Ding-Cheng Chan - Academia.edu (original) (raw)

Papers by Ding-Cheng Chan

The journal of nutrition, health & aging, 2016

Prevention of fragility fractures in older people has become a public health priority, although t... more Prevention of fragility fractures in older people has become a public health priority, although the most appropriate and cost-effective strategy remains unclear. In the present statement, the Interest Group on Falls and Fracture Prevention of the European Union Geriatric Medicine Society (EUGMS), in collaboration with the International Association of Gerontology and Geriatrics for the European Region (IAGG-ER), the European Union of Medical Specialists (EUMS), the International Osteoporosis Foundation - European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis, outlines its views on the main points in the current debate in relation to the primary and secondary prevention of falls, the diagnosis and treatment of bone fragility, and the place of combined falls and fracture liaison services for fracture prevention in older people.

Oncotarget, Jan 3, 2016

Renal tubulointerstitial fibrosis is the common and final pathologic change of kidney in end-stag... more Renal tubulointerstitial fibrosis is the common and final pathologic change of kidney in end-stage renal disease. Interesting, endoplasmic reticulum (ER) stress is known to contribute to the pathophysiological mechanisms during the development of renal fibrosis. Here, we investigated the effects of chemical chaperon sodium 4-phenylbutyrate (4-PBA) on renal fibrosis in vivo and in vitro. In a rat unilateral ureteral obstruction (UUO) model, 4-PBA mimicked endogenous ER chaperon in the kidneys and significantly reduced glucose regulated protein 78 (GRP78), CCAAT/enhancer binding protein (C/EBP) homologous protein (CHOP), activating transcription factor 4 (ATF4), and phosphorylated JNK protein expressions as well as restored spliced X-box-binding protein 1 (XBP1) expressions in the kidneys of UUO rats. 4-PBA also attenuated the increases of α-smooth muscle actin (α-SMA), connective tissue growth factor (CTGF) protein expressions, tubulointerstitial fibrosis, and apoptosis in the kidney...

Oncotarget, Jan 5, 2016

Heat shock protein 60 (HSP60) is a mitochondrial chaperone. Advanced glycation end products (AGEs... more Heat shock protein 60 (HSP60) is a mitochondrial chaperone. Advanced glycation end products (AGEs) have been shown to interfere with the β-cell function. We hypothesized that AGEs induced β-cell hypertrophy and dysfunction through a HSP60 dysregulation pathway during the stage of islet/β-cell hypertrophy of type-2-diabetes. We investigated the role of HSP60 in AGEs-induced β-cell hypertrophy and dysfunction using the models of diabetic mice and cultured β-cells. Hypertrophy, increased levels of p27Kip1, AGEs, and receptor for AGEs (RAGE), and decreased levels of HSP60, insulin, and ATP content were obviously observed in pancreatic islets of 12-week-old db/db diabetic mice. Low-concentration AGEs significantly induced the cell hypertrophy, increased the p27Kip1 expression, and decreased the HSP60 expression, insulin secretion, and ATP content in cultured β-cells, which could be reversed by RAGE neutralizing antibody. HSP60 overexpression significantly reversed AGEs-induced hypertroph...

The Journal of Pathology, 2015

Diabetic myopathy, a less studied complication of diabetes, exhibits the clinical observations ch... more Diabetic myopathy, a less studied complication of diabetes, exhibits the clinical observations characterized by a less muscle mass, muscle weakness, and a reduced physical functional capacity. Accumulation of advanced glycation end products (AGEs), known to play a role in diabetic complications, has been identified in aging human skeletal muscles. However, the role of AGEs in diabetic myopathy remains unclear. Here, we investigated the effects of AGEs on myogenic differentiation and muscle atrophy in vivo and in vitro. We also evaluated the therapeutic potential of alagebrium chloride (Ala-Cl), an inhibitor of AGEs). Muscle fibre atrophy and immunoreactivity for AGEs, Atrogin-1 (a muscle atrophy marker), and phosphorylated AMP-activated protein kinase (AMPK) expressions were markedly increased in human skeletal muscles from patients with diabetes as compared with control subjects. Moreover, in diabetic mice we found increased blood AGEs, less muscle mass, lower muscular endurance, atrophic muscle size, poor regenerative capacity, and increased levels of muscle AGEs, receptor for AGE (RAGE), Atrogin-1, and phosphorylated AMPK, which could be significantly ameliorated by Ala-Cl. Furthermore, in vitro, AGEs (in a dose-dependent manner) reduced myotube diameters (myotube atrophy) and induced Atrogin-1 protein expression in myotubes differentiated from both mouse myoblasts and primary human skeletal muscle-derived progenitor cells. AGEs exerted a negative regulation of myogenesis of mouse and human myoblasts. Ala-Cl significantly inhibited the effects of AGEs on myotube atrophy and myogenesis. We further demonstrated that AGEs induced muscle atrophy/myogenesis impairment via a RAGE-mediated AMPK-down-regulation of the Akt signalling pathway. Our findings support that AGEs play an important role in diabetic myopathy and that an inhibitor of AGEs may offer a therapeutic strategy for managing the dysfunction of muscle due to diabetes or aging.

Journal of medical case reports, 2015

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids is ... more Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids is a brainstem disorder characterized by perivascular pathologic reaction with lymphocyte infiltration and leading to diplopia, facial palsy, dysarthria, and gait ataxia. It was thought to be an autoimmune disorder without distinct pathogenesis. Chronic hepatitis B virus infection has been proposed in correlation with autoimmune diseases, including central nervous system demyelinating disease. Patients with chronic hepatitis B infection may develop the syndrome of chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids. A 34-year-old Taiwanese man who had been a hepatitis B virus carrier for a decade presented to our emergency room. He had influenza symptoms and progressive symptoms of left hemifacial numbness, double vision, and an unsteady gait of 2 days' duration. Chronic lymphocytic inflammation with pontine perivascular enhancement responsive t...

BMJ Open, 2015

To investigate the national prevalence of potentially inappropriate medications (PIMs) prescribed... more To investigate the national prevalence of potentially inappropriate medications (PIMs) prescribed in ambulatory care clinics in Taiwan according to three different sets of regional criteria and the correlates of PIM use. Cross-sectional study. This analysis included older patients who visited ambulatory care clinics in 2009 and represented half of the older population included on the Taiwanese National Health Insurance Research Database. We identified 1 164 701 subjects who visited ambulatory care clinics and were over 65 years old in 2009. PIM prevalence according to the 2012 Beers criteria, the PIM-Taiwan criteria and the PRISCUS criteria was estimated separately, and characteristics of PIM users were explored. Multivariate logistic regression analysis was used to determine patient factors associated with the use of at least one PIM. Leading PIMs for each set of criteria were also listed. The prevalence of having at least one PIM at the patient level was highest with the Beers criteria (86.2%), followed by the PIM-Taiwan criteria (73.3%) and the PRISCUS criteria (66.9%). Polypharmacy and younger age were associated with PIM use for all three sets of criteria. The leading PIMs detected by the PIM-Taiwan and PRISCUS criteria were all included in the 2012 Beers criteria. Non-COX-selective non-steroidal anti-inflammatory drugs in the Beers criteria and benzodiazepines in the PIM-Taiwan and PRISCUS criteria accounted for most leading PIMs. The prevalence of PIMs was high among older Taiwanese patients receiving ambulatory care visits. The prevalence of PIM and its associated factors varied according to three sets of criteria at the population level.

Journal of Orthopaedic Research, 2015

Aging and diabetes are known to be the major cause to affect the progression of osteoarthritis (O... more Aging and diabetes are known to be the major cause to affect the progression of osteoarthritis (OA). Advanced glycation end products (AGEs) have been observed to accumulate in various organs especially in joint tissue and do damage to the joint tissue during aging and diabetes. Synovial angiogenesis and inflammation are observed across the full range of OA severity. The signaling pathway of AGEs on vascular endothelial growth factor (VEGF) production and inflammatory responses in synoviocytes are still unclear. Here, we investigated the role of receptor for AGEs (RAGE) and the signaling pathway involved in AGEs-induced VEGF production and inflammatory responses in human synoviocytes. Human synoviocytes were cultured and treated with AGEs (25-100 µg/ml). AGEs significantly induced the protein expressions of cyclooxygenase-2 (COX-2) and VEGF and the productions of prostaglandin-E2 (PGE2), VEGF, interleukin-6 (IL-6), and metalloproteinase-13 (MMP-13) in human synoviocytes in a dose-dependent manner. Moreover, AGEs markedly activated the phosphorylations of IκB kinase (IKK)α/β, IκBα, and nuclear factor (NF)-κB-p65 proteins in human synoviocytes in a time-dependent manner. Treatment with neutralizing antibody for RAGE statistically significantly decreased the AGEs-induced increase in COX-2, VEGF, PGE2, IL-6, and MMP13 and AGEs-activated NF-κB pathway activation. Taken together, these findings indicate that AGEs are capable of inducing VEGF production and inflammatory responses via RAGE-NF-κB pathway activation in human synoviocytes. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

PloS one, 2015

Bone remodeling has been linked to glucose metabolism in animal studies, but the results of human... more Bone remodeling has been linked to glucose metabolism in animal studies, but the results of human trials were inconclusive. Bisphosphonates may play a role in glucose metabolism through their impacts on bone remodeling enzymes. In this study, we aimed to examine the influence of alendronate usage on the incidence of type 2 diabetes mellitus (DM) among osteoporotic patients. A retrospective cohort study was designed to include osteoporotic patients without DM from a population-based cohort containing 1,000,000 subjects. Patients treated with alendronate (exposed group, N=1,011) were compared with those who received no treatment (age and gender matched non-exposed group, N=3,033). Newly diagnosed DM was identified from medical records by International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9CM) code. The incidence of DM in both groups was calculated for comparison. The non-exposed group had a significantly higher incidence of DM (Odds ratio 1.21, 95% co...

Environmental health perspectives, Jan 10, 2015

Epidemiological studies reported that the prevalence of diabetes in women over 40 years of age, e... more Epidemiological studies reported that the prevalence of diabetes in women over 40 years of age, especially those in the postmenopausal phase, was higher than men in areas with high levels of arsenic in drinking water. The detailed effect of arsenic on glucose metabolism/homeostasis in the postmenopausal condition is still unclear. We investigated the effects of arsenic at doses relevant to human exposure from drinking water on blood glucose regulation in estrogen-deficient female mice. Adult female mice who underwent ovariectomy or sham were exposed to drinking water contaminated with arsenic trioxide (0.05 or 0.5 ppm) in the presence or absence of 17β-estradiol supplementation for 2-6 weeks. Assays related to glucose metabolism were performed. Exposure of normal mice to arsenic significantly increased blood glucose, decreased plasma insulin, and impaired glucose tolerance, but did not induce insulin resistance. Blood glucose and insulin were higher, and glucose intolerance, insulin...

Journal of orthopaedic research : official publication of the Orthopaedic Research Society, 2015

Diabetic hyperglycemia has been suggested to play a role in osteoarthritis. Peroxisome proliferat... more Diabetic hyperglycemia has been suggested to play a role in osteoarthritis. Peroxisome proliferator-activated receptor-γ (PPARγ) was implicated in several pathological conditions including diabetes and inflammation. The detailed effects and mechanisms of hyperglycemia on cartilage damage still need to be clarified. Here, we investigated the role of PPARγ in hyperglycemia-triggered chondrocyte/cartilage damages using a human chondrocyte culture model and a diabetic mouse model. Human chondrocytes were cultured and treated with high concentration of glucose (30 mM) to mimic hyperglycemia in the presence or absence of pioglitazone, a PPARγ agonist. Streptozotocin (STZ) was used to induce mouse diabetes. Our data showed that high glucose induced the protein expressions of cyclooxygenase-2 (COX-2) and production of prostaglandin-E2 (PGE2 ), interleukin-6 (IL-6), and metalloproteinase-13 (MMP-13), but decreased the protein expression of collagen II and PPARγ in human chondrocytes. These a...

PLoS ONE, 2014

Objectives: Taiwanese National Health Insurance (TNHI) provides home healthcare services to patie... more Objectives: Taiwanese National Health Insurance (TNHI) provides home healthcare services to patients with skilled nursing needs who were homebound or lived in nursing homes. Studies on potentially inappropriate medications (PIMs) for older home healthcare service recipients (HHSRs) are growing, but comparisons among newer criteria of PIMs have not been applied. The aim of this study was to explore the prevalence and correlates of PIMs based on three different instruments published after 2010 among older HHSRs.

Pharmacoepidemiology and Drug Safety, 2012

Background Explicit criteria for potentially inappropriate medications (PIMs) developed from othe... more Background Explicit criteria for potentially inappropriate medications (PIMs) developed from other regions were often difficult to apply to a specific territory without significant modifications. Purpose To describe a process of developing a country-specific explicit PIM criteria from quality review of several published PIM criteria, followed by consensus among regional experts in Taiwan.

NDT Plus, 2009

A 60-year-old woman presented with intermittent lowgrade fever and chills for 1 month accompanied... more A 60-year-old woman presented with intermittent lowgrade fever and chills for 1 month accompanied by right flank soreness, poor appetite and marked body weight loss (12 kg within 1 month). Leukocytosis (WBC = 17.75 × 10 9 /l), normocytic anaemia (haemoglobin 6.6 g/dl) and pyuria were noted. Abdominal computed tomography (CT) showed an enlarged right kidney with dilated collecting system filled with hypodense substance (pus) and staghorn stones, which are typical CT findings for xanthogranulomatous pyelonephritis ( ). She received CTguided drainage immediately, and total amount of 300 ml brown-bloody pus was drained out. However, serial urine and pus cultures did not yield any pathogen. After a Correspondence and offprint requests to:

Journal of the Formosan Medical Association, 2011

Journal of the Formosan Medical Association, 2014

Background/Purpose: Polypharmacy is common among Taiwanese older adults. We aim to determine the ... more Background/Purpose: Polypharmacy is common among Taiwanese older adults. We aim to determine the effectiveness of the medication safety review clinics (MSRCs) for solving drug-related problems (DRPs) among older adults prescribed multiple medications. Methods: This prospective case-series intervention study was conducted at the outpatient department of the National Taiwan University Hospital and its BeiHu Branch. Older adults (!65 years) who either had been prescribed !8 chronic medications (drugs prescribed for !28 days) or had visited !3 different physicians during the 3-month screening period were enrolled (N Z 193). DRPs were identified after baseline assessments from a team of geriatricians and pharmacists. Prescribers were contacted with proposed interventions to be administered within 12 weeks. Problem-solving rates (PSRs) at both Week 12 and Week 24 visits were recorded. Stepwise multivariate logistic regression was applied to identify correlates of having at least one unsolved DRP at 24 weeks. Participants (N Z 139) who completed four visits to the MSRCs were analyzed. Results: The mean age was 75.6 AE 6.1 years and 56% of them were men. The mean chronic medication per patient was 9.0 AE 3.1, and the mean DRP per patient was 2.1 AE 1.5.

Journal of Orthopaedic Research, 2014

Proinflammatory cytokine interleukin-1b (IL-1b) stimulates several mediators of cartilage degrada... more Proinflammatory cytokine interleukin-1b (IL-1b) stimulates several mediators of cartilage degradation and plays an important role in the pathogenesis of osteoarthritis (OA). Honokiol, a low molecular weight natural product isolated from the Magnolia officinalis, has been shown to possess anti-inflammatory effect. Here, we used an in vitro model of cartilage inflammation to investigate the therapeutic potential of honokiol in OA. Human OA chondrocytes were cultured and pretreated with honokiol (2.5-10 mM) with or without IL-1b (10 ng/ml). Nitric oxide (NO) production was quantified by Griess reagent. Prostaglandin (PG)E 2 , metalloproteinase-13 (MMP-13), and interleukin-6 (IL-6) productions were quantified by enzyme-linked immunosorbent assay. The expressions of collagen II, cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and nuclear factor kB (NF-kB)-related signaling molecules were determined by Western blotting. Our data showed that IL-1b markedly stimulated the expressions of iNOS and COX-2 and the productions of NO, PGE 2 , and IL-6, which could be significantly reversed by honokiol. Honokiol could also suppress the IL-1b-triggered activation of IKK/IkBa/NF-kB signaling pathway. Moreover, honokiol significantly inhibited the IL-1b-induced MMP-13 production and collagen II reduction. Taken together, the present study suggests that honokiol may have a chondroprotective effect and may be a potential therapeutic choice in the treatment of OA patients. ß

The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 2003

Background. The role of behavioral and psychological symptoms as an independent risk factor of nu... more Background. The role of behavioral and psychological symptoms as an independent risk factor of nursing home placement (NHP) in cognitively impaired elders has been controversial.

The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 2007

Little is known about the terminal trajectories of functional decline among long-term care (LTC) ... more Little is known about the terminal trajectories of functional decline among long-term care (LTC) residents dying with different diseases.

Journal of Geriatric Psychiatry and Neurology, 2007

Little is known about the prevalence and correlates of psychotropic use in community-dwelling eld... more Little is known about the prevalence and correlates of psychotropic use in community-dwelling elders with dementia. Baseline data from 285 community-dwelling elders with a research classification of dementia (based on a neuropsychological battery of 4 tests) and their knowledgeable informants enrolled in the observational Memory and Medical Care Study were analyzed. A total of 33.3% of subjects with a research classification of dementia were clinically diagnosed, 28.8% used at least 1 psychotropic drug, and 61.8% had at least 1 behavioral or psychological symptom of dementia (BPSD). Presence of BPSD was associated with a higher likelihood of a clinical diagnosis of dementia. Multivariate logistic regression showed a clinical diagnosis of dementia, not BPSD, was associated with psychotropic use; clinical recognition of dementia appears to be an intermediate step between presence of BPSD and prescription of psychotropics. In addition, most community-dwelling elders meeting the research criteria for dementia were not clinically diagnosed, despite contact with a physician (89%) in the previous year. (J Geriatr Psychiatry Neurol 2007;20:50-57)