176 resultados para CARDIAC INFLAMMATION
Resumo:
Several chronic infections known to be associated with malignancy have established oncogenic properties. However the existence of chronic inflammatory conditions that do not have an established infective cause and are associated with the development of tumours strongly suggests that the inflammatory process itself provides the prerequisite environment for the development of malignancy. This environment includes upregulation of mediators of the inflammatory response such as cyclo-oxygenase (COX)-2 leading to the production of inflammatory cytokines and prostaglandins which themselves may suppress cell mediated immune responses and promote angiogenesis. These factors may also impact on cell growth and survival signalling pathways resulting in induction of cell proliferation and inhibition of apoptosis. Furthermore, chronic inflammation may lead to the production of reactive oxygen species and metabolites such as malondialdehyde within the affected cells that may in turn induce DNA damage and mutations and, as a result, be carcinogenic. Here it is proposed that the conditions provided by a chronic inflammatory environment are so essential for the progression of the neoplastic process that therapeutic intervention aimed at inhibiting inflammation, reducing angiogenesis and stimulating cell mediated immune responses may have a major role in reducing the incidence of common cancers. © 2001 Cancer Research Campaign http://www.bjcancer.com.
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The link between chronic immune activation and tumorigenesis is well established. Compelling evidence has accumulated that histologic assessment of infiltration patterns of different host immune response components in non-small cell lung cancer specimens helps identify different prognostic patient subgroups. This review provides an overview of recent insights gained in the understanding of the role played by chronic inflammation in lung carcinogenesis. The usefulness of quantification of different populations of lymphocytes, natural killer cells, macrophages, and mast cells within the tumor microenvironment in non-small cell lung cancer is also discussed. In particular, the importance of assessment of inflammatory cell microlocalization within both the tumor islet and surrounding stromal components is emphasized. Copyright © 2010 by the International Association for the Study of Lung Cancer.
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Sedation scales have the potential to facilitate effective procedural sedation and analgesia in the cardiac catheterization laboratory (CCL). For this potential to become realised, a scale that is suitable for use in the CCL either needs to be identified or developed. To identify sedation scales, a review of Medline and CINHAL was conducted. One sedation scale for the CCL, the NASPE SED, and 15 Intensive Care Unit (ICU) scales met the inclusion and exclusion criteria. Analysis of the scale’s item structures and psychometric properties was then performed. None of these scales were deemed suitable for use in the CCL. As such, further research is required to develop a new scale. The new scale should consist of more than one item because it will be the most effective for tracking the patient’s response to medications. Specific tests required to conduct a rigorous evaluation of the new scale’s psychometric properties are outlined in this paper.
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Introduction: Ondansetron is a 5-HT3 receptor antagonist commonly used as an anti-emetic to prevent the nausea and vomiting associated with anti-cancer drugs, cancer radiotherapy, or postoperatively. Recently, the US Food and Drug Administration (FDA) issued a warning for ondansetron due to a potential for prolongation of the QT interval of the electrocardiogram (ECG), a phenomenon that is associated with an increased risk of the potentially fatal arrhythmia torsade de pointes. Areas covered: We undertook a review of the cardiac safety of ondansetron. Our primary sources of information were PubMed (with downloading of full articles), and the internet. Expert opinion: The dose of ondansetron that the FDA has concerns about is 32 mg iv (or several doses that are equivalent to this), which is only used in preventing nausea and vomiting associated with cancer chemotherapy. This suggests that ondansetron may be safe in the lower doses used to prevent the nausea and vomiting in radiation treatment or postoperatively. However, as there is a report that a lower dose of ondansetron prolonged the QT interval in healthy volunteers, this needs to be clarified by the FDA. More research needs to be undertaken of the relationship between QT prolongation and torsades in order that the FDA can produce clear-cut evidence of pro-arrhythmic risk when introducing warnings for this.
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Introduction: Domperidone is a dopamine D2-receptor antagonist developed as an antiemetic and prokinetic agents. Oral domperidone is not approved in the US, but is used in many countries to treat nausea and vomiting, gastroparesis, and as a galactogogue (to promote lactation). The US Food and Drug Administration (FDA) have issued a warning about the cardiac safety of domperidone. Areas covered: The authors undertook a review of the cardiac safety of oral domperidone. Expert opinion: The data from preclinical studies are unambiguous in identifying domperidone as able to produce marked hERG channel inhibition and action potential prolongation at clinically relevant concentrations. The compound’s propensity to augment instability of action potential duration and action potential triangulation are also indicative of proarrhythmic potential. Domperidone should not be administered to subjects with pre-existing QT prolongation/LQTS, subjects receiving drugs that inhibit CYP3A4, subjects with electrolyte abnormalities or with other risk factors for QT-prolongation. With these provisos, it is possible that domperidone may be used as a galactogogue without direct risk to healthy breast feeding women but more safety information should be sought in this situation. Also, more safety information is required regarding risk to breast feeding infants or before domperidone is routinely used in gastroparesis or gastroesphageal reflux in children.
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Aim/Background
TRALI is hypothesised to develop via a two-event mechanism involving both the patieint's underlying morbidity and blood product factors. The storage of cellular products has been implicated in cases of non-antibody mediated TRALI, however the pathophysiological mechanisms are undefined. We investigated blood product storage-related modulation of inflmmatory cells and medicators involved in TRALI.
Methods
In an in vitro mode, fresh human whole blood was mixed with culture media (control) or LPS as a 1st event and "transfused" with 10% (v/v) pooled supernatant (SN) from Day 1 (d1, n=75) or Day 42 (D42, n=113) packed red blood cells (PRBCs) as a 2nd event. Following 6hrs, culture SN was used to assess the overall inflammatory response (cytometric bead array) and a duplicate assay containing protein transport inhibitor was used to assess neutrophil- and monocyte-specific inflmamatory responses using multi-colour flow cytometry. Panels: IL-6, IL-8, IL-10, IL-12, IL-1, TNF, MCP-1, IP-10, MIP-1. One-way ANOVA 95% CI.
Results
In the absence of LPS, exposure to D1 or D42 PRBC-SN reduced monocyte expression of IL-6, IL-8 and Il-10. D42 PRBC-SN also reduced monocyte IP-10, and the overall IL-8 production was increased. In the presence of LPS, D1-PRBC SN only modified overall IP-10 levels which were reduced. However, cf LPS alone, the combination of LPS and D42 PRBC-SN resulted in increased neutrophil and monocyte productionof IL-1 and IL-8 as well as reduced monocyte TNF production. Additionally, LPS and D42 PRBC-SN resulted in overall inflmmatory changes: elevated IL-8,
Resumo:
It was Dvorak in 1986 that postulated 'tumours are wounds that do not heal' as they share common cellular and molecular mechanisms, which are active in both wounds and in cancer tissue. Inflammation is a crucial part of the innate immune system that protects against pathogens and initiates adaptive immunity. Acute inflammation is usually a rapid and self-limiting process, however it does not always resolve. This leads to the establishment of a chronic inflammatory state and provides the perfect environment for carcinogenesis. Inflammation and cancer have long had an association, going back as far as Virchow in 1863, when leucocytes were noted in neoplastic tissue. It has been estimated that approximately 25% of all malignancies are initiated or exacerbated by inflammation caused by infectious agents. Furthermore, inflammation is linked to all of the six hallmarks of cancer (evasion of apoptosis, insensitivity to anti-growth signals, unlimited replicative potential, angiogenesis, increase in survival factors and invasion and metastasis). It is thought that inflammation may play a critical role in lung carcinogenesis given that individuals with inflammatory lung conditions have an increased risk of lung cancer development. Cigarette smoking can also induce inflammation in the lung and smokers are at a higher risk of developing lung cancer than non-smokers. However, exposure to a number of environmental agents such as radon, have also been demonstrated as a causative factor in this disease. This chapter will focus on inflammation as a contributory factor in non small cell lung cancer (NSCLC), concentrating primarily on the pathological involvement of the pro-inflammatory cytokines, TNF-α, IL-1β, and the CXC (ELR+) chemokine family. Targeting of inflammatory mediators will also be discussed as a therapeutic strategy in this disease. © 2013 by Nova Science Publishers, Inc. All rights reserved.
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Ideal coating materials for implants should be able to induce excellent osseointegration, which requires several important parameters, such as good bonding strength, limited inflammatory reaction, balanced osteoclastogenesis and osteogenesis, to gain well-functioning coated implants with long-term life span after implantation. Bioactive elements, like Sr, Mg and Si, have been found to play important roles in regulating the biological responses. It is of great interest to combine bioactive elements for developing bioactive coatings on Ti-6Al-4V orthopedic implants to elicit multidirectional effects on the osseointegration. In this study, Sr, Mg and Si-containing bioactive Sr2MgSi2O7 (SMS) ceramic coatings on Ti-6Al-4V were successfully prepared by plasma-spray coating method. The prepared SMS coatings have significantly higher bonding strength (~37MPa) than conventional pure hydroxyapatite (HA) coatings (mostly in the range of 15-25 MPa). It was also found that the prepared SMS coatings switch the macrophage phenotype into M2 extreme, inhibiting the inflammatory reaction via the inhibition of Wnt5A/Ca2+ and Toll-like receptor (TLR) pathways of macrophages. In addition, the osteoclastic activities were also inhibited by SMS coatings. The expression of osteoclastogenesis related genes (RANKL and MCSF) in bone marrow derived mesenchymal cells (BMSCs) with the involvement of macrophages was decreased, while OPG expression was enhanced on SMS coatings compared to HA coatings, indicating that SMS coatings also downregulated the osteoclastogenesis. However, the osteogenic differentiation of BMSCs with the involvement of macrophages was comparable between SMS and HA coatings. Therefore, the prepared SMS coatings showed multidirectional effects, such as improving bonding strength, reducing inflammatory reaction and downregulating osteoclastic activities, but maintaining a comparable osteogenesis, as compared with HA coatings. The combination of bioactive elements of Sr, Mg and Si into bioceramic coatings can be a promising method to develop bioactive implants with multifunctional properties for orthopaedic application.
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BACKGROUND Experimental and epidemiologic evidence have suggested that chronic inflammation may play a critical role in endometrial carcinogenesis. METHODS To investigate this hypothesis, a two-stage study was carried out to evaluate single-nucleotide polymorphisms (SNP) in inflammatory pathway genes in association with endometrial cancer risk. In stage I, 64 candidate pathway genes were identified and 4,542 directly genotyped or imputed SNPs were analyzed among 832 endometrial cancer cases and 2,049 controls, using data from the Shanghai Endometrial Cancer Genetics Study. Linkage disequilibrium of stage I SNPs significantly associated with endometrial cancer (P < 0.05) indicated that the majority of associations could be linked to one of 24 distinct loci. One SNP from each of the 24 loci was then selected for follow-up genotyping. Of these, 21 SNPs were successfully designed and genotyped in stage II, which consisted of 10 additional studies including 6,604 endometrial cancer cases and 8,511 controls. RESULTS Five of the 21 SNPs had significant allelic odds ratios (ORs) and 95% confidence intervals (CI) as follows: FABP1, 0.92 (0.85-0.99); CXCL3, 1.16 (1.05-1.29); IL6, 1.08 (1.00-1.17); MSR1, 0.90 (0.82-0.98); and MMP9, 0.91 (0.87-0.97). Two of these polymorphisms were independently significant in the replication sample (rs352038 in CXCL3 and rs3918249 in MMP9). The association for the MMP9 polymorphism remained significant after Bonferroni correction and showed a significant association with endometrial cancer in both Asian- and European-ancestry samples. CONCLUSIONS These findings lend support to the hypothesis that genetic polymorphisms in genes involved in the inflammatory pathway may contribute to genetic susceptibility to endometrial cancer. Impact statement: This study adds to the growing evidence that inflammation plays an important role in endometrial carcinogenesis.
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Background and Purpose The β1-adrenoceptor has at least two binding sites, high and low affinity sites (β1H and β1L, respectively), which mediate cardiostimulation. While β1H-adrenoceptor can be blocked by all clinically used β-blockers, β1L-adrenoceptor is relatively resistant to blockade. Thus, chronic β1L-adrenoceptor activation may mediate persistent cardiostimulation, despite the concurrent blockade of β1H-adrenoceptors. Hence, it is important to determine the potential significance of β1L-adrenoceptors in vivo, particularly in pathological situations. Experimental Approach C57Bl/6 male mice were used. Chronic (4 or 8 weeks) β1L-adrenoceptor activation was achieved by treatment, via osmotic mini pumps, with (-)-CGP12177 (10 mg·kg−1·day−1). Cardiac function was assessed by echocardiography and micromanometry. Key Results (-)-CGP12177 treatment of healthy mice increased heart rate and left ventricular (LV) contractility. (-)-CGP12177 treatment of mice subjected to transverse aorta constriction (TAC), during weeks 4–8 or 4–12 after TAC, led to a positive inotropic effect and exacerbated fibrogenic signalling while cardiac hypertrophy tended to be more severe. (-)-CGP12177 treatment of mice with TAC also exacerbated the myocardial expression of hypertrophic, fibrogenic and inflammatory genes compared to untreated TAC mice. Washout of (-)-CGP12177 revealed a more pronounced cardiac dysfunction after 12 weeks of TAC. Conclusions and Implications β1L-adrenoceptor activation provides functional support to the heart, in both normal and pathological (pressure overload) situations. Sustained β1L-adrenoceptor activation in the diseased heart exacerbates LV remodelling and therefore may promote disease progression from compensatory hypertrophy to heart failure.
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Within the cardiac high dependency unit it is currently a member of the surgical team who makes the decision for a patient's chest drain to be removed after cardiac surgery. This has often resulted in delays in discharging one patient and therefore in admitting the next. A pilot study was carried out using a working standard that had been developed, incorporating an algorithmic model. The results have enabled nursing staff in a cardiac high dependency unit to undertake this responsibility independently.
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Tissue engineering and cell implantation therapies are gaining popularity because of their potential to repair and regenerate tissues and organs. To investigate the role of inflammatory cytokines in new tissue development in engineered tissues, we have characterized the nature and timing of cell populations forming new adipose tissue in a mouse tissue engineering chamber (TEC) and characterized the gene and protein expression of cytokines in the newly developing tissues. EGFP-labeled bone marrow transplant mice and MacGreen mice were implanted with TEC for periods ranging from 0.5 days to 6 weeks. Tissues were collected at various time points and assessed for cytokine expression through ELISA and mRNA analysis or labeled for specific cell populations in the TEC. Macrophage-derived factors, such as monocyte chemotactic protein-1 (MCP-1), appear to induce adipogenesis by recruiting macrophages and bone marrow-derived precursor cells to the TEC at early time points, with a second wave of nonbone marrow-derived progenitors. Gene expression analysis suggests that TNFα, LCN-2, and Interleukin 1β are important in early stages of neo-adipogenesis. Increasing platelet-derived growth factor and vascular endothelial cell growth factor expression at early time points correlates with preadipocyte proliferation and induction of angiogenesis. This study provides new information about key elements that are involved in early development of new adipose tissue.
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Apples are rich in polyphenols, which provide antioxidant properties, mediation of cellular processes such as inflammation, and modulation of gut microbiota. In this study we compared genetically engineered apples with increased flavonoids [myeloblastis transcription factor 10 (MYB10)] with nontransformed apples from the same genotype, "Royal Gala" (RG), and a control diet with no apple. Compared with the RG diet, the MYB10 diet contained elevated concentrations of the flavonoid subclasses anthocyanins, flavanol monomers (epicatechin) and oligomers (procyanidin B2), and flavonols (quercetin glycosides), but other plant secondary metabolites were largely unaltered. We used these apples to investigate the effects of dietary flavonoids on inflammation and gut microbiota in 2 mouse feeding trials. In trial 1, male mice were fed a control diet or diets supplemented with 20% MYB10 apple flesh and peel (MYB-FP) or RG apple flesh and peel (RG-FP) for 7 d. In trial 2, male mice were fed MYB-FP or RG-FP diets or diets supplemented with 20% MYB10 apple flesh or RG apple flesh for 7 or 21 d. In trial 1, the transcription levels of inflammation-linked genes in mice showed decreases of >2-fold for interleukin-2 receptor (Il2rb), chemokine receptor 2 (Ccr2), chemokine ligand 10 (Cxcl10), and chemokine receptor 10 (Ccr10) at 7 d for the MYB-FP diet compared with the RG-FP diet (P <0.05). In trial 2, the inflammation marker prostaglandin E2 (PGE2) in the plasma of mice fed the MYB-FP diet at 21 d was reduced by 10-fold (P < 0.01) compared with the RG-FP diet. In colonic microbiota, the number of total bacteria for mice fed the MYB-FP diet was 6% higher than for mice fed the control diet at 21 d (P = 0.01). In summary, high-flavonoid apple was associated with decreases in some inflammation markers and changes in gut microbiota when fed to healthy mice.
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Introduction Older people recovering from cardiac events requiring an acute hospital admission may experience a decline in physical function limiting their ability to return home to their previous accommodation. Subacute inpatient rehabilitation therapies have potential to assist recovery of physical functioning. However, it is unknown whether age influences the length of stay or physical functioning at discharge from subacute inpatient rehabilitation for this population. Objectives This study examined the outcomes of a cohort of older patients recovering from a cardiac event requiring hospitalisation to investigate the association between age and physical function at discharge, as well as age and length of rehabilitation stay. Methods Participants included 145 consecutive inpatient admissions to a subacute geriatric assessment and rehabilitation unit with a cardiac condition as their primary reason for hospital admission. Participants were required to complete a multi-disciplinary physical functioning assessment within 72 hours of admission to the unit, and again within 72 hours prior to discharge from the unit. The primary outcome measure was the Functional Independence Measure motor score. Demographic and clinical information, including length of stay and discharge destination, were also recorded. Results A total n=126 (87%) participants, with a mean (standard deviation) age of 79 (10) years, had both assessments completed and were included in analyses. Participants who had passed away (n=4, 3%), or did not have both assessments completed per protocol were excluded from analyses. Discharge destinations included home (n=101, 80%), residential aged care (n=17, 13%) and another hospital (n=8, 6%). The (median, interquartile range) Functional Independence Measure motor score was higher at discharge (79, 71 to 84) than admission (61, 48 to 71); z=7.75 p<0.001. Age was not associated with Functional Independence Measure motor score at discharge (t= -0.18, p=0.86), or length of stay in the rehabilitation unit (t= -0.52, 0.60). Conclusion Any perception that age may be associated with longer lengths of stay and reduced physical function outcomes among patients with cardiac conditions admitted for subacute inpatient rehabilitation for older adults is not supported data from this investigation. Older age should not be considered a disincentive when considering the suitability of patients with cardiac diagnoses for this type of inpatient rehabilitation or their potential physical functioning outcome.
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Objective: To investigate the potential of inflammation to induce new adipose tissue formation in the in vivo environment. Methods and results: Using an established model of in vivo adipogenesis, a silicone chamber containing a Matrigel and fibroblast growth factor 2 (1 μg/ml) matrix was implanted into each groin of an adult male C57Bl6 mouse and vascularized with the inferior epigastric vessels. Sterile inflammation was induced in one of the two chambers by suspending Zymosan-A (ZA) (200-0.02 μg/ml) in the matrix at implantation. Adipose tissue formation was assessed at 6, 8, 12 and 24 weeks. ZA induced significant adipogenesis in an inverse dose-dependent manner (P<0.001). At 6 weeks adipose tissue formation was greatest with the lowest concentrations of ZA and least with the highest. Adipogenesis occurred both locally in the chamber containing ZA and in the ZA-free chamber in the contralateral groin of the same animal. ZA induced a systemic inflammatory response characterized by elevated serum tumour necrosis factor-α levels at early time points. Aminoguanidine (40 μg/ml) inhibited the adipogenic response to ZA-induced inflammation. Adipose tissue formed in response to ZA remained stable for 24 weeks, even when exposed to the normal tissue environment. Conclusions: These results demonstrate that inflammation can drive neo-adipogenesis in vivo. This suggests the existence of a positive feedback mechanism in obesity, whereby the state of chronic, low-grade inflammation, characteristic of the condition, may promote further adipogenesis. The mobilization and recruitment of a circulating population of adipose precursor cells is likely to be implicated in this mechanism.