The present study evaluated the anti-cancer activity of histone deacetylase (HDAC)-inhibiting CKD-581 in multiple myeloma (MM) and its pharmacological mechanisms. CKD-581 potently inhibited a broad spectrum of HDAC isozymes. It concentration-dependently inhibited proliferation of hematologic cancer cells including MM (MM.1S and RPMI8226) and T cell lymphoma (HH and MJ). It increased the expression of the dishevelled binding antagonist of β-catenin 3 (DACT3) in T cell lymphoma and MM cells, and decreased the expression of c-Myc and β-catenin in MM cells. Additionally, it enhanced phosphorylated p53, p21, cleaved caspase-3 and the subG1 population, and reversely, downregulated cyclin D1, CDK4 and the anti-apoptotic BCL-2 family. Finally, administration of CKD-581 exerted a significant anti-cancer activity in MM.1S-implanted xenografts. Overall, CKD-581 shows anticancer activity via inhibition of the Wnt/β-catenin signaling pathway in hematologic malignancies. This finding is evidence of the therapeutic potential and rationale of CKD-581 for treatment of MM.

BACKGROUND: Vascular endothelial growth factor (VEGF) is an angiogenic peptide that enhances microvascular perfusion. Recently, VEGF is known to have neurotrophic effect and rescues neurons from cell death induced by serum deprivation. To investigate the serial changes in VEGF expression and neuroprotective properties of VEGF during acute ischemia. METHODS: Human cortical-neuroblastoma hybrid cell line (A1G11), human neuroglioma cell line (H4), and human vascular endothelial cell line (ECV304) were placed in the glucose/serum free media and incubated in the hypoxic chamber (94% N2/5% CO2/1% room air) at 37 degrees C. Cell viability was determined by MTT assay. Western blot analysis was performed to detect VEGF and its receptor (VEGFR) expression. To test the protective effect of VEGF, human recombinant VEGF165 was used. RESULTS: Morphological changes and the decrease of cell viability were observed following 6 hr ischemia. In A1G11 cells, VEGF expression was not noted until 3 hr ischemia, but was induced after 6hr and continued to 12 hr and then diminished. In H4 and ECV304, the change of VEGF expression was not observed. VEGFR-2/Flk-1 expression was induced from 6 hr (peak level) to 12 hr in A1G11, and induced after 3 hr and continued to 12hr in ECV304. Administration of VEGF increased cell viability in A1G11 cells at 6 hr, 12 hr and 18 hr ischemia (p=0.009, p=0.01 p=0.013), but not in H4 or ECV304 cells ( p>0.05). CONCLUSION: Ischemia induces VEGF production in neurons and VEGF may exert a direct neuron-specific protective effect through VEGFR-2/Flk receptors during the acute phase of ischemic neuronal injury.
Blotting, Western ; Cell Death ; Cell Line ; Cell Survival ; Endothelial Cells ; Humans ; Hybrid Cells ; Ischemia* ; Neurons ; Perfusion ; Vascular Endothelial Growth Factor A*

Recent studies have reported that the "cholinergic anti-inflammatory pathway" regulates peripheral inflammatory responses via alpha7 nicotinic acetylcholine receptors (alpha7 nAChRs) and that acetylcholine and nicotine regulate the expression of proinflammatory mediators such as TNF-alpha and prostaglandin E2 in microglial cultures. In a previous study we showed that ATP released by beta-amyloid-stimulated microglia induced reactive oxygen species (ROS) production, in a process involving the P2X7 receptor (P2X7R), in an autocrine fashion. These observations led us to investigate whether stimulation by nicotine could regulate fibrillar beta amyloid peptide (1-42) (fA beta(1-42))-induced ROS production by modulating ATP efflux-mediated Ca2+ influx through P2X7R. Nicotine inhibited ROS generation in fA beta(1-42)-stimulated microglial cells, and this inhibition was blocked by mecamylamine, a non-selective nAChR antagonist, and a-bungarotoxin, a selective alpha7 nAChR antagonist. Nicotine inhibited NADPH oxidase activation and completely blocked Ca2+ influx in fA beta(1-42)-stimulated microglia. Moreover, ATP release from fA beta(1-42)-stimulated microglia was significantly suppressed by nicotine treatment. In contrast, nicotine did not inhibit 2',3'-O-(4-benzoyl)-benzoyl ATP (BzATP)-induced Ca2+ influx, but inhibited ROS generation in BzATP-stimulated microglia, indicating an inhibitory effect of nicotine on a signaling process downstream of P2X7R. Taken together, these results suggest that the inhibitory effect of nicotine on ROS production in fA beta(1-42)-stimulated microglia is mediated by indirect blockage of ATP release and by directly altering the signaling process downstream from P2X7R.
Adenosine Triphosphate/analogs & derivatives/metabolism/pharmacology ; Amyloid/*metabolism ; Amyloid beta-Protein/*pharmacology ; Animals ; Calcium/metabolism ; Enzyme Activation/drug effects ; Microglia/cytology/*drug effects/enzymology/*metabolism ; NADPH Oxidase/metabolism ; Nicotine/pharmacology ; Nicotinic Antagonists/pharmacology ; Peptide Fragments/*pharmacology ; Rats ; Rats, Sprague-Dawley ; Reactive Oxygen Species/*metabolism ; Receptors, Nicotinic/*metabolism ; Receptors, Purinergic P2/metabolism

Aucubin is an iridoid glycoside with a wide range of biological activities, including anti-inflammatory, anti-microbial, anti-algesic as well as anti-tumor activities. Recently, it has been shown that aucubin prevents neuronal death in the hippocampal CA1 region in rats with diabetic encephalopathy. In addition, it has protective effects on H2O2-induced apoptosis in PC12 cells. We have shown here that aucubin promotes neuronal differentiation and neurite outgrowth in neural stem cells cultured primarily from the rat embryonic hippocampus. We also investigated whether aucubin facilitates axonal elongation in the injured peripheral nervous system. Aucubin promoted lengthening and thickness of axons and re-myelination at 3 weeks after sciatic nerve injury. These results indicate that administration of aucubin improved nerve regeneration in the rat model of sciatic nerve injury, suggesting that aucubin may be a useful therapeutic compound for the human peripheral nervous system after various nerve injuries.
Animals ; Apoptosis ; Axons* ; CA1 Region, Hippocampal ; Hippocampus ; Humans ; Models, Animal ; Nerve Regeneration ; Neural Stem Cells* ; Neurites* ; Neurons ; PC12 Cells ; Peripheral Nervous System ; Rats ; Regeneration* ; Sciatic Nerve*

PURPOSE: The purpose of the study was to define the prevalence of genital Chlamydia trachomatis and Neisseria gonorrhoeae infections and the status of sexual risk behavior among university students (18-25 years old) in the Capital region of Korea. MATERIALS AND METHODS: Participants filled out a self-administered questionnaire related to sexuality. First-void urine was analyzed for chlamydial and gonococcal infection by strand displacement amplification (BDProbTec(TM) ET, BD Diagnostic Systems, MD USA). RESULTS: A total of 622 students from 15 colleges within 3 universities took part in the study. Their median age was 21, with 39.1% reporting having sexual intercourse at least once. The prevalence of C. trachomatis among sexually active men and women was 8.4% and 10.6%, respectively. Gonococcal infection was noted in one symptomatic male. Factors significantly associated with infection were number of sexual partners in past year and during a lifetime and condom use. CONCLUSIONS: This is the first community-based sexually transmitted infections (STI) screening in South Korea. Urine-based STI screening was both feasible and acceptable in university students in South Korea, and should be considered a routine part of national programs to control STI.
Chlamydia trachomatis ; Coitus ; Condoms ; Female ; Humans ; Korea* ; Male ; Mass Screening ; Neisseria gonorrhoeae ; Prevalence* ; Surveys and Questionnaires ; Risk-Taking ; Sexual Behavior* ; Sexual Partners ; Sexuality

In the article cited above, upper part page in title page has an error. Ending page of the article should be 268, not 269.

BACKGROUND/AIMS: Acute pyelonephritis (APN) is the most common cause of community-onset bacteremia in hospitalized elderly patients. The objectives of this study were to investigate the differences in the clinical and microbiological data of hospitalized elderly and non-elderly women with community-onset APN. METHODS: Women with community-onset APN as a discharge diagnosis were identified from January 2004 to December 2013 using an electronic medical records system. We compared the clinical and microbiologic data in elderly and non-elderly women with community-onset APN due to Enterobacteriaceae. RESULTS: Of the 1,134 women with community-onset APN caused by Enterobacteriaceae, 443 were elderly and 691 were non-elderly women. The elderly group had a lower frequency of upper and lower urinary tract symptoms/signs than the non-elderly. The incidence of bacteremia, extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae, patients with a C-reactive protein (CRP) level > or = 15 mg/dL, and patients with a leukocyte count > or = 15,000/mm3 in the blood, were significantly higher in the elderly group than in the non-elderly group. The proportion of patients requiring hospitalization for 10 days or more was significantly higher in the elderly group compared to the non-elderly group (51.5% vs. 26.2%, p < 0.001). The clinical cure rates at 4 to 14 days after the end of therapy were 98.3% (338/344) and 97.4% (519/533) in the elderly and non-elderly groups, respectively (p = 0.393). CONCLUSIONS: Elderly women with APN exhibit higher serum CRP levels, a higher frequency of bacteremia, a higher proportion of ESBL-producing uropathogens, and require a longer hospitalization than non-elderly women, although these patients may not complain of typical urinary symptoms.
Acute Disease ; Adult ; Age Factors ; Aged ; Anti-Bacterial Agents/therapeutic use ; Community-Acquired Infections/*diagnosis/drug therapy/microbiology ; Electronic Health Records ; Enterobacteriaceae Infections/*diagnosis/drug therapy/microbiology ; Female ; Hospitalization ; Hospitals, University ; Humans ; Middle Aged ; Pyelonephritis/*diagnosis/drug therapy/microbiology ; Remission Induction ; Republic of Korea ; Retrospective Studies ; Risk Factors ; Sex Factors ; Time Factors ; Treatment Outcome ; Urinary Tract Infections/*diagnosis/drug therapy/microbiology

No abstract available.
Acute Disease ; Adult ; Anti-Bacterial Agents/therapeutic use ; Choristoma/*complications/radiography ; Escherichia coli Infections/diagnosis/drug therapy/*microbiology ; Female ; Hernias, Diaphragmatic, Congenital/*complications/radiography ; Humans ; *Kidney ; Predictive Value of Tests ; Pyelonephritis/diagnosis/drug therapy/*microbiology ; Thoracic Diseases/*complications/radiography ; Tomography, X-Ray Computed ; Treatment Outcome

INTRODUCTION: Sore throat and hoarseness often follow general anesthesia administered via a single-lumen endotracheal tube (SLT). Numerous studies have investigated the role of factors as contributing causes, but the influence of double-lumen endobronchial tube (DLT) has not been examined systemically. The goal of this study was to examine the incidence of sore throat and hoarseness after DLT insertion. METHODS: 70 patients who were intubated with SLT or DLT were studied. Sore throat and hoarseness were evaluated after 24~48 hr from extubation of each tubes. RESULTS: In SLT and DLT group, the incidence of sore throat and hoarseness was 14 patients (40%) vs 16 patients (45.7%) and 8 patients (22.8%) vs 10 patients (28.5%), respectively. CONCLUSIONS: There are no statistical differences in incidence of sore throat and hoarseness between SLT and DLT.
Anesthesia, General ; Hoarseness* ; Humans ; Incidence* ; Intubation* ; Pharyngitis*

PURPOSE: Pantothenate kinase-associated neurodegeneration (PKAN), also known as neurodegeneration with brain iron accumulation is an extremely rare degenerative disease. The present study reports a case of retinal pigmentary changes in PKAN. CASE SUMMARY: A 6-year-old girl presented with night blindness and developmental delay. Neurologic examination revealed toe gait and dystonia. Ocular examination showed retinal pigmentary change in the entire retina without optic atrophy. Brain magnetic resonance imaging showed iron deposits in the basal ganglia, the so-called "eye of the tiger" sign. Genetic tests confirmed a mutation in the gene encoding pantothenate kinase 2. Electroretinography demonstrated severe loss of rod and cone responses, prominently reduced in the rod response. The patient was diagnosed with PKAN and pharmacologic treatment started. CONCLUSIONS: In the case of systemic neurological abnormalities with pigmentary retinal change, PKAN should be considered as a differential diagnosis.
Basal Ganglia ; Brain ; Diagnosis, Differential ; Dystonia ; Electroretinography ; Gait ; Humans ; Iron ; Magnetic Resonance Imaging ; Neurologic Examination ; Night Blindness ; Optic Atrophy ; Pantothenate Kinase-Associated Neurodegeneration ; Phosphotransferases ; Phosphotransferases (Alcohol Group Acceptor) ; Retina ; Retinal Degeneration ; Retinaldehyde ; Toes