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In this work, the spectroscopic performances of new cadmium–zinc–telluride (CZT) pixel detectors recently developed at IMEM-CNR of Parma (Italy) are presented. Sub-millimetre arrays with pixel pitch less than 500 µm, based on boron oxide encapsulated vertical Bridgman grown CZT crystals, were fabricated. Excellent room-temperature performance characterizes the detectors even at high-bias-voltage operation (9000 V cm−1), with energy resolutions (FWHM) of 4% (0.9 keV), 1.7% (1 keV) and 1.3% (1.6 keV) at 22.1, 59.5 and 122.1 keV, respectively. Charge-sharing investigations were performed with both uncollimated and collimated synchrotron X-ray beams with particular attention to the mitigation of the charge losses at the inter-pixel gap region. High-rate measurements demonstrated the absence of high-flux radiation-induced polarization phenomena up to 2 × 106 photons mm−2 s−1. These activities are in the framework of an international collaboration on the development of energy-resolved photon-counting systems for high-flux energy-resolved X-ray imaging.

Cadmium–zinc–telluride (CZT) pixel detectors represent a consolidated choice for the development of room-temperature spectroscopic X-ray imagers, finding important applications in medical imaging, often as detection modules of a variety of new SPECT and CT systems. Detectors with 3–5 mm thicknesses are able to efficiently detect X-rays up to 140 keV giving reasonable room-temperature energy resolution. In this work, the room-temperature performance of 3 mm-thick CZT pixel detectors, recently developed at IMEM/CNR of Parma (Italy), is presented. Sub-millimetre detector arrays with pixel pitch less than 500 µm were fabricated. The detectors are characterized by good room-temperature performance even at high bias voltage operation (6000 V cm−1), with energy resolutions (FWHM) of 3% (1.8 keV) and 1.6% (2 keV) at 59.5 keV and 122.1 keV, respectively. Charge-sharing investigations were performed with both uncollimated and collimated synchrotron X-ray beams with particular attention to recovering the charge losses at the inter-pixel gap region. High rate measurements demonstrated the absence of high-flux radiation-induced polarization phenomena up to 25 × 106 photons mm−2 s−1.

Since the late 2000s, the availability of high-quality cadmium zinc telluride (CdZnTe) has greatly increased. The excellent spectroscopic performance of this material has enabled the development of detectors with volumes exceeding 1 cm3 for use in the detection of nuclear materials. CdZnTe is also of great interest to the photon science community for applications in X-ray imaging cameras at synchrotron light sources and free electron lasers. Historically, spatial variations in the crystal properties and temporal instabilities under high-intensity irradiation has limited the use of CdZnTe detectors in these applications. Recently, Redlen Technologies have developed high-flux-capable CdZnTe material (HF-CdZnTe), which promises improved spatial and temporal stability. In this paper, the results of the characterization of 10 HF-CdZnTe detectors with dimensions of 20.35 mm &times, 20.45 mm &times, 2.00 mm are presented. Each sensor has 80 &times, 80 pixels on a 250-m pitch and were flip-chip-bonded to the STFC HEXITEC ASIC. These devices show excellent spectroscopic performance at room temperature, with an average Full Width at Half Maximum (FWHM) of 0.83 keV measured at 59.54 keV. The effect of tellurium inclusions in these devices was found to be negligible, however, some detectors did show significant concentrations of scratches and dislocation walls. An investigation of the detector stability over 12 h of continuous operation showed negligible changes in performance.

In the 2000s, nail polish manufacturers started promoting “3-Free” products, phasing out three widely publicized toxic chemicals: toluene, formaldehyde, and dibutyl phthalate (DnBP). However, DnBP was sometimes replaced by another endocrine-disrupting plasticizer, triphenyl phosphate (TPHP). Many new “n-Free” labels have since appeared, without any standardization on which n chemicals are excluded. This study aimed to compare measured plasticizer content against nail polish labels. First, we summarized definitions of labels. Then, we measured 12 phthalate and 10 organophosphate plasticizers in 40 nail polishes from 12 brands selected for popularity and label variety. We found labels ranging from 3- to 13-Free; 10-Free was the most inconsistently defined (six definitions). Our samples contained TPHP and bis(2-ethylhexyl) phthalate (DEHP) at up to 7940 and 331 μg/g, respectively. The 5- to 13-Free samples had lower TPHP levels than unlabeled or 3-Free samples (median

Liquid-phase catalytic reduction of 1,2,3-substituted 5,6,7,8-tetrahydroisoquinolinium perchlorates was investigated. The reaction proceeds stereodirectionally affording cis-decahydroisoquinolines. The probable scheme of reaction products formation is suggested. The structure of compounds obtained was established by IR and 13C NMR spectroscopy.

Cadmium-zinc-telluride (CZT) arrays with photon-counting and energy-resolving capabilities are widely proposed for next-generation X-ray imaging systems. This work presents the performance of a 2â...mm-thick CZT pixel detector, with pixel pitches of 500 and 250â...μm, dc coupled to a fast and low-noise ASIC (PIXIE ASIC), characterized only by the preamplifier stage. A custom 16-channel digital readout electronics was used, able to digitize and process continuously the signals from each output ASIC channel. The digital system performs on-line fast pulse shape and height analysis, with a low dead-time and reasonable energy resolution at both low and high fluxes. The spectroscopic response of the system to photon energies below (109Cd source) and above (241Am source) the K-shell absorption energy of the CZT material was investigated, with particular attention to the mitigation of charge sharing and pile-up. The detector allows high bias voltage operation (>5000â...Vâ...cm-1) and good energy resolution at moderate cooling (3.5% and 5% FWHM at 59.5â...keV for the 500 and 250â...μm arrays, respectively) by using fast pulse shaping with a low dead-time (300â...ns). Charge-sharing investigations were performed using a fine time coincidence analysis (TCA), with very short coincidence time windows up to 10â...ns. For the 500â...μm pitch array (250â...μm pitch array), sharing percentages of 36% (52%) and 60% (82%) at 22.1 and 59.5â...keV, respectively, were measured. The potential of the pulse shape analysis technique for charge-sharing detection for corner/border pixels and at high rate conditions (250â...kcpsâ...pixel-1), where the TCA fails, is also shown. Measurements demonstrated that significant amounts of charge are lost for interactions occurring in the volume of the inter-pixel gap. This charge loss must be accounted for in the correction of shared events. These activities are within the framework of an international collaboration on the development of energy-resolved photon-counting systems for high-flux energy-resolved X-ray imaging (1-140â...keV).This work presents the performance of a 2â...mm-thick CZT pixel detector, with pixel pitches of 500 and 250â...μm coupled to a custom 16-channel digital readout electronics, performing on-line fast pulse shape and height analysis. Charge-sharing investigations were performed, at both low and high fluxes, using fine time coincidence analysis and pulse shape analysis.

Ultrafast pulsed laser ablation has been investigated as a technique to machine CdWO4 single crystal scintillator and segment it into small blocks with the aim of fabricating a 2D high energy X-ray imaging array. Cadmium tungstate (CdWO4) is a brittle transparent scintillator used for the detection of high energy X-rays and γ-rays. A 6 W Yb:KGW Pharos-SP pulsed laser of wavelength 1028 nm was used with a tuneable pulse duration of 10 ps to 190 fs, repetition rate of up to 600 kHz and pulse energies of up to 1 mJ was employed. The effect of varying the pulse duration, pulse energy, pulse overlap and scan pattern on the laser induced damage to the crystals was investigated. A pulse duration of ≥500 fs was found to induce substantial cracking in the material. The laser induced damage was minimised using the following operating parameters: a pulse duration of 190 fs, fluence of 15.3 J cm−2 and employing a serpentine scan pattern with a normalised pulse overlap of 0.8. The surface of the ablated surfaces was studied using scanning electron microscopy, energy dispersive X-ray spectroscopy, atomic force microscopy and X-ray photoelectron spectroscopy. Ablation products were found to contain cadmium tungstate together with different cadmium and tungsten oxides. These laser ablation products could be removed using an ammonium hydroxide treatment.

OBJECTIVES/GOALS: Lack of blood vessels remains a major obstacle in tissue regeneration. Angiopoietin 1 and 2 modulate angiogenesis through the Tie2 receptor tyrosine kinase. Ang1 activates pAKT to promote endothelial cell survival while Ang2 antagonizes these effects. We aim to dissect the Ang/Tie2 pathway to uncover the molecular basis for these opposing effects. METHODS/STUDY POPULATION: Ang1 and Ang2 bind Tie2 via nearly identical F-domains (Fd). To investigate the molecular basis regulating the Tie2 pathway, we generated a series of computationally designed self-assembling protein scaffolds presenting F-domains in a wide range of valencies and geometries using Rosette Molecular Modeling Suite. We examined the protein kinase activation, cell migration, and blood vessel formation produced by the designed proteins in human umbilical vein endothelial cells. RESULTS/ANTICIPATED RESULTS: Two phenotypic classes were demonstrated by the number of presented F domains: scaffolds presenting 3 or 4 Fd have Ang2 like activity, upregulating pFAK and pERK but not pAKT and failing to induce cell migration and tube formation; scaffolds presenting more than 6 Fd have Ang1 like activity, upregulating the three signaling branches and enhancing cell migration and tube formation. Scaffolds with 8 or more Fd show superagonist activity, producing significantly stronger phenotypes than Ang1. These results suggest that Fd valency largely determines Ang1 vs Ang2 signaling outcomes, and our designed superagonists can outperform Ang1 in vascularization and wound healing. In in vivo experiments, nanoparticles displaying 60 copies of Fd produce significant revascularization in hemorrhagic brains. DISCUSSION/SIGNIFICANCE OF IMPACT: Targeting the Tie2 pathway is a new paradigm in regenerative medicine. Our designed constructs will enable us to generate high-affinity Tie2 agonists and antagonists as drugs to control angiogenesis, enabling tissue regeneration that recapitulates the biological architecture of the native tissue physiology, improving organ transplant outcome.

In the last decade, nail polish manufacturers largely phased out use of the three widely publicized “toxic trio” chemicals, including the plasticizer dibutyl phthalate (DnBP). These &#8...

In preparation for dramatic morphogenetic events of gastrulation, rapid embryonic cell cycles slow at the mid-blastula transition (MBT). In Drosophila melanogaster embryos, down-regulation of cyclin-dependent kinase 1 (Cdk1) activity initiates this slowing by delaying replication of heterochromatic satellite sequences and extending S phase. We found that Cdk1 activity inhibited the chromatin association of Rap1 interacting factor 1 (Rif1), a candidate repressor of replication. Furthermore, Rif1 bound selectively to satellite sequences following Cdk1 down-regulation at the MBT. In the next S phase, Rif1 dissociated from different satellites in an orderly schedule that anticipated their replication. Rif1 lacking potential phosphorylation sites failed to dissociate and dominantly prevented completion of replication. Loss of Rif1 in mutant embryos shortened the post-MBT S phase and rescued embryonic cell cycles disrupted by depletion of the S phase–promoting kinase, cell division cycle 7 (Cdc7). Our work shows that Rif1 and S phase kinases compose a replication timer controlling first the developmental onset of late replication and then the precise schedule of replication within S phase. In addition, we describe how onset of late replication fits into the progressive maturation of heterochromatin during development., Author summary Cells divide rapidly in the early embryos of most animals. However, during a conserved period of development known as the mid-blastula transition (MBT), the cell cycle slows down dramatically. In Drosophila embryos, genome duplication abruptly slows to initiate this cell cycle prolongation. This is achieved through the onset of late replication, a well-recognized phenomenon in which specific sequences of the genome await replication until long after other sequences have finished. Even though this temporal program of replication is a major determinant of the duration of S phase, the factors involved in this process remain unknown. Here, we use genetics and real-time microscopy to visualize replication in developing fly embryos and show that the protein Rap1 interacting factor 1 (Rif1) mediates the introduction of late replication at the MBT. We find that at this stage, Rif1 binds to and selectively delays the replication of large blocks of repetitive DNA known as satellite sequences. During the rapid cell cycles before the MBT, we show that the cyclin-dependent kinase 1 (Cdk1) prevents Rif1 from slowing down DNA replication by driving its removal from the chromatin. The developmental down-regulation of Cdk1 at the MBT allows Rif1 to associate with the satellite sequences and initiate cell cycle slowing. Our work provides new insights into the temporal programming of S phase and into the embryonic origin of late replication.

Although histone acetylation and deacetylation machineries (HATs and HDACs) regulate important aspects of cell function by targeting histone tails, recent work highlights that non-histone protein acetylation is also pervasive in eukaryotes. Here, we use quantitative mass-spectrometry to define acetylations targeted by the sirtuin family, previously implicated in the regulation of non-histone protein acetylation. To identify HATs that promote acetylation of these sites, we also performed this analysis in gcn5 (SAGA) and esa1 (NuA4) mutants. We observed strong sequence specificity for the sirtuins and for each of these HATs. Although the Gcn5 and Esa1 consensus sequences are entirely distinct, the sirtuin consensus overlaps almost entirely with that of Gcn5, suggesting a strong coordination between these two regulatory enzymes. Furthermore, by examining global acetylation in an ada2 mutant, which dissociates Gcn5 from the SAGA complex, we found that a subset of Gcn5 targets did not depend on an intact SAGA complex for targeting. Our work provides a framework for understanding how HAT and HDAC enzymes collaborate to regulate critical cellular processes related to growth and division.

The purpose of this study is that the formulation and characterization of folate-conjugated poly(lactide-co-glycolide)-block-poly(ethyleneglycol)(PLGA-PEG-Folate) nanoparticles loaded with the dual agents; vincristine sulfate(VS) and ε-viniferine(EV). Folate-conjugated nanoparticles are useful vehicles to facilitate active targeting of varies chemotherapeutic agents to cancer cells. PLGA-PEG-folate was synthesized four stages; folic acid activation, PLGA activation, synthesis of folate-PEG-NH2 and synthesis of PLGA-PEG-folate conjugate copolymer. Characterization of the conjugates was performed using FTIR and H‒NMR. Drug loaded nanoparticles was prepared by the nanoprecipitation method. After the formulation of nanoparticles, particle size, polydispersity index and zeta potential were measured using both non-lyophilise and lyophilise formulations. The results were found to be 82.76 ± 22.42/342.2 ± 20.7 nm, 0.311 ± 0.015/0.394 ± 0.04 and −8.33 ± 3.68/8.05 ± 1.69 mV respectively. The drug-loading percentages were found to be 8.87 ± 0.68 and 2.60 ± 0.20 (mean ± SE) for EV and VS, respectively. The free EV was found about 12.00% and EV release from nanoparticles was determined 31.83% at 6 h. In the other hand, VS release did not occur from nanoparticles while free VS reached 100% in same duration. These results suggest that VS and EV loaded PLGA-PEG-folate nanoparticles could be potential delivery system for targeting the drugs to cancer cells. Therefore, in vitro studies with these nanoparticles are already carrying out in our laboratory using varies cancer cells.

Semi-insulating GaAs material of 500 μm thickness grown using the Liquid Encapsulated Czochralski (LEC) method has been compensated with chromium to produce high resistivity single crystals suitable for spectroscopic imaging applications. Results are presented for the performance of three small pixel detectors each with 80×80 pixels on a 250 μm pitch, fabricated with metal contacts and bonded to a spectroscopic imaging ASIC. Current–voltage measurements demonstrated a material resistivity of 2.5×10 9 Ω cm at room temperature. At an optimised bias voltage, the average energy resolution at 60 keV (FWHM) was in the range 2.8–3.3 keV per pixel. An analysis of the voltage dependent X-ray spectroscopy suggests that the electron mobility lifetime ( μτ e ) for each detector is in the range 2.1–4.5×10 −5 cm 2 V −1 . The spectroscopic imaging capability of the detectors is also demonstrated in X-ray absorption spectroscopy measurements.

Cadmium zinc telluride (CZT) is the material of choice for high-energy room-temperature X-ray and γ-ray detectors. However, the performance of pixelated detectors is greatly influenced by the quality of CZT. Crystal defects and impurities are one source of shallow and deep level traps for charge carriers. Fluorescence lifetime of the recombination of optically excited charges may indicate the presence and type of defects and impurities in CZT. Fluorescence lifetime imaging microscopy (FLIM) is used to examine the excited-state lifetime in CZT fabricated by different growth methods and conditions. The FLIM set-up analyzes luminescence emitted from the sample following photo excitation. Samples were optically excited above band gap with a pulsed laser (590 nm) for raster scanning a 220 × 165 µm2 sample area. In-situ room-temperature photoluminescence (PL) and FLIM were recorded simultaneously. In order to analyze the FLIM data, two dominant charge carrier decay processes (τ1, τ2) were identified. The luminescence signal decays with a rapid lifetime of τ1 ≈ 50–200 ps, and a large variety of long-lifetime components τ2 were found in the range of 225–900 ps. CZT grown by multi-tube physical vapor transport (MTPVT) showed extremely long-lived recombination decay times up to 3.5 ns in the vicinity of the interface at growth start. Further away from this interface, the recombination lifetime was in the typical range of fast transitions similar to those found in detector-grade CZT fabricated by travelling heater method. Crystalline material quality strongly influences FLIM lifetime. Time-resolved transients of MTPVT-grown CZT compared with industry-leading detector grade CZT (dots: measured data; lines: fitted exponential decay curves).

We have developed a technique, called Ubiquitin Ligase Substrate Trapping, for the isolation of ubiquitinated substrates in complex with their ubiquitin ligase (E3). By fusing a ubiquitin associated (UBA) domain to an E3 ligase, we were able to selectively purify the polyubiquitinated forms of E3 substrates. Using Ligase Traps of eight different F-box proteins (SCF specificity factors) coupled with mass spectrometry, we identified known, as well as previously uncharacterized substrates. Polyubiquitinated forms of candidate substrates associated with their cognate F-box partner, but not other Ligase Traps. Interestingly, the four most abundant candidate substrates identified for the F-box protein Saf1 were all vacuolar/lysosomal proteins. Analysis of one of these substrates, Prb1, showed that Saf1 selectively promotes ubiquitination of the unprocessed form of the zymogen. This suggests that Saf1 is part of a pathway that targets protein precursors for proteasomal degradation.

AN69 membrane is not suited for diffusion, with an suggested limit at 25 mL/min dialysate flow rate. When prescribing continuous hemodialysis this threshold must be surpassed to achieve. We designed a study aimed to check if a higher dose of dialysis could be delivered efficiently with this membrane. Ten ICU patients under continuous hemodiafiltration with 1.4 m(2) AN69 membrane were included and once a day we set the monitor to exclusively 50 mL/min dialysate flow rate and 250 mL/min blood flow rate and after 15 minutes measured dialysate saturation for urea, creatinine, and β 2-microglobulin. We detected that urea saturation of dialysate was nearly complete (1.1 ± 0.09) for at least 40 hours, while creatinine saturation showed a large dispersion (0.86 ± 0.22) and did not detect any relation for these variables with time, blood flow, or anticoagulation regime. Saturation of β 2-microglobulin was low (0.34 ± 0.1) and decreased discretely with time (r (2) = 0.15, P0.05) and significantly with TMP increases (r (2) = 0.31, P0.01). In our experience AN69 membrane shows a better diffusive capability than previously acknowledged, covering efficiently the range of standard dosage for continuous therapies. Creatinine is not a good marker of the membrane diffusive capability.

A small pixel cadmium zinc telluride detector has been fabricated, assembled and tested at the Rutherford Appleton Laboratory. The detector consists of 74×74 pixels on a 250 μm pitch with a 50 μm spacing. Flat field irradiations with an 241Am γ-ray source have demonstrated that there are significant variations in the number of counts detected by each pixel as well as large differences in the FWHM of the X-ray photo-peak. A 10×10 μm microbeam of 20 keV X-rays has been used to characterise these non-uniformities. These measurements have shown that variations in the counting and spectroscopic performance of individual pixels are due to the presence of a non-uniform electric field within the detector.

Background and Purpose To analyse the relative contribution of β1-, β2- and β3-adrenoceptors (Adrb) to vasodilatation in conductance and resistance vessels, assessing the role of cAMP and/or NO/cGMP signalling pathways. Experimental Approach Rat mesenteric resistance artery (MRA) and aorta were used to analyse the Adrb expression by real-time-PCR and immunohistochemistry, and for the pharmacological characterization of Adrb-mediated activity by wire myography and tissue nucleotide accumulation. Key Results The mRNAs and protein for all Adrb were identified in endothelium and/or smooth muscle cells (SMCs) in both vessels. In MRA, Adrb1 signalled through cAMP, Adrb3 through both cAMP and cGMP, but Adrb2, did not activate nucleotide formation; isoprenaline relaxation was inhibited by propranolol (β1, β2), CGP20712A (β1), and SQ22536 (adenylyl cyclase inhibitor), but not by ICI118,551 (β2), SR59230A (β3), ODQ (soluble guanylyl cyclase inhibitor), L-NAME or endothelium removal. In aorta, Adrb1 signalled through cAMP, while β2- and β3-subtypes through cGMP; isoprenaline relaxation was inhibited by propranolol, ICI118,551, ODQ, L-NAME, and to a lesser extent, by endothelium removal. CL316243 (β3-agonist) relaxed aorta, but not MRA. Conclusion and Implication Despite all three Adrb subtypes being found in both vessels, Adrb1, located in SMCs and acting through the adenylyl cyclase/cAMP pathway, are primarily responsible for vasodilatation in MRA. However, Adrb-mediated vasodilatation in aorta is driven by endothelial Adrb2 and Adrb3, but also by the Adrb2 present in SMCs, and is coupled to the NO/cGMP pathway. These results could help to understand the different physiological roles played by Adrb signalling in regulating conductance and resistance vessels.

Acute kidney injury (AKI) in the ICU frequently requires costly supportive therapies, has high morbidity, and its long-term prognosis is not as good as it has been presumed so far. Consequently, AKI generates a significant burden for the healthcare system. The problem is that AKI lacks an effective treatment and the best approach relies on early secondary prevention. Therefore, to facilitate early diagnosis, a broader definition of AKI should be established, and a marker with more sensitivity and early-detection capacity than serum creatinine – the most common marker of AKI – should be identified. Fortunately, new classification systems (RIFLE, AKIN or KDIGO) have been developed to solve these problems, and the discovery of new biomarkers for kidney injury will hopefully change the way we approach renal patients. As a first step, the concept of renal failure has changed from being a “static” disease to being a “dynamic process” that requires continuous evaluation of kidney function adapted to the reality of the ICU patient.

Objetivo: Evaluar la variabilidad en la detección y prevención de la disfunción renal aguda (DRA) en las unidades de cuidados intensivos (UCI), así como la aplicación de recomendaciones internacionales en este campo (Acute Dialysis Quality Initiative [ADQI] y Acute Kidney Injury Network [AKIN]). Diseño: Estudio multicéntrico prospectivo descriptivo. Ámbito: Un total de 42 UCI (70,7% generales) en 32 hospitales (78% de tercer nivel), participantes en un estudio de prevalencia de DRA (COFRADE). Intervenciones: Encuesta. Variables de interés: Métodos de detección y prevención de DRA y existencia de protocolos para depuración extrarrenal (TDE). Resultados: Para la estimación del filtrado glomerular se usa la creatinina sérica en el 36,6%, el aclaramiento de creatinina en el 41,5%, ecuaciones basadas en una muestra de creatinina sérica en 22% y creatinina sérica aislada en el resto; en ningún caso se utiliza la cistatina-C. Solo el 39,1% de las UCI aplica sistemas de estratificación (13 RIFLE y 3 AKI). El 48,8% no cuenta con protocolos de prevención de DRA, el 31,7% los tiene para nefropatía por contraste, el 7,3% para manejo de nefrotóxicos y el 12,2% para ambos. Por contra, el 63,4% de las unidades cuenta con protocolos de manejo de TDE, el 70,7% aplica programas de formación continuada para estas y el 53,7% cuenta con protocolos de ajuste de dosis de fármacos en estos casos. Conclusiones: Existe amplia variabilidad en cuanto al método de detección de la DRA en nuestras unidades, con escasa aplicación de sistemas de estratificación de daño. El manejo de las TDE despierta más inquietud que la prevención o el diagnóstico de la DRA. Objective: To evaluate variability in the detection and prevention of acute kidney injury (AKI) in the intensive care unit (ICU), and application of the international recommendations in this field (Acute Dialysis Quality Initiative [ADQI] and Acute Kidney Injury Network [AKIN]). Design: A prospective, observational, multicenter study. Setting: A total of 42 ICUs in 32 hospitals (78% in third level hospitals and 70.7% general units) recruited for a study on the prevalence of AKI (COFRADE). Interventions: Survey. Variables: Aspects related to AKI detection and prevention and renal replacement therapy protocols. Results: The method used for estimating glomerular filtration rate was serum creatinine in 36.6%, creatinine clearance in 41.5% and equations in 22%; none reported using cystatin-C. Only 39.1% ICUs acknowledged the use of stratification systems (13 RIFLE and 3 AKIN). A total of 48.8% ICUs had no written protocols for AKI prevention, 31.7% reported using them only for contrast nephropathy, 7.3% for nephrotoxic drugs and 12.2% for both. In contrast, 63.4% participants had written protocols for renal replacement therapy, 70.7% had implemented a training program, and 53.7% had some method for adjusting doses of drugs when on renal replacement therapy. Conclusions: We observed important variability regarding diagnostic criteria and prevention of AKI in Spanish ICUs, the application of ADQI or AKIN recommendations still being low in our units. Renal replacement therapy seems to generate more concern among our intensivists than AKI management.

A fluorescence chemical sensor for C-reactive protein (CRP) was developed based on the selective interaction with CdSe and ZnSe quantum dots (QDs) coated with O-phosphorylethanolamine (PEA). Synthesis procedure and analytical parameters such as pH and ionic strength were studied. The decrease in the fluorescence emission intensity was explained due to the specific interaction of the QDs-PEA with CRP, and a correlation was observed between the quenching of the fluorescence and the concentration of CRP. The accuracy of the proposed method was 0.37% as RSD. The proposed method was applied to screen serum samples, and showed to be sensible at the C-reactive protein concentrations of risks levels.

10-Methyl(phenyl)- and 9,10-diphenylperhydroacridines have been obtained by the catalytic reduction of 10- and 9,10-substituted sym-octahydroacridinium salts. Selective reduction of the furan ring occurred in the case of 9-(2-furyl)-10-phenyl-sym-octahydroacridinium perchlorate. The stereoisomeric composition of the reaction products has been established and a probable scheme for their formation has been proposed.

Purpose We hypothesized that RIFLE based on creatinine clearance (CrCl) is superior to that based on serum creatinine (sCr) or Cockroft-Gault (C-G) because it is an earlier marker of kidney dysfunction. Materials and Methods At day 3 of admission, we compared the RIFLE based on sCr, C-G, and CrCl with 28-day mortality and development of RIFLE-F during intensive care unit stay. Results Percentages in the RIFLE levels were similar for the 3 estimates, but the patients included in each level were different; with CrCl as the reference, κ statistic was 0.29 (95% confidence interval, 0.15-0.43) for sCr and 0.21 (0.07-0.36) for C-G. Mortality at day 28 was 19.3%, with percentages of mortality increasing with RIFLE based in CrCl but not sCr or C-G (area under the curve, 0.57 [45-72] for C-G; 0.57 [44-72] for sCr; and 0.64 [52-79] for CrCl). Logistic regression only showed an independent relationship with mortality for RIFLE measured with CrCl. Conclusions RIFLE classification using sCr or C-G at the third day of admission predicts outcome less accurately than with the use of CrCl. Because of the delay in the rise of sCr after a sudden glomerular filtration rate decrease, RIFLE based in CrCl may represent an advantage in terms of precocity.

A new small pixel cadmium zinc telluride (CZT) detector has been developed for hard X-ray spectroscopy. The X-ray performance of four detectors is presented and the detectors are analysed in terms of the energy resolution of each pixel. The detectors were made from CZT crystals grown by the travelling heater method (THM) bonded to a 20×20 application specific integrated circuit (ASIC) and data acquisition (DAQ) system. The detectors had an array of 20×20 pixels on a 250 μm pitch, with each pixel gold-stud bonded to an energy resolving circuit in the ASIC. The DAQ system digitised the ASIC output with 14 bit resolution, performing offset corrections and data storage to disc in real time at up to 40,000 frames per second. The detector geometry and ASIC design was optimised for X-ray spectroscopy up to 150 keV and made use of the small pixel effect to preferentially measure the electron signal. A 241Am source was used to measure the spectroscopic performance and uniformity of the detectors. The average energy resolution (FWHM at 59.54 keV) of each pixel ranged from 1.09±0.46 to 1.50±0.57 keV across the four detectors. The detectors showed good spectral performance and uniform response over almost all pixels in the 20×20 array. A large area 80×80 pixel detector will be built that will utilise the scalable design of the ASIC and the large areas of monolithic spectroscopic grade THM grown CZT that are now available. The large area detector will have the same performance as that demonstrated here.

The PorGamRays project aims to develop a portable gamma-ray detection system with both spectroscopic and imaging capabilities. The system is designed around a stack of thin Cadmium Zinc Telluride (CZT) detectors. The imaging capability utilises the Compton camera principle. Each detector is segmented into 100 pixels which are read out through custom designed Application Specific Integrated Circuits (ASICs). This device has potential applications in the security, decommissioning and medical fields. This work focuses on the near-field imaging performance of a lab-based demonstrator consisting of two pixelated CZT detectors, each of which is bonded to a NUCAM II ASIC. Measurements have been made with point 133Ba and 57Co sources located ∼ 35 mm from the surface of the scattering detector. Position resolution of ∼ 20 mm FWHM in the x and y planes is demonstrated.

HEXITEC is a collaborative project with the aim of developing a new range of detectors for high-energy X-ray imaging. High-energy X-ray imaging has major advantages over current lower energy imaging for the life and physical sciences, including improved phase-contrast images on larger, higher density samples and with lower accumulated doses. However, at these energies conventional silicon-based devices cannot be used, hence, the requirement for a new range of high Z-detector materials. Underpinning the HEXITEC programme are the development of a pixellated Cadmium Zinc Telluride (CZT) detectors and a pixellated readout ASIC which will be bump-bonded to the detector. The HEXITEC ASIC is required to have low noise (20 electrons rms) and tolerate detector leakage currents. A prototype 20×20 pixel ASIC has been developed and manufactured on a standard 0.35 μm CMOS process.

To estimate the usefulness of 2-h creatinine clearance (CrCl) in the ICU and define variables that may reduce agreement. Prospective study. Polyvalent ICU of a university hospital. 359 patients. We compared 24-h CrCl (CrCl-24h), as the standard measure, with 2-h CrCl (CrCl-2h) (at the start of the period) and the Cockroft–Gault equation (Ck-G). The 2-h sample was lost in two patients (0.6%) and the 24-h sample was lost in 50 patients (13.9%). The mean Ck-G was 87.4 ± 3.05, with CrCl-2h 109.2 ± 4.46 and CrCl-24h 100.9 ± 4.21 ml/min/1.73 m2 (r 2 of 0.88 for CrCl-2h and 0.84 for Ck-G). The differences from ClCr-24h were 21.8 ± 3.3 ( p

The properties required for γ-ray detection of single-crystal Cadmium Manganese Telluride (Cd 1− x Mn x Te) are investigated and samples are evaluated as room temperature radiation detectors. Undoped Cd 1− x Mn x Te crystals are characterised using sub band gap IR microscopy mapping of extended defects, room temperature photoluminescence band-gap measurements, IV measurements and α particle spectroscopy. The band gap energy calculated from room temperature near-band-edge luminescence was found to be 1.70±0.01 eV, corresponding to a manganese fraction in the sample of x =0.13. The hole mobility-lifetime product was measured at 150 K and was found to be of the order of 1×10 −5 cm 2 /V.

Fully spectroscopic x/γ-ray imaging is now possible thanks to advances in the growth of wide-bandgap semiconductors. One of the most promising materials is cadmium zinc telluride (CdZnTe or CZT), which has been demonstrated in homeland security, medical imaging, astrophysics and industrial analysis applications. These applications have demanding energy and spatial resolution requirements that are not always met by the metal contacts deposited on the CdZnTe. To improve the contacts, the interface formed between metal and semiconductor during contact deposition must be better understood. Gold has a work function closely matching that of high resistivity CdZnTe and is a popular choice of contact metal. Gold contacts are often formed by electroless deposition however this forms a complex interface. The prior CdZnTe surface preparation, such as mechanical or chemo-mechanical polishing, and electroless deposition parameters, such as gold chloride solution temperature, play important roles in the formation of the interface and are the subject of the presented work. Techniques such as focused ion beam (FIB) cross section imaging, transmission electron microscopy (TEM), energy dispersive x-ray spectroscopy (EDS), x-ray photoelectron spectroscopy (XPS) and current − voltage (I–V) analysis have been used to characterize the interface. It has been found that the electroless reaction depends on the surface preparation and for chemo-mechanically polished (1 1 1) CdZnTe, it also depends on the A/B face identity. Where the deposition occurred at elevated temperature, the deposited contacts were found to produce a greater leakage current and suffered from increased subsurface voiding due to the formation of cadmium chloride.

We report the development of laboratory based hyperspectral X-ray computed tomography which allows the internal elemental chemistry of an object to be reconstructed and visualised in three dimensions. The method employs a spectroscopic X-ray imaging detector with sufficient energy resolution to distinguish individual elemental absorption edges. Elemental distributions can then be made by K-edge subtraction, or alternatively by voxel-wise spectral fitting to give relative atomic concentrations. We demonstrate its application to two material systems: studying the distribution of catalyst material on porous substrates for industrial scale chemical processing; and mapping of minerals and inclusion phases inside a mineralised ore sample. The method makes use of a standard laboratory X-ray source with measurement times similar to that required for conventional computed tomography.

We examined whether hemodynamic improvement after high-flow hemofiltration predicts survival in patients treated with standard continuous renal replacement therapy (CRRT). This was a prospective, observational cohort study of 169 patients, measuring the mean arterial pressure (MAP) and norepinephrine (NE) dosage before and 24 hours after CRRT. Responders were defined as having a 20% reduction in NE dosage or a 20% rise in MAP with no increase in NE, compared with nonresponders. Patients were considered to be unstable if they were receiving NE or their MAP was lower than 60 mm Hg before CRRT. Of the 169 patients, 68% were men; mean age was 53.8 years (52.7 to 54.9), with a mean Acute Physiology and Chronic Health Evaluation (APACHE) II at admission of 21.8 (21.2 to 22.3), of whom 114 were unstable at the start of CRRT. Overall mortality rate 15 days after the end of CRRT was 54.3% (57.7% in stable vs. 52.9% in unstable patients, p = NS). There were 99 responders and 70 nonresponders, the only differences being NE dosage (higher in responders, p0.01) and mortality rate (responders 30% vs. nonresponders 74.7%, p0.001). In unstable patients, mortality rate was 30% in responders versus 87% in nonresponders (p0.001) (72% sensitivity and 86% specificity for predicting death). Logistic regression analysis showed that the only variables associated with death were APACHE II at admission (OR, 1.06; 95% CI, 1.0 to 1.12), percent creatinine decrease (OR, 0.98; CI, 0.96 to 1.0), and lack of hemodynamic response to CRRT (OR, 7.04; CI, 3.3 to 15.02). Hemodynamic improvement after 24-hour CRRT is a strong predictor of survival.

Renal dysfunction (RD) is a frequent complication after orthotopic liver transplantation (OLT), and it has an unfavorable effect on the prognosis of OLT patients. The purpose of our study was to identify possible risk factors for RD and its impact on survival. The possible relations of pre-, peri-, and postoperative variables to early-onset renal dysfunction (ED) (within the 1st 3 months), late-onset renal dysfunction (LD) (between 3 and 6 months), and chronic renal dysfunction (CRD) (beyond 6 months) was analyzed. We studied 245 liver transplants in 241 patients. RD was found in 64.1% of these patients, and 69% of the patients with RD recovered. LD was found in 16.7% of the transplant patients. In the multivariate analysis, baseline serum creatinine, perioperative volume of transfused bank-red blood cells, Acute Physiology and Chronic Health Evaluation (APACHE) II score at intensive care unit (ICU) admission, and infection were associated with the development of RD. Overall mortality was 27.8% and for the RD group, it was 33.5%. LD, but not ED, was related to lower survival (together with graft dysfunction and APACHE II score at ICU admission). In conclusion, ED is frequent alter OLT and is related to preexisting RD, the volume of transfused bank--red blood cells during surgery, higher APACHE II score at ICU admission, and infection. In general, the prognosis for ED is good, in contrast with that of LD, which is associated with diminished survival.

Since 1997, 15 cases of acute lymphocytic leukemia and one case of acute myelocytic leukemia have been diagnosed in children and teenagers who live, or have lived, in an area centered on the town of Fallon, Nevada. The expected rate for the population is about one case every five years. In 2001, 99 domestic and municipal wells and one industrial well were sampled in the Fallon area. Twenty-nine of these wells had been sampled previously in 1989. Statistical comparison of concentrations of major ions and trace elements in those 29 wells between 1989 and 2001 using the nonparametric Wilcoxon signed-rank test indicate water quality did not substantially change over that period; however, short-term changes may have occurred that were not detected. Volatile organic compounds were seldom detected in ground water samples and those that are regulated were consistently found at concentrations less than the maximum contaminant level (MCL). The MCL for gross-alpha radioactivity and arsenic, radon, and uranium concentrations were commonly exceeded, and sometimes were greatly exceeded. Statistical comparisons using the nonparametric Wilcoxon rank-sum test indicate gross-alpha and -beta radioactivity, arsenic, uranium, and radon concentrations in wells used by families having a child with leukemia did not statistically differ from the remainder of the domestic wells sampled during this investigation. Isotopic measurements indicate the uranium was natural and not the result of a 1963 underground nuclear bomb test near Fallon. In arid and semiarid areas where trace-element concentrations can greatly exceed the MCL, household reverse-osmosis units may not reduce their concentrations to safe levels. In parts of the world where radon concentrations are high, water consumed first thing in the morning may be appreciably more radioactive than water consumed a few minutes later after the pressure tank has been emptied because secular equilibrium between radon and its immediate daughter progeny is attained in pressure tanks overnight.

The possible involvement of potassium channels in central chemosensitivity, with special reference to the Kir1.1 potassium channel, was investigated by studying the CO(2) response of presympathetic neurons in the rostroventrolateral medulla (RVLM) in the absence or presence of various K(+) channel inhibitors. Synaptic input to RVLM neurons was blocked by local injection of omega-agatoxin and omega-conotoxin. Activity of RVLM neurons was measured by recording the electrical activity in preganglionic (WR-T(3)) or postganglionic (renal) sympathetic nerves after perfusion of the lower brainstem via the left vertebral artery with CO(2)-enriched saline solution. Unspecific K(+) channel blockade by BaCl(2) reduced the excitatory response of sympathetic activity after CO(2)-perfusion to 56% of control. A quantitatively similar inhibition of the central CO(2) response was obtained after administration of 9-fluorenylmethylchloroformate (FMOC-Cl) which eliminates pH sensitivity of Kir1 and Kir4.1. Furthermore, two structurally different Kir1 inhibiting toxins, tertiapin and Lq2, also reduced the central CO(2) response to approximately 50% of control. In contrast, charybdotoxin (CTX) had no effect on the CO(2) response. Using RT-PCR the expression of mRNA homologous to rat Kir1 mRNA was identified in the cat medulla oblongata. These data suggest that a modulation of potassium channel activity possibly via Kir1 may contribute to central chemosensitivity.

We used a pixellated hybrid silicon X-ray detector to study the effect of the sharing of generated charge between neighbouring pixels over a range of incident X-ray energies, 13–36 keV. The system is a room temperature, energy resolving detector with a Gaussian FWHM of 265 eV at 5.9 keV. Each pixel is 300 μm square, 300 μm deep and is bump bonded to matching read out electronics. The modelling packages MEDICI and MCNP were used to model the complete X-ray interaction and the subsequent charge transport. Using this software a model is developed which reproduces well the experimental results. The simulations are then altered to explore smaller pixel sizes and different X-ray energies. Charge sharing was observed experimentally to be 2% at 13 keV rising to 4.5% at 36 keV, for an energy threshold of 4 keV. The models predict that up to 50% of charge may be lost to the neighbouring pixels, for an X-ray energy of 36 keV, when the pixel size is reduced to 55 μm.

The STFC Rutherford Appleton Laboratory (U.K.) and Tomsk State University (Russia) have been working together to develop and characterise detector systems based on chromium-compensated gallium arsenide (GaAs:Cr) semiconductor material for high frame rate X-ray imaging. Previous work has demonstrated the spectroscopic performance of the material and its resistance to damage induced by high fluxes of X-rays. In this paper, recent results from experiments at the Diamond Light Source Synchrotron have demonstrated X-ray imaging with GaAs:Cr sensors at a frame rate of 3.7 MHz using the Large Pixel Detector (LPD) ASIC, developed by STFC for the European XFEL. Measurements have been made using a monochromatic 20 keV X-ray beam delivered in a single hybrid pulse with an instantenous flux of up to ~ 1 × 1010 photons s−1 mm−2. The response of 500 μm GaAs:Cr sensors is compared to that of the standard 500 μm thick LPD Si sensors.

Modules of a photon counting pixelated silicon X-ray detector have been built and tested. The modules have a uniform pixel size of 150×150 μm over a silicon detector of 448×64 pixels. The detector is solder bump bonded to readout chips and then onto a molybdenum cooling substrate. Several modules have been built and images obtained with X-rays sources. The detectors work at 200 k photons per second per pixel giving a module counting rate of 6×10 9 photons per second. The modules are designed to be tiled to create larger arrays. The paper shows images obtained from the modules and describes a detector problem caused by adjacent pixels being shorted together.

Simulated and experimental results are presented from a silicon X-ray pixel detector which is bump bonded to a PAC5 pixel array of read-out electronics. When coupled to a matching, fully depleted silicon detector the pre-amplifier is observed to have a linear response up to 80 keV, and a pulse height resolution of around 1 keV FWHM over the range 13–60 keV. The Monte-Carlo N-Particle code has been used to simulate the detector response under illumination from a variety of energies. The excellent agreement observed between simulation and experiment illustrates the predictive abilities of such packages.

Published data and the results of the authors' own investigations on the synthesis of six-membered saturated N-, O-, and S-containing heterocycles by catalytic reduction of pyridinium, pyrylium, and thiopyrylium salts are reviewed. The conditions, laws, and special characteristics of the reactions are considered.

WOS: 000258384400014, Metal complexes of a heptadentate N(5)S(2) donor Schiff-base ligand were synthesized by the template reaction between 2,6-bis(2-aminothiophenoxymethyl)pyridine and 2,2 '-bipyridine-6,6'-dicarboxaldehyde in the presence of Zn(II), Cd(II), Hg(II) and Pb(II) perchlorate salts. The complexes were characterized by IR, 1H NMR, MS-FAB+, and elemental analyses. The mitochondrial activity of U2OS cells after exposure to these complexes was determined by colorimetric assay, which detects the conversion of 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) to formazon. DNA-binding activity of all complexes was also investigated using plasmid DNA pUC18 purified from E. coli.

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Objectives: To determine the predictors of bone mass (in lumbar spine and femoral neck) in healthy older men living in the community. Design: Cross-sectional study. Bone mineral density (BMD) was measured and known predictors of bone mass and bone turnover were assessed. Subjects and setting: 113 independent, healthy men (70 years and over), not taking glucocorticoid therapy and without medical conditions known to affect bone mass and bone turnover, were recruited from recreational and sports clubs in southern Sydney in April/May 1997. Main outcome measures: BMD (measured by dual-energy x-ray absorptiometry); known predictors of bone mass (height; weight; body mass index; calcium level; serum 25-hydroxyvitamin D and free testosterone levels); and markers of bone turnover (serum bone Gla protein and procollagen-1 concentrations, and urinary deoxypyridinoline excretion rates). Results: The mean age of the men was 76.6 years (range, 70-92 years). Mean (SE) BMD of the lumbar spine was 1.143 (0.019)g/cm 2 and that of the femoral neck was 0.897 (0.013) g/cm 2 . BMD values indicating osteoporosis were found in the lumbar spine in 13 men (11.5%) and in the femoral neck in 35 men (31%). The best predictor of lumbar spine BMD was weight (R=0.37; P=0.001), and weight- and age-predicted femoral-neck BMD (R=0.49; P

Mosses have been used as biomonitors of atmospheric pollution for some years, but few studies have been carried out on the effect of NOx emissions from traffic on moss tissue N. Eight species of moss (102 samples) growing on walls or roofs next to roads exposed to different traffic densities were collected from urban and rural sites in the UK. The shoots were sampled for total N, their stable isotope 15N/14N content (δ15N) and heavy metal content (Pb, Zn). There was a lack of correlation between tissue total N and traffic exposure, but a very good correlation between traffic exposure and tissue δ15N. Plants collected near motorways or busy urban roads had δ15N values ranging between +6 and −1‰, while in rural areas with hardly any traffic these ranged from −2 to −12‰. In a separate survey of mosses, the average δ15N of shoots from busy roadsides in London was +3.66‰, whereas from samples collected from farm buildings near poultry or cattle pens it was −7.8‰. This indicates that the two main atmospheric N sources, NOx and NHx, have different δ15N signatures, the former tending to be positive and the latter negative. Tissue concentrations of both Pb and Zn show a strong positive correlation with traffic exposure, with Zn in particular being greater than Pb. The results are discussed with regard to the use of moss tissue Zn as a means for monitoring or mapping pollution from vehicles, and of δ15N as an aid to distinguish between urban (NOx) and rural (NHx) forms of N pollution.

A prototype X-ray detector for energy-dispersive EXAFS has been developed and tested to demonstrate the principle of using silicon microstrip detector technology for this application. Testing took place at the UK Synchrotron Radiation Source, where the absorption spectra of a 5 microm Ni foil and a 25 mM NiCl(2) solution were obtained.

Recent results combining thermoelectrically cooled CdZnTe detectors with a low-noise Pentafet preamplifier are presented. Cooling between −30°C and −40°C reduces the leakage current of the detectors and allows the use of a pulsed reset preamplifier and long shaping times, significantly improving the energy resolution. Mn K α X-rays at 5.9 keV have been observed with a resolution of less than 280 eV FWHM and a peak to background of more than 200:1. The Fano factor of the material has been estimated at 0.11±0.012 at −40°C. The detector requirement for X-ray astronomy will be a photon-counting imaging spectrometer. A 16×16 element, bump bonded pixel detector is described and results from a prototype silicon array presented. The detector is constructed with ASIC amplifiers with a system noise of

The role of nitric oxide (NO) in the regulation of sympathetic activity during hypoxia was studied in anesthetized pigs ( n = 21). Hypoxia (fractional concentration of O2 in inspired air = 0.1) increased pulmonary arterial pressure and decreased arterial blood pressure and peripheral vascular resistance. Renal sympathetic nerve activity (RSNA) was moderately increased during hypoxia but decreased instantaneously on reoxygenation. Blockade of NO synthesis by N G-nitro-l-arginine (l-NNA, 0.3 mmol/l) administered to the ventral surface of the medulla oblongata (VLM) significantly enhanced RSNA increases induced by hypoxia and abolished the RSNA response to reoxygenation. Furthermore,l-NNA significantly reduced peripheral hypoxic vasodilation but did not affect pulmonary vasoconstriction. The inactive enantiomerd-NNA had no measurable effects at the same concentration. Actions ofl-NNA were effectively counteracted by the NO donor S-nitroso- N-acetyl-penicillamine (0.1 mmol/l). Deafferentiation (carotid sinus and vagal nerves cut) abolished sympathetic responses to hypoxia and their modulation by NO. The results suggest that activation of peripheral chemoreceptors induces NO release in the VLM that buffers sympathoexcitation during hypoxia and contributes to sympathoinhibition during reoxygenation.

Background —Endogenous nitric oxide (NO) reduces sympathetic vasoconstriction by attenuating neuronal excitability in the brain stem and inhibition of postganglionic neurotransmission. We studied whether this modulation of sympathetic circulatory control by NO may be altered during chronic administration of NO donor drugs in pigs. Methods and Results —Nitrate tolerance was induced by oral administration of isosorbide dinitrate (ISDN, 4 mg/kg per day for 4 weeks) in eight pigs. Four of them were chronically instrumented for the measurement of mean arterial blood pressure and cardiac output in the conscious state. ISDN treatment caused hemodynamic tolerance to NO donors and significantly increased the hypotensive responses to pharmacologic ganglionic blockade in conscious pigs. In general anesthesia, ISDN-treated animals and age-matched controls (n=5) had similar baseline renal sympathetic nerve activity and in both groups neither inhibition of NO synthases (NOS) nor administration of NO donors to the brain stem by intracerebroventricular (ICV) infusions caused significant changes in baseline renal sympathetic nerve activity. However, whereas sympathoexcitatory responses to glutamate (0.5 mL, 0.1 mol/L, ICV) or electrical stimulation of somatic nerve afferents were significantly potentiated by central NOS inhibition and attenuated by NO donors in controls, these treatments no longer had significant effects in ISDN-treated pigs. Furthermore, reflex sympathetic activation in response to intravenous NO donor treatment was more pronounced in nitrate tolerant animals, which suggests loss of central sympathoinhibitory effects of NO. Subsequent histology on brain stem slices with NADPH-diaphorase as NOS marker revealed significant reduction of NOS density in ISDN-treated pigs. Conclusions —Long-term administration of organic nitrates reduces the number of NO-producing neurons in the brain stem and causes loss of inhibitory effects of NO on sympathetic excitability. This component of tolerance to organic nitrates may be important in patients confronted frequently with sympathetic activation caused by mental and/or physical stressors.

On catalytic reduction of 2,6-diphenylpyrylium salts, hydrogenolysis occurs at the C−O bond with the formation of 1,5-diphenylpentanes. The principal direction of the hydrogenation of 9-phenyl-sym-octahydroxanthylium tetrafluoroborate is the formation of a mixture of products of partial and complete reduction of the heterocycle. The structure of the substances obtained was established by IR and13C NMR spectroscopy.