Pterin metabolism, inflammation and oxidative stress biochemical markers in schizophrenia: Factor analysis and assessment of clinical symptoms associations.

Various aspects of folate and tetrahydrobiopterin (BH4) metabolism disturbances have been detected in patients with schizophrenia.Data were obtained that disturbances in the pterins (folates and BH4) metabolism can be associated with oxidative stress and inflammation, but has not yet been confirmed in clinical studies in schizophrenia. Within the framework of this study, a correlation and factor analysis of biochemical markersof pterin metabolism, inflammation and redox imbalance in patients with schizophrenia was performed in order to test the hypothesis of the single etiopathogenetic node, including the studied biochemical processes. Methods: 125 patients with schizophrenia and 95 healthy volunteers were randomly selected and evaluated with a biochemical examination of BH4, folate, B12, homocysteine, C-reactive protein, interleukin-6, reduced glutathione levels in the blood serum; activity of superoxide dismutase and catalase - in erythrocytes; malondialdehyde - in blood plasma. All patients underwent an examination using standardized psychopathology rating scales. Spearman rank coefficient (ρ) with Benjamini-Hochberg correction was used for the correlation analysis. The principal components analysis (PCA) was used as a factor analysis. Results: Significant correlations were found within groups of pterin metabolism, inflammatory markers and redox-imbalance, and also between separate inflammation, oxidative stress and markers of pterin metabolism. The performed factor analysis made it possible to distinguish two components: 1 - pterin metabolism, 2 - oxidativeinflammatory markers. Despite the weak statistical associations and, possibly, functional relationships between pterin metabolism and oxidative/inflammation markers, each of the components has its own clinical correlates and, probably, a separate contribution to the pathology of schizophrenia.

Tetrahydrobiopterin deficiency in schizophrenia: Biochemical and clinical aspects.

It was reported that the levels of tetrahydrobiopterin (BH4) are reduced in schizophrenia. However, mechanisms of BH4 deficiency in schizophrenia had not been studied precisely. OBJECTIVE: the search of the association between BH4 deficiency in schizophrenia and a range of biochemical and clinical parameters for the evaluation of the possible mechanisms of BH4 loss and its role in the development of the symptoms. METHODS: 93 patients with schizophrenia and 60 healthy volunteers were randomly selected and evaluated with a biochemical examination of BH4, folate, cobalamin (B12), homocysteine, C-reactive protein (CRP), reduced glutathione (GSH) levels in the blood serum.Patients underwent standardized psychopathological examination. RESULTS: In patients, the levels of BH4 and folate were lower (p = 0.001 and p = 0.054, respectively), and the levels of homocysteine were higher (p = 0.012) compared to the control group. BH4 levels directly moderately correlated with folate (ρ = 0.43; p = 0.0029) and B12 levels (ρ = 0.43; p = 0.0020) and inversely moderately correlated with homocysteine levels (ρ = -0.54; p = 0.00015) in patients. Cluster analysis identified schizophrenia biotype characterized by a deficiency of BH4, folate, B12, and hyperhomocysteinemia. The clinical characteristics of this biotype were not specific. CRP and GSH were higher in patients compared to controls, but their association with serum BH4 was not confirmed.

Relationship of zinc level with pathogenetically significant homeostasis disorders in severely burned patients.

The aim of the study was to assess the zinc content and identify the relationship between the concentration of this element and changes in the biochemical status of patients and markers of inflammation during burn shock. We examined 23 patients aged 45.3±16.1 years with burns of I-II-III degree, area of 31-80%. The serum concentrations of zinc, albumin, interleukin-6, C-reactive protein (CRP), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined. The majority of patients (21/23) had severe hypocincemia, correlated with burn area (r=-0.53; p=0.008). A decrease in zinc levels during burn shock was associated with the development of hypoalbuminemia (r=0.52, p=0.01). The association of deviations in ALT and AST activity with changes in zinc concentration was revealed (-0.59<γ<-0.61, 0.008

The effect of hyperoxia on the hemostasiological status of severely burned patients.

The state of the hemostasis system was studied in 9 patients of the middle age group (44 ± 9.94 years) who received thermal trauma on an area of more than 32% (49.4 ± 18.3) of the body surface, accompanied by the development of burn shock. The standard therapy for burn injury was supplemented with HBO sessions. Treatment with hyperbaric oxygen was carried out in pressure chambers BLKS-307, BLKS-307/1. The state of the coagulation, anticoagulant and fibrinolytic links of the hemostasis system, as well as the viscoelastic properties of the blood, were assessed immediately before the HBO session and immediately after it. The total number of comparison pairs was 45. Under the influence of HBO therapy, there was an increase in the activity of antithrombin III (ATIII), protein C (PrS) and a decrease in the viscoelastic properties of blood (p <0.05). Positive deviations in the values of ATIII, Pr C, von Willebrand factor, APTT, prothrombin and thrombin time, fibrinogen, factor XIII, XIIa-dependent fibrinolysis, D-dimers and thromboelastography parameters were revealed. The maximum frequency of their occurrence was recorded for ATIII (95%), the minimum - for the D-dimer (62%). After HBO procedures, undesirable deviations of the hemostatic system parameters were also noted. They were chaotic, were compensated by an increase in the activity of physiological anticoagulants and were not accompanied by complications of a thrombogenic nature. Thus, conducting HBO therapy sessions in the acute period of burn disease increases the activity of physiological anticoagulants and stabilizes the viscoelastic properties of blood. There is a high frequency of occurrence of positive effects of hyperoxia on the components of the hemostasis system. The identification of its undesirable effects indicates the need to monitor the state of the hemostasis system during HBO procedures.

Homocysteine in Schizophrenia: Independent Pathogenetic Factor with Prooxidant Activity or Integral Marker of Other Biochemical Disturbances?

A wide range of studies have demonstrated that hyperhomocysteinemia is associated with the risk of schizophrenia, but currently available assumptions about the direct involvement of homocysteine (Hcy) in the pathogenesis of schizophrenia are hypothetical. It is possible that in vivo Hcy is only a marker of folate metabolism disturbances (which are involved in methylation processes) and is not a pathogenetic factor per se. Only one study has been conducted in which associations of hyperhomocysteinemia with oxidative stress in schizophrenia (oxidative damage to protein and lipids) have been found, and it has been suggested that the oxidative stress may be induced by the elevated Hcy in schizophrenic patients. But the authors did not study the level of reduced glutathione (GSH), as well as possible causes of hyperhomocysteinemia-disturbances of folate metabolism. The aim of this work is to analyze the association of Hcy levels with the following: (1) redox markers in schizophrenia GSH, markers of oxidative damage of proteins and lipids, and the activity of antioxidant enzymes in blood serum; (2) with the level of folate and cobalamin (В12); and (3) with clinical features of schizophrenia measured using the Positive and Negative Syndrome Scale (PANSS). 50 patients with schizophrenia and 36 healthy volunteers, matched by sex and age, were examined. Hcy in patients is higher than in healthy subjects (p = 0.0041), and this may be due to the lower folate level in patients (p = 0.0072). In patients, negative correlation was found between the level of Hcy both with the level of folate (ρ = -0.38, p = 0.0063) and with the level of B12 (ρ = -0.36, p = 0.0082). At the same time, patients showed higher levels of oxidative modification of serum proteins (p = 0.00046) and lower catalase (CAT) activity (p = 0.014). However, Hcy is not associated with the studied markers of oxidative stress in patients. In the group of patients with an increased level of Hcy (>10 µmol/l, n = 42) compared with other patients (n = 8), some negative symptoms (PANSS) were statistically significantly more pronounced: difficulty in abstract thinking (N5, p = 0.019), lack of spontaneity and flow in conversation (N6, p = 0.022), stereotyped thinking (N7, p = 0.013), and motor retardation (G7, p = 0.050). Thus, in patients with schizophrenia, hyperhomocysteinemia caused by deficiency of folate and B12 is confirmed and can be considered a marker of disturbances of vitamin metabolism. The redox imbalance is probably not directly related to hyperhomocysteinemia and is hypothetically caused by other pathological processes or by an indirect effect of Hcy, for example, on the enzymatic antioxidant defence system (CAT activity), which requires further exploration. Further study of the role of Hcy in the pathogenesis of schizophrenia is relevant, since the proportion of patients with hyperhomocysteinemia is high and correlations of its level with negative symptoms of schizophrenia are noted.

Disturbances of the hemostasis system and expression of inflammatory reaction in patients with new coronaviral pneumonia.

Disorders of the hemostatic system and inflammation play a key role in the pathogenesis of new coronavirus pneumonia (NCP), determining its course and outcome. To study the dynamics of the state of the hemostasis system and the severity of the acute phase response in patients with new coronavirus pneumonia. We determined APTT, prothrombin time (PT), fibrinogen (F), D-dimers (D-d), antitrombin III (AT III), C-reactive protein (CRP), platelet count in 22 patients. In 49 patients, the viscoelastic properties of a blood clot were studied by thromboelastography (TEG) with koalin. The age of the patients ranged from 40 to 77 years. According to CT, the severity of 100% cases corresponded to CT2-CT3. Acute respiratory failure (ARF) was diagnosed in 16 patients. A control group included 25 apparently healthy subjects. During hospitalization, patients with NCP were characterized by: an increase in the concentration of D-d, CRP, Fg, lengthening of APTT and PT, ATIII activity and platelet count not differing from the normal range. 10 days after hospitalization and against the background of ongoing therapy, patients with NCP showed positive dynamics in the hemostasiological profile and the severity of the inflammatory response. Thromboelastography indices in patients with LCP did not differ from control values both at hospitalization and on day 10.Thus, in patients with novel coronavirus pneumonia, an increased prothrombotic activity and a pronounced inflammatory response are recorded. Against the background of treatment, there is a positive dynamics in both the coagulation status and the inflammatory response. Additional studies are needed to determine the diagnostic capabilities of thromboelastography in patients with NCP.

[The platelet hemostatic system and prooxidant and antioxidant potentials in the dynamics of burn disease].

Platelet aggregation and prooxidant and antioxidant potentials were studied in patients with burn more than 20% total body surface area for 30 days after injury. There were progressive increases in platelet aggregation, lipid peroxidation, and antioxidant activity. The possible pathogenetic aspects of the findings are discussed.

[Change in erythrocyte sedimentation during compression and decompression]. / Izmeneniie sedimentatsii éritrotsitov pri kompressii i dekompressii.

It is determined that during compression and decompression of blood and blood suspension the main section plane of naturally sedimented erythrocytes assume virtually vertical position and, therefore, sedimentation rate of erythrocytes rises. Also, following compression blood density in vitro is irreversibly increased. The idea of existence of erythrocyte-bonded gas microcavities is discussed.