Vasomotion in human arteries and their regulations based on ion channel regulations: 10 years study.

Vasomotion is the oscillation of vascular tone which gives rise to flow motion of blood into an organ. As is well known, spontaneous contractile organs such as heart, GI, and genitourinary tract produce rhythmic contraction. It imposes or removes pressure on their vessels alternatively for exchange of many substances. It was first described over 150 years ago, however the physiological mechanism and pathophysiological implications are not well understood. This study aimed to elucidate underlying mechanisms and physiological function of vasomotion in human arteries. Conventional contractile force measurement, immunohistochemistry, and Western blot analysis were employed to study human left gastric artery (HLGA) and uterine arteries (HUA). RESULTS: Circular muscle of HLGA and/or HUA produced sustained tonic contraction by high K+ (50 mM) which was blocked by 2 µM nifedipine. Stepwise stretch and high K+ produced nerve-independent spontaneous contraction (vasomotion) (around 45% of tested tissues). Vasomotion was also produced by application of BayK 8644, 5-HT, prostagrandins, oxytocin. It was blocked by nifedipine (2 µM) and blockers of intracellular Ca2+ stores. Inhibitors of Ca2+ -activated Cl- channels (DIDS and/or niflumic acid) and ATP-sensitive K+ (KATP ) channels inhibited vasomotion reversibly. Metabolic inhibition by sodium cyanide (NaCN) and several neuropeptides also regulated vasomotion in KATP channel-sensitive and -insensitive manner. Finally, we identified TMEM16A Ca2+ -activated Cl- channels and subunits of KATP channels (Kir 6.1/6.2 and sulfonylurea receptor 2B [SUR2B]), and c-Kit positivity by Western blot analysis. We conclude that vasomotion is sensitive to TMEM16A Ca2+ -activated Cl- channels and metabolic changes in human gastric and uterine arteries. Vasomotion might play an important role in the regulation of microcirculation dynamics even in pacemaker-related autonomic contractile organs in humans.

Iron is Responsible for Production of Reactive Oxygen Species Regulating Vasopressin Expression in the Mouse Paraventricular Nucleus.

Reactive oxygen species (ROS) act as signaling molecules for maintaining homeostasis, particularly in the regulation of body-fluid balance in the paraventricular nucleus (PVN) of the hypothalamus. However, there has been little discussion regarding the source of ROS generation in this hypothalamic region. Because iron is the most abundant metal in the brain, we hypothesized that iron may act as a source of ROS, which regulate vasopressin (VP) expression. In the present study, we compared the amount of iron in the PVN to that in other forebrain regions of normal ICR mice, and examined the relationship among iron, ROS, and VP in the PVN of the iron-overloaded with iron dextran and iron-chelated mice with deferoxamine. The amount of iron in the PVN was significantly higher than in any of the forebrain regions we examined. The amount of iron in the PVN was significantly increased in iron-overloaded mice, although not in iron-chelated mice. These results suggest that the PVN exhibits high iron affinity. Both ROS production and VP expression in the PVN of iron-overloaded mice were significantly increased relative to levels observed in control mice. VP concentration in blood of iron-overloaded mice was also significantly higher than that of control mice. Interestingly, iron overload did not alter the expression of nitric oxide synthase, another modulator of VP expression. Taken together, our results suggest that high levels of iron in the PVN induce the production of ROS, which regulate VP expression, independent of nitric oxide signaling.

Changes of motor cortical excitability and response inhibition in patients with obsessive­compulsive disorder

Background: Deficits in cortical inhibitory processes have been suggested as underlying pathophysiological mechanisms of obsessive­compulsive disorder (OCD). We examined whether patients with OCD have altered cortical excitability using paired-pulse transcranial magnetic stimulation (TMS). We also tested associations between TMS indices and OCD-related characteristics, including age of onset and response inhibition in the go/no-go paradigm, to examine whether altered cortical excitability contributes to symptom formation and behavioural inhibition deficit in patients with OCD. Methods: We assessed motor cortex excitability using paired-pulse TMS in 51 patients with OCD and 39 age-matched healthy controls. We also assessed clinical symptoms and response inhibition in the go/nogo task. All patients were undergoing treatment with serotonin reuptake inhibitors. We performed repeated-measures multivariate analysis of covariance to compare TMS indices between patients with OCD and controls. Results: Compared to controls, patients with OCD showed a shorter cortical silent period and decreased intracortical facilitation. However, we found no significant difference between groups for resting motor threshold or short-interval intracortical inhibition. In the OCD group, the shortened cortical silent period was associated with a prompt reaction time in the go/no-go task and with early onset of OCD. Limitations: We could not exclude the influence of medications on motor cortex excitability. Conclusion: These findings suggest abnormal cortical excitability in patients with OCD. The associations between cortical silent period and response inhibition and age of onset further indicate that altered cortical excitability may play an important role in the development of OCD.

A study of novel bilateral thermal capsulotomy with focused ultrasound for treatment-refractory obsessive-compulsive disorder: 2-year follow-up.

BACKGROUND: Recently, a new thermal lesioning approach using magnetic resonance-guided focused ultrasound (MRgFUS) was introduced for the treatment of neurologic disorders. However, only 2 studies have used this approach for treatment-refractory obsessive-compulsive disorder (OCD), and follow-up was short-term. We investigated the efficacy and safety of bilateral thermal lesioning of the anterior limb of the internal capsule using MRgFUS in patients with treatment-refractory OCD and followed them for 2 years. METHODS: Eleven patients with treatment-refractory OCD were included in the study. Clinical outcomes were evaluated using the Yale-Brown Obsessive Compulsive Scale, the Clinical Global Impression scale (including improvement and severity), the Hamilton Rating Scale for Depression (HAM-D) and the Hamilton Rating Scale for Anxiety (HAM-A) at 1 week and 1, 3, 6, 12 and 24 months following MRgFUS. Neuropsychological functioning, Global Assessment of Functioning and adverse events were also assessed. RESULTS: After MRgFUS, Yale-Brown Obsessive Compulsive Scale scores decreased significantly across the 24-month follow-up period (mean ± standard deviation, 34.4 ± 2.3 at baseline v. 21.3 ± 6.2 at 24 months, p < 0.001). Scores on the Hamilton rating scales for depression and anxiety also significantly decreased from baseline to 24 months (HAM-D, 19.0 ± 5.3 v. 7.6 ± 5.3, p < 0.001; HAM-A, 22.4 ± 5.9 v. 7.9 ± 3.9, p < 0.001). Global Assessment of Functioning scores improved significantly (35.8 ± 4.9 at baseline v. 56.0 ± 10.3 at 24 months, p < 0.001) and Memory Quotient significantly improved, but other neuropsychological functions were unchanged. The side effects of MRgFUS included headache and vestibular symptoms, but these were mild and transient. LIMITATIONS: The main limitations of this study were the small sample size and the open-label design. CONCLUSION: Bilateral thermal lesioning of the anterior limb of the internal capsule using MRgFUS may improve obsessive-compulsive, depressive and anxiety symptoms in patients with treatment-refractory OCD, without serious adverse effects.

A study of novel bilateral thermal capsulotomy with focused ultrasound for treatment-refractory obsessive-compulsive disorder: 2-year follow-up.

BACKGROUND: Recently, a new thermal lesioning approach using magnetic-resonance-guided focused ultrasound (MRgFUS) was introduced for the treatment of neurologic disorders. However, only 2 studies have used this approach for treatment-refractory obsessive-compulsive disorder (OCD), and follow-up was short-term. We investigated the efficacy and safety of bilateral thermal lesioning of the anterior limb of the internal capsule using MRgFUS in patients with treatment-refractory OCD and followed them for 2 years. METHODS: Eleven patients with treatment-refractory OCD were included in the study. Clinical outcomes were evaluated using the Yale-Brown Obsessive Compulsive Scale, the Clinical Global Impression scale (including improvement and severity), the Hamilton Rating Scale for Depression (HAM-D) and the Hamilton Rating Scale for Anxiety (HAM-A) at 1 week and 1, 3, 6, 12 and 24 months following MRgFUS. Neuropsychological functioning, Global Assessment of Functioning and adverse events were also assessed. RESULTS: After MRgFUS, Yale-Brown Obsessive Compulsive Scale scores decreased significantly across the 24-month follow-up period (mean ± standard deviation, 34.4 ± 2.3 at baseline v. 21.3 ± 6.2 at 24 months, p < 0.001). Scores on the Hamilton rating scales for depression and anxiety also significantly decreased from baseline to 24 months (HAM-D, 19.0 ± 5.3 v. 7.6 ± 5.3, p < 0.001; HAM-A, 22.4 ± 5.9 v. 7.9 ± 3.9, p < 0.001). Global Assessment of Functioning scores improved significantly (35.8 ± 4.9 at baseline v. 56.0 ± 10.3 at 24 months, p < 0.001) and Memory Quotient significantly improved, but other neuropsychological functions were unchanged. The side effects of MRgFUS included headache and vestibular symptoms, but these were mild and transient. LIMITATIONS: The main limitations of this study were the small sample size and the open-label design. CONCLUSION: Bilateral thermal lesioning of the anterior limb of the internal capsule using MRgFUS may improve obsessive-compulsive, depressive and anxiety symptoms in patients with treatment-refractory OCD, without serious adverse effects.

Gamma-knife subcaudate tractotomy for treatment-resistant depression and target characteristics: a case report and review.

Stereotactic subcaudate tractotomy has previously been suggested to be an effective treatment for depression. This is the first study to report the use of gamma-knife subcaudate tractotomy for treatment-resistant depression. A 49-year-old woman with major depressive disorder had been treated for 30 years, with nine suicide attempts during that time. The right and left target maximum diameter was 11 mm within 50 % isodose lines. The target was located more posteriorly and inferiorly than the subgenual cingulate target typically used for deep-brain stimulation. The maximum radiation dose was 130 Gy. During the 4 months after surgery, the patient improved gradually from 23 to 4 according to the Hamilton Rating Scale for Depression and antidepressant medication was discontinued. Target-sized focal lesions were identified and no edema was seen postoperatively. No aggravation or neurologic deficit occurred during the 2.5 years of follow-up. Gamma-knife subcaudate tractotomy for depression is a minimally invasive technique. Investigations of the effectiveness and safety profile in a larger group are warranted.

Subjective memory complaints in an elderly population with poor sleep quality.

OBJECTIVES: The association between sleep disturbances and cognitive decline in the elderly has been putative and controversial. We evaluated the relation between subjective sleep quality and cognitive function in the Korean elderly. METHOD: Among 459 community-dwelling subjects, 352 subjects without depression or neurologic disorders (mean age 68.2 ± 6.1) were analyzed in this study. All the participants completed the Korean version of the consortium to establish a registry for Alzheimer's disease neuropsychological battery (CERAD-KN) as an objective cognitive measure and subjective memory complaints questionnaire (SMCQ). Based on the Pittsburgh sleep quality index, two types of sleepers were defined: 'good sleepers' and 'poor sleepers'. RESULTS: There were 192 good sleepers (92 men) and 160 poor sleepers (51 men). Poor sleepers reported more depressive symptoms and more use of sleep medication, and showed higher SMCQ scores than good sleepers, but there was no difference in any assessments of CERAD-KN. In the regression analysis, depressive symptoms and subjective sleep quality were associated with subjective memory complaints (ß = 0.312, p < 0.001; ß = 0.163, p = 0.005). CONCLUSION: In the elderly without depression, poor sleep quality was associated with subjective memory complaints, but not with objective cognitive measures. As subjective memory complaints might develop into cognitive disorders, poor sleep quality in the elderly needs to be adequately controlled.

Statin pretreatment inhibits the lipopolysaccharide-induced epithelial-mesenchymal transition via the downregulation of toll-like receptor 4 and nuclear factor-κB in human biliary epithelial cells.

BACKGROUND AND AIM: Epithelial-mesenchymal transition (EMT) of biliary epithelial cells (BECs) plays an important role in biliary fibrosis. This study investigated the effects of simvastatin on the lipopolysaccharide (LPS)-induced EMT and related signal pathways in BECs. METHODS: Biliary epithelial cells were exposed to LPS (2 µg/mL) or transforming growth factor ß1 (TGF-ß1) (5 ng/mL) for 5 days. The EMT was assessed by a gain of mesenchymal cell markers (vimentin, N-cadherin, slug, and Twist-1) and a loss of epithelial cell markers (E-cadherin). The effects of simvastatin on the EMT induced by LPS or TGF-ß1 were determined by the changes in the levels of EMT markers and TLR4 and in the c-Jun N-terminal kinase (JNK), p38, and nuclear factor-κB (NF-κB) signaling pathways. RESULTS: Compared with the BECs treated with LPS alone, co-treatment with simvastatin and LPS induced an increase in the expression of E-cadherin and decreases in the expression levels of mesenchymal cell markers. The LPS-induced TLR4 expression level was slightly decreased by co-treatment with simvastatin. LPS-induced BEC growth was markedly inhibited by co-treatment with simvastatin. Furthermore, pretreatment with simvastatin inhibited the LPS-induced EMT in BECs by downregulating NF-κB and JNK phosphorylation. The suppressive effects of simvastatin pretreatment on the induction of the EMT by TGF-ß1 were also demonstrated in H69 cells. CONCLUSIONS: Our results demonstrate that LPS or TGF-ß1 promote the EMT in BECs that that pretreatment with simvastatin inhibited the induced EMT by downregulating toll-like receptor 4 and NF-κB phosphorylation. This finding suggests that simvastatin can be considered a new agent for preventing biliary fibrosis associated with the EMT of BECs.

Comorbid panic disorder as an independent risk factor for suicide attempts in depressed outpatients.

OBJECTIVE: Although comorbid panic disorder is associated with more severe symptoms and poorer therapeutic response in depressive patients, the relationship between panic disorder and risk of suicide attempt has not been confirmed. This study aimed to examine the relationship between comorbid panic disorder and clinical characteristics associated with suicidal risk as well as the likelihood of suicide attempt. METHOD: A total of 223 outpatients with current major depressive disorder participated in the study. Both subjects with panic disorder (33%) and those without panic disorder (67%) were compared based on history of suicide attempts, current psychopathologies, and traits of impulsivity and anger. RESULTS: Subjects with panic disorder had higher levels of impulsivity, depression, and hopelessness and were more likely to report a history of suicide attempts. Subjects with panic disorder were younger at the time of first suicide attempt than those without panic disorder. Logistic regression analyses indicated that comorbid panic disorder was significantly associated with a history of suicide attempts after adjusting for other clinical correlates (odds ratio = 2.8; p < 0.01). CONCLUSIONS: These findings suggest that comorbid panic disorder in patients with major depressive disorder may be associated with a more severe burden of illness and may independently increase the likelihood of suicide attempt.

Preliminary Effectiveness and Sustainability of Group Aerobic Exercise Program in Patients with Schizophrenia.

The objective of this study was to examine the feasibility and sustained effect of a group aerobic exercise program in patients with schizophrenia. Twenty-four schizophrenic patients participated in a group-based individually tailored 90-minute outdoor cycling session per week for 3 months with intervention to enhance motivation. Physical health was evaluated by anthropometric measures, cardiorespiratory (CR) fitness, and blood tests. Mental health was assessed on self-esteem, interpersonal relationship, quality of life, and global function. Attrition rate for the exercise program was 8.3%. Exercise program significantly increased participant's self-esteem, positive relationship, global function, and quality of life. CR fitness significantly improved after 3 months. At the 9-month follow-up, 6 months after program completion, only in interpersonal relationship change the improved effects were maintained. These findings support the feasibility of group aerobic exercise program with high level of adherence and its long-term benefits in positive relationship change.

Myometrial relaxation of mice via expression of two pore domain acid sensitive K(+) (TASK-2) channels.

Myometrial relaxation of mouse via expression of two-pore domain acid sensitive (TASK) channels was studied. In our previous report, we suggested that two-pore domain acid-sensing K(+) channels (TASK-2) might be one of the candidates for the regulation of uterine circular smooth muscles in mice. In this study, we tried to show the mechanisms of relaxation via TASK-2 channels in marine myometrium. Isometric contraction measurements and patch clamp technique were used to verify TASK conductance in murine myometrium. Western blot and immunehistochemical study under confocal microscopy were used to investigate molecular identity of TASK channel. In this study, we showed that TEA and 4-AP insensitive non-inactivating outward K(+) current (NIOK) may be responsible for the quiescence of murine pregnant longitudinal myometrium. The characteristics of NIOK coincided with two-pore domain acid-sensing K(+) channels (TASK-2). NIOK in the presence of K(+) channel blockers was inhibited further by TASK inhibitors such as quinidine, bupivacaine, lidocaine, and extracellular acidosis. Furthermore, oxytocin and estrogen inhibited NIOK in pregnant myometrium. When compared to non-pregnant myometrium, pregnant myometrium showed stronger inhibition of NIOK by quinidine and increased immunohistochemical expression of TASK-2. Finally, TASK-2 inhibitors induced strong myometrial contraction even in the presence of L-methionine, a known inhibitor of stretch-activated channels in the longitudinal myometrium of mouse. Activation of TASK-2 channels seems to play an essential role for relaxing uterus during pregnancy and it might be one of the alternatives for preventing preterm delivery.

Association between the oxytocin receptor gene polymorphism (rs53576) and bulimia nervosa.

OBJECTIVE: Oxytocin circuits are implicated in the regulation of appetite and weight. Variants in the oxytocin receptor (OXTR) gene have been associated with bulimic behaviour. This study aimed to investigate the association between the OXTR gene and eating disorders. METHOD: We genotyped six single nucleotide polymorphisms, rs53576, rs237879, rs2228485, rs13316193, rs2254298 and rs1042778, located within the OXTR gene in Korean patients with eating disorders using the single-base extension method. We studied a total of 262 women, including 69 patients with anorexia nervosa, 90 patients with bulimia nervosa (BN), and 103 healthy women. RESULTS: We found a positive association between the G allele of OXTR rs53576 and BN. In the BN group, the G carriers showed a high score on the behavioural inhibition system. CONCLUSIONS: These findings suggest the involvement of the oxytocinergic system in the mechanism that underlies BN.

Antipsychotic polypharmacy and high-dose prescription in schizophrenia: a 5-year comparison.

OBJECTIVE: The co-prescription of multiple antipsychotic drugs continues to increase despite a lack of evidence supporting this practice. The purpose of this study was to quantify and describe recent trends of antipsychotic polypharmacy in Korean schizophrenic inpatients by comparing prescribed medications between the years of 2005 and 2010. METHODS: We reviewed comprehensive medication profiles of schizophrenic patients discharged from a university psychiatric hospital in 2005 (n=194) or 2010 (n=201). Antipsychotic polypharmacy was defined as the concurrent receipt of two or more chemically distinct antipsychotics for at least 14 days. High antipsychotic dose was defined as a prescribed daily dose to defined daily dose ratio of greater than 1.5. RESULTS: Antipsychotic polypharmacy increased between 2005 (37.1%) and 2010 (48.3%, p=0.025). The most frequently used drug within combinations of antipsychotics was haloperidol in 2005 (51.4%) and quetiapine in 2010 (48.5%). Overall, no changes were observed between 2005 and 2010 in the rate of prescribing high-dose antipsychotics. High-dose antipsychotic monotherapy decreased across years (from 30.4 to 18.4%), but high-dose antipsychotic polypharmacy increased (from 34.0 to 45.3%). Regression analysis revealed that antipsychotic polypharmacy was strongly associated with high doses of prescribed antipsychotics (odds ratio=18.60, p<0.001). CONCLUSIONS: The practice of prescribing multiple antipsychotics to patients with schizophrenia is increasing, and high-dose antipsychotic drugs are more likely to be prescribed in combination than in isolation. The reasons for this pattern of prescription and its impact warrants further study.

Ginsenoside Rg3 inhibits lipopolysaccharide-induced adhesion molecule expression in human umbilical vein endothelial cell and C57BL/6 mice.

Intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), P- and E-selectin play a key role for initiation of vascular inflammation. Ginsenoside, a class of steroid glycosides, is abundant in Panax ginseng root, which has been used for health promotion in Korea. In this study, we investigated the mechanism by which ginsenoside Rg3 may inhibit ICAM-1 and VCAM-1 expressions stimulated with lipopolysaccharide (LPS) in human umbilical vein endothelial cell (HUVEC) and C57BL/6 mice. LPS increased ICAM-1 and VCAM-1 expression. Ginsenoside Rg3 prevented LPS-mediated increase of ICAM-1 and VCAM-1 expression. LPS induced IkappaBα (IκBα) degradation within 1 hr. Ginsenoside Rg3 prevented the IκBα degradation stimulated with LPS. Moreover, ginsenoside Rg3 reduced LPS-mediated THP-1 monocyte adhesion to HUVEC, in a concentration-dependent manner. In C57BL/6 mice, injection of LPS increased aortic ICAM-1 and VCAM-1 expression, which was prevented by ginsenoside Rg3. These data provide a novel mechanism where the ginsenoside Rg3 may provide direct vascular benefits with inhibition of leukocyte adhesion into vascular wall thereby providing prevention against vascular inflammatory disease.

H2 Receptor-Mediated Relaxation of Circular Smooth Muscle in Human Gastric Corpus: the Role of Nitric Oxide (NO).

This study was designed to examine the effects of histamine on gastric motility and its specific receptor in the circular smooth muscle of the human gastric corpus. Histamine mainly produced tonic relaxation in a concentration-dependent and reversible manner, although histamine enhanced contractility in a minor portion of tissues tested. Histamine-induced tonic relaxation was nerve-insensitive because pretreatment with nerve blockers cocktail (NBC) did not inhibit relaxation. Additionally, K(+) channel blockers, such as tetraethylammonium (TEA), apamin (APA), and glibenclamide (Glib), had no effect. However, N(G)-nitro-L-arginine methyl ester (L-NAME) and 1H-(1,2,4)oxadiazolo (4,3-A) quinoxalin-1-one (ODQ), an inhibitor of soluble guanylate cyclase (sGC), did inhibit histamine-induced tonic relaxation. In particular, histamine-induced tonic relaxation was converted to tonic contraction by pretreatment with L-NAME. Ranitidine, the H2 receptor blocker, inhibited histamine-induced tonic relaxation. These findings suggest that histamine produced relaxation in circular smooth muscle of human gastric smooth muscle through H2 receptor and NO/sGC pathways.

Hyperarousal-state of Insomnia Disorder in Wake-resting State Quantitative Electroencephalography.

Objective: : Insomnia is associated with elevated high-frequency electroencephalogram power in the waking state. Although affective symptoms (e.g., depression and anxiety) are commonly comorbid with insomnia, few reports distinguished objective sleep disturbance from affective symptoms. In this study, we investigated whether daytime electroencephalographic activity explains insomnia, even after controlling for the effects of affective symptoms. Methods: : A total of 107 participants were divided into the insomnia disorder (n = 58) and healthy control (n = 49) groups using the Mini-International Neuropsychiatric Interview and diagnostic criteria for insomnia disorder. The participants underwent daytime resting-state electroencephalography sessions (64 channels, eye-closed). Results: : The insomnia group showed higher levels of anxiety, depression, and insomnia than the healthy group, as well as increased beta [t(105) = -2.56, p = 0.012] and gamma [t(105) = -2.44, p = 0.016] spectra. Among all participants, insomnia symptoms positively correlated with the intensity of beta (r = 0.28, p ＜ 0.01) and gamma (r = 0.25, p ＜ 0.05) spectra. Through hierarchical multiple regression, the beta power showed the additional ability to predict insomnia symptoms beyond the effect of anxiety (ΔR2 = 0.041, p = 0.018). Conclusion: : Our results showed a significant relationship between beta electroencephalographic activity and insomnia symptoms, after adjusting for other clinical correlates, and serve as further evidence for the hyperarousal theory of insomnia. Moreover, resting-state quantitative electroencephalography may be a supplementary tool to assess insomnia.

Development and validation of a computer-based measure of symmetry and arranging behavior in obsessive-compulsive disorder: a preliminary study.

OBJECTIVE: While compulsive ordering and arranging, and a preoccupation with symmetry are common presentations of obsessive-compulsive disorder (OCD), little attention has been given to these types of symptoms in the assessment of patients with OCD. The goal of the present study was to develop and evaluate psychometric properties for the objective and quantitative measurement of compulsive symptoms related to symmetry and arranging. METHODS: Thirty-five normal volunteers performed computer-simulated environment tasks under four different conditions with or without a target and distraction. Primary dependent variables included several indices of time and manipulation of arranging behaviors. We evaluated the validity of the task by comparing the novel behavioral measures with standardized measures such as the Symmetry, Ordering and Arranging Questionnaire (SOAQ), Obsessive Compulsive Inventory-Revised (OCI-R), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Barratt Impulsiveness Scale (BIS-11), and Quality of Life Scale (WHOQOL). RESULTS: We found a significant positive correlation between the arrangement time (time to complete the task) with the SOAQ score and the "ordering" subscore of the OCI-R. In addition, the number of manipulations was positively correlated with the SOAQ score and the "ordering" subscore of the OCI-R. There were no significant correlations between behavioral parameters and other scales measuring constructs less relevant to the symptoms of OCD related to ordering/symmetry. There was only a significant main effect of the target on the arrangement time. CONCLUSION: This study demonstrates the good convergent and discriminant validity of this task as a novel behavioral measure for the assessment of arranging compulsion symptoms. We can infer from the results that subjects are likely to spend more time in compulsive arranging when the target for the task is given.

Ginsenoside rg2 inhibits lipopolysaccharide-induced adhesion molecule expression in human umbilical vein endothelial cell.

Vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), P- and E-selectin play a pivotal role for initiation of atherosclerosis. Ginsenoside, a class of steroid glycosides, is abundant in Panax ginseng root, which has been used for prevention of illness in Korea. In this study, we investigated the mechanism(s) by which ginsenoside Rg2 may inhibit VCAM-1 and ICAM-1 expressions stimulated with lipopolysaccharide (LPS) in human umbilical vein endothelial cell (HUVEC). LPS increased VCAM-1 and ICAM-1 expression. Ginsenoside Rg2 prevented LPS-mediated increase of VCAM-1 and ICAM-1 expression. On the other hand, JSH, a nuclear factor kappa B (NF-κB) inhibitor, reduced both VCAM-1 and ICAM-1 expression stimulated with LPS. SB202190, inhibitor of p38 mitogen-activated protein kinase (p38 MAPK), and wortmannin, phosphatidylinositol 3-kinase (PI3-kinase) inhibitor, reduced LPS-mediated VCAM-1 but not ICAM-1 expression. PD98059, inhibitor of mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (MEK/ERK) did not affect VCAM-1 and ICAM-1 expression stimulated with LPS. SP600125, inhibitor of c-Jun N-terminal kinase (JNK), reduced LPS-mediated ICAM-1 but not VCAM-1 expression. LPS reduced IkappaBα (IκBα) expression, in a time-dependent manner within 1 hr. Ginsenoside Rg2 prevented the decrease of IκBα expression stimulated with LPS. Moreover, ginsenoside Rg2 reduced LPS-mediated THP-1 monocyte adhesion to HUVEC, in a concentration-dependent manner. These data provide a novel mechanism where the ginsenoside Rg2 may provide direct vascular benefits with inhibition of leukocyte adhesion into vascular wall thereby providing protection against vascular inflammatory disease.

Mechanism of Relaxation Via TASK-2 Channels in Uterine Circular Muscle of Mouse.

Plasma pH can be altered during pregnancy and at labor. Membrane excitability of smooth muscle including uterine muscle is suppressed by the activation of K(+) channels. Because contractility of uterine muscle is regulated by extracellular pH and humoral factors, K(+) conductance could be connected to factors regulating uterine contractility during pregnancy. Here, we showed that TASK-2 inhibitors such as quinidine, lidocaine, and extracellular acidosis produced contraction in uterine circular muscle of mouse. Furthermore, contractility was significantly increased in pregnant uterine circular muscle than that of non-pregnant muscle. These patterns were not changed even in the presence of tetraetylammonium (TEA) and 4-aminopyridine (4-AP). Finally, TASK-2 inhibitors induced strong myometrial contraction even in the presence of L-methionine, a known inhibitor of stretchactivated channels in myometrium. When compared to non-pregnant myometrium, pregnant myometrium showed increased immunohistochemical expression of TASK-2. Therefore, TASK-2, seems to play a key role during regulation of myometrial contractility in the pregnancy and provides new insight into preventing preterm delivery.