OBJECTIVES: Concentrations of neopterin, kynurenine and kynurenine/tryptophan ratios predict prognosis and the need for oxygen therapy in patients hospitalized for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The aims of the present study were to evaluate the changes of these biomarkers early in the course of infection, the association with the prior coronavirus disease (COVID-19) vaccination and therapeutic administration of Anti-SARS-CoV-2 monoclonal antibodies, investigation of other potential biomarkers including neuropilin, 8-hydroxy-2-deoxyguanosine and 8-hydroxyguanosine in patients hospitalized with SARS-CoV-2 infection and an assessment of these biomarkers and vitamins A, E and D in patients with post-COVID syndrome. METHODS: Urine and blood samples were obtained on the 1st to the 4th day and 4th to 7th day from 108 patients hospitalized with COVID-19. Chromatography tandem mass spectrometry methods were used to analyse neopterin, kynurenine, tryptophan, liposoluble vitamins, and DNA damage biomarkers. RESULTS: A statistically significant decrease of neopterin, kynurenine and kynurenine/tryptophan ratios was observed on after 4th to 7th day of hospitalization, and concentrations of these biomarkers were increased in patients with poor prognosis and subsequent post-COVID syndrome. The concentrations of remaining biomarker and vitamins were not associated with outcomes, although markedly decreased concentrations of vitamin A, E and D were noted. CONCLUSIONS: The concentrations of neopterin, kynurenine and kynurenine/tryptophan ratios decrease during the course of infection SARS-CoV-2 and are associated with the post-COVID syndrome. No other prognostic biomarkers were identified.
- MeSH
- biologické markery * krev MeSH
- COVID-19 * krev MeSH
- dospělí MeSH
- hospitalizace MeSH
- kynurenin * krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- neopterin * krev moč MeSH
- postakutní syndrom COVID-19 MeSH
- SARS-CoV-2 * izolace a purifikace MeSH
- senioři MeSH
- tryptofan * krev MeSH
- vitamin A krev MeSH
- vitamin D krev MeSH
- vitamin E krev MeSH
- vitaminy krev MeSH
- zánět krev MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
The aim of the presented work was to develop a highly sensitive, accurate and rapid analytical method for the determination of concentration levels of tryptophan and its metabolites of kynurenine catabolic pathway, as well as neurotransmitters and their metabolites in complex biological matrices (brain tissue and blood plasma). The developed analytical method consists of analytes separation from the biological matrices by protein precipitation (blood plasma) or solvent extraction (brain tissue), derivatization of the analytes and their detection by high-performance liquid chromatography combined with mass spectrometry. Individual steps of the whole process were optimized and the method was validated in the terms of selectivity, linearity (R2≥0.980), precision (RSD ≤ 13.3%), recovery (≥82.0%), limit of detection (1.8 ng/mL of blood plasma, 2.2 pg/mg of brain tissue) and limit of quantification (2.5 ng/mL of blood plasma, 2.8 pg/mg of brain tissue). The method was subsequently verified by an animal study, where the concentration levels of the analytes in biological matrices (blood plasma and brain tissue) of T. gondii - infected rats and control animals were compared. All the data obtained from the animal study were statistically evaluated. Increased concentration levels of kynurenine catabolic pathway metabolites (e.g. kynurenine, 3-hydroxykynurenine, quinolinic acid) were observed in the case of T. gondii - infected rats in contrast to the control group. The opposite effect was determined in the case of serotonin and its metabolite 5-hydroxyindoleacetic acid, where higher concentration levels were found in blood plasma of healthy subjects. Finally, Principal Component Analysis (PCA) was utilized for a score plot formation. PCA score plots have demonstrated the similarities of individuals within each group and the differences among the groups.
- MeSH
- krevní plazma metabolismus MeSH
- krysa rodu rattus MeSH
- kynurenin analogy a deriváty krev metabolismus MeSH
- kyselina chinolinová krev metabolismus MeSH
- kyselina hydroxyindoloctová krev metabolismus MeSH
- mozek metabolismus MeSH
- neurotransmiterové látky metabolismus MeSH
- potkani Wistar MeSH
- serotonin metabolismus MeSH
- tandemová hmotnostní spektrometrie metody MeSH
- toxoplazmóza krev metabolismus MeSH
- tryptofan metabolismus MeSH
- vysokoúčinná kapalinová chromatografie metody MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Among malignant diseases, chronic myeloid leukaemia (CML) is one of the best suited candidates for immunotherapy. For this purpose it is necessary to broaden the present knowledge on the immunology of this disease. As a part of such a project, the levels of kynurenine (KYN) and neopterin (NPT) were studied in 28 CML patients and in the same number of healthy subjects. At diagnosis, both KYN and NPT levels were found to be elevated in a significant portion of the patients and dependent on their leukocyte count. As in the case of KYN, increased NPT levels dropped after achieving remission. When correlating KYN and NPT levels with a selection of other markers tested, significant association was revealed only in the case of CRP and IL-6. However, there were several patients with increased KYN levels in whom NPT was not detected, and vice versa. The relapse of the disease observed in two patients was accompanied by an increased level of NPT in both cases, but by an increased level of KYN in only one of them. No significant correlation was found between KYN and NPT levels in sera taken at diagnosis. However, when the whole set of sera was taken into consideration, the association became statistically significant. Although the data obtained revealed a number of similarities between KYN and NPT production in CML patients, it also suggested a difference in the kinetics of these two biomarkers' production.
- MeSH
- biologické markery krev MeSH
- C-reaktivní protein metabolismus MeSH
- chronická myeloidní leukemie krev MeSH
- dospělí MeSH
- interleukin-6 krev MeSH
- kynurenin krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- lineární modely MeSH
- mladý dospělý MeSH
- neopterin krev MeSH
- počet leukocytů MeSH
- senioři MeSH
- studie případů a kontrol MeSH
- tryptofan krev MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Indoleamine 2,3-dioxygenase 1 (IDO1), IDO2 and tryptophan 2,3-dioxygenase (TDO) represent some of the key immune regulators. Their increased activity has been demonstrated in a number of human malignancies but not yet in chronic myeloid leukemia (CML). In the present study, the activity of these enzymes was tested in 29 CML patients and 28 healthy subjects by monitoring the kynurenine (KYN)/tryptophan ratio. Serum samples taken prior to the therapy displayed a highly significant difference in KYN levels between the patient and control groups. However, increased KYN levels were detected in only 13 (44.8%) of these CML patients. The KYN levels in pretreatment sera of the patients correlated with the tumor burden. There was also a strong correlation between KYN levels and uric acid levels (UA). This suggests but does not prove the possible involvement of UA in activating IDO family of enzymes. Whenever tested, the increased KYN levels normalized in the course of the therapy. Patients with normal KYN levels in their pretreatment sera and subsequently treated with interferon-α, showed a transitory increase in their KYN levels. The present data indicate that CML should be added to the malignancies with an increased activity of the IDO family of enzymes and suggest that IDO inhibitors may be used in the treatment of CML patients.
- MeSH
- biologické markery krev MeSH
- chronická myeloidní leukemie * MeSH
- dospělí MeSH
- indolamin-2,3,-dioxygenasa MeSH
- kynurenin * krev MeSH
- kyselina močová * MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- tryptofan * krev MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
A new HPLC method for simultaneous determination of neopterin, creatinine, kynurenine and tryptophan in human serum was developed and validated. Monolithic stationary phase's technology (two monolithic columns RP-18e were connected with guard monolithic cartridge 4.6 mm × 50 mm+3.0 mm × 100 mm and 4.6 × 10 mm) and special auto sampler for micro titration plates (samples are storage in dark cooled place protected against evaporation) were combined with easy sample preparation step. As mobile phase 15 mmol/L phosphate buffer at pH 4.50 was used. Neopterin and tryptophan were detected using fluorescent detection and kynurenine and creatinine were detected by diode-array detection. This method may be suitable for large sequences of samples in clinical research and routine practice.
- MeSH
- fosfáty chemie MeSH
- koncentrace vodíkových iontů MeSH
- kreatinin krev MeSH
- kynurenin krev MeSH
- lidé MeSH
- neopterin krev MeSH
- pufry MeSH
- reprodukovatelnost výsledků MeSH
- tryptofan krev MeSH
- vysokoúčinná kapalinová chromatografie přístrojové vybavení metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- biomedicínský výzkum MeSH
- dospělí MeSH
- hypertenze farmakoterapie MeSH
- hypertrofie MeSH
- hypotonické roztoky antagonisté a inhibitory MeSH
- kardiomyopatie farmakoterapie MeSH
- kynurenin krev škodlivé účinky MeSH
- lidé středního věku MeSH
- lidé MeSH
- pyridoxal nedostatek MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- MeSH
- biomedicínský výzkum MeSH
- dospělí MeSH
- hypertenze farmakoterapie MeSH
- hypertrofie MeSH
- hypotonické roztoky antagonisté a inhibitory MeSH
- kardiomyopatie farmakoterapie MeSH
- kynurenin krev škodlivé účinky MeSH
- lidé středního věku MeSH
- lidé MeSH
- pyridoxal nedostatek MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
