Recent studies indicate that reactive oxygen species (ROS) are critically involved in persistent pain primarily through spinal mechanisms, and that mitochondria are the main source of ROS in the spinal dorsal horn. To investigate whether mitochondrial ROS can induce changes in membrane excitability on spinal substantia gelatonosa (SG) neurons, we examined the effects of mitochondrial electron transport complex (ETC) substrates and inhibitors on the membrane potential of SG neurons in spinal slices. Application of ETC inhibitors, rotenone or antimycin A, resulted in a slowly developing and slight membrane depolarization in SG neurons. Also, application of both malate, a complex I substrate, and succinate, a complex II substrate, caused reversible membrane depolarization and enhanced firing activity. Changes in membrane potential after malate exposure were more prominent than succinate exposure. When slices were pretreated with ROS scavengers such as phenyl-N-tert-buthylnitrone (PBN), catalase and 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL), malate-induced depolarization was significantly decreased. Intracellular calcium above 100 microM increased malateinduced depolarization, witch was suppressed by cyclosporin A, a mitochondrial permeability transition (MPT) inhibitor. These results suggest that enhanced production of spinal mitochondrial ROS can induce nociception through central sensitization.
Animals ; Antimycin A ; Calcium ; Catalase ; Central Nervous System Sensitization ; Cyclosporine ; Electron Transport ; Fires ; Horns ; Malates ; Membrane Potentials ; Membranes ; Mitochondria ; Neurons ; Nociception ; Permeability ; Rats ; Reactive Oxygen Species ; Rotenone ; Substantia Gelatinosa ; Succinic Acid

Reactive oxygen species (ROS) and nitrogen species (RNS) are implicated in cellular signaling processes and as a cause of oxidative stress. Recent studies indicate that ROS and RNS are important signaling molecules involved in nociceptive transmission. Xanthine oxidase (XO) system is a well-known system for superoxide anions (O2(.-)) generation, and sodium nitroprusside (SNP) is a representative nitric oxide (NO) donor. Patch clamp recording in spinal slices was used to investigate the role of O2(.-) and NO on substantia gelatinosa (SG) neuronal excitability. Application of xanthine and xanthine oxidase (X/XO) compound induced membrane depolarization. Low concentration SNP (10 microM) induced depolarization of the membrane, whereas high concentration SNP (1 mM) evoked membrane hyperpolarization. These responses were significantly decreased by pretreatment with phenyl N-tert-butylnitrone (PBN; nonspecific ROS and RNS scavenger). Addition of thapsigargin to an external calcium free solution for blocking synaptic transmission, led to significantly decreased X/XO-induced responses. Additionally, X/XO and SNP-induced responses were unchanged in the presence of intracellular applied PBN, indicative of the involvement of presynaptic action. Inclusion of GDP-beta-S or suramin (G protein inhibitors) in the patch pipette decreased SNP-induced responses, whereas it failed to decrease X/XO-induced responses. Pretreatment with n-ethylmaleimide (NEM; thiol-alkylating agent) decreased the effects of SNP, suggesting that these responses were mediated by direct oxidation of channel protein, whereas X/XO-induced responses were unchanged. These data suggested that ROS and RNS play distinct roles in the regulation of the membrane excitability of SG neurons related to the pain transmission.
Animals ; Calcium ; Ethylmaleimide ; Humans ; Membranes ; Neurons* ; Nitric Oxide ; Nitrogen* ; Nitroprusside ; Oxidative Stress ; Rats* ; Reactive Oxygen Species* ; Substantia Gelatinosa* ; Superoxides ; Suramin ; Synaptic Transmission ; Thapsigargin ; Tissue Donors ; Xanthine ; Xanthine Oxidase

OBJECTIVE: A general orientation along the cervical spine could be estimated by external landmarks, and it was useful, quick and less exposable to radiation, but, sometimes it gave reference confusion of target cervical level. The authors reviewed the corresponding between the neck external landmarks and cervical levels. METHODS: Totally 1,031 cervical lateral radiographs of different patients were reviewed in single university hospital. Its compositions were 534 of males and 497 females; 86 of second decades (10-19 years-old), 169 of third decades, 159 of fourth decades, 209 of fifth decades, 275 of sixth decades, and 133 of more than seventh decades (>60 years-old). Reference external landmarks (mandible, hyoid bone, thyroid cartilage, and cricothyroid membrane) with compounding factors were reviewed. RESULTS: The reference levels of cervical landmarks were C2.13 with mandible angle, C3.54 with hyoid bone, C5.12 with thyroid cartilage, and C6.01 with cricothyroid membrane. The reference levels of cervical landmarks were differently observed by sex, age, and somatometric measurement (height) accordingly mandible angle from C1 to C3, hyoid bone from disc level of C2 and C3 to C5, thyroid cartilage from disc level of C3 and C4 to C7, and cricothyroid membrane from C4 to disc level of C7 and T1. CONCLUSION: Surface landmarks only provide general reference points, but not correspond to exact levels of the cervical spine. Intraoperative fluoroscopy ensures a more precise placement to the targeted cervical level.
Female ; Fluoroscopy ; Humans ; Hyoid Bone ; Male ; Mandible ; Membranes ; Neck ; Spine* ; Thyroid Cartilage

Recent studies indicate that reactive oxygen species (ROS) can act as modulators of neuronal activity, and are critically involved in persistent pain primarily through spinal mechanisms. In this study, we investigated the effects of NaOCl, a ROS donor, on neuronal excitability and the intracellular calcium concentration ([Ca2+]i) in spinal substantia gelatinosa (SG) neurons. In current clamp conditions, the application of NaOCl caused a membrane depolarization, which was inhibited by pretreatment with phenyl-N-tert-buthylnitrone (PBN), a ROS scavenger. The NaOCl-induced depolarization was not blocked however by pretreatment with dithiothreitol, a sulfhydryl-reducing agent. Confocal scanning laser microscopy was used to confirm whether NaOCl increases the intracellular ROS level. ROS-induced fluorescence intensity was found to be increased during perfusion of NaOCl after the loading of 2',7'-dichlorofluorescin diacetate (H2DCF-DA). NaOCl-induced depolarization was not blocked by pretreatment with external Ca2+ free solution or by the addition of nifedifine. However, when slices were pretreated with the Ca2+ ATPase inhibitor thapsigargin, NaOCl failed to induce membrane depolarization. In a calcium imaging technique using the Ca2+-sensitive fluorescence dye fura-2, the [Ca2+]i was found to be increased by NaOCl. These results indicate that NaOCl activates the excitability of SG neurons via the modulation of the intracellular calcium concentration, and suggest that ROS induces nociception through a central sensitization.
Animals ; Calcium ; Calcium-Transporting ATPases ; Central Nervous System Sensitization ; Dithiothreitol ; Fluoresceins ; Fluorescence ; Fura-2 ; Humans ; Membranes ; Microscopy, Confocal ; Neurons ; Nociception ; Perfusion ; Rats ; Reactive Oxygen Species ; Substantia Gelatinosa ; Thapsigargin ; Tissue Donors

Although patients with cirrhosis are known to be in a state of “rebalance” in that pro- and anticoagulant factors increase the risk for both bleeding and thrombosis, the prevalence of portal vein thrombosis (PVT) in patients with cirrhosis can be up to 26%. Therefore, physicians should consider anticoagulation for the prevention and management of PVT in patients with cirrhosis who are at high risk of PVT. Vitamin K antagonist or low molecular weight heparin is suggested as the standard treatment for PVT in cirrhosis. With the advent of new direct-acting oral anticoagulants (DOACs), there is a paradigm shift of switching to DOACs for the treatment of PVT in patients with cirrhosis. However, the safety and efficacy of DOACs in the treatment of PVT was not well-known in patients with cirrhosis. Therefore, this review focused on the current knowledge about the efficacy, safety concerns, and hepatic metabolism of DOACs in patients with cirrhosis and PVT.

Although patients with cirrhosis are known to be in a state of “rebalance” in that pro- and anticoagulant factors increase the risk for both bleeding and thrombosis, the prevalence of portal vein thrombosis (PVT) in patients with cirrhosis can be up to 26%. Therefore, physicians should consider anticoagulation for the prevention and management of PVT in patients with cirrhosis who are at high risk of PVT. Vitamin K antagonist or low molecular weight heparin is suggested as the standard treatment for PVT in cirrhosis. With the advent of new direct-acting oral anticoagulants (DOACs), there is a paradigm shift of switching to DOACs for the treatment of PVT in patients with cirrhosis. However, the safety and efficacy of DOACs in the treatment of PVT was not well-known in patients with cirrhosis. Therefore, this review focused on the current knowledge about the efficacy, safety concerns, and hepatic metabolism of DOACs in patients with cirrhosis and PVT.

BACKGROUND: The aim of this study was to examine the clinical characteristics of adrenal incidentalomas discovered by computed tomography (CT) and to investigate metabolic features of subclinical Cushing's syndrome (SCS) in patients with adrenal incidentalomas in a tertiary hospital in Korea. METHODS: This retrospective study examined the clinical aspects of 268 patients with adrenal incidentalomas discovered by CT at Soonchunhyang University Bucheon Hospital. Clinical data and endocrine function of the patients as well as histological findings were obtained from medical records, while anatomic characteristics were analyzed by reviewing imaging studies. Hormonal tests for pheochromocytoma, Cushing's syndrome, and aldosterone-secreting adenoma were performed. RESULTS: Most (n=218, 81.3%) cases were nonfunctioning tumors. Of the 50 patients with functioning tumors (18.7%), 19 (7.1%) were diagnosed with SCS, nine (3.4%) with overt Cushing's syndrome, 12 (4.5%) with primary aldosteronism, and 10 (3.7%) with pheochromocytoma. Malignant tumors (both primary and metastatic) were rare (n=2, 0.7%). Body mass index, fasting glucose, hemoglobin A1c, and total cholesterol were significantly higher in patients with SCS in comparison with those with nonfunctioning tumors. The prevalence of type 2 diabetes mellitus and hypertension were significantly higher in patients with SCS compared with those with nonfunctioning tumors. CONCLUSION: Functioning tumors, especially those with subclinical cortisol excess, are commonly found in patients with adrenal incidentalomas, although malignancy is rare. In addition, patients with SCS in adrenal incidentalomas have adverse metabolic and cardiovascular profiles.
Adenoma ; Body Mass Index ; Cholesterol ; Cushing Syndrome* ; Diabetes Mellitus, Type 2 ; Fasting ; Glucose ; Gyeonggi-do ; Humans ; Hydrocortisone ; Hyperaldosteronism ; Hypertension ; Korea ; Medical Records ; Pheochromocytoma ; Prevalence ; Retrospective Studies ; Tertiary Care Centers

BACKGROUND: Proper physical activities are known to be helpful in the prevention and management of chronic diseases. However, the physical activity level of patients with chronic diseases is low. Therefore, this study aimed to investigate the physical activity compliance of patients with hypertension, diabetes, and dyslipidemia in Korea. METHODS: This study analyzed the 2010-2012 Fifth Korean National Health and Nutrition Examination Survey data. We included 13,873 individuals in the analysis. The level of physical activity compliance was measured by performing multivariate logistic regression analyses. RESULTS: In the univariate analysis, the subjects with hypertension or diabetes tended to comply with the physical activity guidelines less faithfully than their healthy counterparts. The proportion of subjects with hypertension who were insufficiently physically active was 65.4% among the men and 75.8% among the women. For diabetes, the proportions were 66.7% and 76.8%, respectively. No significant difference was found between the subjects with dyslipidemia and their healthy counterparts. In the multivariate logistic regression analysis, no significant difference in physical activity compliance was observed between the subjects with hypertension, diabetes, or dyslipidemia and their healthy counterparts for both sexes. CONCLUSION: The patients with hypertension or diabetes tended to have lower physical activity prevlaence than their healthy counterparts. However, for dyslipidemia, no significant difference was found between the two groups. Given the significance of physical activities in the management of chronic diseases, the physical activities of these patients need to be improved.
Adult* ; Chronic Disease* ; Compliance ; Dyslipidemias ; Female ; Humans ; Hypertension ; Korea ; Logistic Models ; Male ; Motor Activity* ; Nutrition Surveys

BACKGROUND: Several studies showed the relationship between serum homocysteine and pulse wave velocity, but their subjects were confined to high risk group for cardiovascular diseases and recent study revealed no relationship in young healthy adults. We hypothesized that time interval would be needed for serum homocysteine to infl uence pulse wave velocity after exposure to vascular endothelium. The purpose of this study was to determine the relationship between serum homocysteine and pulse wave velocity in middle aged women on the basis of that hypothesis and necessity for further study in general population. METHODS: The study subjects were 110 middle aged women who visited a health promotion center of a general hospital. We collected medical history by means of self-reported questionnaire and measured height, weight, blood pressure and brachial-ankle pulse wave velocity (baPWV). Blood sampling was performed after overnight fasting. We analyzed the relationship between several cardiovascular risk factors and baPWV and performed multiple regression analysis. RESULTS: BaPWV velocity was correlated significantly with age, mean blood pressure, serum homocysteine, total cholesterol and diabetes mellitus, but not with body mass index, high-density lipoprotein cholesterol, triglyceride, creatinine clearance, alcohol intake, hypertension and smoking. In multiple regression, there was a significant association between age (P = 0.04), moderate hyperhomocysteinemia (P = 0.02), mean blood pressure (P < 0.001) and baPWV. CONCLUSION: In middle aged women, there was an independently positive association between serum homocysteine and baPWV
Adult ; Blood Pressure ; Body Mass Index ; Cardiovascular Diseases ; Cholesterol ; Creatinine ; Diabetes Mellitus ; Endothelium, Vascular ; Fasting ; Female ; Health Promotion ; Homocysteine ; Hospitals, General ; Humans ; Hyperhomocysteinemia ; Hypertension ; Lipoproteins ; Middle Aged ; Pulse Wave Analysis ; Risk Factors ; Smoke ; Smoking

This study was conducted to determine if humoral antibody response of foot-and-mouth disease (FMD) vaccine improved in 8-week-old growing pigs born to well-vaccinated sows pre-treated with 60 mg of poly-γ-glutamic acid (γ-PGA) three days before vaccination. Antibody against FMD virus serotype O was measured 0, 2, 4 and 6 weeks post-vaccination, using a PrioCHECK FMDV type O ELISA kit. The results showed that positive antibody reactions against FMDV serotype O antigen among a component of the vaccine significantly increased in response to pre-injection with γ-PGA.
Animals ; Antibody Formation* ; Enzyme-Linked Immunosorbent Assay ; Foot-and-Mouth Disease Virus* ; Foot-and-Mouth Disease* ; Immunity, Humoral ; O Antigens ; Serogroup ; Swine* ; Vaccination