Sickness behaviour pushed too far – the basis of the syndrome seen in severe protozoal, bacterial and viral diseases and post-trauma

Certain distinctive components of the severe systemic inflammatory syndrome are now well-recognized to be common to malaria, sepsis, viral infections, and post-trauma illness. While their connection with cytokines has been appreciated for some time, the constellation of changes that comprise the syndrome has simply been accepted as an empirical observation, with no theory to explain why they should coexist. New data on the effects of the main pro-inflammatory cytokines on the genetic control of sickness behaviour can be extended to provide a rationale for why this syndrome contains many of its accustomed components, such as reversible encephalopathy, gene silencing, dyserythropoiesis, seizures, coagulopathy, hypoalbuminaemia and hypertriglyceridaemia. It is thus proposed that the pattern of pathology that comprises much of the systemic inflammatory syndrome occurs when one of the usually advantageous roles of pro-inflammatory cytokines – generating sickness behaviour by moderately repressing genes (Dbp, Tef, Hlf, Per1, Per2 and Per3, and the nuclear receptor Rev-erbα) that control circadian rhythm – becomes excessive. Although reversible encephalopathy and gene silencing are severe events with potentially fatal consequences, they can be viewed as having survival advantages through lowering energy demand. In contrast, dyserythropoiesis, seizures, coagulopathy, hypoalbuminaemia and hypertriglyceridaemia may best be viewed as unfortunate consequences of extreme repression of these same genetic controls when the pro-inflammatory cytokines that cause sickness behaviour are produced excessively. As well as casting a new light on the previously unrationalized coexistence of these aspects of systemic inflammatory diseases, this concept is consistent with the case for a primary role for inflammatory cytokines in their pathogenesis across this range of diseases

EMPLOYMENT OF A «SIDE POPULATION» APPROACH TO STEM CELL ISOLATION IN NORMAL AND TUMOR TISSUES

Abstract. A combination of fluorescent staining with Hoechst 33342 dye, and flow cytometry of murine bone marrow cells may be used for separation of a side population (SP), which is highly enriched for hematopoietic stem cells capable of long-term hematopoietic reconstitution in lethally irradiated recipients. Recently, this approach was also applied to analysis of SP cells in several types of non-hematopoietic tissues, and malignant tumours. In spite of yet poor definition of phenotype and functional potency of SP cells from various tissues, the method of SP isolation may be a useful tool for analysis and pre-enrichment of stem cell-like cells of different origin. Present review article presents a brief description of Hoechst 33342-staining approach, and of recent reports concerning SP studies in various normal and malignant tissues. (Med. Immunol., vol. 10, N 4-5, pp 319-326)

Rapid detection of oral cancer: Electrophysiological characterization by dielectrophoresis technology

Microengineered medical devices offer many potential benefits for point-of-care healthcare and rapid diagnosis, particularly in the field of rapid cancer detection. We have developed a microengineered system using the electrostatic phenomenon dielectrophoresis (DEP) to non-invasively determine the electrophysiological parameters of normal and cancerous oral brush biopsies, looking at both samples consisting primarily of keratinocytes and those consisting primarily of fibroblasts. The cells were isolated from patients after informed consent and the normal, dysplastic/ cancerous state of oral biopsies were confirmed histopathologycally. Cytoplasmic conductivity and specific membrane capacitance were determined using DEP. Cancerous brush biopsies exhibited significantly different electrophysiological fingerprints to normal oral mucosa. KCND2, a gene encoding a member of voltage-activated potassium ion channels was found to be differentially expressed between CAFs and NOFs