Biomedical subjects

Y Tsuda

Publications and source records attributed to Y Tsuda.

At least 91 records · Page 5Linked to original sources

PubMed1998

Stereoselective disposition of sulbenicillin in humans.

Stereoselective disposition of sulbenicillin (SBPC) epimers in healthy human volunteers was studied in order to clarify the differences in pharmacokinetic behavior between the epimers. Stereospecific high-performance liquid chromatography was used for the determination of SBPC epimers. Plasma protein binding was measured in vitro with an ultrafiltration method. The binding was stereoselective, with the unbound fraction (fu) of the R-epimer being approximately 1.3-fold greater than that of the S-epimer. SBPC was administered intravenously to human volunteers, and concentrations of SBPC in plasma and urinary excretion rates were measured. Renal clearance (CLR) for the unbound drug (approximately 400 ml/min) was greater than the glomerular filtration rate (GFR) (approximately 109 ml/min) for both epimers, suggesting that both epimers are secreted at the renal tubules. Renal tubular secretion appeared to be greater for the S-epimer. When probenecid was coadministered, the CLR values of both epimers were significantly reduced and were approximately equal to the GFR values. CLR was greater for the S-epimer (37.5 and 49.8 ml/min for R-SBPC and S-SBPC, respectively), which was simply due to the greater fu of the S-epimer in plasma. In contrast, total body clearance was greater for the R-epimer (67.8 and 56.3 ml/min for R-SBPC and S-SBPC, respectively) because of the stereoselective degradation of the R-epimer in plasma. It was revealed that stereoselective degradation in the body had significant influence on the disposition of SBPC epimers.

Adult↗

PubMed1998

Orbital tumor in acute myeloid leukemia associated with karyotype 46,XX,t(8;21)(q22;q22): a case report.

Orbital tumor formation in acute myeloid leukemia (AML) is rare as an initial symptom. Furthermore, orbital granulocytic sarcoma (myeloid sarcoma) in pediatric patients is uncommon. We describe a 5-year-old Japanese girl with a left orbital mass as an initial symptom of AML, the mass revealed by computed tomography. Peripheral blood and bone marrow pictures and a chromosomal analysis disclosing 46,XX,t(8;21)(q22;q22) showed AML (M2 according to the French-American-British classification). She was treated with antileukemic chemotherapy systemically. Three weeks after the initiation of chemotherapy, the orbital tumor regressed markedly. AML as an initial symptom of the orbital mass should be fully considered in a differential diagnosis, even in the absence of typical leukemic symptoms, and chromosomal analysis and immunophenotypical analysis may explain the pathogenesis of the extramedullary leukemic tumor.

Acute Disease↗

PubMed1998

Hepatic infarction caused by an embolus from an atherosclerotic lesion--a case report.

Although it has been reported that emboli from atherosclerotic disease may be more frequent than commonly appreciated, hepatic infarction caused by an arterial embolus is an unusual but serious complication. The authors describe a patient who had a secondary liver infarct during anticoagulant treatment for cerebral infarction. The thrombus causing the liver infarction was detected as a low echoic mass by transesophageal echocardiography at the right coronary sinus.

Aged↗

PubMed1998

Purification method for human plasma kallikrein by a new affinity chromatography.

We synthesized a new affinity gel (PKSI-Toyopearl) using a selective synthetic inhibitor of plasma kallikrein (PKSI-527) as an affinity ligand, and employed it for the rapid purification of plasma kallikrein from human plasma. Human plasma activated with kaolin after acid treatment was applied to a PKSI-Toyopearl column. Adsorbed protein was eluted with 50 mM glycine-hydrochloric acid buffer (pH 3.0). Plasma kallikrein was purified 181-fold with a yield of 85% from the kaolin-activated plasma. Further purification was performed by chromatography on a DEAE-Toyopearl 650M column. Plasma kallikrein was finally purified 1720-fold with a 63% yield by these procedures. On sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis, a band was observed at approximately 88 kDa. These findings indicate that PKSI-Toyopearl is a valuable tool for the purification of plasma kallikrein from human plasma.

Blood↗

PubMed1998

Martefragin A, a novel indole alkaloid isolated from red alga, inhibits lipid peroxidation.

Martefragin A (1), a novel indole alkaloid, was isolated from a red alga, Martensia fragilis, by repeated column chromatography. The structure of 1 was elucidated on the basis of spectral analysis of its methyl ester (2), including 1H- and 13C-NMR, 1H-1H correlation spectroscopy (COSY), and 13C-1H COSY. A single crystal X-ray analysis of the hydrochloride of 1 confirmed the assignment. Martefragin A (1) showed inhibitory activity on NADPH-dependent lipid peroxidation in rat liver microsomes. The IC50 values of 1, alpha-tocopherol and ascorbic acid were 2.8, 87 and 200 microM, respectively.

Alkaloids↗

PubMed1998

Design of plasma kallikrein inhibitors: functional and structural requirements of plasma kallikrein inhibitors.

The synthetic plasma kallikrein (PK) inhibitor trans-4-aminomethylcyclohexanecarbonylphenylalanine-4-carboxyme thylanilide (PKSI-527) consists of three parts. Each part was replaced by analogues in an attempt to improve the potency and the selectivity of PKSI-527. Among the peptides examined, trans-4-aminomethylcyclohexanecarbonylphenylalanine-4-carboxyan ilide (peptide 16) inhibited PK with a high selectivity and an IC50 value of 2.7 microM, being as potent as PKSI-527.

Drug Design↗

PubMed1998

Cytotoxic principles of a Bangladeshi crude drug, akond mul (roots of Calotropis gigantea L.).

Three cardenolide glycosides, calotropin (1), frugoside (2), and 4'-O-beta-D-glucopyranosylfrugoside (3), were obtained as the cytotoxic principles of "akond mul" (roots of Calotropis gigantea L.). The cytotoxicity of these compounds against various cell lines of human and mouse origin was tested. They showed similar cell line selectivity to those of cardiac glycosides such as digoxin and ouabain: they are toxic to cell lines of human origin, but not to those from mouse at 2 micrograms/ml.

Animals↗

PubMed1998

[Eosinophilic meningoencephalitis in a case of rheumatoid arthritis].

A 56-year-old man was admitted to our hospital due to gradually developing consciousness disturbance. He had an 11-year history of sero-negative rheumatoid arthritis (Stage III) maintained by daily administration of 10 mg of prednisolone and 300 mg of actarit. On admission, he showed meningeal irritation and a marked increase in eosinophils in his cerebrospinal fulid (CSF) (457/microliter), while eosinophils in his peripheral blood were not increased (0/microliter). Shortly after admission he fell into a coma. Upon measurement in the coma state, his peripheral blood eosinophil count was found to be increased (max: 1742/microliter). Parasitic infection, Angiostrongylus cantonensis in particular, was excluded both by repeated microscopic examination of CSF and by immunological approaches for CSF and serum. Serum examinations showed broad cross-reaction between various parasitic antigens and positive myeloperoxdase-antineutrophil cytoplasmic antibody (18 EU/ml). Three pulses of methylprednisolone (500 mg/day) followed by conventional prednisolone therapy (60 mg/day) was effective for alleviating the signs and symptoms of eosinophilic meningoencephalitis. In this patient, it was considered that the cerebrospinal angiitis resulting in eosinophilic meningoencephalitis had been elicited by immunological abnormalities.

Antibodies, Antineutrophil Cytoplasmic↗

PubMed1998

Increased plasma epinephrine but not reduced heart rate variability leads to ventricular arrhythmias in patients with acute myocardial infarction.

Ventricular arrhythmia observed in the acute stage of myocardial infarction is profoundly related to the autonomic balance. To investigate prediction of ventricular arrhythmia, heart rate variability and plasma catecholamine concentration were simultaneously measured for a week in 17 consecutive patients with first anterior or anteroseptal Q wave infarction treated without specific coronary intervention. The cross-sectional plot of coefficient of variance (= standard deviation of N-N interval/mean N-N interval x 100; %) as a function of plasma epinephrine on the day of admission remained lower than the standard average. Ventricular premature contractions increased in proportion to the plasma epinephrine concentration. In the first week of hospitalization, plasma epinephrine concentration and frequency of premature contraction decreased exponentially, whereas the coefficient of variance showed a modest decline. Ventricular tachycardia refractory to xylocaine with rate accelerating with persistence was observed only in patients with the peak epinephrine concentration > 375 pg/ml. Plasma epinephrine concentration rather than coefficient of variance during sleep after the first acute episode is more closely related to the following triggered ventricular arrhythmia.

Aged↗

PubMed1998

[Significance of percutaneous endoscopic gastrostomy (PEG) in home medical care].

In recent years, reflecting our aging society, the importance of home medical care has been recognized in view of medical economic and patients' needs. We are actively responding to this trend by positioning home medical care as a "new comprehensive medical care" and by organizing home medical care team. Percutaneous endoscopic gastrostomy (PEG) was developed by Ponsky et al. in 1980. While it has been widespread in Europe and America, it has not been much used in Japan yet. PEG does not require complicated hand skills. It is less invasive and sufficiently applicable to severe cases. Also, since the nursing management is easy, it can be carried out at home. It is an enteral feeding method with superb features as described earlier, in view of home medical care that attaches importance to the quality of life (QOL). In this research, we investigated hand skills for PEG and problems with PEG nutrition. Also, we referred to new possibilities for PEG in home medical care. The success of home medical care will depend on the introduction of PEG, which plays a key role in home medical care.

Aged↗

PubMed1997

Nonpolar interactions of thrombin S' subsites with its bivalent inhibitor: methyl scan of the inhibitor linker.

We have designed bivalent thrombin inhibitors, consisting of a nonsubstrate type active site blocking segment, a hirudin-based fibrinogen recognition exosite blocking segment, and a linker connecting these segments. The inhibition provided by the bivalent inhibitors with various linker lengths revealed that a minimum of 15 atoms was required for simultaneous binding of the two blocking segments of the inhibitor to thrombin without significant distortion. The crystal structure of the inhibitors with a 16-atom linker showed some conformational flexibility in the linker portion which still lies deep in the groove joining the active site and the fibrinogen recognition exosite. Since the thrombin S' subsites are not well characterized, we designed a new strategy to search for possible nonpolar interactions between the linker and the thrombin S' subsites. This strategy, the "methyl scan", is based on the incorporation of a methyl side chain at each atom position of the linker by using sarcosine, D,L-alanine, D,L-3-aminoisobutyric acid, or N-methyl-beta-alanine. The methyl groups on the second and the eighth atom positions of the linker, which correspond to the side chains of the P1' and the P3' residues, respectively, improved the affinity of the inhibitors significantly. Further study of the stereospecificity showed that L-Ala at the P1' residue and D-Ala at the P3' residue preferably improved the affinity of the inhibitors 20- and 25-fold, respectively. Molecular modeling calculations using a methyl probe were also carried out to identify favorable nonpolar interacting sites on the thrombin surface. Two sites were identified in the vicinity of the P1' and the P3' residues, supporting the validity of the methyl scan method. Thus, this study has improved our understanding of the interactions taking place in this groove. In particular, we have been able to show that some specific structural features, such as hydrophobic complementarity between the linker and the thrombin S' subsites, could be exploited and make these inhibitors trivalent.

Animals↗

PubMed1997

Determination of ticarcillin epimers in plasma and urine with high-performance liquid chromatography.

A high-performance liquid chromatogaphic method was developed for determining the concentrations of ticarcillin (TIPC) epimers in human plasma and urine. Samples were prepared for HPLC analysis with a solid-phase extraction method and the concentrations of TIPC epimers were determined using reversed-phase HPLC. The mobile phase was a mixture of 0.005 M phosphate buffer (pH 7.0) and methanol (12:1, v/v) with a flow-rate of 1.0 ml/min. TIPC epimers were detected at 254 nm. Baseline separation of the two epimers was observed for both plasma and urine samples with a detection limit of ca. 1 microg/ml with a S/N ratio of 3. No peaks interfering with either of the TIPC epimers were observed on the HPLC chromatograms for blank plasma and urine. The recovery was more than 80% for both plasma and urine samples. C.V. values for intra- and inter-day variabilities were 0.9-2.1 and 1.1-6.4%, respectively, at concentrations ranging between 5 and 200 microg/ml. The present method was used to determine the concentrations of TIPC epimers in plasma and urine following intravenous injection of TIPC to a human volunteer. It was found that both epimers were actively secreted into urine and that the secretion of TIPC was not stereoselective. Plasma protein binding was also measured, which revealed stereoselective binding of TIPC in human plasma.

Adult↗

PubMed1997

Hemorheologic profiles of plasma fibrinogen and blood viscosity from silent to acute and chronic cerebral infarctions.

Hemorheologic changes from silent to acute and chronic cerebral infarction have seldom been reported. We evaluated hemorheologic profiles of the whole blood viscosity, plasma viscosity and fibrinogen level in stroke at-risk patients with silent cerebral infarction, patients with acute or chronic cerebral lacunar infarction, and subjects at low risk for stroke. Hemorheologic profiles were measured in 88 subjects: (1) 36 patients with silent cerebral infarction (mean 64.7 years), who provided no clinical history of having had definitive stroke but showing > 5 mm lesions of cerebral infarction or periventricular hyperintensity (PVH) observed in magnetic resonance imaging (MRI) T2-weighted images; (2) 12 patients with acute cerebral lacunar infarction (mean 69.1 years), measured within 3 days and repeated 1 month after onset; (3) 25 patients with chronic cerebral lacunar infarction (mean 66.2 years), measured 12.5 months after onset; and (4) 15 subjects at low risk for stroke (mean 65.8 years) without cardiovascular risk factors or lesions on MRI. Patients with silent cerebral infarction were subdivided into two groups of less advanced and more advanced grades, based on the number of infarctions or the grade of PVH. Whole blood viscosity (shear rates: 22.5-225.0 s-1), corrected blood viscosity for 45% standard hematocrit (Hct), plasma viscosity, fibrinogen, serum total protein, albumin, and Hct were measured. Plasma fibrinogen levels were lower in silent cerebral infarctions than in chronic cerebral infarctions (P < 0.01), and patients with more advanced grades of silent cerebral infarction showed higher levels of plasma fibrinogen than those with less advanced grades (P < 0.01 and P < 0.05). Whole blood viscosity, corrected blood viscosity (Hct 45%), plasma viscosity and fibrinogen levels in acute cerebral infarction within 3 days after onset were higher significantly than those in subjects at low risk for stroke. Plasma fibrinogen level persisted to be elevated up to 1 month after onset, which continued as well in patients with chronic cerebral infarction. Advanced grades of silent cerebral infarction in stroke at-risk patients are accompanied by elevations of plasma fibrinogen level, which increases further after onset of cerebral infarction; such abnormalities persist up to the chronic stage. Elevated plasma fibrinogen level might reflect progression of atherogenesis in patients with advanced grades of silent cerebral infarction, resulted in an increased probability as to be a risk factor for cerebral infarction.

Acute Disease↗

PubMed1997

Stereoselective pharmacokinetics of ibuprofen in rats: effect of enantiomer-enantiomer interaction in plasma protein binding.

Stereoselective pharmacokinetics of ibuprofen (IB) enantiomers were studied in rats. Unidirectional conversion from R-ibuprofen (R-IB) to S-ibuprofen (S-IB) was observed following intravenous administration. S-IB concentrations in plasma following racemate administration were simulated according to a conventional compartmental model using the parameters obtained after the administration of individual enantiomers, and resulted in overestimation of S-IB concentrations. Binding of IB enantiomers measured in rat plasma was stereoselective, the binding of R-IB being more favorable than that of S-IB. Moreover, there are interactions between IB enantiomers in binding, which may cause the increase of distribution volumes of IB enantiomers in the presence of their antipodes. Hence simulated S-IB concentrations according to a conventional compartment model were significantly greater than those observed. Indeed, when the enantiomer-enantiomer interactions were taken into account, simulation of S-IB concentrations in plasma following racemate administration was in good agreement with observed values. Therefore, interactions between stereoisomers as well as dispositional stereoselectivity have to be considered when pharmacokinetics of stereoisomers after administration of the racemate are compared to those after administration of individual isomers.

Animals↗

PubMed1997

Stereoselectivity and enantiomer-enantiomer interactions in the binding of ibuprofen to human serum albumin.

Binding of ibuprofen (IB) enantiomers to human serum albumin (HSA) was studied using a chiral fluorescent derivatizing reagent, which enabled the measurement of IB enantiomers at a concentration as low 5 x 10(-8) M. Scatchard analyses revealed that there were two classes of binding sites for both enantiomers. For the high affinity site, the number of the binding sites was one for both enantiomers, and the binding constant of R-IB was 2.3-fold greater than that of S-IB. The difference in the affinity at the high affinity site may result in the stereoselective binding of IB enantiomers at therapeutic concentrations. It was confirmed that the high affinity site of IB enantiomers is Site II (diazepam binding site) by using site marker ligands. Also, significant enantiomer-enantiomer interactions were observed in the binding. The binding data were quantitatively analyzed and a binding model with an assumption of competitive interactions only at the high affinity site simulated the binding characteristics of IB enantiomers fairly well.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1997

Effects of rice culture practices on the abundance of Culex mosquitoes (Diptera:Culicidae) in northern Thailand.

In 1991-1993, the density (numbers per 10 dips) and abundance (density x flooded area) of mosquitoes were studied in 3 areas of northern Thailand with different environmental conditions. Culex tritaeniorhynchus Giles, Cx. vishnui Theobald, and Cx. gelidus Theobald were predominant among the 8 Culex species collected. Abundance of these 3 species varied significantly among the 3 areas. Type of habitat classified according to agricultural practices in rainy and dry season significantly influenced larval abundance of Cx. tritaeniorhynchus and Cx. vishnui. Seasonal variation in larval abundance was significant only in Cx. vishnui. The response of the 3 vector mosquitoes to environmental heterogeneity is discussed.

Agriculture↗

PubMed1997

Contribution of the spinal cord to arousal from inhaled anesthesia: comparison of epidural and intravenous fentanyl on awakening concentration of isoflurane.

UNLABELLED: To investigate the contribution of modulation of afferent nociceptive inputs by an opioid in the spinal cord to arousal from inhaled anesthesia, we determined the awakening concentration of isoflurane in 50 unpremedicated patients scheduled for abdominal hysterectomy. Patients were assigned randomly to three groups. Group I received bolus injections of both epidural and intravenous (I.V.) saline, followed by both epidural and I.V. infusions at the rate of 0.2 mL x kg(-1) h(-1). Group II received an I.V. injection of fentanyl 2 microg/kg, followed by an infusion at the rate of 25 ng x kg(-1) x min(-1), and Group III received an epidural injection and infusion in the same administration regimen as Group II. Anesthesia was induced with and maintained by isoflurane in an air/oxygen mixture (fraction of inspired oxygen = 0.5) with no adjuvant drugs. The study drug was administered at the start of retroperitoneal suturing. The awakening concentrations of isoflurane in Groups I, II, and III (mean +/- SD) were 0.32% +/- 0.07%, 0.31% +/- 0.06%, and 0.24% +/- 0.06%, respectively. At that time, plasma fentanyl concentrations in Groups II and III were 1.12 +/- 0.09 ng/mL and 0.65 +/- 0.04 ng/mL, respectively. Epidural fentanyl infusion reduced the awakening concentration of isoflurane more (P < 0.01) than I.V. fentanyl infusion, despite the lower plasma concentration (P < 0.01) in the epidural group. These findings suggest that epidural fentanyl delays arousal from inhaled anesthesia by modulating the afferent nociceptive inputs in the spinal cord. The spinal cord may contribute to arousal from inhaled anesthesia through the regulation of afferent inputs by opioids along with the supraspinal region of the central nervous system (CNS), even if the effects of subarachnoid fentanyl on the higher CNS via the cephalad migration is taken into consideration. IMPLICATIONS: The present study revealed that the spinal cord, the lower level of central nervous system, contributed to arousal from general anesthesia, along with the higher central nervous system, by comparing the concentrations of an inhaled anesthetic, isoflurane, in the expiration of patients receiving systemic or regional administration of an opioid, fentanyl.

Adult↗

PubMed1997

Volume of infarction and blood flow in cerebral embolism.

The value of measuring asymmetry of cerebral perfusion semiquantitatively by single-photon emission computed tomography (SPECT) correlated with measuring the volume of infarction on computed tomography (CT) was evaluated in cerebral embolism. Eighteen patients with acute cerebral embolism (mean age: sixty-nine years) were evaluated. Ten were diagnosed as having middle cerebral artery (MCA) occlusion, 3 as having MCA branch occlusion, and 4 as having unilateral and 1 as having bilateral internal carotid occlusion. The infarct volume was measured, summing up the area of infarction on CT, at 8.5 days, mean time after onset. Outcomes of the patients were classified into three groups: good, fair, or dead, judged by the consequences one month after onset. Regional cerebral blood flow (rCBF) was measured in 9 of 10 surviving patients at one month, mean time after onset, by 123[iodine N-isopropyl-p-iodoamphetamine (IMP) SPECT. Semiquantitative rCBF index of asymmetry (AI) was evaluated from four regions of brain cortex. Eleven patients with < 300 mL infarct and 7 with > or = 300 mL infarct showed a significant difference of outcome with infarct volumes (P < 0.01). The mean AI value in patients with < 150 mL infarct was 31% while it was 52% with > or = 150 mL infarct (P < 0.039). There were significant linear correlations between mean AI values and the volumes of infarction or infarct/brain volume ratios (P < 0.034 or P < 0.018). The significant correlations of the AI values with the volumes of infarction suggest that the measured asymmetry of perfusion evaluated by SPECT could reflect the ultimate tissue damage and residual intact brain volume after cerebral embolism.

Aged↗