Immature platelets in COVID-19 Wolny, Monika; Dittrich, Marcus; Knabbe, Cornelius ...
Platelets (Edinburgh)
34, Issue:
1
Journal Article
Peer reviewed
Open access
Platelets play a critical role in immune response. Coronavirus disease 2019 (COVID-19) patients with a severe course often show pathological coagulation parameters including thrombocytopenia, and at ...the same time the proportion of immature platelets increases. In this study, the platelet count and the immature platelet fraction (IPF) of hospitalized patients with different oxygenation requirements was investigated daily over a course of 40 days. In addition, the platelet function of COVID-19 patients was analyzed. It was found that the number of platelets in patients with the most severe course (intubation and extracorporeal membrane oxygenation (ECMO)) was significantly lower (111.5 ∙ 10
/mL) than in the other groups (mild (no intubation, no ECMO): 203.5 ∙ 10
/mL,
< .0001, moderate (intubation, no ECMO): 208.0 ∙ 10
/mL,
< .0001). IPF tended to be elevated (10.9%). Platelet function was reduced. Differentiation by outcome revealed that the deceased patients had a highly significant lower platelet count and higher IPF (97.3 ∙ 10
/mL,
< .0001, 12.2%,
= .0003).
Currently, it is not well understood how ligands of the aryl hydrocarbon receptor (AhR) modify inflammatory responses triggered by Toll-like receptor (TLR) agonists in human dendritic cells (DCs). ...Here, we show that AhR ligands 2,3,7,8-tetrachlorodibenzo-
p
-dioxin (TCDD), the tryptophan derivatives 6-formylindolo3,2-b carbazole (FICZ), kynurenine (kyn), and the natural dietary compound indole-3-carbinol (I3C) differentially modify cytokine expression in human monocyte-derived DCs (MoDCs). The results show that TLR-activated MoDCs express higher levels of AhR and are more sensitive toward the effects of AhR ligands. Depending on the cytokine, treatment with AhR ligands led to a synergistic or antagonistic effect of the TLR-triggered response in MoDCs. Thus, activation of AhR increased the expression of interleukin (IL)-1β, but decreased the expression of IL-12A in TLR-activated MoDCs. Furthermore, TCDD and FICZ may have opposite effects on the expression of cytochrome P4501A1 (CYP1A1) in TLR8-activated MoDCs indicating that the effect of the specific AhR ligand may depend on the presence of the specific TLR agonist. Gene silencing showed that synergistic effects of AhR ligands on TLR-induced expression of IL-1β require a functional AhR and the expression of NF-κB RelB. On the other hand, repression of IL-12A by TCDD and FICZ involved the induction of the caudal type homeobox 2 (CDX2) transcription factor. Additionally, the levels of DC surface markers were decreased in MoDCs by TCDD, FICZ and I3C, but not by kyn. Overall, these data demonstrate that AhR modulates TLR-induced expression of cytokines and DC-specific surface markers in MoDCs involving NFκB RelB and the immune regulatory factor CDX2.
Platelets, the smallest cells in human blood, known for their role in primary hemostasis, are also able to interact with pathogens and play a crucial role in the immune response. In severe ...coronavirus disease 2019 (COVID-19) cases, platelets become overactivated, resulting in the release of granules, exacerbating inflammation and contributing to the cytokine storm. This study aims to further elucidate the role of platelets in COVID-19 progression and to identify predictive biomarkers for disease outcomes. A comparative proteome analysis of highly purified platelets from critically diseased COVID-19 patients with different outcomes (survivors and non-survivors) and age- and sex-matched controls was performed. Platelets from critically diseased COVID-19 patients exhibited significant changes in the levels of proteins associated with protein folding. In addition, a number of proteins with isomerase activity were found to be more highly abundant in patient samples, apparently exerting an influence on platelet activity via the non-genomic properties of the glucocorticoid receptor (GR) and the nuclear factor κ-light-chain-enhancer of activated B cells (NFκB). Moreover, carbonic anhydrase 1 (CA-1) was found to be a candidate biomarker in platelets, showing a significant increase in COVID-19 patients.
Chronic inflammation and excessive synthesis of extracellular matrix components, such as proteoglycans (PG), by fibroblast- or macrophage-derived myofibroblasts are the hallmarks of fibrotic ...diseases, including systemic sclerosis (SSc). Human xylosyltransferase-I (XT-I), which is encoded by the gene XYLT1, is the key enzyme that is involved in PG biosynthesis. Increased cellular XYLT1 expression and serum XT-I activity were measured in SSc. Nothing is known so far about the regulation of XT-I in immune cells, and their contribution to the increase in measurable serum XT-I activity. We utilized an in vitro model, with primary human CD14+CD16+ monocyte-derived macrophages (MΦ), in order to investigate the role of macrophage polarization on XT-I regulation. The MΦ generated were polarized towards two macrophage phenotypes that were associated with SSc, which were classified as classical pro-inflammatory (M1-like), and alternative pro-fibrotic (M2-like) MΦ. The fully characterized M1- and M2-like MΦ cultures showed differential XT-I gene and protein expressions. The fibrotic M2-like MΦ cultures exhibited higher XT-I secretion, as well as increased expression of myofibroblast marker α-smooth muscle actin, indicating the onset of macrophage-to-myofibroblast transition (MMT). Thus, we identified XT-I as a novel macrophage polarization marker for in vitro generated M1- and M2-like MΦ subtypes, and broadened the view of XT-I as a myofibroblast marker in the process of MMT.
Thrombosis is common in critically ill dogs and causes considerable morbidity and mortality. The direct factor Xa inhibitor apixaban is safe, efficacious, and convenient in humans. This study aimed ...to determine the pharmacokinetics (PK), bioactivity, protein binding, and bioavailability of apixaban following intravenous (IV) and oral (PO) administration to healthy dogs. Six healthy, adult, mixed-breed dogs were administered apixaban 0.18 mg/kg IV and then following a minimum 2-week washout period administered apixaban 0.2 mg/kg PO. Dogs were monitored using an apixaban-calibrated anti-Xa bioassay, prothrombin time (PT) and activated partial thromboplastin time (aPTT) and tissue-factor thromboelastography (TF-TEG). Plasma apixaban concentrations were measured using liquid chromatography-tandem mass spectrometry. Concentration-time plots were constructed, and PK modeling performed using compartmental methods. Administration of IV and PO apixaban was well-tolerated. Following IV administration, mean half-life was 4.1 h, and volume of distribution was 177 ml/kg. Apixaban was highly protein bound (98.6%). Apixaban concentrations and anti-Xa activity were highly correlated (R
0.994,
< 0.0001). Intravenous apixaban significantly prolonged PT at time points up to 1 h, and aPTT at time points up to 0.25 h post-administration. Coagulation times were positively correlated with apixaban concentrations (PT R
0.599,
< 0.0001; aPTT R
0.430,
< 0.0001) and TF-TEG R-time was significantly prolonged 0.25 h post-administration. Following oral administration, mean bioavailability was 28.4%, lag time was 2 h, time to C
was 5 h and the apparent elimination half-life was 3.1 h. Oral apixaban significantly prolonged PT at 4, 6, and 8 h but aPTT and TF-TEG were not consistently affected by oral apixaban. Apixaban concentrations are best monitored using anti-Xa activity. Future studies should determine PK and bioactivity of other doses using commercial tablets and following multidose administration and establish safe, effective dosing ranges in sick dogs.
Immature platelets in COVID-19 Wolny, Monika; Dittrich, Marcus; Knabbe, Cornelius ...
Platelets,
12/31/2023, Volume:
34, Issue:
1
Report
Open access
Platelets play a critical role in immune response. Coronavirus disease 2019 (COVID-19) patients with a severe course often show pathological coagulation parameters including thrombocytopenia, and at ...the same time the proportion of immature platelets increases. In this study, the platelet count and the immature platelet fraction (IPF) of hospitalized patients with different oxygenation requirements was investigated daily over a course of 40 days. In addition, the platelet function of COVID-19 patients was analyzed. It was found that the number of platelets in patients with the most severe course (intubation and extracorporeal membrane oxygenation (ECMO)) was significantly lower (111.5 ∙ 10
6
/mL) than in the other groups (mild (no intubation, no ECMO): 203.5 ∙ 10
6
/mL, p < .0001, moderate (intubation, no ECMO): 208.0 ∙ 10
6
/mL, p < .0001). IPF tended to be elevated (10.9%). Platelet function was reduced. Differentiation by outcome revealed that the deceased patients had a highly significant lower platelet count and higher IPF (97.3 ∙ 10
6
/mL, p < .0001, 12.2%, p = .0003).
What is the context?
Pathological coagulation is a feature of severe cases of COVID-19, with both bleeding complications and thrombosis. Patients with severe COVID-19 are frequently treated with extracorporeal membrane oxygenation (ECMO), which is often associated with bleeding complications. Platelets play an important role in blood clotting. The proportion of immature platelets has been characterized as hyperreactive and associated with high prothrombotic activity. In addition, they are discussed as predictors of COVID-19 disease severity.
What is new?
In grading the severity of disease in our patient cohort, we consider the required oxygenation measures. Thus, the focus is on severe cases requiring intubation and ECMO compared to moderate (intubation, no ECMO) and mild (no intubation, no ECMO) cases.
What is the impact?
This study focuses on severely ill patients who require ECMO treatment. Therefore, this study provides further evidence to use immature platelet fraction to predict the outcome of severe COVID-19 courses.
During the production of beer, and especially beer wort, the main wastes are spent grain and hot trub, i.e., the so-called "hot break." Combined with yeast after fermentation, they represent the most ...valuable wastes. Hot trub is also one of the most valuable by-products. Studies on the chemical composition of these sediments and their rheological properties as waste products will contribute to their effective disposal and even further use as valuable pharmaceutical and cosmetic raw materials. So far, hot trub has been studied for morphology and particle distribution depending on the raw material composition and beer wort extract. However, there are no preliminary studies on the rheological properties of hot trub and hops. In particular, no attention has yet been paid to the dependence of these properties on the hop variety or different protein sources used. The aim of this study was to examine the effect of different hopping methods on hot trub viscosity and beer wort physicochemical parameters. Additionally, the hop solutions were measured at different temperatures. A microbiological analysis of hop sediments was also performed to determine the post-process survival of selected microorganisms in these wastes. For manufacturers of pumps used in the brewing industry, the most convenient material is that of the lowest viscosity. Low viscosity hot trub can be removed at lower velocities, which reduces costs and simplifies washing and transport. The sediments also had similar equilibrium viscosity values at high shear rates.
Biochar improves soil physical, chemical and biological properties. However, there is a very limited number of studies comparing the effect of various doses of biochar and wheat straw with nutrients ...on microbiocenotic composition of soil and their connection with selected biochemical and chemical parameters of soil. The aim of this study was to determine the effect of the addition to the soil of wheat straw (WS) and wheat straw biochar (WSB) (300 °C) at 0.2%, 0.5%, 1%, and 2% doses and the addition of nutrients (MF) on microbial community composition (bacteria, fungi, actinobacteria,
Azotobacter
spp., ammonifiers, nitrifiers, denitrifiers,
C. pasteurianum
), dehydrogenase activity index, carbon and nitrogen fractions contents and the content of water soluble Cu, Cd, Zn, and Pb. It was demonstrated that coapplication of WS and WSB with MF at 1% and 2% doses increased carbon and nitrogen contents in soil and, in particular, their water soluble fractions (DOC and DON). The synergistic effect of biochar and MF contributed to the increase in the population of soil microorganisms. Dehydrogenase activity index in treatments with the addition of WS, WSB and MF was 1.6–4 times higher compared to the control. The content of heavy metals significantly (p ≤ 0.05) affected dehydrogenase activity and the number of nitrifiers and ammonifiers. It was demonstrated that the content of C and N measured for soil microbial biomass in treatments amended with biochar and MF was much greater than in control treatment and MF. However, our studies suggest that the microorganisms’ response to the addition of biochar with nutrients increased the number and intensified the activity of soil microorganisms.
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