The geographical ancestry affects normal hemoglobin values in high-altitude residents

Increasing the hemoglobin (Hb) concentration is a major mechanism adjusting arterial oxygen content to decreased oxygen partial pressure of inspired air at high altitude. Approximately 5% of the world's population living at altitudes higher than 1500 m shows this adaptive mechanism. Notably, there is a wide variation in the extent of increase in Hb concentration among different populations. This short review summarizes available information on Hb concentrations of high-altitude residents living at comparable altitudes (3500-4500 m) in different regions of the world. An increased Hb concentration is found in all high-altitude populations. The highest mean Hb concentration was found in adult male Andean residents and in Han-Chinese living at high altitude, whereas it was lowest in Ethiopians, Tibetans, and Sherpas. A lower plasma volume in Andean high altitude natives may offer a partial explanation. Indeed, male Andean high-altitude natives have a lower plasma volume than Tibetans and Ethiopians. Moreover, Hb values were lower in adult, non-pregnant females than in males; differences between populations of different ancestry were less pronounced. Various genetic polymorphisms were detected in high altitude residents thought to favor life in a hypoxic environment, some of which correlate with the relatively low Hb concentration in the Tibetans and Ethiopians, whereas differences in angiotensin-converting enzyme allele-distribution may be related to elevated Hb in the Andeans. Taken together these results indicate different sensitivity of oxygen dependent control of erythropoiesis or plasma volume among populations of different geographical ancestry, offering explanations for differences in the Hb concentration at high altitude

"So is science …"1 : No evidence for neocytolysis on descending the mountains (Response to Rice and Gunga).

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The Increase in Hemoglobin Concentration With Altitude Differs Between World Regions and Is Less in Children Than in Adults

To compensate for decreased oxygen partial pressure, high-altitude residents increase hemoglobin concentrations [Hb]. The elevation varies between world regions, posing problems in defining cutoff values for anemia or polycythemia. The currently used altitude adjustments (World Health Organization [WHO]), however, do not account for regional differences. Data from The Demographic and Health Survey (DHS) Program were analyzed from 32 countries harboring >4% of residents at altitudes above 1000 m. [Hb]-increase, (ΔHb/km altitude) was calculated by linear regression analysis. Tables show 95% reference intervals (RIs) for different altitude ranges, world regions, and age groups. The prevalence of anemia and polycythemia was calculated using regressions in comparison to WHO adjustments. The most pronounced Δ[Hb]/km was found in East Africans and South Americans while [Hb] increased least in South/South-East Asia. In African regions and Middle East, [Hb] was decreased in some altitude regions showing inconsistent changes in different age groups. Of note, in all regions, the Δ[Hb]/km was lower in children than in adults, and in the Middle East, it was even negative. Overall, the Δ[Hb]/km from our analysis differed from the region-independent adjustments currently suggested by the WHO resulting in a lower anemia prevalence at very high altitudes. The distinct patterns of Δ[Hb] with altitude in residents from different world regions imply that one single, region-independent correction factor for altitude is not be applicable for diagnosing abnormal [Hb]. Therefore, we provide regression coefficients and reference-tables that are specific for world regions and altitude ranges to improve diagnosing abnormal [Hb]

In Vitro Erythropoiesis at Different pO2 Induces Adaptations That Are Independent of Prior Systemic Exposure to Hypoxia

Hypoxia is associated with increased erythropoietin (EPO) release to drive erythropoiesis. At high altitude, EPO levels first increase and then decrease, although erythropoiesis remains elevated at a stable level. The roles of hypoxia and related EPO adjustments are not fully understood, which has contributed to the formulation of the theory of neocytolysis. We aimed to evaluate the role of oxygen exclusively on erythropoiesis, comparing in vitro erythroid differentiation performed at atmospheric oxygen, a lower oxygen concentration (three percent oxygen) and with cultures of erythroid precursors isolated from peripheral blood after a 19-day sojourn at high altitude (3450 m). Results highlight an accelerated erythroid maturation at low oxygen and more concave morphology of reticulocytes. No differences in deformability were observed in the formed reticulocytes in the tested conditions. Moreover, hematopoietic stem and progenitor cells isolated from blood affected by hypoxia at high altitude did not result in different erythroid development, suggesting no retention of a high-altitude signature but rather an immediate adaptation to oxygen concentration. This adaptation was observed during in vitro erythropoiesis at three percent oxygen by a significantly increased glycolytic metabolic profile. These hypoxia-induced effects on in vitro erythropoiesis fail to provide an intrinsic explanation of the concept of neocytolysis

In Vitro Erythropoiesis at Different pO2 Induces Adaptations That Are Independent of Prior Systemic Exposure to Hypoxia

Hypoxia is associated with increased erythropoietin (EPO) release to drive erythropoiesis. At high altitude, EPO levels first increase and then decrease, although erythropoiesis remains elevated at a stable level. The roles of hypoxia and related EPO adjustments are not fully understood, which has contributed to the formulation of the theory of neocytolysis. We aimed to evaluate the role of oxygen exclusively on erythropoiesis, comparing in vitro erythroid differentiation performed at atmospheric oxygen, a lower oxygen concentration (three percent oxygen) and with cultures of erythroid precursors isolated from peripheral blood after a 19-day sojourn at high altitude (3450 m). Results highlight an accelerated erythroid maturation at low oxygen and more concave morphology of reticulocytes. No differences in deformability were observed in the formed reticulocytes in the tested conditions. Moreover, hematopoietic stem and progenitor cells isolated from blood affected by hypoxia at high altitude did not result in different erythroid development, suggesting no retention of a high-altitude signature but rather an immediate adaptation to oxygen concentration. This adaptation was observed during in vitro erythropoiesis at three percent oxygen by a significantly increased glycolytic metabolic profile. These hypoxia-induced effects on in vitro erythropoiesis fail to provide an intrinsic explanation of the concept of neocytolysis

Hemoglobin is an oxygen-dependent glutathione buffer adapting the intracellular reduced glutathione levels to oxygen availability

Fast changes in environmental oxygen availability translate into shifts in mitochondrial free radical production. An increase in intraerythrocytic reduced glutathione (GSH) during deoxygenation would support the detoxification of exogenous oxidants released into the circulation from hypoxic peripheral tissues. Although reported, the mechanism behind this acute oxygen-dependent regulation of GSH in red blood cells remains unknown. This study explores the role of hemoglobin (Hb) in the oxygen-dependent modulation of GSH levels in red blood cells. We have demonstrated that a decrease in Hb O2 saturation to 50% or less observed in healthy humans while at high altitude, or in red blood cell suspensions results in rising of the intraerythrocytic GSH level that is proportional to the reduction in Hb O2 saturation. This effect was not caused by the stimulation of GSH de novo synthesis or its release during deglutathionylation of Hb's cysteines. Using isothermal titration calorimetry and in silico modeling, we observed the non-covalent binding of four molecules of GSH to oxy-Hb and the release of two of them upon deoxygenation. Localization of the GSH binding sites within the Hb molecule was identified. Oxygen-dependent binding of GSH to oxy-Hb and its release upon deoxygenation occurred reciprocally to the binding and release of 2,3-bisphosphoglycerate. Furthermore, noncovalent binding of GSH to Hb moderately increased Hb oxygen affinity. Taken together, our findings have identified an adaptive mechanism by which red blood cells may provide an advanced antioxidant defense to respond to oxidative challenges immediately upon deoxygenation

Long-term exposure to hypoxia inhibits tumor progression of lung cancer in rats and mice

<p>Abstract</p> <p>Background</p> <p>Hypoxia has been identified as a major negative factor for tumor progression in clinical observations and in animal studies. However, the precise role of hypoxia in tumor progression has not been fully explained. In this study, we extensively investigated the effect of long-term exposure to hypoxia on tumor progression <it>in vivo.</it></p> <p>Methods</p> <p>Rats bearing transplanted tumors consisting of A549 human lung cancer cells (lung cancer tumor) were exposed to hypoxia for different durations and different levels of oxygen. The tumor growth and metastasis were evaluated. We also treated A549 lung cancer cells (A549 cells) with chronic hypoxia and then implanted the hypoxia-pretreated cancer cells into mice. The effect of exposure to hypoxia on metastasis of Lewis lung carcinoma in mice was also investigated.</p> <p>Results</p> <p>We found that long-term exposure to hypoxia a) significantly inhibited lung cancer tumor growth in xenograft and orthotopic models in rats, b) significantly reduced lymphatic metastasis of the lung cancer in rats and decreased lung metastasis of Lewis lung carcinoma in mice, c) reduced lung cancer cell proliferation and cell cycle progression <it>in vitro</it>, d) decreased growth of the tumors from hypoxia-pretreated A549 cells, e) decreased Na⁺-K⁺ATPase α1 expression in hypoxic lung cancer tumors, and f) increased expression of hypoxia inducible factors (HIF1α and HIF2α) but decreased microvessel density in the lung cancer tumors. In contrast to lung cancer, the growth of tumor from HCT116 human colon cancer cells (colon cancer tumor) was a) significantly enhanced in the same hypoxia conditions, accompanied by b) no significant change in expression of Na⁺-K⁺ATPase α1, c) increased HIF1α expression (no HIF2α was detected) and d) increased microvessel density in the tumor tissues.</p> <p>Conclusions</p> <p>This study demonstrated that long-term exposure to hypoxia repressed tumor progression of the lung cancer from A549 cells and that decreased expression of Na⁺-K⁺ATPase was involved in hypoxic inhibition of tumor progression. The results from this study provide new insights into the role of hypoxia in tumor progression and therapeutic strategies for cancer treatment.</p

libri liberorum. Sonderheft April 2008: Mitteilungen der Österreichischen Gesellschaft für Kinder- und Jugendliteraturforschung

Editorial Vorwort Einführung Autopsie-Beispiele - 1914 Egon Friedell - 1925 Béla Balázs - 1935 Ernst Gombrich - 1936 Karl Springenschmid - 1942 Marie Moser - 1947 Enrica von Handel-Mazetti - 1948 Friedrich Feld - 1948 Gerti Hartl - 1949 Ernst Joseph Görlich - 1949 Hans Erich Seuberlich Auswahl an Autorinnen und Autoren aus dem Wirkungszeitraum 1900 bis 1950 - Ambros, Josef - Balász, Béla - Busta, Christine - Feld, Friedrich - Ferra-Mikura, Vera - Ginzkey, Franz Karl - Grengg, Maria - Handel-Mazetti, Enrica von - Holgersen, Alma - Jokl, Anna Maria - Kanitz, Otto - Koenig, Alma Johanna - Salten, Felix - Scheibelreiter, Ernst - Scheu-Riesz, Helene - Sonnleithner, A. Th. - Springenschmid, Karl - Tesarek, Anton - Umlauf-Lamatsch, Annelies - Zur Mühlen, Hermynia Ausblick Literatur Form der Dokumentation Anhang: Screenshot

libri liberorum. Jahrgang 6 - Heft 21-22/ Dezember 2005: Mitteilungen der Österreichischen Gesellschaft für Kinder- und Jugendliteraturforschung

Editorial Beiträge und Berichte: - Marianne Rössner: „Erzähl mir was…“ – Gedanken zu einer Kinderbibelausstellung an der Universität Wien - Heidi Lexe: Tagungsbericht: Märchen des Lebens? Vom vielfältigen Vergnügen, Hans Christian Andersen zu illustrieren. 2. Internationales Illustratorenforum, 10./11. Juni 2005, Internationale Jugendbibliothek München - Sonja Schreiner: Die Sektion „Kinder- und Jugendliteratur“ im Rahmen der Tagung Pontes IV: Die Antike in der Alltagskultur der Gegenwart (29. September – 1. Oktober 2005 in Bern) - Daniela Marzoch: Symposion: Felix Salten und die Kinderliteratur seiner Zeit - Sandra Wilfinger-Bak: Prämienvergabe - Marlene Zöhrer: „No Child is an Island” – Übersetzung von Kinder- und Jugendliteratur. 12. Jahrestagung des NCRL und der britischen IBBY Sektion - Karin Haller: „Hoffnung mit Hindernissen“. Zur Situation der österreichischen Kinder- und Jugendliteratur - Ines Wagner: 17. Internationales Kinderfilmfestival, 12.-20. November 2005, Wien - Susanne Blumesberger: Helene Scheu-Riesz (1880-1970). Eine Frau zwischen den Welten Abstracts: - Christiane Moser: Paradise Lost for Children. Innocence and Experience in Philip Pullman’s His Dark Materials Trilogy. Dipl.-Arb., Wien 2005 - Johanna Agnes Müller: „An einen fernen Stern...“ Grete und Josef Leitgebs Übertragung des Kleinen Prinzen aus dem Französischen. Dipl.-Arb., Innsbruck 2005 - Martina Rényi: Der weite Weg. Identitätsfindung als prägendes Merkmal kinderliterarischen Erzählens untersucht an ausgewählten Werken von Christine Nöstlinger, Käthe Recheis und Renate Welsh. Dipl.-Arb., Wien 2004 Lehrveranstaltungen: - Maria E. Dorninger – Universität Salzburg (Germanistisches Institut) - Heidi Lexe – Universität Wien (Germanistisches Institut) - Arno Rußegger – Universität Klagenfurt (Germanistisches Institut) - Ernst Seibert – Universität Wien (Germanistisches Institut) Rezensionen: - Doderer, Klaus: Die Entdeckung der Kinder- und Jugendliteraturforschung. Autobiographische Reflexionen (Ernst Seibert) - Maria E. Dorninger (Hg.): Warum nicht einmal Mittelalter? Lektüreempfehlungen für Schule und Freizeit (Gunda Mairbäurl) - Kaminski, Gerd (Hg.): Tigermütze und Fraisenhaube. Kinderwelten in Österreich und China (Rahel Rosa Neubauer) - Kirchhöfer, Dieter; Gerhart Neuner, Irmgard Steiner, Christa Uhlig (Hg.): Kindheit in der DDR. Die gegenwärtige Vergangenheit (Susanne Blumesberger) - Mikota, Jana: Alice Rühle-Gerstel. Ihre kinderliterarischen Arbeiten im Kontext der Kinder- und Jugendliteratur der Weimarer Republik, des Nationalsozialismus und des Exils (Susanne Blumesberger) - Jutta Schödel: Erziehung im Untertanengeist – wider Willen? Anpassungen und Widerstände in Leben und Werk der Kinderbuchautorin Tony Schumacher (1848–1931) (Gunda Mairbäurl) - Zohar Shavit: A Past Without Shadow. Constructing the Past in German Books for Children (Rahel Rosa Neubauer) Bibliographie: - Sandra Wilfinger-Bak: Bibliographie zur Kinder- und Jugendliteraturforschung ab Mai 200

libri liberorum. Jahrgang 10 - Heft 31-32/ März 2009: Mitteilungen der Österreichischen Gesellschaft für Kinder- und Jugendliteraturforschung

Editorial Beiträge und Hinweise - Ernst Seibert: Heinrich Hoffmann lexikalisch, ikonographisch, ikonologisch - Erica Lillegg-Jené und der Phantastische Realismus im Kinderbuch (Ausstellung, Tagung und Lesungen) - Ernst Seibert: Der kaum bekannte Johannes Mario Simmel - Ulrike Eder: Die Österreichische Gebärdensprache in mehrsprachigen Kinder- und Jugendbüchern - Susanne Blumesberger: Phaidra und die (Kinder- und Jugendliteratur-) Forschung - Susanne Blumesberger: Neue Plätze der Erinnerung in Wien. Bertha-Eckstein-Straße, Ida-Bohatta-Platz und Charlotte-Bühler-Weg - Susanne Blumesberger: Kinder- und Jugendliteratur im Netz von Frauennetzwerken - Ernst Seibert: Volkacher Taler 2008 - Kinderliteratur als kulturelles Gedächtnis – Präsentation und Diskussion Arbeitskreis für historische Kinder- und Jugendliteratur-Forschung - Susanne Blumesberger: Das Handbuch österreichischer Kinder- und Jugendbuchautorinnen - Monika Kiegler-Griensteidl: Historische Kinder- und Jugendliteratur in der Sammlung von Handschriften und alten Drucken der ÖNB - Sarolta Lipóczi: Wissenschaft, Gesamtkunst und Pädagogik im Floris Buch (1840) von Amalia Bezerédj - Gunda Mairbäurl: Forschungsansätze zur Kinder- und Jugendliteratur des 18. Jahrhunderts in Österreich - Gertraud Marinelli-König: Jugendpädagogische Schriften in den böhmischen Ländern vor 1848 - Nikola von Merveldt, Maud D. Rodrigue: Der Schauplatz der Natur und Künste und die Anfänge der Wiener Buchillustration - Veronika Pfolz: Der Graphiker Franz Plachy - Sonja Schreiner: Moderne Kinder- und Jugendliteratur in (neu-)lateinischen Übertragungen - Ernst Seibert: Thesen zur historischen Kinder- und Jugendliteraturforschung in Österreich - Isabella Wasner-Peter: Kinder- und Jugendliteratur in der Wienbibliothek im Rathaus Prämien (Abstracts) - Gisela Aigner: Schwarze Pädagogik und das rebellische Kind, gezeigt an zwei ausgewählten Beispielen der österreichischen Kinder- und Kindheitsliteratur: Renate Welsh Dieda oder das fremde Kind , Franz Innerhofer Schöne Tage. - Tanja Hofer: Auf den Spuren des Vaters – Interdependenzen zwischen allgemeinem und kinder- und jugendliterarischem System dargestellt anhand des Motivs der Vatersuche. - Vera Nowak: Erica Lillegg – Pionierin einer frühen Modernität in der österreichischen Kinderliteratur. - Doris Rupp: Die Don Quixote-Bearbeitung für die Jugend von Christian Carl Andre. Rezensionen - Uwe Baur, Karin Gradwohl-Schlacher: Literatur in Österreich 1938-1945. Handbuch eines literarischen Systems. Band 1 Steiermark. (Susanne Blumesberger) - Otto Brunken, Bettina Hurrelmann, Maria Michels-Kohlhage, Gisela Wilkending (Hg.): Handbuch zur Kinder- und Jugendliteratur. Von 1850 bis 1900. (Jana Mikota) - Ilse Weber: Wann wohl das Leid ein Ende hat. Briefe und Gedichte aus Theresienstadt. Hrsg. von Ulrike Migdal. (Susanne Blumesberger