Electrogenic transport and K(+) ion channel expression by the human endolymphatic sac epithelium.

The endolymphatic sac (ES) is a cystic organ that is a part of the inner ear and is connected to the cochlea and vestibule. The ES is thought to be involved in inner ear ion homeostasis and fluid volume regulation for the maintenance of hearing and balance function. Many ion channels, transporters, and exchangers have been identified in the ES luminal epithelium, mainly in animal studies, but there has been no functional study investigating ion transport using human ES tissue. We designed the first functional experiments on electrogenic transport in human ES and investigated the contribution of K(+) channels in the electrogenic transport, which has been rarely identified, even in animal studies, using electrophysiological/pharmacological and molecular biological methods. As a result, we identified functional and molecular evidence for the essential participation of K(+) channels in the electrogenic transport of human ES epithelium. The identified K(+) channels involved in the electrogenic transport were KCNN2, KCNJ14, KCNK2, and KCNK6, and the K(+) transports via those channels are thought to play an important role in the maintenance of the unique ionic milieu of the inner ear fluid

β-Lapachone Significantly Increases the Effect of Ionizing Radiation to Cause Mitochondrial Apoptosis via JNK Activation in Cancer Cells

β-lapachone (β-lap), has been known to cause NQO1-dependnet death in cancer cells and sensitize cancer cells to ionizing radiation (IR). We investigated the mechanisms underlying the radiosensitization caused by β-lap. cells induced ROS generation, triggered ER stress and stimulated activation of ERK and JNK. Inhibition of ROS generation by NAC effectively attenuated the activation of ERK and JNK, induction of ER stress, and subsequent apoptosis. Importantly, inhibition of ERK abolished ROS generation and ER stress, whereas inhibition of JNK did not, indicating that positive feedback regulation between ERK activation and ROS generation triggers ER stress in response to combined treatment. Furthermore, prevention of ER stress completely blocked combination treatment-induced JNK activation and subsequent apoptotic cell death. In addition, combined treatment efficiently induced the mitochondrial translocation of cleaved Bax, disrupted mitochondrial membrane potential, and the nuclear translocation of AIF, all of which were efficiently blocked by a JNK inhibitor. Caspases 3, 8 and 9 were activated by combined treatment but inhibition of these caspases did not abolish apoptosis indicating caspase activation played a minor role in the induction of apoptosis. cells are treated with combination of IR and β-lap, positive feedback regulation between ERK and ROS leads to ER stress causing JNK activation and mitochondrial translocation of cleaved Bax. The resultant decrease in mitochondrial membrane leads to translocation of AIF and apoptosis

Vitamin D deficiency is associated with disease activity in patients with Crohn’s disease

Background/Aims Previous data suggest that vitamin D has a significant role in inflammatory bowel disease (IBD). We investigated the incidence of vitamin D deficiency in Korean patients with IBD and the correlation between serum vitamin D level and disease activity. Methods We retrospectively analyzed the medical records of patients with IBD whose serum vitamin D levels were checked. Deficiency of 25-hydroxyvitamin D was defined as <20 ng/mL. Disease activity was evaluated using the partial Mayo score for ulcerative colitis (≥2 defined as active disease) and Harvey-Bradshaw index for Crohn’s disease (≥4 defined as active disease). Results We enrolled 87 patients with IBD (ulcerative colitis [UC], 45; Crohn’s disease [CD], 42). Among them, 65.5% (57/87) were men, with a mean age of 44.9±15.1 years (range, 18–75 years). The mean duration of disease was 4.7±4.8 years (range, 0.1–17.1 years). Vitamin D deficiency was found in 73.6% (64/87) of patients with IBD. Patients with IBD (mean vitamin D level, 16.3±9.0 ng/mL) showed lower vitamin D level than the healthy control group (mean vitamin D level, 20.4±7.0 ng/mL), with no statistically significant difference (P=0.136). Disease activity was inversely correlated with vitamin D deficiency in patients with CD (P=0.007). However, no correlation was observed in patients with UC (P=0.134). Conclusions Approximately 75% of Korean patients with IBD showed vitamin D deficiency state. Vitamin D deficiency is associated with disease activity, particularly in patients with CD

Evaluation of Four Commercial IgG- and IgM-specific Enzyme Immunoassays for Detecting Mycoplasma pneumoniae Antibody: Comparison with Particle Agglutination Assay

Diagnosis of Mycoplasma pneumoniae infection is important due to its variable clinical manifestations and absence of response to beta-lactams. Introduction of enzyme immunoassays (EIAs) for serologic diagnosis of M. pneumoniae has made it possible to separate the analyses of specific IgG and IgM antibodies. We compared four different commercial EIAs, ImmunoWELL IgG, IgM (GenBio), Medac IgG, IgA, IgM (Medac), Platelia IgG, IgM (Sanofi Pasteur), and Ridascreen IgG, IgA, IgM (r-Biopharm) with indirect particle agglutination assay (PA), Serodia-MycoII (Fujirebio). We tested 91 specimens from 73 pediatric patients (2-17 yr) hospitalized at a tertiary-care hospital between December 2005 and January 2006. The measurements of IgM EIAs were correlated with PA titers (Spearman's correlation coefficient, from 0.89 to 0.92) with high concordance rates, ranging from 82.4% to 92.3%. However, some negative IgM-EIA results in PA-positive specimens indicated that serial samplings with convalescent sera would be necessary to confirm M. pneumoniae infection

A Case of Portal Vein Thrombosis by Protein C and S Deficiency Completely Recanalized by Anticoagulation Therapy

Portal vein thrombosis (PVT) is a rare form of venous thrombosis that affects the hepatic portal vein flow, which can lead to portal hypertension. Treatment of PVT includes anticoagulants, thrombolysis, insertion of shunts, bypass surgery, and liver transplantation. Single anticoagulation therapy is not regarded as a curative treatment but can be associated with a reduction in new thrombotic episodes. We experienced a case of acute total occlusion of PVT provoked by protein C and S deficiency syndrome. PVT was completely recanalized with oral anticoagulant therapy following low molecular weight heparin therapy

The Changes of Skin Temperature on Hands and Feet During and after T3 Sympathicotomy for Palmar Hyperhidrosis

Unilateral thoracic sympathectomy in patients with palmar hyperhidrosis causes a skin temperature drop in the contralateral hand. A cross-inhibitory effect by the post-ganglionic neurons innervating hands is postulated as a mechanism of contralateral vasoconstriction. The purpose of our study was to evaluate whether this cross-inhibitory effect also occurs in the feet. Twenty patients scheduled for thoracoscopic sympathicotomy due to palmar hyperhidosis were studied. Right T3 sympathicotomy was performed first, followed by left T3 sympathicotomy. The thenar skin temperatures of both hands and feet were continuously monitored using a thermometer and recorded before induction of anesthesia, during the operation, 4 hr after and 1 week later. Following right T3 sympathicotomy, the skin temperature of the ipsilateral hand gradually increased, however the skin temperature of the contralateral hand gradually decreased. Immediately after bilateral sympathicotomy, the skin temperature differences between hands and feet increased, but these differences decreased 1 week later. Our results show that cross-inhibitory control may exist in feet as well as in the contralateral hand. Thus, the release of cross-inhibitory control following T3 sympathicotomy results in vasoconstriction and decrease of skin temperature on the contralateral hand and feet. One week later, however, the temperature balance on hands and feet recovers

The assessment of efficacy of porcine reproductive respiratory syndrome virus inactivated vaccine based on the viral quantity and inactivation methods

<p>Abstract</p> <p>Background</p> <p>There have been many efforts to develop efficient vaccines for the control of porcine reproductive and respiratory syndrome virus (PRRSV). Although inactivated PRRSV vaccines are preferred for their safety, they are weak at inducing humoral immune responses and controlling field PRRSV infection, especially when heterologous viruses are involved.</p> <p>Results</p> <p>In all groups, the sample to positive (S/P) ratio of IDEXX ELISA and the virus neutralization (VN) titer remained negative until challenge. While viremia did not reduce in the vaccinated groups, the IDEXX-ELISA-specific immunoglobulin G increased more rapidly and to significantly greater levels 7 days after the challenge in all the vaccinated groups compared to the non-vaccinated groups (<it>p </it>< 0.05). VN titer was significantly different in the 10⁶PFU/mL PRRSV vaccine-inoculated and binary ethylenimine (BEI)-inactivated groups 22 days after challenge (<it>p </it>< 0.05). Consequently, the inactivated vaccines tested in this study provided weak memory responses with sequential challenge without any obvious active immune responses in the vaccinated pigs.</p> <p>Conclusions</p> <p>The inactivated vaccine failed to show the humoral immunity, but it showed different immune response after the challenge compared to mock group. Although the 10⁶PFU/mL-vaccinated and BEI-inactivated groups showed significantly greater VN titers 22 days after challenge, all the groups were already negative for viremia.</p

A Case of Intestinal Behcet's Disease Similar to Crohn's Colitis

Behcet's disease is a multi-systemic vasculitis and characterized by systemic organ involvement. Although the gastrointestinal and systemic features of Behcet's disease and inflammatory bowel disease overlap to a considerable extent, they are generally viewed as two distinct diseases. A 39-yr-old female was diagnosed as having Behcet's disease. She was admitted to our hospital because of oral and genital ulcer, lower abdominal pain, and frequent diarrhea. Colonosopy showed diffuse involvement of multiple longitudinal ulcers with inflammatory pseudopolyps with a cobblestone appearance and ano-rectal fistula was suspected. These findings are extremely rare in Behcet's disease. However, there were no granulomas, the hallmark of Crohn's colitis. Microscopically, perivasculitis and multiple lymph follicles compatible with Behcet's disease were seen. Although being rarely encountered, multiple longitudinal ulcers, cobblestone appearance, and ano-rectal fistula can develop in Behcet's disease, as in Crohn's colitis. Therefore, Behcet's disease and Crohn's disease may be closely related and part of a spectrum of disease

Psychometric Properties of the Hypomania Checklist-32 in Korean Patients with Mood Disorders

OBJECTIVE The aim of this study was to examine the validity of the Korean version of the Hypomania Checklist-32, second revision (HCL-32-R2) in mood disorder patients. METHODS A total of 454 patients who diagnosed as mood disorder according to Structured Clinical Interview for DSM-IV Axis I Disorders, clinician version (SCID-CV) (bipolar disorder [BD] I, n=190; BD-II, n=72; and major depressive disorder [MDD], n=192) completed the Korean module of the HCL-32-R2 (KHCL-32-R2). RESULTS The KHCL-32-R2 showed a three-factorial structure (eigenvalue ＞2) that accounted for 43.26% of the total variance. Factor 1 was labeled "active/elated" and included 16 items; factor 2, "irritable/distractible" and included 9 items; and factor 3 was labeled "risk-taking/indulging" and included 9 items. A score of 16 or more on the KHCL-32-R2 total scale score distinguished between BD and MDD, which yielded a sensitivity of 70% and a specificity of 70%. MDD and BD-II also could be differentiated at a cut-off of 15 with maximized sensitivity (0.67) and specificity (0.66). Cronbach's alpha of KHCL-32-R2 and its subsets (factors 1, 2, and 3) were 0.91, 0.89, 0.81 and 0.79, respectively. Correlations between KHCL-32-R2 and Montgomery- Asberg Depression Rating Scale, Young Mania Rating Scale and Korean version of Mood Disorder Questionnaire were -0.66 (p=0.41), -0.14 (p=0.9), and 0.61 (p＜0.001), respectively. CONCLUSION The KHCL-32-R2 may be a useful tool in distinguishing between bipolar and depressive patients in clinical settings

Sulforaphane, a natural component of broccoli, inhibits vestibular schwannoma growth in vitro and in vivo

Vestibular schwannoma (VS) is an intracranial tumor that causes significant morbidity, including hearing loss, tinnitus, dizziness, and possibly even death from brainstem compression. However, FDA-approved pharmacologic treatments for VS do not exist. Sulforaphane (SFN) is a naturally occurring isothiocyanate found in cruciferous vegetables, such as broccoli, with potent chemoprotective effects in several cell types. Our objective was to determine whether SFN is effective against VS in vitro and in vivo. Human primary VS cells, HEI-193 schwannoma cells, and SC4 Nf2−/− Schwann cells were used to investigate the inhibitory effects of SFN in vitro. Cell proliferation was assessed by bromodeoxyuridine (BrdU) incorporation, and cell viability and metabolic activity was calculated by MTT assay. Apoptosis was measured by flow cytometry, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining, and Western blot for cleaved caspases. A mouse model with a murine schwannoma allograft was also used to examine the antitumor activity of SFN. SFN exhibited significant antiproliferative activity in schwannoma cells in vitro, via the inhibition of HDAC activity and the activation of ERK. SFN treatment induced apoptosis and cell cycle arrest at the G2/M phase. SFN also significantly inhibited schwannoma growth in vivo. Our preclinical studies motivate a future prospective clinical study of SFN for the treatment of VS