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ID PMID Title PublicationDate abstract
28439487 Modified rice bran hemicellulose inhibits vascular endothelial growth factor-induced angio 2017 Angiogenesis is implicated in diverse pathological conditions such as cancer, rheumatoid arthritis, psoriasis, atherosclerosis, and retinal neovascularization. In the present study, we investigated the effects of modified rice bran hemicellulose (MRBH), a water-soluble hemicellulose preparation from rice bran treated with shiitake enzymes, on vascular endothelial growth factor (VEGF)-induced angiogenesis in vitro and its mechanism. We found that MRBH significantly inhibited VEGF-induced tube formation in human umbilical vein endothelial cells (HUVECs) co-cultured with human dermal fibroblasts. We also observed that MRBH dose-dependently suppressed the VEGF-induced proliferation and migration of HUVECs. Furthermore, examination of the anti-angiogenic mechanism indicated that MRBH reduced not only VEGF-induced activation of VEGF receptor 2 but also of the downstream signaling proteins Akt, extracellular signal-regulated protein kinase 1/2, and p38 mitogen-activated protein kinase. These findings suggest that MRBH has in vitro anti-angiogenic effects that are partially mediated through the inhibition of VEGF signaling.
28331021 Aspergillus niger infection in an immunosuppressed patient confined solely to the brain. 2017 Mar 22 A 68-year-old woman with a background of hypertension, stroke and rheumatoid arthritis presented to her local hospital after a 4-week history of gradual deterioration and increasing confusion with new onset right-sided weakness. Her initial CT scan revealed a rim enhancing mass lesion with surrounding oedema in the left parietal lobe for which she underwent CT stealth-guided biopsy. Microbiology culture of the 2 biopsy samples yielded Aspergillus niger and she was started on the antifungal agent voriconazole. MRI 2 weeks after the procedure also demonstrated radiological findings consistent with intracranial aspergillosis. She later developed leucopenia with neutrophils of 1.5×10(9)/L and her methotrexate and voriconazole were stopped. Voriconazole was changed to oral posaconazole. She did not undergo surgical resection and has continued to improve clinically on posaconazole, with recovery in her white cell count.
27988430 Kinin receptors: Key regulators of autoimmunity. 2017 Feb The central function of the immune system is to protect the host from environmental agents such as microbes or chemicals, thereby preserving the integrity of the body, and preventing the onset of illness and infection. Moreover, the immune system is constantly challenged to discriminate self vs. non-self and mediate the correct response, a phenomenon called self-tolerance. The failure of mechanisms responsible for self-tolerance and induction of an immune response against components of the self, induces autoimmunity and culminates however, in several autoimmune diseases. The precise etiology of autoimmune diseases is not known, although the classic sign of an autoimmune disease is inflammation. In this context, kinins are a family of peptides involved in different physiological and pathological states, comprising inflammatory, vascular and pain processes, and are highly relevant as well as to a variety of diseases including hypertension, kidney diseases, Alzheimer's disease, cancer, obesity, epilepsy and traumatic injuries. These kinin effects are mediated by two related G-protein-coupled receptors named the bradykinin receptors (BKRs), B1 and B2. The kallikrein-kinin system (KKS) and their receptors appear to be involved in both the development and progression of autoimmune diseases, suggesting that modulators of BKRs, administered in monotherapy or in combination with existing therapies, may represent a potential new venue for an effective autoimmune disease treatment. This review article highlights historical and recent progress in understanding the role of BKRs as potential therapeutics for a number of autoimmune diseases, including multiple sclerosis, rheumatoid arthritis, type I diabetes mellitus, inflammatory bowel diseases, and others.
28915774 Pyoderma Gangrenosum: A Current Problem as Much as an Unknown One. 2017 Sep Pyoderma gangrenosum (PG) is a rare neutrophilic inflammatory skin disease, characterized by recurrent skin ulcers, which in almost 50% of cases are associated with systemic autoimmune disorders, including rheumatoid arthritis, chronic hepatitis, inflammatory bowel disease, paraproteinemias and hematological malignancies. A systematic search of literature for PG was carried out using the PubMed, Embase, and Google Scholar databases for the purpose of this review and 2780 articles were retrieved up to February 2017. Inflammation represents the predominant aspect of the disease, but its pathophysiological mechanisms are not completely clear yet, since there are many studies showing only one or more isolated findings of the disease. The goal of PG treatment is to reduce inflammation in order to promote ulcer healing by minimizing side effects of therapy. Several systemic and local treatments are available, but the lack of large randomized double-blind studies results in an absence of a uniform therapeutic standard: thus, more clinical studies are required in order to make head-to-head comparisons between combination and single-drug therapies and to identify specific combination therapies for distinctive clinical patterns of PG.
28706221 CCL11, a novel mediator of inflammatory bone resorption. 2017 Jul 13 Normal bone homeostasis, which is regulated by bone-resorbing osteoclasts and bone-forming osteoblasts is perturbed by inflammation. In chronic inflammatory disease with disturbed bone remodelling, e.g. rheumatoid arthritis, patients show increased serum levels of the chemokine eotaxin-1 (CCL11). Herein, we demonstrate an inflammatory driven expression of CCL11 in bone tissue and a novel role of CCL11 in osteoclast migration and resorption. Using an inflammatory bone lesion model and primary cell cultures, we discovered that osteoblasts express CCL11 in vivo and in vitro and that expression increased during inflammatory conditions. Osteoclasts did not express CCL11, but the high affinity receptor CCR3 was significantly upregulated during osteoclast differentiation and found to colocalise with CCL11. Exogenous CCL11 was internalised in osteoclast and stimulated the migration of pre-osteoclast and concomitant increase in bone resorption. Our data pinpoints that the CCL11/CCR3 pathway could be a new target for treatment of inflammatory bone resorption.
28669703 Design and development of Unani anti-inflammatory cream. 2017 Jul Inflammation is the symptom of many diseases like rheumatoid arthritis and osteoarthritis. Many side effects are associated with the Non-Steroidal Anti-inflammatory Drugs (NSAIDs) used as conventional treatment for these conditions. In Unani, there are large number of single and compound drugs for inflammatory conditions. One dosage form of Unani system of medicine is named as Zimad in which paste is formed by mixing powder in oil, water, herbal extract. Zimadat is prepared just before application and used in many disease conditions as resolving, styptic, astringent, and antiseptic. As the pre-application procedure is difficult and also complicated for patients, hence, the present study attempted to modify the form of Zimad into cream. Various batches of cream of Zimad Mohallil were prepared by using extracts of the formulation and by adding additives. Various physicochemical parameters of prepared cream were carried and compared with market cream. The optimized cream of Zimad Mohallil (F(4)) was selected after preliminary tests and evaluated further. The optimized cream showed good results in physicochemical parameters equivalent to market sample. Zimad Mohallil was converted into convenient cream form by adding minimum additives and benefits could be achieved without any hassle and cumbersome work, which is encountered in crude or paste form. The optimized cream was equivalent to standard market cream.
28587321 Clinical evaluation of CENP-B and Scl-70 autoantibodies in silicosis patients. 2017 Jun Silicosis patients (SIL) suffer from respiratory disorders and dysregulation of autoimmunity. Frequent complications such as rheumatoid arthritis, systemic sclerosis (SSc) and vasculitis are known in SIL. Furthermore, we reported previously that some SIL exhibited better respiratory conditions in association with a worse immunological status. In this study, the clinical roles of anti-CENP-B and Scl-70 autoantibodies in SIL were analyzed. The titer index (Log10) of anti-CENP-B autoantibody in SIL was higher than that of healthy volunteers (HV), and that of SSc was higher than those of HV and SIL. This titer index was positively correlated with an assumed immune status of 1 for HV, 2 for SIL, and 3 for SSc. Moreover, although factor analysis revealed that the titer index of the anti-CENP-B autoantibody formed the same factor with the anti-Scl-70 autoantibody, IgG value and age in SIL cases, another extracted factor indicated that the IgA value and anti-Scl-70 antibody were positively related, but anti-CENP-B showed an opposite pattern in the results of the factor analysis. These findings indicated that the titer index of anti-CENP-B autoantibody may be a biomarker for dysregulation in SIL cases. Future clinical follow-up of SIL may therefore require both respiratory and immunological assessment.
27677781 Immune-to-Brain Communication Pathways in Inflammation-Associated Sickness and Depression. 2017 A growing body of evidence now highlights a key role for inflammation in mediating sickness behaviors and depression. Systemic inflammatory diseases such as rheumatoid arthritis, inflammatory bowel disease, and chronic liver disease have high comorbidity with depression. How the periphery communicates with the brain to mediate changes in neurotransmission and thereby behavior is not completely understood. Traditional routes of communication between the periphery and the brain involve neural and humoral pathways with TNFα, IL-1β, and IL-6 being the three main cytokines that have primarily been implicated in mediating signaling via these pathways. However, in recent years communication via peripheral immune-cell-to-brain and the gut-microbiota-to-brain routes have received increasing attention for their ability to modulate brain function. In this chapter we discuss periphery-to-brain communication pathways and their potential role in mediating inflammation-associated sickness behaviors and depression.
27569557 Osteonecrosis of the Jaw in the Absence of Antiresorptive or Antiangiogenic Exposure: A Se 2017 Jan PURPOSE: Medication-related osteonecrosis of the jaws (MRONJ) is a well-described complication of antiresorptive and antiangiogenic medications. Although osteonecrosis can be associated with other inciting events and medications, such as trauma, infection, steroids, chemotherapy, and coagulation disorders, these are rarely reported in the literature. MATERIALS AND METHODS: This is a six case series of MRONJ associated with medications other than antiresorptive or antiangiogenic drugs. RESULTS: Patient demographics, inciting event, location, stage, imaging findings, and outcome are reported. CONCLUSION: With the continued development and clinical use of new biologic medications for diseases such as cancer and rheumatoid arthritis, it is important to continue to evaluate their effects on the oral cavity. The degree of risk for osteonecrosis in patients taking these new classes of drugs is uncertain but warrants awareness and monitoring.
29348946 Group A Streptococci-Associated Necrotizing Fasciitis following Cat Bite in an Immunocompr 2017 Necrotizing soft tissue infections are characterized clinically by fulminant tissue destruction, systemic signs of toxicity, and high mortality. Accurate diagnosis and appropriate treatment must include early surgical intervention and antibiotic therapy. Mortality rate is very high and could be even higher in an immunocompromised host. We present a 57-year-old female with history of rheumatoid arthritis on oral corticosteroid and methotrexate therapy with painful swelling of the left hand following a cat bite that was diagnosed as having group A streptococcus pyogenes-associated necrotizing fasciitis. Treatment with ampicillin-sulbactam, Clindamycin, and surgical debridement was performed. In spite of all the adequate therapy she succumbed to death from streptococcal toxic shock and related complications after thirty-two days of treatment in intensive care unit. Necrotizing fasciitis is an uncommon but life-threatening complication in immunocompromised hosts. Tissue infections in cat bite wounds are commonly caused by pathogenic bacterium known as Pasteurella multocida. Group A streptococcal infections are not reported following cat bites. A high index of suspicion must be maintained to suspect group A streptococcal associated necrotizing fasciitis following cat bites and an early medical and surgical intervention should be made for any best possible outcome.
29281705 Anti-inflammatory effect of Allium hookeri on carrageenan-induced air pouch mouse model. 2017 Inflammation is a commonly observed immune reaction, and rheumatoid arthritis is a particularly severe inflammatory disease. In this study, we used an air pouch mouse model to evaluate the anti-inflammatory potential of Allium hookeri, which has both been used as a culinary material and a traditional medicine in south-eastern Asia for many years. Allium hookeri suppressed typical symptoms of inflammation, such as condensation of the air pouch membrane, and inhibited the expression of several inducible proinflammatory cytokines such as IL-1β, IL-6, IL-13, and TNF-α. In order to determine the molecules modulating the inflammatory effect of carrageenan treatment, the components in Allium hookeri were analyzed by GC-MS, and linoleic acid, which have anti-inflammatory effect, was detected. From the results, we concluded that the anti-inflammatory effect of Allium hookeri might be attributed to linoleic acid, which could be promising candidates for anti-inflammatory drugs that have no adverse effects.
29256764 Normalizing fibromyalgia as a chronic illness. 2018 Jan Fibromyalgia (FM) is a complex chronic disease that affects 3-10% of the general adult population and is principally characterized by widespread pain, and is often associated with disrupted sleep, fatigue, and comorbidities, among other symptoms. There are many gaps in our knowledge of FM, such that, compared with other chronic illnesses including diabetes, rheumatoid arthritis, and asthma, it is far behind in terms of provider understanding and therapeutic approaches. The experience that healthcare professionals (HCPs) historically gained in developing approaches to manage and treat patients with these chronic illnesses may help show how they can address similar problems in patients with FM. In this review, we examine some of the issues around the management and treatment of FM, and discuss how HCPs can implement appropriate strategies for the benefit of patients with FM. These issues include understanding that FM is a legitimate condition, the benefits of prompt diagnosis, use of non-drug and pharmacotherapies, patient and HCP education, watchful waiting, and assessing patients by FM domain so as not to focus exclusively on one symptom to the detriment of others. Developing successful approaches is of particular importance for HCPs in the primary care setting who are in the ideal position to provide long-term care for patients with FM. In this way, FM may be normalized as a chronic illness to the benefit of both patients and HCPs.
29250057 Update on Dendritic Cell-Induced Immunological and Clinical Tolerance. 2017 Dendritic cells (DCs) as highly efficient antigen-presenting cells are at the interface of innate and adaptive immunity. As such, they are key mediators of immunity and antigen-specific immune tolerance. Due to their functional specialization, research efforts have focused on the characterization of DCs subsets involved in the initiation of immunogenic responses and in the maintenance of tissue homeostasis. Tolerogenic DCs (tolDCs)-based therapies have been designed as promising strategies to prevent and control autoimmune diseases as well as allograft rejection after solid organ transplantation (SOT). Despite successful experimental studies and ongoing phase I/II clinical trials using autologous tolDCs in patients with type 1 diabetes, rheumatoid arthritis, multiple sclerosis, and in SOT recipients, additional basic research will be required to determine the optimal DC subset(s) and conditioning regimens for tolDCs-based treatments in vivo. In this review, we discuss the characteristics of human DCs and recent advances in their classification, as well as the role of DCs in immune regulation and their susceptibility to in vitro or in vivo manipulation for the development of tolerogenic therapies, with a focus on the potential of tolDCs for the treatment of autoimmune diseases and the prevention of allograft rejection after SOT.
29198867 Design and synthesis of novel pyrimidine analogs as highly selective, non-covalent BTK inh 2018 Jan 15 BTK is a promising target for the treatment of multiple diseases such as B cell malignances, asthma, and rheumatoid arthritis. Here, we report the discovery of a series of novel pyrimidine analogs as potent, highly selective, non-covalent inhibitors of BTK. Compound 25d demonstrated higher affinity to an unactivated conformation of BTK that resulted in an excellent kinase selectivity. Compound 25d showed a good oral bioavailability in mice, and significantly inhibits the PCA reaction in mice.
29158650 Partial humeral replacement for peri-prosthetic fractures of the humerus. 2017 Nov INTRODUCTION: Treating peri-prosthetic fractures of the humerus can be very challenging, especially when there is poor bone stock and in the presence of adjacent joint prostheses. We discuss the option of a partial humeral replacement as a salvage procedure for such cases with some technical comments. METHODS: This paper presents a technique which utilises a custom- made cemented connector to incorporate the existing well functioning elbow or shoulder replacement with a commercially available partial humeral replacement (PHR) or to an existing prosthetic humeral stem. RESULTS: Our series involves 6 patients with severe rheumatoid arthritis, all female, with a mean age of 62.5 years. Their surgeries were performed over a span of 10 years, with an average follow up of 49 months. All had a well functioning implant at final follow-up, with a mean Mayo Elbow Performance score of 65. There were no cases of infection, nerve injury or dislocation in our patients. There were 2 deaths in our series, from unrelated medical causes at 2 and 4 years following their surgery. CONCLUSION: Although a partial humeral replacement connected to a well functioning implant is a rare procedure for salvage of a humeral peri-prosthetic fracture, it can be a viable option in certain patient populations. Every attempt should be made to maintain the secondary shoulder stabilisers at the proximal humerus as a functioning unit.
29130873 Influence of Body Mass Index on Clinical Outcomes in Reverse Total Shoulder Arthroplasty. 2017 FALL The purpose of this study was to compare reverse total shoulder arthroplasty (RTSA) outcomes in normal weight, overweight, and obese patients. A RTSA outcomes registry was reviewed for rotator cuff-deficient patients with a minimum 2-year follow-up. Fractures, rheumatoid arthritis, and revisions were excluded. Based on World Health Organization body mass index (BMI) classification, there were 29 normal weight, 50 overweight, and 51 obese patients. All groups demonstrated significant improvements from preoperative to most recent follow-up in function scores, pain, and forward elevation. Obese and overweight groups had significantly worse preoperative rotation than the normal weight group. Postoperatively, there was no significant difference in absolute values or degree of improvement of rotation between groups. There was no significant difference in the incidence of radiographic or clinical complications between groups. Results of this study suggest that BMI has little influence on outcomes or risk of complication following RTSA. Longer-term studies are needed to determine if these results are maintained. (Journal of Surgical Orthopaedic Advances.
29078639 Nodal upstaging: effects of instrumentation and three-dimensional view in clinical stage I 2017 Nodal upstaging after surgical intervention for non-small cell lung cancer (NSCLC) is defined as the presence of unsuspected pathologic hilar (pN1) or mediastinal (pN2) disease detected during the final histopathologic evaluation of surgical specimens. The prevalence of pathologic nodal upstaging is used as a quality measure for the definition of the completeness of the nodal dissection. Risk factors for nodal upstaging may be patient-related (history of tuberculosis, rheumatoid arthritis, and diabetes mellitus), or tumor-related (central tumor, higher T stage, higher SUVmax value, or adenocarcinoma). Actually, the theorical superiority of a minimally invasive resections is the lymph node dissection. Studies may suggest that, expert video-assisted thoracoscopic surgery (VATS) surgeon could do similar lymph node dissection as it is done in open. Robotic surgeons may replicate the results of lymph node dissection in the open techniques. The possible reason for this is the instrumental superiority provided by the higher technology.
29021682 Spontaneous regression of retro-odontoid post traumatic cicatrix following occipitocervica 2017 Jul This case report describes a patient who presented with myelopathy secondary to a large retro-odontoid post traumatic cicatrix. The objective of this study was to discuss the clinical presentation, pathogenesis, imaging, and surgical management of pseudoarthrosis tissue mass associated with odontoid nonunion. Atlantoaxial subluxation (AAS) has been widely reported in patients with rheumatoid arthritis. AAS leads to repeated cycles of partial tear and repair of ligaments around the altantoaxial complex, resulting in the formation of periodontoid mass (pseudotumor). It is thought that formation of retro-odontoid post traumatic mass (cicatrix), in certain cases of odontoid fracture, is because of similar pathology. This is a retrospective review of case note. Here, the patient underwent posterior decompression through a C1-C2 laminectomy and occipitocervical (C0-C4) fusion with instrumentation, which resulted in dramatic improvement in his symptoms and spontaneous regression of retro-odontoid post traumatic cicatrix. We have described an interesting and a rare case of a large pseudoarthrosis tissue mass associated with odontoid nonunion, which regressed following stand-alone posterior instrumentation. To the best of our knowledge, only a handful of such cases of spontaneous regression of retro-odontoid post traumatic cicatrix following occipitocervical fixation have been described in literature, and our case adds to the growing list of such cases and may help in understanding the natural history of the disease process one day. Although rare, post traumatic cicatrix should be considered as a differential diagnosis of enhancing retro-odontoid mass, especially if there is any history of cervical spine trauma.
28967372 A RheuMetric physician checklist to quantitate levels of inflammation, damage and distress 2017 Sep A physician global assessment of patient status (DOCGL) was designed initially to quantitate inflammatory activity in rheumatoid arthritis (RA) clinical trials, in which patients are selected for high levels of activity. However, in patients seen in routine care with various diagnoses, and even in some RA patients selected for clinical trials, DOCGL also may be affected by joint damage and/or patient distress. To clarify DOCGL on a 0-10 visual analogue scale (VAS), 3 additional 0-10 VAS have been developed to record physician estimates of inflammation (DOCINF), damage (DOCDAM), and distress (DOCSTR) (such as fibromyalgia (FM)/depression). Results from 3 locales for these 4 VASs are summarised, including 478 initial-visit patients from Tennessee in 1996 to 2007, 197 initial-visit patients from Pennsylvania in 2008 to 2012, and a random visit of 739 patients from Illinois in 2014 to 2015. Highest DOCGL estimates were seen at the 3 sites in FM, followed by RA and osteoarthritis (OA), spondyloarthropathies (SpA), gout, and systemic lupus erythematosus (SLE). Highest DOCINF (inflammation) estimates were seen in RA and SpA, followed by gout, SLE, FM, and OA. Highest DOCDAM (damage) estimates were in OA, followed by RA, SpA, gout, SLE and FM. Highest DOCSTR (distress) estimates were in FM, followed by OA, RA, SpA, SLE, and gout. In the 2 earlier series, DOCDAM was considerably higher than DOCINF only in OA, and lower in the other diagnoses, although within 50% of DOCINF. In more recent patients from Illinois, mean DOCDAM was higher than DOCINF in all 6 diagnoses. The 0-10 physician VASs depict the expertise of a rheumatologist to distinguish between inflammation, damage and distress in an individual patient and rate levels as quantitative data beyond narrative descriptions. These VASs appear informative for rheumatology care, documentation, and research.
29367528 [Autoimmune diseases and ubiquitin system]. 2017   Cytokines play important roles in the pathogenesis of autoimmune diseases. Anti-TNFα antibody therapy for rheumatoid arthritis, Crohn's disease, and psoriasis has made enough progress to change its treatment goal. This review focuses on the recent advances that have been made in understanding TNFR signaling through ubiquitin system. Genome-wide association studies (GWAS) identified numerous susceptibility loci associated with autoimmune diseases. Ubiquitin related genes TNFAIP3 and TNIP1 have been linked to multiple autoimmune diseases. Here, we review the importance of TNFAIP3 and TNIP1-mediated regulation of ubiquitin-dependent signaling. To monitor the dynamics of ubiquitin chain formation in vivo, we have developed a polyubiquitin-mediated fluorescence complementation (PolyUb-FC) assay. The PolyUb-FC assay has the advantage that monoubiquitination is non-fluorescent and chain-specific poly-ubiquitination can be directly visualized in living cells without using antibodies. The PolyUb-FC will be a useful tool for analyzing the dynamics of polyubiquitin chain generation.