Performance-boosters may damage the brain of athletes! So...
JUST how dangerous is the practice of taking dope to strengthen your chances at an athletic meet? The risk is rather large. Take the case of a cyclist who suffered a blood clot in the brain after taking a proscribed drug. This incident has been reported in the journal Neurology, according to BBC.

Fight against aging: genetic revolution
ON examining a vital area of the brain by following a particular genetic marker, researchers have found a single gene variation that can result in significant nerve cell changes associated with aging. In other words, people who carried the gene showed signs of aging faster than those without the gene.

Research
Antimicrobial peptides
A novel class of antimicrobials against disease
Infectious diseases (diseases produced by specific infecting microbes) remain a major cause of death and debility despite decades of dramatic progress in their treatment and prevention. Hundreds of antimicrobial agents (AMA, defined later) have been developed, many of which are potent, safe and effective against bacteria, viruses, fungi and parasites.

GENERAL CONCERN
Pain not an evil
TOTAL pain relief after injuries or surgery is not only possible but also practised in our region. The methods available are epidural narcotics and regional blocks. In epidural narcotic administration, a thin epidural catheter (18 gauge) is inserted in the patient’s back and is strapped to the skin. Through its injection port, a very small amount of a narcotic medicine, like 2-3 mg of morphine, is injected.

AYURVEDA & TOTAL HEALTH
Dr R. Vatsyayan, Ayurvedacharya
Shatavar for all
KNOWN as shatavari and atirasa in Sanskrit and Asparagus recemosus scientifically, shatavar is a tender climbing plant which grows in the tropical and sub-tropical regions including hills ranging up to 5,000 feet in India. Ayurvedic seers have termed shatavar as a unique herb which works to the benefit of both men and women.

Performance-boosters may damage the brain of athletes! So...

JUST how dangerous is the practice of taking dope to strengthen your chances at an athletic meet? The risk is rather large.

Take the case of a cyclist who suffered a blood clot in the brain after taking a proscribed drug. This incident has been reported in the journal Neurology, according to BBC.

Athletes competing at the Winter Olympics in Salt Lake City have tested positive for a similar drug. The man in question was a Spanish. He suffered a severe headache which was later diagnosed as a "cerebral sinus thrombosis." Doctors ultimately discovered that he had been taking a cocktail of drugs and vitamins, including the banned drug erythropoietin (EPO).

This combination raises the proportion of red blood cells in the blood which in turn enables the athlete to carry more oxygen from the lungs to the muscles. In the process, performance, particularly in endurance events. gets a boost.

But the problem is that because of the increased proportion of red cells, the blood becomes more dense and viscous. In all likelihood, blood clots form as a consequence and block blood vessels. The cyclist’s case is symptomatic of this chain of cause and effect.

Spanish doctor Eduardo Rocha, from the Clinica Universitaria de Navarra, says: "With the practice of blood doping among athletes becoming more popular, more research is necessary to devise new methods of detection, as well as more thorough evaluation of competitive athletes seeking treatment for potential doping complications. Educating athletes about the potential health hazards of performance enhancing drugs would also be beneficial."

EPO use created a major scandal in the world of competitive cycling after one of the Tour de France’s top teams, Festina, was expelled from the 1998 race following drugs finds. The latest positive tests in Salt Lake City involved cross-country skiers, and a new variant of EPO called darbepoitin, which, it is claimed, may be many times more potent.

John Brewer, of the National Sports Science Centre, said that the risks involved with EPO use had been highlighted before. According to him, with EPO the effect is very similar to training developing coronary disease. "The research team is of the opinion that additional studies are needed to clarify is of the opinion that additional studies are needed to clarify the insulin findings, as well as the factors involved in the association between proinsulin and heart disease.

After lab tests for proinsulin became available in the early 1990s, several groups reported that this molecule was a better predictor of heart disease risk than insulin. However, potential differences between men and women had not been studied.

Proinsulin is one of several molecules involved in the formation of insulin in the body that appears to impair blood clotting. increased levels of insulin and proinsulin have been associated with coronary heart disease risk factors such as high blood pressure, high cholesterol levels and obesity. High blood pressure, high cholesterol levels and obesity. High insulin levels have been identified as a coronary disease marker in men.

To evaluate proinsulin’s accuracy as a marker for the disease, researchers evaluated laboratory data on 1.456 middle-aged and elderly white people enrolled in the Rancho Bernardo (California) Heart and Chronic Disease Study. The group comprised 554 men and 902 women aged between 50 and 97 years. All were tested to confirm that they were not diabetic.

The research process involved measurement of insulin, proinsulin and C-petide, a byproduct of insulin production in blood samples taken from the participants. Oh noted that some evidence has indicated that C-peptide also might be a more accurate predictor of heart attack risk than insulin. Medical histories were obtained and electrocardiograms — which evaluate the heart’s electrical activity — conducted for all participants.

It was then found that about a fourth of the Rancho Bernardo group had coronary heart disease, equally distributed among men and women. individuals with coronary heart disease had significantly higher proinsulin levels compared to people without coronary disease, and the difference was apparent in men and women.

Rising proinsulin level more than doubled the likelihood of coronary heart disease in men, and the risk was slightly less than double in women. The association remained significant after the investigators accounted for the effects of a variety of coronary disease risk factors, including age, body mass index (a measure of obesity), blood pressure, and levels of high-density cholesterol (HDL — the good cholesterol that lowers heart disease risk). In contrast, levels of insulin and C-peptide predicted an increased likelihood of coronary heart disease in women but not men.

Oh says: "Our findings suggest that proinsulin may be useful for diagnosing coronary heart disease in men and women." ANI

ON examining a vital area of the brain by following a particular genetic marker, researchers have found a single gene variation that can result in significant nerve cell changes associated with aging. In other words, people who carried the gene showed signs of aging faster than those without the gene.

Researchers at Duke University Medical Center were looking for new clues about why some people experience more rapid age-related brain changes than others. Although the signs of age-related memory loss are widely recognised, researchers are still unsure why some elderly adults retain strong mental capacity well into their 90s while others fall into progressive decline or dementia.

The researchers have found an association between nerve cell changes associated with aging and the presence of a variation of the apolip rotein gene known as apolip rotein E4 (APOE4). This form is carried by approximately 25 per cent of the population and has been linked to increased risk of Alzheimer’s disease, cardiovascular disease and memory loss after head injury or bypass surgery.

"The frontal lobe is the site where the earliest and most consistent effects of aging occur in the brain," said P. Murali Doraiswamy, M.D., a psychiatrist at Duke and lead researcher on the study. "Virtually every mental symptom of normal aging results from decline in frontal lobe functions. When we examined this vital area of the brain by following a particular genetic marker, we found a single gene variation that can result in significant nerve cell changes associated with aging. Of the pe le we studied, those who carried the APOE4 gene experienced a more rapid loss of nerve cell functioning."

"This is an important finding in the study of aging. I believe it will lead to a greater understanding of age-related memory loss and hopefully, one day, to ways of keeping our brains sharper, longer," noted Doraiswamy.

***

A study of chromosomes in cancer cells has concluded that normal cells develop fragile regions when they are exposed to drugs used in chemotherapy and thus plant the seeds of a future cancerous growth while they are killing the current one.

The research was conducted at the Hebrew University of Jerusalem lead Associate Professor of Genetics Batsheva Kerem also renowned for her work on the genetics of cystic fibrosis. She said that her research can lead to the develop ment of more effective and less damaging chemotherapy drugs.

Prof. Kerem explains that in studying the differences between cancerous and healthy cells they found that the chromosomes of cancerous cells break recurrently at specific regions known as "fragile sites."

In a previous study, researchers showed that fragile sites are sites where the mechanism responsible for DNA replication is disturbed. This could lead to breakage resulting in multiple rearrangements of the chromosomes, a striking characteristic of cancer cells.

Prof. Kerem explained that there are some 100 fragile sites in the human genome and five of these sites are now being studied.

"Our work creates a better understanding of how drugs used against cancer work, which will lead to the creation of the next generation of drugs, which can halt the growth of cancerous cells without inducing fragile sites", a researcher said.

***

A molecule called proinsulin is a better indicator of coronary heart disease than insulin. Measuring its levels appears to be an accurate way to predict the ailment in men and women. This is revealed in a report in the online issue of Circulation: Journal of the American Heart Association.

Researchers have found that an elevated level of proinsulin, but not insulin, was associated with about a two-fold increased risk of heart disease in non-diabetic men and women who had suspected but unconfirmed blockages in their coronary blood vessels. This association was stronger in older people.

Jee-Young Oh, who conducted the research while completing a fellowship at the University of California, San Diego, said:. "Measurement of proinsulin might help identify patients who have coronary disease and maybe those who are at high risk".

***

Preliminary results of a new study reveal two new ways to reduce asthma severity in inner-city children.

The results would be presented by researchers at the annual meeting of the American Academy of Allergy, Asthma, and Immunology (AAAAI), which is due to be take place at the Hilton New York hotel.

The six-year investigation is part of the ongoing efforts of the Inner-City Asthma Study, a program supported by the National Institute of Allergy and Infectious Diseases (NIAID) and the National Institute of Environmental Health Sciences (NIEHS).

Established in 1991, the study has involved 12 centers nationwide and about 3,000 children. Its primary aim is to find out why asthma disproportionately affects inner-city children and to test new ways to treat the disease.

The study, since 1996, has been investigating two methods to improve the health of inner-city children with asthma. The first method, called a physician feedback intervention, involves periodic reports to the child’s doctor about the status of the child’s asthma.

The second method, called an environmental intervention, involves identifying and removing asthma triggers such as cigarette smoke or cockroaches from the child’s home.

Initial data suggest these interventions effectively reduce emergency room visits and asthma symptoms for inner-city children. Another symposium at the AAAAI meeting would explore the idea that asthma consists of several subtypes.

These include allergic asthma, exercise-induced asthma, asthma caused by bacterial and fungal infections, asthma in the elderly, and more. Each behaves somewhat differently, is triggered differently, and may respond to different treatments or interventions.

***

Genes & migraine

Geneticists at University of California-Los Angle (UCLA) have discovered that migraine with aura is a hereditary condition.

The findings, which would be published in the March 1 edition of the American Journal of Human Genetics, would enable researchers to isolate the gene that predisposes pe le to the painful disorder.

Dr Aarno Palotie, principal investigator and UCLA professor of pathology and human genetics, said, "For the first time, we have proof of an isolated genetic link to migraine".

"This finding moves us one step closer to isolating the gene that predisposes pe le to migraine headaches with auras", he added.

Palotie’s team analysed genetic markers in blood samples from 50 Finnish families with about three multigenerational members who suffer from the disorder.

Migraine affects about 12 per cent of the population. The headaches are characterised by intense pulsating pain on one side of the head, often with pain behind one eye, nausea, vomiting, and sensitivity to light and noise.

Some migraines are preceded by an aura — neurological symptoms revealed by visual disturbances up to one hour before the headache begins.

Research
Antimicrobial peptides
A novel class of antimicrobials against disease
Dr G. K. Khuller

Infectious diseases (diseases produced by specific infecting microbes) remain a major cause of death and debility despite decades of dramatic progress in their treatment and prevention. Hundreds of antimicrobial agents (AMA, defined later) have been developed, many of which are potent, safe and effective against bacteria, viruses, fungi and parasites. However, advances in the development of the latest AMAs are hampered by the ability of microbes to elude our best strategies and to counterattack with their own strategies for survival.

The term "antibiotic" refers to substances produced by microorganisms, which suppress the growth of, or kill, other microorganisms at very low concentrations. On the other hand, AMA includes synthetic as well as naturally obtained compounds that attenuate microorganisms. In order to understand simply how an AMA may act, let us compare a bacterium with a house. An AMA can (i)impair cell wall synthesis (damage the walls of the house), e.g pencillins, cephalosporins; (ii) inhibit protein synthesis (cut off the fuel supply to the kitchen), e.g tetracydine, erythromycin;. (iii) impair DNA functions (rob the house of its currency) e.g rifampicin and metronidazole; and (iv) interfere with metabolic functions (remove essential ingredients that are required for cooking), e.g sulfonamides, ethambutol. AMAs are life saving if used appropriately. However, their indiscriminate use increases the cost of healthcare, leads to side-effects and drug interactions, and fosters the emergence of resistance, rendering valuable drugs useless.

A novel approach in antimicrobial therapy has been the use of naturally occurring peptides (proteins of less than 100 aminoacids), which are normally found on the skin, mucosal surface and inside the white blood cells of higher animals (including humans). These peptides are normally meant to combat small, moderate degrees of microbial challenges to the body and constitute a part of the innate host-immune response. Their cationic (having a net positive charge on the surface) nature is helpful in damaging microbial membranes as well as in neutralising certain toxic compounds.

Since, they are produced by the body itself, they are harmless to the body’s own cells, at least in the concentration in which they are normally present.

Further, cationic peptides have a number of advantages over other antimicrobial agents, which include their broad spectrum bactericidal activity, synergistic effect with conventional AMAs, effectiveness against drug-resistant microbes and the quick mode of action.

Most interestingly, they also act as anti resistant peptides and remain unaffected by the resistance mechanisms offered by microbes. antimicrobial peptides have a number of other biological activities such as wound-healing, anti-cancer activities, neutralisation of toxins, etc.

Over 2000 cationic peptides have been discovered of which many are in clinical trials also. A few examples are, Histatin for periodontal disease, Neuprex for meningococal infection, Pexiganan for diabetic foot ulcer, Nisin for H.-pylori-induced peptic ulcer, Mycoprex for candidiasis, Meganin for skin infections, Protegrins for oral mucositis caused by cancer chemotherapy and Defensin for systemic infections.

For the past few years, the role of defensins as a therapeutic agent against tuberculosis is being explored in my laboratory and it has been demonstrated to kill M. tuberculosis (Arch. Microbial., 171, 338, 1999; Eur. J. Res 16, 112, 2000, Antimicrob. Agents &Chemothr. 45, 639, 2001).

Besides their chemotherapeutic activity against a number of diseases, antimicrobial peptides can also be used as immunotherapeutic agents due to their ability to boost host immune defense mechanisms. In view of this unique property, these peptides seem to be a suitable adjunct to be used with antituberculous therapy(ATT) particularly to eliminate the persisters left after complete chemotherapy.

Despite the number of advantages over conventional antibiotics, the limitations associated with the use of cationic peptides are yet to be explored. These include toxic side-effects to the host, the inability to be given by the oral route and the high cost of production etc. Studies are going on to devise new strategies to overcome problems associated with the antimicrobial peptides and their clinical use in various infectious diseases.

In conclusion, cationic peptides, a new class of antimicrobials, would certainly offer new weapons in the physicians’ armamentarium.

GENERAL CONCERN
Pain not an evil
Lt Col (Dr) Rajinder Singh

TOTAL pain relief after injuries or surgery is not only possible but also practised in our region. The methods available are epidural narcotics and regional blocks. In epidural narcotic administration, a thin epidural catheter (18 gauge) is inserted in the patient’s back and is strapped to the skin. Through its injection port, a very small amount of a narcotic medicine, like 2-3 mg of morphine, is injected. Since the medicine is injected right where it has to act, the dose required is a fraction of the dose required for intramuscular injection and the duration of action too is very long (12-72 hours as compared to 4-6 hours with intramuscular route). As and when the patient starts to get pain again, a top-up dose is injected through the injection port once again.

Continuous infusion pumps can also be attached to this injection port. Because of a very small dose required at a time and a long duration of action, there is no tendency for addiction, and side-effects are also proportionately little. It takes about 10 to 15 minutes for the procedure to be completed and pain relief is almost immediate and sustained. We prefer to insert an epidural catheter before the surgery so that through the same port local anaesthetic drugs can be injected and surgery carried out followed by the injection of narcotics for postoperative pain relief. This method of pain relief is available for use anywhere in the spinal column from the nape of the neck to the lower back but is most commonly used for relieving the pain of the chest, the abdomen and the lower limb injuries or operations. Once inserted and taken care of, the catheter can remain in place for up to three weeks and that is a long enough time for any pain to get relieved. If required, a catheter can be replaced after that period with a new one in a different space.

For pain relief in injuries/operations of upper limb, brachial plexus (the collection of nerves supplying the upper limb) analgesia is available. A fine catheter is placed within the brachial plexus through a needle and local anaesthetic medicine is injected intermittently providing complete relief of pain to the patient. Since the dose of the medicine required is much below the maximum permissible dose, there are no chances of overdose.

Both procedures mentioned above are quite safe and are in wide use on a large number of patients without any side-effect. However, theoretically, there is a possibility of a haematoma formation (collection of blood at the site of injection), dural puncture (catheter entering the cerebrospinal fluid), both of which may not need any active management, drug-overdose and infection. The last mentioned complication is most important but is easily warded off when an aseptic technique is used for insertion of the catheter and a micro filter is attached to the injection port (routinely done). Other complications decrease exponentially with the experience and expertise of the doctor. Thus, post operative pain relief techniques provide an extremely high patient-satisfaction level with practically no complications and are, therefore, strongly recommended.

A major group comprises strong painkillers like morphine, pethidine and buprenorphine etc.

Therefore, in many medical centers, doctors prefer to prescribe NSAIDS to patients even with severe pain. Although the side-effects of narcotic analgesics are avoided, pain relief is less than satisfactory.

There is a general belief that if a person is injured or has undergone surgery, pain has to occur and it must be endured. The net result is that in our country, no patient expects, much less requests, for total pain relief in the above-noted settings.

————

Lt Col Dr Rajinder Singh is an anaesthesiologist and expert pain-manager at the Command Hospital, Chandimandir.

AYURVEDA & TOTAL HEALTH
Dr R. Vatsyayan, Ayurvedacharya

Shatavar for all

KNOWN as shatavari and atirasa in Sanskrit and Asparagus recemosus scientifically, shatavar is a tender climbing plant which grows in the tropical and sub-tropical regions including hills ranging up to 5,000 feet in India. Ayurvedic seers have termed shatavar as a unique herb which works to the benefit of both men and women.

The shatavar root is sweet-bitter in taste and heavy, unctuous and cold in effect. While it pacifies vata and pitta, its chemical composition consists of various substances which include some glycosides and alkaloids known as saponins and aspergamine.

Shatavar has been described as a cooling nervine tonic with glactagogue (that produces milk in the breasts) and aphrodisiac in effect. Satavar nourishes body tissues and is also endowed with antacid, diuretic, demulcent anti-spansmodic and rejuvenating properties.

Shatavar is the main invigorating ayurvedic medicine for women as is ashwagandha for men though each has good effect on both sexes. Used for regulating menstruation and ovulation, improving lactation, preventing morning sickness and having very good results in cases of infertility, frigidity, leucorrhoea and uterine swellings, shatavar is equally effective in a number of male problems like sexual debility, spermatorrhoea and low sperm count.

A number of other diseases like acidity, piles, hypertension, migraine, gouty arthritis, inflammation of the urinary bladder and problems arising from malnutrition and general debility respond well to the use of shatavar. Shatavar can be used safely as a household remedy in many situations.

Here are some tips:

For women: Shatavar nourishes and cleanses the female reproductive system. If 2 gm of its powder is taken twice a day with milk, it maintains the hormonal balance and helps in having trouble free menopause. It allays many of the post-hysterectomy problems also. Women experiencing excessive hot flushes are relieved if 250 gm of the famous Kamdudha Rasa (mukta yukta)is also given side by side. Shatavar also helps in maintaining normal pregnancy and is generally recommended to women with a history of recurrent abortions.

For men: Shatavar is a reputed herb for vitalising the male reproductive system. It helps to increase the sperm count and forms an important part of almost all classic ayurvedic formulae to cure male sexual insufficiency. Taking two or three times a day 2gm of equal parts of crushed ashwagandha and shatavar is a simple and safe remedy for such patients. The shatavar powder, alone, can be taken as a general tonic. In western countries shatavar is known as asparagus and is added to many food supplements.

Other uses: Ayurvedic texts recommend the use of shatavar for curing acidity. For this purpose the powders of shatavar and amla should be taken with warm milk. Shatavar, gokhru, amla and sugar, all crushed in equal parts, and 2 gm of its powder, make a good home remedy for the chronic inflammation of the urinary bladder and the subsequent burning micturation.

Shatavari Ghrita, Shatavari Mandoor and Shatavaryadi Churna are famous classic ayurvedic formulations. Except mild constipation in a few cases, the use of shatavar is generally safe.

Dr R. Vatsyayan is an ayurvedic consultant based at Sanjivani Ayurvedic Centre, Ludhiana. (Phones: 423500 and 431500; e-mail-sanjivni@satyam.net.in)