Publications by authors named "Chih-Jen Wang"

35 Publications

Repetitive transcranial magnetic stimulation-induced hypomania for an elderly patient with major depressive disorder: a case report.

Int J Geriatr Psychiatry 2021 Mar 16. Epub 2021 Mar 16.

Department of Adult Psychiatry, Kaohsiung Municipal Kai-Syuan Psychiatric Hospital, Kaohsiung, Taiwan.

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http://dx.doi.org/10.1002/gps.5525DOI Listing
March 2021

Non-touch ureteral manipulation of single J ureteral catheterization for robot-assisted cystectomy with intracorporeal ileal conduit.

Asian J Surg 2021 Apr 20;44(4):675. Epub 2021 Feb 20.

Division of Urology, Department of Surgery, Kaohsiung Veterans General Hospital. Electronic address:

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http://dx.doi.org/10.1016/j.asjsur.2021.01.036DOI Listing
April 2021

The CHADS-VASc score predicts chronic kidney disease among patients with atrial fibrillation.

Int Urol Nephrol 2020 Aug 1;52(8):1523-1531. Epub 2020 Jun 1.

Division of Nephrology, Department of Internal Medicine, Changhua Christian Hospital, 135 Nanxiao Street, Changhua, 500, Taiwan, R.O.C..

Background: It is unclear how the CHA2DS2-VASc score can predict subsequent chronic kidney disease (CKD) and end-stage renal disease (ESRD) among atrial fibrillation (AF) patients.

Methods: We identified incident AF patients without CKD between 2000 and 2013 from the National Health Insurance Research Database (NHIRD) of Taiwan and calculated the CHADS-VASc score for each patient. Adjusted hazard ratio (HR) with 95% confidence interval (CI) was estimated from multivariate cause-specific Cox models to assess the risk of CKD and ESRD associated with the CHADS-VASc score.

Results: A total of 8764 participants with AF who did not have CKD were included in the analysis. The mean age was 69.63 ± 13.48 years and 4800 (54.8%) were males. The adjusted HR of CKD displayed a stepwise increase with the increase in the CHADS-VASc score. When compared with those with a CHADS-VASc score of 0, the adjusted HRs of CKD were 1.57 (95% CI 1.09-2.26), 2.04 (95% CI 1.42-2.94), 2.48 (95% CI 1.70-3.62), 2.88 (95% CI 1.95-4.26), 3.29 (95% CI 2.18-4.95) and 4.00 (95% CI 2.61-6.13) for the AF patients with a CHADS-VASc score of 1, 2, 3, 4, 5 and ≥ 6, respectively. Similarly, as the CHADS-VASc score increased, the adjusted HR of ESRD showed a gradual increase.

Conclusions: Patients with a higher CHADS-VASc score were linked to a higher risk of CKD and ESRD in a dose-dependent effect, i.e. the incidence of CKD/ESRD increased with the increasing CHADS-VASc score.
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http://dx.doi.org/10.1007/s11255-020-02514-xDOI Listing
August 2020

FNIH-defined Sarcopenia Predicts Adverse Outcomes Among Community-Dwelling Older People in Taiwan: Results From I-Lan Longitudinal Aging Study.

J Gerontol A Biol Sci Med Sci 2018 05;73(6):828-834

Center for Geriatrics and Gerontology, Taipei Veterans General Hospital, Taiwan.

Background: To evaluate the predictive validity of sarcopenia defined by the Foundation for the National Institutes of Health (FNIH) Sarcopenia Project among Asian older adults.

Methods: Data of the I-Lan Longitudinal Aging Study were obtained for analysis. Overall, 1,839 community-dwelling people aged 50 years and older, capable of completing a 6-m walk, with life expectancy of more than 6 months, and not institutionalized at time of data collection were enrolled for study. Data for subjects aged 65 years and older were obtained for study. The outcome measures were all-cause mortality and a composite adverse outcome which includes hospitalizations, emergency department visits, institutionalization, and falls.

Results: Data of 728 eligible elderly participants (73.4 ± 5.4 years; 52.9% males) were analyzed. The prevalence of FNIH-diagnosed sarcopenia was 9.5%: 11.9% males; 6.7% females. Participants having FNIH-defined sarcopenia were considerably older, frailer, more obese, with poorer physical performance than nonsarcopenic subjects (All p < .001); during mean follow-up of 32.9 ± 8.8 months, they also had 3.8 times higher risk of dying, independent of age, sex, multimorbidity, cognitive function, and nutritional status (hazard ratio = 3.8; 95% confidence interval = 1.26-11.45; p = .018). Moreover, sarcopenia defined by grip strength-BMI ratio (WeakBMI) showed stronger association with composite adverse outcomes than traditional handgrip strength (hazard ratio = 1.99; 95% confidence interval = 1.01-3.93; p = .047 vs hazard ratio = 1.80; 95% confidence interval = 0.89-3.62; p = .102 in fully-adjusted model).

Conclusion: Among community-dwelling older people in Taiwan, participants with FNIH-defined sarcopenia had a significantly greater risk of all-cause mortality and composite falls, emergency department visits, institutionalization, and hospitalization.
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http://dx.doi.org/10.1093/gerona/glx148DOI Listing
May 2018

Impact of living arrangements on clinical outcomes among older patients with dementia or cognitive impairment admitted to the geriatric evaluation and management unit in Taiwan.

Geriatr Gerontol Int 2017 Apr;17 Suppl 1:44-49

Center for Geriatrics and Gerontology, Taipei Veterans General Hospital, Taipei, Taiwan.

Aim: To evaluate the impact of living arrangements on mortality and functional decline among older patients with dementia or cognitive impairment after discharge from a geriatric evaluation and management unit (GEMU) in Taiwan.

Methods: The present retrospective cohort study used data from the Veteran Affairs Comprehensive Geriatric Assessment from January 2015 to May 2016 for analysis. Data of patients aged 65 years and older with dementia or cognitive impairment at admission to the GEMU of Taipei Veterans General Hospital during the study period were retried for study. The Veteran Affairs Comprehensive Geriatric Assessment included demographic characteristics, Clinical Frailty Scale, Braden Scale, St. Thomas's Risk Assessment Tool in Falling Elderly Inpatients Scale, Cumulative Illness Rating Scale for Geriatrics, Barthel Index, Instrumental Activities of Daily Living, Mini-Mental State Examination, Geriatric Depression Scale-5 and Mini-Nutritional Assessment - Short Form, as well as common geriatric syndromes. All patients were categorized into the home care group and institutional care group based on their living arrangement before GEMU admissions. Six-month mortality and decline in Barthel Index were defined as adverse clinical outcomes.

Results: Overall, data of 395 patients were used for analysis. The baseline comparisons showed that the institutional care group was more likely to be unmarried, have lower education, lower risk of falls and less polypharmacy, but more likely to experience functional decline at follow up than the home care group. Multivariate logistic regression showed that male (OR 3.59, 95% CI 1.04-12.38, P = 0.043) and higher Cumulative Illness Rating Scale for Geriatrics score (OR 4.08, 95% CI 1.49-11.19, P = 0.006) were associated with mortality, whereas the institutional care group (OR 0.30, 95% 0.09-0.99, P = 0.048) and lower Braden Scale (OR 0.80, 95% CI 0.67-0.94, P = 0.008) were protective against mortality. However, the institutional care group was independently associated with functional decline during the follow-up period (OR 2.19, 95% CI 1.12-4.29, P = 0.022).

Conclusions: Institutional care was associated with lower 6-month mortality risk for patients with dementia or cognitive impairment after discharge from the GEMU, but this group was more likely to experience functional decline. Further prospective study is required to clarify the clinical impact of living arrangements on long-term outcomes when people with dementia or cognitive impairment are admitted to acute hospitals. Geriatr Gerontol Int 2017: 17 (Suppl. 1): 44-49.
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http://dx.doi.org/10.1111/ggi.13036DOI Listing
April 2017

Association between using medications with anticholinergic properties and short-term cognitive decline among older men: A retrospective cohort study in Taiwan.

Geriatr Gerontol Int 2017 Apr;17 Suppl 1:57-64

Center for Geriatrics and Gerontology, Taipei Veterans General Hospital, Taipei, Taiwan.

Aim: The use of anticholinergic drugs had been strongly linked to adverse health outcomes among older adults, especially in cognitive impairment or dementia. The present study aimed to evaluate the cognitive decline related to the use of anticholinergic drugs among older men living in the veterans' homes in Taiwan.

Methods: This retrospective cohort study was a substudy of The Longitudinal Older Veterans study. A total of 274 residents living in four Taiwan veterans' homes and receiving two consecutive Mini-Mental State Examinations within the interval of 6 months from January 2012 to December 2014 were enrolled in the present study. The medication lists for all participants were reviewed by the same physician, and the anticholinergic properties of the individual medications were evaluated by using the Anticholinergic Cognitive Burden scale. Cognitive decline was defined as the decrease of Mini-Mental State Examinations scores during the study period.

Results: Overall, 139 persons (50.7%) had exposure to anticholinergic drugs at baseline (designated as AC[+]), and the most frequently used anticholinergic drugs were cardiovascular drugs (48.2%), antipsychotics (21.6%), theophylline (20.1%), antidepressants (12.2%), gastrointestinal drugs (11.5%) and antihistamines (8.6%). After adjusting for covariates, AC(+) participants had a significantly higher risk for short-term cognitive decline (OR 2.69, 95% CI 1.36-5.31). After excluding 30 participants using antipsychotics, non-antipsychotics AC(+)participants still had a significantly higher risk for short-term cognitive decline (OR 2.24, 95% CI 1.26-3.99).

Conclusions: Exposure to anticholinergic drugs significantly increased the risk for short-term cognitive decline among older men, and the adverse effects remained similar when antipsychotics were excluded for analysis. A further intervention study is required to evaluate whether reducing anticholinergic burden might improve cognitive function among older adults. Geriatr Gerontol Int 2017: 17 (Suppl. 1): 57-64.
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http://dx.doi.org/10.1111/ggi.13032DOI Listing
April 2017

Recurrent falls and its risk factors among older men living in the veterans retirement communities: A cross-sectional study.

Arch Gerontol Geriatr 2017 May - Jun;70:214-218. Epub 2017 Feb 4.

Center for Geriatrics and Gerontology, Taipei Veterans General Hospital, Taipei, Taiwan; Aging and Health Research Center, National Yang Ming University, Taipei, Taiwan. Electronic address:

Aim: To evaluate the prevalence of recurrent falls and their risk factors among older men living in the Veterans Homes in Taiwan.

Methods: This cross-sectional study enrolled 871 residents and all participants received the comprehensive geriatric assessment, including Barthel Index, Mini-Mental Status Examination (MMSE), Geriatric Depression Scale-5 questions (GDS-5), Mini-Nutrition Assessment Short Form (MNA-SF), the status of urinary incontinence, stool incontinence, polypharmacy, past history of falls, multimorbidity, and medication history.

Results: Overall, 871 subjects (mean age: 85.5±5.2years, all males) participated in this study, whereas 222(25.5%) of them had experienced falls in the past year, and 91 were recurrent fallers. Comparisons between non-fallers, single fallers and recurrent fallers disclosed that they were significantly different in the following characteristics: diabetes mellitus, chronic kidney disease, coronary artery disease, Charlson Comorbidity Index (CCI), Barthel Index, GDS-5, MNA-SF, polypharmacy, use of hypnotics, urinary incontinence, and stool incontinence (P for trend all <0.05). Multiple regression analysis identified that GDS-5 was significantly associated with single falls and recurrent falls (OR 1.256, 95% CI 1.094-1.441, P=0.001 for single fallers; OR 1.480, 95% CI 1.269-1.727, P<0.001 for recurrent fallers). Besides, urinary incontinence was the independently associated with recurrent fallers only (OR 2.369, 95% CI 1.449-3.817, P<0.001), but not single fallers.

Conclusion: Urinary incontinence and depressive symptoms were independent associated factors for falls among older men living in the retirement communities. However, urinary incontinence was associated with recurrent falls, but not single falls. Intervention study is needed to reduce recurrent falls through management of urinary incontinence.
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http://dx.doi.org/10.1016/j.archger.2017.02.001DOI Listing
July 2017

Less Than One-Fifth of People Aged 75 Years or Older in the Real World Were Suitable for SPRINT Results.

J Am Med Dir Assoc 2017 03 17;18(3):271-272. Epub 2017 Jan 17.

Center for Geriatrics and Gerontology, Taipei Veterans General Hospital, Taipei, Taiwan; Aging and Health Research Center, National Yang Ming University, Taipei, Taiwan.

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http://dx.doi.org/10.1016/j.jamda.2016.11.020DOI Listing
March 2017

Urinary Incontinence and Its Association with Frailty Among Men Aged 80 Years or Older in Taiwan: A Cross-Sectional Study.

Rejuvenation Res 2017 Apr 14;20(2):111-117. Epub 2016 Nov 14.

2 Aging and Health Research Center, National Yang Ming University , Taipei, Taiwan .

Aims: To evaluate the prevalence of urinary incontinence (UI) and its association with frailty among men aged 80 years and older in Taiwan.

Methods: Residents living in four veterans retirement communities were invited for study and 440 men aged 80 years and older were enrolled. Comprehensive geriatric assessment was performed for them, which composed of Clinical Frailty Scale, Northern Health and Social Care Trust (HSC)-Continence Assessment Form, Charlson's Comorbidity Index (CCI), Barthel Index (BI), Instrumental Activities of Daily Living (IADL), Mini-Mental State Examination (MMSE), Geriatric Depression Scale-5 (GDS-5), and Mini-Nutritional Assessment-Short Form (MNA-SF).

Results: In this study, the overall prevalence of UI was 19.1% (mostly urgency incontinence and functional incontinence). Univariate analyses were performed to evaluate the associations between UI and other variables. Frailty was more common among subjects with UI than those without (60.7% vs 32.3%, p < 0.001). Besides, subjects with UI had more comorbidity (CCI: 1.40 ± 1.15 vs 0.89 ± 0.89, p < 0.001), poorer physical function (BI: 65.77 ± 33.39 vs 84.12 ± 24.08, p < 0.001; IADL: 3.46 ± 2.64 vs 4.41 ± 2.25, p = 0.003), more depressive symptoms (GDS-5: 1.83 ± 1.78 vs 1.18 ± 1.36, p = 0.02), poorer cognitive function (MMSE: 16.57 ± 7.65 vs 19.37 ± 6.82, p = 0.001), poorer nutritional status (MNA-SF: 10.0 ± 03.03 vs 11.23 ± 2.24, p = 0.001), more polypharmacy (66.7% vs 45.2%, p < 0.001) and higher chance of stool incontinence (22.6% vs 1.7%, p < 0.001). Multivariate logistic regression showed that UI was independently associated with frailty, (odds ratio [OR] = 2.1; 95% confidence interval [CI]: 1.2-3.6; p = 0.012), stool incontinence (OR = 14.4; 95% CI 5.2-39.7; p < 0.001) and depressive symptoms (OR = 1.30; 95% CI 1.10-1.54; p = 0.002).

Conclusions: About one fifth of study subjects had UI (mostly urgency and functional incontinence type), which was significantly associated with frailty, stool incontinence and depressive symptoms. Further study is needed to evaluate the possibilities of reversing these geriatric syndromes by an integrated intervention program.
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http://dx.doi.org/10.1089/rej.2016.1855DOI Listing
April 2017

One-step preparation of hydrophilic carbon nanofiber containing magnetic Ni nanoparticles materials and their application in drug delivery.

J Colloid Interface Sci 2015 Feb 8;440:179-88. Epub 2014 Nov 8.

Center for General Education, Chang Gung University, 259, Wen-Hwa 1st Road, Kwei-Shan, Tao-Yuan 333, Taiwan, ROC. Electronic address:

A one-step process for the synthesis of hydrophilic carbon nanofibers (CNFs) through CO2 hydrogenation on NiNa/Al2O3 was developed for the loading and targeted delivery of the anticancer drug doxorubicin (DOX). CNFs that were synthesized on NiNa/Al2O3 for 9 h at 500 °C exhibited an adequate magnetic response and a large content of hydrophilic oxygen-containing functional groups on the carbon surface, resulting in excellent colloidal solution. The CNF material exhibited a highly efficient capacity for DOX adsorption, particularly at pH 9.0. The loading and release of DOX was strongly pH dependent, possibly due to electrostatic and π-π stacking interactions between DOX and CNF sample. The Langmuir isotherm and pseudo second-order kinetics of DOX-loaded CNFs were well-modeled for the process of DOX adsorption. DOX-loaded CNF targeted cancer cells more selectively and effectively than free DOX and exhibited a marked tendency to kill HeLa cancer cells and reduced toxicity to normal human primary fibroblast (HPF) cells.
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http://dx.doi.org/10.1016/j.jcis.2014.10.073DOI Listing
February 2015

Endoluminal release of ureteral ligature after hysterectomy.

J Formos Med Assoc 2016 Jan 18;115(1):51-3. Epub 2014 Sep 18.

Division of Urology, E-Da Hospital, Kaohsiung, Taiwan. Electronic address:

Iatrogenic ureteral injury is a well-recognized complication of abdominal total hysterectomy. We report a case of a 57-year-old female who underwent abdominal total hysterectomy for a uterine myoma and experienced severe right flank pain postoperatively. The imaging study displayed an obstruction of the right distal ureter. Under ureteroscopy, an extraluminal ligature was released with a holmium:yttrium-aluminum-garnet laser. The stenotic segment was immediately relieved. Two months later, the intravenous urogram illustrated patency of the distal ureter with regression of right hydronephrosis. There was no recurrent hydronephrosis during 1 year of follow-up.
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http://dx.doi.org/10.1016/j.jfma.2014.07.007DOI Listing
January 2016

Alteration of basilar artery rho-kinase and soluble guanylyl cyclase protein expression in a rat model of cerebral vasospasm following subarachnoid hemorrhage.

Biomed Res Int 2014 1;2014:531508. Epub 2014 Jun 1.

Division of Neurosurgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan ; Department of Neurosurgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan ; Department of Neurological Surgery, University of Virginia Health System, Charlottesville, VA 22908, USA.

Background And Purpose: The vasoconstrictor endothelin-1 (ET-1) has been implicated in the pathogenesis of cerebral vasospasm following subarachnoid hemorrhage (SAH). Previous results showed that CGS 26303, an endothelin converting enzyme (ECE) inhibitor, effectively prevented and reversed arterial narrowing in animal models of SAH. In the present study, we assessed the effect of CGS 26303 on neurological deficits in SAH rats. The involvement of vasoactive pathways downstream of ET-1 signaling in SAH was also investigated.

Methods: Sprague-Dawley rats were divided into five groups (n = 6/group): (1) normal control, (2) SAH, (3) SAH+vehicle, (4) SAH+CGS 26303 (prevention), and (5) SAH+CGS 26303 (reversal). SAH was induced by injecting autologous blood into cisterna magna. CGS 26303 (10 mg/kg) was injected intravenously at 1 and 24 hr after the initiation of SAH in the prevention and reversal protocols, respectively. Behavioral changes were assessed at 48 hr after SAH. Protein expression was analyzed by Western blots.

Results: Deficits in motor function were obvious in the SAH rats, and CGS 26303 significantly improved the rate of paraplegia. Expressions of rho-kinase-II and membrane-bound protein kinase C- δ and rhoA were significantly increased, while those of soluble guanylyl cyclase α 1 and β 1 as well as protein kinase G were significantly decreased in the basilar artery of SAH rats. Treatment with CGS 26303 nearly normalized these effects.

Conclusions: These results demonstrate that the rhoA/rho-kinase and sGC/cGMP/PKG pathways play pivotal roles in cerebral vasospasm after SAH. It also shows that ECE inhibition is an effective strategy for the treatment of this disease.
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http://dx.doi.org/10.1155/2014/531508DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4058103PMC
February 2015

Differential hypermethylation of death-associated protein kinase promoter in central neurocytoma and oligodendroglioma.

Biomed Res Int 2014 27;2014:506458. Epub 2014 Apr 27.

Department of Neurosurgery, Kaohsiung Medical University Hospital, 100 Shih-Chuan First Road, Kaohsiung, Taiwan ; Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan ; Department of Neurosurgery, University of Virginia, Charlottesville, VA, USA.

Background: Central neurocytoma and oligodendroglioma are rare tumors of the central nervous system. However, diagnosis between these two types of tumors is challenging due to their many cytological and histological similarities. Death-associated protein kinase (DAPK) is a calcium/calmodulin-regulated serine/threonine protein kinase involved in many apoptosis pathways, and repressed expression of DAPK by promoter hypermethylation has been found in a variety of human cancers. The purpose of this study was to assess DAPK protein expression and promoter hypermethylation in central neurocytoma and oligodendroglioma.

Method: Central neurocytoma and oligodendroglioma samples were obtained from age- and sex-matched patients. DAPK protein expression was performed using immunohistochemical assays in formalin-fixed, paraffin-embedded sections. DAPK promoter hypermethylation was carried out using bisulfite-modified genomic DNA in methylation-specific PCR followed by separation in agarose gels.

Findings: A statistically significant difference (P = 0.021) in DAPK promoter hypermethylation between central neurocytoma (76.9%) and oligodendroglioma (20%) was observed. High levels of DAPK protein expression were generally found in oligodendroglioma (90%), compared with 38.5% in central neurocytoma (P = 0.054; not statistically significant). There was an inverse correlation between DAPK protein expression and DAPK promoter hypermethylation in the cohort of 23 patients (P = 0.002).

Conclusions: The results show that DAPK promoter hypermethylation and repressed expression of DAPK protein were more common in central neurocytoma than in oligodendroglioma. Thus, DAPK promoter hypermethylation could be useful for differential diagnosis between these two types of tumors, whereas DAPK protein expression might be less predictive. The role of DAPK promoter hypermethylation in the pathogenesis of central neurocytoma warrants further study.
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http://dx.doi.org/10.1155/2014/506458DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4022162PMC
February 2015

Arrested growth and spontaneous tumor regression of partially resected low-grade cerebellar astrocytomas in children.

Childs Nerv Syst 2013 Nov 1;29(11):2051-5. Epub 2013 May 1.

Division of Neurosurgery, Department of Surgery, Kaohsiung Medical University Hospital, No 100 Tzyou 1 Rood, Kaohsiung, 807, Taiwan.

Purpose: The prognosis of children with low-grade cerebellar astrocytoma who have partial resection of tumor is largely unpredictable. The purpose of this study was to review the long-term outcome of such patients.

Methods: The medical charts, imaging findings, operative notes, histopathological reports, and survival times of 12 patients with cerebellar astrocytoma were reviewed.

Results: Five patients had total resection and seven had partial resection. Nine patients had grade I histology and three patients had grade II. Follow-up duration ranged from 3 to 25 years. Among the seven patients with residual tumor, five had tumor progression, one had arrested tumor growth, and one had spontaneous tumor regression. Five patients with partial resection received radiotherapy and three had malignant transformation of tumor during follow-up. Six patients, including five who had partial resection, underwent a second operation. One patient with partial resection died of pneumonia 23 years after surgery.

Conclusions: Patients with complete tumor resection had a better prognosis than patients with partial resection. For patients with partial resection, we recommend a "wait and see" policy with surveillance using MRI. The phenomenon of arrested tumor growth and spontaneous tumor regression in patients with cerebellar astrocytoma who have subtotal resection warrants further study.
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http://dx.doi.org/10.1007/s00381-013-2113-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3825417PMC
November 2013

Thyroid hormone regulation of miR-21 enhances migration and invasion of hepatoma.

Cancer Res 2013 Apr 26;73(8):2505-17. Epub 2013 Feb 26.

Liver Research Center, Department of Hepato-Gastroenterology, Chang Gung Memorial Hospital, Linkou, Taiwan.

Thyroid hormone (T(3)) signaling through the thyroid hormone receptor (TRα1) regulates hepatoma cell growth and pathophysiology, but the underlying mechanisms are unclear at present. Here, we have shown that the oncomir microRNA-21 (miR-21) is activated by T(3) through a native T(3) response element in the primary miR-21 promoter. Overexpression of miR-21 promoted hepatoma cell migration and invasion, similar to that observed with T(3) stimulation in hepatoma cells. In addition, anti-miR-21-induced suppression of cell migration was rescued by T(3). The Rac-controlled regulator of invasion and metastasis, T-cell lymphoma invasion and metastasis 1 (TIAM1), was identified as a miR-21 target additionally downregulated by T(3). Attenuation and overexpression of miR-21 induced upregulation and downregulation of TIAM1, respectively. TIAM1 attenuation, in turn, enhanced migration and invasion via the upregulation of β-catenin, vimentin, and matrix metalloproteinase-2 in hepatoma cells. Notably, correlations between TRα1, miR-21, and TIAM1 expression patterns in animal models paralleled those observed in vitro. In the clinic, we observed a positive correlation (P = 0.005) between the tumor/nontumor ratios of TRα1 and miR-21 expression, whereas a negative correlation (P = 0.019) was seen between miR-21 and TIAM1 expression in patients with hepatoma. Our findings collectively indicate that miR-21 stimulation by T(3) and subsequent TIAM1 suppression promotes hepatoma cell migration and invasion.
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http://dx.doi.org/10.1158/0008-5472.CAN-12-2218DOI Listing
April 2013

Plasma levels of transforming growth factor-beta 1 before and after removal of low- and high-grade astrocytomas.

Cytokine 2013 Feb 20;61(2):413-8. Epub 2012 Dec 20.

Division of Neurosurgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.

Transforming growth factor-beta 1 (TGF-β1) has been reported to be a possible marker for a number of tumors, including brain tumors. The aim of this study was to measure the plasma levels of TGF-β1 in patients with low- and high-grade astrocytomas before and after surgery. This prospective study included 14 patients with low-grade astrocytomas and 25 with high-grade astrocytomas who underwent tumor removal and 13 controls (patients who underwent cranioplasty for skull bone defects). Plasma levels of TGF-β1 were measured in all subjects using enzyme-linked immunosorbent assay (ELISA). Receiver operating characteristic (ROC) curve analysis showed that when the level of TGF-β1 before tumor removal was ≥ 2.52 ng/ml, astrocytoma was predicted with a sensitivity of 94.9% and specificity of 100%. The mean plasma level of TGF-β1 in both the low-grade and high-grade astrocytoma groups significantly decreased after tumor removal (p<0.05); there was no significant change in TGF-β1 plasma level of the controls following surgery. Patients with high-grade astrocytomas had a significantly higher mortality rate than patients with low-grade astrocytomas (p=0.019) and significantly shorter survival (p=0.008). A positive correlation between TGF-β1 level after tumor removal and tumor volume was only found in the high-grade astrocytoma group (γ=0.597, p=0.002). The findings show that plasma TGF-β1 level was increased in patients with low-grade and high-grade astrocytoma, and that the levels significantly decreased after tumor removal in both groups. The results provide additional evidence that TGF-β1 might be useful as a tumor marker for astrocytomas.
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http://dx.doi.org/10.1016/j.cyto.2012.11.011DOI Listing
February 2013

Attenuation of cerebral vasospasm following experimental subarachnoid hemorrhage by the bronchodilator KMUP-3.

Acta Neurochir Suppl 2013 ;115:239-46

Poznan University of Medical Sciences, Poznan, Poland.

Delayed cerebral vasospasm is a main cause of morbidity and mortality as well as poor outcome in patients following aneurysmal subarachnoid hemorrhage (SAH). In this study, the effect of the bronchodilator KMUP-3 (7-[2-[4-(4-nitrobenzene)piperazinyl]ethyl]-1,3-dimethylxanthine) on basilar artery narrowing, neurological outcome, and expression of rhoA/rho kinase II (ROCKII), rhoA, and protein kinase C (PKC) γ proteins were evaluated in a rat model of SAH. SAH was induced by double injection of autologous blood into the cistern magna on days 0 and 3. KMUP-3 was administered (0.3 mg/kg/day) by osmotic minipumps implanted subcutaneously (beginning day -3 in pretreatment group and at 1 h after the initiation of the first autologous blood injection in the treatment group). Neurological outcome was assessed by ambulation and placing/stepping reflex responses at 48 h after the second injection of autologous blood. Tissue morphology and protein expression were conducted on day 7 post-day 0 injection. Both KMUP-3 treatment regimens significantly improved neurological outcome and completely attenuated basilar artery narrowing as well as reduced the enhancement of ROCKII, rhoA, and PKCγ protein expression in rats subjected to SAH, compared with normal and untreated SAH rats. These results suggest that KMUP-3 may be a novel agent for the treatment of cerebral vasospasm following SAH.
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http://dx.doi.org/10.1007/978-3-7091-1192-5_43DOI Listing
December 2012

Spin, charge and lattice couplings in Cu-deficient oxysulphide BiOCu0.94S.

J Phys Condens Matter 2012 Jul 7;24(26):266004. Epub 2012 Jun 7.

Department of Physics and Center for Neutron Beam Applications, National Central University, Jhongli 32001, Taiwan.

The electrical and magnetic properties of slightly Cu-deficient BiOCu(0.94)S are investigated using neutron diffraction, ac magnetic susceptibility, magnetization and electrical resistivity measurements. The Cu spins order in a ferromagnetic arrangement below T(C) = 250 K. An antiferromagnetic component develops below 180 K when the crystalline unit cell experiences a sharp thermal contraction upon cooling, resulting in a canted ferromagnetic spin arrangement at low temperatures. In the magnetically ordered state the electrical transport can be described using three-dimensional variable range hopping conduction. An applied magnetic field can effectively reduce the hopping barrier. Spin-charge couplings are clearly revealed when the resistivity departs from the hopping conduction and begins to increase with increasing temperatures above 250 K where the Cu spins become disordered.
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http://dx.doi.org/10.1088/0953-8984/24/26/266004DOI Listing
July 2012

The alteration of plasma TGF-β1 levels in patients with brain tumors after tumor removal.

Kaohsiung J Med Sci 2012 Jun 4;28(6):316-21. Epub 2012 Apr 4.

Division of Neurosurgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.

Transforming growth factor (TGF) β1 may be a candidate for a serologic tumor marker. In this study, the plasma levels of TGF-β1 in patients with brain tumors were measured using enzyme-linked immunosorbent assay before and after tumor removal. Patients were divided into four groups, the control group and the benign, malignant, and metastatic brain tumor groups. All brain tumor groups showed significant increases in the levels of TGF-β1 before tumor removal (6.36 ± 3.94, 17.0 ± 9.7, and 12.2 ± 10.3 ng/ml for the benign, malignant, and metastatic groups, respectively). When compared with the results obtained in the control group (1.12 ± 0.74 ng/ml), significant decreases in TGF-β1 concentrations after total tumor removal were found in both the benign and malignant brain tumor groups (2.55 ± 2.00 and 8.93 ± 5.73 ng/ml, respectively; p = 0.0001 and p = 0.003, respectively). On the other hand, plasma TGF-β1 levels in the metastatic brain tumor group showed a slight but significant increase (14.7 ± 9.3 ng/ml, p = 0.035) after tumor removal. In a case of low-grade astrocytoma, plasma levels of TGF-β1 were found to be 3.6 and 1.1 ng/ml before and after tumor removal, respectively. However, recurrent tumor was noted in this patient 7 months later, and the levels of TGF-β1 were 26.2 and 8.4 ng/ml before and after the second operation, respectively. The data show that plasma TGF-β1 was elevated in the circulation of patients with brain tumors and that significant decreases in TGF-β1 levels were observed after the removal of benign and malignant tumors. The results also suggest that TGF-β1 may be a useful serologic marker for brain tumors.
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http://dx.doi.org/10.1016/j.kjms.2011.11.012DOI Listing
June 2012

Metachronous brain and intramedullary spinal cord metastases from nonsmall-cell lung cancer: a case report.

Kaohsiung J Med Sci 2012 May 22;28(5):289-93. Epub 2012 Feb 22.

School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.

A 44-year-old man had a brain tumor secondary to lung adenocarcinoma and underwent craniectomy to remove the brain tumor. After postoperative whole-brain radiation therapy, he underwent pneumonectomy followed by chemotherapy, mediastinal radiotherapy, and target therapy for lung cancer. Thirty-six months after the initial brain surgery, he suffered from neck pain and right upper limb numbness that rapidly progressed to upper extremity weakness and paralysis in 2 months. Magnetic resonance imaging demonstrated an intramedullary spinal cord lesion at the C4 level. Laminectomy and gross intramedullary tumor removal were performed. The patient's neurological function improved after the operation. Nevertheless, 4 months after the intramedullary tumor removal, he began to show multiple metastases. Unfortunately, the patient died from respiratory failure 8 months after diagnosis with intramedullary spinal cord metastasis. In this case, early diagnosis and aggressive surgical treatment combined with postoperative radiotherapy and chemotherapy might have provided this patient with a prolonged survival and better quality of life.
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http://dx.doi.org/10.1016/j.kjms.2011.11.008DOI Listing
May 2012

Cementless large-head metal-on-metal total hip arthroplasty in patients younger than 60 years--a multicenter early result.

Kaohsiung J Med Sci 2012 Jan 15;28(1):30-7. Epub 2011 Sep 15.

Department of Orthopaedics, National Cheng Kung University Hospital, Tainan, Taiwan.

Large-head metal-on-metal total hip arthroplasty has the theoretical advantages of less wear and better range of motion than traditional polyethylene bearings and seems to be a better choice for young and active patients. We conducted a retrospective study and reported the early results of using such prostheses in 59 patients (70 hips) with a mean age of 43.1 years (range, 23-59 years) at the time of surgery. Osteonecrosis of the femoral head accounted for most diagnoses. Harris Hip Scores and hip range of motion both significantly improved (p<0.001) at an average follow-up of 32.6 months (range, 24-48 months). Only one intraoperative calcar fissure was encountered, and it was fixated by cerclage wiring; there was no infection, dislocation, or osteolysis around either the cup or the stem at the latest follow-up. A postoperative gap in the acetabular component was noted in 24 hips, with a mean depth of 1.11 mm, but this was not correlated with the functional score (p=0.291). Transient thigh pain, which resolved after 6 months, was observed in six patients but was not related to either the postoperative gap or cup inclination (p=1.000 and p=0.664, respectively). All patients resumed their original jobs and recreational activities with little discomfort. Thus far, large-head metal-on-metal total hip arthroplasty has shown excellent early results. The long-term results and the effects of metal debris and potentially elevated serum metal ion levels require further observation.
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http://dx.doi.org/10.1016/j.kjms.2011.06.021DOI Listing
January 2012

Armored brain with chronic headache.

Acta Neurol Belg 2011 Sep;111(3):260

Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.

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September 2011

Immune and inflammatory gene signature in rat cerebrum in subarachnoid hemorrhage with microarray analysis.

Mol Med Rep 2012 Jan 3;5(1):118-25. Epub 2011 Oct 3.

Department of Medical Laboratory Science and Biotechnology, Fooyin University, Kaohsiung, Taiwan, ROC.

Cerebral vasospasm following subarachnoid hemorrhage (SAH) has been studied in terms of a contraction of the major cerebral arteries, but the effect of cerebrum tissue in SAH is not yet well understood. To gain insight into the biology of SAH-expressing cerebrum, we employed oligonucleotide microarrays to characterize the gene expression profiles of cerebrum tissue at the early stage of SAH. Functional gene expression in the cerebrum was analyzed 2 h following stage 1-hemorrhage in Sprague-Dawley rats. mRNA was investigated by performing microarray and quantitative real-time PCR analyses, and protein expression was determined by Western blot analysis. In this study, 18 upregulated and 18 downregulated genes displayed at least a 1.5-fold change. Five genes were verified by real-time PCR, including three upregulated genes [prostaglandin E synthase (PGES), CD14 antigen, and tissue inhibitor of metalloproteinase 1 (TIMP1)] as well as two downregulated genes [KRAB-zinc finger protein-2 (KZF-2) and γ-aminobutyric acid B receptor 1 (GABA B receptor)]. Notably, there were functional implications for the three upregulated genes involved in the inflammatory SAH process. However, the mechanisms leading to decreased KZF-2 and GABA B receptor expression in SAH have never been characterized. We conclude that oligonucleotide microarrays have the potential for use as a method to identify candidate genes associated with SAH and to provide novel investigational targets, including genes involved in the immune and inflammatory response. Furthermore, understanding the regulation of MMP9/TIMP1 during the early stages of SAH may elucidate the pathophysiological mechanisms in SAH rats.
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http://dx.doi.org/10.3892/mmr.2011.614DOI Listing
January 2012

Autoimmunity against hNinein, a human centrosomal protein, in patients with rheumatoid arthritis and systemic lupus erythematosus.

Mol Med Rep 2011 Sep-Oct;4(5):825-30. Epub 2011 Jun 7.

Department of Neurosurgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, R.O.C.

Centrosomes are organelles involved in the organization of the mitotic spindle and may also be the targets of autoantibodies in autoimmune diseases. Human Ninein (hNinein) is a centrosomal autoantigen that is identified by autoimmune patient sera. However, none of the hNinein-specific fragments recognized by the autoantibodies in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) sera have been thoroughly characterized. We thus attempted to identify the fine specificity within the hNinein protein. In this study, four recombinant proteins in two isoforms of hNinein were used as autoantigens along with immunoassays as a molecular tool to investigate the prevalence of hNinein autoreactivity and its specificity in 22 RA and 32 SLE autoimmune disease sera. The data indicated a 50% higher prevalence of isoform 4 hNinein N-terminal autoantibodies in RA sera, whereas 22% of SLE patients were autoreactive to the N-terminal of isoform 4 hNinein compared to only a small percentage of autoreactive normal sera (5%). These results showed that autoepitopes on autoantigen hNinein are restricted to the N-terminal region and that a more significant proportion of RA patients exhibited centrosome reactivity.
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http://dx.doi.org/10.3892/mmr.2011.505DOI Listing
November 2011

Cation exchange interaction between antibiotic ciprofloxacin and montmorillonite.

J Hazard Mater 2010 Nov 15;183(1-3):309-14. Epub 2010 Jul 15.

Department of Earth Sciences, National Cheng Kung University, 1 University Road, Tainan 70101, Taiwan.

Exploring the interactions between antibiotics and soils/minerals is of great importance in resolving their fate, transport, and elimination in the environment due to their frequent detection in wastewater, river water, sewage sludge and soils. This study focused on determining the adsorption properties and mechanisms of interaction between antibiotic ciprofloxacin and montmorillonite (SAz-1), a swelling dioctahedral mineral with Ca(2+) as the main interlayer cation. In acidic and neutral aqueous solutions, a stoichiometric exchange between ciprofloxacin and interlayer cations yielded an adsorption capacity as high as 330 mg/g, corresponding to 1.0 mmol/g. When solution pH was above its pK(a2) (8.7), adsorption of ciprofloxacin was greatly reduced due to the net repulsion between the negatively charged clay surfaces and the ciprofloxacin anion. The uptake of ciprofloxacin expanded the basal spacing (d(001)) of montmorillonite from 15.04 to 17.23 A near its adsorption capacity, confirming cation exchange within the interlayers in addition to surface adsorption. Fourier transform infrared results further suggested that the protonated amine group of ciprofloxacin in its cationic form was electrostatically attracted to negatively charged sites of clay surfaces, and that the carboxylic acid group was hydrogen bonded to the basal oxygen atoms of the silicate layers. The results indicate that montmorillonite is an effective sorbent to remove ciprofloxacin from water.
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http://dx.doi.org/10.1016/j.jhazmat.2010.07.025DOI Listing
November 2010

Interaction between tetracycline and smectite in aqueous solution.

J Colloid Interface Sci 2010 Jan 1;341(2):311-9. Epub 2009 Oct 1.

Faculty of Earth Science, China University of Geosciences, Wuhan 430074, China.

The fate and transport of commonly used antibiotics in soil and groundwater have attracted renewed studies due to increased sensitivities of analytical instruments and thus frequent detections of these compounds even in treated wastewater. Smectite, an important soil component, has large surface area and high cation exchange capacity, while tetracycline (TC) can exist in different forms and charges under different pH conditions. Thus, the interaction between smectite and TC in aqueous systems is of great importance. This research focused on elucidating the mechanisms of TC uptake by smectite, in terms of TC adsorption, cation desorption, and pH changes associated with TC adsorption by smectite and intercalation in smectite. TC adsorption onto smectite was a relatively fast process even though most of the adsorption sites were in the interlayer position involved in intercalation as confirmed by the expansion of d(001) spacing. The TC adsorption capacity was equivalent to 0.74-1.11 times the cation exchange capacity for three of the four smectite minerals studied. Accompanying TC adsorption was simultaneous adsorption of H(+), resulting in protonation of TC on the dimethylamine group. At higher TC input concentrations further adsorption of H(+) resulted in the ratio of H(+) adsorbed to TC adsorbed greater than one, suggesting that additionally adsorbed H(+) could serve as counterions to partially offset the negative charges on the tricarbonyl or phenolic diketone functional groups. The positive correlations between cations desorbed and TC adsorbed, as well as TC adsorbed and H(+) adsorbed, provided a first time evidence to confirm cation exchange as the main mechanism of TC uptake, even under neutral pH conditions.
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http://dx.doi.org/10.1016/j.jcis.2009.09.054DOI Listing
January 2010

Low-grade astrocytoma associated with abscess formation: case report and literature review.

Kaohsiung J Med Sci 2008 May;24(5):262-9

Department of Neurosurgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.

A rare case of low-grade astrocytoma associated with abscess formation occurred in a 52-year-old man presenting with Broca's aphasia. He underwent craniotomy and tumor removal under the impression of brain tumor with necrotic cystic change. Abscess accumulation within the intra-axial tumor was found intraoperatively. Literature related to brain abscess with brain tumor is reviewed, with an emphasis on abscesses with astrocytoma. We discuss the common brain tumors that are associated with abscess, pathogens that coexist with brain tumor, and the pathogeneses of coexisting brain abscess and tumor. It is very important to know how to differentiate between and diagnose a brain abscess and tumor, or brain abscess with tumor, preoperatively from clinical presentation and through the use of computed tomography, conventional magnetic resonance imaging, diffusion-weighted imaging or magnetic resonance spectroscopy.
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http://dx.doi.org/10.1016/S1607-551X(08)70151-7DOI Listing
May 2008

Analysis of surgically treated intraspinal tumors in southern Taiwan.

Kaohsiung J Med Sci 2007 Nov;23(11):573-8

Department of Neurosurgery, Kaohsiung Medical University Hospital, and Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.

The medical records of 117 patients with spinal tumors who underwent surgery with pathologic confirmation from January 1999 to April 2004 at Kaohsiung Medical University Hospital were reviewed. Data from this review were compared with those obtained from the same institution 10 years earlier (covering the period 1988-1995) and from other reported series. There were 69 male and 48 female patients aged from 13 to 87 years old (mean age, 51.9). The most common pathologic findings were metastasis in 45.3% (53/117), nerve sheath tumors in 28.2% (33/117), meningiomas in 12% (14/117) and neuroepithelial tumors in 6% (7/117). The peak ages at diagnosis were 41-50 years and 61-70 years. A slight male predominance was noted for all tumors, except meningiomas. Motor weakness, even paralysis, was the major clinical presentation (64-86%), followed by sensory deficits (50%) and pain (42%). The location of tumors was most often in the thoracic (50.4%; 59/117), lumbosacral (27.4%; 32/117) and cervical spine (22.2%; 26/117) segments. Among the metastatic tumors, the lung (22.6%) and breast (15.1%) were the most common primary sites of origin, followed by unknown origin, the liver (hepatocellular carcinoma), the gastrointestinal tract and the nasopharynx (nasopharyngeal cancer).
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http://dx.doi.org/10.1016/S1607-551X(08)70005-6DOI Listing
November 2007

Attenuation of experimental subarachnoid hemorrhage-induced increases in circulating intercellular adhesion molecule-1 and cerebral vasospasm by the endothelin-converting enzyme inhibitor CGS 26303.

J Neurosurg 2007 Mar;106(3):442-8

Department of Neurosurgery, Kaohsiung Medical University, Kaohsiung, Taiwan.

Object: Adhesion molecules, including intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin, are important mediators of inflammation, and their levels are elevated in the serum of patients following aneurysmal subarachnoid hemorrhage (SAH). The investigators previously found that CGS 26303 is effective in preventing and reversing arterial narrowing in a rabbit model of SAH. The purpose of the present study was to examine whether levels of adhesion molecules are altered after treatment with CGS 26303 in this animal model.

Methods: New Zealand White rabbits were each injected with 3 ml of autologous blood in the cisterna magna, and intravenous treatment with CGS 26303 (30 mg/kg) was initiated 1 hour later. The compound was subsequently administered at 12, 24, and 36 hours post-SAH. Blood samples were collected at 48 hours post-SAH to measure ICAM-1, VCAM-1, and E-selectin levels. After the rabbits had been killed by perfusion-fixation, the basilar arteries (BAs) were removed and sliced, and their cross-sectional areas were measured. Treatment with CGS 26303 attenuated arterial narrowing after SAH. Morphologically, corrugation of the internal elastic lamina of BAs was prominently observed in the SAH only and vehicle-treated SAH groups, but not in the CGS 26303-treated SAH group or in healthy controls. There were no significant differences in the levels of VCAM-1 among the four groups. The levels of E-selectin were increased in all animals subjected to SAH (those in the SAH only, SAH plus vehicle, and SAH plus CGS 26303 groups) compared with healthy controls (no SAH); however, the levels of ICAM-1 in the SAH only and SAH plus vehicle groups were significantly elevated (p < 0.001), and treatment with CGS 26303 reduced ICAM-1 to control levels following SAH.

Conclusions: These results show that ICAM-1 may play a role in mediating SAH-induced vasospasm and that a reduction of ICAM-1 levels after SAH may partly contribute to the antispastic effect of CGS 26303.
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http://dx.doi.org/10.3171/jns.2007.106.3.442DOI Listing
March 2007

Prevention and reversal of vasospasm and ultrastructural changes in basilar artery by continuous infusion of CGS 35066 following subarachnoid hemorrhage.

Exp Biol Med (Maywood) 2006 Jun;231(6):1069-74

Department of Neurosurgery, Kaohsiung Medical University Hospital, No.100, Tzyou 1st Road, Kaohsiung, Taiwan, Republic of China.

Endothelin-1, a potent vasoconstrictive peptide, has been implicated in the pathogenesis of cerebral vasospasm following subarachnoid hemorrhage (SAH). The goal of this study was to evaluate the effect of continuous intravenous infusion of a highly selective endothelin-converting enzyme-1 inhibitor, CGS 35066, on the prevention and reversal of cerebral vasospasm following SAH. New Zealand white rabbits were subjected to SAH by injecting autologous arterial blood into the cisterna magna. Infusion of CGS 35066 at dosages of 1, 3, or 10 mg/kg/ day was initiated either 1 hr and 24 hrs later in the prevention and reversal protocols, respectively. Animals were sacrificed by perfusion-fixation 48 hrs after SAH induction. The cross-sectional areas of basilar arteries were measured using computer-assisted videomicroscopy. Ultrastructural changes in basilar arteries were determined using electron microscopy. CGS 35066 significantly prevented and reversed the arterial narrowing after SAH in all three groups. The mean cross-sectional areas of arteries from animals in both the prevention and reversal protocol groups that received 10 mg/kg/day of CGS 35066 did not differ significantly from those of the healthy controls. Histological studies of the basilar artery in the 10 mg/kg/day treatment group did not show pathomorphological changes, such as corrugation of the endothelium seen at 2 days after SAH induction or vacuole formation in the endothelial cells noted in the vehicle-treated SAH group. These findings suggest that CGS 35066 is a promising therapeutic agent for the prevention and reversal of cerebral vasospasm after SAH. It also prevents the pathological changes in vascular walls due to SAH.
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June 2006