Skeletal Muscle latest member to join the Endocrine Club

Hormones, or chemical proteins that circulate in the blood and regulate body function, have long been known to be produced by just a handful of endocrine glands such as the pituitary, thyroid, parathyroid, adrenals, pancreas and the gonads. Three latest ones to join this exclusive club are intestines, bone and skeletal muscles!

It may sound funny but medical scientists are beginning to discover how some of these large tissues also produce “hormones’ and regulate metabolism.

Skeletal muscles, for instance, produce a wide variety of “hormones”, largely referred to as “MYOKINES”. Their subtle actions range from maintaining blood sugar control (apart from Insulin), keep us in good mood (stretching skeletal muscles has stress busting effects on the brain), improves fat metabolism (converts white fat to brown fat, and reduces its quantity), improves liver functions, regulates bowel movements, and removes cholesterol plaques from blood vessels. 

What goes on between myokines and other organ systems is referred to in scientific circles, as CROSS TALK. The myokines released from muscle fibers during exercise or stretching, interact with other systems and hormones. Some of the important functions recently ascribed to myokines are improved cognition (alertness, learning), ant-depressive actions, reduced stress hormone levels and cardio-protection.

To make it simple, research is showing that those who have been actively exercising are less prone to fatty liver disease and developing diabetes. Indeed they tend to develop Alzheimer’s disease less often and demonstrate less risk for developing cancers.

The discovery came in 2000 when it was realized that exercise caused release of a hormone-like substance called IL-6 (interleukin 6) from muscles into the circulation. It turns out that this IL-6 has anti-inflammatory and health promoting properties from the brain to the liver. 

The only way to get your share of IL-6 release into the circulation, unfortunately, is by stretching and doing some exercise, squeezing your muscles to release it. This set of observations now explains why “healthy” living requires a daily dose of myokines or IL-6, and no pill can help provide that as of now!

Advertisement

What makes Pele feature Health Adda?

The Brazilian soccer legend, Edson Arantes do Nascimento, more popularly known across the world by his nick name Pele, died at the age of 82 of complications arising from colon cancer.

Pele achieved more fame and stature as a sportsman than anyone could possibly have. He started playing football as a child in an impoverished locality kicking socks filled with paper, got recognized for his extraordinary skill and mastery of the game at the age of 16, and went on to play as a professional soccer player for his country bringing Brazil into the world map of soccer.

His mind boggling achievements include scoring a Guinness World record of 1279 goals in 1363 games, becoming the youngest winner of the world cup at 17 and winning the FIFA world cup three times for Brazil. It was not without reason that FIFA conferred on him the title of “Player of the Century”. 

He went on to become a global icon of not just soccer, but sports across the world. He was also known for his philanthropic activities and for working tirelessly to encourage and pull poor children in Latin America out of poverty through the game of soccer.

He played at a time when television had not come into our homes. We tend to therefore forget two things: more recent heroes appear larger in size, and second, television and social media can alter the “size” of icons!

What stands out about Pele was his passion and commitment to what he did. He is famously quoted as saying “I was born to play football, just as Beethoven was born to write music and Michelangelo was born to paint”. I wonder if I found or did justice to a singular life’s purpose!

He was diagnosed to have colon cancer some time ago. At the time it was detected and surgically removed, it had spread to other organs. He was therefore undergoing chemotherapy for widespread cancer. 

He faced his end quite like a true sportsman, gracefully wishing his relatives (his wife, 6 children and other relatives) farewell from his hospital bed a day before he died.

Colon cancer is the third commonest cancer world-wide affecting 2 million people and killing 900,000 annually. The best chance to beat it is to have it detected at an early stage by a “routine” screening colonoscopy at age 45 onwards. 

GERD

Do you get burning sensation behind your chest bone, or have sour food come into your mouth? Do you wake up at night with “heartburn” or “acidity”, and need to drink water or take antacids for relief? If this happens more than once a week, you are suffering from GERD (Gastro-Esophageal Reflux Disease) one of our modern day maladies.

GERD is caused by refluxing of acid that is normally produced by the stomach, into the food pipe or esophagus, due to malfunctioning of the one-way valve located at the stomach-foodpipe junction (GE valve). A recent nation-wide survey from 25 centers, conducted by the Indian Society of Gastroenterology, found that 8.4% of Indians suffer from this disorder. If you are a sufferer, you have 80 million in India for company!

GERD is a lifestyle disorder, but also tends to run in families suggesting a genetic component as well. Its frequency has jumped up in recent decades replacing Irritable Bowel Disease as the commonest GI disorder. 

Obesity. fatty food ( pastries, fried food, cheese, cream), chocolates, pungent spices cause relaxation of the GE valve as do alcohol, nicotine and caffeine and are notorious for causing GERD, accounting for the early morning “heartburn” often experienced after that perfect late night party. 

Diagnosis of GERD is fortunately not difficult as the symptoms are quite typical. The commonest test advised is an endoscopic examination, during whcih the doctor examines whether ulcers have formed in the food pipe or if the lower oesophageal valve is very loose. Long standing severe reflux may occasionally cause scarring and narrowing, and sometimes lead to cancer. 

Changes in life style certainly help. Regular exercise, maintenance of ideal body weight, avoiding all the predisposing foods and beverages, a small early dinner and elevating the head end of the bed, do work. Those who can’t change their ways, prefer to take pills that reduce acid production in the stomach (Proton Pump Inhibitors or PPIs) or tighten the GE valve. They work well, but only as long as you keep taking them.  

Refluxers are confronted with a hard choice of “Pleasure and Pill” or “Frugal Pauper”. Not easy!

ALCOHOL USE and the CAGE Questionnaire

In our present times of frequent social alcohol drinking, it sometimes becomes difficult for the consumer, family or doctor to recognize early symptoms of dependency. 

Alcohol use disorder (AUD) as it is presently called, is the wider all-encompassing term that includes dependency, addiction and withdrawal, and by virtue of its broad range and blurred margins, sounds more acceptable as well.

Medical and mind scientists have relied on recognizing patterns of behavior and consumption, to identify ALCOHOL USE DISORDER and have created several scoring methods.

The CAGE questionnaire, an acronym, is one such, and is the easiest, simplest and most widely used interview tool. It consists of four straight questions that need to be answered with a YES or NO.  

Here they are:

1. Have you ever felt you should cut down on your drinking?
2. Have people annoyed you by criticizing your drinking?
3. Have you ever felt bad or guilty about your drinking?
4. Have you ever had a drink first thing in the morning to steady your nerves or get rid of a hangover (eye-opener)?

Needless to say, the consumer has to answer these questions honestly. Presence of a spouse or relative may help in getting accurate responses to questions 2 and 4.

If any one of the answers is YES, it is time take heed. It will be good to meet a specialist and seek help to cut down or stop.

After consumption, alcohol is carried by the blood stream to different organs of the body. Brain is the organ where its mood – effects (pleasure, desire, relaxation, sleep, anger) find expression while its injurious effects occur more in the liver, pancreas, heart and muscles. 

The effects of alcohol, both on the brain as well as its metabolism and clearance from the body, are regulated by a large number of enzymes ( Alcohol dehydrogenase enzymes and their wide range of polymorphisms) with considerable genetic variations. 

Hence we often hear the stories of someone who is said to have drunk a whole bottle of whisky every day for decades and lived a healthy long life. More often, many tolerate alcohol poorly and can develop liver damage or pancreatitis with as small doses as just a couple of occasional drinks, and find it hard to reconcile their story with that!

The New GI Buddy called Rifaximin

A ray of hope has emerged for a large section of people troubled by loose consistency of stools.

To put things in perspective: loose stools or diarrhea occurring recently and for a short period is quite common, often caused by an infection of the gut, or due to a recently consumed food item that did not agree with the bowel. Most usually settle on their own, but may sometime require a pro-biotic, and occasionally a course of antibiotics.

The new “buddy” emerging for most doctors in recent times, is a drug called rifaximin. What makes this antibiotic a hot favorite is that it remains confined to the gut and does not get absorbed or interfere with other organs. Hence it tends to be very safe.

Antibiotics such as quinolones (norfloxacin, ciprofloxacin ofloxacin) or co-trimoxazoles (Bactrim/ Septran) that were used earlier for treating traveler’s diarrhea or infective diarrhea, were absorbed into the body, and hence were associated with some adverse effects (allergy, nausea, induction of antibiotic resistance with frequent use). They are still useful when one the infection is suspected to have invaded the tissues as suggested by fever or blood in stools. 

Rifaximin seems to be free of major side effects as it is poorly absorbed. It remains restricted largely to the intestinal lumen (>99%) and passes out in the stools.

It also shows “selectivity”, targeting most of the disease-causing germs, while sparing the healthy ones such as Bifidobacterium, Lactobacilli or Bacteroides. Thus the disturbance of gut flora seen with many broad-spectrum antibiotics seem to be less with Rifaximin.

Within a rather short time, Rifaximin has become the most favored prescribed drug for a variety of conditions where policing and targeting of bad intestinal germs seem to be required.

Its indications are now expanding beyond traveler’s diarrhea or acute infective diarrhea.  A section of patients suffering from irritable bowel syndrome of the diarrhea variety (IBS-D), liver cirrhosis with impending or overt coma, and SIBO (small intestinal bacterial overgrowth), all of which are associated with increased or abnormal bacteria in the gut, seem to do well with Rifaximin.

The safety profile of this drug lends itself easily for long term or frequent use, unlike other antibiotics. It is not surprising therefore to find it included in prescriptions frequently, and several pharmaceutical companies adding it in their portfolios.

Ruby’s foodpipe: Corrosive Esophageal Injury

Ruby is finally set to undergo surgery for a blocked and ulcerated food-pipe that has plagued her for twelve long years. Inshallah, if all goes well, this 30 year old frail 40 kg girl might get another chance to live life with grace and vigour, when a loop of intestine replaces her gullet and allows her to eat normal food.

Her problems had begun suddenly twelve years ago when she had accidentally swallowed sulphuric acid, used to clean floors and commodes that her father had kept in a clear water bottle. She still shudders to think of the intense burning, choking and pain, the swelling around her mouth and the agony of drips in hospital. A week later she had noticed difficulty in swallowing food that had progressed to obstructing even the passage of her saliva. She had withered rapidly from a 55 kg energetic girl to a skin-and-bony 20 kg in three months and had become so weak that she needed hospitalization and drips again and again.

It was around then that her association with us started when she had come with a badly damaged food-pipe through which even water would not trickle down. We had managed to pass down a thin wire and dilate the stricture with bougies and balloons to initially allow liquids, and then a bit further to let semi-solids such as sooji, khichri and custards into her stomach. She soon picked up a few kilos and got back on to her feet.

Then the socio-economic factors came into play. Her parents found her protracted illness too expensive, and decided to concentrate on their two other children, leaving Ruby to her fate. Her marriage of a few months broke up. She soon found herself struggling to stay alive, earning Rs 3000/- per month from a lodge as a part-time caretaker, and spending most of it on her two weekly dilatation sessions and her special liquid feeds.

She was advised surgery several times over this period, but had declined. First, there was the issue of expense. Second, no family support. And third, she was mortally scared of losing her voice as she had met someone who indeed had after this kind of surgery.

What then triggered this change of mind now? With her indomitable spirit, she has enrolled for a graduation course that she is pursuing after the day’s work. Further, a benevolent soul, touched by her story, has offered to sponsor her surgery. She, on her part, has finally decided to take the risk and turn the corner. Her ambition now is to leave the unpleasant past behind and create her own future and become independent.

Corrosive injury to the food-pipe is still a common problem in India. While some are due to accident, many occur from suicidal intent in a fit of desperation. Most victims are able to live normal lives with few sessions of endoscopic dilatation, but some like Ruby need more help.

Non-Alcoholic Fatty liver disease – Emerging therapies

In the recent years Non Alcoholic Fatty liver disease (NAFLD) has metamorphosed from an incidental inconsequential disorder to a major cause of early deaths, not just from liver disease and hepatocellular carcinoma, but from cardio-vascular diseases as well. NASH is expected to surpass hepatitis C virus infection as the leading etiology of end-stage liver disease requiring liver transplantation in the next 5 to 15 years.

Insulin resistance appears to be the underlying mechanism that sets pathogenesis of this condition in motion. Hence, the therapeutics of NAFLD has revolved primarily around weight reduction strategies, be it through life style alteration or bariatric surgery. Despite the significant burden to the public health system, there areno FDA-approveddrugs that are specifically tailored for this condition.Therefore, the need for effective treatment that manages the complexpathophysiologic processes of NAFLD, can no longer be ignored.

While the results of currently available therapies such as vitamin E and pioglitazone have been significant for steatosis and inflammation, they have had no effect on fibrosis, which is the strongest indicator of mortality in this condition. The understanding ofthe pathogenesis and progression of NASH has evolved with time and several promising noveltherapies to target and possibly reverse fibrosis are in different phases of clinical trials.

Understanding of NAFLD at the molecular level has led to the development of new compounds that target specific steps in the patho-genetic pathways of this condition. They include a Farnesoid X receptor ligand called Obeticholic acid, agonists of PPAR (peroxisome proliferator-activated receptors such as Saroglitazar and Elafibranor, which are emerging as exciting new ways to treat this condition.

Match Making and Organ Donation

It is not medical research alone, but good match making that is saving thousands of lives. Professors Alvin Roth and Lloyd Shapely, the two Americans who shared this year’s Nobel Prize for economics, could well have won the prize for medicine, feel many health care professionals.

Imagine your spouse has damaged kidneys needing a renal transplant, and you are willing to donate one of yours, but your tissue does not match with what her immune system would accept. There is also somewhere in another city, a couple with a similar problem, but whose donor kidneys match with that of your wife’s, while yours match with hers. Wouldn’t a swap help both? And imagine if the number of donors and recipients were not just two, but thousands. Wouldn’t the matching of organs and donors help all in the fray?

While transplanting of organs has indeed been a great medical achievement, it is the complex ways in which people are matched with limited resources such as donated organs, that has powered the transplant services on the ground and help them achieve the status of large viable programs.

Their seminal work became the founding for the New England Program for Kidney Exchange in Boston. Mohan Foundation is one such working in India.

Lloyd Shapely, a mathematician and regarded as the father of modern match making, posed himself the question fifty  years ago, how individuals in a group of people could be paired up when all had different views on who might be their best partner. He invented the board game ‘So Long Sucker’ based on this principle.

The spirit of inquiry seems to have run in his genes. His father Harlow Shapely was an astronomer in the early nineteen hundreds who helped estimate the true size of the Milky Way Galaxy.

Alvin Roth, who is a professor at Harvard University, and the younger of the two, took Lloyd’s theory of stable allocations to market designs and applications.  Their work has had far reaching applications in health care, matching doctors with hospitals, trainees with fellowship residency programs, students with schools, apart from donated organs with seeking recipients.

It is a pity that their match making theory escaped the attention of our mothers and managers of Indian matrimonial sites. An Indian entrepreneur could do well to apply their theory to match making for marriage. If it has worked well for organ donation, there is good reason that it will help make better “joris” too, with perhaps the “kundli” as an important variable in India!

Madhu and her new liver

Madhu is in the 5^th year of her new life. She had alsmost reached her end because of her failing liver, when on 14^th February 2004, a new liver arrived in Lucknow almost by miracle.

She had been a healthy homemaker and mother till 1994 when she had an attack of jaundice. Unlike the common ones that pass away on their own, this episode was persistent. One doctor after another and with one herbal tonic to be replaced by another, she finally reached the SGPGI. Tests revealed that her chronic liver ailment was not due to the common infective viruses B or C but due to a rare condition called autoimmune hepatitis, a condition in which the body’s defending cells and immune system start attacking its own organs, in her case, her liver.

Autoimmune hepatitis is somewhat rare: it accounts for two percent of all prolonged cases of hepatitis or liver cirrhosis. It affects women five times more often than men, and needs awareness for timely diagnosis. If detected on time, the disease can be controlled with immunesuppressants like corticosteroids.

Madhu had reached us somewhat late and a portion of her liver had already permanently damaged. She was however treated with immunosppressants to preserve the viable portion of her liver. She had her ups and downs, but remnained largely well for almost eight years. By 2002, her liver had become weak; she had water in her abdomen, swelling of her feet and side effects of the medicines as well. It became obvious that only a liver transplantation could get her back to life and health at that stage.

Her husband, a bank emplyee, tried all he could; he consulted various liver transplant centers in India, offered to donate a part of his own liver and took large loans to provide for the increasing costs of her treatment. Unfortunately he was found to have fatty liver that was unsuiatble for donation, and his abdomen was closed. With that almost all hope diasappeared, as there were no suiatable relative in Madhu’s home who could donate her a part of his liver.

On 13^th March 2004, a man who was on a ventilator in one of the hospitals in Delhi following an accident, was pronounced brain-dead. Under such trying circumstances, his relatives gallantly agreed to his liver being extracted for donation to a needy person. Dr Peush Sahni from AIIMS extracted the liver, and flew into Lucknow on 14^th morning. Madhu was taken into the operation theatre and Dr Rajan Saxena and Dr Peush transplanted the new liver into Madhu.  That indeed was destiny! The relatives of the donor were magnanimous enough not to seek publicity for saving someone else’s life, and requested anonymity.

Madhu continues to be well five years on. Her daughter got married this year.  Madhu and her husband, and 5 more such heroes from Lucknow who have been through liver transplantation, have offered to provide counselling to patients and their relatives facing similar challenges, a service which we plan to provide through the Liver Foundation of Uttar Pradesh that kicks off on 19^th of this month.

Irritable Bowel and Barking Dogs

If “love” is the most misunderstood word in society today, “constipation” cannot be far behind. A recent study revealed that 5 to 22 percent of the population across the world are unhappy with the ways their bowels move and they use the same word to describe a variety of symptoms.

“Constipation” means different things to different people, from a feeling of incomplete evacuation (45 percent), straining at stools (30 percent), hard stools (10 percent), bloating and distension (20 percent) to several others. None of these meet the Western medical definition of “constipation” described as passage of less than three stools per week!

How bowel habits differ between peoples and regions, and the urgent need to redifine terms were highlighted during the recent Asia Pacific Digestive Conference in Kuala Lumpur, in which Asian doctors pointed out that the Western definition of constipation was inappropriate for Asians as hardly anyone would actually qualify while many feel they are constipated while passng stools quite liberally.

Bowel habits indeed vary widely not just between peoples and regions, but even between individuals. While many Indians believe that passing atleast one stool per day in the morning is crucial to health, the range could be considerable from three times a day, often after food or meals, to once on alternate days. Timing may not be so important after all as modern lifestyle may not often permit us to sit long on the pot before the early rush to school or work while evenings allowing more time to coax stressed bowels to relax and allow the passage.

Food and exercise are once again being thrown into center stage in debates on bowel habits. Our Indian diets of daal-roti-sabji have adequte amounts of fiber that absorb water and toxins, give volume to stools and stimulate the large intestine to move forward with regularity, keeping our constipation as well as our risk of colon cancer at bay. In USA, bowel cancer has become the commonest of cancers, making doctors advocate colonoscopic examination for screening in everyone above 45. If we change our food habits to burgers, sausage, ham and cheese, we will acquire the risks as well, just as Indian immigrants to western countries have started doing.

A few simple tips can be of use: If stools are hard or infrequent, green veggies, and fruits such as papaya, apple, pear or “bel” can help. If your stool tends to be loose and the frequencies high, try bananas and curd, and cut down on milk and cheese. If “gas” and bloating are your main symptoms, excess of gas forming foods such as sprouts, daals, peas, radish or milk could be the culprits; try cutting down on them and see if it makes a difference.

Unsatisfactory bowels movements however do compete with spouses, bosses, children and work place as a significant cause for unhappiness in life. The solution often lies in treating them as barking street dogs: if you heed them they bark more; if you ignore them, they often stop barking.