A Vaccine To Crack The Cocaine Bugs

Years ago I heard the song "Snowblind" by our one and only Ozzy Osbourne, from his album Speak of the Devil. The meaning of the song is two-fold. Firstly, people in a snowy landscape face such intense reflection of sunlight, that they might go blind. They wear special goggles to restrict sunlight, so that it doesn't burn the macular portion of the retina (the part where light rays are usually focussed.)

Another interpretation of this song could be this that someone gets blinded by the actions of cocaine (also known as snow or crack). That's precisely what Ozzy meant.

Cocaine, an alkaloid obtained from the leaves of Erythroxylum coca, produces euphoria (a feeling of elation) by increasing the amount of dopamine in the brain. Dopamine is normally liberated in brain structures such as the basal ganglia. After it has been liberated and it has finished its action, residual dopamine in the synapse is 'cleared' by dopamine transporters in a process called reuptake. These transporter proteins packs these chemicals back into where it came from (into the axon, as is shown in the picture), hence re-uptake. Cocaine binds with these transporters in such a tight embrace that these transporters fail to function: that is, cocaine functions as dopamine reuptake inhibitor. Dopamine, the pleasure (reward) chemical, which now accumulates in the synapse, gives the person a good kick. Frequent use of it through inhalation or injection (as these routes lead to faster absorption) gives them the feeling of an orgasm, which users refer to as 'rush'. Nucleus Accumbens, an area in the brain, supposedly 'reinforces' this addiction.

So isn't there a way out? Will they have to go on scratching their skin (cocaine produces a typical dermal itching sensation, Magnan sign or the cocaine bugs, where the patient feels as if insects are crawling under their skin)? Scientists are now on the verge of producing a vaccine (TA-CD Vaccine), which not only will cure their addiction but also decrease the severity of its 'withdrawal symptoms'. The human immune system can not recognize cocaine since it is a small molecule. Hence, they are combining parts of inactivated cocaine molecule with inactivated cholera proteins. After you give them a 'shot' of this vaccine, the immune system will now recognize the combine and produce antibodies against coke. Next time cocaine is consumed, the antibodies in the blood will combine with the cocaine molecule and prevent it from reaching the brain, its main seat of action. The vaccine is currently undergoing clinical trials.

Not only cocaine, vaccine is being developed against methamphetamine too (N-methyl amphetamine), another drug of abuse. The mechanism of action of the vaccine is the same. These drugs are still used in clinical practice: cocaine as an anesthetic; methamphetamine analogs, methyl phenidate (RITALIN) and pemoline are widely used in attention deficit hyperactivity disorder or ADHD. But keeping in mind their abuse potential, these drugs should be prescribed weighing the risk-benefit ratio. And when an addiction has already developed, we must cure it, may be by using a vaccine like this.

Last modified: 13 Jul 2009
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The Scent of a Pathogen

Our immune system, the defense ministry of our bodies, tackles extraneous foreign molecules in a variety of ways. It may produce highly specific antibodies which fight against specific pathogens, as an example of 'adaptive immunity'. Or it may act then and there by virtue of 'innate immunity'.

Adaptive immunity takes some time to develop : due to the processing and presentation of antigen and the subsequent production of antibodies. Innate immunity, on the other hand, is inborn: encoded in the genome. They have broad specificity, meaning that one soldier (receptor) can kill a variety of organisms only if they fitted a certain criterion.

This is exactly how innate immunity handles pathogens. The soldiers (cells) in charge of innate immunity first detects the telltale signature trail of the pathogen: PAMPs or Pathogen Associated Molecular Pattern. Some of the examples of this molecular pattern are LPS (lipopolysaccharide of Gram negative bacteria which serves as endotoxin), peptidoglycans of Gram positive bacteria and flagellin of bacterial flagella. These soldiers seek the scent (motif) of the pathogens and sniff them out.

Frequently, these molecules have some mannose (a carbohydrate) residues in them and they are promptly recognized by pathogen recognition receptors. These receptors may be found in the circulation, in soluble form; may be PAMP receptors in macrophage cells, cells in charge of killing and engulfing invaders or may be Toll like receptors, present in macrophages and dendritic cells. Wherever they are located they just look for the signature thumb prints, latch onto them to give them the death kiss. These patterns are shared by more than one pathogen, it will identify and kill 'em all as per its recognition algorithm.

I can't help but mention Lavasoft's adware software in this regard. This antispyware software program looks for unwanted cookies in your hard disk in much the same way. It uses a protocol called code sequence identification to recognize telltale patterns based on its database of past records. You may download the program for free (if you click the link) but how about the physiological program we inherited from our ancestors, more importantly who programmed it?

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Aging, Immunity, Inflammation and Glycation

It has long been known that the level of proinflammatoy cytokines such as interleukins 1,6 and tumor necrosis factor-alpha rise with age, so does inflammatory diseases like cancer, arthritis, with age. Sleep, exercise and other healthy lifestyles lead to a decrease in the level of these substances. For example sleep reduces TNF-alpha, IL1 and IL6, whereas exercise causes a decrease in the acute phase reactant, c-reactive protein (CRP), a substance typically associated with inflammation.

While immunity plays a vital role in protecting our bodies against foreign invaders, excess of it can damage us. There are even some situations where our bodies are unable to distinguish between self and non-self (foreign) proteins, due to a defect in immunity. It then turns itself on against our own proteins. Some researchers argue that this might play a role in aging. Indeed, autoimmune diseases become more frequent with age.

Another contributing factor in aging is glycation. Glucose can bind with non-glucose molecules to form different molecules, this reaction is called glycosylation. Enzymes, catalytic substances, can facilitate this reaction. However, glycosylation can also occur non-enzymatically, it is then known as glycation. In diabetes, we measure the glycated hemoglobin content (HbA1c) to have an overall (and integrated) view of blood sugar control, for the preceding 2-3 months. This is because of two reasons: since the red blood corpuscles (RBC) live for about 120 days, the hemoglobin (Hb) can also be thought of for living as many days; and that glycation reactions being independent of enzymatic activity, will thus reflect the blood sugar concentration. Glycated end products (AGE or advanced glycosylation end products) are frequently referred to as Amadori products, Maillard reactions or Schiff bases; though minute differences exist among them. It is expected that in diabetes, where the blood glucose levels remain elevated, the glycated products will be more. These are responsible for microvascular complications of diabetes such as diabetic nephropathy (kidney/renal failure) and diabetic retinopathy (may lead to blindness). These damages result from AGEs and glucose combining with protein molecules in such a way that these protein molecules become extensively cross-linked. As a result, the protein shape (conformation) changes: they may clump together or their functions may reduce, as a result. Diminution of function is due to its change in structure, both secondary and tertiary (folding), as protein function depends not only on the sequence of its constituent amino acids, but also the way the are arranged in space. Aspirin, carnosine, alpha lipoic acid and some other substances inhibit glycation. On the other hand, synthetic molecules, such as Alt711 can break the cross-links which have already formed. These agents may help us combat aging by interfering with glycation. Thus it is evident that glycation will leave its imprint on aging, by interfering with cell function.

Related posts: Aging: From a General and Evolutionary Perspective; Aging, Mitochondria and Free Radicals; Hayflick limit, Telomere and Aging