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Biomedical subjects

A Mizuno

Publications and source records attributed to A Mizuno.

At least 199 records · Page 11Linked to original sources
PubMed1992

Pharmacokinetics of the new antiplatelet agent 2-methyl-3-(1,4,5,6-tetrahydronicotinoyl)pyrazolo[1,5-a]pyridine in human subjects.

The pharmacokinetics of KC-764 (2-methyl-3-(1,4,5,6-tetrahydronicotinoyl)pyrazolo[1,5-a]pyridine, CAS 94457-09-7) was studied in healthy male adult volunteers after single ascending oral dose and multiple dosing for 7 days. Serum KC-764 concentration attained the peak in 1 h and declined with a half-life of about 2 h at a single oral dose of 5, 10, 20 and 40 mg. No dose dependent pharmacokinetics of KC-764 was demonstrated. Three metabolites were detected in serum, but their concentrations were lower than that of KC-764. 48-h urinary recoveries after single doses were 41.6-46.6% of dose, not being dose-dependent. Urinary recovery of unchanged KC-764 was 1.1-1.6% of dose. Three metabolites were present in greater amount in urine than unchanged KC-764 and two metabolites were less than KC-764. There was little daily variation of serum concentrations and urinary excretion of KC-764 and its metabolites in the multiple dosing (20 mg twice a day) study. The daily and total urinary recovery were same as those after single doses. Food reduced Cmax and tended to delay tmax, but did not influence AUC0----infinity and urinary recovery. Serum protein binding of KC-764 was about 60%, being not dependent on total serum concentration.

Adult↗
PubMed1992

Uric acid as biochemical marker for retinal and optic nerve damage after occlusion and reperfusion of common carotid and vertebral arteries in rat.

Transient retinal and optic nerve ischemia lasting for 20 minutes was produced in Wistar rats by clipping bilateral common carotid arteries and coagulating both vertebral arteries by heat. The uric acid level in the retina and optic nerve were determined by high performance liquid chromatography with electrochemical detection just before induction of ischemia, 20 minutes after induction of ischemia, and after resolution of ischemia. Uric acid content in the optic nerve (28.0 +/- 4.5 ng/mg protein) was about 5 times higher than that in the retina (5.7 +/- 0.8 ng/mg protein) in the control experiment. Ischemia lasting for 20 minutes caused a 2.7-fold increase of uric acid in the optic nerve and a 1.8-fold increase in the retina. Following reperfusion of the blood flow by unclipping of the common carotid arteries, the uric acid level decreased to the control level in both the retina and optic nerve 30 minutes after unclipping, which was followed by 3.1- and 1.6-fold increases in uric acid in the retina and the optic nerve, respectively, at 60 minutes after unclipping. Although ischemia alone causes tissue damage, there is some clinical evidence that greater injury can occur after oxygen is reintroduced to ischemic tissue. Our results indicate that the retina is more likely to be damaged by reperfusion than the optic nerve.

Animals↗
PubMed1991

Pharmacokinetic and pharmacodynamic profiles of vapiprost, a selective, long-lasting thromboxane receptor antagonist, after single and multiple oral administration to healthy volunteers.

A selective thromboxane A2 (TXA2) receptor blocking agent, vapiprost, was orally administered to healthy male Japanese volunteers to investigate the pharmacokinetic and pharmacodynamic properties. The time-profile of vapiprost concentration in plasma was determined and the effects of the drug on platelet aggregation in platelet-rich plasma (PRP) induced by a stable TXA2 receptor agonist U-46619, adenosine diphosphate (ADP) and collagen, and platelet aggregation in whole blood induced by U-46619 ex vivo were simultaneously examined and compared. In the single-dose study (5, 10, and 20 mg/man) the plasma concentrations of the drug were fitted well to a one-compartment open model with a first-order absorption. The area under plasma concentration-time curve (AUC) and maximum plasma concentration (Cmax) showed dose-related increases, whereas the mean elimination half-lives (t1/2) remained approximately constant within the range of 0.99-1.1 hour. The drug was hardly recovered unchanged in urine. The platelet aggregation in PRP induced by collagen or U-46619 and the secondary aggregation by ADP were inhibited; that induced by U-46619 was the most specifically and completely inhibited at 2 hours after administration of any dose. The duration for maintaining the significant inhibition tended to depend on the dose and ranged from 24 to 36 hours after administration, which was much longer than expected from the plasma concentration of drug. The time-profile of inhibiting whole blood platelet aggregation that was induced by U-46619 was almost parallel to that of platelet aggregation in PRP by the same aggregant. The bleeding time was slightly prolonged 2 and 8 hours after administrations of 10 and 20 mg, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1991

A bacteriological study of perforated duodenal ulcers.

Peritoneal fluid sampling and bacteriological examination were performed in 63 patients with perforated duodenal ulcers, and the results compared with those in 175 patients with other perforations. Bacterial culture was positive in 100 per cent of the patients whose perforations occurred in the colon, whereas it was positive in only 44.4 per cent of those with duodenal perforations, being negative in many cases when the interval from perforation to surgery was short. A mixed contamination with both aerobes and anaerobes was usually found in the cases of lower digestive tract perforation, and the isolates from duodenal perforations were uniquely aerobes in most cases. It is suggested that bacteria play a minor role in the pathogenesis of early stage duodenal perforation, which supports the technique of primary closure without indwelling drainage tubes during early stage operations following sufficient peritoneal lavage. Moreover, if the stomach is empty at the time of perforation and the peritonitis is localized, even conservative therapy seems possible, provided it is begun shortly after the perforation.

Adolescent↗
PubMed1991

Facial fibrous dysplasia: report of a case.

A case of facial fibrous dysplasia that involved the left frontal, temporal, malar, and mandibular regions is reported. Conservative recontouring was done several times when the patient was 16 to 23 years of age.

Adolescent↗
PubMed1991

Simplification of a venous occlusion test.

Chronological changes in plasma or serum concentrations of various fibrinolytic parameters, such as tissue-type plasminogen activator, plasminogen activator inhibitor, fibrinopeptide B beta 15-42 and FDP, were examined in 31 healthy volunteers before and after venous occlusion to determine a suitable time of venous stasis and a good parameter for use in a simplified venous occlusion test. After venous stasis for 5 min, a significant increase in the serum concentration of FDP (from 38.3 +/- 21.1 to 100.9 +/- 87.2 ng/ml (n = 24)) was observed, and the increase was parallel with changes in the plasma concentrations of other fibrinolytic parameters. The serum FDP level after 10 min VO was not significantly higher than that after 5 min VO. A significant decrease in ADP-induced platelet aggregation was observed after venous occlusion when measured by the impedance method, but not by the turbidimetric method. Therefore, as a simplified test, the change in the serum concentration of FDP after VO for 5 min was measured. The clinical significance of this simplified test was evaluated in fourteen patients with stenosis of cerebral artery. The mean percentage change in serum FDP concentration after venous stasis in the patients, 34.5 +/- 54.8%, was significantly less than that in normal subjects, 156.5 +/- 90.9%. Similar results were obtained on changes in plasma responses of other fibrinolytic parameters. Measurement of increase in serum FDP concentration after venous occlusion for 5 min should be useful as a screening tests for the hypofibrinolytic or thrombotic state due to vascular dysfunction.

Adult↗
PubMed1991

Ofloxacin in human hair determined by high performance liquid chromatography.

A procedure is presented for quantitating ofloxacin (OFLX) in human scalp hair by high performance liquid chromatography (HPLC) with a fluorescence detector. An octadecylsilane (ODS) column was used and the mobile phase was a mixture of potassium phosphate buffer (pH 2.6) and acetonitrile. The recovery of OFLX was 90.9-93.8% and within- and between-run precisions were 0.35-1.41% and 1.41-5.49% as the coefficient of variation (CV), respectively, when 5-50 ng OFLX was added to 1 mg blank hair. The calibration curve was linear in the range of 0.5-50 ng/tube (0.5 ml). Interference with other quinolone derivatives could be avoided according to the difference in their retention times or fluorescence spectra. Several pieces of hair were obtained from each of twelve healthy male volunteers, who had taken OFLX (100, 300 or 900 mg total dose) over a 1-3 day period 2 weeks before the hair sampling. In all hair samples except one obtained from a volunteer, who had taken the lowest dose, the 2-cm long segments nearest the scalp contained OFLX (5-45 ng/mg hair), while the upper segments did not. A highly significant positive correlation was observed between the total dose and the concentration of OFLX in the 2-cm long hair segments. Such a positive correlation was also revealed in rat hair sampled after repeated i.p. administration of OFLX over a 5-week period. These results suggest that the measurement of OFLX in hair by the present method would be useful for testing patient compliance in clinical pharmacology as well as for application to forensic science.

Adult↗
PubMed1991

Absorption and metabolism of pyridoxamine in mice. I. Pyridoxal as the only form of transport in blood.

[3H]Pyridoxamine was orally administered to mice in physiological amounts, and the distribution of isotope between the six recognized forms of vitamin B6 and pyridoxic acid was determined at different times in the intestine, liver, blood, and brain. After 7 min about 50% of the radioactivity in pyridoxamine had been absorbed by the intestine and transported to the blood and other organs. Labeled pyridoxal phosphate was found in the intestine and liver. Labeled pyridoxamine could not be detected in the peripheral blood, but substantial amounts of labeled pyridoxal and pyridoxal phosphate were found in the blood. However, when a large amount (40-140 nmol) was given, a significant amount of labeled pyridoxamine was found in the blood, together with labeled pyridoxal and pyridoxal phosphate. These results suggest that the intestine and/or liver play a major role in completely converting physiological amounts of pyridoxamine to circulating pyridoxal, which is then taken up and phosphorylated by other organs.

Absorption↗
PubMed1991

[A case report of surgical treatment of acute aortic dissection (DeBakey III B) in association with thoracic aortic aneurysm].

This is a case report of 63-year-old man suffering from DeBakey III B acute dissection in association with thoracic aortic aneurysm. He had been following up for hypertension and thoracic aortic aneurysm. He was brought to the hospital by city ambulance complaining of sudden onset of severe back pain. Emergency operation was carried out. It revealed aneurysm of 90 mm in diameter located just distal to the aortic arch and an intimal tear or entry of the dissection located distal to the left subclavian artery. A low porosity Dacron graft was interposed between the distal aortic arch and middle portion of the thoracic descending aorta using inclusion technique. Systemic circulation was bypassing external iliac vein to artery using pump-oxygenator during aortic clamping. His postoperative course was uneventful. In review of the literature, association of the atherosclerotic aneurysm and acute dissection occurred approximately 5% in the cases of aortic dissection with increasing risk of aneurysmal rupture.

Acute Disease↗
PubMed1991

[Successful repair of TGA with ventricular septal defect, the outflow tract stenosis of the left ventricle and coarctation of the aortic arch].

A 9-month-old boy after the coarctectomy at 5 months old was successfully repaired by Senning procedure with closure of ventricular septal defect and resection of the membranous septal aneurysm causing the outflow tract stenosis of the left ventricle. Retrospectively, this case might have been possible to do Jatene procedure, however, attempts to resect the left ventricular outflow tract stenosis often failed to relieve stenosis completely. Therefore, the intraatrial switch operation seems to be better than the arterial switch operation when there is a possibility to remain left ventricular outflow tract stenosis. True estimation for these cases must await more case studies.

Aorta, Thoracic↗
PubMed1991

Aging and cataractous process of the lens detected by laser Raman spectroscopy.

Raman spectra from the lenses of rat and mouse were measured in situ at various conditions of lens aging and opacification. Laser Raman spectroscopy is a powerful nondestructive structural probe to provide us useful informations such as hydration or dehydration state, thiols and its oxidation or micro-environmental state of tryptophan or tyrosine residuse of the lens proteins. In this paper we summurized our Raman studies on various normal, aged and cataractous lenses. Lens dehydration was a common phenomena during normal aging. Regional distribution of lens water showed lens fiber aging from nucleus to cortex. On the other hand lens hydration was a common in the lens with opacification. Using regional water content as a diagnostic marker, the effect of aldose reductase inhibitor was monitored objectively. Lens slfhydryl (SH) groups were reduced with age and with opacification in general, and concomitant increase in disulfide (S-S) bonds was detected. In ICR/f rat lens the decrease in SH groups and simultaneous increase in S-S bonds were found even before lens opacity was manifest.

Aging↗
PubMed1991

[Clinical study on fleroxacin in surgical infections].

We conducted clinical studies on fleroxacin (FLRX), a new pyridone carboxylic acid derivative, for the treatment of periproctal abscess, secondary infections (due to wounds, burns or surgical operations), mastitis or areolitis and others with once daily dose of 200 mg or 300 mg. We obtained the following results. Clinical efficacy was evaluated in total 27 cases including periproctal abscess 11, secondary infection 8, mastitis or areolitis 6, phlegmon 1 and infected atheroma 1. Clinical efficacies were rated as excellent in 14, good in 9, fair in 4 cases. The overall efficacy rate was 85.2%. Bacteriological studies identified 14 strains of aerobic Gram-positive organisms, 12 of aerobic Gram-negative organisms and 6 of anaerobic organisms. The overall bacteriological efficacies were: eradicated in 26 strains, unchanged 2 and unidentified 4, hence the eradication rate was 92.9%. As for side effects, anorexia and nausea were observed in one of the 27 cases. In clinical laboratory tests, slight elevations of GPT and BUN were observed in 1 case each. We consider FLRX to be a useful antimicrobial agent at once daily dose for surgical infections.

Abscess↗
PubMed1991

[A case report of emergency surgical repair of traumatic transection of thoracic descending aorta].

The injury to the thoracic aorta caused by blunt chest trauma is often fatal. This case is 22-year-old male suffering from transection of the thoracic descending aorta caused by traffic accident. He was transported to our emergency room by an ambulance 15 minutes after the accident. Hundred fifty minutes after arrival to the hospital, we were rush to bring him to the operation theater suspecting serious injury of the thoracic organs in association with left hemothorax. The left standard thoracotomy disclosed the injury of the thoracic descending aorta. Simple cross clamp was applied to the thoracic descending aorta distal to the left subclavian artery for 20 minutes. Completely transected aorta was reapproximated using monofilament 3-0 polypropylene sutures with running manner. He tolerated the procedure well without any complication. His postoperative course was uneventful. He was followed up at the orthopedic department for associated hip fracture thereafter.

Accidents, Traffic↗
PubMed1991

[Supravalvular aortic stenosis syndrome with advanced mitral regurgitation requiring extended aortoplasty and mitral valve replacement: a case report].

This is a case report of a 28-year-old male, suffering from supravalvular aortic stenosis (systolic pressure gradient 60 mmHg) and severe mitral regurgitation associated with elfin face and mental retardation. Severely prolapsed mitral valve with elongated chordae tendineae was replaced with Björk-Shiley mitral valve prosthesis. Simultaneously, extended aortoplasty was carried out using Doty's method. His postoperative course was uneventful. Catheterization study, carried on one month after surgery, revealed complete disappearance of supravalvular aortic stenosis and mitral regurgitation. In review of the literature, as far as we know, report of successful combined correction for supravalvular aortic stenosis and mitral regurgitation is extremely rare.

Adult↗
PubMed1990

[Clinical effects and toxicity of chemotherapy with cisplatin for head and neck cancer--the multi-institutional joint research in Tokai district].

We investigated the clinical effects and toxicity of chemotherapy with Cisplatin (CDDP) for head and neck cancer as the third joint research project of the Tokai Meeting for Head and Neck Tumors. The cases were examined at the cooperating institutions from September 1986 to March 1988. The subjects were 93 cases consisting of 66 patients (intravenous infusion: 47 cases; intraarterial infusion: 19 cases) of PP therapy (CDDP + PEP), 16 cases of PF therapy (CDDP + 5-FU) and 11 cases of PPV therapy (CDDP + PEP + VCR). The regimens of PP therapy were: CDDP 50-100 mg/body x 1 day, PEP 5 mg/body x 5 days (i.v.), and CDDP 10-20 mg/body x 5 days, PEP 5-10 mg/body x 5 days (i.a.). In the regimen of PF therapy, CDDP 80-100 mg/body x 1 day and 5-FU 750-1,000 mg/body x 5 days were administered. In the regimen of PPV therapy, CDDP 80-100 mg/body x 1 day, PEP 5 mg/body x 5 days and VCR 1 mg/body x 1 day were administered. As a rule, two courses of each of the regimens were performed. The total dose of CDDP in intraarterial infusion of PP therapy was significantly less than in intravenous infusion. The major results were as follows: 1) Total response rate was 57.0% on the average, and this was not significantly different among the regimens. 2) The response rate of intraarterial infusion of PP therapy was as high as that for intravenous infusion in spite of the lower CDDP dose. 3) The response rate of oral cavity was significantly higher than that of nasal cavity and paranasal sinuses. 4) In the squamous cell carcinoma, the response rate of the well differentiated type was significantly higher than that of the poorly differentiated type. 5) The leukocyte counts significantly decreased with the intravenous infusion of PP therapy, PF therapy and PPV therapy. 6) The platelet counts significantly decreased with PPV therapy. 7) There were no significant changes with time with Ccr and PaO2 of PP therapy. 8) The frequency of toxicities such as nausea and vomiting was high in the intravenous infusion of PP therapy, PF therapy and PPV therapy. However, the frequency of toxicity was low in the intraarterial infusion of PP therapy.

Adult↗
PubMed1990

Confirmation of lens hydration by Raman spectroscopy.

Lens hydration was monitored by laser Raman spectroscopy in WBN/Kob rats which form spontaneous diabetes at about 1 yr of age and develop cataracts approximately 6 months after the onset of diabetes. Lens hydration in response to chronic hyperglycemic stress in these rats appeared predominantly in the cortical region while the hydration state in the nuclear region was fairly preserved. The 9-month treatment of similarly diabetic rats with the aldose reductase inhibitor Ponalrestat sufficiently suppressed lens hydration in the cortical and nuclear regions.

Aldehyde Reductase↗
PubMed1990

Immunohistochemical localization of glycated protein in diabetic rat kidney.

The localization of glycated protein in the kidney of diabetic rats was examined immunohistochemically with antiserum against glucitol-lysine. In diabetic rats the brush border and basement membrane of the proximal convoluted tubules were strongly immunoreactive with the antiserum but in control rats, only the brush border was weakly reactive. The immunoreactive tubules were more abundant in diabetic rats. No immunoreaction was found in any other structures in the kidney. Glycation of the proximal convoluted tubules may be an alteration in diabetic nephropathy.

Animals↗