Neuroprotective role of quercetin in locomotor activities and cholinergic neurotransmission in rats experimentally demyelinated with ethidium bromide

Aim

The purpose of this study was to investigate whether the flavonoid quercetin can prevent alterations in the behavioral tests and of cholinergic neurotransmission in rats submitted to the ethidium bromide (EB) experimental demyelination model during events of demyelination and remyelination.

Main methods

Wistar rats were randomly distributed into four groups (20 animals per group): Control (pontine saline injection and treatment with ethanol), Querc (pontine saline injection and treatment with quercetin), EB (pontine 0.1% EB injection and treatment with ethanol), and EB + Querc (pontine 0.1% EB injection and treatment with quercetin). The groups Querc and Querc + EB were treated once daily with quercetin (50 mg/kg) diluted in 25% ethanol solution (1 ml/kg) and the animals of the control and EB groups were treated once daily with 25% ethanol solution (1 ml/kg). Two stages were observed: phase of demyelination (peak on day 7) and phase of remyelination (peak on day 21 post-injection). Behavioral tests (beam walking, foot fault and inclined plane test), acetylcholinesterase (AChE) activity and lipid peroxidation in pons, cerebellum, hippocampus, hypothalamus, striatum and cerebral cortex were measured.

Key findings

The quercetin promoted earlier locomotor recovery, suggesting that there was demyelination prevention or further remyelination velocity as well as it was able to prevent the inhibition of AChE activity and the increase of lipidic peroxidation, suggesting that this compound can protect cholinergic neurotransmission.

Significance

These results may contribute to a better understanding of the neuroprotective role of quercetin and the importance of an antioxidant diet in humans to provide benefits in neurodegenerative diseases such as MS.     

Mitochondrial DNA haplogroups and risk of new-onset diabetes among tacrolimus-treated renal transplanted patients

Background and aims

Tacrolimus (Tac) is an immunosuppressive drug widely used to avoid organ rejection. New-onset diabetes after transplantation (NODAT) is a major complication among transplanted patients who receive Tac. The increased risk for NODAT could be partly mediated by the effect of Tac on mitochondria from pancreatic beta-cells. Common and rare mitochondrial DNA variants have been linked to the risk of diabetes. Our aim was to determine whether mtDNA polymorphisms/haplogroups were associated with NODAT in Tac-treated kidney transplanted.

Methods

Seven polymorphisms that define the common European haplogroups were determined in 115 NODAT and 197 no-NODAT patients.

Results

Haplogroup H was significantly more frequent in the NODAT group (50% vs. 35%; p = 0.01, OR = 1.82). There was no difference between patients without and with (n = 106) D2M prior to the transplant.

Conclusions

Mitochondrial haplogroup H was associated with the risk for NODAT among Tac-treated transplanted patients. The reported differences between the mtDNA variants could explain the increased NODAT-risk among H-patients.     

Mixture design as a potential tool in modeling the effect of light wavelength on Dunaliella salina cultivation: an alternative solution to increase microalgae lipid productivity for biodiesel production

Abstract

For a feasible microalgae biodiesel, increasing lipid productivity is a key parameter. An important cultivation parameter is light wavelength (λ). It can affect microalgal growth, lipid yield, and fatty acid composition. In the current study, the mixture design was used as an alternative to model the influence of the λ on the Dunaliella salina lipid productivity. The illumination was considered to be the mixture of different λ (the light colors blue, red, and green). All experiments were performed with and without sodium acetate (4?g/L), as carbon source, allowing the identification of the impact of the cultivation regimen (autotrophic or mixotrophic). Without sodium acetate, the highest lipid productivity was obtained using blue and red light. The use of mixotrophic cultivations significantly enhanced the results. The optimum obtained result was mixotrophic cultivation under 65% blue and 35% green light, resulting in biomass productivity of 105.06 mgL^?1day^?1, a lipid productivity of 53.47 mgL^?1day^?1, and lipid content of 50.89%. The main fatty acids of the oil obtained in this cultivation were oleic acid (36.52%) and palmitic acid (18.31%).     

An Automated High Throughput Screening-Compatible Assay to Identify Regulators of Stem Cell Neural Differentiation

The use of Embryonic Stem Cells (ESCs) holds considerable promise both for drug discovery programs and the treatment of degenerative disorders in regenerative medicine approaches. Nevertheless, the successful use of ESCs is still limited by the lack of efficient control of ESC self-renewal and differentiation capabilities. In this context, the possibility to modulate ESC biological properties and to obtain homogenous populations of correctly specified cells will help developing physiologically relevant screens, designed for the identification of stem cell modulators. Here, we developed a high throughput screening-suitable ESC neural differentiation assay by exploiting the Cell ^maker robotic platform and demonstrated that neural progenies can be generated from ESCs in complete automation, with high standards of accuracy and reliability. Moreover, we performed a pilot screening providing proof of concept that this assay allows the identification of regulators of ESC neural differentiation in full automation.     

Pollen content study of the lower atmosphere in León (Spain) by use of a tethered balloon

This study was undertaken in order to understand thebehaviour of airborne pollen grains, namely therelationship between their concentrations andconcomitant meteorological parameters, at differentaltitudes (ground level, 200, 400 and 600 m) of thelower atmosphere and its daily variations over onesite (the experimental farm of the University ofLeón). The experimental design involved a tetheredballoon (2.25 m³), an ADAS remote meteorologicalstation and an original radio controlled three headedpollen and spore sampler (called GABIS) using theRotorod design. Each head sampled a differentaltitude, while two control samples were taken atground level. Twenty-one takeoffs could be realized inthe 5 weeks period between end of May and end of June1997. Sampling was done early in the morning and sampling time at each altitudewas of 15 minutes. Results show that 45 differenttypes of pollen grains could be collected at this timeof the year and that significant variations could beobserved in the behaviour of the pollen cloud on a dayto day basis, probably because of differentmeteorological situations. Contrary to what isgenerally believed, pollen was in most cases moreabundant at higher altitude – on average by 30% ascompared to ground level – making evident anaerobiological layer of transport at about 500 m aboveground. This was especially the case for trees (Quercus and Castanea). The atmosphere MixingRatio was the most explicative factor at 200 m, whiletemperature dominated significance analysis at both400 and 600 m.     

Pattern of cytokine and chemokine production by THP-1 derived macrophages in response to live or heat-killed Mycobacterium bovis bacillus Calmette-Guérin Moreau strain

Tuberculosis has great public health impact with high rates of mortality and the only prophylactic measure for it is the Mycobacterium bovisbacillus Calmette-Guérin (BCG) vaccine. The present study evaluated the release of cytokines [interleukin (IL)-1, tumour necrosis factor and IL-6] and chemokines [macrophage inflammatory protein (MIP)-1α and MIP-1β] by THP-1 derived macrophages infected with BCG vaccine obtained by growing mycobacteria in Viscondessa de Moraes Institute medium medium (oral) or Sauton medium (intradermic) to compare the effects of live and heat-killed (HK) mycobacteria. Because BCG has been reported to lose viability during the lyophilisation process and during storage, we examined whether exposing BCG to different temperatures also triggers differences in the expression of some important cytokines and chemokines of the immune response. Interestingly, we observed that HK mycobacteria stimulated cytokine and chemokine production in a different pattern from that observed with live mycobacteria.     

Overexpression of csc1-1. A plausible strategy to obtain wine yeast strains undergoing accelerated autolysis

The potential of several alternative genetic engineering based strategies in order to accelerate Saccharomyces cerevisiae autolysis for wine production has been studied. Both constitutively autophagic and defective in autophagy strains have been studied. Although both alternatives lead to impaired survival under starvation conditions, only constitutively autophagic strains, carrying a multicopy plasmid with the csc1-1 allele under the control of the TDH3 promoter, undergo accelerated autolysis in the experimental conditions tested. Fermentation performance is impaired in the autolytic strains, but industrial strains carrying the above-mentioned construction are still able to complete second fermentation of a model base wine. We suggest the construction of industrial yeasts showing a constitutive autophagic phenotype as a way to obtain second fermentation yeast strains undergoing accelerated autolysis.     

Cardiovascular effects of 1,8-cineole,a terpenoid oxide present in many plant essential oils,in normotensive rats

The cardiovascular effects of i.v. treatment with 1,8-cineole, a monoterpenic oxide present in many plant essential oils, were investigated in normotensive rats. This study examined (i) whether the autonomic nervous system is involved in the mediation of 1,8-cineole-induced changes in mean aortic pressure (MAP) and heart rate (HR) and (ii) whether the hypotensive effects of 1,8-cineole could result from its vasodilatory effects directly upon vascular smooth muscle. In both pentobarbital-anesthetized and conscious, freely moving rats, bolus injections of 1,8-cineole (0.3-10 mg/kg, i.v.) elicited similar and dose-dependent decreases in MAP. Concomitantly, 1,8-cineole significantly decreased HR only at the highest dose (10 mg/kg). Pretreatment of anesthetized rats with bilateral vagotomy significantly reduced the bradycardic responses to 1,8-cineole (10 mg/kg) without affecting hypotension. In conscious rats, i.v. pretreatment with methylatropine (1 mg/kg), atenolol (1.5 mg/kg), or hexamethonium (30 mg/kg) had no significant effects on the 1,8-cineole-induced hypotension, while bradycardic responses to 1,8-cineole (10 mg/kg) were significantly reduced by methylatropine. In rat isolated thoracic aorta preparations, 1,8-cineole (0.006-2.6 mM) induced a concentration-dependent reduction of the contraction induced by potassium (60 mM). This is the first physiological evidence that i.v. treatment with 1,8-cineole in either anesthetized or conscious rats elicits hypotension; this effect seems related to an active vascular relaxation rather than withdrawal of sympathetic tone.