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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.
Bone scans, serum tissue-specific polypeptide antigen (TPS), prostate specific antigen (PSA), and neuron-specific enolase (NSE) were assessed in a total of 80 hormonally treated prostate cancer patients. Thirty-nine patients were free of osseous lesions; in 8 subjects, 3 or fewer scintigraphic hot spots were found; in 29 patients, more than 3 bone lesions were recorded. In 3 patients, a partial contribution of endocrine cell cancer structures was found, while in one patient, a homogeneous small cell carcinoma was detected at autopsy. Measurement of the serum PSA test showed a clear-cut rise from stage D0 subjects to stage D2 patients, with a small number of bone lesions (> or = 3). However, a relative decrease in the mean PSA level was measured with further progression in a number of hot spots in bone (> 3). Androgen threshold that is critical for the induction of the PSA (and PAP) expression seems to differ markedly in various cell subpopulations that arise during adenocarcinoma dedifferentiation. This fact explains not only the rise in serum PSA in the majority of progressive and previously castrated subjects after an initial period of hormonal responsiveness, but also a relative decline of androgen-dependent PSA expression with further tumor progression. Localized disease was accompanied with normal or just slightly elevated TPS concentration. In metastatic tumors, serum TPS values revealed a steady increase with the progression in bone. These data seem to reflect not only an increase in tumor proliferation rate with progressively transformed genome, but also the rise in the number of proliferating cells. The presence of nonepithelial transformed tumor structures, such as small cell cancer within a bulk of adenocarcinoma, reduces or normalizes numerical serotests values of both TPS and PSA even during tumor progression. The extent of such decline depends upon the bulk of the endocrine component. The assessment of the above parameters, especially when associated with elevated plasma NSE concentrations, may help in distinguishing an advanced adenocarcinoma with and without elements of malignant neuroendocrine structures. The proposed approach, modified by applying corresponding organ-specific markers, may be checked for its possible general use in staging protocols of various heterogeneous tumors.
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