Proteomics for Identification of Hyperoxia-induced Changes in Protein Expression

Study Overview
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Brief Summary
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Aim of the present study is to investigate the influence of hyperoxia on the protein expression using the differential analysis of protein expression in tissues (proteomics). In the study, blood and urine samples will be collected from participants who undergo a short term hyperoxia using 100% oxgen for 3 hours. Here, gel electrophoresis, protein separation and mass spectroscopy allow to identify affected proteins. Based on these results, different induction factors of proteins will be determined and then assessed using a bioinformatic network analysis regarding the cellular influence.

Detailed Description
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Oxygen is necessary to sustain human life and is used for energy production by oxidation in the mitochondria. Application of oxygen not only increases saturation in the patient's blood, but also has various secondary effects. It is therefore used to treat diseases that impairs body's ability to take up and use oxygen. But even healthy people can suffer from hypoxia when they ascend to high altitude. Here, altitude sickness can lead to potentially fatal complications such as high altitude cerebral edema or high altitude pulmonary edema. Since hypoxia can have disastrous consequences, hyperoxia is often tolerated in many pre- and in-hospital situations. Whereas the effects of hypoxia are well studied, especially publications in the last decade have led to a new perspective on oxygen application. Besides pathophysiological changes as the peripheral vasoconstriction or reduction of contractility, especially changes on cellular level seem to be of great importance. Here, oxidative stress and change of protein synthesis in various organ are focus of current studies. The differential analysis of protein expression in tissues (proteomics) is an important approach for better understanding of the negative effects of hyperoxia. Especially for patients with long-term high oxygen demand the knowledge of cellular changes during hyperoxia can result in new therapeutic approaches and a reduction in the rate of complications. In the present molecular biology study urine and blood samples of healthy volunteers will be collected at specified times after short-term exposure to oxygen. These samples will be analyzed after the study using the differential analysis of protein expression. The aim of this study is to investigate the effects of oxygen on the cell functions by analyzing and subsequent bioinformatic processing of differentially regulated proteins in the blood and urine. After checking the inclusion and exclusion criteria biometric data of the test persons are collected. Before short-term hyperoxia a sample collection of blood and urine will be performed. Here the participants are taken 5 ml of venous blood from the cephalic vein under sterile conditions. To obtain the urine sample spontaneous urine of participants is used. The samples are immediately centrifuged and flash frozen at -80°C. In order to exclude impairment of the lung prior to the short-term hyperoxia a pulmonary function test is carried out by using a hand spirometer. To induce hyperoxia subjects inhale 100% oxygen for 3 hours through a face mask. After carrying out the short term hyperoxia the follow up phase takes place. In this phase blood and urine samples from the subjects will be obtained directly after the hyperoxia (T0), on day 1 (T1), day 3 (T3), day 7 (T7), day 14 (T14), day 21 (T21) and day 28 (T28) after oxygen exposure. All samples will be centrifuged immediately after collection and flash frozen at -80 ° C. To exclude hyperoxia-induced lung impairments, a spirometry is performed during the follow up. After the samples of all subjects were collected the analysis of the samples will be carried out using Proteomics.

Official Title
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Proteomics for Identification of Hyperoxia-induced Changes in Protein Expression

Conditions
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Hyperoxia

Intervention / Treatment
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* Drug: Oxygen (FiO2 1,0)
* Device: Facemask


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: American Society of Anesthesiologists (ASA) 1 >18 years < 50 years Exclusion Criteria: American Society of Anesthesiologists (ASA) > 1 pregnant <18 years > 50 years frequent or recent drug intake

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hyperoxia<br>Participants receive 100% oxygen | Drug: Oxygen (FiO2 1,0)<br>* Participants will inhale Oxygen (FiO2 1,0) via Facemask for 3 hours.<br>Device: Facemask<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of proteomics changes before and after short-term hyperoxia |  | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Spirometry Results: Forced vital capacity (FVC) [L] | Spirometry will be used as a measure of safety to rule out adverse events of oxygen to the lung. | 2 days | 
| Spirometry Results: Forced expiratory volume at one second (FEV1) [L] | Spirometry will be used as a measure of safety to rule out adverse events of oxygen to the lung. | 2 days | 
| Spirometry Results: Forced expiratory flow (FEF25-75) [L/s] | Spirometry will be used as a measure of safety to rule out adverse events of oxygen to the lung. | 2 days | 
| Spirometry Results: Peak expiratory flow (PEF) [L/s] | Spirometry will be used as a measure of safety to rule out adverse events of oxygen to the lung. | 2 days | 
| Vital parameter: Respiratory rate (RR) [1/min] | Vital parameters will be used as a measure of safety to rule out adverse events of oxygen to the vascular system. | 3 hours | 
| Vital parameter: Heart rate (HR) [1/min] | Vital parameters will be used as a measure of safety to rule out adverse events of oxygen to the vascular system. | 3 hours | 
| Vital parameter: Blood pressure (BP) [mmHg] | Vital parameters will be used as a measure of safety to rule out adverse events of oxygen to the vascular system. | 3 hours | 
| Vital parameter: Oxygen saturation (SpO2) [%] | Vital parameters will be used as a measure of safety to rule out adverse events of oxygen to the vascular system. | 3 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Proteomics, Oxygen, Pathways