Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
30338656 Prevalence and predictive value of high-positive rheumatoid factor and anti-citrullinated 2019 Jan AIM: In order to increase diagnostic sensitivity for early disease in rheumatoid arthritis (RA), new classification criteria were approved in 2010 by the American College of Rheumatology and the European League Against Rheumatism. One of the criteria, a high-positive rheumatoid factor (RF) or anti-citrullinated protein antibody (ACPA) level, was given a high score of 3. However, the increased prevalence of RF in patients with chronic hepatitis C virus (HCV) infection markedly diminishes the diagnostic specificity of serum RF for RA in these patients. There are no published data on the prevalence and predictive value of high-positive RF and ACPA; thus, we investigated high-positive RF and ACPA levels in nonarthritic patients with chronic HCV infection. METHOD: Anti-citrullinated protein antibody and total RF were determined in serum from nonarthritic patients with chronic HCV infection (all had HCV RNA viremia). RESULT: In 271 HCV-infected patients, positive RF, positive ACPA, high-positive RF, and high-positive ACPA were detectable in 47.2%, 1.1%, 8.9% and 1.1%, respectively. In these patients, fatty liver was an independent factor for high-positive RF. CONCLUSION: In contrast to RF, ACPA is not increased in HCV infection. High-positive RF is not unusually present in nonarthritic patients with chronic HCV infection. ACPA may have improved value for the diagnosis of RA in this patient population. In patients with HCV infection, fatty liver may be a risk factor for high-positive RF.
29925785 Metabolomic Analysis of Biochemical Changes in the Serum and Urine of Freund's Adjuvant-In 2018 Jun 20 Silkworm excrement (SE), is used as a traditional antirheumatic medicine in China. The present study was designed to investigate the therapeutic efficacy of water fraction of SE (ST) and ethanol fraction of SE (CT) at two different doses on adjuvant induced arthritis (AA) rats. Arthritis severity was evaluated by body weight, paw thickness, histological changes and index of paws oedema and spleen. Serum samples were collected for estimation of biochemical indicators and cytokines. In addition, a metabonomic method based on the ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) had been established to investigate the holistic efficacy of SE by serum and urine. Multivariate statistical approaches, such as partial least-squares discriminant analysis (PLS-DA) and orthogonal projection to latent structures squares-discriminant analysis (OPLS-DA) were built to evaluate the therapeutic effects of SE and find potential biomarkers and metabolic pathways. Administration with SE significantly ameliorated the AA severity, including body weight loss, paw swelling, histological changes and the levels of biochemical index. 33 endogenous metabolites had been identified (10 in serum and 23 in urine) in the AA rats. Urinary and serum metabolic profiling revealed that the metabolites underpin the metabolic pathway including nicotinate and nicotinamide metabolism; pentose and glucuronate interconversions; TCA cycle; beta-Alanine metabolism; purine metabolism and glycolysis or gluconeogenesis. The altered metabolites could be regulated closer to normal level after SE intervention. The results suggested SE possesses substantial anti-arthritic activity and demonstrated that metabonomics is a powerful tool to gain insight in the mechanism of SE formula in therapy.
29391796 In vivo therapeutic efficacy of TNFα silencing by folate-PEG-chitosan-DEAE/siRNA nanopart 2018 BACKGROUND: Tumor necrosis factor-alpha (TNFα), a pro-inflammatory cytokine, has been shown to play a role in the pathophysiology of rheumatoid arthritis. Silencing TNFα expression with small interfering RNA (siRNA) is a promising approach to treatment of the condition. METHODS: Towards this end, our team has developed a modified chitosan (CH) nanocarrier, deploying folic acid, diethylethylamine (DEAE) and polyethylene glycol (PEG) (folate-PEG-CH-DEAE(15)). The gene carrier protects siRNA against nuclease destruction, its ligands facilitate siRNA uptake via cell surface receptors, and it provides improved solubility at neutral pH with transport of its load into target cells. In the present study, nanoparticles were prepared with siRNA-TNFα, DEAE, and folic acid-CH derivative. Nanoparticle size and zeta potential were verified by dynamic light scattering. Their TNFα-knockdown effects were tested in a murine collagen antibody-induced arthritis model. TNFα expression was examined along with measurements of various cartilage and bone turnover markers by performing histology and microcomputed tomography analysis. RESULTS: We demonstrated that folate-PEG-CH-DEAE(15)/siRNA nanoparticles did not alter cell viability, and significantly decreased inflammation, as demonstrated by improved clinical scores and lower TNFα protein concentrations in target tissues. This siRNA nanocarrier also decreased articular cartilage destruction and bone loss. CONCLUSION: The results indicate that folate-PEG-CH-DEAE(15) nanoparticles are a safe and effective platform for nonviral gene delivery of siRNA, and their potential clinical applications warrant further investigation.
29681976 Anti-Inflammatory Effects of p-Coumaric Acid, a Natural Compound of Oldenlandia diffusa, o 2018 OBJECTIVES: In China, Oldenlandia diffusa (OD) is a natural herb that is widely used and has been proven to be effective in the treatment of rheumatoid arthritis (RA). This study aimed to preliminarily reveal the mechanism by which OD exerts its beneficial effect. METHODS: Ultra-performance liquid chromatography photodiode array was applied to identify the absorbable compounds in the plasma of collagen-induced arthritis (CIA) model rats. After 2 weeks, an OD decoction or the identified absorbable compound was administered to CIA rats. Morphology, X-ray images of the joints, pathological images, arthritis index, and cytokine (TNF-α and IL-6) levels were evaluated. RESULTS: p-Coumaric acid (p-CA) was identified as the absorbed compound in plasma. After administration of p-CA solution or the OD decoction, symptoms in the treated rats were alleviated as compared to the untreated model rats, and inflammatory cell infiltration was suppressed. The arthritis index and serum levels of TNF-α and IL-6 were decreased as compared to the control group. CONCLUSIONS: OD may exert its anti-inflammatory effect on RA via its active ingredient, p-CA. This information sheds light on the mechanism by which OD exerts its anti-inflammatory effort in RA and forms the basis for further development of therapeutic agents for RA.
30232853 [Fire-needle Acupuncture Intervention Relieves Ankle-joint Inflammatory Reactions Possibly 2018 Aug 25 OBJECTIVE: To observe the effect of fire-needle acupuncture of "Zusanli" (ST 36) and "Kunlun" (BL 60) on ankle-joint swelling and serum tumor necrosis factor-α (TNF-α) and anti-cyclic citrullinated peptide antibody (ACPA) contents in collagen-induced arthritis (CIA) rats, so as to study its mechanism underlying improvement of rheumatoid arthritis (RA)．. METHODS: Thirty-two male Wistar rats were randomized into control, model, medication (Methotrexate) and fire-needling groups (n＝8 in each). The RA model was established by injecting type Ⅱ chicken collagen (0.1 mol/L) plus Freund's complete adjuvant (primary immunization) and Freund's incomplete adjuvant (immunization once more) into the subcutaneous tissues of the right foot bottom, back and tail root of rats. Fire-needling was applied to the left and right "Zusanli" (ST 36) and "Kunlun" (BL 60) alternatively for 3 times in each acupoint, once daily for 10 days. For rats of the medication group, Methotrexate sodium chloride solution (0.1 mg/100 g) was administrated by gavage, once every 5 days, twice together. The rats' right hind ankle diameter was measured before and after the treatment. The X-ray film of the right ankle was taken, and the contents of serum TNF-α and ACPA were assayed by ELISA. RESULTS: The ankle diameter and serum concentrations of TNF-α and ACPA were significantly increased in the model group compared to the control group (P<0.05), and X-ray film showed swollen and deformed tarsus joints, and narrowing of the joint space. After the intervention, the ankle diameter, serum TNF-α and ACPA levels were considerably decreased in both medication and fire-needle groups compared with the model group (P<0.05). Meanwhile, the joint swelling and bone deformity became relatively milder. There were no significant differences between the medication and fire-needling groups in the ankle diameter and the contents of serum TNF-α and ACPA (P>0.05). CONCLUSION: Fire-needling stimulation of ST 36 and BL 60, similar to Methotrexate, can relieve the inflammatory reactions of hind-ankle joint in CIA rats, which may be related to its effect in down-regulating ACPA and TNF-α levels.
30024392 Assessment of subclinical atherosclerosis in psoriatic arthritis patients without clinical 2018 Jul OBJECTIVE: Cardiovascular disease (CVD) is more prevalent in almost all patients with chronic inflammatory musculoskeletal diseases than in their healthy counterparts. The aim of this study was to assess the presence of subclinical atherosclerosis in patients with psoriatic arthritis (PsA) in comparison with patients with rheumatoid arthritis (RA) and healthy controls. METHODS: A total of 30 patients with PsA, 30 patients with RA, and 30 healthy controls were enrolled in this parallel group study. Demographic, clinical, and laboratory data of the groups were recorded. The Disease Activity Score-28 tool was used for joint assessment. The erythrocyte sedimentation rate and C-reactive protein level were measured as acute phase reactants. Flow-mediated dilatation (FMD) and carotid intima media thickness (CIMT) were also measured in all participants. RESULTS: The median duration of disease in patients with PsA was 60 months (range: 8-216 months). A total of 22 of 30 (73.3%) PsA patients had a diagnosis of psoriasis and 13 (48.1%) had active disease. The study groups were similar with regard to age, gender, and body mass index data. In all, 23 (76.7%) of the PsA patients and 5 (16.7%) of the RA patients were using an anti-tumor necrosis factor alpha therapy (p<0.001). The FMD percentage was significantly smaller in both the PsA and the RA patients than in the healthy controls (p<0.001). The median CIMT was greater in the RA patients compared with the PsA patients and the healthy controls (p=0.008). There was no significant difference in FMD or CIMT between patients with and without an active joint lesion. CONCLUSION: Endothelial functions were impaired in PsA, as in RA, in the absence of conventional risk factors or overt CVD. This finding may show a potential association between PsA, atherosclerosis, and CVD.
29773000 Evaluation of Antiarthritic Activity of Butanol Fraction of Punica granatum Linn. Rind Ext 2018 Available conventional drugs produce several side effects; thus, a potent herbal drug is urgently required for the management of rheumatoid arthritis. The present investigation was performed to evaluate the antiarthritic activity of butanol fraction of Punica granatum Linn. rind methanolic extract (PGBF) against Freund's complete adjuvant (FCA)-induced arthritis in rats. An acute toxicity study of butanol fraction was conducted, accompanied by a study of its antiarthritic activity. Chromatography (thin layer chromatography and high-performance thin layer chromatography) analyses were also conducted. Phytochemical screening of the fraction was performed to confirm the presence of phytoconstituents. For antiarthritic activity, the active butanol fraction was administered at doses of 50 and 75 mg/kg body weight. The antiarthritic activity was evaluated by using biophysical paramaters (arthritic score, body weight, paw volume and joint diameter) and hematological parameters [red blood cell (RBC) count, white blood cell (WBC) count, hemoglobin (Hb) concentration and erythrocyte sedimentation rate (ESR)]. Dexamethasone (5 mg/kg) was selected as the standard. Phytochemical screening of butanol fraction showed the presence of steroids, tannins, flavonoids, irioid glycosides, and phenolic compounds. Acute toxicity studies suggested that butanolic fraction was safe up to a dose of 500 mg/kg. The data regarding biophysical and hematological parameters clearly indicated that the butanol fraction at a 75 mg/kg dose showed a more significant effect (**P<0.01 and ***P<0.001) than the 50 mg/kg dose. The antiarthritic potential of a butanol fraction of Punica granatum Linn. rind extract may be due to the presence of active phytoconstituents such as flavonoids, irioid glycosides, and phenolic compounds. Future studies will provide a new approach in relation to the antiarthritic activity of Punica granatum Linn., and the isolation of its active compound may eventually lead to the development of a new category of the antiarthritic agent.
29375397 The Cerebral Brain-Derived Neurotrophic Factor Pathway, Either Neuronal or Endothelial, Is 2017 Cognitive abilities are largely dependent on activation of cerebral tropomyosin-related kinase B receptors (TrkB) by brain-derived neurotrophic factor (BDNF) that is secreted under a bioactive form by both neurons and endothelial cells. In addition, there is mounting evidence for a link between endothelial function and cognition even though the underlying mechanisms are not well known. Therefore, we investigated the cerebral BDNF pathway, either neuronal or endothelial, in rheumatoid arthritis (RA) that combines both endothelial dysfunction (ED) and impaired cognition. Adjuvant-induced arthritis (AIA) in rats was used as a model of RA. Clinical inflammatory symptoms were evaluated from an arthritis score and brains were collected at day 31 ± 2 post-immunization. Neuronal expression of BDNF and TrkB phosphorylated at tyrosine 816 (p-TrkB) was examined in brain slices. Endothelial BDNF and p-TrkB expression was examined on both brain slices (hippocampal arterioles) and isolated cerebral microvessels-enriched fractions (vessels downstream to arterioles). The connection between endothelial nitric oxide (NO) and BDNF production was explored on the cerebrovascular fractions using endothelial NO synthase (eNOS) levels as a marker of NO production, N(ω)-Nitro-L-arginine methyl ester hydrochloride (L-NAME) as a NOS inhibitor and glyceryl-trinitrate as a slow releasing NO donor. Brain slices displayed lower BDNF and p-TrkB staining in both neurons and arteriolar endothelial cells in AIA than in control rats. For endothelial cells but not neurons, a strong correlation was observed between BDNF and p-TrkB staining. Of note, a strong correlation was also observed between neuronal p-TrkB and endothelial BDNF staining. In cerebral microvessels-enriched fractions, AIA led to decreased BDNF and eNOS levels with a positive association between the 2 parameters. These effects coincided with decreased BDNF and p-TrkB staining in endothelial cells. The exposure of AIA cerebrovascular fractions to GTN increased BDNF levels while the exposure of control fractions to L-NAME decreased BDNF levels. Changes in the cerebral BDNF pathway were not associated with arthritis score. The present study reveals that AIA impairs the endothelial and neuronal BDNF/TrkB pathway, irrespective of the severity of inflammatory symptoms but dependent on endothelial NO production. These results open new perspectives for the understanding of the link between ED and impaired cognition.
29757957 Arthroprotective Effects of Cf-02 Sharing Structural Similarity with Quercetin. 2018 May 14 In this study, we synthesized hundreds of analogues based on the structure of small-molecule inhibitors (SMIs) that were previously identified in our laboratory with the aim of identifying potent yet safe compounds for arthritis therapeutics. One of the analogues was shown to share structural similarity with quercetin, a potent anti-inflammatory flavonoid present in many different fruits and vegetables. We investigated the immunomodulatory effects of this compound, namely 6-(2,4-difluorophenyl)-3-(3-(trifluoromethyl)phenyl)-2H-benzo[e][1,3]oxazine-2,4(3H)-dione (Cf-02), in a side-by-side comparison with quercetin. Chondrocytes were isolated from pig joints or the joints of patients with osteoarthritis that had undergone total knee replacement surgery. Several measures were used to assess the immunomodulatory potency of these compounds in tumor necrosis factor (TNF-α)-stimulated chondrocytes. Characterization included the protein and mRNA levels of molecules associated with arthritis pathogenesis as well as the inducible nitric oxide synthase (iNOS)⁻nitric oxide (NO) system and matrix metalloproteinases (MMPs) in cultured chondrocytes and proteoglycan, and aggrecan degradation in cartilage explants. We also examined the activation of several important transcription factors, including nuclear factor-kappaB (NF-κB), interferon regulatory factor-1 (IRF-1), signal transducer and activator of transcription-3 (STAT-3), and activator protein-1 (AP-1). Our overall results indicate that the immunomodulatory potency of Cf-02 is fifty-fold more efficient than that of quercetin without any indication of cytotoxicity. When tested in vivo using the induced edema method, Cf-02 was shown to suppress inflammation and cartilage damage. The proposed method shows considerable promise for the identification of candidate disease-modifying immunomodulatory drugs and leads compounds for arthritis therapeutics.
29804078 Spinal tophaceous gout presenting in a young adult without pain. 2018 May 26 A 26-year-old man with a medical history of gout and morbid obesity presented with a 7-day history of decreased sensation to light touch and temperature from the feet to the level of the nipples. He also noted incomplete voiding. Laboratory investigations showed an elevated serum uric acid level (10.4 mg/dL, reference range: 3.8-8.7 mg/dL) as well as negative rapid plasma reagin and rheumatoid factor. MRI showed inflammatory changes on multiple spinal levels. Laminectomy was performed, with follow-up biopsy revealing multiple multinucleated giant cells and monosodium urate (MSU) crystals. He was ultimately diagnosed with spinal gout. Patient's symptoms did not resolve immediately after surgery. Yet with the administration of intravenous glucocorticoids and a course of non-steroidal anti-inflammatory drugs, he slowly regained sensation, leaving the hospital with complete resolution of symptoms.
30244460 RNA Interference Ex Vivo. 2018 RNA interference (RNAi) is a widely used technique to regulate the expression of genes and proteins with a high degree of specificity that is not easily accessed by traditional pharmacological approaches. For preclinical research on rheumatoid arthritis (RA), silencing of target genes in primary immune cells can be easily achieved by application of small interfering RNA (siRNA) and synthetic short hairpin RNA (shRNA). Cellular and systemic administration of siRNA or shRNA has been a significant advance in preclinical research on RA. In this chapter, the basic techniques for gene silencing in human-derived peripheral T cells using liposome-dependent siRNA transfection and lentiviral-mediated shRNA delivery, aiming at gene silencing of therapeutic targets, are introduced.
29953985 Effective Desensitization to Tocilizumab in Delayed Hypersensitivity Reaction. 2018 We present tocilizumab desensitization of a 47-year-old woman affected by rheumatoid arthritis with full body delayed erythematous urticarial reaction. Skin test for tocilizumab gave cutaneous reaction after 6 h at 20 mg/mL. The schedule of desensitization was then adapted for non-immediate reaction. We prepared a desensitization procedure reaching the cumulative dose of 516 mg in 5 weeks. After 6 months, the repetition of skin tests had a negative result, with demonstration of tolerance induction. Today the patient has good control of the disease.
29650849 [A Case of Resected Reactive Lymphoid Hyperplasia of Liver Suspected of Hepatocellular Car 2018 Apr A 64-year-old woman who had chronic type C viral hepatitis was referred with a liver tumor detected by magnetic resonance imaging(MRI). She had a history of rheumatoid arthritis which was treated by methotrexate. Ethoxybenzyl-MRI(EOBMRI) showed a low signal in the T1-weighted imaging, a high signal in the T2-weighted imaging and a low signal in the hepatobiliary phase. The tumor was 7 millimeters in diameter at S4, and exhibited enhancement in the arterial phase and wash out in the portal phase by contrast enhanced CT. Imaging findings suggested hepatocellular carcinoma, and we performed partial hepatectomy of S4. Histopathological examination confirmed reactive lymphoid hyperplasia(RLH)of liver. RLH of liver is a rare benign lesion and it is necessary to consider RLH as a differential diagnosis of the liver tumor.
29636683 Yi Shen Juan Bi Pill Ameliorates Bone Loss and Destruction Induced by Arthritis Through Mo 2018 The Yi Shen Juan Bi Pill (YSJB), a traditional Chinese compound herbal drug, has been used as an anti-rheumatic drug in clinical practice. Cartilage and bone destruction of inflamed joints is the hallmark of rheumatoid arthritis (RA). Our previous study suggested that YSJB had a protective effect on joint damage in collagen-induced (CIA) rats. However, the role and the mechanism of YSJB in inflammation-induced bone loss are unavailable. The current study aimed to further evaluate the effect of YSJB on the joint destruction and the systemic bone loss, and to clarify the potential mechanism. CIA model was generated by using collagen II and incomplete Freund's adjuvant in Sprague-Dawley rats. After 4 weeks treatment, arthritic index, tissue pathology, micro-computed tomography scanning (μ-CT), and bone mineral density (BMD) analysis were performed. YSJB decreased arthritic scores and bone destruction; improved the BMD of lumbar vertebrae and bone volume fraction of inflamed joints. Moreover, YSJB significantly decreased the production of serum bone resorption markers, including Tartrate-Resistant Acid Phosphatase (TRACP), N-terminal telopeptide of type I collagen and C-terminal telopeptide of type I collagen. Meanwhile, it increased the level of serum bone formation marker type I collagen N-terminal propeptide. These results revealed that YSJB ameliorated bone destruction and reduced bone loss induced by arthritis. We have previously showed that Tregs inhibited osteoclast differentiation and bone resorption in vitro. Furthermore, others suggested that abnormality of Th1, Th17 may contribute to bone destruction. Here, we showed YSJB significantly up-regulated the percentage of Tregs, while also down-regulated the percentage of Th1 and Th17 cells. Our findings provide the evidence that YSJB ameliorates the severity of disease and joint degradation, and reduces systemic bone loss induced by arthritis. We propose YSJB modulates the balance of T cell phenotype, which affects the activation and differentiation of osteoclasts.
30915189 Ischemic Stroke Secondary to Stylocarotid Variant of Eagle Syndrome. 2019 Apr Eagle syndrome is a rare cause of stroke and results as a complication of the elongated styloid process (ESP), which can cause carotid dissection and consequent ischemic stroke. We report a case of a 42-year-old woman with a past medical history of rheumatoid arthritis who developed left hemispheric ischemic stroke after deep tissue massage. Imaging studies revealed an intimal tear of the left carotid artery bulb and bilaterally ESPs, measuring approximately 6 cm on the right and 4.5 cm on the left. It seems that direct vascular compromise by the anomalous styloid process was the cause of her carotid artery dissection and stroke. Moreover, neck manipulation may have been a contributing factor.
30740386 Death of an Extensor Pollicis Longus due to a Funeral. 2018 Sep INTRODUCTION: Traumatic and atraumatic rupture of the extensor pollicis longus (EPL) tendon has been described as a result of mechanical or biological stresses. Common mechanisms include fractures of the distal radius, rheumatoid arthritis, local injection of steroids, and repetitive motion activities at the wrist. CASE REPORT: We report a case involving the spontaneous rupture of the EPL tendon in a relative of a deceased person who carried her coffin in a wrong way with no other predisposing factors. A three-dimensional simulation model was created in an attempt to illustrate the forces applied at his wrist. CONCLUSION: Our case indicates that carriage of a coffin should be done by four undertakers, ideally of the same height, on their shoulders. Furthermore, a high level of suspicion is needed when tenderness over Lister's tubercle after any type of trauma is encountered.
30632919 Inflammatory bowel diseases and primary immunodeficiency diseases. 2018 Dec Recent advances in molecular biology have provided important insights into the genetic background of various inflammatory diseases. In particular, genome-wide association studies of inflammatory diseases have revealed genetic loci that play critical roles in the pathology of inflammation. Whole-exome and whole-genome sequencing analyses have also identified more than 300 causative genes for primary immunodeficiency diseases (PIDs). Some genetic loci that are associated with inflammatory diseases are mutated in PIDs, suggesting close relationships between inflammation and PIDs. Inflammatory diseases for which genetic associations have been described include inflammatory bowel disease (IBD), multiple sclerosis, rheumatoid arthritis, type 1 diabetes mellitus, and systemic lupus erythematosus. Herein, I discuss about the genetic interactions between IBD and PIDs.
30460599 GP2017: An Adalimumab Biosimilar. 2018 Dec GP2017 (adalimumab) is a biosimilar anti-TNF-α antibody. It is approved in the EU for use in all indications for which reference adalimumab is approved. GP2017 has similar physicochemical and functional properties to those of reference adalimumab, and the pharmacokinetic similarity of the agent has been shown in healthy male volunteers. GP2017 demonstrated clinical efficacy equivalent to that of reference adalimumab in patients with moderate to severe plaque psoriasis or rheumatoid arthritis; the tolerability, safety and immunogenicity profiles of the two agents were also similar. Multiple switching between GP2017 and reference adalimumab (up to four times) had no impact on efficacy, tolerability or immunogenicity. The role of reference adalimumab in the management of autoimmune inflammatory conditions is well established and GP2017 provides an effective biosimilar alternative for patients requiring adalimumab therapy.
30568486 Perception vs pain and beliefs about pain control and Type A behavior pattern in patients 2018 OBJECTIVE: The study aimed at determining the experience of pain taking into consideration beliefs about pain control, Type A behavior pattern and sociodemographic factors in patients with chronic ischemia of the lower extremities or with rheumatoid arthritis (RA). METHODS: The study enrolled 100 patients with peripheral arterial disease (PAD) and 100 patients with RA. The subjective sensation of pain was assessed using the Visual Analog Scale (VAS); beliefs about pain control were analyzed using the Beliefs about Pain Control Questionnaire (BPCQ), taking into consideration internal factors, the influence of physicians and accidental events (chance); and Type A behavior features (haste and competition) were analyzed using the Framingham Type A Scale. The multiple regression model was used to assess associations between the experienced pain and the BPCQ value, the Framingham Type A Scale and sociodemographic factors. RESULTS: The pain intensity degree was found to be comparable in patients with PAD and with RA. The median determined using the VAS was 5.75 in both of the studied groups. In patients with PAD, lower VAS values were associated with the BPCQ - internal factors (P<0.05) whereas a higher VAS value was related to the BPCQ - physicians' influence (P<0.001). In patients with RA, a higher VAS value was associated with BPCQ - physicians' influence (P<0.05), disease duration (P<0.05) and smoking cigarettes (P<0.05). CONCLUSION: Experiencing pain by patients with chronic ischemia of the lower extremities occurs at a moderate level and is beneficially connected with the internal factors and adversely connected with the external factors of beliefs about pain control. Patients with RA reported pain ailments of a moderate level in connection with the adverse influence of the external factors of beliefs about pain control, the duration of the disease and smoking cigarettes. Experiencing pain by patients with chronic ischemia of the lower extremities and RA does not seem to be related to Type A behavior.
28744810 Krüppel-like factor 4 regulates the expression of inducible nitric oxide synthase induced 2018 Jan Krüppel-like factor 4 (KLF4), a zinc finger transcription factor, has been implicated in the inflammation mediated by macrophages and endothelial cells by regulating the expression of inflammatory mediators. Here, we investigated whether KLF4 affects the expression of inducible nitric oxide synthase (iNOS), an important inflammatory mediator, in the human RA fibroblast-like synovial cell line MH7A. A pcDNA3.1-KLF4 plasmid or short interfering RNA KLF4 was transfected into MH7A cells, and the iNOS expression and nitric oxide (NO) production were analyzed by quantitative PCR, immunoblotting, and nitrite measurement. The iNOS promoter activity was determined by luciferase assay. The results showed overexpression of KLF4 increased iNOS expression and NO production in the presence or absence of TNF-α. Conversely, KLF4 knockdown markedly reduced iNOS expression and NO production induced by TNF-α. KLF4 activated the transcription activity of iNOS promoter in MH7A cells stimulated by TNF-α. This study indicates that KLF4 is important for regulating the expression of iNOS by TNF-α in human synoviocytes.