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ID PMID Title PublicationDate abstract
24286565 The natural history of the hemiarthroplasty for displaced intracapsular femoral neck fract 2013 Dec BACKGROUND: Numerous papers have been published on the medium- and long-term results of hemiarthroplasties (HAs) after femoral neck fracture in the elderly. We were not aware of any articles that describe the outcome of HA until the patient dies. METHODS: Between 1975 and 1989, 307 bipolar hemiarthroplasties were performed in 302 consecutive patients with a displaced femoral neck facture. Patients with osteoarthritis of the hip, rheumatoid arthritis (RA), or senile dementia were not included in the study. All patients were followed annually until they died or until they needed a revision operation. RESULTS: The mortality rate was 28% after 1 year, and 63% after 5 years. The last patient who did not need a revision operation died in October 2010. Revision operations for aseptic loosening, protrusion, or both had to be performed in 34 patients (16%). A difference in reoperation rate was observed between patients less than 75 years of age (38%) and those who were older (6%). INTERPRETATION: Apart from age below 75 years, male sex appeared to be predictive of a revision operation. HA is a safe and relatively inexpensive treatment for patients over 75 years of age with a displaced femoral neck fracture.
24223576 Four Promoters of IRF5 Respond Distinctly to Stimuli and are Affected by Autoimmune-Risk P 2013 INTRODUCTION: Autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, and multiple sclerosis affect millions of people worldwide. Interferon regulatory factor 5 (IRF5) contains polymorphisms associated with these autoimmune diseases. Two of these functional polymorphisms are found upstream of the IRF5 gene. rs2004640, which is a single nucleotide polymorphism and the CGGGG insertion/deletion (indel) were studied. IRF5 uses four different promoters for its four first exons: 1A, 1B, 1C, and 1D. Each promoter was analyzed, including functional differences due to the autoimmune-risk polymorphisms. RESULTS: IRF5 promoters were analyzed using ChIP-Seq data (ENCODE database) and the FactorBook database to define transcription factor binding sites. To verify promoter activity, the promoters were cloned into luciferase plasmids. Each construct exhibited luciferase activity. Exons 1A and 1D contain putative PU.1 and NFkB binding sites. Imiquimod, a Toll-like receptor 7 (TLR7) ligand, was used to activate these transcription factors. IRF5 levels were doubled after imiquimod treatment (p < 0.001), with specific increases in the 1A promoter (2.2-fold, p = 0.03) and 1D promoter (2.8-fold, p = 0.03). A putative binding site for p53, which affects apoptosis, was found in the promoter for exon 1B. However, site-directed mutagenesis of the p53 site showed no effect in a reporter assay. CONCLUSION: The IRF5 exon 1B promoter has been characterized, and the responses of each IRF5 promoter to TLR7 stimulation have been determined. Changes in promoter activity and gene expression are likely due to specific and distinct transcription factors that bind to each promoter. Since high expression of IRF5 contributes to the development of autoimmune disease, understanding the source of increased IRF5 levels is key to understanding autoimmune etiology.
24129144 New drugs in systemic lupus erythematosus: when to start and when to stop. 2013 Jul Survival of patients with systemic lupus erythematosus (SLE) has greatly improved compared to earlier decades. However, this improvement appears to have reached a plateau. In addition, damage accrual appears to have an important impact on patient prognosis. In this scenario a number of new drugs targeting different pathways of the immune response are being developed, and some are already available in clinical practice. In clinical practice and in clinical trials, the indications for treating SLE patients with new drugs are active or refractory disease despite standard-of-care treatment. While RCTs are able to document the capacity of new drugs to control the disease in selected patients, many important questions arise from clinical practice and at present are largely unanswered. When should we start a new drug? Should this drug be introduced early, as are anti-TNF drugs in rheumatoid arthritis? Perhaps some drugs should be initiated only after a patient's incomplete response? How many traditional drugs should be used and for how long, before considering a new therapy? Should we stop an effective drug and if yes, when and how? Additional studies and data derived from registries and observational studies will give valuable evidence to answer these questions. In this article, we review indications for the use of new drugs in SLE, and examine existing data on patient outcome after withdrawal, focusing our attention on rituximab and belimumab.
24059264 Genetic diversity in black South Africans from Soweto. 2013 Sep 23 BACKGROUND: Due to the unparalleled genetic diversity of its peoples, Africa is attracting growing research attention. Several African populations have been assessed in global initiatives such as the International HapMap and 1000 Genomes Projects. Notably excluded, however, is the southern Africa region, which is inhabited predominantly by southeastern Bantu-speakers, currently suffering under the dual burden of infectious and non-communicable diseases. Limited reference data for these individuals hampers medical research and prevents thorough understanding of the underlying population substructure. Here, we present the most detailed exploration, to date, of genetic diversity in 94 unrelated southeastern Bantu-speaking South Africans, resident in urban Soweto (Johannesburg). RESULTS: Participants were typed for ~4.3 million SNPs using the Illumina Omni5 beadchip. PCA and ADMIXTURE plots were used to compare the observed variation with that seen in selected populations worldwide. Results indicated that Sowetans, and other southeastern Bantu-speakers, are a clearly distinct group from other African populations previously investigated, reflecting a unique genetic history with small, but significant contributions from diverse sources. To assess the suitability of our sample as representative of Sowetans, we compared our results to participants in a larger rheumatoid arthritis case-control study. The control group showed good clustering with our sample, but among the cases were individuals who demonstrated notable admixture. CONCLUSIONS: Sowetan population structure appears unique compared to other black Africans, and may have clinical implications. Our data represent a suitable reference set for southeastern Bantu-speakers, on par with a HapMap type reference population, and constitute a prelude to the Southern African Human Genome Programme.
24028535 Structure-kinetic relationships--an overlooked parameter in hit-to-lead optimization: a ca 2013 Oct 10 Preclinical models of inflammatory diseases (e.g., neuropathic pain, rheumatoid arthritis, and multiple sclerosis) have pointed to a critical role of the chemokine receptor 2 (CCR2) and chemokine ligand 2 (CCL2). However, one of the biggest problems of high-affinity inhibitors of CCR2 is their lack of efficacy in clinical trials. We report a new approach for the design of high-affinity and long-residence-time CCR2 antagonists. We developed a new competition association assay for CCR2, which allows us to investigate the relation of the structure of the ligand and its receptor residence time [i.e., structure-kinetic relationship (SKR)] next to a traditional structure-affinity relationship (SAR). By applying combined knowledge of SAR and SKR, we were able to re-evaluate the hit-to-lead process of cyclopentylamines as CCR2 antagonists. Affinity-based optimization yielded compound 1 with good binding (Ki = 6.8 nM) but very short residence time (2.4 min). However, when the optimization was also based on residence time, the hit-to-lead process yielded compound 22a, a new high-affinity CCR2 antagonist (3.6 nM), with a residence time of 135 min.
23954699 Osteoimmunology in mucopolysaccharidoses type I, II, VI and VII. Immunological regulation 2013 Dec BACKGROUND: Mucopolysaccharidoses (MPSs) are rare genetic diseases caused by a deficient activity of one of the lysosomal enzymes involved in the glycosaminoglycan (GAG) breakdown pathway. These metabolic blocks lead to the accumulation of GAGs in various organs and tissues, resulting in a multisystemic clinical picture. The pathological GAG accumulation begins a cascade of interrelated responses: metabolic, inflammatory and immunological with systemic effects. Metabolic inflammation, secondary to GAG storage, is a significant cause of osteoarticular symptoms in MPS disorders. OBJECTIVE AND METHOD: The aim of this review is to present recent progress in the understanding of the role of inflammatory and immune processes in the pathophysiology of osteoarticular symptoms in MPS disorders and potential therapeutic interventions based on published reports in MPS patients and studies in animal models. RESULTS AND CONCLUSIONS: The immune and skeletal systems have a number of shared regulatory molecules and many relationships between bone disorders and aberrant immune responses in MPS can be explained by osteoimmunology. The treatment options currently available are not sufficiently effective in the prevention, inhibition and treatment of osteoarticular symptoms in MPS disease. A lot can be learnt from interactions between skeletal and immune systems in autoimmune diseases such as rheumatoid arthritis (RA) and similarities between RA and MPS point to the possibility of using the experience with RA in the treatment of MPS in the future. The use of different anti-inflammatory drugs requires further study, but it seems to be an important direction for new therapeutic options for MPS patients.
23886473 Citalopram suppresses thymocyte cytokine production. 2013 Sep 15 Antidepressant drugs, in particular those targeting the serotonin (5-HT)-reuptake system via the serotonin transporter (5-HTT), are known to exhibit antiinflammatory properties and have demonstrated therapeutic efficacy in rodent models of autoimmune disease like experimental autoimmune encephalomyelitis or experimental rheumatoid arthritis. A crucial difference between animal models and the actual human autoimmune disease is the fact that in animals predominantly induced T cells are studied after sensitization with autoantigen. In humans, however, naturally occurring cytokine-producing T cells might play a significant role as well. For this reason, we investigated the effect of the selective serotonin reuptake inhibitor citalopram on cytokine-producing cells in the thymus of C57BL/6 mice, focusing on the (predominantly) T-cell-produced cytokines IL-2, IL-4 and IL-17. Citalopram was able to strongly reduce the frequency of IL-4- and IL-2-producing cells triggered by CD3 stimulation, but exhibited a less pronounced effect on IL-17-producing cells. 5-HTT expression was found to be very low in thymocytes in comparison with splenocytes, and the effect of free extracellular serotonin on CD3-induced thymocyte cytokine production did not mimic the effect of citalopram. We conclude that citalopram has a potent suppressive effect on cytokine production in the thymus, and that this effect is unlikely to be mediated by elevation of extracellular serotonin levels via the 5-HTT.
23864139 Long-term benefits of radon spa therapy in rheumatic diseases: results of the randomised, 2013 Nov In chronic rheumatic diseases, recent treatment regimens comprise multimodal concepts including pharmacologic, physical/exercise, occupational and psychological therapies. Rehabilitation programmes are used for long-term management of disease. Spa therapy is often integrated in various middle and south European and Asian countries. Here, we investigated radon spa therapy as applied in health resorts compared to a control intervention in rheumatic out-patients. Randomised, blinded trial enroling 681 patients [mean age 58.3 (standard deviation 11.1); female 59.7%] in 7 health resorts in Germany and Austria with chronic back pain (n 1 = 437), osteoarthritis (OA) (n 2 = 230), rheumatoid arthritis (n 3 = 98), and/or ankylosing spondylitis (n 4 = 39); multiple nominations in 146 cases). Outcomes were pain (primary), quality of life, functional capacity, and medication measured before start, after end of treatment, and 3 times thereafter in 3 monthly intervals. Adverse events were documented. To analyse between-group differences, repeated-measures analysis of covariance was performed in metric endpoints and Fisher's exact test in rates. Two-sided significance level of 5% was chosen. Until end of follow-up, superiority of radon therapy was found regarding pain relief (p = 0.032) and analgesic drug consumption (p = 0.007), but not regarding quality of life. Functional capacity was assessed specific to the underlying indication. Significant benefits were found in radon-treated OA patients until 6-month follow-up (p = 0.05), but not until end of study (p = 0.096). Neither the back pain sub-population nor the two smaller patient populations with inflammatory indications benefited significantly in functional capacity. Results suggest beneficial analgesic effects of radon spa therapy in rheumatic diseases until 9 months post-intervention.
23812619 Does enthesopathy relate to M694V gene mutation in patients with Familial Mediterranean fe 2013 Nov Familial Mediterranean fever (FMF) is a systemic hereditary autoinflammatory disorder. The present study aimed to investigate the relationship of enthesitis to FMF and to search the potential association between enthesitis and MEFV gene missense variations in patients with FMF. The study consisted of 72 FMF patients (mean age 29.12 ± 11.47 years, 32 females), 29 patients with ankylosing spondylitis (AS) (mean age 34.14 ± 11.73 years, 16 females), and 34 healthy volunteers (mean age 23.06 ± 6.41 years, 8 females). FMF patients were classified according to the kind of MEFV gene mutation. Doppler ultrasound was used to determine enthesitis based on the Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) scoring system. OMERACT score was significantly different between FMF patients and control group (p < 0.001 in all patients, p = 0.009 in men, and p = 0.002 in women). However, it was not significantly different between FMF and AS patients in both sexes. OMERACT score did not differ between FMF patients with and without M694V gene mutation. The best cutoff point of OMERACT score to predict enthesitis was found as ≥0.5 with sensitivity of 29 %, specificity of 100 %, positive predictive value of 100 %, and negative predictive value of 40 %.
23802098 IL-23R is Epigenetically Regulated and Modulated by Chemotherapy in Non-Small Cell Lung Ca 2013 The Interleukin-23 (IL-23)/IL-23R signaling axis is an important inflammatory pathway, involved in the stimulation and regulation of the T helper (Th) 17 lymphocytes, resulting in the production of IL-17. Aside from auto-immunity, this cytokine has also been linked to carcinogenesis and polymorphisms in the IL-23R gene are associated with an increased risk for the development of a number of different cancers. Activation of the IL-23 pathway results in the up-regulation of STAT3 and it is thought that the pathological consequences associated with this are in part due to the production of IL-17. We have previously identified IL-23A as pro-proliferative and epigenetically regulated in non-small cell lung cancer (NSCLC). The current study aims to evaluate IL-23R in greater detail in NSCLC. We demonstrate that IL-23R is expressed and epigenetically regulated in NSCLC through histone post-translation modifications and CpG island methylation. In addition, Gemcitabine treatment, a chemotherapy drug used in the treatment of NSCLC, resulted in the up-regulation of the IL-23R. Furthermore, Apilimod (STA 5326), a small molecule which blocks the expression of IL-23 and IL-12, reduced the proliferative capacity of NSCLC cells, particularly in the adenocarcinoma (A549) sub-type. Apilimod is currently undergoing investigation in a number of clinical trials for the treatment of auto-immune conditions such as Crohn's disease and Rheumatoid Arthritis. Our results may have implications for treating NSCLC patients with Gemcitabine or epigenetic targeted therapies. However, Apilimod may possibly provide a new treatment avenue for NSCLC patients. Work is currently ongoing to further delineate the IL-23/IL-23R axis in this disease.
23633379 Intra-articular glucocorticoids for acute gout. 2013 Apr 30 BACKGROUND: Although intra-articular glucocorticoids are a commonly used intervention in the treatment of acute gout, there is little evidence to support their safety and efficacy in this setting. OBJECTIVES: To evaluate the safety and efficacy of intra-articular glucocorticoids in the treatment of acute gout. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), Ovid MEDLINE and Ovid EMBASE for studies to 16th October 2012. We also searched the 2010 to 2011 American College of Rheumatology (ACR) and European League against Rheumatism (EULAR) abstracts and performed a handsearch of the reference lists of articles considered for inclusion. SELECTION CRITERIA: Studies were eligible for inclusion if they were randomised controlled trials (RCTs) or controlled clinical trials (CCTs) that used quasi-randomisation methods to allocate participants to treatment and compared intra-articular glucocorticoids to another therapy (active or placebo) in adults with acute gout. Outcomes selected for inclusion were pain, the proportion of participant withdrawals due to adverse events, inflammation, function, patient global assessment of treatment success, quality of life and proportion of particpants with serious adverse events. DATA COLLECTION AND ANALYSIS: Two review authors independently selected the studies for inclusion and planned to extract the data and perform a risk of bias assessment. MAIN RESULTS: No trials were identified that evaluated the efficacy and safety of intra-articular glucocorticoids for acute gout. AUTHORS' CONCLUSIONS: There is presently no evidence from randomised trials to support the use of intra-articular glucocorticoid treatment in acute gout. Evidence suggests intra-articular glucocorticoids may be a safe and effective treatment in osteoarthritis and rheumatoid arthritis. These results may be generalisable to people with acute gout, and the treatment may be especially useful in people when non-steroidal anti-inflammatory drugs or colchicine are contraindicated.
23562586 Monoclonal anti-interleukin-6 receptor antibody attenuates donor-specific antibody respons 2013 Mar Interleukin 6 is an immune regulatory cytokine that impacts the development and maturation of T-cell, B-cell, and antibody producing plasma cells. A monoclonal antibody to the IL-6R (Tocilizumab®) was recently approved by the FDA for treatment of rheumatoid arthritis. Although anti-IL-6R anitbodies can reduce autoantibody levels in human disease, the use of anti-IL-6R for alloantibody suppression has not been examined. Here, we report on our experience with a mousenized rat-anti-mouse IL-6R (mMR16-1) for attenuating donor-specific antibody (DSA) responses. C57BL/6 mice were sensitized with skin allografts from a HLA.A2 transgenic mouse, and treated with intraperitoneal injections of mMR16-1 or control antibody. DSA responses were monitored weekly for 5weeks by measurement of serum anti-HLA.A2 antibodies in a flow cytometric antibody binding assay. Results show that mMR16-1 significantly reduced DSA IgM, IgG2a and IgG1 responses, respectively, while normalizing serum amyloid A (SAA), an acute phase reactant induced by IL-6 (p<0.01 vs. control). mMR16-1 injections increased mononuclear cell apoptosis in the spleens, as detected by annexin V staining and TUNEL. In conclusion, anti-IL6R attenuates de novo DSA responses and suppresses inflammatory markers (SAA). The data indicate that antibody therapy targeting the IL-6/IL-6R pathway may serve as a strategy to suppress DSA generation.
23508984 Increased pulse wave velocity and carotid intima-media thickness in patients with ulcerati 2013 Aug BACKGROUND: Ulcerative colitis (UC) is characterized with chronic, progressive inflammation of the gastrointestinal tract. The association of UC with cardiovascular disease is still a matter of debate. AIM: The aim of this study was to investigate whether carotid intima-media thickness (CIMT) and carotid-femoral pulse wave velocity (cf-PWV) as surrogates of atherosclerosis and arterial stiffness are increased in patients with UC. METHODS: Our study was cross-sectional and observational in design. Baseline characteristics were recorded during interview with the patient. Patients with previous cardiovascular disease, rheumatoid arthritis, chronic renal failure, and infectious and inflammatory disorders other than UC were excluded. Thirty-seven consecutive patients with UC and 30 control participants underwent cf-PWV assessment and CIMT measurement. The diagnosis of UC was based on clinical, radiologic, endoscopic, and histological findings. RESULTS: CIMT, cf-PWV, and C reactive protein were significantly higher in patients with UC. Although linear regression analyses identified UC as an independent predictor of CIMT (β ± SE, 0.39 ± 0.08; p < 0.001), only age independently predicted cf-PWV (β ± SE, 0.08 ± 0.03; p = 0.003) in our study population. Moreover, we revealed higher CIMT and PWV values in patients with higher disease activity and more extensive involvement, compared to patients with mild activity and limited disease. CONCLUSION: We revealed increased pulse wave velocity and CIMT in patients with UC. UC appears to be associated with arterial stiffness and atherosclerotic burden, but the underlying mechanisms require further studies to be identified.
23452869 Clinical factors associated with trabecular bone score. 2013 Jul Dual-energy X-ray absorptiometry (DXA) measurement of bone mineral density (BMD) is the reference standard for diagnosing osteoporosis but does not directly reflect deterioration in bone microarchitecture. The trabecular bone score (TBS), a novel grey-level texture measurement that can be extracted from DXA images, predicts osteoporotic fractures independent of BMD. Our aim was to identify clinical factors that are associated with baseline lumbar spine TBS. In total, 29,407 women ≥50 yr at the time of baseline hip and spine DXA were identified from a database containing all clinical results for the Province of Manitoba, Canada. Lumbar spine TBS was derived for each spine DXA examination blinded to clinical parameters and outcomes. Multiple linear regression and logistic regression (lowest vs highest tertile) was used to define the sensitivity of TBS to other risk factors associated with osteoporosis. Only a small component of the TBS measurement (7-11%) could be explained from BMD measurements. In multiple linear regression and logistic regression models, reduced lumbar spine TBS was associated with recent glucocorticoid use, prior major fracture, rheumatoid arthritis, chronic obstructive pulmonary disease, high alcohol intake, and higher body mass index. In contrast, recent osteoporosis therapy was associated with a significantly lower likelihood for reduced TBS. Similar findings were seen after adjustment for lumbar spine or femoral neck BMD. In conclusion, lumbar spine TBS is strongly associated with many of the risk factors that are predictive of osteoporotic fractures. Further work is needed to determine whether lumbar spine TBS can replace some of the clinical risk factors currently used in fracture risk assessment.
23391629 Open ankle arthrodeses via an anterior approach. 2013 Mar BACKGROUND: In open ankle arthrodesis, debate remains as to which surgical approach and fixation devices should be used. The purpose of this study was to identify union, complication, and patient satisfaction rates of ankle fusions performed at our institution, using the plane between extensor hallucis longus and tibialis anterior with medial tibiotalar screw internal fixation. MATERIALS AND METHODS: A retrospective review was performed of all isolated primary fusions between 2005 and 2009. Eighty-two ankles were identified in 73 patients. All patient records were reviewed, and 57 patients (65 ankles) attended for clinical evaluation and scoring. Age range at surgery was 18 to 75 years (mean, 56.1 years); 8 patients were smokers. Diagnoses were trauma in 52 patients (63%), osteoarthritis in 17, rheumatoid arthritis in 7, Charcot-Marie-Tooth disease in 3, congenital talipes equinovarus in 2, and talar avascular necrosis in 1. Follow-up range was 7 months to 8.3 years (mean, 4 years). RESULTS: Time to union ranged from 8 to 39 weeks (mean, 13.3) with a union rate of 100%. The AOFAS range was 12 to 93 (mean, 70). Eighty percent were "very satisfied" or "satisfied." Major complication rate was 14.6%: 7 malalignments; 3 wound problems; 2 complex regional pain syndrome; and 2 delayed unions, both smokers. CONCLUSIONS: An excellent union rate, high patient satisfaction, and low complication rate were achieved with this technique. Varus malalignment and persistent pain resulted in dissatisfaction. Many patients remained highly active, and bilaterally fused patients functioned as well as unilateral ones. LEVEL OF EVIDENCE: Level IV, retrospective case series.
23357220 Cox-2 gene variants in migraine. 2013 Apr 15 PURPOSE: Migraine is a multifactorial and complex disorder, and any clear diagnostic marker to assess the status of the migraineurs has not been established, yet. Nonsteroidal anti-inflammatory drugs reduce production of prostanoids including PGE2 by inhibiting COX-1 and/or COX-2, and thereby suppress inflammatory pain in patients suffering from rheumatoid arthritis, osteoarthritis, and migraine. Thus, COX-2 regulation is important in the pathogenesis and treatment of migraine. We prospectively investigated COX-2-765G→C and COX-2-1195A→G gene polymorphisms which may account for an increased risk of migraine. METHODS: The present analyses are based on 144 case subjects with migraine disease and 123 non-case subjects. Genotyping of COX-2 gene polymorphisms (COX-2-765G→C, COX-2-1195A→G) was detected by PCR-RFLP. RESULTS: We, for the first time, demonstrated positive association of COX-2 gene variants with an increased risk for development of migraine. Carriers of COX-2-765 C+ genotype in controls were higher than in the patients (57.7% and 36.1% respectively; P<0.0001) and the frequencies of G+ genotype in patients were higher than in the controls (97.9% and 88.6% respectively; P: 0.002). In addition, frequencies of COX-2-765 GG and GC genotypes in patients were higher than in the controls (P<0.0001, P<0.0001 respectively). It seems that COX-2-765 G+ genotype had increased and COX-2-765 C+ genotype had decreased risk for migraine. In COX-2-1195 polymorphism only AG genotype was statistically significantly different in patients than in the controls (P<0.05). CONCLUSIONS: Our findings have suggested that COX-2-765 G+ genotype could facilitate the development of migraine disease.
25383136 Peer mentorship teaches social tools for pain self-management: A case study. 2013 Jan Pain in children can become chronic and disabling, associated with high degrees of social isolation from schooling absences, physical limitations that prevent participation in social settings, and difficulties forming self-identity. This lack of social support network impairs social coping skills and can lead to worsening pain symptoms. OBJECTIVE: In this case study, we describe a new program to disrupt the cycle of social isolation and chronic pain by emphasizing social coping skills via peer mentorship. The program aimed to utilize peers who have learned to self-manage their own chronic pain to assist patients with social coping skills to reduce isolation caused by chronic pain conditions. STUDY GROUP: Children and adolescents with chronic pain. METHODS: This case describes the experience of a 17 year-old, African American boy with diffuse chronic body pain as a participant ("the mentee") in the program; his mentor was a 19 year-old girl with chronic pain associated with rheumatoid arthritis. The mentor received six hours of training and she mentored the patient in 10 weekly sessions. RESULTS: The mentee connected very well with his mentor through sharing similar pain experiences. He demonstrated improvements in positive affect, sleep, social coping, and perception of bodily pain on a variety of quantitative measures. Qualitative data from interviews also suggested that the mentee learned important social coping skills through peer mentorship. CONCLUSIONS: A peer mentoring approach to chronic pain may help alleviate social isolation in adolescents and result in improvements in a number of associated symptoms.
23255063 Anti‑obesity effects of Actinidia polygama extract in mice with high‑fat diet‑induce 2013 Feb Actinidia polygama has been used as a herbal folk medicine for treating pain, gout, rheumatoid arthritis and inflammation. In the present study, the anti‑obesity properties of Actinidia polygama extract (APE) were investigated in mice with high‑fat diet‑induced obesity. APE treatment of high‑fat diet (HFD)‑fed obese mice significantly reduced body weight, adipose tissue mass and serum triglyceride and leptin levels relative to the HFD‑fed mice. Food intake did not differ between the HFD and HFD+APE groups, although the food efficiency ratio (FER) was significantly decreased in the HFD+APE group compared with the HFD group. Histological examination showed that the sizes of the adipocytes were significantly smaller in the HFD+APE group compared with the HFD group. Serum levels of aspartate transaminase were significantly decreased in the HFD+APE mice compared with the HFD‑fed mice, but serum levels of alanine transaminase (ALT), blood urea nitrogen and creatinine were not significantly changed in the HFD+APE mice compared with the levels in the normal diet (ND)‑fed and HFD‑fed mice. These results suggest that APE may be useful for treating metabolic diseases, including obesity and hyperlipidemia, without toxic side‑effects.
23043859 Comparison of indirect immunofluorescence and line immunoassay for autoantibody detection. 2013 Jan OBJECTIVES: The aim of the present paper is to evaluate the diagnostic performance of indirect immunofluorescence (IIF) and line immunoassay (LIA) for autoantibody (autoAb) detection and provide sufficient information to interpret the results of autoAb tests. METHODS: The study included 1,052 patients for whom IIF and LIA tests had been performed simultaneously for a systemic autoimmune disease work-up. All patients were divided into either the systemic autoimmune group or non-autoimmune group, and the systemic autoimmune group was further divided into systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Sjögren's syndrome, systemic sclerosis (SSc), and dermatomyositis/polymyositis (DM/PM). The diagnostic performance of IIF and LIA was analysed according to the distribution of IIF patterns and autoAbs identified by LIA. RESULTS: The overall sensitivity/specificity of IIF and LIA for systemic autoimmune disease was 63.5%/80.3% and 66.1%/83.2%, respectively. IIF showed higher sensitivity for SLE than LIA, but the sensitivity of LIA was higher for Sjögren's syndrome and DM/PM. The speckled pattern was the most commonly observed pattern in systemic autoimmune diseases with the exception of SSc. In the majority of systemic autoimmune diseases and their various IIF patterns, both anti-Ro-52 and anti-SS-A were the most prevalent autoAbs. In addition, a majority of the systemic autoimmune diseases showed specific dominant positive patterns or a combination of IIF and LIA results that were disease specific. CONCLUSIONS: Utilising both methods together not only increased the sensitivity in most cases but also provided more information from the combination of results, augmenting their interpretation with the advantage of simultaneous identification of autoAbs.
22952014 Pharmacological and pathophysiological roles of carnitine/organic cation transporters (OCT 2013 Jan The carnitine/organic cation transporter (OCTN) family consists of three transporter isoforms, i.e. OCTN1 (SLC22A4) and OCTN2 (SLC22A5) in humans and animals and Octn3 (Slc22a21) in mice. These transporters are physiologically essential to maintain appropriate systemic and tissue concentrations of carnitine by regulating its membrane transport during intestinal absorption, tissue distribution and renal reabsorption. Among them, OCTN2 is a sodium-dependent, high-affinity transporter of carnitine, and a functional defect of OCTN2 due to genetic mutation causes primary systemic carnitine deficiency (SCD). Since carnitine is essential for beta-oxidation of long-chain fatty acids to produce ATP, OCTN2 gene mutation causes a range of symptoms, including cardiomyopathy, skeletal muscle weakness, fatty liver and male infertility. These functional consequences of Octn2 gene mutation can be seen clearly in an animal model, jvs mouse, which exhibits the SCD phenotype. In addition, although the mechanism is not clear, single nucleotide polymorphisms of OCTN1 and OCTN2 genes are associated with increased incidences of rheumatoid arthritis, Crohn's disease and asthma. OCTN1 and OCTN2 accept cationic drugs as substrates and contribute to intestinal and pulmonary absorption, tissue distribution (including to tumour cells), and renal excretion of these drugs. Modulation of the transport activity of OCTN2 by externally administered drugs may cause drug-induced secondary carnitine deficiency. Rodent Octn3 transports carnitine specifically, particularly in male reproductive tissues. Thus, the OCTNs are physiologically, pathologically and pharmacologically important. Detailed characterization of these transporters will greatly improve our understanding of the pathology associated with common diseases caused by functional deficiency of OCTNs.