Impact of Anti-Inflammatory Agents on the Gene Expression Profile of Stimulated Human Neutrophils: Unraveling Endogenous Resolution Pathways

Adenosine, prostaglandin E2, or increased intracellular cyclic AMP concentration each elicit potent anti-inflammatory events in human neutrophils by inhibiting functions such as phagocytosis, superoxide production, adhesion and cytokine release. However, the endogenous molecular pathways mediating these actions are poorly understood. In the present study, we examined their impact on the gene expression profile of stimulated neutrophils. Purified blood neutrophils from healthy donors were stimulated with a cocktail of inflammatory agonists in the presence of at least one of the following anti-inflammatory agents: adenosine A2A receptor agonist CGS 21680, prostaglandin E2, cyclic-AMP-elevating compounds forskolin and RO 20-1724. Total RNA was analyzed using gene chips and real-time PCR. Genes encoding transcription factors, enzymes and regulatory proteins, as well as secreted cytokines/chemokines showed differential expression. We identified 15 genes for which the anti-inflammatory agents altered mRNA levels. The agents affected the expression profile in remarkably similar fashion, suggesting a central mechanism limiting cell activation. We have identified a set of genes that may be part of important resolution pathways that interfere with cell activation. Identification of these pathways will improve understanding of the capacity of tissues to terminate inflammatory responses and contribute to the development of therapeutic strategies based on endogenous resolution

Expression and hypoxic regulation of the endothelin system in endocrine cells of human and rat pancreatic islets

CONTEXT: The success of pancreatic islet transplantation depends largely on the capacity of the islet graft to survive the initial phase immediately after transplantation until revascularization is completed. Endothelin-1 (ET-1) is a strong vasoconstrictor which has been involved in solid organ graft failure but is also known to be a potent mitogenic/anti-apoptotic factor which could also potentially enhance the survival of the transplanted islets. OBJECTIVE: Characterization of the endothelin system with regard to a potential endothelin agonist/antagonist treatment. DESIGN: Regulated expression of the endothelin system in human and rat pancreatic islets and beta-cell lines was assessed by means of immunohistochemistry, competition binding studies, western blot, RT-PCR, real-time PCR and transplant studies. RESULTS: ET-1, ETA- and ETB-receptor immunoreactivity was identified in the endocrine cells of human and rat pancreatic islets. The corresponding mRNA was detectable in rat beta-cell lines and isolated rat and human pancreatic islets. Competition binding studies on rat islets revealed binding sites for both receptor types. ET-1 stimulated the phosphorylation of mitogen-activated protein kinase, which was prevented by ETA- and ETB-receptor antagonists. After exposure to hypoxia equal to post-transplant environment oxygen tension, mRNA levels of ET-1 and ETB-receptor of human islets were robustly induced whereas ETA-receptor mRNA did not show significant changes. Immunostaining signals for ET-1 and ETA-receptor of transplanted rat islets were markedly decreased when compared to native pancreatic sections. CONCLUSIONS: In pancreatic islets, ET-1 and its receptors are differentially expressed by hypoxia and after transplantation. Our results provide the biological basis for the study of the potential use of endothelin agonists/antagonists to improve islet transplantation outcome

A "Bioscope" system using double-sided silicon strip detectors and self-triggering read-out chips

: The components and the design of a 640 by 640 channel radiation detection system based on double-sided silicon strip detectors and self-triggering read-out chips are presented. The system has been designed for applications in autoradiography and X-ray imaging in medicine, biology and other fields. Images and results from first tests of the system are shown. ? Work supported by the Ministerium f ur Wissenschaft und Forschung des Landes Nordrhein--Westfalen under contract no. IV A5 \Gamma 106 001 94 and by the German Ministerium f ur Bildung, Wissenschaft, Forschung und Technologie under contract no. 05 6BN10I (3). Post address: Nussallee 12 D-53115 Bonn Germany BONN-HE-96-08 Bonn University September 1996 ISSN-0172-8733 Preprint submitted to Nuclear Instruments and Methods A A "Bioscope" system using double-sided silicon strip detectors and self-triggering read-out chips M. Overdick d,* , A. Czermak e , P. Fischer d , V. Herzog c , A. Kjensmo b , T. Kugelmeier d , K. L..

Hematological, hepatic, and renal evaluation in Aotus azarai infulatus

BackgroundKnowing the physiological ranges of certain hematological and biochemical parameters is necessary for understanding the alterations caused by pathogenic agents and establishing differences between states of health and disease. Hematological evaluations and clinical chemistry were performed on livers and kidneys from owl monkeys with different sexes and age ranges.MethodsForty-one healthy owl monkeys were evaluated (26 males and 15 females) in three different age groups (AG1 = 3 months to 1 year old; AG2 = 2-6 years old; AG3 = over 7 years old). The animals received physical exams, abdominal ultrasounds, and clinical laboratory tests.Results and conclusionsSignificant differences were observed in hematocrit and hemoglobin values between males and females. The levels of alkaline phosphatase in the tissues were significantly influenced by age. There was also a sex influence on blood urea nitrogen and creatinine levels. The results show that some hematological and clinical chemistry parameters in owl monkeys may be influenced by sex and age.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq