19.11.07

Glatiramer acetate (Copaxone) - A mixture that modulates for MS



  • random mixture of synthetic proteins, each made up of four amino acids (glutamic acid, lysine, alanine, and tyrosine - that spells GLATiramer!) that are found in myelin basic protein (MSP), a major protein component of myelin
    • myelin is the phospholipidy stuff that surrounds and electrically insulates certain neurons in the nervous system, permitting an increase in the speed at which they transmit electrical impulses and allowing us to do the complex things with our brains that we do
  • originally developed in the 1960s in an attempt to find drugs for multiple sclerosis (MS), was originally known as Copolymer 1
    • has subsequently been shown to reduce the frequency of relapse in people afflicted with active relapsing-remitting MS
    • MS is a chronic disease that features the loss of the myelin sheath covering neurons (demyelination) as the result of inappropriate inflammation in the central nervous system
  • can modulate the immune system, but unlike the majority of immunomodulators it is neither a steroid (e.g. prednisone) nor an cytokine (e.g. interferon)
    • since it resembles MBP, is thought to be able to compete with myelin for binding to antigen presenting cells and/or block the activation of T cells specific for myelin, ultimately reducing the autoimmune (immune system targeting things that are native to the body) response and allowing time for remyelination (repairing of myelin sheath) of neurons
    • may also induce the release of anti-inflammatory cytokines and suppress the actions of pro-inflammatory cells in the CNS
    • is effectively a vaccination against immune-mediated demyelination
  • injected subcutaneously on a daily basis
  • if you feel that you have a substance abuse problem or someone you love may be addicted to drug and alcohol, contact a California drug rehab center
- Ziemssen T, Schrempf W. Glatiramer Acetate: Mechanisms of Action in Multiple Sclerosis. Int Rev Neurobiol. 2007;79C:537-570.
- http://en.wikipedia.org/wiki/Glatiramer_acetate

6.11.07

Rainbow herbicides: How the US waged war on the forests of Southeast Asia

During the Vietnam War, amidst carpet bombing and My Lai, the United States engaged in a unique form of chemical warfare known as herbicidal warfare. Between 1962 and 1971, Air Force aircraft were employed as souped-up crop dusters to spray defoliants throughout Southeast Asia as part of Operation Ranch Hand. Defoliants are a particular variety of herbicides that kill plants by causing them to lose their leaves. This mode of action made them particularly good at destroying both food crops (primarily rice, which is difficult to incinerate) and jungle canopy, which the Viet Cong took advantage of to hide their activities.

A number of different defoliants, either single chemicals or mixtures, were developed and utilized by the US military in 'Nam. Six of these were assigned a particular colour code, and this colour was painted on the barrels in which the particular agent was stored.

Agent Orange is by far the best known of these "rainbow herbicides", largely due to the fact that it accounted for over half of the roughly 19 million US gallons of defoliant that was sprayed in Vietnam. It consists of a 1:1 mixture of 2,4-dichlorophenoxyacetic acid (2,4-D) and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T). Both of these chemicals are chlorophenoxy synthetic auxin herbicides, which means that they resemble in structure a class of plant growth hormones called auxins (particularly indoleacetic acid (IAA)), enabling them to stimulate rapid and uncontrolled plant cell growth. This causes plants to lose their leaves as they literally grow themselves to death. Chronic exposure to high levels of chlorophenoxy herbicides can potentially lead to kidney damage, reproductive effects, and teratogenicity.

Agent Purple, like Agent Orange, is a mixture of 2,4-D and 2,4,5-T. It was only used between 1962 and 1964.

Agent Pink and Agent Green both contain only 2,4,5-T. Boring.

Agents Purple, Pink, Green, and Orange were all contaminated with trace amounts of TCDD, a dioxin. Dioxins, more technically referred to as polychlorinated dibenzodioxins, are a group of incredibly toxic by-products associated with the production of chlorine-containing herbicides including 2,4,5-T. TCDD is suspected of being responsible for the deaths of millions of Vietnamese. They are capable of causing a number of different cancers, neuropathies, diabetes, and birth defects (e.g. spina bifida) in children born of those exposed. It's a huge problem in Vietnam that continues to this day.

Agent White is a little different. It consists of a 4:1 mixture of 2,4-D and picloram, another synthetic auxin herbicide. Since there is no 2,4,5-T, there is no TCDD. But not to fret, faithful reader, for the picloram that was used was reportedly contaminated with hexachlorobenzene and nitrosamines, both of which can cause cancer. On its own, picloram is a mucous membrane irritant.

Agent Blue contains cacodylic acid, an arsenic-containing herbicide that is very different from the chlorine-containing synthetic auxin pesticides found in the other five agents. Arsenic compounds, like inorganic arsenic, are able to disrupt ATP production in both plants and animals. For plants, this can lead to, among other things, the interruption of water transport, resulting in desiccation and the loss of leaves. For people, multi-system organ failure and cancer are possible toxic outcomes.

References
- http://en.wikipedia.org/wiki/Operation_Ranch_Hand
- http://toxnet.nlm.nih.gov/index.html

5.11.07

This just in: Red Bull and vodka is a bad idea

The online news media is reporting that students who drink energy drink cocktails are more likely to mess themselves up than people who just drink regular old booze. Given the things that people manage to do when trashed exclusively on the sauce, this is some unfortunate news.

Some researchers in the States (Wake Forest University in North Carolina) carried out a web-based survey of 4,721 students. About a quarter of those who took the survey reported mixing an energy drink with their booze within the past 30 days. These special folks were found to be more likely to injure themselves, require medical assistance (read: alcohol poisoning), or get raped/rape someone. Party time!

Energy drinks generally contain high levels of some sort of stimulant. Usually it's a methyxanthine, like caffeine or theobromine. Other ingredients of pharmacological interest include natural products, which are often either herbs such as ginseng or ginkgo or royal jelly that are usually present in insufficient levels to actually produce any sort of medicinal effect, or else are just plants that contain caffeine (e.g. guarana) so as to disguise its presence in the product.

One big problem with energy drink cocktails is that the effects of the stimulant(s) in the energy drink masks feelings of drunkenness, so you don't feel as loaded as you actually are. This can lead to you do stupid things. Additionally, both methylxanthines (caffeine) and alcohol are diuretics. Dosing yourself with both drugs can lead to intensive dehydration, potentially causing cardiovascular problems such as hypotension and tachycardia. Not to mention the worst hangover known to man.

The goal of drug rehabilitation centers is to help individuals achieve and maintain abstinence from drugs and alcohol through a drug treatment program. With California drug rehab, people find a sense of self worth and begin to learn to manage the stresses of an active life without drug and alcohol abuse.

Ferreira SE et al. Effects of energy drink ingestion on alcohol intoxication. Alcohol Clin Exp Res. 2006 Apr;30(4):598-605.

2.11.07

Book Review: How Everyday Products Make People Sick by Paul D. Blanc


In the first two chapters of his book, Dr. Blanc calls to attention the largely forgotten histories of occupational and environmental health hazards and how manufacturers often do everything in their power to oppose efforts to minimize the risks associated with such hazards. He points out how many of the disease that we consider to be modern problems, things like carpal tunnel syndrome and sick building syndrome, are just new names for conditions that have been around for hundreds, even thousands of years. The remainder of the book is largely a series of case studies on a wide range of products that can make you sick. Things like glues, plastics, rayon, rubber, and brass. There's an entire chapter dedicated to the discovery, industrial use, and toxicity of chlorine. Emphasis is placed on both worker exposure during product manufacturing and consumer exposure via product use and environmental pollution. It's genuinely neat stuff, not too dry, and never too scientifically dense. Dr. Blanc does a nice job incorporating interesting personal anecdotes and apt references to pop culture (lots of song lyrics), while effectively utilizing quotations from historical writings (scientific, descriptive, and fictitious) to illustrate his points. It's well written, and it makes me happy.

1.11.07

Penitrem A - The tremor toxin

  • tremorgenic (causing tremors) mycotoxin (fungal toxin) produced by a couple of species of fungi of the genus Penicillium, including P. cyclopium and P. crustosum (a common food spoilage fungus)
  • suspected to be the cause of Ijesha Shakes, a condition that occurs in Western Nigerians that is characterized by incapacitating leg tremors that occur after eating and last for up to a couple of days, with a full recovery thereafter
  • human cases of suspected penitrem A poisoning have been reported, with a presentation of generalized severe muscle tremors (uncontrollable shaking) with loss of mobility and speech, along with diaphoresis (excessive sweating, often associated with shock), and general unhappiness
  • cases of poisoning in dogs have also be reported, so try not to let your puppy eat any moldy food
  • also thought to be responsible for some cases of Grass Staggers, a disease in sheep, horses, and cattle that features ataxia (staggering about) and tremors following grass consumption
    • Penicillium are soil fungi that can be found on grass, so this makes sense
    • the disease is more commonly associated with a magnesium deficiency (hypomagnesaemia)
  • large doses have been shown to cause seizures, massive liver necrosis, and death in lab animals
  • has been shown to modulate the release of neurotransmitters in neural cell cultures and, more excitingly, cause the degeneration of Purkinje cells in the cerebellar cortex
    • the cerebellum is a part of the brain responsible for motor coordination, suggesting that the tremors and ataxia that penitrem A causes are the result of it dropping a world of pain on cerebellar cells
- di Menna ME, Mantle PG. The role of Penicillia in ryegrass staggers. Res Vet Sci. 1978 May;24(3):347-51
- Lewis PR et al. Tremor syndrome associated with a fungal toxin: sequelae of food contamination. Med J Aust. 2005 Jun 6;182(11):582-4. [link to full article]
- Kendrick, B. (2001). The Fifth Kingdom (3rd. ed.). Sidney, British Columbia: Mycologue Publications. [great book on fungi!]
- Walter SL. Acute penitrem A and roquefortine poisoning in a dog. Can Vet J. 2002 May;43(5):372-4. [link to full article]