SciCombinator

Discover the most talked about and latest scientific content & concepts.

Concept: Anti-inflammatory

298

 To investigate the cardiovascular safety of non-steroidal anti-inflammatory drugs (NSAIDs) and estimate the risk of hospital admission for heart failure with use of individual NSAIDs.

Concepts: Hypertension, Glucocorticoid, Non-steroidal anti-inflammatory drug, Anti-inflammatory, Paracetamol, ACE inhibitor

270

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used and have been associated with increased cardiovascular risk. Nonetheless, it remains unknown whether use of NSAIDs is associated with out-of-hospital cardiac arrest (OHCA).

Concepts: Non-steroidal anti-inflammatory drug, Anti-inflammatory, Paracetamol

242

Folklore remedies for pain and inflammation in rheumatoid arthritis include the application of magnets and copper to the skin. Despite the popular use of devices containing magnets or copper for this purpose, little research has been conducted to evaluate the efficacy of such treatments.

Concepts: Inflammation, Clinical trial, Rheumatoid arthritis, Rheumatology, Pain, Non-steroidal anti-inflammatory drug, Anti-inflammatory, Acupuncture

194

There is strong diurnal variation in the symptoms and severity of chronic inflammatory diseases, such as rheumatoid arthritis. In addition, disruption of the circadian clock is an aggravating factor associated with a range of human inflammatory diseases. To investigate mechanistic links between the biological clock and pathways underlying inflammatory arthritis, mice were administered collagen (or saline as a control) to induce arthritis. The treatment provoked an inflammatory response within the limbs, which showed robust daily variation in paw swelling and inflammatory cytokine expression. Inflammatory markers were significantly repressed during the dark phase. Further work demonstrated an active molecular clock within the inflamed limbs and highlighted the resident inflammatory cells, fibroblast-like synoviocytes (FLSs), as a potential source of the rhythmic inflammatory signal. Exposure of mice to constant light disrupted the clock in peripheral tissues, causing loss of the nighttime repression of local inflammation. Finally, the results show that the core clock proteins CRYPTOCHROMES 1 and 2 repressed inflammation within the FLSs, and provide novel evidence that a CRYPTOCHROME activator has anti-inflammatory properties in human cells. We conclude that under chronic inflammatory conditions, the clock actively represses inflammatory pathways during the dark phase. This interaction has exciting potential as a therapeutic avenue for treatment of inflammatory disease.-Hand, L. E., Hopwood, T. W., Dickson, S. H., Walker, A. L., Loudon, A. S. I., Ray D. W., Bechtold, D. A., Gibbs, J. E. The circadian clock regulates inflammatory arthritis.

Concepts: Inflammation, Interleukin 1, Asthma, Rheumatoid arthritis, Vasculitis, Anti-inflammatory, Circadian rhythm, C-reactive protein

183

There is compelling evidence to support an aetiological role for inflammation, oxidative and nitrosative stress (O&NS), and mitochondrial dysfunction in the pathophysiology of major neuropsychiatric disorders, including depression, schizophrenia, bipolar disorder, and Alzheimer’s disease (AD). These may represent new pathways for therapy. Aspirin is a non-steroidal anti-inflammatory drug that is an irreversible inhibitor of both cyclooxygenase (COX)-1 and COX-2, It stimulates endogenous production of anti-inflammatory regulatory ‘braking signals’, including lipoxins, which dampen the inflammatory response and reduce levels of inflammatory biomarkers, including C-reactive protein, tumor necrosis factor- and interleukin (IL)–6 , but not negative immunoregulatory cytokines, such as IL-4 and IL-10. Aspirin can reduce oxidative stress and protect against oxidative damage. Early evidence suggests there are beneficial effects of aspirin in preclinical and clinical studies in mood disorders and schizophrenia, and epidemiological data suggests that high-dose aspirin is associated with a reduced risk of AD. Aspirin, one of the oldest agents in medicine, is a potential new therapy for a range of neuropsychiatric disorders, and may provide proof-of-principle support for the role of inflammation and O&NS in the pathophysiology of this diverse group of disorders.

Concepts: Inflammation, Cyclooxygenase, Anti-inflammatory, Paracetamol, Mental disorder, Schizophrenia, Bipolar disorder, Tumor necrosis factor-alpha

178

Particulate air pollution has been associated with increased risk of cardiopulmonary diseases. However, the underlying mechanisms are not fully understood. We have previously demonstrated that single dose exposure to diesel exhaust particle (DEP) causes lung inflammation and peripheral thrombotic events. Here, we exposed mice with repeated doses of DEP (15 µg/animal) every 2(nd) day for 6 days (a total of 4 exposures), and measured several cardiopulmonary endpoints 48 h after the end of the treatments. Moreover, the potential protective effect of curcumin (the yellow pigment isolated from turmeric) on DEP-induced cardiopulmonary toxicity was assessed. DEP exposure increased macrophage and neutrophil numbers, tumor necrosis factor α (TNF α) in the bronchoalveolar lavage (BAL) fluid, and enhanced airway resistance to methacoline measured invasively using Flexivent. DEP also significantly increased plasma C-reactive protein (CRP) and TNF α concentrations, systolic blood pressure (SBP) as well as the pial arteriolar thrombosis. It also significantly enhanced the plasma D-dimer and plasminogen activator inhibitor-1 (PAI-1). Pretreatment with curcumin by oral gavage (45 mg/kg) 1 h before exposure to DEP significantly prevented the influx of inflammatory cells and the increase of TNF α in BAL, and the increased airway resistance caused by DEP. Likewise, curcumin prevented the increase of SBP, CRP, TNF α, D-dimer and PAI-1. The thrombosis was partially but significantly mitigated. In conclusion, repeated exposure to DEP induced lung and systemic inflammation characterized by TNFα release, increased SBP, and accelerated coagulation. Our findings indicate that curcumin is a potent anti-inflammatory agent that prevents the release of TNFα and protects against the pulmonary and cardiovascular effects of DEP.

Concepts: Inflammation, Blood, Heart, Vein, Anti-inflammatory, C-reactive protein, Tumor necrosis factor-alpha, Air pollution

174

Laboratory evidence suggests that certain specialty dietary supplements have antiinflammatory properties, though evidence in humans remains limited. Data on a nationally representative sample of 9,947 adults from the 1999-2004 cycles of the National Health and Nutrition Examination Survey were used to assess the associations between specialty supplement use and inflammation, as measured by serum high-sensitivity C-reactive protein (hs-CRP) concentration. Using survey-weighted multivariate linear regression, significant reductions in hs-CRP concentrations were associated with regular use of glucosamine (17%, 95% confidence interval (CI): 7, 26), chondroitin (22%, 95% CI: 8, 33), and fish oil (16%, 95% CI: 0.3, 29). No associations were observed between hs-CRP concentration and regular use of supplements containing methylsulfonylmethane, garlic, ginkgo biloba, saw palmetto, or pycnogenol. These results suggest that glucosamine and chondroitin supplements are associated with reduced inflammation in humans and provide further evidence to support an inverse association between use of fish oil supplements and inflammation. It is important to further investigate the potential antiinflammatory role of these supplements, as there is a need to identify safe and effective ways to reduce inflammation and the burden of inflammation-related diseases such as cancer and cardiovascular disease.

Concepts: Inflammation, Chondroitin sulfate, Nutrition, Cardiovascular disease, Anti-inflammatory, C-reactive protein, Ginkgo biloba, Ginkgo

170

Mutations in SOD1 cause hereditary variants of the fatal motor neuron disease amyotrophic lateral sclerosis (ALS). Pathophysiology of the disease is non-cell-autonomous, with toxicity deriving also from glia. In particular, microglia contribute to disease progression. Methylene blue (MB) inhibits the effect of nitric oxide, which mediates microglial responses to injury. In vivo 2P-LSM imaging was performed in ALS-linked transgenic SOD1(G93A) mice to investigate the effect of MB on microglia-mediated inflammation in the spinal cord. Local superfusion of the lateral spinal cord with MB inhibited the microglial reaction directed at a laser-induced axon transection in control and SOD1(G93A) mice. In vitro, MB at high concentrations inhibited cytokine and chemokine release from microglia of control and advanced clinical SOD1(G93A) mice. Systemic MB-treatment of SOD1(G93A) mice at early preclinical stages significantly delayed disease onset and motor dysfunction. However, an increase of MB dose had no additional effect on disease progression; this was unexpected in view of the local anti-inflammatory effects. Furthermore, in vivo imaging of systemically MB-treated mice also showed no alterations of microglia activity in response to local lesions. Thus although systemic MB treatment had no effect on microgliosis, instead, its use revealed an important influence on motor neuron survival as indicated by an increased number of lumbar anterior horn neurons present at the time of disease onset. Thus, potentially beneficial effects of locally applied MB on inflammatory events contributing to disease progression could not be reproduced in SOD1(G93A) mice via systemic administration, whereas systemic MB application delayed disease onset via neuroprotection.

Concepts: Inflammation, Nervous system, Neuron, Spinal cord, Amyotrophic lateral sclerosis, Anti-inflammatory, Glial cell, Motor neuron

169

Triggering receptor expressed on myeloid cells-2 (TREM2) is a microglial surface receptor involved in phagocytosis. Clearance of apoptotic debris after stroke represents an important mechanism to re-attain tissue homeostasis and thereby ensure functional recovery. The role of TREM2 following stroke is currently unclear.

Concepts: Immune system, Inflammation, Apoptosis, Anti-inflammatory, Vesicle, Knockout mouse

168

Angioedema is the end result of deep dermal, subcutaneous and/or mucosal swelling, and is potentially a life-threatening condition in cases where the pharynx or larynx is involved. Drug-induced angioedema has been reported to occur in response to a wide range of drugs and vaccines. Drug-induced angioedema, like other cutaneous drug reactions, has been reported to be most frequently elicited by beta-lactam antibiotics and non-steroidal anti-inflammatory drugs, although reliable data from epidemiologic studies are scarce. Recent reports suggested an increasing role of angiotensin-converting enzyme inhibitors (ACEIs) in the causation of life-threatening angioedema. ACEI-related angioedema is never accompanied by urticaria and occurs via a kinin-dependent mechanism. ACEI-related angioedema not only can start years after beginning the treatment, but it can then recur irregularly while under that treatment. Furthermore, allergy tests are unreliable for the diagnosis of ACEI-related angioedema, and so the relationship between angioedema and ACEIs is often missed and consequently quite underestimated. Accordingly, better understanding of the kinin-dependent mechanism, which is particular to angioedema, is necessary for the appropriate management of drug-induced angioedema.

Concepts: Pharmacology, Drug, Non-steroidal anti-inflammatory drug, Anti-inflammatory, Drug addiction, Penicillin, Angioedema, ACE inhibitor