Questions to ask about your vitamins

June 6, 2010

Hello friend,

Long time, eh? … as my folks say up north, the true north.

Have you wondered about vitamins? Are they necessary? About twenty years ago, I figured ….. I eat plenty of vegetables and fruits, I’m sure I get all the vitamins I need from my diet. As time went on, I read scientific articles about nutrition, dug deeper into the subject, and here’s what I found.

Over the years, there has been a decline in the nutritional quality of fruits and vegetables – this is per data collected by the U.S. Government from 1950 to 1999. And although there are dietary recommendations for vitamins and minerals, these are just to prevent deficiency of nutrients in the body. Optimal nutrition requires an intake of multivitamins and other supplements.

With all that’s available in the market, how would you choose a quality vitamin? I list below ten questions from the book “Secrets of Supplements” by Gloria Askew, RRN and Jerre Paquette, Ph.D. As you can gather, this is not an original write-up from me, however the information that I reproduce below is of paramount importance in choosing the right vitamins for yourself.

” …. Every question on this list should be answered with “yes.” If not, you haven’t found a totally terrific product.

1: Is your multi-supplement primarily a plant-based product that includes vitamins, minerals and phytonutrients? [Phytonutrients means plant nutrients. Only whole plants can provide all the nutrients your body demands].

2. If the multi-supplement is plant-based, is it derived from a variety of plants? [Phytonutrients vary from plant to plant].

3. If the multi-supplement is plant-based  and derived from a variety of plants, does the manufacturer own its own land and grow, harvest, and concentrate its plants? [A rich, broad-spectrum soil is required to produce healthy plants. The more a company out-sources its products, the greater the chances of loss of nutrients and quality control].

4. Does the vitamin supplement contain the whole-plant concentrate, including associated phytonutrients? [Vitamins and minerals and phytonutrients work in partnership with one another, in synergy].

5. Are the supplements certified organic from the soil and seed up?

6. Is the disintegration time on the tablet about 30 minutes or less? [For optimum digestion, they must be broken down and prepared in the stomach, just as food is].

7. Does the manufacturer voluntarily adhere to Good Manufacturing Practices from seed to end product and The Council for Responsible Nutrition for its fish oil products? [The Council’s “Omega-3 Monograph” is the base line for toxin-free, toxic products. The standards cover raw materials, manufacturing, packaging and nutrition].

8. Does the manufacturer assay its entire line for heavy metals, microbiological contaminants and pollutants, and desirable nutrient compounds? [In the United States, supplements are regulated by the Food and Drug Administration (FDA), but they are regulated as food, not drugs. In 2007, the FDA stated that a company manufacturing supplements “does not have to provide FDA with the evidence it relies on to substantiate safety or effectiveness before or after it markets its products.”].

9. Does the manufacturer have published Bio-Assays that I can easily access? [Toxins are common-place in our environment and can overwhelm any goodness present in organic compounds].

10 Does the manufacturer publish an ORAC score (oxygen radical absorbance capacity, a measure of anti-absorbant capacity) on its anti-oxidants that is based on a wide range of free radical groups?

Hope that helps, my friend.

Until next time …. live healthy, live well.

Warm regards,

Dr. Ajit Damodaran

Health education web tutorials

April 1, 2010

Hello friend,

Alright, there is nothing original about the following post. But it is AWESOME!

It’s a link to an interactive web site that gives you all you wished to know about various disease states and treatment. It’s a service provided by the U.S. National Library of Medicine and the National Institutes of Health. There’s a whole bunch of individual tutorials, click on any of them to learn a lot about it. The topics are broadly divided into four categories – Diseases and Conditions, Tests and Diagnostic Procedures, Surgery and Treatment Procedures, and Prevention and Wellness.

The tutorials listed below are interactive health education resources from the Patient Education Institute. Using animated graphics each tutorial explains a procedure or condition in easy-to-read language. You can also listen to the tutorial.

NOTE: These tutorials require a special Flash plug-in, version 6 or above… If you do not have Flash, you will be prompted to obtain a free download of the software before you start the tutorial.

  • Diseases
    and Conditions

Ain’t it great?

Until next time, my friend, take care of yourself and your health.

Warm regards,

Dr. Ajit Damodaran

Chantix – Project Smoking Cessation!

February 11, 2010

Hello my friend,

I trust you’re having a wonderful beginning of the year! Today’s blog is directed at those of your kith and kin who have resolved to quit smoking, and may require some pharmaceutical help to boost their resolution.

The chief drug in cigarette smoke is nicotine, which has addictive characteristics similar to cocaine and heroin. How does nicotine make you feel good? Let’s look at the neurochemical mechanisms involved.

Acetylcholine (ACh) is a principal neurotransmitter in our body, both in the central and peripheral nervous systems. In the central nervous system, Ach is involved with memory and learning (damage to the system that releases Ach is likely involved with Alzheimer’s disease), as well as with arousal and reward pathways. In the peripheral nervous system, Ach activates muscles, and regulates respiration, perspiration, pupil dilation and constriction, digestion, urination and sexual arousal.

Ach produces its effect by stimulating Ach receptors. There are two kinds of Ach receptors, the nicotinic receptors and the muscarinic receptors, named for the fact that the plant alkaloid nicotine has an affinity for the former receptors and another plant alkaloid muscarine has an affinity for the latter receptors.

So, when you smoke a cigarette, how does nicotine act? When you inhale a puff, the nicotine in the smoke is absorbed in the lung and reaches the brain within a few seconds. It binds to the nicotinic receptors in the brain and activates several neurotransmitters in the brain, including dopamine that leads to euphoria, relaxation and later, addiction. Nicotine also binds to nicotinic receptors in the adrenal medulla, stimulating the release of adrenaline leading to increased pulse rate and blood pressure, quicker breathing and increased glucose release into the blood by the liver. This can lead to cardiovascular disease.

By virtue of its increased cholinergic activity, nicotine inhibits programmed cell death, one of the processes by which the body destroys damaged and pre-cancerous cells. Other ingredients of cigarette smoke can be carcinogenic or cancer-producing.

Obviously, it’s a good idea to stop smoking. In recent times, there have been several aids to help us achieve this goal. Chantix (generic name varenicline, it’s known by brand name Champix in Europe) is the most effective prescription medication available since 2006 to help us stop this habit. It comes in the form of tablets, approved for use for a period of 12 weeks. If, during that time period, the individual stops smoking, it has been approved for an additional 12 weeks.

Chantix is a nicotinic receptor partial agonist. It is a derivative of the natural plant alkaloid cytisine. It is a partial agonist of some kinds of nicotinic receptors, which means it binds to the receptor and produces effects that are not quite the entire spectrum of effects produced by nicotine at that receptor. By so doing, it decreases one’s cravings for nicotine and reduces the feel-good euphoria and relaxation produced by the drug. A year-long scientific study shows successful smoking cessation in 23 per cent of the subjects in the study.

Any negatives? Yes. In July 2009, the FDA required its strongest warning, the “black box warning” to be issued with Chantix, warning of possible side-effects of depression, and suicidal thoughts and actions, due to various reports of the same.

On the other hand, a study published in the British Medical Journal in October 2009 studied 10,973 individuals who were using Champix to quit smoking and found insignificant increase in depression or suicidal ideation or actions. This was part of a larger cohort study (also called panel study) of 80,660 individuals who were using various methods of smoking cessation. However, as we dig into the details of this study, the authors do list 18 episodes of self-harm in the 10,973 subjects. Also, the data was collected from a large population of general practitioners in the U.K. All of the deaths did not have full death certificates, so the number of suicides were likely under-reported, per the authors’ admission. In spite of these limitations, thorough statistical evaluation still indicates no significant increase in depression, self-harm or thoughts of the same.

Here are my thoughts. Every drug out there, yes even routine over the counter medication like Advil or ibuprofen, has side effects, some of which can be fatal. We still continue to use these meds as and when necessary. The medical establishment and the citizen evaluates and balances the pros and cons of the medicine and use it as needed.

We apply the same standard to Chantix. The health advantages of smoking cessation are well worth the risks of using pharmaceutical aid to do so. If while using the drug, we feel not-so-good thoughts and feelings, we inform our doctor. The doctor can take us off the medication if that’s the best course of action.

I wish you the best with your resolutions. Until next time, my friend, I wish you good health.

Dr. Ajit Damodaran

Keeping it cheerful!

December 27, 2009

Hello my friend,

Before I launch into this blog ….. I won’t be writing hard science this time. This is more about practical mind stuff, using popular works of psychology.

‘Tis the season of good cheer, isn’t it? It’s not apparent to everyone though. During this time of the year, some of us are affected by a form of depression called seasonal affective disorder.

There are certainly chemical imbalances and mental disorders that require medical intervention  – absolutely! In addition to medicine, let us consider something else. Every mental disorder is a dis – ease of the emotions. Emotions arise in relationships. So, let’s follow a trend of thought – if we heal our relationships, we would heal our emotions (and vice-versa). If we heal our emotions, we would heal our mind. If we heal our mind, we would heal our life. That opens up a whole realm of possibilities, doesn’t it?

Healing our relationships. Of all the relationships in our life, the one that is probably the most central to each of our families and on which all other relationships are based is the marital relationship. How can we strengthen this pivotal point of life?

We study great marriages. We associate ourselves with couples who have weathered life’s storms and are still devoted to each other. We read from experts how to increasingly improve our communication with each other. We study audio programs. We attend seminars that teach us intimacy in communication.

For the purposes of this article, I shall paraphrase from memory the teachings from two of my favorite books: The Five Love Languages by Dr. Gary Chapman, and Love and Respect: The Love She Most Desires; The Respect He Desperately Needs, by Dr. Emerson Eggerichs.

The premise of the former book is this. Let’s say, for example, that the language that I understand the most is English and the language that my wife understands best is Portuguese. She would much prefer that I speak to her in Portuguese than in English. And vice-versa – I’d like her to speak to me in English – that’s what would speak to my heart. In the same way, there are emotional languages of communication. They are:

1. Words of affirmation – in this, a person understands love best when their partner praises them.

2. Quality time – this involves spending time with your spouse with full, undistracted attention.

3. Receiving gifts – where the love is felt best when receiving gifts from one’s loved one, not necessarily expensive gifts.

4. Acts of service – putting in effort to do what could be just a routine task for your loved one.

5. Physical touch – could be as little as a pat on the shoulder or a squeeze on the arm just to convey that you care.

An individual can have one or two favored love languages. We make an effort to find out our spouse’s favored language(s) and express our love in their favored communication.

I really like one of the exercises Dr. Chapman suggests for couples. At the end of the day, ask each other: “how full is your love tank?” – how much do they feel loved? And if the answer you get is, say, 6 out of 10, it is our duty to express love to the other in their preferred love language until their love tank is at a 9 or 10. It sound so simple, doesn’t it? It works ….. as long as there is a commitment to engage in the exercise regularly, whether you feel in the mood to do it or not ….. especially when you don’t feel in the mood.

In the book Love and Respect: The Love She Most Desires; The Respect He Desperately Needs, Dr. Eggerichs explains with the help of psychological studies how the feminine need is to feel unconditional love and how the ultimate masculine desire is to be magnificently respected.

The above two books are masterpieces in practical psychology. It’s totally worth the investment of time in reading them. If you’re not a reader, listen to them on CD. Or watch them on DVD. Modern technology has its advantages! The principles of communication in these are primarily focused on marriage, but you’ll see that they can be applied to all relationships of life. Once you learn these ways, make sure you enhance your communication with all your near and dear ones – your children, your parents, your close relatives, your friends, yes …… even your workplace colleagues ……. and watch your life expand beyond its limits.

Let’s recap the logic presented above. When we read the above books and similar ones, we learn ideas to improve the quality of communication with our loved ones. We keep studying ways of strengthening our communication skills – it’s a lifelong commitment that keeps increasing our quality of the important relationships in life. When there’s a high quality of communication that fulfills us emotionally, we feel more secure in our relationships. This helps us with our mental health, which can possibly help to decrease our dependence on medical intervention. Does that make sense?

May you and your family be blessed this wonderful season!

Until next time, my friend …. take care of yourself and your health.

Warmest regards,

Dr. Ajit Damodaran

Cancer begone – Cisplatin and Taxol

October 25, 2009

Hello friend!

It’s the beautiful fall season already …… nature is amazing, isn’t it? The vibrant green colors of the powerful summer foliage mellow down into the magnificently muted colors of autumn. And before you know it, the leaves are falling, giving way to the skeletal trees of winter. Come spring, the green blossoms again and the whole cycle presents itself yet again. How does nature do it? What is that amazing universal clock that tells flora and fauna exactly what to do at different times? When do plant cells know how to grow? How to give way to new cells? The moisture? The pigmentation? The seasons ……

It’s the same with life, isn’t it? Seasons of life. Spring, summer, fall and winter leading back to spring again. At times, we are in the pink of health. At other times, we are a bit under the weather. And at other times, we get hit hard and we’re really down and out. But you know what? Winter is followed by spring. The world is now waking up to the golden age of nutrition, medicine, lifestyle, positive energy, and health. Even the most dreaded diseases and conditions of the past are being challenged effectively. It’s up to us as individuals to understand that the mindset of the last century is the distant, distant past. We are now in the age of health.

Cancer has been a scary monster …. in the past. Am I saying we should underestimate cancer? Absolutely not. We most certainly have to take the responsibility of submitting ourselves to preventative and diagnostic measures. But, let’s consider we have come head to head with the fact that a loved one has been diagnosed with cancer. What next? There are options – surgery to remove cancerous tumors and localized growths, as well as radiation and chemotherapy to destroy abnormal cancer cells, both localized and diffuse.

Let’s look at chemotherapy, specifically two chemotherapeutic agents: Cisplatin and Taxol – the combination is used for gynecological cancers.

Before we get into that, back to basics. What is cancer? Cancer is an uncontrolled growth of a group of cells. During this growth, the abnormal cells compete for nutrition with normal cells, with the result that they invade and destroy adjacent normal tissue. As the abnormal cells continue to grow, they spread to other tissues of the body through blood and lymph.

Why does cancer occur? It could be due to genetic reasons or exposure to cancer-producing agents or carcinogens like tobacco smoke, chemicals, radiation and viral or bacterial infection. A genetic predisposition to cancer is fed by carcinogens resulting in abnormality in the genetic material or DNA of the cell – that’s the reason for cancer.

How do we stop cancer? How do we decelerate the abnormal cell growth? Cell growth happens in several steps. The cell skeleton or cytoskeleton is formed of microtubules, and there is DNA replication with DNA precursor nucleic acids and DNA crosslinking. The steps are catalyzed by enzymes of different kinds acting on different kinds of receptors. So, there are drugs that interfere with microtubule formation and drugs that prevent microtubule breakdown so that the cytoskeleton is made rigid essentially freezing the cell into uselessness. Taxol is a drug of the latter kind – it prevents microtubule disassembly. Then there are drugs that inhibit DNA replication either by messing with the precursors, enzymes or crosslinking. Cisplatin works by inhibiting crosslinking of DNA. There are also enzyme antagonists, as well as other anti-cancer drugs with miscellaneous mechanisms of action.

Taxol is known by its generic name paclitaxel. It was first extracted in 1967 by scientists Monroe Wall and Mansukh Wani from the bark of a plant Taxus brevifolia (Pacific yew). Satisfying the world demand that developed required a large number of trees. Later, the same compound was chemically synthesized from petrochemicals – the chemical synthesis did not yield a large enough quantity of the drug to be viable. Today, the drug is primarily made by a biotechnological process called plant cell fermentation. A line of cells from the Taxus plant is grown and fermented in large tanks to produce the drug.

Taxol forms a complex with tubulin, the building block of microtubules and prevents the breakdown of microtubules. In rapidly dividing and growing cells, microtubule formation and breakdown are essential steps of the mechanism. Another mechanism that has been seen with taxol is that it induces programmed cell death or apoptosis, by binding to a protein that would otherwise inhibit this process. Thirdly, taxol forms complexes with free-floating tubulin and prevents the formation of microtubules, the skeleton of the cells. It is used to treat cancers of the ovary, bladder, cervix, breast, head, prostate, neck and lung cancers, as well as Kaposi’s sarcoma (a cancer affecting the skin, mouth, and gastrointestinal and respiratory tracts). It is usually administered by the intravenous route.

Taxol destroys normal cells too by manifesting the above mechanisms, which is why there are side effects. However, cancer cells grow at a more rapid rate than normal cells, so taxol destroys cancer cells much more than normal cells. Side effects include brittle and thinning hair, joint pain, nausea and vomiting.

Cisplatin or cisplatinum is, as the name indicates a platinum compound. It was synthesized in the laboratory initially in the 1960s, and approved by the FDA to treat cancer in 1978. It is used to treat cancers of the connective tissue (cartilage, bone and fat), lymphoid tumors, ovarian cancer and lung cancers among others. It cross-links with DNA and prevents cell division. This activates a mechanism of programmed cell death. Cisplatin is usually administered intravenously.

Side effects of intravenous cisplatin include toxicity to kidneys and nerves, as well as hearing loss. It can cause a high degree of nausea and vomiting – which can be treated prophylactically by a combination of Emend (aprepitant), Zofran (ondansetron) and dexamethasone. Cisplatin does not cause hair loss.

There have been papers published, of localized (in situ) administration, when possible, of both cisplatin and taxol, to target cancer cells and minimize the exposure of other body organs to the drugs. This significantly reduces the side effects, thus treating the disease with minimal discomfort to the patient. The appropriateness of this method is of course determined on a case-by-case basis, depending on how localized the tumor is or the cancer cells are.

If you are reading this article, and you have been diagnosed with cancer, I’d like to say something to you. Every single human being has cancer cells in their body. Natural body mechanisms stop cancer cells from taking over and affecting body health. Sometimes however, by a combination of genetic and carcinogenic factors, cancer cells in your body take on a life of their own and overpower the normal body biochemistry. And you look back and wonder – I’ve done everything right, I haven’t smoked, I haven’t lived a life of unhealthy pleasure, I’ve never wished ill on anyone, I haven’t hurt anyone …. at least, not knowingly ….. why is this happening to me? Stop right there …… what you think and do next is critically important!

“Whatsoever things are true, whatsoever things are honest, whatsoever things are just, whatsoever things are pure, whatsoever things are lovely, whatsoever things are of good report: if there be any virtue, and if there be any praise, think on these things.” Let’s look at the science behind these words. Every thought we think releases corresponding nerve and body biochemicals. Good, uplifting thoughts release “healing” biochemicals, whereas sad, depressing, complaining thoughts release ….. let’s just say it …… “harmful” biochemicals. Think those awesome, uplifting thoughts and release “healing” biochemicals in your body to produce an environment where cancer cells cannot reside anymore.

Why do bad things happen to good people? I am not going to attempt to take on such a deep philosophical question. Different spiritual traditions can give you that answer. You will find that answer when it’s the right time. The more pertinent question is – when bad things happen, what do we do next?

How about keeping a gratitude journal? Being thankful for all the blessings in your life? For the ones who love you, your family and friends? Now, this might sound strange, but I’ve heard people being thankful for the most difficult times in their life – when they look back, they realize that it’s been the period of maximum growth of character, personality and spirituality.

And when you do have feelings of despair, anger (even if it be righteous indignation at the injustice of it all), frustration, envy or even worse ….. all those negative thoughts, write it on a piece of tissue and flush it down the drain. Replace the thoughts with the corresponding positive thoughts….. the brain can only think one thought at a time – make that a positive one ….. yes, you have the power. Is that a Pollyanna attitude? Brain and body biochemistry respond better to the irrepressibly optimistic Ms. Pollyanna than the lugubriously pessimistic Mr. Misery. Realism? Who defines realism? Realism for the one child that survived a plane crash recently is diametrically opposed to the realism of the hundreds who did not. Who is to say what your realism is?

Believe in your healing. Believe in your good health. In some awe-inspiring way, your thoughts, your neurochemicals, your biochemicals will be commanding the cancer cells from stopping their misbehavior. And ….. at some point, they will listen!

I wish you the best of health. Until next time,

Yours in good health,

Dr. Ajit Damodaran

Alendronate – for bone supremacy

September 21, 2009

Hello my friend,

Here’s a universal truth – every one of us is growing older – constantly. Every minute. Without exception. And although the effects of age show up slower in some of us than others, they do eventually appear, albeit as unwelcome guests. We’ve got to fight for our youth and health. We can’t just let entropy take over.

One of these unwelcome guests is bone fragility. Why is there a greater risk of fracture as we grow older? Here’s why. Our bone tissue is a dynamic environment. There is constant bone-building and bone breakdown. Bone formation results from the activity of cells called osteoblasts – bone-builders, and bone resorption (breakdown and re-assimilation) due to the activity of bone cells called osteoclasts – bone-breakers. Estrogen is a “female” hormone that is formed in the body of both men and women, appropriate to the age and sex of the individual. Obviously, there is more estrogen in the body of a pre-menopausal woman than a man of the same age.

In less amounts than required to create female sex-specific effects, estrogen inhibits osteoclasts, the bone-breakers, thus minimizing bone resorption. It also activates the bone-building processes. In women, estrogen is primarily made by the ovaries. In men, estrogen is mainly formed by conversion of the male hormone testosterone.

At menopause, the ovaries cease to make estrogen. The drop in estrogen levels results in increased bone resorption and decreased bone formation. This leads to reduction in bone mineral density (BMD) and increased risk of fracture. This condition is called osteoporosis. Although most common in post-menopausal women, it can occur in men too, as well as in men or women with hormonal disturbances, or due to some kinds of medicine (specific steroids called glucocorticoids).

Osteoporosis is prevented/treated with lifestyle changes like exercise, nutrition including calcium and vitamin D and medicine. Bisphosphonates are a class of medicine that have been used effectively in preventing and treating osteoporosis. Nitrogen-containing bisphosphonates are more effective than non-nitrogenous bisphosphonates. Alendronate, sold in the generic form as well as brand Fosamax is a widely used nitrogenous bisphosphonate.

When taken orally, less than one-hundredth of the dose is absorbed under fasting conditions, even less when taken with food. Half of the absorbed medicine is excreted unchanged by the kidneys, the other half is rapidly bound to exposed bone surface in the body. Once it’s absorbed by the bone, its half-life is about 10 years. What that means is that half of the alendronate is rid off by the body in 10 years, then half of the remaining half is eliminated by the body in another 10 years and so on.

Alendronate binds to the osteoclasts (the cells responsible for bone resorption, the bone-breakers), specifically inhibits an enzyme, thus blocking a protein transfer pathway within the osteoclasts. This messes with the functioning of the osteoclasts. As a result, the osteoclasts cease to do their job of bone resorption.

Bone-building continues in the presence of calcium, vitamin D and other factors. This results in increased bone density.

Are there side-effects? All drugs have side-effects. Alendronate can cause ulcers – esophageal (gullet), gastric (stomach) and duodenal (the first section of the small intestine). To reduce the incidence of ulcers, it is required that one sit or stand straight or walk for 30 minutes after ingesting the drug. Taking this medicine with a full glass of water on an empty stomach improves absorption. If dental work is done while on this medication, there is a risk of osteonecrosis (literally means bone death) of the jaw – this is rare on oral administration, more likely when alendronate is administered intravenously, mostly seen in cancer patients.

If alendronate is administered with food or a beverage other than water, absorption is reduced – this is more so with calcium, magnesium or aluminum-containing food or drugs – that includes dairy and antacids. Hormone replacement therapy along with alendronate may help with post-menopausal women.

Alendronate is usually administered in a daily dose of 10 mg or a weekly dose of 70 mg for treatment of osteoporosis. It can be administered in a daily dose as low as 5 mg or a weekly dose of 35 mg for prevention of the same. For Paget’s disease of the bone (enlarged or deformed bones – hereditary or due to a long-standing slow viral infection like measles), it’s a daily dose of 40 mg for six months.

We live in good times. Science, nutrition, lifestyle, medicine and technology give us longer and better quality lives. Are the solutions perfect? Certainly not. Does medicine lead to adverse effects. Of course. However, we can discuss options with our professionals and take the best course of action. Awesome!

My friend, until next time, do take care of yourself and your health.

Dr. Ajit Damodaran

Molecules Possessed (science fiction)

August 8, 2009

Hello friend,

Before medicinal drugs enter the marketplace, they are synthesized in a laboratory, tested in controlled environments and disease models and then, once approved by the authorities, released for medicinal use. As a student, I used to work in such a laboratory. To pass the time, I would fantasize talking to molecules (nerd alert!) – the following is a story I wrote in those days.


Molecules Possessed

Chin was bewilderment personified. “I’m going crazy …..”

Asked his friend Nat: “Why?”

“It’s this molecule.”

“What molecule?”

“It isn’t behaving like a molecule?”

Nat raised an amused eyebrow, “How can a molecule not behave like a molecule?”

“That is just what has me stumped. I’ll explain. See, it was four and a half years ago that I started off on this task of converting a certain chemical to another – of possible medicinal interest.”

“Hmmmmm. And?”

“And after a series of 23 reactions, I was on the brink of success. The last step was the conversion of a bicyclic compound with a side-chain to a tricyclic one.”

“Carry on.”

“After this last reaction which I carried out two days ago most meticulously, I subjected this compund to different spectroscopic determinations.”

“What are these determinations?”

“Methods of identification of a compound.”

“So you did not get the compound expected, is it?”

“That would merely be a disappointment. It wouldn’t challenge one’s sanity like this. The results we have obtained defy logic.”


“Proton N.M.R. spectroscopy, that is one of the kinds of spectroscopy we did on the final compound, gives no signals with this compound – as if there were no hydrogen atoms attached to the carbon atoms in the molecule.”

“What of it? This molecule may not be having hydrogen atoms.”

“Impossible. All other kinds of spectroscopy we did  and the elemental analysis indicates the presence of hydrogen atoms beyond a shadow of doubt. Anyway, as the bicyclic compound I started with in the last reaction has hydrogen atoms, there is no way the product cannot have hydrogen atoms. It defies Chemistry.”

“You do have a problem there.” Pause. “I think the best you can do is get a good night’s sleep, wake up refreshed in the morning, and have a heart-to-heart talk with your molecule.”

“I’m in no mood for your wisecracks.”

“Alright. I’ll leave you alone. Relax, pal. You’ll think of an explanation in due time.”

After Nat left, Chin tried to sleep, but to no avail. Acting on an impulse, he left his room in the hostel and made his way to the laboratory.

The sample of the compound was just where he had left it – on his table. He pulled up a stool and gazed at his sample tube. The words of Nat came back to him. “Have a heart-to-heart talk with your molecule.” He smiled despite himself. How silly? Or was it? Just suppose it were possible? 

And there – like Alice in Wonderland he found himself growing smaller and smaller (no, there was no cake on the table). He slipped into the sample tube. Smaller and smaller. Curiouser and curiouser. 

He could not pinpoint any solid masses. He was in an atmosphere where there clouds of varying densities, sometimes so dense that they were almost solid masses and sometimes so rare that it almost looked as if there were only empty space there.

Chin could sense thoughts. No, they were not thoughts from his own mind. They were from somewhere around. They seemed to be addressing him.

“Hello! You’re new here, aren’t you?”

“I’ve come to meet your hydrogen atoms,” Chin found himself speaking.


“Why are they not giving signals?”

Laughter. All around. No sound, like human laughter. Chin could only sense it. 

“Dash it, this is frustrating.”

“Are you a scientist?”

“A student.”

“And your Ph.D. degree depends on our hydrogen atoms here?”

“I am not really worried about my degree. But that four and a half years of work should go to waste just because some hydrogen atoms want to go to sleep is…. is….” Chin could not find words to express his anguish.

“Don’t get excited. You’ll get all the signals you want.”

“Will you kindly explain what has been going on? And may I know who I am speaking to?

“You are speaking to what IS – to EXISTENCE.”


“It is time your concepts were made clear. How do you define life?”

“I’m not very sure.”

“What is the structural and functional unit of the human body?”

“The cell.”

“What is the cell made of?”

“Atoms and molecules.”

“What are atoms and molecules made up of?”

“Smaller particles – protons, electrons, neutrons …”

“What is the nature of these sub-atomic particles?”

“In what sense?”

“You must be knowing about the dual nature of sub-atomic particles.”

“Yes – these ‘particles’ behave sometimes like particles and sometimes like waves of energy.”

“Okay. You know Einstein’s theory of relativity – about mass and energy being interconvertible; of mass and energy being different personifications of the same thing.”


“So, in essence, your body is made of cells which are made up of atoms and molecules, which are in turn made up of subatomic particles – these particles are not strictly particles – just clouds of dense energy. Ultimately, what do we come to? Your body is made up of dense clouds of energy, as is every object in the universe, as is the universe – only the density is variant. Very, very dense energy projects itself as having mass. Therefore, EXISTENCE is ENERGY, ENERGY is EXISTENCE.”

Chin started feeling giddy. “Do you mean to say that there is no difference between a living body like mine and an inanimate object?”

“Essentially, no. But apparently, yes. What is the difference between a living human body and a dead human body? A living human body performs a multitude of functions in co-ordination. That is, there are countless molecules in the body performing in co-ordination – the body has ‘life’. When this co-ordination is lost at some stage, the body ceases to live. Yet, all the molecules continue to exist. Only the co-ordination is lost. Now, the question is – what causes this co-ordination? The answer is – a certain force.”

Chin was excited. This could be the answer eluding man through the ages. “What is this force?” he asked eagerly.

“A force. It is difficult to explain. You have not quite reached the level of intelligence required to grasp the idea. It will be something like trying to explain Einstein’s theory of relativity to a monkey.”

“Hey!” Chin turned purple with indignation.

“Suffice it to know that it’s some kind of a life-force, a different embodiment of the same energy which holds the sub-atomic particles together in proper order in an atom of a molecule. This ‘life-force’ exists in all living beings. When the life-force goes away, there is no ‘life’ as you know it.

“Okay! I’ve swallowed all this. But in what way is all this connected with my not getting proper signals in the spectrum?”

“It has all the connection. Do you know the theory of N.M.R. spectroscopy?”

“Yes. N.M.R. or Nuclear Magnetic Resonance spectroscopy is based on the principle that in the presence of an external magnetic field, nuclei of atoms absorb electromagnetic radiation of different specific frequencies to undergo transitions among specific orientations. It is this absorption of radiation that gives rise to signals.”

“Right. You see, what happened was this. Some life-force moving around in the vicinity was entrapped by the hydrogen atoms of this molecule. That is, according to your definition of life and death, these hydrogen atoms started having life – and started acting with a will of their own. They occupied the orientation of the lowest energy and refused to absorb electromagnetic radiation. With the result that you go no signals.”

Within Chin’s breast, the initial wonderment gave respectful right-of-way to exasperation, which burst out as a cry. “So, what do I do?”

“Don’t worry. You’ll get your signals tomorrow morning. This ‘life’ was only transitory. The hydrogen atoms are already ‘dead’ according to your definition.”

Chin arose from his slumber. Recollecting his nocturnal experiences, he started wondering, “Was this a dream?” It seemed likely.

Then he remembered that he had been told that he would be getting signals this morning.

Feeling like a fool, he took his sample to the instruments’ room and recorded the spectrum. Perfect. The hydrogen atoms had started giving signals. More puzzled than ever, he wondered what he would tell his Professor and colleagues. All that had happened? They would laugh at him. He was not so sure whether or not to laugh at himself.


Until next time, my friend, take care of yourself and your health.

Dr. Ajit Damodaran

Life is always fair!

June 25, 2009

Hello my friend,

Time for philosophical cerebrations. Logically presented, nevertheless they are just my opinions. Makes perfect sense to me ….. however, you may have a different take on the subject. Isn’t that what makes life beautiful?

To quote Napoleon Hill, “Thoughts are things.” What is the science behind that statement? Where does a thought from? It could be triggered by an event that is perceived by one of our five senses. Or, it could be triggered by a memory. Thirdly, it could be a creative thought, like they say …. from the Universe. Associated with every thought are neurotransmitters and hormones …….  natural brain and body chemicals that are released by nerve cells and other cells. Chemicals are “things”. So …… thoughts are things.

Stressful thoughts release natural chemicals like cortisol and adrenaline that, in excess, can hurt the body. Oh yes, we need cortisol and adrenaline for fight-flight-fright situations. They give us almost superhuman power to react to stressful situations. But if we get into that “hyper” mode at all times, that can create effects like lowered immunity, high blood pressure, increased abdominal fat leading to cardiovascular problems, diabetes, thyroid problems and decreased bone density.

Here’s the problem. In modern society, we live busy lives. As we live our hectic lives, our stress levels are at a constant high, at least moderately high ….. like, we have redefined what normal stress should be.

A majority of stress comes from our judging our own circumstances and others’. We believe that we deserve certain events in our lives. And we want certain events to happen to others, and certain other events not to happen to others. Why? Because we have our own perspective on what we deserve and what others deserve. When we believe we are “good” and yet these “bad” things happen to us. And when we believe someone else has been “bad” and yet “good” things happen to them.

If an individual has good fortune in any area of life, it is because of certain virtues they possess. Let’s take a simple example. Say, a person works hard and smart and becomes a billionaire (millionaire doesn’t cut it anymore, huh?). It’s basic cause and effect. The cause was good work, and the result was good rewards. In another area of life, the same person eats unwisely, does not exercise and suffers ill-health. Here, the cause was bad food and bad lifestyle and the effect was ill-health. It makes perfect sense, doesn’t it?

Let’s extend it. Say, the same person in the example above is not ever charitable. Not charitable with his money, his actions or his words. In fact, he is incredibly rude and even cruel to his employees. We are disgusted by his bad character. We start gossiping about him. Somehow, the story comes down to the fact that he is a horribly bad man and yet the Universe rewards him with good fortune. No, we got it all wrong. His good fortune results from his hard work.

On the other hand, we look at ourselves and see that we are good people. We are kind to our employees, we give to charity and so on. And yet, we are not as rich as the person above. So we come to the erroneous conclusion that our goodness is not being rewarded.

That is not the case at all. Every event in our life is perfectly fair. Every event in everyone’s life is perfectly fair. Does that give us an excuse to be not sympathetic to the troubles that our fellow humans go through? Certainly not. When we share others’ griefs, when we help people face their challenges, we are thinking charitable thoughts, we are doing charitable deeds, and that builds our own character. Good, strong character builds peace in our hearts. Scientifically, that means we develop neurochemical patterns in our brains and bodies that are beneficial to us.

I’m sure a thought must have come to your mind – yes, it’s come to my mind too. Am I saying that it is fair that a child is born in wonderful circumstances and another child is born into misfortune? I cannot make a cruel statement. I do not know the exact reason why one child was placed in the first situation and the other child in the second. Let’s send that question out to the Universe. What I am totally convinced of is that the Universe is in perfect order. We might not be able to see the order, but underlying what could be considered chaos, is a perfect world that works like clockwork. We might not know why the past was, but we can do all that we can to manifest a wonderful future.

Take the example of Oprah Winfrey. Born to a poor, teenage single mother in rural Mississippi, Oprah suffered through many struggles. In spite of her difficult beginnings, she decided to make something of herself. She started her career in a radio station. She then became a local TV co-anchor, and gradually grew to be a brilliantly successful media personality, one of the most influential people on the planet. Oprah is a role model not because of her troubled beginnings, but because she was an overcomer.

Can we assume that there is someone out there who shares Oprah’s birth day and was born in better circumstances? Is it possible that they are not as successful as Oprah? Is it possible that there is someone who was born with a silver spoon and became a total failure in life? You bet.

As we move forward into an awesome future, will there be obstacles? Absolutely. My belief is that the obstacles are the means by which we build the qualities to manifest the magnificence of our future. The heavier the weights we lift, the greater the resistance. The greater the resistance, the more the muscles build. Similarly, the heavier the obstacles in our path to our goals, the more we build mental muscle and character muscle.

The faster we move into the future, the more the obstacles. Another analogy will explain what I mean. If your car is parked in the driveway, and you put your hand out of the window, do you feel the wind? (I’m assuming a non-windy day). Take the car out on a drive through city streets at 25 miles an hour. Do you feel a gentle breeze? Yes. Take the exit onto the highway. You’re now driving at 65 mph. That’s quite a wind, isn’t it?

Obstacles and difficulties are part of the beautiful framework of the perfect Universe. However unfair it might seem, there is a purpose for every event in our lives.

What was the purpose of this philosophical treatise? Just this. When we develop an underlying belief that everything is fair in our world, we stop trying to be the manager of the world. We stop wasting our thoughts on wishing others ill. We stop frustrating ourselves with righteous indignation.

We learn to accept what we have, and we work calmly toward even better, in a spirit of inspirational dissatisfaction or divine discontent. We accept the truth of the Serenity Prayer, “God grant me the serenity to accept the things I cannot change, the courage to change the things I can, and the wisdom to know the difference.”

As we increasingly manifest this wisdom in our being, our health keeps improving. Isn’t that good?

Do take care of yourself and your health. Until next month, G’bye!

Your friend,

Dr. Ajit Damodaran

Omega-3 fatty acids

May 31, 2009

Hello friend,

As we, followed by the rest of the world, increasingly invite creature comforts into our sedentary lifestyles, there is a tendency to obesity. Associated with obesity is metabolic syndrome leading to increasing diabetes and cardiovascular disease, leading to death or at best a decreased quality of life.

Something I read quite some time ago … I think I first read of it in Deepak Chopra’s book Perfect Health …… improving health, slowing the aging process and increasing longevity by caloric restriction. There have been anecdotal reports of individuals practicing this through history. Recently, diets have been developed based on this principle, like the Okinawa diet and the CRON (calorie restriction with optimal nutrition) diet.

The following is a mechanism that is brought into play in caloric restriction. As less food is absorbed from the gastro-intestinal tract into the blood, there is less need for insulin. As a result, there is a decrease in insulin and insulin-like growth factor 1 (IGF-1). By a cascade of cellular mechanisms, this leads to an increase in the activity of a protein in the cell nucleus, called peroxisome proliferator-activated receptor (PPAR) gamma co-activator 1 (PGC-1). PGC-1 and other PPAR activators increase the activity of nuclear receptors that play a major role in the effects of caloric restriction (The Journals of Gerontology Series A: Biological Sciences and Medical Sciences 60:1494-1509 (2005) © 2005 The Gerontological Society of America). They activate lipid transport and lipolysis (fat burning mechanisms). The resulting beneficial effects include decrease in blood pressure, decrease in total and bad cholesterol (LDL), decrease in triglycerides, increase in good cholesterol (HDL), decrease in blood glucose, and through all these, increased longevity.

It has now been shown that omega-3 fatty acids in our diet activate the same factors above that are activated by caloric restriction. In addition, omega-3 fatty acids decrease the levels of  hepatic sterol regulatory element binding proteins (SREBP). These proteins are genetic  transcription factors that are master regulators of lipid homeostasis. Reduction in SREBP results in a decrease in the activity of enzymes responsible for fat biosynthesis and storage. Bottom line, omega-3 fatty acids decrease fat synthesis and storage. So, it may be said that instead of starving yourself, just pop some omega-3 (read the book The Omega Diet by Dr. Artemis Simopoulos). No, please don’t take this as license to be corpulent …. the ill effects of obesity are not cancelled by omega-3 fatty acids.

Alright! What are omega-3 fatty acids? Let’s get back to basics. The macronutrients we ingest in our diet are proteins, carbohydrates and fats. (Fats are a part of a larger group of compounds called lipids. Also, lipids include sterols like cholesterol, phospholipids and others). Fats are a very concentrated form of energy. A gram of fat gives the body more than double the energy of a gram of carbohydrate or a gram of protein. Chemically, all fats are a “three-pronged” glycerol molecule linked via those three “prongs” (ester bonds) to long chain fatty acids. Each long chain fatty acid is a long chain of carbon atoms with hydrogen atoms bonded to the chain of carbon atoms. Each carbon atom (except the one forming the end of the chain) can be bonded to a maximum of two hydrogen atoms. When all the carbon atoms constituting the chain is bonded to the maximum number of hydrogen atoms they can be bonded to, it is called a saturated fatty acid. The triglyceride (that is, the glycerol linked by ester bonds to three fatty acids) is then called a saturated fat molecule. Too much saturated fat, obtained in the diet from dairy products, lard, coconut oil and cottonseed oil, is bad for the cardiovascular system. High levels can also cause breast cancer and prostate cancer. Smoking and regular alcohol ingestion increases the levels of saturated fat in the blood.

In monounsaturated fats, two of the adjoining carbons in the long chain fatty acid are not saturated with hydrogen atoms. They are each attached to only one hydrogen atom and double-bonded to each other. So, two carbon atoms saturated with hydrogen atoms would be bonded as -CH2-CH2-, whereas unsaturated double-bonded carbon atoms would be bonded as -CH=CH-. In polyunsaturated fats, there are more than one double bond in the fatty acid chain. “Omega” is the last letter of the Greek alphabet. Omega means the end. In our discussion, the omega carbon atom is the last carbon atom in the fatty acid chain. Omega-3 fatty acids are those that have a double bond at the carbon atom which is third away from the end of the fatty acid chain. Aha!

Essential fatty acids (EFAs) are those that cannot be synthesized by the human body from other components of the diet or body biochemistry. So, EFAs are required to be part of our diet. There are two groups of EFAs, the omega-3 fatty acids that we discussed above. and the omega-6 fatty acids. The latter are of course those that have a double bond at the carbon atom sixth away from the end of the fatty acid chain.

The balance of omega-3 and omega-6 fatty acids is important in the body. The ideal ratio of omega-6 to omega-3 in the diet is said to be less than 4 is to 1. In the diet of industrialized nations, the typical ratio is 10 to 1 or more. This could be cause for cardiovascular events, arthritis, cancer, depression and other mood disorders, osteoporosis and inflammation. In fact, cumulative research suggests that a lot of modern health conditions have inflammation as the underlying cause. There are signaling molecules in the body called eicosanoids, derived from omega-3 and omega-6 fatty acids. Eicosanoids from omega-6 fatty acids are pro-inflammatory, whereas those derived from omega-3 fatty acids are anti-inflammatory. To maintain equilibrium in these body processes, both omega-3 and omega-6 fatty acids are required, in the right ratio.

The important omega-3 fatty acids in our diet are eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and alpha-linolenic acid (ALA). Research supports the use of EPA and DHA to prevent cardiovascular disease. EPA and DHA are biosynthesized by sea-water microalgae. Fish consume these microalgae and retain large amounts of these omega-3 fatty acids in their bodies. So, consuming fish or omega-3 fatty acids extracted from fish is ….. good for health. Plant omega-3 fatty acids are not EPA or DHA, but ALA. The human body is able to convert ALA to EPA and DHA. Flaxseed is commonly used as a vegetarian alternative to fish oil.

Omega-3 fatty acids have been shown in various research studies to be beneficial against cancer as well as developmental disorders like ADHD and autism. There have also been benefits to the immune system. When given to pregnant women and lactating mothers, the babies were shown to have higher IQs. More and more scientific research gives us greater insights into the benefit of omega-3 fatty acids. We do have to be careful, though, of not slipping into one of our weaknesses in modern society. Excess! If something is good for us, well, more of it must be better. Not really.

Moderation is important. Very large doses of omega-3 can cause hemorrhagic stroke. Also, when someone has congestive cardiac failure, chronic recurrent angina or any condition where the heart is not getting enough blood flow, the normally beneficial stabilizing effect of omega-3 fatty acids is a negative because it slows down the few hyperexcited cells of the heart. This can lead to sudden cardiac death. Bleeding can be excessive in a patient who is already on aspirin and/or warfarin.

Bottom line – omega-3 fatty acids are a blessing. However, excess can be a curse. Balance, balance in everything. So ….. what should the dose be? The National Institutes of Health recommend between 650 and 900 mg daily of EPA and DHA combined, or 2.2 gm of ALA (for vegetarians). Two tablespoonsful of flaxseed contain about 3 gm of ALA.

Be well, my friend. Until next month, take care of yourself and your health.

Warm regards,

Dr. Ajit Damodaran

Celebrex – for pain and arthritis

April 9, 2009

Hello friend,

How are you? Holiday time again. Wish you a happy Easter! It’s good to be stepping into spring, isn’t it?

As we get more physically active in spring, we could possibly be exposed to injuries and ….. pain. Pain …. pain …. we’ll be talking about a prominent pain medication today …….. and toward the end of this article ….. well, we’re going to see a painful account of the state of scientific research today ……..

Let’s talk about the drug celecoxib, commonly known in the U.S. under the brand name Celebrex, and in other countries as Celebra, Cobix, Celcoxx, and Selecap. 

Celecoxib is a non-steroidal anti-inflammatory drug (NSAID – pronounced N-sed) – it is a selective COX-2 enzyme inhibitor. I’ll explain that below. Other NSAIDs, which are non-selective, are aspirin, ibuprofen (available as Advil or Motrin in the U.S., Brufen in India) and naproxen (brand name Aleve) – these are available over the counter. Where does the selectivity come from? Let’s look at the mechanism of action of these drugs.

An enzyme in the body called cyclooxygenase (COX) catalyzes the formation of lipid compounds called prostaglandins. There are different kinds of prostaglandins which have a variety of functions all over the body, including regulation of inflammation and sensitizing central nerve cells to pain, as well as contraction and relaxation of gastrointestinal muscles and secretion of stomach acid for the digestion of food.

There are three kinds of COX enzymes. COX-1 is found in most cells at a steady concentration. Prostaglandins that are responsible for the maintenance and protection of the gastrointestinal lining are dependent on COX-1 for their synthesis. COX-2 is induced at sites of inflammation. They are responsible for the synthesis of prostaglandins that cause inflammation and pain. COX-3 (a genetic variant of COX-1), has been shown to be in the brain and may be involved with prostaglandins and headaches – less is known about this enzyme.

The non-selective NSAIDs like aspirin, ibuprofen and naproxen inhibit both COX-1 and COX-2. Celecoxib selectively inhibits COX-2 thirty times more than it inhibits COX-1. Inhibition of COX-2 is beneficial – it reduces inflammation and pain; whereas inhibition of COX-1 can be a problem – it can damage the stomach lining, leading to ulcers in some patients. Selective COX-2 inhibitors, as the name indicates, selectively inhibit COX-2 and thus reduces inflammation and pain, with minimal gastric side-effects.

Prostaglandins have been shown to have a role in vasodilation (blood vessel dilation). When NSAIDs inhibit prostaglandin synthesis, the net effect on the blood vessels is to increase vascular resistance. This can lead to reduced blood perfusion through the kidney filtration apparatus in susceptible individuals. In patients with less than perfect cardiac ventricular function, this can lead to edema (fluid retention) and congestive heart failure (CHF).

COX-2 inhibitors were shown to have more of these kidney and heart side-effects than non-specific NSAIDs. A couple of COX-2 inhibitors, valdecoxib (Bextra) and rofecoxib (Vioxx), that had greater selectivity for COX-2 than celecoxib, were taken off the market because of greater cardiovascular risks than celecoxib. Although several mechanisms of action have been proposed for the greater cardiovascular toxicity of these COX-2 inhibitors, none of them is a complete explanation.

Aspirin, though an NSAID, has an antiplatelet action which prevents formation of blood clots – hence, it is used by at-risk individuals in a low dose (81 mg) daily regimen for cardiovascular health.

Celecoxib, the drug we are discussing today, is orally absorbed with a peak effect between 2 and 4 hours after ingestion. Its elimination half-life is between 6 and 12 hours – this means half of the drug in the body is eliminated in 6 to 12 hours, then half of the amount left in the body is excreted in the following 6 to 12 hours, and so on….

Celecoxib is used to treat rheumatism, osteoarthritis, acute pain and painful menstruation. Under brand name Onsenal, celecoxib is used to treat familial adenomatous polyposis (FAP), a genetic disease characterized by polyps that grow in the large intestine and/or rectum. These polyps have high levels of COX-2. By inhibiting COX-2, celecoxib decreases the growth of the polyps. Onsenal is generally used in conjunction with surgery to treat FAP.

Alright, let’s talk about ……. twenty-one research articles with fabricated data ….. wha .. aa… at? Yup! Favorable results from Celebrex, Bextra and Vioxx as well as Lyrica and Effexor for pain were made up by a prominent anesthesiologist from Springfield, Massachusetts (as reported in Scientific American, March 10, 2009 as well as Wall Street Journal, March 11, 2009 and Boston Globe, March 11, 2009).

Dr. Scott S. Reuben, Professor of Anesthesiology and Pain Medicine at Baystate Medical Center in Springfield, MA, has been influential in estimated billions of dollars of sales of COX-2 inhibitors (according to Paul White, editor, Anesthesia and Analgesia, February 20, 2009). Reuben recently admitted that he did not do any of those studies. He fabricated results, including inventing patients who never existed and forging the names of co-researchers. Scientific American calls him a medical Madoff (a reference to Bernie Madoff who recently perpetrated a 65 billion dollar investor fraud). Of course, his studies have been retracted by the medical journals they were published in.

No, it’s not all bad. Celebrex, Lyrica and Effexor are not expected to be taken off the market. None of Scott Reuben’s studies were part of the application that the manufacturers made to the US FDA or to drug authorities in other countries. They are still effective drugs.

So, why did Reuben lie? To get financial grants from the pharmaceutical companies involved. It has been reported that Reuben acted alone in the fraud.

Human beings, right? The good, the bad, the ugly….. No, we cannot develop a holier-than-thou attitude. Good does not mean perfect. None of us is perfect. However, it’s true that some imperfections in some people affect large populations of people negatively.

Let us hereby resolve to minimize our own imperfections, eh?

Until next week, do take care of yourself and your health.

Warm regards,

Dr. Ajit Damodaran

Colchicine – for gout

March 18, 2009

Hello friend,

Time has slipped by, hasn’t it …. since the last blog? Time, life …… reminds me of something that leadership teacher Dr. John Maxwell says – you cannot manage your time, you can only manage your life. Here we go ….. to the better management of life …..

As our knowledge of medical science and lifestyle increases, we live longer. As we live longer, there’s no point in living unhealthy lives, is there? A healthy lifestyle is what we intend. We watch our diet, take the right medication when necessary and live healthy, happy lives … right?

Which brings us to the management and treatment of a condition that can be painful. Gout. What is gout? High levels of uric acid in the blood along with acidic blood pH cause deposits of uric acid crystals in the cartilage of joints. This leads to painful, burning acute pain, arthritic symptoms, and with time, chronic gout including the formation of nodules called tophi that show through the skin.

Uric acid is normally present in everyone’s blood. Where does an excess of uric acid come from? Some folk may be genetically prone to it, due to aberrations in purine-pyrimidine metabolism. Purines and pyrimidines are part of amino acids (proteins are formed of amino acids), DNA, RNA, energy production in the body …. a lot of body biochemistry. Specifically, uric acid is created from the breakdown of purines. Gout is more likely in more affluent societies due to high dietary intake of proteins, fats and alcohol. “Poor man’s gout” also exists, because of ingestion of an excess of malt liquor combined with bad nutrition. Gout can also be caused from kidney failure and from lead poisoning. In the U.S., gout occurs in about 0.3 per cent of the population.

Treatment of gout. In the first century A.D., they used the extract of plants belonging to the colchicum genus to treat gout. In 1820, the active ingredient from that extract, an alkaloid named colchicine was extracted from colchicum extract  by a couple of French scientists. Research on this alkaloid showed that it inhibits deposition of uric acid crystals by inhibiting glucose oxidation to lactic acid. This is key in the treatment and prophylaxis of gout. Colchicine also prevents the mobility of white blood cells called neutrophils. This prevents inflammation. The drug is used for acute flare-ups as well as for chronic symptoms and prophylaxis between acute events.

Colchicine is used to treat familial Mediterranean fever, a genetically transmitted inflammatory disease affecting groups of people originating from areas around the Mediterranean sea.  It is also used to treat amyloidosis, a deposition of abnormal amyloid proteins in different organs, as well as to treat scleroderma, a chronic autoimmune disease where the skin or other organs harden. It can be used as preliminary treatment of pericarditis, an inflammation of the fibrous membrane around the heart.

This drug is now being investigated for anti-cancer properties. Colchicine prevents polymerization of microtubules by binding to tubulin, and thus acts as a mitotic poison (mitosis is an essential step in cell division and growth), specifically preventing the growth of cancer cells which have a greater rate of mitosis as compared to normal cells.

Molecular modifications of colchicine are being researched to develop a treatment for cancer. Why the molecular modifications? To increase the therapeutic index – higher effectiveness, lower toxicity.

Speaking of toxicity and therapeutic index, colchicine has a low therapeutic index. High toxicity. Neutropenia (reduction in blood neutrophils), gastrointestinal upset, bone marrow damage and anemia. Acute toxicity include fever, stomach upset and kidney failure.

High levels of uric acid is the primary risk factor for gout. Specifically, it’s not protein, it is a diet high in purines like meat and seafood, that lead to increased levels of uric acid. Meat and seafood consist of muscle, which has mitochondria, which has high quantities of DNA and RNA – that is the source of high purines. High amounts of vegetable protein or dairy protein, not being high in purines, do not lead to increased uric acid. A diet high in sugary soft drinks, because of high fructose corn syrup, leads to high uric acid. Drinking even one beer a day (not other alcoholic drinks) leads to elevated uric acid levels too.

Yup … like I said before … let’s eat and drink intelligently, use medicine when necessary … and live healthy.

Until next time, please do take good care of yourself and your health.

Dr. Ajit Damodaran

Amiodarone, antiarrhythmic agent

February 11, 2009

Hello friend!

Let’s get to the heart of  ….. the human body! It is obviously an essential organ – it pumps the blood that flows in the body, which is responsible for carrying oxygen and nutrients to all the cells of the body and transporting the waste of the cells back to the excretory processes.

It makes sense to keep the heart in working condition, in proper rhythm. Sometimes, the rhythm is affected. How? And what is the solution?

What is responsible for the rhythm of the heart? Pulses of electricity in a section of the heart initiate the process. This is something that happens at a frequency of 60 to 100 times a minute.

Alright, what’s the electricity deal? Like nerve cells, cardiac cells send messages electrochemically. Natural chemicals cause an electrical signal. There are chemical ions in the body that are electrically charged. The important ions are sodium and potassium that have one positive charge each, calcium that has two positive charges and chloride that has one negative charge. Each cell is surrounded by a cell membrane which is semi-permeable – it allows certain ions to pass through and blocks others.

In between sending electrical signals, the cell is at rest. In this state, the inside of the cell is negatively charged compared to the outside of the cell. The resting membrane potential is about -90 mV (millivolts). This means the inside of the cell is 90 mV less than the outside of the cell.

When the cell gets excited, an action potential occurs. In a nerve cell, there has to be a stimulus – a thought or a motor movement or some kind of mental or physical initiation. In a cardiac cell, the specialized conducting nature of the tissue causes it to have an action potential without any external stimulus.  The action potential is caused by a burst of electrical activity caused by a depolarizing current. This means the resting potential of -90 mV moves toward zero mV. When the depolarization of the cell reaches a threshold of about -70 mV, the cell fires an action potential and changes from negative to positive, then plateaus at around zero mV and repolarizes back to -90 mV.

The heart is a muscle with four chambers. The top two smaller chambers are the atria – the left atrium and the right atrium. The lower two chambers are the thick-walled, more muscular ones called the ventricles, left and right. How does the heart work? Two major veins called the superior vena cava and the inferior vena cava carry deoxygenated, impure blood from the upper and lower parts of the body respectively to the right atrium. The right atrium pumps this blood into the right ventricle. The blood is pumped by the right ventricle through the pulmonary artery into the lungs, where it is oxygenated. The purified, oxygenated blood is brought back via the pulmonary vein to the left atrium of the heart, which pumps it into the left ventricle. The left ventricle pumps the blood out into the rest of the body.

So, what is the sequence of events in a heartbeat? A group of cells called the sinoatrial node (SA node) on the wall of the right atrium is the natural pacemaker of the heart. An electrical impulse arises at a specific frequency from the SA node and is conducted through the heart, with a series of precisely timed depolarizations of heart cells in a four-part cycle. The atria contract, while the ventricles remain relaxed and passively full of blood. More and more blood is forced by the atria into the ventricles which keep on expanding to their muscular stretching limit. The valves between the atria and the ventricles close, following which there is a brief period of rest.  Then the ventricles contract – the deoxygenated blood from the left ventricle goes to the lungs as explained above, and the oxygenated blood from the right ventricle goes through the systemic circulation to the rest of the body. Next, the ventricles go back to resting state, and passively fill with blood.

Why would the heartbeat become irregular? It could be one of several reasons. It could be congenital. Or, it could be because of rheumatic heart disease, blood pressure or hyperthyroidism. Other reasons could be an excess of caffeine, alcohol, stress or even some cough and cold medicines sold over the counter.

Antiarrhythmics act on the heart in a variety of ways to slow the conduction so that the heart has the leisure to develop a more regular rhythm. There are different classes of antiarrhythmics based on the mechanism of action. Amiodarone is a Class III antiarrhythmic that blocks the heart’s potassium channels and thereby slows conduction.

Therapy with amiodarone should be started in a hospital under medical supervision. Severe lung problems, sometimes fatal, have arisen as a side-effect. Sometimes, the drug could worsen the heart’s arrhythmia. It may take 2 weeks or even longer for its effect to be seen.

Amiodarone is an iodine-containing medication, so the patient should not be on simultaneous radioactive iodine therapy. This medicine is not to be used during pregnancy or during breast-feeding. The drug can increase the effect of blood-thinner warfarin. It can increase the sensitivity of the skin to the sun. It can even turn the skin blue-gray in color, a condition that can persist for several months after the medication is stopped.

Other side-effects can be tiredness, constipation, loss of appetite, smell or taste changes, nausea and vomiting, dizziness, insomnia, headache, flushing and decreased sexual appetite.

The severe lung problem that amiodarone can cause, that was mentioned above, is interstitial lung disease. In this condition, a dramatically decreased diffusion capacity of the lung is seen on testing – this means that the amount of oxygen transferred from the air in the lungs to the blood is greatly reduced. This can be a deadly condition.

Amiodarone increases the effect of blood thinner warfarin and another type of anti-arrhythmic agent digoxin. Amiodarone is absorbed extensively by the fat tissue in the body, hence remains in the body for a long time. The half-life of excretion of this medicine from the body is a couple of months on an average – that means only about 50 per cent of the medicine is excreted from the body in a couple of months, then in another couple of months about 50 per cent of the remaining amount is excreted, and so on.

Yes, there are all these adverse reactions and side-effects. Yet, amiodarone is very useful in several types of arrhythmia. It is considered a “broad-spectrum” antiarrhythmic, with several effects:

  • It increases the time for the repolarization of the heart after each contraction.
  • It increases the time period in which the heart muscle cells are electrically stimulated in its action potential.
  • It decreases the speed with which the electrical impulses move through the heart’s electrical system.
  • It reduces the speed of the generation of electrical activity in the pacemaker.
  • It reduces the speed of electricity through accessory pathways.
  • It dilates blood vessels, resulting in decrease in blood pressure – this effect is useful in congestive cardiac failure, in which there is a weakening of the heart muscle.

As always, the medical professionals seek to balance out the benefits and the adverse effects of the drug and use it to the patient’s best advantage.

Until next week, do take care of yourself and your health ….

Dr. Ajit Damodaran

Levothyroxine (Synthroid)

January 19, 2009

Hello friend!

I hope your year has started well. Time to look at another drug. Levothyroxine, marketed under brand names Synthroid and Levoxyl, is synthetically manufactured thyroxine (also called T4). T4 is the major hormone secreted by the thyroid gland.

The thyroid hormone is made in the body by the thyroid gland, which is located in the neck. What does the hormone do? What is its role in the body? It plays an important role in metabolism. It is a catalyst in oxidative reactions. The hormone increases oxygen and energy consumption of the body – it increases the basal metabolic rate (BMR)  – BMR is the minimal calorie requirement of the body in resting state. The higher the BMR, the higher the number of calories burnt. This has resulted in a misuse of Levothyroxine for weight loss. The thyroid hormone affects body growth, temperature, heart rate and the force of contraction of the heart.

To be more accurate, thyroid hormones (plural) are secreted by the thyroid gland. The significant thyroid hormones are thyroxine (T4) and triiodothyronine (T3). Iodine is an essential part of the synthesis of the thyroid hormones. Another hormone called thyroid stimulating hormone (TSH) is synthesized and secreted by the pituitary gland in the brain. TSH stimulates the thyroid gland to release T3 and T4. The release of TSH is controlled by negative feedback – the higher the levels of T3 and T4 in the blood, the lower the TSH levels. And, the lower the T3 and T4 levels, the higher the TSH levels. TSH levels can be easily measured in the laboratory, and because of the easy correlation with T3 and T4, TSH is important to diagnose hyperthyroidism or hypothyroidism.

Hypothyroidism is a result of insufficient production of thyroid hormone by the thyroid gland. About three to five per cent of the U.S. population suffer from this condition. There have been reports that as much as ten per cent of the population may be affected if the mildest forms of subclinical hypothyroidism is included. This has a larger implication, because hypothyroidism can result in higher levels of cholesterol in the body, that could result in cardiovascular problems.

Iodine deficiency in diet can cause hypothyroidism – this can be a problem worldwide, however it is not significant in the U.S. Hypothyroidism can also be caused by thyroiditis (inflammation of the thyroid gland). How does the thyroid gland get inflamed? There are many possible reasons  ….. but it typically comes down to this: the body’s immune system …… well, it goes a little crazy. The normal role of the immune system is to develop antibodies against and attack foreign cells like bacteria and viruses. In thyroiditis, the immune system develops antibodies against the cells of the thyroid gland and attacks the thyroid gland cells in a self-destructive, autoimmune type activity.

Hashimoto’s thyroiditis or chronic lymphocytic thyroiditis results from the T-cells of the immune system attacking the thyroid. Post-partum thyroiditis affects about 5% women within one year of giving birth – the symptoms presented are first hyperthyroidism, then it gets back to normal or in about 20 per cent of those affected, it moves further into life-long hypothyroidism. Some kinds of thyroiditis can be genetically acquired. In some individuals, drugs like amiodarone (for the heart) and the anti-viral interferon can attack the thyroid cells and cause thyroiditis.

Common symptoms of hypothyroidism include fatigue, drowsiness, weight gain, increased sensitivity to cold, muscle cramps, low pulse rate, depression and constipation.

Typically the first laboratory test to evaluate hypothyroidism is measuring TSH. The higher the TSH, the greater the hypothyroidism (i.e., the lower the levels of thyroid hormone). The normal range for adults is usually in the range of 0.3 to 5 mIU/L – there are some variations between laboratories where the test is done.

The medication usually prescribed for hypothyroidism is Levothyroxine. It is available in various strengths 25 micrograms to 200 micrograms. It is usually taken on an empty stomach a half hour to one hour before breakfast, with a full glass of water. Antacids that contain calcium, aluminum or magnesium, simethicone, calcium supplements, iron, cholestyramine, colestipol, sucralfate and sodium polystyrene sulfate bind to levothyroxine and reduce the absorption from the stomach into the bloodstream. Therefore none of these listed medications should be taken less than 4 hours from levothyroxine ingestion.

Rarely, there could be temporary hair loss in the first few months of starting levothyroxine. Otherwise, it is a well-tolerated drug. Side-effects often occur if the dosage taken is too high – in this case, symptoms of hyperthyroidism are seen. These include increased sweating, increased appetite and weight loss, fever, increased pulse rate – in extreme causes even leading to a heart attack, high blood pressure and seizures. Side-effects of overdosing with levothyroxine occur 6 hours to 11 days after ingestion.

Every few months, TSH levels are tested to make sure that the dosage of medication is correctly titrated.

With that ……. I hope you have a wonderful week; wish you good health!

Dr. Ajit Damodaran

I resolve …. to keep my resolutions!

January 1, 2009

Hello friend!

Happy New Year to you and yours! On this first day of 2009, we all look forward to great achievements this year.

Let’s think back to the first day of 2008. What were our resolutions? During the course of the year, how successful were we in keeping them? If not, why not? How much of it was due to circumstances beyond our control, and how much due to lack of effort on our part? How could we have done better in 2008? How can we do better in 2009? Time to unleash an age-old tool. When rightly used, habit is a powerful tool ….. simple to use – the key is to use it consistently over a period of time.

Before we go further, let’s tie this to health. Our resolutions could be something like losing excess weight or smoking cessation. Or, it could be controlling our anger. These resolutions are directly related to our health. In addition, when we succeed in keeping our resolutions, our nerves release endorphins and “beneficial” neurotransmitters. When we don’t keep our resolutions, we tend to beat ourselves up at some level, resulting in release of stress hormones like cortisol. This can result in increase of blood pressure, increase of blood sugar, and decreased immune response.

Every habit is regulated by neurochemical patterns. Let us consider the habit of anger. How is the habit formed? What do you do when you feel angry? Take an example. Your kid does something that angers you, like leaving the cap off the toothpaste. What do you do? Do you scream? Jam it back on, muttering under your breath? Realize your kid is still learning and shrug it off? Or anything better or worse or in between?

Let us suppose you screamed (no you didn’t, we are just saying so for the sake of this example). Why do you behave the way you do in this situation? One simple answer is that you are habituated to behaving in this way. Think of the sequence of events that your body’s nervous system goes through. You see the cap off the toothpaste, your optic center gets the information, and it communicates with other parts of your brain.

Let us consider the first time this happens. Where does this reaction come from? It could be from something you witnessed. For instance, perhaps you have seen someone else scream at an irritating circumstance, say an authority figure in your childhood, or your favorite actor in the movies. The reaction to this situation is already in your head. Even supposedly spontaneous actions are already in your head (As a Man Thinketh by James Allen, DeVorss & Company, Camarillo, CA).

During one of these episodes, what happens in your nervous system to cause this reaction? The optic center speaks to your “anger” center which tells you it is okay to get angry, and your vocal cords are given the signal to emit the sound called a “scream.” Now, you have established the sequence for release of certain neurotransmitters. You had the beginnings established in your thought itself, and the entire sequence had been established in your thought. All you needed was the stimulus, the irritating circumstance, and you responded with a scream.

This happens a second time. Now you have already established the path for the release of all the necessary neurotransmitters. You go ahead and use it. And it happens a third time, and a fourth …. and so on. You see how you establish habits?

Now, how do you break an undesirable habit? You stop using that established path, and create a new path of neurotransmitters. How long does it take? Dr. Maxwell Maltz, a plastic surgeon from New York, published his book Psycho-Cybernetics in 1960 – it is still a top seller today. Beginning with studies on subjects who had plastic surgery, he showed that it took 21 days for his patients to have a new self-image after the results of the surgical procedure was evident to others. Further research showed that it took 21 days for new neural pathways to form and for the patients to see themselves as new.

What does this mean? If you want to get rid of a bad habit, give yourself a 21-day challenge. Said Mark Twain, “Habit is habit and not to be flung out of the window by any man, but coaxed downstairs a step at a time.” Consider 21 days as 21 steps. Use will-power, change your environment, get rid of anything that would tempt you to indulge in your habit, trick yourself, announce your resolution to your family, friends or colleagues, make it a wager …. if you break your resolution, you pay someone a determined amount of money – use every arrow in your quiver to stack the odds in your favor. Make sure you succeed in avoiding the bad habit for 21 days.

21 days later, you may choose to go another 21 days, but don’t look at that possibility just yet. Take it 21 days at a time. Fool your brain into thinking, “It’s only 21 days – just 21 baby steps – you can handle it!” You can use the 21-day challenge to form a new desirable habit too. Same logic.

Speaking of forming new desirable neural pathways and obliterating undesirable ones, let’s do some possibility thinking. It’s been shown that the human brain has approximately 100 billion nerve cells. The total number of inter-connections these brain cells make with one another is a ginormous number. According to brain researcher Dr. Robert Ornstein of University of California, San Francisco, the number of possible inter-connections between nerve cells is more than the number of atoms in the universe. So, are we saying that there is no limit to forming good habits and getting rid of bad habits? That we can get better and better as individuals and as a society? Are we saying that the sky is the limit in maximizing one’s potential?

Let’s dig deeper into Dr. Ornstein’s research. Bilateral specialization of the brain is what he is best known for – the concept of the right brain and the left brain. The research he did with his colleague Dr. David Galin leads to an understanding of how the left brain is focused on logical, sequential tasks whereas the right brain is holistically, aesthetically driven. The left brain provides the facts or the “text” and the right brain reads the “context” in a situation ( Their research also shows that during deep prayer or meditation, the electrical activity between the left and right brain becomes co-ordinated, making it easier to establish new neural pathways and thus, new habits.

I hope these ideas help you with keeping your New Year resolutions, and thus feeling good about yourself. I will be thinking good thoughts about you.

Until next week, my friend, please do take care of yourself and your health ……

Dr. Ajit Damodaran

Calmly active, actively calm

December 26, 2008

Dear friend,

Merry Christmas! May you and your loved ones be showered with blessings this wonderful day, and every day ….

It is the day to write a brief article today on a topic conducive to peace and goodwill. Peace and goodwill to one’s own self, which leads to peace and goodwill to all. And good health.

A healthy spiritual life is a significant factor in good health. The organized study of the relationship between spiritual faith and healing has even been given a name, the ‘epidemiology of religion’ (Dr. Jeff Levin, author of Essentials of Complementary and Alternative Medicine – co-authored with Dr. Wayne Jonas).

Prayer and a deeper connection to the universe result in a greater orderliness of brain functioning. This results in improved cardiovascular health and decreased risk of depression. This would obviously lead to greater longevity and an improved quality of life. Okay, even from a purely self-serving viewpoint, believing in God and prayer and meditation is good for health. Dr. Larry Dossey in his book Healing Words, and Dr. Bernie Siegel in his book Love, Medicine and Miracles present some excellent case studies on prayer and healing.

Dr. Herbert Benson, Professor of Medicine at Harvard Medical School Mind-Body Medical Institute says about meditation, “The relaxation response comprises an assortment of physiological changes: a decrease below resting levels in oxygen consumption, heart rate, breathing rate and muscle tension – plus a decrease in blood pressure in some people and a shift from normal waking brain patterns to a pattern in which slower brain waves predominate.”

When the mind is in a calm, undisturbed state, brain waves called alpha waves are registered on the electroencephalogram (EEG). In meditation, one can go into states more tranquil than the alpha state. When you develop a habit of regular prayer/meditation, you carry the effects of that into your active life. You find yourself in the “zone” as you go about your daily activities. This “calmly active, actively calm” (to quote Yogananda) state of mind and body essentially carries your deep prayer into your 24-hour routine.

That does not mean walking around like a zombie. It means being calmly in control of your emotions no matter what the situation. No unnecessary release of cortisol, adrenaline and other stress hormones. Nerves of steel, blood pressure totally under control, breathing calmly…. all conducive to good health. 

My friend, until next week, please do take care of yourself and your health.

Dr. Ajit Damodaran

Antipsychotic Seroquel

December 19, 2008

Dear friend,

The mind …… what a vast ocean of knowledge, pun intended. The mind can be so, so complicated. Controlling one’s mind is probably the most difficult task in the world. I hear Tiger Woods has tremendous mind control and focus. I know that contributes to his being probably the best golfer in the world.

The mind …..posing some philosophical questions. Where does the mind begin? Where does it end? Is it limited to the brain? Does it extend to the body? Does it extend beyond the mind and body? What about consciousness? What is consciousness? Is that chemistry? Physics? Metaphysics? No, I won’t get into all that ….. these are answers each of us finds on our own.

Alright ….. pulling myself back down to earth …. from a totally practical perspective, there are so many stimuli that are fed to the mind. Each of us has such varied responses to the same stimuli, partly dependent on our conditioning from years past. Every one of us has varying degrees of activity of different neurotransmitters in our central and peripheral nervous systems ….. some of it balanced, others unbalanced. When, for whatever reason, there is an imbalance of neurotransmitters in the brain, a combination of wise psychiatric counsel and medication can improve the quality of life.

Quetiapine (pronounced kwe-tie-a-peen) is sold under the brand name Seroquel. It is the most commonly prescribed antipsychotic drug in America. Psychosis is “osis” of the “psyche” (Greek origin) – literally, abnormal condition of the mind. Seroquel was introduced in 1997 as a treatment for schizophrenia.

In schizophrenia (from Greek “schizein” = to split, “phren” = mind), there is increased activity of neurotransmitter dopamine in one of the major dopamine pathways in the brain called mesolimbic pathway. This pathway is involved with emotions of motivation and re-inforcement. The exact mechanism of action of Seroquel is not known, but it is proposed that its primary effect is from antagonism of a type of dopamine receptor D2 and a type of serotonin receptor 5-HT2.  Dopamine and serotonin are neurotransmitters. Dopamine is involved in motor activity, cognition, motivation and reward, sleep, mood, attention and learning. Serotonin modulates sleep, sexuality, anger, aggression, body temperature, mood and appetite.

In addition, Seroquel is metabolized to the active metabolite norquetiapine. In non-human subjects (primates), norquetiapine was shown to inhibit norepinephrine transporter (NET). First of all, what is norepinephrine? Norepinephrine, also called noradrenaline, is a relative of epinephrine or adrenaline. Norepinephrine is a neurotransmitter that plays a role in attention and focus as well as depression. In fight-flight-fright situations, norepinephrine is also released as a stress hormone, but that’s a different story.

NET, that was referred to above, is a protein that helps the reuptake of the neurotransmitter norepinephrine back into its pre-synaptic storage vesicles (for a detailed description of this kind of re-uptake process, please refer to last week’s article on sertraline).

When norquetiapine inhibits NET, it prevents the re-uptake of norepinephrine. This increases the levels of norepinephrine in specific areas of the brain, which contributes to the anti-depressant effect.

Seroquel is also used in the treatment of bipolar disorder. Bipolar disorder is characterized by depressive and manic phases. Seroquel is useful in the depressive episodes. It is used alone, or in combination with lithium or Depakote (divalproex). The combination therapy is useful because lithium and Depakote are particularly useful in stabilizing mood in the manic phases of bipolar disorder.

Off-label uses of Seroquel include Tourette’s syndrome (a tic disorder characterized by involuntary movements and verbal utterances), autism, alcoholism, restless legs syndrome, obsessive-compulsive disorder and post-traumatic stress disorder (PTSD). Speaking of PTSD, check out – well-written scientific blog on November 11, 2008 (Veteran’s Day).

Seroquel has also been used as a sedative for sleep and anxiety disorders. Antagonism of the histamine H1 receptor has been proposed for the sedative effect of the drug. Yes, histamine is another neurotransmitter.

Sedation is a side-effect of Seroquel when it is not used for that purpose. Orthostatic hypotension (drop in blood pressure when you suddenly stand) is another side-effect mediated by antagonism of adrenergic alpha1 receptors. Weight gain can be a significant side-effect. There have been claims that the use of this medication can lead to diabetes. Tardive dyskinesia – uncontrollable movements of the face, tongue or other parts of the body – is a possible side-effect. Rarely, use of the drug can lead to neuroleptic malignant syndrome. This is characterized by muscle rigidity, fever, unstable blood pressure and delirium possibly leading to coma. The enzyme creatine phosphokinase (CPK) levels are raised due to high muscle activity – this enzyme is a product of muscle breakdown. If this happens, the drug is to be stopped immediately and supportive treatment given – circulatory and ventilatory, sometimes in intensive care.

Seroquel has addiction potential. “Suzie-Q” is its street name. It’s also been called “quell”. It has been snorted, injected intravenously sometimes with cocaine, and used as a “downer” to come off cocaine or amphetamine.

Let’s make a transition from the streets of society to the corridors of power in the world. Is it possible that some of the villainous leaders of history could have been psychotic? Hmmm …. could antipsychotic drugs have prevented some genocides? Who knows? Just some food for thought.

Until next week, please take care of yourself and your health.

Dr. Ajit Damodaran

Nerve cell talk – sertraline (Zoloft)

December 5, 2008

Dear friend,


I’m sure you had an awesome Thanksgiving. I’m sure there was plenty of food intake. Felt really sleepy after that dinner? The turkey ….. all that tryptophan …… really? That part about the tryptophan …. a little exaggeration ….. did you know that chicken has about the same amount of tryptophan as turkey?


So how about the popular idea that turkey has high amounts of the amino acid tryptophan and that’s what has the soporific effect? Actually, you feel sleepy because of all the carbohydrate you ingest. What’s the mechanism? When the carbohydrates are absorbed into the blood, insulin is released. One of the effects of insulin is absorption of amino acids circulating in the blood. The amino acids that are favored in this absorption by cells are not tryptophan – which means there is a higher percentage of tryptophan left in the blood.


Part of the tryptophan remaining in the blood is absorbed into the brain. In the brain stem, the tryptophan is converted into a neurotransmitter called serotonin. This is a natural calming, even sedating nerve chemical. In another part of the brain, in a pea-sized organ called the pineal gland, some of the serotonin is converted into a hormone called melatonin. Melatonin is the hormone that is released by the pineal gland in response to darkness and induces sleep – it plays a role in the body’s daily circadian rhythm or biological cycle. That’s the reason for the zzzzzs.


Speaking of the neurotransmitter serotonin (chemical name 5-hydroxy tryptamine), it is a neurotransmitter that plays a major role in our feelings and emotions. Serotonin modulates sleep, mood, appetite, sexuality, anger, anxiety and depression. Which means that its biological formation, metabolic and transportation pathways in the body offer ways to manipulate the levels of serotonin in the brain and body, and produce beneficial therapeutic effects.


Research has produced several families of drugs to increase serotonin levels and thereby provide a remedy for depression. One of the most effective classes of drugs is called SSRIs (selective serotonin re-uptake inhibitors). What do they do? They prevent the reuptake of already biosynthesized serotonin into the pre-synaptic cells of the nerves. Wait a minute. What’s pre-synaptic?


Backing up …… Let’s define “synapse”. Synapses are junctions between nerve cells, or between nerve cells and other body cells. There are hundreds of trillions of nerve cells in the human brain. One nerve cell “talks” to other cells across these junctions. How? The “initiating” nerve cell is called the pre-synaptic cell. In the pre-synapse, docked to the membrane, there are microscopic “bags” called synaptic vesicles that store neurotransmitters. So, how exactly is the message sent across. Associated with every thought, every emotion, there is an electrical current that moves across the pre-synaptic nerve cell. The current reaches the synapse, electrically stimulates the synaptic vesicles and opens up channels in the vesicles to let calcium ions come in. These calcium ions activate certain calcium-sensitive proteins to cause the vesicles release neurotransmitters contained within them. The neurotransmitters travel across the synaptic cleft, the narrow space between the pre-synaptic and post-synaptic cells, and bind to receptor cells on the post-synaptic cells. This results in the activation of the receptor cells, following which there is an appropriate action from the post-synaptic cell. What action is that? It could be a transmission of the same message onward to other nerve cells through the similar processes. Or, let’s say the post-synaptic cell is a muscle cell – the appropriate action could be muscle movement, in combination with a whole bunch of other muscle cells.


Now, all the neurotransmitter molecules released by the pre-synaptic cell does not bind to the post-synaptic cell. Some of the molecules just diffuse in the synaptic cleft. Some of these diffused molecules are metabolized by enzymes to metabolites. And some of the diffused molecules are re-absorbed by the pre-synaptic cell.


This last process, the re-absorption …… re-uptake …… is the process that is of interest to us. A selective serotonin re-uptake inhibitor (SSRI) selectively prevents the re-uptake of serotonin by the pre-synaptic cells.


Sertraline (trade name Zoloft in the U.S., Lustral in the U.K., Zosert in India) is the most prescribed anti-depressant in the U.S. It is an SSRI used for treatment of major depression, obsessive-compulsive disorder (OCD), panic disorder, post-traumatic stress disorder (PTSD), premenstrual dysphoric disorder (PMDD) and social anxiety disorder (SAD). Unlabeled and investigational indications are eating disorders, generalized anxiety disorder (GAD), impulse control disorders, and treatment of mild dementia-associated agitation in non-psychotic patients.


Black-box warnings are required to given with anti-depressants. They can increase the risk of suicidal thinking in patients upto 24 years of age. Sertraline is not approved for use in major depressive disorder (MDD) in children, but is approved for treatment of OCD in children 6 years of age and above. It is not approved for treatment of bipolar depression.


This medicine should not be taken with other medicines called monoamine oxidase inhibitors (MAOI) – in fact, not even within 14 days of taking an MAOI. Why not? It leads to something called serotonin syndrome. What is that? MAOIs as well as several other drugs decrease the breakdown of serotonin, resulting in high concentrations of serotonin in the brain. Serotonin syndrome creates symptoms such as confusion, hallucinations, fever, high blood pressure, tremors and muscle twitching.


Possible side-effects include headache, nausea, dry mouth, upset stomach, decreased interest in sex or decreased sexual ability.


If sertraline administration is suddenly stopped, withdrawal symptoms include emotional instability, dizziness, headache and bad dreams. In pregnant women, the drug does cross the placenta and reach the child. Sertraline is also secreted in breast-milk.


A theory suggests that depression and other psychiatric complaints are a result of an imbalance of brain chemistry, popularly called chemical imbalance. Critics of this theory state that it is largely promoted by pharmaceutical companies so that they can sell more medication. Whatever be the case, there are situations where depression is effectively treated by using anti-depressants like sertraline, resulting in improvement in the quality of life. It is upto the medical professionals treating the patient to determine whether the depression can be treated by psychological counseling and change of lifestyle including setting and working toward goals in various aspects of life, or whether the condition requires drug therapy.


Until next week, my friend, take care of your health, take care of yourself.


Dr. Ajit Damodaran



Happy Thanksgiving!

November 24, 2008

Hello friend,

I wish you a wonderful Thanksgiving with your family and friends.

See you next week, stay well!

Dr. Ajit Damodaran

Advair – for asthma and COPD

November 20, 2008

Hello friend!

Greetings! Let’s talk about breath. Can you think of anything more important to life than breath? What if you find it difficult to breathe? That’s what happens with conditions like asthma and chronic obstructive pulmonary disease (COPD). 

Advair is the brand name of an inhaler combination of two drugs, fluticasone (a steroid derivative – a very mild dose, don’t worry) and salmeterol (a beta-2 agonist), used for control of asthma, COPD and chronic bronchitis. It is available all over the world under different brand names – for example, it is available as Seretide in the United Kingdom, and as ForAir in India.

What is asthma? It is a chronic disease of the respiratory system. It’s when the immune system of the body becomes overprotective. It starts looking at simple things like dust and pollen as the enemy (remember the movie Conspiracy Theory starring Mel Gibson? – our body starts behaving like Mel Gibson’s character). The airways get constricted, and there is release of mucus along with inflammation. As a result, there is difficulty breathing, and in acute episodes, wheezing, shortness of breath and cough.

The mechanism of constriction of the airways in the lungs is blockage of the beta-2-adrenergic receptors of the smooth muscle by an immune system component, Immunoglobulin E.  This is accompanied by inflammation. Until recently, the main theory advanced has been that immune cells called helper T cells were the main culprits creating the inflammation response.

Recently, a couple of Boston researchers advanced another theory – the main players may not be helper T cells, but natural killer T cells ( Natural killer T cells are also immune system cells. Of course, a lot more research has to be done before establishing in detail the role of natural killer T cells. There is a possibility that this discovery may be the beginning of even more advances in the medicinal treatment of asthma.

Genetic and environmental factors are involved. Children seem to suffer from asthma more in developed countries. A hypothesis that has been suggested is that due to increased hygiene and aggressive use of antibiotics in children, certain beneficial bacteria in the gastro-intestinal tract of children are wiped out. This modifies the immune system, resulting in asthma. Emotional stress can also cause asthma, the suggested mechanism involving the immune system. Environmental factors such as automobile and industrial pollution, cigarette smoke and extensive exposure to cold air act as triggers to evoke an asthma attack, especially when there is a predisposition due to genetics or a compromised immune response.

The practice of yoga has been reported to reduce asthma. A journal report (Thorax 2002 Feb;57(2):110-5) -Sahaja yoga in the management of moderate to severe asthma: a randomised controlled trial, by Manocha et al from the Natural Therapies Unit, Royal Hospital for Women, NSW, Australia draws the following conclusion: “This randomised controlled trial has shown that the practice of Sahaja yoga does have limited beneficial effects on some objective and subjective measures of the impact of asthma. Further work is required to understand the mechanism underlying the observed effects and to establish whether elements of this intervention may be clinically valuable in patients with severe asthma”. Yoga is known to reduce stress. Since it is known that stress is a contributor to asthma, could the reduction in stress be one of the mechanisms by which yoga controls asthma?

COPD. Very similar to asthma, except that the constriction of the airways is not easily reversible, and progressively gets worse with age. With time, the lung tissue gets destroyed and causes emphysema. The cause of COPD is partly genetic, coupled with cigarette smoke, pollution, occupational air hazards, frequent lung infection and a diet that includes a lot of cured meat. Even a history of cigarette smoking that leads to long-term inflammation in the lungs can spark an auto-immune response leading to COPD, many years after cessation of the smoking habit. In later stages, COPD can lead to pulmonary high blood pressure and cor pulmonale (right ventricular dilation and hypertrophy in the heart).

Fluticasone, the steroid component of Advair, reduces inflammation in the airways. In the inhaled form, it is directly delivered to the lungs where the inflammation has occurred, and is not significantly delivered to the rest of the body, resulting in fewer steroid side-effects.

Salmeterol is a long-acting beta-2 agonist or LABA. It acts on the beta-2 adrenergic receptor, thus relaxing the muscles around the airways to prevent wheezing and shortness of breath.

For the long-term treatment of asthma and COPD, Advair is inhaled by mouth twice daily.

Advair is not to be used for acute symptoms of asthma or COPD. For these, your doctor will have prescribed a short-acting beta-2 agonist. Also, do not use Advair if you have a severe allergy to milk proteins. This medication has not been approved for use during pregnancy or while breast-feeding.

Common side-effects are upper respiratory infections, thrush in the mouth and throat, headache, hoarseness and voice changes, bronchitis, cough and nausea/vomiting. In children with asthma, Advair may cause infections in the ear, nose and throat. Make sure you rinse your mouth with water after each dose, and spit the water out.

Now for some controversy. Salpeter at al at the Santa Clara Valley Medical Center published an article in 2006 (“Meta-analysis: effect of long-acting beta-agonists on severe asthma exacerbations and asthma-related deaths” Ann Intern Med 144 (12): 904–12). The authors say in a press release: “These agents can improve symptoms through bronchodilation at the same time as increasing underlying inflammation and bronchial hyper-responsiveness, thus worsening asthma control without any warning of increased symptoms. Three common asthma inhalers containing the drugs salmeterol or formoterol may be causing four out of five US asthma-related deaths per year and should be taken off the market”. Essentially, they are saying that symptoms are the body’s way of asking for help. When we mask the symptoms, the disease continues to worsen, but the lack of symptoms prevent us from realizing it – and that can and has lead to death.

Here’s a response to the above opinion: “Salpeter and colleagues … assert that salmeterol may be responsible for 4000 of the 5000 asthma-related deaths that occur in the United States annually. However, when salmeterol was introduced in 1994, more than 5000 asthma-related deaths occurred per year. Since the peak of asthma deaths in 1996, salmeterol sales have increased about 5-fold, while overall asthma mortality rates have decreased by about 25%, despite a continued increase in asthma diagnoses. In fact, according to the most recent data from the National Center for Health Statistics, U.S. asthma mortality rates peaked in 1996 (with 5667 deaths) and have decreased steadily since. The last available data, from 2004, indicate that 3780 deaths occurred. Thus, the suggestion that a vast majority of asthma deaths could be attributable to LABA use is inconsistent with the facts.” – Harold Nelson and Paul Dorinsky, 2006, Annals of Internal Medicine, 145 (9), 706.

Dr. Salpeter’s response to the above letter: “It is true that the asthma death rate increased after salmeterol was introduced, then peaked and is now starting to decline despite continued use of the long-acting beta-agonists. This trend in death rates can best be explained by examining the ratio of beta-agonist use to inhaled corticosteroids… In the recent past, inhaled corticosteroid use has increased steadily while long-acting beta-agonist use has begun to stabilize and short-acting beta-agonist use has declined… Using this estimate, we can imagine that if long-acting beta-agonists were withdrawn from the market while maintaining high inhaled corticosteroid use, the death rate in the United States could be reduced significantly …” 2006, Annals of Internal Medicine, 145 (9), 708-710.

As a result of published research, beginning 2005, the Advair label has a warning that the drug might increase the chance of asthma attacks that can result in death.

Here’s the bottom line. The benefits of using Advair far outweigh the risk, even of death. The incidence of death is about one in a 1000. On the other hand, the use of Advair improves the quality of life, and saves lives by allowing patients to breathe better and longer.

Until next week, breathe deeply. Live well. Please take care of yourself and your health.

Dr. Ajit Damodaran

Drinking water

November 11, 2008

Hello friend,

I’m writing this on Veteran’s Day, November 11 – over the decades, our veterans have sacrificed much to protect our way of life. If you are a veteran, thank you, thank you! And if you’re not, just as I’m not, please make sure you thank at least one veteran today.

Thus far, I’ve been writing articles on drugs. How about water? Kind of important for health, isn’t it? Well, in 2004, about half of the world’s population had no access to safe drinking water. One of the Millennium Development Goals of the United Nations, in collaboration with several international organizations including the Rotary Club, is to halve, by 2015, the proportion of people without sustainable access to safe drinking water and basic sanitation. So, we’re hoping that by 2015, about 75% of the world will have access to safe drinking water.

What kind of water is good for drinking? The Environmental Protection Agency (EPA) of the U.S. has a list of contaminants – these are microorganisms, different kinds of chemicals and radioactive contaminants – that have been assigned maximum contaminant levels (MCL) which are enforced by law, and maximum contaminant level goals (MCLG) which are not enforced by law. The MCLG is that level below which there is no known or expected risk to health. What’s the difference between MCL and MCLG again? Let’s take an example. The MCLG for coliform bacteria including fecal coliform and E. coli (which is a measure of fecal contamination) is 0 per cent. The MCL is 5 per cent. How is that percentage arrived at? More than 5.0% samples total coliform-positive in a month. (For water systems that collect fewer than 40 routine samples per month, no more than one sample can be total coliform-positive per month.) Every sample that has total coliform must be analyzed for either fecal coliforms or E. coli. If there are two consecutive total coliform-positive samples, and one is also positive for E.coli fecal coliforms, that water has an MCL violation.

In plain English, the ideal situation is there should be never any contamination. Zero. However, for practical purposes, there can be a very slight contamination, as explained above. For more details, please read To find out the quality of drinking water where you live (in the U.S.), please contact your local government to send you a Consumer Confidence Report (CCR) – they should be automatically sending it to you once a year. You can also check the EPA website at http://www.epa.safewater/ccr/whereyoulive.html to get the same information. You may be surprised to know that many a time, the contaminant levels exceed the MCLs.

There have been recent press reports about traces of medicine that we consume are being found in drinking water supply. An report in September 2008 is titled Drugs in water affect 46 million in U.S.  The article goes on to say “The drug residues detected in water supplies are generally flushed into sewers and waterways through human excretion. Many of the pharmaceuticals are known to slip through sewage and drinking water treatment plants.” Disgusting? You bet. But America still has better water supply than most places in the world.

What’s the solution to the problem? As far as water for drinking, we make sure that it is filtered. Get one of the top filters recommended by (pay attention specifically to what contaminants are filtered by your filter of choice and what contaminants you have in your water supply) and if you’d like, boil the water as a second step. As far as water for other purposes at home, the contamination is not significant. However, if you’d rather, there are filters available to purify the entire water supply into your home.

Bottled water? As we live our present lifestyle as movers and shakers (yup, talkin’ about you), we consume bottled water. The U.S. alone consumed more than 9,000 million gallons of bottled water in 2007, double that in the year 2000 (in excess of 4,500 million gallons that year).

Guess what? Bottled water is less regulated than tap water. It is regulated by the Food and Drug Administration which requires that bottled water be as safe as tap water. However, whereas the EPA requires that government-certified labs test tap water daily, the FDA requires only once-a-year testing. The EPA has set controls on bacteria, the FDA has not. Need more such facts? Go to (that’s the website of Natural Resources Defense Council).

With all this information, what bottled water should we drink? The website provides you that info – that’s the website of the International Bottled Water Association (IBWA). Any member of that association provides you with bottled water with contaminants, if any, below FDA standards. I got this information and some more above from the book The Seven Pillars of Health, by Dr. Don Colbert, MD (published by Siloam).

How much water should we drink? A rule of thumb does say eight 8-ounce glasses of water a day. Or, total water intake in ounces should be half of our body weight in pounds (that includes the water we get from fruit and vegetables – if we are getting the right number of portions, that would be about a quart of water – so, considering an average body weight, the actual amount of water we should drink would probably be about eight 8 ounce glasses of water a day). But of course, it does vary with body weight, the climate, active or sedentary lifestyle and so on. Another suggestion that has been offered is to drink enough water where you urinate every three to five hours, and the urine is colorless to light yellow. This much we do know, generally we tend to drink a lot less of water than we should. I do need to let you know, any major change in your water intake or dietary habits must be undertaken only in consultation with your physician.

Drinking water does mean drinking water – not coffee, tea, caffeinated drinks and so on. Caffeine is a diuretic, commonly called a fluid medication – it makes the body get rid of more water through urine than the volume consumed.

Why is drinking enough water important? Here are several reasons why. Our body is primarily aqueous. The brain and the muscles are 75 per cent water, the bones are 22 per cent. Water carries oxygen and nutrients to every cell of the body. Blood is an aqueous medium of blood constituents. Water also gets rid of waste from the body. It cushions joints and protects vital organs. It’s great for skin health too.

What if you don’t drink enough water? Dehydration. Headaches, low blood pressure, dizziness, fainting, muscle cramps …. in extreme cases, delirium, unconsciousness, leading to death. About age 50 onward, we don’t feel as thirsty as we used to when the body loses water. With the result that there’s increased possibility of dehydration. When senior citizens have pneumonia, if it is accompanied by dehydration, there is a theory that the body is not able to create enough fluid to get rid of microorganisms in the phlegm. Nursing homes and caregivers to senior citizens do have to keep this in mind and make sure that their wards get adequate water, with the understanding that they have diminished thirst sensation and may not always ask for water.

Even if we don’t have symptoms of dehydration, being mildly dehydrated is also not ideal for health. We do have to make sure we drink enough water to be healthy. Just a visual, if it helps – with enough water, we look like healthy grapes, without enough water we look like shriveled, dry raisins – or prunes. Oooh – graphic, huh?

Improving health, comfort and appearance by drinking pure water? Perfect! That’s just the beginning, of course. The foods we eat, the lifestyle we lead and even the thoughts we think, the emotions we feel …. over time, all have effects on the water-holding capacity of the plasma proteins and subsequently the ability of plasma to nourish different tissues and organs – Dr. R.D. Kulkarni, MD, my research adviser when I did my Masters’ Degree in Pharmacy at the University of Mumbai, India, explains these concepts in his book Principles of Pharmacology in Ayurved, (Ayurved, literally the science of life in Sanskrit, is the traditional system of medicine in India). Dr. Kulkarni is a doctor of modern medicine, formerly Post-Doctoral Fellow in Medicine at the Johns Hopkins Hospital in Baltimore, Professor of Pharmacology retired from the University of Mumbai, who used his logical powers of modern pharmacology to evaluate the ancient medicinal tradition of India.

Take care of yourself and your health. We’ll meet again next week!

Dr. Ajit Damodaran

The Flu Vaccine – Saving Lives

November 5, 2008

Hello friend!

Smallpox was eradicated in 1979. Polio is almost eradicated, thanks to the WHO, the UNICEF and the Rotary Club. How was this accomplished? Answer in one word – vaccination.

So anytime you hear anyone speak passionately against vaccination, remember smallpox and polio. If it were not for vaccination, a lot more people would be paralyzed or ….. dead. Historically, vaccination originated in China and India a couple of millenniums (would that be “millennia”?) ago.

How does vaccination work?

Let’s consider influenza or the flu. It is caused by a virus. The virus attacks the body and causes flu symptoms. How? It latches on to membrane cells of the nose, throat and lungs, and uses up the cell constituents to grow and reproduce, killing the host cells in the process. This causes runny nose, coughing, sneezing, headache, fever – all the flu symptoms are caused by the body trying to get rid of the waste cells and the virus. If someone already has asthma or emphysema, the symptoms obviously get worse. In the weak or the elderly, flu can lead to death. Yes, there are about 36,000 deaths every year due to the flu and associated infections and causes, in the U.S. alone.

When the virus attacks the body, the body’s immune system rises to the occasion and fights the virus. It creates antibodies against the virus. However, the virus creates the symptoms of the disease too. If the virus is killed and then injected intramuscularly as a flu vaccine, it creates the same antibody response without evoking the symptoms of flu. The vaccine can also be given intranasally – it’s available under the brand name FluMist. It contains attenuated or weakened live flu virus (LAIV = Live Attenuated Influenza Vaccine). Although the viruses are live, they cannot give you the flu, although they can give you mild symptoms like runny nose, nasal congestion, headache, sore throat and chills. The viruses are cold-adapted, meaning they can cause mild infection only in the cool temperatures of the nose, not the warmer temperatures of the lungs. The intranasal vaccine is given only to healthy individuals between 2 and 49 years of age, who are not pregnant.

How effective is the flu vaccine? The flu virus strains keep on changing genetically by a couple of mechanisms. So the vaccine that is developed this year is 70 to 90% effective in healthy individuals, and less so in unhealthy and elderly individuals, but will be less effective next year. So the vaccine has to be reformulated next year, and every year to keep up with the genetic changes, that scientists try to predict to the best of their ability. Typically, the flu vaccine is tri-valent. It is effective against the 2 strains of influenza A viruses and one strain of influenza B virus likely to be the most dominant that year. There is approximately a six-month lag time between the time the prediction is made and the flu vaccine is available. The process is co-ordinated by the World Health Organization.

Even though the trivalent vaccine is created to be specifically effective against 3 strains of influenza virus, it is also partially effective against related strains of the viruses genetically close to the three. Also, an indirect advantage of getting vaccinated is to reduce the chances of being a carrier of the virus to elderly or unhealthy kith and kin, and to the community in general. This is the reason why health care professionals are encouraged to get flu vaccination annually.

Research in the field of genetics continues to make the vaccine more effective over time. Kudos to my friends doing that research.

Possible side effects of the flu vaccine are headache, mild fever, discomfort at the site of injection, and muscle ache. They shouldn’t last long. Please contact your doctor if they do. Rarely, the body responds rather intensely to the viral antigen, resulting in the Guillain-Barre syndrome – it’s an auto-immune reaction of the body, resulting in paralysis in the lower limbs spreading to the upper limbs. If this happens, immediate treatment with intravenous immunoglobulins and plasma filtration is required.

The vaccine is manufactured in chicken eggs. If you are allergic to eggs, please be aware that you might be allergic to the i.m. vaccine too.

A controversy that has received press is the long-term effect of a preservative called thimerosal, an organo-mercury compound that is used in flu vaccine. There have been questions as to whether thimerosal causes autism in children. The Institute of Medicine panel of 2004 could not find any evidence of the same. However, the American Academy of Pediatrics (AAP) decided to err on the side of safety and continue not using thimerosal in vaccines for children. In fact, in 1999 the AAP and the Centers for Disease Control (CDC) recommended the phasing out of thimerosal from vaccines for children, and that has been done for most vaccines.

As we understand the positives and negatives of this precautionary measure against the flu, the positives overwhelmingly trump the negatives. Personally, methinks the greatest positive is that, even if we are healty enough not to get the flu, getting the flu-shot reduces the chances of our carrying the virus to folks less healthy than us. What price can we put on that? And if there is ever a time that our body defenses are down, be it due to physical or emotional factors, does it not make more sense to have beefed up the body’s defenses?

Is health not better than disease? And for 36,000 people each year, is life not better than death? This year, you could be saving the life of someone you love.

Please go get the flu shot. The earliest you can get it in North America is in September. But you can get the flu shot in later months too. Typically flu season peaks around January or later, although it can hit as early as October too. For some reason, it happens during the cold season.

Please take care of yourself and your health.

Dr. Ajit Damodaran

Warfarin – blood thinner

October 28, 2008

Hello friend,

Thank you for reading. I am really enjoying writing my weekly blog. As I write, and as I receive responses to my writing, my understanding of the basics of pharmacology of each medication is strengthened. Win-win situation, eh?

This week, I’ll be writing on rat poison and blood thinner. What a combination!

Warfarin was first synthesized in the laboratories of the University of Wisconsin at Madison. The Wisconsin Alumni Research Foundation (WARF) funded the research – hence the name warfarin, derived from WARF. It was originally introduced as a rodent killer in the late 1940s. Because of the blood thinning properties of warfarin, it caused hemorrhage in rodents leading to death. In the 1950s, the therapeutic anticoagulant activities of this compound in humans were discovered and begun to be used. Warfarin prevents thrombosis and embolism.

What is thrombosis? It’s a blood clot that prevents the regular flow of blood. How does that happen? Suppose there is an injury to a blood vessel. The natural defenses of the body come into play. The platelets in the blood and fibrin combine to form a clot so as to prevent blood loss. Of course, there can be degrees of clot formation. What if the body gets into high gear and forms a really big clot? Could it be so large that it blocks much of the diameter of the blood vessel? What if it breaks free and travels through the blood stream and lodges itself into another part of the blood stream? (this is called an embolism). And, why would such a large clot be formed? It could be an infection or an injury in a blood vessel, genetic or auto-immune reasons that make the body over-react to such stimulus, it could be that the blood is moving slowly, say when you sit in a confined space for a long period of time without much movement, or it could be a combination of these factors.

A couple of the more devastating effects of thrombosis/embolism is a heart attack or a stroke. How do we prevent it? That’s where warfarin helps.

Warfarin is the generic name of the drug. It is marketed in the generic form, as well as under the brand names Coumadin and Jantoven. It is used to treat or prevent blood clots in the veins (venous thrombosis) or lungs (pulmonary embolism) or following heart valve replacement, to name a few conditions.

What is the mechanism of action? It inhibits an enzyme called vitamin K epoxide reductase. This is an enzyme that plays a significant role in activating certain clotting factors in the blood. Warfarin is called a vitamin K antagonist.

When warfarin is used as a drug, it is very important to regularly monitor its effects and adjust the dose accordingly. This is done by measuring INR (international normalized ratio), a blood test that measures the clotting efficacy of the blood. Genetics plays a role in the response of the individual to warfarin. Also, warfarin interacts with other drugs like antibiotics and thyroid medication,  as well as with some kinds of food, especially those with high vitamin K, like spinach, kale and collards. It interacts with herbs like ginseng, St. John’s wort, gingko biloba as also garlic and ginger.

The primary side-effect is excessive bleeding and bruising. When the INR rises, there could be bleeding from the gums, in the stools or bleeding from the nose. It’s important to avoid engaging in sports and other activities that might cause injury and bleeding, and to be gentle while brushing one’s teeth and shaving.

A less common but severe complication can occur especially when initiating warfarin treatment. A natural anti-coagulant factor that occurs in the body is protein C. Warfarin reduces the levels of protein C faster than it reduces the coagulant factors. In individuals that have a genetic problem with originally lower levels of protein C, the sudden reduction of protein C causes a paradoxical coagulation, resulting in massive thrombosis – this can lead to skin necrosis (literally skin death) and gangrene. To avoid this, another anticoagulant heparin can be given intravenously along with the beginning of warfarin therapy.

There have been some reports of increased osteoporosis-related fracture in patients on warfarin therapy. This could be due to reduction in bone minerals or vitamin K deficiency from long-term use of warfarin.

Rarely, there can be severe pain and darkening of toes, typically the big toe, to the point of what’s been called the purple toe syndrome. This is due to cholesterol particles breaking loose from atherosclerotic plaque and migrating (cholesterol embolism) to the blood vessels of the feet.

Despite the side-effects and the need for regular monitoring, warfarin is a very useful drug. If someone has had a heart attack, it is used to reduce the risk of stroke and further heart problems.

I hope the information was useful. Until next week, please take care of yourself and your health …..

Dr. Ajit Damodaran

Lisinopril – for blood pressure

October 19, 2008

Hello, my friend,

In South America, there is a venomous pit viper called jararaca. Medicine from a snake? Absolutely!

In 1970, experiments were published about a peptide (a small protein) called bradykinin potentiating factor (BPF) derived in Brazil from the venom of the snake Bothrops jararaca (that’s the scientific name). BPF inhibits an enzyme found in our body called angiotensin converting enzyme (ACE). When ACE is inhibited, there is a reduction in blood pressure.

In the mid-1970s, a drug called captopril was synthesized from BPF. That was the first medication for high blood pressure in the class ACE inhibitors.

What is blood pressure (BP)? Why is it important? BP is the force that’s created against the walls of arteries as blood is transported through the body. Too much pressure can damage the arterial walls. When you take BP, it appears as two numbers. The higher number is the systolic pressure, which is the measure of the pressure when the heart pumps blood into the arteries. The lower number is the diastolic pressure, the pressure when the heart rests between beats. For an adult, the normal blood pressure is 120/80 or less. With an excited emotional state or activity, BP does rise temporarily, but it comes back to resting state.

When the BP stays consistently high, the condition is called hypertension. Over a period of time, that can lead to heart problems, kidney problems, damage of the retina in the eye, or stroke. As BP increases slowly with time, we don’t feel any symptoms. The first symptom could be death. This is why hypertension has been called the silent killer. Routine visits to the doctor now become even more important, don’t they? Catch it early, and control it.

Essential hypertension is when there appears to be no root cause – however, there are risk factors – men  are more likely to have it than women, and blacks more than whites in America. More salt in the diet, not enough potassium, calcium or magnesium in the diet, stress, obesity, diabetes, chronic uncontrolled alcohol intake, and lack of physical activity are all risk factors.

Secondary hypertension is when it is because of another condition, often kidney disease.

One of the primary mechanisms by which our body controls blood pressure is a physiological process called the renin angiotensin system. How does that work?

Certain kidney cells produce and store an enzyme called renin. This enzyme is released when there is a fall in blood pressure, or reduced sodium levels in the blood, when we are faced with a fight-flight-fright situation that activates our sympathetic nervous system, or the kidney is exposed to hormone-like substances called prostaglandins or medicinal drugs called beta-agonists.

Renin acts on a substance produced by the liver, called angiotensinogen, which circulates in the blood. The product is a peptide called angiotensin I. An enzyme called angiotensin converting enzyme (ACE) cleaves angiotensin I to produce the peptide hormone angiotensin II. Most of this last reaction happens in the capillaries of our lungs.

Angiotensin II (AII) is a very powerful agent to increase blood pressure. It does so by constricting blood vessels, and by activating the adrenal gland to release aldosterone. Aldosterone causes the kidney to reabsorb more sodium and water as a result of which there is increase in the volume of blood. This causes an increase in blood pressure. AII increases BP by a couple more mechanisms. It causes the medulla to increase cardiac output, and stimulates the hypothalamus to increase our thirst and to stimulate antidiuretic hormone (ADH) which gets the kidney to reabsorb even more water. As a result of these two mechanisms, our blood volume increases even more, causing an increase in BP.

It stands to reason that by controlling the effects of angiotensin II, we can decrease blood pressure, doesn’t it? What if we were to inhibit the enzyme that catalyzes the conversion of angiotensin I to angiotensin II? That would result in less production of AII.

That’s exactly what an ACE inhibitor does. An ACE inhibitor is a competitive inhibitor of ACE. Being structurally similar to angiotensin I, the ACE inhibitor links to ACE molecules, not leaving enough ACE to act on Angiotensin I. This means less Angiotensin II is formed.

As we saw earlier, captopril was the first in this class of anti-hypertensive drugs. The second drug was enalapril. The third, that was introduced in the early 1990s, was lisinopril (brand names in the U.S. are Prinivil and Zestril).

Lisinopril is different from other ACE inhibitors in that it does not have to be converted by the liver into another entity to activate it. It is water-soluble, penetrates body tissue very well, stays in the body for a long time (as a result, it can be given as a once-daily dose) and is excreted unchanged in the urine. Lisinopril can be used with other medicine to treat congestive heart disease or to improve survival in patients after a heart attack.

This medicine may cause dizziness or even fainting when you first start using it. Make sure you don’t drive or use any heavy machinery before you know how your body reacts to this medicine. Inform your doctor immediately if you have difficulty breathing, tightness in the chest, or swelling of face or lips, or rash/hives. Also tell your doctor immediately if you have unusual heartbeat, nausea or diarrhea, change in amount of urine, unusual joint pain or muscle pain. Drink plenty of water if engaging in activities that cause perspiration. Rarely, it can lower your resistance to infection – avoid close contact with people who have colds or other infections. If you take anti-diabetic medications, lisinopril may affect your blood sugar – please do monitor your blood sugar carefully. This drug should not be used by pregnant women. It’s unknown if it’s secreted in breast milk. It’s better not to take it while breast-feeding.

Cough is a fairly common side-effect with lisinopril and other ACE inhibitors. If it gets bothersome, tell your doctor.

Control of high blood pressure is very important to prevent heart, brain, eye, kidney and other problems as we grow older. When there is a slight consistent increase in blood pressure, your doctor will probably ask you to enforce lifestyle changes – like getting regular exercise, dietary changes like more plant-based food, less sodium, enough potassium (typically at least 3,500 mg. per day) less fat, reduction in calorie intake, controlling cholesterol through diet and medication, and so on. Deep breathing exercises like in yoga, connecting emotionally to loved ones at a deeper level, having a pet like a dog or a cat to get some unconditional love, lots of good humor and laughter, and prayer …… all of this induces a feeling of well-being and helps in good cardiovascular health.

However, if all of that is not enough, and if medication is necessary, a diuretic medication and an ACE inhibitor can be the first line of medication.

Whatever it takes, my friend, whatever it takes! Until we meet next week …. please do make your health a high priority!

Take care …. of yourself and your health ….

Dr. Ajit Damodaran

Metformin – medication for Diabetes type 2

October 13, 2008

Hello friends!

The drug metformin is the subject of our discussion today.

In certain cultures, diabetes mellitus, a condition that causes hyperglycemia or high blood sugar, has been called the rich man’s disease. That’s a reference to type 2 diabetes which is associated with an over-abundance of food intake and resulting obesity.

In people with no diabetes, as the glucose in the blood increases, the beta cells of the pancreas release a hormone called insulin, that sets off biochemical processes resulting in the use of sugar for energy or storage of sugar in the body. In diabetics, this biochemistry is compromised.

Most people with diabetes have one of two kinds, type 1 and type 2. There are several other forms of diabetes too, but that can be the subject of another article. Type 1 diabetes is due to deficient production and/or release of insulin by insulin-producing beta cells, possibly due to genetic factors. Some scientists have suggested that some type 1 diabetes could be due to an auto-immune mechanism, where the body destroys its own beta cells in response to a viral infection. Insulin injections are pretty much the only way the blood sugar can be controlled in type 1 diabetes.

Type 2 diabetes or adult onset diabetes mellitus is the focus of our interest here. There are genetic and environmental factors at work here. The beta cells make insulin, but the body is not able to use it properly. In recent times, the incidence of diabetes has risen to almost pandemic proportions. Worldwide, 6% of the adult population is afflicted. In the USA, 7-8% of the population are diabetics. Increase in diet and decrease in physical activity are to blame. There is a condition called metabolic syndrome – abdominal fat, high blood pressure, high triglycerides, low high-density lipoprotein or HDL, and insulin resistance – these are all risk factors.

Let’s step back for a moment. So, there’s an increase in blood glucose. What’s the big deal? Here’s what happens. We eat food. The food is absorbed. Routine biochemical pathways create glucose from the carbohydrates we eat. Glucose levels rise in the blood. Insulin that is synthesized by the beta cells of the pancreas is released, resulting in the uptake of glucose by body cells – as a result, the blood glucose levels fall to normal levels. In diabetes, blood glucose levels remain high.

In extreme cases, when blood glucose levels are too high, the blood osmotically draws out water from cells. The kidney gets rid of the extra water with dissolved glucose in the urine. This can lead to dehydration, electrolyte imbalance and eventually diabetic coma.

When blood glucose levels remain chronically high, the cells lining blood vessels absorb high levels of glucose. These link to proteins and thicken the blood vessel membrane. This makes the blood vessel weak.

Microvascular (micro = small, vascular = pertaining to blood vessels) damage is when small blood vessels are weakened – this results in a lot of diabetic complications. When the small blood vessels of the retina are affected, the resulting diabetic retinopathy can even lead to blindness. Diabetic neuropathy is when the small blood vessels in the feet and hands are affected – it creates a tingling sensation, numbness and can lead to skin ulcers, even cell death and gangrene. Amputation may be necessary. Diabetic nephropathy is damage to the small blood vessels of the kidneys, leading to chronic kidney failure, necessitating dialysis. Diabetic cardiomyopathy is damage to small blood vessels of the heart.

Macrovascular damage affects the arteries. This can lead to a heart attack, stroke, peripheral vascular disease with poor circulation in the extremities, and death of muscle tissue. These problems can be accelerated by high cholesterol and atherosclerosis.

See what problems are created by high blood glucose?

What happens once type 2 diabetes mellitus is diagnosed? The American Diabetes Association recommends diet, exercise and first-line treatment with metformin. The brand names of metformin are Glucophage and Glumetza, among others. It belongs to the biguanide class of antidiabetic medicine. Historically, a plant called French lilac (scientific name Galega officinalis) has been used since the Middle Ages to treat diabetes. A chemical called guanidine is the active ingredient. Metformin is a chemical derivative of guanidine.

What does metformin do? It uses insulin better. What is the mechanism of action? It boosts the activity of a liver enzyme called adenosine monophosphate-activated protein kinase (AMPK). This results in an increased expression of a genetic factor called SHP (small heterodimer partner) which inhibits the genetic expression of a couple of liver enzymes. This results in decreased glucose synthesis by the liver. Metformin also induces better binding of insulin to insulin receptors – due to which there is better utilization of glucose by peripheral cells. It also decreases the absorption of glucose by the gastro-intestinal tract. And, it decreases the breakdown of fat for energy.

Some other beneficial effects of metformin are reduction of LDL cholesterol and triglycerides, and weight loss.

Metformin has very few side-effects. Gastrointestinal upset can occur – nausea, diarrhea and flatulence. This can be reduced by administering extended release metformin tablets, or by starting with a low dose and slowly increasing the dose, and by taking it with food. Lactic acidosis is another possible side effect, mostly in patients with less than perfect liver and kidney function. In this situation, there is too much lactic acid build-up – this happens when glucose is used with not enough oxygen. It results in irregular breathing, and gastro-intestinal upset.

So far, modern medicine has no cure for diabetes. The only option available is treatment, so that blood glucose levels are maintained at normal levels. If this is done by means of right eating and exercise as mentioned above, and the prescribed medication, one can live long, productive lives. If the glucose levels are allowed to rise, or even fluctuate, we saw how it can affect all essential systems of our body. If you have been diagnosed with diabetes, please do make sure you check your blood glucose levels regularly, as directed by your doctor.

And, as we have discussed before …. think good thoughts, and laugh a lot ……. Wish you good health!

Let’s connect again …… same time next week ……..

Dr. Ajit Damodaran

Neurochemistry of the spoken word

October 8, 2008

Hello my friends!

Thank you for that magnificent response to my blog last week – some posted on the blog, but most in the form of personal e-mails. By far, the greatest response I got was to the statement I made, “Ah, the biochemistry of human emotions!” This week, I bow to public request, and write on something close to my heart. I may actually include something like this from time to time – a wider perspective on life and healing.

Please be aware that this article comprises mostly scientific fact, and some personal opinion. I am aware that you may possibly opine differently, and I invite you to share your thoughts

The power of thought. The power of emotion. The power of the spoken word. The healing that results when we are able to tap into the magnificent realms that lie within us. Let’s look at it logically. A thought arises in our mind. What actually happens? Let’s say the thought is a memory. The memory is a code stored in our brain in the form of certain natural nerve chemicals called neurotransmitters. To express it simply, let’s say a memory is a certain combination, a certain specific chain of neurotransmitters. They activate themselves, either out of the blue (not that the brain cells are blue), or in response to a stimulus that comes into the brain via our five senses.

Let’s say it’s a funny memory. It releases neurotransmitters, which in turn release another cascade of neurotransmitters, there are all these neurotransmitters firing all over the body, our mouth opens into a smile, our eyes twinkle, then our belly and chest and rib-cage get involved, there is expulsion of air through our mouth and we laugh. When we laugh, more neurotransmitters are released, we release “happy” neurotransmitters called endorphins, which are the body’s natural opiates – which create a sense of well-being and get rid of pain in the body. The body’s immune system manifests itself in peak performance, and you’re fighting fit to ward of illness.

Endorphins and other “beneficial” neurotransmitters are also released when we engage in other activities. Have you heard of falling in love to ward off a cold? Totally makes sense scientifically. When you have the “in love” feeling, your endorphins are dancing in glee, and your immune system is flexing its muscle. Also, aerobic exercise of any kind, creating the “runner’s high”, engaging in charitable and healing activity, creating the “helper’s high” (did you ever wonder why Mother Teresa never fell ill as she spent her life healing fellow humans with the worst illnesses?) – all these activities activate beneficial neurotransmitters and induce well-being and immunity.

The power of the spoken word. This is spoken of in cultures all around the world. In India, where I grew up, there was a statement I grew up with, that translates to “Speak only the auspicious.” Why is that important? In the discussion above, we saw the power of thought and emotion. One could argue that although it is our goal to hold every thought captive, most of us might find it difficult to control our thoughts. Not impossible, just difficult. Alright. However …. the next step in the sequence can be achieved by any one of us. Speaking the thought. When we speak, we concretize what might have been merely an abstract, nebulous thought. We give our thoughts form. May I go so far as to say ….. our words become flesh! Oooohhhh …. am I getting spiritual on you? I call it getting scientific on you. Permit me…..

When we speak words, the sound generated fall on others’ ears. Specifically, on their tympanic membrane, the ear-drum. The vibrations caused by the sound get transmitted through the auditory nerves in the form of ….. you got it …. neurotransmitters. Neurotransmitters are solid matter. They are part of your “flesh” – so, did your words become flesh? (I heard Dr. Deepak Chopra teach this a few years ago). The thoughts provoked by the words go and get stored in the brain of the listener. The words “you loser!” establish themselves in the brain of the listener as a negative thought. On the other hand, the words “you awesome winner!” establish themselves in the brain of the listener as a positive thought. The more the intensity behind those words, the more powerful the effect on the listener. If the listener is in a vulnerable state, especially if you are an authority figure or a loved one, those words become prophetic.

And what happens to you, the speaker? Those same words fall on your ears too – they create vibrations in your tympanic membrane too. And since you are speaking them, you are the creator of those words. Negative words spoken by you come back to haunt you. You start believing in those negative words about others. Let’s not get into deep philosophy here, but everything always comes around full circle.

Suppose someone is ill. The doctors might even have said they are terminally ill. What happens typically? Friends and relatives, even close relatives start acting as if the patient were already dead. The person might even be in a coma. They stand at their bedside and speak inauspicious words. Please do remember that when someone is in a coma, their brain can still register your words – even if they may not remember anything consciously when they wake up.

Listen up! Statistics are certainly a useful tool of science. That’s all – a tool. Never let a tool be the master of your belief. Anecdotally, there are myriad cases of recovery from the jaws of death. Do you agree? I have personally known individuals with advanced stages of cancer, and other disease, who the medical establishment had all but washed their hands off of. They laughed in the face of “the beast”, kicked it in its teeth, and proceeded to recover. They continue to live good lives, set goals in life, achieve those goals, and live on purpose. Of course, if the patient has goals in life to reach, or even better, has a major purpose in life that they are driven toward, that increases the chances of recovery.

What if a situation that faces you is one more case of miraculous recovery? Hmmm? Can you categorically say it will not be. Call me naïve …. as a person of science, I choose to focus on the positive, on the spirit of overcoming all odds, because I believe what I focus on expands.

Let’s say, you buy a Toyota Camry one day. Do you see a lot more Camrys on the road than you did before? Yes, you do. Why? There are so many stimuli that hit the brain constantly. If you became aware of everything at the same time, you wouldn’t be able to handle it. So, our brain, in its intuitive wisdom uses an apparatus called the Ascending Reticular Activating System (ARAS) which is situated at the core of the brain stem between the medulla oblongata and the midbrain. It filters out what you don’t consider important or just routine, and gets you to pay attention to the important. When you bought the Camry, that was foremost in your mind, therefore you noticed all the Camrys around you. Make sense?

If you include in your belief structure that being positive is crucially important, you will train your brain to focus on the positive. And that attracts positive events into your life because that’s where your attention is. Using cancer as an example, every single individual’s body has normal, healthy, good cells and abnormal, malignant, cancerous cells. Shocked? It’s true.

In a case of diagnosed cancer, it is a fact that cancer cells tend to grow uncontrollably. I know. But didn’t we just agree that perfectly healthy people also have cancerous cells in their body? Why do those cancer cells not grow exponentially? Some factor stops them, right? My belief says, if I speak to the good cells to increase their strength, to express that factor that gets rid of the cancer cells, it will happen. Will it be immediate? Maybe yes, maybe not. If not, why not? Well, we may have years and years of negative thoughts and beliefs stored away in our brain. With some individuals, it can take time to dilute away all that junk, and develop new belief structures. With other individuals, it might be instantaneous. How? Maybe an intensely emotional positive belief takes over and washes away all the negative belief. Could that be how “miraculous” healings took place?

So ……. when you hear of someone who is ill, remember, your words have power – the power to heal, or the power to destroy. Let your words be of strength, healing, life. Be very aware of the words you speak or the words you write on paper or e-mail or SMS. Go forth and use your powers wisely. Speak only auspicious words. When you pray for a person, don’t jump to “may their soul rest in peace”. Pray for their healing. Not wimpy, unbelieving, desperate prayers, but confident, bold prayers of belief. There are several books and articles by well-respected members of the medical and scientific establishment on the effect of individual prayer and group prayer. Dr. Herbert Benson is a name that comes to mind – he has some well-researched books and articles. More than a decade ago, my niece did a scientific study on prayer when she was in high school – a well-designed placebo-controlled double blind study on the effect of prayer on the growth of plants and another study on the lowering of crime in a town. She got positive results in both.

Quoting from U.S. Government National Institutes of Health’s National Center for Complementary and Alternative Medicine: “Evidence from randomized controlled trials and, in many cases, systematic reviews of the literature, suggests that —- Mechanisms may exist by which the brain and central nervous system influence immune, endocrine, and autonomic functioning, which is known to have an impact on health. —– Neurochemical and anatomical bases may exist for some of the effects of mind-body approaches.” Now, the National Institutes of Health (NIH) are very, very careful before they make a statement. They make sure they have plenty of resources to back them. Please visit their website to research those resources.

We all have unresourceful or negative thoughts and we have resourceful or positive thoughts. The key is to replace the former with the latter. Long-term, it’s doable. For immediate purposes though, it’s better to start with replacing unresourceful words that we speak with resourceful words.

If the above discussion makes sense to you, would you like to begin? It’s a journey. I’m on the journey – been on it for years. The beginning is a decision away. Then, only a matter of managing that decision daily. Good decisions and daily discipline – that’s the journey. Like leadership guru Dr. John Maxwell defines success in his book Today Matters, “If you make a few key decisions and manage them well in your daily agenda, you will succeed”.

My friends, I wish you success! Here’s to your good health! See you next week …

Dr. Ajit Damodaran

Hello world!

September 10, 2008

Beginning the first week of October 2008, I will be writing a brief article once a week, on health and pharmacy related matters. It could be an article on a commonly used prescription medication, a commonly used nutraceutical product or anything health-related.

I wish you good health.

Dr. Ajit Damodaran

Cystic Fibrosis … in search of a cure ……

February 8, 2016

Some of these names for health challenges sound ….. scary? Not to worry …. research is being conducted worldwide to combat the scariest sounding diseases!

Cystic fibrosis – how does it happen? It’s a genetic disorder which creates a build-up of thick mucus in the lungs, the pancreas as well as liver, kidneys and intestine. Hmmm ….. why does the disorder occur?

Our genetic code is a blueprint for everything that happens in our body. Okay! We know that mucus is produced in the body – it’s produced in the respiratory tract, in the mouth, stomach, intestine, reproductive system, eyes, ears and so on. It’s a protective fluid, one of its important functions being preventing infection. Healthy mucus is usually clear and thin. When there is threat of attack from an infectious agent like a virus or a bacteria or an allergy-causing agent, more mucus is secreted …. and it can get thick and green or yellow in color from the body fighting infection.

How is mucus formed? It is secreted by mucous membranes. The membrane has a protein called CFTR (alright, the full form is Cystic Fibrosis Transmembrane Conductance Regulator) which regulates the transport of chloride and thiocyanate ions across membranes.

Oof!!!! Enough of big words. Sometimes there are defects in the way CFTR is formed in the body, because there are defects in the genetic blueprint. As a result, the mucus is thick. This condition is called Mucoviscidosis or Cystic Fibrosis. The thick mucus can clog up the lungs and create an environment for bacterial infections, leading to respiratory failure if the infection is not controlled. In the pancreas, it can manifest itself as the ducts being blocked, leading to cyst formation and fibrosis (formation of scar tissue) – that’s the origin of the name “cystic fibrosis”. Male infertility because of failure of sperm transportation is another way the disease manifests itself.

Over the years, Cystic Fibrosis has been treated by treating its symptoms. So, when there is infection of the respiratory system, it’s treated with antibiotics. Saline is inhaled to clear the airways. Pancreatic enzymes are used to help digestion in the absence of proper pancreatic secretion. Regular exercise improves lung function.

Okay, that’s symptomatic treatment. Is there a cure on the horizon? Well, there’s good news!

There have been a couple of thousand identified mutations or defects in the genetic blueprint that cause defects in the CFTR protein. About 4 per cent of identified Cystic Fibrosis cases are due to a specific defect called the G551D mutation. A drug called Ivacaftor (brand name Kalydeco) was launched in the year 2012 as a CFTR potentiator. It binds to membrane channels in Cystic Fibrosis due to the G551D mutation in such a way that the defective channel of transport of chloride ions is opened up. As a result, the mucus is not thick any more.

The same drug also had some efficacy in a few more defects of the CFTR protein.

Wait … there’s more ….

Ivacaftor is a CFTR potentiator. In 2015, it was launched as a combination drug with the drug Lumacaftor, which is a CFTR corrector, which increases the traffic of CFTR to the cell surface. Ivacaftor/Lumacaftor is marketed as brand name Orkambi. The combination makes it useful for more patients,

Gene therapy is another field where research is being carried out, where the normal CFTR gene is introduced in the cells to create normal function. Not much success yet.

And, there’s a drug called Ataluren that is being tested rather successfully to treat Cystic Fibrosis. It works by taking the mutant genetic code and manipulating it to create normal CFTR protein. More results are awaited.

As can be seen, the treatment for Cystic Fibrosis is getting better and better. Breakthrough research creates better outcomes and greater maintenance of health and longevity. And with the best minds in research cerebrating together, a cure is on the horizon ….. that’ll be joyful news indeed!!

Wishing you increasingly good health,

Dr. Ajit Damodaran