Several studies suggested the association of COVID-19 with systemic oxidative stress, in particular with lipid peroxidation and vascular stress. Therefore, this study aimed to evaluate the ...antioxidant signaling in the plasma of eighty-eight patients upon admission to the Clinical Hospital Dubrava in Zagreb, of which twenty-two died within a week, while the other recovered. The differences between the deceased and the survivors were found, especially in the reduction of superoxide dismutases (SOD-1 and SOD-2) activity, which was accompanied by the alteration in glutathione-dependent system and the intensification of the thioredoxin-dependent system. Reduced levels of non-enzymatic antioxidants, especially tocopherol, were also observed, which correlated with enhanced lipid peroxidation (determined by 4-hydroxynonenal (4-HNE) and neuroprostane levels) and oxidative modifications of proteins assessed as 4-HNE-protein adducts and carbonyl groups. These findings confirm the onset of systemic oxidative stress in patients with severe SARS-CoV-2, especially those who died from COVID-19, as manifested by strongly reduced tocopherol level and SOD activity associated with lipid peroxidation. Therefore, we propose that preventive and/or supplementary use of antioxidants, especially of lipophilic nature, could be beneficial for the treatment of COVID-19 patients.
Although the COVID-19 pandemic has ended, it is important to understand the pathology of severe SARS-CoV-2 infection associated with respiratory failure and high mortality. The plasma proteome, ...including protein modification by lipid peroxidation products in COVID-19 survivors (COVID-19; n = 10) and deceased individuals (CovDeath; n = 10) was compared in samples collected upon admission to the hospital, when there was no difference in their status, with that of healthy individuals (Ctr; n = 10). The obtained results show that COVID-19 development strongly alters the expression of proteins involved in the regulation of exocytosis and platelet degranulation (top 20 altered proteins indicated by analysis of variance; p-value (False Discovery Rate) cutoff at 5%). These changes were most pronounced in the CovDeath group. In addition, the levels of 4-hydroxynonenal (4-HNE) adducts increased 2- and 3-fold, whereas malondialdehyde (MDA) adducts increased 7- and 2.5-fold, respectively, in COVID-19 and CovDeath groups. Kinases and proinflammatory proteins were particularly affected by these modifications. Protein adducts with 15-deoxy-12,14-prostaglandin J2 (15d-PGJ2) were increased 2.5-fold in COVID-19 patients, including modifications of proteins such as p53 and STAT3, whereas CovDeath showed a decrease of approximately 60% compared with Ctr. This study for the first time demonstrates the formation of lipid metabolism products—protein adducts in plasma from survived and deceased COVID-19 patients, significantly distinguishing them, which may be a predictor of the course of SARS-CoV-2 infection.
As a result of SARS-CoV-2 infection, inflammation develops, which promotes oxidative stress, leading to modification of phospholipid metabolism. Therefore, the aim of this study is to compare the ...effects of COVID-19 on the levels of phospholipid and free polyunsaturated fatty acids (PUFAs) and their metabolites produced in response to reactions with reactive oxygen species (ROS) and enzymes (cyclooxygenases-(COXs) and lipoxygenase-(LOX)) in the plasma of patients who either recovered or passed away within a week of hospitalization. In the plasma of COVID-19 patients, especially of the survivors, the actions of ROS and phospholipase A2 (PLA2) cause a decrease in phospholipid fatty acids level and an increase in free fatty acids (especially arachidonic acid) despite increased COXs and LOX activity. This is accompanied by an increased level in lipid peroxidation products (malondialdehyde and 8-isoprostaglandin F2α) and lipid mediators generated by enzymes. There is also an increase in eicosanoids, both pro-inflammatory as follows: thromboxane B2 and prostaglandin E2, and anti-inflammatory as follows: 15-deoxy-Δ-12,14-prostaglandin J2 and 12-hydroxyeicosatetraenoic acid, as well as endocannabinoids (anandamide-(AEA) and 2-arachidonylglycerol-(2-AG)) observed in the plasma of patients who recovered. Moreover, the expression of tumor necrosis factor α and interleukins (IL-6 and IL-10) is increased in patients who recovered. However, in the group of patients who died, elevated levels of N-oleoylethanolamine and N-palmitoylethanolamine are found. Since lipid mediators may have different functions depending on the onset of pathophysiological processes, a stronger pro-inflammatory response in patients who have recovered may be the result of the defensive response to SARS-CoV-2 in survivors associated with specific changes in the phospholipid metabolism, which could also be considered a prognostic factor.
•Reduced health-related quality of life (HQOL), fatigue and psychological distress are common in rheumatoid arthritis (RA).•Physical activity should be an integral part of RA management yet there is ...a lack of RA-targeted exercise programs.•A 12-week Yoga in Daily Life program was not associated with change in HQOL in RA patients.•Significant and sustained improvements with yoga were observed in fatigue and mood. The yoga program proved safe and feasible.•Yoga in Daily Life program could be of benefit in facilitating physical activity in RA and complement standard RA management.
To explore the feasibility and effectiveness of a yoga program in improving health-related quality of life (HQOL), physical and psychological functioning in rheumatoid arthritis (RA) patients.
Single-centre parallel-arms randomized controlled trial comparing yoga (n = 30) and education control group (n = 27).
Tertiary care University hospital.
A 12-week yoga program, based on the Yoga in Daily Life system, included 2x weekly/90-minute sessions. The control group had 1xweekly/60-minute educational lectures on arthritis-related topics.
Assessments were performed at baseline, 12 (post-intervention) and 24 weeks (follow-up). The primary outcome was change in The Short Form-36 (SF-36) HQOL at 12 weeks. Linear regression analysis was adjusted for baseline scores.
No significant between-group differences were found for SF-36 (all p > 0.05). At 12 weeks the adjusted mean difference between groups favoured yoga for Functional Assessment of Chronic Illness Therapy-fatigue (5.08 CI 1.29 to 8.86; p = 0.009) and Hospital Anxiety and Depression Scale (HADS)-depression (−1.37 CI −2.38 to −0.36); p = 0.008) and at 24 weeks for HADS-anxiety (−1.79 CI −3.34 to − 0.23; p = 0.025), while the impact on fatigue was sustained (5.43 CI 1.33 to 9.54, p = 0.01). The program had no impact on RA disease activity. Feasibility outcomes included recruitment rate 16 %, retention 80.7 %, and adherence to yoga 87.5 vs 82.7 % for control. No serious adverse events were recorded.
Yoga in Daily Life program was not associated with change in health-related quality of life of RA patients. Significant improvements in fatigue and mood were observed at postintervention and follow-up. This yoga program was found feasible and safe for patients and may complement standard RA treat-to-target strategy.
The aim of this study was to evaluate selected parameters of redox signaling and inflammation in the granulocytes of COVID-19 patients who recovered and those who died. Upon admission, the patients ...did not differ in terms of any relevant clinical parameter apart from the percentage of granulocytes, which was 6% higher on average in those patients who died. Granulocytes were isolated from the blood of 15 healthy people and survivors and 15 patients who died within a week, and who were selected post hoc for analysis according to their matching gender and age. They differed only in the lethal outcome, which could not be predicted upon arrival at the hospital. The proteins level (respective ELISA), antioxidant activity (spectrophotometry), and lipid mediators (UPUPLC–MS) were measured in the peripheral blood granulocytes obtained via gradient centrifugation. The levels of Nrf2, HO-1, NFκB, and IL-6 were higher in the granulocytes of COVID-19 patients who died within a week, while the activity of cytoplasmic Cu,Zn-SOD and mitochondrial Mn-SOD and IL-2/IL-10 were lower in comparison to the levels observed in survivors. Furthermore, in the granulocytes of those patients who died, an increase in pro-inflammatory eicosanoids (PGE2 and TXB2), together with elevated cannabinoid receptors 1 and 2 (associated with a decrease in the anti-inflammatory 15d-PGJ2), were found. Hence, this study suggests that by triggering transcription factors, granulocytes activate inflammatory and redox signaling, leading to the production of pro-inflammatory eicosanoids while reducing cellular antioxidant capacity through SOD, thus expressing an altered response to COVID-19, which may result in the onset of systemic oxidative stress, ARDS, and the death of the patient.
Major findings of the pilot study involving 21 critically ill patients during the week after admission to the critical care unit specialized for COVID-19 are presented. Fourteen patients have ...recovered, while seven passed away. There were no differences between them in respect to clinical or laboratory parameters monitored. However, protein adducts of the lipid peroxidation product 4-hydroxynonenal (HNE) were higher in the plasma of the deceased patients, while total antioxidant capacity was below the detection limit for the majority of sera samples in both groups. Moreover, levels of the HNE-protein adducts were constant in the plasma of the deceased patients, while in survivors, they have shown prominent and dynamic variations, suggesting that survivors had active oxidative stress response mechanisms reacting to COVID-19 aggression, which were not efficient in patients who died. Immunohistochemistry revealed the abundant presence of HNE-protein adducts in the lungs of deceased patients indicating that HNE is associated with the lethal outcome. It seems that HNE was spreading from the blood vessels more than being a consequence of pneumonia. Due to the limitations of the relatively small number of patients involved in this study, further research on HNE and antioxidants is needed. This might allow a better understanding of COVID-19 and options for utilizing antioxidants by personalized, integrative biomedicine approach to prevent the onset of HNE-mediated vitious circle of lipid peroxidation in patients with aggressive inflammatory diseases.
An oxidative degradation product of the polyunsaturated fatty acids, 4-hydroxynonenal (4-HNE), is of particular interest in cancer research due to its concentration-dependent pleiotropic activities ...affecting cellular antioxidants, metabolism, and growth control. Although an increase in oxidative stress and lipid peroxidation was already associated with prostate cancer progression a few decades ago, the knowledge of the involvement of 4-HNE in prostate cancer tumorigenesis is limited. This study investigated the appearance of 4-HNE-protein adducts in prostate cancer tissue by immunohistochemistry using a genuine 4-HNE monoclonal antibody. Plasma samples of the same patients and samples of the healthy controls were also analyzed for the presence of 4-HNE-protein adducts, followed by metabolic profiling using LC-ESI-QTOF-MS and GC-EI-Q-MS. Finally, the analysis of the metabolic pathways affected by 4-HNE was performed. The obtained results revealed the absence of 4-HNE-protein adducts in prostate carcinoma tissue but increased 4-HNE-protein levels in the plasma of these patients. Metabolomics revealed a positive association of different long-chain and medium-chain fatty acids with the presence of prostate cancer. Furthermore, while linoleic acid positively correlated with the levels of 4-HNE-protein adducts in the blood of healthy men, no correlation was obtained for cancer patients indicating altered lipid metabolism in this case. The metabolic pathway of unsaturated fatty acids biosynthesis emerged as significantly affected by 4-HNE. Overall, this is the first study linking 4-HNE adduction to plasma proteins with specific alterations in the plasma metabolome of prostate cancer patients. This study revealed that increased 4-HNE plasma protein adducts could modulate the unsaturated fatty acids biosynthesis pathway. It is yet to be determined if this is a direct result of 4-HNE or whether they are produced by the same underlying mechanisms. Further mechanistic studies are needed to grasp the biological significance of the observed changes in prostate cancer tumorigenesis.
Thorough understanding of metabolic changes, including lipidome alteration, associated with the development of COVID-19 appears to be crucial, as new types of coronaviruses are still reported. In ...this study, we analyzed the differences in the plasma phospholipid profiles of the deceased COVID-19 patients, those who recovered and healthy people. Due to identified abnormalities in plasma phospholipid profiles, deceased patients were further divided into two subgroups (D1 and D2). Increased levels of phosphatidylethanolamines (PE), phosphatidylcholines (PC) and phosphatidylserines (PS) were found in the plasma of recovered patients and the majority of deceased patients (first subgroup D1) compared to the control group. However, abundances of all relevant PE, PC and PS species decreased dramatically in the plasma of the second subgroup (D2) of five deceased patients. These patients also had significantly decreased plasma COX-2 activity when compared to the control, in contrast to unchanged and increased COX-2 activity in the plasma of the other deceased patients and recovered patients, respectively. Moreover, these five deceased patients were characterized by abnormally low CRP levels and tremendous increase in LDH levels, which may be the result of other pathophysiological disorders, including disorders of the immune system, liver damage and haemolytic anemia. In addition, an observed trend to decrease the autoantibodies against oxidative modifications of low-density lipoprotein (oLAb) titer in all, especially in deceased patients, indicate systemic oxidative stress and altered immune system that may have prognostic value in COVID-19.
Abstract Objectives COVID-19 in it is more severe form is characterized by a hyperinflammatory condition, hypercoagulation state and the appearance of pulmonary microembolism. In this study we wanted ...to correlate levels of D-Dimer, protein C, protein S and antithrombin 3 with severity of disease and clinical outcome. Methods We included 134 of patients who were divided in 3 groups regarding oxygen support (high flow oxygen therapy, mechanical ventilation and oxygen supplementation with nasal cannula or mask). Results Concentration of D-Dimer, and activity of protein C and antithrombin 3 are presented as mean±SD and differed significantly between patients on mechanical ventilation (3.26 ± 1.15 mg/L, 86 ± 22.55 %, 81.21 ± 17.61 %)/HFNO (2.35 ± 1.68 mg/L, 109.6 ± 26.96 %, 94.67 ± 17.49 %)/BNC (1.37 ± 1.17 mg/L, 116.92 ± 28.16 %, 103.29 ± 15.63 %) with p<0.001 for all parameters. Mortality in oxygen group was 10.9 %, in HFNC group 40.7 % and in mechanical ventilated group 80 %. Conclusions determination of anticoagulant factors in COVID-19 patients may indicate which of them are at increased risk of developing severe disease, venous thromboembolism and fatal clinical outcome.
Aviation noise represents an important hazard for hearing loss among military pilots as they are continuously exposed to excessive noise during flight operations. Modern military aircraft, due to ...their maneuverability and tactical capabilities, require increasing engine power, while noise protection is limited only to the personal protective equipment which protects to a limited extent. Previous generations of helicopter pilots in the Croatian Air Force (CAF) used GSSH-A-18 headphones, whereas Gentex HGU-56/P helmets have been in use in CAF since 2004, primarily as mechanical protection for the head and secondarily to protect hearing. A study on hearing threshold measurements was performed on multi-purpose transport helicopter pilots who used headphones and helmets, respectively. The population of pilots who used GSSH-A-18 headphones had significantly higher hearing loss at higher frequencies, in the left ear, and in the speech area compared to the group using Gentex HGU-56/P helmets. The results of this study confirm the benefit of using of the Gentex HGU-56/P helmet to preserve the pilots’ hearing.
Zrakoplovna buka predstavlja važnu opasnost za gubitak sluha među vojnim pilotima, budući da su kontinuirano izloženi prekomjernoj buci tijekom letačkih operacija. Moderno vojno zrakoplovstvo zbog svojih manevarskih sposobnosti i taktičkih mogućnosti zahtjeva povećanje snage motora, dok je zaštita od buke ograničena na osobnu zaštitnu opremu koja štiti do određene granice. Prijašnje generacije pilota helikoptera u Hrvatskom ratnom zrakoplovstvu (HRZ) koristile su GSSH-A-18 slušalice, dok su Gentex HGU-56/P kacige u upotrebi u HRZ-u od 2004. godine; primarno kao mehanička zaštita za glavu te sekundarno kao zaštita sluha. Studija o mjerenju praga sluha provedena je kod pilota višenamjenskih transportnih helikoptera, koji su koristili slušalice, odnosno kacige. Populacija pilota koja je koristila GSSH-A-18 slušalice imala je znatno viši gubitak sluha na visokim frekvencijama u lijevom uhu i u govornom području, u usporedbi s grupom koja je koristila kacige Gentex HGU-56/P. Rezultati ovog istraživanja potvrđuju korist korištenja kacige Gentex HGU-56/P pri očuvanju sluha pilota.
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