Elevated D-Dimer as a Marker For Thromboembolic Events in Pediatric Patients With Covid-19: A Systematic Review

Abstract Background: The 2019 Coronavirus disease is known to cause thromboembolic events. There is little information on the severe COVID-19 consequences in children. Objectives: To determine whether elevated D-dimer levels in the pediatric population with COVID-19 are a risk marker for the development of thromboembolic events. If so, D-dimer levels could be used to determine prophylactic anticoagulation measures if needed. Methods: This is a systematic review, performed according to the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and registered in the International Prospective Register of Systematic Reviews (PROSPERO) database. The last database search update was on December 14, 2021, resulting in 79 documents for analysis. Data were taken from various databases and queried by topic, keyword, or abstract. Results: Of the 79 articles found, only seven were selected for this analysis. Of these articles, only one had thromboembolic events. In the other articles, D-dimer levels were elevated but were considered controversial in terms of predicting events, with no clear association between the magnitude of D-dimer change and the magnitude of thrombosis risk. Conclusions: Although used for adults, D-dimer was not a good parameter for assessing the risk of thromboembolic events in individuals younger than 21 years. The main shortcomings are the fact that D-dimer increases with any type of inflammation and is, therefore, not a specific marker, and that it is elevated in many patients even without the occurrence of thromboembolic events.

Glyphosate-based herbicide impairs energy metabolism and increases autophagy in C6 astroglioma cell line.

Several investigators demonstrated that glyphosate formulations produce neurotoxicity associated with oxidative stress, alterations in glutamatergic system, inhibition of acetylcholinesterase activity and mitochondrial dysfunction. However, the underlying molecular mechanisms following exposure to this herbicide on astrocytes are unclear. Thus, the aim of the present study was to determine the activity of enzymes related to energy metabolism, in addition to oxidative stress parameters, mitochondrial mass, nuclear area, and autophagy in astrocytes treated with a glyphosate-based herbicide. Our results showed that 24 h exposure to a glyphosate-based herbicide decreased (1) cell viability, (2) activities of mitochondrial respiratory chain enzymes and creatine kinase (CK), (3) mitochondrial mass, and (4) nuclear area in rat astroglioma cell line (C6 cells). However, non-protein thiol (NPSH) levels were increased but catalase activity was not changed in cells exposed to the herbicide at non-cytotoxic concentrations. Low glyphosate concentrations elevated content of cells positive to autophagy-related proteins. Nuclear factor erythroid 2-related factor (Nrf2), NAD(P)H dehydrogenase [quinone] 1 (NQO1) and PTEN-induced kinase 1 (PINK1) labeling were not markedly altered in cells exposed to glyphosate at the same concentrations that an increase in NPSH levels and positive cells to autophagy were found. It is conceivable that mitochondria and CK may be glyphosate-based herbicides targets. Further, autophagy induction and NPSH increase may be mechanisms initiated to avoid oxidative stress and cell death. However, more studies are needed to clarify the role of autophagy in astrocytes exposed to the herbicide and which components of the formulation might be triggering the effects observed here.

Neopterin as a potential cytoprotective brain molecule.

Neopterin, a byproduct of the tetrahydrobiopterin de novo pathway, is found in increased levels in cerebrospinal fluid and plasma and significantly increases upon damage, infection or during immune system activation. The production of this compound seems almost restricted to the monocyte/macrophage linage cells, in response to interferon-γ stimulation. However, it is unclear whether and which nervous cells are able to synthesize neopterin, respond to any stressor applied extracellularly, or even the role of the compound in the central nervous system. Here we propose a potential cytoprotective role of neopterin in the brain, and show evidence that cultured rat astrocytes are responsive to the molecule; the pterin elicited increased hemeoxygenase-1 cellular content and decreased oxidative stress induced by mitochondrial dysfunction. Further studies are needed to clarify neopterin's cytoprotective effects in the central nervous system, and its potential role in different neuroinflammatory diseases.

Diphenyl diselenide administration enhances cortical mitochondrial number and activity by increasing hemeoxygenase type 1 content in a methylmercury-induced neurotoxicity mouse model.

Interest in biochemistry of organoselenium compound has increased in the last decades, mainly due to their chemical and biological activities. Here, we investigated the protective effect of diphenyl diselenide (PhSe)2 (5 µmol/kg), in a mouse model of methylmercury (MeHg)-induced brain toxicity. Swiss male mice were divided into four experimental groups: control, (PhSe)2 (5 µmol/kg, subcutaneous administration), MeHg (40 mg/L, in tap water), and MeHg + (PhSe)2. After the treatment (21 days), the animals were killed and the cerebral cortex was analyzed. Electron microscopy indicated an enlarged and fused mitochondria leading to a reduced number of organelles, in the MeHg-exposed mice. Furthermore, cortical creatine kinase activity, a sensitive mitochondrial oxidative stress sensor, was almost abolished by MeHg. Subcutaneous (PhSe)2 co-treatment rescued from MeHg-induced mitochondrial alterations. (PhSe)2 also behaved as an enhancer of mitochondrial biogenesis, by increasing cortical mitochondria content in mouse-receiving (PhSe)2 alone. Mechanistically, (PhSe)2 (1 µM; 24 h) would trigger the cytoprotective Nrf-2 pathway for activating target genes, since astroglial cells exposed to the chalcogen showed increased content of hemeoxygenase type 1, a sensitive marker of the activation of this via. Thus, it is proposed that the (PhSe)2-neuroprotective effect might be linked to its mitoprotective activity.

The effects of lead and copper on the cellular architecture and metabolism of the red alga Gracilaria domingensis.

The effect of lead and copper on apical segments of Gracilaria domingensis was examined. Over a period of 7 days, the segments were cultivated with concentrations of 5 and 10 ppm under laboratory conditions. The samples were processed for light, confocal, and electron microscopy, as well as histochemistry, to evaluate growth rates, mitochondrial activity, protein levels, chlorophyll a, phycobiliproteins, and carotenoids. After 7 days of exposure to lead and copper, growth rates were slower than control, and biomass loss was observed on copper-treated plants. Ultrastructural damage was primarily observed in the internal organization of chloroplasts and cell wall thickness. X-ray microanalysis detected lead in the cell wall, while copper was detected in both the cytoplasm and cell wall. Moreover, lead and copper exposure led to photodamage of photosynthetic pigments and, consequently, changes in photosynthesis. However, protein content and glutathione reductase activity decreased only in the copper treatments. In both treatments, decreased mitochondrial NADH dehydrogenase activity was observed. Taken together, the present study demonstrates that (1) heavy metals such as lead and copper negatively affect various morphological, physiological, and biochemical processes in G. domingensis and (2) copper is more toxic than lead in G. domingensis.

Effects of natural radiation, photosynthetically active radiation and artificial ultraviolet radiation-B on the chloroplast organization and metabolism of Porphyra acanthophora var. brasiliensis (Rhodophyta, Bangiales).

We undertook a study of Porphyra acanthophora var. brasiliensis to determine its responses under ambient conditions, photosynthetically active radiation (PAR), and PAR+UVBR (ultraviolet radiation-B) treatment, focusing on changes in ultrastructure, and cytochemistry. Accordingly, control ambient samples were collected in the field, and two different treatments were performed in the laboratory. Plants were exposed to PAR at 60 µmol photons m-2 s-1 and PAR + UVBR at 0.35 W m-2 for 3 h per day during 21 days of in vitro cultivation. Confocal laser scanning microscopy analysis of the vegetative cells showed single stellate chloroplast in ambient and PAR samples, but in PAR+UVBR-exposed plants, the chloroplast showed alterations in the number and form of arms. Under PAR+UVBR treatment, the thylakoids of the chloroplasts were disrupted, and an increase in the number of plastoglobuli was observed, in addition to mitochondria, which appeared with irregular, disrupted morphology compared to ambient and PAR samples. After UVBR exposure, the formation of carpospores was also observed. Plants under ambient conditions, as well as those treated with PAR and PAR+UVBR, all showed different concentrations of enzymatic response, including glutathione peroxidase and reductase activity. In summary, the present study demonstrates that P. acanthophora var. brasiliensis shows the activation of distinct mechanisms against natural radiation, PAR and PAR+UVBR.