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Biomedical subjects

Wei-Tien Chang

Publications and source records attributed to Wei-Tien Chang.

At least 19 recordsLinked to original sources

Hypothermia-induced cardioprotection using extended ischemia and early reperfusion cooling.

Optimal timing of therapeutic hypothermia for cardiac ischemia is unknown. Our prior work suggests that ischemia with rapid reperfusion (I/R) in cardiomyocytes can be more damaging than prolonged ischemia alone. Also, these cardiomyocytes demonstrate protein kinase C (PKC) activation and nitric oxide (NO) signaling that confer protection against I/R injury. Thus we hypothesized that hypothermia will protect most using extended ischemia and early reperfusion cooling and is mediated via PKC and NO synthase (NOS). Chick cardiomyocytes were exposed to an established model of 1-h ischemia/3-h reperfusion, and the same field of initially contracting cells was monitored for viability and NO generation. Normothermic I/R resulted in 49.7 +/- 3.4% cell death. Hypothermia induction to 25 degrees C was most protective (14.3 +/- 0.6% death, P < 0.001 vs. I/R control) when instituted during extended ischemia and early reperfusion, compared with induction after reperfusion (22.4 +/- 2.9% death). Protection was completely lost if onset of cooling was delayed by 15 min of reperfusion (45.0 +/- 8.2% death). Extended ischemia/early reperfusion cooling was associated with increased and sustained NO generation at reperfusion and decreased caspase-3 activation. The NOS inhibitor N(omega)-nitro-L-arginine methyl ester (200 microM) reversed these changes and abrogated hypothermia protection. In addition, the PKCepsilon inhibitor myr-PKCepsilon v1-2 (5 microM) also reversed NO production and hypothermia protection. In conclusion, therapeutic hypothermia initiated during extended ischemia/early reperfusion optimally protects cardiomyocytes from I/R injury. Such protection appears to be mediated by increased NO generation via activation of protein kinase Cepsilon; nitric oxide synthase.

Animals↗

Postresuscitation myocardial dysfunction: correlated factors and prognostic implications.

OBJECTIVE: To evaluate the clinical factors correlated with postresuscitation myocardial dysfunction and the prognostic implication such dysfunction may have. DESIGN AND SETTING: Prospective observational study in a university medical center PATIENTS: 58 adult patients successfully resuscitated from nontraumatic out-of-hospital cardiac arrest over 2 years. MEASUREMENTS AND RESULTS: Echocardiographic evaluation of the left ventricular systolic and diastolic functions was performed 6 h postresuscitation and was analyzed in correlation to the clinical features and resuscitation factors. Univariate analysis revealed left ventricular ejection fraction (LVEF) to be significantly lower in patients with hypertension, past history of myocardial infarction, resuscitation duration longer than 20 min, defibrillation, and use of more than 5 mg epinephrine. Isovolumic relaxation time (IVRT) was significantly longer in patients with noncardiac cause and initial rhythm of nonventricular fibrillation/tachycardia. Multiple regression analysis showed epinephrine dose and past history of myocardial infarction to be independent factors for LVEF, while the cause of cardiac arrest was independently associated with IVRT. For prognosis, 27 patients survived to hospital discharge. Both LVEF under 40% and IVRT 100 ms or longer were associated with poor survival outcomes. In Cox regression analysis IVRT 100 ms or longer served as an independent factor predicting poor survival prognosis. CONCLUSIONS: Postresuscitation left ventricular dysfunction is correlated with a number of clinical factors, among which past history of myocardial infarction, epinephrine dose, and the cause of cardiac arrest play independent roles. Meanwhile, IVRT 100 ms or longer 6 h postresuscitation predicts poor survival outcomes and serves as a marker of poor prognosis.

Aged↗

Urban air pollution and emergency admissions for cerebrovascular diseases in Taipei, Taiwan.

AIMS: This study was designed to evaluate the association between urban air pollutants and emergency admissions for cerebrovascular diseases. METHODS AND RESULTS: Daily emergency admissions for cerebrovascular diseases (ICD-9-CM, 430-437) to the National Taiwan University Hospital were regressed against daily concentrations of carbon monoxide (CO), nitrogen dioxide (NO(2)), sulphur dioxide (SO(2)), ozone (O(3)), and particulate matters with aerodynamic diameter <2.5 (PM(2.5)) and 10 microm (PM(10)) from 12 April 1997 to 31 December 2002 in Taipei metropolitan areas by the Poisson regression models adjusting for meteorological conditions and temporal trends. Single-pollutant models showed O(3) lagged 0 day, CO lagged 2 days, and PM(2.5) and PM(10) lagged 3 days were significantly associated with increasing emergency admissions for cerebrovascular diseases and CO lagged 2 days was significantly associated with increasing emergency admissions for strokes (ICD-9-CM, 430-434). Such association remained significant for O(3), CO, and cerebrovascular admissions after adjusting for PM(2.5) and PM(10) in two-pollutant models. The odds ratios were 1.021-1.022 per 31.3 ppb O(3) and 1.023-1.031 per 0.8 ppm CO, respectively. However, only CO was significantly associated with emergency admissions for stroke in the three-pollutant models with CO, O(3), and PM(2.5) or PM(10). CONCLUSION: Emergency admissions for cerebrovascular diseases among adults were positively associated with increasing urban air pollution levels of O(3) lagged 0 day and CO lagged 2 days in Taipei.

Aged↗

Antioxidant effects of ginsenoside Re in cardiomyocytes.

We have previously demonstrated that American ginseng berry extract exhibited significant protection against oxidant-mediated injury in cardiomyocytes. To extend this work, we sought to investigate the antioxidant effects of Re, a protopanaxatriols-type and single chemical integrant present in American ginseng berry extract, using the same chick cardiomyocyte model of oxidant injury as well as ESR spectroscopy in a cell-free chemical system. In cells exposed to 2 h of H2O2 (0.5 mM), pretreatment with Re (0.05, 0.1, or 0.5 mg/ml for 2 h) significantly attenuated 2',7'-dichlorofluorescein (DCF) fluorescence by 51% (from 1345+/-67 to 658+/-46 a.u., P<0.001), and remarkably reduced cell death (from 51.5+/-3.0% to 11.8+/-1.5%, P<0.001, compared to the control). Similar results were also observed in cells exposed to antimycin A (100 microM), a mitochondrial electron transport chain site III inhibitor which increases endogenous oxidative stress. In the ESR study, however, Re failed to reduce the formation of the superoxide/DMPO adduct and DPPH radicals. These results suggest that ginsenoside Re functions as an antioxidant, protecting cardiomyocytes from oxidant injury induced by both exogenous and endogenous oxidants, and that its protective effects may be mostly attributed to scavenging H2O2 and hydroxyl radicals.

Animals↗

Curry leaf (Murraya koenigii Spreng.) reduces blood cholesterol and glucose levels in ob/ob mice.

We observed that curry leaf (Murraya koenigii) extract possesses the property to decrease blood cholesterol and blood glucose levels in diabetic ob/ob mice. Mice received daily intraperitoneal injections of 80 mg/kg curry leaf extract for 10 consecutive days. The extract significantly decreased blood cholesterol level from 277.6 +/- 16.6 mg/d (day 0) to 182.0 +/- 15.3 mg/d (day 10, p < 0.01 compared with the change in vehicle group). The extract also significantly decreased blood glucose level from 387.0 +/- 15.6 mg/dl (day 0) to 214.0 +/- 26.6 mg/dl (day 10, p < 0.01). In addition, body weight was reduced after extract treatment. Our data suggest that curry leaf may be proved to be of clinical importance in improving the management of high cholesterol level and type 2 diabetes.

Animals↗

Scutellaria baicalensis decreases ritonavir-induced nausea.

BACKGROUND: Protease inhibitors, particularly ritonavir, causes significant gastrointestinal disturbances such as nausea, even at low doses. This ritonavir-induced nausea could be related to its oxidative stress in the gut. Alleviation of drug-induced nausea is important in effectively increasing patients' compliance and improving their quality of life. Conventional anti-emetic drugs can only partially abate the symptoms in these patients, and their cost has also been a concern. Rats respond to nausea-producing emetic stimuli by increasing consumption of non-nutritive substances like kaolin or clay, a phenomenon known as pica. In this study, we used this rat pica model to evaluate the effects of Scutellaria baicalensis, a commonly used oriental herbal medicine, on ritonavir-induced nausea. RESULTS: Rats treated with 20 mg/kg ritonavir significant caused increases of kaolin consumption at 24 to 48 hr (P < 0.01). Pretreatment with 0.3 and 3 mg/kg Scutellaria baicalensis extract significantly decreased ritonavir-induced kaolin intake in a dose-related manner (P < 0.01). Compared to vehicle treatment, the extract completely prevented ritonavir-induced kaolin consumption at dose 3 mg/kg. The area under the curves (AUC) for kaolin intake from time 0 to 120 hr for vehicle only, ritonavir only, SbE 0.3 mg/kg plus ritonavir, and SbE 3 mg/kg plus ritonavir were 27.3 g x hr, 146.7 g x hr, 123.2 g x hr, and 32.7 g x hr, respectively. The reduction in area under the curves of kaolin intake from time 0 to 120 hr between ritonavir only and SbE 0.3 mg/kg plus ritonavir, ritonavir only and SbE 3 mg/kg plus ritonavir were 16.0% and 77.7%, respectively. CONCLUSION: Scutellaria baicalensis significantly attenuated ritonavir-induced pica, and demonstrated a potential in treating ritonavir-induced nausea.

Journal Article↗

Pneumatosis intestinalis and hepatic portal venous gas after CPR.

Pneumatosis intestinalis and hepatic portal venous gas are usually associated with severe intra-abdominal pathologies. As diagnostic technologies advanced, a number of variant etiologies have been identified. We report 2 cases in which pneumatosis intestinalis and hepatic portal venous gas developed after prolonged cardiopulmonary resuscitation (CPR). The pathogenic mechanism was most probably bowel infarction caused by poor mesenteric perfusion during and after CPR. Limited cardiac output during prolonged resuscitation and severe vasoconstriction after large doses of epinephrine and vasopressors might both contribute to the compromised mesenteric perfusion. The risk seems especially high for old patients with severe atherosclerosis. Once it happens, the prognosis is extremely poor. In patients of cardiac arrests receiving prolonged CPR, catastrophic complications like this should be considered in the postresuscitation phase, especially those with multiple risk factors like old age, severe atherosclerosis, and use of large doses of vasoconstrictors.

Aged↗

A patient-tailored N-acetylcysteine protocol for acute acetaminophen intoxication.

BACKGROUND: Hepatotoxicity as a result of acetaminophen(APAP) intoxication has become an important problem, but early intervention with N-acetylcysteine (NAC) is effective in preventing hepatic injury. Two NAC regimens are currently approved for acute APAP intoxication: NAC administered orally every 4 hours for 72 hours, and NAC administered intravenously for 20 hours within 8 to 10 hours after ingestion of a potentially hepatotoxic amount of APAP. However, clinical observations suggest that a variable treatment duration may be more appropriate than use of these predetermined, fixed-duration protocols. OBJECTIVES: This study investigated the tolerability and efficacy of a patient-tailored NAC protocol for acute APAP intoxication by comparing the incidence of hepatotoxicity in patients receiving this protocol and in historical controls receiving 1 of 2 fixed-duration protocols: oral NAC for 72 hours and intravenous NAC for 20 hours within 8 to 10 hours after ingestion of a potentially hepatotoxic amount of APAP. METHODS: This was a retrospective case series study that included all patients admitted through the emergency department (ED) of the National Taiwan University Hospital with a diagnosis of APAP intoxication between October 1997 and October 2002. According to the patient-tailored protocol, which had been used in the ED since 1997, patients with a serum APAP concentration above the limit for possible risk based on a modified Rumack-Matthew nomogram received oral treatment with NAC 140 mg/kg, followed by maintenance doses of 70 mg/kg every 4 hours. NAC treatment was discontinued when the APAP concentration was <10 mg/L and serum aspartate aminotransferase (AST) was <40 IU/L. For the purposes of assessing clinical outcomes, patients were divided into 3 groups based on duration of treatment: the short-course group (</=36 hours), the intermediate-course group (37-72 hours), and the long-course group (>/=73 hours). The primary outcome measure was development of hepatotoxicity, defined as a serum AST or alanine aminotransferase concentration >1000 IU/L. RESULTS: Twenty-seven patients were included in the study, 17 in the short-course group, 4 in the intermediate-course group, and 6 in the long-course group. The mean (SD) durations of NAC treatment in the respective groups were 22.1 (5.5) hours, 45.0 (8.2) hours, and 97.3 (33.2) hours. All 6 patients (22%) in the long-course group had hepatotoxicity (peak AST range, 1083-9770 IU/L); their treatment duration ranged from 80 to 164 hours. No patients in the short- or intermediate-course group had evidence of hepatotoxicity. One woman in the long-course group in whom initiation of NAC treatment was delayed by 28 hours died of fulminant hepatic failure. The overall incidence of hepatotoxicity was similar to that in the historical controls. CONCLUSIONS: In this retrospective case series inpatients who received patient-tailored NAC therapy for acute APAP intoxication, the incidence of hepatotoxicity was low and comparable to that in historical controls who received treatment with 1 of 2 fixed-duration regimens. Use of this protocol may have the potential to shorten hospital stays without increasing the risk to patients. However, the sample size was small, and the findings require confirmation in prospective clinical trials.

Acetaminophen↗

Successful resuscitation after sudden death in a one year old infant who sustained a blunt chest injury after a fall from 10 m.

Sudden cardiac arrest due to blunt anterior chest wall impact (Commotio Cordis) usually occurs in young athletes who are struck by a baseball or other projectile in the precordium. Survival is extremely rare if the induced ventricular fibrillation (VF) is not defibrillated immediately at the scene. We report here a rare case of a one-year-old infant survivor of cardiac arrest caused by blunt chest impact during an accidental fall from a fourth story window. Eye witnesses reported to have seen him land on the front of his chest directly onto the plastic rain cover on the ground floor. He was transferred to a nearby hospital within minutes, where ventricular fibrillation was recorded. Immediate cardiopulmonary resuscitation and defibrillation and was successful. He recovered without any subsequent sequelae. To the best of our knowledge, this rare incident represents the first time that an infant has survived such cardiac arrest in these circumstances that has been recorded in the literature. This has implications for the management of paediatric fall injuries.

Accidental Falls↗

The value of portable ultrasound for evaluation of cardiomegaly patients presenting at the emergency department.

OBJECTIVES: The purpose of this study was to evaluate the value of a hand-carried portable ultrasound device in the emergency department for patients with cardiomegaly and evaluate its impact on diagnosis and treatment. We compared the results of the portable ultrasound with the results of physical examination and with standard echocardiograph (SE) in the cardiomegaly patients in emergency department. BACKGROUND: Recently, small portable ultrasound devices have been introduced, and they need more extensive study to evaluate their application. METHODS: We used the OptiGo (Agilent Technologies, Andover, MA) portable device to evaluate emergency patients, and compared it with two SE devices available for this study, the Hewlett Packard (Sono 5500; Andover, MA) or the Vingmed (System V; Horten, Norway). Each of 100 patients was studied by physical examination first then examined with the portable ultrasound and standard echocardiography. The yields from physical examination and portable echocardiography were compared and results of the standard and portable were also compared. RESULTS: There were a total of 243 cardiovascular findings detected by the standard echocardiographic examination in the 100 patients studied. Cardiac examination failed to detect 40% of the overall findings but the portable device missed only 17% of all findings. The portable device evaluated 201 conditions correctly (83%) and missed relevant clinical findings in 37 (17%) as compared to standard echocardiography, but in only 12 (5%) were these findings of major importance As an overall measure of diagnostic value, the portable device would have added to clinical judgment, thus boosting diagnostic accuracy from 62% to 83%. CONCLUSIONS: Portable ultrasound technology can provide rapid, readily available and important clinical information for emergency physicians in the management of emergency patients with cardiomegaly.

Adult↗

Better adherence to the guidelines during cardiopulmonary resuscitation through the provision of audio-prompts.

OBJECTIVE: Quality assurance to optimize clinical resuscitation performance is important. The aims of the present study were to identify the deficiencies in the clinical practice of resuscitation by motion analysis of video-recorded cardiopulmonary resuscitation (CPR), and to evaluate the effectiveness of quality improvement strategies based on audio-prompt methods. MATERIALS AND METHODS: A two-stage prospective trial was conducted. The first stage (observation group) was designed to identify any major clinical nonconformity to current resuscitation guidelines by videotaped CPR sessions. The second stage (intervention group) was designed to evaluate the effectiveness of audio prompts in ameliorating the problems identified at the first stage. The demographic data of patients and CPR variables between the two groups were analysed. RESULTS: A total of 30 resuscitation attempts were recorded during study period: 17 patients were in the observation group and 13 patients in the intervention group. Inadequate number of chest compressions per minute, lack of re-oxygenation during prolonged intubation attempts and unnecessary hands-off periods were identified as the three most important deficiencies in CPR practice. Compared to the observation group, the intervention group showed a significant improvement in the hands-off period per minute during CPR (12.7 +/- 5.3 s versus 16.9+/-7.9 s, P < 0.05), the total hands-off time during CPR (164 +/- 94 s versus 273 +/- 153 s, P < 0.05), the proportion of intubation attempts taking under 20 s (56.3% versus 10%, P < 0.05). CONCLUSIONS: Audio-prompts can improve the adherence to current CPR guidelines in the clinical setting significantly. The quality improvement measures described in this study are helpful in translating CPR knowledge into clinical practice.

Adult↗

Polyphenol contents in grape-seed extracts correlate with antipica effects in cisplatin-treated rats.

BACKGROUND: Grape-seed (Vitis spp.) extract (GSE) is a widely used antioxidant dietary supplement. Chemotherapeutic agents such as cisplatin induce oxidative damage in the gastrointestinal tract and cause nausea and vomiting. MATERIALS AND METHODS: A rat model of simulated emesis was used to observe that cisplatin significantly increased kaolin consumption (or pica). Three GSEs from different sources were used in this study. RESULTS: High-performance liquid chromatographic analysis of five major constituents (gallic acid, catechin, epicatechi, procyanidin B2, and epicatechin gallate) revealed that each constituent had different levels in the three GSEs. Extract #1, prepared in the laboratory of the investigators, had the lowest total polyphenol content (27.27 mg/g); Extract #2, obtained from a dietary supplement company in the United States, had a somewhat higher level (35.84 mg/g); and Extract #3, obtained from China, had the highest level (194.21 mg/g). Subsequently these GSEs were intraperitoneally administered in rats to evaluate their ability to decreasing cisplatin induced pica. At 10 mg/kg all three GSEs, with varying degrees of effect, decreased cisplatin-induced pica. The areas under the curves of kaolin intake from time 0 to 72 hours, compared to those in the cisplantin-only group, were reduced 45% for Extract #1 (p < 0.01), 54% for Extract #2 (p < 0.01), and 66% Extract #3 (p < 0.001). CONCLUSIONS: The study data showed variable polyphenol contents and proportions in the three GSEs correlated to variable pharmacologic effects, indicating the importance of standardization of herbal product preparations. However further increasing of the GSE doses reversed the antipica effects of GSEs, probably because of their pro-oxidant effects. Results from this study suggest that an appropriate dose of GSE has therapeutic value in treating cisplatin-induced emesis.

Animals↗

Hawthorn: potential roles in cardiovascular disease.

Hawthorn (Crataegus) may play a role in the prevention and treatment of cardiovascular diseases such as hypertension, hyperlipidemia, and in particular, congestive heart failure. Evidence is accumulating that hawthorn may induce anti-ischemia/reperfusion-injury, anti-arrhythmic, hypolipidemic and hypotensive effects. These beneficial effects may in part be due to the presence of antioxidant flavonoid components. While a number of studies have been performed to evaluate the clinical efficacy of hawthorn, an international, multicenter, prospective clinical study including a large number of New York Heart Association (NYHA) class II/III heart failure patients is ongoing to test hawthorn's long-term therapeutic effects. Further clinical trials as well as pharmacokinetic and mechanistic studies are needed to explore and confirm its effectiveness, safety and pharmacological mechanism.

Cardiovascular Diseases↗

Effects of ganoderma lucidum extract on chemotherapy-induced nausea and vomiting in a rat model.

Chemotherapy is highly cytotoxic, causing a number of severe adverse effects such as nausea and vomiting. Herbal medicines, which can often be used on a daily basis for prolonged treatment, may be clinically beneficial. Ganoderma lucidum or Lingzhi mushroom has been recognized as a remedy in treating a number of medical conditions, including balancing immunity and decreasing drug-induced side effects. It has been shown that rats react to emetic stimuli, like the chemotherapy agent cisplatin, by increased consumption of kaolin, known as pica; and this rat model has been utilized to evaluate novel anti-emetic compounds. In this study, we evaluated the effects of a G. lucidum extract (SunRecome, the most commonly used Lingzhi mushroom extract in China) in attenuating cisplatin-induced nausea and vomiting in the rat pica model. We observed that intraperitoneal cisplatin injection caused a significant increase in kaolin intake at 24, 48, 72 and 96 hours, reflecting cisplatin's nausea and vomiting action. This cisplatin-induced kaolin intake dose-dependently decreased after 1, 3 and 10 mg/kg G. lucidum extract injection (p < 0.01). In addition, there was a significant reduction of food intake after cisplatin. The cisplatin-induced food intake reduction improved significantly after G. lucidum extract administrations in a dose-related manner (p < 0.01), suggesting a supportive effect of the extract on general body condition. Future controlled clinical trials are needed to evaluate the safety and effectiveness of this herbal medication.

Animals↗

Ascorbate supplement reduces oxidative stress in dyslipidemic patients undergoing apheresis.

OBJECTIVE: The effect of ascorbate treatment on apheresis-induced oxidative stress in uremic and dyslipidemic patients was evaluated. METHODS AND RESULTS: We developed a chemiluminescence-emission spectrum and high-performance liquid chromatography analysis to assess the effect of ascorbate supplement on plasma reactive oxygen species (ROS) scavenging activity and oxidized lipid/protein production in hyperlipidemic and uremic patients undergoing apheresis. Apheresis was efficient in reduction of atherogenic lipoproteins, complement, fibrinogen, soluble intercellular adhesion molecule-1, and oxidative parameters including phosphatidylcholine hydroperoxide (PCOOH), malonaldehyde, methylguanidine, and diotyrosine. Apheresis itself, however, activated leukocytes to increase ROS activity and reduced the plasma ROS scavenging activity. Ascorbate administration selectively diminished apheresis-enhanced H2O2 and inflammatory mediators such as tumor necrosis factor alpha (TNF-alpha) and monocyte chemoattractant protein-1. Chronically dyslipidemic and uremic patients undergoing biweekly apheresis plus ascorbate treatment had lower levels of C-reactive protein and PCOOH than did those without ascorbate treatment during a 6-month follow-up study period. CONCLUSIONS: We demonstrate that apheresis with ascorbate treatment provides a therapeutic potential in reducing atherosclerotic risk via inhibition of H2O2-induced oxidative stress in patients with uremia or dyslipidemia.

Adult↗