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Biomedical subjects

W C Shyu

Publications and source records attributed to W C Shyu.

At least 19 recordsLinked to original sources
PubMed2006

The application of stem cells in the treatment of ischemic diseases.

Ischemia causes oxygen deprivation, cell injury and related organ dysfunction. Although ischemic injury may be local, it involves many biochemical changes in different cell types. The ability of stem cells to differentiate into different cell lineages provides the possibility of their use in treating a variety of diseases requiring tissue repair or reconstitution, such as stroke, ischemic retinopathy, myocardial infarction, ischemic disorders of the liver, ischemic renal failure, and ischemic limb dysfunction. Several cell types including embryonic stem cells, various progenitor and stem cells of hematopoietic or mesenchymal origin have been used in attempts to reconstitute injured tissue. Xenologous or autologous stem cells may be administered either through the peripheral vascular system or directly by regional injection. The stem cells are then guided to the infarct site by homing signals. Either by cell differentiation or paracrine effects, stem cells or progenitor cells participate in the reconstruction of a favorable microenvironment resulting in neovascularization and tissue regeneration that eventually improve the physiological function of organs with ischemic damage.

Animals↗
PubMed2004

The use of radiolabeled compounds for ADME studies in discovery and exploratory development.

Radiolabeled compounds are excellent investigative tools and widely used to carry out ADME studies during drug discovery and development stages. The most commonly used radioisotopes are 14C and 3H. 3H materials are generally easier to synthesize than 14C materials. Therefore, a variety of probes and substrates used in in vitro assays are labeled with 3H. Since synthesis of 14C material requires intensive resources, it is usually not available until after a molecule is considered for potential development or after the molecule enters the development phase. Improvement in the technology in radiochemistry has enabled the use of radiolabeled compounds earlier in pre-clinical and clinical development to address mechanistic issues. For in vitro studies, radiolabeled probes are utilized to test affinity with various transporters, to perform metabolism comparison among species and to assess possible formation of reactive metabolites. For in vivo studies, radiolabeled compounds are employed to identify and elucidate metabolites formed, to investigate the extent of absorption, bioavailability, tissue distribution, mass balance, routes of excretion, and pre-systemic metabolism. Due to the significant impact of radiolabeled studies on drug development, these studies will be performed earlier than have been in the past and will continue to be an integral part of drug discovery and development.

Animals↗
PubMed2001

Genome-wide hypomethylation in hepatocellular carcinogenesis.

Aberrant genome-wide hypomethylation has been thought to be related to tumorigenesis. However, its mechanism and implications in hepatocellular carcinogenesis remain to be elucidated. Samples of hepatoma (hepatocellular carcinoma, HCC) and paired non-HCC liver tissues were obtained from 17 HCC patients. Normal liver tissues obtained from three individuals were used as controls. Compared with the paired non-HCC liver tissues, genome-wide 5-methylcytosine content in HCC was reduced in all of the tested HCC samples (P < 0.001). Conversely, genome-wide 5-methylcytosine content did not significantly differ among normal, noncirrhotic, and cirrhotic liver tissues. Moreover, the degree of reduced DNA methylation was related to late histopathological HCC grade (P = 0.005) and large tumor size (P = 0.079). Compared with the paired non-HCC liver tissues, expression of DNA methyltransferases DNMT-1, DNMT-3A, and DNMT-3B and the DNA methyltransferase-like gene, DNMT-2, was up-regulated in 53, 41, 59, and 47% of the HCC samples, respectively. Surprisingly, small amounts of LINE-1 retrotransposon transcripts were detected in HCC and non-HCC as well as normal liver tissues, and the expression levels were not significantly different in HCC compared with the paired non-HCC or normal liver tissues. Of interest, the 3' ends of these LINE-1 transcripts were truncated. Our findings suggest that genome-wide hypomethylation in HCC is a continuing process that persists throughout the lifetime of the tumor cells rather than a historical event occurring in precancer stages or in cell origins for HCC. Up-regulation of DNA methyltransferases might simply be a result of increased cell proliferation in cancer. In addition, our results did not support the hypothesis of activation of transposable elements in HCC via genome-wide hypomethylation.

5-Methylcytosine↗
PubMed2001

Comparisons of the cost-effectiveness among hospital chronic care, nursing home placement, home nursing care and family care for severe stroke patients.

AIM: This study compared the cost and effectiveness of long-term institutional care and home care for stroke patients with severe physical disabilities. BACKGROUND: Whether home care is more economical or effective than institutional care for patients with chronic illnesses remains controversial when the cost of family labour is considered. Thus, decisions concerning the appropriate type of care setting for patients with severe chronic illness remain difficult. METHODS: From November 1995 to March 1996, 313 hospitalized stroke patients with severe physical disabilities treated at one of five hospitals in the Taipei metropolitan area were followed from the day of hospital discharge until the third month after discharge. These 313 patients were divided into four groups as follows: (1) 106 who were admitted to a chronic care unit in a hospital, (2) 60 who were admitted to nursing homes, (3) 60 who received professional home nursing care and (4) 87 who returned home without receiving professional care. The change of physical functional status in the patient was examined as the difference between activities of daily living (ADL) scores measured at discharge and at the end of the third month after discharge. RESULTS: Information on family costs for caregiving, including pay for long-term services utilized, labour costs for caregiving and out-of-pocket expenditures for miscellaneous materials was obtained during a weekly telephone interview. The results indicated that caring for patients in their own homes was not only more expensive but was also less effective in improving ADL scores than caring for patients in nursing homes and in chronic care units of hospitals. CONCLUSIONS: The results suggest that caring for patients with severe physical disabilities in institutions is more appropriate than caring of them at home.

Activities of Daily Living↗
PubMed2001

Estimation of the family cost of private nursing home care versus home care for patients with dementia in Taiwan.

BACKGROUND: Although overall estimates of the cost of dementia in Taiwan have been published, the relative cost of home care versus nursing home care for these patients is unclear. This study estimated the costs of home care and nursing home care for families of patients with either Alzheimer's disease or vascular dementia in Taiwan. METHODS: Data from previous reports were used to estimate costs of home care and nursing home care for families of patients with dementia, as well as the prevalence of dementia in Taiwan. RESULTS: The cost of home care per patient per month was NT$85,256 for patients with Alzheimer's disease and NT$74,152 for patients with vascular dementia. Labor was the predominant factor (96%) in home care. When the cost of labor was deducted from the calculation, the family cost per patient per month was reduced to NT$4,059 for Alzheimer's disease and NT$2,956 for vascular dementia. For patients receiving nursing home care, costs per month per patient were estimated to be NT$28,972 for patients with Alzheimer's disease and NT$31,576 for those with vascular dementia. Nursing home fees were the major component of costs incurred by families (at least 78% of total family costs). For both Alzheimer's disease and vascular dementia, payment for nursing home services amounted to approximately one-third of the labor costs of home care. CONCLUSIONS: These results indicate that nursing home placement for dementia patients provides a labor cost-savings for families in Taiwan.

Aged↗
PubMed2000

Heat shock modulates prion protein expression in human NT-2 cells.

The pathological hallmarks of Prion disease are cortical spongiform changes and neuronal loss, which are induced by the accumulation of the scrapie-isoform prion protein (PrP(Sc)). PrP(Sc) is derived from a post-translational modification of the cellular form of prion protein (PrP(C)). Heat-shock proteins, a group of molecular chaperones, are involved in the degradation of denatured proteins and post-translational folding of newly synthesized polypeptides. In an attempt to examine any possible relationship between heat shock stress and an induction of prion protein (PrP), human NT-2 cells were treated with heat shock at 42 degrees C for 30 min. After heat-shock treatment, both the level of mRNA and PrP(C) protein were analyzed at various time points by Northern and Western blot, respectively. There was a 1.5- to 2.5-fold increase in PrP mRNA levels 1 and 3h following heat shock. In addition, a two-fold increase in protein level of PrP was found 3 h after heat-shock treatment. These results suggest that cellular stress induces the elevation of both PrP mRNA and protein synthesis. The up-regulation of prion-protein mRNA and protein, implies that PrP may play a role in cellular stress.

Gene Expression Regulation↗
PubMed2000

Creutzfeldt-Jakob disease: heat shock protein 70 mRNA levels in mononuclear blood cells and clinical study.

Prion diseases such as Creutzfeldt-Jakob disease (CJD) are associated in most cases with the accumulation of an unusual isoform of prion protein (PrPSC). PrPSC is derived from the abnormal folding of the cellular isoform of prion protein (PrPC). On the other hand, heat shock protein is known to ensure proper protein assembly and folding and to facilitate proteolytic digestion of abnormal or denatured proteins. Many studies have therefore hypothesized that heat shock protein is linked to prion disease. We examined the relationship between heat shock protein HSP70 and prion disease in CJD patients. HSP70 mRNA levels in mononuclear blood cells (MBCs) were compared in 14 CJD patients (10 confirmed by histo-pathological study), 12 vascular dementia (VD) patients, 16 patients with Parkinson's disease and dementia (PD) and 14 nondemented control subjects. The possible correlation between HSP70 mRNA expression levels and clinical findings was also evaluated. HSP70 mRNA expression levels in MBCs were measured by northern blotting. HSP70 mRNA levels in MBCs from patients with CJD were significantly higher than those from patients with VD or PD and in nondemented controls. Age at symptom onset, dementia severity, disease duration and neuroimaging grade of CJD patients were not correlated with relative HSP70 mRNA levels. No significant relationship between HSP70 mRNA levels and ageing was found. These results suggest that measurement of HSP70 mRNA in MBCs might provide an auxiliary tool for the diagnosis of CJD.

Aged↗
PubMed1999

Sensitive triple-quadrupole mass spectrometric assay for the determination of BMS-181885, a 5-HT1 agonist, in human plasma following solid phase extraction.

A sensitive, selective, accurate, precise and reproducible triple-quadrupole liquid chromatographic-mass spectrometric assay was developed and validated for BMS-181885 (I), a 5HT1 agonist, in human plasma using BMS-181101 as the internal standard (IS). The method involved solid phase extraction of plasma containing I and the IS using Isoelute CN cartridges. The supernatant was then evaporated to dryness at 40 degrees C. The residue was dissolved in 100 microL of the injecting solvent. The HPLC column was ODS-3, 2 x 100 mm. The mobile phase comprised 10 mM ammonium formate (pH = 4) and acetonitrile, 55:45 v/v, used in an isocratic condition. The mass spectrometer was programmed to admit the protonated molecules at m/z 461 (I) and m/z 370 (IS) via the first quadrupole filter and to select reaction monitoring of ions at m/z 152 for I and IS for the quantification. Standard curves were fitted to a weighted quadratic function over the concentration range 0.2-200 ng/mL. The lowest standard concentration (0.2 ng/mL) was experimentally established as the lower limit of quantitation of the assay. The mean predicted quality control concentrations deviated within +/- 11% of the corresponding nominal values; the intra-assay and inter-assay precisions were within 7.0% relative standard deviation. I was stable in the injection solvent at 4 degrees C for at least 24 h and for at least three freeze-thaw cycles. Freezer stability of I in plasma was demonstrated for at least 3 months. The extraction recovery of I was established as 97%. The validated assay was applied to a pharmacokinetic study of I in humans.

Analysis of Variance↗
PubMed1999

The willingness of families caring for victims of stroke to pay for in-home respite care--results of a pilot study in Taiwan.

This contingent survey was designed to investigate the willingness of family caregivers of stroke victims to pay for in-home respite care. Between September 1996 and December 1996, a designated family member from each family of 174 vascular accident patients hospitalized in the Taipei Metropolitan Area, including two medical centers, received the first interview during preparation and planning for discharge of the patient from the hospital, and follow up interview in their own homes at the end of the second month after the patient was discharged from the hospital. A willingness to pay for in-home respite care was measured as the percentage of monthly family income which would be sacrificed to receive the respite care. Logistic regressions were used to perform multivariate analysis. The willingness to pay for respite care ranged from US$ 363 to 2182, and 42.5% of the family caregivers interviewed indicated a willingness to pay at least 50% of monthly family income for respite care. Family income was strongly associated with the amount of money that family caregivers were willing to pay for respite care. After results were adjusted for the effect of variance in income level, the degree of dependence of patients on the caregiver was significantly associated with the percentage of monthly family income for respite care. The more severe the physical dysfunction of patient, the higher the willingness to pay for in-home respite care utilization. Initially, respite care could be provided to families caring for patients with severe dysfunction, and then the scope enlarged to include caregivers taking care of patients with mild dysfunction.

Caregivers↗
PubMed1999

Cost comparisons between family-based care and nursing home care for dementia.

A prospective study was carried out in Taiwan to measure the family cost of caregiving at home for 289 patients newly diagnosed with dementia (106 with senile-type dementia, 171 with vascular-type dementia). Their families were first interviewed in the outpatient department and then followed for 1 month after the dementia diagnosis was made. Simultaneously, the costs for providing nursing home care to patients with dementia were calculated using accounting data reported from six nursing homes. Comparisons were made between the amount and type of cost encountered by families and by nursing homes to determine whether family-based care was cheaper and more appropriate than nursing home care for dementia patients with different functional levels. The results showed that higher costs were encountered for caregiving at home when the patients had severe dependence. This tendency was more evident for patients with senile dementia than for patients with vascular-type dementia. The cost of labour was an important expense for families caring for patients at home (at least 85% of family costs). Our findings suggest that, when family labour cost is considered, nursing home care is less expensive than family-based care for long-term care, especially for dementia patients with severe or moderate dependence. Nursing home care is also a better choice when patients have great need for multiple health services.

Adult↗
PubMed1999

Estimation of costs due to hospitalization for first-ever stroke patients in northern Taiwan.

BACKGROUND: The need for healthcare services and the related costs for stroke patients may rise steadily in the future. Even with the predictable and substantial burden of stroke, little effort has been devoted to measuring the population-based direct medical and nonmedical costs in Taiwan. METHODS: Data from the study "Epidemiological Study of Stroke, Diabetes, and Cardiovascular Disease," which included 8,705 people older than 35 years of age, and the study "Costs of Stroke," which included 660 first-ever stroke patients, were used for the cost calculations. The cost of hospital care for stroke patients was obtained in two steps. First, the incidence of stroke and readmissions within one year were tallied; the sum was then multiplied by the average length of stay. Second, the total medical and nonmedical costs were divided by the sum obtained from step 1. The resulting quotient obtained was the cost of hospital care for stroke patients per day. RESULTS: There were 6,691 incidents of stroke and stroke-related readmissions in 1995 (4,041 men and 2,650 women). The total person-days of hospital stay were 233,569 days (144,264 for men and 89,305 days for women). The average medical and nonmedical costs of hospital care per person-day was US $251.4 (NT $6,788 at an exchange rate of US $1 = NT $27). Cost for men (US $287, NT $7,749) was more than for women (US $208, NT $5,616). The total direct costs of hospital care were US $58,710,000 (NT $1,585,000,000) in 1995. CONCLUSIONS: An average of US $1,682,000 (NT $45,410,000) in hospital care costs for stroke could have been saved in 1995 if the person-day stay had been decreased by only one day.

Cerebrovascular Disorders↗
PubMed1998

Sensitive liquid chromatographic-mass spectrometric assay for the simultaneous quantitation of nefazodone and its metabolites hydroxynefazodone m-chlorophenylpiperazine and triazole-dione in human plasma using single-ion monitoring.

A sensitive, selective, accurate, precise and reproducible high-performance liquid chromatographic-mass spectrometric (LC-MS) assay was developed and validated for the simultaneous determination of nefazodone (NEF), hydroxynefazodone (OH-NEF), m-chlorophenylpiperazine (mCPP), and triazole-dione (Dione) in human plasma using trazodone (TRZ) as the internal standard (I.S.). The method involved simultaneous protein precipitation with acetonitrile and liquid-liquid extraction with methylene chloride, after which the organic layer was evaporated to dryness. The residue was reconstituted in 25% acetonitrile in 10 mM ammonium formate (pH 4.0), and an aliquot was injected onto a BDS Hypersil C18 column at a flow-rate of 0.3 ml/min. The mobile phase comprising of 10 mM ammonium formate (pH 4) and acetonitrile in 55:45 (v/v) was used in an isocratic condition. The mass spectrometer was programmed to admit the protonated molecules at m/z 197.0 (mCPP), 372.0 (I.S.) 470.4 (NEF), 458.1 (Dione), and 486.2 (OH-NEF). Standard curves were linear (r2 > or = 0.995) over the concentration range of 4-1000 ng/ml for Dione and 2-500 ng/ml for other analytes. The lowest standard concentrations were the lower limit of quantitation for each analyte. The mean predicted quality control (QC) concentrations for all analytes deviated less than -12.1% from the corresponding nominal values; the intra-assay and inter-assay precision of the assay for all analytes were within 7.0% relative standard deviation. All analytes including I.S. were stable in the injection solvent at room temperature for at least 24 h. The extraction recovery of the various analytes ranged from 67.3 to 86.5%. The validated assay was applied to a pharmacokinetic study of nefazodone.

Antidepressive Agents, Second-Generation↗
PubMed1998

High-performance liquid chromatographic-electrochemical assay for the quantitation of BMS-181885 in monkey plasma.

A high-performance liquid chromatographic-electrochemical assay was developed and validated for the quantitation of BMS-181885 (I), an anti-migraine agent, in monkey plasma. The assay involved a solid-phase extraction of I and BMY-46317 (internal standard; I.S.) on a 1-ml cyano cartridge using the automatic solid-phase extraction cartridge (ASPEC) system. Immediately following the conditioning of the cyano column (3 ml of methanol and 2 ml of 1% glacial acetic acid), plasma (0.25 ml) was loaded on to the column. The column was then washed with a 3 ml of 0.1 M ammonium acetate buffer (pH 6). The final elution of the analytes was performed using 2 ml of methanol. The eluate was then evaporated to dryness (gentle stream of nitrogen at 40 degrees C) and the residue was dissolved in the mobile phase and injected on to a YMC basic column (15 cm x 4.6 mm; 5 microm particle size) at a flow-rate of 1 ml/min. A mixture of 0.1 M ammonium acetate at pH 6-acetonitrile-methanol (70:20:10, v/v) was used as the mobile phase. Standard curves, with a lower limit of quantitation of 2 ng/ml of I were linear (r2> or =0.998; range: 2-50 ng/ml). Based on the analysis of the quality control (QC) samples, the assay was both accurate and precise. The stability of I was established following freeze-thaw cycles and storage at or below -20 degrees C. The extraction recovery of I from monkey plasma was about 82%. The validated assay method was applied to determine the pharmacokinetics of I in monkeys following a single 1 mg/kg intravenous dose.

Animals↗
PubMed1998

Lack of effect of food on the oral bioavailability of irbesartan in healthy male volunteers.

This study was conducted to evaluate the effects of a high-fat meal on the oral bioavailability of an 300-mg irbesartan tablet in healthy male volunteers. Sixteen healthy young male volunteers participated in this single-center, open-label, single-dose, crossover study. Each volunteer received a single 300-mg irbesartan tablet under fasted conditions and 5 minutes after a high-fat breakfast, with administrations separated by a 7-day washout period. Serial blood samples were collected over a 72-hour period, and plasma samples were analyzed for irbesartan using a validated high-performance liquid chromatography/fluorescence procedure. Food had no statistically significant effects on the peak concentration (Cmax) and area under the concentration-time curve (AUC) of irbesartan. The presence of food was associated with a slightly prolonged time to maximum concentration (tmax) and half-life (t1/2), but the differences were not statistically significant. The results of this study indicate that food does not affect the bioavailability of irbesartan. Thus, irbesartan can be administered without regard to meals.

Administration, Oral↗
PubMed1998

Oral bioavailability and disposition characteristics of irbesartan, an angiotensin antagonist, in healthy volunteers.

Absolute oral bioavailability and disposition characteristics of irbesartan, an angiotensin II receptor antagonist, were investigated in 18 healthy young male volunteers. Subjects received [14C] irbesartan as a 30-minute intravenous infusion (50 mg), [14C] irbesartan orally as a solution (50 mg or 150 mg), or irbesartan capsule (50 mg). Irbesartan was rapidly and almost completely absorbed after oral administration, and exhibited a mean absolute oral bioavailability of 60% to 80%. Mean total body clearance was approximately 157 mL/min, and renal clearance was 3.0 mL/min. Volume of distribution at steady state was 53 L to 93 L, and terminal elimination half-life was approximately 13 to 16 hours. Hepatic extraction ratio was low (0.2). There were no major circulating metabolites, and approximately 80% of total plasma radioactivity was attributable to unchanged irbesartan. Regardless of route of administration, approximately 20% of dose was recovered in urine and the remainder in feces.

Administration, Oral↗
PubMed1998

The effects of age and gender on the pharmacokinetics of irbesartan.

AIMS: Single dose pharmacokinetics and safety of irbesartan, an angiotensin II receptor antagonist, were evaluated in healthy young and elderly male and female subjects. METHODS: Irbesartan was administered as two 25 mg capsules after a 10 h fast to 12 young men, 12 young women, 12 elderly men and 12 elderly women. Serial blood and urine sample were collected up to 96 h after the dose. Plasma and urine samples were analysed for irbesartan by h.p.l.c./fluorescence methods. RESULTS: No statistically significant gender effects were observed in peak plasma concentration (Cmax), area under the curve (AUC), and terminal elimination half-life (t1/2) of irbesartan. The geometric mean AUC and Cmax increased by about 43% and 49%, respectively, in the elderly subjects. Also the time to peak was significantly shorter in the elderly subjects compared with that observed in the young subjects. Renal clearance ofirbesartan was significantly reduced in the elderly females but this reduction is not likely to be of any clinical relevance since less than 3% of the administered dose of irbesartan is excreted unchanged in the urine. CONCLUSIONS: Although there was an effect of age on the pharmacokinetics of irbesartan, based on the safety and efficacy profile, no adjustment in irbesartan dosage is necessary with respect to age or gender.

Adolescent↗
PubMed1998

Willingness of families caring for victims of dementia to pay for nursing home care: results of a pilot study in Taiwan.

In order to examine the value family caregivers attach to the benefits associated with nursing home services, this contingent survey was designed to investigate the willingness of family caregivers of dementia victims to pay for nursing home care. A total of 136 members of families of dementia patients from the department of neurology and psychiatry of four medical centers in Taiwan were interviewed by phone. These family members provided in-home care for dementia victims and had expressed the need for nursing home placement. These family caregivers were asked to explicitly state the maximum amount of family income per month they are able to give up to receive nursing home services. The willingness to pay (WTP) for nursing home care ranged from US$185 to $2,407 per month, and 37.5 percent of the family caregivers interviewed indicated a willingness to pay at least 50 percent of the monthly family income for nursing home placement. The amount of monthly family income was strongly associated with the WTP for nursing home care in dollars. Age and education of the caregiver, and accessibility of nursing home care were significantly associated with WTP in both cost range and percentage of monthly family income. Interviewees who were older than 65 years (odds ratio is 3.52), and educated equal to or above senior high school (odds ratio is 5.57) were inclined to pay at least 50 percent of monthly family income for nursing home placement. As other variables were adjusted, respondents older than 65 years were willing to pay US$208.4 per month more than those younger than 65 years for nursing home placement; and the educated equal to or above senior high school were inclined to pay US$171.9 per month more than those with less than a senior high school education. The easier it was to find nursing home agencies near the residence, the more willing the family was to pay at least 50 percent of their monthly family income for nursing home services; with an odds ratio of 16.51. The families with the higher accessibility to nursing home agencies were willing to pay US$174.3 per month more than caregivers with lower accessibility. Family caregivers, who were older than 65 years, educated above the senior high school level, with a higher family income, and easier accessibility to nursing home services, were likely to attach higher economic values to nursing home placement.

Aged↗