Tain-Junn Cheng

The association between arsenic exposure from drinking water and cerebrovascular disease mortality in Taiwan.

BACKGROUNDnChronic arsenic exposure is associated with a variety of diseases, including cancer, peripheral vascular disease, and diabetes. However, its association with cerebrovascular diseases (CVD) has not yet been resolved. The aim of this study is to explore this association in Taiwan using nation-wide data.nnnMATERIALS AND METHODSnWe analyzed mortality data in Taiwan from 1971 to 2005 and choose two geographic areas with populations suffering from chronic exposure to arsenic in drinking water for study, the blackfoot disease endemic area (BFDEA) in the southwest and Lan-Yang Basin (LYB) in the northeast parts of Taiwan. The Chia-Yi and Tainan Counties, which surround the BFDEA, and the nation of Taiwan as a whole were used as reference populations. Direct standardized mortality rates and gender-specific indirect standardized mortality ratios (SMRs) were calculated for the four populations.nnnRESULTSnThe direct standardized mortality rate for CVD in Taiwan decreased from 2.46/10(3) person-year in 1971 to 0.63/10(3) person-year in 2005, and women had significantly lower mortality than men (SMR = 0.80; p < 0.05). The CVD mortality rates of populations with chronic arsenic exposure were significantly higher than the reference populations (SMR ranging from 1.06 to 1.09 in men and 1.12 to 1.14 in women; p < 0.05). The BFDEA had higher CVD mortality rates than the LYB, with SMR = 1.05 (p < 0.05) in men and SMR = 1.04 (p = 0.05) in women.nnnCONCLUSIONnIn Taiwan, while CVD mortality decreased in both genders between 1971 and 2005, chronic arsenic exposure from drinking water was associated with increased risks of CVD.

Atherosclerosis induced by arsenic in drinking water in rats through altering lipid metabolism

Arsenic in drinking water is a global environmental health problem, and the exposure may increase cardiovascular and cerebrovascular diseases mortalities, most likely through causing atherosclerosis. However, the mechanism of atherosclerosis formation after arsenic exposure is still unclear. To study the mechanism of atherosclerosis formation after arsenic exposure and explore the role of high cholesterol diet (HCD) in this process, we fed spontaneous hypertensive rats and Wistar Kyoto rats with basal diet or HCD and provided with them drinking water containing arsenic at different ages and orders for 20 consecutive weeks. We measured high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), total cholesterol, triglycerides, heat shock protein 70 (HSP 70), and high sensitive C-reactive protein (hs-CRP) at predetermined intervals and determined expressions of cholesteryl ester transfer protein-1 (CETP-1) and liver X receptor β (LXRβ) in the liver. Atherosclerosis was determined by examining the aorta with hematoxylin and eosin stain. After 20 weeks, we found arsenic, alone or combined with HCD, may promote atherosclerosis formation with transient increases in HSP 70 and hs-CRP. Early combination exposure decreased the HDL-C/LDL-C ratio without changing the levels of total cholesterol and triglyceride until 30 weeks old. Both CETP-1 and LXRβ activities were suppressed, most significantly in early combination exposure. In conclusion, arsenic exposure may induce atherosclerosis through modifying reverse cholesterol transport in cholesterol metabolism and suppressing LXRβ and CEPT-1 expressions. For decreasing atherosclerosis related mortality associated with arsenic, preventing exposure from environmental sources in early life is an important element.

Prognosis of young ischemic stroke in Taiwan: impact of prothrombotic genetic polymorphisms

We investigated the effects of genetic factors on the prognosis of cerebral infarction in young adults in Taiwan. Because ischemic stroke with arterial occlusion or undetermined etiology is more likely to be related to a genetic prothrombotic state, 231 patients younger than 50 years (mean age 44.6 years, range 25 to 49 years) with acute ischemic stroke due to large artery atherosclerosis (n=90), small artery occlusion (n=114) or undetermined cause (n=27) were recruited and prospectively followed up for pre-determined outcome. On each patient, we screened the PlA1/PlA2 polymorphism of the platelet glycoprotein IIIa gene, 4G/5G polymorphism of the plasminogen activator inhibitor-1 gene, G10976A polymorphism of the factor VII gene, C677T polymorphism of the methylenetetrahydrofolate reductase gene, and 27 base-pair repeat polymorphism of the endothelial nitric oxide synthase gene. End points were the composite outcome events of stroke, myocardial infarction, and death from all causes. During a mean duration follow-up of 29 months, composite outcome events occurred in 33 patients. There was a higher annual incidence rate of composite outcome events during the first year (9.1%, 95% CI 5.9-13.9%) than in the subsequent 2 years (2.6%, 95% CI 1.2-5.6%, p=0.038). None of the genetic polymorphism was associated with the composite outcome events. Past history of coronary artery disease or cerebrovascular disease was the only independent predictor of the composite outcome events (HR 3.71, 95% CI 1.69-8.14, p=0.001) at the Cox regression analysis. Our data indicate that the prothrombotic genetic polymorphisms do not have a significant influence on the prognosis in young ischemic stroke due to arterial occlusion or undetermined causes in Taiwan.

Risk of carotid atherosclerosis is associated with low serum paraoxonase (PON1) activity among arsenic exposed residents in Southwestern Taiwan.

To understand whether human paraoxonase 1 (PON1) would modulate the risk for arsenic-related atherosclerosis, we studied 196 residents from an arseniasis-endemic area in Southwestern Taiwan and 291 age- and sex-matched residents from a nearby control area where arsenic exposure was found low. Carotid atherosclerosis was defined by a carotid artery intima-media wall thickness (IMT) of >1.0 mm. Prevalence of carotid atherosclerosis was increased in the arseniasis-endemic area as compared to the control area after adjustment for conventional risk factors (OR=2.20, p<0.01). The prevalence was positively associated with cumulative arsenic exposure (mg/L-year) in a dose-dependent manner. Multiple logistic regression analysis showed that in the endemic group, low serum PON1 activity was an independent risk factor for atherosclerosis (OR=4.18 low vs. high, p<0.05). For those of low PON1 activity and high cumulative arsenic exposure, the odds ratio for the prevalence of atherosclerosis was further increased up to 5.68 (p<0.05). No significant association was found between atherosclerosis and four polymorphisms of the PON gene cluster (PON1 -108C/T, PON1 Q192R, PON2 A148G, PON2 C311S). However, genetic frequencies of certain alleles including PON1 Q192, PON2 G148 and PON2 C311 were found increased in the endemic group as compared to the controls and a general Chinese population, indicating a possible survival selection in the endemic group after a long arsenic exposure history. Our results showed a significant joint effect between arsenic exposure and serum PON1 activity on carotid atherosclerosis, suggesting that subjects of low PON1 activity may be more susceptible to arsenic-related cardiovascular disease.

Differential anti-diabetic effects and mechanism of action of charantin-rich extract of Taiwanese Momordica charantia between type 1 and type 2 diabetic mice.

Momordica charantia Linn. (Cucurbitaceae), also called bitter melon, has traditionally been used as a natural anti-diabetic agent for anti-hyperglycemic activity in several animal models and clinical trials. We investigated the differences in the anti-diabetic properties and mechanism of action of Taiwanese M. charantia (MC) between type 1 diabetic (T1D) and type 2 diabetic (T2D) mice. To clarify the beneficial effects of MC, we measured non-fasting glucose, oral glucose tolerance, and plasma insulin levels in KK/HIJ mice with high-fat diet-induced diabetes (200 mg/kg/day of charantin-rich extract of MC [CEMC]) and in ICR mice with STZ-induced diabetes. After 8 weeks, all the mice were exsanguinated, and the expression of the insulin-signaling-associated proteins in their tissue was evaluated, in coordination with the protective effects of CEMC against pancreatic β-cell toxicity (in vitro). Eight weeks of data indicated that CEMC caused a significant decline in non-fasting blood glucose, plasma glucose intolerance, and insulin resistance in the KK/HIJ mice, but not in the ICR mice. Furthermore, CEMC decreased plasma insulin and promoted the sensitivity of insulin by increasing the expression of GLUT4 in the skeletal muscle and of IRS-1 in the liver of KK/HIJ mice; however, CEMC extract had no effect on the insulin sensitivity of ICR mice. In vitro study showed that CEMC prevented pancreatic β cells from high-glucose-induced cytotoxicity after 24 h of incubation, but the protective effect was not detectable after 72 h. Collectively, the hypoglycemic effects of CEMC suggest that it has potential for increasing insulin sensitivity in patients with T2D rather than for protecting patients with T1D against β-cell dysfunction.

Exploring critical factors influencing physicians' acceptance of mobile electronic medical records based on the dual-factor model: a validation in Taiwan

BackgroundWith respect to information management, most of the previous studies on the acceptance of healthcare information technologies were analyzed from “positive” perspectives. However, such acceptance is always influenced by both positive and negative factors and it is necessary to validate both in order to get a complete understanding. This study aims to explore physicians’ acceptance of mobile electronic medical records based on the dual-factor model, which is comprised of inhibitors and enablers, to explain an individual’s technology usage. Following an earlier healthcare study in the USA, the researchers conducted a similar survey for an Eastern country (Taiwan) to validate whether perceived threat to professional autonomy acts as a critical inhibitor. In addition, perceived mobility, which is regarded as a critical feature of mobile services, was also evaluated as a common antecedent variable in the model.MethodsPhysicians from three branch hospitals of a medical group were invited to participate and complete questionnaires. Partial least squares, a structural equation modeling technique, was used to evaluate the proposed model for explanatory power and hypotheses testing.Results158 valid questionnaires were collected, yielding a response rate of 33.40%. As expected, the inhibitor of perceived threat has a significant impact on the physicians’ perceptions of usefulness as well as their intention to use. The enablers of perceived ease of use and perceived usefulness were also significant. In addition, as expected, perceived mobility was confirmed to have a significant impact on perceived ease of use, perceived usefulness and perceived threat.ConclusionsIt was confirmed that the dual-factor model is a comprehensive method for exploring the acceptance of healthcare information technologies, both in Western and Eastern countries. Furthermore, perceived mobility was proven to be an effective antecedent variable in the model. The researchers believe that the results of this study will contribute to the research on the acceptance of healthcare information technologies, particularly with regards to mobile electronic medical records, based on the dual-factor viewpoints of academia and practice.

Epidemiology of treated attention-deficit/hyperactivity disorder (ADHD) across the lifespan in Taiwan: a nationwide population-based longitudinal study.

Objectives We used insurance claims of a nationally representative population-based cohort to assess the longitudinal treated prevalence and incidence of attention-deficit/hyperactivity disorder (ADHD) in children, adolescents and adults. Methods Participants were identified from among National Health Insurance enrollees in Taiwan from 1999 to 2005. We identified study subjects who had at least one service claim during these years with a principal diagnosis of ADHD. A total of 6,173 patients were recorded in the treated ADHD cohort during the 6-year study. Results There was a significant increase in the treated prevalence rate of ADHD during the study period, from 64.65 per 100,000 in 2000 to 145.40 per 100,000 in 2005 (pu200a=u200a.001). An increase in the treated incidence rate of ADHD, from 44.67 per 100,000 in 2000 to 81.20 per 100,000 in 2005, was also observed (pu200a=u200a.013). However, the treated prevalence of ADHD was still lower than that of the community data in Taiwan. The peak treated prevalence of ADHD was at age 7–12 years for both males and females, and the peak treated incidence of ADHD was at age 0–6 for females and age 7–12 for males. Overall, the treated incidence and prevalence rates dropped abruptly after age 13–18 (both p<.001) for males and females (p<.001 for both). Male vs. female ratios of treated prevalence and incidence were both above 1 before age 25–30 years, but below 1 thereafter. Conclusion Although an increasing number of people with ADHD sought treatment during 1999–2005 in Taiwan, the treated prevalence of ADHD was still lower than that of the community data. The treated incidence and prevalence of ADHD fell dramatically after age 13–18. However, more women than men sought treatment in adulthood. There may be under-diagnosis and under-treatment of ADHD, especially among females and adults.

Room-temperature super-extraction system (RTSES) optimizes the anxiolytic- and antidepressant-like behavioural effects of traditional Xiao-Yao-San in mice

BackgroundXiao-Yao-San (XYS) is a Chinese medicinal formula for treating anxiety and depression. This study aims to evaluate the use of a room-temperature super-extraction system (RTSES) to extract the major active components of XYS and enhance their psycho-pharmacological effects.MethodsThe neuroprotective roles of XYS/RTSES against reserpine-derived neurotoxicity were evaluated using a glial cell injury system (in vitro) and a depression-like C57BL/6 J mouse model (in vivo). The anxiolytic-behavioural effects were measured by the elevated plus-maze (EPM) test and the antidepressant effects were evaluated by the forced swimming test (FST) and tail suspension test (TST). Glucose tolerance and insulin resistance were assayed by ELISA. The expression of 5-HT1A receptors in the prefrontal cortex was examined by western blotting.ResultsXYS/RTSES (300 μg/mL) diminished reserpine-induced glial cell death more effectively than either XYS (300 μg/mL) or fluoxetine (30 μM) at 24 h (Pu2009=u20090.0481 and Pu2009=u20090.054, respectively). Oral administration of XYS/RTSES (500 mg/kg/day) for 4 consecutive weeks significantly elevated the ratios of entries (open arms/closed arms; Pu2009=u20090.0177) and shuttle activity (Pu2009=u20090.00149) on the EPM test, and reduced the immobility time by 90% on the TST (Pu2009=u20090.00000538) and FST (Pu2009=u20090.0000053839). XYS/RTSES also improved the regulation of blood glucose (Pu2009=u20090.0305) and increased the insulin sensitivity (Pu2009=u20090.0093). The Western blot results indicated that the activation of cerebral 5-HT1A receptors may be involved in the mechanisms of XYS/RTSES actions.ConclusionThe RTSES could provide a novel method for extracting effective anxiolytic- and antidepressant-like substances. XYS/RTSES improved the regulation of blood glucose and increased the insulin sensitivity in reserpine-induced anxiety and depression. Neuroprotection of glial cells and activation of cerebral 5-HT1A receptors were also involved.

Macrophage mediated anti-proliferation effects of Anthodia camphorata non-polysaccharide based extracts on human hepatoma cells.

It has been reported that medicinal mushrooms might induce different types of immune responses. Anthodia camphorata (A. camphorata) has attracted much attention for its therapeutic effects in treating hepatoma. We tested this anti-tumor effects using immunomodulation of macrophages and extracts of A. camphorata. We evaluated the anti-proliferation effects of various extracts of A. camphorata from fruiting bodies (AC-FB), mycelium of solid-state cultures (AC-SS), liquid-state cultures (AC-LS) and polyaccharide extracts from liquid-state cultures (AC-PS), and extracts of A. camphorata stimulated RAW 264.7 macrophage cell-conditioned mediums (MC-CMs). We measured cell proliferation and, did migration assays by cell cycle analysis and by observing apoptosis-related proteins (AKT, PARP-1, and NF-κB) and the mRNA expression of cytokines (TNF-α and IL-1β) of macrophages in human hepatoma cell lines. Our results revealed that two of the extracts (AC-FB and AC-SS) had better anti-proliferation effects, implying an immunomodulatory role the macrophages might play. This outcome is consistent with findings that AC-FB and AC-SS increase mRNA expression of TNF-α and the corresponding expression of apoptosis-related proteins on activation of MC-CMs, while A. camphorata polysaccharides induce macrophage-derived anti-tumor activities in human hepatoma cells via IL-1β and Akt activation. These results indicate that anti-tumor effects exerted by modulation of macrophage activation of A. camphorate may be influenced by the other constituents which (contained little or no polysaccharide) of A. camphorata.

Risk of Shingles in Adults with Primary Sjogren's Syndrome and Treatments: A Nationwide Population-Based Cohort Study.

Background Primary Sjögrens syndrome (pSS) is associated with immunological dysfunctions—a well-known risk factor of shingles. This study aimed to examine the incidence and risk of shingles in adults with pSS and pharmacological treatments. Methods This retrospective population-based cohort study was conducted using National Health Insurance claims data. Using propensity scores, 4,287 pSS adult patients and 25,722-matched cohorts by age, gender, selected comorbidities and Charlson comorbidity index scores were identified. Kaplan-Meier analysis and Cox regression were conducted to compare the differences in developing shingles. In pSS, oral and eye dryness are treated with substitute agents. Extraglandular features are often treated with pharmacological drugs including steroids and immunosuppressants. pSS patients were grouped as follows: no pharmacological drugs, steroids alone; immunosuppressants alone; combined therapies. Results During the follow-up, 463 adults with pSS (10.80%) and 1,345 control cohorts (5.23%) developed shingles. The cumulative incidence of shingles in pSS patients (18.74/1,000 patient-years) was significantly higher than controls (8.55/1,000 patient-years). The adjusted hazard ratio (HR) of shingles was 1.69 (95% confidence interval (CI) 1.50–1.90). In age-subgroup analyses, incidences of shingles in pSS increased with age and peaked in pSS patients aged ≧60; however, adjusted HRs decreased with age. Compared to control cohorts with no drugs, adjusted HRs for shingles in pSS patients were ranked from high to low as: combined therapies (4.14; 95% CI 3.14–5.45) > immunosuppressants alone (3.24; 95% CI 2.36–4.45) > steroids alone (2.54; 95% CI 2.16–2.97) > no pharmacological drugs (2.06; 95% CI 1.76–2.41). Rates of shingles-associated hospitalization and postherpetic neuralgia were 5.62% and 24.41%, both of which were significantly higher than those (2.60%; 13.01%) in the control cohorts. Conclusions Adults with pSS were at greater risk for shingles than control cohorts. Drug exposures significantly increased the risk of shingles in pSS.