Effects of glucocorticoids on polyamine metabolism in liver and spleen of guinea pig during sensitization

Summary. Glucocorticoids are potent anti-inflammatory and immunosuppressive agents. As endogenous inhibitors of cytokine synthesis, glucocorticoids suppress immune activation and uncontrolled overproduction of cytokines, preventing tissue injury. Also, polyamine spermine is endogenous inhibitor of cytokine production (inhibiting IL-1, IL-6 and TNF synthesis). The idea of our work was to examine dexamethasone effects on the metabolism of polyamines, spermine, spermidine and putrescine and polyamine oxidase activity in liver and spleen during sensitization of guinea pigs. Sensitization was done by application of bovine serum albumin with addition of complete Freund’s adjuvant. Our results indicate that polyamine amounts and polyamine oxidase activity increase during immunogenesis in liver and spleen. Dexamethasone application to sensitized and unsensitized guinea pigs causes depletion of polyamines in liver and spleen. Dexamethasone decreases polyamine oxidase activity in liver and spleen of sensitized guinea pigs, increasing at the same time PAO activity in tissues of unsensitized animals.     

Chronic psychological stress activates BMP4‐dependent extramedullary erythropoiesis

Psychological stress affects different physiological processes including haematopoiesis. However, erythropoietic effects of chronic psychological stress remain largely unknown. The adult spleen contains a distinct microenvironment favourable for rapid expansion of erythroid progenitors in response to stressful stimuli, and emerging evidence suggests that inappropriate activation of stress erythropoiesis may predispose to leukaemic transformation. We used a mouse model to study the influence of chronic psychological stress on erythropoiesis in the spleen and to investigate potential mediators of observed effects. Adult mice were subjected to 2 hrs daily restraint stress for 7 or 14 consecutive days. Our results showed that chronic exposure to restraint stress decreased the concentration of haemoglobin in the blood, elevated circulating levels of erythropoietin and corticosterone, and resulted in markedly increased number of erythroid progenitors and precursors in the spleen. Western blot analysis revealed significantly decreased expression of both erythropoietin receptor and glucocorticoid receptor in the spleen of restrained mice. Furthermore, chronic stress enhanced the expression of stem cell factor receptor in the red pulp. Moreover, chronically stressed animals exhibited significantly increased expression of bone morphogenetic protein 4 (BMP4) in the red pulp as well as substantially enhanced mRNA expression levels of its receptors in the spleen. These findings demonstrate for the first time that chronic psychological stress activates BMP4‐dependent extramedullary erythropoiesis and leads to the prolonged activation of stress erythropoiesis pathways. Prolonged activation of these pathways along with an excessive production of immature erythroid cells may predispose chronically stressed subjects to a higher risk of leukaemic transformation.     

A knowledge-based system for the strategic control level of robots in flexible manufacturing cells

The strategic control level synthesis for robots is related to a hierarchical robot control problem. The main control problem at the strategic control level is to select the model and algorithm to be used by the lower control level to execute the given robot task. Usually there are several lower control level models and algorithms that can be used by the robot control system for every robot task. Strategic control level synthesis depends on the particular robot system application. In a typical application, when the robot system is used in a flexible manufacturing system for manipulating various part types, the robot tasks executed by the robot system depend on the manufacturing processes in the system. If the robot system is applied in another flexible manufacturing system, dedicated to other manufacturing processes, another set of robot tasks might be needed to perform the necessary operations. Therefore, the quantity and the kind of knowledge required in the system for the strategic control level differ from one application to another. Such a fact creates the appropriate conditions for employing some artificial intelligence techniques. This article describes a knowledge-based system approach to the strategic control level synthesis problem.     

Influence of resistance training on cardiorespiratory endurance and muscle power and strength in young athletes

The purpose of this study was to investigate the influence of additional resistance training on cardiorespiratory endurance in young (15.8 ± 0.8 yrs) male basketball players. Experimental group subjects (n=23) trained twice per week for 12 weeks using a variety of general free-weight and machine exercises designed for strength acquisition, beside ongoing regular basketball training program. Control group subject (n=23) participated only in basketball training program. Oxygen uptake (VO(2max)) and related gas exchange measures were determined continuously during maximal exercise test using an automated cardiopulmonary exercise system. Muscle power of the extensors and flexors was measured by a specific computerized tensiometer. Results from the experimental group (VO(2max) 51.6 ± 5.7 ml.min(-1).kg(-1) pre vs. 50.9 ± 5.4 ml.min(-1).kg(-1) post resistance training) showed no change (p>0.05) in cardiorespiratory endurance, while muscle strength and power of main muscle groups increased significantly. These data demonstrate no negative cardiorespiratory performance effects on adding resistance training to ongoing regular training program in young athletes.     

Secoiridoid glycosides production by Centaurium maritimum (L.) Fritch hairy root cultures in temporary immersion bioreactor

Secoiridoid glycosides are naturally occurring phytochemicals of great importance for the food and pharmaceutical industry because of their various biological activities. Certain Gentiana and Centaurium species, which are recognized as the most important sources of these compounds, have become critically endangered due to overexploitation. In this study we describe a laboratory-scale approach for further implementation in large-scale production of secoiridoid glycosides, using a hairy root culture system of Centaurium maritimum L. Fritch, an underutilized and phytochemically unexplored species. Hairy roots were induced by Agrobacterium rhizogenes strain A40M70GUS and grown in Erlenmeyer flasks, as well as in RITA^® temporary immersion bioreactors (TIBs). About 2–4 times higher biomass production rate and up to 8 times higher total secoiridoid glycosides production rate were achieved in RITA^® bioreactors. Among the selected hairy root lines, line HR3 cultured in RITA^® TIBs proved to be the most efficient considering both biomass and secoiridoid glycosides production rate.     

Effect of monosodium glutamate on oxidative stress and apoptosis in rat thymus

It has been demonstrated that administration of high concentrations of monosodium glutamate (MSG), induce oxidative stress in different organs, but not in thymus. In the present study we examined the role of oxidative stress in MSG-induced thymocyte apoptosis. MSG was administrated intraperitoneally (4 mg/g of body weight) for six consecutive days. Animals were sacrificed at 1st, 7th, and 15th day after last MSG dose. MSG administration to animals significantly increased apoptotic rate of thymocytes (P < 0.01), together with significant increase of malondialdehyde (MDA) level (P < 0.001) and xanthine oxidase (XO) activity (P < 0.01), in time dependent manner. Catalase activity, during examination period, was significantly decreased (0 < 0.01). Obtained results showed that MSG treatment induced oxidative stress in thymus, which may have an important role in thymocyte apoptosis induced by MSG.     

Microarray and Proteomic Analyses of Myeloproliferative Neoplasms with a Highlight on the mTOR Signaling Pathway

The gene and protein expression profiles in myeloproliferative neoplasms (MPNs) may reveal gene and protein markers of a potential clinical relevance in diagnosis, treatment and prediction of response to therapy. Using cDNA microarray analysis of 25,100 unique genes, we studied the gene expression profile of CD34⁺ cells and granulocytes obtained from peripheral blood of subjects with essential thrombocythemia (ET), polycythemia vera (PV) and primary myelofibrosis (PMF). The microarray analyses of the CD34⁺ cells and granulocytes were performed from 20 de novo MPN subjects: JAK2 positive ET, PV, PMF subjects, and JAK2 negative ET/PMF subjects. The granulocytes for proteomic studies were pooled in 4 groups: PV with JAK2 mutant allele burden above 80%, ET with JAK2 mutation, PMF with JAK2 mutation and ET/PMF with no JAK2 mutation. The number of differentially regulated genes was about two fold larger in CD34⁺ cells compared to granulocytes. Thirty-six genes (including RUNX1, TNFRSF19) were persistently highly expressed, while 42 genes (including FOXD4, PDE4A) were underexpressed both in CD34⁺ cells and granulocytes. Using proteomic studies, significant up-regulation was observed for MAPK and PI3K/AKT signaling regulators that control myeloid cell apoptosis and proliferation: RAC2, MNDA, S100A8/9, CORO1A, and GNAI2. When the status of the mTOR signaling pathway related genes was analyzed, PI3K/AKT regulators were preferentially up-regulated in CD34⁺ cells of MPNs, with down-regulated major components of the protein complex EIF4F. Molecular profiling of CD34⁺ cells and granulocytes of MPN determined gene expression patterns beyond their recognized function in disease pathogenesis that included dominant up-regulation of PI3K/AKT signaling.