Jen-Chun Wang

Post-injury baicalein improves histological and functional outcomes and reduces inflammatory cytokines after experimental traumatic brain injury.

Traumatic brain injury (TBI) triggers a complex series of inflammatory responses that contribute to secondary tissue damage. The aim of this study was to investigate the effect of baicalein, a flavonoid possessing potent anti‐inflammatory properties, on functional and histological outcomes and inflammatory cytokine expression, following TBI in rats.

Inhibition of hypoxia inducible factor-1α attenuates abdominal aortic aneurysm progression through the down-regulation of matrix metalloproteinases.

Hypoxia inducible factor-1α (HIF-1α) pathway is associated with many vascular diseases, including atherosclerosis, arterial aneurysms, pulmonary hypertension and chronic venous diseases. Significant HIF-1α expression could be found at the rupture edge at human abdominal aortic aneurysm (AAA) tissues. While our initial in vitro experiments had shown that deferoxamine (DFO) could attenuate angiotensin II (AngII) induced endothelial activations; we unexpectedly found that DFO augmented the severity of AngII-induced AAA, at least partly through increased accumulation of HIF-1α. The findings promoted us to test whether aneurysmal prone factors could up-regulate the expression of MMP-2 and MMP-9 through aberrantly increased HIF-1α and promote AAA development. AngII induced AAA in hyperlipidemic mice model was used. DFO, as a prolyl hydroxylase inhibitor, stabilized HIF-1α and augmented MMPs activities. Aneurysmal-prone factors induced HIF-1α can cause overexpression of MMP-2 and MMP-9 and promote aneurysmal progression. Pharmacological HIF-1α inhibitors, digoxin and 2-ME could ameliorate AngII induced AAA in vivo. HIF-1α is pivotal for the development of AAA. Our study provides a rationale for using HIF-1α inhibitors as an adjunctive medical therapy in addition to current cardiovascular risk-reducing regimens.

Adverse cardiovascular effects of nitrogen-containing bisphosphonates in patients with osteoporosis: A nationwide population-based retrospective study ☆

BACKGROUND Bisphosphonates (BPs) are a class of medications used for the treatment of osteoporosis. Nitrogen-containing BPs (N-BPs) are more potent than non-nitrogenous BPs in terms of their effects on osteoporosis. We examined the effects of N-BPs on osteoporosis in patients included in a large population-based cohort study. METHODS Based on the National Health Insurance Research Database of Taiwan, we identified 1258 patients with osteoporosis who had received N-BP treatment from 2005 through 2010. RESULTS During the retrospective observation period, N-BP users had significantly higher incidence rates of hypertension, acute ischemic stroke, atrial fibrillation (Af), and congestive heart failure (CHF), and lower rates of hyperlipidemia than patients who did not use N-BPs. Overall, N-BP users had a higher incidence of cardiovascular events at the end of the follow-up period. After adjustment for age, sex, and comorbidities, the risk of developing cardiovascular events was significantly high for patients using N-BPs. Patients who received N-BP therapy also had a higher risk of Af and CHF than those who did not during the five-year follow-up period. CONCLUSION We provide evidence that patients with osteoporosis using N-BP therapy have an increased risk of CHF and Af. This potential risk should be weighed against the reduction in the risk of osteoporotic fractures.

Measurement of basilar artery diameter in dogs: CT evaluation correlated with arteriography

SummaryIn this study we have used a computed tomographic (CT) method using profile analysis to measure the diameter of the basilar artery. In a search for a noninvasive and repeatable method to substitute for the traditional arteriography in the evaluation of the degree of cerebral vasospasm, we employed both CT and arteriography to measure the diameter of the basilar artery in eight adult mongrel dogs weighing between 7 and 12 kg. In three of these animals, assessments were made before and after subarachnoid hemorrhage (SAH) induced by injecting autologous arterial blood into the cistern magna. It was found that the basilar artery diameter as evaluated by CT was 47% larger than that measured by arteriography. However, there was a very good correlation (n=63, r=0.75, p<0.001) between the two methods. This paper presents a new model for the measurement of the basilar artery diameter, one which may also provide a safer method for the evaluation of vasospasm in humans.

Increased risk of malignancy in patients with an aortic aneurysm: a nationwide population-based retrospective study

Background Cardiovascular disease and malignancy have numerous similarities and possible interactions, as these diseases share several risk factors, epidemiological features and biological signaling pathways. Data regarding the risk of malignancy in patients with aortic aneurysm (AA) are scarce. We aimed to determine whether patients with AA have an increased risk of malignancy. Materials and Methods The data for the nationwide population-based retrospective cohort study described herein were obtained from the Taiwan National Health Insurance Research Database (NHIRD). We selected adult patients who had been newly diagnosed with AA and were followed up between 2000 and 2010. We excluded patients who had been diagnosed with AA and malignancy prior to the date of the AA diagnosis. The control cohort was selected from individuals who had no history of AA and was selected with 1:4 matching according to co-morbidities and medication history. The outcome was a diagnosis of malignancy and the cumulative incidence of AA. Results A total of 10,933 patients diagnosed with AA were identified. The patients with an AA had a significantly higher cumulative risk of developing malignancies in subsequent years than the patients without an AA (log rank test < 0.001). Similarly, patients with malignancies had a significantly higher cumulative risk of developing an AA in subsequent years than patients without malignancies (log rank test < 0.001). Conclusions Patients with an AA were shown to have a substantially increased risk of developing a variety of malignancies compared with patients without AAs. Healthcare professionals should be aware of this increased risk when treating patients with AAs.

Obstructive Sleep Apnoea and Aortic Aneurysm: A Nationwide Population-Based Retrospective Study

Objective: To determine whether patients with obstructive sleep apnoea (OSA) have an increased risk of aortic aneurysm (AA). Methods: The data for the nationwide population-based retrospective cohort study described here were obtained from the Taiwan National Health Insurance Research Database (NHIRD). We selected adult patients who had been newly diagnosed as having OSA and were followed up between 2000 and 2010. We excluded patients who had been diagnosed as having AA before the date of the new OSA diagnosis. The control cohort consisted of individuals who had no OSA history. The patients and the control cohort were selected by 1: 4 matching according to the following baseline variables: sex, age, index year, and comorbidities. The outcome measure was AA diagnosis. Results: In total, 31,274 patients diagnosed as having OSA were identified. Compared to patients without OSA, they had no significantly discrepant cumulative risk of developing AA in subsequent years (p from log-rank test = 0.442). We used the Cox proportional-hazards regression model, which found that only male sex, older age, diabetes mellitus, chronic obstructive pulmonary disease (COPD), and coronary artery disease were independently associated with AA occurrence among subjects with an OSA diagnosis. OSA was not associated with AA development. On the other hand, in the subgroup of COPD, patients with OSA had a higher incidence of risk of AA than those without OSA. Conclusion: When compared to those without OSA, patients with OSA do not have an increased AA risk.

Association between Atrial Fibrillation and Aortic Aneurysms: A Population-Based Cohort Study

Objective: Atrial fibrillation (AF) is the most common form of sustained arrhythmia. Several molecular pathways associated with the pathogenesis of AF also participate in the initiation and progression of aortic aneurysm (AA). In this study, we aimed to evaluate potential associations between AA and AF. Patients and Methods: The data for this nationwide population-based retrospective cohort study were obtained from Taiwan’s National Health Insurance Research Database (NHIRD). All medical conditions for each case and the controls were categorized using the 9th revision of the International Classification of Diseases (ICD-9). Odds ratios and 95% confidence intervals for associations between AF and AA were estimated using Cox regression and adjusted for comorbidities. Results: Our analyses included 116,225 AF cases and 116,225 propensity score-matched controls. Compared with the controls, the patients with AF exhibited a significantly increased risk of developing an AA (adjusted hazard ratio, HR 1.243, p < 0.001). Another cohort of 19,776 patients diagnosed with AA were identified, and 19,776 propensity score-matched patients were included as controls. Patients who had AA were also at an increased risk of developing AF (adjusted HR 1.187, p < 0.001). Heart failure (HF) was a common risk factor for both AA and AF. Conclusion: There are associations between AF and AA. HF is a mutual risk factor for the development of AF and AA.

Association between dementia and unintentional poisoning in Taiwan

PurposeOlder people with dementia are a particularly vulnerable group and have an increased risk of poisoning. We investigated the correlation between dementia and the risk of unintentional poisoning in a retrospective, longitudinal and nationwide population-based study.MethodsOverall, 27,438 patients with dementia were selected from the National Health Insurance Research Database of Taiwan between 1 January 2000 to 31 December 2010, and 109,752 controls were propensity score-matched by gender, age, index year, and presence of heart failure, liver disease, renal disease, and cancers. After adjustment for confounding factors, Cox proportional hazards analysis was used to compare the risk of poisoning during follow-up.ResultsAmong dementia patients, 100 (0.36%) had unintentional poisoning events compared to 350 (0.32%) controls. Cox proportional hazards regression revealed that the patients were more likely to develop poisoning than the controls (hazard ratio [HR]: 2.721, 95% CI = 2.162–3.424, p < 0.001). After adjustment for sex, age, monthly income, urbanization level, geographic region, and comorbidities, the HR for poisoning was 2.385 (95% CI = 1.883–3.021, p < 0.001).ConclusionsPatients with dementia have a high risk of unintentional poisoning, and appropriate prescription medications and careful review of dementia patient compliance are important.

Increased risk of aortic aneurysm and dissection in patients with Sjögren’s syndrome: a nationwide population-based cohort study in Taiwan

Objectives Sjögren’s syndrome (SS) is a systemic autoimmune disorder. Several molecular pathways and the activation of matrix metalloproteinases associated with the pathogenesis of SS participate in the initiation and progression of aortic aneurysm (AA) and aortic dissection (AD). In this study, we aimed to evaluate whether patients with SS exhibit an increased risk of AA or AD. Methods We conducted a retrospective cohort study using a database extracted from Taiwan’s National Health Insurance Research Database. All medical conditions for each case and control were categorised using the International Classification of Diseases, Ninth Revision. HRs and 95% CIs for associations between SS and AA/AD were estimated using Cox regression and adjusted for comorbidities. Results Our analyses included 10 941 SS cases and 43 764 propensity score-matched controls. Compared with the controls, the patients with SS exhibited a significantly increased risk of developing an AA or AD (adjusted HR=3.642, p<0.001). Subgroup analysis revealed that compared with patients without SS, patients with primary and secondary SS both exhibited a significantly increased risk of developing AA or AD (adjusted HR=1.753, p=0.042; adjusted HR=3.693, p<0.001). Conclusion Patients with SS exhibit increased risks of developing AA or AD, and healthcare professionals should be aware of this risk when treating patients with SS. Increased aortic surveillance may be required for patients with SS.

Fucoidan attenuates angiotensin II-induced abdominal aortic aneurysms through the inhibition of c-Jun N-terminal kinase and nuclear factor κB activation

Background: Rupture of abdominal aortic aneurysm (AAA) is one of the leading causes of sudden death among the elderly. Most incidental AAAs are below the threshold for intervention at the time of detection; however, there is no evidence that commonly used cardiovascular drugs have clinical beneficial effects on AAA progression. Therefore, in addition to current cardiovascular risk‐reducing treatments, an adjunctive medical therapy targeting the regulation of extracellular matrix metabolism is still required in the clinical setting. Fucoidan is an extract of brown seaweed and a sulfated polysaccharide. Emerging evidence suggests that fucoidan has potential cardiovascular applications. Numerous investigations of fucoidan in diseases of the cardiovascular system have mainly focused on its pleiotropic anti‐inflammatory effects. Specifically, fucoidan has been shown to have matrix metalloproteinase (MMP)‐reducing effects in several studies. We aimed to evaluate the beneficial effect of fucoidan on aneurysmal growth in a murine model of aortic aneurysm and further provide a rationale for using fucoidan as a medical adjunctive therapy. Methods: A murine model of angiotensin II (Ang II)‐induced AAA was used to assess the therapeutic effects of fucoidan on AAA growth in vivo. The characteristics and quantification of AAAs were determined in situ. Human umbilical vein endothelial cells were used for studying the involved pathways in vitro. Western blotting was used to detect the involved signaling pathways both in vivo and in vitro. Results: Treatment with fucoidan significantly reduced the incidence of AAA formation. Administration of fucoidan significantly attenuated Ang II‐induced aortic expansion from 1.56 ± 0.76 mm to 1.09 ± 0.30 mm. Administration of fucoidan significantly suppressed MMP‐2 and MMP‐9 activities and reduced the grade of elastin degradation in vivo. In vitro, we found that fucoidan could ameliorate the Ang II‐induced phosphorylation of c‐Jun N‐terminal kinase and nuclear factor &kgr;B p65, and it further reduced MMP and reactive oxygen species production. Conclusions: Fucoidan inhibits the progression of experimental AAA growth through the attenuation of proinflammatory nuclear factor &kgr;B and c‐Jun N‐terminal kinase activation. Fucoidan could be a potential medical adjunctive therapy for small AAAs. Clinical Relevance: Currently, there is no evidence that commonly used cardiovascular drugs have clinical beneficial effects on abdominal aortic aneurysm progression. Fucoidan inhibited the progression of experimental abdominal aortic aneurysm growth through the attenuation of proinflammatory nuclear factor &kgr;B and c‐Jun N‐terminal kinase activation.