Category Archives: Toxicology

tablet

Worried Sick- the Nocebo Effect

A synthetic form of thyroxine called Eltroxin, chemically and biologically identical to natural thyroxine, has been in use for over forty years. It is used effectively to treat hypothyroidism which if left untreated can result in a range of symptoms up to and including heart disease. In 2007 GlaxoSmithKline moved its manufacture from Canada to Germany. At the same time they updated the actual tablet, changing its physical form but leaving the active ingredient the same.

Shortly thereafter in New Zealand a trickle of reports of adverse side effects not seen before were received by a health monitoring organization. After the new side effects began to show up in the press, reports of the new symptoms skyrocketed over a thousand fold even though the only difference was the appearance of the pills, not the chemistry.

A study by a team of Italian gastroenterologists involved patients who were lactose intolerant and a control group who weren’t. The subjects were told that the study involved examining the effects of lactose on the gut. Even though the subjects were given only a glucose tablet which can not cause symptoms, forty four percent of those intolerant and and 26 percent of those tolerant, reported gastrointestinal problems.

Many here in the US and overseas suffer from a so called WiFi syndrome. A range of symptoms including nausea, head aches, joint pain etc. occur when they know they are exposed to electromagnetic fields, but only if they know they are exposed. There is absolutely no evidence that the EMF can cause these symptoms.

These examples are only three of hundreds of examples of what is know as the nocebo effect, from latin for “I shall harm”. In years past this may have been referred to as a form of mass hysteria, now more benignly called a psychogenic illness. In some cases it has been shown that the mere suggestion of a possible symptom or side effect can cause a biochemical change in the body which results in the symptom, but only from the suggestion.

This was shown elegantly in an animal model using rats. They were trained by classical Pavlovian training to become asthmatic. First the experimenters gave the rats a natural substance, histamine, which causes an asthma reaction and paired that with the ringing of a bell. In subsequent trials just the bell ringing would cause the rats to release excess histamine into their blood, thus triggering an asthma attack. If rats can be trained to become asthmatic, shouldn’t it be true that people who have asthma reactions could be trained to not react?

The nocebo effect is the evil twin of the better known placebo effect, latin for “I shall please”.

nocebo and placebo

nocebo and placebo

Any benefits of homeopathic medicine, and much folk medicine are a result of the placebo effect, including modern day agents associated with Traditional Chinese Medicine, acupuncture, much of chiropractic, and over the counter medications called nutritional supplements.

The question as to whether society should allow profit from the sale of placebos is a moral one. Should some one make money by suggesting that a nostrum will do something, even if it only works for believers? It sure works for Madison Avenue. Ca-ching.

poison ivy

Poison Ivy

The old adage “leaves of three, let it be” helps to identify and therefore avoid poison ivy. The plant is polymorphic, growing as ground cover, small shrubs up to two or three feet high, or a climbing vine. It is often confused with virginia creeper which has five leaves. Formally named Toxicodendron radicans, it and other related plants contain urushiol (oo-rush-ee-ol) . The substance is present in all parts of the plant; leaves, stems, roots, and berries. Poison ivy, poison oak, and poison sumac are known to cause the characteristic itchy, blistering rash.

Virginia-Creeper

Virginia-Creeper

Other plants such as cashews also have urushiol when raw and must be properly processed, shelled and roasted, to remove the plant oil. Lacquer, the stuff that produces the beautiful shiny finish in furniture, contains small amounts of urushiol and can affect hypersensitive individuals. The name urushiol comes from the Japanese name for Lacquer, urushi.

The first time, or first few times one is exposed there usually isn’t a reaction. Only after being exposed does one become sensitized and on second exposure develop the itchy rash. This is because urushiol is an allergen, something which causes an allergic reaction , and and the allergy has to be “learned” by exposure.

Actually it is a bit more complex. Only proteins, very large molecules, can cause an allergic reaction. Much of our bodies are protein so our immune system must be able to distinguish our proteins and foreign proteins. Antibodies develop as a method to rid the body of foreign protein. A whole cascade of chemical reactions occur once the immune system identifies a foreign protein. Urushiol is not a protein but a substance know as a hapten. Haptens are small molecules which can chemically react with protein. Once a protein, for example the keratin of our skin, has reacted reacted with urushiol our bodies no longer recognize the protein as “self” but rather as foreign.

Urushiol is a fat soluble oleoresin, which means that it can penetrate the skin within an hour or two. There it reacts, “labels” the protein, and sets the allergic reaction in motion, the rash occurring several hours after exposure. Heavier exposures result in a faster reaction.

This has lead to the misconception that the allergen may be carried through the blood. For example heavy exposure to the back of the hand and only slight exposure to the upper arm means that the rash will show up on the hand first and arm only later.

Another misconception is that the fluid present in the blisters contains the poison. Once the blisters form, the poison is long gone. You can’t get a reaction just by coming in contact with someone else’s rash. You can be exposed by secondary contact however. There is a fairly wide variation is sensitivity so exposure and subsequent reaction can occur when a sensitive person handles the clothes of a less sensitive person.

In extreme cases, people are exposed by inhaling smoke particulates from burning poison ivy. This can be dangerous as the rash occurs in the throat and even in the lungs.

Syrian Civil War and Sarin, a WMD

The drums of war seem to be getting louder. In August 2012 President Obama said “ a whole bunch of chemical weapons moving around …that’s a red line for us.” The crossing of the red line would then imply that the US should become involved in the two year old Syrian civil war. So far the evidence seems limited and far from conclusive.

If nothing else we should be wary of weak evidence of the possession or use of weapons of mass destruction as justification for going to war. So lets examine what we do know. What we have to go on is soil samples that were smuggled out of Syria. Laboratory analysis of the samples suggested traces of a nerve gas known as Sarin. Actually because Sarin is quite reactive the only thing to be detected would be hydrolysis products due to the reaction with water in the air or soil. Also there was hearsay evidence of witnesses claiming to have seen victims of exposure to Sarin.

Sarin is a very toxic nerve agent. It actually isn’t a gas but rather a liquid designed to be aerosolized, meaning sprayed as a fine mist. Contact with bare skin or especially inhalation causes a number of symptoms ranging from heavy salivation, profuse sweating, muscle cramps, convulsions and death resulting from respiratory paralysis. Not pretty, huh?

Sarin is a member of a class of poisons known as Acetyl Choline Esterase Inhibitors. Other substances that have the same effect, but lower toxicity are a number of insecticides. Even the relatively safe house and garden type insecticides kill insects by the same mechanism. So how do they work?

Imagine you want to wiggle your big toe. A message travels from your brain via several nerves “talking” to each other to get the signal all the way to your toe. For the signal to get from one nerve to the next requires the opening and then closing of a “gate.”Synapse_Illustration_unlabeled.svg The gate opening allows the signal and the closing stops the signal. If the gate doesn’t close your toe would continue to wiggle. That is the way Sarin and other Acetyl Choline Esterase Inhibitors work. They keep the gate open. A small stimulation of a nerve can’t be turned off. The affected tissue is overstimulated. When the affected tissue is the chest muscles, your breathing is disrupted.

Now back to the weapons of mass destruction. Recall the President Obama said “bunches of” WMDs. The evidence so far for the presence or use is inconclusive. We don’t know who used them if they were used at all. We don’t know how much was used but the only evidence suggests limited rather than widespread use. We don’t know where they were used or how many people were affected. This is not the evidence we need to spend our blood and treasure yet again in the middle east.

Silent Spring Redux

Rachel Carson wrote her now famous book Silent Spring fifty years ago. In her book she documented the unintended effect of the use of persistent insecticides such as DDT. DDT (Dichloro Diphenyl Trichloroethane) when introduced was heralded as a tremendous advance in technology in the battle between humans and insects for our food supply.

Previously available insecticides were toxic to all forms of life. The so called first generation pesticides include agents such as Lead Arsenate which contain both Lead and Arsenic. Nicotine from tobacco plants also has historical use. These substances are acutely toxic to humans and pests alike.

DDT and other second generation pesticides were thought to be much safer as they have much lower toxicity to mammals and birds compared to insect toxicity. Further, these substances were persistent meaning that insecticide application occurred less frequently. An unintended consequence of the use of these insecticides was their bioaccumulation.

The littlest critters are eaten by little critters, who are in turn eaten by slightly bigger ones. The higher up in the food chain, the higher the accumulated dose of insecticide. The problem with birds, raptors in particular is not acute toxicity but an effect on egg shell thickness. Eagles, hawks, and some sea birds weren’t killed directly by the pesticides, but rather had trouble reproducing because the thin egg shells broke.

When the problem of bioaccumulation was recognized a new generation of pesticides was developed. The third generation of insecticides are of a relatively low toxicity to non-target organisms, but more importantly much less stable in the environment. But once again unintended consequences rears its head.

This third generation of insecticides includes a class of compounds called neonicotinoids. As their name implies they are structurally related to nicotine but have more specificity in their toxicity towards insects. Imidacloprid is an example and is in widespread use around the world. It is used against many insect species especially agricultural pests.

The neonicotinoids were developed and put to use in the middle of the 1990s with considerable success. It has only recently come to notice that a connection exists between these compounds and a condition called colony collapse disorder (CCD). Around 2005 it was noticed that wild honey bees were disappearing. Bee keepers also noticed that the number of bees in their hives were decreasing to the point of collapse hence the name. What was happening was poorly understood as there weren’t any dead bodies and as every murder mystery follower knows it’s hard to get a conviction without a dead body. The only thing known about CCD was that bees went out in the morning but didn’t come back in the evening.

Two recent studies published in Science have made the connection. Using the equivalent of radio collars for bees, scientists were able to show that bees exposed to minute quantities of neonicotinoids were not killed outright. They essentially were made stupid, too stupid to find their way back to the colony. The insecticide is taken up into the tissues of plants where it finds its way to the nectar and pollen. Bees collect the nectar and pollen, are intoxicated and get lost. It’s as simple as that. But that is a big deal, as over thirty percent of food crops worldwide require pollination by bees.

Originally published in the Russellville Courier, August 2012

On Potatos and Poisons

What do foods such as potatoes and tomatoes have in common with cigarettes, pretty (Italian) women and various toxic drugs? They are all members of or derived from the same family of plants called Solanaceae. [sole-ah -nay-see-ee]

These plants are found around the world. The new world contributed edible potatoes, tomatoes, and chili peppers whereas eggplants are from the old world, specifically India. It is hard to imagine what Italians put on their pasta or what fed the Irish before the Colombian Exchange, a term used to denote the world wide trade in goods which developed after the globe was united in trade following Columbus’ discovery of the new world.

Solanaceae contributes in addition to valuable foodstuffs, numerous toxic plants including what is arguably the most toxic plant on earth- tobacco. The active ingredient is nicotine which is both additive and toxic. Fifteen percent of the world’s population and close to a third of all adults use tobacco. The World Health Organization calls tobacco addiction the leading preventable cause of death worldwide, killing over five million people a year.

One of the more interesting members of Solanaceae is Atropa Belladonna, also called Deadly Nightshade. The genus name Atropa comes from the name of one of the three fates of Greek mythology. Atropos would end the existence of mortals by “cutting the thread of life”, an obvious reference to the lethality of the plant. These and other members of Solanaceae contain Tropane alkaloids which interfere with nervous transmission. This property has been taken advantage of as both an agent of murder and as useful medicinal agents.

An integral part of an Ophthalmic exam (eye exam) involves putting drops of an Atropine solution in the eye. Today derivatives of Atropine with a much shorter duration of action are used, but I digress. Here’s where the Belladonna part comes in. Bella donna means beautiful woman in Italian. As early as the middle ages, women would use a tincture (dilute alcohol solution) of the plant to dilate their pupils, thus producing a more beautiful appearance.

Studies have shown that photographs of women retouched to enlarge the pupils are viewed as more attractive than photographs of women with smaller pupils. Not surprisingly, The rather racy slang “bedroom eyes” has the same origin. The opposite seems true. “Beady eyes” or small pupils is a pejorative term.

And while I’m on pupil size, I should mention that human infants have very large pupils. It is said that this is due to the underdeveloped musculature necessary to constrict the pupils. But is it underdeveloped eye muscles or an evolutionary adaption of the infant to be viewed as more attractive?

An eye can threaten like a loaded and levelled gun, or it can insult like hissing or kicking; or, in its altered mood, by beams of kindness, it can make the heart dance for joy.

– Ralph Waldo Emerson

From bedroom eyes to boiled potatoes and eye exams to eggplant parmigiana , its about Solanaceae.

Originally published in the Russellville Courier, January 1, 2012