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Author: Stephen J. Klemawesch, MD

Circadian Cycles

Circadian Cycles

The New England Journal of Medicine recently had a review article on circadian mechanisms.  What was once thought to simply control sleep/wake periodicity and females’ monthly cycles is now known to control our complex physiology even down to a cellular level.  Also, they are not unique to humans but have been present in all life forms (plant and animal) for the past 3 billion years. 

This universal presence indicates that circadian cycles are critical for both fitness and survival of all species. 

In humans there are two types of circadian clocks: the master clock in the brain and individual clocks in individual cells.  In the brain, the main timepiece is found in an area comprised of about 20,000 nerve cells called the suprachiasmatic nucleus (SCN).  But, the key input to this area comes from our eyes via photo receptor cones and rods.  The input of light sets the pacemaker cells in the SCN to our specific cycle.  These pacemakers can only reset themselves by one hour per day.    Thus, travel across multiple time zones requires one day for each zone crossed to reset.  This is called jet lag.  But many people experience a similar disruption due to “social jet lag” which occurs when sleep time varies a lot due to work/school hours versus weekends. 

Another source of disruption occurs due to the frequent use of electronic devices such as computers and smart phones.  The blue light emitted by electronics has a very strong clock resetting effect. 

Individual cells contain clock genes referred to as CLOCK-BAMAL1 that regulate DNA, RNA and protein synthesis.  By so doing, cells will perform best at certain times of the day and poorly at other times.  This has important ramifications for our immune systems and allergy.  It has

been shown that allergic reactions are more likely to be severe when there is a dysregulated clock. 

Immune defense against infection can be similarly impaired. Inflammatory diseases such as inflammatory bowel disease and arthritis worsen with clock dysfunction.  Even immune protection against cancer is reduced in shift workers and in people with frequent alterations in circadian cycles.  This has been very clearly shown for breast cancer, colon cancer and prostate cancer.  Curiously, exposure to artificial light at night increases the risk for melanomas, independent of degree of sun exposure.  Also, morning sunlight is more likely to promote skin cancer development than sunlight later in the day.

So, I guess Tom Hank’s character Chuck Noland said it best in the movie Castaway: “We live and we die by time and we must not commit the sin of turning our back on time.” 

Topical Steroids & Bone Density

Topical Steroids & Bone Density

It has been known for a long time that systemic steroids can affect bone density.  This effect is both dose and durations of therapy related. 

Until recently, there has not been a good scientific study of topical steroids and bones.  Danish scientists recently Finished (pun intended) a 15-year study of 723,000 adults using topical steroids.  They found that long term use of medium or high potency steroids did contribute to the development of osteoporosis and also increased risk for bone fractures.   

CrossFit vs Crosswords

CrossFit vs Crosswords

By: Sasha Klemawesch, MD

A few years ago, I wrote about a potential vaccine for Alzheimers. We are still a while away from having one on the market, especially since the initial trials had to be aborted due to brain swelling and other unwanted side effects. (Don’t lose hope though, a new formulation is in development and undergoing clinical validation studies.)

But in the meantime, there are many non-pharmacologic things you can do to keep your brain healthy.

When asked, “What’s the best thing to do to keep your mind sharp and ward off dementia?” Most people (myself included) would answer “crosswords” or some other sort of brain teaser. Turns out…. Yes … and/but … No.

In his new book, “Keep Sharp”, Dr Sanjay Gupta discusses strategies for preserving brain function, and he talks about the myth of the crossword puzzle. If you are someone who does crosswords, or sudoku’s, or some other form of mental exercise every day, you might not be getting as much benefit from them as you had hoped. Over time it becomes a ‘practice-makes-perfect’ phenomenon, where your brain learns how to perform the task and therefore it is no longer a struggle to complete it. The key to enhancing cognitive function (at any age) is to challenge the brain. You want to create new neural connections and force it to forge new pathways. By doing so you literally and figuratively grow your brain size. But the only way to form new neuronal paths is to engage in new activities.

If you love crosswords, by all means, keep doing them. But add in different sorts of puzzles, like cryptograms or kakuros. Even better, do something physically stimulating rather than just mentally so. Physical activity is one of THE most important aspects of maintaining a healthy brain. And despite the name of this article, you do not have to start dead-lifting 300 lbs. or running triathlons. A little exercise goes a long way.

If you spend a good deal of the day watching TV, simply standing at each commercial – yes, just standing up – will have enormous benefits. Better yet, stand and do squats. If you are more a book reader, get up at the end of each

chapter and walk around the kitchen island 10 times or march in place for 1 minute. It might sound inconsequential, but those little things will add up. Even better than doing a few minutes here and there inside your house would be to get outside in the fresh air for a walk. And if you can do it with a friend, all the better. Dr Gupta calls that a “brain trifecta.” By (1) moving, (2) socializing and (3) destressing, you “measurably detoxify” your brain, and the spontaneity inherent to friendly conversations means your brain can’t anticipate what will come up during the interaction, so you end up engaging multiple regions of it. Also, research has shown that there is an inverse proportion between your risk of cognitive decline and the size of your social network.

Finally, don’t waste your time on supplements. There is no magic pill that can prevent cognitive decay. Eating a healthy balanced diet with lots of fresh fruits and veggies, while limiting refined sugar and saturated fats will get you the antioxidants and brain food you need.

Antibodies after Covid-19

Antibodies after Covid-19

Two recently completed studies on people who sustained mild (non-hospitalized) infections with Covid revealed good immune response for the three months of the study.  The recovered patients had both lymphocyte and antibody immunity to Covid.  This is good news.  What isn’t known yet is how long this immunity will last.  Studies are ongoing in this regard. 

COVID Vaccine in Older Adults

COVID Vaccine in Older Adults

Development of safe and effective vaccines for Covid-19 have been a global priority for thousands of scientists.  Most of the participants in the varied trials are young and middle-aged adults.  This has led to a concern that the good results in younger adults might not apply to older adults.  Older age is a major risk factor for individuals having more severe disease and fatal outcome.  It is also known that in general older adults do not have as robust an immune response to vaccination as do younger adults. 

Emory University just completed a study of the m-RNA-1273 vaccine in older adults with their results being published in the New England Journal of Medicine.  They looked at two age groups:  56-70 years, and greater than 71 years.  Both groups received the recommended initial dose followed by the booster dose 28 days later.

The laboratory markers that were analyzed were assessment of T-cell response, and assessment of neutralizing antibody production.  Both T-cells and antibodies are critical in providing protection against Covid-19.  As it turns out, both age groups had excellent responses in their T-cells and antibodies. 

The other parameter that was studied was adverse events, including: arthralgia, fatigue, fever, chills, headache, muscle ache, nausea, local reaction at injection site, and pain at injection site.  First of all, there were no serious adverse events.  Secondly, the side effects were similar in both groups with two exceptions: the 71 and older group were more likely to experience fatigue and fever than the 56-70 age group. 

These results should be a source of reassurance and comfort to all those baby-boomers out there.

When Bitter is Sweet

When Bitter is Sweet

Asthma affects millions of people worldwide.  The pathophysiology is complex but involves exaggerated smooth muscle contraction in the airways along with inflammation that in a chronic state causes airway remodeling (narrowing).  The majority of current therapies for asthma address these two issues.  Bronchodilators relax the smooth muscles and anti-inflammatories treat the inflammation.  Despite the panoply of these medications there are still many asthmatics who either don’t respond as well as desired or have untoward side effects from the medications. 

Recent research at our local USF has uncovered a new potentially unique mechanism via bitter taste receptors (TAS2R).  Bitter taste receptors are found in many animals, including humans, and are thought to have evolved as a survival mechanism to both sense and avoid potentially harmful food sources.   As it turns out, stimulating these receptors causes airway smooth muscles to relax by a mechanism completely different from currently available bronchodilators. 

It also seems that stimulating TAS2R receptors in the nose and lungs can promote an innate immune response against inhaled irritants and microbes, and can also improve clinical function.  Remember that cilia are the microscopic hairs whose motion helps remove allergens, irritants and microbes from our respiratory system.  So, having the cilia beat more quickly is a good thing.

Of course, this research is very preliminary but the exciting aspect is it may prove to be an extremely safe new approach to treating asthma.  Perhaps Mary Poppins was wrong about “the spoonful of sugar”. 

PPI’s and Mast Cells

PPI’s and Mast Cells

PPI’s aka protein pump inhibitors have been a true God-send for millions of patients with upper gastrointestinal problems: from reflux to gastritis to ulcers.  In large part they have supplanted the previously developed H-2 blockers:  Zantac, Axid, Pepcid and Tagamet. 

Both groups of medicines work by reducing production of the stomach acid, hydrochloric acid.  The chemical formula for this acid is HCI because it is made up of a hydrogen ion (also known as a proton) and a chloride ion.

Now, based on research at Harvard University, PPI’s may have a novel role in treating allergy.  It has been known for quite some time that PPI’s are very helpful in treating a severe form of esophagitis caused by allergy known as eosinophilic esophagitis (EOE).  Until the Harvard studies the reigning theory for the PPI’s benefit was that they controlled excess acid from further injuring the already allergy-inflamed esophagus.  And though this pathophysiology is probably still part of the benefit of the PPI’s it turns out they also exert an effect on the allergic MAST cells.

MAST cells cause allergic inflammation by releasing their cellular contents (contained in granules) including proteases, cytokines, and histamine.  As it turns out PPI’s block some non-gastric proton pumps including the one found inside MAST cells.  Blocking this intracellular proton pump changes the internal pH (acidity) of the MAST cells which interferes with their release of inflammatory molecules.  However, not all PPI’s exert this effect.  To date the only two known to do so are omeprazole and esomeprazole. 

The Harvard researchers hope to extend these findings to find even better ways to “deflate” the MAST cells and their inflammatory granules. 

Dear Dr. K; Can food allergy cause migraines?

Dear Dr. K; Can food allergy cause migraines?

Migraines are caused by genetic makeup but can be precipitated by many factors including food allergy.  The genetic science of migraine is very complex and still evolving.  Suffice it to say that it can be monogenetic or polygenetic.  Monogenetic means a single gene causes the individual to be prone to migraines whereas polygenetic means a whole variety of genes can play a role. 

Migraine headache has a complex physiology that involves vascular (blood vessel) changes, electrical changes, and chemical changes (especially involving neurotransmitters) in the brain.  If an individual inherits genes that impact two or more of these mechanisms then they tend to have greater difficulties with the headaches. 

It has been known for a long time that certain foods can trigger migraines separate from the issue of food allergy.  These foods exert their effect via one of the three mechanisms:  vascular, electrical, or chemical.  And the list includes:  chocolate, cheese, liver, beer, wine, vinegar, nuts, mushrooms, smoked and pickled meat/fish, beef concentrates (bouillon), eggs, yoghurt, soy sauce, MSG and foods containing nitrites (bacon, hot dogs, etc.).

These foods have potential to affect any individual with migraines.  It is probably best to add caffeine to the list in that either withdrawal from caffeine or variations in intake of caffeine can cause migraines. 

With respect to food allergy this would only apply to individuals who are atopic.  And any given food has a potential to precipitate migraine.  The basis for food allergy and migraine is a function of the release of histamines and inflammatory molecules from ingesting the allergic food.

One good way to ferret food-headache issues is to keep a diet/headache diary.  Sometimes its combinations of foods that create a problem, not single exposures.  A diet diary is very helpful in gaining this type of insight. 

Dear Dr. K; Are you personally going to take the coronavirus vaccine?

Dear Dr. K; Are you personally going to take the coronavirus vaccine?

Yes. And let me tell you why.  In 1720 the average life expectancy in this country was 25.  A hundred years later in 1820 it was 41.  Then in 1920 it hit 54.  Currently it is in the mid-70’s.  Despite all the marvels of modern medicine from antibiotics, to trans-vascular heart surgery, to organ transplantation, the major reasons for this improvement in life expectancy boil down to the big three S’s:  sanitation, shoes, and shots.

It is hard to believe but the “why didn’t I think of that” realization that the sources of drinking water should be kept separate from human and animal waste is very recent.  It came with the scientific discovery of microbes (viruses and bacteria) and how they are transmitted.

Then the universal use of footwear came into play.  Prior to that innovation a majority of humans went bare-footed for at least part of the year depending on climate.  As a result, most humans picked up worm infestations through their bare feet that found their way to the intestinal tract: hookworms primarily, but also other species.  Once the worms set up housekeeping in the GI tract, they were there to stay (until the person died).  Their presence affected health in two ways: reducing available calories and vitamins from food intake, and by causing chronic anemia. 

The final “S” is shots, as in vaccines.  In 1798 Edward Jenner developed smallpox vaccination.  About 90 years later Louis Pasteur, often called the father of immunotherapy, developed anthrax and rabies vaccines.  It wasn’t until 1924 that Emil Von Behring developed the tetanus vaccine.  The polio pandemic was stopped in 1955 when Jonas Salk developed the polio vaccine.  Prior to vaccines, those five diseases killed countless millions of children and adults. 

It all comes down to the old adage of “an ounce of prevention is worth a pound of cure”.  Sanitation, shoes, and shots all work by preventing illness.  So, yes, I will get the coronavirus vaccine. 

Covid-19 and Allergy

Covid-19 and Allergy

Harvard researchers recently published their findings regarding allergic disorders and susceptibility to Covid-19.  The study was conducted on 220,000 people between January and May of this year. 

Previous to this study it has been known that people at greater risk for and from this virus include those: over 65, with pre-existing lung disease, with chronic kidney disease, with diabetes, with hypertension, with heart disease, obesity, with cancer, smokers, with immune compromising illnesses, with organ transplants and with HIV.  Now it appears that underlying allergy also confers greater risk. 

It has been known for many years that underlying allergic respiratory problems predispose to other types of respiratory infections from colds, to ear and sinus infections to bronchitis and pneumonia.  It has also been known for years that treating the underlying allergy reduces this risk.  Now, it seems that allergy predisposes to both catching Covid-19 and having a more serious outcome.  People with either allergic rhinitis or asthma have this increased risk.  The scientists feel the increased risk from allergy is probably multifactorial, but one aspect recently discovered is an increase in one of the cellular attachment proteins: TMPRSS2.

In order to enter the human body Covid-19 has to use certain available “doors” called cell receptors.  The more “doors” available, the more readily the virus can enter.  Allergic inflammation increases the number of TMPRSS2 doors.

The researchers went on to speculate that having good control of the allergic condition (and thereby reducing the inflammation) should help reduce this increased risk.