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Preclinical studies in animals and human clinical trials question whether the endothelial glycocalyx layer is a clinically important permeability barrier. Glycocalyx breakdown products in plasma mostly originate from 99.6–99.8% of the endothelial surface not involved in transendothelial passage of water and proteins. Fragment concentrations correlate poorly with in vivo imaging of glycocalyx thickness, and calculations of expected glycocalyx resistance are incompatible with measured hydraulic conductivity values. Increases in plasma breakdown products in rats did not correlate with vascular permeability. Clinically, three studies in humans show inverse correlations between glycocalyx degradation products and the capillary leakage of albumin and fluid.

Fluid normally exchanges freely between the plasma and interstitial space and is returned primarily via the lymphatic system. This balance can be disturbed by diseases and medications. In inflammatory disease states, such as sepsis, the return flow of fluid from the interstitial space to the plasma seems to be very slow, which promotes the well-known triad of hypovolemia, hypoalbuminemia, and peripheral edema. Similarly, general anesthesia, for example, even without mechanical ventilation, increases accumulation of infused crystalloid fluid in a slowly equilibrating fraction of the extravascular compartment. Herein, we have combined data from fluid kinetic trials with previously unconnected mechanisms of inflammation, interstitial fluid physiology and lymphatic pathology to synthesize a novel explanation for common and clinically relevant examples of circulatory dysregulation. Experimental studies suggest that two key mechanisms contribute to the combination of hypovolemia, hypoalbuminemia and edema; (1) acute lowering of the interstitial pressure by inflammatory mediators such as TNFα, IL-1β, and IL-6 and, (2) nitric oxide-induced inhibition of intrinsic lymphatic pumping.

Reusable catalysts based on earth-abundant metals with a broad applicability in organic synthesis are a key to a more sustainable production of fine chemicals, pharmaceuticals and agrochemicals. Herein, we report on a nanostructured nickel catalyst for the general and selective synthesis of primary amines via reductive amination, employing ammonia dissolved in water. Our catalyst, which operates at low temperature and pressure, is highly active, reusable and easy to handle. The synthesis from a specific nickel complex and γ-Al 2 O 3 is straightforward, with the ligand–metal combination of this complex being crucial. Aldehydes (including purely aliphatic ones), aryl–alkyl, dialkyl and diaryl ketones can all be converted smoothly into primary amines. In addition, the amination of pharmaceuticals, bioactive compounds and natural products is demonstrated. Many functional groups—including hydrogenation-sensitive examples—are tolerated. We expect that our findings will inspire others to develop reusable and nanostructured earth-abundant metal catalysts for complex organic transformations. Reusable catalysts based on earth-abundant metals could offer inexpensive and sustainable routes in organic synthesis. Here a nickel catalyst—formed by pyrolysis of a nickel complex on a γ-Al 2 O 3 support—is shown to be highly active for synthesis of primary amines via reductive amination. The catalyst operates with aqueous ammonia and either aldehydes or ketones, tolerating a wide range of functional groups.

Background Kinetic analysis of crystalloid fluid yields a central distribution volume ( V c ) of the same size as the expected plasma volume (approximately 3 L) except during general anesthesia during which V c might be only half as large. The present study examined whether this difference is due to influence of the intravascular albumin balance. Methods A population volume kinetic analysis according to a three-compartment model was performed based on retrospective data from 160 infusion experiments during which 1–2.5 L of crystalloid fluid had been infused intravenously over 20–30 min. The plasma dilution based on blood hemoglobin (Hb) and plasma albumin (Alb) was measured on 2,408 occasions and the urine output on 454 occasions. One-third of the infusions were performed on anesthetized patients while two-thirds were given to awake healthy volunteers. Results The Hb-Alb dilution difference was four times greater during general anesthesia than in the awake state (+ 0.024 ± 0.060 versus − 0.008 ± 0.050; mean ± SD; P  < 0.001) which shows that more albumin entered the plasma than was lost by capillary leakage. The Hb-Alb dilution difference correlated strongly and positively with the kinetic parameters governing the rate of fluid transfer through the fast-exchange interstitial fluid compartment ( k 12 and k 21 ) and inversely with the size of V c . Simulations suggest that approximately 200 mL of fluid might be translocated from the interstitial space to the plasma despite ongoing fluid administration. Conclusions Pronounced plasma volume expansion early during general anesthesia is associated with a positive intravascular albumin balance that is due to accelerated lymphatic flow. This phenomenon probably represents adjustment of the body fluid volumes to anesthesia-induced vasodilatation.

Stems of dicotyledonous plants consist of an outer epidermis, a cortex, a ring of secondarily thickened vascular bundles and interfascicular cells, and inner pith parenchyma cells with thin primary walls. It is unclear how the different cell layers attain and retain their identities. Here, we show that WRKY transcription factors are in part responsible for the parenchymatous nature of the pith cells in dicotyledonous plants. We isolated mutants of Medicago truncatula and Arabidopsis thaliana with secondary cell wall thickening in pith cells associated with ectopic deposition of lignin, xylan, and cellulose, leading to an ∼50% increase in biomass density in stem tissue of the Arabidopsis mutants. The mutations are caused by disruption of stem-expressed WRKY transcription factor (TF) genes, which consequently up-regulate downstream genes encoding the NAM, ATAF1/2, and CUC2 (NAC) and CCCH type (C3H) zinc finger TFs that activate secondary wall synthesis. Direct binding of WRKY to the NAC gene promoter and repression of three downstream TFs were confirmed by in vitro assays and in planta transgenic experiments. Secondary wall-bearing cells form lignocellulosic biomass that is the source for second generation biofuel production. The discovery of negative regulators of secondary wall formation in pith opens up the possibility of significantly increasing the mass of fermentable cell wall components in bioenergy crops.

Plant cell walls are comprised largely of the polysaccharides cellulose, hemicellulose, and pectin, along with ∼10% protein and up to 40% lignin. These wall polymers interact covalently and noncovalently to form the functional cell wall. Characterized cross-links in the wall include covalent linkages between wall glycoprotein extensins between rhamnogalacturonan II monomer domains and between polysaccharides and lignin phenolic residues. Here, we show that two isoforms of a purified Arabidopsis thaliana arabinogalactan protein (AGP) encoded by hydroxyproline-rich glycoprotein family protein gene At3g45230 are covalently attached to wall matrix hemicellulosic and pectic polysaccharides, with rhamnogalacturonan I (RG I)/homogalacturonan linked to the rhamnosyl residue in the arabinogalactan (AG) of the AGP and with arabinoxylan attached to either a rhamnosyl residue in the RG I domain or directly to an arabinosyl residue in the AG glycan domain. The existence of this wall structure, named ARABINOXYLAN PECTIN ARABINOGALACTAN PROTEIN1 (APAP1), is contrary to prevailing cell wall models that depict separate protein, pectin, and hemicellulose polysaccharide networks. The modified sugar composition and increased extractability of pectin and xylan immunoreactive epitopes in apap1 mutant aerial biomass support a role for the APAP1 proteoglycan in plant wall architecture and function.

Purpose To increase our knowledge about the causes and physiological consequences of concentrated urine, the relevance of which in the general population is uncertain. Methods Twenty healthy volunteers (mean age 42 years) recorded all intake of food and water for 2 weeks. During the 2nd week, they increased their daily consumption of water by 716 mL (32%). The volunteers delivered a 24-h and a morning urine sample for analysis of osmolality and creatinine during the first 4 days of both weeks, and a sample each time they voided on the other days. The water content of food and liquid was calculated and the body fluid volumes were measured by bioimpedance. Haemodynamic stability was assessed with the passive leg-raising test. Results There was a curvilinear correlation between the daily intake of water and biomarkers measured in the 24-h collection of urine (coefficient of determination 0.37–0.70). Habitual low intake of water was associated with larger body fluid volumes. The increased fluid intake during the 2nd week was best reflected in the 24-h collection (−15 and −20% for the osmolality and creatinine, respectively, P  < 0.002), while morning urine and body fluid volumes were unchanged. Increased fluid intake improved the haemodynamic stability in volunteers with a low intake of water (< median), but only in those who had minimally concentrated morning urine. Conclusions The 24-h collection reflected recent intake of fluid, whereas the morning urine seemed to mirror long-term corrections of the fluid balance. Concentrated urine was associated with larger body fluid volumes.

This prospective experimental study evaluated the disposition of a crystalloid and a colloid solution in 10 healthy cats under general anesthesia. Each cat was randomly assigned to receive either 20 mL/kg of a balanced isotonic crystalloid solution (PLA) or 5 mL/kg of 6% tetrastarch 130/0.4 solution (T-HES), administered over 15 minutes, in a 2-period, 2-treatment crossover design. Blood samples were collected, and urine output was measured during a 3-hour experimental period. Plasma dilution was calculated using serial hemoglobin concentrations and red blood cell count. Volume kinetics (distribution and elimination) of each fluid were determined using non-linear mixed effects pharmacokinetic modeling software. Data from a previous study with a similar methodology in healthy conscious cats were included in the population kinetic analysis, revealing anesthesia as a significant covariate for k 21 (peripheral-to-central intercompartmental rate constant) for PLA and k 10 (dilution-dependent first-order elimination rate constant) for T-HES. Cumulative urine output under general anesthesia was approximately 3.5 times lower for PLA and 2.5 times lower for T-HES compared to conscious cats. Overall, our data suggest that the elimination of PLA and T-HES is markedly reduced, and a bolus of PLA produces a short period of plasma expansion with the potential to cause significant peripheral fluid accumulation in cats during general anesthesia.

A central tenet of plant defense theory is that adaptation to the abiotic environment sets the template for defense strategies, imposing a trade-off between plant growth and defense. Yet this trade-off, commonly found among species occupying divergent resource environments, may not occur across populations of single species. We hypothesized that more favorable climates and higher levels of herbivory would lead to increases in growth and defense across plant populations. We evaluated whether plant growth and defense traits covaried across 18 populations of showy milkweed (Asclepias speciosa) inhabiting an east-west climate gradient spanning 25° of longitude. A suite of traits impacting defense (e.g., latex, cardenolides), growth (e.g., size), or both (e.g., specific leaf area [SLA], trichomes) were measured in natural populations and in a common garden, allowing us to evaluate plastic and genetically based variation in these traits. In natural populations, herbivore pressure increased toward warmer sites with longer growing seasons. Growth and defense traits showed strong clinal patterns and were positively correlated. In a common garden, clines with climatic origin were recapitulated only for defense traits. Correlations between growth and defense traits were also weaker and more negative in the common garden than in the natural populations. Thus, our data suggest that climatically favorable sites likely facilitate the evolution of greater defense at minimal costs to growth, likely because of increased resource acquisition.

Aberrant elimination patterns after intravenous infusion of albumin 20% may predispose to persistent vascular overload or hyper‐oncoticity. In the present report, the frequency of deviating elimination patterns was studied by visual examination followed by calculations of the volume and albumin kinetics over 5 hours in 86 volunteers and clinical patients who received 3 mL/kg albumin 20% over 30 min (mean, 231 mL). Constant and virtually unchanged plasma volume expansion (i.e., steady state) developed after 21% of all infusions and developed most often during surgery (64%) but rarely in volunteers (3%). The subsequent kinetic analysis associated such steady state with slow capillary filtration (−27% vs. all others, p < 0.01). Steady state or a gradual increase of the plasma oncotic pressure occurred in 28% and was characterized by fast turnover of fluid, which taken together resulted in a dehydrating effect. By contrast, steady state for plasma albumin was associated with a 48% lower capillary leakage rate constant for albumin (p < 0.001) as compared to the other experiments. In conclusion, steady state for plasma volume and increasing colloid osmotic pressure after infusion of albumin 20% was more dependent on variations in fluid kinetics than on albumin kinetics.