30 November 2006

Chemotherapy kills more brain cells than cancer cells ...


CNS progenitor cells and oligodendrocytes are targets of chemotherapeutic agents in vitro and in vivo
Joerg Dietrich, Ruolan Han, Yin Yang, Margot Mayer-Pröschel and Mark Noble
Department of Biomedical Genetics, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA
Journal of Biology 2006, 5:22 doi:10.1186/jbiol50
Published 30 November 2006

Abstract

Background
Chemotherapy in cancer patients can be associated with serious short- and long-term adverse neurological effects, such as leukoencephalopathy and cognitive impairment, even when therapy is delivered systemically. The underlying cellular basis for these adverse effects is poorly understood.

Results
We found that three mainstream chemotherapeutic agents – carmustine (BCNU), cisplatin, and cytosine arabinoside (cytarabine), representing two DNA cross-linking agents and an antimetabolite, respectively – applied at clinically relevant exposure levels to cultured cells are more toxic for the progenitor cells of the CNS and for nondividing oligodendrocytes than they are for multiple cancer cell lines. Enhancement of cell death and suppression of cell division were seen in vitro and in vivo. When administered systemically in mice, these chemotherapeutic agents were associated with increased cell death and decreased cell division in the subventricular zone, in the dentate gyrus of the hippocampus and in the corpus callosum of the CNS. In some cases, cell division was reduced, and cell death increased, for weeks after drug administration ended.

Conclusion
Identifying neural populations at risk during any cancer treatment is of great importance in developing means of reducing neurotoxicity and preserving quality of life in long-term survivors. Thus, as well as providing possible explanations for the adverse neurological effects of systemic chemotherapy, the strong correlations between our in vitro and in vivo analyses indicate that the same approaches we used to identify the reported toxicities can also provide rapid in vitro screens for analyzing new therapies and discovering means of achieving selective protection or targeted killing.

28 November 2006

Resveratrol: Life extension effects

When an item makes the New York Times, it becomes part of the historical record. In biological sciences, the journal Nature serves a similar purpose. The definitive article on resveratrol's life extending effects appeared in Nature this month.

Resveratrol improves health and survival of mice on a high-calorie diet
Nature 444, 337-342 (16 November 2006) doi:10.1038/nature05354; Received 10 August 2006; Accepted 19 October 2006; Published online 1 November 2006
Joseph A. Baur, Kevin J. Pearson, Nathan L. Price, Hamish A. Jamieson, Carles Lerin, Avash Kalra, Vinayakumar V. Prabhu, Joanne S. Allard, Guillermo Lopez-Lluch, Kaitlyn Lewis, Paul J. Pistell, Suresh Poosala, Kevin G. Becker, Olivier Boss, Dana Gwinn, Mingyi Wang, Sharan Ramaswamy, Kenneth W. Fishbein, Richard G. Spencer, Edward G. Lakatta, David Le Couteur, Reuben J. Shaw, Placido Navas, Pere Puigserver, Donald K. Ingram, Rafael de Cabo and David A. Sinclair

Resveratrol (3,5,4'-trihydroxystilbene) extends the lifespan of diverse species including Saccharomyces cerevisiae, Caenorhabditis elegans and Drosophila melanogaster. In these organisms, lifespan extension is dependent on Sir2, a conserved deacetylase proposed to underlie the beneficial effects of caloric restriction. Here we show that resveratrol shifts the physiology of middle-aged mice on a high-calorie diet towards that of mice on a standard diet and significantly increases their survival. Resveratrol produces changes associated with longer lifespan, including increased insulin sensitivity, reduced insulin-like growth factor-1 (IGF-I) levels, increased AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor-gamma coactivator 1alpha (PGC-1alpha) activity, increased mitochondrial number, and improved motor function. Parametric analysis of gene set enrichment revealed that resveratrol opposed the effects of the high-calorie diet in 144 out of 153 significantly altered pathways. These data show that improving general health in mammals using small molecules is an attainable goal, and point to new approaches for treating obesity-related disorders and diseases of ageing.

04 November 2006

Pentagon pushes for complete freedom to violate all environment regulations

As a West Point graduate, former fighter pilot, USAF Academy faculty member, and long time supporter of national security (11 Air medals and a Distinguished Flying Cross for heroism in combat), I strongly urge you to hold the military accountable for any violation of environmental regulations. They have unleashed everything from plutonium to rocket fuel on unsuspecting populations and have routinely tested biological agents to the detriment of those unknowingly sprayed with them. Military activities can be devastating worldwide and the Pentagon is now pressuring Congress to allow them freedom from all environmental regulations. This is not necessary for national security. It is all about the money and the freedom to be lazy, incompetent, and deadly without any risk of being held accountable.

The latest identified risk is widespread contamination of people, water, and food supply from perchlorates in rocket fuel. I have incorporated frequencies for this in my toxic metals and chemicals frequency set which I will publish later this year.

The Organic Consumers organization has made it easy for you to send letters to your Congresspeople on this issue:

The National Academy of Sciences (NAS) has released its long anticipated report on the human health effects of perchlorates, a byproduct of rocket fuel. Perchlorates, which are a common pollutant near military sites, have recently BEEN FOUND IN DRINKING WATER IN 35 STATES AS WELL AS IN 93 PERCENT OF LETTUCE AND MILK.

Along with the report, the Environmental Protection Agency (EPA) has set drinking water standards indicating that perchlorates are roughly TEN TIMES MORE TOXIC to humans than the Department of Defense has been claiming. Perchlorates can inhibit thyroid function, cause birth defects and lower IQs, and are considered particularly dangerous to children. Monitoring wells across the U.S. are now finding perchlorate levels as high as 30,000 times what the EPA indicates would be safe exposure.

To avoid liability, the Pentagon is currently pressuring Congress to pass a new bill that states the military does not have to adhere to any environmental regulations (as a matter of national security).

Please take 30 seconds to send a quick online letter urging your Congressperson to protect the nation's food and water by reducing perchlorate pollution. Take action and learn more about this issue here: http://www.organicconsumers.org/perchlorate.htm

Please also forward this message to interested friends and colleagues. (source: Organic Consumers Association http://www.organicconsumers.org)

03 November 2006

The Evidence is In: Flu vaccines are ineffective at best



About 85% of medicine is not evidence based, despite protestations of medical boards and physicians. The effectiveness of flu vaccines is one of the areas where evidence is most lacking. Opinion, assertion, and bombastic pronouncements without solid evidence to support clinical statements is pervasive.

The only thing that is well documented about flu vaccines is some of their negative side effects. This problem is now reaching the medical journals. Is this the next menopausal hormone therapy or VIOXX myth to be exploded?

T. Jefferson, "Influenza vaccination: policy versus evidence," British Medical Journal, vol. 333, pp. 912-915, October 28, 2006 2006.
  • Public policy worldwide recommends the use of inactivated influenza vaccines to prevent seasonal outbreaks
  • Because viral circulation and antigenic match vary each year and non-randomised studies predominate, systematic reviews of large datasets from several decades provide the best information on vaccine performance
  • Evidence from systematic reviews shows that inactivated vaccines have little or no effect on the effects measured
  • Most studies are of poor methodological quality and the impact of confounders is high
  • Little comparative evidence exists on the safety of these vaccines
  • Reasons for the current gap between policy and evidence are unclear, but given the huge resources involved, a re-evaluation should be urgently undertaken