Effect of carbon disulphide on the cardiovascular system

Biochemical, histological and electron-microscopic examinations of the heart and the aorta of albino rats exposed to carbon disulphide in concentrations of 10, 50, 100 and 200 mg . m-3 were carried out. Changes in the metabolic and energetic processes in the myocardium and in the quantitative and qualitative characteristics of the connective tissue of the aortal vessel wall were observed. The established disorders follow the dose-effect dependence. The authors studied the effect of carbon disulphide in concentrations of 10 and 50 mg . m-3 on the electrophoretic spectrum of serum proteins, the quantitative and qualitative characteristics of fibrous structures in the myocardium and the aorta of albino rats fed on atherogenic diet (cholesterol, cholic acid and vitamin D2). The combination of carbon disulphide with the atherogenic factor leads to intensification of changes in the cardiovascular system and in serum proteins, observed after independent exposure to either of the factors. The combination of atherogenic diet and 10 mg . m-3 carbon disulphide induced symptoms of intoxication, decreased survival of the animals, and the developing sclerotic process was found to be more severe and to progress more rapidly than in animals subject to atherogenic diet alone. The obtained results testify to cardiovascular effect of carbon disulphide. The observed atherogenic effect of carbon disulphide in low concentrations is most probably connected with its direct effect on the myocardium and the vessels.     

M13 DNA fingerprinting, a new tool for classification and identification of Lactobacillus spp.

The optimal conditions for the application of M13 DNA fingerprinting to the genus Lactobacillus were determined. Comparative fingerprint analysis of representative strains of Lactobacillus delbrueckii subsp. delbrueckii, Lact. delbrueckii subsp. lactis, Lact. delbrueckii subsp. bulgaricus, Lact. helveticus and Lact. casei permitted the differentiation of species, subspecies and individual strains and the quantitative determination of their genetic relatedness. The results confirm the high specificity of M13 DNA fingerprinting and indicate that it might be used in the classification of Lactobacillus spp.     

Changes in the miRNA-mRNA Regulatory Network Precede Motor Symptoms in a Mouse Model of Multiple System Atrophy: Clinical Implications

Multiple system atrophy (MSA) is a fatal rapidly progressive α-synucleinopathy, characterized by α-synuclein accumulation in oligodendrocytes. It is accepted that the pathological α-synuclein accumulation in the brain of MSA patients plays a leading role in the disease process, but little is known about the events in the early stages of the disease. In this study we aimed to define potential roles of the miRNA-mRNA regulatory network in the early pre-motor stages of the disease, i.e., downstream of α-synuclein accumulation in oligodendroglia, as assessed in a transgenic mouse model of MSA. We investigated the expression patterns of miRNAs and their mRNA targets in substantia nigra (SN) and striatum, two brain regions that undergo neurodegeneration at a later stage in the MSA model, by microarray and RNA-seq analysis, respectively. Analysis was performed at a time point when α-synuclein accumulation was already present in oligodendrocytes at neuropathological examination, but no neuronal loss nor deficits of motor function had yet occurred. Our data provide a first evidence for the leading role of gene dysregulation associated with deficits in immune and inflammatory responses in the very early, non-symptomatic disease stages of MSA. While dysfunctional homeostasis and oxidative stress were prominent in SN in the early stages of MSA, in striatum differential gene expression in the non-symptomatic phase was linked to oligodendroglial dysfunction, disturbed protein handling, lipid metabolism, transmembrane transport and altered cell death control, respectively. A large number of putative miRNA-mRNAs interaction partners were identified in relation to the control of these processes in the MSA model. Our results support the role of early changes in the miRNA-mRNA regulatory network in the pathogenesis of MSA preceding the clinical onset of the disease. The findings thus contribute to understanding the disease process and are likely to pave the way towards identifying disease biomarkers for early diagnosis of MSA.     

Alterations in the content and physiological role of sphingomyelin in plasma membranes of cells cultured in three-dimensional matrix

Naringenin (NGEN), a naturally occurring citrus flavonone, has shown cytotoxicity in various human cancer cell lines as well as inhibitory effects on tumor growth. It has been also shown to access the brain and there is an increasing interest in its therapeutic applications. The up-regulated expression of Cx43 leads to the suppression of tumorigenicity with promoted apoptotic events. In this study, we investigated the in vivo effect of NGEN in fostering apoptosis in cerebrally implanted C6 glioma cells rat model. We analysed the expression of Cx43, caspase-3, caspase-9, Cyt C, Bcl-2 and Bax in vivo by immunoblot analysis and the ultra structure of brain cells by transmission electron microscopy. Supplementation of NGEN to experimental animals modulated Bcl-2/Bax ratio and up-regulation of caspase-3 and 9. NGEN was also found to up-regulate the expression of Cx43. These findings provide evidence that NGEN’s apoptotic effect, modulation of Bcl-2/Bax ratio leads to release of Cyt C from mitochondria, thereby activation of caspase-3 and caspase-9 is mediated by enhanced expression of Cx43. These observations were well supported by the transmission electron microscopic results which showed the characteristic apoptotic features. In conclusion, our findings demonstrate that NGEN promotes apoptosis in rat C6 glioma model.     

Testing biological activity of model Maillard reaction products: studies on gastric smooth muscle tissues

Water-soluble Maillard reaction products obtained from five different model systems were investigated for their effects upon the mechanical activity of rat gastric smooth muscle. Most of the total Maillard reaction products applied at concentration of 1.5 mg/ml evoked contractions; among them the product obtained from arginine and glucose (Arg-Glc) produced the most powerful contractions. The product obtained from glycine and ascorbic acid (Gly-AsA) was the only one that brought about relaxation response. The high molecular weight fractions (>3,500 Da) isolated from the reaction systems Arg-Glc and Gly-AsA demonstrated effects similar in type and amplitude to those evoked by non-fractioned reaction products. The results obtained suggest that moieties of molecules acting upon the muscle tonus originate mainly from lysine and arginine residues; that these structures are available in both low and high molecular pools in similar concentrations, and most likely these fragments act upon membrane-located cellular structures involved in calcium transport.     

Enhanced resistance to Salmonella enterica serovar Typhimurium infection in mice after coumarin treatment

Coumarin and its derivatives are naturally occurring substances with multiple biological activities. Here we demonstrate that prophylactic peroral administration of coumarin or 7-hydroxycoumarin (7-OHC) enhances resistance to subsequent lethal Salmonella enterica Serovar Typhimurium infection in mice. 7-OHC decreased bacterial load in liver and spleen, and enhanced phagocytosis and bacterial killing by macrophages when applied in vitro and in vivo. 7-OHC treatment induced significant NO release in peritoneal macrophage cultures. The observed protective effect correlated with the induction of Th1-associated cytokines, such as IL-12, IFN-gamma, and TNF-alpha. These data demonstrate a clear immunomodulatory potential of coumarins which might have important therapeutic implications to enhance resistance to infection.     

Intravenous Immunoglobulin with Enhanced Polyspecificity Improves Survival in Experimental Sepsis and Aseptic Systemic Inflammatory Response Syndromes

Sepsis is a major cause for death worldwide. Numerous interventional trials with agents neutralizing single proinflammatory mediators have failed to improve survival in sepsis and aseptic systemic inflammatory response syndromes. This failure could be explained by the widespread gene expression dysregulation known as “genomic storm” in these patients. A multifunctional polyspecific therapeutic agent might be needed to thwart the effects of this storm. Licensed pooled intravenous immunoglobulin preparations seemed to be a promising candidate, but they have also failed in their present form to prevent sepsis-related death. We report here the protective effect of a single dose of intravenous immunoglobulin preparations with additionally enhanced polyspecificity in three models of sepsis and aseptic systemic inflammation. The modification of the pooled immunoglobulin G molecules by exposure to ferrous ions resulted in their newly acquired ability to bind some proinflammatory molecules, complement components and endogenous “danger” signals. The improved survival in endotoxemia was associated with serum levels of proinflammatory cytokines, diminished complement consumption and normalization of the coagulation time. We suggest that intravenous immunoglobulin preparations with additionally enhanced polyspecificity have a clinical potential in sepsis and related systemic inflammatory syndromes.     

Response of wheat restricted‐tillering and vigorous growth traits to variables of climate change

The response of wheat to the variables of climate change includes elevated CO₂, high temperature, and drought which vary according to the levels of each variable and genotype. Independently, elevated CO₂, high temperature, and terminal drought affect wheat biomass and grain yield, but the interactive effects of these three variables are not well known. The aim of this study was to determine the effects of elevated CO₂ when combined with high temperature and terminal drought on the high‐yielding traits of restricted‐tillering and vigorous growth. It was hypothesized that elevated CO₂ alone, rather than combined with high temperature, ameliorates the effects of terminal drought on wheat biomass and grain yield. It was also hypothesized that wheat genotypes with more sink capacity (e.g. high‐tillering capacity and leaf area) have more grain yield under combined elevated CO₂, high temperature, and terminal drought. Two pairs of sister lines with contrasting tillering and vigorous growth were grown in poly‐tunnels in a four‐factor completely randomized split‐plot design with elevated CO₂ (700 µL L^?1), high day time temperature (3 °C above ambient), and drought (induced from anthesis) in all combinations to test whether elevated CO₂ ameliorates the effects of high temperature and terminal drought on biomass accumulation and grain yield. For biomass and grain yield, only main effects for climate change variables were significant. Elevated CO₂ significantly increased grain yield by 24–35% in all four lines and terminal drought significantly reduced grain yield by 16–17% in all four lines, while high temperature (3 °C above the ambient) had no significant effect. A trade‐off between yield components limited grain yield in lines with greater sink capacity (free‐tillering lines). This response suggests that any positive response to predicted changes in climate will not overcome the limitations imposed by the trade‐off in yield components.     

Mesenchymal stem cells in a transgenic mouse model of multiple system atrophy: immunomodulation and neuroprotection

Background

Mesenchymal stem cells (MSC) are currently strong candidates for cell-based therapies. They are well known for their differentiation potential and immunoregulatory properties and have been proven to be potentially effective in the treatment of a large variety of diseases, including neurodegenerative disorders. Currently there is no treatment that provides consistent long-term benefits for patients with multiple system atrophy (MSA), a fatal late onset α-synucleinopathy. Principally neuroprotective or regenerative strategies, including cell-based therapies, represent a powerful approach for treating MSA. In this study we investigated the efficacy of intravenously applied MSCs in terms of behavioural improvement, neuroprotection and modulation of neuroinflammation in the (PLP)-αsynuclein (αSYN) MSA model.

Methodology/Principal Findings

MSCs were intravenously applied in aged (PLP)-αSYN transgenic mice. Behavioural analyses, defining fine motor coordination and balance capabilities as well as stride length analysis, were performed to measure behavioural outcome. Neuroprotection was assessed by quantifying TH neurons in the substantia nigra pars compacta (SNc). MSC treatment on neuroinflammation was analysed by cytokine measurements (IL-1α, IL-2, IL-4, IL-5, IL-6, IL-10, IL-17, GM-CSF, INFγ, MCP-1, TGF-β1, TNF-α) in brain lysates together with immunohistochemistry for T-cells and microglia.Four weeks post MSC treatment we observed neuroprotection in the SNc, as well as downregulation of cytokines involved in neuroinflammation. However, there was no behavioural improvement after MSC application.

Conclusions/Significance

To our knowledge this is the first experimental approach of MSC treatment in a transgenic MSA mouse model. Our data suggest that intravenously infused MSCs have a potent effect on immunomodulation and neuroprotection. Our data warrant further studies to elucidate the efficacy of systemically administered MSCs in transgenic MSA models.     

Role of antioxidant enzymes in survival of conidiospores of Aspergillus niger 26 under conditions of temperature stress

AIMS: A better understanding of the role of antioxidant enzymes, superoxide dismutase (SOD) and catalase (CAT) in the protection of Aspergillus niger spores against thermal stress. METHODS AND RESULTS: Conidiospores from A. niger 26 were subjected to wide range of temperatures (30, 50, 60 and 80 degrees C). The stress response was investigated by the determination of spore germination and mycelial growth of survivors under submerged cultivation. Exposure to any temperature above the optimal value induced an increase in SOD and CAT activities. PAGE demonstrated enhanced level of Cu/ZnSOD under stress conditions. We compared the influence of heat shock and superoxide-generating agent paraquat on growth and antioxidant enzyme defence and found different response to the both type of stresses. CONCLUSIONS: Heat stress elicits the enhanced synthesis of enzymes whose functions are to scavenge reactive oxygen species. These results suggested an association between thermal and oxidative stress. SIGNIFICANCE AND IMPACT OF THE STUDY: Evidence is provided for the possibility that oxidative stress plays a major role in the effect of heat in low eucaryotes such as A. niger. This knowledge may be of importance in controlling both fermentation and pathogenicity.