Browse

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

ID PMID Title PublicationDate abstract
24090941 Liver abnormalities in connective tissue diseases. 2013 Aug The liver is a lymphoid organ involved in the immune response and in the maintenance of tolerance to self molecules, but it is also a target of autoimmune reactions, as observed in primary liver autoimmune diseases (AILD) such as autoimmune hepatitis, primary biliary cirrhosis, and primary sclerosing cholangitis. Further, the liver is frequently involved in connective tissue diseases (CTD), most commonly in the form of liver function test biochemical changes with predominant cholestatic or hepatocellular patterns. CTD commonly affecting the liver include systemic lupus erythematosus, antiphospholypid syndrome, primary Sjögren's syndrome, systemic sclerosis, dermatomyositis, polimyositis, and anti-synthetase syndrome, while overlap syndromes between AILD and CTD may also be diagnosed. Although liver cirrhosis and failure are extremely rare in patients with CTD, unusual liver conditions such as nodular regenerative hyperplasia or Budd-Chiari syndrome have been reported with increasing frequency in patients with CTD. Acute or progressing liver involvement is generally related to viral hepatitis reactivation or to a concomitant AILD, so it appears to be fundamental to screen patients for HBV and HCV infection, in order to provide the ideal therapeutic regimen and avoid life-threatening reactivations. Finally, it is important to remember that the main cause of biochemical liver abnormalities in patients with CTD is a drug-induced alteration or coexisting viral hepatitis. The present article will provide a general overview of the liver involvement in CTD to allow rheumatologists to discriminate the most common clinical scenarios.
22212410 Hypokalemic periodic paralysis in Sjogren's syndrome secondary to distal renal tubular aci 2013 Jul We report a 53-year-old Turkish female presented with progressive weakness and mild dyspnea. Laboratory results demonstrated severe hypokalemia with hyperchloremic metabolic acidosis. The urinary anion gap was positive in the presence of acidemia, thus she was diagnosed with hypokalemic paralysis from a severe distal renal tubular acidosis (RTA). Immunologic work-up showed a strongly positive ANA of 1:3,200 and positive antibodies to SSA and SSB. Schirmer's test was abnormal. Autoimmune and other tests revealed Sjögren syndrome as the underlying cause of the distal renal tubular acidosis. Renal involvement in Sjogren's syndrome (SS) is not uncommon and may precede sicca complaints. The pathology in most cases is a tubulointerstitial nephritis causing among other things, distal RTA, and, rarely, hypokalemic paralysis. Treatment consists of potassium repletion, alkali therapy, and corticosteroids. Primary SS could be a differential in women with acute weakness and hypokalemia.
24758276 Investigational drugs for treating psoriatic arthritis. 2014 Jul INTRODUCTION: Psoriatic arthritis (PsA) is an inflammatory arthritis occurring in up to 30% of patients with psoriasis and can lead to progressive joint damage and disability. The emergence of 'biological' treatments, typified by the TNF inhibitors, has significantly advanced treatment of psoriatic disease over the last two decades and has led to an expanding field of drugs designed to target specific pathways identified in the pathogenesis of the disease. AREAS COVERED: This review article describes current knowledge pertaining to genetic susceptibility and that gleaned from animal models. It discusses putative drug targets and drugs in development, up to Phase II, while acknowledging that many of these drugs are being investigated in rheumatoid arthritis and psoriasis rather than PsA alone. EXPERT OPINION: Ongoing trials of some of these drugs, such as the JAK inhibitors, appear particularly promising, while the evolution of dual-targeting therapies affords the aspiration of enhanced efficacy, safety and remission. Paramount to the future of drug discovery and development is the affordability of these agents to the healthcare purchaser as well as their accessibility to the patient.
25362659 Etiopathogenic role of surfactant protein d in the clinical and immunological expression o 2015 Jan OBJECTIVE: To analyze the etiopathogenic role of genetic polymorphisms and serum levels of surfactant protein-D (SP-D) in primary Sjögren syndrome (pSS). METHODS: We analyzed 210 consecutive patients with pSS. SFTPD genotyping (M11T polymorphism rs721917) was analyzed by sequence-based typing and serum SP-D by ELISA. RESULTS: Thirty-two patients (15%) had the Thr11/Thr11 genotype, 80 (38%) the Met11/Met11 genotype, and 96 (46%) the Met11/Thr11 genotype; 2 patients could not be genotyped. Patients carrying the Thr11/Thr11 genotype had a higher prevalence of renal involvement (13% vs 1% and 4% in comparison with patients carrying the other genotypes, p = 0.014). Serum SP-D levels were analyzed in 119 patients (mean 733.94 ± 49.88 ng/ml). No significant association was found between serum SP-D levels and the SP-D genotypes. Higher mean values of serum SP-D were observed in patients with severe scintigraphic involvement (851.10 ± 685.69 vs 636.07 ± 315.93 ng/ml, p = 0.038), interstitial pulmonary disease (1053.60 ± 852.03 vs 700.36 ± 479.33 ng/ml, p = 0.029), renal involvement (1880.64 ± 1842.79 vs 716.42 ± 488.01 ng/ml, p = 0.002), leukopenia (899.83 ± 661.71 vs 673.13 ± 465.88 ng/ml, p = 0.038), positive anti-Ro/SS-A (927.26 ± 731.29 vs 642.75 ± 377.23 ng/ml, p = 0.006), and positive anti-La/SS-B (933.28 ± 689.63 vs 650.41 ± 428.14 ng/ml, p = 0.007), while lower mean values of serum SP-D were observed in patients with bronchiectasis (489.49 vs 788.81 ng/ml, p = 0.019). CONCLUSION: In pSS, high SP-D levels were found in patients with severe glandular involvement, hypergammaglobulinemia, leukopenia, extraglandular manifestations, and positive anti-Ro/La antibodies. The specific association between SP-D levels and pulmonary and renal involvements may have pathophysiological implications.
24573508 Newly diagnosed adult-onset Still's disease with pure red cell aplasia in pregnancy. 2014 Jul BACKGROUND: Adult-onset Still's disease (AOSD) is a rare inflammatory disease of unknown etiology that can present for the first time during pregnancy. Pure red cell aplasia (PRCA) is another rare condition that seldom is in association with AOSD. Herein, we have reported a newly diagnosed case with AOSD and PRCA in a previously healthy pregnant woman. CASE DESCRIPTION: A 25-year-old primigravida lady presented with fever, malaise, and arthralgia at 26 weeks of gestation. She had an extensive evaluation that led to the diagnosis of AOSD. Preliminary blood tests displayed a severe anemia with hemoglobin 5.1 g/dL, leukocytosis (total white blood cells count of 26,000 μL(-1)), normal mean corpuscular volume, normal mean corpuscular hemoglobin, normal platelet count, and a low reticulocyte count (0.2 %). The condition was diagnosed as AOSD associated with PRCA. She was treated with prednisolone and had immediate and dramatic improvement. CONCLUSION: AOSD and PRCA in pregnancy are rare conditions. The recognition of these clinical syndromes may lead to earlier diagnosis and thus prevent the expensive investigations. Both conditions have a dramatic improvement upon using corticosteroids therapy.
23374667 [MALT-type parotid lymphoma--a case report and the review of the literature]. 2013 Jan Primary lymphomas of the salivary glands are rare. It is estimated that they constitute no more than 5% of all lymphomas in different locations. The most common subtype developing in parotid glands is marginal zone B-cell mucosa associated lymphoid tissue type lymphoma (MALT) that belongs to a group of low-grade tumours. There are many factors associated with the incidence of that proliferative process: environmental and infectious agents as well as immune deficiency states. We describe a case of primary non-Hodgkin's lymphoma of the parotid gland arising in the background of previously undiagnosed and untreated Sjögren's syndrome in a 52-year-old woman. The article concerns a short review of the literature regarding etiology, symptoms, treatment and survival prognosis in that rare disease as well. MALT lymphomas should always be considered in the differential diagnosis of the tumors and swelling of the parotid gland area. A special, regular monitoring should include all patients with Sjögren's syndrome as those with the proven greater risk of developing that proliferative disease. The role of the laryngologist in the case of MALT-type lymphoma of the parotid gland should focus on a diagnosis and possible tumor cytoreduction with maximal saving of the facial nerve. The essential treatment of this pathology is one of the oncologists and haematologists.
22928476 Comparison of autologous serum eye drops with different diluents. 2013 Jan PURPOSE: To compare the effect of autologous serum eye drops with different diluents in patients with dry eyes and persistent epithelial defects. METHODS: Patients of Sjögren's syndrome (Group I), non-Sjögren's syndrome (group II) with dry eye, and persistent epithelial defects (Group III) were included. The eyes of each group were randomly treated with one of the following autologous serum eye drops: 100% serum (AS(100)), 50% serum with normal saline (AS(50NS)); 50% serum with sodium hyaluronate (AS(50HA)); or 50% serum with ceftazidime (AS(50CEF)). The differences in dry eye symptoms, Schirmer test I, tear break-up time (TBUT), corneal staining, and speed in epithelial healing were studied. RESULTS: In Group I, AS(100) showed fewer symptoms than AS(50NS), AS(50HA) and AS(50CEF) (all p < 0.01). AS(100) showed significantly better effect than AS(50NS), AS(50HA) and AS(50CEF) in decreasing corneal staining at the time point of 12-week post-treatment (p = 0.041, p < 0.001 and p < 0.001, respectively). In Group II, AS(100) was more effective than AS(50CEF) in decreasing symptoms and decreasing corneal staining (all p < 0.05). There was no significant difference in symptom and corneal staining between AS(100) and AS(50NS). In Group III, AS(100) was the most effective in achieving quick epithelial closure. CONCLUSION: In the eyes with Sjögren syndrome and persistent epithelial defects, AS(100) was the most effective in decreasing symptoms, corneal epitheliopathy and promoting fast closure of wound. In the eyes with non-Sjögren syndrome, AS(100) and AS(50NS) have similar effects in decreasing symptoms and corneal epitheliopathy.
24129139 Can traditional disease-modifying anti-rheumatic drugs be withdrawn or tapered in psoriati 2013 Jul Psoriatic arthritis (PsA) is a complex, multisystem disease with musculoskeletal and skin manifestations frequently associated with features of the metabolic syndrome. For many years, treatment strategies were largely borrowed from the rheumatoid arthritis literature, with clinical trials of traditional DMARDs in PsA often inadequate and using limited outcome measures. Nonetheless, DMARDs - in particular, methotrexate - remain the treatment of first choice for most rheumatologists treating this disease, especially for those with prominent polyarticular involvement. While there is no agreed definition of remission in PsA, a number of longitudinal studies suggests that remission can be achieved in approximately 25% of patients treated with traditional DMARDs, with drug-free remission possible in <10%. There are many unanswered questions, and this review concludes by highlighting a research agenda which aims to address some of the most critical questions for physicians and patients alike faced with deciding if treatment should be withdrawn or continued when disease remission is achieved.
24032618 Adult onset Still's disease as a paraneoplastic syndrome--a case report and review of the 2013 Adult onset Still's disease (AOSD) is a systemic inflammatory disease with unknown etiology and characterized by evanescent salmon pink rash, sore throat, liver dysfunction, lymphadenopathy, hepatosplenomegaly, arthritis, and leukocytosis. It is a diagnosis of exclusion; however, there are case reports in the literature about patients with malignancies and AOSD-like signs and symptoms. Here we report a patient with AOSD seems to be associated with sarcomatoid renal cell carcinoma. This phenomenon is not distinguishable from primary AOSD either in presentation or in treatment; except for the main purpose of the management should be targeted to the underlying malignancy.
23999819 A possible genetic association with chronic fatigue in primary Sjögren's syndrome: a cand 2014 Feb Fatigue is prevalent and disabling in primary Sjögren's syndrome (pSS). Results from studies in chronic fatigue syndrome (CFS) indicate that genetic variation may influence fatigue. The aim of this study was to investigate single nucleotide polymorphism (SNP) variations in pSS patients with high and low fatigue. A panel of 85 SNPs in 12 genes was selected based on previous studies in CFS. A total of 207 pSS patients and 376 healthy controls were genotyped. One-hundred and ninety-three patients and 70 SNPs in 11 genes were available for analysis after quality control. Patients were dichotomized based on fatigue visual analogue scale (VAS) scores, with VAS <50 denominated "low fatigue" (n = 53) and VAS ≥50 denominated "high fatigue" (n = 140). We detected signals of association with pSS for one SNP in SLC25A40 (unadjusted p = 0.007) and two SNPs in PKN1 (both p = 0.03) in our pSS case versus control analysis. The association with SLC25A40 was stronger when only pSS high fatigue patients were analysed versus controls (p = 0.002). One SNP in PKN1 displayed an association in the case-only analysis of pSS high fatigue versus pSS low fatigue (p = 0.005). This candidate gene study in pSS did reveal a trend for associations between genetic variation in candidate genes and fatigue. The results will need to be replicated. More research on genetic associations with fatigue is warranted, and future trials should include larger cohorts and multicentre collaborations with sharing of genetic material to increase the statistical power.
23576645 Primary presentation with acute flaccid quadriparesis in Sjogren's syndrome sans sicca. 2013 Apr 9 We report the case of a 40-year-old housewife, who presented with vomiting since past 5 days and weakness of all four limbs since 1 day. Clinical examination confirmed the presence of flaccid quadriparesis with preserved tendon reflexes. Routine laboratory parameters showed severe hypokalaemia. On further evaluation she was diagnosed to have type 1 renal tubular acidosis secondary to Sjogren's syndrome. Sicca symptoms were conspicuous by their absence.
23388327 [Protective mechanism of XinFeng capsule on Sojgren syndrome rat pulmonary function based 2013 Feb OBJECTIVE: To explore the effect of XinFeng capsule (XFC) on pulmonary function of Sjogren syndrome (SS) rat and on the TGF-β1-ERK1 signal pathway. METHODS: A total of 50 SD rats were randomly divided into normal control group, model control group and hydroxychloroquine sulfate (HCQ) group, radix paeoniae alba (total glucosides of paeony capsules, TGP) group, XFC treatment group, with 10 in each group. Except for the normal control group, the other group rats were induced to establish SS models by injecting the complete Freund's adjuvant and the same rat submandibular gland antigen (0.2 mL mixture) into bilateral posterior paw metatarsus. All the animals were examined with lung function detection instrument. Meanwhile, we recorded the changes in water consumption and body mass of the rats and observed the expressions of ERK1 and TGF-β1 using immunohistochemistry and serum cell factors (IL-17, IL-4) using ELISA. RESULTS: Compared with the normal control group, the model controls had reduced body mass, lower IL-4 level, increased water consumption, submandibular gland/lung index, submandibular gland pathological score, ERK1, TGF-β1 integral and IL-17 level (P<0.01 or P<0.05), and decreased pulmonary function parameter (P<0.01 or P<0.05). Compared with model control group, in XFC treatment group body mass, pulmonary function parameter FEF(50);, maximum midexpiratory flow rate (MMF), and IL-4 expression level increased, while water consumption, submandibular gland/lung index, submandibular gland pathological score, serum IL-17 expression, ERK1, TGF-β1 integral decreased (P<0.01 or P<0.05). XFC group rats were elevated in FEF(25);, FEF(75);, MMF (P<0.01 or P<0.05) and lowered in body mass and IL-17 level (P<0.01) as compared with the HCQ group, and the pulmonary function parameters and IL-17 level all went down as compared with the TGP group (P<0.01 or P<0.05). CONCLUSION: Lung function of SS rats degrades, which may be related to TGF-β1-ERK1 signal pathway activation. XFC can down-regulate TGF-β1 level, inhibit ERK1 phosphorylation, ameliorate immune inflammation and improve lung function.
24372293 Diagnostic accuracy of anti-alpha-fodrin antibodies for primary Sjögren's syndrome. 2014 Sep OBJECTIVES: To estimate the diagnostic accuracy of anti-alpha-fodrin antibodies for primary Sjögren's syndrome (pSS). METHODS: Sixty-four pSS subjects and 108 non-pSS patients were prospectively enrolled in this study. Serum anti-alpha-fodrin IgA and IgG were detected by ELISA in a blind fashion. The diagnostic accuracy of anti-alpha-fodrin antibodies was assessed by receiver operating characteristic (ROC) curve analysis. Logistic regression was used to investigate whether anti-alpha-fodrin antibodies could improve the accuracy of pSS diagnosis if used in addition to anti-SSA and anti-SSB. RESULTS: The areas under the ROC curves for anti-alpha-fodrin IgG and IgA were 0.69 (95% confidence interval (CI): 0.60-0.77) and 0.63 (95% CI: 0.54-0.72), respectively (P < 0.01 for both). The optimal diagnostic thresholds for anti-fodrin IgG and IgA were 11.75 U/ml and 9.75 U/ml, respectively, with a sensitivity of 0.59 and 0.55, and a specificity of 0.75 and 0.73, respectively. Anti-alpha-fodrin IgG and IgA antibodies were associated with pSS after adjustment for anti-SSA and anti-SSB. CONCLUSIONS: Anti-alpha-fodrin IgG and IgA antibodies are useful diagnostic markers which may improve the accuracy of pSS diagnosis.
24040065 Prognostic factors in interstitial lung disease associated with primary Sjögren's syndrom 2013 INTRODUCTION: Interstitial lung disease associated with primary Sjögren's syndrome (pSS-ILD) shows several patterns such as nonspecific interstitial pneumonia (NSIP) and usual interstitial pneumonia (UIP). Although UIP is a well-recognized prognostic determinant in idiopathic interstitial pneumonias, whether this is also the case in pSS-ILD is unclear. The objectives of this study were to evaluate the prognostic effect of UIP, and to identify the prognostic factors in pSS-ILD. METHODS: A retrospective review of medical records identified 33 consecutive patients with pathologically-proven pSS-ILD. Each patient was classified into each ILD pattern by multidisciplinary analysis. Baseline clinical-radiologic-pathologic characteristics and survival rates were compared between the ILD patterns. Finally, the prognostic factors in pSS-ILD were assessed by univariate and subsequent multivariate analyses using Cox's proportional hazards regression model. RESULTS: pSS-ILD patients were diagnosed with NSIP (n = 22) or UIP (n = 11). The median follow-up period was 110 months, and five-year survival rate was 87.3% in the total patient population. The prognosis of the UIP patients was not significantly different from that of the NSIP patients (NSIP to UIP, hazard ratio [HR]: 0.77, 95% confidence interval [CI]: 0.18-3.36, P = 0.73). Multivariate analysis identified PaCO2 (HR: 1.68 per 1 Torr increase, 95% CI: 1.24-2.28, P < 0.01), extent of reticular abnormality on high-resolution CT (HR: 4.17 per 1-grade increment, 95% CI: 1.18-14.73, P = 0.03), and severity of fibroblastic foci (HR: 9.26 per 1-grade increment, 95% CI: 1.74-49.35, P < 0.01) as prognostic factors in pSS-ILD. CONCLUSIONS: UIP in pSS-ILD was not related to poorer prognosis than NSIP. Assessment of detailed clinical-radiologic-pathologic findings is more important than distinguishing UIP to evaluate prognosis in this disease.
23335582 Pain severity and neuropathic pain symptoms in primary Sjögren's syndrome: a comparison s 2013 Aug OBJECTIVE: To compare clinical characteristics and patient-reported outcomes in seropositive versus seronegative primary Sjögren's syndrome (SS) patients and to investigate the effect of serologic status on the prevalence of chronic pain, comorbidity, and health quality. METHODS: Pain severity and neuropathic pain symptoms, comorbidity, and health status were assessed in 108 primary SS patients. Differences between patient groups were assessed by t-test and chi-square test, as well as adjusted pain-affect associations. The effect of predictor variables on pain severity was examined with multivariate regression. RESULTS: Pain severity was greater (P = 0.003) and physical function (P = 0.023) was reduced in the seronegative patients. Prevalence of neuropathic pain, depression, anxiety, and disability was similar between groups. Chronic pain, defined as daily pain for >3 months, was reported by 65% of seropositive (n = 65) and 75% of seronegative (n = 40) patients. After adjustment for age, sleep quality, and psychological distress, the difference in pain severity between seropositive and seronegative patients remained significant. CONCLUSION: Chronic pain is pervasive in both seropositive and seronegative primary SS patients, while pain severity and functional impairment are greater in seronegative patients. Neuropathic pain is equally prevalent and is the predominant pain phenotype in patients with moderate to severe pain. Accurate assessment of pain phenotypes is needed for more effective management of chronic pain in primary SS. The focus of future research should be to standardize assessment of pain and to identify the factors contributing to more severe pain in seronegative patients.
25445630 [Differences of spectral Doppler in psoriatic arthritis and onychomycosis]. 2014 Nov OBJECTIVE: To evaluate the use of the spectral Doppler (SDoppler) to quantify inflammatory activity and to detect nail echotextural differences in patients with psoriatic arthritis and onychomycosis. METHODS: Two patients, one with psoriatic arthritis but with no joint pain nor nail clinical change and the other with onychomycosis and rheumatoid arthritis were included. The gray scale ultrasound study, showed changes in the regular presence of echotexture at the nail insertion, thickening of the nail bed and loss of trilaminar nail pattern. The spectral Dopplerresistance index (RI), detects the inflammatory process in nail entheses. RESULTS: Seven distal interphalangeal (DIP) joints in both patients were evaluated in two planes, getting nine RI. In the patient with psoriatic arthritis the author found: loss of normal trilaminar nail plate aspect, and nail beds and DIP joint capsules preserved. The spectral Doppler showed RI<1, with mean±SD=0.50±0.75 in the microcirculation at nail entheses, with characterization of a bone erosion in the third left DIP joint, with RI=0.38 and 0.63 in transverse and longitudinal planes, respectively. The patient with onychomycosis showed the following changes: hypoechogenicity at nail insertion; loss of nail shape, and spectral Doppler in nail entheses with RI>1, with mean±SD=1.71±0.98. CONCLUSION: The use of ultrasound can detect changes in the nail beds in these diseases. Future studies will further characterize these changes.
25152629 Efficacy and safety profile of combination of tramadol-diclofenac versus tramadol-paraceta 2014 OBJECTIVE: We aimed to evaluate the safety and efficacy of a fixed-dose combination (FDC) of tramadol and diclofenac versus a standard approved FDC of tramadol and paracetamol, in patients with acute moderate to severe pain. METHODS: A total of 204 patients with moderate to severe pain due to acute musculoskeletal conditions (n=52), acute flare of osteoarthritis (n=52), acute flare of rheumatoid arthritis (n=50), or postoperative pain (n=50) were enrolled in the study at baseline. Each disease category was then randomized to receive either of two treatments for 5 days: group A received an FDC of immediate-release tramadol hydrochloride (50 mg) and sustained-release diclofenac sodium (75 mg) (one tablet, twice daily), and group B received an FDC of tramadol hydrochloride (37.5 mg) and paracetamol (325 mg) (two tablets every 4-6 hours, up to a maximum of eight tablets daily). The primary efficacy end points were reductions in pain intensity from baseline at day 3 and day 5 as assessed by a Visual Analog Scale (VAS) score. RESULTS: Group A showed a significant reduction in the VAS score for overall pain from baseline on day 3 (P=0.001) and day 5 (P<0.0001) as compared with group B. The combination of tramadol-diclofenac resulted in few mild to moderate adverse events (nausea, vomiting, epigastric pain, and gastritis), which required minimal management, without any treatment discontinuation. The number of adverse events in group A was nine (8.82%) compared with 22 (21.78%) in group B, after 5 days of treatment. CONCLUSION: An FDC of tramadol-diclofenac showed a significantly greater reduction in pain intensity and was well tolerated compared with tramadol-paracetamol, resulting in better analgesia in patients suffering from moderate to severe pain due to acute musculoskeletal conditions, postoperative pain following orthopedic surgery, or acute flare of osteoarthritis and rheumatoid arthritis.
25086406 The structural basis of differential inhibition of human calpain by indole and phenyl α-m 2014 Sep Excessive activity of neutrophils has been linked to many pathological conditions, including rheumatoid arthritis, cancer and Alzheimer's disease. Calpain-I is a Ca(2+)-dependent protease that plays a key role in the extravasation of neutrophils from the blood stream prior to causing damage within affected tissues. Inhibition of calpain-I with small molecule mercaptoacrylic acid derivatives slows the cell spreading process of live neutrophils and so these compounds represent promising drug leads. Here we present the 2.05 and 2.03 Å co-crystal X-ray structures of the pentaEF hand region, PEF(S), from human calpain with (Z)-3-(4-chlorophenyl)-2-mercaptoacrylic acid and (Z)-3-(5-bromoindol-3-yl)-2-mercaptoacrylic acid. In both structures, the α-mercaptoacrylic acid derivatives bind between two α-helices in a hydrophobic pocket that is also exploited by a leucine residue of the endogenous regulatory calpain inhibitor calpastatin. Hydrophobic interactions between the aromatic rings of both inhibitors and the aliphatic residues of the pocket are integral for tight binding. In the case of (Z)-3-(5-bromoindol-3-yl)-2-mercaptoacrylic acid, hydrogen bonds form between the mercaptoacrylic acid substituent lying outside the pocket and the protein and the carboxylate group is coplanar with the aromatic ring system. Multiple conformations of (Z)-3-(5-bromoindol-3-yl)-2-mercaptoacrylic acid were found within the pocket. The increased potency of (Z)-3-(5-bromoindol-3-yl)-2-mercaptoacrylic acid relative to (Z)-3-(4-chlorophenyl)-2-mercaptoacrylic acid may be a consequence of the indole group binding more deeply in the hydrophobic pocket of PEF(S) than the phenyl ring.
23608542 Chikungunya-related arthritis: case report and review of the literature. 2013 Oct INTRODUCTION: Chikungunya fever often presents with severe arthritis/arthralgias, high fever, myalgias, headache, and maculopapular rash (Chow et al., 2011 [1]; Das et al., 2010 [2]; Mizuno et al., 2011 [3]; Powers, 2010 [4]; Sissoko et al., 2010 [5]; Staples et al., 2009 [6]). Persistent arthritis/arthralgias commonly develop after symptomatic infection and are the most common long-term complication (Chow et al., 2011 [1]; Powers, 2010 [4]; Sissoko et al., 2010 [5]; Staples et al., 2009 [6]). The small joints are most often affected in a symmetric pattern that can mimic adult rheumatoid arthritis (RA) (Mizuno et al., 2011 [3]; Bouquillard and Combe, 2009 [7]; Chabbra et al., 2008 [8]; Jaffar-Bandjee et al., 2009 [9]; Simon et al., 2007 [10]). OBJECTIVE: We present a case of Chikungunya virus (CHIKV)-induced arthritis and review the literature surrounding Chikungunya-induced arthritis/arthralgias and associated musculoskeletal (MSK) manifestations. METHODS: A Medline search was completed from 1946--November 2011. Key words included Chikungunya virus and arthritis. A PubMed search was completed from 1996--November 2011. Search terms included Chikungunya virus, etiology, and fever. Searches were limited to humans and English language publications. Additional relevant articles were obtained from the reference lists.
24854354 Frequent conversion of tuberculosis screening tests during anti-tumour necrosis factor the 2015 Oct OBJECTIVES: To determine the rate of tuberculosis (TB) screening test conversion during anti-tumour necrosis factor (TNF) therapy in rheumatic patients with negative baseline screening. METHODS: This was a prospective study of rheumatic patients with negative baseline TB screening (tuberculin skin test (TST): <5 mm, and negative T-SPOT.TB, QuantiFERON-TB Gold In Tube (QFT-GIT) and chest X-ray) treated with anti-TNF agents. All patients underwent re-screening for TB with all assays 1 year later. Factors associated with TB test conversion were analysed and compared between 'converters' and 'non-converters'. RESULTS: Seventy patients (mean age 50.6±15.5 years) with rheumatic disease (33 with rheumatoid arthritis, 33 with spondyloarthropathies and 4 with other conditions) were enrolled. Patients were treated with different anti-TNFs (27 with adalimumab, 14 etanercept, 16 infliximab, 8 golimumab, 5 certolizumab pegol) for 1 year. Twenty patients (29%) displayed conversion of at least one screening assay 12 months after anti-TNF therapy: conversion of TST occurred in 9 (13%), T-SPOT.TB in 7 (10%) and QFT-GIT in 5 (7%). Only one patient had concomitant conversion of more than one screening test. Univariate and multivariate analysis revealed that only infliximab was associated with a decreased rate of TB screening assay conversion (OR 0.048, 95% CI 0.004 to 0.606, p=0.017). No patient (40% received isoniazid therapy) developed active TB during follow-up (27±12 months). CONCLUSIONS: Approximately one third of patients with negative baseline TB screening develop conversion of at least one screening test during anti-TNF treatment. These findings should be considered when designing re-screening strategies and contemplating latent TB therapy.