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ID PMID Title PublicationDate abstract
23008213 The inactivation mechanism of human group IIA phospholipase A(2) by Scalaradial. 2012 Oct 15 Secretory phospholipases A(2) (sPLA(2)s) are implicated in the pathogenesis of several inflammation diseases, such as rheumatoid arthritis, septic shock, psoriasis, and asthma. Thus, an understanding of their inactivation mechanisms could be useful for the development of new classes of chemical selective inhibitors. In the marine environment, several bioactive terpenoids possess interesting anti-inflammatory activity, often through covalent and/or noncovalent inactivation of sPLA(2). Herein, we report the molecular mechanism of human group IIA phospholipase A(2) (sPLA(2)-IIA) inactivation by Scalaradial (SLD), a marine 1,4-dialdehyde terpenoid isolated from the sponge Cacospongia mollior and endowed with a significant anti-inflammatory profile. Our results have been collected by a combination of biochemical approaches, advanced mass spectrometry, surface plasmon resonance, and molecular modeling. These suggest that SLD acts as a competitive inhibitor. Indeed, the sPLA(2)-IIA inactivation process seems to be driven by the noncovalent recognition process of SLD in the enzyme active site and by chelation of the catalytic calcium ion. In contrast, covalent modification of the enzyme by the SLD dialdehyde moiety emerges as only a minor side event in the ligand-enzyme interaction. These results could be helpful for the rational design of new PLA(2) inhibitors that would be able to selectively target the enzyme active site.
22952014 Pharmacological and pathophysiological roles of carnitine/organic cation transporters (OCT 2013 Jan The carnitine/organic cation transporter (OCTN) family consists of three transporter isoforms, i.e. OCTN1 (SLC22A4) and OCTN2 (SLC22A5) in humans and animals and Octn3 (Slc22a21) in mice. These transporters are physiologically essential to maintain appropriate systemic and tissue concentrations of carnitine by regulating its membrane transport during intestinal absorption, tissue distribution and renal reabsorption. Among them, OCTN2 is a sodium-dependent, high-affinity transporter of carnitine, and a functional defect of OCTN2 due to genetic mutation causes primary systemic carnitine deficiency (SCD). Since carnitine is essential for beta-oxidation of long-chain fatty acids to produce ATP, OCTN2 gene mutation causes a range of symptoms, including cardiomyopathy, skeletal muscle weakness, fatty liver and male infertility. These functional consequences of Octn2 gene mutation can be seen clearly in an animal model, jvs mouse, which exhibits the SCD phenotype. In addition, although the mechanism is not clear, single nucleotide polymorphisms of OCTN1 and OCTN2 genes are associated with increased incidences of rheumatoid arthritis, Crohn's disease and asthma. OCTN1 and OCTN2 accept cationic drugs as substrates and contribute to intestinal and pulmonary absorption, tissue distribution (including to tumour cells), and renal excretion of these drugs. Modulation of the transport activity of OCTN2 by externally administered drugs may cause drug-induced secondary carnitine deficiency. Rodent Octn3 transports carnitine specifically, particularly in male reproductive tissues. Thus, the OCTNs are physiologically, pathologically and pharmacologically important. Detailed characterization of these transporters will greatly improve our understanding of the pathology associated with common diseases caused by functional deficiency of OCTNs.
22931588 The effects of oncostatin M on trophoblast cells: influence on matrix metalloproteinases-2 2012 Nov Oncostatin M (OSM), a cytokine of the interleukin-6 (IL-6) family, can either promote or inhibit cell growth in various normal and tumor cells and is expressed in rheumatoid arthritis, multiple sclerosis, multiple myeloma, and other inflammatory conditions. We investigated one of the possible mechanisms involved in trophoblast invasion using the human placental cell line derived from first trimester extravillous trophoblasts (HTR8SVneo): modulation of matrix metalloproteinase (MMP)-2 and -9 expression and enzymatic activity. And we addressed also the effects of exogenous OSM on the in vitro invasion activity of HTR8SVneo cells. We found that OSM enhanced the constitutive RNA and protein expressions of MMP-2 and MMP-9 in HTR8SVneo cell lines. Also, OSM treatment increased significantly the enzymatic activity of MMP-2 on gelatin zymography. The effects OSM on enzymatic activity of MMP-9 was not significant. We found that OSM increased invasion activities of HTR8SVneo cells in time-dependent and dose-dependent manners. This study suggests that OSM enhances invasion activities of extravillous trophoblasts during the first trimester through the increased enzyme activity of gelatinases, especially MMP-2.
22832708 Clinical studies with chemokine receptor-5 (CCR5)-inhibitors. 2012 Sep PURPOSE OF REVIEW: To summarise recently published clinical studies of chemokine receptor-5 (CCR5)-blockers, including the small-molecule blocker, maraviroc (MVC) and CCR5-monoclonal antibodies for HIV. MVC may have immunomodulating properties through CCR5-blockade. MVC appears well tolerated and penetrates the central nervous system. For these reasons, MVC is being investigated in immunodiscordance, prevention of IRIS and in HCV-HIV co-infection. Novel techniques allow tropism assignment via sequencing of proviral DNA; this testing platform is being utilised in MVC switch studies in those with HIV viraemia below the level of quantification. MVC is being utilised in regimen intensification studies for HIV associated neurocognitive disease. RECENT FINDINGS: MVC has no anti-inflammatory activity in rheumatoid arthritis. MVC appears well tolerated in hepatitis virus co-infected patients and MVC-intensification in HCV-HIV co-infection suggests a favourable impact on liver fibrosis. Early pilot data suggests MVC intensification may have functional benefit in the CNS. There is a growing body of data on tropism testing using proviral DNA; this technology is being utilised in MVC switch studies. CCR5-monoclonal antibodies administered subcutaneously are promising in Phase II development. SUMMARY: The place of MVC as an anti-HIV drug in the switch setting and as an immunomodulator is yet to be fully determined.
22775422 Sinomenium acutum: a review of chemistry, pharmacology, pharmacokinetics, and clinical use 2012 Aug CONTEXT: Sinomenium acutum (Thumb.) Rehd. et Wils. (Menispermaceae, SA) has been used as a traditional Chinese medicine in the treatment of various diseases for hundreds of years; it possesses favorable effects against autoimmune diseases, especially rheumatoid arthritis (RA). A great number of investigations have been done on SA in the last decade, but they are usually scattered across various publications. OBJECTIVE: The purpose of this article is to summarize and review the published scientific information about the chemical constituents, pharmacological effects, pharmacokinetics, and clinic applications of this plant since 2000. RESULTS: The information for 89 cases included in this review was compiled. The SA contains alkaloids, sterols, phospholipids, and some other components. A great deal of pharmacological and clinic research has been done on sinomenine, a main compound from SA, which mainly focuses on the immune system, cardiovascular system, and nervous system. CONCLUSION: Previous studies strongly support its potential as an effective adaptogenic herbal remedy. There is no doubt that SA is being widely used now and will have extraordinary potential for the future.
22748868 Impact of overactive bladder on work productivity. 2012 Jul OBJECTIVE: To evaluate the impact of overactive bladder (OAB) on work productivity in a large, population-based study in the United States, with an overrepresentation of minorities. METHODS: This cross-sectional, Internet-based survey was conducted among men and women aged 18-70. The lower urinary tract symptoms (LUTS) tool was used to assess symptoms over past 4 weeks. OAB was defined by urinary urgency of at least "sometimes" and/or urgency urinary incontinence (UUI). Outcomes included work status, Work Productivity and Activity Impairment Questionnaire--General Health (WPAI-GH) and Specific Health (WPAI-SH), and questions about the impact of urinary symptoms on work. Descriptive statistics were used to evaluate group differences (no/minimal symptoms [NMS] vs OAB). Logistic regressions evaluated predictors of unemployment status controlling for comorbid conditions, risk factors, and demographic variables. RESULTS: The response rate was 57%. A total of 5795 men and women were included in the analysis (OAB, 2323; NMS, 3472). OAB cases were significantly more likely to be unemployed (men, 44%; women, 54%) compared to those with NMS (men, 24%; women, 41%). Mean work productivity and activity impairment (WPAI) percent impairment while working was as follows: 19% and 21% among men and women with OAB; NMS, 4% and 7%. Significant differences were found for all urinary-specific WPAI-SHP items and other condition-specific outcomes. Men with OAB were 1.5 times more likely to be unemployed as compared to those with NMS when covariates were controlled for, whereas the association between OAB and unemployment in multivariate analysis was nonsignificant among women. CONCLUSION: Comparison with other outcomes suggests that OAB impairs work at levels comparable to other serious chronic conditions, including rheumatoid arthritis and asthma.
22634722 Expanding the clinical indications for α(1)-antitrypsin therapy. 2012 Sep 7 α(1)-Antitrypsin (AAT) is a 52-kDa circulating serine protease inhibitor. Production of AAT by the liver maintains 0.9-1.75 mg/mL circulating levels. During acute-phase responses, circulating AAT levels increase more than fourfold. In individuals with one of several inherited mutations in AAT, low circulating levels increase the risk for lung, liver and pancreatic destructive diseases, particularly emphysema. These individuals are treated with lifelong weekly infusions of human plasma-derived AAT. An increasing amount of evidence appears to suggest that AAT possesses not only the ability to inhibit serine proteases, such as elastase and proteinase-3 (PR-3), but also to exert antiinflammatory and tissue-protective effects independent of protease inhibition. AAT modifies dendritic cell maturation and promotes T regulatory cell differentiation, induces interleukin (IL)-1 receptor antagonist and IL-10 release, protects various cell types from cell death, inhibits caspases-1 and -3 activity and inhibits IL-1 production and activity. Importantly, unlike classic immunosuppressants, AAT allows undeterred isolated T-lymphocyte responses. On the basis of preclinical and clinical studies, AAT therapy for nondeficient individuals may interfere with disease progression in type 1 and type 2 diabetes, acute myocardial infarction, rheumatoid arthritis, inflammatory bowel disease, cystic fibrosis, transplant rejection, graft versus host disease and multiple sclerosis. AAT also appears to be antibacterial and an inhibitor of viral infections, such as influenza and human immunodeficiency virus (HIV), and is currently evaluated in clinical trials for type 1 diabetes, cystic fibrosis and graft versus host disease. Thus, AAT therapy appears to have advanced from replacement therapy, to a safe and potential treatment for a broad spectrum of inflammatory and immune-mediated diseases.
22632748 Molecular link mechanisms between inflammation and cancer. 2012 Inflammation is part of the body's response to internal and external environmental stimuli that normally eliminate the aggressor agent and restore the tissue physiology. However, when it becomes chronic, it can cause several pathologies such as cardiovascular, diabetes, rheumatoid arthritis, Alzheimer's autoimmune diseases and cancer. Currently, epidemiological data indicate that over 25% of all cancers are related to chronic infections and other types of unresolved inflammation. Further evidence of this relationship is the fact that prolonged use of non-steroidal anti-inflammatory drugs (NSAIDs) has been associated with reduced risk to developing many types of cancers. Some randomized trials have shown that NSAIDs have protective action against colon adenomas, breast, prostate, and lung cancers. The inflammation present on tumor microenvironment is characterized by leukocyte infiltration, ranging in size, distribution and composition, as: tumor-associated macrophages (TAM), mast cells, dendritic cells, natural killer (NK) cells, neutrophils, eosinophils and lymphocytes. These cells produce a variety of cytotoxic mediators such as reactive oxygen and nitrogen species (ROS and RNS respectively), serine and cysteine proteases, membrane perforating agents, matrix metalloproteinase (MMP), tumor necrosis factor α (TNFα), interleukins (IL-1, IL-6, IL-8), interferons (IFNs) and enzymes, as cyclooxygenase-2 (COX-2), lipooxygenase-5 (LOX-5) and phospholipase A2 (PLA2), which activate or are activated by transcription factors as nuclear factor κB (NF-κB) and signal transducers and activators of transcription-3 (STAT3). Initially this paper will briefly review the main mediators present on tumor microenvironment, addressing the cytokines, chemokines, transcription factors, eicosanoid, and kinins and later, will present an overview of the role of inflammation in the different steps of carcinogenesis.
22581255 Skeletal and extraskeletal actions of denosumab. 2012 Aug Osteoclasts and osteoblasts define skeletal mass, structure and strength through their respective actions in resorbing and forming bone. This remodeling process is orchestrated by the actions of hormones and growth factors, which regulate a cytokine system comprising the receptor activator of nuclear factor κB ligand (RANKL), its receptor RANK and the soluble decoy receptor osteoprotegerin (OPG). Bone resorption depends on RANKL, which determines osteoclast formation, activity and survival. Importantly, cells of the osteoblastic lineage mainly provide RANKL and therefore, are central in the regulation of osteoclast functions. Catabolic effects of RANKL are inhibited by OPG, a TNF receptor family member that binds RANKL, thereby preventing the activation of its receptor RANK, which is expressed by osteoclast precursors. Because this cytokine network is pivotal for the regulation of bone mass in health and diseases, including osteoporosis, rheumatoid arthritis and malignant bone conditions, it has been successfully used for the generation of a targeted therapy to block osteoclast actions. The clinical approval of denosumab, a fully monoclonal antibody against RANKL, provides a novel option to treat bone diseases with a potent, targeted and reversible inhibitor of bone resorption. Although RANKL is also expressed by endothelial cells, T lymphocytes, synovial fibroblasts and various tumor cells, no meaningful clinical extraskeletal effects have been reported after administration of denosumab. This article summarizes the molecular and cellular basis of the RANKL/RANK/OPG system and presents preclinical and clinical studies on the skeletal actions of denosumab.
22488912 Bioinformatics analysis reveals transcriptome and microRNA signatures and drug repositioni 2012 Dec BACKGROUND: Inflammatory bowel disease (IBD) is a complex disorder involving pathogen infection, host immune response, and altered enterocyte physiology. Incidences of IBD are increasing at an alarming rate in developed countries, warranting a detailed molecular portrait of IBD. METHODS: We used large-scale data, bioinformatics tools, and high-throughput computations to obtain gene and microRNA signatures for Crohn's disease (CD) and ulcerative colitis (UC). These signatures were then integrated with systemic literature review to draw a comprehensive portrait of IBD in relation to autoimmune diseases. RESULTS: The top upregulated genes in IBD are associated with diabetogenesis (REG1A, REG1B), bacterial signals (TLRs, NLRs), innate immunity (DEFA6, IDO1, EXOSC1), inflammation (CXCLs), and matrix degradation (MMPs). The downregulated genes coded tight junction proteins (CLDN8), solute transporters (SLCs), and adhesion proteins. Genes highly expressed in UC compared to CD included antiinflammatory ANXA1, transporter ABCA12, T-cell activator HSH2D, and immunoglobulin IGHV4-34. Compromised metabolisms for processing of drugs, nitrogen, androgen and estrogen, and lipids in IBD correlated with an increase in specific microRNA. Highly expressed IBD genes constituted targets of drugs used in gastrointestinal cancers, viral infections, and autoimmunity disorders such as rheumatoid arthritis and asthma. CONCLUSIONS: This study presents a clinically relevant gene-level portrait of IBD subtypes and their connectivity to autoimmune diseases. The study identified candidates for repositioning of existing drugs to manage IBD. Integration of mice and human data point to an altered B-cell response as a cause for upregulation of genes in IBD involved in other aspects of immune defense such as interferon-inducible responses.
22418285 [How to optimize the antiTNF alpha therapy in spondylitis?]. 2012 Mar TNFalpha inhibitors have been a major advance in the treatment of spondyloarthropathies, having demonstrated their safety and efficacy, with higher response and survival rates than those observed in patients with rheumatoid arthritis. The fact that disease modifying anti-arthritic drugs (DMARD) have shown utility in the treatment of this disease, especially in the axial forms, gives them greater importance, since it is known that up to 30%of patients do not respond to treatment with non-steroidal anti-inflammatory drugs. However, we must take into account that these drugs are expensive and not without side effects, so it is necessary to optimize their use. We intend to review the use of antiTNF alpha in spondyloarthropathies and review the available evidence on strategies that can help with their rational use.
22374516 Folic acid-functionalized human serum albumin nanocapsules for targeted drug delivery to c 2012 May 10 Activated synovial macrophages play a key role in Rheumatoid Arthritis (RA). Recent studies have shown that folate receptor beta (FRβ) is specifically expressed by activated macrophages. Therefore a folate-based nanodevice would provide the possibility of delivering therapeutic agents to activated macrophages without affecting normal cells and tissues. This study shows for the first time the sonochemical preparation of HSA nanocapsules avoiding toxic cross linking chemicals and emulsifiers used in other methods. Production of HSA nanocapsules was optimized leading to a diameter of 443.5 ± 9.0 nm and a narrow size distribution indicated by a polydispersity index (PDI) of 0.066 ± 0.080. Nanocapsules were surface modified with folic acid (FA) and the FA content was determined to be 0.38 and 6.42 molecules FA per molecule HSA, depending on the surplus of FA employed. Dynamic light scattering was used to determine size, PDI and zetapotential of the produced nanocapsules before and after surface modification. FA distribution on the surface of HSA nanocapsules was localized three-dimensionally after fluorescence labeling using confocal laser scanning microscopy (CLSM). Furthermore, specific binding and internalization of HSA nanocapsules by FRβ-positive and FRβ-negative macrophages, obtained from human peripheral blood mononuclear cells, was demonstrated by flow cytometry. FRβ-expressing macrophages showed an increased binding for FA-modified capsules compared with those without FA.
22365818 Do the indications, results, and complications of reverse shoulder arthroplasty change wit 2012 Nov BACKGROUND: The goal of this study was to compare 2 consecutive series of 240 reverse total shoulder arthroplasties (TSA) in order to evaluate if the increase in surgeon experience modified the indications, clinical and radiographic results, and rate of complications. MATERIAL AND METHODS: Two hundred forty reverse TSA performed between July 2003 and March 2007 were clinically and radiographically evaluated by an independent examiner with a minimum follow-up of 2 years and compared with a previous published study (240 cases implanted by the same 2 surgeons between May 1995 and June 2003). RESULTS: The main etiology remained cuff tear arthropathy with an increase noted between the 2 studies. The rate of revision arthroplasty as an etiology decreased from 22.5% to 9.1%. Conversely, the rate of rheumatoid arthritis increased from 0.4% to 6.3%. The average postoperative Constant score was significantly better than the first series (66.9 vs 59.7, P < .001). The postoperative complication rate decreased with increased experience (from 19% to 10.8%), with dislocations reducing (from 7% to 3.2%), and infections reducing (from 4% to 0.9%). However, the number of nerve palsies increased. The revision rate decreased from 7.5% to 5%. The rate of glenoid notching remained stable, but the severity of notching decreased. CONCLUSION: Experience did not lead us to operate on younger patients, but significantly modified patient selection, results, and complications. Increased experience with the reverse shoulder arthroplasty did not reduce the rate of glenoid notching.
22250652 To cardiovascular disease and beyond: new therapeutic perspectives of statins in autoimmun 2012 Jun Statins have been successfully used in patients with hypercholesterolemia and cardiovascular diseases, but there is increasing evidence that they exert effects by much exceeding the lowering of cholesterol levels. Statins have antiatherosclerotic, antiinflammatory, antioxidant, immunomodulatory and antithrombotic effects. These "pleiotropic" effects stem from their inhibition of prenylation of the small GTP-binding proteins Ras and Rho, and to the disruption, or depletion, of cholesterol rich membrane micro-domains (membrane rafts). Through these pathways statins modulate immune responses by altering cytokine levels and by affecting the function of cells involved in both innate and adaptive responses. Anti-inflammatory and immunosuppressory properties of statins provide the rationale for their potential application in conditions in which the inflammation and immune response represent key pathogenic mechanisms, such as antiphospholipid syndrome, rheumatoid arthritis and systemic lupus erythematosus. Reduction of atherosclerosis progression in autoimmunity is also a very important effect. Statins pathways of action in systemic autoimmune diseases, and their potential therapeutic use are discussed in this review. The inhibition of mevalonate pathway by statins impairs modification of Ras and Rho GTPases, which play key roles in signaling pathways related to tumor formation, metastasis and cell death. There is experimental and clinical evidence that statins may improve the therapeutic outcome of anticancer drugs. Thus, this review will also discuss recent insights into the molecular mechanisms underlying the anticancer effects of statins and their assessment as promising candidates for inclusion into current therapeutic regimens for the treatment of malignant diseases.
22204815 Galectin-9 ameliorates herpes simplex virus-induced inflammation through apoptosis. 2012 Jun Galectin-9 (Gal-9) has been identified as a Tim-3 ligand (L). The Tim-3-Tim-3L interaction serves as a specific down-regulator of the Th1 immune response. It has been reported that Tim-3 expression is higher in patients with inflammatory disorders such as rheumatoid arthritis compared to controls. In a herpes simplex virus-induced Behcet's disease (BD) mouse model, Tim-3 was expressed in a similarly high level. The expression of Gal-9 in macrophages from BD-like mice was lower than in asymptomatic BD normal mice; therefore, we injected 100 μg of Gal-9 into BD-like mice five times at 3 day intervals and subsequently observed changes in symptoms over 15 days. Gal-9 improved the symptoms of inflammation, decreased the severity score, and increased regulatory T cell expression in treated mice. Moreover, pro-inflammatory cytokine levels were lower in the Gal-9-treated group compared to the control group. Therefore, in the present study, Tim-3-Tim-3L interaction was found to influence inflammatory symptoms in BD-like mice.
22194966 Detection and quantification of citrullinated chemokines. 2011 BACKGROUND: Posttranslational deimination or citrullination by peptidylarginine deiminases (PAD) regulates the biological function of proteins and may be involved in the development of autoimmune diseases such as rheumatoid arthritis and multiple sclerosis. This posttranslational modification of arginine was recently discovered on inflammatory chemokines including CXCL8 and CXCL10, and significantly reduced their biological activity. To evaluate the importance of these modified chemokines in patients, methods for the detection and quantification of citrullinated chemokines are needed. Since citrullination only results in an increase of the protein mass with one mass unit and the loss of one positive charge, selective biochemical detection is difficult. Therefore, we developed an antibody-based method to specifically detect and quantify citrullination on a protein of interest. METHODOLOGY/PRINCIPAL FINDINGS: First, the citrullinated proteins were chemically modified with antipyrine and 2,3-butanedione at low pH. Such selectively modified citrullines were subsequently detected and quantified by specific antibodies raised against a modified citrulline-containing peptide. The specificity of this two-step procedure was validated for citrullinated CXCL8 ([Cit(5)]CXCL8). Specific detection of [Cit(5)]CXCL8 concentrations between 1 and 50 ng/ml was possible, also in complex samples containing an excess of contaminating proteins. This novel detection method was used to evaluate the effect of lipopolysaccharide (LPS) on the citrullination of inflammatory chemokines induced in peripheral blood mononuclear cells (PBMCs) and granulocytes. LPS had no significant effect on the induction of CXCL8 citrullination in human PBMCs and granulocytes. However, granulocytes, known to contain PAD, were essential for the production of significant amounts of [Cit(5)]CXCL8. CONCLUSION/SIGNIFICANCE: The newly developed antibody-based method to specifically detect and quantify chemically modified citrullinated proteins is proven to be effective. This study furthermore demonstrates that granulocytes were essential to obtain significant levels of [Cit(5)]CXCL8. For human PBMCs and granulocytes stimulation with LPS did not affect the citrullination of CXCL8.
22160883 In vitro characterization of chitosan gels for buccal delivery of celecoxib: influence of 2012 Mar Celecoxib (Cx) shows high efficacy in the treatment of osteoarthritis and rheumatoid arthritis as a result of its high specificity for COX-2, without gastrolesivity or interference with platelet function at therapeutic concentrations. Besides of anti-inflammatory effects, Cx also has a potential role for oral cancer chemoprevention. For these conditions, oral administration in long-term treatment is a concern due to its systemic side effects. However, local application at the site of injury (e.g., buccal inflammation conditions or chemoprevention of oral cancer) is a promising way to reduce its toxicity. In this study, the in vitro characterization of mucoadhesive chitosan (CHT) gels associated to Azone® was assessed to explore the potential buccal mucosal administration of Cx in this tissue. Rheological properties of gels were analyzed by a rheometer with cone-plate geometry. In vitro Cx release and permeability studies used artificial membranes and pig cheek mucosa, respectively. Mucoadhesion were measured with a universal test machine. CHT gels (3.0%) containing 2.0% or 3.0% Az showed more appropriate characteristics compared to the others: pH values, rheology, higher amount of Cx retained in the mucosa, and minimal permeation through mucosa, besides the highest mucoadhesion values, ideal for buccal application. Moreover, the flux (J) and amounts of drug released decreased with increased CHT and Az concentrations. CHT gels (3.0%) associated with 2.0% or 3.0% Az may be considered potential delivery systems for buccal administration of Cx.
22160513 Follow-up investigation of open trigger digit release. 2012 May PURPOSE: The purpose of this retrospective study was to identify the postoperative complications and disorders associated with open trigger finger release. Factors that were investigated by this study included demographic details, the number of digits affected, BMI, level of manual strain, trauma, received systemic medication, hand dominance, pre-treatment with steroid injection, and concomitant diseases. METHODS: One hundred and three patients, who underwent open release surgery for 117 trigger fingers and thumbs, were followed up until complete resolution of all complaints. Patients' age, BMI, hand dominance, occupational manual strain, and previous medical history regarding trigger finger or thumb were obtained. Associated conditions and medical treatment, trauma, and previous hand surgical interventions were included as well. Details regarding duration of complaints, ROM, visual analogue pain scale, swelling, recurrence of the disease following previous surgical release, and persistence of complaints following corticosteroid injection were examined. RESULTS: The dominant hand was not significantly more frequently affected than the non-dominant hand. Occupation also did not influence the incidence of trigger digit. Patients with systemic steroid therapy had a significantly shorter duration of postoperative symptoms with a mean duration of 29.3 days (range, 28-31 days ± 1.3). Significantly less postoperative swelling was noticed in patients with a pre-surgical steroid injection. The mean duration of symptoms before and after surgery was significantly shorter for a trigger thumb than for trigger finger. DISCUSSION: Open trigger digit release constitutes an adequate low-risk surgical procedure for treatment of trigger digit. In this study, we could show that the incidence of this disease is not significantly correlated with the manual strain, trauma, BMI, hand dominance or concomitant diseases like diabetes mellitus, rheumatoid arthritis, renal insufficiency, and hypothyroidism. Additionally, this study illustrates the importance of a careful postoperative follow-up treatment to avoid potential persistent functional limitations.
22116823 IL-17 silencing does not protect nonobese diabetic mice from autoimmune diabetes. 2012 Jan 1 The long-held view that many autoimmune disorders are primarily driven by a Th1 response has been challenged by the discovery of Th17 cells. Since the identification of this distinct T cell subset, Th17 cells have been implicated in the pathogenesis of several autoimmune diseases, including multiple sclerosis and rheumatoid arthritis. Type 1 diabetes has also long been considered a Th1-dependent disease. In light of the emerging role for Th17 cells in autoimmunity, several recent studies investigated the potential of this subset to initiate autoimmune diabetes. However, direct evidence supporting the involvement of Th17 cells in actual pathogenesis, particularly during spontaneous onset, is lacking. In this study, we sought to directly address the role of IL-17, the cytokine by which Th17 cells are primarily characterized, in the pathogenesis of autoimmune diabetes. We used lentiviral transgenesis to generate NOD mice in which IL-17 is silenced by RNA interference. The loss of IL-17 had no effect on the frequency of spontaneous or cyclophosphamide-induced diabetes. In contrast, IL-17 silencing in transgenic NOD mice was sufficient to reduce the severity of myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis, consistent with reports that IL-17 deficiency is protective in this experimental model of multiple sclerosis. We concluded that IL-17 is dispensable, at least in large part, in the pathogenesis of autoimmune diabetes.
22086673 Anti-inflammatory and anti-nociceptive effects of the ethanolic extracts of Alkanna frigid 2012 Jul Alkanna species are used in Iranian traditional medicine for treatment of rheumatoid arthritis and other inflammatory diseases. This study was designed to evaluate the anti-inflammatory and anti-nociceptive effects of Alkanna frigida and Alkanna orientalis ethanolic extracts via the carrageenan-induced paw edema test and formalin test in rat and mouse, respectively. Ethanolic extracts of plant root were prepared and were injected intraperitoneally 60 min before carrageenan-induced inflammation or formalin-induced nociception at 100, 200 and 400 mg/kg. Anti-inflammatory effects of plants were monitored for 3 h after carrageenan injection and anti-nociceptive effects were evaluated during the first hour after formalin injection. Diclofenac, a well-known anti-inflammatory and anti-nociceptive agent, was used as a positive control. Our results show that, in contrast to Alkanna orientalis, ethanolic extract of Alkanna frigida significantly decreases carrageenan-induced inflammation at 400 mg/kg, especially 3 h after inflammation induction. Both Alkanna frigida and Alkanna orientalis ethanolic extracts possess a remarkable anti-nociceptive effect at each dose (100, 200 and 400 mg/kg) in a dose-dependent manner during the first hour after formalin injection.The present findings provide more evidence for the potential anti-nociceptive effect of Alkanna sp. and the anti-inflammatory effect of Alkanna frigida. It supports their traditional indication in the treatment of pain and inflammatory-related diseases. These useful effects may result from the inhibitory interaction of the plant ethanolic extract with cyclooxygenase-2 enzyme and the subsequent reduction in prostaglandin production.