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Oxidative stress, which refers to cellular damage caused by reactive oxygen intermediates, has been implicated in many disease processes, especially age-related disorders. Many trials investigating use of antioxidants in protecting different tissues against oxidative stress have been conducted, but the results are ambiguous.
Inflammation is generally associated with enhanced oxidative stress and widespread endothelial dysfunction. In the present study, the infusion of LPS, which is a cell wall component of Gram-negative bacteria and a major mediator in the pathogenesis of septic shock, will be used as a standardized experimental model of systemic inflammatory response in humans. The assessment of outcome parameters will include measurements of ocular blood flow, forearm blood flow and plasma concentration of cytokines. Measurements of ocular hemodynamics provide an unique chance to investigate local blood flow in humans non-invasively. Moreover, the retina is especially susceptible to oxidative stress because of its high consumption of oxygen, its high polyunsaturated fatty acid content, and its exposure to visible light. Evidence from literature clearly supports a role for oxidative stress in pathophysiology of several ocular diseases including diabetic retinopathy and age-related macular degeneration. To investigate the retinal vascular reactivity we will use systemic hyperoxia as a stimulus. The measurement of forearm blood flow will be use to assess endothelial function. The main study objective is to investigate the effect of oral vitamins and minerals supplementation on impaired retinal vascular reactivity after LPS administration.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1 | Active Comparator |
| |
| 2 | Placebo Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| vitamin and mineral supplement | Drug | dose: 4 tablets daily for two weeks vitamin A 7160 IU, vitamin C 113mg, vitamin E 100IU, zinc 17.4mg, copper 0.4mg |
|
| Measure | Description | Time Frame |
|---|---|---|
| Retinal blood flow | in total 8x on 2 study days |
| Measure | Description | Time Frame |
|---|---|---|
| Choroidal blood flow | in total 4x on 2 study days | |
| Flow mediated dilation (FMD) of brachial artery assessed with ultrasound | in total 4x on 2 study days | |
| Blood pressure, heart rate |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Michael Wolzt, MD | Department of Clinical Pharmacology, Medical University of Vienna | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department of Clinical Pharmacology, Medical University of Vienna | Vienna | 1090 | Austria |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 19684008 | Derived | Pemp B, Polska E, Karl K, Lasta M, Minichmayr A, Garhofer G, Wolzt M, Schmetterer L. Effects of antioxidants (AREDS medication) on ocular blood flow and endothelial function in an endotoxin-induced model of oxidative stress in humans. Invest Ophthalmol Vis Sci. 2010 Jan;51(1):2-6. doi: 10.1167/iovs.09-3888. Epub 2009 Aug 13. |
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| Escherichia coli Endotoxin (LPS) | Drug | dose: 2 ng/kg (corresponding to 20 IU/kg), intravenous bolus over 5 minutes on both study days |
|
|
| 100% O2 | Drug | breathing for 30 minutes, 2 breathing periods on both study days |
|
| nitroglycerin | Drug | dose: 0,8 mg sublingual, applied during FMD measurements on both study days |
|
|
| on 2 study days |
| Body temperature | on 2 study days |
| Concentration of cytokines in plasma | on 2 study days |
| ID | Term |
|---|---|
| D004927 | Escherichia coli Infections |
| ID | Term |
|---|---|
| D004756 | Enterobacteriaceae Infections |
| D016905 | Gram-Negative Bacterial Infections |
| D001424 | Bacterial Infections |
| D001423 | Bacterial Infections and Mycoses |
| D007239 | Infections |
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| ID | Term |
|---|---|
| D014815 | Vitamins |
| C044101 | endotoxin, Escherichia coli |
| D008070 | Lipopolysaccharides |
| D005996 | Nitroglycerin |
| ID | Term |
|---|---|
| D018977 | Micronutrients |
| D045505 | Physiological Effects of Drugs |
| D020228 | Pharmacologic Actions |
| D020164 | Chemical Actions and Uses |
| D000078622 | Nutrients |
| D005502 | Food |
| D000066888 | Diet, Food, and Nutrition |
| D010829 | Physiological Phenomena |
| D019602 | Food and Beverages |
| D006001 | Glycoconjugates |
| D002241 | Carbohydrates |
| D011135 | Polysaccharides, Bacterial |
| D011134 | Polysaccharides |
| D008055 | Lipids |
| D000942 | Antigens, Bacterial |
| D000941 | Antigens |
| D001685 | Biological Factors |
| D004731 | Endotoxins |
| D001427 | Bacterial Toxins |
| D014118 | Toxins, Biological |
| D009574 | Nitro Compounds |
| D009930 | Organic Chemicals |
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