The effects of physical exercise on plasma levels of relaxin, NTproANP, and NTproBNP in patients with ischemic heart disease

The insulin-like and vasodilatatory polypeptide relaxin (RLX), formerly known as a pregnancy hormone, has gained interest as a potential humoral mediator in human heart failure. Controversy exists about the relation between plasma levels of RLX and the severity of heart failure. The present study was designed to determine the course of RLX, atrial, and brain natriuretic peptide (NT-proANP and NT-proBNP) during physical exercise in patients with ischemic heart disease (IHD) and to relate hormone levels to peak cardiac power output (CPO) as a measure of cardiopulmonary function with prognostic relevance. 40 patients with IHD were studied during right-heart-catheterization at rest and during supine bicycle ergometry. RLX, NTproBNP, and NTproANP were determined before, during exercise, and after recovery. NT-proANP and NT-proBNP levels increased during maximal charge, and recovery while RLX levels decreased. Cardiac power output at maximal charge correlated inversely with NTproANP and NTproBNP but positively with RLX. Patients with high degree heart failure (CPO < 1.96 W) had higher NTproANP and NTproB-NP and lower RLX levels than patients with low degree heart failure. While confirming the role of NTproANP and NTproBNP as markers for the severity of heart failure, the present data do not support the concept that plasma levels of RLX are related to the severity of myocardial dysfunction and that systemic RLX acts as a compensatory vasodilatatory response hormone in ischemic heart disease

Endothelial Progenitor Cells and Cardiovascular Events in Patients with Chronic Kidney Disease – a Prospective Follow-Up Study

BACKGROUND: Endothelial progenitor cells (EPCs) mediate vascular repair and regeneration. Their number in peripheral blood is related to cardiovascular events in individuals with normal renal function. METHODS: We evaluated the association between functionally active EPCs (cell culture) and traditional cardiovascular risk factors in 265 patients with chronic kidney disease stage V receiving hemodialysis therapy. Thereafter, we prospectively assessed cardiovascular events, e.g. myocardial infarction, percutaneous transluminal coronary angioplasty (including stenting), aorto-coronary bypass, stroke and angiographically verified stenosis of peripheral arteries, and cardiovascular death in this cohort. RESULTS: In our patients EPCs were related only to age (r=0.154; p=0.01). During a median follow-up period of 36 months 109 (41%) patients experienced a cardiovascular event. In a multiple Cox regression analysis, we identified EPCs (p=0.03) and patient age (p=0.01) as the only independent variables associated with incident cardiovascular events. Moreover, a total of 70 patients died during follow-up, 45 of those due to cardiovascular causes. Log rank test confirmed statistical significance for EPCs concerning incident cardiovascular events (p=0.02). CONCLUSIONS: We found a significant association between the number of functionally active EPCs and cardiovascular events in patients with chronic kidney disease. Thus, defective vascular repair and regeneration may be responsible, at least in part, for the enormous cardiovascular morbidity in this population

Un enfoque fisiológico para los procesos oceánicos y los cambios glaciares-interglaciares del CO2 atmosférico

18 pages, 6 figures, 1 table[EN] One possible path for exploring the Earth’s far-from-equilibrium homeostasis is to assume that it results from the organisation of optimal pulsating systems, analogous to that in complex living beings. Under this premise it becomes natural to examine the Earth’s organisation using physiological-like variables. Here we identify some of these main variables for the ocean’s circulatory system: pump rate, stroke volume, carbon and nutrient arterial-venous differences, inorganic nutrients and carbon supply, and metabolic rate. The stroke volume is proportional to the water transported into the thermocline and deep oceans, and the arterial-venous differences occur between recently-upwelled deep waters and very productive high-latitudes waters, with atmospheric CO2 being an indicator of the arterial-venous inorganic carbon difference. The metabolic rate is the internal-energy flux (here expressed as flux of inorganic carbon in the upper ocean) required by the system’s machinery, i.e. community respiration. We propose that the pump rate is set externally by the annual cycle, at one beat per year per hemisphere, and that the autotrophic ocean adjusts its stroke volume and arterial-venous differences to modify the internal-energy demand, triggered by long-period astronomical insolation cycles (external-energy supply). With this perspective we may conceive that the Earth’s interglacial-glacial cycle responds to an internal organisation analogous to that occurring in living beings during an exercise-recovery cycle. We use an idealised double-state metabolic model of the upper ocean (with the inorganic carbon/nutrients supply specified through the overturning rate and the steady-state inorganic carbon/nutrients concentrations) to obtain the temporal evolution of its inorganic carbon concentration, which mimics the glacial-interglacial atmospheric CO2 pattern[ES] Un posible camino para el estudio de la homeóstasis fuera-de-equilibrio de la tierra es suponer que resulta de la organización de sistemas pulsátiles optimizados, análoga a aquélla en seres vivos complejos. Bajo esta premisa parece natural examinar la organización de la tierra utilizando variables de tipo fisiológico. Aquí identificamos algunas de las principales variables del sistema circulatorio oceánico: tasa de bombeo del corazón, volumen de latido, diferencias arteriovenosas de carbono y nutrientes, suministro de carbono y nutrientes inorgánicos, y tasa metabólica. El volumen de latido es proporcional al transporte de agua hacia la termoclina y océano profundo, y las diferencias arterio-venosas ocurren entre las aguas profundas recientemente afloradas y aquellas altamente productivas de altas latitudes, con el CO2 atmosférico siendo un indicador de la diferencia arterio-venosa de carbono inorgánico. La tasa metabólica es el flujo de energía interna (aquí expresado como flujo de carbono inorgánico en el océano superior) requerido por la maquinaria que sostiene el sistema, i.e. respiración total de la comunidad. Se propone que la tasa de latido está impuesta externamente, un latido por año por hemisferio, y que el océano autotrófico ajusta su volumen de latido y las diferencias arteriovenosas a cambios en la demanda de energía interna, inducido por ciclos de insolación astronómica de largo período (suministro de energía externa). Bajo esta perspectiva podemos concebir que el ciclo interglacial-glacial de la tierra responde a una organización interna análoga a la que ocurre en seres vivos durante un ciclo de ejercicio-recuperación. Se utiliza un modelo metabólico idealizado de dos estados para el océano superior (con el suministro de carbono/nutrientes inorgánicos especificado mediante la tasa de recirculación de aguas profundas y las concentraciones de carbono/nutrientes inorgánicos en estado estacionario) para obtener la evolución temporal de su concentración de carbono inorgánico, la cual mimetiza el patrón glacial-interglacial del CO2 atmosféricoThis work was supported by the Spanish government through the CANOA project (CTM2005-00444/MAR)Peer reviewe

Low oxygen tension primes aortic endothelial cells to the reparative effect of tissue-protective cytokines

Erythropoietin (EPO) has both erythropoietic and tissue-protective properties. The EPO analogues carbamylated EPO (CEPO) and pyroglutamate helix B surface peptide (pHBSP) lack the erythropoietic activity of EPO but retain the tissue-protective properties that are mediated by a heterocomplex of EPO receptor (EPOR) and the β common receptor (βCR). We studied the action of EPO and its analogues in a model of wound healing where a bovine aortic endothelial cells (BAECs) monolayer was scratched and the scratch closure was assessed over 24 h under different oxygen concentrations. We related the effects of EPO and its analogues on repair to their effect on BAECs proliferation and migration (evaluated using a micro-Boyden chamber). EPO, CEPO and pHBSP enhanced scratch closure only at lower oxygen (5%), while their effect at atmospheric oxygen (21%) was not significant. The mRNA expression of EPOR was doubled in 5% compared to 21% oxygen, and this was associated with increased EPOR assessed by immunofluorescence and Western blot. By contrast βCR mRNA levels were similar in 5% and 21% oxygen. EPO and its analogues increased both BAECs proliferation and migration, suggesting that both may be involved in the reparative process. The priming effect of low oxygen tension on the action of tissue-protective cytokines may be of relevance to vascular disease, including atherogenesis and restenosis

Circulating endothelial cells and angiogenic serum factors during neoadjuvant chemotherapy of primary breast cancer

Circulating endothelial cells (CECs) as well as bone-marrow-derived endothelial precursor cells (EPC) play an important role in neovascularisation and tumour growth. To study the impact of neoadjuvant chemotherapy on the amounts of CEC and their precursor cells, mature CEC and their progenitors were quantified by flow cytometry in peripheral blood of breast cancer patients during anthracycline and/or taxane based neoadjuvant chemotherapy and subsequent surgery in comparison to age-matched healthy controls. Cell numbers were tested for correlation with serum levels of angiopoietin-2, erythropoietin, endostatin, endoglin, VEGF and sVCAM-1 as well as clinical and pathological features of breast cancer disease. Circulating endothelial cells were significantly elevated in breast cancer patients and decreased during chemotherapy, whereas EPC (CD34+/VEGFR-2+) as well as their progenitor cell population CD133+/CD34+ and the population of CD34+ stem cells increased. Concomitantly with the increase of progenitor cells an increase of VEGF, erythropoietin and angiopoietin-2 was observed. These data suggest that chemotherapy can only reduce the amounts of mature CEC, probably reflecting detached cells from tumour vessels, whereas the EPC and their progenitors are mobilised by chemotherapy. Since this mobilisation of EPC may contribute to tumour neovascularisation an early antiangiogenic therapy in combination with chemotherapy could be beneficial for the success of cancer therapy

Circulating Endothelial Progenitor Cells in Kidney Transplant Patients

Background: Kidney transplantation (RTx) leads to amelioration of endothelial function in patients with advanced renal failure. Endothelial progenitor cells (EPCs) may play a key role in this repair process. The aim of this study was to determine the impact of RTx and immunosuppressive therapy on the number of circulating EPCs. Methods: We analyzed 52 RTx patients (58613 years; 33 males, mean 6 SD) and 16 age- and gender-matched subjects with normal kidney function (57617; 10 males). RTx patients received a calcineurin inhibitor (CNI)-based (65%) or a CNI-free therapy (35%) and steroids. EPC number was determined by double positive staining for CD133/VEGFR2 and CD34/VEGFR2 by flow cytometry. Stromal cell-derived factor 1 alpha (SDF-1) levels were assessed by ELISA. Experimentally, to dissociate the impact of RTx from the impact of immunosuppressants, we used the 5/6 nephrectomy model. The animals were treated with a CNI-based or a CNI-free therapy, and EPCs (Sca+cKit+) and CD26+ cells were determined by flow cytometry. Results: Compared to controls, circulating number of CD34+/VEGFR2+ and CD133+/VEGFR2+ EPCs increased in RTx patients. There were no correlations between EPC levels and statin, erythropoietin or use of renin angiotensin system blockers in our study. Indeed, multivariate analysis showed that SDF-1 – a cytokine responsible for EPC mobilization – is independently associated with the EPC number. 5/6 rats presented decreased EPC counts in comparison to control animals. Immunosuppressive therapy was able to restore normal EPC values in 5/6 rats. These effects on EPC number were associated with reduced number of CD26+ cells, which might be related to consequent accumulation of SDF-1. Conclusions: We conclude that kidney transplantation and its associated use of immunosuppressive drugs increases the number of circulating EPCs via the manipulation of the CD26/SDF-1 axis. Increased EPC count may be associated to endothelial repair and function in these patients.

In situ functionalization of a cellulosic-based activated carbon with magnetic iron oxides for the removal of carbamazepine from wastewater

The main goal of this work was to produce an easily recoverable waste-based magnetic activated carbon (MAC) for an efficient removal of the antiepileptic pharmaceutical carbamazepine (CBZ) from wastewater. For this purpose, the synthesis procedure was optimized and a material (MAC4) providing immediate recuperation from solution, remarkable adsorptive performance and relevant properties (specific surface area of 551 m2 g-1 and saturation magnetization of 39.84 emu g-1) was selected for further CBZ kinetic and equilibrium adsorption studies. MAC4 presented fast CBZ adsorption rates and short equilibrium times (< 30-45 min) in both ultrapure water and wastewater. Equilibrium studies showed that MAC4 attained maximum adsorption capacities (qm) of 68 ± 4 mg g-1 in ultrapure water and 60 ± 3 mg g-1 in wastewater, suggesting no significant interference of the aqueous matrix in the adsorption process. Overall, this work provides evidence of potential application of a waste-based MAC in the tertiary treatment of wastewaters.publishe

Erythropoietin in the intensive care unit: beyond treatment of anemia

Erythropoietin (EPO) is the major hormone stimulating the production and differentiation of red blood cells. EPO is used widely for treating anemia of critical illness or anemia induced by chemotherapy. EPO at pharmacological doses is used in this setting to raise hemoglobin levels (by preventing the apoptosis of erythroid progenitor cells) and is designed to reduce patient exposure to allogenic blood through transfusions. Stroke, heart failure, and acute kidney injury are a frequently encountered clinical problem. Unfortunately, in the intensive care unit advances in supportive interventions have done little to reduce the high mortality associated with these conditions. Tissue protection with EPO at high, nonpharmacological doses after injury has been found in the brain, heart, and kidney of several animal models. It is now well known that EPO has anti-apoptotic effects in cells other than erythroid progenitor cells, which is considered to be independent of EPOs erythropoietic activities. This review article summarizes what is known in preclinical models of critical illness and discusses why this does not correlate with randomized, controlled clinical trials