Protective effect of bronchial challenge with hypertonic saline on nocturnal asthma

Inhalation of hypertonic saline (HS) causes bronchoconstriction in asthmatic subjects. Repeated inhalation of HS leads to substantially reduced bronchoconstriction, known as the refractory period. Refractoriness due to different stimuli has also been described (cross-refractoriness). Nocturnal asthma is defined as an increase in symptoms, need for medication, airway responsiveness, and/or worsening of lung function that usually occurs from 4 to 6 am. Our objective was to determine the effect of refractoriness on nocturnal asthma. The challenge test consisted of inhalations of 4.5% saline with increasing durations until a reduction of 20% in forced expiratory volume in 1 s (FEV1) (PD20HS) or total time of 15.5 min. Twelve subjects with nocturnal asthma were challenged with HS at 16:00 and 18:00 h and FEV1 was measured at 4:00 h. One to 2 weeks later, FEV1 was determined at 16:00 and 4:00 h. LogPD20HS at 18:00 h was significantly greater than logPD20HS at 16:00 h, 0.51 ± 0.50 and 0.69 ± 0.60 mg, respectively (P = 0.0033). When subjects underwent two HS challenges in the afternoon, mean (± SD) FEV1 reduction was 206 ± 414 mL or 9.81 ± 17.42%. On the control day (without challenge in the afternoon) FEV1 reduction was 523 ± 308 mL or 22.75 ± 15.40% (P = 0.021). Baseline FEV1 values did not differ significantly between the control and study days, 2.48 ± 0.62 and 2.36 ± 0.46 L, respectively. The refractory period following HS challenges reduces the nocturnal worsening of asthma. This new concept may provide beneficial applications to asthmatic patients.

Sildenafil decreases rat tracheal hyperresponsiveness to carbachol and changes canonical transient receptor potential gene expression after antigen challenge

Inhibition of type-5 phosphodiesterase by sildenafil decreases capacitative Ca2+ entry mediated by transient receptor potential proteins (TRPs) in the pulmonary artery. These families of channels, especially the canonical TRP (TRPC) subfamily, may be involved in the development of bronchial hyperresponsiveness, a hallmark of asthma. In the present study, we evaluated i) the effects of sildenafil on tracheal rings of rats subjected to antigen challenge, ii) whether the extent of TRPC gene expression may be modified by antigen challenge, and iii) whether inhibition of type-5 phosphodiesterase (PDE5) may alter TRPC gene expression after antigen challenge. Sildenafil (0.1 µM to 0.6 mM) fully relaxed carbachol-induced contractions in isolated tracheal rings prepared from naive male Wistar rats (250-300 g) by activating the NO-cGMP-K+ channel pathway. Rats sensitized to antigen by intraperitoneal injections of ovalbumin were subjected to antigen challenge by ovalbumin inhalation, and their tracheal rings were used to study the effects of sildenafil, which more effectively inhibited contractions induced by either carbachol (10 µM) or extracellular Ca2+ restoration after thapsigargin (1 µM) treatment. Antigen challenge increased the expression of the TRPC1 and TRPC4 genes but not the expression of the TRPC5 and TRPC6 genes. Applied before the antigen challenge, sildenafil increased the gene expression, which was evaluated by RT-PCR, of TRPC1 and TRPC6, decreased TRPC5 expression, and was inert against TRPC4. Thus, we conclude that PDE5 inhibition is involved in the development of an airway hyperresponsive phenotype in rats after antigen challenge by altering TRPC gene expression.

Animal models of prenatal immune challenge and their contribution to the study of schizophrenia: a systematic review

Prenatal immune challenge (PIC) in pregnant rodents produces offspring with abnormalities in behavior, histology, and gene expression that are reminiscent of schizophrenia and autism. Based on this, the goal of this article was to review the main contributions of PIC models, especially the one using the viral-mimetic particle polyriboinosinic-polyribocytidylic acid (poly-I:C), to the understanding of the etiology, biological basis and treatment of schizophrenia. This systematic review consisted of a search of available web databases (PubMed, SciELO, LILACS, PsycINFO, and ISI Web of Knowledge) for original studies published in the last 10 years (May 2001 to October 2011) concerning animal models of PIC, focusing on those using poly-I:C. The results showed that the PIC model with poly-I:C is able to mimic the prodrome and both the positive and negative/cognitive dimensions of schizophrenia, depending on the specific gestation time window of the immune challenge. The model resembles the neurobiology and etiology of schizophrenia and has good predictive value. In conclusion, this model is a robust tool for the identification of novel molecular targets during prenatal life, adolescence and adulthood that might contribute to the development of preventive and/or treatment strategies (targeting specific symptoms, i.e., positive or negative/cognitive) for this devastating mental disorder, also presenting biosafety as compared to viral infection models. One limitation of this model is the incapacity to model the full spectrum of immune responses normally induced by viral exposure.

Glial cell activity is maintained during prolonged inflammatory challenge in rats

We evaluated the expression of glial fibrillary acidic protein (GFAP), glutamine synthetase (GS), ionized calcium binding adaptor protein-1 (Iba-1), and ferritin in rats after single or repeated lipopolysaccharide (LPS) treatment, which is known to induce endotoxin tolerance and glial activation. Male Wistar rats (200-250 g) received ip injections of LPS (100 µg/kg) or saline for 6 days: 6 saline (N = 5), 5 saline + 1 LPS (N = 6) and 6 LPS (N = 6). After the sixth injection, the rats were perfused and the brains were collected for immunohistochemistry. After a single LPS dose, the number of GFAP-positive cells increased in the hypothalamic arcuate nucleus (ARC; 1 LPS: 35.6 ± 1.4 vs control: 23.1 ± 2.5) and hippocampus (1 LPS: 165.0 ± 3.0 vs control: 137.5 ± 2.5), and interestingly, 6 LPS injections further increased GFAP expression in these regions (ARC = 52.5 ± 4.3; hippocampus = 182.2 ± 4.1). We found a higher GS expression only in the hippocampus of the 6 LPS injections group (56.6 ± 0.8 vs 46.7 ± 1.9). Ferritin-positive cells increased similarly in the hippocampus of rats treated with a single (49.2 ± 1.7 vs 28.1 ± 1.9) or repeated (47.6 ± 1.1 vs 28.1 ± 1.9) LPS dose. Single LPS enhanced Iba-1 in the paraventricular nucleus (PVN: 92.8 ± 4.1 vs 65.2 ± 2.2) and hippocampus (99.4 ± 4.4 vs 73.8 ± 2.1), but had no effect in the retrochiasmatic nucleus (RCA) and ARC. Interestingly, 6 LPS increased the Iba-1 expression in these hypothalamic and hippocampal regions (RCA: 57.8 ± 4.6 vs 36.6 ± 2.2; ARC: 62.4 ± 6.0 vs 37.0 ± 2.2; PVN: 100.7 ± 4.4 vs 65.2 ± 2.2; hippocampus: 123.0 ± 3.8 vs 73.8 ± 2.1). The results suggest that repeated LPS treatment stimulates the expression of glial activation markers, protecting neuronal activity during prolonged inflammatory challenges.

Ocorrência de Vibrio vulnificus em alguns alimentos de origem marinha

Vibrio vulnificus é uma bactéria Gram-negativa que habita águas marinhas. É patogênica para o homem e a doença está associada ao consumo de frutos do mar, com aproximadamente 60% dos casos sendo fatais em pacientes imunocomprometidos. O objetivo desta pesquisa foi estudar a ocorrência de V. vulnificus em amostras de alguns alimentos de origem marinha. As amostras de ostras, mariscos e camarões foram coletadas nos períodos de abril-agosto de 1993, maio-setembro de 1994 e fevereiro de 1995. De 55 amostras de ostras, 36 (65%) foram positivas para V. vulnificus; das 19 amostras de mariscos, 8 (42,1%) foram positivas e das 7 amostras de camarão, 1 (4,3%) foi positiva para esta bactéria. Os resultados permitiram-nos concluir que a bactéria foi recuperada durante todos os meses de análise, demonstrando que estes alimentos, principalmente quando consumidos crus, são potencialmente perigosos para os seres humanos na faixa de risco.

Vibrio parahaemolyticus produtores de urease isolados a partir de ostras (Crassostrea rizophorae) coletadas in natura em restaurantes e mexilhões (Perna perna) de banco natural

A presença de Vibrio parahaemolyticus foi avaliada em 50 amostras de moluscos bivalves marinhos compostas por 40 amostras de ostras coletadas em 15 restaurantes do Rio de Janeiro e 10 amostras de mexilhões capturados de banco natural em Ponta de Itaipú - Niterói. Foram empregadas a técnica do Número Mais Provável (NMP) para a enumeração de V. parahaemolyticus utilizando Caldo Glicosado Salgado com Teepol (GSTB) e Água Peptonada Alcalina (APA) com 3% de cloreto de sódio (NaCl). Paralelamente foi realizada técnica de enriquecimento em APA com 1 e 3% de NaCl. Decorrido o período de incubação de ambas as técnicas, foi realizado plaqueamento em ágar TCBS (Tiossulfato Citrato Bile Sacarose). Todas as cepas de V. parahaemolyticus isoladas através das duas técnicas foram testadas para o fenômeno de Kanagawa e, quanto à produção de urease. Do total de 141 cepas de V. parahaemolyticus isoladas, 62% revelaram-se urease positivas e, dentre estas, os sorotipos predominantes foram O10:K?, O11:K? e O3:K57 dentre o total de 24 sorotipos urease positivos identificados. Embora todas as cepas de V. parahaemolyticus tenham sido Kanagawa negativas, os resultados apontam elevada incidência desta espécie em ostras comercializadas em restaurantes.

Vibrio spp. isolados a partir de mexilhões (Perna perna) in natura e pré-cozidos de Estação Experimental de Cultivo, Rio de Janeiro, RJ, Brasil

A análise microbiológica dos mexilhões reflete a qualidade do habitat aquático, pois estes animais podem reter em seus organismos diversos patógenos, dentre os quais aqueles pertencentes à família Vibrionaceae. No presente estudo foi avaliada a presença de Vibrio spp. em mexilhões (in natura e pré-cozidos), comercializados na Estação Experimental de Cultivo de Mexilhões, situada em Jurujuba, Niterói, Rio de Janeiro. Foram avaliadas 86 amostras, tomando como procedimento, o enriquecimento em Água Peptonada Alcalina (APA) adicionada de 1 e 3% de NaCl, isolamento em Agar Tiossulfato Citrato Bile Sacarose (TCBS) e confirmação das colônias típicas por análise bioquímica. Dentre as 12 espécies de Vibrio identificadas destacaram-se como de maior prevalência as espécies Vibrio alginolyticus, V. cholerae não-O1, V. parahaemolyticus, V. carchariae e Vibrio vulnificus. A relevância epidemiológica destes patógenos associada a casos de gastrenterite humana após consumo de mexilhões crus ou parcialmente cozidos, reforça a importância de alertar as autoridades de Vigilância Sanitária sobre sua presença na cadeia alimentar e seus riscos para a Saúde Pública.

Ocurrence of Vibrio spp., positive coagulase staphylococci and enteric bacteria in oysters (Crassostrea gigas) harvested in the south bay of Santa Catarina island, Brazil

The aim of this study was to assess the contamination of oysters (Crassostrea gigas), harvested in six different regions of the South Bay of Santa Catarina Island, with Coliforms at 45 ºC, Escherichia coli, Vibrio spp., positive coagulase staphylococci, and Salmonella sp. over a period of one year. One hundred eighty oyster samples were collected directly from their culture sites and analyzed. Each sample consisted of a pool of 12 oysters. All of the samples analyzed showed absence of Salmonella, 18 (10%) samples showed presence of Escherichia coli, 15 (8.3%) samples were positive for V. alginolyticus, and Vibriocholerae was detected in 4 samples (2.2%). The counts of positive-coagulase staphylococci varied from <10 to 1.9 x 102 CFU.g-1, whereas the counts of Coliforms at 45 ºC and E. coli ranged from <3 to 1.5 x 102 MPN.g-1 and <3 and 4.3 x 10 MPN.g-1, respectively. Counts of V. parahaemolyticus and V. vulnificus ranged between <3 and 7 MPN.g-1, for both microorganisms. This suggests the need for monitoring these Vibrios contamination in oysters. Based on the results of the microbiological assays, the samples analyzed showed acceptable bacteriological quality, i.e., they were within the parameters established by Brazilian Legislation.

Incentivising Innovation? The competition law approach to the new challenge clauses in the competition rules for technology licensing agreements of the EU

Tutkielman aiheena on EU:n kilpailuoikeudellinen lähestymistapa challenge-lausekkeisiin teknologinsiirtosopimuksia koskevassa ryhmäpoikkeusasetuksessa. Teknologian lisensoinnin katsotaan olevan tärkeä väline teknologian kehityksen levittämisessä ja innovaation edistämisessä. Joissakin tapauksissa lisenssisopimus voi sisältää kilpailua rajoittavia lausekkeita, joiden voidaan kuitenkin nähdä hyödyttävän kilpailua kokonaisuutta arvostellen. Tällaisia lausekkeita ovat niin sanotut ”no-challenge” – lauseke, eli sopimusehto, jonka nojalla lisenssinsaaja sitoutuu olemaan haastamatta lisensoidun immateriaalioikeuden pätevyyttä ja ”termination-on-challenge” – lauseke, joka antaa lisensoijalle haastettaessa oikeuden päättää lisenssisopimus. Tutkielmassa perehdytään challenge -lausekkeiden hyväksyttävyyden arviointiin Euroopan unionin kilpailuoikeuden näkökulmasta uuden 1.5.2014 voimaan tulleen ryhmäpoikkeusasetuksen valossa. Muissa kuin yksinoikeuksia luovissa teknologiansiirtosopimuksissa olevat termination-on-challenge – lausekkeita tulee uusimmassa ryhmäpoikkeusetuksessa aina perustua yritysten itse suorittamaan tapauskohtaiseen arviointiin. No-challenge – lausekkeet ovat jatkossakin aiemman käytännön mukaisesti ryhmäpoikkeuksen soveltamisalan ulkopuolella. Komission on perustellut challenge - lausekkeiden jättämistä asetuksen ulkopuolelle julkisella intressillä, joka on päästä eroon mitättömistä immateriaalioikeuksista. Komission on katsonut, että challenge – lausekkeiden kilpailua rajoittava ominaisuus on mitättömien immateriaalioikeuksien esiintyminen markkinoilla, mikä osaltaan vääristää kilpailua ja hidastaa toimijoiden markkinoille pääsyä. Toisaalta lausekkeiden voidaan sanoa edistävän kilpailua, sillä ne usein tarjoavat immateriaalioikeuden haltijalle riittävän oikeussuojan ja kannustimen lisensoida teknologia, mikä lisää kilpailua, keksijöiden kannustimia panostaa innovaatioihin sekä vähentää transaktiokustannuksia. Tutkielman keskeinen tulos on ennen kaikkea challenge-lausekkeiden kilpailuvaikutusten tunnistamisessa ja komission perusteluiden kriittisessä arvioinnissa. Komission linjauksen perustelut eivät saa riittävää tukea ottaen huomioon vaikutustenarvioinnin, EU:n tuomioistuinkäytännön sekä taloustieteellisen lähestymistavan. Tutkielman tulosten pohjalta ja tukeutuen eri oikeuslähteisiin, taloustieteellisiin argumentteihin ja oikeusvertailevaan tutkimukseen, on mahdollista tehdä johtopäätöksiä niistä seikoista ja argumenteista, joilla on merkitystä uuden politiikkalinjauksen kilpailuvaikutuksiin.

"Our aim is to challenge this conventional wisdom". Luokkatutkimuksen keskusteluja Sosiologia-lehdessä ja British Journal of Sociologyssa 1970–2010

Tutkielmani aiheena on sosiologisen luokkatutkimuksen erot ja vaiheet Suomessa ja Iso-Britanniassa neljän vuosikymmenen aikana. Keskeinen tutkimuskysymykseni on, minkälaisia muutoksia suomalaisessa ja brittiläisessä luokkatutkimuskeskustelussa on tapahtunut vuosina 1970–2010, ja miten maiden sisäiset painotukset sosiologisessa luokkatutkimuksessa eroavat toisistaan. Empiirinen tutkimusaineisto koostuu suomalaisen Sosiologian ja brittiläisen British Journal of Sociologyn vuosina 1970–2010 julkaistuista luokkatutkimusartikkeleista. Tarkastelen aineistoani ja sen diskursseja luokasta Foucault'n tiedonarkeologista tutkimusotetta soveltaen. Historian keskeisyys kyseisessä lähestymistavassa sopii tämän tutkimuksen historialliseen tutkimusasetelmaan. Tiedonarkeologinen näkökulma erottuu diskurssianalyysin perinteistä siten, että se ei ole kiinnostunut esimerkiksi kirjoittajien positioinnista erilaisiin valta-asemiin, vaan teksteistä sekä niiden suhteista toisiinsa ja historialliseen tekstien jatkumoon. Haasteelliseksi tutkimukselle osoittautui mm. luokkatutkimuksen rajaaminen foucault'laisittain niin, että saataisiin tutkittavien diskurssien kokonaisuus ja suhteet esiin mahdollisimman hyvin. Diskurssien muutosten ohella olen myös tarkastellut luokkatutkimuksen artikkelimäärien prosentuaalista osuutta kaikista tutkimusartikkeleista vuosittain. Tuloksissa näkyy joitakin eroja maiden välillä, mutta osaksi myös samankaltaisia kehityskulkuja. Muutoksia näkyy esimerkiksi keskustelujen luokkateoreettisissa painotuksissa ja puheessa luokan selitysvoimasta.

In search of good relationships to music : understanding aspiration and challenge in developing music school teacher practices

This study focuses on teacher practices in publicly funded music schools in Finland. As views on the aims of music education change and broaden, music schools across Europe share the challenge of developing their activities in response. In public and scholarly debate, there have been calls for increased diversity of contents and concepts of teaching. In Finland, the official national curriculum for state-funded music schools builds on the ideal that teaching and learning should create conditions which promote ‘a good relationship to music’. The meaning of this concept has been deliberately left open in order to leave room for dialogue, flexibility, and teacher autonomy. Since what is meant by ‘good’ is not defined in advance, the notion of ‘improving’ practices is also open to discussion. The purpose of the study is to examine these issues from teachers’ point of view by asking what music school teachers aim to accomplish as they develop their practices. Methodologically, the study introduces a suggestion for building empirical research on Alperson’s ‘robust’ praxial approach to music education, a philosophical theory which is strongly committed to practitioner perspectives and musical diversity. A systematic method for analysing music education practices, interpretive practice analysis, is elaborated with support from interpretive research methods originally used in policy analysis. In addition, the research design shows how reflecting conversations (a collaborative approach well-known in Nordic social work) can be fruitfully applied in interpretive research and combined with teacher inquiry. Data have been generated in a collaborative project involving five experienced music school teachers and the researcher. The empirical material includes transcripts from group conversations, data from teacher inquiry conducted within the project, and transcripts from follow-up interviews. The teachers’ aspirations can be understood as strivings to reinforce the connection between musical practices and various forms of human flourishing such that music and flourishing can sustain each other. Examples from their practices show how the word ‘good’ receives its meaning in context. Central among the teachers’ concerns is their hope that students develop a free and sustainable interest in music, often described as inspiration. I propose that ‘good relationships to music’ and ‘inspiration’ can be understood as philosophical mediators which support the transition from an indeterminate ‘interest in music’ towards specific ways in which music can become a (co-)constitutive part of living well in each person’s particular circumstances. Different musical practices emphasise different aspects of what is considered important in music and in human life. Music school teachers consciously balance between a variety of such values. They also make efforts to resist pressure which might threaten the goods they think are most important. Such goods include joy, participation, perseverance, solid musical skills related to specific practices, and a strong sense of vitality. The insights from this study suggest that when teachers are able to create inspiration, they seem to do so by performing complex work which combines musical and educational aims and makes general positive contributions to their students’ lives. Ensuring that teaching and learning in music schools remain as constructive and meaningful as possible for both students and teachers is a demanding task. The study indicates that collaborative, reflective and interdisciplinary work may be helpful as support for development processes on both individual and collective levels of music school teacher practices.

13/5/20, Colombes, l'équipe du Metropolitan-Club gagnante du Challenge du Mille [dont Armand] Burtin [et Maurice] de Coninck : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 59256

13/5/20, Colombes, Challenge du Mille, l'arrivée de Burtin, vainqueur : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 59257