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ID PMID Title PublicationDate abstract
24003934 Targeting gp130 to prevent inflammation and promote insulin action. 2013 Sep Obesity and type 2 diabetes are now the most prevalent metabolic diseases in the Western world and the development of new strategies to treat these metabolic diseases is most warranted. Obesity results in a state of chronic low-grade inflammation in metabolically active tissues such as the liver, adipose tissue, brain and skeletal muscle. Work in our laboratory has focussed on the role of the cytokine interleukin-6 (IL)-6 and other IL-6-like cytokines that signal through the gp130 receptor complex. We have focussed on the role of blocking IL-6 trans-signalling to prevent inflammation on the one hand, and activating membrane-bound signalling to promote insulin sensitivity on the other hand. Since the cloning of the IL-6 gene nearly 30  years ago, a pattern has emerged associating IL-6 with a number of diseases associated with inflammation including rheumatoid arthritis (RA), Crohn's disease and several cancers. Accordingly, tocilizumab, an IL-6 receptor-inhibiting monoclonal antibody, is now useful for the treatment of RA. However, this may not be the most optimal strategy to block inflammation associated with IL-6 and may result in unwanted side effects that, paradoxically, could actually promote metabolic disease.
23841940 Dolosigranulum pigrum keratitis: a three-case series. 2013 Jul 10 BACKGROUND: Dolosigranulum pigrum is a commensal inhabitant of the upper respiratory tract suspected to be responsible for ocular infections but no well-described case of D. pigrum corneal infection has been reported. Herein culture and PCR-sequencing-based investigations of corneal scraping specimens confirmed D. pigrum keratitis in three patients. CASE PRESENTATION: Three elderly patients presented with unilateral keratitis. None was a corneal-contact lens wearer, one had previous cataract surgery and another suffered rheumatoid arthritis sicca syndrome. Culturing the corneal scraping specimen was positive for two cases and PCR-sequencing of bacterial 16S rDNA in the presence of negative controls identified D. pigrum in three cases. The two D. pigrum isolates were in-vitro susceptible to penicillin G, amoxicillin, doxycycline, rifampicin and gentamicin. In all cases, surgical treatment of corneal thinning was necessary, but corneal perforation occurred in two cases despite intensive antimicrobial treatment with ticarcillin, gentamicin and vancomycin or levofloxacin eye drops leading to enucleation in one case. CONCLUSIONS: D. pigrum is the likely cause of corneal infection in three patients, with effective antibiotic treatment in two patients.
23836469 Interaction of serum amyloid A with human cystatin C--assessment of amino acid residues cr 2013 Sep Secondary amyloid A (AA) amyloidosis is an important complication of some chronic inflammatory diseases, primarily rheumatoid arthritis (RA). It is a serious, potentially life-threatening disorder caused by the deposition of AA fibrils, which are derived from the circulatory, acute-phase-reactant, serum amyloid A protein (SAA). Recently, a specific interaction between SAA and the ubiquitous inhibitor of cysteine proteases--human cystatin C (hCC)--has been proved. Using a combination of selective proteolytic excision and high-resolution mass spectrometry, the binding sites in the SAA and hCC sequences were assessed as SAA(86-104) and hCC(96-102), respectively. Here, we report further details concerning the hCC-SAA interaction. With the use of affinity tests and florescent ELISA-like assays, the amino acid residues crucial for the protein interaction were determined. It was shown that all amino acid residues in the SAA sequence, essential for the formation of the protein complex, are basic ones, which suggests an electrostatic interaction character. The idea is corroborated by the fact that the most important residues in the hCC sequence are Ser-98 and Tyr-102; these residues are able to form hydrogen bonds via their hydroxyl groups. The molecular details of hCC-SAA complex formation might be helpful for the design of new compounds modulating the biological role of both proteins.
23805154 Circulating inflamma-miRs in aging and age-related diseases. 2013 Evidence on circulating microRNAs (miRNAs) is indisputably opening a new era in systemic and tissue-specific biomarker research, highlighting new inter-cellular and inter-organ communication mechanisms. Circulating miRNAs might be active messengers eliciting a systemic response as well as non-specific "by-products" of cell activity and even of cell death; in either case they have the potential to be clinically relevant biomarkers for a number of physiopathological processes, including inflammatory responses and inflammation-related conditions. A large amount of evidence indicates that miRNAs can exert two opposite roles, activating as well as inhibiting inflammatory pathways. The inhibitory action probably relates to the need for activating anti-inflammatory mechanisms to counter potent proinflammatory signals, like the nuclear factor kappaB (NF-κB) pathway, to prevent cell and tissue destruction. MiRNA-based anti-inflammatory mechanisms may acquire a crucial role during aging, where a chronic, low-level proinflammatory status is likely sustained by the cell senescence secretome and by progressive activation of immune cells over time. This process entails age-related changes, especially in extremely old age, in those circulating miRNAs that are capable of modulating the inflammatory status (inflamma-miRs). Interestingly, a number of such circulating miRNAs seem to be promising biomarkers for the major age-related diseases that share a common chronic, low-level proinflammatory status, such as cardiovascular disease (CVD), type 2 diabetes mellitus (T2DM), Alzheimer Disease (AD), rheumatoid arthritis (RA), and cancers.
23625375 Mobile microbiome: oral bacteria in extra-oral infections and inflammation. 2013 Jun The link between oral infections and adverse systemic conditions has attracted much attention in the research community. Several mechanisms have been proposed, including spread of the oral infection due to transient bacteremia resulting in bacterial colonization in extra-oral sites, systemic injury by free toxins of oral pathogens, and systemic inflammation caused by soluble antigens of oral pathogens. Mounting evidence supports a major role of the systemic spread of oral commensals and pathogens to distant body sites causing extra-oral infections and inflammation. We review here the most recent findings on systemic infections and inflammation complicated by oral bacteria, including cardiovascular disease, adverse pregnancy outcomes, rheumatoid arthritis, inflammatory bowel disease and colorectal cancer, respiratory tract infections, and organ inflammations and abscesses. The recently identified virulence mechanisms of oral species Fusobacterium nucleatum, Porphyromonas gingivalis, Streptococcus mutans, and Campylobacter rectus are also reviewed. A pattern emerges indicating that only select subtype(s) of a given species, e.g., F. nucleatum subspecies animalis and polymorphum and S. mutans non-c serotypes, are prone to extra-oral translocation. These findings advocate the importance of identification and quantification of potential pathogens at the subtype levels for accurate prediction of disease potential.
23363555 Nitrogen monoxide inhibits haem synthesis in mouse reticulocytes. 2013 Apr 1 AI (anaemia of inflammation) often manifests in patients with chronic immune activation due to cancer, chronic infections, autoimmune disorders, rheumatoid arthritis and other diseases. The pathogenesis of AI is complex and involves cytokine-mediated inhibition of erythropoiesis, insufficient erythropoietin production and diminished sensitivity of erythroid progenitors to this hormone, and retention of iron in haemoglobin-processing macrophages. NO (nitric oxide) is a gaseous molecule produced by activated macrophages that has been identified as having numerous effects on iron metabolism. In the present study, we explore the possibility that NO affects iron metabolism in reticulocytes and our results suggest that NO may also contribute to AI. We treated reticulocytes with the NO donor SNP (sodium nitroprusside). The results indicate that NO inhibits haem synthesis dramatically and rapidly at the level of erythroid-specific 5-aminolaevulinic acid synthase 2, which catalyses the first step of haem synthesis in erythroid cells. We also show that NO leads to the inhibition of iron uptake via the Tf (transferrin)-Tf receptor pathway. In addition, NO also causes an increase in eIF2α (eukaryotic initiation factor 2α) phosphorylation levels and decreases globin translation. The profound impairment of haem synthesis, iron uptake and globin translation in reticulocytes by NO raises the possibility that this gas may also contribute to AI.
23359562 The autoimmunity risk variant LYP-W620 cooperates with CSK in the regulation of TCR signal 2013 The protein tyrosine phosphatase LYP, a key regulator of TCR signaling, presents a single nucleotide polymorphism, C1858T, associated with several autoimmune diseases such as type I diabetes, rheumatoid arthritis, and lupus. This polymorphism changes an R by a W in the P1 Pro rich motif of LYP, which binds to CSK SH3 domain, another negative regulator of TCR signaling. Based on the analysis of the mouse homologue, Pep, it was proposed that LYP and CSK bind constitutively to inhibit LCK and subsequently TCR signaling. The detailed study of LYP/CSK interaction, here presented, showed that LYP/CSK interaction was inducible upon TCR stimulation, and involved LYP P1 and P2 motifs, and CSK SH3 and SH2 domains. Abrogating LYP/CSK interaction did not preclude the regulation of TCR signaling by these proteins.
23328064 [Cervical retro-odontoid pseudo-tumor treated with posterior decompression surgery]. 2013 A cervical retro-odontoid pseudo-tumor, which is considered as a reactive fibrocartilaginous mass, is a rare condition in cervical myelopathy. A 63-year-old male, with repeated neck axial movements by a long-term leisure-time cycling, developed subacute myelopathy. Cervical MRI showed a mass lesion at the retro-odontoid region, compressing to the upper spinal cord. After detailed systemic and local examinations that ruled out primary or metastatic malignancy and inflammatory disorders such as rheumatoid arthritis or chronic kidney diseases, a retro-odontoid pseudo-tumor was diagnosed clinically. The patient underwent posterior C1-laminectomy without tumor resection and its pathological confirmation. After the surgery, his neurological signs of cervical myelopathy improved, and a follow-up MRI one year later showed a mild reduction of the tumor size. The neuro-physicians should recognize the relatively benign pseudotumor in cervical myelopathy, because the tumor size usually shows no further enlargement or regression only after decompression surgery without tumor resection.
23246354 Clinical characteristics of the patients with systemic amyloidosis in 2000-2010. 2013 May BACKGROUND: The epidemiology of systemic amyloidosis has been changing in the last decades. We aim to describe the clinical characteristics of the patients seen at our institution with systemic amyloidosis in 2000-2010 and compare them with previous Spanish series. PATIENTS AND METHODS: An observational, retrospective study was performed on all patients admitted to a tertiary hospital in Madrid, Spain who had been diagnosed of amyloidosis from January 2000 to December 2010. Patients without a proven diagnosis of amyloidosis, with dialysis-associated, senile, or localized forms of amyloidosis were excluded from the study. A systematic review was made of the clinical records, collecting the demographic, clinical and biochemical variables at diagnosis and patients' outcome. RESULTS: A total of 55 patients were studied, 24 (44%) of whom had AL amyloidosis, 30 (56%) AA amyloidosis, and 1 a familiar form. The most frequent underlying disorders were rheumatoid arthritis (9 patients, 30%) and ankylosing spondylitis (4 cases, 13%). The kidneys were the most frequently involved organ (36 patients, 67%) with nephrotic-range proteinuria at diagnosis (3.4 ± 3.7 g/24 h). Median time to diagnosis was 3 months (interquartile range [IQR]: 1-17). Median follow-up time was 24 months (IQR: 10-91). During follow-up 31 patients died; 18 of those deaths were related to amyloidosis. CONCLUSIONS: Renal dysfunction dominates the course of systemic amyloidosis, which does not seem to have changed in the last decades. We have observed an important delay in the diagnosis of these processes. Therefore, it is necessary to maintain a high degree of clinical suspicion regarding these conditions.
23231541 Novel methods and strategies in the discovery of TACE inhibitors. 2013 Feb INTRODUCTION: Tumor necrosis factor-α (TNF-α) is a key player in inflammation and joint damage in rheumatoid arthritis (RA). One treatment approach to exclude TNF-α from the biological system is by inhibiting tumor necrosis factor-alpha converting enzyme (TACE), the enzyme responsible for the production of its active form. To date, a number of TACE inhibitors have been reported in the literature from various strategies and methods. AREAS COVERED: The following article presents the design and development strategies for the discovery of novel TACE inhibitors which could be of therapeutic utility for the alleviation of inflammatory conditions. The review is based on literature of the subject from 2005 onward. EXPERT OPINION: Discovery of a selective TACE inhibitor has remained a major goal for many academic and pharmaceutical industrial research laboratories for quite some time. Identification of selective TACE inhibitors has proved elusive until recently due to structural similarities between TACE and MMPs. The differences in the shape and size of the S1' pocket of TACE and MMPs could be exploited to design selective TACE inhibitors devoid of any MMP inhibitory activity in the near future. It would be a Herculean task to develop a specific TACE inhibitor for clinical treatment of RA because binding subsites of TACE and MMPs are quite similar. However, developments taking place currently in the field as well as in the application of molecular modeling techniques at a wider scale could yet provide clinically useful selective TACE inhibitors in the not too distant future.
23176380 Focus on systemic lupus erythematosus in indigenous Australians: towards a better understa 2013 Mar The incidence and prevalence of autoimmune diseases such as rheumatoid arthritis, primary Sjögren syndrome, scleroderma and systemic lupus erythematosus (SLE) varies with geography and ethnicity. For example, SLE is reported to be more common in populations such as African-Caribbeans and Indigenous Australians (IA). As well as socio-economic status, variation in severity of disease may also show ethnic variability. The initial presentation of SLE in IA, in the context of a unique genetic background and distinctive environmental influences, is often florid with a recurring spectrum of clinical phenotypes. These clinical observations suggest a unique pathway for autoimmunity pathogenesis in this population. For instance, the high prevalence of bacterial infections in IA, particularly group A streptococcus, may be a potential explanation not only for increased incidence and prevalence of SLE but also the commonly florid acute disease presentation and propensity for rapidly progressive end organ threatening disease. This article will review the state of research in autoimmune disease of IA, consider key findings related to autoimmune disease in this population and propose a model potentially to explain the involvement of innate immunity and chronic infection in autoimmune disease pathogenesis. Ultimately, understanding of SLE at this level could affect management and result in personalised and targeted therapies to improve the health status of IA as well as better understanding of SLE pathogenesis per se.
22876959 Optimized methods for in vitro and in vivo anti-inflammatory assays and its applications i 2013 Jan Inflammatory diseases including, different types of rheumatic diseases are the major problems associated with the presently available non-steroidal anti-inflammatory agents. The numbers of plant derived drugs have been screened for their anti-inflammatory and anti-arthritic activity. Drug development in the recent times often relies on use of natural and synthetic drugs, which are promising candidates as therapeutic agents for prevention of diseases and disorders. These drugs possess different chemical structures, with wide range of therapeutic activities. The mechanism of Inflammation mainly involve in development of serious diseases, such as cancer, rheumatoid arthritis, sprains, bronchitis, muscle pains, chronic inflammatory bowel disease, persistent asthma, and liver fibrosis. Development of inflammatory events basically related to various chemicals, such as glucocorticoids (GCs) and mometasone furoate (MF); endogenous factors such as tumor necrosis factor alpha (TNF-α); enzymes and proteins such as copper and zinc-superoxide dismutase (SOD), proinflammatory peptide substance (PPS), RGD peptides, interleukin-4 (IL-4), IL-10, interferon-γ (IFN-γ), COX, LOX, cytokines such as interleukin-1 (IL-1); reactive oxygen species (ROS), nitric oxide (NO) and prostaglandin E2; as well as pro-inflammatory cells such as T and NK cells are well known to have an important role. Based on these correlations, numerous assays were used for inflammatory mechanism research, which was described in this paper.
22711544 Inhibition of proinflammatory biomarkers in THP1 macrophages by polyphenols derived from c 2013 Apr Antiinflammatory compounds in the diet can alleviate excessive inflammation, a factor in the pathogenesis of common diseases such as rheumatoid arthritis, atherosclerosis and diabetes. This study examined three European herbs, chamomile (Matricaria chamomilla), meadowsweet (Filipendula ulmaria L.) and willow bark (Salix alba L.), which have been traditionally used to treat inflammation and their potential for use as antiinflammatory agents. Aqueous herbal extracts and isolated polyphenolic compounds (apigenin, quercetin and salicylic acid, 0-100 μM) were incubated with THP1 macrophages, and interleukin (IL)-1β, IL-6 and tumour necrosis factor-alpha (TNF-α) were measured. At concentrations of 10 μM, both apigenin and quercetin reduced IL-6 significantly ( p < 0.05). Apigenin at 10 μM and quercetin at 25 μM reduced TNF-α significantly ( p < 0.05). Amongst the herbal extracts, willow bark had the greatest antiinflammatory activity at reducing IL-6 and TNF-α production. This was followed by meadowsweet and then chamomile. The lowest effective antiinflammatory concentrations were noncytotoxic (MTT mitochondrial activity assay). The Comet assay, which was used to study the protective effect of the isolated phenols against oxidative damage, showed positive results for all three polyphenols. These are the first findings that demonstrate the antiinflammatory capacity of these herbal extracts.
25274075 Managing chronic pain in adults with haemophilia: current status and call to action. 2015 Jan Haemophilic arthroses are associated with acute pain during bleeding episodes and with chronic pain caused by arthritic complications of repeated bleeding into joints. Unlike other conditions (e.g. osteoarthritis, rheumatoid arthritis, sickle cell disease), there are limited data on pain management in haemophilia. Management of arthritic individuals and those with sickle cell disease relies heavily on administration of acetaminophen, non-steroidal anti-inflammatory drugs (NSAIDs) and opioid analgesics. In haemophilia, acetaminophen often has limited efficacy at therapeutic doses, offering a narrow dosing range in those with liver disease due to chronic hepatitis C. NSAIDs can effectively manage pain in patients with haemophilia, but these agents are potentially associated with a significant risk of precipitating or exacerbating bleeding complications in an already coagulopathic population. Opioids have proven effective in osteoarthritis and sickle cell disease, but outcomes data in those with haemophilia are virtually non-existent. Patients with haemophilia are at least as vulnerable as other chronic pain populations to opioid-related adverse events and to developing abusive behaviours and addiction. Despite pain management strategies for patients with haemophilia being far from optimal, the predominant precept of haemophilia management still applies. As such, it is critically important to aggressively reverse or prevent acute symptomatic bleeding in a timely and effective manner to at least minimize pain and progressive joint damage. This review should serve as a call to action to prioritize pain management in haemophilia care and spur interest in the development, improvement and standardization of tools to assess and manage acute and chronic pain in haemophilia.
25260818 [Depression and rheumatism: options for measuring depression]. 2014 Oct BACKGROUND: The importance of depressive diseases in the treatment of rheumatism patients cannot be denied. It is well-known from publications in the English speaking literature that the proportion of depressive diseases lies between 10% and 45% in patients with rheumatoid arthritis (RA). However, clearly increased numbers can also be seen in a direct comparison with corresponding prevalence rates in the normal population for other diseases included in the category of rheumatism. OBJECTIVE: This manuscript focusses on the possibilities and challenges in measuring states of depressive mood that might serve as an indicator of depressive diseases in the context of treatment of rheumatism. MATERIAL AND METHODS: A search of the current literature was carried out and the results were evaluated. RESULTS: Starting from appropriate background knowledge, the current state of science is discussed while subsequently taking a closer look at a choice of internationally recognized assessment tools which are feasible for use in rheumatology. Finally, this overview is accompanied by hints for hands-on practice and suggestions on how to respond to conspicuous test results indicative of a depressive mood. DISCUSSION AND CONCLUSION: The potential benefits of appropriate screening with measurement instruments are considered to be high for rheumatism patients. The measurement tools presented must be suitably selected for the individual purpose and for each rheumatology institution. In view of test application consideration must be given not only to the total score but also to the individual responses to test items. In cases of conspicuous test results the further approach must be agreed together with the patient and by choosing adequate treatment options for the situation. In cases of acute suicidal tendencies acceptance, care and support are of key importance, while the precautionary presentation in a specialist clinic must be initiated.
25254011 Interleukin-17 in human inflammatory diseases. 2014 Aug Human Th17 pro-inflammatory cells are currently defined as cells that produce IL-17A and F, tumor necrosis factor (TNF)-α, IL-6, IL-21, IL-22 and IL-23. Recently discovered related molecules are forming a family of cytokines, the IL-17 family, IL-17A, IL-17B, IL-17C, IL-17D, IL-17E and IL-17F. The associated receptors for the IL-17 family identified are IL-17R, IL-17RH1, IL-17RL (receptor like), IL-17RD and IL-17RE. This review introduces the roles of IL-17 and Th17 cells in human autoimmune diseases. Studies have shown that T cells with inflammatory effects on epithelial, endothelial and fibroblast cells express IL-17. Th17 cells are supposed to be involved in various autoimmune diseases, such as rheumatoid arthritis, psoriasis, multiple sclerosis, and inflammatory bowel diseases. Base on the biologic functions and regulation, IL-17 has regulatory roles in host defense and chronic inflammation which result in tissue damage and autoimmunity. So the IL-17 links links innate and adaptive immunity and has both beneficial and pathological effects on the immune system. This paper will focus on the possible roles of IL-17 in autoimmune diseases, a fundamental player in immune regulation.
25248239 [Antibodies against alfa-enolase as an indication of inflammatory process in patients with 2014 INTRODUCTION: Celiac disease (CD) is an autoimmunological gluten sensitive enteropathy occuring to genetically predisposed individuals. Active CD is accompanied by presence of multiple antibodies. Anti alpha enolase antibodies were reported in several autoimmunological disorders like rheumatoid arthritis, primary sclerosing cholangitis. Data about its presence and role in CD is avaricious. AIM: The aim of this study was to determine presence of anti alpha enolase antibodies in CD, correlation with gluten exposure, presence of anti tranglutaminase antibodies and Marsh scale. METHODS: Sera from 31 patients with CD (21 females, 10 males) and 6 healthy subjects were collected. Evaluation of CD activity and adherence to gluten free diet were obtained by serology tests (presence of endomyslum antibodies and/or anti transglutamineses in IgA or IgG classes) and histological hallmarks. Anti alpha enolase antibodies were identified in sera using ELISA kit. Titres of anti alpha enolase antibodies were identified among patients with newly diagnosed CD, CD patients non adhering to gluten free diet (GFD), adhering to GFD and among healthy subjects. RESULTS: Mean titre of anti alpha enolase antibodies was higher in CD patients (both treated and non treated) in comparison to control group, respectively 1.1 ng/mL, and 0.795 ngl mL. Among CD patients non adhering to gluten free diet mean titre was 1.4 ng/mL. CONCLUSIONS: Higher anti alpha enolase antibodies titres in non treated CD suggest usefulness of its measurement. These antibodies might be a novel marker of chronic inflammation among CD patients non adhering to GFD.
25147440 The effects of amphiregulin induced MMP-13 production in human osteoarthritis synovial fib 2014 Osteoarthritis (OA) belongs to a group of degenerative diseases. Synovial inflammation, cartilage abrasion, and subchondral sclerosis are characteristics of OA. Researchers do not fully understand the exact etiology of OA. However, matrix metalloproteinases (MMPs), which are responsible for cartilage matrix degradation, play a pivotal role in the progression of OA. Amphiregulin (AREG) binds to the EGF receptor (EGFR) and activates downstream proteins. AREG is involved in a variety of pathological processes, such as the development of tumors, inflammatory diseases, and rheumatoid arthritis. However, the relationship between AREG and MMP-13 in OA synovial fibroblasts (SFs) remains unclear. We investigated the signaling pathway involved in AREG-induced MMP-13 production in SFs. AREG caused MMP-13 production in a concentration- and time-dependent manner. The results of using pharmacological inhibitors and EGFR siRNA to block EGFR revealed that the EGFR receptor was involved in the AREG-mediated upregulation of MMP-13. AREG-mediated MMP-13 production was attenuated by PI3K and Akt inhibitors. The stimulation of cells by using AREG activated p65 phosphorylation and p65 translocation from the cytosol to the nucleus. Our results provide evidence that AREG acts through the EGFR and activates PI3K, Akt, and finally NF-kappaB on the MMP-13 promoter, thus contributing to cartilage destruction during osteoarthritis.
25580285 The prevalence of antinuclear antibodies in patients with sarcoidosis. 2014 Introduction. Sarcoidosis, which is a chronic inflammatory granulomatous disease, can mimic different rheumatologic diseases including connective tissue diseases. Antinuclear antibodies are the markers used for connective tissue diseases. Aim. To determine antinuclear antibody frequency and any possible correlation with clinical and laboratory data in sarcoidosis patients. Material and Method. Forty-two sarcoidosis patients, 45 rheumatoid arthritis patients, and 45 healthy volunteers who were followed up in rheumatology outpatient clinic were included in this study. Demographic, clinical, serological, and radiological data of all patients were recorded. Antinuclear antibodies were determined with indirect immunofluorescent method and 1/100 titration was accepted as positive. The cases that were ANA positive were evaluated with immunoblot method. Results. Average age of the 42 patients (10 males) with sarcoidosis was 45.2 (20-70 years), and average disease duration was 3.5 years. ANA positivity was detected in 12 (28.5%) patients with sarcoidosis (1/100 in 10 patients, 1/320 in two patients), in 19 of RA patients (42.2%), and in two of healthy volunteers in low titer (P < 0.001). In the subgroup analysis made by immunblot test, one patient had anticentromere antibody, one had anti-Ro antibody, one had anti-Scl-70 antibody, one had anti-dsDNA antibody, and eight patients were negative. The two patients who had anticentromere and anti-Scl-70 antibodies had also Sjögren's syndrome and scleroderma diagnosis, respectively. Discussion. The prevalence of ANA in patients with sarcoidosis was found to be significantly higher than healthy control group and lower than RA patients. This result shows that ANA may have an important role in the pathogenesis of sarcoidosis and also could be important in revealing the overlap syndromes of sarcoidosis-connective tissue diseases. Further studies with larger series are necessary in this subject.
25473363 Flavonoid constituents, cytotoxic and antioxidant activities of Gleditsia triacanthos L. l 2014 Dec Gleditsia triacanthos L. is a deciduous tree belonging to the family Fabaceae. It possesses important biological activities as anti-mutagenic, anticancer, cytotoxic and treating rheumatoid arthritis. The total ethanol extract (EtOHE) and successive extracts (petroleum ether, chloroform, ethyl acetate, and aqueous ethanol) were prepared from the leaves. Eight flavone glycosides and two flavone aglycones named vicenin-I (1), vitexin (2), isovitexin (3), orientin (4), isoorientin (5), luteolin-7-O-ß-glucopyranoside (6), luteolin-7-O-ß-galactopyranoside (7), apigenin-7-O-ß-glucopyranoside (8), luteolin (9) and apigenin (10) were isolated from the aqueous ethanol extract of G. triacanthos L. leaves. Potent cytotoxic activity of the EtOHE extract was observed against the liver (IC50 = 1.68 μg), breast (IC50 = 0.74 μg), cervix (IC50 = 1.28 μg), larynx (IC50 = 0.67 μg) and colon (IC50 = 2.50 μg) cancer cell lines. Cytotoxic activity of compounds 2, 4, 6 and 8 against, the liver, breast and colon cancer cell lines was also proved. Evaluation of the in-vivo antioxidant activity of the EtOHE and successive extracts revealed that the highest activity was exhibited by 100 mg of EtOHE (97.89% potency) as compared with vitamin E (100% potency). Compound 6 showed 91.8% free radical scavenging activity.