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Interplay among hypoxia, iron and inflammation
Italy (SISM) - University of Milan, Milan
Department of Health Science
Michele Samaja, Anna Caretti, Sara Ottolenghi
Michele Samaja, Anna Caretti, Sara Ottolenghi
Type of Research Project
- Clinical Project with Laboratory work
What is the background of the project?
Hypoxia, or lack of oxygen, can occur in both physiological (high altitude) and pathological (respiratory diseases) conditions. In this narrative review, we introduce high altitude pulmonary edema (HAPE), acute respiratory distress syndrome (ARDS), Chronic Obstructive Pulmonary Disease (COPD) and Cystic Fibrosis (CF) as examples of maladaptation to hypoxia, and highlight some of the potential mechanisms influencing the prognosis of the affected patients. Among the specific pathways modulated in response to hypoxia, iron metabolism has been widely explored in recent years. Recent studies emphasize hepcidin as highly involved in the compensatory response to hypoxia in healthy subjects. A less investigated field in the adaptation to hypoxia is sphingolipid (SPL) metabolism, especially through ceramide (Cer) and sphingosine-1-phosphate (S1P). Both individually and in concert, iron and SPL are active players of the (mal)adaptation to physiological hypoxia, which can result in pathological HAPE.
What is the aim of the project?
Our aim is to identify pathways and/or markers involved in the physiological adaptation to low atmospheric pressures (high altitudes) that may be involved in pathological adaptation to hypoxia as it occurs in pulmonary inflammatory diseases. Hepcidin, Cer, S1P and their interplay in hypoxia are raising growing interest both as prognostic factors and therapeutical targets.
What techniques and methods are used?
Collecting informed consent from patients, critical examination of blood analysis reports, blood sample processing (e.g., anticolagulant to be used, timing, centrufugation, storage conditions), some analytical laboratory techniques, such as enzyme-linked immunosorbent assay (ELISA) and radioimmunoassay (RIA), spectrophotometry with appropriate standards and internal controls, data reduction (e.g., selecting data to be reported and plotted), preparation of reports, appropriate statistical analysis, principles of scientific integrity.
What is the role of the student?
- The student will observe the practical experiments but will be highly involved in the analysis of the results
- If the project includes “lab work”
- the student will take active part in the practical aspect of the project
- The tasks will be done under supervision
What are the tasks expected to be accomplished by the student?
The student will learn how to collect the informed consent from patients, how to critically understand blood analysis reports, how to process blood samples (e.g., anticolagulant to be used, timings, centrufugations, storage conditions), how to perform some analytical laboratory tecniques with particular attention to ELISA and RIA methods, spectrophotometry methods, with appropriate standards and internal controls. Finally, he/she will learn how to proceed to data reduction (e.g., selecting data to be plotted), prepare reports and run appropriate statistical analysis. Special care will be devoted to the principles of scientific integrity.
Will there be any theoretical teaching provided (preliminary readings, lectures, courses, seminars etc)
Yes: scientific literature, preliminary readings, lectures, courses, seminars.
What is expected from the student at the end of the research exchange? What will be the general outcome of the student?
- The student will prepare a scientific report - No specific outcome is expected
What skills are required of the student? Is there any special knowledge or a certain level of studies needed?
A willingness to learn. Subjects passed: Biochemistry, Physiology, Pathology, Critical Care, Pneumology
Are there any legal limitations in the student’s involvement
Type of students accepted
This project accepts: - Medical students - Graduated students (less than 6 months)
- Wittkamp; C.; Traeger; L.; Ellermann; I.; Eveslage; M.; & Steinbicker; A. U. (2018). Hepcidin as a potential predictor for preoperative anemia treatment with intravenous iron—A retrospective pilot study. PLoS ONE; 13(8); 1–16. https://doi.org/10.1371/journal.pone.0201153
- Khiroya; H.; & Turner; A. M. (2015). The role of iron in pulmonary pathology. Multidisciplinary Respiratory Medicine; 10(1); 1–7. https://doi.org/10.1186/s40248-015-0031-2
- Gassmann; M.; & Muckenthaler; M. U. (2015). Adaptation of iron requirement to hypoxic conditions at high altitude. Journal of Applied Physiology; 119(12); 1432–1440. https://doi.org/10.1152/japplphysiol.00248.2015
- Boshuizen; M.; Binnekade; J. M.; Nota; B.; van de Groep; K.; Cremer; O. L.; Tuinman; P. R.; … Verboom; D. M. (2018). Iron metabolism in critically ill patients developing anemia of inflammation: a case control study. Annals of Intensive Care; 8(1). https://doi.org/10.1186/s13613-018-0407-5
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