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Hospital de Órbigo, Spain

Urbanowicz M.,Hospital 12 de Octubre
American Journal of Dermatopathology | Year: 2016

ABSTRACT:: Infectious angiogenesis is the biological response of neoangiogenesis induced by infectious organisms. The authors present 3 exemplary entities which show paradigmatic clinico-pathological settings of infectious angiogenesis: Bacillary angiomatosis, Orf (ecthyma contagiosum), and Kaposi sarcoma. The authors review the literature and elucidate etiopathogenetic pathways leading to the phenomenon of neovascularization stimulated by infectious organisms. The authors describe the clinical and histological pictures, interactions between microorganisms and host cells, and changes that occur within cellular structures, as well as angiogenic factors that underpin infectious angiogenesis. The importance of chronic inflammation and tumor angiogenesis is emphasized. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved. Source

Ruilope L.M.,Hospital 12 de Octubre | Dukat A.,Comenius University | Bohm M.,Saarland University | Lacourciere Y.,Laval University | And 2 more authors.
The Lancet | Year: 2010

Background: LCZ696 is a first-in-class inhibitor of the angiotensin II receptor and neprilysin. We aimed to establish whether the dual actions of LCZ696 lead to further lowering of blood pressure, compared with the angiotensin-receptor blocker valsartan. Methods: 1328 patients aged 18-75 years with mild-to-moderate hypertension were randomly assigned (double-blind) to 8 weeks' treatment in one of eight groups: 100 mg (n=156 patients), 200 mg (n=169), or 400 mg (n=172) LCZ696; 80 mg (n=163), 160 mg (n=166), or 320 mg (n=164) valsartan; 200 mg AHU377 (n=165); or placebo (n=173). The primary endpoint was the mean difference across the three single-dose pairwise comparisons of LCZ696 versus valsartan (100 mg vs 80 mg, 200 mg vs 160 mg, and 400 mg vs 320 mg) in mean sitting diastolic blood pressure during the 8-week treatment period. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00549770. Findings: 1215 patients completed the 8-week treatment period. The average reduction in mean sitting diastolic blood pressure across the doses of LCZ696 versus the appropriate comparator dose of valsartan showed significantly greater reductions with LCZ696 (mean reduction: -2·17 mm Hg, 95% CI -3·28 to -1·06; p<0·0001). The reduction in mean sitting diastolic blood pressure was significantly different for 200 mg LCZ696 versus 160 mg valsartan (-2·97 mm Hg, 95% CI -4·88 to -1·07, p=0·0023) and for 400 mg LCZ696 versus 320 mg valsartan (-2·70 mm Hg, -4·61 to -0·80, p=0·0055). LCZ696 was well tolerated and no cases of angio-oedema were reported; only three serious adverse events occurred during the 8-week treatment period, of which none was judged to be related to the study drug, and no patients died. Interpretation: Compared with valsartan, dual-acting LCZ696 provides complementary and fully additive reduction of blood pressure, which suggests that the drug holds promise for treatment of hypertension and cardiovascular disease. Funding: Novartis. © 2010 Elsevier Ltd. All rights reserved. Source

Kidney transplant is the best therapy to manage end-stage kidney failure. The main barriers limiting this therapy are scarcity of cadaveric donors and the comorbidities of the patients with end-stage kidney failure, which prevent the transplant. Living kidney donor transplant makes it possible to obviate the problem of scarcity of cadaveric donor organs and also presents better results than the cadaveric transplant. The principal indication of living kidney donor transplant is preemptive transplant. This will allow the patient to avoid the complications of dialysis and it has also been demonstrated that it has better results than the transplant done after dialysis has been initiated. Priority indications of living donor transplant are also univitelline twins and HLA identical siblings. We will also have very favorable conditions when the donor is young and male. On the contrary, the living donor transplant will have worse results if the donors are over 60-65 years and the recipients are young, this possibly being a relative contraindication. There is an absolute contraindication for the living donation when the recipient has diseases with high risk of aggressive relapse in the grafts: - Focal and segmental hyalinosis that have had early relapse in the first transplant. - Atypical hemolytic uremic syndrome due to deficit or malfunction of the complement regulatory proteins. - Early development of glomerulonephritis due to anti-glome-rular basement membrane antibody in patients with Alport Syndrome. - Primary hyperoxaluria. © 2010 Revista Nefrología. Órgano Oficial de la Sociedad Española de Nefrología. Source

Mann J.F.E.,Ludwig Maximilians University of Munich | Green D.,Quintiles | Jamerson K.,University of Michigan | Ruilope L.M.,Hospital 12 de Octubre | And 3 more authors.
Journal of the American Society of Nephrology | Year: 2010

In the short term, the endothelin antagonist avosentan reduces proteinuria, but whether this translates to protection from progressive loss of renal function is unknown. We examined the effects of avosentan on progression of overt diabetic nephropathy in a multicenter, multinational, double-blind, placebocontrolled trial. We randomly assigned 1392 participants with type 2 diabetes to oral avosentan (25 or 50 mg) or placebo in addition to continued angiotensin-converting enzyme inhibition and/or angiotensin receptor blockade. The composite primary outcome was the time to doubling of serum creatinine, ESRD, or death. Secondary outcomes included changes in albumin-to-creatinine ratio (ACR) and cardiovascular outcomes. We terminated the trial prematurely after a median follow-up of 4 months (maximum 16 months) because of an excess of cardiovascular events with avosentan. We did not detect a difference in the frequency of the primary outcome between groups. Avosentan significantly reduced ACR: In patients who were treated with avosentan 25 mg/d, 50 mg/d, and placebo, the median reduction in ACR was 44.3, 49.3, and 9.7%, respectively. Adverse events led to discontinuation of trial medication significantly more often for avosentan than for placebo (19.6 and 18.2 versus 11.5% for placebo), dominated by fluid overload and congestive heart failure; death occurred in 21 (4.6%; P = 0.225), 17 (3.6%; P = 0.194), and 12 (2.6%), respectively. In conclusion, avosentan reduces albuminuria when added to standard treatment in people with type 2 diabetes and overt nephropathy but induces significant fluid overload and congestive heart failure. Copyright © 2010 by the American Society of Nephrology. Source

News Article
Site: http://phys.org/chemistry-news/

Different studies have demonstrated that the ebola virus infection process starts when the virus reaches the cellular DC-SIGN receptor to infect the dendritic cells (of the immune system). European researchers have designed a "giant" molecule formed by thirteen fullerenes covered by carbohydrates which, by blocking this receptor, are able to inhibit the cell infection by an artificial ebola virus model. In this study, published in Nature Chemistry, researchers from the Universidad Complutense de Madrid/IMDEA-Nanociencia, the Instituto de Investigación Sanitaria Hospital 12 de Octubre (Madrid), and the Instituto de Investigaciones Químicas del CSIC-Universidad de Sevilla have collaborated, together with three european research groups (CNRS/Université de Strasbourg, France and Université de Namur, Belgium). "Fullerenes are hollow cages exclusively formed by carbon atoms", explains Nazario Martín, Professor of Organic Chemistry in the UCM and main author of the study. In this work, scientists have employed C60 fullerene, which is formed by 60 carbon atoms and has the shape of a truncated icosahedron, which resembles a football ball. These molecules decorated with specific carbohydrates (sugars) present affinity by the receptor used as an entry point to infect the cell and act blocking it, thus inhibiting the infection. Researchers employed an artificial ebola virus by expressing one of its proteins, envelope protein GP1, responsible of its entry in the cells. In a model in vitro, this protein is covering a false virus, which is able of cell infection but not of replication. "We have employed a cell model previously described in our lab which consists in a cell line of human lymphocytes expressing DC-SIGN receptor, which facilitates the entry of the virus in Dendritic Cells", points out Rafael Delgado, researcher of the Hospital 12 de Octubre, and other of the authors of the study. By blocking this receptor and inhibiting the virus infection, the authors think that the dissemination of the virus would decrease and the immune response increase, but this idea has still to be developed with in vivo studies. The biggest fullerene system in the lab The system designed by the chemists, based on carbon nanostructures developed in the UCM, mimic the presentation of carbohydrates surrounding virus like ebola or VIH. The team has achieved an unprecedented success in fullerene chemistry and dendritic growth: connecting in one synthetic step twelve fullerene units, each with ten sugars, to other central fullerene, creating a globular superstructure with 120 sugar moieties on its surface, "this is the fastest dendrimeric growth developed in a laboratory up to now" says Beatriz Illescas, Professor in the UCM and coauthor of the work. According to scientists, the results highlight the potential of these giant molecules as antiviral agents. "This work open the door to the design and preparation of new systems to inhibit the pathogens infection in cases where the current therapies are not effective or are inexistent, as occurs with the ebola virus", clarifies Martín. After these experiments on the cellular level, researchers will study the behavior of these systems in animal models, starting with mice. "We will study, on the one hand, the pharmacokinetics and, on the other, the antiviral activity in vivo" explains Javier Rojo, researcher of the Instituto de Investigaciones Químicas del CSIC and other of the authors of the study. Once the most effective compound has been identified, studies using the true ebola virus could be carried out. Explore further: New study identifies how ebola virus avoids the immune system More information: Nazario Martín et al. "Synthesis of giant globular multivalent glycofullerenes as potent inhibitors in a model of Ebola virus infection", Nature Chemistry, 9th November 2015. DOI: 10.1038/nchem.2387

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