Evaluation of Experimental Autoimmune Uveitis in Mice Treated with FTY720

PURPOSE. FTY720 (fingolimod) is an immunomodulatory drug capable of preventing T-cell migration to inflammatory sites by binding to and subsequently downregulating the expression of sphingosine-1 phosphate receptor 1 (S1P(1)) leading in turn to T-cell retention in lymphoid organs. Additional effects of FTY720 by increasing functional activity of regulatory T cells have recently been demonstrated, raising the conversion of conventional T cells into regulatory T cells and affecting the sequestration of regulatory T cells in normal mice. In this study, the action of FTY720 in the ocular autoimmune model in mice was investigated. METHODS. Mice were immunized with 161-180 peptide and pertussis toxin and were treated with 1 mg/kg/d FTY720 by gavage (7-21 days postimmunization [dpi]) or left untreated. Spleen cells, harvested 21 dpi, were cultured and assayed for cytokine production. Draining lymph node, spleen, and eye cells 21 dpi were assayed for quantification of T-cell populations. Disease severity was evaluated by histologic examination of the enucleated eyes at 21 and 49 dpi. In addition, anti-IRBP antibodies were analyzed by ELISA. RESULTS. FTY720 was effective in suppressing the experimental autoimmune uveitis score. Although there was a reduction in the number of eye-infiltrating cells, FTY did not prevent Treg accumulation at this site. FTY720 leads to a significant increase of CD4(+)IFN-gamma(+) and CD4(+)Foxp3(+) cell percentages in lymph nodes, suggesting that this site could be the source of Treg cells found in the eye. CONCLUSIONS. The data showed that treatment in vivo with FTY720 was able to suppress EAU in mice. These results are indicative of the possible therapeutic use of FTY720 in ocular autoimmune processes. (Invest Ophthalmol Vis Sci. 2010;51:2568-2574) DOI:10.1167/iovs.09-4769

Coronary reserve impairment prevents the improvement of left ventricular dysfunction and adversely affects the long-term outcome of patients with hypertensive dilated cardiomyopathy

In hypertension, left ventricular (LV) hypertrophy develops as an adaptive mechanism to compensate for increased afterload and thus preserve systolic function. Associated structural changes such as microvascular disease might potentially interfere with this mechanism, producing pathological hypertrophy. A poorer outcome is expected to occur when LV function is put in jeopardy by impaired coronary reserve. The aim of this study was to evaluate the role of coronary reserve in the long-term outcome of patients with hypertensive dilated cardiomyopathy. Between 1996 and 2000, 45 patients, 30 of them male, with 52 +/- 11 years and LV fractional shortening <30% were enrolled and followed until 2006. Coronary flow velocity reserve was assessed by transesophageal Doppler of the left anterior descending coronary artery. Sixteen patients showed >= 10% improvement in LV fractional shortening after 17 +/- 6 months. Coronary reserve was the only variable independently related to this improvement. Total mortality was 38% in 10 years. The Cox model identified coronary reserve (hazard ratio = 0.814; 95% CI = 0.72-0.92), LV mass, low diastolic blood pressure, and male gender as independent predictors of mortality. In hypertensive dilated cardiomyopathy, coronary reserve impairment adversely affects survival, possibly by interfering with the improvement of LV dysfunction. J Am Soc Hypertens 2010;4(1):14-21. (C) 2010 American Society of Hypertension. All rights reserved.

Kuvad och jämlik på planeten Vinter : Le Guins feministiska science fiction-roman The Left Hand of Darkness ur Foucaults maktperspektiv

Studien är en applicering av Foucaults Övervakning och straff på science fiction-romanen The Left Hand of Darkness av Le Guin. Fokus låg på hur makten drabbar huvudkaraktärerna; syftet var att notera hur de gör motstånd mot maktutövningen och att ta fasta på alternativa maktrelationer som kan influera verkligt politiskt arbete mot en bättre, mer jämlik värld. Att använda Foucaults idéer på liknande sätt är vanligt. Analysen består av sex sekvenser som utspelar sig på planeten Vinter i The Left Hand of Darkness. Landsförvisningar för att återupprätta härskarens makt, både avsaknaden och upprättandet av framstegsmyt och en etik som förespråkar jämlikhet utmärkte monarkin Karhide; kuvade kroppar i disciplinens förtecken och en makt som är sammantvinnad med vetandet kännetecknade byråkratin Orgoreyn. Slutsats: Det är nödvändigt att uppoffra sig för att få till stånd förändringar. Den politiske visionären kan dessutom ha användning för en särskild etik, en mindre aggressiv framstegsmyt och horisontellt samarbete.

Mobilidades Urbanas - The Mobilities Turn in the Social Sciences

Em uma conjuntura de expansão urbana, intensificação do consumo, mudança climática e escassez de petróleo, o tema das mobilidades assume inquestionável importância econômica, social e ambiental. O seminário internacional "Mobilidades Urbanas: Alicerces para Pesquisas Transnacionais" volta-se, por um lado, para a fomentação do debate em torno do paradigma das novas mobilidades - envolvendo mobilidade espacial e socioeconômica, entre outras - e de sua aplicabilidade no contexto brasileiro; por outro, para a capacitação de pesquisadores cujas investigações tematizam os processos de mobilidade social e espacial a partir de perspectivas comparativas e transnacionais.

The Developing Left Superior Cervical Ganglion of Pacas (Agouti Paca)

In this study the main question investigated was the number and size of both binucleate and mononucleate superior cervical ganglion (SCG) neurons and, whether post-natal development would affect these parameters. Twenty left SCGs from 20 male pacas were used. Four different ages were investigated, that is newborn (4 days), young (45 days), adult (2 years), and aged animals (7 years). By using design-based stereo-logical methods, that is the Cavalieri principle and a physical disector combined with serial sectioning, the total volume of ganglion and total number of mononucleate and binucleate neurons were estimated. Furthermore, the mean perikaryal (somal) volume of mononucleate and binucleate neurons was estimated using the vertical nucleator. The main findings of this study were a 154% increase in the SCG volume, a 95% increase in the total number of mononucleate SCG neurons and a 50% increase in the total volume of SCG neurons. In conclusion, apart from neuron number, different adaptive mechanisms may coexist in the autonomic nervous system to guarantee a functional homeostasis during ageing, which is not always associated with neuron losses. Anat Rec, 292:966-975, 2009. (C) 2009 Wiley-Liss, Inc.

The informational turn in Philosophy: any novelty in the study of Mind?

The concept of information is analyzed starting from Adams' hypothesis in The Informational Turn in Philosophy, according to which there has been a far-reaching turn in Philosophy following the publication of Turing's article "Computing Machinery and Intelligence". Adams maintains that new guidelines are being indicated in philosophical research, having the concept of "information" as the basis for treatment of classical problems, such as the relationships between mind-body, perception-action, and the nature of knowledge, amongst others. Partially agreeing with Adams, we believe, however, that his hypothesis faces difficulties, the most fundamental of which concerns the different meanings given to the concept of information. We argue that even though the concept of information underlying the mechanicist proposal of Turing, according to which "to think is to compute", is indeed being employed in Philosophy, this is not because of its mechanistic nature, but mainly due to the representationist presupposition dominant in this area. From this point of view, the informational turn in philosophy would not provide any great novelty, given that since the earliest days philosophical approaches to the nature of mind have always been mainly representationist. The novelty would not lie specifically in the Turing thesis, but in reflections on the nature of information, especially ecological information, and its relation to action.