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ID PMID Title PublicationDate abstract
23295700 Deep remission: a new concept? 2012 Crohn's disease (CD) is a chronic inflammatory disorder characterized by periods of clinical remission alternating with periods of relapse defined by recurrent clinical symptoms. Persistent inflammation is believed to lead to progressive bowel damage over time, which manifests with the development of strictures, fistulae and abscesses. These disease complications frequently lead to a need for surgical resection, which in turn leads to disability. So CD can be characterized as a chronic, progressive, destructive and disabling disease. In rheumatoid arthritis, treatment paradigms have evolved beyond partial symptom control alone toward the induction and maintenance of sustained biological remission, also known as a 'treat to target' strategy, with the goal of improving long-term disease outcomes. In CD, there is currently no accepted, well-defined, comprehensive treatment goal that entails the treatment of both clinical symptoms and biologic inflammation. It is important that such a treatment concept begins to evolve for CD. A treatment strategy that delays or halts the progression of CD to increasing damage and disability is a priority. As a starting point, a working definition of sustained deep remission (that includes long-term biological remission and symptom control) with defined patient outcomes (including no disease progression) has been proposed. The concept of sustained deep remission represents a goal for CD management that may still evolve. It is not clear if the concept also applies to ulcerative colitis. Clinical trials are needed to evaluate whether treatment algorithms that tailor therapy to achieve deep remission in patients with CD can prevent disease progression and disability.
23261775 The inflammasome: pathways linking psychological stress, depression, and systemic illnesse 2013 Jul Stress is a common occurrence in everyday life and repeated or traumatic stress can be a precipitating factor for illnesses of the central nervous system, as well as peripheral organ systems. For example, severe or long-term psychological stress can not only induce depression, a leading illness worldwide, but can also cause psychosomatic diseases such as asthma and rheumatoid arthritis. Related key questions include how psychological stress influences both brain and peripheral systems, and what detection mechanisms underlie these effects? A clue is provided by the discovery of the pathways underlying the responses to host "danger" substances that cause systemic diseases, but can also contribute to depression. The inflammasome is a protein complex that can detect diverse danger signals and produce the accompanying immune-inflammatory reactions. Interestingly, the inflammasome can detect not only pathogen-associated molecules, but also cell damage-associated molecules such as ATP. Here, we propose a new inflammasome hypothesis of depression and related comorbid systemic illnesses. According to this hypothesis, the inflammasome is a central mediator by which psychological and physical stressors can contribute to the development of depression, and as well as a bridge to systemic diseases. This hypothesis includes an explanation for how psychological stress can influence systemic diseases, and conversely how systemic diseases can lead to psychiatric illnesses. The evidence suggests that the inflammasome may be a new target for the development of treatments for depression, as well as psychosomatic and somato-psycho diseases.
23259625 MDHAQ/RAPID3 can provide a roadmap or agenda for all rheumatology visits when the entire M 2012 The management of rheumatoid arthritis (RA) depends more on the patient history than most other chronic diseases. A patient questionnaire provides a uniform, quantitative, protocolized, "scientific" patient history, with documented prognostic significance for work disability and mortality in RA greater than radiographs and laboratory tests and capacity to distinguish active from control treatment in clinical trials and to monitor clinical care with equivalent or greater significance than joint counts or laboratory tests. Therefore, a "scientific" approach to care of a person with a rheumatic disease involves review of patient function, pain, global status, fatigue, RAPID3, review of systems, self-report joint count, and recent medical history on an MDHAQ before conversation with the patient. This practice may be viewed as analogous to a doctor reviewing blood pressure, hemoglobin A1c, viral load, or radiograph before meeting with a patient who has hypertension, diabetes, HIV, or a healing fracture to provide a roadmap or agenda for the visit. Some sites have implemented RAPID3 without the remainder of MDHAQ, a practice that is discouraged. The MDHAQ requires only 5 to 10 minutes of the patient's time and involves a single sheet of paper, which is needed for a simple RAPID3, or even a patient global estimate of status to score a DAS28 or CDAI. Completion of MDHAQ/RAPID3 by each patient at each visit in the infrastructure of care with review by the doctor helps prepare the patient for the visit, improves doctor-patient communication, saves time for the doctor, and provides a roadmap or agenda for the visit.
23214307 Deficiencies and excessive human complement system activation in disorders of multifarious 2012 Jan Complement is an integral part of the immune system protecting the host organism against invasion and proliferation of various microorganisms. It is also involved in the removal of the body's own damaged and altered cells. Activation of the complement system is a very precise process and it is strictly controlled by regulatory proteins present in both plasma and at host cells' surfaces. C3 protein plays a major role in the complement activation and generation of immune responses. Deficiencies of the C3 and other complement components, so-called early and late complement proteins, contribute to the emergence of recurrent bacterial, viral and fungal infections. The low level of mannose-binding lectin is also important. This protein plays a protective role in the early stages of infection and in the control of inflammation. Its deficit is one of the most common reasons for human immunodeficiency, observed in microbial infections as well as in autoimmune diseases such as rheumatoid arthritis. On the other hand, the excessive activation of complement proteins is often discovered to be the reason for many diseases. These include e.g. autoimmune diseases, Alzheimer's syndrome, schizophrenia, atypical hemolytic-uremic syndrome, angioedema, macular degeneration, and Crohn's disease.
23210942 Diseases that turn African hair silky. 2012 Nov BACKGROUND: African hair in its natural state poses tenacious grooming challenges; consequently a large portion of the African cosmetic industry is focused on means to relax the tight curls of African hair to make the hair more manageable. In malnourished and hypoproteinemic states, African hair straightens in an uncomplimentary manner. Recently, we observed that in certain diseases African hair changes to a desirable silky wavy texture. METHOD: To identify the diseases that turn African hair silky and their parameters we examined 5612 dermatology patients at a tertiary hospital in Nigeria. We then studied the clinical and basic laboratory parameters of those patients whose diseases were accompanied by the silky hair change. RESULT: Silky hair change similar to the hair of the African neonatal child was observed in five diseases, namely AIDS, rheumatoid arthritis, systemic lupus erythematosus, pulmonary tuberculosis with cachexia, and Behçet's disease. CONCLUSION: Our study identified retrogression of African hair to the neonatal structure in five diseases. Anemia of chronic illness, high erythrocyte sedimentation rate, and mild hypocalcemia were significant laboratory parameters. This is an important observation, which should excite and advance research into the nature and structure of African hair. The causes of structural hair changes should include these five diseases.
23199973 [Whipple disease revealed by anti-TNFα therapy]. 2013 Feb INTRODUCTION: Whipple disease is a rare infectious disease with protean clinical manifestations. This infection may mimic chronic inflammatory rheumatisms such as rheumatoid arthritis or spondylarthritis. In this context, introduction of a biotherapy after a diagnostic hesitation does not always lead to early complications. Sometimes, the clinical degradation follows an initial improvement, encouraging continuation of the immunosuppressive treatment and leading consequently to a greater diagnostic delay. CASE REPORTS: We report two cases of Whipple disease diagnosed in the context of an inflammatory disease with anti-TNFα failure. The first patient was a 53-year-old man who presented with an axial and peripheral spondylarthritis who was treated with etanercept and adalimumab. The second was a 42-year-old man who received adalimumab and then etanercept for a peripheral spondylarthritis. CONCLUSION: Whipple disease should be suspected in all patients who present with a chronic inflammatory rheumatism that is partially or not controlled with anti-TNFα therapy and who had persisting elevated acute phase reactants.
23194156 Growth and differentiation of prechondrogenic cells on bioactive self-assembled peptide na 2013 Jan 14 Restoration of cartilage defect remains a challenge, as the current treatments are ineffective to return tissue to its health. Thus, developing therapies for treatment of cartilage tissue damage caused by common joint diseases including osteoarthritis, rheumatoid arthritis, and accidents is crucial. Sulfated glycosaminoglycan molecules are vital constituents of both developing and mature cartilage extracellular matrix. The interplay between regulator proteins and glycosaminoglycan molecules has an essential role in coordinating differentiation, expansion, and patterning during cartilage development. In this study, we exploited the functional role of an extracellular matrix on chondrogenic differentiation by imitating extracellular matrix both chemically by imparting functional groups of native glycosaminoglycans and structurally through peptide nanofiber network. For this purpose, sulfonate, carboxylate, and hydroxyl groups were incorporated on self-assembled peptide nanofibers. We observed that when ATDC5 cells were cultured on functional peptide nanofibers, they rapidly aggregated in insulin-free medium and formed cartilage-like nodules and deposited sulfated glycosaminoglycans shown by Safranin-O staining. Moreover, collagen II and aggrecan gene expressions revealed by qRT-PCR were significantly enhanced, which indicated the remarkable bioactive role of this nanofiber system on chondrogenic differentiation. Overall, these results show that glycosaminoglycan mimetic peptide nanofiber system provides a promising platform for cartilage regeneration.
22943044 Mast cells, disease and gastrointestinal cancer: A comprehensive review of recent findings 2012 Jul 1 Paul Ehrlich, a German scientist, discovered what is known as the mast cell in the late 1800's, which has proven to be an important player in the immune system of vertebrates. Mast cells are ubiquitous throughout the tissues of the human body and play numerous roles, both beneficial and destructive. We know they are important in our army of immunity warrior cells, which defend us against viruses, bacteria and parasitic invaders. They are also very well known for the havoc they wreak, causing uncomfortable symptoms due to their release of histamine and other mediators which cause the all too familiar itching, sneezing, urticaria and rhinorrhea of allergic responses. Mast cell activities are diverse and include painful inflammatory reactions in autoimmune conditions such as rheumatoid arthritis. In the gastrointestinal system, mast cells are implicated in diverse actions such as increased gastric acid secretion, polyp formation and uncomfortable conditions such as Irritable Bowel Syndrome. The role of immunology and mast cells in these areas is intriguing but less well understood than their role in allergic responses. Because mast cells have been implicated in both physiologic as well as pathogenic processes, they have been the subjects of avid study. Review of the current literature on mast cell biology reveals that there are many studies of their presence within the tumor microenvironment and evidence, which supports mast cell influence on tumor angiogenesis, tumor invasion, and immune suppression. The studies reviewed in this article concentrate largely on mast cells in human GI malignancies. This review also provides background information regarding mast cells, such as their origination, their location within the body, how they are activated and how they function as mediators.
22897386 A review on advanced atrioventricular block in young or middle-aged adults. 2012 Nov Complete atrioventricular block is a relatively uncommon arrhythmia that is nonetheless increasingly seen in elderly people of developed countries, due to the increase in life expectancy. Congenital and degenerative etiologies are the most commonly seen among young and old patients, respectively. However, scientific literature is surprisingly scarce regarding the etiology of complete atrioventricular block in the asymptomatic otherwise healthy young and middle-aged adult population. Coronary artery disease, autoimmune disorders such as systemic lupus erythematosus or rheumatoid arthritis, history of acute or chronic infectious or hypersensitivity myocarditis, infiltrative processes, hypothyroidism, congenital cardiopathies such as left ventricular noncompaction or Ebstein anomaly, lamin A/C mutations, and pathologic hypervagotony and idiopathic degenerative scleroatrophy of the atrioventricular junctional specialized tissue (Lenegre-Lev disease) are among the most frequent etiologies of complete atrioventricular block in young or middle-aged adults. To our knowledge, no comprehensive review on the specificities of the investigation warranted in this age group has ever been developed, nor have the implications of particular diagnoses on treatment modalities been appropriately addressed. We aim at reviewing the most frequent differential diagnoses of advanced atrioventricular block in otherwise healthy asymptomatic or mildly symptomatic young or middle-aged adults and their impact on therapeutic options. Additionally, we suggest a diagnostic algorithm that may be helpful in this group of patients.
22750507 An overview of the chemistry and biology of reactive aldehydes. 2013 Jun The nonenzymatic free radical generation of reactive aldehydes is known to contribute to diseases of sustained oxidative stress including rheumatoid arthritis, atherosclerosis, neurodegeneration, and a number of liver diseases. At the same time, the accumulation of lipid electrophiles has been demonstrated to play a role in cell signaling events through modification of proteins critical for cellular homeostasis. Given the broad scope of reactivity profiles and the ability to modify numerous proteomic and genomic processes, new emphasis is being placed on a systems-based analysis of the consequences of electrophilic adduction. This review focuses on the generation and chemical reactivity of lipid-derived aldehydes with a special focus on the homeostatic responses to electrophilic stress.
22711924 Visceral leishmaniasis mimicking autoimmune hepatitis, primary biliary cirrhosis, and syst 2012 Jun Visceral leishmaniasis (VL) is a life-threatening infection caused by Leishmania species. In addition to typical clinical findings as fever, hepatosplenomegaly, and cachexia, VL is associated with autoimmune phenomena. To date, VL mimicking or exacerbating various autoimmune diseases have been described, including systemic lupus erythematosus (SLE), rheumatoid arthritis, and autoimmune hepatitis (AIH). Herein, we presented a patient with VL who had overlapping clinical features with SLE, AIH, as well as antimitochondrial antibody (AMA-M2) positive primary biliary cirrhosis.
22642304 Improving solubility and pharmacokinetics of meloxicam via multiple-component crystal form 2012 Jul 2 Meloxicam is a nonsteroidal anti-inflammatory drug prescribed for rheumatoid arthritis, osteoarthritis, postoperative pain and fever. Meloxicam exhibits low solubility in acidic aqueous media and a slow onset of action in biological subjects. An oral dosage form of meloxicam with enhanced aqueous solubility is desired to enable a faster onset of action and its use for mild-to-medium-level acute pain relief. With this in mind, we examine the solubility and pharmacokinetics of 12 meloxicam cocrystals with carboxylic acids. Dissolution studies of meloxicam and its cocrystals were performed in pH 6.5 phosphate buffer solutions at 37 °C. In addition, pharmacokinetic profiles over four hours were acquired after oral administration of a 10 mg/kg (meloxicam equivalent) solid suspension in rats. The majority of meloxicam cocrystals were found to achieve higher meloxicam concentrations in dissolution media and enhanced oral absorption compared to that of pure meloxicam. All meloxicam cocrystals were converted to meloxicam form I when the slurry reached equilibrium. To better understand how cocrystallization impacts the absorption of meloxicam after oral administration, correlations between the in vitro and in vivo data were explored. The results suggest that the meloxicam cocrystals with a faster dissolution rate would exhibit increased oral absorption and an earlier onset of action.
22449935 Nanomedicines for inflammatory diseases. 2012 Inflammation is the body's natural defense mechanism in response to many diseases including infection, cancer, and autoimmune disease. Since the birth of nanotechnology at the end of the twentieth century, scientists have been utilizing the pathophysiologic features of inflammation, mainly leaky vasculature and the overexpression of biomarkers, to design nanomedicines that can deliver drugs with passive and active targeting mechanisms to inflamed tissue sites and achieve effective therapy. Recent advances in nanomedicine research have provided scientists with nanocarriers of many unique and tunable properties to match the specific requirements for the treatment of different inflammatory disease conditions. In this chapter, we describe some of the materials and methods used in the preparation and characterization of these nanomedicines, approaches used for the evaluation of their efficacy on a cellular and organ level, as well as available animal models. We also show how safety and biodistribution studies using anti-inflammatory nanomedicines are conducted in our laboratory for the treatment of rheumatoid arthritis animal models.
22430652 Cardiopulmonary arrest following cervical epidural injection. 2012 Mar Epidural steroid injection is a common treatment for the management of pain in a wide variety of patients. It is generally well tolerated and perceived to have few side effects, with a low risk of serious complications. Only a handful of reports exist that describe life-threatening complications such as subdural hematoma, respiratory depression, vasovagal response, and pneumocephalus. This is a case report of a 67-year-old woman with a relatively unremarkable past medical history, other than rheumatoid arthritis, osteoarthritis, and hypertension, who suffered from chronic neck pain treated with cervical epidural steroid injection at the C6-C7 level. She went into immediate cardiopulmonary arrest following the injection. She was brought to the emergency department by ambulance and resuscitated, and was found to have pneumocephalus. Ultimately, she made a relatively full recovery over the following weeks. Cardiopulmonary arrest is a rare but potentially deadly side effect of epidural steroid injection. To the best of our knowledge, this is the first report of such an arrest following a steroid injection in the cervical spinal region. There are several possible mechanisms for the immediate arrest, including cardioacceleratory center blockade, severe vasovagal response, iatrogenic pneumocephalus, and involvement of the phrenic nerve followed by apnea. Our conclusion in this case is that the most likely scenario was injection of the C6-C7 level led to a blockade of the cardiac accelerator fibers located just below in the T1-T4 spinal level, causing a sympathetic blockade and profound bradycardia, leading to cardiopulmonary arrest.
22365757 Molecular modeling study of cyclic pentapeptide CXCR4 antagonists: new insight into CXCR4- 2012 Mar 15 CXCR4 is a G-protein coupled receptor that is associated with many diseases such as breast cancer metastasis, HIV infection, leukemic disease and rheumatoid arthritis, and is thus considered an attractive drug target. Previously, we identified a cyclic pentapeptide, FC131, that is a potent antagonist for CXCR4. In this study, we constructed a three dimensional model of the CXCR4-FC131 complex. To investigate the backbone flexibility of FC131, we performed molecular dynamics simulations of FC131 based on the NMR structure of FC131, and obtained snapshot structures from the trajectories which were used to model the docking pose of FC131 into CXCR4. Our final model of the CXCR4-FC131 complex is partially different from the X-ray crystal structure of CXCR4-CVX15 and suggests water-mediated interactions. Nevertheless, this docking pose is consistent with the experimental data. We believe our model will aid in the discovery and development of small-molecule antagonists for CXCR4.
22204900 Sex differences and genomics in autoimmune diseases. 2012 May Autoimmune diseases (AIDs) are believed to be multifactorial diseases that commonly involve multiple organ systems. About three fourth of the patients afflicted with AIDs are women suggesting that sex differences impact the incidence of AID. However, the proportion of females to males suffering from AID varies depending on the disease. The response to some AID therapeutics also differs in females versus males, suggesting that enrollment of adequate numbers of women and men is important in clinical trials for development of AID drugs. It is known for a long time that genetic factors are important contributors to AID susceptibility. Currently available information suggests that multiple genes with modest association to AID contribute to susceptibility to AID. Also, the associations may differ for the various ethnicities. The major histocompatibility (MHC) locus appears to be a major genetic factor that confers susceptibility to multiple AIDs, even though the locus is complex and has the highest density of genes in the human genome. Thus, the association of different AIDs could be with different genes in the MHC locus. Among the non-MHC genes, some of the risk alleles are shared between different AIDs, but may not be common to all AIDs. For example, genetic polymorphisms in the Protein Tyrosine Phosphatase-22 (PTPN22) gene have reproducibly shown to have association with systemic lupus erythematosus (SLE), Graves' disease (GD), rheumatoid arthritis (RA) and multiple sclerosis (MS), but not with psoriasis. Identification of factors responsible for risk for developing AID and the of the pathways underlying these diseases are likely to help understand subsets of disease, identify responders to a specific treatment and develop better therapeutics for AID.
22172712 Sex differences in spontaneous versus induced animal models of autoimmunity. 2012 May There is a supposed link between autoimmune diseases and sex hormones. To better understand the pathogenesis of human autoimmune diseases, an animal model is a good tool that can also help in developing novel therapeutics for diseases. Animal models of diseases can be divided into naturally occurring or induced by physical, chemical, or biological factors. Most human autoimmune diseases like systemic lupus erythematosus (SLE), Sjogren's syndrome (SS), primary biliary cirrhosis (PBC), Hashimoto's thyroiditis (HT), rheumatoid arthritis (RA), and multiple sclerosis (MS) have increased incidence and prevalence in females, but so far, sex differences and hormone therapy in spontaneous or chemical induced animal models of autoimmunity are not entirely clear. Possible reasons for the differing incidence and prevalence of autoimmune diseases in human and animal models is the focus of interest. This review described the known effects of the female sex hormones, estrogen and progesterone, on immune cells in order to clarify sex differences in autoimmune diseases. Data from both human and autoimmune animal studies were reviewed to determine reasons for these differences, and to integrate the role of sex differences and hormone therapy in spontaneous- versus chemical-induced animal models of human autoimmune diseases to clarify sex differences in autoimmunity.
22068796 Refractory erythrodermic psoriasis in a child with an excellent outcome by using etanercep 2011 Jul Psoriasis affects 0.12% to 0.71% of all children. Erythrodermic psoriasis is an uncommon but serious disorder, occurring in less than 1.5% of cases. Tumor necrosis factor-alpha blockers (TNF-α) are a new class of drugs used to treat moderate to severe psoriasis refractory to conventional therapies. Etanercept is a TNFα receptor fusion protein, approved by the FDA for treating juvenile rheumatoid arthritis. We present the case of a 7-year-old suffering from plaque psoriasis since 8 months old which evolved into erythroderma refractory to cyclosporine and methotrexate. Patient responded excellently to etanercept, with no adverse side effects.
22036611 Quantitative analysis predicts the relative therapeutic efficacy of different forms of CTL 2011 Dec Modulating the activities of costimulatory molecules controlling immune responses holds considerable promise for immunotherapy. CTLA4Ig (abatacept), a soluble version of the T cell-expressed membrane receptor CTLA-4, is approved for the treatment of rheumatoid arthritis. Like natural CTLA-4 molecules, CTLA4Ig ligates B7-1 and B7-2 on antigen presenting cells, preventing CD28-mediated costimulation of T cells. However, CTLA4Ig can also prevent ligation of CTLA-4, potentially blocking vital inhibitory signals, thereby augmenting immunity. There have been no quantitative analyses of the likely effects of CTLA4Ig on costimulatory interactions at the immunological synapse. We present a mathematical model, based on rigorous biophysical and expression data, for simulating the effects of abatacept and a mutated derivative, LEA29Y, on the synaptic interactions of CD28 and CTLA-4. The simulations reveal an unexpectedly large window within which CD28, but not CTLA-4, ligation is blocked by CTLA4Ig, perhaps explaining the efficacy of abatacept at the recommended therapeutic dose (10mg/kg) and its relative safety. However, the simulations suggest that the present dosing regimen is close to the maximum theoretically safe dose. The simulations also show that, within the therapeutic window, LEA29Y enhances the interaction of CTLA-4 with the more potent of its two native ligands, B7-1. They also suggest that CTLA-4 ligation by B7-1 could, in principle, be enhanced by further decreasing the off-rate of CTLA4Ig for binding to B7-2. Our findings therefore offer molecular explanations for why LEA29Y might prove to be more effective than abatacept in a clinical setting, and suggest ways in which its therapeutic efficacy could be further optimised.
22021700 Serotonergic descending inhibition in chronic pain: design, preliminary results and early 2011 Nov AIM: We examined whether activation of serotonergic descending pathways improves pain inhibition during exercise in patients with chronic fatigue syndrome (CFS) and comorbid fibromyalgia (FM) in comparison with rheumatoid arthritis (RA) and sedentary, healthy controls in a double-blind randomized controlled trial with cross-over design. PATIENTS AND METHODS: Three female CFS/FM patients, one female RA patient and two healthy women were randomly allocated to the experimental group (2 ml of citalopram intravenously) or the placebo group (2 ml of 0.9% NaCl intravenously). Participants performed a submaximal exercise protocol, preceded and followed by an assessment of endogenous pain inhibition. Seven days later, groups were crossed over. RESULTS: Significant side-effects were observed in all, but one participant immediately after intravenous administration of citalopram. One CFS/FM patient withdrew because of severe post-exertional malaise. CONCLUSION: It was decided that proceeding with the study would be unethical. No conclusion could be made regarding pain inhibition during exercise in CFS/FM compared to RA and controls.