Imbalances in serum angiopoietin concentrations are early predictors of septic shock development in patients with post chemotherapy febrile neutropenia

Background: Febrile neutropenia carries a high risk of sepsis complications, and the identification of biomarkers capable to identify high risk patients is a great challenge. Angiopoietins (Ang -) are cytokines involved in the control microvascular permeability. It is accepted that Ang-1 expression maintains endothelial barrier integrity, and that Ang-2 acts as an antagonizing cytokine with barrier-disrupting functions in inflammatory situations. Ang-2 levels have been recently correlated with sepsis mortality in intensive care units. Methods: We prospectively evaluated concentrations of Ang-1 and Ang-2 at different time-points during febrile neutropenia, and explored the diagnostic accuracy of these mediators as potential predictors of poor outcome in this clinical setting before the development of sepsis complications. Results: Patients that evolved with septic shock (n = 10) presented higher levels of Ang-2 measured 48 hours after fever onset, and of the Ang-2/Ang-1 ratio at the time of fever onset compared to patients with non-complicated sepsis (n = 31). These levels correlated with sepsis severity scores. Conclusions: Our data suggest that imbalances in the concentrations of Ang-1 and Ang-2 are independent and early markers of the risk of developing septic shock and of sepsis mortality in febrile neutropenia, and larger studies are warranted to validate their clinical usefulness. Therapeutic strategies that manipulate this Ang-2/Ang-1 imbalance can potentially offer new and promising treatments for sepsis in febrile neutropenia

Islet-Like Cell Aggregates Generated from Human Adipose Tissue Derived Stem Cells Ameliorate Experimental Diabetes in Mice

BACKGROUND: Type 1 Diabetes Mellitus is caused by auto immune destruction of insulin producing beta cells in the pancreas. Currently available treatments include transplantation of isolated islets from donor pancreas to the patient. However, this method is limited by inadequate means of immuno-suppression to prevent islet rejection and importantly, limited supply of islets for transplantation. Autologous adult stem cells are now considered for cell replacement therapy in diabetes as it has the potential to generate neo-islets which are genetically part of the treated individual. Adopting methods of islet encapsulation in immuno-isolatory devices would eliminate the need for immuno-suppressants. METHODOLOGY/PRINCIPAL FINDINGS: In the present study we explore the potential of human adipose tissue derived adult stem cells (h-ASCs) to differentiate into functional islet like cell aggregates (ICAs). Our stage specific differentiation protocol permit the conversion of mesodermic h-ASCs to definitive endoderm (Hnf3β, TCF2 and Sox17) and to PDX1, Ngn3, NeuroD, Pax4 positive pancreatic endoderm which further matures in vitro to secrete insulin. These ICAs are shown to produce human C-peptide in a glucose dependent manner exhibiting in-vitro functionality. Transplantation of mature ICAs, packed in immuno-isolatory biocompatible capsules to STZ induced diabetic mice restored near normoglycemia within 3-4 weeks. The detection of human C-peptide, 1155±165 pM in blood serum of experimental mice demonstrate the efficacy of our differentiation approach. CONCLUSIONS: h-ASC is an ideal population of personal stem cells for cell replacement therapy, given that they are abundant, easily available and autologous in origin. Our findings present evidence that h-ASCs could be induced to differentiate into physiologically competent functional islet like cell aggregates, which may provide as a source of alternative islets for cell replacement therapy in type 1 diabetes

Impact of phenolic-rich olive leaf extract on blood pressure, plasma lipids and inflammatory markers: a randomised controlled trial

Purpose Dietary polyphenols have been demonstrated to favourably modify a number of cardiovascular risk markers such as blood pressure (BP), endothelial function and plasma lipids. We conducted a randomised, double-blind, controlled, crossover trial to investigate the effects of a phenolic-rich olive leaf extract (OLE) on BP and a number of associated vascular and metabolic measures. Methods A total of 60 pre-hypertensive [systolic blood pressure (SBP): 121–140 mmHg; diastolic blood pressure (DBP): 81–90 mmHg] males [mean age 45 (±SD 12.7 years, BMI 26.7 (±3.21) kg/m2] consumed either OLE (136 mg oleuropein; 6 mg hydroxytyrosol) or a polyphenol-free control daily for 6 weeks before switching to the alternate arm after a 4-week washout. Results Daytime [−3.95 (±SD 11.48) mmHg, p = 0.027] and 24-h SBP [−3.33 (±SD 10.81) mmHg, p = 0.045] and daytime and 24-h DBP [−3.00 (±SD 8.54) mmHg, p = 0.025; −2.42 (±SD 7.61) mmHg, p = 0.039] were all significantly lower following OLE intake, relative to the control. Reductions in plasma total cholesterol [−0.32 (±SD 0.70) mmol/L, p = 0.002], LDL cholesterol [−0.19 (±SD 0.56) mmol/L, p = 0.017] and triglycerides [−0.18 (±SD 0.48), p = 0.008] were also induced by OLE compared to control, whilst a reduction in interleukin-8 [−0.63 (±SD 1.13) pg/ml; p = 0.026] was also detected. Other markers of inflammation, vascular function and glucose metabolism were not affected. Conclusion Our data support previous research, suggesting that OLE intake engenders hypotensive and lipid-lowering effects in vivo

Stress, ageing and their influence on functional, cellular and molecular aspects of the immune system

The immune response is essential for keeping an organism healthy and for defending it from different types of pathogens. It is a complex system that consists of a large number of components performing different functions. The adequate and controlled interaction between these components is necessary for a robust and strong immune response. There are, however, many factors that interfere with the way the immune response functions. Stress and ageing now consistently appear in the literature as factors that act upon the immune system in the way that is often damaging. This review focuses on the role of stress and ageing in altering the robustness of the immune response first separately, and then simultaneously, discussing the effects that emerge from their interplay. The special focus is on the psychological stress and the impact that it has at different levels, from the whole system to the individual molecules, resulting in consequences for physical health

Coma hipopotasémico: a propósito de un caso

Introduction: coma is the extreme degradation of consciousness. A syndrome characterized by a loss of vegetative functions, as an expression of acute and severe brain dysfunction.Presentation of the case: a 65-year-old male patient who two years ago commenced showing signs of loss of consciousness for two days In inter-crisis periods the studies did not confirm positive results. He was brought to the emergency room in a state of hyporeflexic coma. All parameters were normal except for a very discrete metabolic alkalosis and severe hypokalemia with 1,3 millimoles of potassium. General measures and complementary examinations were performed. Potassium values were replenished. As the potassium values standardized, a process of consciousness recovery was initiated. It was interpreted as a hypokalemic coma.Conclusions: hypopotassemia is a common imbalance, with repercussions in the different systems; this imbalance can result in alterations of the cardiovascular dynamics, progressive muscle weakness and coma. Therefore, in case of symptoms similar to hypokalemia, it is required to work on its diagnosis and treatment.Introducción: El coma es la máxima degradación del estado de conciencia. Síndrome caracterizado por una pérdida de las funciones de la vida de relación y conservación de las de la vida vegetativa, como expresión de una disfunción cerebral aguda y grave.Presentación del caso: paciente masculino de 65 años de edad que hace dos años comenzó con cuadros de pérdida de conciencia por espacio de dos días. En períodos intercrisis los estudios no arrojaron resultados positivos. Es traído a servicio de urgencia en estado de coma hiporrefléctico. Se tomaron medidas generales y se realizaron complementarios. Todo en parámetros de normalidad excepto por una muy discreta alcalosis metabólica y una hipocaliemia severa con 1,3 mili moles de potasio. Se reponen valores de potasio. En la medida que los valores de potasio se recuperaban se iniciaba un proceso de recuperación de la conciencia. Se interpreta como un coma hipopotasémico.Conclusiones: la hipopotasemia es un desbalance común, con repercusiones en los diferentes sistemas, que puede causar desde alteraciones de la dinámica cardiovascular, debilidad muscular progresiva y coma.  De ahí que ante sintomatologías similares a una hipopotasemia se deba trabajar en su diagnóstico y tratamiento.