Effect of cortical-medullary gradient for ammonia on urinary excretion of ammonia

Effect of cortical-medullary gradient for ammonia on urinary excretion of ammonia. Previous studies suggested that a portion of ammonia secreted into the proximal tubule may diffuse directly from Henle's loop into the medullary collecting duct. Since water is absorbed along the course of the descending portion of the loop, it was proposed that the concentration of ammonia increased in loop fluid, and that rapid diffusibility of the free base would facilitate the delivery of ammonia into medullary interstitium where a high level could be maintained by the countercurrent exchange process. In this schema it was proposed that there was an ammonia concentration gradient between medullary structures and cortex, and recovery of ammonia by the medullary collecting duct due to the low pH in tubule fluid at that site. The present study was designed to evaluate this hypothesis by estimating ammonia concentrations in medullary and cortical tissue, and by correlating medullary levels with secretion rate into the inner medullary collecting duct. In control animals the concentration of total ammonia (NH4+ + NH3+) in inner medullary vasa recta was 9.2 ± 1.5 µmoles/ml, a level 100-fold higher than the cortical level of 0.10 ± 0.01. During acute acidosis the medullary level rose to 22.5 ± 2.7 µmoles/ml, but in acute acidosis during mannitol infusion the level fell to 8.0 ± 1.2. The rate of ammonia secretion into inner medullary collecting duct fluid correlated directly with medullary vasa recta ammonia concentration. These data provide evidence for a steep ammonia concentration gradient between the medulla and cortex, and suggest that the diffusion gradient across collecting duct epithelium governs the rate of the addition of ammonia to collecting duct fluid.Effet du gradient cortico-médulaire d'ammoniaque sur l'excrétion urinaire d'ammoniaque. Des études antérieures ont suggéré qu'une partie de l'ammoniaque sécrété dans le tubule proximal pourrait diffuser directement de l'anse de Henlé jusqu'au canal collecteur médullaire. Puisque de l'eau est réabsorbée le long de la partie descendante de l'anse, on a proposé que la concentration d'ammoniaque augmenterait dans le liquide de l'anse, et que la diffusibilité rapide de la base libre pourrait faciliter l'apport d'ammoniaque dans l'interstitium médullaire où son niveau élevé pourrait être maintenu par le processus d'échange à contre-courant. Dans ce schéma, il a été proposé qu'il y avait un gradient de concentration d'ammoniaque entre les structures médullaires et le cortex et une récupération de l'ammoniaque par le canal collecteur médullaire en raison du faible pH du liquide tubulaire à ce niveau. Cette étude a été conçue pour évaluer cette hypothèse en estimant les concentrations d'ammoniaque dans le tissu médullaire et cortical, et en corrélant les niveaux médullaires avec la vitesse de sécrétion dans le canal collecteur médullaire interne. Chez les animaux contrôles, la concentration d'ammoniaque total (NH4+ + NH3+) dans les vasa recta médullaires internes était de 9,2 ± 1,5 µmoles/ml, une valeur 1 000 fois plus élevée que le niveau cortical de 0,10 ± 0.01. Pendant une acidose aiguë, le niveau médullaire s'élevait à 22,5 ± 2,7 μmoles/ml, mais en acidose aiguë au cours d'une perfusion de mannitol, le niveau chutait à 8,0 ± 1,2. La vitesse de sécrétion d'ammoniaque dans le liquide du canal collecteur médullaire interne était directement corrélée avec la concentration d'ammoniaque dans les vasa recta médullaires. Ces données apportent la preuve d'un fort gradient de concentration d'ammoniaque entre la médullaire et le cortex, et suggèrent que le gradient de diffusion à travers l'épithélium du canal collecteur gouverne la vitesse d'addition de l'ammoniaque au liquide du canal collecteur

Mid-infrared Imaging of a Circumstellar Disk Around HR 4796: Mapping the Debris of Planetary Formation

We report the discovery of a circumstellar disk around the young A0 star, HR 4796, in thermal infrared imaging carried out at the W.M. Keck Observatory. By fitting a model of the emission from a flat dusty disk to an image at lambda=20.8 microns, we derive a disk inclination, i = 72 +6/-9 deg from face on, with the long axis of emission at PA 28 +/-6 deg. The intensity of emission does not decrease with radius as expected for circumstellar disks but increases outward from the star, peaking near both ends of the elongated structure. We simulate this appearance by varying the inner radius in our model and find an inner hole in the disk with radius R_in = 55+/-15 AU. This value corresponds to the radial distance of our own Kuiper belt and may suggest a source of dust in the collision of cometesimals. By contrast with the appearance at 20.8 microns, excess emission at lambda = 12.5 microns is faint and concentrated at the stellar position. Similar emission is also detected at 20.8 microns in residual subtraction of the best-fit model from the image. The intensity and ratio of flux densities at the two wavelengths could be accounted for by a tenuous dust component that is confined within a few AU of the star with mean temperature of a few hundred degrees K, similar to that of zodiacal dust in our own solar system. The morphology of dust emission from HR 4796 (age 10 Myr) suggests that its disk is in a transitional planet-forming stage, between that of massive gaseous proto-stellar disks and more tenuous debris disks such as the one detected around Vega.Comment: 9 pages, 4 figures as LaTex manuscript and postscript files in gzipped tar file. Accepted for publication in Astrophysical Journal Letters. http://upenn5.hep.upenn.edu/~davidk/hr4796.htm

A blinded comparison of fluticasone propionate with budesonide via powder devices in adult patients with moderate-to-severe asthma: a clinical evaluation

In Vitro and in vivo data have demonstrated that there are detectable differences between inhaled corticosteroids commonly used to treat asthma. However, controversy still remains as to whether these differences translate into clinical benefits. This 12-week, international, randomized, doubleblind, parallel-group study was undertaken to compare the efficacy and safety of fluticasone propionate (FP) 800 μg daily, administered as a powder via the Diskhaler®, and budesonide (BUD) 1600 μg daily, administered using the Turbuhaler®, in adult patients with moderate-tosevere asthma. A total of 518 patients participated in the study, 256 of whom received FP and 262 BUD. Assessment of mean morning peak expiratory flow (PEF) over the 12-week treatment period revealed a statistically significant difference in efficacy between FP 800 μg daily and BUD 1600 μg daily in favour of FP (p = 0.003), with an overall improvement of 20.9 l/min with FP compared with 12.4 l/min on BUD. Statistically significant differences in favour of FP were seen over the 12 weeks for mean evening PEF (p = 0.04), diurnal PEF variation (p = 0.03) and percentage predicted PEF (p = 0.003), as well as forced expiratory volume (p = 0.008), forced vital capacity (p = 0.02) and PEF (p = 0.005) measured at clinic visits. The median percentage of symptom-free nights increased over the 12-week study period in both treatment groups, with similar changes seen for the median percentage of days with symptom score < 2, rescue medication use and exacerbations of asthma. The incidence of adverse events was found to be comparable in the two treatment groups. The geometric mean ratios of serum cortisol levels were found to be 1.03 for FP, indicating no mean hypothalamic-pituitary-adrenal axis suppression from baseline, and 0.93 for BUD (p = 0.0002 compared with FP). In summary, FP 800 μg daily showed a greater efficacy/safety ratio in the treatment of moderate-to-severe asthma than BUD 1600 μg daily

Biogeophysical impacts of peatland forestation on regional climate changes in Finland

Land cover changes can impact the climate by influencing the surface energy and water balance. Naturally treeless or sparsely treed peatlands were extensively drained to stimulate forest growth in Finland over the second half of 20th century. The aim of this study is to investigate the biogeophysical effects of peatland forestation on regional climate in Finland. Two sets of 18-year climate simulations were done with the regional climate model REMO by using land cover data based on pre-drainage (1920s) and post-drainage (2000s) Finnish national forest inventories. In the most intensive peatland forestation area, located in the middle west of Finland, the results show a warming in April of up to 0.43 K in monthly-averaged daily mean 2 m air temperature, whereas a slight cooling from May to October of less than 0.1 K in general is found. Consequently, snow clearance days over that area are advanced up to 5 days in the mean of 15 years. No clear signal is found for precipitation. Through analysing the simulated temperature and energy balance terms, as well as snow depth over five selected subregions, a positive feedback induced by peatland forestation is found between decreased surface albedo and increased surface air temperature in the snow-melting period. Our modelled results show good qualitative agreements with the observational data. In general, decreased surface albedo in the snow-melting period and increased evapotranspiration in the growing period are the most important biogeophysical aspects induced by peatland forestation that cause changes in climate. The results from this study can be further integrally analysed with biogeochemical effects of peatland forestation to provide background information for adapting future forest management to mitigate climate warming effects. Moreover, they provide insights about the impacts of projected forestation of tundra at high latitudes due to climate change

Penetration depth of low-coherence enhanced backscattered light in sub-diffusion regime

The mechanisms of photon propagation in random media in the diffusive multiple scattering regime have been previously studied using diffusion approximation. However, similar understanding in the low-order (sub-diffusion) scattering regime is not complete due to difficulties in tracking photons that undergo very few scatterings events. Recent developments in low-coherence enhanced backscattering (LEBS) overcome these difficulties and enable probing photons that travel very short distances and undergo only a few scattering events. In LEBS, enhanced backscattering is observed under illumination with spatial coherence length L_sc less than the scattering mean free path l_s. In order to understand the mechanisms of photon propagation in LEBS in the subdiffusion regime, it is imperative to develop analytical and numerical models that describe the statistical properties of photon trajectories. Here we derive the probability distribution of penetration depth of LEBS photons and report Monte Carlo numerical simulations to support our analytical results. Our results demonstrate that, surprisingly, the transport of photons that undergo low-order scattering events has only weak dependence on the optical properties of the medium (l_s and anisotropy factor g) and strong dependence on the spatial coherence length of illumination, L_sc, relative to those in the diffusion regime. More importantly, these low order scattering photons typically penetrate less than l_s into the medium due to low spatial coherence length of illumination and their penetration depth is proportional to the one-third power of the coherence volume (i.e. [l_s \pi L_sc^2 ]^1/3).Comment: 32 pages(including 7 figures), modified version to appear in Phys. Rev.

The effects of intravenous lipid emulsion on hemodynamic recovery and myocardial cell mitochondrial function after bupivacaine toxicity in anesthetized pigs

Local anesthetic toxicity is thought to be mediated partly by inhibition of cardiac mitochondrial function. Intravenous (i.v.) lipid emulsion may overcome this energy depletion, but doses larger than currently recommended may be needed for rescue effect. In this randomized study with anesthetized pigs, we compared the effect of a large dose, 4 mL/kg, of i.v. 20% Intralipid (R) (n = 7) with Ringer's acetate (n = 6) on cardiovascular recovery after a cardiotoxic dose of bupivacaine. We also examined mitochondrial respiratory function in myocardial cell homogenates analyzed promptly after needle biopsies from the animals. Bupivacaine plasma concentrations were quantified from plasma samples. Arterial blood pressure recovered faster and systemic vascular resistance rose more rapidly after Intralipid than Ringer's acetate administration (p <0.0001), but Intralipid did not increase cardiac index or left ventricular ejection fraction. The lipid-based mitochondrial respiration was stimulated by approximately 30% after Intralipid (p <0.05) but unaffected by Ringer's acetate. The mean (standard deviation) area under the concentration-time curve (AUC) of total bupivacaine was greater after Intralipid (105.2 (13.6) mg.min/L) than after Ringer's acetate (88.1 (7.1) mg.min/L) (p = 0.019). After Intralipid, the AUC of the lipid-un-entrapped bupivacaine portion (97.0 (14.5) mg.min/L) was 8% lower than that of total bupivacaine (p <0.0001). To conclude, 4 mL/kg of Intralipid expedited cardiovascular recovery from bupivacaine cardiotoxicity mainly by increasing systemic vascular resistance. The increased myocardial mitochondrial respiration and bupivacaine entrapment after Intralipid did not improve cardiac function.Peer reviewe

Unselected brain imaging in suspected meningitis delays lumbar puncture, can prolong hospitalisation and may increase antibiotic costs - a pilot study

Background: Antibiotics reduce mortality in bacterial meningitis; a lumbar puncture (LP) will demonstrate that many patients with suspected meningitis do not need them; but delays reduce chances of culture, particularly if N8 h. Guidelines advise a LP without brain imaging unless specific features are present. Objective: We assessed the duration of hospitalisation and inpatient costs incurred with delays in LP in a Northwest of England teaching hospital. Methods: We screened the cerebrospinal fluid (CSF) database to identify patients with suspected meningitis over 3 months (07–09/ 2010). Data were recorded from clinical case notes; costs were calculated with established datasets and the British national formulary. Results: 142 patients were screened; 35 had a suspected CNS infection; 10 had a CNS infection proven: 3 bacterial meningitis; 4 aseptic meningitis and 3 viral encephalitis. Brain imaging delayed the LP for 19 (54%), (11.08 vs 5.29 hrs, p= 0.10); ten (53%) did not need imaging. 11 (42%) of those given antibiotics before the LP were delayed N8 h. For patients with aseptic meningitis and those who had a CNS infection excluded, without prior antibiotics, the delay in LP increased duration of hospitalisation (r=0.94, p=0.02 and r=0.96, p=0.01 respectively). Overall there was no trend with LP delays and antibiotic cost. However, 4 patients had antibiotics continued despite negative cultures; 2 of whom had the LP delayed N8 h, with an antibiotic cost of £215.96. Conclusion: Inappropriate brain imaging often delayed the LP; in patients who did not need antibiotics this led to longer hospitalisation

Age-differential relationships among dopamine D1 binding potential, fusiform BOLD signal, and face-recognition performance

Facial recognition ability declines in adult aging, but the neural basis for this decline remains unknown. Cortical areas involved in face recognition exhibit lower dopamine (DA) receptor availability and lower blood-oxygen-level-dependent (BOLD) signal during task performance with advancing adult age. We hypothesized that changes in the relationship between these two neural systems are related to age differences in face-recognition ability. To test this hypothesis, we leveraged positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) to measure D1 receptor binding potential (BPND) and BOLD signal during facerecognition performance. Twenty younger and 20 older participants performed a face-recognition task during fMRI scanning. Face recognition accuracy was lower in older than in younger adults, as were D1 BPND and BOLD signal across the brain. Using linear regression, significant relationships between DA and BOLD were found in both age-groups in face-processing regions. Interestingly, although the relationship was positive in younger adults, it was negative in older adults (i.e., as D1 BPND decreased, BOLD signal increased). Ratios of BOLD:D1 BPND were calculated and relationships to face-recognition performance were tested. Multiple linear regression revealed a significant Group BOLD:D1 BPND Ratio interaction. These results suggest that, in the healthy system, synchrony between neurotransmitter (DA) and hemodynamic (BOLD) systems optimizes the level of BOLD activation evoked for a given DA input (i.e., the gain parameter of the DA input-neural activation function), facilitating task performance. In the aged system, however, desynchronization between these brain systems would reduce the gain parameter of this function, adversely impacting task performance and contributing to reduced face recognition in older adults

The Debris Disk Around HR 8799

We have obtained a full suite of Spitzer observations to characterize the debris disk around HR 8799 and to explore how its properties are related to the recently discovered set of three massive planets orbiting the star. We distinguish three components to the debris system: (1) warm dust (T ~150 K) orbiting within the innermost planet; (2) a broad zone of cold dust (T ~45 K) with a sharp inner edge, orbiting just outside the outermost planet and presumably sculpted by it; and (3) a dramatic halo of small grains originating in the cold dust component. The high level of dynamical activity implied by this halo may arise due to enhanced gravitational stirring by the massive planets. The relatively young age of HR 8799 places it in an important early stage of development and may provide some help in understanding the interaction of planets and planetary debris, an important process in the evolution of our own solar system.Comment: emulateapj format, 13 pages, 10 figures, accepted to Ap

Confirming the Primarily Smooth Structure of the Vega Debris Disk at Millimeter Wavelengths

Clumpy structure in the debris disk around Vega has been previously reported at millimeter wavelengths and attributed to concentrations of dust grains trapped in resonances with an unseen planet. However, recent imaging at similar wavelengths with higher sensitivity has disputed the observed structure. We present three new millimeter wavelength observations that help to resolve the puzzling and contradictory observations. We have observed the Vega system with the Submillimeter Array (SMA) at a wavelength of 880 μm and an angular resolution of 5"; with the Combined Array for Research in Millimeter-wave Astronomy (CARMA) at a wavelength of 1.3 mm and an angular resolution of 5"; and with the Green Bank Telescope (GBT) at a wavelength of 3.3 mm and angular resolution of 10". Despite high sensitivity and short baselines, we do not detect the Vega debris disk in either of the interferometric data sets (SMA and CARMA), which should be sensitive at high significance to clumpy structure based on previously reported observations. We obtain a marginal (3σ) detection of disk emission in the GBT data; the spatial distribution of the emission is not well constrained.We analyze the observations in the context of several different models, demonstrating that the observations are consistent with a smooth, broad, axisymmetric disk with inner radius 20–100 AU and width ≾50 AU. The interferometric data require that at least half of the 860 μm emission detected by previous single-dish observations with the James Clerk Maxwell Telescope be distributed axisymmetrically, ruling out strong contributions from flux concentrations on spatial scales of ≾100 AU. These observations support recent results from the Plateau de Bure Interferometer indicating that previous detections of clumpy structure in the Vega debris disk were spurious