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ID PMID Title PublicationDate abstract
25354676 Myasthenia gravis and risks for comorbidity. 2015 Jan Myasthenia gravis (MG) is an autoimmune disorder leading to skeletal muscle weakness and fatigability. MG subgroups are defined according to pathogenetic autoantibody (against acetylcholine receptor, muscle-specific tyrosine kinase or lipoprotein receptor-related protein 4), thymus pathology and clinical manifestations. MG patients have an increased risk for concordant autoimmune disease, in particular with early onset MG. Most common comorbidities are thyroid disease, systemic lupus erythematosus and rheumatoid arthritis. Cardiomyositis and subclinical heart dysfunction have been described in patients with thymoma MG and late onset MG but represent no major threat. A thymic lymphoepithelioma implies an increased risk for another cancer. Autoimmune MG represents no distinct cancer risk factor, although lymphomas and a few other cancer types have been reported with slightly increased frequency. Severe MG-related muscle weakness means a risk for respiratory failure and respiratory tract infection. Drug MG treatment can lead to side-effects. Thymectomy is regarded as a safe procedure both short and long term. Non-MG-related comorbidity represents a diagnostic and therapeutic challenge, especially in elderly patients. Diagnostic accuracy and optimal follow-up is necessary to identify and treat all types of coexisting disease in MG.
24557050 Postsurgical pyoderma gangrenosum after autologous breast reconstruction: case report and 2015 Mar Pyoderma gangrenosum (PG) is a rare skin disorder of unknown etiology that is believed to be part of the spectrum of neutrophilic dermatoses. Although 25% to 50% of cases are idiopathic, PG is associated with systemic disease in up to 70% of patients, most notably inflammatory bowel disease, rheumatoid arthritis, and paraproteinemia. Although a multitude of PG cases after breast reduction have been reported, only recently has an association of PG with breast reconstruction been acknowledged. In the present article, the case of postsurgical PG (PSPG) after autologous breast reconstruction is presented along with a review of the literature. The importance of early diagnosis and initiation of appropriate treatment is discussed. The authors discuss the possibility that the increased number of breast reconstructions being performed may increase the incidence of PSPG cases seen by plastic surgeons. As such, it is critical to remove PSPG from the list of "exotic" diseases and place it higher on the list of differential diagnoses as delays in treatment can result in debilitating complications with substantial patient morbidity.
26621939 Improvements in the management of neutropenic sepsis: lessons learned from a district gene 2015 Dec Neutropenic sepsis is a life-threatening condition with mortality rates reported to range between 2 and 21% in adults. It can occur following chemotherapy treatment, due to disease (such as haematological conditions affecting the bone marrow) and in patients on disease-modifying agents (such as patients receiving methotrexate for rheumatoid arthritis). Appropriate emergency treatment is essential and achieving intravenous antibiotic door-to-needle time of less than 1 hour is a key target. Shortfalls in the management of patients presenting to teams with limited expertise in this area were identified in the National Confidential Enquiry into Patient Outcome and Death report in 2008, leading to recommendations including the need for an acute oncology service (AOS) at all hospitals with either an emergency department or medical admissions unit. Practice at Weston General Hospital has been audited at three time points since 2008 (in 2008, 2011 and 2013-14) during which there have been several service developments relevant to the management of neutropenic sepsis, including the introduction of an AOS in June 2013. The percentage of patients in which intravenous antibiotic 1-hour door-to-needle time was achieved has improved from 14% (2008) to 31% (2011) to 79% (2013-14) and neutropenic sepsis mortality has decreased from 39% (2008) to 14% (2011) to 0% (2013-14).
26180616 Unilateral C1 Lateral Mass and C2 Pedicle Screw Fixation for Atlantoaxial Instability in R 2015 Jun OBJECTIVE: Bilateral C1 lateral mass and C2 pedicle screw fixation (C1LM-C2P) is an ideal technique for correcting atlantoaxial instability (AAI). However, the inevitable situation of vertebral artery injury or unfavorable bone structure may necessitate the use of unilateral C1LM-C2P. This study compares the fusion rates of the C1 lateral mass and C2 pedicle screw in the unilateral and bilateral methods. METHODS: Over five years, C1LM-C2P was performed in 25 patients with AAI in our institute. Preoperative studies including cervical X-ray, three-dimensional computed tomography (CT), CT angiogram, and magnetic resonance imaging were performed. To evaluate bony fusion, measurements of the atlanto-dental interval (ADI) and CT scans were performed in the preoperative period, immediate postoperative period, and postoperatively at 1, 3, 6, and 12 months. RESULTS: Unilateral C1LM-C2P was performed in 11 patients (44%). The need to perform unilateral C1LM-C2P was due to anomalous course of the vertebral artery in eight patients (73%) and severe degenerative arthritis in three patients (27%). The mean ADI in the bilateral group was 2.09 mm in the immediate postoperative period and 1.75 mm in 12-months postoperatively. The mean ADI in the unilateral group was 1.82 mm in the immediate postoperative period and 1.91 mm in 12-months postoperatively. Comparison of ADI measurements showed no significant differences in either group (p=0.893), and the fusion rate was 100% in both groups. CONCLUSION: Although bilateral C1LM-C2P is effective for AAI from a biomechanical perspective, unilateral screw fixation is a useful alternative in patients with anatomical variations.
28164049 A Case Report of Bisphosphonate-induced Bilateral Osteoporotic Subtrochanteric Fracture Fe 2016 Sep INTRODUCTION: Osteoporosis is a significant health-care problem characterized by excessive skeletal fragility, susceptibility to low-trauma fractures in men as well as women. Any abnormality of the bone that reduces the strength of the bone predisposes it to mechanical failure during normal activity or with minimum trauma. The mechanical failure manifests itself as a fracture, and this fracture must be recognized as a pathological fracture if the patient is to be treated properly. Osteoporosis is one of the leading causes of such pathological fractures and accounts for 1.5 million fractures annually. In the following case report, we present a 56-year-old postmenopausal female patient with bilateral pathological subtrochanteric fracture femurii due to intake of bisphosponates for 4 years for osteoporosis. Bilateral pathological subtrochanteric femurii fractures are extremely uncommon injuries which occur in adults who sustain injuries due to trivial trauma. A variety of management modalities has been tried to treat this complex fracture pattern. Standard fixation treatment is intramedullary nailing. CASE REPORT: A postmenopausal female of rheumatoid arthritis aged 56 years, presented to our emergency department with a history of trivial fall at home. Following the fall, she was unable to bear weight on bilateral feet and complained of deformity. History revealed consumption of bisphosphonates (tablet alendronate 10 mg) for the last 4 years and glucocorticoids for rheumatiod arthritis. Radiographs were taken, which revealed bilateral pathological subtrochanteric fracture femurii. After obtaining necessary fitness, the patient was taken up for surgery. Closed reduction and Internal fixation with long proximal femoral nail were done. Bisphosphonate intake was stopped and teriparatide 20 µg/day subcutaneously given for 3 months. Fracture healed after 3 months and patient resumed her daily activities. CONCLUSION: In people taking long-term bisphoshponate therapy, symptomatic cortical stress reactions accompanied by evidence of a stress line across the cortical thickening suggest an increased risk of a complete stress fracture. The patients should be informed about the prodromal symptoms like pain and swelling, following this bisphosphonates should be stopped and teriparatide has to be started for osteoporosis.
28115968 Medicinal Plants of the Australian Aboriginal Dharawal People Exhibiting Anti-Inflammatory 2016 Chronic inflammation contributes to multiple ageing-related musculoskeletal and neurodegenerative diseases, cardiovascular diseases, asthma, rheumatoid arthritis, and inflammatory bowel disease. More recently, chronic neuroinflammation has been attributed to Parkinson's and Alzheimer's disease and autism-spectrum and obsessive-compulsive disorders. To date, pharmacotherapy of inflammatory conditions is based mainly on nonsteroidal anti-inflammatory drugs which in contrast to cytokine-suppressive anti-inflammatory drugs do not influence the production of cytokines such as tumour necrosis factor-α or nitric oxide. However, their prolonged use can cause gastrointestinal toxicity and promote adverse events such as high blood pressure, congestive heart failure, and thrombosis. Hence, there is a critical need to develop novel and safer nonsteroidal anti-inflammatory drugs possessing alternate mechanism of action. In this study, plants used by the Dharawal Aboriginal people in Australia for the treatment of inflammatory conditions, for example, asthma, arthritis, rheumatism, fever, oedema, eye inflammation, and inflammation of bladder and related inflammatory diseases, were evaluated for their anti-inflammatory activity in vitro. Ethanolic extracts from 17 Eucalyptus spp. (Myrtaceae) were assessed for their capacity to inhibit nitric oxide and tumor necrosis factor-α production in RAW 264.7 macrophages. Eucalyptus benthamii showed the most potent nitric oxide inhibitory effect (IC(50)  5.57 ± 1.4 µg/mL), whilst E. bosistoana, E. botryoides, E. saligna, E. smithii, E. umbra, and E. viminalis exhibited nitric oxide inhibition values between 7.58 and 19.77 µg/mL.
27966012 [Surface replacement of proximal interphalangeal joints using CapFlex-PIP]. 2017 Feb OBJECTIVE OF SURGERY: The cementless implantation of the surface replacement CapFlex-PIP enables pain relief, preservation of motion, improves lateral stability and corrects axis deviation in proximal interphalangeal (PIP) joints of patients with primary and secondary PIP osteoarthritis. INDICATIONS: Painful PIP joints as a result of degenerative or posttraumatic osteoarthritis with restriction of motion. Secondary inflammatory destruction of PIP joints in rheumatoid arthritis with low inflammatory activity and good bone conditions. CONTRAINDICATIONS: Destruction of PIP joints with severe bone loss, osseous defects and chronic joint luxation. Joint destruction induced by florid or subacute bacterial arthritis. Skin infections. SURGICAL TECHNIQUE: Dorsal or palmar incision over the affected PIP joint while sparing the peritendinous tissue. Exposure of the proximal phalangeal head and meticulous bone resection. Precontouring of the bone bed for proximal prosthesis. Insertion of the trial prosthesis. Exposure of the distal base and resection in the correct axis. Determination of distal prosthesis size and height of the polyethylene inlay. Insertion of the trial prosthesis without bone protrusion. After clinical and radiological control, implantation of the final prosthesis. FOLLOW-UP: Long finger splint, palmar flexor support splint for 2-3 weeks with active mobilization. Then active free mobilization with a twin bandage. After 6 weeks radiological check and free functional mobilization. RESULTS: The active range of motion of 50 patients increased from 43.4° before surgery to 55.9° after 1 year with concomitant pain relief (6.5 to 2.2). In one case revision surgery was required due to traumatic rupture of the radial collateral ligament and four secondary tenolyses were performed.
26940286 Safety profile of anakinra in the management of rheumatologic, metabolic and autoinflammat 2016 May Anakinra is a biologic response modifier that competitively antagonises the biologic effects of interleukin-1, the ancestor pleiotropic proinflammatory cytokine produced by numerous cell types, found in excess in the serum, synovial fluid and any involved tissues of patients with many inflammatory diseases. The magnitude of the risk of different infections, including Mycobacterium tuberculosis (Mtb) infection, associated with the large use of anakinra in many rheumatologic, metabolic or autoinflammatory disorders is still unknown. In addition, it is unclear whether this effect is modified by the concomitant use of antirheumatic drugs and corticosteroids. The rates of development of Mtb disease in patients treated with anakinra due to rheumatoid arthritis, systemic autoinflammatory diseases, Schnitzler's syndrome, Behçet's disease, adult-onset Still disease, systemic juvenile idiopathic arthritis, gout and diabetes mellitus have been usually very low. However, clinicians must carefully weigh the benefits of biological drugs against their risks, particularly in patients prone to infections. Additional data are needed to understand whether this risk of Mtb infection and reactivation are representative of a class effect related to biologics or whether anakinra bears specifically an intrinsic lower risk in comparison with other biologic drugs.
26347121 [Biosimilars in rheumatology. Development and results of clinical trials]. 2015 Oct BACKGROUND: This article presents the design of clinical trials for the development of biosimilars in the European Union and the United States, with special focus on inflammatory diseases. METHODS: All information available in PubMed and the Internet relating to the clinical development of biosimilars in inflammatory rheumatic conditions (e.g. rheumatoid arthritis, psoriasis, psoriatic arthritis and ankylosing spondylitis) was collated. The European Medicines Agency (EMA) and US Food and Drug Administration (FDA) websites were screened for guidelines on biosimilars. RESULTS: More than 10 years ago the EMA began to publish guidelines for the development of biosimilars and several biosimilars have now been approved. In the USA the FDA has published guidance for the nonclinical and clinical development of biosimilars but until early 2015 no biosimilar had been approved. CONCLUSION: Clinical trials aim to resolve uncertainties that may remain following nonclinical development regarding the similarity of the proposed biosimilar with the reference product. Pharmacokinetic and pharmacodynamic studies are essential for early clinical development and further phase 3 clinical studies. Factors to be considered in the clinical process include study population, design, endpoints, sample size, duration and analytical methods.
25784380 Biologic basis of osteoarthritis: state of the evidence. 2015 May PURPOSE OF REVIEW: Evidence accumulated since 2010 indicates that human osteoarthritis should now be reclassified as a systemic musculoskeletal disease rather than a focal disorder of synovial joints. RECENT FINDINGS: Inflammation was seen as the key component promoting synovitis as well as progression of cartilage and bone destruction in osteoarthritis. Thus, metabolic-triggered inflammation involving cytokines, adipokines, abnormal metabolites, acute phase reactants and even complement, all appear to play major roles in osteoarthritis pathophysiology. Immune-mediated inflammation involving T cells and B cells as well as macrophages is now considered a common finding in osteoarthritis synovial tissue. Many experimental and clinical analyses showed that the proinflammatory cytokines, which stimulate matrix metalloproteinase and a disintegrin and metalloproteinase with thrombospondin motif gene transcription in normal and osteoarthritis human chondrocyte cultures, are also present at significantly elevated levels in the synovial fluid of osteoarthritis patients compared with nonarthritic synovial fluids. SUMMARY: Human osteoarthritis is a systemic musculoskeletal disorder involving activation of innate and adaptive immune systems accompanied by inflammation exemplified by the elevated production of proinflammatory cytokines, which play a significant role in the progression of the disease. The future of novel therapies for osteoarthritis should consider developing drug development strategies designed to inhibit proinflammatory cytokine-induced signal transduction. These strategies have been successful in the development of drugs for the treatment of rheumatoid arthritis.
25760962 Phagocyte NADPH oxidase and specific immunity. 2015 May 1 The phagocyte NADPH oxidase NOX2 produces reactive oxygen species (ROS) and is a well-known player in host defence. However, there is also increasing evidence for a regulatory role of NOX2 in adaptive immunity. Deficiency in phagocyte NADPH oxidase causes chronic granulomatous disease (CGD) in humans, a condition that can also be studied in CGD mice. Clinical observations in CGD patients suggest a higher susceptibility to autoimmune diseases, in particular lupus, idiopathic thrombocytopenic purpura and rheumatoid arthritis. In mice, a strong correlation exists between a polymorphism in a NOX2 subunit and the development of autoimmune arthritis. NOX2 deficiency in mice also favours lupus development. Both CGD patients and CGD mice exhibit increased levels of immunoglobulins, including autoantibodies. Despite these phenotypes suggesting a role for NOX2 in specific immunity, mechanistic explanations for the typical increase of CGD in autoimmune disease and antibody levels are still preliminary. NOX2-dependent ROS generation is well documented for dendritic cells and B-lymphocytes. It is unclear whether T-lymphocytes produce ROS themselves or whether they are exposed to ROS derived from dendritic cells during the process of antigen presentation. ROS are signalling molecules in virtually any cell type, including T- and B-lymphocytes. However, knowledge about the impact of ROS-dependent signalling on T- and B-lymphocyte phenotype and response is still limited. ROS might contribute to Th1/Th2/Th17 cell fate decisions during T-lymphocyte activation and might enhance immunoglobulin production by B-lymphocytes. In dendritic cells, NOX2-derived ROS might be important for antigen processing and cell activation.
26330334 Joint production of IL-22 participates in the initial phase of antigen-induced arthritis t 2015 Sep 2 INTRODUCTION: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by neutrophil articular infiltration, joint pain and the progressive destruction of cartilage and bone. IL-22 is a key effector molecule that plays a critical role in autoimmune diseases. However, the function of IL-22 in the pathogenesis of RA remains controversial. In this study, we investigated the role of IL-22 in the early phase of antigen-induced arthritis (AIA) in mice. METHODS: AIA was induced in C57BL/6, IL-22(-/-), ASC(-/-) and IL-1R1(-/-) immunized mice challenged intra-articularly with methylated bovine serum albumin (mBSA). Expression of IL-22 in synovial membranes was determined by RT-PCR. Articular hypernociception was evaluated using an electronic von Frey. Neutrophil recruitment and histopathological analyses were assessed in inflamed knee joint. Joint levels of inflammatory mediators and mBSA-specific IgG concentration in the serum were measured by ELISA. RESULTS: The IL-22 mRNA expression and protein levels in synovial tissue were increased during the onset of AIA. In addition, pharmacological inhibition (anti-IL-22 antibody) and genetic deficiency (IL-22(-/-) mice) reduced articular pain and neutrophil migration in arthritic mice. Consistent with these findings, recombinant IL-22 joint administration promoted articular inflammation per se in WT mice, restoring joint nociception and neutrophil infiltration in IL-22(-/-) mice. Moreover, IL-22-deficient mice showed reduced synovitis (inflammatory cell influx) and lower joint IL-1β levels, whereas the production of IL-17, MCP-1/CCL2, and KC/CXCL1 and the humoral immune response were similar, compared with WT mice. Corroborating these results, the exogenous administration of IL-22 into the joints induced IL-1β production in WT mice and reestablished IL-1β production in IL-22(-/-) mice challenged with mBSA. Additionally, IL-1R1(-/-) mice showed attenuated inflammatory features induced by mBSA or IL-22 challenge. Articular nociception and neutrophil migration induced by IL-22 were also reduced in ASC(-/-) mice. CONCLUSIONS: These results suggest that IL-22 plays a pro-inflammatory/pathogenic role in the onset of AIA through an ASC-dependent stimulation of IL-1β production.
27537585 Multifocal pigmented villonodular synovitis in a child: A case report. 2016 Aug INTRODUCTION: Pigmented villonodular synovitis (PVNS) is a rare, benign proliferative disorder of the synovial membrane that typically presents in adults and affects a single joint. Multifocal PVNS is very rare, particularly in childhood. We reported a rare case of multifocal PVNS affecting over 20 joints in a child. CLINICAL PROCEDURE: A 7-year-old female patient had a 6-month history of multifocal joints swelling with mild pain. She was diagnosed as polyarticular juvenile idiopathic arthritis at a local hospital. Naproxen, methotrexate, infliximab, and pavlin were used to treat the patient for 2 months. However, the treatment had no effect, the joints swelling remained. The patient was then transferred to our hospital. Physical examination revealed multiple joints swelling, especially in the shoulders joints. Puncture fluid from a shoulder joint was bloody. Magnetic resonance imaging (MRI) revealed synovial thickening and hemosiderin deposition. Biopsy of joint synovium found villous nodules, the invasion of foam cells, and hemosiderin deposition. By collecting all of the evidence, the diagnosis of PVNS was confirmed. CONCLUSIONS: PVNS was easily misdiagnosed as rheumatoid arthritis and the formal treatment was usually delayed. This case described here is the first case of PVNS involving such a large numbers of joints that has been reported in the literature.
27397539 Semi-varying coefficient multinomial logistic regression for disease progression risk pred 2016 Nov 20 This paper proposes a risk prediction model using semi-varying coefficient multinomial logistic regression. We use a penalized local likelihood method to do the model selection and estimate both functional and constant coefficients in the selected model. The model can be used to improve predictive modelling when non-linear interactions between predictors are present. We conduct a simulation study to assess our method's performance, and the results show that the model selection procedure works well with small average numbers of wrong-selection or missing-selection. We illustrate the use of our method by applying it to classify the patients with early rheumatoid arthritis at baseline into different risk groups in future disease progression. We use a leave-one-out cross-validation method to assess its correct prediction rate and propose a recalibration framework to evaluate how reliable are the predicted risks. Copyright © 2016 John Wiley & Sons, Ltd.
27955675 CD24 enrichment protects while its loss increases susceptibility of juvenile chondrocytes 2016 Dec 12 BACKGROUND: Diseases associated with human cartilage, including rheumatoid arthritis (RA) and osteoarthritis (OA) have manifested age, mechanical stresses and inflammation as the leading risk factors. Although inflammatory processes are known to be upregulated upon aging, we sought to gain a molecular understanding of how aging affects the tissue-specific response to inflammation. In this report, we explored the role of cluster of differentiation 24 (CD24) in regulating differential inflammatory responses in juvenile and adult human chondrocytes. METHODS: Differential cell-surface CD24 expression was assessed in juvenile and adult chondrocytes along with human induced pluripotent stem cell (hiPSC)-derived neonatal chondrocytes through gene expression and fluorescence-activated cell sorting (FACS) analyses. Loss of function of CD24 was achieved through silencing in chondrocytes and the effects on the response to inflammatory cues were assessed through gene expression and NFκB activity. RESULTS: CD24 expression in chondrocytes caused a differential response to cytokine-induced inflammation, with the CD24(high) juvenile chondrocytes being resistant to IL-1ß treatment as compared to CD24(low) adult chondrocytes. CD24 protects from inflammatory response by reducing NFκB activation, as an acute loss of CD24 via silencing led to an increase in NFκB activation. Moreover, the loss of CD24 in chondrocytes subsequently increased inflammatory and catabolic gene expression both in the absence and presence of IL-1ß. CONCLUSIONS: We have identified CD24 as a novel regulator of inflammatory response in cartilage that is altered during development and aging and could potentially be therapeutic in RA and OA.
27847517 Association between Air Pollution and the Development of Rheumatic Disease: A Systematic R 2016 Objective. Environmental risk factors, such as air pollution, have been studied in relation to the risk of development of rheumatic diseases. We performed a systematic literature review to summarize the existing knowledge. Methods. MEDLINE (1946 to September 2016) and EMBASE (1980 to 2016, week 37) databases were searched using MeSH terms and keywords to identify cohort, case-control, and case cross-over studies reporting risk estimates for the development of select rheumatic diseases in relation to exposure of measured air pollutants (n = 8). We extracted information on the population sample and study period, method of case and exposure determination, and the estimate of association. Results. There was no consistent evidence of an increased risk for the development of rheumatoid arthritis (RA) with exposure to NO(2), SO(2), PM(2.5), or PM(10). Case-control studies in systemic autoimmune rheumatic diseases (SARDs) indicated higher odds of diagnosis with increasing PM(2.5) exposure, as well as an increased relative risk for juvenile idiopathic arthritis (JIA) in American children <5.5 years of age. There was no association with SARDs and NO(2) exposure. Conclusion. There is evidence for a possible association between air pollutant exposures and the development of SARDs and JIA, but relationships with other rheumatic diseases are less clear.
27170508 Toll-like receptors and chronic inflammation in rheumatic diseases: new developments. 2016 Jun In the past few years, new developments have been reported on the role of Toll-like receptors (TLRs) in chronic inflammation in rheumatic diseases. The inhibitory function of TLR10 has been demonstrated. Receptors that enhance the function of TLRs, and several TLR inhibitors, have been identified. In addition, the role of the microbiome and TLRs in the onset of rheumatic diseases has been reported. We review novel insights on the role of TLRs in several inflammatory joint diseases, including rheumatoid arthritis, systemic lupus erythematosus, gout and Lyme arthritis, with a focus on the signalling mechanisms mediated by the Toll-IL-1 receptor (TIR) domain, the exogenous and endogenous ligands of TLRs, and the current and future therapeutic strategies to target TLR signalling in rheumatic diseases.
26666667 Ibuprofen Induces Mitochondrial-Mediated Apoptosis Through Proteasomal Dysfunction. 2016 Dec In routine course of life, nonsteroidal anti-inflammatory drugs (NSAIDs) are widely prescribed antipyretic, analgesic, and anti-inflammatory drugs. It is a well-proposed notion that treatment of NSAIDs may induce anti-proliferative effects in numerous cancer cells. Ibuprofen from isobutylphenylpropanoic acid is NSAID and used to relieve fever, pain, and inflammation. It is also used for juvenile idiopathic arthritis, rheumatoid arthritis, patent ductus arteriosus, and for pericarditis. Despite few emerging studies have expanded the fundamental concept that the treatment of NSAIDs influences apoptosis in cancer cells, however the NSAID-mediated precise mechanisms that determine apoptosis induction without producing adverse consequences in variety of cancer cells are largely unknown. In our present study, we have observed that ibuprofen reduces proteasome activity, enhances the aggregation of ubiquitylated abnormal proteins, and also elevates the accumulation of crucial proteasome substrates. Ibuprofen treatment causes mitochondrial abnormalities and releases cytochrome c into cytosol. Perhaps, the more detailed study is needed in the future to elucidate the molecular mechanisms of NSAIDs that can induce apoptosis without adverse effects and produce effective anti-tumor effects and consequently help in neurodegeneration and ageing.
26457127 NSAIDs and Cardiovascular Diseases: Role of Reactive Oxygen Species. 2015 Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most commonly used drugs worldwide. NSAIDs are used for a variety of conditions including pain, rheumatoid arthritis, and musculoskeletal disorders. The beneficial effects of NSAIDs in reducing or relieving pain are well established, and other benefits such as reducing inflammation and anticancer effects are also documented. The undesirable side effects of NSAIDs include ulcers, internal bleeding, kidney failure, and increased risk of heart attack and stroke. Some of these side effects may be due to the oxidative stress induced by NSAIDs in different tissues. NSAIDs have been shown to induce reactive oxygen species (ROS) in different cell types including cardiac and cardiovascular related cells. Increases in ROS result in increased levels of oxidized proteins which alters key intracellular signaling pathways. One of these key pathways is apoptosis which causes cell death when significantly activated. This review discusses the relationship between NSAIDs and cardiovascular diseases (CVD) and the role of NSAID-induced ROS in CVD.
25940579 Safety of nonsteroidal antiinflammatory drugs in patients with cardiovascular disease. 2015 May Nonsteroidal antiinflammatory drugs (NSAIDs) are used in the management of a variety of conditions, but their prevalence is likely underreported as a result of widespread availability and the perception that nonprescription therapies are unnecessary to report during medication history taking. However, NSAIDs are associated with a number of adverse effects, especially in patients with cardiovascular disease (CVD). Patients with CVD and comorbidities for which NSAIDs may provide symptomatic relief (e.g., osteoarthritis, rheumatoid arthritis) tend to be older, which places them at greater risk of harm. For these reasons, the use of NSAIDs in patients with CVD is a significant public health concern. An understanding of the risks associated with NSAIDs is critical for clinicians across practice settings. In this review, we detail the safety of NSAIDs in patients with CVD, provide recommendations on their use in specific disease states, and discuss therapeutic alternatives.