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S T Wu

Publications and source records attributed to S T Wu.

At least 19 recordsLinked to original sources
PubMed2001

High-performance liquid chromatographic assay for the determination of 2'-deoxy-3'-thiacytidine (lamivudine) in human plasma.

A method for the quantification of 2'-deoxy-3'-thiacytidine (lamivudine, 3-TC), which incorporated the use of 3-isobutyl-methylxanthine as internal standard (I.S.) was developed and validated in human plasma, using HPLC with UV absorbance detection. Using solid-phase extraction, 3-TC and I.S. were selectively extracted from human plasma. Subsequently, chromatographic separation was performed using a YMC phenyl column with ion-pair chromatography and detection at 270 nm. The method was validated over a concentration range of 10 to 5,000 ng/ml using 0.5 ml of human plasma. The extraction recovery for both 3-TC and I.S. was greater than 95%. The determination of inter- and intra-day precision (RSD) was less than 10% at all concentration levels, while the inter- and intra-day accuracy (% difference) was less than 6%.

Chromatography, High Pressure Liquid↗
PubMed2001

Applied anatomy of the V-shaped fibular osteomyocutaneous flap in reconstruction of the hindfoot.

To establish the applied anatomy of the V-shaped fibular osteomyocutaneous flap pedicled on the peroneal vessels, cadaver dissections were made in 60 lower limbs and 40 calcanei were examined to sum up the features of calcaneal biomechanics on the stability of the foot and the blood supply of the fibular osteomyocutaneous flap. There were four anastomoses and large communicating branches between the lower segment of the peroneal artery and the anterior and posterior tibial arteries. The flap was well supplied by a retrograde circulation through these anastomoses. A suitable length of pedicle was 20 cm. In the sagittal section of the calcaneus passing through the center of the articular surface for the cuboid bone, the arrangement of the trabeculae formed a triangular zone. The V-shaped flap corresponds nicely with the calculated lines of stress evoked by the weight of the body. The procedure may provide a new method for hindfoot reconstruction. This flap meets the criteria outlined for composite tissue reconstruction of defects of the extremities and biomechanics of the hindfoot, especially for calcaneal and cuboid defects.

Adult↗
PubMed2001

[Reconstruction of heel by reversed island fibular musculocutaneous flap].

OBJECTIVE: To explore the anatomical basis of blood supply and heel reconstruction by reversed island fibular musculocutaneous flap. METHODS: The blood supply of fibular musculocutaneous flap and the biomechanical characteristics of heel were studied by anatomical examination. One case with right heel full defect because of explosion injury was repaired by transfer of reversed island fibular vessels. The fibular flap was 14 cm in length with part of peroneus muscle and long flexor muscle of great toe. RESULTS: The lower part of fibular artery had plentiful anastomosis with anterior tibial artery and posterior tibial artery, which could provide ideal reversed blood supply. The rotatory point of vessel pedicle could be chosen according to the need of operation. The lowest site might be above 6 cm to lateral malleolus, and the vessel pedicle was 20 cm in length. The morphological feature of the reversed island fibular musculocutaneous flap was suitable to the biomechanical character of heel. The patient achieved satisfactory clinical result, the musculocutaneous flap survived well for 10 months of follow-up. CONCLUSION: The reversed island fibular musculocutaneous flap provide a new method for repairing the severe heel defect, especially in full defect of calcaneus and cuboid bone.

Adult↗
PubMed2000

Risperidone in acutely exacerbated schizophrenia: dosing strategies and plasma levels.

BACKGROUND: The optimal risperidone dosing strategy for acute schizophrenia requires elucidation. Furthermore, plasma levels of risperidone and its active metabolite (9-hydroxyrisperidone) at a given dose vary greatly among different individuals. For patients who metabolize risperidone slowly, a medium dose results in excessively high plasma levels, which might be related to adverse events and perhaps poor response. We thus investigated whether dose reduction to diminish adverse reactions associated with ordinary risperidone doses could still yield efficacy for acutely exacerbated schizophrenia. METHOD: Thirty-one newly hospitalized Chinese patients with acute exacerbation of schizophrenia (DSM-IV) entered this prospective, 6-week open trial. Risperidone doses were titrated to 6 mg/day (if tolerable) over 3 days, but were lowered thereafter if side effects appeared. Efficacy and side effect assessments were conducted on days 0, 4, 14, 28, and 42. Endpoint steady-state plasma levels of risperidone and 9-hydroxyrisperidone were analyzed by high performance liquid chromatography with ultraviolet detection. RESULTS: Thirty patients completed the trial. Of them, 17 tolerated the 6-mg target dose well, while the other 13 received lower final doses (mean +/- SD = 3.6 +/- 0.9 mg, p = .0001) for curtailing treatment-emergent side effects. At endpoint, 92.3% of the 13 low-dose individuals responded to treatment (20% or more reduction in the total Positive and Negative Syndrome Scale score), compared with 52.9% of the 17 high-dose subjects (p < .05). No significant between-group differences were revealed in other minor efficacy measures. Of note, endpoint plasma levels of the active moiety (risperidone plus 9-hydroxyrisperidone) were similar between the low- and high-dose groups (40.4 +/- 31.1 ng/mL vs. 49.7 +/- 13.4 ng/mL, NS). CONCLUSION: The results of this preliminary trial suggest that up to 6 mg of risperidone is efficacious in treating patients with acute exacerbation of schizophrenia. Nearly 60% of the patients could tolerate a 6-mg dose. For the other 40%, reducing dosages to 3.6 +/- 0.9 mg for relieving side effects still yielded efficacy. The 2 dose groups were comparable in the endpoint steady-state plasma drug concentrations.

Acute Disease↗
PubMed1998

Increase of reactive oxygen species (ROS) in endothelial cells by shear flow and involvement of ROS in shear-induced c-fos expression.

Intracellular reactive oxygen species (ROS) may participate in cellular responses to various stimuli including hemodynamic forces and act as signal transduction messengers. Human umbilical vein endothelial cells (ECs) were subjected to laminar shear flow with shear stress of 15, 25, or 40 dynes/cm2 in a parallel plate flow chamber to demonstrate the potential role of ROS in shear-induced cellular response. The use of 2',7'-dichlorofluorescin diacetate (DCFH-DA) to measure ROS levels in ECs indicated that shear flow for 15 minutes resulted in a 0.5- to 1.5-fold increase in intracellular ROS. The levels remained elevated under shear flow conditions for 2 hours when compared to unsheared controls. The shear-induced elevation of ROS was blocked by either antioxidant N-acetyl-cysteine (NAC) or catalase. An iron chelator, deferoxamine mesylate, also significantly reduced the ROS elevation. A similar inhibitory effect was seen with a hydroxyl radical (.OH) scavenger, 1,3-dimethyl-2-thiourea (DMTU), suggesting that hydrogen peroxide (H202), .OH, and possibly other ROS molecules in ECs were modulated by shear flow. Concomitantly, a 1.3-fold increase of decomposition of exogenously added H2O2 was observed in extracts from ECs sheared for 60 minutes. This antioxidant activity, abolished by a catalase inhibitor (3-amino-1,2,4-triazole), was primarily due to the catalase. The effect of ROS on intracellular events was examined in c-fos gene expression which was previously shown to be shear inducible. Decreasing ROS levels by antioxidant (NAC or catalase) significantly reduced the induction of c-fos expression in sheared ECs. We demonstrate for the first time that shear force can modulate intracellular ROS levels and antioxidant activity in ECs. Furthermore, the ROS generation is involved in mediating shear-induced c-fos expression. Our study illustrates the importance of ROS in the response and adaptation of ECs to shear flow.

Acetylcysteine↗
PubMed1998

Ventricular fibrillation-induced intracellular Ca2+ overload causes failed electrical defibrillation and post-shock reinitiation of fibrillation.

Despite high efficacy, electrical defibrillation shocks can fail or ventricular fibrillation (VF) is reinitiated after the application of the initial shock. The goal of this study was to determine whether [Ca2+]i overload, induced by VF itself, can cause failed electrical defibrillation and post-shock reinitiation of VF. For this purpose, we simultaneously measured [Ca2+]i transients (assessed by indo-1 fluorescence) and defibrillation energies (assessed by a modified implantable cardioverter defibrillator) in intact perfused rat hearts during pacing-induced sustained VF (10 min) in the absence of ischemia. We found that increasing [Ca2+]i during VF (by increasing [Ca2+]o from 3 to 6 mM) increased the defibrillation threshold (DFT) from 1.9 +/- 0.6 to 3.5 +/- 0.5 J/g (P<0.05) and also increased the total defibrillation energy (TDE) required for stabilization of sinus rhythm from 15.6 +/- 7.7 to 48.6 +/- 7.42 J/g (P<0.05). In addition, both DFT and TDE correlated linearly with [Ca2+]i (r=0.69 and 0.83, P<0.05). Furthermore, shortening the duration of VF from 10 to 1.5 min tended to limit [Ca2+]i overload and decreased TDE. Finally, all successful defibrillation shocks led to a sudden reduction of VF-induced [Ca2+]i overload (-115 +/- 3%). In contrast, failed shocks did not alter [Ca2+]i. Incomplete reduction of [Ca2+]i overload after initially successful shocks were often followed by synchronized spontaneous [Ca2+]i oscillations and subsequent reinitiation of VF. In conclusion, the present study showed for the first time that VF-induced [Ca2+]i overload can cause failed electrical defibrillation and post-shock reinitiation of VF. Because VF inevitably causes [Ca2+]i overload, this finding might be a crucial mechanism of failed defibrillation and spontaneous reinitiation of VF.

Animals↗
PubMed1997

Stereoselective high-performance liquid chromatography determination of propranolol and 4-hydroxypropranolol in human plasma after pre-column derivatization.

A stereoselective reversed-phase HPLC assay to quantify S-(-) and R-(+) enantiomers of propranolol and 4-hydroxypropranolol in human plasma was developed. The method involved liquid-liquid extraction for sample clean-up and employed 2,3,4,6-tetra-O-acetyl-beta-glucopyranosyl isothiocyanate as a pre-column chiral derivatization reagent. The internal standard used was 4-methylpropranolol. The derivatized products were separated on an Altex C18 column using a mixture of acetonitrile-water-phosphoric acid-triethylamine (58:42:0.1:0.06 and 50:50:0.15:0.06, v/v, for propranolol and 4-hydroxypropranolol, respectively) as mobile phase. The detection of propranolol derivatives was made at lambda(ex)=280 nm and lambda(em)=325 nm, and the corresponding 325 and 400 nm were used for 4-hydroxypropranolol derivatives. The assay was linear from 1 to 100 ng/ml and from 2 to 50 ng/ml using 0.5 ml of human plasma for propranolol and 4-hydroxypropranolol enantiomers, respectively. The present assay is used to quantify the enantiomers of propranolol and 4-hydroxypropranolol, respectively, in human plasma for pharmacokinetic studies.

Adrenergic beta-Antagonists↗
PubMed1997

Determination of amiprilose in human plasma by high-performance liquid chromatography with fluorimetric detection.

A reversed-phase HPLC method to quantify amiprilose in human plasma is described. The method involves liquid-liquid extraction of amiprilose and the internal standard from plasma. The extracted compounds are derivatized with 1,8-naphthalic dicarboxylic acid using 2-chloro-1-methylpyridinium iodide as a coupling reagent. The derivatized products are separated on a reversed-phase column and monitored fluorimetrically using 280 nm and 340 nm as excitation and emission wavelengths, respectively. The derivatized products which exhibit two peaks on chromatogram, are shown to be the interconvertible isomers. This assay has been used in pharmacokinetic studies of amiprilose in humans.

Adjuvants, Immunologic↗
PubMed1997

Intracellular Ca2+ handling and vulnerability to ventricular fibrillation in spontaneously hypertensive rats.

Spontaneously hypertensive rats (SHR) with ventricular hypertrophy show an increased vulnerability for the development of potentially lethal ventricular arrhythmias such as ventricular fibrillation (VF). The mechanisms of this increased vulnerability are not fully understood but may be related to abnormal intracellular Ca2+ ([Ca2+]i) handling under stress conditions. We therefore investigated whether [Ca2+]i handling is abnormal in hypertrophied hearts of SHR without heart failure during stimulation stress, and if so whether abnormal [Ca2+]i handling is a determinant of the increased vulnerability to VF in SHR. [Ca2+]i was measured by indo-1 surface fluorescence in perfused hearts of 8- to 10-month-old control Wistar-Kyoto rats (WKY) and age-matched SHR. The state of [Ca2+]i handling was analyzed during three different forms of stimulation stress: rapid pacing, the long rest period after cessation of rapid pacing, and preprogrammed ventricular stimulation that was simultaneously used for the determination of VF threshold. The pulse number VF threshold was used as an index to determine vulnerability to VF and to analyze the relationship of [Ca2+]i handling to vulnerability. Although VF thresholds were lower in SHR than in WKY, we found that both demonstrated similar [Ca2+]i handling during stimulation stress. The extent and rate of [Ca2+]i accumulation during rapid pacing and those of the [Ca2+]i decline after cessation of pacing were similar in SHR and WKY. In addition, the relationship between [Ca2+]i and VF threshold was unaltered in SHR. Thus, we conclude that [Ca2+]i handling is normal in hypertrophied hearts of SHR without heart failure during stimulation stress and that it is not a determinant of the increased vulnerability to VF in SHR.

Animals↗
PubMed1996

Importance of calcium for the vulnerability to ventricular fibrillation detected by premature ventricular stimulation: single pulse versus sequential pulse methods.

Vulnerability to ventricular fibrillation (VF) is frequently evaluated by VF threshold, a variable which may not be free of confounding factors and which may not be sensitive to all factors contributing to vulnerability. Therefore, we tested whether VF threshold determination affects intracellular free Ca2+ ([Ca2+]i) and whether VF thresholds are sensitive to changes in [Ca2+]i. For this purpose, we analysed [Ca2+]i by surface fluorometry and indo-1 in intact perfused rat hearts undergoing VF threshold determination by a single pulse method and tested whether such thresholds are lowered by increased [Ca2+]i. Additionally, we sought to determine the importance of Ca2+ for the vulnerability to VF under nonischemic conditions. For this purpose, we measured VF thresholds by a new pulse number method which scanned the vulnerable period by an increasing number of sequential pulses at increasing prematurity but constant intensity. We found that VF threshold determination by a single pulse method led to a rise in systolic [Ca2+]i. However, this rise does not perturb VF threshold interpretation because such thresholds were insensitive to changes in [Ca2+]i. Nevertheless, [Ca2+]i is of importance for the vulnerability to VF under nonischemic conditions because the number of VF-free tolerated premature pulses was dependent on [Ca2+]i. This relationship may only be detectable if evaluated by sequential pulse methods. These findings suggest that the method of VF threshold determination may be crucial for the result of studies testing Ca2+ antagonists or situations of altered [Ca2+]i and could explain controversial results of VF threshold studies testing Ca2+ antagonists by varying methods.

Animals↗
PubMed1996

Rapid adaptation of myocardial calcium homeostasis to short episodes of ischemia in isolated rat hearts.

Short episodes of ischemia and reperfusion (ischemic preconditioning) have been shown to attenuate the detrimental rise in intracellular free Ca2+ ([Ca2+]i) caused by subsequent sustained ischemia. The purpose of this study was to investigate the detailed time course of [Ca2+]i during such short episodes of ischemia and reperfusion. [Ca2+]i was measured at a high time resolution by surface fluorometry and indo-1 in isolated perfused rat hearts during three episodes of 5 minutes of ischemia followed by 5 minutes of reperfusion. We found that the rise in systolic [Ca2+]i was significantly smaller during the second (191% +/- 67%) and third (194% +/- 75%) episodes of ischemia than during the first episode (289% +/- 75%, P < 0.05 vs both subsequent episodes). This attenuated rise in systolic [Ca2+]i was preserved during perfusion with low extracellular Na+ (105.5 mmol/L [Na+]o). During short episodes of ischemia and reperfusion, [Ca2+]i rises less during the second and third ischemic episode than during the first episode. Thus one transient ischemic stimulus led to a rapid adaptation of [Ca2+]i homeostasis to subsequent ischemic conditions. Such a rapid adaptation might be an important mechanism of the ischemic preconditioning phenomenon in protecting against ischemic injury.

Adaptation, Physiological↗
PubMed1995

Role of intracellular calcium in the antiarrhythmic effect of procainamide during ventricular fibrillation in rat hearts.

Increased intracellular calcium (calcium overload) is considered one of the factors that can initiate ventricular fibrillation. In addition, ventricular fibrillation itself can cause and possibly maintain calcium overload. The goal of this study was to determine whether the class IA antiarrhythmic agent procainamide can reduce calcium overload during ventricular fibrillation and, if so, whether this reduction could be responsible for the recovery of the left ventricular function after defibrillation. For this purpose, the effects of 0.1 mmol/L of procainamide perfusion on left ventricular developed pressure, cardiac rate, and intracellular calcium during pacing-induced ventricular fibrillation were measured in isolated perfused rat hearts. Intracellular calcium was assessed by surface fluorometry after indo 1 loading. The concentration of procainamide was selected such that approximately half of the hearts would functionally recover from fibrillation. Cardiac rate and intracellular calcium were compared among four groups, depending on both the perfusate used and the recovery of left ventricular developed pressure at the end of the experiment. We found that procainamide reduced intracellular calcium to steady-state levels in hearts in which left ventricular function completely recovered (developed pressure > 67% of the steady-state value). However, intracellular calcium remained elevated in partially recovered hearts (33% < or = pressure < or = 67%) and in nonrecovered hearts (pressure < 33%). Thus procainamide can reduce calcium overload during ventricular fibrillation, and this reduction could be responsible for the recovery of left ventricular function after defibrillation. This reduction was use dependent, that is, dependent on high cardiac rates during fibrillation rather than on the decrease of cardiac rates before or during defibrillation.

Analysis of Variance↗
PubMed1995

Contractile and intracellular Ca2+ decay in potentiated contractions following multiple extrasystolic beats.

Developed pressure and intracellular Ca2+ ([Ca2+i) decay in postextrasystolic beats following multiple extrasystolic contractions (ESCs) was evaluated with surface fluorometry in atrioventricular-blocked perfused rat hearts loaded with Indo-1. After priming pacing at 400 ms intervals, 1-25 ESCs were interposed with a 160 ms interval, followed by 30 postextrasystolic beats with a 400 ms interval. Both left ventricular developed pressure and the amplitude of the Indo-1 fluorescence ratio (F400/F510: an index of [Ca2+]i) increased in a monoexponential manner with an increase in the number of ESCs. Both potentiated left ventricular developed pressure and the amplitude of F400/F510 transients returned to control in a monoexponential fashion. Consistent with this exponential decay, the relationship between developed pressure or the amplitude of F400/F510 transients in a postextrasystolic beat and that in the preceding beat was linear and the slope of a fitted line (recirculation fraction; RF) was evaluated as an index of rapidity of decay. The number of ESCs did not affect RF of developed pressure and the amplitude of F400/F510 transients. Reducing extracellular Ca2+ concentration (1.25 --> 0.55 mM), and perfusion with an acidic solution (pH = 6.8) significantly decreased RF of both developed pressure (0.85 +/- 0.06 --> 0.78 +/- P < 0.05 and 0.85 +/- 0.07 --> 0.78 +/- 0.06, n=8, P < 0.05, respectively) and the amplitude of F400/F510 (0.87 +/- 0.06 --> 0.78 +/- 0.05, P < 0.05, and 0.89 +/- 0.08 --> 0.78 +/- 0.07, P < 0.05, respectively). This study confirmed that, in all conditions evaluated, contractile decay was determined by [Ca2+]i decay and RF of contractile decay was an accurate estimate of [Ca2+]i decay in physiologically paced isolated perfused rat hearts.

Acidosis↗
PubMed1995

Acute amiodarone terminates ventricular fibrillation by modifying cellular Ca++ homeostasis in isolated perfused rat hearts.

Intravenous amiodarone has an acute antiarrhythmic action, which may be mediated by effects on intracellular calcium concentration [Ca++]i. We evaluated termination of pacing-induced ventricular fibrillation (VF) and associated changes in [Ca++]i by acute amiodarone in isolated perfused rat hearts loaded with the [Ca++]i indicator 1-(2-amino-5-(6-carboxy-2- indolyl)phenoxy)-2-(2-amino-5-methylphenoxy)ethane-N,N,N',N'-tetraacetic acid pentaacetoxymethyl ester. [Ca++]i was evaluated with surface fluorometry through fiberoptics placed on the interventricular septum. Two minutes after VF induction, hearts were perfused with amiodarone (n = 12, 10 micrograms/ml for 5 min followed by 1 micrograms/ml), low extracellular calcium concentration [Ca++]o (n = 12, 0.2 mM) or a control perfusate (n = 12, no treatment). VF termination during a 30-min observation period was significantly more frequent with amiodarone (92%) and with low [Ca++]o (75%) compared with no treatment (17%, P < .05). In nontreated hearts without recovery, [Ca++]i, expressed as a percentage of the base-line amplitude, increased continuously from 206% +/- 44% to 529% +/- 138% during 30-min VF (P < .05). In hearts that recovered with amiodarone and low [Ca++]o, [Ca++]i decreased significantly from 273% +/- 55% and 273% +/- 99% before treatment to 122% +/- 95% and 50% +/- 80% before defibrillation, respectively (P < .05). VF frequency was also significantly decreased with amiodarone. The nature of [Ca++]i transients in VF has not been fully known. Power spectrum analysis disclosed that [Ca++]i transients responded to every one or two electrocardiographic signals in VF with the highest frequency of 22 Hz.(ABSTRACT TRUNCATED AT 250 WORDS)

Amiodarone↗
PubMed1995

Intracellular calcium transients underlying interval-force relationship in whole rat hearts: effects of calcium antagonists.

OBJECTIVES: Much of the understanding about the cardiac interval-force relationship of the whole heart, including mechanical restitution and postextrasystolic potentiation (PESP), has been inferred from isolated muscle studies. We tested whether results from isolated muscles about intracellular Ca2+([Ca2+]i) transients underlying the interval-force relationship can be substantiated in whole hearts. Additionally, we investigated whether Ca2+ antagonists could alter [Ca2+]i transients underlying mechanical restitution and postextrasystolic potentiation. METHODS: [Ca2+]i transients were studied in isolated perfused rat hearts by surface fluorometry and Indo-1. Using computer-controlled pacing protocols, we performed restitution curves for left ventricular developed pressure and [Ca2+]i (developed pressure and [Ca2+]i plotted as a function of extrasystolic intervals). To quantify restitution curves, we fitted monoexponential functions to plots and analyzed their shift and slope. Then, we used Ca2+ antagonists, low extracellular Ca2+([Ca2+]o) and PESP to modify restitution curves. [Ca2+]i transients in isolated rat hearts were interpreted as Ca2+ released from the sarcoplasmic reticulum. RESULTS: Interval-dependent changes in developed pressure were strongly correlated to interval-dependent changes in the amplitude of [Ca2+]i transients in isolated whole rat hearts. Additionally, nifedipine and low [Ca2+]o led to similar downward shifts but not to a changed slope of restitution curves for [Ca2+]i. On the other hand, PESP increased the slope of restitution curves for [Ca2+]i. Furthermore, the effect of PESP on developed pressure was blunted by high concentrations of Ca2+ antagonists. CONCLUSIONS: The results from isolated muscles about [Ca2+]i transients underlying the interval-force relationship could be substantiated in whole hearts. Additionally, low [Ca2+]i (induced by nifedipine or low [Ca2+]o) decreased the maximal Ca2+ release of the sarcoplasmic reticulum but did not change the release kinetics. On the other hand, PESP presumably accelerated Ca2+ release kinetics of the sarcoplasmic reticulum.

Animals↗
PubMed1994

Determination of DMP 728, a IIb/IIIa receptor antagonist, in rat and dog plasma by high-performance liquid chromatography with fluorimetric detection.

A specific and sensitive HPLC assay for the determination of DMP 728 in dog and rat plasma has been developed. The method involves solid-phase extraction of DMP 728 and the internal standard from plasma using a C2 column. The extracted compounds are derivatized with benzoin under alkaline conditions. Using a mixture of acetonitrile and 0.1 M potassium phosphate buffer (25:75, v/v, pH 7.4) as mobile phase, the derivatized products are separated on a Regis semipermeable surface C8 column and monitored fluorometrically using 325 nm and 425 nm as excitation and emission wavelengths, respectively. The assay is linear from 2.5 to 1000 ng/ml in dog plasma and from 5 to 1000 ng/ml in rat plasma. The limit of quantitation is 2.5 ng/ml using 0.5 ml of dog plasma and 5 ng/ml using 0.5 ml of rat plasma. The assay has been used in pharmacokinetic studies of DMP 728 in dogs and rats.

Acetonitriles↗