Leukocyte sequestration in pulmonary microvessels and lung injury following systemic complement activation in rabbits

Inflammatory reactions are associated with sequestration of leukocytes in the lung. Complement activation leads to accumulation of leukocytes in alveolar septa and alveoli, to lung edema and hemorrhage. Although in organs other than the lung leukocytes interact with the vascular endothelium only in postcapillary venules, alveolar capillaries are considered to be the site of leukocyte sequestration in the lung. However, pulmonary venules and arterioles have not been investigated systematically after complement activation so far, A closed thoracic window was implanted in anesthetized rabbits; leukocytes and red blood cells were stained, and the movement of these cells was measured in superficial pulmonary arterioles, venules and alveolar capillaries using fluorescence video microscopy before and 30 and 60 min after infusion of cobra venom factor (CVF). Erythrocyte velocity and macrohemodynamic conditions did not change after CVF infusion and were not different from the sham-treated controls. The number of sticking leukocytes increased significantly compared to baseline and control: by 150% in arterioles and in venules and by 740% in alveolar capillaries within 60 min after CVF infusion. The width of alveolar septa in vivo was significantly enlarged after CVF infusion, indicating interstitial pulmonary edema. At the end of the experiments, myeloperoxidase activity was higher in the CVF group, showing leukocyte sequestration in the whole organ. It is concluded that complement activation by CVF induces leukocyte sequestration in lung arterioles, venules and alveolar capillaries and leads to mild lung injury

La justice cosmopolite (histoire des principes et enjeux contemporains)

La justice cosmopolite présuppose la justice dans l ordre interne d un État ainsi que la justice internationale, en se différenciant aussi bien de l une que de l autre pour s interroger sur le juste et l injuste qui porte sur l être humain en tant que tel et en tant qu individu singulier, au-delà de son statut en tant que habitant, ressortissant ou citoyen d un État, prenant ainsi aussi en compte les générations futures et l environnement. Être cosmopolite est une condition à dimension individuelle et collective, liée à la construction de soi (un soi cosmopolite), à la manière de penser et de vivre dans sa dimension quotidienne (l action sous un angle cosmopolite), ainsi qu à une réflexion sur ce qu est le juste et l injuste cosmopolite, sur l émergence des groupes sociaux qui exigent le cosmopolitisme et sur la normativité des institutions nationales, internationales et supranationales qui veulent le réaliser. Ainsi, la notion de justice cosmopolite se révèle être un objet commun au champ de la philosophie, des sciences politiques, de la sociologie, des sciences de la culture, de la psychologie sociale ainsi que du droit. Nous analysons d abord les enjeux de la justice cosmopolite tels qu ils ont été formulés aux XVIII et XIX siècles chez Hobbes, Kant, Hegel et Alexander von Humboldt, en confrontant ses idées avec les débats contemporains; ensuite, les nouveaux problématiques de la justice cosmopolite qui se dessinent au XX siècle avec Freud, Kelsen, la Théorie Critique et Bourdieu; et enfin, quelques enjeux fondamentaux contemporains de la justice cosmopolite : les droits humains, le droit humanitaire, le droit des minorités et l espace public mondial.Cosmopolitan justice presupposes justice in the order of a State as well as international justice, but differs from these two forms in that it questions the just and unjust concerning human beings as such and as a unique individual, beyond one s status as a resident, national or citizen of a State, and also takes into account future generations and the environment. Being cosmopolitan has an individual and collective dimension related to the construction of the self (a cosmopolitan self), to one s way of thinking and living in its everyday dimension (action from a cosmopolitan standpoint) and a reflection on what is just and unjust cosmopolitanism, the emergence of social groups that require cosmopolitanism and the normativity of national, international and supranational institutions that want to achieve it. Thus, the notion of cosmopolitan justice proves to be a common object in the field of philosophy, political science, sociology, cultural studies, social psychology and law. This thesis first analyzes the challenges of cosmopolitan justice as they were formulated in the eighteenth and nineteenth centuries by Hobbes, Kant, Hegel and Alexander von Humboldt, comparing their ideas with contemporary debates (Part I). It then analyzes new issues regarding cosmopolitan justice that emerged in the twentieth century with Freud, Kelsen, Critical Theory and Bourdieu (Part II). Finally, an analysis is offered on fundamental contemporary issues of cosmopolitan justice, such as human rights, humanitarian law, the rights of minorities and global public space (Part III).NANTERRE-PARIS10-Bib. élec. (920509901) / SudocSudocFranceF

Tyrosine kinase inhibitor SU6668 represses chondrosarcoma growth via antiangiogenesis in vivo

BACKGROUND: As chondrosarcomas are resistant to chemotherapy and ionizing radiation, therapeutic options are limited. Radical surgery often cannot be performed. Therefore, additional therapies such as antiangiogenesis represent a promising strategy for overcoming limitations in chondrosarcoma therapy. There is strong experimental evidence that SU6668, an inhibitor of the angiogenic tyrosine kinases Flk-1/KDR, PDGFRbeta and FGFR1 can induce growth inhibition of various primary tumors. However, the effectiveness of SU6668 on malignant primary bone tumors such as chondrosarcomas has been rarely investigated. Therefore, the aim of this study was to investigate the effects of SU6668 on chondrosarcoma growth, angiogenesis and microcirculation in vivo. METHODS: In 10 male severe combined immunodeficient (SCID) mice, pieces of SW1353 chondrosarcomas were implanted into a cranial window preparation where the calvaria serves as the site for the orthotopic implantation of bone tumors. From day 7 after tumor implantation, five animals were treated with SU6668 (250 mg/kg body weight, s.c.) at intervals of 48 hours (SU6668), and five animals with the equivalent amount of the CMC-based vehicle (Control). Angiogenesis, microcirculation, and growth of SW 1353 tumors were analyzed by means of intravital microscopy. RESULTS: SU6668 induced a growth arrest of chondrosarcomas within 7 days after the initiation of the treatment. Compared to Controls, SU6668 decreased functional vessel density and tumor size, respectively, by 37% and 53% on day 28 after tumor implantation. The time course of the experiments demonstrated that the impact on angiogenesis preceded the anti-tumor effect. Histological and immunohistochemical results confirmed the intravital microscopy findings. CONCLUSION: SU6668 is a potent inhibitor of chondrosarcoma tumor growth in vivo. This effect appears to be induced by the antiangiogenic effects of SU6668, which are mediated by the inhibition of the key angiogenic receptor tyrosine kinases Flk-1/KDR, PDGFRbeta and FGFR1. The experimental data obtained provide rationale to further develop the strategy of the use of the angiogenesis inhibitor SU6668 in the treatment of chondrosarcomas in addition to established therapies such as surgery

Kosmos: Vom Umgang mit der Welt zwischen Ausdruck und Ordnung

Die lange Geschichte der Kosmologie mündete nicht einfach in der Spezialdisziplin der physikalischen Lehre vom Universum. Vielmehr ist die Gegenwart von einer „kosmologischen Unruhe“ gekennzeichnet, welche anzeigt, dass heute zentrale Fragen nach der Welt und unserer Stellung in der Welt neue Antworten verlangen. Ein Blick in die Geschichte und Vielfalt der Kosmologie zeigt eine „Ausdrucksform“, die sich nicht auf die Funktion des Weltbildes beschränkt, sondern viele andere Zwecke verfolgen kann und sich auf komplizierte Weise in die intellektuellen, theoretischen, aber auch politischen, ethischen und praktischen Kontexte ihrer Zeit einschreibt. Der vorliegende Band zeichnet dies in vielen Fallstudien nach, die von der Vorgeschichte bis zur heutigen Erdsystemwissenschaft reichen.The long history of cosmology did not simply end in the specialised discipline of the physical study of the universe. Rather, the times we live in are characterised by a "cosmological restlessness", which indicates that today central questions about the world and our position in it demand new answers. A look at the history and diversity of cosmology reveals a "form of expression" that is not limited to the function of a worldview (a picture of the world), but can pursue many other purposes and inscribes itself in complicated ways in the intellectual, theoretical, but also political, ethical and practical contexts of its time. This volume portrays this in many case studies, ranging from prehistory to present-day Earth system science

Kosmos: Vom Umgang mit der Welt zwischen Ausdruck und Ordnung

Die lange Geschichte der Kosmologie mündete nicht einfach in der Spezialdisziplin der physikalischen Lehre vom Universum. Vielmehr ist die Gegenwart von einer „kosmologischen Unruhe“ gekennzeichnet, welche anzeigt, dass heute zentrale Fragen nach der Welt und unserer Stellung in der Welt neue Antworten verlangen. Ein Blick in die Geschichte und Vielfalt der Kosmologie zeigt eine „Ausdrucksform“, die sich nicht auf die Funktion des Weltbildes beschränkt, sondern viele andere Zwecke verfolgen kann und sich auf komplizierte Weise in die intellektuellen, theoretischen, aber auch politischen, ethischen und praktischen Kontexte ihrer Zeit einschreibt. Der vorliegende Band zeichnet dies in vielen Fallstudien nach, die von der Vorgeschichte bis zur heutigen Erdsystemwissenschaft reichen.The long history of cosmology did not simply end in the specialised discipline of the physical study of the universe. Rather, the times we live in are characterised by a "cosmological restlessness", which indicates that today central questions about the world and our position in it demand new answers. A look at the history and diversity of cosmology reveals a "form of expression" that is not limited to the function of a worldview (a picture of the world), but can pursue many other purposes and inscribes itself in complicated ways in the intellectual, theoretical, but also political, ethical and practical contexts of its time. This volume portrays this in many case studies, ranging from prehistory to present-day Earth system science

Kosmos: Vom Umgang mit der Welt zwischen Ausdruck und Ordnung

Die lange Geschichte der Kosmologie mündete nicht einfach in der Spezialdisziplin der physikalischen Lehre vom Universum. Vielmehr ist die Gegenwart von einer „kosmologischen Unruhe“ gekennzeichnet, welche anzeigt, dass heute zentrale Fragen nach der Welt und unserer Stellung in der Welt neue Antworten verlangen. Ein Blick in die Geschichte und Vielfalt der Kosmologie zeigt eine „Ausdrucksform“, die sich nicht auf die Funktion des Weltbildes beschränkt, sondern viele andere Zwecke verfolgen kann und sich auf komplizierte Weise in die intellektuellen, theoretischen, aber auch politischen, ethischen und praktischen Kontexte ihrer Zeit einschreibt. Der vorliegende Band zeichnet dies in vielen Fallstudien nach, die von der Vorgeschichte bis zur heutigen Erdsystemwissenschaft reichen.The long history of cosmology did not simply end in the specialised discipline of the physical study of the universe. Rather, the times we live in are characterised by a "cosmological restlessness", which indicates that today central questions about the world and our position in it demand new answers. A look at the history and diversity of cosmology reveals a "form of expression" that is not limited to the function of a worldview (a picture of the world), but can pursue many other purposes and inscribes itself in complicated ways in the intellectual, theoretical, but also political, ethical and practical contexts of its time. This volume portrays this in many case studies, ranging from prehistory to present-day Earth system science

The selective Cox-2 inhibitor Celecoxib suppresses angiogenesis and growth of secondary bone tumors: An intravital microscopy study in mice

BACKGROUND: The inhibition of angiogenesis is a promising strategy for the treatment of malignant primary and secondary tumors in addition to established therapies such as surgery, chemotherapy, and radiation. There is strong experimental evidence in primary tumors that Cyclooxygenase-2 (Cox-2) inhibition is a potent mechanism to reduce angiogenesis. For bone metastases which occur in up to 85% of the most frequent malignant primary tumors, the effects of Cox-2 inhibition on angiogenesis and tumor growth remain still unclear. Therefore, the aim of this study was to investigate the effects of Celecoxib, a selective Cox-2 inhibitor, on angiogenesis, microcirculation and growth of secondary bone tumors. METHODS: In 10 male severe combined immunodeficient (SCID) mice, pieces of A549 lung carcinomas were implanted into a newly developed cranial window preparation where the calvaria serves as the site for orthotopic implantation of the tumors. From day 8 after tumor implantation, five animals (Celecoxib) were treated daily with Celecoxib (30 mg/kg body weight, s.c.), and five animals (Control) with the equivalent amount of the CMC-based vehicle. Angiogenesis, microcirculation, and growth of A549 tumors were analyzed by means of intravital microscopy. Apoptosis was quantified using the TUNEL assay. RESULTS: Treatment with Celecoxib reduced both microvessel density and tumor growth. TUNEL reaction showed an increase in apoptotic cell death of tumor cells after treatment with Celecoxib as compared to Controls. CONCLUSION: Celecoxib is a potent inhibitor of tumor growth of secondary bone tumors in vivo which can be explained by its anti-angiogenic and pro-apoptotic effects. The results indicate that a combination of established therapy regimes with Cox-2 inhibition represents a possible application for the treatment of bone metastases