Neurokinin-1 receptor, a new modulator of lymphangiogenesis in obese-asthma phenotype

Aims: Obesity and asthma are widely prevalent and associated disorders. Recent studies of our group revealed that Substance P (SP) is involved in pathophysiology of obese-asthma phenotype in mice through its selective NK1 receptor (NK1-R). Lymphangiogenesis is impaired in asthma and obesity, and SP activates contractile and inflammatory pathways in lymphatics. Our aim was to study whether NK1-R expression was involved in lymphangiogenesis on visceral (VAT) and subcutaneous (SAT) adipose tissues and in the lungs, in obeseallergen sensitized mice. Main methods: Diet-induced obese and ovalbumin (OVA)-sensitized Balb/c mice were treated with a selective NK1-R antagonist (CJ 12,255, Pfizer Inc., USA) or placebo. Lymphatic structures (LYVE-1+) and NK1-R expression were analyzed by immunohistochemistry. A semi-quantitative score methodology was used for NK1-R expression. Key findings: Obesity and allergen-sensitization together increased the number of LYVE-1+ lymphatics in VAT and decreased it in SAT and lungs. NK1-R was mainly expressed on adipocyte membranes of VAT, blood vessel areas of SAT, and in lung epithelium. Obesity and allergen-sensitization combined increased the expression of NK1-R in VAT, SAT and lungs. NK1-R antagonist treatment reversed the effects observed in lymphangiogenesis in those tissues. Significance: The obese-asthma phenotype in mice is accompanied by increased expression of NK1-R on adipose tissues and lung epithelium, reflecting that SP released during inflammation may act directly on these tissues. Blocking NK1-R affects lymphangiogenesis, implying a role of SP, with opposite physiological consequences in VAT, and in SAT and lungs. Our results provide a clue for a novel SP role in the obese-asthma phenotype.

Electro-remediação de solos contaminados com pesticidas

O herbicida bentazona (2,2-dióxido de 3-isopropil (1H) -benzo-2,1,3-triadiazin-4- ona) é um herbicida pós emergente selectivo, com uso recomendado para a cultura do arroz. Apresenta baixa persistência no solo, onde é adsorvido pelos colóides minerais e orgânicos, e um tempo de meia vida inferior a 2 semanas, associado a um elevado potencial de lixiviação e contaminação de águas subterrâneas. Nos estudos efectuados até ao momento, a bentazona não é degradada pelos microrganismos, o que levou à necessidade de procurar outras técnicas de remoção do pesticida. Foi estudada uma técnica inovadora, a electro-remediação, que consiste na aplicação de uma corrente contínua de baixa intensidade à matriz contaminada, funcionando o campo eléctrico formado como “agente de limpeza”. Este campo arrasta os contaminantes pela matriz, por acção de processos de transporte, nomeadamente, electromigração, electroosmose e electroforese. Foram realizados quatro ensaios, num solo colhido num arrozal, onde se procedeu à contaminação forçada do solo com uma solução de bentazona, submetendo-o à acção dum campo eléctrico durante vários dias. Os teores de bentazona no solo, após extracção com solvente por sonicação, e nas soluções de anólito e católito, após extracção por fase sólida, foram determinados por cromatografia líquida de alta eficiência. Concluiu-se que a bentazona é mobilizada no solo pela acção do campo eléctrico e esta remoção é dependente do pH.

Cobalt complexes with pyrazole ligands as catalyst precursors for the peroxidative oxidation of cyclohexane: Z-ray absorption spectroscopy studies and biological applications

[CoCl(-Cl)(Hpz(Ph))(3)](2) (1) and [CoCl2(Hpz(Ph))(4)] (2) were obtained by reaction of CoCl2 with HC(pz(Ph))(3) and Hpz(Ph), respectively (Hpz(Ph)=3-phenylpyrazole). The compounds were isolated as air-stable solids and fully characterized by IR and far-IR spectroscopy, MS(ESI+/-), elemental analysis, cyclic voltammetry (CV), controlled potential electrolysis, and single-crystal X-ray diffraction. Electrochemical studies showed that 1 and 2 undergo single-electron irreversible (CoCoIII)-Co-II oxidations and (CoCoI)-Co-II reductions at potentials measured by CV, which also allowed, in the case of dinuclear complex 1, the detection of electronic communication between the Co centers through the chloride bridging ligands. The electrochemical behavior of models of 1 and 2 were also investigated by density functional theory (DFT) methods, which indicated that the vertical oxidation of 1 and 2 (that before structural relaxation) affects mostly the chloride and pyrazolyl ligands, whereas adiabatic oxidation (that after the geometry relaxation) and reduction are mostly metal centered. Compounds 1 and 2 and, for comparative purposes, other related scorpionate and pyrazole cobalt complexes, exhibit catalytic activity for the peroxidative oxidation of cyclohexane to cyclohexanol and cyclohexanone under mild conditions (room temperature, aqueous H2O2). Insitu X-ray absorption spectroscopy studies indicated that the species derived from complexes 1 and 2 during the oxidation of cyclohexane (i.e., Ox-1 and Ox-2, respectively) are analogous and contain a Co-III site. Complex 2 showed low invitro cytotoxicity toward the HCT116 colorectal carcinoma and MCF7 breast adenocarcinoma cell lines.

Retificador trifásico controlado com fator de potência quase unitário

Dissertação de Mestrado para obtenção do grau de Mestre em Engenharia Eletrotécnica Ramo Automação e Eletrónica Industrial

NAVA enhances tidal volume and diaphragmatic electro-myographic activity matching: a Range90 analysis of supply and demand.

Neurally adjusted ventilatory assist (NAVA) is a ventilation assist mode that delivers pressure in proportionality to electrical activity of the diaphragm (Eadi). Compared to pressure support ventilation (PS), it improves patient-ventilator synchrony and should allow a better expression of patient's intrinsic respiratory variability. We hypothesize that NAVA provides better matching in ventilator tidal volume (Vt) to patients inspiratory demand. 22 patients with acute respiratory failure, ventilated with PS were included in the study. A comparative study was carried out between PS and NAVA, with NAVA gain ensuring the same peak airway pressure as PS. Robust coefficients of variation (CVR) for Eadi and Vt were compared for each mode. The integral of Eadi (ʃEadi) was used to represent patient's inspiratory demand. To evaluate tidal volume and patient's demand matching, Range90 = 5-95 % range of the Vt/ʃEadi ratio was calculated, to normalize and compare differences in demand within and between patients and modes. In this study, peak Eadi and ʃEadi are correlated with median correlation of coefficients, R > 0.95. Median ʃEadi, Vt, neural inspiratory time (Ti_ ( Neural )), inspiratory time (Ti) and peak inspiratory pressure (PIP) were similar in PS and NAVA. However, it was found that individual patients have higher or smaller ʃEadi, Vt, Ti_ ( Neural ), Ti and PIP. CVR analysis showed greater Vt variability for NAVA (p < 0.005). Range90 was lower for NAVA than PS for 21 of 22 patients. NAVA provided better matching of Vt to ʃEadi for 21 of 22 patients, and provided greater variability Vt. These results were achieved regardless of differences in ventilatory demand (Eadi) between patients and modes.

NCoR1 is a conserved physiological modulator of muscle mass and oxidative function.

Transcriptional coregulators control the activity of many transcription factors and are thought to have wide-ranging effects on gene expression patterns. We show here that muscle-specific loss of nuclear receptor corepressor 1 (NCoR1) in mice leads to enhanced exercise endurance due to an increase of both muscle mass and of mitochondrial number and activity. The activation of selected transcription factors that control muscle function, such as MEF2, PPARβ/δ, and ERRs, underpins these phenotypic alterations. NCoR1 levels are decreased in conditions that require fat oxidation, resetting transcriptional programs to boost oxidative metabolism. Knockdown of gei-8, the sole C. elegans NCoR homolog, also robustly increased muscle mitochondria and respiration, suggesting conservation of NCoR1 function. Collectively, our data suggest that NCoR1 plays an adaptive role in muscle physiology and that interference with NCoR1 action could be used to improve muscle function.

alphaENaC-mediated lithium absorption promotes nephrogenic diabetes insipidus.

Lithium-induced nephrogenic diabetes insipidus (NDI) is accompanied by polyuria, downregulation of aquaporin 2 (AQP2), and cellular remodeling of the collecting duct (CD). The amiloride-sensitive epithelial sodium channel (ENaC) is a likely candidate for lithium entry. Here, we subjected transgenic mice lacking αENaC specifically in the CD (knockout [KO] mice) and littermate controls to chronic lithium treatment. In contrast to control mice, KO mice did not markedly increase their water intake. Furthermore, KO mice did not demonstrate the polyuria and reduction in urine osmolality induced by lithium treatment in the control mice. Lithium treatment reduced AQP2 protein levels in the cortex/outer medulla and inner medulla (IM) of control mice but only partially reduced AQP2 levels in the IM of KO mice. Furthermore, lithium induced expression of H(+)-ATPase in the IM of control mice but not KO mice. In conclusion, the absence of functional ENaC in the CD protects mice from lithium-induced NDI. These data support the hypothesis that ENaC-mediated lithium entry into the CD principal cells contributes to the pathogenesis of lithium-induced NDI.

The near ultraviolet absorption spectrum of phosgene /

The near ultraviolet absorption of phosgene has been assigned to a * 1 1 ~.--n, A;-- Al electronic transition from vapour phase spectra recorded under conditions of high resolution and low_t~mperature. Progressions in Vi, v2' V3' V4 and V4 ha\1e been identified in the spectrum and have been analyzed in terms of vibronic transitions between a planar ground and a nonplanar excited state. A ba~rier height of 3170 cm~l:and a nona planar equilibrium angle of 32.5 were calculated for the upper state from a fit of the energy levels of a Lorentzian-guadratic potential func- ~ion to the observed levels of V 4 . ' ~he false ori- 3in, 41 0 , of the spectrum has been assigned to the band at 33,631 cm -1 . An oscillator strength of -3 1 . 1 f = 1. a x 10 has been obtained for the A - A 2 1 transition.

The measurement of the optical absorption cross section of photosystem 1 and photosystem 2 from whole live cells of porphyridium cruentum, in light state 1 and light state 2

The optical cross section of PS I in whole cells of Porphyridium cruentum (UTEX 161), held in either state 1 or state 2, was determined by measuring the change in absorbance at 820nm, an indication of P700+; the X-section of PS2 was determined by measuring the variable fluorescence, (Fv-Fo)/Fo, from PS2. Both cross-sections were 7 determined by fitting Poisson distribution equations to the light saturation curves obtained with single turnover laser flashes which varied in intensity from zero to a level where maximum yield occurred. Flash wavelengths of 574nm, 626nm, and 668nm were used, energy absorbed by PBS, by PBS and chla, and by chla respectively. There were two populations of both PSi and PS2. A fraction of PSi is associated with PBS, and a fraction of PS2 is free from PBS. On the transition S1->S2, only with PBS-absorbed energy (574nm) did the average X-section of PSi increase (27%), and that of PS2 decrease (40%). The fraction of PSi associated with PBS decreased, from 0.65 to 0.35, and the Xsection of this associated PS 1 increased, from 135±65 A2 to 400±300A2. The cross section of PS2 associated with PBS decreased from 150±50 A2 to 85±45 A2, but the fraction of PS2 associated with PBS, approximately 0.75, did not change significantly. The increase in PSi cross section could not be completely accounted for by postulating that several PSi are associated with a single PBS and that in the transition to state2, fewer PSi share the same number of PBS, resulting in a larger X-section. It is postulated that small changes occur in the attachment of PS2 to PBS causing energy to be diverted to the attached PSi. These experiments support neither the mobile-PBS model of state transitions nor that of spillover. From cross section changes there was no evidence of energy transfer from PS2 to PSi with 668nm light. The decrease in PS2 fluorescence which occurred at this wavelength cannot be explained by energy transfer; another explanation must be sought. No explanation was found for an observed decrease in PSi yield at high flash intensities.