Oxidative-antioxidant imbalance and impaired glucose metabolism in schizophrenia

Schizophrenia is a neurodevelopmental disorder featuring chronic, complex neuropsychiatric features. The etiology and pathogenesis of schizophrenia are not fully understood. Oxidative-antioxidant imbalance is a potential determinant of schizophrenia. Oxidative, nitrosative, or sulfuric damage to enzymes of glycolysis and tricarboxylic acid cycle, as well as calcium transport and ATP biosynthesis might cause impaired bioenergetics function in the brain. This could explain the initial symptoms, such as the first psychotic episode and mild cognitive impairment. Another concept of the etiopathogenesis of schizophrenia is associated with impaired glucose metabolism and insulin resistance with the activation of the mTOR mitochondrial pathway, which may contribute to impaired neuronal development. Consequently, cognitive processes requiring ATP are compromised and dysfunctions in synaptic transmission lead to neuronal death, preceding changes in key brain areas. This review summarizes the role and mutual interactions of oxidative damage and impaired glucose metabolism as key factors affecting metabolic complications in schizophrenia. These observations may be a premise for novel potential therapeutic targets that will delay not only the onset of first symptoms but also the progression of schizophrenia and its complications

Inflammatory markers and left ventricular diastolic dysfunction in a family-based population study

Background: Heart failure affects patients with normal left ventricular systolic function (heart failure with preserved ejection fraction [HFPEF]) and those with reduced ejection fraction (HFREF). The treatment of HFPEF remains an unresolved issue. Aims: We sought to determinate the relationship between inflammatory markers and left ventricular diastolic dysfunction (LVDD) in a family-based population study. Methods: A total of 303 participants from the general population (55% women, median age 49 years and 45% men, median age 40 years) underwent echocardiography and measurement of serum inflammatory markers: C-reactive protein (CRP), myeloperoxidase (MPO), and interleukin 6 (IL-6). Results: Serum IL-6 concentration correlated with peak transmitral late diastolic velocity (A) and pulmonary vein systolic-to-di­astolic velocity (S/D) ratio (p < 0.01). Moreover, a significant correlation between IL-6 concentration and E/A ratio and early diastolic peak velocities of the mitral annulus displacement (E’) was observed. The association of IL-6 concentration and peak transmitral early diastolic velocities (E) and the E/E’ ratio (p < 0.05) was noted in men. In addition, the CRP concentration was shown to have an effect on E/A ratio in women (p < 0.05). A significant correlation between the CRP concentration and S/D ratio was observed both in women (p < 0.01) and men (p < 0.05). No significant correlation was found between the level of MPO and LVDD parameters. Additionally, only one predictive model was identified; E’ was found to be dependent on IL-6, age, and heart rate in men (p < 0.001, R2 = 0.611). Conclusions: The above results suggest that inflammation may lead to the onset of LVDD, probably via vascular endothelial dysfunction

Heme Oxygenase-1 Accelerates Cutaneous Wound Healing in Mice

Heme oxygenase-1 (HO-1), a cytoprotective, pro-angiogenic and anti-inflammatory enzyme, is strongly induced in injured tissues. Our aim was to clarify its role in cutaneous wound healing. In wild type mice, maximal expression of HO-1 in the skin was observed on the 2nd and 3rd days after wounding. Inhibition of HO-1 by tin protoporphyrin-IX resulted in retardation of wound closure. Healing was also delayed in HO-1 deficient mice, where lack of HO-1 could lead to complete suppression of reepithelialization and to formation of extensive skin lesions, accompanied by impaired neovascularization. Experiments performed in transgenic mice bearing HO-1 under control of keratin 14 promoter showed that increased level of HO-1 in keratinocytes is enough to improve the neovascularization and hasten the closure of wounds. Importantly, induction of HO-1 in wounded skin was relatively weak and delayed in diabetic (db/db) mice, in which also angiogenesis and wound closure were impaired. In such animals local delivery of HO-1 transgene using adenoviral vectors accelerated the wound healing and increased the vascularization. In summary, induction of HO-1 is necessary for efficient wound closure and neovascularization. Impaired wound healing in diabetic mice may be associated with delayed HO-1 upregulation and can be improved by HO-1 gene transfer

Development and optimization of an in vitro blood lactate determination method to assess the regulation of bioenergetic pathways in cells.

Praca przedstawia problem patomechanizmów neuropsychiatrycznych z udziałem zmienionego metabolizmu bioenergetycznego, w którym pośredniczą mleczany, ze szczególnym uwzględnieniem cyklu kwasów trójkarboksylowych, jego udziału, rozwoju i tworzenia występujących w komórkach organizmu adaptacji do stresu, biologicznych reakcjach na stres i złożonych psychopatologiach związanych ze stresem. Komórki naszego ciała, w tym neurony wykorzystują glukozę, aminokwasy i różne metabolity pośrednie jako podstawowe źródło energii. W warunkach tlenowych glukoza jest całkowicie spalana przez tkanki na drodze cyklu kwasu trójkarboksylowego (cykl TCA) do dwutlenku węgla. Alternatywnie, glukoza może być katabolizowana beztlenowo poprzez glikolizę do mleczanu, który stanowi potencjalny składnik odżywczy dla tkanek i zmienionych chorobowo neuronów. Zmieniony metabolizm energetyczny mózgu w schizofrenii może być przyczyną gromadzenia się mleczanu i obniżonego pH nie tylko w mózgu, ale także na obwodzie.Praca badawcza polegała na określeniu stężenia mleczanów we krwi chorych na schizofrenię w trakcie dekompensacji psychotycznej (zaostrzenia objawów psychotycznych), w dwóch punktach czasowych – po przyjęciu na oddział (F20 n=1) oraz po 12 tygodniach leczenia, w trakcie remisji objawów (F20 n=2), w porównaniu z grupą osób zdrowych. Oznaczenie stężenia mleczanów przeprowadzono metodą kinetyczną z wykorzystaniem spektrofotometrii. Wyniki: Stężenie mleczanów różniło się istotnie statystycznie w grupie F20 n=1 w porównaniu do grupy kontrolnej, jednak obserwowane różnice nie pojawiły się w grupie F20 n=2.Wnioski: Zmieniony metabolizm energetyczny związany ze zmianą stężenia mleczanów we krwi osób chorych na schizofrenię może służyć jako skuteczny cel w ocenie progresji i skuteczności leczenia tej choroby.The paper presents the problem of neuropsychiatric pathomechanisms involving altered bioenergetic metabolism mediated by lactate, with particular emphasis on the tricarboxylic acid cycle, its participation, development and formation of adaptations to stress occurring in the body's cells, biological stress responses and complex stress-related psychopathologies. Our body's cells, including neurons, use glucose, amino acids and various intermediate metabolites as their primary source of energy. Under aerobic conditions, glucose is completely burned by tissues via the tricarboxylic acid cycle (TCA cycle) to carbon dioxide. Alternatively, glucose can be catabolized anaerobically via glycolysis to lactate, which is a potential nutrient for tissues and diseased neurons. The altered energy metabolism of the brain in schizophrenia can cause lactate accumulation and lowered pH not only in the brain but also in the periphery.The research work consisted in determining the concentration of lactate in the blood of patients with schizophrenia during psychotic decompensation, at two time points - after admission to the ward (F20 n = 1) and after 12 weeks of treatment (F20 n = 2), compared to the group of healthy people. Determination of lactate concentration was performed by the kinetic method with the use of spectrophotometry.Results: Lactate concentration differed significantly in the F20 n = 1 group compared to the control group, but the observed differences did not appear in the F20 n = 2 group.Conclusions: The altered energy metabolism associated with the change in blood lactate concentration in patients with schizophrenia may serve as an effective target in assessing the progression and effectiveness of the treatment of this disease

Modelling information for the burnishing process in a cyber-physical production system

Currently, the manufacturing management board applies technologies in line with the concept of Industry 4.0. Cyber-physical production systems (CPSs) mean integrating computational processes with the corresponding physical ones, i.e., allowing work at the operational level and at the strategic level to run side by side. This paper proposes a framework to collect data and information from a production process, namely, the burnishing one, in order to monitor real-time deviations from the correct course of the process and thus reduce the number of defective products within the manufacturing process. The proposed new solutions consist of (i) the data and information of the production process, acquired from sensors, (ii) a predictive model, based on the Hellwig method for errors in the production process, relying on indications of a machine status, and (iii) an information layer system, integrating the process data acquired in real time with the model for predicting errors within the production process in an enterprise resource planning (ERP) system, that is, the business intelligence module. The possibilities of using the results of research in managerial practice are demonstrated through the application of an actual burnishing process. This new framework can be treated as a solution which will help managers to monitor the production flow and respond, in real time, to interruptions