The CBMTS VII at the Swiss National SPIEZ LABORATORY
from 13-18 April 2008 will have some exceptionally timely and important presentations. Amongst them will be:
Emerging Infections in Asian Part of Russia
Prof. Dr. Sergey V. Netesov,
The Novosibirsk State University, Russia
During the last twenty years there has been a growing understanding among experts that, from among the entire spectrum of infectious diseases, viral infections pose a major threat to human health. The main reasons for that are as follows: viruses are not susceptible to antibiotics, the spectrum of antivirals available is limited, and viruses are able to cause chronic progressing infections. In addition, there are difficulties in effective vaccine development against, for example, hepatitis C and HIV. There are also natural animal reservoirs of some viruses which have a tremendous potential for mutations and evolution. The greatest and most unpredictable threat is posed by so-called emerging and re-emerging infections.
The emerging infections appear mainly because animal viruses continue to genetically evolve and, sooner or later, they become pathogenic for humans. There are numerous examples of this type of emerging infections: SARS-associated coronavirus, H5N1, H7N7 and H9N2 avian influenza viruses, monkeypox virus in the USA in 2003, West Nile virus in the USA and Russia, etc. These emerging infections have sometimes occurred in the Asian part of Russia in the past, but during recent decades, partially because of global warming and increase of tourism, they are occurring more frequently. Probably, the first reported case of an emerging infection in Russia was the occurrence of Omsk hemorrhagic fever (OHF) in Omsk and in Novosibirsk regions in the 1960s. It is believed now that OHF virus emerged as a result of adaptation of tick-borne encephalitis virus to musk rat that had been introduced and acclimatized in Siberia in the 1930s. Sixty years later, causative agents of the following infections, which had not widely occurred there before, emerged in said territories: West Nile virus, avian influenza viruses (both came with migratory birds), and a M.tuberculosis bacterium causing multidrug-resistant tuberculosis. In the 1990s, massive expansion of hepatitis C and HIV-1 viruses occurred in this territory; hepatitis A virus strains related to West American strains also appeared in the Asian part of Russia. Thus, unintentional importation of new viral and bacterial strains into Russia is taking place.
So, the situation with emerging and re-emerging infections in the Asian part of Russia shows once again that infectious agents, especially those of zoonotic nature, do not respect any political or geographical borders, and only significant differences between countries in terms of climate might stop them. Therefore, we all should work hard to develop international collaborations for thorough monitoring to improve the effective control of such infectious diseases as avian influenza, HIV, tuberculosis, viral hepatitis, West Nile hemorrhagic fever, etc. We should improve for vaccine, diagnostics and treatments to be better prepared for new epidemics and to significantly diminish the consequences of coming new epidemics and epizootics.
Gastrointestinal Radiation Injury: Significance, Mechanisms, and Countermeasures
Prof. Dr. Martin Hauer-Jensen,
University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA
Injury to the bone marrow and gastrointestinal tract are the main determinants of survival after radiation exposure, because of their rapidly proliferating stem/progenitor cell compartments. Significant progress has been made in the medical management of radiation-induced bone marrow injury. In contrast, the management of gastrointestinal radiation injury remains symptomatic and underdeveloped.
The notion that the expression of intestinal radiation injury relates strictly to killing of rapidly proliferating crypt cells has been supplanted. Instead, it is now recognized that functional changes in several other cellular compartments, notably the microvascular endothelium, the intestinal immune system, and the enteric nervous system, contribute critically to the initial expression of radiation injury, to the recovery from radiation injury, and to the subsequent occurrence of delayed post-radiation sequelae. The recognition of the importance of these non-cytocidal and secondary effects has prompted a change in the efforts to develop medical countermeasures against radiation. Hence, the focus has shifted away from compounds that interfere directly with the cytotoxic effects of radiation (eg, free radical scavengers, cytoprotective agents) and is now directed more toward compounds that instead target the pathophysiological manifestations of radiation injury.
This presentation will provide an overview of the clinical significance and pathogenesis of intestinal radiation toxicity. Novel mechanistic concepts will be pointed out, with specific emphasis on the role of endothelial cell dysfunction and neuroimmune interactions in the pathogenesis of intestinal radiation injury. Finally, a variety of strategies that are currently under development to prevent or mitigate intestinal radiation toxicity will be discussed.
Metal-ion Complexes as Potential New Broad-spectrum Antiviral Drugs
Eddie L. Chang, presenting author.
Center for Bio/Molecular Science and Engineering, Naval Research Laboratory
We have been developing a novel type of antiviral drug based on small metal-chelator complexes that are highly positively charged and can bind tightly to DNA/RNA. We believe these structures have the ability to become effective broad-spectrum antiviral drugs. We describe here one type of Co(III) system, cobalt(III) hex ammine (Cohex), that is fully coordinated at all positions by ammonia ligands. Unlike previously studied systems, Cohex does not hydrolyze nucleotides, but, in contrast to tetraazamacrocycle chelator complexes, Cohex does show an ability to significantly inhibit virus replication in both a dose- and time-dependent manner. Upon co-incubation with Sindbis virus and Cohex, a dose-dependent decrease in virus replication was observed at both 24 and 48 hours post infection as evidenced by plaque assay. Inhibition was seen over the concentration range of 0 to 5 mM Cohex at 48 hours, with possible maximal efficacy at 0.6 mM to 1.2 mM Cohex. We have recently expanded the studies to include the effects of timing on treatment and also the inhibitory effects of Cohex on Adenoviruses. For example, using propidium iodide (PI) as a stain marker for dead cells, we find that Cohex brings about an enhancement of survival of Adenovirus-infected cells (A549), similar to that found for Sindbis (using BHK cells). We are also beginning to address questions about the possible routes of interactions that may form the basis of this antiviral effect.
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