scholarly journals Association of Low Molecular Weight Plasma Aminothiols with the Severity of Coronavirus Disease 2019

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Evgeny Vladimirovich Kryukov ◽  
Alexander Vladimirovich Ivanov ◽  
Vladimir Olegovich Karpov ◽  
Valery Vasil’evich Alexandrin ◽  
Alexander Mikhaylovich Dygai ◽  
...  

Objective. Aminothiols (glutathione (GSH), cysteinylglycine (CG)) may play an important role in the pathogenesis of coronavirus disease 2019 (COVID-19), but the possible association of these indicators with the severity of COVID-19 has not yet been investigated. Methods. The total content ( t ) and reduced forms ( r ) of aminothiols were determined in patients with COVID-19 ( n = 59 ) on admission. Lung injury was characterized by computed tomography (CT) findings in accordance with the CT0-4 classification. Results. Low tGSH level was associated with the risk of severe COVID-19 ( tGSH ≤ 1.5   μ M , mild vs. moderate/severe: risk   ratio   RR = 3.09 , p = 0.007 ) and degree of lung damage ( tGSH ≤ 1.8   μ M , CT < 2 vs. CT ≥ 2 : RR = 2.14 , p = 0.0094 ). The rGSH level showed a negative association with D-dimer levels ( ρ = − 0.599 , p = 0.014 ). Low rCG level was also associated with the risk of lung damage ( rCG ≤ 1.3   μ M , CT < 2 vs. CT ≥ 2 : RR = 2.28 , p = 0.001 ). Levels of rCG ( ρ = − 0.339 , p = 0.012 ) and especially tCG ( ρ = − 0.551 , p = 0.004 ) were negatively associated with platelet count. In addition, a significant relationship was found between the advanced oxidation protein product level and tGSH in patients with moderate or severe but not in patients with mild COVID-19. Conclusion. Thus, tGSH and rCG can be seen as potential markers for the risk of severe COVID-19. GSH appears to be an important factor to oxidative damage prevention as infection progresses. This suggests the potential clinical efficacy of correcting glutathione metabolism as an adjunct therapy for COVID-19.

Author(s):  
Luca Costanzo ◽  
Simona Antonina Grasso ◽  
Francesco Paolo Palumbo ◽  
Giorgio Ardita ◽  
Luigi Di Pino ◽  
...  

The development of coagulopathy is emerging as one of the most significant poor prognostic features in COVID-19 pneumopathy. Thromboembolic manifestations such as pulmonary embolism and disseminated intravascular coagulation (DIC) have been reported and resulted in poor prognosis for the patient. Starting from the evidence in the literature, the purpose of this paper is to analyze potential mechanism involved in coagulation impairment following COVID-19 infection and identify possible vascular therapeutic strategies. D-dimer, a protein product of fibrin degradation, has been found elevated in the most severe cases and correlated to mortality. Potentially involved factors in the impairment of coagulation caused by viral infection include the dysregulated inflammatory response, platelet and endothelial dysfunction with impaired fibrinolysis. Heparin is an anticoagulant molecule that also showed anti-inflammatory properties and a potential antiviral effect. A favorable outcome was highlighted with the use of LMWH in severe patients with COVID-19 who meet the SIC criteria (sepsis-induced coagulopathy) or with markedly high D-dimer. The use of low molecular weight heparin could prevent thromboembolic complications in COVID-19 pneumopathy. However, the correct timing of prophylaxis according to the stage of COVID-19 disease and the appropriate therapeutic dosage to use in severe cases need further researches. Keywords: COVID-19, pneumonia, thrombosis, coagulopathy, D-dimer, low molecular weight heparin. Одним из наиболее неблагоприятных прогностических признаков пневмопатии при COVID-19 является развитие коагулопатии. У пациентов с COVID-19 наблюдались признаки тромбоэмболии, например тромбоэмболия легочной артерии и ДВС-синдром, что негативно сказывалось на здоровье пациента. Целью исследования является анализ потенциального механизма нарушения свертывания крови у пациентов, перенесших COVID-19, и определение возможных терапевтических стратегий. Было обнаружено, что у пациентов с тяжелой формой заболевания уровень D-димера, белкового продукта распада фибрина, повышен и напрямую взаимосвязан со смертностью. К факторам, влияющим на нарушение коагуляции, вызванной вирусной инфекцией, относятся неуправляемый воспалительный процесс, тромбоцитарная и эндотелиальная дисфункция с нарушением фибринолиза. Гепарин, являясь прямым антикоагулянтом, также обладает противовоспалительными свойствами и выраженным противовирусным эффектом. Благоприятный исход наблюдался при использовании низкомолекулярного гепарина у тяжелых пациентов с COVID-19 с коагулопатией, вызванной сепсисом, или высоким уровнем D-димера. Использование низкомолекулярного гепарина может предотвратить тромбоэмболические осложнения пневмопатии у пациентов с COVID-19. Тем не менее точное время профилактики в зависимости от стадии заболевания COVID-19 и соответствующая терапевтическая дозировка, которая может быть использована в тяжелых случаях, требуют дальнейших исследований. Ключевые слова: COVID-19, пневмония, тромбоз, коагулопатия, D-димер, низкомолекулярный гепарин.


Author(s):  
К.А. Никифорова ◽  
В.В. Александрин ◽  
П.О. Булгакова ◽  
А.В. Иванов ◽  
Э.Д. Вирюс ◽  
...  

Цель. Установить влияние неспецифического адреноблокатора карведилола на редокс-статус низкомолекулярных аминотиолов (цистеин, гомоцистеин, глутатион) в плазме крови при моделировании глобальной ишемии головного мозга у крыс. Методика. Нами была использована модель глобальной ишемии (пережатие общих сонных артерий с геморрагией длительностью 15 мин). Препарат вводили за 1 ч до операции. Уровни аминотиолов измеряли через 40 мин после начала реперфузии. Анализ уровня аминотиолов проводили методом жидкостной хроматографии. Результаты. Установлено, что у крыс, не подвергавшихся ишемии, карведилол в дозе 10 мг/кг вызывает рост редокс-статуса цистеина и глутатиона (в 3 и 3,5 раза соответственно по сравнению с контролем, p = 0,04 и p = 0,008) за счет увеличения их восстановленных форм. При ишемии данного эффекта не наблюдалось. Редокс-статус у крыс с ишемией на фоне карведилола (Цис = 0,85 ± 0,14%, Глн = 1,8 ± 0,7%, Гцис = 1,1 ± 0,8%) оставался таким же низким, как и у крыс с ишемией без введения карведилола (р > 0,8). Заключение. Полученный результат демонстрирует, что в условиях ишемии головного мозга карведилол не оказывает эффекта на гомеостаз аминотиолов плазмы крови, несмотря на выраженный антиоксидантный эффект в нормальных условиях. Aim. Effect of a nonspecific adrenergic antagonist carvedilol on the redox status of plasma low-molecular-weight aminothiols (cysteine, homocysteine, glutathione) was studied in rats with global cerebral ischemia (occlusion of common carotid arteries with hemorrhage). Methods. A model of global ischemia (occlusion of common carotid arteries with 15-min hemorrhage) was used. The drugs were administered one hour before the operation. Aminothiol levels were measured by HPLC with UV detection at 40 minutes after the onset of reperfusion. Results. Carvedilol 10 mg/kg increased the redox status of cysteine and glutathione in rats not exposed to ischemia (3 and 3.5 times, respectively, compared with the control, p = 0.04 and p = 0.008, respectively) but not of homocysteine, by increasing their reduced forms. However, this effect was not observed in ischemia. In rats with ischemia treated with carvedilol, the redox status (Cys = 0.85 ± 0.14%, GSH = 1.8 ± 0.7%, Hcys = 1.1 ± 0.8%) remained low similar to that in rats with ischemia not treated with carvedilol (p >0.8, 0.8, and 0.9, respectively). Conclusion. Carvedilol did not affect the homeostasis of blood plasma thiols in cerebral ischemia despite the pronounced antioxidant effect under the normal conditions.


2020 ◽  
pp. 73-80
Author(s):  
Leyla Sadraddin kyzy Valiyeva ◽  
Viktor Ivanovich Deyneka ◽  
Yelena Yur'yevna Oleynits ◽  
Gul'shan Kagraman kyzy Rahimova ◽  
Natiga Asker kyzy Nabieva

In corn grains, anthocyanins pigments accumulate – belonging to the class of flavanoids, products of the secondary metabolism of plants and which are low molecular weight antioxidants. Numerous epidemiological studies have shown that the use of foods rich in anthocyanins leads to a significant reduction in diabetes, obesity, cardiovascular and oncological diseases. Compared to an equal amount of vegetables and fruits containing anthocyanins, more of them are present in the grain in bound form. Participating in the metabolism in the lower parts of the gastrointestinal tract, they have a beneficial effect on maintaining health. To analyze the total content and determine the composition of anthocyanins in grains of 21 samples of corn from the collection of the National Gene Bank of Azerbaijan, in order to identify promising samples in breeding to increase the content of anthocyanins, we used the method of high-performance liquid chromatography with reverse phase (HPLC) with spectrophotometric and mass spectrometric detection. The grains of the test samples identified mainly cyanidin-3-glucoside and pelargonidin-3-glucoside, as well as the isomeric products of their mono- and diacylation with malonic acid. Pelargonidin-3-glucoside derivatives prevailed in the grain extracts of some of the samples studied. Corn samples were selected as starting material for further breeding work to create local forms of corn with improved nutritional and therapeutic properties.


2021 ◽  
Author(s):  
Giulia Besutti ◽  
Paolo Giorgi Rossi ◽  
Marta Ottone ◽  
Lucia Spaggiari ◽  
Simone Canovi ◽  
...  

Abstract Inflammatory burden is associated with COVID-19 severity and outcomes. Residual computed tomography (CT) lung abnormalities have been reported after COVID-19. The aim was to evaluate the association between inflammatory burden during COVID-19 and residual lung CT abnormalities collected on follow-up CT scans performed 2–3 and 6–7 months after COVID-19, in severe COVID-19 pneumonia survivors. C-reactive protein (CRP) curves describing inflammatory burden during the clinical course were built, and CRP peaks, velocities of increase, and integrals were calculated. Other putative determinants were age, sex, mechanical ventilation, lowest PaO2/FiO2 ratio, D-dimer peak, and length of hospital stay (LOS). Of the 259 included patients (median age 65 years; 30.5% females), 202 (78%) and 100 (38.6%) had residual, predominantly non-fibrotic, abnormalities at 2-3 and 6-7 months, respectively. In age- and sex-adjusted models, best CRP predictors for residual abnormalities were CRP peak (odds ratio [OR] for one standard deviation [SD] increase=1.79; 95% confidence interval [CI]=1.23-2.62) at 2-3 months and CRP integral (OR for one SD increase=2.24; 95%CI=1.53-3.28) at 6-7 months. Hence, inflammation is associated with short- and medium-term lung damage in COVID-19. Other severity measures, including mechanical ventilation and LOS, but not D-dimer, were mediators of the relationship between CRP and residual abnormalities.


Weed Science ◽  
1986 ◽  
Vol 34 (5) ◽  
pp. 669-675 ◽  
Author(s):  
James L. Hilton ◽  
Parthasarathy Pillai

Tridiphane [2-(3,5-dichlorophenyl)-2-(2,2,2-trichloroethyl)oxirane] inhibited growth of seedling corn (Zea maysL. ‘DK T 1100’), wheat (Triticum aesetivumL. ‘Arthur’), and sorghum (Sorghum vulgarePers. ‘DK 42Y’) in growth chamber experiments. These inhibitions were partially circumvented by simultaneous treatment with OTC (L-2-oxothiazolidine-4-carboxylic acid). Tridiphane, atrazine [6-chloro-N-ethyl-N′-(1-methylethyl)-1,3,5-triazine-2,4-diamine], and OTC each increased levels of low molecular weight thiols (glutathione) in intact roots of treated corn seedlings, but only OTC did in excised roots. Tridiphane and atrazine caused a decrease in thiol content of excised roots. Tridiphane treatments reduced the amount of glutathioneS-transferase activity extractable from corn roots, and this reduction was circumvented partially by OTC applied in combination with tridiphane. These data present evidence that tridiphane interference with cysteine or glutathione metabolism can be reversed by increasing cellular content of cysteine.


Author(s):  
А.Ю. Буланов ◽  
Е.В. Ройтман

В отсутствие достаточной базы доказательной медицины самым ценным становится мнение экспертов, опирающихся на свой опыт и опыт коллег. COVID-19-ассоциированная коагулопатия имеет характер тромбовоспаления. Назначение гепаринов — нефракционированного или, главным образом, низкомолекулярного (НМГ) призвано преодолеть его, поскольку гепарин обладает не только антикоагулянтным эффектом, но и оказывает непрямое и прямое противовоспалительное дейст вие. Поэтому назначение НМГ как минимум в профилактических дозах показано всем госпитализированным пациентам. Система гемостаза у пациентов с COVID-19, прежде всего у тяжелых, требует лабораторной оценки количества тромбоцитов, содержания Д-димера, протромбинового отношения или процентов протромбина по Квику и концентрации фибриногена. Анализ данных показал, что своеобразие коронавирусного гемостаза формирует гиперфибриногенемия, которая становится явным фактором гепаринорезистентности. Для преодоления последней назначение увеличенных (промежуточных или лечебных) доз НМГ выглядит перспективным решением. Достаточность назначения уместно определить либо по анти- Ха активности или (как экспресс-оценка) по тромбоэластрограмме. In the absence of a suffi cient base of evidence-based medicine, the most valuable becomes the expert’s opinion as a mirror of both personal and collegial experience. COVID-19-associated coagulopathy has a character of a thromboinfl ammation. The heparins — unfractionated or mainly low molecular weight heparins (LMWH) are intended to overcome it, since heparins have not only an anticoagulant effect but both an indirect and direct anti-infl ammatory effects as well. So that LMWH are indicated for all in-hospital patients. Patients with COVID-19, especially in severe cases, require laboratory testing of platelet count, D-dimer, prothrombin ratio or prothrombin percents by Quick and fi brinogen. Data analysis showed that a feature of coronavirus hemostasis is hyperfibrinogenemia that becomes an overt factor for heparin resistance. To overcome the latter, an adjusting doses of LMWH toward intermediate or therapeutic looks like a promising way. The suffi ciency of the adjusted LMWH dose is appropriate determining either with anti- Xa activity or thromboelastographically as express testing. Key words: hemostasis, COVID-19-associated coagulopathy, fibrinogen, low molecular weight heparins


2020 ◽  
Vol 27 (1) ◽  
pp. 151-154 ◽  
Author(s):  
Jana Libertinova ◽  
Eva Meluzinova ◽  
Eva Nema ◽  
Petra Rockova ◽  
Martin Elisak ◽  
...  

Alemtuzumab as a treatment of highly active multiple sclerosis causes a rapid decrease in inflammatory activity due the lysis of immune cells. Subsequent cytokine release determines the infusion-associated reaction that is a frequent adverse event of alemtuzumab treatment. Recently, serious cardiovascular and thrombotic adverse reactions following alemtuzumab infusion have been described. In our study, the dynamics of coagulation parameters were analyzed in 13 multiple sclerosis patients treated with alemtuzumab. An immediate, significant increase in the level of D-dimer was observed after the first administration of alemtuzumab. This observation provides evidence of coagulation activation and the potential risk of thrombotic complications with this therapy. Prophylactic low molecular weight heparin pretreatment maybe considered in patients receiving alemtuzumab.


2010 ◽  
Vol 104 (07) ◽  
pp. 92-99 ◽  
Author(s):  
Ludwig Traby ◽  
Alexandra Kaider ◽  
Rainer Schmid ◽  
Alexander Kranz ◽  
Peter Quehenberger ◽  
...  

SummaryNon-surgical cancer patients are at high thrombotic risk. We hypothesised that the prothrombotic state is reflected by elevated thrombin generation and can be mitigated by increasing the low-molecularweight heparin (LMWH) dose. Non-surgical cancer patients were randomised to enoxaparin 40 or 80 mg. D-dimer, prothrombin fragment F1+2 (F1+2) and peak thrombin (PT) were measured 2, 4, 6 hours (h) after LMWH (day 1) and daily for 4 days. A total of 22 and 27 patients received enoxaparin 40 and 80 mg, respectively. D-dimer and F1+2 moderately decreased after 6 h in both groups. After enoxaparin 80 mg, D-dimer baseline levels [median (quartiles)] decreased from day 1 to 4 [1054.9 (549.5, 2714.0) vs. 613.0 (441.1, 1793.5) ng/ml] (p<0.0001), while no difference was seen after 40 mg. Baseline PT levels [median (quartiles)] were 426.2 nM (347.3, 542.3) (40 mg) and 394.0 nM (357.1, 448.8) (80 mg). After 80 mg, PT significantly decreased to 112.4 nM (68.5, 202.4), 57.1 nM (38.0, 101.2) and 43.6 nM (23.4, 112.8) after 2, 4 and 6 h, which was lower than after 40 mg (p=0.003). After 80 mg, PT decreased from day 1 to 4 [358.6 nM (194.2, 436.6); p=0.06] while no difference was seen after 40 mg. In conclusion, in cancer patients coagulation activation and thrombin generation is substantially increased. Peak thrombin levels are sensitive to the anticoagulant effects of LMWH at different dosages. The prothrombotic state is substantially attenuated by higher LMWH doses.


Holzforschung ◽  
2000 ◽  
Vol 54 (3) ◽  
pp. 255-261 ◽  
Author(s):  
Sara Canas ◽  
M. Conceição Leandro ◽  
M. Isabel Spranger ◽  
A. Pedro Belchior

Summary The influence of botanical species (Quercus and Castanea sativa) and geographical origin (Portugal—three different sites, France and North America) on the qualitative and quantitative content of some extractable low molecular weight phenolic compounds was assessed by HPLC. Chestnut wood had the highest total content of low molecular weight phenolic compounds, followed by the Portuguese oaks and the French oaks, whereas the American oak had the lowest content of these compounds. The contents of phenolic acids, phenolic aldehydes, scopoletin and umbelliferone were significantly different among the studied woods. Both the botanical species and the geographical origin affect the content of low molecular weight organic compounds of woods used in Portuguese cooperage. The results also show that the botanical species seem to be more important than the geographical origin to explain the difference in the wood phenolic composition. So, the separation of trees according to their origin is of considerable interest for coopers and winemakers to choose wisely the woods for the ageing of brandies.


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