Risk factors associated with intracranial hemorrhage in neonates with persistent pulmonary hypertension on ECMO

BACKGROUND: Up to 40% of infants with persistent pulmonary hypertension (PPHN) remains refractory to conventional therapies, and extracorporeal membrane oxygenation (ECMO) is offered as an effective support for this group. However, ECMO is a highly invasive and risky procedure with devastating complications such as intracranial hemorrhage (ICH). In this study, we aimed to determine the risk factors for ICH in infants with PPHN. METHODS: A case-control study of patients admitted to the pediatric intensive care unit (PICU) with PPHN requiring ECMO support was conducted. The study was carried out at a 25-bed PICU in large urban tertiary care children’s hospital. A total number of 32 subjects were studied. Patients with and without ICH during ECMO were evaluated for activated clotting time (ACT), heparin dosing, platelet count, coagulation profile such as activated partial thromboplastin time (aPTT), prothrombin time (PT), international normalized ratio (INR), fibrinogen level, vital signs including heart rate and mean arterial pressure (MAP), transfusion history, gestational age, and severity of pre-ECMO illness as possible risk factors. RESULTS: Low fibrinogen level (115 ± 13 mg/dl) and low platelet counts (37.4 ± 18.3 Thousand/μl) were associated with higher incidence of ICH (p = 0.009 and p = 0.005, respectively). Elevated MAP (69 ± 4.34 mmHg) was also noticed in ICH patients (p = 0.006). CONCLUSIONS: Results demonstrated that low fibrinogen level and low platelet count were associated with ICH in PPHN patients on ECMO. While on ECMO support, maintaining fibrinogen and platelet counts within normal ranges seems crucial to prevent ICH in PPHN patients. This is the first report identifying low fibrinogen level among the risk factors for ICH in infants with PPHN on ECMO support

Introduction of an agent-based multi-scale modular architecture for dynamic knowledge representation of acute inflammation

<p>Abstract</p> <p>Background</p> <p>One of the greatest challenges facing biomedical research is the integration and sharing of vast amounts of information, not only for individual researchers, but also for the community at large. Agent Based Modeling (ABM) can provide a means of addressing this challenge via a unifying translational architecture for dynamic knowledge representation. This paper presents a series of linked ABMs representing multiple levels of biological organization. They are intended to translate the knowledge derived from in vitro models of acute inflammation to clinically relevant phenomenon such as multiple organ failure.</p> <p>Results and Discussion</p> <p>ABM development followed a sequence starting with relatively direct translation from in-vitro derived rules into a cell-as-agent level ABM, leading on to concatenated ABMs into multi-tissue models, eventually resulting in topologically linked aggregate multi-tissue ABMs modeling organ-organ crosstalk. As an underlying design principle organs were considered to be functionally composed of an epithelial surface, which determined organ integrity, and an endothelial/blood interface, representing the reaction surface for the initiation and propagation of inflammation. The development of the epithelial ABM derived from an in-vitro model of gut epithelial permeability is described. Next, the epithelial ABM was concatenated with the endothelial/inflammatory cell ABM to produce an organ model of the gut. This model was validated against in-vivo models of the inflammatory response of the gut to ischemia. Finally, the gut ABM was linked to a similarly constructed pulmonary ABM to simulate the gut-pulmonary axis in the pathogenesis of multiple organ failure. The behavior of this model was validated against in-vivo and clinical observations on the cross-talk between these two organ systems</p> <p>Conclusion</p> <p>A series of ABMs are presented extending from the level of intracellular mechanism to clinically observed behavior in the intensive care setting. The ABMs all utilize cell-level agents that encapsulate specific mechanistic knowledge extracted from in vitro experiments. The execution of the ABMs results in a dynamic representation of the multi-scale conceptual models derived from those experiments. These models represent a qualitative means of integrating basic scientific information on acute inflammation in a multi-scale, modular architecture as a means of conceptual model verification that can potentially be used to concatenate, communicate and advance community-wide knowledge.</p

Antioxidative protection of dietary bilberry, chokeberry and Lactobacillus plantarum HEAL19 in mice subjected to intestinal oxidative stress by ischemia-reperfusion

<p>Abstract</p> <p>Background</p> <p>Ischemia-reperfusion (I/R) in the intestines is an inflammatory condition which activates leukocytes and reactive oxygen species (ROS) and leads to lipid peroxidation and DNA damage. Bilberry and chokeberry fruits are rich sources of polyphenols which may act as antioxidants and prevent lipid peroxidation. Lactic acid bacteria (LAB) may improve microbial status in the intestines and increase the metabolic activity towards polyphenolic degradation. The aim of the study was to clarify antioxidative effects of bilberry and chokeberry fruits alone and with addition of a LAB-strain, <it>Lactobacillus plantarum </it>HEAL19, in an I/R-model in mice.</p> <p>Methods</p> <p>Male BALB/cJ mice were fed the experimental diets for 10 days. Diets consisted of standard chow supplemented with either bilberry (<it>Vaccinium myrtillus</it>) or chokeberry (<it>Aronia × prunifolia</it>) powder alone or in combination with the LAB-strain <it>Lactobacillus plantarum </it>HEAL19. I/R-injury was induced by holding superior mesenteric artery clamped for 30 minutes followed by reperfusion for 240 minutes. Thereafter, colonic and caecal tissues and contents were collected. Malondialdehyde (MDA) was used as indicator of lipid peroxidation and was measured by a calorimetric assay, lactobacilli were cultured on Rogosa agar plates and <it>Enterobacteriaceae </it>on VRBG agar plates, anthocyanins and phenolic acids were analysed by HPLC-DAD-ESI-MSn.</p> <p>Results</p> <p>MDA was significantly decreased in the colon of groups fed bilberry alone (p = 0.030) and in combination with <it>L. plantarum </it>HEAL19 (p = 0.021) compared to the IR-control but not in chokeberry-fed groups. Supplementation with bilberry or chokeberry alone reduced the total number of lactobacilli on the mucosa. Higher concentrations of anthocyanins were found in the colon than in the caecum content of mice. A more varied composition of different anthocyanins was also observed in the colon content compared to the caecum of bilberry-fed mice. Phenolic acids formed by microbial degradation of the dietary polyphenols in the gut could be detected. More phenolic metabolites were found in the intestines of bilberry-fed mice than in the chokeberry-fed ones.</p> <p>Conclusions</p> <p>Bilberry alone and in combination with <it>L. plantarum </it>HEAL19 exerts a better protection against lipid peroxidation than chokeberry. These dietary supplements may be used to prevent or suppress oxidative stress.</p

Effect of atenolol pre-treatment in heart damage in a model of intestinal ischemia-reperfusion

Purpose: To investigate the effects of atenolol in inflammatory mediator and oxidative stress in a myocardial injury by intestinal ischemia/reperfusion in rat model. Methods: Adult Wistar male rats were randomly (n= 8), anesthetized and divided in: Sham: submitted to operation only; group SS+ IR: intravenous saline infusion following superior mesenteric artery occlusion during 60 minutes (ischemia) and open for 120 minutes (reperfusion); group AT+ IR: intravenous atenolol infusion (2 mg/kg) following superior mesenteric artery occlusion during 60 minutes (ischemia) and open for 120 minutes (reperfusion); and group AT+ I+ AT+ R: intravenous atenolol infusion following superior mesenteric artery occlusion during 60 minutes (ischemia) and in the time 45 minutes other atenolol doses were administrated and the artery was open for 120 minutes (reperfusion), all animals were submitted to muscular relaxation for mechanical ventilation. In the end of experiment the animals were euthanized and the hearts tissue were morphology analyzed by histology and malondialdehyde by ELISA, and the plasma were analyzed for tumor necrosis factor-alpha by ELISA. Results: The group SS+ IR demonstrated the higher malondialdehyde levels when compared with the atenolol treated-groups (p= 0.001) in the heart tissue. The tumor necrosis factoralpha level in plasma decrease in the treated groups when compared with SS+ IR group (p= 0.001). Histology analyses demonstrate pyknosis, edema, cellular vacuolization, presence of inflammatory infiltrate and band contraction in the heart tissue of the rats. Conclusion: Atenolol significantly reduce the degree of cardiac damage after intestinal ischemia-reperfusion.FAPESPUniv Fed Sao Paulo, UNIFESP, Postgrad Program Translat Med, Sao Paulo, BrazilUniv Fed Sao Paulo, Dept Surg, Div Anesthesia Pain & Intens Med, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Postgrad Program Pharmacol, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Dept Pharmacol, Sao Paulo, SP, BrazilUNESP, Vet Med Sch, Aracatuba, SP, BrazilUniv Fed Sao Paulo, Dept Surg, Div Cardiol, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Postgrad Program Translat Med, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, UNIFESP, Postgrad Program Translat Med, Sao Paulo, BrazilUniv Fed Sao Paulo, Dept Surg, Div Anesthesia Pain & Intens Med, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Postgrad Program Pharmacol, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Dept Pharmacol, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Dept Surg, Div Cardiol, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Postgrad Program Translat Med, Sao Paulo, SP, BrazilWeb of Scienc

Antimesenteric jejunal diverticulosis after a remote history of necrotising enterocolitis: a case report

Jejunal diverticulosis is a rare, acquired pathology of the small bowel. While most patients are asymptomatic, the condition is difficult to diagnose. It may present with chronic abdominal pain, diarrhoea, bloating and complications including malabsorption, diverticulitis, bleeding, intestinal obstruction or perforation. This is a case presentation of a 27-year-old woman with a history of necrotising enterocolitis (NEC) requiring surgical resection as a premature newborn who presented with recurrent abdominal pain and was found to have several small bowel diverticula intraoperatively. She underwent resection with complete resolution of symptoms over a 2-year follow-up. This is the first case report to suggest that small bowel diverticular disease as a long-term complication of NEC may result in chronic morbidity in long-term survivors