Biomedical subjects

N Kosaka

Publications and source records attributed to N Kosaka.

At least 37 records · Page 2Linked to original sources

PubMed1998

Effect of benidipine hydrochloride, a dihydropyridine-type calcium antagonist, on the function of mouse osteoblastic cells.

The effects of benidipine hydrochloride (BD), a dihydropyridine-type calcium antagonist, on the growth and alkaline phosphatase (ALPase) activity were studied in cultures of mouse osteoblastic cells. BD (0.1-10 nM) increased the ALPase activity of osteoblastic cells and reduced cell proliferation incubated for 48 h. This reduction of cell growth did not appear to be due to cell death. On the other hand, nifedipine and amlodipine (1 nM) had no effect. BD (0.1-10 nM) enhanced the effects of 1,25(OH)2D3 on osteoblastic cells, the decreased cell growth and increased ALPase activity. These findings suggest that BD regulates the growth and differentiation of osteoblasts and stimulates the function of these cells as well as 1,25(OH)2D3.

Alkaline Phosphatase↗

PubMed1998

[The chemical structure of new substance as the metabolite of baicalin and time profiles for the plasma concentration after oral administration of sho-saiko-to in human].

Baicalin (BG) is one of the major components of Sho-Saiko-To. We found a new substance as the metabolite of BG in human plasma after oral administration of Sho-Saiko-To. The metabolite was identified as baicalein 6-O-sulfate (BS) by comparing its retention time in HPLC and electrospray ionization mass spectra (ESI-MS)/MS methods with that of an authentic sample. Time profiles for the plasma concentrations of BS and BG after oral administration of Sho-Saiko-To (EK-9) at a daily dose (6 g), were investigated in 14 healthy male volunteers. The determination for the concentrations of BS and BG in human plasma was developed by the HPLC method using electrochemical detector (ECD). Each 1 ml of the plasma specimen was used for the solid phase extraction. The calibration curves of BS and BG showed a good linearity between 5 and 300 ng/ml. The quantitative limits of BS and BG in human plasma were 5 ng/ml. Using this method, BS was detected after 1 h, reached a maximum level at 5 h and then decreased to the level less than the quantitative limit after 36 h, and the plasma level of BS showed a slight peak at 24 h. BG was detected after 1 h, reached a maximum level at 5 h and then decreased to the level less than the quantitative limit after 36 h, and the plasma level of BG showed two peaks at 12 h and 24 h.

Administration, Oral↗

PubMed1998

[Effect of KW-8232 on bone turnover in ovariectomized rats].

The effects of 3-[bis(4-hydroxyphenyl)methyl]-2-[4-(2-chlorophenyl)- piperazin-1-ylcarbonyl]-1-(2-dimethylamino ethyl) indole methanesulfonate (KW-8232) on the bone turnover in ovariectomized (OVX) rats were studied by the oral administration for 6 weeks. KW-8232 inhibited the decreased bone mineral densities of the femur and tibia in OVX rats. OVX induced the increase of serum alkaline phosphatase and osteocalcin levels, markers of high bone turnover, and also increased urinary hydroxyproline, pyridinoline and deoxypyridinoline excretion, markers of bone resorption. KW-8232 significantly inhibited the increase of serum alkaline phosphatase level at doses of 10 and 30 mg/kg and the increase of osteocalcin level at a dose of 3 mg/kg. KW-8232 (1 mg/kg) markedly suppressed the OVX-induced increase of urinary hydroxyproline, pyridinoline and deoxypyridinoline excretion. KW-8232 didn't affect serum calcium level, but significantly decreased urinary calcium excretion at doses of 10 and 30 mg/kg. These results suggest that KW-8232 decreased bone loss in this model by suppressing bone resorption.

Alkaline Phosphatase↗

PubMed1998

Effect of KW-8232, a novel anti-osteoporotic agent, on bone loss in sciatic neurectomized rats.

The purpose of this study was to evaluate the effects of 3-[bis(4-hydroxyphenyl)methyl]-2-[4-(2-chlorophenyl)-piperazin-1-+ ++ylcarbonyl]-1-(2-dimethylaminoethyl) indole methanesulfonate (KW-8232), a novel anti-osteoporotic agent, on bone loss in neurectomized rats. We also investigated the effect of KW-8232 on bone resorption in this animal model. Male Sprague-Dawley rats underwent unilateral hind-limb immobilization by sciatic neurectomy. KW-8232 (3, 10 and 30 mg/kg, p.o.) was effective in inhibiting femoral bone loss. KW-8232 decreased urinary pyridinoline and deoxypyridinoline excretion. These results indicate that KW-8232 effectively prevents the bone loss due to immobilization.

Amino Acids↗

PubMed1998

Acute effects of nasal continuous positive airway pressure on 24-hour blood pressure and catecholamines in patients with obstructive sleep apnea.

To assess the acute effects of nasal continuous positive airway pressure (CPAP) on the 24-hour blood pressure and the secretion of catecholamines in urine and plasma, we investigated the changes in the 24-hour blood pressure and urinary and plasma concentrations of epinephrine (E) and norepinephrine (NE) in 26 men with obstructive sleep apnea (OSA) with and without nasal CPAP. Nasal CPAP resulted in significant decreases in the daytime diastolic pressure (from 86 +/-16 mmHg to 83+/-12 mmHg), the nighttime diastolic pressure (from 81+/-12 mmHg to 77+/-9 mmHg) and the nighttime systolic pressures (from 125+/-15 mmHg to 120+/-10 mmHg). There was no significant difference between patients with and without CPAP in the daytime or nighttime urinary E level, but patients who received CPAP showed a significant decrease in daytime urinary NE level (from 156+/-112 microg/14h to 119+/-101 microg/14h) and nighttime urinary NE level (from 143+/-91 microg/10h to 112+/-65 microg/10h). The morning plasma level of NE also decreased (from 371+/-181 pg/ml to 273 +/-148 pg/ml) in patients who received nasal CPAP (p<0.02), but the plasma level of E remained unchanged. There were no correlations between PSG parameters and the reductions in blood pressure and the catecholamine levels induced by nasal CPAP. These findings suggest that OSA contributes, at least in part, to the development of systemic hypertension by increasing sympathetic nervous activity.

Biomarkers↗

PubMed1998

[Long-term effects of nasal continuous positive airway pressure on pulmonary function and blood gas data in patients with obstructive sleep apnea syndrome].

To evaluate the long-term effects of nasal continuous positive airway pressure (NCPAP) on pulmonary function and blood gas levels in patients with obstructive sleep apnea syndrome (OSAS), we examined the pulmonary functions and blood gases in 25 male patients with OSAS before and after NCPAP treatment. After 22 months of treatment (titration: 13 cm H2O), no significant changes were observed in the patients' spirograms, pulmonary gas volumes, or diffusion capacity. However, PaO2 levels increased significantly (p < 0.01), from 73.8 mmHg to 79.5 mmHg; PaCO2 levels decreased significantly (p < 0.05), from 45.6 mmHg to 44.2 mmHg; and A-aDO2 levels also decreased significantly (p < 0.05), from 18.7 mmHg to 15.0 mmHg. The patients were divided into a hypoventilated group (PaCO2 > 45 mmHg; 11 cases) and normoventilated group (PaCO2 < or = 45 mmHg; 14 cases). After NCPAP treatment, increased PaO2 and decreased PaCO2 levels were observed in the hypoventilated group, and increased PaO2 and decreased A-aDO2 levels were observed in the normoventilated group. These results suggest that long-term NCPAP treatment improves gas exchange in OSAS patients without influencing the results of pulmonary function tests.

Adult↗

PubMed1998

PET imaging of prostate cancer using carbon-11-choline.

UNLABELLED: Prostate cancer is difficult to visualize using current techniques. Recently, 31P magnetic resonance spectroscopy has revealed that the tumor, in general, is characterized by an increased uptake of choline into the cell to meet increased synthesis of phosphatidylcholine, an important cell membrane phospholipid. We succeeded in using 11C-choline to visualize prostate cancer and its local metastasis in PET. METHODS: PET was performed on 10 prostate cancer patients from the level of pelvis to the lower abdomen. After transmission scanning, 370 MBq 11C-choline were injected intravenously. The emission scan was performed 5-15 min postinjection. Finally, PET images were displayed so that each pixel was painted by a specified color representing the degree of the standardized uptake value (SUV). The 11C-choline image was compared with the 18F-fluorodeoxyglucose (FDG) image obtained from the same patient. RESULTS: Imaging of prostate cancer and its local metastasis was difficult when 18F-FDG was used because, within the pelvis, the areas of high uptake were concealed by the overwhelmingly abundant radioactivity in urine (in ureters and bladder). By contrast, it was easy when 11C-choline was used because the urinary activity was negligible and tumor uptake was marked. The radioactivity concentration of 11C-choline in prostate cancer and metastatic sites was at an SUV of more than three in most cases. The SUV of 18F-FDG was considerably lower than that of 11C-choline. CONCLUSION: Prostate cancer and its local metastasis were visualized clearly in PET using 11C-choline.

Adenocarcinoma↗

PubMed1997

Cloning, functional expression and tissue distribution of rabbit alpha1a-adrenoceptor.

A cDNA clone, which has an open reading frame of 1398 nucleotides encoding a 466-amino-acid peptide, has been isolated from rabbit liver cDNA library. Compared with the peptide sequence, it shows high homology to alpha1a adrenoceptors of human, bovine and rat. We expressed this clone in COS-7 and investigated the pharmacological properties, revealing similarity to those of human alpha1a adrenoceptors. Competitive RT/PCR has detected the mRNA in variety of rabbit tissues, especially abundantly in liver, vas deferens, brain, and aorta, but not in heart.

Amino Acid Sequence↗

PubMed1997

Brain tumors: detection with C-11 choline PET.

PURPOSE: To evaluate the effectiveness of positron emission tomography (PET) with carbon-11 choline in brain tumor imaging. MATERIALS AND METHODS: A rat glioma cell line (C6) was incubated with C-14 choline; the time course of uptake and metabolism was determined in vitro. C-11 choline was injected intravenously in tumor-bearing rats; the time course of distribution in organs was determined. C-11 choline also was injected intravenously in 20 patients (aged 6-86 years) with brain tumors and two volunteers (aged 38 and 58 years); distribution of the tracer in the brain was determined. Regional cerebral blood flow was measured by using oxygen-15 water on the same day. RESULTS: C-14 choline was metabolized to phosphoryl choline in glioma cells. The uptake of C-11 choline by glioblastoma cells was three to four times higher than that in the rat brain. All brain tumors took up more C-11 choline than did normal brain; thus, brain tumors that were not treated, as well as those that were treated with surgery or radiation therapy, were depicted. The tumor-normal brain uptake ratio of C-11 choline in brain tumor did not correlate with the O-15 water regional blood flow in the corresponding area. CONCLUSION: C-11 choline PET can depict brain tumors effectively. This method was clinically useful in patients who had undergone surgery.

Adult↗

PubMed1997

PET imaging of brain tumor with [methyl-11C]choline.

UNLABELLED: This article describes a new method of [11C]choline synthesis for intravenous injection. We aimed at the utilization of this compound for brain tumor imaging with PET. METHODS: After [11C]carbon dioxide production in a cyclotron and the subsequent [11C]methyl iodide synthesis, [methyl-11C]choline was synthesized by the reaction of [11C]methyl iodide with "neat" dimethylaminoethanol at 120 degrees C for 5 min. Purification was achieved by evaporation of the reactants followed by passage of the aqueous solution of the product through a cation-exchange resin cartridge. The time required for overall chemical processing, excluding the cyclotron operation, was 15 min. Radiochemical yield was > 98%. Radiochemical purity was > 98%. Chemical purity was > 90% (dimethylaminoethanol was the only possible impurity). Specific radioactivity of the product was > 133 GBq/mumol. The whole body distribution was examined in rabbits with PET. Clinical studies were performed in patients with brain tumor using PET after intravenous injection of 370 MBq of [11C]choline. RESULTS: In rabbits,[11C]choline was taken up from blood by various tissues very rapidly, and the radioactivity remaining in blood became almost negligible 5 min after intravenous injection. Taking advantage of this characteristic, we obtained stable tissue distribution images of human brain using PET. In patients with brain tumor, PET produced clearly delineated positive images of the tumors. CONCLUSION: Carbon-11-choline can be used for obtaining clear images of brain tumor in PET.

Adenoma↗

PubMed1996

Evaluation of gamma camera-based measurement of individual kidney function using iodine-123 orthoiodohippurate.

Gamma camera-based clearance techniques which use the renal uptake ratio (RUR) of the radiotracer are available to estimate the effective renal plasma flow (ERPF) and glomerular filtration rate. To evaluate the accuracy of these techniques, we measured RUR by an optimized procedure and compared it with standard ERPF. Iodine-123 orthoiodohippurate (OIH) scintigraphy and simultaneous para-aminohippurate clearance study for measuring standard ERPF were performed in three hospitals in 24 patients with normal or mildly impaired renal function. 123I-OIH was injected intravenously and 10-s consecutive imaging of the kidneys was started when the abdominal aorta was seen. The attenuation coefficient for 123I was measured in each hospital using the same water-equivalent absorption materials and used for the attenuation correction. After subtracting background radioactivity, RURs were defined as the count ratios of fractional renal uptakes based on the integral from 1 to 2, 2 to 3, 1.5 to 2.5 and 1 to 3 min after the injection of 123I-OIH in relation to injected doses using the following three procedures in respect of attenuation correction: (1) RUR without attenuation correction, (2) RUR with fractional renal uptake corrected by the measured attenuation coefficient, (3) RUR with the total injected dose corrected by the absorption material. To decide upon the appropriate correction method and time interval, RURs were compared with standard ERPF. Among the three correction methods, procedure 2 showed the highest correlation between RUR and standard ERPF, but the correlation coefficient was low (r=0.75). No significant difference was observed among the RURs of each time interval. Individual kidney function measured from early renal uptake may be inaccurate even when appropriate correction is made for attenuation, background activity or time lag between injection and data acquisition. Gamma camera-based measurement of renal function using 123I-OIH is limited with regard to accuracy and reproducibility, though it is convenient and non-invasive.

Adult↗

PubMed1994

[Effect of KW-5805 on gastric mucus changes induced by water immersion-restraint stress and aspirin in rats].

The effects of 5-[2-(diethylamino)ethyl]amino-5,11-dihydro[1]benzoxepino[3,4- b]pyridine trihydrochloride (KW-5805) on the changes of gastric mucus induced by stress and aspirin were studied in rats. Water immersion-restraint stress time-dependently decreased the gastric adherent mucus content and induced gastric ulcers. Aspirin, administered orally at 200 mg/kg, reduced the gastric adherent mucus level and produced gastric erosions. The diminution of gastric mucus reached a maximum at 3 hr, and a gradual return to the non-treatment value was observed subsequently. Pretreatment with KW-5805, given orally at 3, 10 or 30 mg/kg, dose-dependently prevented stress- and aspirin-induced mucus depletion and gastric ulceration. Gastric mucus glycoprotein levels, indicated by the contents of hexose and hexosamine, were also decreased by aspirin. KW-5805 pretreatment (30 mg/kg, p.o.) significantly inhibited the diminution of mucus glycoproteins. KW-5805 also increased the gastric adherent mucus content and the amount of glycoproteins in normal rats. These results suggested that the stimulating effects of KW-5805 on the secretion and storage of gastric mucus may account for some of its antiulcer properties.

Animals↗

PubMed1994

[Effect of 5-[2-(diethylamino)ethyl]amino-5,11- dihydro[1]benzoxepino[3,4-b]pyridine trihydrochloride (KW-5805) on the biosynthesis of rat gastric mucus].

The effect of 5-[2-(diethylamino)ethyl]amino-5,11- dihydro[1]benzoxepino[3,4-b]pyridine trihydrochloride (KW-5805) on the activity of an enzyme regulating gastric mucous aminosugar metabolism was studied in rats. Restraint and water-immersion stress decreased the gastric mucosal glucosamine synthetase activity and induced gastric ulcers. The decrease of the enzyme activity reached a maximum at 1 hr and then returned to the non-stressed value. Pretreatment with KW-5805 at oral doses of 3 and 30 mg/kg inhibited the decrease of the enzyme activity and the gastric adherent mucus content and gastric ulceration induced by the stress. KW-5805 (30 mg/kg, p.o.) increased the enzyme activity in normal rats and also prevented the decrease of gastric mucosal N-acethylglucosamine kinase activity in the stressed rats. KW-5805 stimulated the activities of gastric mucosal. UDP-N-acethylglucosamine 4-epimerase and UDP-galactosyltransferase in in vitro. These results suggested that the antiulcerogenic effect of KW-5805 might be due to the activation of an enzyme regulating the biosynthesis of gastric mucus resulting in the reinforcement of gastric mucosal defensive mechanisms.

Administration, Oral↗

PubMed1994

Effects of KW-5805, a new antiulcer agent, on experimental gastric and duodenal ulcers, gastric mucosal lesions by necrotizing agents and gastric acid secretion.

Effects of KW-5805, a new antiulcer agent, on various experimental ulcers, necrotizing agent-induced gastric lesions and gastric acid secretion in rats were compared with those of pirenzepine and cimetidine. KW-5805 showed antiulcer activities against experimental gastric and duodenal ulcers (ED50 = 1.2-10.0 mg/kg, p.o.). KW-5805 effectively inhibited gastric lesions induced by various necrotizing agents (ED50 = 4.5-39.8 mg/kg, p.o.). In addition, the cytoprotective effect of KW-5805 was not affected by indomethacin, but reserved by N-ethylmaleimide. These antiulcer and cytoprotective effects of KW-5805 were more potent than those of pirenzepine and cimetidine. In pylorus-ligated rats, intraduodenal KW-5805 administration at 30 mg/kg showed a weak antisecretory effect, which was 3-10 times less potent than those of pirenzepine and cimetidine. In rats with acute gastric fistula, intravenous injection of KW-5805 reduced methacholine-stimulated gastric acid secretion at doses of 10 and 30 mg/kg and inhibited tetragastrin-induced acid secretion at 30 mg/kg. These results indicate that KW-5805 has potent and broad antiulcer properties, which are probably exerted by its potent cytoprotective effect in addition to its antisecretory effect.

Animals↗

PubMed1992

[Metabolism of 99mTc-ethyl cysteinate dimer (99mTc-ECD) in blood--mainly in vitro].

Metabolism of 99mTc-ethyl cysteinate dimer (99mTc-ECD) in blood was studied mainly in vitro. When 99mTc-ECD was mixed with blood taken from 12 subjects, the octanol extraction ratio of ECD (y) decreased rapidly and the octanol extraction ratio-time profile well fitted a monoexponential curve (y = Ae-kt/1000, A, k: constant, t: time after mixing). The k value and hematocrit (Ht) were significantly correlated (k = 0.376Ht-3.27, r = 0.897, p less than 0.001), therefore, it was suggested that the majority of the enzyme which dissolves ECD exists in red blood cells. When ECD was mixed with blood, there were more hydrophilic products of ECD in plasma than those generated by the enzyme in plasma. In vivo input function of 99mTc-ECD was calculated by arterial blood sampling and octanol extraction. The duration of effective input was relatively short, which was attributed to rapid decrease of octanol extraction ratio in vivo.

Brain↗

PubMed1991

CT and MR appearance of focal nodular hyperplasia of the liver in children with biliary atresia.

Two children with biliary atresia are described in whom focal nodular hyperplasia of the liver occurred following portoenterostomy. The lesions were low-or iso-dense on unenhanced CT and became hypodense post-contrast enhancement. There was normal 99mTc phytate on hepatic colloid scintigraphy. On T2-weighted spin echo MR images, there was increased signal intensity within the masses, and the surrounding liver parenchyma was divided by linear septa in one of the two cases.

Biliary Atresia↗

PubMed1991

[Bone scan "flare" in patients irradiated to formerly false negative bone metastasis].

We discuss three cases irradiated to their bone metastases. 99mTc-MDP bone scan before irradiation showed normal uptake in the lesions. In all the cases, the irradiation therapy was effective, but focal increased uptake area corresponding to the site of bone metastasis was revealed by the follow-up bone scan one to three months after irradiation. We concluded that the change of tracer uptake was so-called flare in formerly false negative lesion. The cause of this phenomenon was considered either elevation of osteoblastic activity with control of tumor or progression of osteolysis until tumor got well-controlled.

Aged↗

PubMed1991

[Intra-arterial and intraportal infusion liver scintigraphy using 99mTc-labeled colloid].

Intra-arterial infusion liver scintigraphy was performed in 11 patients with primary or metastatic liver tumor, and intraportal infusion liver scintigraphy was performed in 6 patients for prophylaxis of liver metastasis from colorectal cancer. 99mTc-Sn colloid or 99mTc-phytate was administered through the catheter of which tip was placed in the portal vein or the hepatic artery, and then liver image was obtained. When 99mTc-phytate was infused intra-arterially, significant amount of the infused tracer passed through the liver and we could not get sufficient information to assess the distribution of drug administered through the catheter. On the other hand, intraportal infusion liver scintigraphy using 99mTc-Sn colloid or 99mTc-phytate and intra-arterial infusion liver scintigraphy using 99mTc-Sn colloid revealed heterogeneity of liver uptake, tracer uptake in spleen, low uptake area corresponding to the liver tumor and high uptake area around it. The findings will be clinically useful, and these methods are thought to be helpful to confirm the satisfactory drug distribution.

Adult↗