Glucocorticoid receptor alters isovolumetric contraction and restrains cardiac fibrosis

Corticosteroids directly affect the heart and vasculature and are implicated in the pathogenesis of heart failure. Attention is focussed upon the role of the mineralocorticoid receptor (MR) in mediating pro-fibrotic and other adverse effects of corticosteroids upon the heart. In contrast, the role of the glucocorticoid receptor (GR) in the heart and vasculature is less well understood. We addressed this in mice with cardiomyocyte and vascular smooth muscle deletion of GR (SMGRKO mice). Survival of SMGRKO mice to weaning was reduced compared with that of littermate controls. Doppler measurements of blood flow across the mitral valve showed an elongated isovolumetric contraction time in surviving adult SMGRKO mice, indicating impairment of the initial left ventricular contractile phase. Although heart weight was elevated in both genders, only male SMGRKO mice showed evidence of pathological cardiomyocyte hypertrophy, associated with increased myosin heavy chain-β expression. Left ventricular fibrosis, evident in both genders, was associated with elevated levels of mRNA encoding MR as well as proteins involved in cardiac remodelling and fibrosis. However, MR antagonism with spironolactone from birth only modestly attenuated the increase in pro-fibrotic gene expression in SMGRKO mice, suggesting that elevated MR signalling is not the primary driver of cardiac fibrosis in SMGRKO mice, and cardiac fibrosis can be dissociated from MR activation. Thus, GR contributes to systolic function and restrains normal cardiac growth, the latter through gender-specific mechanisms. Our findings suggest the GR:MR balance is critical in corticosteroid signalling in specific cardiac cell types

Cytotoxic activity of proteins isolated from extracts of Corydalis cava tubers in human cervical carcinoma HeLa cells

<p>Abstract</p> <p>Background</p> <p><it>Corydalis cava </it>Schweigg. & Koerte, the plant of numerous pharmacological activities, together with the studied earlier by our group <it>Chelidonium majus </it>L. (Greater Celandine), belong to the family <it>Papaveraceae</it>. The plant grows in Central and South Europe and produces the sizeable subterraneous tubers, empty inside, which are extremely resistant to various pathogen attacks. The <it>Corydalis sp. </it>tubers are a rich source of many biologically active substances, with the extensive use in European and Asian folk medicine. They have analgetic, sedating, narcotic, anti-inflammatory, anti-allergic and anti-tumour activities. On the other hand, there is no information about possible biological activities of proteins contained in <it>Corydalis cava </it>tubers.</p> <p>Methods</p> <p>Nucleolytic proteins were isolated from the tubers of <it>C. cava </it>by separation on a heparin column and tested for DNase activity. Protein fractions showing nucleolytic activity were tested for cytotoxic activity in human cervical carcinoma HeLa cells. Cultures of HeLa cells were conducted in the presence of three protein concentrations: 42, 83 and 167 ng/ml during 48 h. Viability of cell cultures was appraised using XTT colorimetric test. Protein fractions were separated and protein bands were excised and sent for identification by mass spectrometry (LC-ESI-MS/MS).</p> <p>Results</p> <p>The studied protein fractions showed an inhibiting effect on mitochondrial activity of HeLa cells, depending on the administered dose of proteins. The most pronounced effect was obtained with the highest concentration of the protein (167 ng/ml) - 43.45 ± 3% mitochondrial activity of HeLa cells were inhibited. Mass spectrometry results for the proteins of applied fractions showed that they contained plant defense- and pathogenesis-related (PR) proteins.</p> <p>Conclusions</p> <p>The cytotoxic effect of studied proteins toward HeLa cell line cells has been evident and dependent on increasing dose of the protein. The present study, most probably, represents the first investigations on the effect of purified PR proteins from tuber extracts of a pharmacologically active plant on cell lines.</p

Spatial Distribution, Air-Water Fugacity Ratios and Source Apportionment of Polychlorinated Biphenyls in the Lower Great Lakes Basin

Polychlorinated biphenyls (PCBs) continue to be contaminants of concern across the Great Lakes. It is unclear whether current concentrations are driven by ongoing primary emissions from their original uses, or whether ambient PCBs are dominated by their environmental cycling. Freely dissolved PCBs in air and water were measured using polyethylene passive samplers across Lakes Erie and Ontario during summer and fall, 2011, to investigate their spatial distribution, determine and apportion their sources and to asses their air–water exchange gradients. Average gaseous and freely dissolved ∑29 PCB concentrations ranged from 5.0 to 160 pg/m3 and 2.0 to 55 pg/L respectively. Gaseous concentrations were significantly correlated (R2 = 0.80) with the urban area within a 3−20 km radius. Fugacity ratios indicated that the majority of PCBs are volatilizing from the water thus acting as a secondary source for the atmosphere. Dissolved PCBs were probably linked to PCB emissions from contaminated sites and areas of concern. Positive matrix factorization indicated that although volatilized Aroclors (gaseous PCBs) and unaltered Aroclors (dissolved PCBs) dominate in some samples, ongoing non-Aroclor sources such as paints/pigments (PCB 11) and coal/wood combustion showed significant contributions across the lower Great Lakes. Accordingly, control strategies should give further attention to PCBs emitted from current use sources

Levels and sources of PCDDs, PCDFs and dl-PCBs in the water ecosystems of central Poland — A mini review

Polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) are unwanted by-products in a variety of industrial and thermal processes. They have been present on Earth long before the human era, since they may be also formed as a result of forest fires or volcanic explosions. Polychlorinated biphenyls (PCBs) in turn, have been intentionally produced by humans. Poland was a minor producer of PCB mixtures (Chlorofen and Tarnol), which were a source of direct and indirect environmental diffusion with PCB and less with PCDDs/PCDFs. Industrial accidents with PCDDs/PCDFs were absent in Poland. Their stability and resistance to thermal breakdown made them very dangerous for environment and, in consequence, due to their environmental persistence, bioaccumulation and biomagnification in the terrestrial and aquatic food chains, to humans. Humans may become affected by PCDDs/PCDFs and PCBs through environmental (soil and water contamination, fish and food), occupational (incinerators; pulp, paper and metallurgy industry; copper production), or accidental (Seveso accident) exposure. The aim of this review was to evaluate environmental hazard caused by PCDDs, PCDFs and dioxin-like-PCBs in the central region of Poland based on the accessible data on diffusion of those compounds in sediments and riverine, reservoir and storm water from our previous studies and discussed in the context of other achievements in Poland and elsewhere

Mercury in the bottom sediments of the lower Vistula river ecosystem, Poland - A role of the anthropogenic factor

Total mercury concentrations were determined in surface layer of sediments collected in 1998-2001 from several locations along the Lower Vistula River, Poland. The wet digestion (HNO$_3$-H$_2$SO$_4$) method used for sample preparation was both repeatable and quantitative and allowed mercury determination by cold vapour atomic absorption spectrometry (CV-AAS). The sediment samples collected from sites located very close to, or within, the urbanized and industrialized areas showed elevated mercury concentrations, reaching up to 370 ng/g dry weight on the average. Geochemical index (I$_{\rm geo}$) approach was used to compare “post-industrial” mercury concentration in sediments with natural (“pre-industrial”) sediment mercury background

Wpływ wilgotności na wartość niektórych cech ziarna gryki odmiany Panda

Gryka jest gatunkiem, który zachował wiele cech rośliny dzikiej, między innymi niekończący się wzrost i długi okres wegetacji. Przy zbiorze jednofazowym zachodzi konieczność desykacji roślin. W trakcie zbioru ziarna gryki ulegają zawilgoceniu, często do 24%. W hodowli roślin coraz częściej zwraca się uwagę na cechy fizyczne ziaren, co pozwala na otrzymywanie odmian o bardziej dorodnych ziarnach, odpornych na uszkodzenia podczas zbioru, transportu czy przechowywania. Badano zmiany niektórych cechy fizycznych ziaren gryki w różnych warunkach wilgotności. Do badań przyjęto następujące poziomy wilgotności nasion: 9, 12, 15, 18, 21 i 24%. Badaniami objęto zakres wilgotności, jaki może wystąpić w okresie zbioru czy magazynowania. Warunki klimatyczne jakie wystąpiły w 2008 roku były korzystne dla gryki, otrzymano plon nasion w wysokości 1,9 t*ha-1, o masie 1000 ziaren równej 26,8 g, co świadczy o dorodności i dobrym wypełnieniu ziarna. W pozostałych latach otrzymano niższe plony nasion o masie 1000 nasion około 25-26 g. Nie stwierdzono istotnego wpływu warunków klimatycznych w poszczególnych latach na wartości badanych cech fizycznych ziaren. Zmiany w poziomie wilgotności ziarna warunkowały zmiany wartości badanych cech. U większości badanych cech ich wartość wzrastała wraz ze wzrostem wilgotności ziaren, z tym że u kąta zsypu i usypu najniższe wartości otrzymano przy wilgotności ziarna 15%, przy wyższym poziomie wilgotności ziarna wartości tych cech rosły. Porowatość ziaren była ujemnie skorelowana z ich wilgotnością, Stwierdzono, że wraz ze wzrostem wilgotności ziaren porowatość masy ziarna ulegała zmniejszeniu.Influence of moisture on the value of some properties of a buckwheat seed of Panda variety Buckwheat is a variety, which have maintained many properties of a wild plant, inter alia a non-finite growth and a long period of vegetation. At the one-stage crop there is a necessity to dry plants. During harversting, buckwheat seeds get moist, frequently up to 24 %. More and more often, attention is paid to the physical properties of seeds during plant cultivation, which allows for obtaining varieties of very splendid seeds, resistant to damaging during harvesting, transporting or storing. Changes of some physical properties of buckwheat seeds in different moisture conditions were researched. The following levels of seeds moisture were accepted to the research: 9, 12, 15, 18, 21 i 24%. The research included the scope of moisture, which may occur during harvesting or storing. Climatic conditions, which occurred in 2008, were favourable for buckwheat; the obtained crop of seeds was in the amount of 1.9 t*ha-1, of the mass of 1000 seeds equal to 26.8 g, what proves ripeness and good filling of a seed. In the remaining years, lower crops of seeds of the mass of 1000 seeds -approx. 25-26 g were obtained. No significant influence of climatic conditions in particular years on the value of the examined physical properties of seeds was determined. Changes in the level of moisture conditioned changes of values of the examined properties. The value of the majority of the examined properties was increasing along with the increase of seeds moisture, however, at the angle of slide and the angle of repose, the lowest values were obtained at the seeds moisture of 15%, at the higher level of seeds moisture values of these properties were rising. Porosity of seeds was negatively correlated with their moisture. It was determined that with the growth of seeds moisture, the porosity of seeds mass decreased