TY  - JOUR
A1  - Elgheznawy, Amro
A1  - Öftering, Patricia
A1  - Englert, Maximilian
A1  - Mott, Kristina
A1  - Kaiser, Friederike
A1  - Kusch, Charly
A1  - Gbureck, Uwe
A1  - Bösl, Michael R.
A1  - Schulze, Harald
A1  - Nieswandt, Bernhard
A1  - Vögtle, Timo
A1  - Hermanns, Heike M.
T1  - Loss of zinc transporters ZIP1 and ZIP3 augments platelet reactivity in response to thrombin and accelerates thrombus formation in vivo
JF  - Frontiers in Immunology
N2  - Zinc (Zn2+) is considered as important mediator of immune cell function, thrombosis and haemostasis. However, our understanding of the transport mechanisms that regulate Zn2+ homeostasis in platelets is limited. Zn2+ transporters, ZIPs and ZnTs, are widely expressed in eukaryotic cells. Using mice globally lacking ZIP1 and ZIP3 (ZIP1/3 DKO), our aim was to explore the potential role of these Zn2+ transporters in maintaining platelet Zn2+ homeostasis and in the regulation of platelet function. While ICP-MS measurements indicated unaltered overall Zn2+ concentrations in platelets of ZIP1/3 DKO mice, we observed a significantly increased content of FluoZin3-stainable free Zn2+, which, however, appears to be released less efficiently upon thrombin-stimulated platelet activation. On the functional level, ZIP1/3 DKO platelets exhibited a hyperactive response towards threshold concentrations of G protein-coupled receptor (GPCR) agonists, while immunoreceptor tyrosine-based activation motif (ITAM)-coupled receptor agonist signalling was unaffected. This resulted in enhanced platelet aggregation towards thrombin, bigger thrombus volume under flow ex vivo and faster in vivo thrombus formation in ZIP1/3 DKO mice. Molecularly, augmented GPCR responses were accompanied by enhanced Ca2+ and PKC, CamKII and ERK1/2 signalling. The current study thereby identifies ZIP1 and ZIP3 as important regulators for the maintenance of platelet Zn2+ homeostasis and function.
KW  - platelets
KW  - zinc
KW  - ZIP
KW  - thrombin
KW  - signaling
KW  - thrombosis
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-320154
VL  - 14
ER  - 
TY  - JOUR
A1  - Dresen, Ellen
A1  - Pimiento, Jose M.
A1  - Patel, Jayshil J.
A1  - Heyland, Daren K.
A1  - Rice, Todd W.
A1  - Stoppe, Christian
T1  - Overview of oxidative stress and the role of micronutrients in critical illness
JF  - Journal of Parenteral and Enteral Nutrition
N2  - Inflammation and oxidative stress represent physiological response mechanisms to different types of stimuli and injury during critical illness. Its proper regulation is fundamental to cellular and organismal survival and are paramount to outcomes and recovery from critical illness. A proper maintenance of the delicate balance between inflammation, oxidative stress, and immune response is crucial for resolution from critical illness with important implications for patient outcome. The extent of inflammation and oxidative stress under normal conditions is limited by the antioxidant defense system of the human body, whereas the antioxidant capacity is commonly significantly compromised, and serum levels of micronutrients and vitamins significantly depleted in patients who are critically ill. Hence, the provision of antioxidants and anti-inflammatory nutrients may help to reduce the extent of oxidative stress and therefore improve clinical outcomes in patients who are critically ill. As existing evidence of the beneficial effects of antioxidant supplementation in patients who are critically ill is still unclear, actual findings about the most promising anti-inflammatory and antioxidative candidates selenium, vitamin C, zinc, and vitamin D will be discussed in this narrative review. The existing evidence provided so far demonstrates that several factors need to be considered to determine the efficacy of an antioxidant supplementation strategy in patients who are critically ill and indicates the need for adequately designed multicenter prospective randomized control trials to evaluate the clinical significance of different types and doses of micronutrients and vitamins in selected groups of patients with different types of critical illness.
KW  - critical illness
KW  - vitamins
KW  - vitamin C
KW  - inflammation
KW  - medical nutrition therapy
KW  - oxidative stress
KW  - selenium
KW  - trace elements
KW  - micronutrients
KW  - vitamin D
KW  - zinc
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-318186
VL  - 47
SP  - S38
EP  - S49
ER  - 
TY  - JOUR
A1  - Notz, Quirin
A1  - Herrmann, Johannes
A1  - Schlesinger, Tobias
A1  - Helmer, Philipp
A1  - Sudowe, Stephan
A1  - Sun, Qian
A1  - Hackler, Julian
A1  - Roeder, Daniel
A1  - Lotz, Christopher
A1  - Meybohm, Patrick
A1  - Kranke, Peter
A1  - Schomburg, Lutz
A1  - Stoppe, Christian
T1  - Clinical Significance of Micronutrient Supplementation in Critically Ill COVID-19 Patients with Severe ARDS
JF  - Nutrients
N2  - The interplay between inflammation and oxidative stress is a vicious circle, potentially resulting in organ damage. Essential micronutrients such as selenium (Se) and zinc (Zn) support anti-oxidative defense systems and are commonly depleted in severe disease. This single-center retrospective study investigated micronutrient levels under Se and Zn supplementation in critically ill patients with COVID-19 induced acute respiratory distress syndrome (ARDS) and explored potential relationships with immunological and clinical parameters. According to intensive care unit (ICU) standard operating procedures, patients received 1.0 mg of intravenous Se daily on top of artificial nutrition, which contained various amounts of Se and Zn. Micronutrients, inflammatory cytokines, lymphocyte subsets and clinical data were extracted from the patient data management system on admission and after 10 to 14 days of treatment. Forty-six patients were screened for eligibility and 22 patients were included in the study. Twenty-one patients (95%) suffered from severe ARDS and 14 patients (64%) survived to ICU discharge. On admission, the majority of patients had low Se status biomarkers and Zn levels, along with elevated inflammatory parameters. Se supplementation significantly elevated Se (p = 0.027) and selenoprotein P levels (SELENOP; p = 0.016) to normal range. Accordingly, glutathione peroxidase 3 (GPx3) activity increased over time (p = 0.021). Se biomarkers, most notably SELENOP, were inversely correlated with CRP (r\(_s\) = −0.495), PCT (r\(_s\) = −0.413), IL-6 (r\(_s\) = −0.429), IL-1β (r\(_s\) = −0.440) and IL-10 (r\(_s\) = −0.461). Positive associations were found for CD8\(^+\) T cells (r(_s\) = 0.636), NK cells (r\(_s\) = 0.772), total IgG (r\(_s\) = 0.493) and PaO\(_2\)/FiO\(_2\) ratios (r\(_s\) = 0.504). In addition, survivors tended to have higher Se levels after 10 to 14 days compared to non-survivors (p = 0.075). Sufficient Se and Zn levels may potentially be of clinical significance for an adequate immune response in critically ill patients with severe COVID-19 ARDS.
KW  - acute respiratory distress syndrome
KW  - selen
KW  - zinc
KW  - critical care
KW  - oxidative stress
KW  - nutrient supplementation
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-241112
SN  - 2072-6643
VL  - 13
IS  - 6
ER  -