13 research outputs found
Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function
Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes
Self-insertion of needles: An unusual cause of empyema thoracis and its thoracoscopic management
Intrapulmonary aberrant needles are rare in clinical practice. Most
common cause till date is the intra-thoracic migration of pins and
wires commonly used in treatment of fractures and dislocations of upper
extremity. Some cases of traumatic intra-thoracic insertion of needles
have also been reported. We report a patient of empyema thoracis due to
unusual habit of self-insertion of needles in his body because of some
myth. The patient was successfully managed by video-assisted
thoracoscopic surgery
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Aging and cancer
A substantial increase in the number of elderly people in the populations of developed nations in the coming years has been projected. Persons 65 years and older are at significantly higher risk of developing cancer when compared to younger individuals. There is a resulting increase in cancer incidence as well as mortality in this advanced age group. It is important to know how changes in physiological reserve and functional status in elderly patients, polypharmacy issues, comorbidities, and other age-related problems can affect cancer prognosis and management. Elderly patients are not adequately represented in clinical trials, thus creating a relative lack of information related to specific issues about elderly cancer patients and their care. Nevertheless, there is a substantial amount of guidance available, and in this review we will address selected issues of importance when considering the approach to the older cancer patient
Self-insertion of needles: An unusual cause of empyema thoracis and its thoracoscopic management
Intrapulmonary aberrant needles are rare in clinical practice. Most common cause till date is the intra-thoracic migration of pins and wires commonly used in treatment of fractures and dislocations of upper extremity. Some cases of traumatic intra-thoracic insertion of needles have also been reported. We report a patient of empyema thoracis due to unusual habit of self-insertion of needles in his body because of some myth. The patient was successfully managed by video-assisted thoracoscopic surgery