Spongelike alginate nanoparticles as a new potential system for the delivery of antisense oligonucleotides.

The aim of this study was to design a new antisense oligonucleotide (ON) carrier system based on alginate nanoparticles and to investigate its ability to protect ON from degradation in the presence of serum. Pharmacokinetics and tissue distribution of ON-loaded nanoparticles have been determined after intravenous administration. An original and dynamic process for ON loading into polymeric nanoparticles has been applied. It is based on the diffusion of ON or ON/polylysine complex into the nanoparticle or the alginate gel, respectively. Indeed, the single coincubation of ON with nanoparticles led, within a few days, to an extremely efficient association. The diffusion kinetic of ON was shown to be dependent on several parameters, incubation temperature, ON concentration, presence or absence of polylysine, polylysine molecular weight, and nanoparticle preparation procedure. This new alginate-based system was found to be able to protect [33P]-radiolabeled ON from degradation in bovine serum medium and to modify their biodistribution, as an important accumulation of radioactivity was observed in the lungs, in the liver, and in the spleen after intravenous administration into mice. ON may be associated efficiently with calcium alginate in a colloidal state. Such nanosponges are promising carriers for specific delivery of ON to lungs, liver, and spleen.     

Stable isotopes in fish otoliths discriminate between lagoonal and oceanic residents of Taiaro Atoll (Tuamotu Archipelago, French Polynesia)

 The fully enclosed Taiaro lagoon is hypersaline (42.5 psu) and non-tidal; constant salinity and water level result from strong evaporation balanced by low percolation through the lagoon floor. Seawater can flow over the atoll rim during exceptionally high seas and may then replenish lagoonal communities with propagules of oceanic origin. The distinctive water chemistry of the lagoon suggests a possible way of identifying these immigrants. We established this potential by analysing stable isotopes of carbon and oxygen in the recent growth layers of otoliths of two adult reef fishes, Chaetodon ulietensis and Acanthurus triostegus, collected from both sides of the atoll rim. Fish from the two locations were discriminated by their isotopic signatures, suggesting that analysis of the microchemical signatures deposited during the larval development could be used in future work to determine which individuals and species complete their life-cycles in this unusual lagoon. Accepted: 28 August 1997     

Effect of menthol on human temperature sensitivity

Application of 1% methol, which, along with cold, activates specific thermosensitive ionic channels, changes the number of functioning cold receptors on the skin of the forearm similarly to the cold exposure test; however, it does not affect the number of heat receptors and does not significantly change the threshold of cold sensation. Group variants of responses to menthol that indicate individual differences in the sensitivity of skin receptors to the effects of methol and cold have been found. The results obtained give grounds to suggest that, from the variant of response to menthol (a decrease, increase, or absence of changes in the number of functioning cold receptors 5 min after menthol application), it is possible to predict specific features of response to cold.     

Lipase-catalyzed transamidation of non-activated amides in organic solvent

A novel biocatalytic reaction of transamidation of non-activated amides with amines is reported. Among 45 different lipolytic and proteolytic enzymes tested, only the lipase from Candida antarcticawas able to catalyze this reaction. The reaction proceeded with up to ca. 80% conversion in anhydrous methyl tert-butyl ether and worked with both N-substituted and unsubstituted amides. The biocatalytic transamidation is an equilibrium process and, therefore, higher conversions to the desired amide were achieved by using increased concentrations of the amine nucleophile.     

Effect of Feed Restriction on Performance and Postprandial Nutrient Metabolism in Pigs Co-Infected with Mycoplasma hyopneumoniae and Swine Influenza Virus

As nutritional status and inflammation are strongly connected, feeding and nutritional strategies could be effective to improve the ability of pigs to cope with disease. The aims of this study were to investigate the impact of a feed restriction on the ability of pigs to resist and be tolerant to a coinfection with Mycoplasma hyopneumoniae (Mhp) and the European H1N1 swine influenza virus, and the consequences for nutrient metabolism, with a focus on amino acids. Two groups of specific pathogen-free pigs were inoculated with Mhp and H1N1 21 days apart. One group was fed ad libitum, the other group was subjected to a two-week 40% feed restriction starting one week before H1N1 infection. The two respective mock control groups were included. Three days post-H1N1 infection, 200 g of feed was given to pigs previously fasted overnight and serial blood samples were taken over 4 hours to measure plasma nutrient concentrations. Throughout the study, clinical signs were observed and pathogens were detected in nasal swabs and lung tissues. Feed-restricted pigs presented shorter hyperthermia and a positive mean weight gain over the 3 days post-H1N1 infection whereas animals fed ad libitum lost weight. Both infection and feed restriction reduced postprandial glucose concentrations, indicating changes in glucose metabolism. Post-prandial plasma concentrations of the essential amino acids histidine, arginine and threonine were lower in co-infected pigs suggesting a greater use of those amino acids for metabolic purposes associated with the immune response. Altogether, these results indicate that modifying feeding practices could help to prepare animals to overcome an influenza infection. Connections with metabolism changes are discussed.     

Biochemical and phenotypical correction of an envelope mutant of Salmonella typhimurium

Salmonella typhimurium DA 361 bears an env D1 mutation with the following abnormal phenotypical and biochemical characteristics: a) it autolyses at stationary phase in nutrient broth; b) it grows in chains of short rods; c) it is a poor maltose fermenter and d) it has a diphosphatidylglycerol (DPG) content twice as high than its isogenic non-lytic pair DA 362 (env D+) and LT2, of which both are derivatives. Growth of DA 361 in the presence of 400 mM ethanol leads on a 50% decrease of DPG level, thereby equalling its PG/DPG ratio with those of the control strain. Consequently, a correction on the other phenotypical and biochemical anomalies are induced since the DA 361 strain decreases its autolytic activity, ferments normally maltose and appear as rods undifferentiated from DA 362.     

Characteristics of the maintenance of the upright posture in subjects touching an external object while standing on a moving or immobile platform

Postural sway was compared for humans touching an external object while standing on an immobile or slowly moving posturographic platform. When the platform moves, the central nervous system may interpret the movement of the point of the contact with the external object as the movement of the body relative to the support or as the movement of the support itself. Thus, the information concerning the body position that is provided by the touch becomes ambiguous. It was demonstrated that contact with an external object during standing on an unstable support leads to a decrease in support sway. When a subject stands on a moving platform, this decrease is smaller than in the case of an immobile platform. Contact with an external object causes a decrease in postural responses to shank muscle vibrations on an immobile platform. On a moving platform, this decrease is nonsignificant. The change in postural sway depending on the unambiguity of afferent information is discussed in terms of the interaction between afferent signals of different modalities on the basis of the body scheme in subjects maintaining balance.Translated from Fiziologiya Cheloveka, Vol. 31, No. 1, 2005, pp. 59–65.Original Russian Text Copyright © 2005 by Kazennikov, Shlykov, Levik.