Characterization of Interleukin 10 gene variations and serum levels as predictive factors for the clinical outcome of Non-Hodgkin Lymphoma patients and Analysis of molecular mechanisms of Interleukin 10 gene regulation in B cells

Beim aggressiven Non-Hodgkin Lymphom (aNHL) handelt es sich um eine heterogene Gruppe lymphatischer Erkrankungen. Obwohl heutige Behandlungsregime hohe Ansprechraten erzielen können, erreichen viele Patienten keine komplette Remission. Für eine Verbesserung der Behandlungsstrategien sind zuverlässige und klinisch anwendbare prognostische Marker erforderlich. Vorherige Studien weisen darauf hin, dass das Zytokin Interleukin 10 (IL10) eine Rolle sowohl bei der Initiierung als auch für den Verlauf von Lymphomen spielen könnte. Bisherige Daten zu Assoziationen von IL10 Genvariationen und dem IL10 Serumspiegel mit dem klinischen Verlauf von aNHL sind widersprüchlich. Daher ist das Ziel dieser Studie zu klären, ob diese beiden Faktoren prognostische Relevanz für den klinischen Verlauf von aNHL in unabhängigen größeren klinischen Studienkohorten haben sowie die molekularen Mechanismen zu untersuchen, die hierzu beitragen. Insgesamt wurden 1724 aNHL Patienten von drei verschiedenen klinischen Studien (NHL-B, RICOVER-60 und MInT) in diese Studie eingeschlossen. 604 Patienten kamen aus der RICOVER-60 Studie, wobei von 523 Patienten Serumproben verfügbar waren. Überlebenszeitanalysen zeigten, dass Patienten mit niedrigen IL10 Serumspiegeln im Vergleich zu Patienten mit erhöhten IL10 Serumspiegeln einen besseren klinischen Verlauf aufwiesen. Dies gilt auch für Patienten, die mit Rituximab zusätzlich zu Chemotherapie behandelt worden sind, welches die heutige Standardtherapie ist. Dies weist darauf hin, dass der IL10 Serumspiegel prognostische Relevanz für das klinische Ergebnis von aNHL haben könnte. Die Behandlung von Zielzellen mit IL10 in in vitro Versuchen scheint zu einer Reduktion der Rituximab-vermittelten antikörperabhängigen zellulären Zytotoxizität (antibody dependent cellular cytotoxicity (ADCC)), nicht aber der Komplement-vermittelten Zytotoxizität (complement dependent cytotoxicity (CDC)) zu führen. Des Weiteren konnte gezeigt werden, dass in der RICOVER-60 Kohorte homozygote Träger des IL10-11.668AA ein besseres Behandlungsergebnis zeigen als Träger der anderen zwei Genotypen (OS: HR=0.6; CI= 0.38-0.95; EFS: HR=0.6; CI= 0.41-0.87). Diese Genvariation befindet sich innerhalb einer evolutionär konservierten Sequenz. Mittels Chromatin Immunopräzipitation (ChIP) modifizierter Histone konnte ermittelt werden, dass die Region um den IL10-11.668G/A sowie andere konservierte Sequenzen in transformierten B-Zellen Enhancer spezifische Histon Modifikationen aufweisen. Sie scheinen also in die Regulation des IL10 Gens involviert zu sein. Zudem wurde eine sehr lange nicht-kodierende RNA identifiziert, die vom IL10 Genlokus transkribiert wird. Die Ergebnisse dieser Studie bestätigen, dass IL10 eine wichtige Rolle für den Klinischen Verlauf von aNHL spielt, und liefern neue Erkenntnisse über Struktur und Regulation des IL10 Gens

Mycophenolate mofetil inhibits lymphocyte binding and the upregulation of adhesion molecules in acute rejection of rat kidney allografts.

Mycophenolate mofetil (MMF) interacts with purine metabolism and possibly with the expression of adhesion molecules. In the present study, we analysed the expression of these molecules in transplanted kidney allografts treated with RS LBNF1 kidneys were orthotopically transplanted into Lewis rats and either treated with RS (20 mg/kg/day) or vehicle. Rats were harvested 3, 5 and 7 days following transplantation. For binding studies, fresh-frozen sections of transplanted kidneys were incubated with lymph node lymphocytes (LNL) derived from transplanted rats. Additionally, immunohistology was performed with various monoclonal antibodies. In general, MMF resulted in better preservation of graft structure by 7 days. Cellular infiltration and tubular atrophy were less pronounced. At day 3, macrophages were diminished in MMF-treated animals to a high extent, while the number of T cells was almost identical to that of controls. In addition, the number of cells positive for MHC class II and LFA-1 was reduced in the MMF-treated animals. These findings correlated with the binding results. Three days following engraftment, LNL bound to MMF-treated kidneys to a lesser extent compared to controls. In conclusion, MMF resulted in a markedly reduced leucocytic infiltrate, presumably based on a reduced expression of lymphocytic adhesion molecules and an interaction with macrophages

Natureza e percepção de valores

Esse texto apresenta algumas questões introdutórias à pesquisa sobre a percepção dos valores a partir do contato íntimo com a natureza, considerando o contexto educativo sob a égide do direito liberal. Nature and Value Perception Abstract This essay focuses on some introductory questions of the investigation into the perception of values based on the intimate contact with nature, taking into account the educational context within the frame of liberal rights

SUSTENTABILIDADE NO PROJETO: SITUAÇÃO E PERSPECTIVAS

Apresentação mesa redonda ENSUS 2018Palestra proferida em mesa redonda ENSUS 2018FAPES

Natureza e percepção de valores

Esse texto apresenta algumas questões introdutórias à pesquisa sobre a percepção dos valores a partir do contato íntimo com a natureza, considerando o contexto educativo sob a égide do direito liberal. Nature and Value Perception Abstract This essay focuses on some introductory questions of the investigation into the perception of values based on the intimate contact with nature, taking into account the educational context within the frame of liberal rights

VÁZQUEZ Y DEL ÁRBOL, E. (2014). DERECHO CIVIL COMPARADO APLICADO A LA TRADUCCIÓN JURÍDICO-JUDICIAL. REINO UNIDO Y ESPAÑA. MADRID: DYKINSON.

VÁZQUEZ Y DEL ÁRBOL, E. (2014). DERECHO CIVIL COMPARADOAPLICADO A LA TRADUCCIÓN JURÍDICO-JUDICIAL. REINO UNIDO YESPAÑA. MADRID: DYKINSON. VÁZQUEZ Y DEL ÁRBOL, E. (2014). DERECHO CIVIL COMPARADOAPLICADO A LA TRADUCCIÓN JURÍDICO-JUDICIAL. REINO UNIDO YESPAÑA. MADRID: DYKINSON.

Anti-inflammatory treatment strategies for ischemia/reperfusion injury in transplantation

Inflammatory reactions in the graft have a pivotal influence on acute as well as long-term graft function. The main reasons for an inflammatory reaction of the graft tissue are rejection episodes, infections as well as ischemia/reperfusion (I/R) injury. The latter is of particular interest as it affects every solid organ during the process of transplantation. I/R injury impairs acute as well as long-term graft function and is associated with an increased number of acute rejection episodes that again affect long-term graft outcome

Sentir o “Paraíso” no Pantanal: reflexões sobre percepção e valoração ambientais

This paper analises the construction of the mith around the environment and the landscape of Pantanal. The mith is perceived as paradise’s model to be enjoyed for tourism activities. In this perspective, it unveils the mith of “Pantanal-Paradise” like the contradiction that emerges through expansion of tourism’s activities oriented for the market’s logical

Feminist Activism Through the Arts in Late 19th Century and Early 20th Century. A Diachronic Comparative Study Between Portugal And Brazil

Brazil and Portugal are two countries that, although geographically located on different continents, share a history (from 1500 to 1822 when Brazil was a Portuguese colony) and the same language (Portuguese), and both have very high rates of domestic violence and situations of gender inequality. Growing fundamentalist and ultraconservative parties around the world are threatening gender equality and women’s conquest for rights. In Portugal and Brazil, new parties with extremist discourses and ideologies that perpetuate patriarchal societies are also growing. It is crucial to continue breaking paradigms and remembering history, particularly the moments marked by the struggle for human rights. Many women have fought for their rights, advocated for gender equality, and worked toward building women’s citizenship in and through education. Looking particularly at Brazil’s post-independence period, we conducted a diachronic comparative study of feminist activist artists from these two countries and found inspiring examples of feminine resistance and resilience. We analysed different female approaches that surprised us with their originality and creativity. We looked at the similarities and differences between how Portuguese and Brazilian women with access to culture and art—painting, music, literature, etc.—positioned and manifested themselves in the face of these social and cultural inequalities in the late 19th and early 20th centuries. The women artists that we studied have reached professional status as artists, which has allowed them to become financially independent. Thus, they have been able to leave the private sphere and enter the public and international sphere

Male gender predisposes to development of endotoxic shock in the rat

Objective: After intravenous (i.v.) injection of lipopolysaccharide (LPS) macrophages release nitric oxide (NO) due to the expression of the inducible NO synthase (iNOS). After LPS NO is abundantly produced also in the cardiovascular system and may contribute to the development of hypotension and shock. Since the immune response, the synthesis of NO and the regulation of blood pressure (BP) differ between males and females, in the present study the effect of LPS on BP, renal function, the plasma and urinary concentration of the metabolites of NO as well as the splenic and aortic expression of the iNOS gene were compared between male and female rats. Methods: BP and renal function were measured in anesthetized rats following the i.v. injection of LPS (E. coli, 4 mg/kg). The NOx and NOx (metabolites of NO=NOx) concentration was measured by the Griess reaction. The iNOS gene expression was studied by RT-PCR. Results: Four hours after LPS, BP of males (n=9) was reduced by 63+/-12 mmHg versus 10+/-4 in females (n=7, P<0.005). Aminoguanidine, a selective inhibitor of iNOS, prevented the reduction of BP in males. The plasma concentration of NOx (P-NOx, mu M) was lower in hypotensive males (128+/-20) than in normotensive females (235+/-29, P<0.005). Males also exhibited lower urinary NO, excretion (UNOxV) after LPS (P<0.001 vs, females). Prior castration of males provided protection against hypotension (fall of BP: -4+/-4 mmHg, n=6, P<0.02 versus males) and resulted in higher P-NOx as well as UNOxV (both P<0.001 versus males and not different from females). Prior ovariectomy (n=5) had no influence on the hemodynamic and NOx response to LPS. Male rats displayed enhanced aortic iNOS/beta-actin ratio relative to females after LPS (n=3 in each group, P<0.05). Conclusions: (1) Male gender may sensitize to LPS-induced shock and (2) sensitivity of males to endotoxin is associated with an attenuated, not exaggerated total rate of NO synthesis