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ID PMID Title PublicationDate abstract
24347992 Corticosteroid-related central nervous system side effects. 2013 Dec Corticosteroids have been used since the 50s as anti-inflammatory and immunosuppressive drugs for the treatment of several pathologies such as asthma, allergy, rheumatoid arthritis, and dermatological disorders. Corticosteroids have three principal mechanisms of action: 1) inhibit the synthesis of inflammatory proteins blocking NF-kB, 2) induce the expression of anti-inflammatory proteins by IkB and MAPK phosphatase I, and 3) inhibit 5-lipoxygenase and cyclooxygenase-2. The efficacy of glucocorticoids in alleviating inflammatory disorders results from the pleiotropic effects of the glucocorticoid receptors on multiple signaling pathways. However, they have adverse effects: Growth retardation in children, immunosuppression, hypertension, hyperglycemia, inhibition of wound repair, osteoporosis, metabolic disturbances, glaucoma, and cataracts. Less is known about psychiatric or side effects on central nervous system, as catatonia, decreased concentration, agitation, insomnia, and abnormal behaviors, which are also often underestimated in clinical practice. The aim of this review is to highlight the correlation between the administration of corticosteroids and CNS adverse effects, giving a useful guide for prescribers including a more careful assessment of risk factors and encourage the use of safer doses of this class of drugs.
23871515 AMPK: mediating the metabolic effects of salicylate-based drugs? 2013 Oct Salicylates are among the oldest medicinal compounds known to humans, and have been used to reduce fever, pain, and inflammation. The major oral salicylates are aspirin and salsalate, both of which are rapidly metabolized to salicylate in vivo. Owing to its acetyl group, aspirin irreversibly inhibits cyclo-oxygenases and thus blocks platelet aggregation, whereas salsalate has been used for treatment of inflammatory diseases such as rheumatoid arthritis. Recently, beneficial effects of salicylates in type 2 diabetes and cancer have been proposed. This has led to renewed interest in understanding how these simple molecules have such diverse and multifaceted effects. Here we discuss the idea that AMP-activated protein kinase (AMPK) might mediate some effects of salicylate-based drugs, particularly by modulating cellular metabolism.
23861028 Overexpression of methyl-CpG-binding protein 2 and autoimmunity: evidence from MECP2 dupli 2013 Aug Methyl-CpG-binding protein 2 (MeCP2) is a key transcriptional regulator that can induce either silencing or activation of target genes. Genetic polymorphisms in the MECP2/IRAK1 locus have been associated with increased susceptibility to multiple autoimmune diseases such as lupus, primary Sjogren's syndrome, and more recently rheumatoid arthritis. Data from our group suggest that the disease risk variant in this locus is associated with gain of MeCP2 function. Recent findings indicate that MECP2 duplication in human results in defective T helper cell type 1 (T(H)1) response and IFN-γ production. Herein, we discuss the data from children with MECP2 duplication, human lupus, and from the human MECP2 transgenic and Mecp2 deficient mice to support a link between MECP2 overexpression and autoimmunity. We also provide findings from an Mecp2 deficient mouse that independently support a role for MeCP2 in the immune response and specifically in IFN-γ expression.
23832439 [An innovative approach to the treatment of immune-mediated glomerular diseases]. 2013 Jan Conventional treatment of most glomerular immune-mediated diseases is based mainly on the use of cytotoxic immunosuppressants and corticosteroids. Although this has resulted in improved survival, patients may suffer severe, sometimes life-threatening, adverse events. The increasing need for safer and more effective drugs along with burgeoning new insights into the pathogenesis of these disorders has aroused interest in a variety of biological agents. In this context, clinical trials involving the B-cell depletion agent Rituximab have been especially promising. Rituximab is a monoclonal antibody to the CD20 antigen on B-cells that was initially designed and approved for the treatment of non-Hodgkins B-cell lymphoma in 1997. Over the last 15 years, it has emerged as a potent immunosuppressant for several immune-mediated diseases, initially for the treatment of rheumatoid arthritis , with FDA approval in 2007. Subsequently its use has been extended into several other fields, including the treatment of glomerulonephritis. Recently (April 2011), the FDA approved Rituximab for the treatment of ANCA-associated vasculitis. However, given its efficacy, tolerability and safety profile in comparison to conventional treatment regimens, it has been also studied in off-label use for many other glomerular diseases, including membranous nephropathy, lupus nephritis, and mixed cryoglobulinemia.
23797763 [Cuff tear arthropathy – long-term results of reverse total shoulder arthroplasty]. 2013 Jul The results after reverse total shoulder arthroplasty for cuff tear arthropathy are superior and the complications fewer than for other etiologies, such as rheumatoid arthritis, fracture, fracture sequelae or even revision. The improvements in function and pain are excellent whereas rotation may be unaffected. Revisions and complications can be encountered in the first 3 years and the survival curve of the prosthesis is still good after 10 years with 90%. Progressive functional and radiological deterioration is observed after 9 years in approximately 30% of the patients without apparent problems with the prosthesis. Notching is progressive with incidence and size over time, without a proven correlation to the functional results but remains a major concern. Modification of the implants, the operative techniques and experience could significantly improve the results and reduce the rate of complications. Lateralization of the center of rotation and smaller inclination angles have a positive effect on the rate of notching and the range of motion, especially for the rotation. New prosthetic designs and operative techniques attempt to implement a combination of the biomechanical improvements. Reverse shoulder arthroplasty remains a challenging operation with a high rate of complications. The results depend on the etiology and the function of the remaining muscles and therefore on the experience and the skill of the surgeon to implement the appropriate biomechanical factors. Because of the concerns regarding the longevity, reverse shoulder arthroplasty should be reserved for the elderly over 70 years of age.
23740459 Vernal keratoconjunctivitis: atopy and autoimmunity. 2013 May BACKGROUND: Vernal Keratoconjunctivitis (VKC) is a rare chronic ocular inflammatory disease and it mainly affects boys in the first decade of life. Although it is a self-limiting disease, patients may present many phases characterized by an exacerbation of inflammatory symptoms with a consequent decline of the quality of life. PURPOSE: define the clinical and immunological profile of patients affected by VKC and investigate their familiar history of autoimmune disorders and their autoimmunity pattern. PATIENTS AND METHODS: 28 children were enrolled (20 males, 71%) aged between 4 and 14 years of life affected by VKC. Family history of allergic and immunological diseases was collected for each patient. In particular, it was asked whether some components of their families were affected by Hashimoto's thyroiditis, type I diabetes, psoriasis or rheumatoid arthritis and Systemic Lupus Erythematosus (SLE). All VKC children underwent a serological evaluation of anti-nuclear antibodies (ANA). RESULTS: A family history of immunological disorders was found in 46% of patients, 28% of Hashimoto's thyroiditis, 14% of type I diabetes, 14% of psoriasis, and 1 of Systemic Lupus Erythematosus. Furthermore, 35% of patients was ANA positive and they corresponded to patients with a higher ocular score and with the most important clinical symptoms. CONCLUSIONS: the detection of ANA positivity and of a familiar history of autoimmune disorders in a high percentage of children with VKC may help us to better understand the association of this ocular inflammatory disease with systemic autoimmune disorders and atopic condition.
23629578 Cardiovascular effects of common analgesics. 2013 Apr The clycoxygenase (COX) enzyme forms locally active prostaglandins responsible for producing inflammation and pain. Classical non-steroidal anti-inflammatory drugs (NSAID) inhibit the COX-2 enzyme that produces inflammatory prostaglandins as well as the COX-1 enzyme that produces gastric mucosa protecting prostaglandins. By specifically inhibiting only the COX-2 enzyme, coxibs thus reduce pain but do not damage the gastric mucosa. However, COX-2 at the vascular endothelium produces antithrombotic prostaglandins, and so by inhibiting COX-2 enzyme, the coxibs promote thrombosis. Rofecoxib and valdecoxib have been withdrawn because of the adverse cardiovascular events they induce. Amongst presently available coxibs cardiovascular risk is highest with enterocoxib and lowest with celecoxib. NSAIDS also increase cardiovascular events, the risk is highest with diclofenac and lowest with naproxen. Paracetamol and corticosteroids induce hypertension, while steroids also adversely affect the heart from metabolic change as well as fluid retention. Aspirin is an anti-thrombotic agent because of its ability to inhibit the COX-1 enzyme that produces the pro-aggregatory thromboxane. However, it increases gastrointestinal bleeding, can promote fluid retention and is nephrotoxic, all of which may lead to adverse cardiovascular outcomes. Patients at especially high risk of cardiovascular events from analgesic use include the elderly, and those with heart failure, hypertension, rheumatoid arthritis, chronic renal disease, chronic obstructive airway disease and previous myocardial infarction, cerebrovascular disease or peripheral vascular disease. Adverse cardiovascular events can occur within a week of initiation of analgesic treatment.
23601421 The role of ghrelin in anorexia-cachexia syndromes. 2013 Anorexia, sarcopenia, and cachexia are common complications of many chronic conditions including cancer, rheumatoid arthritis, HIV infection, aging, and chronic lung, heart, or kidney disease. Currently, there is no effective treatment for muscle atrophy or wasting conditions although they typically take a significant toll on the quality of life of patients and are associated with poor prognosis and decreased survival. Ghrelin affects multiple key pathways in the regulation of body weight, body composition, and appetite in the setting of cachexia that may lead to an increase in appetite and growth hormone secretion and a reduction in energy expenditure and inflammation. The net effect is increased lean body mass and fat mass preservation. In this chapter, we review the mechanisms of action of ghrelin and present the available data in animal models and human trials using ghrelin or ghrelin mimetics in different settings of cachexia.
23472773 Quality-of-life, health service use, and costs associated with syncope. 2013 Jan Syncope is a prevalent condition that is associated with high morbidity, health service use, and costs. Syncope negatively impacts multiple domains of quality-of-life, including physical health, mental health, and functional status. The morbidity associated with recurrent syncope is equivalent to chronic conditions such as severe rheumatoid arthritis and low back pain. Frequency of syncope events is related to worse morbidity, suggesting that effective diagnosis and management can improve quality-of-life. There is a high incidence of health service use associated with syncope, including 740,000 annual emergency department visits and 460,000 hospital admissions in the United States. Rates of admission and inpatient diagnostic testing are characterized by high variance and low clinical utility. Finally, the evaluation of syncope is associated with high costs. Hospital costs associated with the inpatient evaluation of syncope exceed $2.4 billion per year in the United States. Improved diagnostic and treatment algorithms are urgently needed to improve patient quality-of-life, reduce health service use, and lower costs related to the evaluation of syncope.
23322270 The role of IL-6 in bone marrow (BM)-derived mesenchymal stem cells (MSCs) proliferation a 2013 Dec Rheumatoid arthritis (RA) is the most common degenerative arthritic cartilage and represents a disease where the prospect of stem cell therapy offers considerable hope. Currently, bone marrow (BM) represents the major source of mesenchymal stem cells (MSCs) for cell therapy. In the pathology of RA, the pro-inflammatory cytokines, such as interleukin 6 (IL-6) play a pivotal role. To investigate the direct role of IL-6 in the chondrogenic differentiation of murine MSCs (mMSCs), we isolate MSCs from the murine bone marrow, and induce MSCs chondrogenesis with different concentrations of IL-6 in vitro. Through detecting the histological and histochemical qualities of the aggregates, we demonstrate that IL-6 inhibited the differentiation of MSCs into chondrocytes in the dose-dependence manner. These findings suggest that possible strategies for improving the clinical outcome of cartilage repair procedures.
25034081 Safety and efficacy of etanercept in children with the JIA categories extended oligoarthri 2015 Jan The approval of etanercept for the treatment of the juvenile idiopathic arthritis (JIA) categories extended oligoarthritis (ExtOA), enthesitis-related arthritis (ERA) and psoriasis arthritis (PsA) was recently added to the approval for the treatment of polyarticular-course JIA (PA). This study aims to evaluate the efficacy and safety of etanercept in a large number of patients with the additional JIA categories. The Biologika in der Kinderrheumatologie (BIKER) registry documents baseline demographics, clinical characteristics and disease activity parameters. Efficacy was determined using the PedACR 30/50/70 response criteria and the Juvenile Arthritis Disease Activity Score (JADAS)-10. Safety assessments were based on adverse events' reports. Until December 2012, a total of 1,678 JIA patients, incorporating 238 ERA, 315 ExtOA and 127 PsA patients were included. JADAS-10 demonstrated marked improvement compared to baseline after 3 to 24 months in ExtOA [16.1 ± 7.6 (baseline), 5.1 ± 5.2 (3 months), 3.0 ± 3.5 (24 months)]; ERA (15.3 ± 7.2, 4.4 ± 4.7, 4.0 ± 4.9) and PsA (14.7 ± 6.4, 5.0 ± 4.6, 5.3 ± 6.4). Compared to patients with PA, the rate of serious adverse events [relative risk (RR) 1.39 (0.95-2.03, p = 0.08)] and nonserious [1.18 (1.02-1.35; p = 0.03)] adverse events were elevated. The rate of uveitis flares was significantly higher in PsA (3.3/100 patient-years), ExtOA (2.8/100 patient-years) and ERA (2.7/100 patient-years) than in rheumatoid factor (RF)-negative polyarticular JIA (1.3/100 pat.yrs) or RF-positive polyarticular JIA (0.27/100 patient-years). Reports on chronic inflammatory bowel disease were numerically more frequent in ExtOA, ERA and PsA. Administration of etanercept in patients with the JIA categories ExtOA, ERA and PsA is safe and very efficacious in children. Attention should be paid to the occurrence of extraarticular autoimmunopathies.
25646037 Free radicals: properties, sources, targets, and their implication in various diseases. 2015 Jan Free radicals and other oxidants have gained importance in the field of biology due to their central role in various physiological conditions as well as their implication in a diverse range of diseases. The free radicals, both the reactive oxygen species (ROS) and reactive nitrogen species (RNS), are derived from both endogenous sources (mitochondria, peroxisomes, endoplasmic reticulum, phagocytic cells etc.) and exogenous sources (pollution, alcohol, tobacco smoke, heavy metals, transition metals, industrial solvents, pesticides, certain drugs like halothane, paracetamol, and radiation). Free radicals can adversely affect various important classes of biological molecules such as nucleic acids, lipids, and proteins, thereby altering the normal redox status leading to increased oxidative stress. The free radicals induced oxidative stress has been reported to be involved in several diseased conditions such as diabetes mellitus, neurodegenerative disorders (Parkinson's disease-PD, Alzheimer's disease-AD and Multiple sclerosis-MS), cardiovascular diseases (atherosclerosis and hypertension), respiratory diseases (asthma), cataract development, rheumatoid arthritis and in various cancers (colorectal, prostate, breast, lung, bladder cancers). This review deals with chemistry, formation and sources, and molecular targets of free radicals and it provides a brief overview on the pathogenesis of various diseased conditions caused by ROS/RNS.
25051624 HPTLC method for simultaneous determination of piperine, embeline, and carvone in the ayur 2014 May Churnas are an important group of formulations used by traditional physicians to treat various types of diseases. The principle of using a churna is based on the fact that the therapeutic value of most substances greatly increases when they are reduced to a very fine state of subdivision. Catpusphadhya churna, as per the Ayurvedic system of Indian medicine, is used for acute rheumatoid arthritis. In the present study, an attempt was made to develop an HPTLC method for the quantitative determination of piperine, embeline, and carvone in a laboratory-prepared formulation. Raw materials used in formulations were obtained from two different suppliers and were subjected to methanol extractions by using a Soxhlet apparatus. Piperine, embeline, and carvone were quantified in the extracts by using HPTLC. The detection and quantification were performed at 254 nm. The formulation contained 2.35% (w/w) of piperine, 4.86% (w/w) of embeline, and 1.48% (v/w) of carvone. Linearity studies indicated that piperine, embeline, and carvone were in the linear ranges, while the recovery studies revealed a recovery of 99.32% (w/w) of piperine, 101.82% (w/w) of embeline, and 100.09% (v/w) of carvone, thus proving the accuracy of the analysis. The developed HPTLC method resolved and quantified piperine, embeline, and carvone effectively, so it could be an important method for the QC of polyherbal formulations.
25032080 Spontaneous flexor tendon rupture due to atraumatic chronic carpal instability. 2014 May Background Spontaneous flexor tendon rupture is considered to be invariably associated with previous hand/wrist injury or systemic disease such as rheumatoid arthritis. Case Description A 54-year-old man presented with a 4-month history of mild ulnar wrist pain and spontaneous left little finger flexion loss in the absence of distant/recent trauma and systemic arthropathy. Surgical exploration confirmed a zone IV left little finger flexor digitorum profundus (FDP5) attritional rupture (100%), ring finger flexor digitorum profundus (FDP4) attenuation (40%) and a disrupted lunotriquetral ligament and volar-ulnar wrist capsule. Volar subluxation of the narrowed carpal tunnel resulted in flexor tendon attrition against the hamate hook. A side-to-side tendon transfer was performed along with a lunotriquetral ligament repair and temporary Kirschner wire fixation. At 6 months the patient had full active, synchronous flexion of the ring and little fingers and reduced wrist pain. Literature Review Traumatic flexor tendon ruptures have been reported following distal radius/hamate hook fractures, from carpal bone osteophytes, accessory carpal bones and intraosseous ganglia. Attritional ruptures caused by chronic, degenerative carpal pathology are less common. Clinical Relevance This case highlights an unusual cause of flexor tendon rupture due to chronic carpal instability.
24944829 Review on Effectiveness of Primary Prophylaxis in aPLs with and without Risk Factors for T 2014 Context. Antiphospholipid antibodies syndrome is an autoimmune disorder that is characterized by the association between presence of antiphospholipid antibodies and risk of thrombosis and/or pregnancy morbidity. Objectives. To systematically review the evidence for primary prophylaxis in patients with antiphospholipids antibodies syndrome or APS with or without other traditional risk factors of thrombosis when they did not have any thrombotic event yet. Methods. PubMed, the Cochrane Library, and Allied Health Literature were searched for studies that examined the efficacy and safety of primary prophylaxis in aPL patients from 1990 to February 2013. We examined literature looking at patients with aPLs with other risk factors for thrombosis and aPLs with no additional risk factors for thrombosis. Conclusion. We concluded that, in patients with aPLs, primary prophylaxes with HCQ and aspirin have been observed to reduce the frequency of thrombotic events in the case of asymptomatic aPL-positive patients with SLE. We also in this study concluded that LDA was effective in patients with autoimmune diseases. Independent cardiovascular risk factors include autoimmune defects such as SLE, rheumatoid arthritis, and atherosclerosis, where overall venous thrombosis will be induced by systemic inflammation. This review concludes that HCQ is an effective primary approach when compared to aspirin.
24718937 HMGB1 in hormone-related cancer: a potential therapeutic target. 2014 Jun High-mobility group box 1 (HMGB1) is a dynamic nuclear protein participating in transcription, chromatin remodelling, and DNA recombination and repair processes. Accumulating evidence indicates that its function now extends beyond the nucleus, notably its extracellular role in inflammation. HMGB1 is implicated as a late mediator of sepsis and is also believed to promote atherosclerosis and other inflammatory diseases such as rheumatoid arthritis and systemic lupus erythematosus. Interestingly, deregulation of HMGB1 is shown to be associated with the hallmarks of cancer development. Moreover, several clinical studies have shown that HMGB1 is a promising biomarker for a variety of cancer types. In this review, we provide novel insights into the role and mechanisms of HMGB1, in particular, to hormone-related cancers and its potential to serve as a therapeutic target.
24198985 Paraneoplastic autoimmunity associated with testicular myeloid sarcoma and chronic myelomo 2013 Myeloid sarcomas are rare extramedullary solid tumors composed of immature myeloid cells. The clinical presentations of these malignant neoplasms are highly variable, ranging from asymptomatic to localized mass effect. Here, we report an unusual case of myeloid sarcoma of the testis found in association with chronic myelomonocytic leukemia where the presenting symptoms were autoimmune pericarditis and migratory arthralgias and myalgias that preceded testicular enlargement by nearly three months. Treatment with both radical orchiectomy and leukemia-directed chemotherapy led to immediate reductions in symptom severity, suggesting that these early symptoms were paraneoplastic in origin. Review of the literature identified the association between hematological malignancies, including chronic myelomonocytic leukemia, and paraneoplastic autoimmune phenomena with features similar to polymyalgia rheumatica and rheumatoid arthritis. Importantly, rheumatologic symptoms related to these disease entities may be easily dismissed as vague or unrelated complaints or treated as purely rheumatologic conditions, thus delaying the formal diagnoses. Clinicians must recognize the common association between possible paraneoplastic rheumatologic symptoms and hematologic malignancies such as chronic myelomonocytic leukemia.
24171271 Novel and emerging therapies safeguarding health of humans and their companion animals: a 2013 Feb 1 Modern medicine has helped to a great extent to eradicate and cure several diseases of mankind and animals. But the existence of incurable diseases like cancer, Acquired Immunodeficiency Syndrome (AIDS), diabetes or rheumatoid arthritis, side effects of allopathic medicine, increasing trend of antibiotic resistance and chemicals and biopesticides causing dietary risk have made the situation more critical than ever before. Thus, it has become a matter of concern for the scientists and researchers to develop novel therapies. Bacteriophage therapy to treat pathogenic bacterial infections, virophage therapy for conservation of global system and avian egg yolk antibody therapy for designing prophylactic strategies against Gastrointestinal (GI) diseases are interesting approaches. Others include the use of cytokines as adjunctive immunomodulators, gene therapy focusing on diseases caused by single gene defects, RNAi technology to suppress specific gene of interest and apoptins for cancer treatment. Stem cell therapy against several diseases and ailments has also been discussed. The use of nanoparticles for better drug delivery, even though costly, has been given equal importance. Nevertheless, immunomodulation, be it through physiological, chemical or microbial products, or through essential micronutrients, probiotics, herbs or cow therapy prove to be cost-effective, causing minimum adverse reactions when compared to allopathy. Development in the field of molecular biology has created an enormous impact on vaccine development. The present review deals with all these novel and emerging therapies essential to safeguard the health of humans and companion animals.
25500868 ROR nuclear receptors: structures, related diseases, and drug discovery. 2015 Jan Nuclear receptors (NRs) are ligand-regulated transcription factors that regulate metabolism, development and immunity. The NR superfamily is one of the major classes of drug targets for human diseases. Retinoic acid receptor-related orphan receptor (ROR) α, β and γ belong to the NR superfamily, and these receptors are still considered as 'orphan' receptors because the identification of their endogenous ligands has been controversial. Recent studies have demonstrated that these receptors are regulated by synthetic ligands, thus emerge as important drug targets for the treatment of multiple sclerosis, rheumatoid arthritis, psoriasis, etc. Studying the structural basis and ligand development of RORs will pave the way for a better understanding of the roles of these receptors in human diseases. Here, we review the structural basis, disease relevance, strategies for ligand identification, and current status of development of therapeutic ligands for RORs.
24045522 [Investigation on a group of autistic children: risk factors and medical social considerat 2013 AIMS: The aim of this work is to study the association between autism in a group of autistic children and risk factors for specific familiar diseases and developmental disease in the early years of life, through a medical social investigation. MATERIALS AND METHODS: For this study, we have submitted an anamnestic questionnaire to 29 autistic children and their families in a South Italy region (Basilicata), collecting data about children and their parents. RESULTS: The results show that many children have a family history of autoimmune diseases (psoriasis, rheumatoid arthritis, celiac disease, Takayasu's arteritis), allergies and food intolerances, suggesting a putative involvement of the immune system in autism etiopathogenesis. Analyzing residences areas of patients, Potenza and Matera, with their environmental factors (radioactive waste repositories, incinerators, intensive farming), we demonstrate that the particular territorial characteristics don't affect autism. CONCLUSIONS: Autistic disorder is a spectrum of neurologic disorders complex both in etiopathogenesis and healthcare. So we aim to continue the study already undertaken on cytokines of autistic subjects serum and to extend it through biomolecular approaches assessing the presence of specific genetic polymorphisms in order to identify the physiopathogenetic mechanisms underlying the disease and to evaluate the predictive risk with the aim to improve care interventions.