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ID PMID Title PublicationDate abstract
26935090 [Physiological Role of K(+) Channels in the Regulation of T Cell Function]. 2016 Potassium ion (K(+)) channels play an important role in the modulation of calcium ion (Ca(2+)) signaling via control of the membrane potential. In T-lymphocytes, the voltage-gated K(+) channel, KV1.3, and the intermediate-conductance Ca(2+)-activated K(+) channel, KCa3.1, predominantly contribute to K(+) conductance, and are responsible for cell proliferation, differentiation, apoptosis and infiltration. Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, afflicts more than 0.1% of the population worldwide. In the chemically-induced IBD model mouse, an increase in KCa3.1 activity was observed in mesenteric lymph node CD4(+) T-lymphocytes, concomitant with an upregulation of KCa3.1 and a positive KCa3.1 regulator, NDPK-B. Pharmacological blockade of the KCa3.1 K(+) channel by TRAM-34 and/or ICA17043 elicited 1) a significant decrease in IBD severity, as assessed by diarrhea, visible fecal blood, inflammation and crypt damage of the colon; and 2) restoration of the expression levels of KCa3.1 and Th1 cytokines in CD4(+) T-lymphocytes in the IBD model. Recent studies have indicated the impact of K2P5.1 upregulation in T lymphocytes on the pathogenesis of autoimmune diseases such as rheumatoid arthritis and multiple sclerosis. The K2P5.1 K(+) channel is therefore highlighted as a potent therapeutic target in managing the pathogenesis of autoimmune diseases. Alternatively, pre-mRNA splicing of ion channels is associated with the development and progression of various diseases, including autoimmune diseases. Therefore, mRNA-splicing mechanisms underlying the transcriptional regulation of K2P5.1 K(+) channels may be a new strategic therapeutic target for autoimmune and inflammatory diseases.
26884285 Falls in RAC-OST-POL Study: epidemiological study in postmenopausal women aged over 55 yea 2016 INTRODUCTION: Falls are often noted in elderly women. They may have serious clinical consequences. The aim of the study is the presentation of epidemiological data on falls in postmenopausal women. MATERIAL AND METHODS: A total of 978 women in mean age 65.9 ± 7.6 years from the population of Raciborz district were included. In a questionnaire the following data were gathered: falls in last 12 months, place of stay, kind of job, marital status, education, smoking, underlying diseases, and used medications. RESULTS: Falls occurred in 328 women (33.5%). The number of falls correlated positively with increasing age, (r = 0.13, p < 0.0001). The falls rate was not related to weight and height, but weak, significant correlation with body mass index was noted (r = 0.076, p< 0.05). Among 286 women with prior osteoporotic fracture falls were present in 40.9%, which was significantly more than the 30.4% seen in women without fracture (Chi-square test; 10.05; df = 1; p < 0.01). Falls were fewer often among women from the city of Raciborz (29.8%) than in women from the rural population (39.7%). After adjustment for age, rural stay, diabetes type 1, renal failure, rheumatoid arthritis, bronchial asthma, and depression revealed influence on falls occurrence. As was shown by logistic regression, age, rural stay, prior fracture, diabetes type 1, bronchial asthma, and depression increased the risk of fall. The cumulative number of these risk factors correlated with the number of falls (r = 0.22, p < 0.000001). CONCLUSIONS: Falls are common among postmenopausal women, and their occurrence is modified by several factors including age, place of stay, and some co-morbidities.
26708681 [Polymyalgia rheumatica update, 2015]. 2016 Jan 3 Polymyalgia rheumatica is an inflammatory musculoskeletal disorder of people aged 50 years or over, characterised by pain, aching and morning stiffness in the shoulder girdle and often hip girdle and neck. Marked systemic inflammation and rapid response to corticosteroid therapy are characteristic features. Giant cell arteritis is a well-known association of polymyalgia rheumatica. Recent clinical evidence and scientific results in the field have provided new challenges for rheumatologists. Besides the aspecific - although characteristic - proximal syndrome, less well recognizable and more variable distal musculoskeletal manifestations were observed. Magnetic resonance and ultrasound studies showed mild, remitting and non-erosive synovitis, with dominating inflammation of the extraarticular synovial structures. As no pathognostic sign is known, the diagnosis of polymyalgia rheumatica is based on its differential diagnosis, differentiation from the polymyalgia mimics; particularly from elderly onset inflammatory arthritides, such as elderly onset rheumatoid arthritis and late onset seronegative spondylarthritis. In 2012 the international polymyalgia rheumatica work group under the guidance of the American College of Rheumatology and European League Against Rheumatism elaborated new classification criteria, the scoring algorythm of which is based on clinical symptoms, with ultrasonography increasing the specificity. Corticosteroids remain the cornerstone of the therapy of polymyalgia rheumatica. No effective steroid-sparing drug has been found to date. Corticosteroids are generally needed for 1-1.5 years, though some patients have a chronic-relapsing course and require corticosteroids for several years. Well known corticosteroid-related side effects (diabetes, hypertension, hyperlipidaemia and osteoporosis) cause significant morbidity and economic burden on the society. Novel therapeautic approaches are on trial. Early recognition of the disease, early start of corticosteroids and a well-defined course, prevention and management of side effects are everyday tasks for rheumatologists and family doctors. Knowledge of polymyalgia rheumatica is essential for all medical specialties.
26707133 Anti-inflammatory activity of Kochia scoparia fruit on contact dermatitis in mice. 2016 Feb The mature fruit of Kochia scoparia (L.) Schrad. is widely administered in China and Korea as a medicinal herb for treatment of skin diseases, diabetes mellitus and rheumatoid arthritis. The present study investigated the effects of methanol extracts of K. scoparia dried fruit (MEKS) on ear swelling, histopathological changes (such as epidermal acanthosis, spongiosis and immune cell infiltration) and cytokine production in 1-fluoro-2,4-dinitrofluorobenzene (DNFB)-induced contact dermatitis mice. Topical application of MEKS inhibited DNFB-induced ear thickness and weight increases, as well as DNFB-induced epidermal acanthosis, spongiosis and immune cell infiltration. In addition, treatment with MEKS significantly decreased the levels of tumor necrosis factor-α, interferon-γ and monocyte chemotactic protein-1 in inflamed tissues. These data indicate that the mature fruit of K. scoparia has the potential to be administered for the treatment of inflammatory skin diseases and that the anti-inflammatory action of K. scoparia is involved in the inhibition of type 1 T helper cell skewing reactions.
26370701 T cell epitopes and post-translationally modified epitopes in type 1 diabetes. 2015 Nov Type 1 diabetes (T1D) is an autoimmune disease in which progressive loss of self-tolerance, evidenced by accumulation of auto-antibodies and auto-reactive T cells that recognize diverse self-proteins, leads to immune-mediated destruction of pancreatic beta cells and loss of insulin secretion. In this review, we discuss antigens and epitopes in T1D and the role that post-translational modifications play in circumventing tolerance mechanisms and increasing antigenic diversity. Emerging data suggest that, analogous to other autoimmune diseases such as rheumatoid arthritis and celiac disease, enzymatically modified epitopes are preferentially recognized in T1D. Modifying enzymes such as peptidyl deiminases and tissue transglutaminase are activated in response to beta cell stress, providing a mechanistic link between post-translational modification and interactions with the environment. Although studies of such responses in the at-risk population have been limited, current data suggests that breakdown in tolerance through post-translational modification represents an important checkpoint in the development of T1D.
26324422 Inhibition of RANKL-induced osteoclastogenesis through the suppression of the ERK signalin 2015 Nov Astragaloside IV (AS-IV) is a natural plant extract that enhances osteoblast activity, and therefore, has the potential to treat osteoclast‑related diseases. Such diseases include osteoporosis, periodontal disease, rheumatoid arthritis and aseptic prosthesis loosening. However, data associating the effects of AS‑IV on osteoclasts are limited. The aim of the present study was to assess the effect of AS‑IV on osteoclasts in vitro and in vivo. The in vitro studies demonstrated that AS‑IV exerts potent inhibitory effects on the ligand of the receptor activator of nuclear factor‑κB‑induced osteoclastogenesis and revealed the mechanism of action of AS‑IV, which inhibited osteoclastogenesis by suppression of the extracellular signal‑regulated kinase signaling pathway. The in vivo studies proved that AS‑IV attenuated titanium particle‑induced osteolysis in a mouse calvarial model. Collectively, the findings of the study suggest that AS‑IV is a potential natural agent for the treatment of osteoclast-related diseases.
26240517 TL1A/DR3 axis involvement in the inflammatory cytokine network during pulmonary sarcoidosi 2015 BACKGROUND: TNF-like ligand 1A (TL1A), a recently recognized member of the TNF superfamily, and its death domain receptor 3 (DR3), firstly identified for their relevant role in T lymphocyte homeostasis, are now well-known mediators of several immune-inflammatory diseases, ranging from rheumatoid arthritis to inflammatory bowel diseases to psoriasis, whereas no data are available on their involvement in sarcoidosis, a multisystemic granulomatous disease where a deregulated T helper (Th)1/Th17 response takes place. METHODS: In this study, by flow cytometry, real-time PCR, confocal microscopy and immunohistochemistry analyses, TL1A and DR3 were investigated in the pulmonary cells and the peripheral blood of 43 patients affected by sarcoidosis in different phases of the disease (29 patients with active sarcoidosis, 14 with the inactive form) and in 8 control subjects. RESULTS: Our results demonstrated a significant higher expression, both at protein and mRNA levels, of TL1A and DR3 in pulmonary T cells and alveolar macrophages of patients with active sarcoidosis as compared to patients with the inactive form of the disease and to controls. In patients with sarcoidosis TL1A was strongly more expressed in the lung than the blood, i.e., at the site of the involved organ. Additionally, zymography assays showed that TL1A is able to increase the production of matrix metalloproteinase 9 by sarcoid alveolar macrophages characterized, in patients with the active form of the disease, by reduced mRNA levels of the tissue inhibitor of metalloproteinase (TIMP)-1. CONCLUSIONS: These data suggest that TL1A/DR3 interactions are part of the extended and complex immune-inflammatory network that characterizes sarcoidosis during its active phase and may contribute to the pathogenesis and to the progression of the disease.
26117975 [Analysis of pregnancy, labor and neonatal course in babies with prenatally-diagnosed comp 2015 May INTRODUCTION: Complete heart block (third-degree atrioventricular block) is a defect of the conduction system of the heart, in which the impulse generated in the sinoatrial node does not propagate to the ventricles, and thus the latter contract independently of the atria. A third-degree atrioventricular block can be either congenital or acquired. In 60-70% of the cases, the congenital heart block results from destruction of the conduction system of the fetal heart by anti-Ro/SSA and anti-La/SSB antibodies present in maternal serum. The antibodies are synthesized in the course of autoimmune maternal conditions, most often systemic lupus erythematosus or rarer rheumatoid arthritis, dermatomyositis or Sjögren's syndrome. The complete block can occur as an isolated defect or be associated with structural anomalies of the fetal heart. MATERIAL AND METHODS: A total of five patients whose fetuses were diagnosed with the third-degree atrioventricular block have been hospitalized at the Department of Obstetrics, Medical University of Gdansk between 2012 and 2014. RESULTS: We present the data of the five patients, hospitalized at the Department of Obstetrics, Medical University of Gdansk, whose fetuses were diagnosed prenatally with the complete heart block. The cases differ in terms of etiology clinical outcome, and postnatal treatment. All data are presented in Table I. CONCLUSIONS: We emphasize the role of appropriate pregnancy management and careful monitoring of the fetal condition. From obstetrical perspective, it is important to monitor the condition of fetuses with the third-degree atrioventricular block ultrasonographically and echocardiographically; in turn, cardiotocography is less useful in this setting. Therefore, a non-reactive cardiotocographic tracing should not constitute an indication for a preterm delivery. An affected fetus should be delivered in a tertiary center for perinatal care that cooperates with a pediatric cardiology center. An efficient program for cardologic prenatal care and close cooperation between obstetricians, neonatologists, pediatric cardiologists, and cardiac surgeons constitute the key to a successful outcome.
26108728 Autophagy protects meniscal cells from glucocorticoids-induced apoptosis via inositol tris 2015 Sep Intra-articular injection of glucocorticoids (GCs) has been widely used in the management of osteoarthritis and rheumatoid arthritis. Nevertheless, several studies showed that GCs had toxic effects on chondrocytes as well as synovial cells. Previously we reported the protective role of autophagy in the degeneration of meniscal tissues. However, the effects of GCs on autophagy in the meniscal cells have not been fully elucidated. To investigate whether GCs can regulate autophagy in human meniscal cells, the meniscal cells were cultured in vitro and exposed in the presence of dexamethasone. The levels of apoptosis and autophagy were investigated via flow cytometry as well as western blotting analysis. The changes of the aggrecanases were measured using real-time PCR. The role of autophagy in dexamethasone-induced apoptosis was investigated using pharmacological agents and RNA interference technique. An agonist of inositol 1,4,5-trisphosphate receptor (IP3R) was used to investigate the mechanism of dexamethasone-induced autophagy. The results showed that dexamethasone induced autophagy as well as apoptosis in normal human meniscal cells. Using RNA interference technique and pharmacological agents, our results showed that autophagy protected the meniscal cells from dexamethasone-induced apoptosis. Our results also indicated that dexamethasone increased the mRNA levels of aggrecanases. This catabolic effect of dexamethasone was enhanced by 3-MA, the autophagy inhibitor. Furthermore, our results showed that dexamethasone induced autophagy via suppressing the phosphorylation of IP3R. In summary, our results indicated that autophagy protected meniscal cells from GCs-induced apoptosis via inositol trisphosphate receptor signaling.
26030228 MicroRNA regulation of lymphocyte tolerance and autoimmunity. 2015 Jun Understanding the cell-intrinsic cues that permit self-reactivity in lymphocytes, and therefore autoimmunity, requires an understanding of the transcriptional and posttranscriptional regulation of gene expression in these cells. In this Review, we address seminal and recent research on microRNA (miRNA) regulation of central and peripheral tolerance. Human and mouse studies demonstrate that the PI3K pathway is a critical point of miRNA regulation of immune cell development and function that affects the development of autoimmunity. We also discuss how miRNA expression profiling in human autoimmune diseases has inspired mechanistic studies of miRNA function in the pathogenesis of multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, type 1 diabetes, and asthma.
25684197 Association of TNFAIP3 and TNFRSF1A variation with multiple sclerosis in a German case-con 2015 Apr Variations in two genes of the tumour necrosis factor (TNF) alpha pathway have been implicated in the pathogenesis of autoimmune diseases: polymorphisms in the TNFRSF1A gene, encoding TNF receptor 1, showed significant association with MS in genomewide association scans, and variation in or near the TNFAIP3 gene, coding for a negative regulator of NFkB, was associated with MS, systemic lupus erythematosus, diabetes and rheumatoid arthritis. This study aimed at investigating association of MS with variation in the TNFRSF1A gene as well as in the TNFAIP3 gene region in an independent German case-control cohort. Four hundred and ninety-seven unrelated patients with MS and 878 healthy controls were genotyped with restriction enzyme digestion or TaqMan assays for three polymorphisms in the TNFRSF1A gene and seven in the region of the TNFAIP3 gene. Allele, genotype and haplotype frequencies were compared between cases and controls by chi-square testing. We found significant association of rs10499194, located in the intergenic region upstream of TNFAIP3, with MS (pc = 3.4 × 10(-4) ). Further, the intronic SNP rs1800693 in TNFRSF1A showed moderate association (pc = 0.033) with MS. In conclusion, evidence is accumulating that polymorphisms in both TNFAIP3 and TNFRSF1A genes play a role in MS pathogenesis. Additional studies are warranted to further elucidate the role of TNF pathway variation for MS development.
25622759 Pulmonary manifestations of pyoderma gangrenosum: 2 cases and a review of the literature. 2015 Apr Pyoderma gangrenosum (PG) is a rare ulcerative neutrophilic dermatologic disease that occasionally is accompanied by extracutaneous manifestations, amongst these is pulmonary involvement. The etiology is unknown. More than 50% of PG cases are associated with an underlying systemic disease such as inflammatory bowel disease, rheumatoid arthritis, hematological disorder or malignancy. Extracutaneous manifestations are rare and only 29 cases of pulmonary involvement have been reported previously in the literature. Pyoderma gangrenosum is usually diagnosed in the third to sixth decade, but early debut in childhood is also described. Skin manifestations are usually evident before pulmonary involvement, although primary lung affection is seen. Pulmonary involvement is diagnosed simultaneously or from a few weeks up to several years after the diagnosis of cutaneous PG. The most important differential diagnoses are lung cancer, lung abscess and Wegener's granulomatosis. Histological specimens will exclude these diagnoses. The treatment of PG is immune modulation, but due to the rarity of the disease, only one randomized treatment trials exists [1] and the long term course of PG with pulmonary involvement is unknown. We present two cases of pulmonary manifestations of pyoderma gangrenosum and a review of the literature.
25573438 Phytantriol-based in situ liquid crystals with long-term release for intra-articular admin 2015 Aug The purpose of this study was to develop an injectable in situ liquid crystal formulation for intra-articular (IA) administration, and in situ forming a viscous liquid crystalline gel with long-term release of sinomenine hydrochloride (SMH) upon water absorption. The pseudo-ternary phase diagram of phytantriol (PT)-ethanol (ET)-water was constructed, and isotropic solutions were chosen for further optimization. The physicochemical properties of isotropic solutions were evaluated, and the phase structures of liquid crystalline gels formed by isotropic solutions in excess water were confirmed by crossed polarized light microscopy (CPLM) and small-angle X-ray scattering (SAXS). In vitro drug release studies were conducted by using a dialysis membrane diffusion method. The optimal in situ cubic liquid crystal (ISV2) (PT/ET/water, 64:16:20, w/w/w) loaded with 6 mg/g of SMH showed a suitable pH, showed to be injectable, and formed a cubic liquid crystalline gel in situ with minimum water absorption within the shortest time. The optimal ISV2 was able to sustain the drug release for 6 days. An in situ hexagonal liquid crystal (ISH2) system was prepared by addition of 5% vitamin E acetate (VitEA) into PT in the optimal ISV2 system to improve the sustained release of SMH. This ISH2 (PT/VitEA/ET/water, 60.8:3.2:16:20, w/w/w/w) was an injectable isotropic solution with a suitable pH range. The developed ISH2 was found to be able to sustain the drug release for more than 10 days and was suitable for IA injection for the treatment of rheumatoid arthritis (RA).
25480980 Two distinct leukotriene B4 receptors, BLT1 and BLT2. 2015 Feb Leukotriene B4 (LTB4) is a potent inflammatory mediator derived from arachidonic acid. Two G protein-coupled receptors for LTB4 have been identified: a high-affinity receptor, BLT1, and a low-affinity receptor, BLT2. Both receptors mainly couple to pertussis toxin-sensitive Gi-like G proteins and induce cell migration. 12(S)-hydroxy-5Z,8E,10E-heptadecatrienoic acid (12-HHT) was identified to bind BLT2 with higher affinity than LTB4. Expression of BLT1 was confirmed in type 1 helper T cells, type 2 helper T cells, type 17 helper T cells, effector CD8(+) T cells, dendritic cells and osteoclasts in addition to granulocytes, eosinophils and macrophages, and BLT1-deficient mice showed greatly reduced phenotypes in models of various inflammatory diseases, such as peritonitis, bronchial asthma, rheumatoid arthritis, atherosclerosis and osteoporosis. In mice, BLT2 expression is restricted to intestinal epithelial cells and epidermal keratinocytes. BLT2-deficient mice showed enhanced colitis after administration of dextran sulfate, possibly due to reduced intestinal barrier function. An aspirin-dependent reduction in 12-HHT production was responsible for delayed skin wound healing, showing that the 12-HHT/BLT2 axis also plays an important role in skin biology. BLT1 and BLT2 are therefore potential targets for the development of novel drugs.
25376844 Different fingerprinting strategies to differentiate Porana sinensis and plants of Erycibe 2015 Jan Plants of Erycibe are widely used in traditional Chinese medicine for the treatment of joint pain and rheumatoid arthritis. With the reduction of Erycibe resources in the wild, Porana sinensis has been widely used as a substitute. However, it is important to understand the chemical distinctions between the two kinds of plants and identify their individual chemical markers. In this study, multiwavelength chromatographic fingerprint and precursor ion fingerprint techniques were used in conjunction with chemometric tools to fingerprint and thus differentiate between plant samples. The similar results obtained from different fingerprints prove the reliability of the two fingerprints. Results obtained from principal component analysis and orthogonal projection to latent structures discriminant analysis identified similarities between the chemical components of P. sinensis and plants of Erycibe. However, concentrations of 4-caffeoylquinic acid, 3,5-dicaffeoylquinic acid, 3,4-dicaffeoylquinic acid, and 4,5-dicaffeoylquinic acid were higher in P. sinensis than in plants of Erycibe, suggesting that P. sinensis may be more effective in medical treatments of some diseases than Erycibe.
25326115 Clinical Experience of the Use of CT-P13, a Biosimilar to Infliximab in Patients with Infl 2015 Apr BACKGROUND: CT-P13 is the first biosimilar monoclonal antibody to infliximab. However, the antibody was tested only in rheumatoid arthritis and ankylosing spondylitis, which demonstrated equivalence to the originator in efficacy, safety, and pharmacokinetic profile. Extrapolation of its efficacy and safety to other pathologies is tenuous. Interchangeability with its originator is another unclear area. AIM: We aimed to describe the experience of CT-P13 use in inflammatory bowel disease at a tertiary center. METHODS: Seventeen subjects diagnosed with Crohn's disease (CD, n = 8) or ulcerative colitis (UC, n = 9) who were administered CT-P13 from November 2012 to October 2013 at Dongguk University Ilsan Hospital were retrospectively enrolled. Medical records analyzed included patients' characteristics, previous history of anti-tumor necrosis factor administration, response and remission to this biosimilar antibody, disease flare-up, and adverse drug reaction. RESULTS: Male-female ratio was 1.8. Mean age was 35.4 years (range 15-57). Mean number of CT-P13 administrations was 4.2 ± 1.9. Induction treatments were done in five UC and three CD patients. Clinical response and remission at 8 weeks were achieved in seven patients (five UC and two CD). One CD patient did not respond to CT-P13. Nine patients in maintenance with the originator were interchanged with CT-P13 (four UC and five CD patients). One UC patient experienced arthralgia and CT-P13 was discontinued. One patient experienced loss of response during the study period. CONCLUSIONS: CT-P13 may have biosimilarity and interchangeability with its originator in inflammatory bowel disease. A large, randomized, double-blind, prospective study is needed.
24599726 The AGRIculture and CANcer (AGRICAN) cohort study: enrollment and causes of death for the 2015 Jan OBJECTIVE: To elaborate and describe a large prospective agricultural cohort including males and females in France with various agricultural activities and to study causes of death. METHODS: To date, few large prospective cohorts have been conducted among agricultural population. AGRIculture and CANcer cohort is a large prospective cohort of subjects in agriculture studying cancer among active and retired males and females, farm owners and workers, living in eleven areas of France with a population-based cancer registry. RESULTS: Enrollment was conducted from 2005 to 2007 with a postal questionnaire. In January 2008, 180,060 individuals (54 % males, 54 % farm owners, 50 % retired) were enrolled. Mortality was studied until December 2009 (605,956 person-years with standardized mortality ratio (SMR) by comparison with the general population of the areas. Over this period, 11,450 deaths 6,741 in men and 4,709 in women were observed, including 3,405 cancer-related deaths. SMRs were significantly reduced for global mortality (SMR = 0.68, 95 % CI 0.67-0.70 in males and SMR = 0.71, 95 % CI 0.69-0.73 in females) and for death by cancer (SMR = 0.67, 95 % CI 0.65, 0.70 in males and SMR = 0.76, 95 % C: 0.71, 0.80 in females). These results were mainly explained by less frequent smoking-related causes of death (lung cancer, cardiovascular diseases). Nonsignificant excesses of death were observed only for rheumatoid arthritis and arthrosis, suicides (in females), death for event of undetermined intent (in males) and breast cancer in male agricultural workers. CONCLUSIONS: These first results are the first ones obtained in France based on a large prospective agricultural cohort showing that farmers would be in healthier condition than the general population.
24577431 Persistence of noncancer-related musculoskeletal chronic pain among community-dwelling old 2015 Jan OBJECTIVE: To determine the persistence of chronic pain among community-dwelling older persons and to identify factors related to persistent chronic pain. METHODS: In this prospective longitudinal study, a random sample of Finnish community-dwelling people aged 76 years and older (n=256) were interviewed annually by a trained nurse at 3 time points. Data on prevalence, duration, location, and intensity of musculoskeletal pain, analgesic use, demographics, and health characteristics were collected during the interviews. RESULTS: Chronic pain was reported by 48.9% of the participants at baseline, with 74.4% of them experiencing persistent chronic pain, that is, they reported chronic pain at all 3 study points. Persistent chronic pain was associated with poor self-rated health (adjusted odds ratio [AOR]=2.26, 95% confidence interval [95% CI] 1.03-4.98), mobility difficulties (AOR=2.80, 95% CI, 1.22-6.43), and arthrosis or rheumatoid arthritis (AOR=3.07, 95% CI, 1.47-6.42) when compared with persons without chronic pain. However, only 15% of the persons with persistent chronic pain were using analgesics on a regular basis, and one out of every 5 was not taking any analgesics. CONCLUSIONS: Chronic musculoskeletal pain is a highly persistent condition among community-dwelling older persons and it is related to poor health and mobility difficulties. In addition, the use of daily analgesic is low despite the continuous nature of chronic pain.
27868161 Neutrophil plasticity enables the development of pathological microenvironments: implicati 2016 Dec INTRODUCTION: The pathological course of several chronic inflammatory diseases, including cystic fibrosis, chronic obstructive pulmonary disease, and rheumatoid arthritis, features an aberrant innate immune response dominated by neutrophils. In cystic fibrosis, neutrophil burden and activity of neutrophil elastase in the extracellular fluid have been identified as strong predictors of lung disease severity. REVIEW: Although neutrophils are generally considered to be rigid, pre-programmed effector leukocytes, recent studies suggest extensive plasticity in how neutrophil functions unfold upon recruitment to peripheral tissues, and how they choose their ultimate fate. Indeed, upon migration to cystic fibrosis airways, neutrophils display dysregulated lifespan, metabolic activation, and altered effector and regulatory functions, consistent with profound adaptation and phenotypic reprogramming. Licensed by signals present in cystic fibrosis airway microenvironment to survive and develop these novel functions, neutrophils orchestrate, in partnership with the epithelium and with the resident microbiota, the evolution of a pathological microenvironment. This microenvironment is defined by altered proteolytic, redox, and metabolic balance and the presence of stable luminal structures in which neutrophils and microbes coexist. CONCLUSIONS: The elucidation of molecular mechanisms driving neutrophil plasticity in vivo will open new treatment opportunities designed to modulate, rather than block, the crucial adaptive functions fulfilled by neutrophils. This review aims to outline emerging mechanisms of neutrophil plasticity and their participation in the building of pathological microenvironments in the context of cystic fibrosis and other diseases with similar features.
27862093 Bioanalytical method for the estimation of co-administered esomeprazole, leflunomide and i 2017 May The present study represents a connection between basic science and clinical applied science through providing a bioanalytical method for the analysis of certain co-administered drugs used for the treatment of rheumatoid arthritis. The studied drugs are esomeprazole, leflunomide and ibuprofen. The proposed bioanalytical method is a simple reversed phase high performance liquid chromatographic method using micellar mobile phase. The method is conducted using a Shim-pack VP-ODS (150 mm × 4.6 mm ID) stainless steel column at ambient temperature with ultraviolet detection at 285 nm. The micellar mobile phase consisted of 0.1 m sodium dodecyl sulfate, 10% n-propanol, 0.3% triethylamine in 0.02 m orthophosphoric acid (pH 3.5) and is pumped at a flow rate of 1.0 mL/min. The calibration curve was rectilinear over the concentration range of 0.1-5.0, 0.5-10.0 and 1.0-20.0 μg/mL for esomeprazole, leflunomide and ibuprofen respectively. The proposed method was successfully applied to the analysis of these drugs in dosage forms. The method is extended to the in-vitro, in-vivo determination of these drugs in spiked and real human plasma samples.