. The initial dissolution process of the anhydrate was analyzed by a dissolution kinetics equation involving the phase transformation process from anhydrate to monohydrate. The maximal concentration, the dissolution rate constant, and the rate constant of the phase transition process were estimated. The thermodynamic parameters for the dissolution processes of the anhydrate and monohydrate were obtained from van't Hoff plots and Arrhenius plots, respectively. The results of the intrinsic solubility and dissolution parameters of anhydrate and monohydrate suggest the possibility that the difference in the dissolution rates of the anhydrate and monohydrate affect the bioavailability of nitrofurantoin preparation. Information on the dissolution behavior of nitrofurantoin pseudopolymorphs is therefore useful for designing high-quality preparations.

In Vitro Techniques↗
PubMed1992

Rapid myocardial perfusion imaging with 99Tcm-teboroxime and a three-headed SPECT system: a comparative study with 201Tl.

99Tcm-teboroxime is a new myocardial perfusion agent with a high first pass extraction and rapid myocardial washout. The usefulness of 99Tcm-teboroxime was evaluated for detection of myocardial ischaemia using a three-headed single photon emission tomography (SPECT) system which allows for rapid data acquisition. The subjects consisted of 14 patients, including seven with ischaemic heart disease, four with cardiomyopathy and three others. After the 99Tcm-teboroxime injection, dynamic data was collected every minute for 15 min with continuous rotation. High-quality SPECT images could be obtained by reconstructing the serial scans from 2 to 8 min. The sensitivity, specificity and accuracy of the 99Tcm-teboroxime study for the detection of the ischaemic region were not significantly different from those of the 201Tl study. Myocardial clearance was slow in the ischaemic lesion and in the myocardium of cardiomyopathy patients, while the coronary angiograms did not show any abnormality. These results therefore indicate that the rapid SPECT imaging and myocardial clearance of 99Tcm-teboroxime obtained with a three-headed SPECT system were useful for the detection of myocardial ischaemia.

Adolescent↗
PubMed1992

Amorphism and physicochemical stability of spray-dried frusemide.

The physicochemical properties of amorphous forms of frusemide, prepared by spray-drying at 50 or 150 degrees C, and their hygroscopic stability at temperatures of 25 and 40 degrees C, and at 0 and 75% relative humidity were investigated. The glass transition temperature of the amorphous form A was 44.2 degrees C as measured by differential scanning calorimetry, while that of the amorphous form B was 54.4 degrees C. The activation energies for glass transition and crystallization processes were calculated from the differential scanning calorimetry thermograms of amorphous forms A and B, respectively. Stability determined by X-ray diffraction at 0% relative humidity, 25 and 40 degrees C suggested that form B was more stable than form A. However, the stability of form A at 75% relative humidity and 25 and 40 degrees C was similar to that of form B.

Drug Stability↗
PubMed1992

CBF and oxygen metabolism in hemodialysis patients: effects of anemia correction with recombinant human EPO.

To investigate the effects of anemia correction with recombinant human erythropoietin (rhEPO) on both cerebral blood flow and oxygen metabolism in hemodialysis (HD) patients, the regional cerebral blood flow (rCBF), oxygen extraction (rOEF), and metabolic rate for oxygen (rCMRO2) were measured by positron emission tomography in five HD patients, and the data were compared with eight nondemented controls who had neither anemia nor uremia. In the HD patients, 1,500 U of rhEPO were administered intravenously three times a week to achieve a 10% increase in hematocrit (Hct) as an absolute value. Before rhEPO administration, the hemispheric rCMRO2 in HD patients was 1.48 +/- 0.09 (SE) ml.min-1.100 ml-1, which was significantly lower than that of 2.18 +/- 0.10 in the controls (P less than 0.01). In contrast, both rCBF and rOEF were significantly greater in the HD patients than the control, being 40 +/- 3 vs. 32 +/- 3 ml.min-1.100 ml-1 for rCBF (P less than 0.02) and 49 +/- 1 vs. 38 +/- 1% for rOEF (P less than 0.001). After treatment with rhEPO, Hct rose significantly from 21 +/- 1 to 31 +/- 1% in HD patients (P less than 0.001). There were significant reductions in both the hemispheric rCBF to 32 +/- 1 ml.min-1.100 ml-1 (P less than 0.01) and rOEF to 42 +/- 1% (P less than 0.01). However, the hemispheric rCMRO2 remained low at 1.58 +/- 0.06 ml.min-1.100 ml-1 even after rhEPO treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Combined effects of laser irradiation and chemical inhibitors on the dissolution of dental enamel.

It has previously been shown that the susceptibility of human teeth to acid dissolution can be reduced by the presence of various chemical agents in the dissolution medium or by pretreatment of the teeth with laser irradiation. Now synergism between these two approaches to improving acid resistance has been demonstrated. Extracted human teeth were irradiated with a continuous-wave carbon dioxide laser at a wavelength of 10.6 microns. Energy doses of either 65 or 130 J/cm2 given over periods of 2 or 4 s, respectively, were applied and the teeth subjected to a severe acid challenge (0.1 M acetate buffer, pH 4.5, no calcium or phosphate common ion present) for 24 h. Mineral loss was assessed by measurement of mineral density profiles with quantitative microradiography. Experiments were carried out in the presence or absence of three chemical inhibitors with distinctly different mechanisms of action: ethane-1-hydroxy-1, 1-diphosphonic acid, fluoride, and dodecylamine HCl. Laser irradiation alone was found to lead to increased resistance of the teeth to acid challenge, with the higher energy dose being more effective than the lower dose. Each of the chemical inhibitors was effective on both lased and unlased teeth, with the percent reduction of dissolution greater when the inhibitors were applied to teeth lased with an energy dose of 130 J/cm2 which were already more resistant to acid challenge than were unlased teeth or teeth lased with a dose of 65 J/cm2.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗