Brain oxidative stress in a triple-transgenic mouse model of Alzheimer disease

Alzheimer disease (AD) is a neurodegenerative disease which is characterized by the presence of extracellular senile plaques mainly composed of amyloid-beta peptide (Abeta), intracellular neurofibrillary tangles, and selective synaptic and neuronal loss. AD brains revealed elevated levels of oxidative stress markers which have been implicated in Abeta-induced toxicity. In the present work we addressed the hypothesis that oxidative stress occurs early in the development of AD and evaluated the extension of the oxidative stress and the levels of antioxidants in an in vivo model of AD, the triple-transgenic mouse, which develops plaques, tangles, and cognitive impairments and thus mimics AD progression in humans. We have shown that in this model, levels of antioxidants, namely, reduced glutathione and vitamin E, are decreased and the extent of lipid peroxidation is increased. We have also observed increased activity of the antioxidant enzymes glutathione peroxidase and superoxide dismutase. These alterations are evident during the Abeta oligomerization period, before the appearance of Abeta plaques and neurofibrillary tangles, supporting the view that oxidative stress occurs early in the development of the disease.     

Climate and prevalence of atopic eczema in 6- to 7-year-old school children in Spain. ISAAC PhASE III

Atopic eczema (AE) is a chronic skin disease. Recent reports indicate that the worldwide prevalence of AE is increasing and that various environmental factors are implicated in its aetiology. Climatic conditions have been related with AE prevalence, and Spain has varying climatic conditions. The aim of this study is to document the possible climatic influence on the prevalence of AE in schoolchildren aged 6–7 years in three different climatic regions in Spain. We conducted a cross-sectional population-based survey of 28,394 schoolchildren aged 6–7 years from 10 Spanish centres in three different climatic regions. The mean participation rate was 76.5%. AE prevalence was assessed using the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire and the Spanish Academy of Dermatology criteria used in Spain to diagnose AE. The data, including annual temperature, precipitation, relative humidity and the annual number of sunny hours per climatic region, were obtained from the Spanish National Institute of Meteorology. Different AE prevalences were found in all three climatic regions studied: Atlantic, 32.9; Mediterranean 28.3; and Continental 31.2 per 100 children studied (p < 0.005). AE was positively associated with precipitation and humidity, and was negatively associated with temperature and the number of sunny hours. The results show that AE is significantly dependent on meteorological conditions.     

Elicitation of different Panax ginseng transformed root phenotypes for an improved ginsenoside production

We tested the effect of the presence in the culture medium of chitosan, vanadyl sulfate or methyl jasmonate on growth and ginsenoside production of three stable hairy root lines of Panax ginseng C.A. Meyer showing different morphological phenotypes C-M, HR-M and T-M. The response depended upon line phenotype, specificity of the elicitor and the stage of growth at which the lines were treated. The highest ginsenoside yield was found when methyl jasmonate was added during the progressive deceleration growth phase (on day 25 of culture). In this case, the ginsenoside content reached at the end of the culture (day 28) by root lines C-M, HR-M and T-M was, respectively, 2, 1.8 and 4 times higher than the highest content achieved, also at the end of the culture, by the corresponding untreated root lines. Under the same conditions, the ginsenoside content in the presence of vanadyl sulfate also increased considerably, while with chitosan it clearly decreased. The ginsenoside pattern in response to the presence of the elicitors is also considered.     

Synthetic peptides mimicking the interleukin-6/gp130 interaction: a two-helix bundle system. Design and conformational studies.

The objective of our study was to mimic in a typical reductionist approach the molecular interactions observed at the interface between the gp130 receptor and interleukin-6 during formation of their complex. A peptide system obtained by reproducing some of the interleukin-6/gp130 molecular interactions into a two-helix bundle structure was investigated. The solution conformational features of this system were determined by CD and NMR techniques. The CD titration experiments demonstrated that the interaction between the designed peptides is specific and based on a well-defined stoichiometry. The NMR data confirmed some of the structural features of the binding mechanism as predicted by the rational design and indicated that under our conditions the recognition specificity and affinity can be explained by the formation of a two-helix bundle. Thus, the data reported herein represent a promising indication on how to develop new peptides able to interfere with formation of the interleukin-6/gp130 complex.     

Syntrophic interactions among anode respiring bacteria (ARB) and Non‐ARB in a biofilm anode: electron balances

We demonstrate that the coulombic efficiency (CE) of a microbial electrolytic cell (MEC) fueled with a fermentable substrate, ethanol, depended on the interactions among anode respiring bacteria (ARB) and other groups of micro‐organisms, particularly fermenters and methanogens. When we allowed methanogenesis, we obtained a CE of 60%, and 26% of the electrons were lost as methane. The only methanogenic genus detected by quantitative real‐time PCR was the hydrogenotrophic genus, Methanobacteriales, which presumably consumed all the hydrogen produced during ethanol fermentation (～30% of total electrons). We did not detect acetoclastic methanogenic genera, indicating that acetate‐oxidizing ARB out‐competed acetoclastic methanogens. Current production and methane formation increased in parallel, suggesting a syntrophic interaction between methanogens and acetate‐consuming ARB. When we inhibited methanogenesis with 50 mM 2‐bromoethane sulfonic acid (BES), the CE increased to 84%, and methane was not produced. With no methanogenesis, the electrons from hydrogen were converted to electrical current, either directly by the ARB or channeled to acetate through homo‐acetogenesis. This illustrates the key role of competition among the various H₂ scavengers and that, when the hydrogen‐consuming methanogens were present, they out‐competed the other groups. These findings also demonstrate the importance of a three‐way syntrophic relationship among fermenters, acetate‐consuming ARB, and a H₂ consumer during the utilization of a fermentable substrate. To obtain high coulombic efficiencies with fermentable substrates in a mixed population, methanogens must be suppressed to promote new interactions at the anode that ultimately channel the electrons from hydrogen to current. Biotechnol. Bioeng. 2009;103: 513–523. © 2009 Wiley Periodicals, Inc.     

Neuro-protective effects of carbamazepine on sleep patterns and head and body shakes in kainic acid-treated rats

The aim of this work was to analyze the effect of carbamazepine (CBZ) on sleep patterns and on “head and body shakes” and to determine the role of serotonin (5-HT) in a model of kainic-induced seizures. Thirty male Wistar rats (280–300 g) were used for polygraphic sleep recording. After a basal recording, the rats were allocated into three groups: kainic acid-treated animals (KA; 10 mg/kg; n = 10), carbamazepine-treated animals (CBZ; 30 mg/kg; n = 10) and animals injected with KA 30 min after pretreatment with CBZ (CBZ + KA; n = 10). Polygraphic recordings were performed for 10 h for 3 days, with the exception of the CBZ group, which were observed for 1 day. In order to measure the head and body shakes that occurred over that time, a behavioral assessment was performed in two additional groups of KA (n = 10) and CBZ + KA (n = 10) animals. After 10 h of behavioral assessment, the rats were sacrificed, and the levels of 5-HT and 5-hydroxy-indol-acetic acid (5-HIAA) were analyzed. We compared these findings with the results from a group of rats without pharmacological intervention (n = 10). All of the recordings were performed from 08:00 to 18:00 h. Data analysis: the electrographic parameters, head and body shake counting and monoamine concentrations were analyzed by an ANOVA test. Differences of *p ≤ 0.01 and **p ≤ 0.001 were considered statistically significant. Our results showed that CBZ exerted a protective effect on sleep pattern alterations induced by KA, which when administered alone caused a complete inhibition of sleep for the first 10 h after administration. Although there was a reduction in the amount of sleep after the administration of KA in CBZ-pretreated animals, sleep inhibition was incomplete. In addition, CBZ decreased the frequency of head and body shakes by 60% as compared to KA. The 5-HT and 5-HIAA levels in the pons were increased in the KA and KA + CBZ groups. Our conclusion is that in addition to decreasing seizure intensity, CBZ facilitates the partial recovery of sleep. These results suggest that CBZ provides neuro-protective effects on sleep and against seizures.     

Protective effect and relation structure-activity of nonivamide and iododerivatives in several models of lipid oxidation

The introduction of an iodine atom on the vanillyl moiety of nonivamide causes a switch in the vanilloid activity (TRPV1 antagonism versus TRPV1 desensitization) and nullifies the aversive properties of capsaicinoids. In the present study we investigated the effect of iodination in the vanillyl moiety on the antioxidant activity of capsaicinoids. To this aim, we have compared the protective effects of nonivamide and three iododerivatives, 2-iodononivamide (2IN), 5-iodononivamide (5IN), and 6-iodononivamide (6IN) in a series of in vitro models of lipid oxidation, namely the autoxidation and the FeCl₃-mediated oxidation of linoleic acid at 37 °C and the thermal (140 °C), solvent-free oxidation of cholesterol. All tested compounds could protect linoleic acid and cholesterol against oxidative degradation, the order of potency being: nonivamide > 5IN > 6IN ≈ 2IN. Our results show that, in general, the introduction of an iodine atom on the vanillyl moiety of nonivamide causes a decrease in the antioxidant activity, and this effect is sensitive to the position of iodine on the aromatic ring, with 5IN substantially retaining the efficacy of nonivamide to protect linoleic and cholesterol against free radical attack. Moreover, the pre-treatment with 5IN, at noncytotoxic concentrations, significantly preserved LDL from Cu²⁺-induced oxidative damage at 37 °C for 2 h, inhibiting the reduction of polyunsaturated fatty acids and cholesterol and the increase of their oxidative products. The results of the present work suggest that 5IN exerts useful antioxidant properties in different in vitro systems of lipid peroxidation. This, coupled to its lacks of pungency and TRPV1 inhibiting properties, qualifies this phenolic compound as an attractive candidate for further investigations in vivo.     

Microbial communities and activities in alpine and subalpine soils

Soil samples were collected along two slopes (south and north) at subalpine (1500–1900 m, under closed vegetation, up to the forest line) and alpine altitudes (2300–2530, under scattered vegetation, above the forest line) in the Grossglockner mountain area (Austrian central Alps). Soils were analyzed for a number of properties, including physical and chemical soil properties, microbial activity and microbial communities that were investigated using culture-dependent (viable heterotrophic bacteria) and culture-independent methods (phospholipid fatty acid analysis, FISH). Alpine soils were characterized by significantly ( P <0.01) colder climate conditions, i.e. lower mean annual air and soil temperatures, more frost and ice days and higher precipitation, compared with subalpine soils. Microbial activity (soil dehydrogenase activity) decreased with altitude; however, dehydrogenase activity was better adapted to cold in alpine soils compared with subalpine soils, as shown by the lower apparent optimum temperature for activity (30 vs. 37 °C) and the significantly ( P <0.01–0.001) higher relative activity in the low-temperature range. With increasing altitude, i.e. in alpine soils, a significant ( P <0.05–0.01) increase in the relative amount of culturable psychrophilic heterotrophic bacteria, in the relative amount of the fungal population and in the relative amount of Gram-negative bacteria was found, which indicates shifts in microbial community composition with altitude.     

Inhibition of growth and ochratoxin A biosynthesis in <Emphasis Type="Italic">Aspergillus carbonarius</Emphasis> by flavonoid and nonflavonoid compounds

The effect of naturally occurring phenolic compounds on Aspergillus carbonarius growth and ochratoxin A (OTA) production was studied. Caffeic acid and the flavonoids, rutin and quercetin, were added to Czapek Yeast Extract agar at concentrations ranging between 50 and 500 mg/l. All phenolic compounds had a significant influence on growth rate and lag phase of A. carbonarius at 250 mg/l. The growth was completely inhibited with 500 mg/l. In comparison with the control, a significant decrease in OTA production was observed with all phenolic compounds. In general, effect on growth was less evident than effect on toxin production. An inhibitory effect on growth and OTA production, as concentration was increased was observed in all cases. The response of A. carbonarius to the flavonoids, rutin and quercetin, was similar. The inhibitory effect of these natural phenolic compounds on fungal growth and OTA production could be an alternative to the use of chemical fungicides.