Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
ID | PMID | Title | PublicationDate | abstract |
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29925476 | Autoimmune diseases are associated with an increased risk of schizophrenia: A nationwide p | 2018 Dec | OBJECTIVES: Studies have suggested a possible autoimmune contribution in a subset of patients with schizophrenia. The purpose of this study was to determine if a history of autoimmune diseases (AD) is associated with an increased risk of later onset of schizophrenia. METHODS: Taiwan's National Health Insurance Research Database was used to identify a total of 64,817 AD patients and an equal number of age-matched control patients. The incidence rates of schizophrenia with a maximum follow-up period of 10 years between patients with and without AD were compared using a Cox proportional hazard model to estimate the hazard ratio (HR) and 95% confidence interval (95% CI). RESULTS: The main finding was the discovery of a higher incidence of subsequent schizophrenia in patients with AD (HR: 1.72, 95% CI: 1.23-2.4) after adjustment for other demographic characteristics. Specifically, the risk of schizophrenia was observed to be a significant increase in systemic lupus erythematosus (3.73, 2.07-6.72), rheumatoid arthritis (2.89, 1.97-4.23), dermatomyositis (5.85, 1.32-25.94) and autoimmune vasculitis (2.44, 1.17-5.06). Also, this study revealed some potential risk factors for developing schizophrenia, including younger age (less than or equal to 50 years) and some comorbidities (hypertension, chronic obstructive pulmonary disease, and alcohol use disorder). Conversely, this study found that steroid use was a potential protective factor for the development of schizophrenia. CONCLUSIONS: This study found that AD were associated with an increased risk of developing schizophrenia, suggesting that the abnormal autoimmune process was associated with an increase in the expression of psychiatric disturbances. | |
29843804 | Building a patient-centered and interprofessional training program with patients, students | 2018 May 30 | BACKGROUND: A common approach to enhance patient-centered care is training care professionals. Additional training of patients has been shown to significantly improve patient-centeredness of care. In this participatory design and evaluation study, patient education and medical education will be combined by co-creating a patient-centered and interprofessional training program, wherein patients, students and care professionals learn together to improve patient-centeredness of care. METHODS: In the design phase, scientific literature regarding interventions and effects of student-run patient education will be synthesized in a scoping review. In addition, focus group studies will be performed on the preferences of patients, students, care professionals and education professionals regarding the structure and content of the training program. Subsequently, an intervention plan of the training program will be constructed by combining these building blocks. In the evaluation phase, patients with a chronic disease, that is rheumatoid arthritis, diabetes and hypertension, and patients with an oncologic condition, that is colonic cancer and breast cancer, will learn together with medical students, nursing students and care professionals in training program cycles of three months. Process and effect evaluation will be performed using the plan-do-study-act (PDSA) method to evaluate and optimize the training program in care practice and medical education. A modified control design will be used in PDSA-cycles to ensure that students who act as control will also benefit from participating in the program. DISCUSSION: Our participatory design and evaluation study provides an innovative approach in designing and evaluating an intervention by involving participants in all stages of the design and evaluation process. The approach is expected to enhance the effectiveness of the training program by assessing and meeting participants' needs and preferences. Moreover, by using fast PDSA cycles and a modified control design in evaluating the training program, the training program is expected to be efficiently and rapidly implemented into and adjusted to care practice and medical education. | |
29729412 | Sustained intra-articular release of celecoxib in an equine repeated LPS synovitis model. | 2018 Jul | Synovial inflammation is an important characteristic of arthritic disorders like osteoarthritis and rheumatoid arthritis. Orally administered non-steroidal anti-inflammatory drugs (NSAIDs) such as celecoxib are among the most widely prescribed drugs to manage these debilitating diseases. Intra-articular delivery in biodegradable in situ forming hydrogels overcomes adverse systemic effects and prolongs drug retention in the joint. In this study two formulations of celecoxib (40 mg/g and 120 mg/g) in a propyl-capped PCLA-PEG-PCLA triblock copolymer were sequentially evaluated in a multiple LPS challenge equine synovitis model. Intra-articular release and systemic exposure to celecoxib and local changes at joint level were evaluated longitudinally. A single intra-articular injection of the high dose (HCLB)-gel or low dose (LCLB)-gel showed a sustained and controlled intra-articular release in both inflamed and healthy joints together with very low systemic exposure. Synovitis and lameness were moderate respectively very mild in this model due to the low concentration LPS (0.25 ng/joint). Both celecoxib formulations had a mild, transient effect on inflammatory and structural synovial fluid biomarkers but these returned to baseline within one week of administration. The HCLB-gel showed a significant inhibition in peak white blood cell concentration at 8 h after LPS induction. Elevated levels of celecoxib were observed in the joint for up to 30 days but no overall anti-inflammatory effects could be observed, which was thought to be due to the moderate synovitis. As there were no long-term adverse effects, sustained intra-articular release of celecoxib from in situ forming hydrogels should be evaluated further for its effects on longer-term relief of inflammatory joint pain in humans and animals. | |
29709064 | Effects of moderate intensity static magnetic fields on osteoclastic differentiation in mo | 2018 Jul | Although we recently demonstrated that static magnetic fields (SMFs) of 3, 15, and 50 mT stimulate osteoblastic differentiation, the effects of SMFs on osteoclastogenesis are still poorly understood. This study focused on the suppressive effects of SMFs on receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclastogenesis and bone resorption. Direct SMFs inhibit RANKL-induced multinucleated osteoclast formation, tartrate-resistant acid phosphatase activity, and bone resorption in mouse bone marrow-derived macrophage cells. The conditioned medium from osteoblasts treated with SMFs also resulted in the inhibition of osteoclast differentiation as well as resorption. The RANKL-induced expression of osteoclast-specific transcription factors, such as c-Fos and NFATc1, was remarkably downregulated by SMF at 15 mT. In addition, SMF inhibited RANKL-activated Akt, glycogen synthase kinase 3β (GSK3β), extracellular signal-regulated kinase, c-jun N-terminal protein kinase, mitogen-activated protein kinase (MAPK), and nuclear factor-κB (NF-κB) formation. These findings indicate that SMF-mediated attenuation of RANKL-induced Akt, GSK3β, MAPK, and NF-κB pathways could contribute to the direct and indirect inhibition of osteoclast formation and bone resorption. Therefore, SMFs could be developed as a therapeutic agent against periprosthetic or peri-implant osteolysis. Additionally, these could be used against osteolytic diseases such as osteoporosis and rheumatoid arthritis. Bioelectromagnetics. 39:394-404, 2018. © 2018 Wiley Periodicals, Inc. | |
29705949 | A network map of IL-33 signaling pathway. | 2018 Sep | Interleukin-33 (IL-33) is a member of the IL-1 family of cytokines that play a central role in the regulation of immune responses. Its release from epithelial and endothelial cells is mediated by pro-inflammatory cytokines, cell damage and by recognition of pathogen-associated molecular patterns (PAMPs). The activity of IL-33 is mediated by binding to the IL-33 receptor complex (IL-33R) and activation of NF-κB signaling via the classical MyD88/IRAK/TRAF6 module. IL-33 also induces the phosphorylation and activation of ERK1/2, JNK, p38 and PI3K/AKT signaling modules resulting in the production and release of pro-inflammatory cytokines. Aberrant signaling by IL-33 has been implicated in the pathogenesis of several acute and chronic inflammatory diseases, including asthma, atopic dermatitis, rheumatoid arthritis and ulcerative colitis among others. Considering the biomedical importance of IL-33, we developed a pathway resource of signaling events mediated by IL-33/IL-33R in this study. Using data mined from the published literature, we describe an integrated pathway reaction map of IL-33/IL-33R consisting of 681 proteins and 765 reactions. These include information pertaining to 19 physical interaction events, 740 enzyme catalysis events, 6 protein translocation events, 4 activation/inhibition events, 9 transcriptional regulators and 2492 gene regulation events. The pathway map is publicly available through NetPath ( http://www.netpath.org /), a resource of human signaling pathways developed previously by our group. This resource will provide a platform to the scientific community in facilitating identification of novel therapeutic targets for diseases associated with dysregulated IL-33 signaling. Database URL: http://www.netpath.org/pathways?path_id=NetPath_120 . | |
29663644 | Biomimetic sulfated polyethylene glycol hydrogel inhibits proteoglycan loss and tumor necr | 2019 Apr | This study aimed to evaluate the potential of an anti-inflammatory polyethylene glycol (PEG) hydrogel for osteoarthritis (OA) management in an OA in vitro model. Freshly isolated porcine chondrocytes were maintained in high-density cultures to form cartilage-like three-dimensional micromasses. Recombinant porcine tumor necrosis factor-alpha (TNF-α) was used to induce OA-like changes. Normal and OA-like micromasses were treated with dendritic polyglycerol sulfate-based PEG hydrogel. Live/dead staining showed that all micromasses remained vital and presented similar morphological characteristics. Safranin-O staining demonstrated a typical depletion of glycosaminoglycans in TNF-α-treated micromasses but not in the presence of the hydrogel. There was no distinct difference in immunohistochemical detection of type II collagen. Microarray data showed that rheumatoid arthritis and TNF signaling pathways were down regulated in hydrogel-treated OA-like micromasses compared to nontreated OA-like micromasses. The hydrogel alone did not affect genes related to OA such as ANPEP, COMP, CXCL12, PTGS2, and TNFSF10, but it prevented their regulation caused by TNF-α. This study provides valuable insights toward a fully synthetic hydrogel for the intra-articular treatment of OA. The findings proved the potential of this hydrogel to prevent the development of TNF-α-induced OA with regard to proteoglycan loss and TNF-α-induced expression pattern without additional signs of differentiation and inflammation. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2018. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 490-500, 2019. | |
29551506 | Genome-wide association study in ethnic Russians suggests an association of the MHC class | 2018 Jun 15 | Heredity is a well-known risk factor for varicose veins, but genetic basis of this condition remains poorly studied. Our aim was to conduct a large-scale genetic association study for primary varicose veins (PVVs) in the population of ethnic Russians. An initial scan using Illumina HumanExome-12 v1.0 BeadChip was performed for 273 patients with PVVs and 250 controls without a history of chronic venous disease and other venous disorders. After quality control and removal of monomorphic markers, 25,424 common and 48,232 rare variants were included in the analysis. 42 single nucleotide polymorphisms (SNPs) were genotyped in the independent replication cohort of 447 PVVs patients and 443 controls. Association of common variants with PVVs was investigated by logistic regression, and the impact of rare variants was analyzed using sequence kernel association test. No effect of low frequency alleles has been revealed in our study. Common variant analysis identified a promising signal at chromosome 6 within classical major histocompatibility complex (MHC) class III subregion. The most strongly associated SNP in a combined analysis that reached a suggestive significance level of 3.2e-05 was polymorphism rs4151657 in the complement factor B gene. Testing for potential pleiotropy with other traits indicated that the same causal variant in this region increases the risk of rheumatoid arthritis and has a negative impact on human height. Our results provide suggestive evidence for the involvement of the MHC class III genes in the pathogenesis of PVVs. Further independent studies are needed to confirm our pilot findings. | |
29536646 | Testing the potency of anti-TNF-α and anti-IL-1β drugs using spheroid cultures of human | 2018 Jul | Inflammation plays a major role in progression of rheumatoid arthritis, a disease treated with antagonists of tumor necrosis factor-alpha (TNF-α) and interleukin 1β (IL-1β). New in vitro testing systems are needed to evaluate efficacies of new anti-inflammatory biological drugs, ideally in a patient-specific manner. To address this need, we studied microspheroids containing 10,000 human osteoarthritic primary chondrocytes (OACs) or chondrogenically differentiated mesenchymal stem cells (MSCs), obtained from three donors. Hypothesizing that this system can recapitulate clinically observed effects of anti-inflammatory drugs, spheroids were exposed to TNF-α, IL-1β, or to supernatant containing secretome from activated macrophages (MCM). The anti-inflammatory efficacies of anti-TNF-α biologicals adalimumab, infliximab, and etanercept, and the anti-IL-1β agent anakinra were assessed in short-term microspheroid and long-term macrospheroid cultures (100,000 OACs). While gene and protein expressions were evaluated in microspheroids, diameters, amounts of DNA, glycosaminoglycans, and hydroxiproline were measured in macrospheroids. The tested drugs significantly decreased the inflammation induced by TNF-α or IL-1β. The differences in potency of anti-TNF-α biologicals at 24 h and 3 weeks after their addition to inflamed spheroids were comparable, showing high predictability of short-term cultures. Moreover, the data obtained with microspheroids grown from OACs and chondrogenically differentiated MSCs were comparable, suggesting that MSCs could be used for this type of in vitro testing. We propose that in vitro gene expression measured after the first 24 h in cultures of chondrogenically differentiated MSCs can be used to determine the functionality of anti-TNF-α drugs in personalized and preclinical studies. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 34:1045-1058, 2018. | |
29525348 | Synthesis, molecular docking study and thymidine phosphorylase inhibitory activity of 3-fo | 2018 Aug | Thymidine phosphorylase (TP) over expression plays role in several pathological conditions, such as rheumatoid arthritis, chronic inflammatory diseases, psoriasis, and tumor angiogenesis. The inhibitor of this enzyme plays an important role in preventing the serious threat due to over expression of TP. In this regard, a series of seventeenanalogs of 3-formylcoumarin (1-17) were synthesized, characterized by (1)HNMR and EI-MS and screened for thymidine phosphorylaseinhibitory activity. All analogs showed a variable degree of thymidine phosphorylase inhibition with IC(50) values ranging between 0.90 ± 0.01 and 53.50 ± 1.20 μM when compared with the standard inhibitor 7-Deazaxanthine having IC(50) value 38.68 ± 1.12 μM. Among the series, fifteenanalogs such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 15, 16 and 17 showed excellent inhibition which is many folds better than the standard 7-Deazaxanthine whiletwo analogs 13 and 14 showed good inhibition. The structure activity relationship (SAR) was mainly based upon by bring about difference of substituents on phenyl ring. Molecular docking study was carried out to understand the binding interaction of the most active analogs. | |
29444435 | PTPN2 Regulates Inflammasome Activation and Controls Onset of Intestinal Inflammation and | 2018 Feb 13 | Variants in the gene locus encoding protein tyrosine phosphatase non-receptor type 2 (PTPN2) are associated with inflammatory disorders, including inflammatory bowel diseases, rheumatoid arthritis, and type 1 diabetes. The anti-inflammatory role of PTPN2 is highlighted by the fact that PTPN2-deficient mice die a few weeks after birth because of systemic inflammation and severe colitis. However, the tissues, cells, and molecular mechanisms that contribute to this phenotype remain unclear. Here, we demonstrate that myeloid cell-specific deletion of PTPN2 in mice (PTPN2-LysMCre) promotes intestinal inflammation but protects from colitis-associated tumor formation in an IL-1β-dependent manner. Elevated levels of mature IL-1β production in PTPN2-LysMCre mice are a consequence of increased inflammasome assembly due to elevated phosphorylation of the inflammasome adaptor molecule ASC. Thus, we have identified a dual role for myeloid PTPN2 in directly regulating inflammasome activation and IL-1β production to suppress pro-inflammatory responses during colitis but promote intestinal tumor development. | |
29409496 | Gold nanoparticles improve metabolic profile of mice fed a high-fat diet. | 2018 Feb 6 | BACKGROUND: Obesity is a high risk for multiple metabolic disorders due to excessive influx of energy, glucose and lipid, often from a western based diet. Low-grade inflammation plays a key role in the progression of such metabolic disorders. The anti-inflammatory property of gold compounds has been used in treating rheumatoid arthritis in the clinic. Previously we found that pure gold nanoparticles (AuNPs, 21 nm) also possess anti-inflammatory effects on the retroperitoneal fat tissue following intraperitoneal injection, by downregulating tumor necrosis factor (TNF) α. However, whether such an effect can change the risk of metabolic disorders in the obese has not been well studied. The study employed C57BL/6 mice fed a pellet high fat diet (HFD, 43% as fat) that were treated daily with AuNPs [low (HFD-LAu) or high (HFD-HAu) dose] via intraperitoneal injection for 9 weeks. In the in vitro study, RAW264.7 macrophages and 3T3-L1 adipocytes were cultured with low and high concentrations of AuNPs alone or together. RESULTS: The HFD-fed mice showed a significant increase in fat mass, glucose intolerance, dyslipidemia, and liver steatosis. The HFD-LAu group showed an 8% reduction in body weight, ameliorated hyperlipidemia, and normal glucose tolerance; while the HFD-HAu group had a 5% reduction in body weight with significant improvement in their glucose intolerance and hyperlipidemia. The underlying mechanism may be attributed to a reduction in adipose and hepatic local proinflammatory cytokine production, e.g. TNFα. In vitro studies of co-cultured murine RAW264.7 macrophage and 3T3-L1 adipocytes supported this proposed mechanism. CONCLUSION: AuNPs demonstrate a promising profile for potential management of obesity related glucose and lipid disorders and are useful as a research tool for the study of biological mechanisms. | |
29248714 | FOXQ1/NDRG1 axis exacerbates hepatocellular carcinoma initiation via enhancing crosstalk b | 2018 Mar 28 | Cancer associated fibroblast (CAF) is a well-known microenvironment contributor for the development of hepatocellular carcinoma (HCC), while forkhead box (FOX) proteins are also critical to exacerbate HCC malignancy. However, whether FOX proteins are involved in the crosstalk between CAFs and HCC cells remains unclear. In the present study, we reveal that CAFs induce forkhead box Q1 (FOXQ1) expression, and N-myc downstream-regulated gene 1 (NDRG1) is therefore trans-activated to enhance HCC initiation. Intriguingly, pSTAT6/C-C motif chemokine ligand 26 (CCL26) signaling is induced by FOXQ1/NDRG1 axis, thus recruiting hepatic stellate cells (HSCs), the main cellular source of CAFs, to the tumor microenvironment. Thereby, tumor initiating properties are enhanced at least partly through a positive feedback loop between CAFs and HCC cells. Importantly, leflunomide, a pSTAT6 inhibitor that has been approved for the treatment of rheumatoid arthritis, significantly blocks the loop and HCC progression. High expression of CAF marker, ACTA2, and induced FOXQ1/NDRG1 axis in HCC tissues predict unfavorable prognosis. Collectively, our findings uncover a positive feedback loop between CAFs and FOXQ1/NDRG1 axis in neoplastic cells to drive HCC initiation, thus providing new potential therapeutic targets for HCC. | |
29214470 | Clinical and anti-aging effect of mud-bathing therapy for patients with fibromyalgia. | 2018 Jul | Spa bathing is known as a medical treatment for certain diseases causing chronic pains. Spa water contains mineral components which lower the specific heat of the water, resulting in a higher efficiency to warm body-core temperature. This phenomenon yields pain-relieving effect for rheumatoid arthritis, low back pain, sciatic neuralgia, fibromyalgia, etc. Here we introduce medical and biological effects of mud-spa-bathing therapy for fibromyalgia other than pain relief, the changes of blood examination data, and the telomere length of circulating leukocytes. The enrolled 7 patients with fibromyalgia syndrome were hospitalized and were subject to daily mud bathing at 40 °C for 10 min for about a month. Then, their subjective pain was reduced to about a quarter in average. They also showed lowered serum triglyceride and C-reactive protein level, maintaining the levels of aspartate transaminase and creatine phosphokinase, and increases of the red blood cell count, the serum albumin level, and the serum LDL-cholesterol level in comparison with cases without mud-bathing therapy, suggesting that mud bathing prevents inflammation and muscle atrophy and improves nutritional condition in fibromyalgia. In addition, the analysis of telomere length of peripheral leukocytes revealed a trend of negative correlation between telomere shortening and laboratory data change of hemoglobin and serum albumin. These telomeric changes can be explained hypothetically by an effect of mud bathing extending life-span of circulating leukocytes. | |
29983171 | Hip fractures in the non-elderly-Who, why and whither? | 2018 Aug | Nonelderly hip fracture patients have gathered little scientific attention, and our understanding of the group may be biased by patient case-mix and lack of follow-up. Preconceptions may thwart adequate investigation of bone health and other comorbidities. This literature review focusses on who these patients between 20 and 60 years are, how to treat them and how to evaluate the outcome. 2-11% of the hip fractures occur in non-elderly, equally common in men and women. Every second to forth patient smoke, have chronic diseases, and abuse alcohol. Poor self-rated health, sleep disturbances, low cognitive function and education are associated with increased hip fracture risk in young adults. Bone health is poorly investigated, but literature suggest young patients to have lower bone mineral density regardless of trauma mechanism. Studies contradict on whether surgery within 8-12 h reduce the risk of avascular necrosis in femoral neck fractures (FNF). Based on rationality, surgery ought to be performed promptly, in order to reduce pain and permit rehabilitation. There is no convincing support from the existing literature to use open reduction. Good reduction is mandatory, preferably using a closed reduction technique. The failure rate following internal fixation of displaced FNF in younger patients can be as high as 59%. In some cases a displaced FNF is better treated with a primary arthroplasty; in case of rheumatoid arthritis or osteoarthritis for example. Complications after extracapsular fractures vary from 6 to 23%. The relatively few studies looking at functional outcome in non-elderly use a multitude of outcome measures, precluding comparisons. Many non-elderly patients seem not to fully recover. While some non-elderly hip fracture patients are healthy individuals sustaining high energy trauma, others have low-energy fractures and comorbidities including reduced bone strength (either as a primary or secondary condition). i.e. non-delaying medical optimization, proper surgical technique, bone health investigation and secondary fracture prevention is necessary. Younger hip fracture patients are at risk of permanent loss of function, and negative socioeconomic and psychological consequences. High-energy trauma does not exclude the presence of osteopenia. A hip fracture in adulthood and middle-age is very seldom caused by bad luck only! | |
28556961 | Hydroxychloroquine affects bone resorption both in vitro and in vivo. | 2018 Feb | We recently showed that patients with primary Sjögren syndrome (pSS) have significantly higher bone mineral density (BMD) compared to healthy controls. The majority of those patients (69%) was using hydroxychloroquine (HCQ), which may have favorable effects on BMD. The aim of the study was to evaluate whether HCQ modulates osteoclast function. Osteoclasts were cultured from PBMC-sorted monocytes for 14 days and treated with different HCQ doses (controls 1 and 5 μg/ml). TRAP staining and resorption assays were performed to evaluate osteoclast differentiation and activity, respectively. Staining with an acidification marker (acridine orange) was performed to evaluate intracellular pH at multiple timepoints. Additionally, a fluorescent cholesterol uptake assay was performed to evaluate cholesterol trafficking. Serum bone resorption marker β-CTx was evaluated in rheumatoid arthritis patients. HCQ inhibits the formation of multinuclear osteoclasts and leads to decreased bone resorption. Continuous HCQ treatment significantly decreases intracellular pH and significantly enhanced cholesterol uptake in mature osteoclasts along with increased expression of the lowdensity lipoprotein receptor. Serum β-CTx was significantly decreased after 6 months of HCQ treatment. In agreement with our clinical data, we demonstrate that HCQ suppresses bone resorption in vitro and decreases the resorption marker β-CTx in vivo. We also showed that HCQ decreases the intracellular pH in mature osteoclasts and stimulates cholesterol uptake, suggesting that HCQ induces osteoclastic lysosomal membrane permeabilization (LMP) leading to decreased resorption without changes in apoptosis. We hypothesize that skeletal health of patients with increased risk of osteoporosis and fractures may benefit from HCQ by preventing BMD loss. | |
30508984 | Are Pain Beliefs, Cognitions, and Behaviors Influenced by Race, Ethnicity, and Culture in | 2018 Nov | BACKGROUND: Chronic pain has been considered as a biopsychosocial condition in which cognitive and emotional factors as well as biological factors significantly affect perception of pain. Race, ethnicity and culture have a crucial impact on illness beliefs, health care preferences, help-seeking behaviors, and acceptance of medical interventions. OBJECTIVES: The aim of the present study was to systematically review the current evidence regarding the racial, ethnic and cultural alterations and differences in pain beliefs, cognitions, and behaviors in patients with chronic musculoskeletal pain (MSKP). STUDY DESIGN: Systematic review. METHODS: This systematic review was conducted and reported in accordance with the Preferred Reporting Items for Systematic reviews and Meta-analyses guidelines (PRISMA). PubMed and Web of Science were searched. A first screening was conducted based on title and abstract of the articles. In the second screening, full-texts of the remaining articles were evaluated for the fulfilment of the inclusion criteria. The risk of bias was assessed with the modified Newcastle-Ottawa Scale. RESULTS: A total of 11 articles were included. The methodological quality of the included studies ranged from low to moderate. There is moderate evidence that African-Americans use more praying, hoping, and emotion-focused coping strategies than Caucasians. There is also preliminary evidence regarding the differences in some coping strategies such as distraction, catastrophizing, and problem-focused solving between African-Americans and Caucasians. Preliminary evidence exists regarding the differences in pain coping strategies between the US and Portugal; the US and Singapore; and among 4 French-speaking countries. It is found that Spanish patients with fibromyalgia (FM) have more negative illness perceptions than Dutch patients. There is preliminary evidence that Caucasians have higher self-efficacy than African-Americans. There is also preliminary evidence that New Zealanders have more internal health expectancies than patients from the US. Preliminary evidence is demonstrated that Caucasians with rheumatoid arthritis (RA) have more positive control beliefs than African-Americans. Lastly, there is preliminary evidence that patients from the US believe that they are more disabled, while Singaporeans interpret the pain more by a traditional biomedical perspective. LIMITATIONS: Only 11 articles were included. The small number of articles, wide range of assessment methods, and substantial risk of bias in the included studies led the investigator to draw conclusions cautiously. CONCLUSION: Preliminary to moderate evidence shows the differences in coping strategies, illness perceptions, self-efficacy, fear avoidance beliefs, locus of control, and pain attitudes in different populations. Further prospective and longitudinal studies using standard definitions for race, ethnicity or culture and valid questionnaires for each population are warranted to explore the racial, ethnic and cultural discrepancies in pain beliefs, cognitions, and behaviours. KEY WORDS: Chronic pain, musculoskeletal pain, pain beliefs, pain cognitions, pain behaviors, race, ethnicity, culture. | |
30458182 | Anti-inflammatory effects of Ang-(1-7) via TLR4-mediated inhibition of the JNK/FoxO1 pathw | 2019 Mar | Targeting inflammation is considered a challenging pharmacological strategy to prevent or delay the development of inflammatory diseases, such as severe asthma, Crohn's disease, and rheumatoid arthritis. The angiotensin-(1-7) -Mas axis ((Ang-(1-7)-Mas axis) was confirmed to antagonize the effects of the Angiotensin II-AT(1) receptor axis and the latter is reported to regulate cardiovascular and renal function, as well as contribute to the inflammatory process. In this paper, we aim to explore the crucial effect of Ang-(1-7) in inflammation and disclose the mechanisms in lipopolysaccharide (LPS)-induced murine macrophages RAW264.7. We found that Ang-(1-7) inhibited the production and secretion of tumor necrosis factor-α and interleukin-6 in a concentration-dependent manner in LPS-induced macrophages. The overexpression of TLR4, phospho-JNK, and FoxO1 induced by LPS were also inhibited by incubation with Ang-(1-7). These inhibitory effects were reversed by A-779. Moreover, we also used a selective JNK inhibitor Sp600125 to further corroborate the involvement of TLR4, JNK, and FoxO1 in the anti-inflammatory action of Ang-(1-7). Our research reveals a new mechanism that Ang-(1-7) may drive anti-inflammatory effects via the Mas receptor through inhibition of the TLR4-mediated JNK/FoxO1 signaling pathway in LPS-induced macrophages. Our findings open new perspectives of Ang-(1-7)-Mas axis in local inflammation. | |
30347274 | Preparation, characterization, and evaluation of celecoxib eutectic mixtures with adipic a | 2019 Jan 10 | Celecoxib (CEL) is a selective cyclooxygenase-2 (COX-2) inhibitor therapeutically indicated for the treatment of rheumatoid arthritis, osteoarthritis, acute pain, and inflammation. However, its poor solubility and dissolution rate significantly hinders its broader application. In this study, eutectic mixtures, as binary pharmaceutical compositions of CEL with adipic acid (ADI) and saccharin (SAC), were identified through a phase diagram and Tammann's triangle intended to improve the wettability and dissolution rate of poorly water-soluble CEL. The contact angles at 0s in the liquid-solid interface were approximately θs (theta) 79.7 ± 0.50° and 86.65 ± 0.45° for CEL-ADI and CEL-SAC, respectively, which were much lower than the value obtained for CEL (92.05 ± 0.75° θ). Moreover, a comparison of the disk intrinsic dissolution rate and powder dissolution properties demonstrated that eutectic mixtures significantly increased the dissolution rate compared with CEL and physical mixtures. A general relationship was elucidated and indicated that the dissolution rate was increased as the contact angle decreased (correlation coefficient, r = 0.9966 ± 0.0031). Therefore, CEL-ADI and CEL-SAC eutectics may offer a novel formulation strategy to enhance the solubility and oral bioavailability of CEL. | |
30295599 | [Interposition and Suspension Arthroplasty of Carpometacarpal Joint of the Thumb Using the | 2018 | PURPOSE OF THE STUDY The aim of the study was to present the surgical technique combining the interposition and suspension arthroplasty using the TIE-IN implant as a treatment option for advanced symptomatic to final stage rhizarthrosis. MATERIAL AND METHODS Since 2015 we have performed the interposition arthroplasty combined with suspension arthroplasty using the TIE-IN implant in 12 patients, mostly indicated for stage IV rhizarthrosis. In two cases stage III rhizarthrosis with concomitant trapezium destruction was present. In two other cases the patients suffered from secondary osteoarthrosis associated with rheumatoid arthritis. Pain under loads was present in all the patients, of whom in 10 patients also the pain at rest occurred. Preoperatively, a total of 10 patients showed subluxation of the first carpometacarpal joint of 50% of the articular surface width. The ratio between the dominant and non-dominant extremity was 1:1. As a part of the evaluation, correlation was established between the preoperative findings and the postoperative results at 3 months follow-up. The examination included the assessment of pain intensity by VAS scale, the range of motion measurement - by Kapandji thumb opposition test, handgrip strength test and functional evaluation using the scoring systems - DASH score, modified DASH score for thumb, and modified Wrightington score. RESULTS No intraoperative or postoperative complications such as infection, complex regional pain syndrome, implant failure or failed surgical procedure were reported in the given group of patients. The pain at rest ceased in all 12 patients. The VAS pain intensity score improved from the preoperative average of 5.8 to 0.8 postoperatively. The range of motion in all the patients with stage IV rhizarthrosis substantially improved. The average Kapandji thumb opposition score increased from 6.9 preoperatively to 9.5 postoperatively. DISCUSSION There are multiple surgical treatment options for advanced rhizarthrosis. Apart from the combination of interposition and suspension arthroplasty referred to above, it is trapeziometacarpal (TMC) arthrodesis on the one hand and carpometacarpal joint total arthroplasty on the other hand. The arthrodesis continues to be a fairly frequently used procedure, despite the final limitation of thumb movement. It is because of this loss of fine motor function why it is not the preferred technique for treating advanced rhizarthrosis at our department. On the very contrary, the total replacement of the TMC joint is at our department as well as at many other departments the treatment of choice for advanced symptomatic rhizarthrosis since in conservative resection of the articular surfaces the biomechanics of the carpometacarpal joint of the thumb is preserved. As an outcome, this technique combines the advantages of other surgical methods by ensuring full painless range of motion and strength of the joint as opposed to other techniques, which mostly result either in a limited movement, or in a loss of grip strength. There is a whole range of resection arthroplasty techniques available. From simple trapeziectomy, which leads to the radial column collapse and ultimately to a major functional deficit, up to various interposition or suspension arthroplasty techniques with the resulting range of motion, stability and thus grip strength depending on the technique applied. CONCLUSIONS By applying the combination of the interposition and suspension arthroplasty of the carpometacarpal joint of the thumb using the TIE-IN implant we preserve the length of the thumb, its stability, and thus achieve the recovery of adequate thumb range of motion and grip strength. Our conclusions are in correlation with the results obtained at reference centres. Key words:rhizarthrosis, trapeziometacarpal prosthesis, arthroplasty, trapezium implant. | |
30238726 | [Risk factors associated with interleukin 6 level in serum after total knee arthroplasty]. | 2018 Aug 15 | OBJECTIVE: To explore the risk factors associated with interleukin 6 (IL-6) level in serum after total knee arthroplasty (TKA). METHODS: A retrospective study was made on the clinical data of 273 patients underwent primary unilateral TKA between July 2015 and April 2017. There were 50 males and 223 females with an average age of 66.3 years (range, 36-89 years), and the body mass index (BMI) was (25.5±3.7) kg/m (2). Of them, 256 patients suffered with osteoarthritis, and the other 17 patients with rheumatoid arthritis. Univariate analysis was made to find the related factors between IL-6 level in serum at 1 day after operation and preoperative data including gender, age, BMI, diagnosis, comorbidities, preoperative American Society of Anesthesiologists (ASA) grade, preoperative varus or valgus deformity, range of motion of the knee, preoperative level of C-reactive protein (CRP) and IL-6 in serum, operation time, intraoperative blood loss, usage of drainage tube and catheter, and dosage of tranexamic acid and dexamethasone used on day of operation. Furthermore, the multiple linear regression analysis was performed to identify the risk factors. RESULTS: The operation time was (79.7±15.6) minutes, and the intraoperative blood loss was (107.8±25.3) mL. Drainage tubes were used in 111 patients and catheters were used in 41 patients after operation. The dosage of tranexamic acid and dexamethasone used on day of operation were (3.2±0.8) g and (15.1±6.6) mg, respectively. The levels of IL-6 in serum were (4.48±3.05), (42.65±37.09), and (28.21±26.44) pg/mL before operation and at 1 and 3 days after operation, respectively. Univariate analysis showed that the level of IL-6 in serum at 1 day after operation was significantly higher in variables as follows: age, diagnosis, history of lung infection, range of motion, preoperative levels of CRP and IL-6 in serum, intravenous dosage of tranexamic acid and dexamethasone on day of operation ( P<0.05). Multiple linear regression analysis showed that range of motion less than 90°, intravenous dosage of tranexamic acid on day of operation less than 3 g, and dosage of dexamethasone on day of operation less than 10 mg were significant risk factors ( P<0.05). CONCLUSION: Range of motion less than 90°, intravenous dosage of tranexamic acid on day of operation less than 3 g, and dosage of dexamethasone on day of operation less than 10 mg were independent risk factors that resulted in increased level of IL-6 in serum at 1 day after TKA. |