Publications (27)38.53 Total impact
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Article: Effects of acetaldehyde on action potentials and ca currents in single atrial myocytes from the bullfrog.
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ABSTRACT: Aim: The purpose of the present study was to examine the effects of acetaldehyde on the contractile force and membrane potentials and currents in the bullfrog heart. Methods: Contractile force was recorded using right atrial tissues, and membrane potentials and currents were measured by using whole cell patch clamp methods in right atrial myocytes. Results: Acetaldehyde at 500 µmol/l and 1 mmol/l increased the contractile force significantly. Acetaldehyde at 300 and 500 µmol/l increased the overshoot and the plateau of electrically induced action potentials in a concentration-dependent and reversible manner, while the resting membrane potential did not change. The duration of the action potential (APD(90)) measured at the 90% repolarization level was shortened. The L-type Ca(2+) current (I(Ca)) increased significantly when 300 and 500 µmol/l were applied. The fast transient inward current, the inward rectifying potassium current and the outward delayed-rectifier potassium current were not changed following acetaldehyde application (500 µmol/l or 1 mmol/l). Conclusion: These results suggest that acetaldehyde increased the I(Ca), thereby increased the contractile force, the overshoot and the plateau of action potentials. The shortening of APD(90) may be due to the acceleration of the current decay during the I(Ca) inactivation phase.Pharmacology 01/2012; 90(3-4):216-22. · 1.79 Impact Factor -
Article: [Mechanism of alcohol consumption-mediated Th2-polarized immune response].
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ABSTRACT: Alcohol consumption impairs Th1-mediated cellular immune responses and enhances serum IgE levels. It has been reported that the elevated IgE levels are associated with a Th2 polarization response, but the mechanisms for enhancing Th2 polarization by the ethanol treatment remain to be elucidated. The aim of this review is to present and discuss the mechanism of Th2 polarization response by alcohol. IL-12 production by APCs such as monocytes, macrophages, and dendritic cells (DCs) preferentially leads to Th1 polarization. Acute ethanol consumption results in a significant decrease in IL-12 production in LPS-stimulated DCs and a CD40/CD40L interaction between CD40 on the DCs and CD40 ligand expressed on activated T cells. This suggests that Th2 polarization by ethanol is caused by impaired IL-12 production from APCs. In contrast, the induction of IL-10 by LPS is enhanced by ethanol treatment, suggesting that elevated IL-10 may play a role in ethanol-induced suppression of IL-12. However, ethanol inhibited IL-12 production in LPS-stimulated DCs devoid of IL-10 (IL-10/DC), suggesting that down-regulation of IL-12 by ethanol is independent of the IL-10 levels. Furthermore, several studies report that PGE2, cAMP and linolic acid, and endogenous lipid mediators released in inflammatory conditions, also inhibit IL-12 production. These inhibitory effects are similar to the IL-12 inhibition by ethanol. In addition, increase in the levels of these lipid mediators is induced by ethanol treatment. Alternatively, cytokine signaling studies indicate that IL-12 production by DCs is negatively regulated by PI3K and GSK-3, but positively regulated by p38 MAPK, mTOR, and NF-kappa B. Thus, it seems possible that ethanol may interact on the upstream of IL-12 producing a signal pathway. In fact, ethanol alters the stability of cell membrane, and suppresses clustering of TLR4 and recruitment of signaling molecules into lipid rafts, where it associates with the Ser/Thr kinase and the adaptor proteins, and forms a signaling complex. Down-regulation of lipid raft signaling is results in the impaired IL-12 production leading to the Th1 polarization, and causes CD4+ T cells to differentiation toward the Th2 lineage.Nihon Arukōru Yakubutsu Igakkai zasshi = Japanese journal of alcohol studies & drug dependence 06/2011; 46(3):319-36. -
Article: Quantitative analysis of crystalline pharmaceuticals in tablets by pattern-fitting procedure using X-ray diffraction pattern.
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ABSTRACT: A pattern-fitting procedure using an X-ray diffraction pattern was applied to the quantitative analysis of binary system of crystalline pharmaceuticals in tablets. Orthorhombic crystals of isoniazid (INH) and mannitol (MAN) were used for the analysis. Tablets were prepared under various compression pressures using a direct compression method with various compositions of INH and MAN. Assuming that X-ray diffraction pattern of INH-MAN system consists of diffraction intensities from respective crystals, observed diffraction intensities were fitted to analytic expression based on X-ray diffraction theory and separated into two intensities from INH and MAN crystals by a nonlinear least-squares procedure. After separation, the contents of INH were determined by using the optimized normalization constants for INH and MAN. The correction parameter including all the factors that are beyond experimental control was required for quantitative analysis without calibration curve. The pattern-fitting procedure made it possible to determine crystalline phases in the range of 10-90% (w/w) of the INH contents. Further, certain characteristics of the crystals in the tablets, such as the preferred orientation, size of crystallite, and lattice disorder were determined simultaneously. This method can be adopted to analyze compounds whose crystal structures are known. It is a potentially powerful tool for the quantitative phase analysis and characterization of crystals in tablets and powders using X-ray diffraction patterns.International journal of pharmaceutics 10/2010; 398(1-2):33-8. · 2.96 Impact Factor -
Article: Ca2+ extrusion via Na+-Ca2+ exchangers in rat odontoblasts.
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ABSTRACT: Intracellular Ca(2+) is essential to many signal transduction pathways, and its level is tightly regulated by the Ca(2+) extrusion system in the plasma membrane, which includes the Na(+)-Ca(2+) exchanger (NCX). Although expression of NCX1 isoforms has been demonstrated in odontoblasts, the detailed properties of NCX remain to be clarified. In this study, we investigated localization and ion-transporting/pharmacologic properties of NCX isoforms in rat odontoblasts. We characterized both the reverse and forward modes of NCX activity in odontoblasts in a dental pulp slice preparation. Ca(2+) influx by reverse NCX activity was measured by fura-2 fluorescence. Ca(2+) efflux by forward NCX activity elicited inward Na(+) current as measured by perforated-patch clamp recording. For immunohistochemical analysis, cryostat sections of incisors were incubated with antibodies against NCX. Immunohistochemical observation revealed localization of NCX1 and NCX3 in the distal membrane of odontoblasts. Inward currents by forward NCX activity showed dependence on external Na(+). Fura-2 fluorescence measurement revealed that Ca(2+) influx by reverse NCX activity depended on extracellular Ca(2+) concentration, and that this influx was blocked by NCX inhibitor KB-R7943 in a concentration-dependent manner. However, Ca(2+) influx by NCX showed a slight sensitivity to SEA0400 (a potent NCX1 inhibitor), indicating that expression potencies in odontoblasts were NCX3 > NCX1. These results suggest that odontoblasts express NCX1 and NCX3 at the distal membrane, and that these isoforms play an important role in the Ca(2+) extrusion system as well as in the directional Ca(2+) transport pathway from the circulation to the dentin-mineralizing front.Journal of endodontics 04/2010; 36(4):668-74. · 2.95 Impact Factor -
Article: Effects of Acetaldehyde on Membrane Potentials and Ionic Currents in Single Cardiac Myocytes
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ABSTRACT: The effect of acetaldehyde on membrane potential and ionic currents in guinea-pig single ventricular myocytes using whole-cell voltage-clamp methods was studied.Exposure to acetaldehde at concentrations between 0.3 and 1 mM increased the overshoot and plateau phase of action potentials in a dose-dependent and reversible manner. The duration of action potentials measured at 90% repolarization was prolonged by acetaldehyde. Potassium currents were not affected by acetaldehyde at concentrations up to 1 mM. Voltage-dependent Ca2+ current (ICa) increased significantly when 0.3 mM acetaldehyde was applied. The effect of acetaldehyde on membrane potential and ionic currents was not modified by the β-adrenergic receptor blocker propranolol. Application of isoproterenol increased ICa in the presence of acetaldehyde.The results suggest that the increased ICa produced by acetaldehyde was not mediated through β1-adrenergic receptor or intracellular adenylate cyclase stimulation.Pharmacy and Pharmacology Communications. 02/2010; 5(9):565 - 570. -
Article: Effects of Thiopental on Contractile and Electrophysiological Properties of Single Canine Left Ventricular Cells
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ABSTRACT: The effects of thiopental on contraction, membrane potential and membrane ionic currents were studied in single canine left ventricular cells. Thiopental 10−5 and 10−4 mol/1 reduced the cell-shortening from 7.02 ± 0.64 μm to 5.66 ± 1.39 and 3.48 ± 0.64 μm respectively (mean±S. D, N = 10, 0.5 Hz). This effect was enhanced in higher (>1.0 Hz) electrical stimulation frequencies. Also, thiopental decreased the plateau phase and shortcned the duration of action potential. On the other hand, voltage clamp experiment revealed that thiopental 10−6, 10−5, and 10−4 mol/1 reduced peak Ca2+ current from 520±48 pA to 387 ± 60 pA, 261 ± 84 pA, and 84 ± 36 pA respectively (mean + S. D., N = 8), and showed a use-dependent block of Ca2+ current. However, only a high dose of thiopental (10−4 mol/1) inhibited the Na4 current. We conclude that the negative inotropic effect of thiopental on the heart is mediated mainly via inhibition of the Ca2+ current.Pharmacology & Toxicology 03/2009; 82(2):98 - 102. -
Article: Effects of Propofol on Contractile Response and Electrophysiological Properties in Single Guinea‐Pig Ventricular Myocyte
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ABSTRACT: Effects of propofol on contractile response, action potential, resting membrane potential and L-type voltage-dependent calcium channel current were examined in guinea-pig single cardiac myocyte. Propofol (10−4 M) inhibited contractile response induced by electrical stimulation (83.6% of control, n=5), but did not change the resting membrane potential. On the other hand, propofol reduced the overshoot of action potential (10−4 M), and shortened the duration of action potential (10−5 and 10−4 M). Whole-cell voltage clamp experiment showed inhibition of L-type calcium channel current (ICa, 10−5 M: 90.8+1.39, 10−4 M: 83.4+1.53% of control, n=5). In addition, propofol showed use-dependent block of ICa. It is concluded that negative inotropic effect of propofol is caused by suppression of action potential, and that inhibition of ICa plays a role in shortening of the duration of action potential.Pharmacology & Toxicology 03/2009; 85(5):111 - 114. -
Article: Electrophysiological properties of AQP6 in mouse parotid acinar cells.
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ABSTRACT: Salivary gland acinar cells secrete large amounts of water and electrolytes, where aquaporins (AQPs) are thought to be involved in the secretion. In the present study, we investigated expression/localization of AQP6, and the anion transporting properties of AQP6 in mouse parotid acinar cells. RT-PCR, western blotting and immunohistochemical analyses revealed expression of AQP6 in acinar cells, localized in apical membrane. Voltage ramp from -100 mV to +100 mV at a holding potential of -60 mV elicited outwardly-rectifying currents, in the presence of extracellular Cl(-) channel blockers and intracellular solution with 150 mM Cs(+). These outward currents were increased when extracellular Cl(-) was replaced by Br(-), NO(3)(-), I(-), or SCN(-), accompanying a negative shift of reversal potentials. The outward current was enhanced by extracellular Hg(2+). These results were consistent with the biophysical properties of transfected AQP6 oocytes or HEK cells, which indicate that the AQP6 channel is functionally expressed in parotid acinar cells, and suggest that AQP6 contributes to secretion of anions in parotid acinar cells.The Journal of Medical Investigation 01/2009; 56 Suppl:347-9. -
Article: Cardiovascular Action of Nuatigenosido from Solanum sisymbriifolium.
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ABSTRACT: The root of Solanum sisymbriifolium. Lam (Solanceae), a perennial herb, has been used as a traditional medicine possessing diuretic and antihypertensive properties in Paraguay. It was reported that extracts from this plant exerted hypotensive effects in rats. Nuatigenosido was isolated from the extract as one of the prospective active compounds. We have investigated its pharmacological actions. The current study demonstrated the following results: (1) Nuatigenosido at 100 µg/kg and 1 mg/kg i.v. lowered blood pressure in rats, (2) nuatigenosido at 10−6 and 10−5 M augmented the contractile force in the right atrium of a bullfrog, and (3) nuatigenosido at 10−7 M increased the overshoot amplitude in frog atrial myocytes, action potential durations were shortened, the calcium current (ICa) was increased, and the delayed outward potassium current was increased. From these results, it is suggested that nuatigenosido may play an important role in the therapeutic effects of this herb.10/2008; 44(5):378-381. -
Article: Effects of Barakol on Aconitine-induced Cardiac Arrhythmias
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ABSTRACT: Barakol, isolated from leaves of Cassia siamea Lam., was investigated on aconitine-induced cardiac arrhyihmias in anesthetized rats. The bolus intravenous injection of aconitine induced ventricular fibrillation (VF) and ventricular tachycardia (VT). Pretreatment with barakol (10 mg/kg i.v.) reduced the incidence of aconitine-induced VF and VT, as well as mortality. However, pretreatment with verapamil (1 mg/kg) was ineffective on aconitine-induced ventricular arrhythmias and mortality. Tetrodotoxin (5 µg/kg i.v.) also significantly reduced the incidence of VF, VT and mortality induced by aconitine. Our results suggest that intracellular Na + loading plays an important role in aconitine-induced ventricular arrhyihmias. We concluded that the mechanisms of the protective effects of barakol on aconitine-induced cardiac toxicity may relate to the prevention of intracellular Na + accumulation.09/2008; 37(2):105-108. -
Article: Hypotensive and hypertensive effects of acetaldehyde on blood pressure in rats.
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ABSTRACT: Intravenous injection of acetaldehyde produced hypotensive actions in pentobarbital-anaesthetised whole rats, but hypertensive actions in pithed rats. The hypotensive effects of acetaldehyde in whole rats were abolished by pre-treatment with yohimbine. In pithed rats, the hypertensive effects of acetaldehyde were significantly attenuated by prazosin and phentolamine, and in rats that had been pre-treated with reserpine. Our results suggest that the hypertensive actions of acetaldehyde in pithed rats are due to the release of catecholamines, which subsequently leads to vasoconstriction. In whole rats the hypotensive actions of acetaldehyde may be due to alpha2-adrenoceptor stimulation in the central nervous or peripheral system.Nihon Arukōru Yakubutsu Igakkai zasshi = Japanese journal of alcohol studies & drug dependence 06/2008; 43(3):188-93. -
Article: Prediction of aminoglycoside response against methicillin-resistant Staphylococcus aureus infection in burn patients by artificial neural network modeling.
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ABSTRACT: To predict the response of aminoglycoside antibiotics (arbekacin: ABK) against methicillin-resistant Staphylococcus aureus (MRSA) infection in burn patients after considering the severity of the burn injury by using artificial neural network (ANN). Predictive performance was compared with logistic regression modeling. The physiologic data and some indicators of the severity of the burn injury were collected from 25 burn patients who received ABK against MRSA infection. A three-layered ANN architecture with six neurons in the hidden layer was used to predict the ABK response. The response was monitored using three clinical criteria: number of bacteria, white blood cell count, and C-reactive protein level. Robustness of models was investigated by the leave-one-out cross-validation. The peak plasma level, serum creatinine level, duration of ABK administration, and serum blood sugar level were selected as the linear input parameters to predict the ABK response. The area of the burn after skin grafting was the best parameter for assessing the severity of the burn injury in patients to predict the ABK response in the ANN model. The ANN model with the severity of the burn injury was superior to the logistic regression model in terms of predicting the performance of the ABK response. Based on the patients' physiologic data, ANN modeling would be useful for the prediction of the ABK response in burn patients with MRSA infection. Severity of the burn injury was a parameter that was necessary for better prediction.Biomedecine [?] Pharmacotherapy 02/2008; 62(1):53-8. · 2.00 Impact Factor -
Article: Crystallization kinetics of amorphous griseofulvin by pattern fitting procedure using X-ray diffraction data.
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ABSTRACT: A pattern fitting procedure using X-ray powder diffraction patterns was applied to study the crystallization kinetics of amorphous griseofulvin. From the optimized parameters obtained by pattern fitting, a change in the quantity and quality of griseofulvin crystals with crystallization was also investigated. Amorphous griseofulvin was prepared by cooling the melts followed by pulverization. X-ray diffraction patterns of amorphous griseofulvin were repeatedly measured every 20 h. The observed pattern was separated into crystalline diffraction intensity and amorphous scattering intensity by the nonlinear least-squares procedure. The fitting between the observed and simulated diffraction patterns was satisfactorily independent of the degree of crystallinity. Since a good linear relationship was found in a plot of amorphous scattering intensity against crystalline diffraction intensity, the degree of crystallinity can be determined according to Hermans' method. The diffraction peak width increased with higher diffraction angles with crystallization. The crystallization was biphasic: fast and slow crystallization with the growth of low disordered crystals and disordered crystals, respectively. The pattern fitting procedure is a powerful tool to analyze the X-ray diffraction patterns of semicrystalline materials. This procedure can simultaneously analyze the degree of crystallinity and crystal disorder in semicrystalline samples during crystallization.Pharmaceutical Research 06/2007; 24(5):880-7. · 4.09 Impact Factor -
Article: Effects of thiopental on Ca2+ currents and intracellular Ca2+ transient in single atrial cells from guinea pig.
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ABSTRACT: The effects of thiopental on Ca2+ currents and intracellular Ca2+ transient in single atrial cells from guinea pigs were studied by means of a whole-cell voltage-clamp method and Ca2+-sensitive fluorescent dye. Thiopental inhibited L-type voltage-dependent Ca2+ currents in a concentration-dependent manner (IC50=2.8.10(-5) mol/l). Moreover, the mode of Ca2+ current inhibition by thiopental showed no use dependency. Electrical stimulation-induced intracellular Ca2+ transient was significantly suppressed by 10(-5) mol/l thiopental. However, the caffeine-sensitive Ca2+ releasing pathway from sarcoplasmic reticulum was not affected by thiopental. Our results indicate that thiopental inhibits L-type Ca2+ currents, but not release of Ca2+ from sarcoplasmic reticulum. These results suggest that the negative inotropic action of thiopental is mainly due to inhibition of L-type Ca2+ channels in guinea pig atrial myocytes.Pharmacology 02/2007; 80(1):33-9. · 1.79 Impact Factor -
Article: Sphingosine-1-phosphate effects on guinea pig atrial myocytes: Alterations in action potentials and K+ currents.
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ABSTRACT: Sphingosine-1-phosphate (S-1-P), a potent lysophospholipid mediator which is released from platelets during clotting, activates a G-protein-gated inwardly rectifying K+ current (GIRK) in atrial and sino-atrial node myocytes. We denote this current I(K(S-1-P).) A similar GIRK, which is activated by acetylcholine (ACh) and denoted I(K(ACh)), is expressed in atrium. It shortens the action potential duration (APD) and reduces the effective refractory period (ERP). We have examined the effect of S-1-P on APD in guinea pig atrial myocytes by characterizing the rectification properties of I(K(S-1-P)) and evaluating whether I(K(S-1-P)) and I(K(ACh)) exhibit convergence/occlusion. Membrane potential and K+ currents were recorded from guinea pig atrial myocytes. Inwardly rectifying K+ currents were recorded using a ramp voltage clamp waveform between +30 to -130 mV from a holding potential of -7 mV. Agonist-induced current changes were obtained by subtracting the control current. S-1-P (1 and 10 nM) altered both passive and active properties of atrial myocytes. S-1-P increased the threshold current for excitation and decreased the time constant of the subthreshold electrotonic potentials. In addition, both APD50 and APD90 were decreased substantially. Voltage clamp analysis showed that the outward conductance of I(K(IR)) (G(K(IR)out)) was 134.8+/-11.3 pS pF(-1) (n = 19) in S-1-P (100 nM), and 207.0+/-19.6 pS pF(-1) (n = 18) in ACh (10 microM). The ratio of G(K(IR)out):G(K(IR)in) was about 0.7 for both S-1-P and ACh. The EC50 values for the activation of G(K(IR)out) and G(K(IR)in) by S-1-P were 1.6 and 1.3 nM, respectively. Addition of S-1-P (100 nM) after the effect of ACh (10 microM) had developed fully caused very little additional change. I(K(S-1-P)) is carried by weakly inwardly-rectifying K+ channels that are the same as those activated by ACh. This K+ current can markedly shorten APD in guinea pig atrial myocytes. This effect would be expected to increase the incidence of atrial rhythm disturbances.Cardiovascular Research 05/2006; 70(1):88-96. · 6.06 Impact Factor -
Article: The effects of sevoflurane and propofol on QT interval and heterologously expressed human ether-a-go-go related gene currents in Xenopus oocytes.
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ABSTRACT: Sevoflurane can induce prolongation of the cardiac QT interval by inhibiting the repolarization phase of the action potential. This may occur as a result of inhibition of the human ether-a-go-go related gene (HERG) channel. To clarify the mechanisms of anesthetics on HERG channels, we monitored the electrocardiogram and measured QT intervals in the guinea pig in the presence of sevoflurane and propofol. Sevoflurane (1%-4%) prolonged QTc dose-dependently (7.5%-21.2%), but propofol did not affect it. Furthermore, HERG channels were expressed in Xenopus oocytes and outward HERG currents were obtained on step depolarization from a holding potential of -70 mV. Repolarization to -70 mV from positive test potentials resulted in large outward tail currents. Sevoflurane (1%-4%), in a dose-dependent manner, inhibited the HERG outward tail currents (9.7%-26.6%), whereas steady-state currents were inhibited only at large concentrations. The time constant of the converging current was decreased in the presence of sevoflurane, but the inactivation and activation curves were not shifted. Propofol did not affect these currents within the clinically relevant concentration. In conclusion, compared with steady-state currents, sevoflurane was more potent in inhibiting the outward tail currents, suggesting that sevoflurane may modulate the HERG channel kinetics in its inactivated state.Anesthesia and analgesia 02/2006; 102(1):98-103. · 3.08 Impact Factor -
Article: Structural equation modeling of qualification of pharmacists to improve subjected quality of life in cancer patients.
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ABSTRACT: To establish structural equation model (SEM) of subjected quality of life (QOL) in cancer patients taking into account qualification of pharmacists. The SEM model was constructed from correlation matrix of the scores of answers of questions to both patients and pharmacists. Data were collected from 15 cancer patients who hospitalized and took opioid analgesics for pain control. The patients were asked 18 questions and pharmacists were asked seven questions. From the correlation matrix among scores of answers, a reasonable model was explored by SEM. Health-related QOL (HRQOL) in cancer patients can be modeled by latent variables consist of contributions from physical, emotional and functional domains. The fitting between data and the model was acceptable by statistical goodness-of-fit (GOF) index. The modeled HRQOL by SEM was weakly correlated with subjected QOL in patients, indicating that subjected QOL in patients would be affected not only by above latent variables but other variables. The model taking into account qualification of pharmacists to improve subjected QOL in patients was also made by SEM. The model was reasonably explained and fitting between data and the model was acceptable from some statistical index. The final model suggests that pharmacist can raise subjected QOL in patients through restraining unpleasant side effects. The qualification of pharmacists to improve subjected QOL in patients can be modeled by SEM. The final model suggests that pharmacists with qualification to assess patients' pain status contribute to raise subjected quality of life in cancer patients.Journal of pharmacy & pharmaceutical sciences: a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques 02/2005; 8(3):544-51. · 1.65 Impact Factor -
Article: Artificial neural network modeling to predict the plasma concentration of aminoglycosides in burn patients.
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ABSTRACT: The goal was to use an artificial neural network model to predict the plasma concentration of aminoglycosides in burn patients and identify patients whose plasma antibiotic concentration would be sub-therapeutic based on the patients' physiological data and taking into account burn severity. Physiological data and some indicators of burn severity were collected from 30 burn patients who received arbekacin. A three-layer artificial neural network with five neurons in the hidden layer was used to predict the plasma concentration of arbekacin. Linear modeling for prediction of plasma concentration and logistic regression modeling for the classification of patients were also used and the predictive performance was compared to results from the artificial neural network model. Dose, body mass index, serum creatinine concentration and amount of parenteral fluid were selected as covariates for the plasma concentration of arbekacin. Area of burn after skin graft was a good covariate for indicating burn severity. Predictive performance of the artificial neural network model including burn severity was much better than linear modeling and logistic regression analysis. An artificial neural network model should be helpful for the prediction of plasma concentration using patients' physiological data, and burn severity should be included for improved prediction in burn patients. Because the relationship between burn severity and plasma concentration of aminoglycosides is thought to be nonlinear, it is not surprising that the artificial neural network model showed better predictive performance compared to the linear or logistic regression models.Biomedecine [?] Pharmacotherapy 06/2004; 58(4):239-44. · 2.00 Impact Factor -
Article: Characterization of monoclinic crystals in tablets by pattern-fitting procedure using X-ray powder diffraction data.
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ABSTRACT: The purpose of this study is to characterize the monoclinic crystals in tablets by using X-ray powder diffraction data and to evaluate the deformation feature of crystals during compression. The monoclinic crystals of acetaminophen and benzoic acid were used as the samples. The observed X-ray diffraction intensities were fitted to the analytic expression, and the fitting parameters, such as the lattice parameters, the peak-width parameters, the preferred orientation parameter and peak asymmetric parameter were optimized by a non-linear least-squares procedure. The Gauss and March distribution functions were used to correct the preferred orientation of crystallites in the tablet. The March function performed better in correcting the modification of diffraction intensity by preferred orientation of crystallites, suggesting that the crystallites in the tablets had fiber texture with axial orientation. Although a broadening of diffraction peaks was observed in acetaminophen tablets with an increase of compression pressure, little broadening was observed in the benzoic tablets. These results suggest that "acetaminophen is a material consolidating by fragmentation of crystalline particles and benzoic acid is a material consolidating by plastic deformation then occurred rearrangement of molecules during compression". A pattern-fitting procedure is the superior method for characterizing the crystalline drugs of monoclinic crystals in the tablets, as well as orthorhombic isoniazid and mannitol crystals reported in the previous paper.International Journal of Pharmaceutics 07/2003; 259(1-2):27-37. · 3.35 Impact Factor -
Article: [Mechanism of QT interval prolongation induced by sevoflurane in guinea-pig ventricular myocyte].
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ABSTRACT: Sevoflurane causes QT interval prolongation clinically, but its precise mechanism has not been clarified. We examined the mechanism of QT interval prolongation induced by sevoflurane by means of electrophysiological technique in guinea-pig ventricular myocyte. Electrocardiogram was recorded in guinea-pig and effect of sevoflurane (1, 2, 4%) was examined. Action potential (AP), delayed rectified potassium current (IKr), and L-type calcium channel current (ICa) were monitored as whole-cell current and by voltage clamp techniques in guinea-pig single ventricular myocytes. Sevoflurane was applied by bubbling into the bathing solution. Sevoflurane (1, 2, 4%) increased QTc value. Sevoflurane prolonged the duration of AP at 2%, but shortened it at 6%. IKr was reduced to 35% of control in the presence of 2% sevoflurane, but a higher concentration (6%) did not show further inhibition. ICa was reduced only to 87% of control in the presence of 2% sevoflurane and the reduction was dose-dependent (4, 6%). Sevoflurane 2% inhibited IKr, but it showed only slight inhibition on ICa. Because the duration of AP is regulated by ICa (plateau phase) and IKr (repolarization), greater inhibition of IKr than ICa could result in prolongation of AP. It is suggested that this mechanism may play a role in QT interval prolongation under sevoflurane anesthesia.Masui. The Japanese journal of anesthesiology 06/2003; 52(5):482-8.
Top co-authors
Top Journals
Institutions
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2001–2010
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Toho University
Funabashi, Chiba-ken, Japan
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2008
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Universidad Nacional de Asunción
San Lorenzo, Departamento Central, Paraguay
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1994–2002
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Toyama Medical and Pharmaceutical University
Toyama-shi, Toyama-ken, Japan
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