SARS-CoV-2 infection activating a novel variant of the NOTCH3 gene and subsequently causing development of CADASIL.

Introduction: In the following study we describe the diagnostic process and further case analysis of a 30-year-old woman admitted with typical COVID-19 symptoms, who subsequently developed additional symptoms suggesting cerebral autosomal dominant arteriopathy with sub-cortical infarcts and leukoencephalopathy (CADASIL). Material and methods: Other than the standard diagnostic procedures, whole genome sequencing (WGS) was used, which led to following findings. A new variant of the NOTCH3 gene, which led to CADASIL-like symptoms, was found, and it had been most likely activated by the SARS-CoV-2 infection. This novel variant in NOTCH3 has not been found in existing databases and has never been mentioned in research concerning CADASIL before. Results: Furthermore, after subjecting the patient's close relatives to WGS it was found that no other examined person demonstrated the same genetic mutation. Conclusions: It seems therefore that the new variant of NOTCH3 is of de novo origin in the patient's genome. Additionally, the relatively early onset of CADASIL and the unexpectedly severe COVID-19 infection suggest that the two occurred simultaneously: the infection with SARS-CoV-2 accelerated development of CADASIL symptoms and the unusual variant of the NOTCH3 gene contributed to the more severe course of COVID-19.

PRP-fibrinogen gel-like chondrocyte carrier stabilized by TXA-preliminary study.

Three dimensional scaffolds are becoming increasingly popular in the treatment of cartilage defects. Platelet-rich plasma (PRP) and fibrinogen can be used potentially as a three dimensional cell delivery vehicle. PRP is a fraction of plasma containing high levels of growth factors such as PDGF, IGF-I and TGF-I, which stimulate chondrocyte to synthesize extracellular matrix. The aim of this study was to prepare grafts based on fibrinogen, and PRP with fibrinogen as a chondrocyte carrier. Another goal was to estimate tranexamic acid as an antifibrynolytic agent in chondrocyte grafts and in monolayer culture for about 3 weeks. 450 ml blood was collected to produce fibrinogen and PRP from a Regional Blood Center voluntary donor. To prepare gel grafts, chondrocytes were mixed with PRP and, fibrinogen and then with thrombin in calcium chloride. Different doses of tranexamic acid or aprotinin were used to stabilize the constructs. Grafts were cultivated for 4 weeks in vitro to evaluate and compare their disintegration. Grafts were stable for the entire observation period and revealed no shrinkage. During graft storage, cells appeared to be viable, and cell migration from the graft to the culture plate was observed. Chondrocyte graft preparation based on PRP and fibrinogen is a promising method. PRP-fibrinogen carrier in combination with cells constitutes highly plastic and adhesive grafts. Tranexamic acid can be used as an anti-fibrinolytic agent in chondrocyte graft preparation instead of aprotinin.

[Characteristic of adverse reactions after blood components transfusion]. / Charakterystyka powiklan po przetoczeniu skladników krwi.

The adverse transfusion reaction is usually defined as an unwanted reaction occurring in a recipient during or after a blood transfusion or its components. Adverse reaction can occur even in 10% of recipients. The after transfusion reactions can be divided with regard to its causes: infectious and non-infectious, of immunologic and non-immunologic. Blood component transfusions can be related to unfavorable transfusion reaction of early or delayed character.

[The influence of smoking on plasma non-enzymatic antioxidant concentrations in active smokers (preliminary report)]. / Wplyw czynnego palenia papierosów na stezenie nieenzymatycznych antyoksydantów w osoczu krwi (doniesienie wstepne).

Tobacco smoke contains many reactive oxygen species (ROS) that cause oxidative stress. Crucial role in defending the organism against ROS play vitamins E and A. The aim of the study was to investigate the influence of tobacco smoke on concentration of main ingredients of these vitamins alpha-tocopherol and gamma-tocopherol, as well as retinol. The study population consisted of 104 healthy males between the age of 34 and 45 years. Survey questionnaire and determination of plasma cotinine concentration were used to divide the group into smokers (62 males) and non-smokers (42 males). The arbitrary threshold value of plasma cotinine concentration was set to 15 ng/ml. High performance liquid chromatography (HPLC) was used to estimate the plasma concentration of alpha- and gamma-tocopherol, retinol and cotinine. Within the smoking part of the study population a significantly lower (by 12.5%) concentration of alpha-tocopherol, and non-significantly higher (by 15.7%) concentration of gamma-tocopherol was ascertained, when compared to the plasma concentration of those compounds in the non-smoking group. Practically no difference in concentration of retinol was found between the two studied groups. In order to determine the magnitude of interdependency between the extensiveness of exposure to tobacco smoke and the concentration of analyzed antioxidants, correlations between their plasma concentrations and plasma concentration of cotinine were investigated. A significant, moderate and negative correlation of alpha-tocopherol versus cotinin was determined, in the smoking group as well as in the entire study population (r = -0.291 and r = - 0,317, respectively). Other relationship: gamma-tocopherol versus cotinine and retinol versus cotinine did not show any correlation. The obtained results suggest that tobacco smoke weakens the organism's antioxidant barrier by decreasing the concentration of plasma alpha-tocopherol, while not influencing significantly the plasma concentration of gamma-tocopherol and retinol.

[The influence of tobacco smoke on plasma atherogenic compounds levels in active smokers (preliminary report)]. / Wplyw dymu tytoniowego na stezenie aterogennych zwiazków w osoczu krwi palaczy czynnych (doniesienie wstepne).

The aim of the study was to evaluate the influence of tobacco smoke on plasma concentration of atherogenic compounds, namely total homocysteine (tHcy), symmetric dimethylarginine (SDMA) and asymmetric dimethylarginine (ADMA). The study population consisted of 104 healthy males between the age of 34 and 45 years. Survey questionnaire and determination of plasma cotinine concentration were used to divide the group into smokers (62 males) and non-smokers (42 males). The arbitrary threshold value of plasma cotinine concentration was set to 15 ng/ml. High performance liquid chromatography (HPLC) was used to estimate the plasma concentration of tHcy, ADMA, SDMA and cotinine. Significantly higher (by 38.5%) plasma concentration of tHcy in the group of active smokers in comparison with non-smokers was observed. The concentration of ADMA and SDMA was found out to be higher by 12.8% and 13.5% respectively, however those differences were highly non-significant. Positive significant correlation between concentration of tHcy and cotinine was determined, in the smoking group as well as in the entire study population (r = 0.303, P = 0.017; r 0.257, P = 0.009 respectively). There was no evidence, however, of correlation between the concentration of both ADMA and SDMA and cotinine. Correlation between the concentrations of atherogenic parameters showed weak but significant correlations for tHcy versus ADMA and tHcy versus SDMA and high for the ADMA versus SDMA correlations (r = 0.671 in the smoking group and r = 0.672 in the entire population). The results obtained indicate that tobacco smoke probably has a weak influence on smokers' plasma ADMA and SDMA concentration, while significant rising the concentration of homocysteine, an independent risk factor of atherosclerosis.