Vitamin D3 receptor is highly expressed in Hodgkin's lymphoma

Background: Hodkin s lymphoma is one of the most frequent lymphoma in western world. Despite an overall good prognosis some patients suffer relapsing tumors which are difficult to cure. Over a long period Vitamin D has been shown to be a potential treatment for cancer. Vitamin D acts via the vitamin D receptor, a nuclear receptor, acting as an inducible transcription factor. We aimed to investigate the expression of vitamin D receptor as potential therapeutic target structure in Hodgkin s lymphoma as well as in non Hodgkin s lymphoma. Methods: We used a panel of 193 formalin fixed tissues of lymphoma cases consisting of 55 cases of Hodgkin s lymphoma and 138 cases on several non Hodgkin s lymphoma entities. Results: Vitamin D receptor is strongly expressed in Hodgkin s lymphoma, regardless of the subentity with an overall positivity of 80% of all Hodgkin lymphoma cases. In contrast, only about 17% of the analyzed non Hodgkin s lymphoma of B-cell origin showed positivity for vitamin D receptor. Predominant nuclear localization of vitamin D receptor in Hodgkin s lymphoma suggests activated status of the vitamin D receptor. Conclusions: From this study, we conclude that vitamin D receptor plays a potentially important role in pathogenesis of Hodgkin s lymphoma but not in non Hodgkin s lymphoma. Further investigations of mutational status and functional studies may shed some light in functional relevance of vitamin D receptor signaling in Hodgkin s lymphoma

Cabecinhas, R. & Cunha, L. (Eds.) (2008). Comunicação intercultural. Perspectivas, dilemas e desafios. Porto: Campo das Letras.

As a result of the Conference “Intercultural communication: perspectives, dilemmas and challenges”..

Surface-air energy exchange over eastern Venezuela as related to streamflow and cumulonimbus cloud systems

CER70-71DSR22.September 1970.Includes bibliographical references (page 32).This report was prepared under contract no. N00014-68-0493-0002 between the Office of Naval Research and Colorado State University.Solar and net radiation measurements made during the Venezuelan International Meteorological-Hydrological Experiment (VIM-HEX) conducted in Venezuela in the summer of 1969 are discussed, and the results presented in two separate parts of this paper. In the first part it is shown that the average net radiation surplus observed at the ground is converted to sensible and latent heat transfer to the atmosphere. The sensible heat transfer can be computed directly from morning and afternoon clear-day temperature soundings. It is shown that the ratio of sensible to latent heat transfer over eastern Venezuela during the study period is about 0.63. Based on the total energy balance at the earth's surface, and dense rain-gauge measurements made over the study area, a stream runoff of 0.07 cm/day per unit area is computed. This compares quite well with the observed runoff per unit area of 0.09 cm/day. It is concluded that single station meteorological measurements coupled with areal rainfall data can give a first approximation to the hydrology of a small tropical region over the time period of a month or so. In the second part of this report the radiation data is nondimensionalized by comparison with a standard, and the values are located with respect to the center of an associated mesosystem photographed by the VIM-HEX radar facility. The radius of the observed radiation parameter from the center of the mesosystem is also non-dimensional zed. In this reference system it is observed that there is a sharp decrease in solar radiation and net radiation within the mesosystem boundaries, and a rapid increase outside the boundaries. It is concluded that the direct supply of energy from the ground decreases toward the center of a tropical disturbance over land and may vanish completely. In this respect the land-based tropical cumulonimbus differs significantly from oceanic mesosystems, where the supply of sensible and latent energy from the water actually increases toward the center with very little diurnal control.Under contract no. N00014-68-0493-0002

”A cor da esperança” : as representações de Nelson Mandela na revista Veja

Buscamos aqui analisar as diferentes representações de Nelson Mandela a partir da revista Veja, a mais vendida do Brasil com uma venda média de 1.200.000 exemplares por semana. Foram observadas 188 matérias jornalísticas em que Mandela foi mencionado pela revista, entre os anos de 1978 e 2009. De preso político a presidente de seu país, Mandela foi sendo representado de diversas formas e nosso questionamento busca perceber qual memória coletiva pode ter resultado destas transformações. Quem é Nelson Mandela a partir da Veja? Que valores sua imagem carrega? Como as representações da revista se transformaram ao longo dos anos? Representação será aqui tratada a partir das discussões de Stuart Hall, como local de encontro entre significados e linguagem em uma cultura. A revista Veja será entendida, então, como local onde signos e imagens representam sentidos compartilhados em uma sociedade, ao mesmo tempo em que atualiza ou modifica esses significados. Sua relação com a memória será estabelecida a partir dos contributos de Halbwachs, Wertsch e Anderson, que buscam compreender as interseções entre cultura, identidade e memória coletiva.This paper aims at analyzing the different representations of Nelson Mandela from the magazine Veja, the most sold in Brazil with an average sale of 1,200,000 copies a week. We observed 188 news stories in which Mandela was mentioned by the magazine, between the years 1978 and 2009. From political prisoner to president of his country, Mandela was being represented in different ways and this research seeks to understand the collective memory that may be resulting from these changes. Who is Nelson Mandela from Here? What values its image loads? How the representations in the magazine have been transformed over the years? Representation will be treated here, departing from the discussion of Stuart Hall, as a place of encounter between language and meaning in a given culture. The magazine Veja will be understood, then, as a place where signs and images represent shared meanings in a society, while at the same time updates or modifies these meanings. Its relationship with the memory will be established from the contributions of Halbwachs, Wertsch and Anderson, who seek to understand the intersections between culture, identity and collective memory

Vitamin D3receptor is highly expressed in Hodgkin’s lymphoma

BACKGROUND: Hodgkin lymphoma (HL) is one of the most frequent lymphoma in the western world. Despite a good overall prognosis, some patients suffer relapsing tumors which are difficult to cure. Over a long period Vitamin D has been shown to be a potential treatment for cancer. Vitamin D acts via the vitamin D receptor, a nuclear receptor, acting as an inducible transcription factor. We aimed to investigate the expression of vitamin D receptor as a possible diagnostic marker and potential therapeutic target in HL as well as in B-cell derived non-Hodgkin lymphoma (B-NHL). METHODS: We used a panel of 193 formalin fixed tissues of lymphoma cases consisting of 55 cases of HL and 138 cases on several B-NHL entities. RESULTS: Vitamin D receptor is strongly expressed in tumor cells of HL, regardless of the sub entity with an overall positivity of 80% of all HL cases. In contrast, only about 17% of the analyzed origin-NHL showed positivity for vitamin D receptor. The detection of nuclear localization of vitamin D receptor in the tumor cells of HL suggests activated status of the vitamin D receptor. CONCLUSIONS: Our study suggests VDR as a specific marker for tumor cells of HL, but not of B-NHL subtypes. Further, the observed nuclear localization suggests an activated receptor status in tumor cells of HL. Further investigations of mutational status and functional studies may shed some light in functional relevance of vitamin D receptor signaling in HL

Untersuchungen zum Einsatz des Therapeutischen Drug Monitorings von Clozapin, Olanzapin und Risperidon bei stationären und ambulanten Patienten des Zentrums für Seelische Gesundheit im Klinikum Stuttgart

In dieser Arbeit wurde unter klinischen Bedingungen die Verteilung im Therapeutischen Bereich für die AAP Clozapin, Olanzapin und Risperidon von in einem Gemeindekrankenhaus einer deutschen Großstadt psychiatrisch behandelter Patienten untersucht und nachfolgend beurteilt, ob durch Berechnung von dosisbezogenen Bereichen und Metabolit- zu Parent-Verhältnissen Blutkonzentrationen außerhalb des TR erklärt werden können. Unsere Ergebnisse zeigten, daß sich 22% bis 50% der betrachteten Patienten nicht im empfohlenen Therapeutischen Referenzbereich befanden. Die Therapeutischen Referenzbereiche sind statistisch ermittelte Größen für ein heterogenes Gesamtkollektiv und umfassen nur die Streuung von +/- 1 SD um den Mittelwert entsprechend den 68 % aus den AGNP-Untersuchungen. Es ist daher logisch, dass viele Patienten, vor allem unter Komedikation, nicht in diese Bereiche fallen. Dies haben die hier vorgelegten Untersuchungen bestätigt, wobei für Olanzapin und Risperidon die Daten der AGNP reproduziert werden konnten. Für eine individuelle Optimierung der Pharmakotherapie sollte daher besser ein individueller therapeutischer Bereich ermittelt werden, in dem der Patient einen klinisch positiven Effekt zeigt und keine UAWs entwickelt. Wenn dieser Bereich gefunden ist, kann über die Bestimmung von C/D und M/P bei groben Veränderungen rückgeschlossen werden, ob z. B. eine Komedikation für diese Abweichungen verantwortlich ist oder der Patient nicht compliant war. In unserer Arbeit konnten bei den Patienten unterhalb des empfohlenen Therapeutischen Bereichs in mehr als der Hälfte der Fälle fehlende Adhärenz (C/D), fehlerhafte Dosierung (C/D) oder eine beschleunigte Stoffwechsellage (M/P) als mögliche Ursachen eruiert werden. Bei Patienten oberhalb des Therapeutischen Referenzbereichs konnte in 40% der Fälle eine inhibierte Stoffwechsellage (M/P) als wahrscheinliche Ursache festgestellt werden. Bei der Therapieeinleitung können genetische Polymorphismen im CYP-System über den Phänotyp erkannt werden, wodurch Dosisanspassungen oder ein Wechsel der Medikation erfolgen können. Die Bestimmung des Phänotpys über das M/P-Verhältnis ist weit kostengünstiger als ein pharmakogenetisches Screening vor Einleitung einer Therapie, das dann in jedem Fall eine TDM nach sich zieht, um den Patienten adäquat zu dosieren, falls keine therapeutische Alternative gefunden werden kann. Somit ist ein Ergebnis unserer Arbeit, daß neben einer Bestimmung von Blutkonzentrationen von Antipsychotika eine Berechnung dosisbezogener Bereiche sowie von Metabolit-/Parent-Verhältnissen nützliche Werkzeuge zur Individualisierung und Optimierung der Psychopharmakotherapie in der Psychiatrie sein können. Im zweiten Teil der Arbeit, der Auswertung der klinischen Behandlungsverläufe und der aufgetretenen UAW unter Berücksichtigung der Verteilung im therapeutischen und dosisbezogenen Bereich, zeigte sich zwar kein eindeutig statistisch signifikanter Zusammenhang mit klinischen Behandlungsergebnissen oder typischen UAW, jedoch tendenziell positive Assoziationen zwischen entsprechender Verteilung im therapeutischen und dosisbezogenen Bereich für die hier untersuchten Antipsychotika. Bei mittlerweile hoch sensitiven und präzisen labormedizinischen Verfahren, die bei einem TDM von Psychopharmaka zur Anwendung kommen, könnte ein Gegenstand weiterer Studien eine Präzisierung der definierten Faktoren und Referenzbereiche sein, um noch genauere Vorhersagen über den Behandlungsverlauf oder das Auftreten von UAW treffen zu können. Weiter könnten durch ergänzende Arbeiten in Zusammenarbeit von Labormedizinern und klinisch tätigen Psychiatern weitere Erkenntnisse zum TDM von AP unter Berücksichtigung fachspezifischer Schwerpunkte und Expertisen gewonnen werden

Saúde Mascarada: tensionamentos e apropriações do personagem Zé Gotinha durante a pandemia brasileira

O presente trabalho dá continuidade à proposta de compreender personagens ficcionais como celebridades. Partindo do pressuposto de que estes seres imaginários possuem também poder de mobilização e reflexão de valores e anseios dentro de um determinado contexto, buscou-se aqui analisar três momentos em que o Zé Gotinha, figura símbolo da vacinação brasileira, atuou durante a pandemia de covid-19, entre final de 2020 e meados de 2021. Para tal, este artigo propôs pensar sua articulação em meio ao imaginário político atual a partir de uma breve recuperação de campanhas de vacinação anteriores, que construíram uma imagem do Zé Gotinha que foi tensionada nas disputas de sentido da esfera pública e ressignificada por usuários de redes sociais na disputa com a narrativa governamental.This research provided continuity to a proposal of understanding fictional characters as celebrities. Assuming that these imaginary beings can mobilize and reflect values and wishes in a given context, the paper analyzes three moments in which Zé Gotinha, mascot of Brazilian vaccination, was invoked during the COVID-19 pandemic, between late 2020 and mid-2021. To this end, the text reflects on its articulation amidst the current political imaginary by resuming previous vaccination campaigns, which built an image of Zé Gotinha that was tensioned within public disputes of meaning and resignified by social media users against the State’s narrative

Targeting coagulation factor XII provides protection from pathological thrombosis in cerebral ischemia without interfering with hemostasis

Formation of fibrin is critical for limiting blood loss at a site of blood vessel injury (hemostasis), but may also contribute to vascular thrombosis. Hereditary deficiency of factor XII (FXII), the protease that triggers the intrinsic pathway of coagulation in vitro, is not associated with spontaneous or excessive injury-related bleeding, indicating FXII is not required for hemostasis. We demonstrate that deficiency or inhibition of FXII protects mice from ischemic brain injury. After transient middle cerebral artery occlusion, the volume of infarcted brain in FXII-deficient and FXII inhibitor–treated mice was substantially less than in wild-type controls, without an increase in infarct-associated hemorrhage. Targeting FXII reduced fibrin formation in ischemic vessels, and reconstitution of FXII-deficient mice with human FXII restored fibrin deposition. Mice deficient in the FXII substrate factor XI were similarly protected from vessel-occluding fibrin formation, suggesting that FXII contributes to pathologic clotting through the intrinsic pathway. These data demonstrate that some processes involved in pathologic thrombus formation are distinct from those required for normal hemostasis. As FXII appears to be instrumental in pathologic fibrin formation but dispensable for hemostasis, FXII inhibition may offer a selective and safe strategy for preventing stroke and other thromboembolic diseases