Researchers have discovered that the inhibition in mice of an arterial wall protein, inducible nitric oxide synthase or NOS2, is capable of reversing aortic disease in Marfan syndrome – characterized by aortic, skeletal and ocular abnormalities – and In other forms of aneurysm. The results of the study, published in the journal Nature Medicine, suggest an important role of NOS2 protein inhibitors for the treatment of thoracic aortic aneurysms. Therefore, researchers have already contacted the pharmaceutical industry to determine the efficacy of these drugs in clinical trials with Marfan patients, underscoring the translational nature of the research.
An aneurysm is an abnormal dilatation or widening of a portion of an artery due to a pathological weakness of the vessel wall that may progress to rupture. It is an indolent pathology, which for a long period of time causes minimal or no, but also virulent, symptomatology, since it can suddenly experience catastrophic, often fatal complications. These characteristics make it essential to have an early and accurate diagnosis, a rigorous follow-up and a treatment with surgery at the right time.
Because the risk of aortic rupture increases with the degree of dilation of the artery, current pharmacological treatments for these diseases, including Marfan syndrome, seek to reduce mechanical stress on the aortic wall by decreasing the energy of cardiac contraction and Blood pressure. However, these drugs do not prevent the structural deterioration of the aortic wall, so they are not very effective in preventing their rupture. Surgical treatment is the only really effective, but it is not harmless, so it is indicated when the risk of aortic rupture is greater than that of surgery. Moreover, it does not improve or stop the intrinsic problem of the aortic wall, which is progressive and is not confined to a specific anatomical segment. Therefore, it is essential to identify the mechanisms responsible for the degeneration of the aortic wall and to discover new pharmacological targets to favorably modify the natural evolution of these diseases.
Therapeutic targets
In the published work the researchers have analyzed the molecular mechanisms involved in the formation and progression of thoracic aortic aneurysm. In this way, they identified two possible therapeutic targets: the metalloproteinase ADAMTS1 and the nitric oxide synthase NOS2. The results demonstrate that Adamts1-deficient mice develop a disease similar to Marfan's syndrome and, more importantly, genetic or pharmacological inactivation of NOS2 prevents and reverses aortopathy in ADAMTS1-deficient mice and in mice with Marfan syndrome experimental.
Dr. Nistal, leader of the IDIVAL group who has collaborated on the project, explains: “This work represents a significant advance in our understanding of the underlying molecular pathology in Marfan disease and other related diseases, and opens up new and hopeful pathways The finding of regression of aortic dilatation in elderly animals and aggressive models of Marfan seems to me to be particularly relevant, because it provides us with pharmacological tools with an etiopathogenic basis that may allow to effectively address the treatment, not only of the More aggressive neonatal forms of the disease, but of patients of any age. For our group it has been a privilege to collaborate in a project of high scientific level and with a perspective of translational research”.
Application in humans will still require time
Dr. Hurlé, a researcher at the Department of Physiology and Pharmacology at the University of Cantabria and coauthor, warns: “We must be cautious when transferring the conclusions obtained in experimental animal models to human disease. However, the efficacy of NOS2-specific inhibitory drugs in reversing aortic dilatation in mice models encourages clinical trials for both the treatment of Marfan syndrome and other similar aortic diseases”.
Reference: Oller J, Méndez-Barbero N, Ruiz EJ, Villahoz S, Renard M, Canelas LI, Briones AM, Alberca R, Lozano-Vidal N, Hurlé MA, Milewicz D, Evangelista A, Salaices M, Nistal JF, Jiménez-Borreguero LJ, De Backer J, Campanero MR, Redondo JM. Nitric oxide mediates aortic disease in mice deficient in the metalloprotease Adamts1 and in a mouse model of Marfan syndrome. Nat Med. 2017 Jan 9. doi: 10.1038/nm.4266. [Epub ahead of print] PubMed PMID: 28067899.
This week the journal Science has published in the editorial a paper in which have collaborated researchers from the University Hospital Marqués de Valdecilla and the University of Cantabria. The work has also been referenced in BioCentury. This reference marks a real milestone and points out the enormous interest and projection of the discoveries that […]
Mutua Madrileña Foundation’s XIV Call for Health Research Grants 2017 has already been opened until March 9 at 3:00 p.m.
Mutua Madrileña Foundation wants to continue giving greater relevance to clinical research excellence and therefore, this call will award 15 projects to teams of researchers with recognized experience.
Projects presented should be exclusively clinical research work, developed in accredited Health Research Institutes, and developed in one of the following four areas:
– Oncology: specifically gynecological cancer (cervix, ovaries and uterus).
– Transplants: exclusively strategies of improvement in the obtaining and use of organs for transplants.
– Traumatology and sequels: including neurological trauma.
– Rare diseases: manifested in childhood.
In order to further promote the figure of young researchers, the foundation will give special attention to projects in which the principal researcher is under 40 years of age at the closing date of the call.
The maximum amount requested per project, cannot exceed 150,000 euros.
Grants are intended for research projects with a duration of at least one year and a maximum of three years.
The same researcher, whether principal investigator or associate, may not coincide in more than one project submitted to the current call. In addition, no more than two projects may be funded by the same Accredited Health Research Institute (IIS).
The deadline for submission of applications from February 1 to March 9, 2017 at 3:00 p.m.
The application to participate in this call will be made exclusively online through the website of the Foundation http://www.fundacionmutua.es/Ayudas-a-la-Investigacion.html
Mutua Madrileña Foundation’s XIV Call for Health Research Grants 2017 has already been opened until March 9 at 3:00 p.m. Mutua Madrileña Foundation wants to continue giving greater relevance to clinical research excellence and therefore, this call will award 15 projects to teams of researchers with recognized experience. Projects presented should be exclusively clinical research […]
El Diario Montañés
El Diario Montañés Acta Sanitaria La Vanguardia
El Diario Montañés 20 Minutos ABC SER Cantabria Gaceta Médica
20 Minutos Acta Sanitaria Europapress
Our ability to control infectious diseases is continuously being eroded by antimicrobial resistance, a current major health problem worldwide. A large proportion of the research activities in our group is related to the study of physiological and biochemical aspects of the mechanisms of resistance to antimicrobial agents in bacteria. We consider clinical relevant Enterobacteria and non-fermenters, among others.
Our laboratory belongs to Idival’s Clinical and Molecular Microbiology Group and is contributing to the “Resistance Program” of the Spanish network for research on infection diseases (Red Española de Investigación en Patología Infecciosa, REIPI) supported by the Institute of Health Carlos III (ISCIII). This network is devoted to the study of different clinical and microbiological aspects of infections caused by resistant bacteria of clinical relevance, an important problem in many Spanish hospitals.
Immunofluorescence image showing a human immune cell (green) killing Acinetobacter baumannii bacteria (red).
Answering the need for studies of the mechanisms involved in the antimicrobials and host-pathogen relationship, we also seek to develop a multi-disciplinary research on host-pathogen interactions in these clinical relevant multi-drug-resistant (MDR) species by using cell sorting, advanced microscopy, and genomics.
Institute of Health Carlos III has granted the research lines of this group in the Strategic Action in Health 2016 with a total amount of 86.515€. The project under the name “Integrated biology of the infection and antimicrobial resistance in Acinetobacter baumannii and A. pittii” is led by the researcher Miguel Servert José Ramos and it will be developed at IDIVAL.
From right to left; Santiago Redondo Salvo, María Lázaro-Díez, Itziar Chapartegui González and Dr. José Ramos Vivas.
The main objectives in this project are:
1) To develop new tools for the study of host-pathogen interactions in Acinetobacter spp.
Nuestras capacidad para controlar las enfermedades infecciosas se ve continuamente erosionada por la aparición y dispersión de resistencia a los antibióticos, lo que es ya un problema mundial grave.
Una gran parte de las actividades de investigación de nuestro grupo está relacionada con el estudio de aspectos fisiológicos y bioquímicos de la resistencia bacteriana a los antibióticos. En nuestro laboratorio de Microbiología Celular del Instituto IDIVAL estudiamos enterobacterias (Enterobacter, Klebsiella), bacterias no fermentadoras (Acinetobacter) y Gram positivos (Staphylococcus aureus), entre otras.
Fotografía de inmunofluorescencia que muestra una célula del sistema inmunitario humano atacando bacterias de la especie multirresistente Acinetobacter baumannii (rojo).
El laboratorio pertenece al Grupo de investigación Microbiología Clínica y Molecular que forma parte de la Red Española de Investigación en Patología Infecciosa (REIPI), apoyada por el Instituto de Salud Carlos III (ISCIII) número de Expediente PI 16/01103. Esta red está dedicada al estudio de los distintos aspectos clínicos y microbiológicos de las infecciones causadas por bacterias resistentes a los antibióticos, un problema que es ya importante en los hospitales Españoles.
Respondiendo a la necesidad de buscar nuevas estrategias para combatir a estas bacterias, nuestro laboratorio realiza estudios sobre su interacción con células humanas. Para ello, desarrollamos una investigación multidisciplinar, desarrollando una serie de herramientas que nos permitirán caracterizar dichas interacciones y poder así buscar nuevas dianas terapéuticas y nuevos tratamientos contra estas bacterias multirresistentes (MDR).
El Instituto de Salud Carlos III ha financiado las líneas de este grupo en un proyecto liderado por el investigador Miguel Servet José Ramos en la convocatoria de la Acción Estratégica en Salud 2016 en concreto el proyecto titulado: Biología integrada de la infección y la resistencia antimicrobiana en Acinetobacterbaumannii and A. pittii, dotado con 86.515€, y que se desarrollará en el Instituto de Investigación Sanitaria Valdecilla (IDIVAL).
Equipo de Investigación: María Lázaro Díez, Itziar Chapartegui González y Santiago Redondo.
Los principales objetivos de este proyecto son:
1) Desarrollar nuevas herramientas para el estudio de las interacciones de Acinetobacter con células humanas.
2) Estudiar el impacto de distintas concentraciones de antibióticos contra las biocapas formadas por estas bacterias.
3) Estudiar la dinámica de la producción de vesículas por estas bacterias durante la formación de biocapas o durante su interacción con células humanas.
4) Realizar un análisis detallado de la respuesta inmunitaria de células humanas cuando se enfrentan a estos patógenos.
Fotografía electrónica de barrido mostrando un coágulo sanguíneo humano invadido por bacterias de la especie Acinetobacter baumannii. (azul).
Nuestras capacidad para controlar las enfermedades infecciosas se ve continuamente erosionada por la aparición y dispersión de resistencia a los antibióticos, lo que es ya un problema mundial grave.
Una gran parte de las actividades de investigación de nuestro grupo está relacionada con el estudio de aspectos fisiológicos y bioquímicos de la resistencia bacteriana a los antibióticos. En nuestro laboratorio de Microbiología Celular del Instituto IDIVAL estudiamos enterobacterias (Enterobacter, Klebsiella), bacterias no fermentadoras (Acinetobacter) y Gram positivos (Staphylococcus aureus), entre otras.
Fotografía de inmunofluorescencia que muestra una célula del sistema inmunitario humano atacando bacterias de la especie multirresistente Acinetobacter baumannii (rojo).
El laboratorio pertenece al Grupo de investigación Microbiología Clínica y Molecular que forma parte de la Red Española de Investigación en Patología Infecciosa (REIPI), apoyada por el Instituto de Salud Carlos III (ISCIII) número de Expediente PI 16/01103. Esta red está dedicada al estudio de los distintos aspectos clínicos y microbiológicos de las infecciones causadas por bacterias resistentes a los antibióticos, un problema que es ya importante en los hospitales Españoles.
Respondiendo a la necesidad de buscar nuevas estrategias para combatir a estas bacterias, nuestro laboratorio realiza estudios sobre su interacción con células humanas. Para ello, desarrollamos una investigación multidisciplinar, desarrollando una serie de herramientas que nos permitirán caracterizar dichas interacciones y poder así buscar nuevas dianas terapéuticas y nuevos tratamientos contra estas bacterias multirresistentes (MDR).
El Instituto de Salud Carlos III ha financiado las líneas de este grupo en un proyecto liderado por el investigador Miguel Servet José Ramos en la convocatoria de la Acción Estratégica en Salud 2016 en concreto el proyecto titulado: Biología integrada de la infección y la resistencia antimicrobiana en Acinetobacterbaumannii and A. pittii, dotado con 86.515€, y que se desarrollará en el Instituto de Investigación Sanitaria Valdecilla (IDIVAL).
Equipo de Investigación: María Lázaro Díez, Itziar Chapartegui González y Santiago Redondo.
Los principales objetivos de este proyecto son:
1) Desarrollar nuevas herramientas para el estudio de las interacciones de Acinetobacter con células humanas.
2) Estudiar el impacto de distintas concentraciones de antibióticos contra las biocapas formadas por estas bacterias.
3) Estudiar la dinámica de la producción de vesículas por estas bacterias durante la formación de biocapas o durante su interacción con células humanas.
4) Realizar un análisis detallado de la respuesta inmunitaria de células humanas cuando se enfrentan a estos patógenos.
Fotografía electrónica de barrido mostrando un coágulo sanguíneo humano invadido por bacterias de la especie Acinetobacter baumannii. (azul).
Nuestras capacidad para controlar las enfermedades infecciosas se ve continuamente erosionada por la aparición y dispersión de resistencia a los antibióticos, lo que es ya un problema mundial grave.
Una gran parte de las actividades de investigación de nuestro grupo está relacionada con el estudio de aspectos fisiológicos y bioquímicos de la resistencia bacteriana a los antibióticos. En nuestro laboratorio de Microbiología Celular del Instituto IDIVAL estudiamos enterobacterias (Enterobacter, Klebsiella), bacterias no fermentadoras (Acinetobacter) y Gram positivos (Staphylococcus aureus), entre otras.
Fotografía de inmunofluorescencia que muestra una célula del sistema inmunitario humano atacando bacterias de la especie multirresistente Acinetobacter baumannii (rojo).
El laboratorio pertenece al Grupo de investigación Microbiología Clínica y Molecular que forma parte de la Red Española de Investigación en Patología Infecciosa (REIPI), apoyada por el Instituto de Salud Carlos III (ISCIII) número de Expediente PI 16/01103. Esta red está dedicada al estudio de los distintos aspectos clínicos y microbiológicos de las infecciones causadas por bacterias resistentes a los antibióticos, un problema que es ya importante en los hospitales Españoles.
Respondiendo a la necesidad de buscar nuevas estrategias para combatir a estas bacterias, nuestro laboratorio realiza estudios sobre su interacción con células humanas. Para ello, desarrollamos una investigación multidisciplinar, desarrollando una serie de herramientas que nos permitirán caracterizar dichas interacciones y poder así buscar nuevas dianas terapéuticas y nuevos tratamientos contra estas bacterias multirresistentes (MDR).
El Instituto de Salud Carlos III ha financiado las líneas de este grupo en un proyecto liderado por el investigador Miguel Servet José Ramos en la convocatoria de la Acción Estratégica en Salud 2016 en concreto el proyecto titulado: Biología integrada de la infección y la resistencia antimicrobiana en Acinetobacterbaumannii and A. pittii, dotado con 86.515€, y que se desarrollará en el Instituto de Investigación Sanitaria Valdecilla (IDIVAL).
Equipo de Investigación: María Lázaro Díez, Itziar Chapartegui González y Santiago Redondo.
Los principales objetivos de este proyecto son:
1) Desarrollar nuevas herramientas para el estudio de las interacciones de Acinetobacter con células humanas.
2) Estudiar el impacto de distintas concentraciones de antibióticos contra las biocapas formadas por estas bacterias.
3) Estudiar la dinámica de la producción de vesículas por estas bacterias durante la formación de biocapas o durante su interacción con células humanas.
4) Realizar un análisis detallado de la respuesta inmunitaria de células humanas cuando se enfrentan a estos patógenos.
Fotografía electrónica de barrido mostrando un coágulo sanguíneo humano invadido por bacterias de la especie Acinetobacter baumannii. (azul).
Our ability to control infectious diseases is continuously being eroded by antimicrobial resistance, a current major health problem worldwide. A large proportion of the research activities in our group is related to the study of physiological and biochemical aspects of the mechanisms of resistance to antimicrobial agents in bacteria. We consider clinical relevant Enterobacteria and […]
According to the strategy of Valdecilla Biosanitary Strategic Health Program 2017 to attract talent, IDIVAL has convened Valdecilla Mentoring, a mentoring program for new residents.
-Mentoring. The candidate will have a mentor proposed by the scientific management of IDIVAL, in agreement with the Head of the service of the specialty that will follow the evolution of the residence with special attention in the aspects of research.
– Research funds. From the second year the candidate will have a € 8,000 scholarship for the development of research activities to be managed according to IDIVAL project management standards.
– Itinerary Training. From the second year, the address of IDIVAL together with the Training Coordinator of the University Hospital Marqués de Valdecilla and in agreement with the Head of Service of the corresponding specialty will propose specific training in research that may include specific rotations inside and outside the Hospital. This includes attendance at research seminars and doctoral program.
– Institutional presence. The candidate will be invited periodically to the meetings of the Teaching Commission and Internal Scientific Council to monitor their training.
– PhD thesis. One of the objectives of the program is that the resident can advance in developing its doctoral thesis during the residence.
– Prioritized access to other IDIVAL support programs such as Next-Val or Post MIR Valdecilla.
This program will be open to applications within the first 8 weeks of incorporation to the University Hospital Marques de Valdecilla as a resident.
More information can be found in the following link:
According to the strategy of Valdecilla Biosanitary Strategic Health Program 2017 to attract talent, IDIVAL has convened Valdecilla Mentoring, a mentoring program for new residents. This program, aimed to future specialists of University Hospital Marques de Valdecilla, promotes the recruitment of graduates who have achieved a leading number in the MIR exam and proposes a […]
El Diario Montañés Infosalus 20 Minutos Redacción Médica Alerta
IDIVAL convenes for a third year a 24-month fellowship that can be extended to 36 months of research management training. The selected candidate will develop a tutored training itinerary, specifically designed, with periodic evaluations and presentation of an annual report (in the last month of each year) with a tutor's report that should be positive for continuity of the aid.
The training itinerary will include rotators for the different areas of the Central Support Unit and may include external rotators.
The training plan will be developed under the supervision of teams of managers who provide support to researchers in the dissemination and promotion of calls for research grants, preparation and application of projects presented to different calls, and support in the Implementation of these projects. These managers also perform tasks related to the fulfillment of the obligations that the IDIVAL Foundation must undertake.
Some of the specific issues that are planned as part of the training path of this program include acquisition of knowledge related to sources of funding, regulation of clinical research, compliance with research regulations, recruitment of staff and procurement of goods and services in Research projects, economic reporting, audits, liaison with funding agencies, and development of industrial protection.
In this way the management of research forms a discipline whose formation requires knowledge of diverse nature, for which IDIVAL proposes a training plan in research management through the following call.
The call will be open until February 28, 2017
More information on the IDIVAL help
IDIVAL convenes for a third year a 24-month fellowship that can be extended to 36 months of research management training. The selected candidate will develop a tutored training itinerary, specifically designed, with periodic evaluations and presentation of an annual report (in the last month of each year) with a tutor's report that should be positive […]
