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Biomedical subjects

K Hanada

Publications and source records attributed to K Hanada.

At least 55 records · Page 3Linked to original sources
PubMed2001

Intestinal first-pass metabolism of eperisone in the rat.

PURPOSE: The purpose of this study was to clarify quantitatively the contribution of the intestine to the first-pass metabolism of eperisone in rats. METHODS: The systemic availabilities of eperisone were estimated by administering the drug into the duodenum, portal vein, and femoral vein in rats in vivo. The first-pass metabolism of eperisone was confirmed in the perfused rat small intestine in situ. Metabolism of eperisone to an omega-1-hydroxylated metabolite (HMO), the first step of eperisone metabolism, was studied using rat intestinal microsomes in vitro. RESULTS: The bioavailabilities in the intestine were 0.176 and 0.0879 at administration rates of 100 and 25 mg/h/kg, respectively, whereas those in the liver were 0.532 and 0.486, respectively. In the intestinal perfusion experiment, the appearance clearance to the portal vein from the intestinal lumen was much lower than the elimination clearance from the intestinal lumen, resulting in high metabolic clearance of eperisone in the small intestine. Eperisone was biotransformed to HMO by rat intestinal microsomes, and this was inhibited by alpha-naphthoflavone and an anti-rat CYP1A antibody. CONCLUSIONS: Those data strongly suggest that eperisone may be metabolized to HMO by CYP1A in rat intestinal microsomes during the first-pass through the epithelium of the small intestine.

Algorithms↗
PubMed2001

Optimal atrioventricular delay setting determined by evoked QT interval in patients with implanted stimulus-T-driven DDDR pacemakers.

Cardiac function is improved by optimizing the atrioventricular (AV) delay. An automatic optimizing function of AV delay may be necessary to achieve the most favourable haemodynamic state in paced patients. The QT interval may change when cardiac function is improved by optimizing the AV delay. The QT or stimulus-T interval is used as a sensor for rate-responsive pacemakers. Evoked (e) QT interval is measured as the time duration from the ventricular pace pulse (stimulus) and the T-sense point that is the steepest point of the intracardiac T wave (stimulus-T interval). The relationship between AV delay, eQT interval and cardiac function was studied in 10 patients (73 +/- 10 (SD) years old) with an implanted stimulus-T-driven DDDR pacemaker. Cardiac output (CO) and pulmonary capillary wedge pressure (PCWP) were measured by Swan-Ganz catheter. The AV delay was prolonged stepwise by 30 ms. Electrocardiogram event markers which indicated ventricular spike and sensed T wave were recorded, and the interval between two event markers was measured as eQT interval. When AV delay was changed from 240 ms to the AV delay at which CO was maximal (172 +/- 33 ms), eQT interval prolonged from 346 +/- 60 to 353 +/- 62 ms (P < 0.01). There was a significant positive correlation between the optimal AV delay at which CO was maximal (172 +/- 33 ms) and the optimal AV delay which was predicted from the maximum eQT interval (179 +/- 37 ms, r = 0.92, P < 0.001). When AV delay was changed from 240 ms to the predicted optimal AV delay, CO increased from 4.2 +/- 0.7 to 4.5 +/- 0.81.min-1 (P < 0.001) and PCWP was decreased from 7.1 +/- 4.0 to 5.7 +/- 3.1 mmHg (P < 0.05). In conclusion, the optimal AV delay can be predicted from the eQT interval which is sensed by an implanted pacemaker. Automatic setting of the optimal AV delay may be achieved by the QT sensor of an implanted pacemaker.

Aged↗
PubMed2001

Condylar bony change, disk displacement, and signs and symptoms of TMJ disorders in orthognathic surgery patients.

OBJECTIVE: We sought to investigate the relationship between condylar bony change and disk displacement with respect to the signs and symptoms of temporomandibular joint (TMJ) disorders in patients undergoing orthognathic surgery. STUDY DESIGN: We performed a cross-sectional retrospective study of the pretreatment helical computed tomography scans of 129 orthognathic surgery patients. RESULTS: Condylar bony change, unilaterally or bilaterally, was found in 35.7% of the subjects and 24.4% of the joints. Disk displacement, unilaterally or bilaterally, was seen in 41.4% of the subjects and 29.5% of the joints. The type of craniofacial deformity was significantly associated with condylar bony change and disk displacement. No association of clinical symptoms with respect to craniofacial deformity, condylar bony change, or disk displacement was found except in the case of TMJ sounds. CONCLUSION: The results suggested that craniofacial deformity might be related to TMJ disorders, but the only clinical symptom associated with types of craniofacial deformity was TMJ sounds.

Adolescent↗
PubMed2001

Condylar bony change and self-reported parafunctional habits in prospective orthognathic surgery patients with temporomandibular disorders.

OBJECTIVE: The purpose of this study was to investigate the relationship between self-reported parafunctional habits and condylar bony change and disk displacement in orthognathic surgery patients with signs and symptoms of temporomandibular joint disorders. STUDY DESIGN: This is a cross-sectional retrospective study of pretreatment helical computed tomography scans and questionnaires of 94 female orthognathic surgery patients. RESULTS: Condylar bony change, unilaterally or bilaterally, was found in 56.4% of the subjects, or 43.6% of the joints. Disk displacement, unilaterally or bilaterally, was seen in 59.6% of the subjects, or 45.7% of the joints. Bruxism and clenching was significantly associated with condylar bony change and disk displacement. Subjects with 3 or more parafunctional habits showed a significantly higher rate of bilateral condylar bony change. CONCLUSION: Our results suggest that bruxism and clenching might be related to deterioration of the temporomandibular joint and that the greater the number of parafunctional habits a subject has, the higher the risk of condylar bony change.

Bruxism↗
PubMed2001

Sex-related differences in the renal disposition of the acidic metabolite of clentiazem in rat.

1. Sex-related differences in the renal excretion of the acidic compounds (+)-(2S,3S)-8-chloro-2,3,4,5-tetrahydro-3-hydroxy-2-(4-hydroxyphenyl)-4-oxo-1,5-benzothiazepin-5-acetic acid (MA4; one of the acidic metabolites of clentiazem), probenecid (PB) and methotrexate (MTX) have been investigated in the 7-week-old male and female Sprague-Dawley rat using an in vivo renal clearance technique. 2. The extent of plasma protein binding of MA4, PB and MTX was approximately 96, 95 and 65%, respectively, and it did not differ significantly between the male and female rat. On the other hand, the unbound renal clearance (CLrf) of MA4 in the female was approximately 300 times higher than that in male, and the ratio of this clearance to the glomerular filtration rate (GFR) was approximately 10, suggesting that MA4 undergoes extensive active renal secretion in the female. Furthermore, the CLrf/GFR ratio was significantly decreased by co-administration of PB. In contrast, no sex-related difference in the renal excretion of PB could be detected because its CLrf was very low and reabsorption contributed extensively to its renal disposition. The CLrf/GFR for MTX was approximately 2.5 but did not differ significantly between the male and female. 3. The renal organic anion transport systems in rat show sex-related differences and have different substrate-specific characteristics.

Animals↗
PubMed2001

Role of DNA ligase in the illegitimate recombination that generates lambdabio-transducing phages in Escherichia coli.

We studied the role of DNA ligase in illegitimate recombination in Escherichia coli. A temperature-sensitive mutation in the lig gene reduced the frequency with which lambdabio-transducing phages were generated to 10-14% of that of wild type under UV irradiation. Reintroduction of the lig gene into this mutant restored the frequency of recombinant phage generation to that of wild type. Furthermore, overexpression of DNA ligase enhanced illegitimate recombination by 10-fold with or without UV irradiation. In addition, when DNA ligase was present in only limited amounts, UV-induced or spontaneous illegitimate recombination occurred exclusively at hotspot sites that have relatively long sequences of homology (9 or 13 bp). However, when DNA ligase was overexpressed, most of the illegitimate recombination took place at non-hotspot sites having only short sequences of homology (<4 bp). Thus, the level of ligase activity affects the frequency of illegitimate recombination, the length of sequence homology at the recombination sites, and the preference for recombination at hotspots, at least after UV irradiation. These observations support our hypothesis that the illegitimate recombination that generates lambdabio-transducing phages is mediated by the DNA break-and-join mechanism.

Base Sequence↗
PubMed2001

Population pharmacokinetic analysis of cisplatin and its metabolites in cancer patients: possible misinterpretation of covariates for pharmacokinetic parameters calculated from the concentrations of unchanged cisplatin, ultrafiltered platinum and total platinum.

BACKGROUND: Usually, total and filtered platinum concentrations in plasma are monitored after cisplatin administration. However, these concentrations represent a mixture of unchanged cisplatin and metabolites. In this work, we studied population pharmacokinetic analysis based on these platinum concentrations. METHODS: Twenty-seven patients (23 males, four females) were administered cisplatin (60-100 mg/m2) with intravenous constant infusion for 90 min. Blood samples were taken at about three points per patient. The concentrations of cisplatin and platinum in the plasma were determined by high-performance liquid chromatography and atomic absorption spectrometry, respectively. Population pharmacokinetic analysis was performed using the program NONMEM (Version V) with the one- or two-compartment model with zero-order infusion. RESULTS: The clearance and volume of distribution for all platinum species studied were significantly related to the body surface area of the patients. Only the clearance of filtered platinum was significantly related to urinary N-acetyl-beta-D-glucosaminidase and the other covariates were not related to these pharmacokinetic parameters with respect to unchanged cisplatin and total platinum concentrations. CONCLUSION: The dosage regimen based on the filtered platinum concentration which is usually monitored may result in possible misinterpretation because the detected covariate is different between unchanged cisplatin and filtered platinum.

Aged↗
PubMed2001

A case of anterior open bite developing during adolescence.

Imaging studies have reported on the relationship between temporomandibular joint (TMJ) degeneration and facial deformity. These studies have suggested that mandibular growth is affected by TMJ degeneration, resulting in altered skeletal structure as mandibular retrusion. However, there are very few longitudinal case reports on TMJ osteoarthrosis (OA). Progressive open bite occurred in an adolescent patient with TMJ OA. Cephalometric analysis showed a downward and backward rotated mandible, and a labial inclination of the upper incisor. Magnetic resonance imaging showed internal derangement without reduction and erosion in the right and the left condyles. Although the cause of open bite is unclear in this case, tongue thrusting, and internal derangements in the temporomandibular joint were suspected as causes of the open bite.

Bone Resorption↗
PubMed2001

Role of DnaB helicase in UV-induced illegitimate recombination in Escherichia coli.

To study the involvement of DNA replication in UV-induced illegitimate recombination, we examined the effect of temperature-sensitive dnaB mutations on illegitimate recombination and found that the frequency of illegitimate recombination was reduced by an elongation-deficient mutation, dnaB14, but not by an initiation-deficient mutation, dnaB252. This result indicates that DNA replication is required for UV-induced illegitimate recombination. In addition, the dnaB14 mutation also affected spontaneous or UV-induced illegitimate recombination enhanced by the recQ mutation. Nucleotide sequence analyses of the recombination junctions showed that DnaB-mediated illegitimate recombination is short homology dependent. Previously, Michel et al. (B. Michel, S. Ehrlich, and M. Uzest, EMBO J. 16:430--438, 1997) showed that thermal treatment of the temperature-sensitive dnaB8 mutant induces double-stranded breaks, implying that induction of illegitimate recombination occurs. To explain the discrepancy between the observations, we propose a model for DnaB function, in which the dnaB mutations may exhibit two types of responses, early and late responses, for double-stranded break formation. In the early response, replication forks stall at damaged DNA, resulting in the formation of double-stranded breaks, and the dnaB14 mutation reduces the double-stranded breaks shortly after temperature shift-up. On the other hand, in the late response, the arrested replication forks mediated by the dnaB8 mutation may induce double-stranded breaks after prolonged incubation.

Bacterial Proteins↗
PubMed2001

Stereoselective pharmacokinetics and pharmacodynamics of disopyramide and its metabolite in rabbits.

The extent to which interactions between enantiomers of disopyramide and between disopyramide and its metabolite, mono-N-dealkylated disopyramide (MND), contribute to stereoselectivity of the anti-arrhythmic effect has been investigated in rabbits by measuring the prolongation of the QUc interval. The plasma unbound fraction of disopyramide enantiomers was constant at a concentration range of 1.44-28.9 microM. An intravenous infusion study of the disopyramide enantiomer or racemate suggested that the S-enantiomer had a pharmacological effect, determined by linear regression analysis, approximately 3.3-times more potent than that of the R-enantiomer. Furthermore, the effect caused by racemic disopyramide was the sum of that elicited by both enantiomers individually. No significant difference was observed between the slope of linear regression analysis of intravenous infusion and that of intravenous bolus injection. Single intravenous bolus injection of MND did not affect the QUc intervals. In conclusion, the S-enantiomer of disopyramide was approximately 3.3-times more potent pharmacologically than the R-enantiomer. The relationship between plasma concentration of the disopyramide enantiomers and pharmacological effect was the sum of each enantiomer individually.

Action Potentials↗
PubMed2001

Stereoselective pharmacokinetics and pharmacodynamics of verapamil and norverapamil in rabbits.

We have estimated the pharmacokinetic and pharmacodynamic interactions of verapamil (VP) enantiomers and also the interaction between VP and its metabolite, norverapamil (NVP). ECGs of conscious rabbits were studied to determine the pharmacokinetics of VP enantiomers and racemic NVP in relation to their prolongation effect on PR intervals, which were used as an index of VP's antiarrhythmic effect. Plasma free fractions of VP enantiomers showed constant values at concentrations ranging from 0.022 to 1.10 microm. There were no interactions between enantiomers or between VP and NVP. The pharmacological effect of the S-enantiomer (S-VP), which was determined by linear regression analysis, showed it was about 20 times more potent than that of the R-enantiomer (R-VP). The effect of racemic VP was the simple sum of those elicited by both enantiomers. These relationships were not significantly different between intravenous infusion and bolus injection. Simultaneous intravenous infusion of NVP had no influence on the PR intervals. In conclusion, we demonstrated that the relationship between plasma unbound concentration of VP enantiomers and their pharmacological effect was the simple sum of two enantiomers.

Animals↗
PubMed2001

A new double cuff sphygmotonometer for accurate blood pressure measurement.

Accurate measurement of blood pressure (BP) is essential in the diagnosis and treatment of hypertension, but neither auscultatory nor oscillometric methods measure intra-arterial BP accurately in all circumstances. Algorithms for automatic BP-measuring devices differ from manufacturer to manufacturer, and no clear authorized algorithm criteria have yet been established. We have devised a double-cuff sphygmotonometer to measure BP on the basis of clear algorithms, and investigated the accuracy of this new method by comparing it with the photo-oscillometric method, which is the most accurate method for non-invasive measurement of intra-arterial BP. In the new method, a small cuff (3x6 cm) replaces the photo-sensor in the brachial cuff (13x24 cm) of the photo-oscillometric device, and BP is determined by means of the oscillation within the small cuff. The comparison based on procedures of AAMI-protocol was performed in 136 hypertensive patients and 54 normotensive subjects. The difference in systolic BP between the photooscillometric and double-cuff methods was -2.26+/-2.31 mmHg (89% under 5 mmHg), and the corresponding difference in diastolic BP was 1.9+/-2.50 mmHg (94% under 5 mmHg). In conclusion, we have devised a new double-cuff method which improves on the photo-oscillometric method, and although it seems to be less accurate than the photo-oscillometric method, the clarity of its algorithm makes it superior to the conventional oscillometric and auscultatory methods employing only one cuff.

Algorithms↗
PubMed2001

Acute effects of E-3174, a human active metabolite of losartan, on the cardiovascular system in tachycardia-induced canine heart failure.

The aim of this study was to evaluate the acute effects of E-3174, a human active metabolite of the AT1 receptor antagonist, losartan, on hemodynamic functions in dogs with severe heart failure (HF). In dogs, insignificant plasma levels of E-3174 are present following administration of losartan, and therefore, the effects of these two drugs can be studied independently in the dog. HF was established by rapid pacing of the right ventricle (250-270 beats/min) for 4 weeks. We examined changes in cardiovascular functions after acute intravenous administration of losartan (1 mg/kg) and E-3174 (0.3 and 1 mg/kg), as well as an ACE inhibitor, enalapril (0.3 and 1 mg/kg), under condition of HF. The HF before treatment was characterized by increases in pre- and after-load of the left ventricle (LV), consequent low cardiac output, and LV dilatation. E-3174 at 0.3 and 1 mg/kg reduced pulmonary artery pressure (-13+/-6% and -22+/-3% from baseline, respectively, p<0.05), pulmonary capillary wedge pressure (-18+/-4% and -36+/-10%, p<0.05) and mean arterial pressure (-24+/-2% and -36+/-7%, p<0.05), increased stroke volume (SV: +12+/-7% p>0.05; +36 +/-19%, p<0.05), and reduced peripheral resistance (-23+/-5% and -41+/-9%, p<0.05), but had no effect on the first derivative of left ventricular pressure (dP/dt/P) or the time constant for relaxation. Effects of losartan at 1 mg/kg were similar to those of 0.3 mg/kg of E-3174. Enalapril at 1 mg/kg caused changes comparable to those seen after E-3174 administration (1 mg/kg), except that the increase in SV (+16+/-8%, p<0.05) with enalapril was not as great as that with E-3174. Both losartan at 1 mg/kg and E-3174 at 0.3 and 1 mg/kg increased fractional shortening to a similar extent (FS: +52+/-12%, +47+/-8% and +56+/-8%), while enalapril at 0.3 and 1 mg/kg had no significant effects on FS. Reflex elevation of plasma renin activity induced by 1 mg/kg of E-3174 was similar to that caused by 1 mg/kg of enalapril, suggesting that the two drugs achieved similar inhibition of the endogenous renin angiotensin system. Our study demonstrated that acute blockade of the AT1 receptor with E-3174 reduced elevated pre- and after-load and consequently increased stroke volume in a canine HF model. With the exception of changes in stroke volume, these effects of E-3174 were comparable to those produced by enalapril, and were 3 times stronger than those by losartan.

Angiotensin Receptor Antagonists↗
PubMed2001

Characterization of phagocytic hemocytes in Ornithodoros moubata (Acari: Ixodidae).

Effects of fetal bovine serum (FBS) and complement on phagocytic activity in Ornithodaros moubata (Murray 1877) hemocytes and protease activity in the hemocytes were examined. At least three morphologically different cell types, granulocytes, plasmatocytes, and prohemocytes, were detected in hemolymph of O. moubata, and granulocytes and plasmatocytes showed phagocytic activity. FBS altered phagocytic activity of granulocytes, and complement affected phagocytic activity of plasmatocytes. Ticks were inoculated with fluorescent polystyrene beads in combination with FBS or complement. The average number of beads in granulocytes was significantly higher in the FBS injected group than the control (P < 0.01). The percentage of bead-ingesting plasmatocytes in complement inoculated ticks was significantly lower than that in heat-inactivated complement inoculated and control ticks (P < 0.05). Proteases of tick hemocytes localized in small granules in the cytoplasm not only in phagocytic hemocytes but also in prohemocytes. Results suggested modulation of tick hemocyte function through serum components, and digestion of phagocytosed foreign bodies in the hemocytes.

Animals↗
PubMed2001

Pathophysiological roles of endogenous endothelin-1 in dogs with chronic heart failure produced by rapid right ventricular pacing.

This study was designed to analyze the pathophysiological role of the endogenous endothelin (ET) system and the therapeutic approach to congestive heart failure (CHF) with ET(A)/ET(B) receptor antagonists in a canine CHF model. After 3 weeks of rapid right ventricular pacing (240 beats/min), concentrations of immunoreactive ET-1 in dogs increased approximately 2-fold in plasma and in the left and right ventricles but not in the lung. There were no meaningful changes in the density and affinity of total ET receptors, or in the ratio of ET(A) to ET(B) receptors. To clarify the functional role of endogenous ET, we examined the effects of acute injection of J-104132 (1 and 3 mg/kg i.v.), an ET(A)/ET(B) receptor antagonist, on cardiovascular and renal function in dogs with CHF. Compared with vehicle, J-104132 at both doses significantly decreased pulmonary artery pressure (PAP), pulmonary capillary wedge pressure (PCWP), and mean arterial pressure (MAP), and increased cardiac output (CO) and renal blood flow. J-104132 had no effects on heart rate and cardiac contractility. In addition, we examined whether J-104132 has an additive effect in the presence of enalaprilat. J-104132 (1 mg/kg i.v.) administered after enalaprilat (0.05 mg/kg i.v.) induced further decreases in MAP, PCWP and PAP, and further increases in CO, resulting in further decreases in total peripheral resistance. These results indicate that the endogenous ET system is exaggerated in CHF and has a detrimental effect on cardiac function. Therefore, J-104132 given alone or as combination therapy may play a beneficial role in the treatment of CHF in humans.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2001

[Epilepsy in patients with severe motor and intellectual disabilities: a long-term follow-up].

Long-term prognosis of epilepsy was investigated on 117 institutionalized patients with severe motor and intellectual disabilities, who were above 15 years of age in 1977, for a 20-year-period from 1977 to 1997. The incidence of epilepsy was 64.1% (75 patients), which was active in 28 patients (37.3%). The patients with the most severe psychomotor disabilities (bedridden and DQ < 20) showed the highest incidence of epilepsy (85.0%). Patients who died during the follow-up period showed higher incidence of active epilepsy (p < 0.01). During the follow-up of 94 surviving patients, persistence, relapse, and onset of seizures were frequent in patients with most severe intellectual disability, whereas those with less severe intellectual disability (20 < DQ < 35) were all seizure-free. Twenty-one patients had active epilepsy; symptomatic partial epilepsy in 17 (81.0%) and generalized epilepsy in 4 (19.0%). Notably, 5 of the 6 patients with persistent frequent seizures had age-dependent epileptic encephalopathy; persistent Lennox-Gastaut syndrome (LGS) (2 patients), severe epilepsy with multiple independent spike foci evolved from West syndrome (WS) and LGS (2 patients), and partial epilepsy with the history of LGS (1 patient).

Adolescent↗