<Emphasis Type="Italic">In vitro</Emphasis> Enhancement of Lactate Esters on the Percutaneous Penetration of Drugs with Different Lipophilicity

Lactate esters are widely used as food additives, perfume materials, medicine additives, and personal care products. The objective of this work was to investigate the effect of a series of lactate esters as penetration enhancers on the in vitro skin permeation of four drugs with different physicochemical properties, including ibuprofen, salicylic acid, dexamethasone and 5-fluorouracil. The saturated donor solutions of the evaluated drugs in propylene glycol were used in order to keep a constant driving force with maximum thermodynamic activity. The permeability coefficient (K _p), skin concentration of drugs (SC), and lag time (T), as well as the enhancement ratios for K _p and SC were recorded. All results indicated that lactate esters can exert a significant influence on the transdermal delivery of the model drugs and there is a structure-activity relationship between the tested lactate esters and their enhancement effects. The results also suggested that the lactate esters with the chain length of fatty alcohol moieties of 10–12 are more effective enhancers. Furthermore, the enhancement effect of lactate esters increases with a decrease of the drug lipophilicity, which suggests that they may be more efficient at enhancing the penetration of hydrophilic drugs than lipophilic drugs. The influence of the concentration of lactate esters was evaluated and the optimal concentration is in the range of 5∼10 wt.%. In sum, lactate esters as a penetration enhancer for some drugs are of interest for transdermal administration when the safety of penetration enhancers is a prime consideration.     

Software Replica of Minimal Living Processes

There is a long tradition of software simulations in theoretical biology to complement pure analytical mathematics which are often limited to reproduce and understand the self-organization phenomena resulting from the non-linear and spatially grounded interactions of the huge number of diverse biological objects. Since John Von Neumann and Alan Turing pioneering works on self-replication and morphogenesis, proponents of artificial life have chosen to resolutely neglecting a lot of materialistic and quantitative information deemed not indispensable and have focused on the rule-based mechanisms making life possible, supposedly neutral with respect to their underlying material embodiment. Minimal life begins at the intersection of a series of processes which need to be isolated, differentiated and duplicated as such in computers. Only software developments and running make possible to understand the way these processes are intimately interconnected in order for life to appear at the crossroad. In this paper, I will attempt to set out the history of life as the disciples of artificial life understand it, by placing these different lessons on a temporal and causal axis, showing which one is indispensable to the appearance of the next and how does it connect to the next. I will discuss the task of artificial life as setting up experimental software platforms where these different lessons, whether taken in isolation or together, are tested, simulated, and, more systematically, analyzed. I will sketch some of these existing software platforms: chemical reaction networks, Varela’s autopoietic cellular automata, Ganti’s chemoton model, whose running delivers interesting take home messages to open-minded biologists.     

Skipper impoverishment on large West Mediterranean islands (Lepidoptera Hesperioidea): deterministic,historical and stochastic factors

Biogeographical analyses are applied to skipper (Hesperioidea) presence/absence data from the Western Mediterranean mainland and the three largest islands (Sardinia, Corsica and Sicily) in order to identify potential conservation issues. The analyses performed on species, both collectively and individually, indicate that regional species richness and occurrence in the Mediterranean zone are largely predicted by latitude and area but that islands have impoverished faunas. Several species, predicted to be present on these islands from logistic regression of their continental distributions, are actually absent. The number of species predicted to be present from logistic regression analyses for each island, closely matched the number of species predicted to occur in regional-focused multiple regression analysis. This suggests that missing species have been identified. When compared with species that occur in Sicily and Corsica, the missing species are shown to differ for ecological traits, mainly those linked to altitudinal tolerance. No ecological distinctions were disclosed for Sardinian skippers suggesting a mainly stochastic colonisation. These results, and those from an analogous study carried out on Papilionoidea, point to Hesperioidea having (i) overall more impoverished faunas on islands and (ii) being subject to stochastic or historical colonisation events more than Papilionoidea. Species not predicted to occur on islands based on their mainland distributions and ecological traits, are foci for conservation attention. However, as many species becoming extinct on the islands may be irreplaceable, all species, in particular the Sardinian ones, deserve to be conserved.     

Habitat preference in the critically endangered yellow‐tailed woolly monkey (Lagothrix flavicauda) at La Esperanza,Peru

Habitat loss is one of the main threats to wildlife. Therefore, knowledge of habitat use and preference is essential for the design of conservation strategies and identification of priority sites for the protection of endangered species. The yellow‐tailed woolly monkey (Lagothrix flavicauda Humboldt, 1812), categorized as Critically Endangered on the IUCN Red List, is endemic to montane forests in northern Peru where its habitat is greatly threatened. We assessed how habitat use and preference in L. flavicauda are linked to forest structure and composition. The study took place near La Esperanza, in the Amazonas region, Peru. Our objective was to identify characteristics of habitat most utilized by L. flavicauda to provide information that will be useful for the selection of priority sites for conservation measures. Using presence records collected from May 2013 to February 2014 for one group of L. flavicauda, we classified the study site into three different use zones: low‐use, medium‐use, and high‐use. We assessed forest structure and composition for all use zones using 0.1 ha Gentry vegetation transects. Results show high levels of variation in plant species composition across the three use zones. Plants used as food resources had considerably greater density, dominance, and ecological importance in high‐use zones. High‐use zones presented similar structure to medium‐ and low‐use zones; thus it remains difficult to assess the influence of forest structure on habitat preference. We recommend focusing conservation efforts on areas with a similar floristic composition to the high‐use zones recorded in this study and suggest utilizing key alimentation species for reforestation efforts.     

Analysis of Flow Phenomena in Gastric Contents Induced by Human Gastric Peristalsis Using CFD

This paper uses computational fluid dynamics to simulate and analyze intragastric fluid motions induced by human peristalsis. We created a two-dimensional computational domain of the distal stomach where peristalsis occurs. The motion of the gastric walls induced by an antral contraction wave (ACW) on the wall of the computational domain was well simulated using a function defined in this study. Retropulsive flow caused by ACW was observed near the occluded region, reaching its highest velocity of approximately 12 mm/s in the narrowest region. The viscosity of the model gastric contents applied in this study hardly affected the highest velocity, but greatly affected the velocity profile in the computational domain. The shear rate due to gastric fluid motion was calculated using the numerical output data. The shear rate reached relatively high values of approximately 20 s⁻¹ in the most occluded region. The shear rate profile was almost independent of the fluid viscosity. We also simulated mass transfer of a gastric digestive enzyme (pepsin) in model gastric content when peristalsis occurs on the gastric walls. The visualized simulation results suggest that gastric peristalsis is capable of efficiently mixing pepsin secreted from the gastric walls with an intragastric fluid.     

The role of pH* and buffer capacity in the recovery of function of smooth muscle cooled to −13 °C in unfrozen media

It has often been suggested that pH changes may be implicated in the injury sustained by biological systems during cooling. This particular mechanism of cryoinjury, however, has received little attention undoubtedly because of the difficulties encountered in making accurate pH measurements at low temperatures.New pH* scales established for some mixtures of dimethyl sulfoxide and water at low temperatures are used in this study to assess the effect of pH* and buffering ability upon the integrity of mammalian smooth muscle stored at −13 °C in a variety of unfrozen solutions containing 30% (w/v) Me₂SO. Smooth muscle, as a component of every organ, is a good model tissue intermediate between cells and organs. Furthermore, its overall function is conveniently tested by measuring isometric contractile responses to the drug histamine. In this way the function of strips of guinea pig taenia coli were examined at 37 °C before and after storage at −13 °C in potassiumrich media containing a variety of zwitterionic buffers. Functional recovery depends markedly on the pH* with a welldefined optimum at the surprisingly high pH*₋₁₃ of 9.2. In medium containing TES buffer, which has a maximum buffer capacity at pH*₋₁₃= 8.6, the cooled muscles recover 50% of their control contractility but in medium containing the buffer Tricine, which has a maximum capacity at the optimum pH* for recovery, the contractile response upon rewarming improves to 70%.These data are the first to quantify the effect of pH in cryopreservation on a sound theoretical basis and some of the possible underlying mechanisms are discussed.     

Influence of ionic strength and pH on the interaction between high-affinity heparin and antithrombin

Binding constants for the binding of high-affinity heparin to antithrombin at different ionic strengths were determined by fluorescence titrations and were also estimated from dissociation curves of the heparin-antithrombin complex. These curves were monitored by near-ultraviolet circular dichroism or fluorescence. The dependence of the binding constant on the activity of NaCl suggested that maximally 5–6 charged groups are directly involved in the interaction between the two macromolecules. Major pH-dependent changes of the interaction, as evident by changes of the spectroscopic properties of the complex between the molecules, were found to occur below pH 5.5 and above pH 8.5. The acid change, which was irreversible, was most likely caused by an irreversible conformational change of antithrombin. At alkaline pH, however, the gross conformation of antithrombin was stable up to pH 12, while the affinity of high-affinity heparin for antithrombin began to decrease markedly at pH 8.5. The dissociation curve, which was reversible, had a midpoint around pH 9.5. This is compatible with the loss of affinity being caused by either a local conformational change, by ionization of tyrosine or by titration of one or more amino groups.     

Relationship between postabsorptive respiratory exchange ratio and plasma free fatty acid concentrations

The relationship between overnight postabsorptive (fasting) respiratory exchange ratio (RER) and plasma FFA concentrations was addressed using data from three separate protocols, each of which involved careful control of the antecedent diet. Protocol 1 examined the relationship between fasting RER and the previous daytime RER. In Protocol 2 fasting, RER and plasma palmitate concentrations were measured in 29 women and 31 men (body mass index <30 kg·m⁻²). Protocol 3 analyzed data from Nielsen et al. (Nielsen, S., Z. K. Guo, J. B. Albu, S. Klein, P. C. O''Brien, M. D. Jensen. 2003. Energy expenditure, sex and endogenous fuel availability in humans. J. Clin. Invest. 111: 981-988.) to understand how fasting RER and palmitate concentrations relate within individuals during four consecutive measurements. The results were as follows: 1) Fasting RER was correlated (r = 0.74, P < 0.001) with the previous day''s average RER, and less so with RER variability. 2) Fasting RER was correlated (r = −0.39, P = 0.007) with fasting plasma palmitate concentrations. 3) The pattern of the RER/palmitate relationship was similar within individuals and between individuals; a negative slope was observed significantly more often than a positive slope (χ² test; P < 0.001). Our findings suggest that, despite a fixed food quotient, the slight departures from energy equilibrium in a controlled General Clinical Research Center environment can effect plasma FFA concentrations. We suggest that including indirect calorimetry as part of FFA metabolism studies may aid in data interpretation.