Studien in Mäusen über die Rolle des thymischen Hormones Thymulin in der Neonatalperiode als Reifungsfaktor für das neuroendokrine System

Cover and Table of Contents Introduction Hypothesis and Research Objectives Animals, Materials and Methods Experimental Results Discussion Future Directions ReferencesThe thymic peptide thymulin was discovered, purified and sequenced in the 70s. In a series of early studies, thymulin was thoroughly characterized in relation to its immunological actions. It was shown to be involved in several aspects of intra- and extrathymic T-cell differentiation. Further studies revealed that thymulin secretion was affected by a complex endocrine network involving most adenohypophyseal and peripheral hormones, and that thymulin itself strongly influences the neuroendocrine system. In the present doctoral thesis anti-thymulin specific antibodies were generated in rabbits and chickens. An ELISA for thymulin was set up using mammalian antibodies. Rabbit antisera were specific for thymulin but chicken antibodies were found to produce strong nonspecific interactions when used in ELISA. Long- (33 days) and short- (7 days) term neonatal immunoneutralization studies on mice employing the anti-thymulin antibodies raised in rabbits revealed a strong reduction in the serum levels of most anterior pituitary hormones (LH, FSH, PRL, TSH and GH) when the treated animals reached an adult age. Pituitary cell populations were also affected by the treatment. Additionally, body weight decreased and thymic cellularity increased in the thymulin-deprived animals. We conclude that thymulin has a general facilitatory action on anterior pituitary hormone secretion and that this thymic peptide plays a key role during early life for the development of a proper neuroendocrine balance in adult animals.Das thymische Peptid Thymulin wurde in den 70er Jahren entdeckt, purifiziert und sequenziert. In einer Reihe von Studien wurde Thymulin eingehend hinsichtlich seiner immunologischen Funktionen charakterisiert. Es wurde gezeigt, dass es an zahlreichen Aspekten intra- und extrathymischer T-Zell- Differenzierung beteiligt ist. Weitere Studien ergaben, dass die Sekretion von Thymulin durch ein komplexes Netzwerk gesteuert wird, an dem adenohypophysäre und periphere Hormone beteiligt sind, und dass Thymulin seinerseits sehr starken Einfluss auf das neuroendokrine System hat. In der vorliegenden Doktorarbeit wurden anti-Thymulin-spezifische Antikörper in Kaninchen und Hühnern generiert. Ein ELISA für Thymulin wurde auf der Basis polyklonaler Kaninchenantikörper entwickelt. Kaninchenseren stellten sich als spezifisch für Thymulin heraus, wohingegen Hühnerantikörper starke unspezifische Interaktionen im ELISA zeigten. Neonatale Langzeit- (33 Tage) und Kurzzeit- (7 Tage) Immunoneutralisierungs-Studien in Mäusen führten nach Erreichen des Erwachsenenalters zu stark reduzierten Serumspiegeln adenohypophysärer Hormone (LH, FSH, PRL, TSH, GH). Die Morphologie hypophysärer Zellen zeigte in diesem Experiment ebenfalls Veränderungen. Außerdem waren in den Thymulin-defizienten Tieren das Körpergewicht erniedrigt und der Zellgehalt des Thymus erhöht. Es kann gefolgert werden, dass Thymulin eine generelle sekretionsfördernde Wirkung auf die Adenohypophyse hat und dass dieses Peptid in der Neonatalperiode eine Schlüsselrolle für die normale Entwicklung des späteren neuroendokrinen Gleichgewichtes hat

Cholera ante portas - The re-emergence of cholera in Kinshasa after a ten-year hiatus.

International audienceBackground: Cholera is an endemic disease in certain well-defined areas in the east of the Democratic Republic of Congo (DRC). The west of the country, including the mega-city Kinshasa, has been free of cases since mid 2001 when the last outbreak ended. Methods and Findings: We used routinely collected passive surveillance data to construct epidemic curves of the cholera cases and map the spatio-temporal progress of the disease during the first 47 weeks of 2011. We compared the spatial distribution of disease spread to that which occurred in the last cholera epidemic in Kinshasa between 1996 and 2001. To better understand previous determinants of cholera spread in this region, we conducted a correlation analysis to assess the impact of rainfall on weekly health zone cholera case counts between December 1998 and March 2001 and a Generalized Linear Model (GLM) regression analysis to identify factors that have been associated with the most vulnerable health zones within Kinshasa between October 1998 and June 1999. In February 2011, cholera reemerged in a region surrounding Kisangani and gradually spread westwards following the course of the Congo River to Kinshasa, home to 10 million people. Ten sampled isolates were confirmed to be Vibrio cholerae O1, biotype El Tor, serotype Inaba, resistant to trimethoprim-sulfa, furazolidone, nalidixic acid, sulfisoxaole, and streptomycin, and intermediate resistant to Chloramphenicol. An analysis of a previous outbreak in Kinshasa shows that rainfall was correlated with case counts and that health zone population densities as well as fishing and trade activities were predictors of case counts. CONCLUSION: Cholera is particularly difficult to tackle in the DRC. Given the duration of the rainy season and increased riverine traffic from the eastern provinces in late 2011, we expect further increases in cholera in the coming months and especially within the mega-city Kinshasa. We urge all partners involved in the response to remain alert.Didier Bompangue and Silvan Vesenbeckh contributed equally to this work. *corresponding author: Silvan Vesenbeckh, Harvard School of Public Health ([email protected])Didier Bompangue is Associate Professor in the Department of Microbiology (University of Kinshasa) andEpidemiologist in the DRC Ministry of Health. He was involved in the investigations of the described outbreak since February 2011