The cytokine erythropoietin (EPO) possesses potent neuroprotective activity against a variety of potential brain injuries, including transient ischemia and reperfusion. It is currently unknown whether EPO will also ameliorate spinal cord injury. Immunocytochemistry performed using human spinal cord sections showed abundant EPO receptor immunoreactivity of capillaries, especially in white matter, and motor neurons within the ventral horn. We used a transient global spinal ischemia model in rabbits to test whether exogenous EPO can cross the blood-spinal cord barrier and protect these motor neurons. Spinal cord ischemia was produced in rabbits by occlusion of the abdominal aorta for 20 min, followed by saline or recombinant human (rHu)-EPO (350, 800, or 1,000 units/kg of body weight) administered intravenously immediately after the onset of reperfusion. The functional neurological status of animals was better for rHu-EPO-treated animals 1 h after recovery from anesthesia, and improved dramatically over the next 48 h. In contrast, saline-treated animals exhibited a poorer neurological score at 1 h and did not significantly improve. Histopathological examination of the affected spinal cord revealed widespread motor neuron injury associated with positive terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling in control but not in rHu-EPO-treated animals. These observations suggest both an acute as well as a delayed beneficial action of rHu-EPO in ischemic spinal cord injury. Because rHu-EPO is currently used widely with an excellent safety profile, clinical trials evaluating its potential to prevent motor neuron apoptosis and the neurological deficits that occur as a consequence of ischemic injury are warranted.

Erythropoietin (EPO) is a neuroprotective cytokine in models of ischemic and nervous system injury, where it reduces neuronal apoptosis and inflammatory cytokines and increases neurogenesis and angiogenesis. EPO also improves cognition in healthy volunteers and schizophrenic patients. We studied the effect of EPO administration on the gene-expression profile in the ischemic cortex of rats after cerebral ischemia at early time points (2 and 6 h). EPO treatment up-regulated genes already increased by ischemia. Hierarchical clustering and analysis of overrepresented functional categories identified genes implicated in synaptic plasticity-Arc, BDNF, Egr1, and Egr2, of which Egr2 was the most significantly regulated. Up-regulation of Arc, BDNF, Dusp5, Egr1, Egr2, Egr4, and Nr4a3 was confirmed by quantitative PCR. We investigated the up-regulation of Egr2/Krox20 further because of its role in neuronal plasticity. Its elevation by EPO was confirmed in an independent in vivo experiment of cerebral ischemia in rats. Using the rat neuroblastoma B104, we found that wild-type cells that do not express EPO receptor (EPOR) do not respond to EPO by inducing Egr2. However, EPOR-expressing B104 cells induce Egr2 early upon incubation with EPO, indicating that Egr2 induction is a direct effect of EPO and that EPOR mediates this effect. Because these changes occur in vivo before decreased inflammatory cytokines or neuronal apoptosis is evident, these findings provide a molecular mechanism for the neuroreparative effects of cytokines and suggest a mechanism of neuroprotection by which promotion of a plastic phenotype results in decreased inflammation and neuronal death.microarrays | ischemia-reperfusion injury | neurotrophins | early genes | neuronal cells S ince our first report (1), several studies have documented the neuroprotective effect of erythropoietin (EPO) in models of ischemic and traumatic brain injury (reviewed in refs. 2-4) and the role of endogenous EPO in ischemic preconditioning (5). Multiple mechanisms can account for the action of EPO, including inhibition of neuronal apoptosis (6) and decreased neuroinflammation (7,8). EPO also activates repair, in particular through promotion of neurogenesis, oligodendrogenesis, and angiogenesis (9, 10), as well as mobilization of endothelial progenitor cells (11). It also improves cognition, long-term potentiation (LTP), and synaptic plasticity (4,(12)(13)(14).However, the early effects of EPO responsible for its neuroprotective activities are not understood, and there even is debate whether the classical EPO receptor (EPOR) alone mediates these effects or an additional tissue-protective coreceptor is required (15-18).In the study presented here, we investigated the effect of EPO on the gene-expression profile of the brain using the rat model of cerebral ischemia induced by middle cerebral artery occlusion (MCAO) with which we performed most of the studies on EPO.To identify early events induced by EPO, experiments were carried out at the time points 2 and 6 h post-MCAO, when ...

While a number of similarities were found between Turkish anaesthesiologists and those from other countries, some specific differences could be identified, particularly related to consensus decision-making and sharing information with other providers and the value of Ethics Committees in the decision-making process.

Background: Necrotizing enterocolitis (NEC) is an important neonatal disease with a high mortality rate; erythropoietin (Epo) is a hematopoietic growth factor. Functional Epo receptors are in the fetal and postnatal small bowel and their ligands are available for binding. Excessive nitric oxide (NO) production by an isoform of NO synthase inducible by inflammatory stimuli leads to changes in vascular permeability and tissue injury. The aim of this study was to investigate NO formation in an experimental model of NEC and the possible role of NO in the protection Epo provides against NEC. Methods: Twenty-four Wistar albino rat pups were divided into three groups: group 1 = control; group 2 = hypoxia-reoxygenation and saline; group 3 = hypoxia-reoxygenation and recombinant human EPO (rhEpo) pretreatment. rhEpo was given 750 U/kg/week by intraperitoneal injection 3 times a week for 2 weeks. On the 15th day, hypoxia was induced by placing the pups in a 100% CO₂ chamber for 5 min. After the hypoxia period the pups were reoxygenated for 10 min with 100% O₂ and returned to their mothers. All pups were killed 4 h after the hypoxia-reoxygenation period was over. The abdomen was opened and representative samples of injured areas were taken for histopathologic examination. Then nitrite levels were determined in the intestine by Griess Reagent. Results: On histopathological examination, injury scores in group-2 animals were found to be significantly higher than in group-3 animals (p = 0.001). Significantly increased intestinal nitrite levels were found in group-2 rats compared to the rats of groups 1 and 3 (p = 0.001 and p = 0.001, respectively). There was a positive correlation between the histological findings and the intestinal nitrite levels in group-2 and -3 animals (r = 0.94, p = 0.001; r = 0.99, p = 0.001, respectively). Conclusion: The present study demonstrates that the Epo-pretreated group had decreased levels of NO and limited mucosal necrosis in intestinal tissue samples. We believe that these results deserve further experimental studies in order to elucidate the possible effector mechanisms involved in the inhibitory relationship between Epo, NO and NEC.

Introduction. We sought to identify possible risk factors associated with mortality in patients with high-risk pulmonary embolism (PE) after intensive care unit (ICU) admission. Patients and Methods. PE patients, diagnosed with computer tomography pulmonary angiography, were included from two ICUs and were categorized into groups: group 1 high-risk patients and group 2 intermediate/low-risk patients. Results. Fifty-six patients were included. Of them, 41 (73.2%) were group 1 and 15 (26.7%) were group 2. When compared to group 2, need for vasopressor therapy (0 vs 68.3%; p < 0.001) and need for invasive mechanical ventilation (6.7 vs 36.6%; p = 0.043) were more frequent in group 1. The treatment of choice for group 1 was thrombolytic therapy in 29 (70.7%) and anticoagulation in 12 (29.3%) patients. ICU mortality for group 1 was 31.7% (n = 13). In multivariate logistic regression analysis, APACHE II score >18 (OR 42.47 95% CI 1.50–1201.1), invasive mechanical ventilation (OR 30.10 95% CI 1.96–463.31), and thrombolytic therapy (OR 0.03 95% CI 0.01–0.98) were found as independent predictors of mortality. Conclusion. In high-risk PE, admission APACHE II score and need for invasive mechanical ventilation may predict death in ICU. Thrombolytic therapy seems to be beneficial in these patients.

Background Mortality in critically ill patients with coronavirus disease 2019 (COVID‐19) is high, therefore, it is essential to evaluate the independent effect of new‐onset atrial fibrillation (NOAF) on mortality in patients with COVID‐19. We aimed to determine the incidence, risk factors, and outcomes of NOAF in a cohort of critically ill patients with COVID‐19. Methods We conducted a retrospective study on patients admitted to the intensive care unit (ICU) with a diagnosis of COVID‐19. NOAF was defined as atrial fibrillation that was detected after diagnosis of COVID‐19 without a prior history. The primary outcome of the study was the effect of NOAF on mortality in critically ill COVID‐19 patients. Results NOAF incidence was 14.9% (n = 37), and 78% of patients (n = 29) were men in NOAF positive group. Median age of the NOAF group was 79.0 (interquartile range, 71.5‐84.0). Hospital mortality was higher in the NOAF group (87% vs 67%, respectively, P = .019). However, in multivariate analysis, NOAF was not an independent risk factor for hospital mortality (OR 1.42, 95% CI 0.40‐5.09, P = .582). Conclusions The incidence of NOAF was 14.9% in critically ill COVID‐19 patients. Hospital mortality was higher in the NOAF group. However, NOAF was not an independent risk factor for hospital mortality in patients with COVID‐19.

No abstract

No abstract