PURPOSE: Anti-rheumatic agents target common molecular pathways of inflammation in rheumatoid arthritis (RA) and periodontitis. The purpose of this study was to determine the relative effect of anti-rheumatic agents on the levels of inflammatory biomarkers and periodontal inflammation in RA patients with periodontitis. METHODS: A systematic review and meta-analysis were conducted of studies comparing periodontal parameters of inflammation, such as bleeding on probing, and biomarkers of inflammation in RA patients with periodontitis and healthy adults with and without periodontitis. The search included the electronic databases MEDLINE, Cochrane Database of Systematic Reviews, and Google Scholar, inclusive through October 2011, with no language restrictions. Hand searches were conducted of the bibliographies of related journals and systematic reviews. Observational and interventional studies assessing the effects of antirheumatic therapy qualified for inclusion. Two reviewers performed independent data extraction and risk-of-bias assessment. Of the 187 identified publications, 13 studies fulfilled the inclusion criteria. RESULTS: When compared to healthy adults without periodontitis, RA subjects were found to have significantly higher levels of bleeding on probing and limited evidence of higher levels of interleukin-1beta and tumor necrosis factor-alpha (TNF-alpha) in gingival crevicular fluid and saliva. No consistent differences were found in periodontal parameters and inflammatory biomarkers between RA subjects and adults with periodontitis. Studies evaluating the effect of anti-TNF-alpha therapy in RA subjects with periodontitis have yielded inconsistent results. CONCLUSIONS: There are limited data, however, to suggest that anti-TNF-alpha agents can reduce local production of inflammatory cytokines and periodontal inflammation in RA patients with periodontitis.
Adult ; Antirheumatic Agents ; Arthritis, Rheumatoid ; Biomarkers ; Cytokines ; Electronics ; Electrons ; Gingival Crevicular Fluid ; Hand ; Hemorrhage ; Humans ; Inflammation ; Interleukin-1beta ; Periodontitis ; Saliva ; Tumor Necrosis Factor-alpha

Disasters ; Medicine ; Physical And Rehabilitation Medicine ; Rehabilitation

Chemotherapy-induced cancer cell secretomes promote resistance due, in part, to a predominant glycolytic energy metabolism, which drives aggressive cancer cell proliferation. However, the characterization of these secretomes and the molecular events that associate them with acquired drug resistance remain poorly understood. In this study, we show that secretomes of cancer cells with high-level paclitaxel resistance stimulated cell proliferation and suppressed drug-induced apoptosis of drug-sensitive cells. We also found that drug (docetaxel)-stimulated induction of interferon-α (IFN-α), IFN-λ and tumor necrosis factor-α (TNF-α) release in drug-sensitive cells was lowered by these secretomes. The promotion of cell proliferation by paclitaxel-resistant (PacR) cancer cell secretomes was associated, in part, with an increase in S phase of the cell cycle and downregulation of the cell death pathway that supports escape from apoptosis. In addition, we also found that the regulation of targeted glycolysis in PacR cancer cells alters the effects of the secretomes on cell growth, apoptosis, ATP generation and acquired drug resistance. Further study revealed that the deletion of FOXO3a transcription exacerbates glycolytic shift-induced apoptosis by rescuing TRAIL expression. By generating a docetaxel–cross-resistant PacR cancer cell line (PacR/DCT), we further clarified the role of FOXO3a in glycolysis-associated mediation of P-glycoprotein/ABCB1 hyperactivity that induces docetaxel cross-resistance. These findings suggest that suppression of the cellular energy supply by targeting glycolysis may inhibit the multiplicity of acquired chemotherapy resistance. Therefore, the therapeutic inhibition of FOXO3a might direct glycolysis to induce apoptosis and overcome multidrug resistance in cancer cells.
Adenosine Triphosphate ; Apoptosis* ; Cell Cycle ; Cell Death ; Cell Line ; Cell Proliferation ; Down-Regulation ; Drug Resistance ; Drug Resistance, Multiple ; Drug Therapy ; Energy Metabolism ; Glycolysis ; Necrosis ; Negotiating ; Paclitaxel ; S Phase ; United Nations*

It is known that penile erection is mediated primarily through the release of a nonadrenergic noncholinergic (NANC) neurotransmitter which has been recently identified as nitric oxide (NO). To evaluate whether the endothelium is involved in neurally mediated relaxation in corpus cavernosum, we determined electrical field stimulation (EFS) induced relaxation in both the presence and absence of endothelium, and we tested the effect of an inhibitor of NO synthase, NG-nitro-L-arginine (NOARG), in the absence of endothelium to examine if de-endothelialized tissue can still generate NO. Isolated corpus cavernosal strips from New Zealand White rabbits were used for isometric tension study using organ chambers. The endothelium was removed through denuding tissue. After the tissue was contracted with norepinephrine, EFS was performed at frequencies of 5, 15 and 40 Hz in the presence of guanethidine and atropine to evaluate NANC-selective nerural relaxation. The relaxation induced by EFS was observed after preincubation with NOARG(10(-4) M) for 30 minutes. L-arginine (10(-3) M) was then added for 30 minutes in the presence of NOARG before a second set of EFS studies were performed. Following norepinephrine precontraction, EFS relaxed corporal strips in both the intact and de-endothelialized strips. However, deendothelialization significantly impaired EFS induced relaxation (p< 0.05). NOARG attenuated relaxation induced by EFS and the addition of L-arginine reversed the inhibitory effect of NOARG in the strips with endothelium. In the strips without endothelium, NOARG still inhibited EFS induced relaxation. This relaxation was reversed by the addition of L-arginine.
Animal ; Endothelium/physiology ; Male ; Muscle Relaxation ; Neurons/metabolism ; Nitric Oxide/*physiology ; *Penile Erection ; Penis/innervation/*physiology ; Rabbits

The expression of both constitutive and inducible forms of nitric oxide synthase (NOS) was investigated by immunohistochemical staining of formalin-fixed paraffin-embedded sections in normal and Listeria monocytogenes-infected brains of goats. In normal control goats, a small number of neurons showed immunoreactivity of both iNOS and nNOS, and the number of iNOS-positive neurons was higher than the number of nNOS-positive neurons. In natural listeriosis, listeria antigens were easily immunostained in the inflammatory cells of microabscesses. In this lesion, the immunoreactivity of iNOS in neurons was more intense than the control, but nNOS was not. In microabscesses, nNOS was weakly visualized in macrophages and neutrophils, while iNOS was expressed in macrophages, but not in neutrophils. These findings suggest that normal caprine brain cells, including neurons, constitutively express iNOS and nNOS, and the expressions of these molecules is increased in Listeria monocytogenes infections. Furthermore, inflammatory cells, including macrophages, expressing both nNOS and iNOS may play important roles in the pathogenesis of bacterial meningoencephalitis in goat.
Animals ; Brain/cytology/*enzymology ; Glial Fibrillary Acidic Protein/analysis ; Goat Diseases/*enzymology ; Goats ; Immunohistochemistry ; Listeria Infections/enzymology/*veterinary ; Neurons/*enzymology ; Nitric Oxide Synthase/*analysis ; Nitric Oxide Synthase Type I ; Nitric Oxide Synthase Type II

BACKGROUND: Osteoporosis and attributable fractures are disruptive health events that can cause short and long-term cost consequences for families, health service and government. In this fracture-based scenario analysis we evaluate the broader public economic consequences for the Korean government based on fractures that can occur at 3 different ages.METHODS: We developed a public economic modelling framework based on population averages in Korea for earnings, direct taxes, indirect taxes, disability payments, retirement, pension payments, and osteoporosis health costs. Applying a scenario analysis, we estimated the cumulative average per person fiscal consequences of osteoporotic fractures occurring at different ages 55, 65, and 75 compared to average non-fracture individuals of comparable ages to estimate resulting costs for government in relation to lost tax revenue, disability payments, pension costs, and healthcare costs. All costs are calculated between the ages of 50 to 80 in Korean Won (KRW) and discounted at 0.5%.RESULTS: From the scenarios explored, fractures occurring at age 55 are most costly for government with increased disability and pension payments of KRW 26,048,400 and KRW 41,094,206 per person, respectively, compared to the non-fracture population. A fracture can result in reduction in lifetime direct and indirect taxes resulting in KRW 53,648,886 lost tax revenue per person for government compared to general population.CONCLUSIONS: The fiscal consequences of osteoporotic fractures for government vary depending on the age at which they occur. Fiscal benefits for government are greater when fractures are prevented early due to the potential to prevent early retirement and keeping people in the labor force to the degree that is observed in non-fracture population.
Costs and Cost Analysis ; Employment ; Health Care Costs ; Health Services ; Humans ; Korea ; Models, Economic ; Osteoporosis ; Osteoporotic Fractures ; Pensions ; Republic of Korea ; Retirement ; Taxes

BACKGROUND: Neck and shoulder pain (NSP) is fairly common in adolescents, which is associated with a high prevalence of NSP found during adulthood as well; therefore, its significance during adolescence should not be underestimated. We surveyed the prevalence of recurrent NSP, lifestyle, and risk factors in Korean high school students, and examined the influence of recurrent NSP on the quality of life. METHODS: Nine hundred thirty one male students (16-19 years old) from two academic high schools in Seoul were included in this study. The survey consisted of a questionnaire to assess the prevalence of recurrent NSP, with questions regarding having an occurrence more than once a week, characteristics of NSP, activity and lifestyle of the students, and the risk factors for recurrent NSP. A 36-item Short Form questionnaire was also examined. RESULTS: We found that 44.3% of the high school students surveyed had recurrent NSP (more than once a week) and the overall prevalence of NSP was 79.1%. The average sitting time was 10.2 +/- 2.7 h/day. 59.0% did not sit straight, 14.7% used assisting devices during reading, and 11.9% answered that they stretched regularly. Found from their self assessed health, frequent fatigue and frequent depressed mood presented significant associations with the higher prevalence of recurrent NSP. CONCLUSIONS: Korean high school students had a high prevalence of recurrent NSP. Clinical attention is needed for the prevention and resolution of recurrent NSP found in high school students.
Adolescent ; Fatigue ; Humans ; Life Style ; Male ; Neck ; Neck Pain ; Prevalence ; Surveys and Questionnaires ; Risk Factors ; Shoulder ; Shoulder Pain

PURPOSE: To investigate whether histogram analysis of the hepatobiliary phase on gadoxetate enhanced-MRI could be used as a quantitative index for determination of liver cirrhosis. MATERIALS AND METHODS: A total of 63 patients [26 in a normal liver function (NLF) group and 37 in a cirrhotic group] underwent gadoxetate-enhanced MRI, and hepatobiliary phase images were obtained at 20 minutes after contrast injection. The signal intensity of the hepatic parenchyma was measured at four different regions of interest (ROI) of the liver, avoiding vessels and bile ducts. Standard deviation (SD), coefficient of variation (CV), and corrected CV were calculated on the histograms at the ROIs. The distributions of CVs calculated from the ROI histogram were examined and statistical analysis was carried out. RESULTS: The CV value was 0.041+/-0.009 (mean CV+/-SD) in the NLF group, while that of cirrhotic group was 0.071+/-0.020. There were statistically significant differences in the CVs and corrected CV values between the NLF and cirrhotic groups (p<0.001). The most accurate cut-off value among CVs for distinguishing normal from cirrhotic group was 0.052 (sensitivity 83.8% and specificity 88.5%). There was no statistically significant differences in SD between NLF and cirrhotic groups (p=0.307). CONCLUSION: The CV of histograms of the hepatobiliary phase on gadoxetate-enhanced MRI may be useful as a quantitative value for determining the presence of liver cirrhosis.
Adult ; Aged ; Aged, 80 and over ; Contrast Media/diagnostic use ; Female ; Gadolinium DTPA/diagnostic use ; Humans ; Liver Cirrhosis/*diagnosis ; Magnetic Resonance Imaging/methods ; Male ; Middle Aged ; Retrospective Studies ; Young Adult

Regulation of cell volume is an important aspect of cellular homeostasis during neural activity. This volume regulation is thought to be mediated by activation of specific transporters, aquaporin, and volume regulated anion channels (VRAC). In cultured astrocytes, it was reported that swelling-induced mitogen-activated protein (MAP) kinase activation is required to open VRAC, which are thought to be important in regulatory volume decrease and in the response of CNS to trauma and excitotoxicity. It has been also described that sodium fluoride (NaF), a recognized G-protein activator and protein phosphatase inhibitor, leads to a significant MAP kinase activation in endothelial cells. However, NaF's effect in volume regulation in the brain is not known yet. Here, we investigated the mechanism of NaF-induced volume change in rat and mouse hippocampal slices using intrinsic optical signal (IOS) recording, in which we measured relative changes in intracellular and extracellular volume as changes in light transmittance through brain slices. We found that NaF (1~5 mM) application induced a reduction in light transmittance (decreased volume) in CA1 hippocampus, which was completely reversed by MAP kinase inhibitor U0126 (10 µM). We also observed that NaF-induced volume reduction was blocked by anion channel blockers, suggesting that NaF-induced volume reduction could be mediated by VRAC. Overall, our results propose a novel molecular mechanism of NaF-induced volume reduction via MAP kinase signaling pathway by activation of VRAC.
Animals ; Astrocytes ; Brain ; Cell Size ; Endothelial Cells ; Fluorides* ; GTP-Binding Proteins ; Hippocampus ; Homeostasis ; Mice ; Phosphotransferases* ; Rats ; Sodium Fluoride

Regulation of cell volume is an important aspect of cellular homeostasis during neural activity. This volume regulation is thought to be mediated by activation of specific transporters, aquaporin, and volume regulated anion channels (VRAC). In cultured astrocytes, it was reported that swelling-induced mitogen-activated protein (MAP) kinase activation is required to open VRAC, which are thought to be important in regulatory volume decrease and in the response of CNS to trauma and excitotoxicity. It has been also described that sodium fluoride (NaF), a recognized G-protein activator and protein phosphatase inhibitor, leads to a significant MAP kinase activation in endothelial cells. However, NaF's effect in volume regulation in the brain is not known yet. Here, we investigated the mechanism of NaF-induced volume change in rat and mouse hippocampal slices using intrinsic optical signal (IOS) recording, in which we measured relative changes in intracellular and extracellular volume as changes in light transmittance through brain slices. We found that NaF (1~5 mM) application induced a reduction in light transmittance (decreased volume) in CA1 hippocampus, which was completely reversed by MAP kinase inhibitor U0126 (10 µM). We also observed that NaF-induced volume reduction was blocked by anion channel blockers, suggesting that NaF-induced volume reduction could be mediated by VRAC. Overall, our results propose a novel molecular mechanism of NaF-induced volume reduction via MAP kinase signaling pathway by activation of VRAC.
Animals ; Astrocytes ; Brain ; Cell Size ; Endothelial Cells ; Fluorides* ; GTP-Binding Proteins ; Hippocampus ; Homeostasis ; Mice ; Phosphotransferases* ; Rats ; Sodium Fluoride