Tumor cells have the ability to exploit stromal cells to facilitate metastasis. By using malignant melanoma as a model, we show that the stroma adjacent to metastatic lesions is enriched in the known metastasis-promoting protein S100A4. S100A4 stimulates cancer cells to secrete paracrine factors, such as inflammatory cytokines IL8, CCL2 and SAA, which activate stromal cells (endothelial cells and monocytes) so that they acquire tumor-supportive properties. Our data establishes S100A4 as an inducer of a cytokine network enabling tumor cells to engage angiogenic and inflammatory stromal cells, which might contribute to pro-metastatic activity of S100A4. 相似文献
Objective - Insulin is a vasodilating agent and it was hypothesized that insulin (GIK) could improve systemic and regional oxygenation in cardiac surgery with cardiopulmonary bypass (CPB). Two questions were addressed: 1) Does insulin improve central mixed and hepatic venous oxygenation during CPB? and 2) Does this treatment reduce systemic levels of the proinflammatory mediators C3a and IL-6? Design - Prospective, randomized, controlled study at a university hospital. Thirty patients were included and 16 of these received an infusion of insulin, glucose and potassium (GIK) using an euglycemic clamp technique. The insulin infusion was started during hypothermia, 15 min before rewarming. Blood gases and hemodynamic parameters were measured during hypothermia (before the insulin infusion was started), during rewarming at 35°C, and 30 min after CPB was discontinued. Inflammatory markers were measured: preoperatively, during hypothermia and 2 h after CPB. Results - GIK was associated with reduced systemic vascular resistance ( p = 0.02 vs the control group), higher bypass pump flow ( p = 0.001), higher central mixed oxygen saturation ( p = 0.036) and oxygen tension ( p = 0.001) and higher hepatic venous oxygen saturation ( p = 0.04) and oxygen tension ( p = 0.006). C3a and IL-6 increased during surgery in both groups but there were no differences between the groups. Conclusion - 1) GIK infusion improved central mixed and hepatic venous oxygenation in patients undergoing heart surgery. 2) During the conditions of this study, this had no effect on the proinflammatory mediators C3a and IL-6. 相似文献
Globally, the number of people who die with dementia is increasing. The importance of a palliative approach in the care of people with dementia is recognised and there are national polices to enhance current care. In the UK implementation of these polices is promoted by the National Institute for Health and Care Excellence (NICE) Dementia Quality Standards (QS). Since publication of the QS new care interventions have been developed.
Aim
To explore critically the current international research evidence on effect available to inform NICE Dementia QS relevant to end of life (EOL) care.
Design
We used systematic review methods to seek the research evidence for three statements within the Dementia QS. These are those that recommend: (1) a case management approach, (2) discussing and consideration of making a statement about future care (SFC) and (3) a palliative care assessment (PCA). We included evaluative studies of relevant interventions that used a comparative design, such as trials and cohort studies, and measured EOL care outcomes for persons dying with moderate to severe dementia. Our primary outcome of interest was whether the intervention led to a measurable impact on wellbeing for the person with dementia and their family. We assessed included studies for quality using a scale by Higginson and colleagues (2002) for assessment of quality of studies in palliative care, and two authors undertook key review processes. Data sources included Cinahl, Embase, and PsychINFO from 2001 to August 2014. Our search strategy included free text and medical subject headings relevant to population and recommended care.
Results
We found seven studies evaluating a care intervention; four assessed SFC, three PCA. None assessed case management. Studies were of weak design; all used retrospective data and relied on others for precise record keeping and for accurate recall of events. There was limited overlap in outcome measurements. Overall reported benefits were mixed.
Conclusions
Quality statements relevant to EOL care are useful to advance practice however they have a limited evidence base. High quality empirical work is needed to establish that the recommendations in these statements are best practice.
We have previously shown that the homeostatic chemokine CXCL13 is up-regulated in monocytes in atherosclerosis, mediating anti-apoptotic and anti-inflammatory effects.
Objective
To investigate the regulation of CXCL13s receptor, CXCR5.
Methods/patients
In vitro studies in THP-1 and primary monocytes and studies of CXCR5 expression in thrombus material obtained at the site of plaque rupture during myocardial infarction (MI).
Results
Our major findings were: (i) toll-like receptor agonists and particularly β-adrenergic receptor activation and releasate from thrombin-activated platelets increased CXCR5 mRNA levels in monocytes. (ii) The platelet-mediated induction of CXCR5 involved prostaglandin E2/cAMP/protein kinase A-dependent as well as RANTES-dependent pathways with NFκB activation as a potential common down-stream mediator. (iii) Releasate from thrombin-activated platelets augmented the anti-inflammatory effects of CXCL13 in monocytes at least partly by enhancing the effects of CXCL13 on CXCR5 expression. (iv) We found strong immunostaining of CXCR5 in thrombus material obtained at the site of plaque rupture in patients with ST elevation MI (STEMI) and in unstable carotid lesions, co-localized with platelets.
Conclusion
Our findings suggest that platelet-mediated signaling through CXCR5 may be active in vivo during plaque destabilization, potentially representing a counteracting mechanism to inflammation. 相似文献
Aquaporin‐4 (AQP4), the predominant water channel in the brain, is expressed in astrocytes and ependymal cells. In rodents AQP4 is highly polarized to perivascular astrocytic endfeet and loss of AQP4 polarization is associated with disease. The present study was undertaken to compare the expression pattern of AQP4 in human and mouse cortical astrocytes. Cortical tissue specimens were sampled from 11 individuals undergoing neurosurgery wherein brain tissue was removed as part of the procedure, and compared with cortical tissue from 5 adult wild‐type mice processed similarly. The tissue samples were immersion‐fixed and prepared for AQP4 immunogold electron microscopy, allowing quantitative assessment of AQP4's subcellular distribution. In mouse we found that AQP4 water channels were prominently clustered around vessels, being 5 to 10‐fold more abundant in astrocytic endfoot membranes facing the capillary endothelium than in parenchymal astrocytic membranes. In contrast, AQP4 was markedly less polarized in human astrocytes, being only two to three‐fold enriched in astrocytic endfoot membranes adjacent to capillaries. The lower degree of AQP4 polarization in human subjects (1/3 of that in mice) was mainly due to higher AQP4 expression in parenchymal astrocytic membranes. We conclude that there are hitherto unrecognized species differences in AQP4 polarization toward microvessels in the cerebral cortex. 相似文献
The limitations of catgut, which has been the only available absorbably suture material for surgical work are well known. In the present study, catgut and PGA (Dexon) are compared in 123 patients undergoing neck surgery with respect to wound complications. Dexon appears to offer a favourable alternative since this synthetic, absorbable suture material produces fewer early tissue reactions. 相似文献
This article presents findings from a study of 301 Norwegian nursing students' opinions of their future career. The initial survey took place 7 months after the commencement of nursing training in 1998/99 with a follow-up after 2 1/2 years. Data was collated using a questionnaire with closed questions and supplemented by semi-structured in-depth, audio taped interviews concerning the students' professional socialisation. The findings from the initial survey indicate that motives like human contact, helping others and job security (i.e. low risk of being laid off) were important. Plans for further education after finishing the bachelor programme in nursing were abundant. Analysis of the second data-set will show whether there is a change in the students' plans for their future education and career. For nearly 80% of the students it was very important that the bachelor degree could serve as a basis for further education. Multiple regression analysis showed that nursing students who emphasise this importance are less interested in giving care and help to others, and this attitude is confirmed in the interviews. Career preferences were often midwifery, public health or practice in high tech areas like anaesthetics, and not care for chronically ill or elderly patients; areas where there is a shortage of nurses. 相似文献