BACKGROUND: The serotonin type 3 receptors are diffusely distributed in both the central and the peripheral nervous system. Physiological and pathophysiological processes thought to be mediated by this receptor include nausea and vomiting, peripheral nociception and central antinociception, conditioned aversion response to drugs, anxiety, and cognition. Because of the structural similarity between the nicotinic acetylcholine receptor and the 5HT3 receptor, we investigated the effects of clinically used neuromuscular blockers on the 5HT3 receptor function related with PONV. METHODS: A cDNA clone encoding the full length murine 5HT3a receptor was subcloned into an oocyte expression vector and 50 ng of cRNA transcribed in vitro injected per oocyte. After 24 72 h incubation, oocytes were placed into a recording chamber continuously perfused with frog Ringer's solution and electrophysiological recordings were obtained by the two electrode voltage clamp technique. Serotonin with or without the various drugs were bath applied by a computer controlled solenoid valve. Peak currents induced by the drug applications were measured and dose responses were obtained. RESULTS: The 5HT3 receptor expression in Xenopus oocyte was identified by the pharmacologic tools. Serotonin induced rapid inward currents, and thus was showed dose-dependent: KD = 2.5 micrometer, Hill coefficiency = 2.09. Inhibition by the neuromuscular blockers showed dose-dependence and their inhibitory potency on 5HT3 receptor (IC50) was in order of d-tubocurarine (0.046 micrometer) > vecuronium (16.32 micrometer) > gallamine (1,169 micrometer). CONCLUSIONS: There was a different inhibitory effect of nicotinic cholinergic antagonists, clinically used neuromuscular blockers, on the 5HT3 receptor and a judicious selection of them might contribute to reducing the incidence of PONV clinically.
Anxiety ; Baths ; Cholinergic Antagonists ; Clone Cells ; Cognition ; DNA, Complementary ; Electrodes ; Gallamine Triethiodide ; Incidence ; Nausea ; Neuromuscular Blockade* ; Neuromuscular Blocking Agents* ; Nociception ; Oocytes* ; Peripheral Nervous System ; Postoperative Nausea and Vomiting ; Receptors, Nicotinic ; RNA, Complementary ; Serotonin* ; Tubocurarine ; Vecuronium Bromide ; Vomiting ; Xenopus*

BACKGROUND: The serotonin type 3 receptors are diffusely distributed in both the central and the peripheral nervous system. Physiological and pathophysiological processes thought to be mediated by this receptor include nausea and vomiting, peripheral nociception and central antinociception, conditioned aversion response to drugs, anxiety, and cognition. Because of the structural similarity between the nicotinic acetylcholine receptor and the 5HT3 receptor, we investigated the effects of clinically used neuromuscular blockers on the 5HT3 receptor function related with PONV. METHODS: A cDNA clone encoding the full length murine 5HT3a receptor was subcloned into an oocyte expression vector and 50 ng of cRNA transcribed in vitro injected per oocyte. After 24 72 h incubation, oocytes were placed into a recording chamber continuously perfused with frog Ringer's solution and electrophysiological recordings were obtained by the two electrode voltage clamp technique. Serotonin with or without the various drugs were bath applied by a computer controlled solenoid valve. Peak currents induced by the drug applications were measured and dose responses were obtained. RESULTS: The 5HT3 receptor expression in Xenopus oocyte was identified by the pharmacologic tools. Serotonin induced rapid inward currents, and thus was showed dose-dependent: KD = 2.5 micrometer, Hill coefficiency = 2.09. Inhibition by the neuromuscular blockers showed dose-dependence and their inhibitory potency on 5HT3 receptor (IC50) was in order of d-tubocurarine (0.046 micrometer) > vecuronium (16.32 micrometer) > gallamine (1,169 micrometer). CONCLUSIONS: There was a different inhibitory effect of nicotinic cholinergic antagonists, clinically used neuromuscular blockers, on the 5HT3 receptor and a judicious selection of them might contribute to reducing the incidence of PONV clinically.
Anxiety ; Baths ; Cholinergic Antagonists ; Clone Cells ; Cognition ; DNA, Complementary ; Electrodes ; Gallamine Triethiodide ; Incidence ; Nausea ; Neuromuscular Blockade* ; Neuromuscular Blocking Agents* ; Nociception ; Oocytes* ; Peripheral Nervous System ; Postoperative Nausea and Vomiting ; Receptors, Nicotinic ; RNA, Complementary ; Serotonin* ; Tubocurarine ; Vecuronium Bromide ; Vomiting ; Xenopus*

OBJECTIVE: To identify the correlation between change in spinal deformities after surgical release and age at the time of surgery, and the effectiveness of surgical release in patients with neglected congenital muscular torticollis (CMT). METHODS: This was a retrospective study of 46 subjects with neglected CMT who had undergone surgical release at age ≥5 years at a tertiary medical center between January 2009 and January 2014. Spinal deformities were measured on anteroposterior plain radiographs of the cervical and whole spine, both preoperatively and postoperatively, to assess 3 parameters: cervicomandibular angle (CMA), lateral shift (LS), and Cobb angle (CA). We analyzed the change in spinal deformities after surgical release in consideration of age at the time of surgery. RESULTS: The median age at the time of surgery was 12.87 years. All 3 parameters showed significant improvement after surgical release (median values, pre- to post-surgery: CMA, 12.13° to 4.02°; LS, 18.13 mm to 13.55 mm; CA, 6.10° to 4.80°; all p<0.05). There was no significant correlation between age at the time of surgery and change in CMA (R=0.145, p=0.341) and LS (R=0.103, p=0.608). However, CA showed significant improvement with increasing age (R=0.150, p=0.046). CONCLUSION: We assessed the correlation between change in spinal deformities after surgical release and age at the time of surgery. We found that that surgical release is effective for spinal deformities, even in older patients. These findings enhance our understanding of the effectiveness and timing of surgical release in patients with neglected CMT.
Congenital Abnormalities ; Humans ; Retrospective Studies ; Spine ; Torticollis* ; Treatment Outcome

OBJECTIVE: To evaluate the craniofacial asymmetry in adults with neglected congenital muscular torticollis (CMT) by quantitative assessment based on craniofacial three-dimensional computed tomography (3D-CT). METHODS: Preoperative craniofacial asymmetry was measured by 3D-CT for 31 CMT subjects > or =18 years of age who visited a tertiary medical center and underwent 3D-CT between January 2009 and December 2013. The relationship between the age and the severity of craniofacial asymmetry was analyzed in reference to anteroposterior length asymmetry of the frontal bone and zygomatic arch, vertical and lateral displacements of the facial landmarks, and mandibular axis rotation. RESULTS: The age at CT was 27.71+/-7.02 years (range, 18-44 years). All intra-class correlation coefficients were higher than 0.7, suggesting good inter-rater reliability (p<0.05) of all the measurements. The frontal and the zygomatic length ratio (i.e., the anteroposterior length asymmetry on the axial plane) was 1.06+/-0.03 and 1.07+/-0.03, respectively, which was increased significantly with age in the linear regression analysis (r2=0.176, p=0.019 and r2=0.188, p=0.015, respectively). The vertical or lateral displacement of the facial landmarks and rotation of the mandibular axis did not significantly correlate with age (p>0.05). CONCLUSION: Craniofacial asymmetry of neglected CMT became more severe with age in terms of anteroposterior length asymmetry of the ipsilateral frontal bone and zygomatic arch on the axial plane even after growth cessation. This finding may enhance the understanding of therapeutic strategies for craniofacial asymmetry in adults with neglected CMT.
Adult* ; Axis, Cervical Vertebra ; Craniofacial Abnormalities ; Facial Asymmetry ; Frontal Bone ; Humans ; Linear Models ; Torticollis* ; Zygoma

Nitric oxide (NO) elevates intracellular calcium. But the actions of calcium in NO-induced cell death are not well understood. This study was carried out to investigate the signal transduction pathways of calcium and NO-induced cytotoxicity in H9c2 cardiac myoblasts by using NO donor compounds such as sodium nitroprusside (SNP) and S-nitroso-N-acetylpenicillamine (SNAP). Pretreatment of intracellular calcium chelating agent (BAPTA/AM) or L-type calcium channel blockers (nicardipine, nifedipine, diltiazem and veraparmil) or T-type calcium channel blocker (flunarizine) blocked SNP-induced cytotoxicity respectively only in a three hours. However, thapsigargin (TG), which inhibits endoplasmic reticulum dependent Ca(2+)-ATPase and thereby increases cytosolic Ca(2+), augmented SNP-induced cytotoxicity. The protective effect of BAPTA/AM was inhibited by treatment of protein synthesis inhibitor, cyclohexamide. In addition, pyrrolidine dithiocarbamate (PDTC), NF-kB inhibitor, attenuates the protective effect of BAPTA/AM against SNP-induced cytotoxicity. It is indicated that the protective effect of BAPTA/AM against NO-induced cytotoxicity might be due to the expression of protein related to activation of NFkB. From these results, it is concluded that SNP-induced cytotoxicity is mediated by calcium in a 3 hours via down regulation of protein expression rleated to activation of NFkB.
Calcium Channels, L-Type ; Calcium Channels, T-Type ; Calcium* ; Cell Death ; Cytosol ; Diltiazem ; Down-Regulation ; Endoplasmic Reticulum ; Humans ; Myoblasts, Cardiac* ; NF-kappa B ; Nifedipine ; Nitric Oxide ; Nitroprusside ; S-Nitroso-N-Acetylpenicillamine ; Signal Transduction* ; Thapsigargin ; Tissue Donors

Paclitaxel (taxol) is known as effective drug inhibition of cell cycle encouraging activity in human ovarian and metastatic breast cancers and malignant melanoma. It is an antimicrotubule agent that is believed to mediate its antineoplastic effects by inducing mitotic arrest followed by apoptosis. The relation between phorbol 12 myristate 13 acetate (PMA), protein kinase C (PKC) activator, and taxol-induced apoptosis is not well understood until now. This study was performed to investigate the effects of PMA on the signal transduction pathways of taxol-induced apoptosis in MCF-7 human breast carcinoma cells. Taxol-induced apoptosis is attenuated by curcumine, JNK inhibitor, and pyrrolidine dithiocarbamate (PDTC), inhibitor of NFkB. Pretreatment with PKC activator (PMA) or protein kinase A (PKA) activators (forskolin and dibutyryl cAMP) inhibited taxol-induced apoptosis in MCF-7 cells. In addition, thapsigargin, a specific inhibitor of endoplasmic reticulum(ER) Ca(2+)-ATPase and CaCl2, also blocked the activation of caspases by taxol. From these results suggest that taxol-induced apoptosis may be mediated via JNK or NFkB pathway and PKC activation.
Apoptosis ; Breast ; Breast Neoplasms ; Caspases ; Cell Cycle ; Curcumin ; Cyclic AMP-Dependent Protein Kinases ; Humans ; MCF-7 Cells* ; Melanoma ; Myristic Acid ; Paclitaxel ; Protein Kinase C ; Signal Transduction ; Thapsigargin

During inflammation of the colon, cells of the gut mucosa produce or express numerous inflammatory mediators, such as tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1 beta), and intercellular adhesion molecule 1 (ICAM-1). These mediators have been implicated as contributory factors to the inflammatory process, which results in colitis during inflammatory bowel disease (IBD). Rebamipide is an anti-gastric ulcer drug with anti-inflammatory properties in vivo and in vitro. The effects of Rebamipide on IBD have not been largely evaluated. Therefore, this study investigated the potential of Rebamipide to regulate the production of inflammatory mediators such as TNF-alpha, IL-1beta, and ICAM-1. Mice with trinitrobenzene sulfonic acid (TNBS)-induced colitis (IBD animal model), were treated intrarectally with 2 mM Rebamipide. Body weight, macro- and micro-histological scores, and activity were evaluated. As an index of tissue edema, the thickness of the colonic wall was measured between the serosal surface and the luminal surface of the mucosa. TNF-alpha, IL-1 beta, and ICAM-1 were detected by immunohistochemical staining. Rebamipide treatment of mice exhibiting TNBS-induced colitis dramatically improved the clinical and histopathological findings of inflammation. In addition, Rebamipide suppressed TNF-alpha, IL-1 beta, and ICAM-1 expression in TNBS-treated animals. Taken together, these findings suggest that Rebamipide is a potential therapeutic agent for treating patients with IBD.
Animals ; Body Weight ; Colitis ; Colon* ; Down-Regulation* ; Edema ; Humans ; Inflammation ; Inflammatory Bowel Diseases ; Intercellular Adhesion Molecule-1* ; Interleukin-1beta ; Mice ; Mucous Membrane ; Phenobarbital ; Tumor Necrosis Factor-alpha* ; Ulcer

BACKGROUND: Using data from a large national stroke registry, we aimed to investigate the incidence and determinants of in-hospital and post-discharge recovery after acute ischemic stroke and the independence of their occurrence. METHODS: In-hospital recovery was defined as an improvement of 4 points or > 40% in the National Institutes of Health Stroke Scale (NIHSS) score from admission to discharge. Post-discharge recovery was defined as any improvement in the modified Rankin Scale (mRS) score from discharge to 3 months after stroke onset. Two analytic methods (multivariate and multivariable logistic regression) were applied to compare the effects of 18 known determinants of 3-month outcome and to verify whether in-hospital and post-discharge recovery occur independently. RESULTS: During 54 months, 11,088 patients with acute ischemic stroke meeting the eligibility criteria were identified. In-hospital and post-discharge recovery occurred in 36% and 33% of patients, respectively. Multivariate logistic regression with an equality test for odds ratios showed that 7 determinants (age, onset-to-admission time, NIHSS score at admission, blood glucose at admission, systolic blood pressure, smoking, recanalization therapy) had a differential effect on in-hospital and post-discharge recovery in the way of the opposite direction or of the same direction with different degree (all P values < 0.05). Both in-hospital and post-discharge recovery occurred in 12% of the study population and neither of them in 43%. The incidence of post-discharge recovery in those with in-hospital recovery was similar to that in those without (33.8% vs. 32.7%, respectively), but multivariable analysis showed that these 2 types of recovery occurred independently. CONCLUSION: Our findings suggest that, in patients with acute ischemic stroke, in-hospital and post-discharge recovery may occur independently and largely in response to different factors.
Blood Glucose ; Blood Pressure ; Humans ; Incidence ; Logistic Models ; National Institutes of Health (U.S.) ; Odds Ratio ; Prognosis ; Registries ; Smoke ; Smoking ; Stroke

Background: and Purpose To evaluate the outcome events and bleeding complications of the European Society of Cardiology (ESC) guideline-matched oral anticoagulant therapy for patients with acute ischemic stroke and atrial fibrillation (AF). Methods: Patients with acute ischemic stroke and AF from a nationwide multicenter registry (Korean ATrial fibrillaTion EvaluatioN regisTry in Ischemic strOke patieNts [K-ATTENTION]) between January 2013 and December 2015 were included in the study. Patients were divided into the ESC guideline-matched and the non-matched groups. The primary outcome was recurrence of any stroke during the 90-day follow-up period. Secondary outcomes were major adverse cerebrovascular and cardiovascular events, ischemic stroke, intracranial hemorrhage, acute coronary syndrome, allcause mortality, and major hemorrhage. Propensity score matching and logistic regression analyses were performed to assess the effect of the treatments administered. Results: Among 2,321 eligible patients, 1,126 patients were 1:1 matched to the ESC guidelinematched and the non-matched groups. As compared with the non-matched group, the ESC guideline-matched group had a lower risk of any recurrent stroke (1.4% vs. 3.4%; odds ratio [OR], 0.41; 95% confidence interval [CI], 0.18 to 0.95). The risk of recurrent ischemic stroke was lower in the ESC guideline-matched group than in the non-matched group (0.9% vs. 2.7%; OR, 0.32; 95% CI, 0.11 to 0.88). There was no significant difference in the other secondary outcomes between the two groups. Conclusions ESC guideline-matched oral anticoagulant therapy was associated with reduced risks of any stroke and ischemic stroke as compared with the non-matched therapy.

BACKGROUND AND PURPOSE: The clinical implications of echocardiography findings for long-term outcomes in atrial fibrillation (AF)-related stroke patients are unknown. METHODS: This was a substudy of the Korean ATrial fibrillaTion EvaluatioN regisTry in Ischemic strOke patieNts (K-ATTENTION), which is a multicenter-based cohort comprising prospective stroke registries from 11 tertiary centers. Stroke survivors who underwent two-dimensional transthoracic echocardiography during hospitalization were enrolled. Echocardiography markers included the left-ventricle (LV) ejection fraction (LVEF), the left atrium diameter, and the ratio of the peak transmitral filling velocity to the mean mitral annular velocity during early diastole (E/e′ ratio). LVEF was categorized into normal (≥55%), mildly decreased (>40% and <55%), and severely decreased (≤40%). The E/e′ ratio associated with the LV filling pressure was categorized into normal (<8), borderline (≥8 and <15), and elevated (≥15). Kaplan-Meier and Cox regression analyses were performed for recurrent stroke, major adverse cardiac events, and all-cause death. RESULTS: This study finally included 1,947 patients. Over a median follow-up of 1.65 years (interquartile range, 0.42–2.87 years), the rates of recurrent stroke, major adverse cardiac events, and all-cause death were 35.1, 10.8, and 69.6 cases per 1,000 person-years, respectively. Multivariable analyses demonstrated that severely decreased LVEF was associated with a higher risks of major adverse cardiac events [hazard ratio (HR), 3.91; 95% confidence interval (CI), 1.58–9.69] and all-cause death (HR, 1.95; 95% CI, 1.23–3.10). The multivariable fractional polynomial plot indicated that recurrent stroke might be associated with a lower LVEF. CONCLUSIONS: Severe LV systolic dysfunction could be a determinant of long-term outcomes in AF-related stroke.
Atrial Fibrillation ; Cohort Studies ; Diastole ; Echocardiography ; Follow-Up Studies ; Heart Atria ; Hospitalization ; Humans ; Prospective Studies ; Registries ; Stroke ; Survivors