Endothelin Receptor A Antagonism Attenuates Renal Medullary Blood Flow Impairment in Endotoxemic Pigs

BACKGROUND: Endothelin-1 is a potent endogenous vasoconstrictor that contributes to renal microcirculatory impairment during endotoxemia and sepsis. Here we investigated if the renal circulatory and metabolic effects of endothelin during endotoxemia are mediated through activation of endothelin-A receptors. METHODS AND FINDINGS: A randomized experimental study was performed with anesthetized and mechanically ventilated pigs subjected to Escherichia coli endotoxin infusion for five hours. After two hours the animals were treated with the selective endothelin receptor type A antagonist TBC 3711 (2 mg⋅kg(-1), n = 8) or served as endotoxin-treated controls (n = 8). Renal artery blood flow, diuresis and creatinine clearance decreased in response to endotoxemia. Perfusion in the cortex, as measured by laser doppler flowmetry, was reduced in both groups, but TBC 3711 attenuated the decrease in the medulla (p = 0.002). Compared to control, TBC 3711 reduced renal oxygen extraction as well as cortical and medullary lactate/pyruvate ratios (p<0.05) measured by microdialysis. Furthermore, TBC 3711 attenuated the decline in renal cortical interstitial glucose levels (p = 0.02) and increased medullary pyruvate levels (p = 0.03). Decreased creatinine clearance and oliguria were present in both groups without any significant difference. CONCLUSIONS: These results suggest that endothelin released during endotoxemia acts via endothelin A receptors to impair renal medullary blood flow causing ischemia. Reduced renal oxygen extraction and cortical levels of lactate by TBC 3711, without effects on cortical blood flow, further suggest additional metabolic effects of endothelin type A receptor activation in this model of endotoxin induced acute kidney injury

2015/16 seasonal vaccine effectiveness against hospitalisation with influenza a(H1N1)pdm09 and B among elderly people in Europe: Results from the I-MOVE+ project

We conducted a multicentre test-negative caseâ\u80\u93control study in 27 hospitals of 11 European countries to measure 2015/16 influenza vaccine effectiveness (IVE) against hospitalised influenza A(H1N1)pdm09 and B among people aged â\u89¥ 65 years. Patients swabbed within 7 days after onset of symptoms compatible with severe acute respiratory infection were included. Information on demographics, vaccination and underlying conditions was collected. Using logistic regression, we measured IVE adjusted for potential confounders. We included 355 influenza A(H1N1)pdm09 cases, 110 influenza B cases, and 1,274 controls. Adjusted IVE against influenza A(H1N1)pdm09 was 42% (95% confidence interval (CI): 22 to 57). It was 59% (95% CI: 23 to 78), 48% (95% CI: 5 to 71), 43% (95% CI: 8 to 65) and 39% (95% CI: 7 to 60) in patients with diabetes mellitus, cancer, lung and heart disease, respectively. Adjusted IVE against influenza B was 52% (95% CI: 24 to 70). It was 62% (95% CI: 5 to 85), 60% (95% CI: 18 to 80) and 36% (95% CI: -23 to 67) in patients with diabetes mellitus, lung and heart disease, respectively. 2015/16 IVE estimates against hospitalised influenza in elderly people was moderate against influenza A(H1N1)pdm09 and B, including among those with diabetes mellitus, cancer, lung or heart diseases

Bistability of the BiOi complex and its implications on evaluating the acceptor removal

The dependencies of the B$_{i}$O$_{i}$ defect concentration on doping, irradiation fluence and particle type in p-type silicon diodes have been investigated. We evidenced that large data scattering occurs for fluences above $10^{12}$ 1 MeV neutrons/cm$^2$, becoming significant larger for higher fluences. We show that the B$_{i}$O$_{i}$ defect is metastable, with two configurations A and B, of which only A is detected by Deep Level Transient Spectroscopy and Thermally Stimulated Currents techniques. The defect's electrical activity is influenced by the inherent variations in ambient and procedural experimental conditions, resulting not only in a large scattering of the results coming from the same type of measurement but making any correlation between different types of experiments difficult. It is evidenced that the variations in [B$_{i}$O$_{i}^\mathrm{A}$] are triggered by subjecting the samples to an excess of carriers, by either heating or an inherent short exposure to ambient light when manipulating the samples prior to experiments. It causes $\approx$7h variations in both, the [B$_{i}$O$_{i}^\mathrm{A}$] and in the effective space charge. The analyses of structural damage in a diode irradiated with 10$^{19}$ 1 MeV neutrons/cm$^2$ revealed that the Si structure remains crystalline and vacancies and interstitials organize in parallel tracks normal to the Si-SiO$_{2}$ interface

Parameter Identification for a New Circuit Model Aimed to Predict Body Water Volume

Intracellular and extracellular water volumes in the human body have been computed using a sequence of models starting with a linear first order RC circuit (Cole model) and finishing with the De Lorenzo model. This last model employs a fractional order impedance whose parameters are identified using the frequency characteristics of the impedance module and phase, the latter being not unique. While the Cole model has a two octaves frequency validity range, the De Lorenzo model can be used for three decades. A new linear RC model, valid for a three decades frequency range, is proposed. This circuit can be viewed as an extension of the Cole model for a larger frequency interval, unlike similar models proposed by the same authors