Oxidation of exogenous carbohydrate during prolonged exercise: the effects of the carbohydrate type and its concentration.

We studied rates of exogenous carbohydrate (CHO) oxidation during 90 min of cycling exercise in trained cyclists exercising at 70% of maximal oxygen consumption (VO2max) when they ingested glucose, sucrose, or glucose polymer solutions at concentrations of 7.5%, 10% or 15%. Drinks were labelled with [U-14C]glucose or sucrose and were ingested at a rate of 100 ml.10 min-1. Rates of oxidation of the ingested CHO were calculated from the specific radio-activity of the labelled CHO, expired 14CO2 and carbon dioxide output (VCO2). Total CHO oxidation, determined from oxygen consumption and VCO2 was not influenced by CHO type or concentration. Gastric emptying (P = 0.01) and the rate of exogenous CHO oxidation (P = 0.028) was greatest for the glucose polymer solutions, and least for glucose. Although gastric emptying (P = 0.006) decreased with increasing CHO concentration, CHO delivery to the intestine and exogenous CHO oxidation increased linearly with increasing CHO concentration. The percentage of the CHO delivered to the intestine that was oxidized ranged from 30.0% for 7.5% CHO to 38.1% for 15% CHO. Our results indicated that the rate of gastric emptying for CHO was not controlled to provide a constant rate of energy delivery as is commonly believed and that factors subsequent to gastric emptying limit the rate of exogenous CHO oxidation from the ingested solution.     

Effect of lipid phase transition on the binding of anions to dimyristoylphosphatidylcholine liposomes

Temperature dependence of the electrophoretic mobility of multilamellar liposomes prepared from dimyristoylphosphatidylcholine was measured in the presence of salts with different anions in aqueous solutions. It was established that specific binding of anions to liposome surface induced a pronounced zeta potential (electrostatic potential at the hydrodynamic plane of shear). A combination of Langmuir, Gouy-Chapman, and Boltzmann equations was used to describe the dependence of the zeta potential on the concentration of anions. The values of binding constants (K) and maximum numbers of binding sites per unit area (σ_max) were determined by this method. The sequence for anion affinities to liposome surface was found to be as follows: trinitrophenol >ClO₄⁻ >I⁻ >SCN⁻ >Br⁻ >NO₃⁻ >Cl⁻ SO₄²⁻. A sharp increase in the negative zeta potential was detected at the temperature of phase transition of the lipid from the gel to liquid-crystalline state. It was found that the parameter K did not change at lipid phase transition and the shifts in zeta potential might be due to alterations of σ_max. The binding sites were considered as defects in the package of lipid molecules in membranes.     

Allocation of scarce resources in Africa during COVID‐19: Utility and justice for the bottom of the pyramid?

The COVID‐19 pandemic has raised important universal public health challenges. Conceiving ethical responses to these challenges is a public health imperative but must take context into account. This is particularly important in sub‐Saharan Africa (SSA). In this paper, we examine how some of the ethical recommendations offered so far in high‐income countries might appear from a SSA perspective. We also reflect on some of the key ethical challenges raised by the COVID‐19 pandemic in low‐income countries suffering from chronic shortages in health care resources, and chronic high morbidity and mortality from non‐COVID‐19 causes. A parallel is drawn between the distribution of severity of COVID‐19 disease and the classic “Fortune at the bottom of the pyramid” model that is relevant in SSA. Focusing allocation of resources during COVID‐19 on the ‘thick’ part of the pyramid in Low‐to‐Middle Income Countries (LMICs) could be ethically justified on utilitarian and social justice grounds, since it prioritizes a large number of persons who have been economically and socially marginalized. During the pandemic, importing allocation frameworks focused on the apex of the pyramid from the global north may therefore not always be appropriate. In a post‐COVID‐19 world, we need to think strategically about how health care systems can be financed and structured to ensure broad access to adequate health care for all who need it. The root problems underlying health inequity, exposed by COVID‐19, must be addressed, not just to prepare for the next pandemic, but to care for people in resource poor settings in non‐pandemic times.     

Anti-Inflammatory Effects of Adult Stem Cells in Sustained Lung Injury: A Comparative Study

Lung diseases are a major cause of global morbidity and mortality that are treated with limited efficacy. Recently stem cell therapies have been shown to effectively treat animal models of lung disease. However, there are limitations to the translation of these cell therapies to clinical disease. Studies have shown that delayed treatment of animal models does not improve outcomes and that the models do not reflect the repeated injury that is present in most lung diseases. We tested the efficacy of amnion mesenchymal stem cells (AM-MSC), bone marrow MSC (BM-MSC) and human amniotic epithelial cells (hAEC) in C57BL/6 mice using a repeat dose bleomycin-induced model of lung injury that better reflects the repeat injury seen in lung diseases. The dual bleomycin dose led to significantly higher levels of inflammation and fibrosis in the mouse lung compared to a single bleomycin dose. Intravenously infused stem cells were present in the lung in similar numbers at days 7 and 21 post cell injection. In addition, stem cell injection resulted in a significant decrease in inflammatory cell infiltrate and a reduction in IL-1 (AM-MSC), IL-6 (AM-MSC, BM-MSC, hAEC) and TNF-α (AM-MSC). The only trophic factor tested that increased following stem cell injection was IL-1RA (AM-MSC). IL-1RA levels may be modulated by GM-CSF produced by AM-MSC. Furthermore, only AM-MSC reduced collagen deposition and increased MMP-9 activity in the lung although there was a reduction of the pro-fibrogenic cytokine TGF-β following BM-MSC, AM-MSC and hAEC treatment. Therefore, AM-MSC may be more effective in reducing injury following delayed injection in the setting of repeated lung injury.     

Molecular PET imaging of HSV1-tk reporter gene expression using [18F]FEAU

Non-invasive imaging of transgene expression requires the appropriate combination of a reporter gene and a reporter probe. [18F]FEAU positron emission tomography (PET) is used for the assessment of herpes simplex virus type-1 thymidine kinase gene expression. Hybrid AAV phage (termed AAVP) can be adapted to transduce mammalian cells by targeting to a specific receptor. We evaluated a targeted AAVP vector using [18F]FEAU PET. This protocol describes [18F]FEAU production and dosing, micro-PET imaging and image analysis. 2-Deoxy-2-trifluoromethanesulfonyl-1,3,5-tri-O-benzoyl-alpha-D-ribofuranose is radio-fluorinated, converted into its 1-bromo derivative and coupled with protected 5-ethyl uracil. The coupled product is hydrolyzed and purified using HPLC. Tumor-bearing animals targeted with either retroviral or AAVP vectors are anesthetized and injected with [18F]FEAU (0.1 mCi per mouse); this is followed 2 h after injection by imaging on a micro-PET. Production of [18F]FEAU requires approximately 3.5 h from the end of bombardment. PET imaging studies require 2-3 h (depending on the number of animals) after synthesis of [18F]FEAU.     

Introduction pathways of economically costly invasive alien species

Biological Invasions - Introduction pathways play a pivotal role in the success of Invasive Alien Species (IAS)—the subset of alien species that have a negative environmental and/or...     

Structural effects of covalent inhibition of phospholipase A2 suggest allosteric coupling between membrane binding and catalytic sites

Phospholipase A(2) (PLA(2)) binds to membranes and catalyzes phospholipid hydrolysis, thus initiating the biosynthesis of lipid-derived mediators of inflammation. A snake-venom PLA(2) was completely inhibited by covalent modification of the catalytic histidine 48 by p-bromophenacyl bromide. Moreover, His(48) modification affected PLA(2) structure, its membrane-binding affinity, and the effects of PLA(2) on the membrane structure. The native PLA(2) increased the order parameter of fluid membranes, whereas the opposite effect was observed for gel-state membranes. The data suggest membrane dehydration by PLA(2) and the formation of PLA(2)-membrane hydrogen bonding. The inhibited PLA(2) had lower membrane-binding affinity and exerted weaker effects on membrane hydration and on the lipid-order parameter. Although membrane binding resulted in formation of more flexible alpha-helices in the native PLA(2), which corresponds to faster amide hydrogen exchange, the modified enzyme was more resistant to hydrogen exchange and experienced little structural change upon membrane binding. The data suggest that 1), modification of a catalytic residue of PLA(2) induces conformational changes that propagate to the membrane-binding surface through an allosteric mechanism; 2), the native PLA(2) acquires more dynamic properties during interfacial activation via membrane binding; and 3), the global conformation of the inhibited PLA(2), including the alpha-helices, is less stable and is not influenced by membrane binding. These findings provide further evidence for an allosteric coupling between the membrane-binding (regulatory) site and the catalytic center of PLA(2), which contributes to the interfacial activation of the enzyme.