Органопротективная эффективность эпросартана у больных хроническим гломерулонефритом

The 12-week open uncontrollable study of eprosartan organoprotective efficacy was performed in 15 patients with chronic glomerulonephritis. Study results showed high organoprotective efficacy of eprosartan, prescribed in a dose of 600 mg daily, which is expressed as anti-proteinuric, anti-hematuric actions, positive dynamics of intraglomerular hemodynamics parameters, decreased left ventricular hypertrophy and stiffness and also normalized vasomotoric functions of brachial artery endothelium.Проведено 12-недельное открытое неконтролируемое исследование органопротективной эффективности эпросартана у 15 пациентов с хроническим гломерулонефритом. Результаты исследования свидетельствуют о высокой органопротективной эффективности эпросартана, назначенного в дозе 600 мг в сутки, которая проявляется в виде антипротеинурического, антигематурического действия, положительной динамики параметров внутриклубочковой гемоциркуляции, уменьшения гипертрофии и жесткости левого желудочка, а также нормализации сосудодвигательной функции эндотелия плечевой артерии

Selective BRAFV600E Inhibitor PLX4720, Requires TRAIL Assistance to Overcome Oncogenic PIK3CA Resistance

Documented sensitivity of melanoma cells to PLX4720, a selective BRAFV600E inhibitor, is based on the presence of mutant BRAFV600E alone, while wt-BRAF or mutated KRAS result in cell proliferation. In colon cancer appearance of oncogenic alterations is complex , since BRAF, like KRAS mutations, tend to co-exist with those in PIK3CA and mutated PI3K has been shown to interfere with the successful application of MEK inhibitors. When PLX4720 was used to treat colon tumours, results were not encouraging and herein we attempt to understand the cause of this recorded resistance and discover rational therapeutic combinations to resensitize oncogene driven tumours to apoptosis. Treatment of two genetically different BRAFV600E mutant colon cancer cell lines with PLX4720 conferred complete resistance to cell death. Even though p-MAPK/ ERK kinase (MEK) suppression was achieved, TRAIL, an apoptosis inducing agent, was used synergistically in order to achieve cell death by apoptosis in RKOBRAFV600E/PIK3CAH1047 cells. In contrast, for the same level of apoptosis in HT29BRAFV600E/PIK3CAP449T cells, TRAIL was combined with 17-AAG, an Hsp90 inhibitor. For cells where PLX4720 was completely ineffective, 17-AAG was alternatively used to target mutant BRAFV600E. TRAIL dependence on the constitutive activation of BRAFV600E is emphasised through the overexpression of BRAFV600E in the permissive genetic background of colon adenocarcinoma Caco-2 cells. Pharmacological suppression of the PI3K pathway further enhances the synergistic effect between TRAIL and PLX4720 in RKO cells, indicating the presence of PIK3CAMT as the inhibitory factor. Another rational combination includes 17-AAG synergism with TRAIL in a BRAFV600E mutant dependent manner to commit cells to apoptosis, through DR5 and the amplification of the apoptotic pathway. We have successfully utilised combinations of two chemically unrelated BRAFV600E inhibitors in combination with TRAIL in a BRAFV600E mutated background and provided insight for new anti-cancer strategies where the activated PI3KCA mutation oncogene should be suppressed

Unified Spectral Technique Application for Study of Radiator Behavior Near Planar Layered Composites

The Unified Spectral Technique (UST) is a rigorous analytical approach for calculating power fluxes of any type of source and losses in multilayered dielectric structures of canonical geometries. This method is a reasonable addition to the eigenfunctions technique. An important advantage of the method is that the power fluxes are represented in an explicit form via their spectra, avoiding cumbersome calculations via field components. In this paper, this approach is specified for a case of planar multilayered structures, including those made of composite materials. Results of computations for the simplest types of radiators (electric and magnetic dipoles) in proximity of parallel-plane composite layers, comprised of a dielectric base and conducting inclusions with concentrations below and above percolation threshold, are analyzed

Wpływ zielonych dachów na jakość wody deszczowej oraz wybrane problemy ekoploatacyjne - studium przypadku

Shopping centres usually occupy large areas of land development. However, their roofs are rarely used for purposes related to rainwater management and introduction of active biological surfaces. In Bielsko-Biała, thanks to the initiative of the originator and architect, an intense green roof was created on the rooftop of a shopping centre. In addition to the primary role of the roof as a garden that makes the housing estate more attractive, it also collects some of the rainwater and delays its outflow to the sewage system. Plants, shrubs and trees planted on the roof are watered almost exclusively with water collected in a tank located under the building, intended for retaining rainwater. These waters are pretreated before they reach the tank, i.e. they filter through the root layer of plants growing on the roof, and through the biologically active layer (substrate). This paper highlights some of the operating problems of the selected green roof. The authors focused on assessing the toxicity of rainwater flowing down from hardened surfaces on the roof of the shopping centre and the area occupied by the green roof. Relevant toxicity studies on these waters have been carried out in this regard. The research hypothesis that rainwater percolating through the selected soil material is not toxic and stimulates test plant growth was put forward. Tests of semichronic toxicity with the seeds of white mustard (Sinapis alba L.) prove that all the rainwater samples showed a stimulating effect on the test plant. The average root growth stimulation value during the period considered was –125%. It was confirmed that rainwater did not show toxic properties for white mustard seeds (Sinapis alba L.) and can be used for watering the garden constituting the green roof of a selected research facility. In the case of rainwater pH, it was found that the pH is adequate and has no toxic effect on the selected white mustard test plant (Sinapis alba L.). It confirms that the rainwater retained in this way can be used to water the green roof. The selected research facility meets the requirements set for green roofs

Spectroscopy of infrared transitions of Pr3+ ions in Ga-Ge-Sb-Se glasses

International audienceElectronic transitions of Pr3+ ions in Ga-Ge-Sb-Se glasses corresponding to emissions in the infrared region were studied by means of absorption and emission spectroscopies and fluorescence lifetimes measurements. Transition probabilities, radiative lifetimes, branching ratios, and quantum efficiencies of most of the emission transitions including the infrared ones occurring around 1.3, 1.7, and 2.4 μm were estimated based on a standard Judd-Ofelt analysis

C3a Receptor Signaling Inhibits Neurodegeneration Induced by Neonatal Hypoxic-Ischemic Brain Injury

Hypoxic-ischemic neonatal encephalopathy due to perinatal asphyxia is the leading cause of brain injury in newborns. Clinical data suggest that brain inflammation induced by perinatal insults can persist for years. We previously showed that signaling through the receptor for complement peptide C3a (C3aR) protects against cognitive impairment induced by experimental perinatal asphyxia. To investigate the long-term neuropathological effects of hypoxic-ischemic injury to the developing brain and the role of C3aR signaling therein, we subjected wildtype mice, C3aR deficient mice, and mice expressing biologically active C3a in the CNS to mild hypoxic-ischemic brain injury on postnatal day 9. We found that such injury triggers neurodegeneration and pronounced reactive gliosis in the ipsilesional hippocampus both of which persist long into adulthood. Transgenic expression of C3a in reactive astrocytes reduced hippocampal neurodegeneration and reactive gliosis. In contrast, neurodegeneration and microglial cell density increased in mice lacking C3aR. Intranasal administration of C3a for 3 days starting 1 h after induction of hypoxia-ischemia reduced neurodegeneration and reactive gliosis in the hippocampus of wildtype mice. We conclude that neonatal hypoxic-ischemic brain injury leads to long-lasting neurodegeneration. This neurodegeneration is substantially reduced by treatment with C3aR agonists, conceivably through modulation of reactive gliosis

Power Absorption of Near Field of Elementary Radiators in Proximity of a Composite Layer

Near-field behavior of elementary electric and magnetic dipoles close to a plane layer (or layers) of engineered composite materials is analyzed using the rigorous analytical approach. Some results of computations are represented for composite media containing conductive inclusions. These composites provide shielding mainly due to absorption of electromagnetic energy. The effect of conductivity of inclusions and their geometry (through their aspect ratio) on the absorption and radiation efficiency of a radiator near composite layers is analyzed

Molecular analysis of the pre-BCR complex in a large cohort of patients affected by autosomal-recessive agammaglobulinemia

Autosomal-recessive agammaglobulinemia is a rare and heterogeneous disorder, characterized by early-onset infections, profound hypogammaglobulinemia of all immunoglobulin isotypes and absence of circulating B lymphocytes. To investigate the molecular basis of the disease, 23 patients with early-onset disease and no mutations in Bruton tyrosine kinase, the gene responsible for X-linked agammaglobulinemia, were selected and analyzed by direct sequencing of candidate genes. Two novel mutations in the mu heavy chain (mu HC) gene (IGHM) were identified in three patients belonging to two unrelated families. A fourth patient carries a previously described G> A nucleotide substitution at the -1 position of an alternative splice site in IGHM; here, we demonstrate that this mutation is indeed responsible for aberrant splicing. Comparison of bone marrow cytofluorimetric profiles in two patients carrying different mutations in the IGHM gene suggests a genotype-phenotype correlation with the stage at which B-cell development is blocked. Several new single nucleotide polymorphisms (SNPs) both in the mu HC and in the lambda 5-like/VpreB-coding genes were identified. Two unrelated patients carry compound heterozygous variations in the VpreB1 gene that may be involved in disease ethiology