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1.  Effect of an Oral Hygienic Care Program for Stroke Patients in the Intensive Care Unit 
Yonsei Medical Journal  2013;55(1):240-246.
The effects of an oral hygienic care program (OHCP) have been reported in several diseases. However, no study exists investigating the influence of an OHCP on stroke patients or patients in the intensive care unit (ICU) has been reported, thus we sought to investigate the potential effect of an OHCP.
Materials and Methods
Fifty-six consecutive stroke patients who were admitted to the ICU were randomly assigned to two groups: the intervention (29 patients) and control groups (27 patients). The OHCP included tooth brushing with an inter-dental brush and tongue cleaner and cleaning with chlorhexidine was administered to patients by one dentist once per day during admission in the ICU (mean, 2.2 weeks). The plague index, gingival index, clinical attachment loss, and colonization degree of candida albicans were assessed.
After OHCP, the plaque index, gingival index, and colonization degree of candida albicans in saliva showed a significant decrease in the intervention group compared to those of the control group (p<0.05). However, no significant difference was observed in clinical attachment loss and the colonization degree of candida albicans on the tongue (p>0.05).
Our OHCP was effective in improving the oral hygienic status and periodontal health of stroke patients during their stay in the ICU. Therefore, we recommend administration of the OHCP for stroke patients during their stay in the ICU.
PMCID: PMC3874900  PMID: 24339313
Oral health promotion; stroke; intensive care unit
2.  Perceived Causality Can Alter the Perceived Trajectory of Apparent Motion 
Psychological science  2013;24(4):10.1177/0956797612458529.
When objects collide, human observers perceive not only motion but also causal relations, such as which object caused the other to move. In the present experiments, we investigated whether such causal interpretations can actually influence the perceived path of apparent motion. Displays contained two alternately flashing motion targets positioned at either end of a semicircular occluder. Two additional “context objects” moved in such a way that the motion targets appeared to collide with and launch them. The collision was manipulated so that it was consistent with apparent motion either along the straight path between the targets or along a curved path passing behind the occluder. Subjects almost exclusively perceived motion consistent with the implied launch, which suggests that causally coherent interpretations can influence basic perceptual processes.
PMCID: PMC3838432  PMID: 23474831
motion perception; causality; visual perception; cognition
3.  A Case of Anisakiasis Invading the Stomach and the Colon at the Same Time after Eating Anchovies 
Clinical Endoscopy  2013;46(3):293-296.
Anisakiasis of the gastrointestinal tract is caused by the ingestion of raw fish or uncooked food infested with Anisakis larvae. A large number of cases of gastric anisakiasis have been reported in countries where the eating of raw fish is customary. However, there have been few reports of anisakiasis of the colon confirmed by colonoscopy and also very few reports of endoscopic ultrasonographic findings of anisakiasis. A 47-year-old man had epigastric pain with nausea after eating raw anchovies. Endoscopy found a living tubular structure penetrating into the lesser curvature of the stomach and the midtranseverse colon area. It was withdrawn with biopsy forceps. We report a case of anisakiasis simultaneously invading the stomach and the colon confirmed by endosopic utrasonographic findings and biopsy findings.
PMCID: PMC3678070  PMID: 23767043
Anisakiasis; Endoscopy; Endosonography
4.  Establishment of a murine model for radiation-induced bone loss using micro-computed tomography in adult C3H/HeN mice 
Laboratory Animal Research  2013;29(1):55-62.
Bone changes are common sequela of radiation therapy for cancer. The purpose of this study was to establish an experimental model of radiation-induced bone loss in adult mice using micro-computed tomography (µCT). The extent of changes following 2 Gy gamma irradiation (2 Gy/min) was studied at 4, 8, 12 or 16 weeks after exposure. Adult mice that received 1, 2, 4 or 6 Gy of gamma-rays were examined 12 weeks after irradiation. Tibiae were analyzed using µCT. Serum markers and biomechanical properties were measured and the osteoclast surface was examined. A significant loss of trabecular bone in tibiae was evident 12 weeks after exposure. Measurements performed after irradiation showed a dose-related decrease in trabecular bone volume fraction (BV/TV) and bone mineral density (BMD), respectively. The best-fitting dose-response curves were linear-quadratic. Taking the controls into accounts, the lines of best fit were as follows: BV/TV (%)= -0.071D2-1.799D+18.835 (r2=0.968, D=dose in Gy) and BMD (mg/cm3) = -3.547D2-14.8D+359.07 (r2=0.986, D=dose in Gy). Grip strength and body weight did not differ among the groups. No dose-dependent differences were apparent among the groups with regard to mechanical and anatomical properties of tibia, serum biochemical markers and osteoclast activity. The findings provide the basis required for better understanding of the results that will be obtained in any further studies of radiation-induced bone responses.
PMCID: PMC3616210  PMID: 23573109
Radiation; bone loss; murine model; microcomputed tomography
5.  Temporal profiles of synaptic plasticity-related signals in adult mouse hippocampus with methotrexate treatment☆ 
Neural Regeneration Research  2012;7(21):1651-1658.
Methotrexate, which is used to treat many malignancies and autoimmune diseases, affects brain functions including hippocampal-dependent memory function. However, the precise mechanisms underlying methotrexate-induced hippocampal dysfunction are poorly understood. To evaluate temporal changes in synaptic plasticity-related signals, the expression and activity of N-methyl-D-aspartic acid receptor 1, calcium/calmodulin-dependent protein kinase II, extracellular signal-regulated kinase 1/2, cAMP responsive element-binding protein, glutamate receptor 1, brain-derived neurotrophic factor, and glial cell line-derived neurotrophic factor were examined in the hippocampi of adult C57BL/6 mice after methotrexate (40 mg/kg) intraperitoneal injection. Western blot analysis showed biphasic changes in synaptic plasticity-related signals in adult hippocampi following methotrexate treatment. N-methyl-D-aspartic acid receptor 1, calcium/calmodulin-dependent protein kinase II, and glutamate receptor 1 were acutely activated during the early phase (1 day post-injection), while extracellular signal-regulated kinase 1/2 and cAMP responsive element-binding protein activation showed biphasic increases during the early (1 day post-injection) and late phases (7–14 days post-injection). Brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor expression increased significantly during the late phase (7–14 days post-injection). Therefore, methotrexate treatment affects synaptic plasticity-related signals in the adult mouse hippocampus, suggesting that changes in synaptic plasticity-related signals may be associated with neuronal survival and plasticity-related cellular remodeling.
PMCID: PMC4308769  PMID: 25657706
hippocampus; methotrexate; neurotrophic factor; synaptic plasticity-related signal; neural regeneration
6.  The ameliorative effect of silibinin against radiation-induced lung injury: protection of normal tissue without decreasing therapeutic efficacy in lung cancer 
Silibinin has been known for its role in anti-cancer and radio-protective effect. Radiation therapy for treating lung cancer might lead to late-phase pulmonary inflammation and fibrosis. Thus, this study aimed to investigate the effects of silibinin in radiation-induced lung injury with a mouse model.
In this study, we examined the ability of silibinin to mitigate lung injury in, and improve survival of, C57BL/6 mice given 13 Gy thoracic irradiation and silibinin treatments orally at 100 mg/kg/day for seven days after irradiation. In addition, Lewis lung cancer (LLC) cells were injected intravenously in C57BL/6 mice to generate lung tumor nodules. Lung tumor-bearing mice were treated with lung radiation therapy at 13 Gy and with silibinin at a dose of 100 mg/day for seven days after irradiation.
Silibinin was shown to increase mouse survival, to ameliorate radiation-induced hemorrhage, inflammation and fibrosis in lung tissue, to reduce the number of inflammatory cells in the bronchoalveolar lavage fluid (BALF) and to reduce inflammatory cell infiltration in the respiratory tract. In LLC tumor injected mice, lung tissue from mice treated with both radiation and silibinin showed no differences compared to lung tissue from mice treated with radiation alone.
Silibinin treatment mitigated the radiation-induced lung injury possibly by reducing inflammation and fibrosis, which might be related with the improved survival rate. Silibinin might be a useful agent for lung cancer patients as a non-toxic complementary approach to alleviate the side effects by thorax irradiation.
PMCID: PMC4499198  PMID: 26143275
Silibinin; Irradiation; Lung fibrosis; BALF; Lewis lung cancer; Mice
7.  Coniferyl Aldehyde Attenuates Radiation Enteropathy by Inhibiting Cell Death and Promoting Endothelial Cell Function 
PLoS ONE  2015;10(6):e0128552.
Radiation enteropathy is a common complication in cancer patients. The aim of this study was to investigate whether radiation-induced intestinal injury could be alleviated by coniferyl aldehyde (CA), an HSF1-inducing agent that increases cellular HSP70 expression. We systemically administered CA to mice with radiation enteropathy following abdominal irradiation (IR) to demonstrate the protective effects of CA against radiation-induced gastrointestinal injury. CA clearly alleviated acute radiation-induced intestinal damage, as reflected by the histopathological data and it also attenuated sub-acute enteritis. CA prevented intestinal crypt cell death and protected the microvasculature in the lamina propria during the acute and sub-acute phases of damage. CA induced HSF1 and HSP70 expression in both intestinal epithelial cells and endothelial cells in vitro. Additionally, CA protected against not only the apoptotic cell death of both endothelial and epithelial cells but also the loss of endothelial cell function following IR, indicating that CA has beneficial effects on the intestine. Our results provide novel insight into the effects of CA and suggest its role as a therapeutic candidate for radiation-induced enteropathy due to its ability to promote rapid re-proliferation of the intestinal epithelium by the synergic effects of the inhibition of cell death and the promotion of endothelial cell function.
PMCID: PMC4452689  PMID: 26029925
8.  Morphometric Study of the Anterior Thalamoperforating Arteries 
To evaluate the morphometry of the anterior thalamoperforating arteries (ATPA).
A microanatomical study was performed in 79 specimens from 42 formalin-fixed adult cadaver brains. The origins of the ATPAs were divided into anterior, middle, and posterior segments according to the crowding pattern. The morphometry of the ATPAs, including the premammillary artery (PMA), were examined under a surgical microscope.
The anterior and middle segments of the ATPAs arose at mean intervals of 1.75±1.62 mm and 5.86±2.05 mm from the internal carotid artery (ICA), and the interval between these segments was a mean of 3.17±1.64 mm. The posterior segment arose at a mean interval of 2.43±1.46 mm from the posterior cerebral artery (PCA), and the interval between the middle and posterior segments was a mean of 3.45±1.39 mm. The mean numbers of perforators were 2.66±1.19, 3.03±1.84, and 1.67±0.98 in the anterior, middle, and posterior segments, respectively. The PMA originated from the middle segment in 66% of cases. A perforator-free zone was located >2 mm from the ICA in 30.4% and >2 mm from the PCA in 67.1% of cases.
Most perforators arose from the anterior and middle segments, within the anterior two-thirds of the posterior communicating artery (PCoA). The safest perforator-free zone was located closest to the PCA. These anatomical findings may be helpful to verify safety when treating lesions around the PCoA and in the interpeduncular fossa.
PMCID: PMC4479716  PMID: 26113962
Anterior thalamoperforating artery; Premammillary artery; Perforator-free zone
9.  Diallyl Disulfide Prevents Cyclophosphamide-Induced Hemorrhagic Cystitis in Rats through the Inhibition of Oxidative Damage, MAPKs, and NF-κB Pathways 
Biomolecules & Therapeutics  2015;23(2):180-188.
This study investigated the possible effects and molecular mechanisms of diallyl disulfide (DADS) against cyclophosphamide (CP)-induced hemorrhagic cystitis (HC) in rats. Inflammation response was assessed by histopathology and serum cytokines levels. We determined the protein expressions of nuclear transcription factor kappa-B (NF-κB), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and tumor necrosis factor-α (TNF-α), oxidative stress, urinary nitrite-nitrate, malondialdehyde (MDA), and 8-hydroxy-2’-deoxyguanosine (8-OHdG). Finally, we studied the involvement of mitogen-activated protein kinases (MAPKs) signaling in the protective effects of DADS against CP-induced HC. CP treatment caused a HC which was evidenced by an increase in histopathological changes, proinflammatory cytokines levels, urinary nitrite-nitrate level, and the protein expression of NF-κB, COX-2, iNOS, TNF-α, p-c-Jun N-terminal kinase (JNK), and p-extracellular signal regulated kinase (ERK). The significant decreases in glutathione content and glutathione-S-transferase and glutathione reductase activities, and the significant increase in MDA content and urinary MDA and 8-OHdG levels indicated that CP-induced bladder injury was mediated through oxidative DNA damage. In contrast, DADS pretreatment attenuated CP-induced HC, including histopathological lesion, serum cytokines levels, oxidative damage, and urinary oxidative DNA damage. DADS also caused significantly decreased the protein expressions of NF-κB, COX-2, iNOS, TNF-α, p-JNK, and p-ERK. These results indicate that DADS prevents CP-induced HC and that the protective effects of DADS may be due to its ability to regulate proinflammatory cytokines production by inhibition of NF-κB and MAPKs expressions, and its potent anti-oxidative capability through reduction of oxidative DNA damage in the bladder.
PMCID: PMC4354320  PMID: 25767687
Cyclophosphamide; Hemorrhagic cystitis; Diallyl disulfide; Oxidative damage; MAPKs; NF-κB
10.  Protective effects of pine bark extract against cisplatin-induced hepatotoxicity and oxidative stress in rats 
Laboratory Animal Research  2014;30(4):174-180.
We investigated the protective effects of pine bark extract (pycnogenol®, PYC) against cisplatin-induced hepatotoxicity and oxidative stress in rats. Twenty-four male rats were divided into the following four groups: (1) vehicle control, (2) cisplatin (7.5 mg/kg), (3) cisplatin & PYC 10 (10 mg/kg/day), and (4) cisplatin & PYC 20 (20 mg/kg/day). A single intraperitoneal injection of cisplatin induced hepatotoxicity, as evidenced by an increase in serum aminotransferase and histopathological alterations, including degeneration/necrosis of hepatocytes, vacuolation, and sinusoidal dilation. In addition, an increase in the malondialdehyde (MDA) concentration and a decrease in the reduced glutathione (GSH) content and catalase (CAT), superoxide dismutase (SOD), and glutathione S-transferase (GST) activities were observed in the cisplatin-treated rat hepatic tissues. In contrast, PYC treatment effectively prevented cisplatin-induced hepatotoxicity, including the elevation of aminotransferase and histopathological lesions, in a dosedependent manner. Moreover, PYC treatment also induced antioxidant activity by decreasing MDA level and increasing GSH content and SOD and GST activities in liver tissues. These results indicate that PYC has a protective effect against acute hepatotoxicity induced by cisplatin in rats, and that the protective effects of PYC may be due to inhibiting lipid peroxidation and increasing antioxidant activity.
PMCID: PMC4306705  PMID: 25628728
Cisplatin; hepatotoxicity; oxidative stress; pine bark extract; protective effects
11.  Knockdown of Bcl-xL Enhances Growth-Inhibiting and Apoptosis-Inducing Effects of Resveratrol and Clofarabine in Malignant Mesothelioma H-2452 Cells 
Journal of Korean Medical Science  2014;29(11):1464-1472.
Mcl-1 and Bcl-xL, key anti-apoptotic proteins of the Bcl-2 family, have attracted attention as important molecules in the cell survival and drug resistance. In this study, we investigated whether inhibition of Bcl-xL influences cell growth and apoptosis against simultaneous treatment of resveratrol and clofarabine in the human malignant mesothelioma H-2452 cells. Resveratrol and clofarabine decreased Mcl-1 protein levels but had little effect on Bcl-xL levels. In the presence of two compounds, any detectable change in the Mcl-1 mRNA levels was not observed in RT-PCR analysis, whereas pretreatment with the proteasome inhibitor MG132 led to its accumulation to levels far above basal levels. The knockdown of Bcl-xL inhibited cell proliferation with cell accumulation at G2/M phase and the appearance of sub-G0/G1 peak in DNA flow cytometric assay. The suppression of cell growth was accompanied by an increase in the caspase-3/7 activity with the resultant cleavages of procaspase-3 and its substrate poly (ADP-ribose) polymerase, and increased percentage of apoptotic propensities in annexin V binding assay. Collectively, our data represent that the efficacy of resveratrol and clofarabine for apoptosis induction was substantially enhanced by Bcl-xL-lowering strategy in which the simultaneous targeting of Mcl-1 and Bcl-xL could be a more effective strategy for treating malignant mesothelioma.
Graphical Abstract
PMCID: PMC4234912  PMID: 25408576
Mesothelioma, Malignant; Mcl-1; Bcl-xL; Resveratol; Clofarabine; Apoptosis
12.  High-mobility ambipolar ZnO-graphene hybrid thin film transistors 
Scientific Reports  2014;4:4064.
In order to combine advantages of ZnO thin film transistors (TFTs) with a high on-off ratio and graphene TFTs with extremely high carrier mobility, we present a facile methodology for fabricating ZnO thin film/graphene hybrid two-dimensional TFTs. Hybrid TFTs exhibited ambipolar behavior, an outstanding electron mobility of 329.7 ± 16.9 cm2/V·s, and a high on-off ratio of 105. The ambipolar behavior of the ZnO/graphene hybrid TFT with high electron mobility could be due to the superimposed density of states involving the donor states in the bandgap of ZnO thin films and the linear dispersion of monolayer graphene. We further established an applicable circuit model for understanding the improvement in carrier mobility of ZnO/graphene hybrid TFTs.
PMCID: PMC3920279  PMID: 24513629
13.  Protective effect of diallyl disulfide on cyclophosphamide-induced testicular toxicity in rats 
Laboratory Animal Research  2013;29(4):204-211.
This study investigated the protective effects of diallyl disulfide (DADS) against cyclophosphamide (CP)-induced testicular toxicity in male rats. DADS was gavaged to rats once daily for 3 days at 100 mg/kg/day. One hour after the final DADS treatment, the rats were given a single intraperitoneal dose of 150 mg/kg CP. All rats were killed and necropsied on day 56 after CP treatment. Parameters of testicular toxicity included reproductive organ weight, testicular sperm head count, epididymal sperm motility and morphology, epididymal index, and histopathologic examinations. The CP treatment caused a decrease in body weight, testicular sperm head count, epididymal sperm motility, and epididymal index. The histopathological examination revealed various morphological alterations, characterized by degeneration of spermatogonia/spermatocytes, vacuolization, and decreased number of spermatids/spermatocytes in the testis, and cell debris and mild oligospermia in the ductus epididymis. In contrast, DADS pretreatment effectively attenuated the testicular toxicity caused by CP, including decreased sperm head count, epididymal sperm motility, and epididymal index and increased histopathological alterations in the testis and epididymis. These results indicate that DADS attenuates testicular toxicity induced by CP in rats.
PMCID: PMC3879339  PMID: 24396385
Cancer chemotherapy; cyclophosphamide; testicular toxicity; diallyl disulfide; protective effect
14.  Effect of Korean Red Ginseng on radiation-induced bone loss in C3H/HeN mice 
Journal of Ginseng Research  2013;37(4):435-441.
This study investigated the effects of Korean Red Ginseng (KRG) on radiation-induced bone loss in C3H/HeN mice. C3H/HeN mice were divided into sham and irradiation (3 Gy, gamma-ray) groups. The irradiated mice were treated for 12 wk with vehicle, KRG (per os, p.o.) or KRG (intraperitoneal). Serum alkaline phosphatase (ALP), tartrate-resistant acid phosphatase, estradiol level, and biomechanical properties were measured. Tibiae were analyzed using micro-computed tomography. Treatment of KRG (p.o., 250 mg/kg of body weight/d) significantly preserved trabecular bone volume, trabecular number, structure model index, and bone mineral density of proximal tibia metaphysic, but did not alter the uterus weight of the mice. Serum ALP level was slightly reduced by KRG treatment. However, grip strength, mechanical property, and cortical bone architecture did not differ among the experimental groups. The results indicate that KRG can prevent radiation-induced bone loss in mice.
PMCID: PMC3825858  PMID: 24233384
Panax ginseng; Korean Red Ginseng; Radiation; Bone loss; Trabecular bone
15.  Possible Role of the Glycogen Synthase Kinase-3 Signaling Pathway in Trimethyltin-Induced Hippocampal Neurodegeneration in Mice 
PLoS ONE  2013;8(8):e70356.
Trimethyltin (TMT) is an organotin compound with potent neurotoxic effects characterized by neuronal destruction in selective regions, including the hippocampus. Glycogen synthase kinase-3 (GSK-3) regulates many cellular processes, and is implicated in several neurodegenerative disorders. In this study, we evaluated the therapeutic effect of lithium, a selective GSK-3 inhibitor, on the hippocampus of adult C57BL/6 mice with TMT treatment (2.6 mg/kg, intraperitoneal [i.p.]) and on cultured hippocampal neurons (12 days in vitro) with TMT treatment (5 µM). Lithium (50 mg/kg, i.p., 0 and 24 h after TMT injection) significantly attenuated TMT-induced hippocampal cell degeneration, seizure, and memory deficits in mice. In cultured hippocampal neurons, lithium treatment (0–10 mM; 1 h before TMT application) significantly reduced TMT-induced cytotoxicity in a dose-dependent manner. Additionally, the dynamic changes in GSK-3/β-catenin signaling were observed in the mouse hippocampus and cultured hippocampal neurons after TMT treatment with or without lithium. Therefore, lithium inhibited the detrimental effects of TMT on the hippocampal neurons in vivo and in vitro, suggesting involvement of the GSK-3/β-catenin signaling pathway in TMT-induced hippocampal cell degeneration and dysfunction.
PMCID: PMC3734066  PMID: 23940567
16.  Effects of the Temporary Placement of a Self-Expandable Metallic Stent in Benign Pyloric Stenosis 
Gut and Liver  2013;7(4):417-422.
The use of self-expandable metallic stents (SEMS) is an established palliative treatment for malignant stenosis in the gastrointestinal tract; therefore, its application to benign stenosis is expected to be beneficial because of the more gradual and sustained dilatation in the stenotic portion. We aimed in this prospective observational study to evaluate the efficacy and safety of temporary SEMS placement in benign pyloric stenosis.
Twenty-two patients with benign stenosis of the prepylorus, pylorus, and duodenal bulb were enrolled and underwent SEMS placement. We assessed symptom improvement, defined as an increase of at least 1 degree in the gastric-outlet-obstruction scoring system after stent insertion.
No major complications were observed during the procedures. After stent placement, early symptom improvement was achieved in 18 of 22 patients (81.8%). During the follow-up period (mean 10.2 months), the stents remained in place successfully for 6 to 8 weeks in seven patients (31.8%). Among the 15 patients (62.5%) with stent migration, seven (46.6%) showed continued symptomatic improvement without recurrence of obstructive symptoms.
Despite the symptomatic improvement, temporary SEMS placement is premature as an effective therapeutic tool for benign pyloric stenosis unless a novel stent is developed to prevent migration.
PMCID: PMC3724029  PMID: 23898381
Benign pyloric stenosis; Self-expandable metallic stent
17.  4-Week repeated oral dose toxicity study of 1,4-dichlorobutane in rats 
Laboratory Animal Research  2013;29(1):48-54.
The present study investigated the potential subacute toxicity of 1,4-dichlorobutane by a 4-week repeated oral dose in Sprague-Dawley rats. The test article was administered once daily by gavage to male rats at dose levels of 0, 100, 300, and 1,000 mg/kg/day for 4 weeks. All rats were sacrificed at the end of the treatment period. During the test period, clinical signs, mortality, body weight, hematology, serum biochemistry, gross findings, and organ weight were examined. At 1,000 mg/kg/day, an increase in the clinical signs and weights of the liver and kidneys was observed in the male rats. Serum biochemical investigations revealed an increase in alanine aminotransferase, alkaline phosphatase, total cholesterol, total bilirubin, phospholipids, blood urea nitrogen, and gamma glutamyl transferase levels. There were no treatment-related adverse effects in the low and middle-dose groups. In the present experimental conditions, the target organs were determined to be liver and kidney. The no-observed-adverse-effect level was considered to be 300 mg/kg/day in rats.
PMCID: PMC3616209  PMID: 23573108
1,4-Dichlorobutane; subacute toxicity; target organ; no-observed-adverse-effect level
18.  Bisphosphonate-induced Severe Hypocalcemia - A Case Report - 
Journal of Bone Metabolism  2012;19(2):139-145.
Bisphosphonate generally seems to be safe, but hypocalcemia may occasionally develop in the course of bisphosphonate treatment. Hypocalcemia induced by bisphosphonate is usually mild and asymptomatic, but unrecognized or poorly treated hypocalcemia can lead to life-threatening state. A 78-year-old woman who had a history of hip arthroplasty and intravenous zoledronate treatment for femur neck fracture was presented to emergency department with altered mental status. It turned out that her symptom was due to severe hypocalcemia which was caused by intravenous zoledronate treatment. She also had renal dysfunction. She was treated by intravenous calcium gluconate and calcitriol administration. This case supports the need for evaluation of renal dysfunction, vitamin D deficiency and parathyroid gland dysfunction before bisphosphonate treatment and accurate monitoring of plasma calcium and creatinine levels. In addition, vitamin D and calcium supply during treatment with bisphosphonate is mandatory.
PMCID: PMC3780919  PMID: 24524045
Bisphosphonates; Hypocalcemia; Osteoporosis
19.  Anatomical Morphometric Study of the Cervical Uncinate Process and Surrounding Structures 
The purpose of this study is to elucidate the anatomic relationships between the uncinate process and surrounding neurovascular structures to prevent possible complications in anterior cervical surgery.
Twenty-eight formalin-fixed cervical spines were removed from adult cadavers and were studied. The authors investigated the morphometric relationships between the uncinate process, vertebral artery and adjacent nerve roots.
The height of the uncinate process was 5.6-7.5 mm and the width was 5.8-8.0 mm. The angle between the posterior tip of the uncinate process and vertebral artery was 32.2-42.4°. The distance from the upper tip of the uncinate process to the vertebral body immediately above was 2.1-3.3 mm, and this distance was narrowest at the fifth cervical vertebrae. The distance from the posterior tip of the uncinate process to the nerve root was 1.3-2.0 mm. The distance from the uncinate process to the vertebral artery was measured at three different points of the uncinate process : upper-posterior tip, lateral wall and the most antero-medial point of the uncinate process, and the distances were 3.6-6.1 mm, 1.7-2.8 mm, and 4.2-5.7 mm, respectively. The distance from the uncinate process tip to the vertebral artery and the angle between the uncinate process tip and vertebral artery were significantly different between the right and left side.
These data provide guidelines for anterior cervical surgery, and will aid in reducing neurovascular injury during anterior cervical surgery, especially in anterior microforaminotomy.
PMCID: PMC3488636  PMID: 23133716
Anterior cervical surgery; Foraminotomy; Uncinate process, Vertebral artery; Nerve root
20.  Curved apparent motion induced by amodal completion 
We investigated whether amodal completion can bias apparent motion (AM) to deviate from its default straight path toward a longer curved path, which would violate the well-established principle that AM follows the shortest possible path. Observers viewed motion sequences of two alternating rectangular tokens positioned at the ends of a semicircular occluder, with varying interstimulus intervals (ISIs; 100–500 ms). At short ISIs, observers tended to report simple straight-path motion—that is, outside the occluder. But at long ISIs, they became increasingly likely to report a curved-path motion behind the occluder. This tendency toward reporting curved-path motion was influenced by the shape of tokens, display orientation, the gap between tokens and the occluder, and binocular depth cues. Our results suggest that the visual system tends to minimize unexplained absence of a moving object, as well as its path length, such that AM deviates from the shortest path when amodal integration of motion trajectory behind the curved occluder can account for the objective invisibility of the object during the ISI.
PMCID: PMC3437265  PMID: 22069082
Apparent motion; Occlusion; Amodal completion; Tunnel effect
21.  Role of vitamin D-binding protein in isocyanate-induced occupational asthma 
Experimental & Molecular Medicine  2012;44(5):319-329.
The development of a serological marker for early diagnosis of isocyanate-induced occupational asthma (isocyanate-OA) may improve clinical outcome. Our previous proteomic study found that expression of vitamin D-binding protein (VDBP) was upregulated in the patients with isocyanate-OA. In the present study, we evaluated the clinical relevance of VDBP as a serological marker in screening for isocyanate-OA among exposed workers and its role in the pathogenesis of isocyanate-OA. Three study groups including 61 patients with isocyanate-OA (group I), 180 asymptomatic exposed controls (AECs, group II), 58 unexposed healthy controls (NCs, group III) were enrolled in this study. The baseline serum VDBP level was significantly higher in group I compared with groups II and III. The sensitivity and specificity for predicting the phenotype of isocyanate-OA with VDBP were 69% and 81%, respectively. The group I subjects with high VDBP (≥ 311 µg/ml) had significantly lower PC20 methacholine levels than did subjects with low VDBP. The in vitro studies showed that TDI suppressed the uptake of VDBP into RLE-6TN cells, which was mediated by the downregulation of megalin, an endocytic receptor of the 25-hydroxycholecalciferol-VDBP complex. Furthermore, toluene diisocyanate (TDI) increased VEGF production and secretion from this epithelial cells by suppression of 1,25-dihydroxycholecalciferol [1,25(OH)2D3] production. The findings of this study suggest that the serum VDBP level may be used as a serological marker for the detection of isocyanate-OA among workers exposed to isocyanate. The TDI-induced VEGF production/secretion was reversed by 1,25(OH)2D3 treatment, which may provide a potential therapeutic strategy for patients with isocyanate-OA.
PMCID: PMC3366325  PMID: 22314196
asthma, occupational; biological markers; isocyanates; low density lipoprotein receptor-related protein-2; vascular endothelial growth factorA; vitamin D-binding protein
22.  Waffle-Cone Technique Using Solitaire AB Stent 
The waffle-cone technique is a modified stent application technique, which involves protrusion of the distal portion of a stent into an aneurysm fundus to provide neck support for subsequent coiling. The authors report two cases of wide necked basilar bifurcation aneurysms, which were not amenable to stent assisted coiling, that were treated using the waffle-cone technique with a Solitaire AB stent. A 58-year-old woman presented with severe headache. Brain CT showed subarachnoid hemorrhage and angiography demonstrated a ruptured giant basilar bifurcation aneurysm with broad neck, which was treated with a Solitaire AB stent and coils using the waffle-cone technique. The second case involved an 81-year-old man, who presented with dizziness caused by brain stem infarction. Angiography also demonstrated a large basilar bifurcation unruptured aneurysm with broad neck. Solitaire AB stent deployment using the waffle-cone technique, followed by coiling resulted in near complete obliteration of aneurysm. The waffle-cone technique with a Solitaire AB stent can be a useful alternative to conventional stent application when it is difficult to catheterize bilateral posterior cerebral arteries in patients with a wide-necked basilar bifurcation aneurysm.
PMCID: PMC3377880  PMID: 22737303
Wide-necked aneurysm; Waffle-cone technique; Solitaire AB stent
23.  Spermatotoxic effects of α-chlorohydrin in rats 
Laboratory Animal Research  2012;28(1):11-16.
This study was conducted to investigate the potential effects of α-chlorohydrin (ACH) on epididymal function and antioxidant system in male rats. The test chemical was administered to male rats by gavage at doses of 0, 3, 10, and 30 mg/kg/day for 7 days. Twenty-four male rats were randomly assigned to four experimental groups, with six rats in each group. Spermatotoxicity was assessed by measurement of reproductive organ weight, testicular sperm head count, epididymal sperm motility and morphology, histopathologic examination, and oxidative damage analysis in rats. At 30 mg/kg/day, an increase in the incidence of clinical signs, epididymis weight, and gross necropsy findings of the epididymis, a decrease in the sperm motility, and an increased incidence of histopathological changes of the epididymis were observed in a dose-dependent manner. At 10 mg/kg/day, an increased incidence of clinical signs and histopathological changes and decreased sperm motility were observed. In the oxidative damage analysis, an increase in the malondialdehyde concentration and a decrease in the glutathione content and glutathione peroxidase and catalase activities in the epididymal tissue were detected at ≥3 mg/kg/day. The results show that graded doses of ACH elicit depletion of the antioxidant defense system and that the spermatotoxicity of ACH may be due to the induction of oxidative stress.
PMCID: PMC3315198  PMID: 22474469
α-Chlorohydrin; oxidative stress; reproductive dysfunction; sperm
24.  Fast neutron irradiation deteriorates hippocampus-related memory ability in adult mice 
Object recognition memory and contextual fear conditioning task performance in adult C57BL/6 mice exposed to cranial fast neutron irradiation (0.8 Gy) were examined to evaluate hippocampus-related behavioral dysfunction following acute exposure to relatively low doses of fast neutrons. In addition, hippocampal neurogenesis changes in adult murine brain after cranial irradiation were analyzed using the neurogenesis immunohistochemical markers Ki-67 and doublecortin (DCX). In the object recognition memory test and contextual fear conditioning, mice trained 1 and 7 days after irradiation displayed significant memory deficits compared to the sham-irradiated controls. The number of Ki-67- and DCX-positive cells decreased significantly 24 h post-irradiation. These results indicate that acute exposure of the adult mouse brain to a relatively low dose of fast neutrons interrupts hippocampal functions, including learning and memory, possibly by inhibiting neurogenesis.
PMCID: PMC3317449  PMID: 22437529
fast neutron; hippocampus; learning and memory; neurogenesis
25.  Bilateral Vertebral Artery Dissecting Aneurysms Presenting with Subarachnoid Hemorrhage Treated by Staged Coil Trapping and Covered Stents Graft 
The treatment of bilateral vertebral artery dissecting aneurysms (VADAs) presenting with subarachnoid hemorrhage (SAH) is still challenging. The authors report a rare case of bilateral VADA treated with coil trapping of ruptured VADA and covered stents implantation after multiple unsuccessful stent assisted coiling of the contralateral unruptured VADA. A 44-year-old woman was admitted to our hospital because of severe headache and sudden stuporous consciousness. Brain CT showed thick SAH and intraventricular hemorrhage. Cerebral angiography demonstrated bilateral VADA. Based on the SAH pattern and aneurysm configurations, the right VADA was considered ruptured. This was trapped with endovascular coils without difficulty. One month later, the contralateral unruptured VADA was protected using a stent-within-a-stent technique, but marked enlargement of the left VADA was detected by 8-months follow-up angiography. Subsequently two times coil packing for pseudosacs resulted in near complete occlusion of left VADA. However, it continued to grow. Covered stents graft below the posterior inferior cerebellar artery (PICA) origin and a coronary stent implantation across the origin of the PICA resulted in near complete obliteration of the VADA. Covered stent graft can be used as a last therapeutic option for the management of VADA, which requires absolute preservation of VA flow.
PMCID: PMC3358603  PMID: 22639713
Vertebral artery dissecting aneurysm; SAH; Stent assisted coiling; Trapping; Covered stent graft; Endovascular embolization

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