PEGylated PAMAM dendrimers loading oxaliplatin with prolonged release and high payload without burst effect

Oxaliplatin (OXA) was coupled to PEGylated polyamidoamine dendrimers of fourth generation (G4-PEG@OXA) in the comparison to PEGylated ones of odd generation (G3.5-PEG@OXA). Proton nuclear magnetic resonance and Fourier-transform infrared spectroscopy were used to confirm the successful incorporation of OXA as well as the synthesis of carrier systems. Both two types of carrier systems exhibited in sphere nanoparticle shape with size of less than 100 nm that was in the range being able to cause toxicity on cancer cells. The average drug loading efficiency (DLE) of G4-PEG@OXA was obtained at 84.63% that was higher than DLE of G3.5-PEG of 75.69%. The release kinetic of G4-PEG@OXA and G3.5-PEG@OXA did not show any burst release phenomenon while free OXA was released over 40% at the first hour. The sustainable release of OXA was achieved when it was encapsulated in these carriers, but the G4 generation liberated OXA (3.4%-6.4%) slower than G3.5 one (11.9%-22.8%). The in vitro cytotoxicities of G4-PEG@OXA were evaluated in HeLa cell lines using resazurin assay and live/dead staining test. Although the free OXA showed a rather moderate killing ability, the G4-PEG@OXA still displayed the low viability of HeLa that was better to the result of G3.5-PEG@OXA due to released OXA amount. The benefit of this system was to overcome the burst release phenomenon to minimize OXA toxicity without compromising its efficiency.     

Fate of fluoroquinolone antibiotics in Vietnamese coastal wetland ecosystem

Vietnamese coastal wetlands have traditionally been used for shrimp farming, but with the expansion of commercial shrimp farming and the associated clearance of mangroves, these valuable ecosystems have been rapidly degraded. The application of veterinary antibiotics in shrimp culture is one of the major threats to Vietnamese mangroves. These antibiotics are released into the environment through wastewater streams from shrimp ponds and cause environmental problems as well as the occurrence of antibiotic resistant bacteria. However, there is only a limited amount of information available on the occurrence and fate of antibiotics in Vietnamese mangroves. Ciprofloxacin and norfloxacin are two of most commonly fluoroquinolones used in shrimp culture. Laboratory experiments were therefore carried out using saline shrimp pond water to investigate the fate of both antibiotics in a coastal wetland ecosystem. Furthermore, two wetland plant species (Ceratophyllum demersum and Chrysopogon zizanioides), were used for studying phytoremediation of both antibiotics through a hydroponic experiment. Both ciprofloxacin and norfloxacin were photodegradable but at a slow rate, whereas the biodegradation seemed to be insignificant. If given at an initial concentration of 5 or 10?mg/L, a higher removal of antibiotics was achieved using C. demersum: 40?% for norfloxacin and 44?C39?% for ciprofloxacin, respectively. With C. zizanioides, ciprofloxacin and norfloxacin were reduced by 40?C38 and 36?C34?%, respectively. These results indicated that phytoremediation could be effective in the removal of both antibiotics.     

Correlation between enzyme activities and routine metabolic rate in Drosophila

To determine whether enzyme activity is correlated with physiological performance, we analysed the relationship between routine metabolic rate and published data on activity of 12 enzymes from nine species of Drosophila. The enzymes are involved in several aspects of intermediary metabolism including glycolysis. Multiple regression on phylogenetically independent contrasts revealed significant and positive correlations between in vitro enzyme activity and routine metabolic rate. The regression analysis included body size and locomotor activity level as covariates. This result suggests that there may be energetic costs associated with increased enzyme capacity.     

Anterior–posterior patterning of neural differentiated embryonic stem cells by canonical Wnts,Fgfs, Bmp4 and their respective antagonists

Embryonic stem (ES) cells are pluripotent and can differentiate into every cell type of the body. Next to their potential in regenerative medicine, they are excellent tools to study embryonic development. In this work the processes of neural induction and neural patterning along the antero‐posterior (A/P) body axis are studied and evidence suggests a two step mechanism for these events. First, neural induction occurs by default in the primitive ectoderm, forming anterior neural tissue and thereafter, a series of factors can posteriorize this anterior neurectoderm. In a gain‐of‐function/loss‐of‐function approach using mouse ES cells, we show that Fgf2 has the strongest caudalizing potential of all Fgfs tested. Furthermore, Bmp4 and Wnt3a, but not Wnt1, can caudalize the neurectodermal cells. The effect of the antagonists of these factors was also examined and though Dkk1 and Noggin clearly have an effect that opposes that of Wnt3a and Bmp4 respectively, they fail to anteriorize the neurectoderm. The patterning effect of SU5402, an Fgf receptor inhibitor, was rather limited. These data confirm that in the mouse, two steps are involved in neural patterning and we show that while Fgf4, Fgf8 and Wnt1 have no strong patterning effect, Fgf2, Wnt3a and Bmp4 are strong posteriorizing factors.     

Rat neurophysiological taste responses to salt solutions

1. Neurophysiological studies on the chemoresponsive tongueunits of the rat geniculate ganglion readily detected and furthercharacterized the two major functional neural groups designatedas ‘acid’ and ‘salt’ units by otherinvestigators in chorda tympani recordings. Units belongingto either of these groups were initially identified on the basisof their responses to a series of chemical solutions (a TestSeries) developed to distinguish unit groups in the geniculateganglion of the cat, dog and goat. 2. The nature of active ionicspecies effective in stimulating the units of the two differentgroups was further elaborated by studying their responses toa variety of salt solutions. From these studies, it was concludedthat the optimum molecular species for the acid units is anacid, where an acid is defined as a Br0nsted acid or protondonating molecule. A variety of molecular species may be activein solution, including some nitrogen compounds. Responses tosalt solutions by acid units are determined in part by the actionof the cation functioning as a Brønsted acid (NH₄), orin promoting proton donor molecules in water (mainly H₃O⁺).The salt units, on the other hand, are almost exclusively responsiveto solutions containing Na ⁺ and Li⁺. All other solutions werevirtually inactive. It was concluded that under a wide varietyof environmental conditions, Na+ would be the exclusive stimulusfor the salt units. Na⁺ and Li⁺ were found to be highly stimulatingwhen accompanied by a wide variety of solute anions, althoughthose containing the halogens (Cl^–, F^–, I^–,Br^–) were among the most stimulatory compounds tested.3. The establishment that the stimulus is a proton donor moleculefor the acid units and the Na⁺ and Li⁺ for the salt units hasprofound theoretical implications for the taste receptor. Biophysicalmodels of taste receptors are reviewed with respect to thisimproved understanding of the stimuli for the two types of units.It is suggested, after consideration of certain basic biochemicalaspects of the situation, that the acid receptor (possibly animidazole group) forms, as part of a protein, a proton conductingcircuit for driving an intracellular energy process devotedto proton sensing transmission. It is further suggested, inlight of the extreme specificity shown to Na ⁺, that receptorattachment is of the multidentate ligand variety and is probablylinked to Na⁺, K⁺ transport across the cell membrane, as proposedby DeSimone et al. (1981).     

Solution spatial structure of 'long' neurotoxin M9 from the scorpion Buthus eupeus by 1H-NMR spectroscopy

1H-NMR spectra of Buthus eupeus neurotoxin M9 (66 amino acid residues, four disulfide bonds) reveal two slowly exchangeable conformations at acidic pH. The spatial structure of the conformer prevailing under physiologically relevant conditions has been determined from two-dimensional 1H-NMR data treated by means of a distance geometry algorithm and refined by molecular modelling. Interrelation between the structure and function of mammalian neurotoxin M9 is discussed by comparing its conformation with those of the scorpion insectotoxins which exhibit different biological specificity (insectotoxins v-2, v-3 and I5A).     

Filamentous vibriophage fs2 encoding the rstC gene integrates into the same chromosomal region as the CTX phage [corrected]

The genome of the filamentous phage of Vibrio cholerae fs2 was found to contain rstC and rstB1 (truncated) genes downstream of ORF500. att-fs2-dir and att-fs2-rev sequences homologous to that of att-CTXphi were found between orf500 and rstC of the fs2 genome. This prompted us to search for the integration site of fs2 in the genomes of V. cholerae O1 and O139. The genome of fs2 was found to integrate downstream of attRS of the CTXphi phage, which integrated into chromosome I of V. cholerae O1 and O139. When infected with fs2, a fimbriate strain of V. cholerae O1 appeared to reduce fimbrial production in an adult rabbit ileal loop assay.