Aging and Alzheimer's disease: Searching for novel molecular cues

Tese de Doutoramento em Ciências da Saúde

Poly-N-acetyl glucosamine expression in Staphylococcus epidermidis biofilm cells affects the immune response and promotes tissue pathology in infected hosts

Staphylococcus epidermidis is a biofilm - forming bacterium and a leading etiological agent of nosocomial infections. The ability to establish biofilms on indwelling medical devices is a key virulence factor for this bacterium. Still, the influence of poly - N - acetyl glucosamine (PNAG), the major component of the extracellular biofilm matrix, in the host immune response has been scarcely studied. Here, t h is influence was assessed in mice challenged i.p. with PNAG - p roducing (WT) and isogenic - mutant lacking PNAG (M10) bacteria grown in biofilm - inducing conditions. Faster bacterial clearance was observed in the mice infected with WT bacteria than in M10 - infected counterparts , which w as accompanied by earlier neutrophil recruitment and higher IL - 6 production. Interestingly, in the WT - infected mice, but not in those infected with M10 , elevated serum IL - 10 was detected . To further study the effe ct of PNAG in the immune response, mice were primed with WT or M10 biofilm bacteria and subsequently infected with WT biofilm - released cells. WT - primed mice presented a higher frequency of splenic IFN - γ + and IL - 17 + CD4 + T cells, and more severe liver patho logy than M10 - primed counterparts. Nevertheless, T reg cells obtained from the WT - primed mice presented a higher suppressive function than those obtained from M10 - primed mice. This effect was abrogated when IL - 10 - deficient mice were similarly primed and infected indicating that PNAG promotes the differentiati on of highly suppressive T reg cells by a mechanism dependent on IL - 10. Altogether, these results provide evidence help ing explain ing the coexistence of inflammation and bacterial persistence often observed in biofilm - originated S. epidermidis infections

Influence of different activated carbons on Ochratoxin A decrease in wines

The presence of mycotoxins in foodstuff is a matter of concern for food safety. Wines can also be contaminated with these toxicants. Several authors have demonstrated the presence of mycotoxins in wine, especially ochratoxin A (OTA) [1]. As these toxicants can never be completely removed from the food chain, many countries have defined levels in food in order to attend health concerns. The maximum acceptable level of OTA in wines is 2.0 µg/kg according to the Commission regulation No. 1881/2006 [2]. Although, higher levels of OTA have been detected in several wine samples. In order to reduce OTA to safer levels, several oenological products can be used in wine; including activated carbons, as shown in previous experiments. Regarding this, the aim of present study was to evaluate the effectiveness of several activated carbons for reducing the amount of OTA present in white and red wines as well as to evaluate their effect on wines physicochemical characteristics. Wine samples were artificially supplemented with OTA at a final concentration of 10.0 µg/L. The different activated carbons were applied at the concentration recommended by the manufacturer in order to evaluate their efficiency in reducing OTA levels. A mixture composed by gelatine, bentonite and activated carbon reduced 80% of OTA concentration in white wine. The same mixture was however less efficient in red wine, achieving only a reduction of 55%. Thereafter, the effect of activated carbon was evaluated in a red wine, achieving reductions of 66%. Considering these results more assays are being performed with other commercial activated carbons, in order to evaluate their efficiency. These results may provide valuable information for winemakers. Knowing the effect of commercial activated carbons they may choose most appropriate products to remove OTA, thus enhancing wine safety and quality.

Anti-inflammatory and antinociceptive activities of Bauhinia monandra leaf lectin

A galactose-specific lectin from Bauhinia monandra leaves (BmoLL) have been purified through ammonium sulphate fractionation followed by guar gel affinity chromatography column. This study aimed to evaluate the potential anti-inflammatory and antinociceptive activity of pure BmoLL in mice. Anti-inflammatory activity was evaluated by 1% carrageenan-induced inflammation in mice treated with BmoLL. Acetic acid-induced abdominal writhing and hot plate methods evaluated antinociceptive activity. BmoLL significantly inhibited the carrageenan-induced paw edema by 47% (30 mg/kg) and 60.5% (60 mg/kg); acetylsalicylic acid (ASA, 100 mg/kg) showed inhibition of 70.5%, in comparison to controls. Leukocyte migration, an immune response to the inflammation process, was significantly reduced in presence of BmoLL; in mice treated with \ASA\ the decrease in leukocyte migration was similar to 15 mg/kg of the lectin. BmoLL at doses of 15, 30 and 60 mg/kg significantly reduced the number of animal contortions by 43.1, 50.1 and 71.3%, respectively.BmoLL leukocyte migration was significantly reduced; in mice treated with \ASA\ the decrease in leukocyte migration was similar to 15 mg/kg of the lectin. BmoLL at doses of 15, 30 and 60 mg/kg significantly reduced the number of animal contortions by 43.1, 50.1 and 71.3%, respectively. The lectin (30 and 60 mg/kg) showed a significant effect in the hot plate assay. BmoLL anti-inflammatory and antinociceptive effects were dose-dependent. The search for new and natural compounds, with minimal side effects, to control pain and inflammation, is constantly increasing. BmoLL has great potential as a natural anti-inflamatory product that can be explored for pharmacological purposes.