Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Expression of Fas (CD95) and Fas ligand on peripheral blood mononuclear cells in critical illness and association with multiorgan dysfunction severity and survival

Objective: This was an exploratory study with three goals: a) to quantify the expression of the apoptotic receptor Pas and its ligand (FasL) on peripheral blood mononuclear cells (PBMCs) in patients with, or at risk for, multiple organ dysfunction syndrome (MODS); b) to compare this expression with the respective expression in matched controls; and c) to explore the association with MODS severity and survival. Design: Repeated-measures correlational and cross-sectional design. Setting: The surgical, medical, and the trauma/burn intensive care unit of an academic institution. Patients: Thirty-five adult, critically ill patients meeting the diagnostic criteria for systemic inflammatory response syndrome (SIRS) with MODS, or at risk for MODS, were followed for 14 days, Thirty-five non-SIRS controls matched with patients for age, gender, and race comprised the control group. Interventions: Peripheral blood sampling every 48 hrs. Measurements/Main Results:T cells were considerably depleted in SIRS/MODS patients (p < .001), and Fas and FasL expression on PBMCs (flow cytometric analysis) was elevated significantly compared with controls (p < .001), In contrast to controls, non-T cells were the major sources of Fas and Fast in SIRS/MODS patients (p < .01). Expression of Fas and FasL exhibited a bimodal correlation with severity (p < .03). High severity patients demonstrated increasing Pas and fast expression with increasing severity in contrast to declining expression in moderately severe patients. Fas and Fast measurements were significantly and positively associated with the likelihood of survival (p < .05). Conclusions: Dysregulation in the expression of apoptotic receptors Pas and Fast, at least in PBMCs, may be involved in the pathophysiology of SIRS, the related lymphocytopenia, and the onset of MODS and the related morbidity and mortality rates

Soluble fas levels correlate with multiple organ dysfunction severity, survival and nitrate levels, but not with cellular apoptotic markers in critically ill patients

Apoptosis is a mode of programmed cell death (PCD). Transduction of apoptotic signals results in cellular suicide. Organ specific apoptosis has been proposed as a factor in multiple organ dysfunction syndrome (MODS), Fas is a widely occurring apoptotic signal receptor molecule expressed by almost any type of cell, which is also released in a soluble circulating form (circulating fas, sfas), in this exploratory study, we investigated the association of sfas with severity, survival, known mediators of multiple organ dysfunction, and cellular apoptotic markers on peripheral blood mononuclear cells (PBMC) in a group of 35 patients with MODS and in 35 matched controls. Critically ill patients with MODS had significantly elevated sfas levels compared to controls over time (P <.001). Increased serum concentration of circulating fas was associated with increased severity of multiple organ dysfunction. Non-survivors exhibited significantly higher sfas levels compared to survivors (P<.01) and increasing sfas was inversely associated with the likelihood of survival (P<.05). Circulating fas levels correlated highly with serum nitrate concentration, but not with fas and fasL expression on PBMC of critically ill patients. TNF-<alpha> and IL-6, although they appear to be mediators of both apoptosis and MODS, had no association with sfas. These results are suggestive of the need for further investigation on the role of apoptotic signaling in the development of MODS. They also suggest a potential prognostic value of sfas for SIRS/MODS clinical outcomes

Association between lymphocyte expression of the apoptotic receptor Fas and pain in critically ill patients

Elizabeth DE Papathanassoglou,1,* Meropi DA Mpouzika,2,* Margarita Giannakopoulou,3 Evangelos Bozas,3 Nicos Middleton,2 George Tsiaousis,2 Andreas Karabinis4,5 1Faculty of Nursing, University of Alberta, Edmonton, AB, Canada; 2Department of Nursing, Cyprus University of Technology, Limassol, Cyprus; 3Department of Nursing, School of Health Sciences, National and Kapodistrian University of Athens, 4Surgical Care Unit, The Onassis Cardiac Surgery Center, Kallithea, 5School of Medicine, National and Kapodistrian University of Athens, Athens, Greece *These authors contributed equally to this work Objective: Lymphocyte apoptosis in critical illness is associated with immunosuppression. We explored for the first time the associations between pain ratings and expression of the apoptotic receptor Fas on B and T cells in critically ill patients and the potential mediating effects of adrenocorticotropic hormone (ACTH), cortisol, and substance P (SP).Design: This is an exploratory correlational study with repeated measurements (14 days follow-up) and cross-sectional comparisons.Setting: This study was conducted in a state hospital in the metropolitan area of Athens, Greece.Participants: The participants were 36 consecutive critically ill patients and 36 matched controls.Outcome measures: Pain measured by the self-reported numeric rating scale [NRS], the behavioral pain scale, and the pain assessment scale was the primary outcome measure. Flow cytometry (Fas), electrochemiluminescence (ACTH and cortisol) and enzyme-linked immunosorbent assay (SP) were used. Mixed linear models for repeated measurements and bivariable associations at discrete time points were employed.Results: Significant pain at rest was noted. Pain ratings associated with Fas expression on cytotoxic T cells (P=0.041) and B cells (P=0.005), even after adjustment for a number of clinical treatment factors (P=0.006 and P=0.052, respectively). On the day that more patients were able to communicate, Fas on B cells (r=0.897, P=0.029) and cytotoxic T cells (r=0.832; P=0.037) associated with NRS ratings. Associations between pain ratings and ACTH serum levels were noted (P<0.05). When stress neuropeptide levels were added to the model, the statistical significance of the associations between pain ratings and Fas expression was attenuated (P=0.052–0.063), suggesting that stress neuropeptides may partially mediate the association.Conclusion: Preliminary evidence for the association between pain and lymphocyte apoptotic susceptibility is provided. The role of pain management in maintaining immunocompetence in critical illness is worth exploring. Keywords: lymphocyte apoptosis, pain, critical illness, adrenocorticotropic hormone, cortisol, substance

Anxiety symptoms and quality of interaction among oncology nurses: a correlational, cross-sectional study

To explore the severity of Anxiety Symptoms (AS) among Greek oncology nursing personnel, the degree of satisfaction from professional relationships, and potential association between them. Method: A descriptive cross-sectional correlational study was performed in 2 Greek Oncology Hospitals, in 72 members of nursing personnel. Hamilton Anxiety Scale was used for the assessment of AS severity and the Index of Work Satisfaction subscale "Satisfaction from Interaction" for the degree of satisfaction from professional relationships among nursing personnel (NN) and between nursing personnel and physicians (NP). Results: 11% of the sample reported clinical AS [>= 26, scale range (SR): 0-52]. Satisfaction from NN [5.10 (SD: 1.04), SR: 1-7], and NP [4.21 (SD: 0.77), SR: 1-7] professional interaction were both moderate. Statistically significantly associations were observed between clinical AS and satisfaction from NN (p= 0.014) and NP (p= 0.013) professional interaction. Conclusions: Anxiety reduction interventions and improvement of professional relationships are essentials in order to reduce oncology nurses' psychological distress