Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this first comparative in vitro study, linoleyl hydroxamic acid (LHA), a simple and stable derivative of linoleic acid, was tested as an inhibitor of several enzymes involved in arachidonic acid metabolism in mammals. The tested enzymes were human recombinant 5-lipoxygenase (h5-LO), porcine leukocyte 12-LO, rabbit reticulocyte 15-LO, ovine cyclooxygenases 1/2 (COX1/COX2), and human microsomal prostaglandin E synthase-1 (mPGES-1). Potato tuber and soybean lipoxygenases (ptLOX and sLOX, respectively) were studied for comparative purposes. LHA inhibited most of the tested enzymes with the exception of mPGES-1. The LHA inhibitory activity increased as follows: mPGES-1 (no inhibition)<<COX1 = COX2<h5-LO = sLOX = ptLOX<12-LO<<15-LO. The IC(50) values for COX1/COX2, h5-LO, 12-LO, and 15-LO were 60, 7, 0.6, and 0.02 muM, respectively. sLOX was the only tested enzyme that was capable of aerobic oxygenation of LHA, producing 13-hydroperoxy-LHA. The enzyme rapidly inactivated during the reaction. Therefore, LHA could be used as an effective LO/LOX inhibitor without affecting COX1/COX2 and mPGES-1. Possible implications of this observation include treating diseases and pathological states that are caused by (or lead to) hyperproduction of LO-derived metabolites, e.g., inflammation, cardiovascular disorders, cancer, asthma, allergies, psoriasis, and stroke.
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PMID:Inhibition of lipoxygenases and cyclooxygenases by linoleyl hydroxamic acid: comparative in vitro studies. 1830 12

Psoriasis is a common, chronic inflammatory and frequently severe skin disease. Recent epidemiologic studies have documented an increased cardio-vascular mortality in psoriasis patients. Our own work focuses on endothelial cells as mediators for the development of inflammatory infiltrates and more recently as a victim of injury caused by infiltrating cells. In this context, we have measured systemic effects of this seemingly cutaneous inflammation, which results in a metabolic state much like that in patients developing diabetes mellitus and insulin resistance. The latter is an important pathomechanism causing endothelial cell dysfunction and subsequently cardiovascular diseases such as myocardial infarction or stroke. Co-morbidities observed in psoriatic patients therefore represent complications of the accompanying systemic inflammation and are likely to be mediated through the mechanism of insulin resistance. As psoriasis is a risk factor for cardiovascular diseases, its adequate management must include the treatment of other known risk factors. Dermatologists should discuss the elevated cardiovascular risk with their psoriasis patients and encourage them not to smoke and to normalize their body weight.
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PMID:Research in practice: the systemic aspects of psoriasis. 1856 7

Pathological angiogenesis is a hallmark of various ischemic diseases (insufficient vessel growth) but also of cancer and metastasis, inflammatory diseases, blindness, psoriasis or arthritis (excessive angiogenesis). In response to ischemia (reduced blood flow and oxygen supply), new blood vessels form in order to compensate for the lack of perfusion. This natural process could protect them from the consequences of atherosclerotic diseases (myocardial angina, infarction, hindlimb arteriopathy or stroke). However, neovessel formation is altered in many patients. A better understanding of the mechanisms of functional vessel formation is a pre-requisite to improving the treatment of ischemic pathologies. To this end, it is essential to create easily accessible animal models in which vessel formation can be both manipulated and studied. In this review, we will describe different angiogenic mouse models in the context of cardiovascular diseases, either in an ischemic context (hindlimb ischemia, heart ischemia, skin model) or in a non-ischemic context (plug and eye assay, wound healing, ovarian model). We will also discuss quantitative techniques for assessing angiogenesis in these assays.
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PMID:Mouse models to study angiogenesis in the context of cardiovascular diseases. 1927 76

IL-20, an IL-10 family member, is involved in various inflammatory diseases, such as psoriasis, rheumatoid arthritis, and atherosclerosis. We investigated whether hypoxia in vitro and an in vivo model of ischemic stroke would up-regulate IL-20 expression. In vitro, IL-20 expression increased in hypoxic HaCaT, HEK293 cells, chondrocytes, monocytes, and glioblastoma cells. Inhibition of hypoxia-inducible factor 1alpha inhibited CoCl(2)-induced IL-20 expression. We identified two putative hypoxia response elements in the human il20 gene promoter. Promoter activity assays showed that CoCl(2) mimicked hypoxia-activated luciferase reporter gene expression. In vivo, experimental ischemic stroke up-regulated IL-20 in the sera and brain tissue of rats. IL-20 stained positively in glia-like cells in peri-infarcted lesions, but not in contralateral tissue. Administration of IL-20 mAb ameliorated ischemia-induced brain infarction of rats after experimental ischemic stroke. In vitro, RT-PCR analysis showed that glioblastoma cells, GBM8901, expressed IL-20 and its receptor subunits IL-20R1, IL-20R2, and IL-22R1. IL-20 induced cell proliferation in GBM8901 cells by activating the JAK2/STAT3 and ERK1/2 pathways. IL-20 also induced production of IL-1beta, IL-8, and MCP-1 in GBM8901 cells. We conclude that IL-20 was responsive to hypoxia in vitro and in the ischemic stroke model and that up-regulation of IL-20 in the ischemic brain may contribute to brain injury.
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PMID:IL-20 is regulated by hypoxia-inducible factor and up-regulated after experimental ischemic stroke. 1934 80

Psoriasis is a chronic Th-1 and Th-17 inflammatory disease. Chronic inflammation has also been associated with atherosclerosis and thrombosis. The purpose of this study was to determine the risk of stroke in patients with psoriasis. We conducted a population-based cohort study of patients seen by general practitioners participating in the General Practice Research Database in the United Kingdom, 1987-2002. Mild psoriasis was defined as any patient with a diagnostic code of psoriasis, but no history of systemic therapy. Severe psoriasis was defined as any patient with a diagnostic code of psoriasis and a history of systemic therapy consistent with severe psoriasis. The unexposed (control) population was composed of patients with no history of a psoriasis diagnostic code. When adjusting for major risk factors for stroke, both mild (hazard ratio (HR) 1.06, 95% confidence interval (CI) 1.0-1.1) and severe (1.43, 95% CI 1.1-1.9) psoriasis were independent risk factors for stroke. The excess risk of stroke attributable to psoriasis in patients with mild and severe disease was 1 in 4,115 per year and 1 in 530 per year, respectively. Patients with psoriasis, particularly if severe, have an increased risk of stroke that is not explained by major stroke risk factors identified in routine medical care.
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PMID:The risk of stroke in patients with psoriasis. 1974 78

Chondroitin sulphate (CS) is a natural glycosaminoglycan present in the extracellular matrix and is formed by the 1-3 linkage of D-glucuronic acid to N-acetylgalactosamine. In chondrocytes, CS diminishes interleukin-1 beta(IL-1beta)-induced increases in p38 mitogen-activated protein kinase (p38MAPK) and signal-regulated kinase 1/2 (Erk1/2) phosphorylation, and decreases nuclear factor-kappaB (NF-kappaB) nuclear translocation and as a consequence, reduces the formation of pro-inflammatory cytokines, IL-1beta and TNF-alpha, and pro-inflammatory enzymes, such as phospholipase A2 (PLA2), cyclooxygenase 2 (COX-2) and nitric oxide synthase-2 (NOS-2). The mechanism of action of CS explains its beneficial effect on the cartilage, synovial membrane and subchondral bone. On the other hand, in vivo, CS given orally prevents hepatic NF-kappaB nuclear translocation, suggesting that systemic CS may elicit an anti-inflammatory effect in many tissues besides the articulation. There is preliminary evidence showing that in human beings, CS may be of benefit in other diseases where inflammation is an essential marker, such as psoriasis and atherosclerosis. The review of the literature suggest that CS might also be of interest for the treatment of other diseases with an inflammatory and/or autoimmune character, such as inflammatory bowel disease, degenerative diseases of the central nervous system and stroke, multiple sclerosis and other autoimmune diseases.
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PMID:Immunomodulatory and anti-inflammatory effects of chondroitin sulphate. 1952 43

Psoriasis is a disease mediated by Th1 and Th17 cytokines that has different phenotypes (plaque, guttate, pustular, and erythrodermic type). Aside from the well known psoriatic arthritis, associated disorders may occur more frequently than expected, including Crohn's disease, anxiety/depression, and metabolic syndrome. This is based on a constellation of different factors, including abdominal obesity, atherogenic dyslipidemia, hypertension, and glucose intolerance, and is a strong predictor of type 2 diabetes, cardiovascular disease, and stroke. People with moderate to severe psoriasis have more risk for cardiac disease, presumably due to the inflammatory nature of psoriasis, causing inflammatory changes in coronary arteries. The strong association between psoriasis and obesity potentially makes psoriasis an important healthcare issue. Since cardiovascular risk factors are higher in psoriatic patients, dermatologists treating moderate to severe psoriasis should screen for their presence, thus approaching psoriasis as a potential multisystem disorder.
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PMID:Clinical aspects and comorbidities of psoriasis. 1966 31

Psoriasis is a chronic inflammatory, immune-mediated skin disease, which may cause significant deterioration in the quality of life. Recent evidence indicates that psoriasis and psoriatic arthritis are frequently associated with cardiometabolic diseases including myocardial infarction, stroke, diabetes, obesity, dyslipidemia and non-alcoholic fatty liver disease. Although the causal relationship between cardiometabolic comorbidities and psoriasis has not yet been completely proven, it appears that obesity is a relevant risk factor for the development of psoriasis and metabolic syndrome. In addition, moderate to severe psoriasis itself is a risk factor for cardiovascular disease and the metabolic syndrome. Some common genetic traits as well as inflammatory mechanisms may underlie the development of psoriasis and cardiometabolic comorbidities. The presence of comorbidities has important implications in the global approach to patients with psoriasis. Traditional systemic anti-psoriatic agents could negatively affect cardiometabolic comorbidities, and may have important interactions with drugs commonly used by psoriasis patients. In contrast, the recent findings that the risk of myocardial infarction is markedly reduced in rheumatoid arthritis patients who respond to anti-TNF-alpha therapy compared with non-responders supports the hypothesis that the anti-inflammatory effect of TNF-alpha blockers might potentially reduce the cardiovascular risk also in psoriasis patients. Finally, patients with moderate to severe psoriasis should be treated promptly and effectively, should also be encouraged to drastically correct their modifiable cardiovascular risk factors, in particular obesity and smoking habit.
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PMID:Cardiometabolic comorbidities and the approach to patients with psoriasis. 2009 57

Psoriasis is an inflammatory, immune-mediated cutaneous disorder that has recently been recognized as systemic disease that is associated with multiple comorbidities such as depression, obesity, and the metabolic syndrome. The metabolic syndrome is the constellation of abdominal obesity, dyslipidemia, hypertension and insulin resistance, and presence of the metabolic syndrome significantly increases a patient's risk for cardiovascular disease, stroke and type 2 diabetes. Recent studies have found that psoriasis patients are at increased risk for metabolic syndrome as well as the individual components of metabolic syndrome, and the two diseases appear linked through a common mechanism of inflammation. Speculation exists as to whether this association is causative or whether it is the result of other habits seen in psoriasis patients, such as increased rates of smoking, alcohol consumption, and sedentary lifestyle, which add to the complexity of the association between psoriasis and the metabolic syndrome. However, psoriasis treatments have been shown to reduce the risk of developing metabolic syndrome components and comorbidities. Future studies are needed to better understand the nature of this relationship and the implications this could have for management and treatment of patients with psoriasis.
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PMID:Psoriasis and the metabolic syndrome. 2041 20

Current epidemiological data support the association between psoriasis and cardiovascular (CV) risk, in apparent correlation with psoriasis severity. Although less unanimously, evidence of an increased prevalence of CV diseases among psoriasis patients has been reported, including ischemic heart disease, cerebrovascular, peripheral vascular and heart structural disorders. In particular, various studies showed a correlation between psoriasis and major CV events (i.e., myocardial infarction, stroke), while others investigated subclinical changes of blood vessels, such as intima-media thickness increase, arterial stiffness and coronary artery calcification. A series of different mechanisms, like traditional CV risk or iatrogenic risk factors, inflammation, hemostasis dysregulation, hyperhomocysteinemia, and shared genetic susceptibility, are thought to underlie this epidemiological association. Among these elements, inflammation and its related cytokine milieu, including Th1-mediated response and Th17/Treg imbalance, C reactive protein and the newly implicated osteopontin are considered to play a primary role, even if yet to be fully understood.
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PMID:Psoriasis and cardiovascular disease. 2041 21


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