The Effects of Dasatinib in Experimental Acute Respiratory Distress Syndrome Depend on Dose and Etiology

Background/Aims: Evidence suggests that tyrosine-kinase inhibitors may attenuate lung inflammation and fibrosis in experimental acute respiratory distress syndrome (ARDS). We hypothesized that dasatinib, a tyrosine-kinase inhibitor, might act differently depending on the ARDS etiology and the dose. Methods: C57/BL6 mice were divided to be pre-treated with dasatinib (1mg/kg or 10mg/kg) or vehicle (1% dimethyl-sulfoxide) by oral gavage. Thirty-minutes after pre-treatment, mice were subdivided into control (C) or ARDS groups. ARDS animals received Escherichia coli lipopolysaccharide intratracheally (ARDSp) or intraperitoneally (ARDSexp). A new dose of dasatinib or vehicle was administered at 6 and 24h. Results: Forty-eight hours after ARDS induction, dasatinib 1mg/kg yielded: improved lung morphofunction and reduced cells expressing toll-like receptor (TLR)-4 in lung, independent of ARDS etiology; reduced neutrophil and levels of interleukin (IL)-6, IL-10 and transforming growth factor (TGF)-β in ARDSp. The higher dose of dasatinib caused no changes in lung mechanics, diffuse alveolar damage, neutrophil, or cells expressing TLR4, but increased IL-6, vascular endothelial growth factor (VEGF), and cells expressing Fas receptor in lung in ARDSp. In ARDSexp, it improved lung morphofunction, increased VEGF, and reduced cells expressing TLR4. Conclusion: Dasatinib may have therapeutic potential in ARDS independent of etiology, but careful dose monitoring is required. © 2015 S. Karger AG, Basel

Influence of apical oxygen on the extent of in-plane exchange interaction in cuprate superconductors

In high Tc superconductors the magnetic and electronic properties are determined by the probability that valence electrons virtually jump from site to site in the CuO2 planes, a mechanism opposed by on-site Coulomb repulsion and favored by hopping integrals. The spatial extent of the latter is related to transport properties, including superconductivity, and to the dispersion relation of spin excitations (magnons). Here, for three antiferromagnetic parent compounds (single-layer Bi2Sr0.99La1.1CuO6+delta, double-layer Nd1.2Ba1.8Cu3O6 and infinite-layer CaCuO2) differing by the number of apical atoms, we compare the magnetic spectra measured by resonant inelastic x-ray scattering over a significant portion of the reciprocal space and with unprecedented accuracy. We observe that the absence of apical oxygens increases the in-plane hopping range and, in CaCuO2, it leads to a genuine 3D exchange-bond network. These results establish a corresponding relation between the exchange interactions and the crystal structure, and provide fresh insight into the materials dependence of the superconducting transition temperature.Comment: 9 pages, 4 figures, 1 Table, 42 reference

Reproducibility of acute pulmonary vein isolation guided by the ablation index.

BACKGROUND: Atrial fibrillation (AF) ablation outcome is still operator dependent. Ablation Index (AI) is a new lesion quality marker that has been demonstrated to allow acute durable pulmonary vein (PV) isolation followed by a high single-procedure arrhythmia-free survival. This prospective, multicenter study was designed to evaluate the reproducibility of acute PV isolation guided by the AI. METHODS: A total of 490 consecutive patients with paroxysmal (80.4%) and persistent AF underwent first time PV encircling and were divided in four study groups according to operator preference in choosing the ablation catheter (a contact force [ST] or contact force surround flow [STSF] catheter) and the AI setting (330 at posterior and 450 at anterior wall or 380 at posterior and 500 at anterior wall). Radiofrequency was delivered targeting interlesion distance ≤6 mm. RESULTS: The rate of first-pass PV isolation (ST330 90 ± 16%, ST380 87 ± 19%, STSF330 90 ± 17%, STSF380 91 ± 15%, P = .585) was similar among the four study groups, whereas procedure (ST330 129 ± 44 minutes, ST380 144 ± 44 minutes, STSF330 120 ± 72 minutes, STSF380 125 ± 73 minutes, P < .001) and fluoroscopy time (ST330 542 ± 285 seconds, ST380 540 ± 416 seconds, STSF330 257 ± 356 seconds, STSF380 379 ± 454 seconds, P < 0.001) significantly differed. The difference in the rate of first-pass isolation was not statistical different (P = .06) among the 12 operators that performed at least 15 procedures. CONCLUSIONS: An ablation protocol respecting strict criteria for contiguity and quality lesion results in high and comparable rate of acute PV isolation among operator performing ablation with different catheters, AI settings, procedure, and fluoroscopy times

Aharonov-Bohm interferences from local deformations in graphene

One of the most interesting aspects of graphene is the tied relation between structural and electronic properties. The observation of ripples in the graphene samples both free standing and on a substrate has given rise to a very active investigation around the membrane-like properties of graphene and the origin of the ripples remains as one of the most interesting open problems in the system. The interplay of structural and electronic properties is successfully described by the modelling of curvature and elastic deformations by fictitious gauge fields that have become an ex- perimental reality after the suggestion that Landau levels can form associated to strain in graphene and the subsequent experimental confirmation. Here we propose a device to detect microstresses in graphene based on a scanning-tunneling-microscopy setup able to measure Aharonov-Bohm inter- ferences at the nanometer scale. The interferences to be observed in the local density of states are created by the fictitious magnetic field associated to elastic deformations of the sample.Comment: Some bugs fixe

Pharmaceutical services for endemic situations in the Brazilian Amazon: organization of services and prescribing practices for Plasmodium vivax and Plasmodium falciparum non-complicated malaria in high-risk municipalities

<p>Abstract</p> <p>Background</p> <p>In spite of the fact that pharmaceutical services are an essential component of all malaria programmes, quality of these services has been little explored in the literature. This study presents the first results of the application of an evaluation model of pharmaceutical services in high-risk municipalities of the Amazon region, focusing on indicators regarding organization of services and prescribing according to national guidelines.</p> <p>Methods</p> <p>A theoretical framework of pharmaceutical services for non-complicated malaria was built based on the Rapid Evaluation Method (WHO). The framework included organization of services and prescribing, among other activities. The study was carried out in 15 primary health facilities in six high-risk municipalities of the Brazilian Amazon. Malaria individuals ≥ 15 years old were approached and data was collected using specific instruments. Data was checked by independent reviewers and fed to a data bank through double-entry. Descriptive variables were analyzed.</p> <p>Results</p> <p>A copy of the official treatment guideline was found in 80% of the facilities; 67% presented an environment for receiving and prescribing patients. Re-supply of stocks followed a different timeline; no facilities adhered to forecasting methods for stock management. No shortages or expired anti-malarials were observed, but overstock was a common finding. On 86.7% of facilities, the average of good storage practices was 48%. Time between diagnosis and treatment was zero days. Of 601 patients interviewed, 453 were diagnosed for <it>Plasmodium vivax</it>; of these, 99.3% received indications for the first-line scheme. Different therapeutic schemes were given to <it>Plasmodium falciparum </it>patients. Twenty-eight (4.6%) out of 601 were prescribed regimens not listed in the national guideline. Only 5.7% individuals received a prescription or a written instruction of any kind.</p> <p>Conclusions</p> <p>The results show that while diagnostic procedure is well established and functioning in the Brazilian malaria programme, prescribing is still an activity that is actually not performed. The absence of physicians and poor integration between malaria services and primary health services make for the lack of a prescription or written instruction for malaria patients throughout the Brazilian Amazon. This fact may lead to a great number of problems in rational use and in adherence to medication.</p

Matrix metalloproteinases (MMP-2,9) and their tissue inhibitors (TIMP-1,2) as novel markers of stress response and atherogenesis in children with chronic kidney disease (CKD) on conservative treatment

The system of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) may play a key role in atherogenesis of chronic kidney disease (CKD) patients by its impact on matrix accumulation. Connections with inflammation, stress, or endothelial dysfunction are also probable. However, the data on correlations between these parameters in CKD patients are scarce in adults and absent in children. The aim of our study was to evaluate serum concentrations of MMP-2, MMP-9, TIMP-1, and TIMP-2, as well as their correlations with markers of stress response (Hsp90-α, anti-Hsp60), endothelial dysfunction (sE-selectin), and inflammation (high-sensitivity C-reactive protein) in CKD children treated conservatively. Thirty-seven patients were divided into two groups according to the CKD stage (gr.CKDI, 19 children with CKD stages 2–3; gr.CKDII, 18 subjects with CKD stages 4–5). Twenty-four age-matched healthy subjects served as controls. Serum concentrations of MMP-2, MMP-9, TIMP-1, TIMP-2, Hsp90-α, anti-Hsp60, and sE-selectin were assessed by ELISA. Median values of MMP-2, MMP-9, TIMP-1, and TIMP-2 were significantly higher in all CKD children vs. controls and were increased in patients with CKD stages 4–5 vs. CKD stages 2–3. Hsp90-α, anti-Hsp60, sE-selectin, and glomerular filtration rate predicted the values of MMPs and TIMPs. Chronic kidney disease in children is characterized by MMP/TIMP system dysfunction, aggravated by the progression of renal failure. Correlations between examined parameters, heat shock proteins, and markers of endothelial damage suggest the possibility of MMP/TIMP application as indicators of stress response and atherogenesis in children with CKD on conservative treatment