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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chitosan is widely used to treat patients with hypoxia-induced diseases such as ischemia, neuronal death, cerebral stroke, and cerebral infarction. Using the ELISA method, we examined the effect of high molecular weight water-soluble chitosan (WSC) on inflammatory cytokine production in the desferrioxamine (DFX, known to mimic hypoxia)-stimulated human mast cell line HMC-1. DFX significantly increased interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-alpha production compared with the control in a time-dependent manner (p<0.05), but did not affect IL-1alpha production and mRNA expression. The increase in IL-6, IL-8, and TNF-alpha levels was significantly inhibited by WSC in a dose-dependent manner with IC(50) values of 0.77, 0.88, and 2.5 microg/ml, respectively. The maximal inhibition rate of IL-6, IL-8, and TNF-alpha production by WSC was 64+/-9.7%, 80+/-9.4% and 54+/-4.5%, respectively. In addition, WSC inhibited DFX-induced activation of nuclear factor (NF)-kappaB. In conclusion, these results suggest that WSC is an inhibitor of NF-kappaB under hypoxic conditions, which might explain its beneficial effect in the treatment of hypoxia-induced inflammatory diseases.
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PMID:Inhibitory effect of high molecular weight water-soluble chitosan on hypoxia-induced inflammatory cytokine production. 1273 19

The problem of heat stress continues to plague military combat units deployed worldwide. Heat stroke is the most severe form of heat illness and carries 10% mortality despite intervention. Proteolytic and pyrogenic pro-inflammatory mediators, such as IL-6, are released into peripheral circulation in heat illness. It is not known how these mediators affect the outcome of heat illness. Identifying relationships between release of proinflammatory mediators and extent of rhabdomyolysis may lead to an intervention to reduce severity of outcome. This article presents the most current knowledge regarding the physiologic and pathophysiologic manifestations of heat illness. Based on this current state of the science the article introduces a study that will be conducted to address military unique heat stress research.
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PMID:The relationship between proinflammatory mediators and heat stress induced rhabdomyolysis in exercising marines. 1275 82

Central nervous system and peripheral inflammation is important in the responses to ischaemic stroke, and may also predispose to its development. We aimed to identify (1) the extent to which a peripheral inflammatory response is activated in patients following acute stroke, and (2) whether there was evidence for preexisting peripheral inflammation. Thirty-six patients with ischaemic stroke within 12 h of onset of symptoms had serial blood samples taken up to 12 months for analysis of markers of inflammation. Thirty-six control subjects, individually matched for age, sex and degree of atherosclerosis, were also studied. Median C-reactive protein (CRP) was elevated, relative to controls (2.08 mg/l), from admission (4.31 mg/l) (p</=0.001) until 3 months (2.90 mg/l) (p</=0.01), the greatest elevation occurring at 5-7 days (17.67 mg/l) (p</=0.001). Elevations were also seen in erythrocyte sedimentation rate (ESR) and white blood cell (WBC) count until 3 months. Median plasma IL-6 was also elevated, relative to controls (9 pg/ml), by 24 h after onset of symptoms (22 pg/ml) (p</=0.01), and remained elevated at 5-7 days (23 pg/ml) (p</=0.01), but not at 3 months. Less marked elevations in these markers were seen in patients without evidence of infection except for IL-6, which was not increased in the absence of infection. These data provide evidence of an early and sustained peripheral inflammatory response to acute ischaemic stroke in patients with or without evidence of infection. The very early increase in concentrations of inflammatory markers after stroke may either be induced by stroke itself, or may indicate a preexisting inflammatory condition in stroke patients which may contribute to the development of stroke.
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PMID:An early and sustained peripheral inflammatory response in acute ischaemic stroke: relationships with infection and atherosclerosis. 1279 26

The concept of the vulnerable patient has arrived. Enhanced diagnostic methods will eventually permit accurately finding and treating these patients and their disease. Clinical Cardiologists now recognize that coronary atherosclerosis is two pathophysiologically distinct syndromes: stable and unstable. Stable coronary syndromes result from fixed, severe stenoses limiting blood flow and causing secondary myocardial ischemia. The unstable acute coronary syndromes are frequently catastrophic and are pathophysiologically distinct. They result from different cell subsets causing vascular inflammatory syndromes rather than gradual lumen constriction by plaque. Though pathophysiologically distinct, they may show common pathophysiology when a ruptured plaque heals and progressively becomes a critical stenosis. For the present hs-CRP measurement is the strongest correlative factor for future clinical events due to arterial inflammation: myocardial infarction, unstable angina, stroke, and peripheral vascular disease in both diseased and apparently healthy, asymptomatic patients. The CRP plasma level also is the best risk assessment in patients with either stable or unstable angina, long term after myocardial infarction, and in patients undergoing revascularization therapies. One study showed the only independent cardiovascular risk indicators using multivariate, age adjusted and traditional risk analysis were CRP and Total/HDL cholesterol ratio. If CRP, IL-6, and ICAM-1 levels are added to lipid levels, risk assessment can be improved over lipids alone. The prevalence of high-risk subjects in the general population is low, amplifying diagnostic problems for vulnerable plaque. Since no test yet has high sensitivity or specificity, diagnostic errors are high, with many false positives and negatives. Sensitivity or specificity must be increased by developing a risk marker panel, or by simultaneously finding other markers that themselves are highly sensitive and specific for vulnerable plaque.
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PMID:Detecting vulnerable plaque using peripheral blood: inflammatory and cellular markers. 1280 Apr 2

Through continuous cardiac output monitoring, we investigated the temporal relationship between hemodynamic changes and plasma cytokines in a cancer patient who developed collateral sepsis to immunotherapy. A 52-year-old male with metastatic renal cell carcinoma received interleukin-2 (IL-2) infusion completing 72 h of administration. The patient developed 3 sepsis-like states including systemic inflammatory response syndrome (SIRS), shock, and multiple organ dysfunction syndrome (MODS). Hemodynamic parameters including systemic vascular resistance index (SVRI), left ventricular stroke work index (LVSWI) and cardiac index (CI) were measured over 60 h. Peripheral blood was drawn when SVRI dropped 20% in the patient and plasma cytokines including TNF-alpha, IL-6 and IL-1beta were measured using ELISA. After 60 h of immunotherapy, the patient showed a 63.4% decrease in SVRI, 54.5% decrease in LVSWI and 65.4% increase in CI. The evaluation of systemic cytokines revealed different kinetic patterns: (i) a sustained increase in TNF-alpha levels through all 3 sepsis-like states; (ii) IL-6 increased preferentially during SIRS and shock, while up/down-responses were found during MODS; (iii) IL-1beta was undetectable during the entire study period. A high temporal relationship between hemodynamic changes and plasma TNF-alpha, but not IL-6, was found. Although there are factors other than cytokines that can alter vascular resistance, this finding could represent an approach to evaluate the course of hemodynamia and probably the systemic cytokine expression after IL-2 administration in renal cancer.
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PMID:Continuous cardiac output and hemodynamic monitoring: high temporal correlation between plasma TNF-alpha and hemodynamic changes during a sepsis-like state in cancer immunotherapy. 1280 81

Cytokines are important hormonal mediators, produced in tissues undergoing defence, growth and repair processes. Infection and inflammation in particular result in a cascade of cytokine induction that acts to maintain tissue homeostasis. Most cytokines act within the injured tissues, although some have an endocrine action, recruiting distant tissues in defence of the tissue producing the cytokine and many are important for regulating acquired immunity in secondary lymphoid tissues. Induction of interleukin-1 (IL-1), tumour necrosis factor (TNF) and IL-6 highlight the way in which local tissue cytokine responses are induced and act. Since most cytokines act locally, cytokine measurement presents several difficulties. Only where cytokines (such as IL-6) have a systemic action are plasma cytokine concentrations really meaningful. The presence of cytokine antagonists and soluble cytokine receptors, often released in concert with their respective cytokine agonists, presents additional complexity to interpretation. Measurement and manipulation of cytokines can contribute towards an understanding of their pathophysiological role in both experimental and clinical settings. This includes measurement of plasma IL-6, which has striking relationships to tissue inflammation. Its value is exemplified by some recent studies of stroke patients, where IL-6 reflects not only the initial response but also clinical outcome and survival.
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PMID:The pathophysiological role of cytokines. 1293 51

This study investigates the association of several inflammatory markers with subclinical and clinical cardiovascular disease in older men and women. Data are from the baseline assessment of 3,045 well-functioning persons aged 70 to 79 years, participating in the Health, Aging and Body Composition study. The study sample was divided into 3 groups: "cardiovascular disease" (diagnosis of congestive heart failure, coronary artery disease, peripheral artery disease, or stroke), "subclinical cardiovascular disease" (positive findings on the Rose questionnaire for angina or claudication, ankle-brachial index <0.9, or electrocardiographic abnormalities), and "no cardiovascular disease." Serum levels of interleukin (IL)-6, C-reactive protein (CRP), tumor necrosis factor (TNF)-alpha, and the soluble receptors IL-6 soluble receptor, IL-2 soluble receptor, TNF soluble receptor I, and TNF soluble receptor II were assessed. Of those with IL-6 levels in the highest compared with the lowest tertile, the odds ratio (OR) for subclinical cardiovascular disease was 1.58 (95% confidence interval [CI] 1.26 to 1.97) and for clinical cardiovascular disease was 2.35 (95% CI 1.79 to 3.09). A similar association was found for TNF-alpha (OR 1.48, 95% CI 1.16 to 1.88 and OR 2.05, 95% CI 1.55 to 2.72, respectively). In adjusted analyses, CRP was not significantly associated with overall subclinical or clinical cardiovascular disease, although additional analyses did find a strong specific association between CRP and congestive heart failure (OR 1.64, 95% CI 1.11 to 2.41). Of the soluble cytokine receptors, only TNF soluble receptor I showed a significant association with clinical cardiovascular disease. Thus, our findings suggest an important role for IL-6 and TNF-alpha in clinical as well as subclinical cardiovascular disease. In this study, CRP had a weaker association with cardiovascular disease than the cytokines.
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PMID:Inflammatory markers and cardiovascular disease (The Health, Aging and Body Composition [Health ABC] Study). 1294 70

The activation of microglial cells is involved in the pathogenesis of a variety of neurodegenerative diseases, stroke and traumatic brain injuries. Recent studies suggest that protein acetylation can affect the extent of inflammatory responses. Our aim was to elucidate whether histone deacetylase inhibitors, inducers of protein hyperacetylation, regulate the inflammatory response in neural models of inflammation in vitro and whether neurone-glia interactions affect this regulation. Interestingly, we observed that histone deacetylase inhibitors, such as trichostatin A (TSA) and suberoylanilide hydroxamic acid, strongly potentiated the lipopolysaccharide (LPS)-induced inflammatory response in murine N9 and rat primary microglial cells as well in neural co-cultures and hippocampal slice cultures. TSA clearly potentiated the LPS-induced expression of interleukin (IL)-6 and inducible nitric oxide synthase mRNAs, as well as the secretion of cytokines IL-6, tumour necrosis factor-alpha and macrophage inflammatory protein (MIP)-2, and nitric oxide (NO). Co-culture and slice culture experiments showed that the presence of astrocytes and neurones did not stimulate or prevent the pro-inflammatory potentiation induced by histone deacetylase inhibitor in microglial cells. The potentiation of cytokine and NO responses was blocked by the nuclear factor kappa B (NF-kappa B) inhibitors caffeic acid phenethyl ester and helenalin, demonstrating that the NF-kappa B signalling pathway is involved. The DNA-binding activity of the NF-kappa B complex was strongly increased by LPS treatment but not enhanced by TSA. This suggests that potentiation of the inflammatory response is not dependent on the level of cytoplasmic NF-kappa B activation or DNA-binding activity but that site of action may be at the level of transcriptional regulation. Our results suggest that environmental stresses, ageing, diet and diseases that regulate protein acetylation status may also affect the inflammatory response.
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PMID:Regulation of microglial inflammatory response by histone deacetylase inhibitors. 1451 Nov 18

1. There is evidence that hydroxyl radicals are accumulated and oxidative stress is produced in multiple organs, including the brain, of rats with heat stroke. Herein, we investigated the effect on heat stroke-induced circulatory shock and cerebral ischaemic injury of two free radical scavengers, namely mannitol and alpha-tocopherol. 2. Urethane-anaesthetized rats were exposed to heat stress (ambient temperature 42 degrees C) to induce heat stroke. Control rats were exposed to 24 degrees C. Mean arterial pressure and cerebral blood flow after the onset of heat stroke were significantly lower in heat stroke rats than in control rats. However, cerebral free radicals, lipid peroxidation and the neuronal damage score were greater in heat stroke rats compared with control rats. Similarly, plasma cytokines, including tumour necrosis factor-alpha, interleukin (IL)-1beta and IL-6, were significantly higher in heat stroke rats compared with their normothermic controls. 3. Pretreatment with alpha-tocopherol (20 mg/kg, i.v.) or mannitol (10%, i.v.) 30 min before the onset of heat exposure significantly attenuated heat stroke-induced arterial hypotension, cerebral ischaemia and neuronal damage, the increased free radical formation and lipid peroxidation in the brain and the increased plasma levels of cytokines. Pretreatment with alpha-tocopherol or mannitol resulted in a prolongation of survival time in heat stroke. 4. These results demonstrate that although pretreatment with alpha-tocopherol and mannitol does not prevent the heat stroke syndrome entirely, an attenuation of the syndrome is observed.
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PMID:Protective effects of alpha-tocopherol and mannitol in both circulatory shock and cerebral ischaemia injury in rat heatstroke. 1451 13

Sixteen patients with acute middle cerebral artery stroke were studied to correlate neuroinflammatory markers with perfusion- and diffusion-weighted magnetic resonance imaging (MRI) lesion volumes (PWI and DWI). At arrival (less than 6 hours), plasmatic matrix metalloproteinase (MMP)-9, MMP-2, interleukin (IL)-6, IL-8, intercellular adhesion molecule (ICAM)-1, and tumor necrosis factor (TNF)-alpha were serially measured (by ELISA), and MRI was performed. In cerebral ischemia, tissue destruction seems related to matrix metalloproteinases expression because baseline MMP-9 was the only predictor of the infarct volume measured as a DWI lesion (lineal regression: b = 0.50, 0.25-0.74; P < 0.001). Moreover, the extent of hypoperfused brain area (PWI) was associated with a proinflammatory cytokine release in the next hours (TNF-alpha and IL-6).
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PMID:Plasmatic level of neuroinflammatory markers predict the extent of diffusion-weighted image lesions in hyperacute stroke. 1466 35


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