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ID PMID Title PublicationDate abstract
25594234 Frequency and causes of C-reactive protein and erythrocyte sedimentation rate disagreement 2015 Jan AIM: C-reactive protein (CRP) and the erythrocyte sedimentation rate (ESR) are often ordered together in patients with suspected infection or inflammation. However, the test results can disagree in as many as 33% of patients. Our aim was to further examine CRP/ESR disagreements and their stability on repeat testing. METHODS: We analyzed simultaneously ordered CRP and ESR results in 70 adult patients who had been tested on three separate occasions a median of 4 weeks apart. RESULTS: Initial CRP/ESR disagreements occurred in 14 of the 70 patients (20%; 95% CI, 12-31). Only four of these 14 patients had stable CRP/ESR disagreements throughout the study (two with lupus nephritis and one with osteomyelitis had persistent high ESR/normal CRP disagreements and one with rheumatoid arthritis had a persistent high CRP/normal ESR disagreement). The other 10 patients with initial CRP/ESR disagreements later exhibited CRP/ESR agreements. Of the 56 patients with initial CRP/ESR agreements, only 10 developed a CRP/ESR disagreement (or disagreements) on subsequent testing. CONCLUSION: CRP/ESR disagreements are common in clinical practice. Three mechanisms were identified to explain CRP/ESR disagreements: (i) slight fluctuations in the CRP and ESR around the upper limits of normal for these tests; (ii) development of an intercurrent illness; and (iii) different time courses of CRP and ESR elevations, in which the CRP rose and fell faster than the ESR.
27407221 The effect of leptin on the respiratory burst of human neutrophils cultured in synovial fl 2015 OBJECTIVES: Leptin is a hormone responsible for nutritional status and immune competence coordination. In rheumatoid arthritis (RA) increased leptin levels were observed in both serum and synovial fluid. Its influence on development of the disease still remains unclear. So far, research on leptin's influence on the emission of reactive oxygen intermediates (ROI) measured with chemiluminescence (CL) has provided unclear and contradictory results. In this study, we evaluated the influence of leptin on oxidative activity of neutrophils isolated from blood of healthy volunteers and cultured in different amounts of synovial fluid (SF) from patients with RA. MATERIAL AND METHODS: Neutrophils' oxidative metabolism was measured by two types of CL. The first one, luminol-dependent CL (CL-lum), allows one to determine phagocytic activity and the level of ROI generated in a myeloperoxidase-dependent manner. The second method used was lucigenin-dependent CL (CL-luc), which monitors ROI production dependent on the NADPH oxidase enzyme complex located in the cell membranes of neutrophils and enables one to determine the scope of extracellular ROI emission. RESULTS: Neutrophils stimulated by opsonized zymosan show a decrease in the level of CL-lum, proportional to the increasing concentration of both SF and serum collected from healthy donors. The observed effect of decreased CL-lum may, therefore, be dependent on the physical conditions (viscosity of fluids used). None of these experiments showed any effect of leptin on the level of CL-lum. CONCLUSIONS: The present study showed that leptin does not affect the level of any of the CL types in inactive neutrophils incubated in normal serum, and it does not affect the level of oxidative activity in resting neutrophils incubated with SF. However, leptin influences extracellular ROI emission (measured by CL-luc). Leptin reduces extracellular emission of ROI, and this effect is dependent on concentration and duration of exposure to leptin.
25043266 Nondisseminated histoplasmosis of the trachea. 2016 Mar Histoplasma capsulatum can rarely affect the trachea. We report the case of a 68-year-old woman with rheumatoid arthritis on immunosuppressive therapy who presented with fevers, worsening shortness of breath, nonproductive cough and subjective throat hoarseness and fullness. Chest computed tomography demonstrated no tracheal findings. Bronchoscopy found mucosal irregularity, nodularity and vesicular regions in the proximal trachea extending seven centimeters distal to the vocal cords. Also seen was an edematous, exudative left vocal cord with polyps and an ulcerative lesion. Silver staining and culture and wash of the tracheal biopsy revealed Histoplasma capsulatum. She was treated with oral itraconazole then briefly on intravenous amphotericin for rising Histoplasma urinary antigen levels. She continued treatment 24 months following diagnosis with minimal dyspnea. Histoplasma tracheitis has been proposed as an indicator of disseminated infection. However, our patient did not demonstrate other organ manifestations. Histoplasma tracheitis should be considered in a differential diagnosis of tracheal lesions even in the absence of systemic involvement.
24964172 The efficiency of granulocyte colony-stimulating factor in hemorrhagic mucositis and febri 2015 Methotrexate (MTX) remains one of the most frequently used anti-metabolite agents in dermatology. MTX is an analog of folate that competitively and irreversibly inhibits dihydrofolate reductase. Oral mucositis is a common side effect of chemotherapy drugs and is characterized by erythema, pain, poor oral intake, pseudomembranous destruction, open ulceration and hemorrhage of the oral mucosa. In this paper, we report a 32-year-old female with a case of mucositis due to MTX intoxication that resulted from an overdose for rheumatoid arthritis. The patient had abdominal pain, vomiting, and nausea. During follow-up, the patient's white blood cell count was found to be 0.9 × 10(9)/L (4-10 × 10(9)/L). The patient developed fever exceeding 40 °C. The patient was consulted to the hematology service. They suggested using granulocyte colony-stimulating factor for febrile neutropenia. On the fifth day of treatment, the white blood cell count reached 5.3 × 10(9)/L and the patient's fever and mucositis started to resolve. Here, we presented a case of hemorrhagic mucositis and febrile neutropenia resulted from high-dose MTX that responded very well to granulocyte colony-stimulating factor treatment and we reviewed the literature.
32262290 Surface engineering of porous silicon to optimise therapeutic antibody loading and release 2015 May 28 The proinflammatory cytokine, tumor necrosis factor-α (TNF-α), is elevated in several diseases such as uveitis, rheumatoid arthritis and non-healing chronic wounds. Adding Infliximab, a chimeric IgG1 monoclonal antibody raised against TNF-α, to chronic wound fluid can neutralise human TNF-α, thereby providing a potential therapeutic option for chronic wound healing. However, to avoid the need for repeated application in a clinical setting, and to protect the therapeutic antibody from the hostile environment of the wound, suitable delivery vehicles are required. Porous silicon (pSi) is a biodegradable high surface area material commonly employed for drug delivery applications. In this study, the use of pSi microparticles (pSi MPs) for the controlled release of Infliximab to disease environments, such as chronic wounds, is demonstrated. Surface chemistry and pore parameters for Infliximab loading are first optimised in pSi films and loading conditions are transferred to pSi MPs. Loading regimens exceeding 60 μg of Infliximab per mg of pSi are achieved. Infliximab is released with zero-order release kinetics over the course of 8 days. Critically, the released antibody remains functional and is able to sequester TNF-α over a weeklong timeframe; suitable for a clinical application in chronic wound therapy.
28167927 Autoimmune/Inflammatory Syndrome Induced by Adjuvants and Thyroid Autoimmunity. 2016 The autoimmune/inflammatory syndrome induced by adjuvants (ASIA), presented by Shoenfeld and Agmon-Levin in 2011, is an entity that incorporates diverse autoimmune conditions induced by the exposure to various adjuvants. Adjuvants are agents that entail the capability to induce immune reactions. Adjuvants are found in many vaccines and used mainly to increase the response to vaccination in the general population. Silicone has also been reported to be able to induce diverse immune reactions. Clinical cases and series of heterogeneous autoimmune conditions including systemic sclerosis, systemic lupus erythematosus, and rheumatoid arthritis have been reported to be induced by several adjuvants. However, only a small number of cases of autoimmune thyroid disorder have been included under the umbrella of ASIA syndrome. Indeed, clinical cases of Hashimoto's thyroiditis and/or subacute thyroiditis were observed after the exposure to vaccines as well as silicone implantation. In our review, we aimed to summarize the current knowledge on ASIA syndrome presented as endocrinopathies, focusing on autoimmune thyroid disorders associated with the various adjuvants.
27729225 MicroRNA mediated network motifs in autoimmune diseases and its crosstalk between genes, f 2017 Jan Autoimmune diseases (AIDs) are incurable but suppressible diseases whose molecular mechanisms are yet to be elucidated. In this work, we selected five systemic autoimmune diseases such as Rheumatoid Arthritis (RA), Type 1 Diabetes (T1D), Inflammatory Bowel Disease (IBD), Autoimmune Thyroid Disease (ATD) and Systemic Lupus Erythematosus (SLE). Heterogeneous data such as miRNA, transcription factor (TF), target genes and protein-protein interactions involved in these AIDs were integrated to understand their roles at different functional levels of miRNA such as transcription initiation, gene regulatory network formation and post transcriptional regulation. To understand the functional characteristics of these complex biological networks, they can be simplified as network motifs (sub networks) and motif-motif interacting pairs (MMIs). The network motif patterns and motif-motif interacting pairs that occur for the selected five diseases were identified. To further understand the functional association between AIDs, functions and pathways were determined using gene set enrichment analysis and five selected immune signaling pathways (ISPs). The crosstalk within AIDs and between the immune signaling pathways (ISPs) could provide novel insights in deciphering disease mechanisms. This study represents the first investigation of miRNA-TF regulatory network for AIDs and its association with ISPs using sub-network motifs.
27747512 Chronic Diarrhea Associated with High Teriflunomide Blood Concentration. 2016 Jun OBJECTIVE: To report the case of a patient treated with leflunomide that presented with chronic diarrhea associated with high teriflunomide blood concentration. An 84-year-old woman taking leflunomide 20 mg once daily for the past 2 years to treat rheumatoid arthritis (RA) was investigated for severe chronic diarrhea that had been worsening for the past 5 months. The patient's general condition progressively deteriorated and included electrolyte imbalances and a transient loss of consciousness. Therefore, hospitalization was required. Teriflunomide blood concentration was 156 mg/L. After 11 days of cholestyramine washout therapy, teriflunomide blood concentration was reduced to 6 mg/L. As the teriflunomide levels decreased, diarrhea improved. All other possible causes of diarrhea were ruled out. The patient's diarrhea finally resolved 26 days after treatment with cholestyramine. DISCUSSION: Diarrhea is a known adverse effect of leflunomide. In this report, the severe diarrhea was associated with high blood teriflunomide concentrations. Available data suggests an association between teriflunomide concentrations greater than 50 mg/L and lower disease activity, but toxic teriflunomide levels still have to be clarified. CONCLUSION: Further studies are needed to establish the optimal therapeutic levels of teriflunomide. However, therapeutic drug monitoring of teriflunomide blood concentrations may be helpful to improve effectiveness and to prevent toxicity in patients taking leflunomide for RA, particularly in those with suboptimal therapeutic response to leflunomide or in patients with toxicity suspected to be induced by leflunomide.
27609063 Confirmatory analysis of etanercept in equine plasma by LC-MS for doping control. 2017 Sep Etanercept is a protein-based medication for the treatment of human patients with rheumatoid arthritis and other autoimmune-based diseases; its pharmacological action is to inhibit and antagonize tumour necrosis factor alpha. Etanercept was rumoured to be used in horse racing in North America. To detect such use, the aim of this study was to develop a liquid chromatography-mass spectrometry (LC-MS) method for confirmation of etanercept in equine plasma. Etanercept was extracted from plasma by anti-human IgG antibody linked to magnetic beads. The analyte was reduced and alkylated, and then digested by trypsin. Tryptic peptides (T1 from human tumour necrosis factor receptor 2 of etanercept, T15 and T27 from human IgG1 of the protein) were employed for detection and confirmation of the analyte. The limit of detection was 5 ng/mL, and the limit of confirmation 10 ng/mL. This method is specific for confirmation of etanercept, as assessed using the results from BLAST and SEQUEST searches. The results from SEQUEST searches also revealed an unexpected unique specificity of product ion spectrum of IgG1 T27 with only a single product ion for identification of etanercept. It is the first report for such a finding, to the authors' knowledge. The method was successful in analyses of the plasma samples collected post administration of etanercept to horses. Etanercept was detected up to 11 days post administration. This method will be helpful for confirmation of etanercept or other protein-based drugs consisting of human IgG1, in equine drug testing. Copyright © 2016 John Wiley & Sons, Ltd.
27580439 [Arthroscopic Synovectomy of the Wrist in Chondrocalcinosis]. 2016 Aug BACKGROUND: Operative treatment of chondrocalcinosis (calcium pyrophosphate dihydrate deposition disease=CPPD disease) of the wrist is hardly ever mentioned in the literature. Since the chronic, recurrent type of this disease resembles rheumatoid arthritis (RA) as well as osteoarthritis, the author has performed arthroscopic synovectomy of the wrist, which achieves excellent results in RA und offers high patient comfort as an atraumatic procedure with low morbidity. This article presents the experience made with arthroscopic synovectomy in CPPD disease of the wrist. PATIENTS AND METHODS: Out of 74 arthroscopic synovectomies in 71 patients with symptomatic CPPD disease of the wrist, 46 operations in 43 patients were followed for an average of 26.6 months after surgery. 15 women and 28 men at an average age of 64.5 (42-90) years had a telephone interview and were asked for pain, functional impairment and satisfaction with the intervention. Intraoperative and histologic findings were recorded. According to the Romano Classification, there was SCAC (scaphoid chondrocalcinosis advanced collapse) I in 6 cases (13%), SCAC II in 18 (39%), SCAC III in 9 (19.5%) and SCAC IV in 3 cases (6.5%). In 10 X-rays, classification according to Romano was not possible. RESULTS: There was a significant reduction in pain at rest and on weight-bearing as well as a significant improvement in hand function. 74% of patients would chose to undergo the intervention again. Arthroscopy revealed the typical symptoms of CPPD disease in all cases. In 38 out of the 46 operations, a histologic examination was performed and was positive in 20 cases. CONCLUSIONS: Arthroscopic synovectomy of the wrist in patients with CPPD disease provides high patient satisfaction regardless of the radiologic stage. The procedure is atraumatic with low morbidity and high patient comfort. The Romano Classification should be supplemented by an additional early stage, SCAC 0. More often than suspected, CPPD disease may be responsible for wrist pain of unknown origin even in middle-aged patients.
27407283 Social implications of rheumatic diseases. 2016 Social consequences of a disease constitute limitations in performing roles relating to working life as well as family and social life caused by the disease, mainly chronic. The aim of the study was to analyze the social consequences of rheumatic diseases in the aspect of disability pensions with respect to incapacity for work and quality of life. The occurrence of rheumatic diseases is related not only to increased risk of different types of organic changes, but above all disability. In Europe almost 50% of persons suffering from diseases of the musculoskeletal system who are currently unemployed were breadwinners. Nearly 60% of them received legal disability status. The loss of work ability is, among other things, the consequence of progressive disability. In Europe 40% of persons suffering from rheumatoid arthritis (RA) had to stop working due to the disease. Most of the persons diagnosed with RA were of working age. It results in the decrease in the quality of life as well as economic difficulties (decreased incomes and increased disease-related costs). In Poland the results of the analysis of the Social Insurance Institution (ZUS) of first-time disability recognition issued for the purpose of disability pensions in 2014 showed that the incapacity for work was caused by diseases relating to general health condition (65.5%). Diseases of the musculoskeletal system were the cause of partial inability to work of 21.6% of persons who received a disability pension for the first time (as many as 5,349 certificates were issued). Early diagnosis and implementation of effective treatment are the necessary conditions for a patient to sustain activity, both professional and social, which is of crucial importance to reduce the negative effects of the disease.
27031898 Metastatic muscle abscesses complicating infected total hip arthroplasty. 2016 A 73-year-old woman with rheumatoid arthritis presented to our institution with infection of her right total hip arthroplasty. On admission, a draining sinus tract over the hip and a palpable mass in the left lower posterior region of the neck were detected. The contrast CT scan showed a large abscess in the trapezius muscle and multiple abscesses involving muscle of the neck and right shoulder. Intraoperative specimens from the muscle abscess were positive for presumably the same methicillin-resistant Staphylococcus aureus that sustained the prosthetic joint infection. Prolonged intravenous daptomycin led to remission of the muscle abscess and control of the prosthetic joint infection. The patient refused revision total hip arthroplasty and oral cotrimoxazole was prescribed for chronic suppression of the infection. Three years after the primary surgery there was stable remission of the prosthetic joint infection. This rare case demonstrates the severity of prosthetic joint infections sustained by multiresistant bacteria in immunocompromised hosts, which may result in their bacteraemic spread.
26949177 Biologics for the treatment of autoimmune renal diseases. 2016 Apr Biological therapeutics (biologics) that target autoimmune responses and inflammatory injury pathways have a marked beneficial impact on the management of many chronic diseases, including rheumatoid arthritis, psoriasis, inflammatory bowel disease, and ankylosing spondylitis. Accumulating data suggest that a growing number of renal diseases result from autoimmune injury - including lupus nephritis, IgA nephropathy, anti-neutrophil cytoplasmic antibody-associated glomerulonephritis, autoimmune (formerly idiopathic) membranous nephropathy, anti-glomerular basement membrane glomerulonephritis, and C3 nephropathy - and one can speculate that biologics might also be applicable to these diseases. As many autoimmune renal diseases are relatively uncommon, with long natural histories and diverse outcomes, clinical trials that aim to validate potentially useful biologics are difficult to design and/or perform. Some excellent consortia are undertaking cohort studies and clinical trials, but more multicentre international collaborations are needed to advance the introduction of new biologics to patients with autoimmune renal disorders. This Review discusses the key molecules that direct injurious inflammation and the biologics that are available to modulate them. The opportunities and challenges for the introduction of relevant biologics into treatment protocols for autoimmune renal diseases are also discussed.
26920148 Clinical and regulatory perspectives on biosimilar therapies and intended copies of biolog 2016 May Biologics are vital to the management of patients with rheumatic and musculoskeletal diseases such as rheumatoid arthritis and other inflammatory and autoimmune conditions. Nevertheless, access to these highly effective treatments remains an unmet medical need for many people around the world. As patents expire for existing licensed biologic (originator) products, biosimilar products can be approved by regulatory authorities and enter clinical use. Biosimilars are highly similar copies of originator biologics approved through defined and stringent regulatory processes after having undergone rigorous analytical, non-clinical, and clinical evaluations. The introduction of high-quality, safe, and effective biosimilars has the potential to expand access to these important medicines. Biosimilars are proven to be similar to the originator biologic in terms of safety and efficacy and to have no clinically meaningful differences. In contrast, "intended copies" are copies of originator biologics that have not undergone rigorous comparative evaluations according to the World Health Organization recommendations, but are being commercialized in some countries. There is a lack of information about the efficacy and safety of intended copies compared with the originator. Furthermore, they may have clinically significant differences in formulation, dosages, efficacy, or safety. In this review, we explore the differences between biosimilars and intended copies and describe key concepts related to biosimilars. Familiarity with these topics may facilitate decision making about the appropriate use of biosimilars for patients with rheumatic and musculoskeletal diseases.
26890460 Orthognathic Surgery in Patients With Large Condylar Destructions. 2016 Mar Condylar resorption is understood as changes in shape and volume of the condylar bone, due to local, systemic, and iatrogenic factors. The occurrence of condylar resorption after orthognathic surgery can occur when the condylar repositioning in mandibular fossa is performed improperly. In addition, systemic diseases such as osteoarthritis and rheumatoid arthritis seem to influence this process. The aim of this study was to report 3 cases of patients with severe condylar alterations, submitted to orthognathic surgery for treatment of dentofacial deformities. Considerations regarding the diagnosis, surgical planning (counterclockwise rotation), surgical techniques (bilateral sagittal split osteotomy, bimaxillary osteotomies, rigid fixation, maxillomandibular fixation period), and results (short terms) are discussed.
26790377 Novel organ-slice culturing system to simulate meniscal repair: Proof of concept using a s 2016 Sep Meniscal injuries can occur secondary to trauma or be instigated by the changes in knee-joint function that are associated with aging, osteo- and rheumatoid arthritis, disturbances in gait, and obesity. Sixty percent of persons over 50 years of age manifest signs of meniscal pathology. The surgical and arthroscopic measures that are currently implemented to treat meniscal deficiencies bring only transient relief from pain and effect but a temporary improvement in joint function. Although tissue-engineering-based approaches to meniscal repair are now being pursued, an appropriate in-vitro model has not been conceived. The aim of this study was to develop an organ-slice culturing system to simulate the repair of human meniscal lesions in vitro. The model consists of a ring of bovine meniscus enclosing a chamber that represents the defect and reproduces its sequestered physiological microenvironment. The defect, which is closed with a porous membrane, is filled with fragments of synovial tissue, as a source of meniscoprogenitor cells, and a fibrin-embedded, calcium-phosphate-entrapped depot of the meniscogenic agents BMP-2 and TGF-β1. After culturing for 2 to 6 weeks, the constructs were evaluated histochemically and histomorphometrically, as well as immunohistochemically, for the apoptotic marker caspase 3 and collagen types I and II. Under the defined conditions, the fragments of synovium underwent differentiation into meniscal tissue, which bonded with the parent meniscal wall. Both the parent and the neoformed meniscal tissue survived the duration of the culturing period without significant cell losses. The concept on which the in-vitro system is based was thus validated. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1588-1596, 2016.
26676089 Anterolateral Portal Is Less Painful than Superolateral Portal in Knee Intra-Articular Inj 2015 Dec PURPOSE: Intra-articular knee injections are commonly performed in clinical practice for treating various knee joint disorders such as osteoarthritis and rheumatoid arthritis. When selecting the portal for injection, not only intra-articular needle accuracy but also procedural pain should be taken into consideration. The purpose of this study was to determine whether injection through anterolateral portal provokes less pain and provides better pain relief compared to superolateral portal. MATERIALS AND METHODS: A total of 60 patients with primary osteoarthritis of the knee receiving intra-articular injections were randomized into 2 groups according to the type of portal approach; anterolateral or superolateral. All patients received hyaluronic acid (20 mg) and triamcinolone (40 mg) as the first injection followed by second and third injections of hyaluronic acid on a weekly basis. Underlying knee pain, procedural pain, and knee pain at 4 weeks were evaluated using visual analogue scale (VAS). RESULTS: Injection through anterolateral portal provoked less pain (VAS, 1.5±1.3) than the superolateral portal (VAS, 1.5 vs. 2.7; p=0.004). No differences were found in the degree of pain relief at weeks between the two groups (p=0.517). CONCLUSIONS: We recommend the use of anterolateral portal for intra-articular knee injection as it provokes less pain and comparably short-term pain relief than the superolateral portal.
26579520 β cell ER stress and the implications for immunogenicity in type 1 diabetes. 2015 Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by hyperglycemia due to progressive immune-mediated destruction of insulin-producing pancreatic islet β cells. Although many elegant studies have identified β cell autoantigens that are targeted by the autoimmune response, the mechanisms by which these autoantigens are generated remain poorly understood. Normal β cell physiology includes a high demand for insulin production and secretion in response to dynamic glucose sensing. This secretory function predisposes β cells to significantly higher levels of endoplasmic reticulum (ER) stress compared to nonsecretory cells. In addition, many environmental triggers associated with T1D onset further augment this inherent ER stress in β cells. ER stress may increase abnormal post-translational modification (PTM) of endogenous β cell proteins. Indeed, in other autoimmune disorders such as celiac disease, systemic lupus erythematosus, multiple sclerosis, and rheumatoid arthritis, abnormally modified neo-antigens are presented by antigen presenting cells (APCs) in draining lymph nodes. In the context of genetic susceptibility to autoimmunity, presentation of neo-antigens activates auto-reactive T cells and pathology ensues. Therefore, the ER stress induced by normal β cell secretory physiology and environmental triggers may be sufficient to generate neo-antigens for the autoimmune response in T1D. This review summarizes what is currently known about ER stress and protein PTM in target organs of other autoimmune disease models, as well as the data supporting a role for ER stress-induced neo-antigen formation in β cells in T1D.
26511867 The emerging role of aryl hydrocarbon receptor in the activation and differentiation of Th 2016 Jan The aryl hydrocarbon receptor (AHR) is a cytoplasmic transcription factor, which plays an essential role in the xenobiotic metabolism in a wide variety of cells. The AHR gene is evolutionarily conserved and it has a central role not only in the differentiation and maturation of many tissues, but also in the toxicological metabolism of the cell by the activation of metabolizing enzymes. Several lines of evidence support that both AHR agonists and antagonists have profound immunological effects; and recently, the AHR has been implicated in antibacterial host defense. According to recent studies, the AHR is essential for the differentiation and activation of T helper 17 (Th17) cells. It is well known that Th17 cells have a central role in the development of inflammation, which is crucial in the defense against pathogens. In addition, Th17 cells play a major role in the pathogenesis of several autoimmune diseases such as rheumatoid arthritis. Therefore, the AHR may provide connection between the environmental chemicals, the immune regulation, and autoimmunity. In the present review, we summarize the role of the AHR in the Th17 cell functions.
26470648 Diminazene aceturate--An antiparasitic drug of antiquity: Advances in pharmacology & thera 2015 Dec Diminazene aceturate (C14H15N7.2C4H7NO3) is an aromatic diamidine that was developed more than six decades ago and has been marketed until today for the control of trypanosomiasis. In recent years, however, this trypanocidal compound has been extensively studied with respect to its therapeutic potential and has consequently attracted much interest for the development of further research. The objective of this study was to conduct a systematic review on diminazene aceturate regarding its pharmacological properties. In this way, databases were searched for articles (ScienceDirect, Scopus, PubMed, Web of Science and SciFinder) and patents (INPI, USPTO, WIPO, DPMA, SIPO, DERWENT, CIPO and EPO). For the development of this review, 115 articles and 22 patents were selected and analyzed. It was thus possible to highlight several researches that have investigated alternatives in order to improve success in the treatment of animal trypanosomiasis, by using new drugs in associations with diminazene aceturate, as well as looking for new pharmacological applications for this compound, such as leishmanicidal, amebicidal, anti-pneumocystis, anti-rheumatoid arthritis, antihypertensive agent, and mainly as an activator of angiotensin-converting enzyme 2. Another pharmacological property still little studied is the inhibition of acid-sensitive ion channels (ASIC1a, ASIC1b, ASIC2a and ASIC3), which are related to the development of various diseases. Collectively, these studies conducted by several research groups extend the use of diminazene aceturate beyond the antitrypanosomal activity and suggest promising new applications.