פרסומים

Cerebral malaria (CM) is a major cause of death of Plasmodium falciparum infection. Misdiagnosis of CM often leads to treatment delay and mortality. Conventional brain imaging technologies are rarely applicable in endemic areas. Here we address the unmet need for a simple, non-invasive imaging methodology for early diagnosis of CM. This study presents the diagnostic and therapeutic monitoring using liposomes containing the FDA-approved fluorescent dye indocyanine green (ICG) in a CM murine model. Increased emission intensity of liposomal ICG was demonstrated in comparison with free ICG. The Liposomal ICG's emission was greater in the brains of the infected mice compared to naïve mice and drug treated mice (where CM was prevented). Histological analyses suggest that the accumulation of liposomal ICG in the cerebral vasculature is due to extensive uptake mediated by activated phagocytes. Overall, liposomal ICG offers a valuable diagnostic tool and a biomarker for effectiveness of CM treatment, as well as other diseases that involve inflammation and blood vessel occlusion.

Cerebral malaria (CM) is a major cause of death of Plasmodium falciparum infection. Misdiagnosis of CM often leads to treatment delay and mortality. Conventional brain imaging technologies are rarely applicable in endemic areas. Here we address the unmet need for a simple, non-invasive imaging methodology for early diagnosis of CM. This study presents the diagnostic and therapeutic monitoring using liposomes containing the FDA-approved fluorescent dye indocyanine green (ICG) in a CM murine model. Increased emission intensity of liposomal ICG was demonstrated in comparison with free ICG. The Liposomal ICG’s emission was greater in the brains of the infected mice compared to naive mice and drug treated mice (where CM was prevented). Histological analyses suggest that the accumulation of liposomal ICG in the cerebral vasculature is due to extensive uptake mediated by activated phagocytes. Overall, liposomal ICG offers a valuable diagnostic tool and a biomarker for effectiveness of CM treatment, as well as other diseases that involve inflammation and blood vessel occlusion.[on SciFinder (R)]

Various chemical, natural, or synthetic in origin, crosslinking methods have been proposed over the years to stabilise collagen fibers. However, an optimal method has yet to be identified. Herein, we ventured to assess the potential of 4-star poly(ethylene glycol) ether tetrasuccinimidyl glutarate, as opposed to glutaraldehyde (GTA), genipin and carbodiimide, on the structural, physical and biological properties of collagen fibers. The 4-star poly(ethylene glycol) ether tetrasuccinimidyl glutarate induced an intermedium surface smoothness, denaturation temperature and swelling. The 4-star poly(ethylene glycol) ether tetrasuccinimidyl glutarate fibers had significantly higher stress at break values than the carbodiimide fibers, but significantly lower than the GTA and genipin fibers. With respect to strain at break, no significant difference was observed among the crosslinking treatments. The 4-star poly(ethylene glycol) ether tetrasuccinimidyl glutarate fibers exhibited significantly higher cell metabolic activity and DNA concentration that all other crosslinking treatments, promoted consistently cellular elongation along the longitudinal fiber axis and by day 7 they were completely covered by cells. Collectively, this work clearly demonstrates the potential of 4-star poly(ethylene glycol) ether tetrasuccinimidyl glutarate as collagen crosslinker. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 914-922, 2016.

Abstract Various chemical, natural, or synthetic in origin, crosslinking methods have been proposed over the years to stabilise collagen fibers. However, an optimal method has yet to be identified. Herein, we ventured to assess the potential of 4-star poly(ethylene glycol) ether tetrasuccinimidyl glutarate, as opposed to glutaraldehyde (GTA), genipin and carbodiimide, on the structural, physical and biological properties of collagen fibers. The 4-star poly(ethylene glycol) ether tetrasuccinimidyl glutarate induced an intermedium surface smoothness, denaturation temperature and swelling. The 4-star poly(ethylene glycol) ether tetrasuccinimidyl glutarate fibers had significantly higher stress at break values than the carbodiimide fibers, but significantly lower than the GTA and genipin fibers. With respect to strain at break, no significant difference was observed among the crosslinking treatments. The 4-star poly(ethylene glycol) ether tetrasuccinimidyl glutarate fibers exhibited significantly higher cell metabolic activity and DNA concentration that all other crosslinking treatments, promoted consistently cellular elongation along the longitudinal fiber axis and by day 7 they were completely covered by cells. Collectively, this work clearly demonstrates the potential of 4-star poly(ethylene glycol) ether tetrasuccinimidyl glutarate as collagen crosslinker. ? 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 914?922, 2016.

First-principles anharmonic calculations are carried out for the CH stretching vibrations of isolated toluene and compared with the experimental infrared spectra of isotopologues of toluene in a Ne matrix at 3 K and of liquid toluene at room temperature. The calculations use the vibrational self-consistent field method and the B3LYP potential surface. In general, good agreement is found between the calculations and experiments. However, the spectrum of toluene in a Ne matrix is more complicated than that predicted theoretically. This distinction is discussed in terms of matrix-site and resonance effects. Interestingly, the strongest peak in the CH stretching spectrum has similar widths in the liquid phase and in a Ne matrix, despite the very different temperatures. Implications of this observation to the broadening mechanism are discussed. Finally, our results show that the B3LYP potential offers a good description of the anharmonic CH stretching band in toluene, but a proper description of matrix-site and resonance effects remains a challenge.

Many dietary compounds, including resveratrol, are potent inhibitors of CYP3A4. Here we examined the potential to predict inhibition capacity of dietary polyphenolics using an in silico and in vitro approaches and synthetic model compounds. Mono, di and tri-acetoxy resveratrol were synthesized, a cell line of human intestine origin and microsomes from rat liver served to determine their in vitro inhibition of CYP3A4 and compared to that of resveratrol. Docking simulation served to predict the affinity of the synthetic model compounds to the enzyme. Modelling of the enzyme’s binding site revealed three types of interaction: hydrophobic, electrostatic and H-bonding. The simulation revealed that each of the examined acetylations of resveratrol led to the loss of important interactions of all types. Tri-acetoxy resveratrol was the weakest inhibitor in vitro despite being the more lipophilic and having the highest affinity for the binding site. The simulation demonstrated exclusion of all interactions between tri-acetoxy resveratrol and the heme due to distal binding, highlighting the complexity of the CYP3A4 binding site, which may allow simultaneous accommodation of two molecules. Finally, the use of computational modelling may serve as a quick predictive tool to identify potential harmful interactions between dietary compounds and prescribed drugs.

Abstract Secondary metabolites and synthetic iminosugars that structurally resemble monosaccharides are potent inhibitors of α-glucosidase activity. The enzyme is core in cleaving sucrose in phloem feeding insects and it also plays a crucial role of reducing osmotic stress via the formation of oligosaccharides. Inhibition of hydrolysis by iminosugars should result in nutritional deficiencies and/or disruption of normal osmoregulation. Deoxynojirimycin (DNJ) and 2 N-alkylated analogs [N-butyl DNJ (NB-DNJ) and N-nonyl DNJ (NN-DNJ)] were the major iminosugars used throughout the study. The extensive experiments conducted with α-glucosidase of the whitefly Bemisia tabaci indicated the competitive nature of inhibition and that the hydrophilic DNJ is a potent inhibitor in comparison to the more hydrophobic NB-DNJ and NN-DNJ compounds. The same inhibitory pattern was observed with the psyllid Cacopsylla bidens α-glucosidase. In contrast to the above pattern, enzymes of the aphids, Myzus persicae and Aphis gossypii were more sensitive to the hydrophobic iminosugars as compared to DNJ. In vivo experiments in which adult B. tabaci were fed dietary iminosugars, show that the hydrophilic DNJ was far less toxic than the lipophilic NB-DNJ and NN-DNJ. It is proposed that this pattern is attributed to the better accessibility of the hydrophobic NN-DNJ to the α-glucosidase membrane-bound compartment in the midgut. Based on the inhibitory effects of certain polyhydroxy N-alkylated iminosugars, α-glucosidase of phloem feeding hemipterans could serve as an attractive target site for developing novel pest control agents.

Poly(lactic acid) and its copolymers have revolutionized the field of drug delivery due to their excellent biocompatibility and tunable physico-chemical properties. These copolymers have served the healthcare sector by contributing many products to combat various diseases and for biomedical applications. This article provides a comprehensive overview of clinically used products of poly(lactic acid) and its copolymers. Multi-dimension information covering product approval, formulation aspects and clinical status is described to provide a panoramic overview of each product. Moreover, leading patented technologies and various clinical trials on these products for different applications are included. This review focuses on marketed injectable formulations of PLA and its copolymers.