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ID PMID Title PublicationDate abstract
29085738 Detections of Screw Penetration during Volar Plating for Distal Radius Fractures. 2017 Nov Background  We evaluated the detection for screw penetration on the dorsal cortex of the radius in serial oblique, dorsal tangential, and radial groove radiographic views in volar plating fixation. Materials and Methods  Eight screw positions were set in each of the four cadaveric radii. Screw 1 was placed in the styloid subregion, whereas screws 2 and 3 were placed just proximal to the styloid and were defined for the radial region of the radius. Screws 4 (distal to the extensor pollicis longus [EPL] groove), 5 (the distal half of the groove), and 6 (the proximal half of the groove) were placed in the central region of the radius. Screws 7 (just medial to the groove) and 8 (sigmoid notch subregion) were positioned in the ulnar region of the radius. The screws were overlengthened by 1 and 2 mm and were evaluated in three radiographic views. Results  Penetrations in the radial region were fully visible in supinated oblique views with 1- and 2-mm overlengthened screws. The penetration of screw 4 was clearly observable over a considerable range of views. However, the 1-mm penetration of screw 5 was not detectable at any angle of projection. Detection of the ulnar region screw was the most difficult among the three regions with oblique views. In the dorsal tangential view, the 1-mm penetration of screw 4 was not observed in any of the four radii, but the penetration of screw 5 was detectable in all the radii. The screws 2, 3, 5, 7, and 8 were readily detectable. The screw 4 was barely seen in the radial groove view, while the screws 5 and 6 were readily detectable. Conclusion/Clinical Relevance  Appropriate combinations of these well-known radiological views are essential for the overall detection of penetrated screws during plating in distal radius fractures.
27390293 Effects of Belimumab on Flare Rate and Expected Damage Progression in Patients With Active 2017 Jan OBJECTIVE: To investigate effectiveness and safety of belimumab in patients with active systemic lupus erythematosus (SLE) in a clinical practice setting. METHODS: Sixty-seven patients with active SLE, mean ± SD age 39.3 ± 10.2 years, from 2 Italian prospective cohorts were treated with belimumab (10 mg/kg on day 0, 14, 28, and then every 28 days) added to background therapy. The Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index, the Disease Activity Score in 28 joints (DAS28), 24-hour proteinuria, the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) activity score, anti-double-stranded DNA (anti-dsDNA), C3 and C4 levels, and prednisone daily dose were recorded at baseline, month 3, 6, 9, 12, 18, and 24. Arthritis was subdivided into "classical" (CLP) and "rheumatoid-like"; skin manifestations into acute (ACLE), subacute (SCLE), and chronic. SLE flares, defined according to the SLEDAI Flare Index, were calculated before and after belimumab initiation. Adverse events were carefully evaluated during treatment. Statistics were performed by the SPSS package (version 21.0). RESULTS: Mean ± SD followup was 16.2 ± 9.5 months. Main refractory manifestations treated with belimumab were musculoskeletal (37.3%), mucocutaneous (22.4%), and renal (23.9%). SLEDAI-2K, prednisone daily dose, anti-dsDNA, DAS28, CLASI, and 24-hour proteinuria decreased during treatment. DAS28 score decreased in patients with polyarthritis (P < 0.001), particularly in those with CLP (P < 0.001), and CLASI decreased in patients with skin manifestation (P = 0.003), either ACLE (P = 0.051) or SCLE (P = 0.047). Flare rate was lower 1 and 2 years after belimumab initiation than in the periods before (P = 0.001). Belimumab was well-tolerated and no damage accrual was observed after initiation. CONCLUSION: Belimumab was effective and safe in a clinical practice setting; it decreased the number of flares and hindered damage progression in patients with active SLE.
29283173 CYP3A4 inducer and inhibitor strongly affect the pharmacokinetics of triptolide and its de 2018 Aug Triptolide is the most active ingredient of Tripterygium wilfordii Hook F, which is used to treat rheumatoid arthritis. (5R)-5-Hydroxytriptolide is a hydroxylation derivative of triptolide with a reduced toxicity. To investigate the metabolic enzymes of the two compounds and the drug-drug interactions with enzyme inducers or inhibitors, a series of in vitro and in vivo experiments were conducted. In vitro studies using recombinant human cytochrome P450 enzyme demonstrated that cytochrome P450 3A4 (CYP3A4) was predominant in the metabolism of triptolide and (5R)-5-hydroxytriptolide, accounting for 94.2% and 64.2% of the metabolism, respectively. Pharmacokinetics studies were conducted in male SD rats following administration of triptolide or (5R)-5-hydroxytriptolide (0.4 mg/kg, po). The plasma exposure to triptolide and (5R)-5-hydroxytriptolide in the rats was significantly increased when co-administered with the CYP3a inhibitor ritonavir (30 mg/kg, po) with the values of AUC(0-∞) (area under the plasma concentration-time curve from time zero extrapolated to infinity) being increased by 6.84 and 1.83 times, respectively. When pretreated with the CYP3a inducer dexamethasone (50 mg·kg(-1)·d(-1), for 3 d), the AUC(0-∞) values of triptolide and (5R)-5-hydroxytriptolide were decreased by 85.4% and 91.4%, respectively. These results suggest that both triptolide and (5R)-5-hydroxytriptolide are sensitive substrates of CYP3a. Because of their narrow therapeutic windows, clinical drug-drug interaction studies should be carried out to ensure their clinical medication safety and efficacy.
29212985 Bone Formation Parameters of the Biopsied Ilium Differ between Subtrochanteric and Diaphys 2017 Dec Atypical femoral fractures (AFFs) are defined as atraumatic or low-trauma fractures located in the subtrochanteric or diaphyseal sites. Long-term bisphosphonates (BPs) are administered to prevent fragility fractures in patients with primary osteoporosis or collagen diseases who are already taking glucocorticoids (GCs). Long-term BP use is one of the most important risk factors for AFFs. Its pathogenesis is characterized by severely suppressed bone turnover (SSBT), but whether the characteristics of patients are different regarding to location of fracture site remains unknown. In this study, we compared the characteristics and bone histomorphometric findings between subtrochanteric and diaphyseal sites in patients with BP-associated AFFs. Nine women with BP-associated AFFs were recruited, including 3 with systemic lupus erythematosus, 2 with rheumatoid arthritis, 2 with primary osteoporosis, 1 with polymyalgia rheumatica, and 1 with sarcoidosis. Patients were divided into the subtrochanteric group (n = 5; average age, 52 years; BP treatment, 5.9 years) and the diaphyseal group (n = 4; average age, 77 years; BP treatment, 2.6 years). Compared with the diaphyseal group, the subtrochanteric group had significantly higher daily GC doses (average, 10.9 vs. 2.3 mg/day) and significantly lower serum 25-hydroxyvitamin-D levels (17.8 vs. 25.6 ng/mL). Bone histomorphometry of the biopsied iliac bone showed SSBT in 3 cases (subtrochanteric, n = 1; diaphyseal, n = 2). Osteoid volume and trabecular thickness were significantly lower in the subtrochanteric group than in the diaphyseal group. Bone formation was inhibited more severely in subtrochanteric than in the diaphyseal group due to the higher GC doses used.
28926469 A Survey of Glucocorticoid Adverse Effects and Benefits in Rheumatic Diseases: The Patient 2017 Dec OBJECTIVE: The aim of this study was to explore, from the patient's perspective, the beneficial and adverse effects (AEs) of glucocorticoids (GCs) in patients with rheumatic diseases, to be used in the development of a patient-reported outcome measure. METHODS: A cross-sectional survey, capturing benefits and AEs of GC use, was administered to 2 groups of patients: (1) those attending a tertiary rheumatology clinic with various rheumatic diseases who had used GCs within the past year and (2) patients from the Hospital for Special Surgery rheumatoid arthritis database. RESULTS: Cohort 1 had 55 GC users, and cohort 2 had 95 GC users and 29 nonusers. The majority of GC users in both cohorts reported at least 1 AE (100%, 86%). The AE prevalence per person was 50% higher in cohort 1 compared with GC users in cohort 2 (7.7 vs. 5.3; AE ratio, 1.5; 95% confidence interval, 1.3-1.7) and 2-fold greater in cohort 2 GC users compared with GC nonusers (5.3 vs. 2.6; AE ratio, 2.0; 95% confidence interval, 1.6-2.6). In both cohorts, AEs identified as "worst" by GC users included skin thinning/easy bruising, sleep disturbance, mood disturbance, and change in facial shape. Most felt GCs helped their disease "a lot" (78%/62%) and that the benefits were greater than the AEs (55%/64%). Many AEs were more frequent in GC users than in nonusers. CONCLUSIONS: Patients receiving GC therapy for rheumatic conditions report a large number of AEs and those that have the greatest life impact are often difficult for physicians to measure. These results will inform the development of a patient-reported outcome measure to capture the effects of GCs from the patient's perspective.
28786745 PTPN22 regulates NLRP3-mediated IL1B secretion in an autophagy-dependent manner. 2017 Sep 2 A variant within the gene locus encoding PTPN22 (protein tyrosine phosphatase, non-receptor type 22) emerged as an important risk factor for auto-inflammatory disorders, including rheumatoid arthritis, systemic lupus erythematosus and type 1 diabetes, but at the same time protects from Crohn disease, one of the 2 main forms of inflammatory bowel diseases. We have previously shown that loss of PTPN22 results in decreased NLRP3 (NLR family pyrin domain containing 3) activation and that this effect is mediated via enhanced NLRP3 phosphorylation. However, it is unclear how phosphorylation of NLRP3 mediates its inhibition. Here, we demonstrate that loss of macroautophagy/autophagy abrogates the inhibitory effect on NLRP3 activation observed upon loss of PTPN22. Phosphorylated, but not nonphosphorylated NLRP3 is found in autophagosomes, indicating that NLRP3 phosphorylation mediates its inactivation via promoting sequestration into phagophores, the precursors to autophagosomes. This finding shows that autophagy and NLRP3 inflammasome activation are connected, and that PTPN22 plays a key role in the regulation of those 2 pathways. Given its role in inflammatory disorders, PTPN22 might be an attractive therapeutic target, and understanding the cellular mechanisms modulated by PTPN22 is of crucial importance.
28705378 Reliability of Cardiovascular Risk Calculators to Estimate Accurately the Risk of Cardiova 2017 Sep 1 Chronic inflammation is an independent risk factor for cardiovascular disease (CVD), but most risk calculators, including the Framingham risk score (FRS) and the American College of Cardiology (ACC)/American Heart Association (AHA) risk score do not account for it. These calculators underestimate cardiovascular risk in patients with rheumatoid arthritis and systemic lupus erythematosus. To date, how these scores perform in the estimation of CVD risk in patients with sarcoidosis has not been assessed. In this study, the FRS and the ACC/AHA risk score were calculated for a previously identified cohort of patients with incident cases of sarcoidosis in Olmsted County, Minnesota, United States, from 1989 to 2013 as well as their gender- and age-matched comparators. The standardized incidence ratio (SIR) was estimated as the ratio of the predicted and observed numbers of CVD events. All CVD events were identified by diagnosis codes and were verified by individual medical record reviews. The predicted number of CVD events among 188 cases by FRS was 11.8 and the observed number of CVD events was 34, which corresponded to an SIR of 2.88 (95% confidence interval 2.06 to 4.04). FRS underestimated the risk of CVD events in patients with sarcoidosis by gender, age and severity of sarcoidosis. The predicted number of CVD events among cases by ACC/AHA risk score was 4.6 and the observed number of CVD events was 19, corresponding to an SIR of 4.11 (95% confidence interval 2.62 to 6.44). In conclusion, the FRS and the ACC/AHA risk score underestimate the risk of CVD in patients with sarcoidosis.
28699503 Metabolic Syndrome: Sex-Related Cardiovascular Risk and Therapeutic Approach. 2017 BACKGROUND: The metabolic syndrome (MetS) is a cluster of risk factors for the development of cardiovascular diseases (CVD) and type 2 diabetes (T2DM). According to several meta-analyses, it has been shown that the cardiovascular (CV) risk conferred by the MetS is higher in women in comparison with men. There are many possible reasons to explain a higher CV risk in women with MetS: the most important differences can be attributed to distribution of central adiposity, lipid profile and hormones, but also differences in platelet biology and biochemistry play an important role. METHODS: In this article we performed a research using PubMed database reviewing the evidence in literature (in particular clinical trials and meta-analyses) or lack of evidence/ biased information regarding the distribution by gender of MetS components and associated CV risk and we intended to provide a consequent gender perspective to the treatment of MetS and CV risk. RESULTS: Twenty-three papers were evaluated searching for sex differences in the prevalence of MetS and CV risk. We also identified fifty-six papers dealing with sex differences in adiposity, insulin resistance and hormonal regulation. In terms of gender-specific expression of MetS in chronic disease we analyzed thirty-one papers focusing the attention on non-alcoholic fatty liver disease, polycystic ovarian syndrome, gestational diabetes mellitus, rheumatoid arthritis and HIV infection. We also evaluated twenty papers focusing on gender differences in platelet biology/reactivity and thirty-three papers on the gender approach in the treatment of MetS. The CV risk conferred by MetS segregates differently according to gender; differences between sexes may depend on the different representation of MetS components, gender-specific genetic, acquired metabolic and hormonal milieu and finally on a differential interaction between known risk factors and genderspecific properties, resulting in different degrees of pathophysiological events eventually leading to atherothrombosis. Regarding a potential sex-related therapeutic approach, even if gender-related differences exist in the pharmacokinetics of drugs for differences in body composition, plasma protein binding, metabolizing enzymes and difference in excretion characteristics, we have to acknowledge that women are under-represented in clinical trials, thus preventing from adequately challenging the efficacy and safety of drugs in this gender. CONCLUSION: While ncreasing knowledge exists regarding pathophysiological differences between genders in the prevalence of MetS components as well as in the associated cardiometabolic risk, underrepresentation of women in clinical trials and underutilization of guideline therapy, for instance in women with ischemic heart disease, largely flaw the interpretation of epidemiological and clinical evidence. Efforts should be undertaken to fight the so-called "Yentl syndrome" and to promote gender-specific drug trials, or at least studies where subgroup analyses by gender are pre-specified.
28643937 Proinflammatory effects and mechanisms of calprotectin on human gingival fibroblasts. 2017 Dec BACKGROUND AND OBJECTIVE: Calprotectin (S100A8/A9) is a heterodimer of S100A8 and S100A9 and is associated with multiple inflammatory diseases, including Crohn's disease, rheumatoid arthritis and periodontitis. Levels of calprotectin are elevated in the gingival crevicular fluid of patients with periodontitis; however, the effects of calprotectin on human gingival fibroblasts (HGFs) remain unknown. This study investigated the proinflammatory activity of calprotectin on HGFs and the functional receptors and signaling pathways engaged by calprotectin. MATERIAL AND METHODS: HGFs were stimulated by equimolar concentrations of S100A8 and/or S100A9, and the expression levels of interleukin (IL)-6 and IL-8 were detected using real-time quantitative polymerase chain reaction and enzyme-linked immunosorbent assays. The calprotectin receptors were identified by pre-incubating HGFs with the toll-like receptor (TLR) 4 inhibitor or the antibody targeting the advanced glycation end product receptor (RAGE). The involvement of reactive oxygen species (ROS) and signaling pathways were also investigated by treating HGFs with ROS inhibitor or specific pathway inhibitors, respectively. RESULTS: S100A9 and S100A8/A9 significantly upregulated IL-6 and IL-8 expression, which was inhibited upon treatment with the TLR4 inhibitor TAK242. Pretreatment with RAGE-blocking antibodies did not affect cytokine expression. Additionally, S100A9 promoted the production of IL-6 and IL-8 from HGFs via different signaling pathways. IL-6 expression was upregulated via the NF-κB, c-Jun amino-terminal kinase (JNK) 1/2 and p38 mitogen-activated protein kinase (MAPK) pathways, and IL-8 expression was upregulated via NF-κB, p38, JNK1/2 and extracellular-regulated kinase 1/2 MAPK pathways. The release of both cytokines was dependent upon the production of ROS. CONCLUSION: Our findings suggest that calprotectin exerts proinflammatory effects on HGFs via the S100A9 subunit and TLR4-mediated NF-κB and MAPK signaling pathways.
28301084 The Effect of Verapamil, a P-Glycoprotein Inhibitor, on the Pharmacokinetics of Peficitini 2017 Nov Peficitinib is an orally administered, once-daily Janus kinase inhibitor currently in development for the treatment of rheumatoid arthritis. It has been shown to be a P-glycoprotein (P-gp) substrate in vitro. The effects of verapamil, an inhibitor of the efflux pump P-gp, on the pharmacokinetic profile of peficitinib were assessed in this open-label, single-center, single-sequence, crossover drug-interaction study. Twenty-four healthy volunteers received a single 150-mg dose of peficitinib on days 1 and 12 of a 14-day treatment period and received verapamil 80 mg 3 times daily on days 5-14. Repeated-dose administration of verapamil increased mean peficitinib AUC(inf) , AUC(last) , and C(max) by 27%, 27%, and 39%, respectively, and also increased the mean AUC and C(max) of peficitinib metabolites H1, H2, and H4. Coadministration of verapamil with peficitinib 150 mg was generally well tolerated. Overall, the most commonly reported adverse event was headache, which occurred in 5 subjects (21%); all reported adverse events were grade 1 severity, with the exception of 1 grade 2 incident of vomiting.
28235825 Genome-Wide Screen Reveals sec21 Mutants of Saccharomyces cerevisiae Are Methotrexate-Resi 2017 Apr 3 Drug resistance is a consequence of how most modern medicines work. Drugs exert pressure on cells that causes death or the evolution of resistance. Indeed, highly specific drugs are rendered ineffective by a single DNA mutation. In this study, we apply the drug methotrexate, which is widely used in cancer and rheumatoid arthritis, and perform evolution experiments on Baker's yeast to ask the different ways in which cells become drug resistant. Because of the conserved nature of biological pathways between yeast and man, our results can inform how the same mechanism may operate to render human cells resistant to treatment. Exposure of cells to small molecules and drug therapies imposes a strong selective pressure. As a result, cells rapidly acquire mutations in order to survive. These include resistant variants of the drug target as well as those that modulate drug transport and detoxification. To systematically explore how cells acquire drug resistance in an unbiased manner, rapid cost-effective approaches are required. Methotrexate, as one of the first rationally designed anticancer drugs, has served as a prototypic example of such acquired resistance. Known methotrexate resistance mechanisms include mutations that increase expression of the dihydrofolate reductase (DHFR) target as well as those that maintain function yet reduce the drug's binding affinity. Recent evidence suggests that target-independent, epistatic mutations can also result in resistance to methotrexate. Currently, however, the relative contribution of such unlinked resistance mutations is not well understood. To address this issue, we took advantage of Saccharomyces cerevisiae as a model eukaryotic system that combined with whole-genome sequencing and a rapid screening methodology, allowed the identification of causative mutations that modulate resistance to methotrexate. We found a recurrent missense mutation in SEC21 (orthologous to human COPG1), which we confirmed in 10 de novo methotrexate-resistant strains. This sec21 allele (S96L) behaves as a recessive, gain-of-function allele, conferring methotrexate resistance that is abrogated by the presence of a wild-type copy of SEC21 These observations indicate that the Sec21p/COPI transport complex has previously uncharacterized roles in modulating methotrexate stress.
28160026 Assessing Risk of Osteoporotic Fractures in Primary Care: Development and Validation of t 2017 Jun We aimed to develop and validate the FRActure Health Search (FRA-HS) score for prediction of risk of osteoporotic fractures in primary care in Italy. We selected a cohort of patients aged 40 years between 1999 and 2002. They were followed until the occurrence of osteoporotic fracture, death, end of data registration, or end of data availability (December 31, 2012). Age, sex, history of osteoporotic fractures, secondary osteoporosis, long-term use of corticosteroids, rheumatoid arthritis, body mass index, smoking, and alcohol abuse/alcohol-related diseases, and the interaction terms sex*use of corticosteroids and age*secondary osteoporosis were entered in a competing-risk regression (Fine and Gray method) to predict the risk of hip/femur or overall major osteoporotic fractures. The coefficients were combined to obtain the FRA-HS for individual patients. Explained variance, discrimination, and calibration measures were computed to evaluate the models accuracy. The final model was tested using an independent data source. The FRA-HS explained 47.36 and 20.6% of the variation for occurrence of hip/femur and overall major osteoporotic fractures, respectively. Area Under Curve was 0.77 and 0.73, respectively. Predicted/observed ratios revealed a margin of error lower than 30% in the 80% of the population. After stratifying by sex, prediction models for hip/femur fractures confirmed acceptable accuracy in both sexes, while poor explained variance (<20%) was observed for overall major fractures. These findings indicate that FRA-HS might be implemented in primary care for risk prediction of hip/femur fractures. General practitioners could be therefore supported by this tool in clinical decision making.
27888057 Association between rs2294020 in X-linked CCDC22 and susceptibility to autoimmune diseases 2017 Jan Autoimmune diseases often share common susceptibility genes. Most genetic variants associated with susceptibility to systemic lupus erythematosus are also associated with other autoimmune diseases. The X-linked variant rs2294020 is positioned in exon 7 of the CCDC22 gene. The encoded protein functions in the regulation of NF-κB, a master regulator in immune response. The aim of this study is to investigate whether the rs2294020 polymorphism may be a general susceptibility factor for autoimmunity. We evaluated case-control association between the occurrence of rs2294020 and different autoimmune diseases, including new data for systemic lupus erythematosus and previous genome-wide association studies (GWAS) (though most did not analyse the X chromosome) of psoriasis, celiac disease, Crohn's disease, ulcerative colitis, multiple sclerosis, vitiligo, type-1 diabetes, rheumatoid arthritis, and ankylosing spondylitis. Cases from patients affected by amyotrophic lateral sclerosis and type-2 diabetes were also included in the study. We detected nominal significant associations of rs2294020 with systemic lupus erythematosus (additive model test: p=0.01), vitiligo (p=0.016), psoriasis (p=0.038), and in only one of two studies of multiple sclerosis (p=0.03). Our results suggest that rs2294020 is associated with the risk of several autoimmune diseases in European populations, specifically with diseases that present themselves, among else, in the skin.
28624334 Seasonality and autoimmune diseases: The contribution of the four seasons to the mosaic of 2017 Aug Autoimmune diseases (ADs) are a heterogeneous groups of diseases that occur as a results of loss of tolerance to self antigens. While the etiopathogeneis remain obscure, different environmental factors were suggested to have a role in the development of autoimmunity, including infections, low vitamin D levels, UV radiation, and melatonin. Interestingly, such factors possess seasonal variation patterns that could influence disease development, severity and progression. Vitamin D levels which reach a nadir during late winter and early spring is correlated with increased disease activity, clinical severity as well as relapse rates in several disease entities including multiple sclerosis (MS), non-cutaneous flares of systemic lupus erythematosus (SLE), psoriasis, and rheumatoid arthritis (RA). Additionally, immunomodulatory actions of melatonin secretion ameliorate the severity of several ADs including MS and SLE. Melatonin levels are lowest during spring, a finding that correlates with the highest exacerbation rates of MS. Further, melatonin is postulated to be involved in the etiopathogenesis of inflammatory bowel diseases (IBD) through it influence on adhesion molecule and therefore transcription factor expression. Moreover, infections can mount to ADs through pro-inflammatory cytokine release and human antigen mimicry. Seasonal patterns of infectious diseases are correlated with the onset and exacerbation of ADs. During the winter, increased incidence of Epstein-Barr virus (EBV) infectious are associated with MS and SLE flares/onset respectively. In addition, higher Rotavirus infections during the winter precedes type 1 diabetes mellitus onset (T1DM). Moreover, Escherichia coli (E. coli) infection prior to primary biliary cirrhosis (PBC) and T1DM disease onset subsequent to Coxachievirus infections are seen to occur during late summer, a finding that correlate with infectious agents' pattern of seasonality. In this review, the effects of seasonality on the onset, relapses and activity of various ADs were discussed. Consideration of seasonal variation patterns of ADs can possibly provide clues to diseases pathogenesis and lead to development of new approaches in treatment and preventative care.
28539742 Neutralization of Inflammation by Inhibiting In vitro and In vivo Secretory Phospholipase 2017 Apr BACKGROUND: Inflammation is a normal and necessary prerequisite to healing of the injured tissues. Inflammation contributes to all disease process including immunity, vascular pathology, trauma, sepsis, chemical, and metabolic injuries. The secretory phospholipase A(2) (sPLA(2)) is a key enzyme in the production of pro-inflammatory mediators in chronic inflammatory disorders such as rheumatoid arthritis, coronary heart disease, diabetes, and asthma. The sPLA(2) also contribute to neuroinflammatory disorders such as Parkinson's, Alzheimer's, and Crohn's disease. AIMS: The present study aims to investigate the inhibition of human sPLA(2) by a popular medicinal herb Boerhaavia diffusa Linn. as a function of anti-inflammatory activity. MATERIALS AND METHODS: The aqueous and different organic solvents extracts of B. diffusa were prepared and evaluated for human synovial fluid, human pleural fluid, as well as Vipera russelli and Naja naja venom sPLA(2) enzyme inhibition. RESULTS: Among the extracts, the ethanol extract of B. diffusa (EEBD) showed the highest sPLA(2) inhibition and IC(50) values ranging from 17.8 to 27.5 μg. Further, antioxidant and lipid peroxidation activities of B. diffusa extract were checked using 2,2-diphenyl-1-picrylhydrazyl radical, thiobarbituric acid, and rat liver homogenate. The antioxidant activity of EEBD was more or less directly proportional to in vitro sPLA(2) inhibition. Eventually, the extract was subjected to neutralize sPLA(2)-induced mouse paw edema and indirect hemolytic activity. The EEBD showed similar potency in both the cases. CONCLUSIONS: The findings suggest that the bioactive molecule/s from the EEBD is/are potentially responsible for the observed in vitro and in vivo sPLA(2) inhibition and antioxidant activity. SUMMARY: The present study aims to investigate the inhibition of human sPLA(2) by a popular medicinal herb Boerhaavia diffusa Linn. as a function of anti inflammatory activity. Abbreviation Used: EEBD: Ethanolic extract of boerhaavia diffusa, sPLA(2): Secretory phospholipase A(2), HSF: Human synovial fluid, HPF: Human pleural fluid, VRV-PLA2-V: Vipera russelli phospholipase A2, NN-PLA(2)-I: Naja naja phospholipase A(2).
28508950 Malignancy as a comorbidity in rheumatic diseases: a retrospective hospital-based study. 2018 Jan Patients with Rheumatic diseases (RDs) are at an increased risk of malignancies compared with the general population. The aim of this study was to examine the relative frequency of several cancers in a single homogeneous cohort of patients with different RDs. Patients diagnosed with rheumatoid arthritis (RA), Ankylosing spondylitis (AS), Sjögren's syndrome (SS), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), dermatomyositis (DM), or polymyositis were included. Out of 3982 adult residents admitted to the division of rheumatology, 61 malignancies were observed. The 2009 National Central Cancer Registry (NCCR) of China served as the reference for calculating standardized ratio (SR). The malignancy frequency had no difference between RDs with malignancy and the general population. Patients with SS and DM/PM showed an increased risk of non-Hodgkin's lymphoma (SR for SS patients = 9.709, 95% confidence interval (CI) = 4.602 to 17.916; SR for DM/PM = 35.714, 95% CI = 25.001 to 49.527). Patients with DM/PM and SSc showed an increased risk of lung cancer (SR for DM/PM = 10.638, 95% CI = 5.245 to 19.131; SR for SSc patients = 7.752, 95% CI = 3.295 to 15.309). Patients with SS and DM/PM showed an increased risk of ovary cancer (SR for SS patients = 8.177, 95% CI = 3.566 to 15.888; SR for DM/PM = 32.258, 95% CI = 22.126 to 45.490). Patients with SLE showed an increased risk of cervix cancer (SR for AS patients = 6.897, 95% CI = 2.748 to 14.144). Patients with AS showed an increased risk of pancreas cancer (SR for AS patients = 7.576, 95% CI = 2.181 to 15. 071). Different RDs have an increased risk of particular cancers. Among hematologic cancers, the risk of non-Hodgkin's lymphoma was higher than general population. Among solid tumors, the risk of cancers of the lung, ovary, cervix, and pancreas was higher than general population.
28302448 Aconitine: A potential novel treatment for systemic lupus erythematosus. 2017 Mar BACKGROUND: Aconitum plants have been widely used in China for thousands of years. Recent evidences indicate that aconitine, the main active ingredient of Aconitum, has immunomodulatory properties that might be useful for treating autoimmune diseases, such as rheumatoid arthritis. In this study, we conducted a pilot study to explore the effect and mechanisms of aconitine on the treatment of systemic lupus erythematosus. METHODS: A pristane-induced murine model was used. The pristane-induced mice were treated with aconitine (25, 75 μg kg(-1) d(-1), po) for 9 weeks. Every three weeks, proteinuria was detected to monitor the kidney damage and blood was collected to measure serum levels of autoantibodies, besides the kidney pathological examination. The major B cell activating factor and major pro-inflammatory mediators, PGE2, IL-17a and IL-6, were also detected. RESULTS: We found that aconitine significantly improved the mouse health, decreased the elevated blood leukocyte counts, reduced the serum level of anti-double-stranded DNA (anti-dsDNA) antibody, greatly ameliorated renal histopathologic damage and reduced IgG deposit in glomerular. Furtherly, the levels of PGE2, IL-17a and IL-6, were found to have decreased in aconitine treated mice. CONCLUSION: We have demonstrated that aconitine can inhibit the progression of disease and ameliorate the pathologic lesion of systemic lupus erythematosus.
28281463 What is the clinical significance of anti-Sm antibodies in systemic lupus erythematosus? A 2017 Jul OBJECTIVES: To investigate the clinical value of anti-Sm antibodies in diagnosis and monitoring of systemic lupus erythematosus (SLE) and their ability to predict lupus flares compared with that of anti-dsDNA antibody and complement (C3) assays. METHODS: Autoantibodies against Smith antigen (Sm) and double-stranded DNA (dsDNA) in sera from SLE (n=232), myositis (n=26), systemic sclerosis (n=81), Sjögren's syndrome (n=88), and rheumatoid arthritis patients (n=165) and healthy donors (n=400) were determined by using enzyme-linked immunosorbent assays (both from Euroimmun). New thresholds for both autoantibodies were calculated by receiver operating characteristics (ROC) curve analysis. Cross-sectional, longitudinal and predictive analyses of anti-Sm and disease activity were also performed. RESULTS: Sensitivities of 25.9% for anti-Sm (cut-off: 3.6 relative units/ml) and 30.2% for anti-dsDNA (cut-off 157.4 international units/ml) were obtained at a specificity of 99%. 14.8% of anti-dsDNA-negative patients were positive for anti-Sm, and more than half (51.4%) of anti-dsDNA-positive patients were also positive for anti-Sm. Anti-Sm antibodies were associated with age (p=0.0174), the number of ACR criteria (p=0.0242), the ACR criteria renal (p=0.0350) and neurologic disorder (p=0.0239), the BILAG category constitutional symptoms (p=0.0227), fatigue (p=0.0311) and cross-sectional disease activity (r=0.2519, p=0.0224). Although no correlations with lupus activity were observed in the longitudinal and predictive analysis, a remarkable association was found between anti-Sm and proteinuria. CONCLUSIONS: Anti-Sm antibodies are essential for diagnosis of SLE, especially in anti-dsDNA-negative patients. However, our data suggest that anti-Sm monitoring is only helpful in SLE patients with active lupus nephritis.
28260984 Age-related trends in injection site reaction incidence induced by the tumor necrosis fact 2017 Tumor necrosis factor-α (TNF-α) inhibitors are increasingly being used as treatment for rheumatoid arthritis (RA). However, the administration of these drugs carries the risk of inducing injection site reaction (ISR). ISR gives rise to patient stress, nervousness, and a decrease in quality of life (QoL). In order to alleviate pain and other symptoms, early countermeasures must be taken against this adverse event. In order to improve understanding of the risk factors contributing to the induction of ISR, we evaluated the association between TNF-α inhibitors and ISR by applying a logistic regression model to age-stratified data obtained from the Food and Drug Administration Adverse Event Reporting System (FAERS) database. The FAERS database contains 7,561,254 reports from January 2004 to December 2015. Adjusted reporting odds ratios (RORs) (95% Confidence Intervals) were obtained for interaction terms for age-stratified groups treated with etanercept (ETN) and adalimumab (ADA). The adjusted RORs for ETN* ≥ 70 and ADA* ≥ 70 groups were the lowest among the age-stratified groups undergoing the respective monotherapies. Furthermore, we found that crude RORs for ETN + methotrexate (MTX) combination therapy and ADA + MTX combination therapy were lower than those for the respective monotherapies. This study was the first to evaluate the relationship between aging and ISR using the FAERS database.
29226391 Experience with leflunomide as treatment and as secondary prophylaxis for cytomegalovirus 2018 Feb BACKGROUND: Data concerning the use of leflunomide-a drug approved for rheumatoid arthritis with in vitro anticytomegalovirus (CMV) activity-in lung transplant (LT) recipients are scarce. AIMS: To report the use of leflunomide in LT recipients diagnosed with CMV infection/disease. MATERIAL AND METHODS: We performed a single-center retrospective study including LT recipients who received leflunomide for CMV infection or as secondary prophylaxis after viremia clearance. We also conducted a full systematic PubMed search until June 30, 2017. RESULTS: We identified 5 LT recipients in our center plus 7 patients reported in the literature. All patients had previously received ganciclovir (GCV) and foscarnet (FOS), with drug-induced adverse effects described in 6 recipients (50%). Antiviral resistance mutations were observed in 8 patients (66.7%). Leflunomide was prescribed for CMV infection in 9 of 12 patients (75%) and as secondary prophylaxis in 3 patients (25%). Initial decrease of CMV viremia after starting leflunomide was observed in 7 of 9 recipients (77.7%), although this response was only transient in 2 patients. Long-term suppression of CMV viremia was reported in 7 of 12 patients (58.3%). In 3 recipients (25%), leflunomide was discontinued due to adverse effects. DISCUSSION: Our study has some limitations, such as the small number of patients included, its retrospective nature, and absence of leflunomide drug monitoring in serum. Notwithstanding, in our experience, leflunomide proved to be particularly effective as an anti-CMV secondary prophylaxis treatment and for clearing low-grade viremia. Moreover, leflunomide combined with a short course of GCV or intravitreal FOS also proved to be very effective in some patients. CONCLUSION: Leflunomide, alone or in combination, could be an effective treatment in selected LT recipients with GCV-resistant CMV infection and as secondary prophylaxis. Further studies are necessary.