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Biomedical subjects

I Muraoka

Publications and source records attributed to I Muraoka.

At least 19 recordsLinked to original sources

Venous occlusion to the lower limb attenuates vasoconstriction in the nonexercised limb during posthandgrip muscle ischemia.

We investigated the effects of increases in calf volume on cardiovascular responses during handgrip (HG) exercise and post-HG exercise muscle ischemia (PEMI). Seven subjects completed two trials: one control (no occlusion) and one venous occlusion (VO) session. Both trials included a baseline measurement followed by 15 min of rest (REST), 2 min of HG, and 2 min of PEMI. VO was applied at 100 mmHg via cuffs placed around both distal thighs during REST, HG, and PEMI. Mean arterial pressure, heart rate, forearm blood flow (FBF) in the nonexercised arm, and forearm vascular resistance (FVR) in the nonexercised arm (FVR) were measured. During REST and HG, there were no significant differences between trials in all parameters. During PEMI in the control trial, mean arterial pressure and FVR were significantly greater and FBF was significantly lower than baseline values (P < 0.05 for each). In contrast, in the VO trial, FBF and FVR responses were different from control responses. In the VO trial, FBF was significantly greater than in the control trial (4.7 +/- 0.5 vs. 2.5 +/- 0.3 ml x 100 ml(-1) x min(-1), P < 0.05) and FVR was significantly lower (28.0 +/- 4.8 vs. 49.1 +/- 4.6 units, respectively, P < 0.05). These results indicate that increases in vascular resistance in the nonexercised limb induced by activation of the muscle chemoreflex can be attenuated by increases in calf volume.

Adult↗

[Development of sigma-receptor ligands and clinical trials].

There are at least two classes of sigma-receptors, termed sigma 1 and sigma 2. Recently, the sigma 1-receptor has been completely sequenced in different species. The amino acid sequences of the different purified proteins are highly homologous, but it shares no homology to know mammalian proteins. These results suggest that the sigma 1 receptor is a distinct entity from any often known receptors. sigma-Receptors are involved in many physiological functions. Therefore, sigma-ligands show many different pharmacological effects such as glucose utilization, neuroprotective, antipsychotic, antidepressive, anxiolytic, nootropic, antiepileptic, antiabuse, antitussive, antidiarrhea, anti-inflammatory, tear protein releasing stimulant and central anti-micturition reflex actions. These results suggest that sigma-receptors are very promising targets for the development of new drugs that have new mechanisms of action.

Animals↗

Temporal effect of muscle contraction on respiratory sinus arrhythmia.

The purpose of this investigation was to compare the heart rate variability at respiratory frequency (HRVRF) in muscle contractions during the inspiratory phase with that during the expiratory phase. Eight volunteers performed pedaling on a cycle ergometer, twice a cycle of respiration (4 sec) against a load of 0.25 Nm/kg BW, of which the timing was adjusted to twice during the inspiration phase (I), once during the expiration, once during the inspiration (EI), or twice during the expiration phase (E). Spectral analysis was applied to the R-R intervals of each condition. The amplitude of HRVRF in E was less than half of 1 (9 +/- 2 msec versus 23 +/- 2 msec). The results indicate that the timing of muscle contraction can affect the heart rate variability even at the frequency band of respiration.

Adult↗

Influence of two different modes of resistance training in female subjects.

In resistance training, it has been empirically accepted that muscle hypertrophy is developed by low intensity and high volume training, while muscle strength and power are developed by high intensity and low volume training. The purpose of the present study was to investigate the influence of two different modes of resistance training on isokinetic strength and muscle cross-sectional area (CSA) in females. Eleven females, who had no experience in resistance training, participated in this study and were randomly divided into two groups. The former consisted of 4-5 sets of 15-20 RM (repetition maximum) with sufficient rest between sets (Group H), while the latter consisted of 8-9 sets of 4-6R M with 90 s of rest between sets (Group S). The former was assumed to be appropriate for muscle hypertrophy and the latter muscle strength, respectively. All subjects completed isotonic knee extension exercise three times a week for 8 weeks. Measurements were made on quadriceps muscle cross-sectional area (CSA) and isokinetic torques at 0, 60, 180, and approximately 300 degrees before training, at the fifth week and the end of training period. Muscle CSA was defined as the sum of CSA measured at 30, 50 and 70% of femur length. After training, muscle CSA had significantly increased in both groups: 3.3 +/- 0.7% (p < .05) for group H and 3.6 +/- 1.1% (p < .05) for group S, respectively. While the changes in isokinetic torque were 43.4 +/- 47.5% (p < .05) for group H and 27.4 +/- 31.3% (p < .05) for group S, respectively. In both groups the percentage changes of the isokinetic strength were significantly higher than those of the CSA. No significant difference in these variables were found between the two groups. These results suggest that during the early phase of resistance training two different modes of resistance training may have similar effects on muscle CSA and isokinetic strength in untrained females.

Adult↗

Long-lasting effect of training on insulin responsiveness in the rat.

In vivo insulin sensitivity and responsiveness were assessed in rats one day (Day 1), seven days (Day 7), and 3 weeks (Day 21) after cessation of training, using a 2-stage sequential hyperinsulinemic euglycemic clamp technique (insulin infusion rate: 4.4 mU.kg-1.min-1 and 26.4 mU.kg-1.min-1). The day after the last bout of exercise, the glucose infusion rate (GIR-L: 4.4 mU-dose), which is an index of insulin sensitivity, was significantly higher in the trained group (11.5 +/- 1.1 mg.kg-1.min-1) than in the control group (6.1 +/- 0.6 mg.kg-1.min-1; p < 0.01). Detraining decreased GIR-L significantly, to 7.4 +/- 0.5 (Day 7: p < 0.01) and 7.4 +/- 0.5 mg.kg-1.min-1 (Day 21: p < 0.05). Insulin responsiveness, assessed by response to a 26.4 mU-dose of insulin (GIR-H), was also increased by training, from 21.8 +/- 1.2 mg.kg-1.min-1 (control) to 32.9 +/- 1.2 (Day 1, p < 0.01). Seven days after cessation of training period the level was nearly identical (33.4 +/- 1.0 mg.kg-1.min-1) and remained high 3 weeks after training (30.8 +/- 1.0: p < 0.01, vs control). These data indicate that insulin responsiveness remains elevated for 3 weeks after training, although insulin sensitivity is reversed within seven days. These results may be attributed to changes in body composition or long-lasting changes in post-receptor mechanisms.

Animals↗

Biliary and renal excretions of cefpiramide in Eisai hyperbilirubinemic rats.

Eisai hyperbilirubinemic mutant rats (EHBRs) with conjugated hyperbilirubinemia were recently derived from Sprague-Dawley rats (SDRs). The pharmacokinetic characteristics of the beta-lactam antibiotic cefpiramide (CPM), which is mainly excreted into bile, were investigated in 10- and 20-week-old EHBRs and were compared with those in 20-week-old healthy SDRs. The pharmacokinetic parameters of CPM after an intravenous administration of 20 mg/kg of body weight were estimated for each rat by noncompartmental methods. When compared with age-matched healthy SDRs, significant decreases (by approximately 30%) in the systemic clearance of CPM were observed in 20-week-old EHBRs. The biliary clearance of CPM in 20-week-old EHBRs markedly decreased to less than 10% of that in age-matched healthy SDRs, while total urinary recovery of unchanged CPM increased to threefold and renal clearance doubled. However, no significant differences in any of the pharmacokinetic parameters of CPM were observed between the two groups of EHBRs. There were no significant differences among the three groups in the steady-state volume of distribution of CPM. The present study indicates that hyperbilirubinemia induces an increase in the urinary excretion ability of CPM in return for a reduction in the biliary excretion.

Aging↗

Effects of traditional Chinese medicines on pharmacokinetics of levofloxacin.

The effects of single coadministrations of one of three traditional Chinese medicines, Hotyu-ekki-to, Rikkunshi-to, and Juzen-taiho-to, on the pharmacokinetics of levofloxacin (LVFX) were investigated with eight healthy volunteers in an open, random crossover fashion. Subjects each received a single oral dose of LVFX (200 mg) alone and then with a single coadministration of each Chinese medicine. There were no significant differences in any pharmacokinetic parameters of LVFX between the groups. Also, no significant changes in the urinary recovery (> 80%) and renal clearance of LVFX were observed. These results indicate that the Chinese medicines tested have no significant effect on the rate and extent of bioavailability or renal excretion of LVFX.

Adult↗

Influence of age on the disposition and renal handling of enprofylline in rats.

The effects of ageing on the pharmacokinetics, renal handling and protein binding of enprofylline were investigated in 6-, 13- and 18-month-old male Fischer 344 rats. Concentrations of enprofylline in plasma and urine were determined by HPLC, and pharmacokinetic parameters were estimated by model-independent methods. No significant differences in the volume of distribution, systemic clearance of enprofylline or urinary recovery of unchanged enprofylline (> 85%) were observed among any of the groups of rats. The dissociation constant and free fatty acid concentration in plasma increased with age. Age-dependent decreases in the systemic clearance for unbound drug were observed, and the volume of distribution for unbound drug tended to decrease with age. The ratio of systemic clearance for unbound drug to the glomerular filtration rate (GFR) decreased with ageing. Ageing was associated with decreases in the apparent maximum capacity of transport (Vmax)(223.33, 160.24 and 142.98 micrograms min-1 kg-1 for 6-, 13- and 18-month-old rats, respectively) and in the tubular secretory intrinsic clearance (Vmax/Km) of enprofylline (75.45, 51.03 and 44.13 mL min-1 kg-1, respectively), while a slight change in the Michaelis-Menten constant (Km) was observed. These results indicate that the mechanism responsible for age-related changes in the disposition and renal handling of enprofylline may be responsible for a decrease in the ability of the tubular anion transport system.

Aging↗

Lack of effect of Chinese medicines on bioavailability of ofloxacin in healthy volunteers.

Recently, Chinese medicines have become available as OTC drugs and are frequently prescribed with Western medicine for the treatment of various chronic diseases. In this study, the effect of the Chinese medicines Sho-saiko-to (TJ-9), Rikkunshi-to (TJ-43) and Sairei-to (TJ-114) on the bioavailability of ofloxacin (OFLX) was investigated in seven volunteers in an open, random crossover fashion. Subjects received a single oral dose of OFLX (200 mg) alone and with coadministrations of each Chinese medicine, at one-week intervals. Plasma and urine samples were analyzed by high-performance liquid chromatography. No significant differences in any estimated bioavailability parameters of OFLX were observed between the two phases. The urinary recovery of OFLX excreted within 24 h after the administration of OFLX alone, 80.6 +/- 3.9% (mean +/- SEM), was not significantly different from those after the coadministrations of the Chinese medicines (79.7 +/- 5.1% for TJ-9, 76.8 +/- 2.3% for TJ-43 and 80.3 +/- 5.3% for TJ-114), suggesting that there was no difference in the systemic availability of the four doses. These findings indicate that the Chinese medicines studied have no significant effect on the rate and extent of bioavailability of OFLX.

Administration, Oral↗

The effect of lipopolysaccharide on the disposition of xanthines in rats.

The effect of lipopolysaccharide (LPS) isolated from Klebsiella pneumoniae O3 on the pharmacokinetic behaviour and metabolism of the xanthines, theophylline and 1-methyl-3-propylxanthine (MPX), which are mainly metabolized by the liver, was investigated in rats. LPS was infused at 0.25 mg kg-1 over a period of 20-30 min, 2 h before the administration of theophylline (10 mg kg-1) or MPX (2.5 mg kg-1). Concentrations of both xanthines in plasma and concentrations of the parent drug and metabolites in urine were measured by HPLC. Model-independent methods were applied to estimate the pharmacokinetic parameters for both xanthines. No significant changes in the pharmacokinetic parameters or metabolism of theophylline were observed in rats pretreated with LPS. However, the total body clearance and volume of distribution of MPX were significantly increased by pretreatments with LPS. Significant decreases in the binding capacity and number of binding sites on the albumin molecule were observed in the presence of LPS. Changes occurring in the protein binding behaviour as a result of the introduction of LPS is a primary factor which not only increases the volume of distribution but also increases total body clearance. These results indicate that LPS has no effect on the pharmacokinetics and metabolic pathway of theophylline although it changes the disposition of MPX due to decreases in the extent of the protein binding of MPX which is highly bound to protein.

Animals↗

Autonomic control of heart rate during physical exercise and fractal dimension of heart rate variability.

The objectives of the present study were to investigate autonomic nervous system influence on heart rate during physical exercise and to examine the relationship between the fractal component in heart rate variability (HRV) and the system's response. Ten subjects performed incremental exercise on a cycle ergometer, consisting of a 5-min warm-up period followed by a ramp protocol, with work rate increasing at a rate of 2.0 W/min until exhaustion. During exercise, alveolar gas exchange, plasma norepinephrine (NE) and epinephrine (E) responses, and beat-to-beat HRV were monitored. HRV data were analyzed by "coarse-graining spectral analysis" (Y. Yamamoto and R. L. Hughson. J. Appl. Physiol. 71: 1143-1150, 1991) to break down their total power (Pt) into harmonic and nonharmonic (fractal) components. The harmonic component was further divided into low-frequency (0.0-0.15 Hz) and high-frequency (0.15-0.8 Hz) components, from which low-frequency and high-frequency power (Pl and Ph, respectively) were calculated. Parasympathetic (PNS) and sympathetic (SNS) nervous system activity indicators were evaluated by Ph/Pt and Pl/Ph, respectively. From the fractal component, the fractal dimension (DF) and the spectral exponent (beta) were calculated. The PNS indicator decreased significantly (P < 0.05) when exercise intensity exceeded 50% of peak oxygen uptake (VO2 peak). Conversely, the SNS indicator initially increased at 50-60% VO2peak (P < 0.05) and further increased significantly (P < 0.05) at > 60% VO2peak when there were also more pronounced increases in NE and E.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Cerebral hemorrhage in a case of antiphospholipid antibody syndrome].

We describe a 36-year-old man with antiphospholipid antibody syndrome complicated by cerebral hemorrhage. In December 1991 he was brought to another hospital with sudden onset of left hemiparesis and status epilepticus. He had been well previously. A CT scan and MRI showed a cerebral hematoma located in the right frontoparietal region. Twelve days later he was transferred to our hospital. Although a CT scan, MRI, and cerebral angiography were repeated, they did not reveal any abnormality regarding an etiology. Only persistently abnormal finding in laboratory studies was positive for lupus anticoagulant and anticardiolipin antibody, i.e. antiphospholipid antibodies. There was no serological evidence of SLE or other autoimmune diseases. Stereotactic biopsy of the hematoma wall and scalp artery showed no abnormality. Based on above findings we conclude that antiphospholipid antibodies have played an important role for the hemorrhage. Antiphospholipid antibody syndrome should be considered in a case of an unexplained cerebral hemorrhage especially in a young and normotensive patient.

Adult↗

Cardiac autonomic regulation after moderate and exhaustive exercises.

The purpose of this study was to investigate the recovery kinetics of cardiac autonomic regulation after acute exercises related to exercise intensity. Firstly, eight healthy subjects performed two kinds of constant load exercises at the work rate corresponding to 20% and 100% of the individual ventilatory threshold (VT) in addition to the exhaustive incremental exercise using a cycle ergometer. Blood pressure (BP) and oxygen uptake (VO2) were measured during 9 to 10 min after the exercises as well as the beat-by-beat recording of R-R intervals. Coarse graining spectral analysis (CGSA) was applied to heart rate variability (HRV) data sets of 5 min before exercise, last 5 min during exercise, and 8 to 10 min after exercise. The low frequency (0-0.15 Hz; LO) and the high frequency (0.15-0.5 Hz: HI) areas under power spectra were calculated for evaluating sympathetic (LO/HI) and vagal (HI) activities. The recovery for 10 min was sufficient to settle both VO2 and BP even after the exhaustion. Comparing to the pre-exercise value, however, HI was still suppressed until 10 min after the 100% VT exercise (522 +/- 300 vs. 122 +/- 63 msec2, p less than 0.05) while it was recovered at 10 min after the 20% VT one (353 +/- 122 vs. 487 +/- 159msec2). Secondly, six healthy subjects performed an incremental cycle exercise until exhaustion. The R-R intervals were monitored beat-by-beat during 30 min after exercise. The CGSA was applied to every five min data set of HRV during recovery phase.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[A patient with gigantic heterotopic gray matter with epileptic seizures].

We report a patient with partial seizure and gigantic heterotopic gray matter. A 23-year-old young man was admitted to our hospital with complaints of frequent epileptic seizures and psychiatric symptoms. There was psychomotor delay in infancy. At the age of 4 years, afebrile convulsions appeared on several occasions. Seizures characterized by a lapse of consciousness started at the age of 13 years. He often stayed in a fantasy world and became very emotional at such time. Cranial CT demonstrated an irregularity in the wall of right lateral ventricle and disappearance of the posterior horn on the same side. This lesion, adjacent to that wall, had a signal intensity that was similar to that of the gray matter on each sequence in MRI. Histopathology of this lesion showed a number of large and small neurons. Therefore, heterotopic gray matter was diagnosed. MRI demonstrated wide cortices suggesting polymicrogyria in the right parietal lobe. Complex partial seizures with eye deviation to the left were recognized. Interictal EEG showed frequent high voltage spikes in the right temporal, fronto-temporal and parieto-occipital areas independently. Therefore, epileptic foci were thought to exist in or around those lesions.

Adult↗

Dose-dependent pharmacokinetics of enprofylline and its renal handling in rats.

The effect of dosage on the pharmacokinetics of the potent bronchodilator enprofylline (3-propylxanthine; PX) and its renal handling were investigated in rats. Enprofylline (PX) was administered iv in dosages of 2.5, 10, 20, and 40 mg/kg, and PX concentration in plasma and urine was determined by HPLC. The pharmacokinetic parameters were estimated by model-independent methods. The disappearance of PX from plasma was delayed as dosage was increased. The corresponding pharmacokinetic parameters also showed dose dependency; increases in the volume of distribution (Vd) and mean residence time (MRT) and a decrease in total body clearance (CLT) were observed as dosage was increased from 2.5 to 40 mg/kg. Approximately 80% of the dose, however, was excreted in urine as unchanged PX. Plasma protein binding studies of PX showed concentration dependency and allowed determination of binding parameters, with an apparent dissociation constant (Kd) of 162.50 microM and a binding capacity (nP) of 565.23 microM. Some pharmacokinetic parameters for unbound PX calculated by total plasma concentration and binding parameters also showed dose-dependent characteristics. However, no significant change in Vd for unbound PX was observed among administered doses, indicating that the distribution of PX into the body tissues is not changed by an increase in dosage. Renal clearance of unbound PX significantly increased as plasma concentration decreased. The maximum transport capacity (Vmax) and the Michaelis-Menten constant (Km) for tubular secretion were 60.53 micrograms/min and 2.27 micrograms/mL, respectively. The aim of the present study is to demonstrate that both saturable tubular secretion and concentration-dependent protein binding are responsible for the dose-dependent pharmacokinetics of PX in rats.

Animals↗

Pharmacokinetic characteristics of N7-substituted theophylline derivatives and their interaction with quinolone in rats.

Disposition of diprophylline (DPP) and proxyphylline (PXP) and the effect of enoxacin on their disposition were investigated in rats. Concentrations of the two drugs in plasma and urine were measured by HPLC. The pharmacokinetic parameters of the two drugs were estimated by model-independent methods. Although the chemical structures of the two drugs are very similar, remarkable differences in the disposition of the two drugs were observed. Total body clearance (CLT) of DPP was 1.77 L/h/kg, which was sevenfold greater than that of PXP (0.26 L/h/kg). Diprophylline was excreted in an almost completely unchanged form in the urine, but only 50% of PXP was excreted. However, no binding of either drug to proteins in rat plasma was observed. The DPP renal clearance (CLR) was 1.75 L/h/kg, approximately 13-fold the CLR for PXP (0.13 L/h/kg) and sevenfold the rat glomerular filtration rate. This study indicates that in rats, DPP is mainly excreted by active tubular secretion and that renal tubular reabsorption contributes to renal excretion of PXP with glomerular filtration. No significant changes in any pharmacokinetic parameters of the two drugs were observed when they were coadministered with enoxacin, compared with the drug administered alone, suggesting that enoxacin had no effect on the pharmacokinetics of either drug.

Aminophylline↗

Effect of mequitazine on the pharmacokinetics of theophylline in asthmatic patients.

The effect of an oral anti-allergic drug, mequitazine, on the pharmacokinetics of theophylline has been investigated in seven asthmatic patients. They received chronic theophylline therapy (a sustained-release theophylline tablet 200-400 mg b.d. at 12 h intervals) and coadministered mequitazine 6 mg for 3 weeks. Plasma theophylline concentration-time curves and the urinary excretion of theophylline and its major metabolites before and after coadministration of mequitazine were compared. No significant change in the pharmacokinetic parameters of theophylline or in the urinary recovery of unchanged drug and its metabolites was observed. Thus, mequitazine did not influence the pharmacokinetics of theophylline and it should be safe for coadministration to asthmatic patients on chronic theophylline therapy.

Aged↗