Glibenclamide enhances neurogenesis and improves long-term functional recovery after transient focal cerebral ischemia

Glibenclamide is neuroprotective against cerebral ischemia in rats. We studied whether glibenclamide enhances long-term brain repair and improves behavioral recovery after stroke. Adult male Wistar rats were subjected to transient middle cerebral artery occlusion (MCAO) for 90 minutes. A low dose of glibenclamide (total 0.6mg) was administered intravenously 6, 12, and 24 hours after reperfusion. We assessed behavioral outcome during a 30-day follow-up and animals were perfused for histological evaluation. In vitro specific binding of glibenclamide to microglia increased after pro-inflammatory stimuli. In vivo glibenclamide was associated with increased migration of doublecortin-positive cells in the striatum toward the ischemic lesion 72 hours after MCAO, and reactive microglia expressed sulfonylurea receptor 1 (SUR1) and Kir6.2 in the medial striatum. One month after MCAO, glibenclamide was also associated with increased number of NeuN-positive and 5-bromo-2-deoxyuridine-positive neurons in the cortex and hippocampus, and enhanced angiogenesis in the hippocampus. Consequently, glibenclamide-treated MCAO rats showed improved performance in the limb-placing test on postoperative days 22 to 29, and in the cylinder and water-maze test on postoperative day 29. Therefore, acute blockade of SUR1 by glibenclamide enhanced long-term brain repair in MCAO rats, which was associated with improved behavioral outcome.

Concentration of Airborne Staphylococcus aureus (MRSA and MSSA), Total Bacteria, and Endotoxins in Pig Farms.

Pigs are very often colonized by Staphylococcus aureus and transmission of such pig-associated S. aureus to humans can cause serious medical, hygiene, and economic problems. The transmission route of zoonotic pathogens colonizing farm animals to humans is not well established and bioaerosols could play an important role. The aim of this study was to assess the potential occupational risk of working with S. aureus-colonized pigs in Switzerland. We estimated the airborne contamination by S. aureus in 37 pig farms (20 nursery and 17 fattening units; 25 in summer, 12 in winter). Quantification of total airborne bacterial DNA, airborne Staphylococcus sp. DNA, fungi, and airborne endotoxins was also performed. In this experiment, the presence of cultivable airborne methicillin-resistant S. aureus (MRSA) CC398 in a pig farm in Switzerland was reported for the first time. Airborne methicillin-sensitive S. aureus (MSSA) was found in ~30% of farms. The average airborne concentration of DNA copy number of total bacteria and Staphylococcus sp. measured by quantitative polymerase chain reaction was very high, respectively reaching values of 75 (± 28) × 10(7) and 35 (± 9.8) × 10(5) copy numbers m(-3) in summer and 96 (± 19) × 10(8) and 40 (± 12) × 10(6) copy numbers m(-3) in winter. Total mean airborne concentrations of endotoxins (1298 units of endotoxin m(-3)) and fungi (5707 colony-forming units m(-3)) exceeded the Swiss recommended values and were higher in winter than in summer. In conclusion, Swiss pig farmers will have to tackle a new emerging occupational risk, which could also have a strong impact on public health. The need to inform pig farmers about biological occupational risks is therefore crucial.

Redução de fósforo em dietas para frangos com base em valores de equivalência da fitase

O objetivo deste trabalho foi avaliar o uso de valores de equivalência da fitase como base para redução de fósforo disponível (P-disp) em dietas para frangos. Foram avaliados dez planos nutricionais com seis repetições de 15 aves cada uma. Avaliaram-se: desempenho, teor de cinzas na tíbia e custo da ração. De 1 a 7 e de 36 a 42 dias de idade, as aves receberam dieta basal; de 8 a 21 dias, dieta sem fitase contendo 3,9 g kg-1 de P-disp e quatro dietas com fitase contendo de 1,1 a 2,5 g kg-1 de P-disp; e de 22 a 35 dias, dieta sem fitase contendo 3,4 g kg-1 de P-disp mais dieta com fitase contendo 1,6 g kg-1 de P-disp. O melhor plano nutricional foi composto pelas dietas: 4,7 g kg-1 de P-disp sem fitase (1 a 7 dias); 2,0 g kg-1 de P-disp suplementada com fitase (8 a 21 dias); 3,4 g kg-1 de P-disp em ração sem fitase (22 a 35 dias); e 3,0 g kg-1 de P-disp em ração sem fitase (36 a 42 dias). A redução do P-disp ocorre no período de 8 a 21 dias de idade e corresponde a 2,0 g kg-1 de ração suplementada com fitase.

Port-Royal i la visibilitat de la història de la lingüística

L"article presenta l"entorn històric de les gramàtiques universals del segle xvii. Descriu el moviment cultural de l"abadia de Port-Royal, en els vessants religiós, polític, pedagògic i científic. Analitza els principis de la Grammaire générales et raisonne d"Antonie Arnauld i Claude Lancelot. Considera la relació de la gramàtica amb la Logique d"A. Aranuld i Pierre. Nicole. I examina la recepció que ha tingut la gramàtica de Port-Royal a la història de la Lingüística, en especial a partir de la tesi de Noam Chomsky sobre la lingüística cartesiana. La controvertida postura de Chomsky, rebutjada per la crítica, instrueix sobre els processos de construcció de la historiografia

Contribuição da heterogeneidade de linhas de regressão para a recomendação de novas cultivares

O objetivo deste trabalho foi evidenciar a contribuição da análise da heterogeneidade das linhas de regressão para a recomendação de novas cultivares, pela metodologia de Eberhart & Russell. Um experimento com dez genótipos de arroz, avaliados em oito ambientes, foi utilizado para ilustração da metodologia. Utilizou-se o delineamento de blocos ao acaso com três repetições. A soma dos quadrados da interação genótipo x ambiente (GxA) foi decomposta para avaliação da heterogeneidade das linhas de regressão e dos desvios acumulados da linearidade. A heterogeneidade das linhas de regressão foi analisada com o uso do teste t sobre os coeficientes de regressão linear dos genótipos. Os dois componentes ortogonais da interação GxA foram significativos. A análise da heterogeneidade das linhas de regressão permitiu detectar incoerências na adaptabilidade dos genótipos, o que diminui as chances de recomendações equivocadas de cultivares. Os genótipos foram classificados de acordo com a eficiência da metodologia de Eberhart & Russell em explicar a natureza do desempenho genotípico diante das mudanças nos ambientes. A avaliação da heterogeneidade das linhas de regressão contribui para a recomendação mais efetiva de novas cultivares com a metodologia de Eberhart & Russell.

CX3CR1 is a modifying gene of survival and progression in Amyotrophic Lateral Sclerosis

The objective of this study was to investigate the association of functional variants of the human CX3CR1 gene (Fractalkine receptor) with the risk of Amyotrophic Lateral Sclerosis disease (ALS), the survival and the progression rate of the disease symptoms in a Spanish ALS cohort. 187 ALS patients (142sporadic [sALS] and 45 familial) and 378 controls were recruited. We investigated CX3CR1 V249I (rs3732379) and T280M (rs3732378) genotypes and their haplotypes as predictors of survival, the progression rate of the symptoms (as measured by ALSFRS-R and FVC decline) and the risk of suffering ALS disease. The results indicated that sALS patients with CX3CR1 249I/I or 249V/I genotypes presented a shorter survival time (42.21±4.82) than patients with 249V/V genotype (67.48±7.28; diff=-25.27 months 95%CI [-42.09,-8.45]; p=0.003). The survival time was shorter in sALS patients with spinal topography and CX3CR1 249I alleles (diff -29.78 months; 95%CI [-49.42,-10.14]; p=0.003). The same effects were also observed in the spinal sALS patients with 249I-280M haplotype (diff=-27.23 months; 95%CI [-49.83,-4.64]; p=0.018). In the sALS group, the CX3CR1 249I variant was associated with a faster progression of the disease symptoms (OR= 2.32; 95IC%[1.24, 4.33]; p=0.007). There was no evidence for association of these two CX3CR1 variants with ALS disease risk. The association evidenced herein is clinically relevant and indicates that CX3CR1 could be a disease-modifying gene in sALS. The progression rate of the disease"s symptoms and the survival time is affected in patients with one or two copies of the CX3CR1 249I allele. The CX3CR1 is the most potent ALS survival genetic factor reported to date. These results reinforce the role of the immune system in ALS pathogenesis.

Rapid improvement of canine cognitive dysfunction with immunotherapy designed for Alzheimer's disease

Immunotherapy against amyloid-β(Aβ) may improve rodent cognitive function by reducing amyloid neuropathology and is being validated in clinical trials with positive preliminary results. However, for a complete understanding of the direct and long-term immunization responses in the aged patient, and also to avoid significant side effects, several key aspects remain to be clarified. Thus, to investigate brain Aβ clearance and Th2 responses in the elderly, and the reverse inflammatory events not found in the immunized rodent, better Alzheimer"s disease (AD) models are required. In the aged familiar canine with a Cognitive Dysfunction Syndrome (CDS) we describe the rapid effectiveness and the full safety profile of a new active vaccine candidate for human AD prevention and treatment. In these aged animals, besidesa weak immune system, the antibody response activated a coordinated central and peripheral Aβ clearance, that rapidly improved their cognitive function in absence of any side effects. Our results also confirm the interest to use familiar dogs to develop innovative and reliable therapies for AD.

La logique ou L'art de penser : contenant outre les règles communes, plusieurs observations nouvelles propres à former le jugement ([Reprod.])

Collection : Archives de la linguistique française ; 15