The cationic polymers may interact with the negatively charged layer of mucus in the eye surface and induce a significant increase in the precorneal residence time of the preparations (Dillen et al., 2006). In addition, recent studies indicating Eudragit E100®
is well tolerated in rabbit eyes (Quinteros, 2010) support the potential use of EuCl-OFX in the design of an ophthalmic formulation. Furthermore, the potentiator effect described for Eudragit E100® against P. aeruginosa Selleck Tigecycline may be a useful tool to broaden the spectrum of antibiotics whose clinical use is limited by the impermeability of the bacterial OM. The authors would like to thank Dr A. Barnes for providing clinical strains. This work was supported by grants from SECyT-UNC, CONICET and ANPCYT. RXDX-106 chemical structure V.L.R. would like to thank CONICET for a fellowship. “
“Comparative studies showed that, like Trypanosoma cruzi, Trypanosoma brucei exhibits functional cytosolic and mitochondrial malic enzymes (MEs), which are specifically linked to NADP. Kinetic studies provided evidence that T. cruzi and T. brucei MEs display similarly high affinities towards NADP+ and are also almost equally efficient in catalyzing the production of NADPH. Nevertheless, in contrast to the cytosolic ME from T. cruzi, which is highly activated by l-aspartate (over 10-fold), the T.
brucei homologue is slightly more active (50%) in the presence of this amino acid. In T. brucei, both isozymes appear to be clearly more abundant in the insect stage, although they can be immunodetected in the bloodstream forms. By contrast, in T. cruzi the expression of the mitochondrial ME seems to be clearly upregulated in amastigotes, whereas the cytosolic isoform appears to be more abundant in the insect stages of the parasite. It might
be hypothesized that in those environments where glucose is very low or absent, these pathogens depend on NADP-linked dehydrogenases such as the MEs for NADPH production, as in those conditions the pentose phosphate Mirabegron pathway cannot serve as a source of essential reducing power. American and African trypanosomes are the causative agents of some of the most neglected diseases. These parasitic protozoa infect a great number of people every year, but the current clinical treatments are far from satisfactory, with the available drugs being toxic and of low efficacy (Barrett et al., 2003; Urbina & Docampo, 2003). Therefore, understanding the biochemical peculiarities of these pathogens is of great importance for public health. Trypanosomes have complex life cycles. The insect stages of these pathogens develop in the gut of specific insect vectors; however, when infecting mammals these parasites colonize very different microenvironments. The bloodstream forms of Trypanosoma brucei actively grow in the blood of the mammalian host, a medium naturally rich in glucose.