Exogenously incorporated ketocarotenoids in large unilamellar vesicles. Protective activity against peroxidation

The ability of astaxanthin and canthaxanthin as chain-breaking antioxidants was studied in Cu(2+)-initiated peroxidation of phosphatidylcholine large unilamellar vesicles (LUVs). Both carotenoids increased the lag period that precedes the maximum rate of lipid peroxidation, though astaxanthin showed stronger activity. For these experiments, different amounts of xanthophylls were exogenously added to previously made LUVs, non-incorporated pigment being afterwards removed. Differential scanning calorimetry assays with L-beta,gamma-dimyristoyl-alpha-phosphatidylcholine LUVs demonstrated that xanthophylls incorporated as described interact with the lipid matrix becoming interspersed among the phospholipid molecules.     

Methanogenic and perchloroethylene-dechlorinating activity of anaerobic granular sludge

The biodegradation and toxicity of tetrachloroethylene (C₂Cl₄) and trichloroethylene (C₂HCl₃) were studied with different anaerobic enrichment cultures using the following electron donors: acetate, propionate, butyrate, methanol, formate and hydrogen. All of them sustained dechlorination except propionate, for which C₂Cl₄ biodegradation rates were not significant. The best results were obtained with butyrate. Hydrogen appeared to be a relevant electron donor for dechlorination with the present cultures. In the presence of specific inhibitors such as bromoethanesulphonate or molybdate, a slight inhibition of dechlorination was observed. According to dechlorination kinetics, Monod-type behaviour was observed up to 120 μM C₂Cl₄ or 200 μM C₂HCl₃ with K _s values around 7 μM for both compounds. Dechlorination was partially inhibited at higher concentrations. In contrast, methanogens, or at least methane production, were more sensitive to the presence of chlorinated ethylenes and inhibition of methanogenesis was observed to different extents over all the C₂Cl₄/C₂HCl₃ concentration range tested, even at the lowest concentrations. Received: 17 April 1998 / Received revision: 18 June 1998 / Accepted: 19 June 1998     

The Role of <Emphasis Type="SmallCaps">l</Emphasis>-arginine in Inclusion Complexes of Omeprazole with Cyclodextrins

In this study, we investigate how the effect of l-arginine (ARG) and cyclodextrins upon omeprazole (OME) stability and solubility. The effect of the presence of ARG on the apparent stability constants (K_1:1) of the inclusion complexes formed between OME and each cyclodextrin, β-cyclodextrin (βCD), and methyl-β-cyclodextrin (MβCD) is studied by phase solubility diagrams and nuclear magnetic resonance (NMR) spectroscopy. The interaction of OME with those cyclodextrins, in the presence of ARG, is characterized using NMR spectroscopy and molecular dynamics simulations. ARG significantly increases the drug solubility and complex stability, in comparison to inclusion complexes formed in its absence. The effect is more pronounced for the OME:βCD complex. ARG also contributes to a larger stability of OME when free in aqueous solution. The combination of ARG with cyclodextrins can represent an important tool to develop stable drug formulations.     

Indirect mechanism of histamine-induced nociception in temporomandibular joint of rats

A considerable amount of evidence suggests that temporomandibular joint (TMJ) pain associated with temporomandibular disorder results, at least in part, from an inflammatory episode. Although histamine can cause pain, it is not clear whether this mediator induces nociception in the TMJ. In this study, we investigated the contribution of endogenous histamine to formalin-induced nociception in the TMJ of rats. We also investigated whether the administration of histamine induces nociception in the TMJ and, if so, whether this effect is mediated by an indirect action on primary afferent nociceptors. Local administration of the H1-receptor antagonist pyrilamine prevented formalin-induced nociception in the TMJ in a dose-dependent manner. Local administration of histamine (250 microg) in the TMJ induced nociceptive behavior that was inhibited by co-administration of the lidocaine N-ethyl bromide quaternary salt QX-314 (2%) or the selective H1-receptor antagonist pyrilamine (400 microg). Nociception induced by histamine was also inhibited by pre-treatment with sodium cromoglycate (800 microg) and by co-administration of the 5-HT(3) receptor antagonist tropisetron (400 mug), while pyrilamine (400 mug) did not inhibit nociception induced by 5-hydroxytryptamine (5-HT, 250 microg) in the TMJ. Furthermore, histamine, in a dose that did not induce nociception by itself, strongly enhanced 5-HT-induced nociception. Finally, the administration of a sub-threshold dose of 5-HT (100 microg), but not of histamine (100 microg), elicited nociception in the TMJ previously challenged with the inflammatory agent carrageenan (100 microg). In conclusion, these data suggest that histamine induces TMJ nociception by an indirect mechanism involving endogenous release of 5-HT and activation of 5-HT(3) receptors on sensory afferents. It is proposed that histamine activates the H1 receptor to induce the release of 5-HT which depolarizes the nociceptor by activating 5-HT(3) receptor.     

Two novel dermonecrotic toxins LiRecDT4 and LiRecDT5 from brown spider (Loxosceles intermedia) venom: from cloning to functional characterization

Loxoscelism (the condition produced by the bite of brown spiders) has been reported worldwide, but especially in warmer regions. Clinical manifestations include skin necrosis with gravitational spreading while systemic loxoscelism may include renal failure, hemolysis and thrombocytopenia. The venom contains several toxins, of which the best biochemically and biologically studied is the dermonecrotic toxin, a phospholipase-D. Purified toxin induces cutaneous and systemic loxoscelism, especially necrotic lesions, hematological disturbances and renal failure. Herein, we describe cloning, heterologous expression and purification of two novel dermonecrotic toxins: LiRecDT4 and LiRecDT5. The recombinant proteins stably expressed in Escherichia coli cells were purified from culture supernatants in a single step using Ni(2+)-chelating chromatography producing soluble proteins of 34 kDa (LiRecDT4) and 37 kDa (LiRecDT5). Circular dichroism analysis evidenced correctly folding for toxins but differences in secondary structures. Both proteins were recognized by whole venom serum antibodies and by a specific antibody to dermonecrotic toxin. Also, recombinant toxins with phospholipase activity induced experimental skin lesions and caused a massive inflammatory response in rabbit skin dermis. Nevertheless, toxins displayed different effects upon platelet aggregation, increase in vascular permeability and not caused death in mice. These characteristics in combination with functional studies illustrates that a family of dermonecrotic toxins exists, and includes two novel members that are useful for future structural and functional studies. They will also be useful in biotechnological ends, for example, as inflammatory and platelet aggregating studies, as antigens for serum therapy source and for lipids biochemical research.     

Impact of microbial transformation of food on health - from fermented foods to fermentation in the gastro-intestinal tract

Fermentation of food components by microbes occurs both during certain food production processes and in the gastro-intestinal tract. In these processes specific compounds are produced that originate from either biotransformation reactions or biosynthesis, and that can affect the health of the consumer. In this review, we summarize recent advances highlighting the potential to improve the nutritional status of a fermented food by rational choice of food-fermenting microbes. The vast numbers of microbes residing in the human gut, the gut microbiota, also give rise to a broad array of health-active molecules. Diet and functional foods are important modulators of the gut microbiota activity that can be applied to improve host health. A truly multidisciplinary approach is required to increase our understanding of the molecular mechanisms underlying health beneficial effects that arise from the interaction of diet, microbes and the human body.     

Solid Dispersions of Imidazolidinedione by PEG and PVP Polymers with Potential Antischistosomal Activities

Solid dispersions have been used as a strategy to improve the solubility, dissolution rate, and bioavailability of poor water-soluble drugs. The increase of the dissolution rate presented by (5Z)-3-(4-chloro-benzyl)-5-(4-nitro-benzylidene)-imidazolidine-2,4-dione (LPSF/FZ4) from the solid dispersions is related to the existence of intermolecular interactions of hydrogen bond type (>N–H^...O<) between the amide group (>N–H) of the LPSF/FZ4 and the ether group (–O–) of the polyethyleneglycol polymer, or the carbonyl (C=O) of the polyvinylpyrrolidone polymer (PVP). The intensity of these interactions is directly reflected in the morphology acquired by LPSF/FZ4 in these systems, where a new solid phase, in the form of amorphous aggregates of irregular size, was identified through scanning electron microscopy and confirmed in the characterizations achieved using X-ray diffraction and thermal analysis of DSC. The solid dispersions with the polymer PVP, in higher concentrations, were revealed to be the best option to be used in the formulations of LPSF/FZ4 in both theoretical and experimental studies.     

Quantum chemical modeling of perovskite: An investigation of piezoelectricity in ferrite of yttrium

In a previous article, we used Hartree-Fock (HF) theory to study the piezoelectricity in BaTiO₃. In this paper, we applied the Douglas-Kroll-Hess second order scalar relativistic method to investigate the possible piezoelectric properties in the perovskite YFeO₃ structure, which has not yet been studied experimentally. The 30s20p13d and 31s21p17d Gaussian basis sets for the Fe (⁵D) and Y (²D) atoms, respectively, were built with the Generator Coordinate HF method. After contraction to [13s7p5d] and [13s8p7d], in combination with the 20s14p/6s4p basis set for the O (³P) atom from literature, they had their quality evaluated using calculations of the total and the orbital energies for the ²FeO⁺¹ and ¹YO⁺¹ fragments. The dipole moment, the total energy, and the total atomic charges in YFeO₃ in C_s space group were calculated. The results and the analysis lead us to believe that the perovskite YFeO₃ does not present piezoelectric properties.