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

Successful mycophenolate mofetil therapy in nine patients with idiopathic retroperitoneal fibrosis

Objective. To assess the therapeutic benefit of mycophenolate mofetil (MMF) in retroperitoneal fibrosis (RF). Methods. MMF 2 g/day and prednisone 1 mg/kg were initiated in nine patients with radiological (9/9) and histological verification (2/9) of idiopathic RF. Out of nine patients, seven needed bilateral ureteral stenting due to extensive hydronephrosis. Results. All patients experienced regression of radiological extension. Out of seven patients, five were free of ureteral catheters after a mean of 5.6 months and two remained on stenting due to secondary stenosis. Within 6 months mean creatinine and CRP fell from 2.5 to 1.2 mg/dl and from 4.0 to 1.4 mg/dl, respectively. MMF was discontinued after a mean of 27 months. Prednisone was tapered to zero after a mean of 7 months. Side-effects were urinary tract infections in 7/9 patients and impaired glucose tolerance in 3/9. No recurrence occurred after withdrawal of glucocorticoids and MMF in 7/9 patients after a mean overall follow-up of 55 months (range 12-120). Conclusions. Treatment with MMF and glucocorticoids was successful in inducing partial or complete and lasting remission in RF. The results suggest the use of MMF as additional immunosuppressive optio

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

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

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

Essays in Development Economics and Global Health

The chapters in this dissertation provide insights into different aspects of the SDG research agenda. The chapters also both incorporate publicly available secondary data sources as well as newly collected survey data. Depending on the chapter, analyses were done either for a pooled sample or a single country. Chapters II-V address questions around SDGs #2 Zero Hunger and #3 Good Health and Well-Being, by incorporating secondary data from between 56-61 different low- and middle-income countries in pooled analyses. Chapter VI addresses the interface of SDGs #1 No poverty and #3 Good Health and Well-Being by looking at the Kenyan labor market impacts from COVID-19 mobility restrictions. While Kenya has been subject to extensive development research before, it is important to highlight that there are certain restrictions regarding representability of Chapter VI for other low-and middle-income countries, given that Kenya varies considerably in terms of social structure, culture, and political environment from other African countries, let alone other LMICs from Asia or South America.2023-10-0

Expression of Foxp3 in colorectal cancer but not in Treg cells correlates with disease progression in patients with colorectal cancer

Background: Regulatory T cells (Treg) expressing the transcription factor forkhead-box protein P3 (Foxp3) have been identified to counteract anti-tumor immune responses during tumor progression. Besides, Foxp3 presentation by cancer cells itself may also allow them to evade from effector T-cell responses, resulting in a survival benefit of the tumor. For colorectal cancer (CRC) the clinical relevance of Foxp3 has not been evaluated in detail. Therefore the aim of this study was to study its impact in colorectal cancer (CRC). Methods and Findings: Gene and protein analysis of tumor tissues from patients with CRC was performed to quantify the expression of Foxp3 in tumor infiltrating Treg and colon cancer cells. The results were correlated with clinicopathological parameters and patients overall survival. Serial morphological analysis demonstrated Foxp3 to be expressed in cancer cells. High Foxp3 expression of the cancer cells was associated with poor prognosis compared to patients with low Foxp3 expression. In contrast, low and high Foxp3 level in tumor infiltrating Treg cells demonstrated no significant differences in overall patient survival. Conclusions: Our findings strongly suggest that Foxp3 expression mediated by cancer cells rather than by Treg cells contribute to disease progression

Towards an Ecological Approach in Telecollaboration

In recent years, telecollaboration has been allowing the practice of foreign languages as well as the contact between people from different countries and cultures (O’DOWD, 2003, 2013, 2016, 2018; TELLES, 2015a, 2015b). According to O’Dowd (2013, 2018), telecollaboration refers to the use of online technologies in the context of language education between students who are geographically dispersed. This study aimed at discussing, through an ecological approach, which focuses on the relationship of people with the environment, different aspects that influenced the participants’ interaction in the telecollaborative sessions. For the interpretative analysis, data from telecollaborative sessions, experience reports, interviews and reflective diaries were included. The data analysis revealed five aspects that influenced the participants’ interaction in the telecollaborative sessions, among them “restricted language abilities”, “concern because the telecollaborative session was being video-recorded” and “technical problems”. In order to deal with various contexts (e.g. online and face-to-face classes), we suggest that different approaches are needed, and the ecological approach, used in this study, seems to be one of them

A construção de identidades em atividades telecolaborativas: negociando posicionamentos dos sujeitos

O’Dowd (2018) defines telecollaboration as the use of online technologies in the context of language teaching and learning between students who are geographically dispersed. For Risager (2007), interaction between individuals from different cultures gives rise to cultural representations and, as Rodrigues (2013) puts it, such an interaction triggers the participants’ cultural identities. In this sense, this study sought to explore identity construction through cultural representations in telecollaborative activities. For the interpretative analysis, which was based on scholars such as Tajfel and Turner (1979), Woodward (2000), Salomão (2011) and Dervin (2014), data from telecollaborative sessions, a mediation session, an experience report, Facebook private messages and an interview were included. The outcomes revealed that the participants, through the telecollaborative activities, could highlight people’s characteristics according to specific social groups, in addition to having had an occasion to express dissatisfaction regarding particular issues.O’Dowd (2018) define la telecolaboración como el uso de tecnologías en línea en la enseñanza-aprendizaje de idiomas entre estudiantes que se encuentran dispersos geográficamente. Para Risager (2007), la interacción entre individuos de diferentes culturas da lugar a representaciones culturales y, como explica Rodrigues (2013), esta interacción desencadena las identidades culturales de los participantes. En este sentido, este estudio buscó explorar la construcción de identidades a través de representaciones culturales en actividades de telecolaboración. Para el análisis interpretativo, que se basó en investigadores como Tajfel y Turner (1979), Woodward (2000), Salomão (2011) y Dervin (2014), se incluyeron datos de sesiones de telecolaboración, una sesión de mediación, un informe de experiencia, mensajes privados en Facebook y una entrevista. Los resultados revelaron que los participantes, por medio de actividades de telecolaboración, pudieron resaltar características de personas según grupos sociales específicos, además de haber tenido la oportunidad de expresar descontento con respecto a cuestiones particulares.O’Dowd (2018) define telecolaboração como a utilização de tecnologias online no contexto do ensino e aprendizagem de línguas entre estudantes que se encontram geograficamente dispersos. Para Risager (2007), a interação entre indivíduos de diferentes culturas dá origem a representações culturais e, como Rodrigues (2013) explica, esta interação desencadeia as identidades culturais dos participantes. Neste sentido, este estudo procurou explorar a construção de identidades por meio de representações culturais em atividades telecolaborativas. Para a análise interpretativa, que se embasou em pesquisadores como Tajfel e Turner (1979), Woodward (2000), Salomão (2011) e Dervin (2014), foram incluídos dados de sessões de telecolaboração, uma sessão de mediação, um relato de experiência, mensagens privadas no Facebook e uma entrevista. Os resultados revelaram que os participantes, através das atividades telecolaborativas, puderam destacar características de pessoas segundo grupos sociais específicos, além de terem tido a oportunidade de manifestar descontentamento no que diz respeito a questões particulares

SUSTENTABILIDADE NO PROJETO: SITUAÇÃO E PERSPECTIVAS

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