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(Santiago de Chile) Novel therapeutics proposals for pulmonary hypertension of the neonate in lambs gestated under chronic hypoxia at the Andean highlands.
Universidad de Chile
Pathophysiology Program, ICBM, Faculty of Medicine
Manuel Oyarzun, PhD.
Emilio Herrera, PhD.
Type of Research Project
- Basic science
What is the background of the project?
This project is under the grant entitled: To be born high and flat (Andean Altiplano): healing vascular function and pulmonary arterial hypertension by a combined treatment in neonatal lambs, funded by FONDECYT(Fondo Nacional de Desarrollo Cient
What is the aim of the project?
This grant aims to understand the biology of oxidative stress as an ethiology of neonatal pulmonary hypertension at high altitude. Further, identifying the mechanisms underlying this pulmonary hypertension will allow us to propose better therapeutic approaches to this clinical burden. Currently, we are evaluating the use of postnatal melatonin to treat the oxidative stress effects induced by high-altitude in the perinatal period.
What techniques and methods are used?
Using an integrative approach at the systems, isolated organ, cellular and molecular levels, we are determining whether: oxidative stress is enhanced in the postnatal period of the high altitude lamb, if this condition is a determinant of the pulmonary hypertension, and if the treatment with melatonin in neonates complicated with sustained fetal hypoxia at highlands prevents the developmental programming of neonatal pulmonary hypertension. At a current stage (2012), we are using laboratory techniques such as PCR, Western blot, Immunohistochemistry and morphohistological analysis.
What is the role of the student?
- The student will mainly observe
- The student will observe the practical experiments but will be highly involved in the analysis of the results
What are the tasks expected to be accomplished by the student?
The student will learn to design, program and perform experiments in the Lab. (PCR, qRT- PCR, WB, IHC), from the sample preparation until the results analysis and discussion. To achieve these, the student shall develop practical skills, critical thinking and effective teamwork. Finally, the student will join discussions to insert the experimental results in current knowledge (clinical, biochemical and molecular) of neonatal pulmonary hypertension.
Will there be any theoretical teaching provided (preliminary readings, lectures, courses, seminars etc)
Preliminary readings such as papers related with the research.
What is expected from the student at the end of the research exchange? What will be the general outcome of the student?
- No specific outcome is expected
What skills are required of the student? Is there any special knowledge or a certain level of studies needed?
There are no specific training or skills required, but we recommend highly disciplined, organized and motivated students. In this way, students will be able to get the maximum benefits of learning and applying the scientific method.
Are there any legal limitations in the student’s involvement
In the period of June-July of every year, we are travelling to the “International Center for Andean Studies” at Putre, 3600 mts to perform experimental work with sheeps (in vivo and ex vivo). Students are welcome to participate in these activities but some of the costs (flights, insurance) may not be included. We are working under strict bioethical conditions and local committee approval, it is imperative that the students are agree with use of animal models for research porpuses.
Type of students accepted
This project accepts: - Medical students - Graduated students (less than 6 months) - Pre-Medical students from the American-British system
- Llanos et al. Fetal and postnatal pulmonary circulation in the Alto Andino. Placenta. 32 Suppl 2:S100-3; 2011.
- Herrera et al. Long term exposure to high altitude chronic hypoxia during gestation induces neonatal pulmonary hypertension at sea level. Am J Physiol Regul Integr Comp Physiol. 299(6):R1676-84; 2010.
- Herrera et al. Carbon monoxide and pulmonary vasodilatation in neonatal llamas (Lama glama) at the Andean altiplano. Cardiovasc Res. 77(1):197-201; 2008.
- Herrera et al. Sildenafil reverses hypoxic pulmonary hipertensión in highland and lowland newborn sheep. Pediatr Res. 63(2):169-175; 2008.
- Giussani et al. Developmental programming of cardiovascular dysfunction by prenatal hypoxia and oxidative stress. PLoS One. 7(2):e31017; 2012.
- Herrera et al. Antioxidant treatment alters peripheral vascular dysfunction induced by postnatal glucocorticoid therapy in rats. PLoS One. 5(2):e9250; 2010.
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