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Alpha-gal Revisited

Alpha-gal Revisited

Several years ago, this newsletter discussed a new form of anaphylaxis due to tick bites.  The syndrome is peculiar in several ways.  Most importantly the anaphylaxis is delayed from the exposure by several hours.  Also, it occurs after eating mammalian meat such as beef and pork. 

Alpha-gal is a glycoprotein that is found in mammalian meats.  The patient becomes sensitized to the alpha-gal from a tick bite because the ticks secrete alpha-gal in their saliva when they bite humans.  In order to diagnose the condition, the patient needs to be tested for alpha-gal.  They do not show a positive response to the standard allergy tests for beef, pork, etc. 

The new twist is that certain round worms, such as Ascaris lumbricoides also contain alpha-gal and infestation with these worms can lead to the same syndrome. 

Clusterin

Clusterin

Another molecule (Clusterin) has been discovered that protects the brain from inflammation and is generated by exercise.  Several years ago, neuroscientists discovered irisin as a protection for brain inflammation that is produced by exercise.

The current concept regarding dementia is that it occurs due to chronic inflammation in the brain with resultant scar tissue (amyloid plaque).  In this regard scientists have studied patients with early dementia and have found an improvement in cognitive function via a daily exercise routine.   The exercise leads to increased production of both irisin and Clusterin.

Dear Dr. K;

Dear Dr. K;

Thank you for keeping an open dialogue with me about Covid vaccines.  As you know, I opted against vaccination.  However, over Christmas I caught Covid, but luckily it was a mild flu like illness.  So, I guess I should be OK from here on out. 

I’m glad your illness was mild, but I’m a little hesitant about predicting how things will play out in the future.  First of all, just as vaccination doesn’t provide iron-clad protection so too natural immunity via infection is not 100% effective in preventing re-infection.  Therefore, with the extended nature of the pandemic, following Covid avoidance precautions still makes sense. 

Another concern I have is the frequency of post-Covid sequelae especially neurologic ones.  By now, the general public is well aware of Covid illness’ predilection to impact the sense of taste/smell.  As it turns out, this is just the tip of the proverbial iceberg.  At this point in the pandemic, it seems that roughly 70% of infected individuals suffer some sort of extended neurological issue.  For many it’s the smell/taste scenario and for others protracted headaches.  Of much graver concern is research done by Oxford University on 45,000 people in the UK which showed loss of brain mass as measured by CT scanning.  The loss was primarily in the frontal and temporal lobes which subserve the senses of taste and smell but also cognition. 

In this regard, the Oxford scientists conducted performance tests on some of the Covid patients and found they were slower in processing information than non-infected counterparts.  Also, there was no correlation between the severity of the illness (hospitalized verses non-hospitalized) and the loss of brain matter. 

These facts set up a comparison with Alzheimer’s disease where a common symptom is loss of sense of smell along with frontal/temporal lobes pathology.  In fact, some neuro scientists posit that Alzheimer’s disease is caused by chronic inflammation in genetically susceptible individuals to a prior viral infection.  What isn’t known is the potential for brain mass recovery in these individuals.  Neuroplasticity allows marked recovery of the brain from many insults.  Perhaps this will still be true with “Covid brain”.  But for now, I think it’s still best to not catch the illness. 

Gut Microbiome and Prostate Cancer

Gut Microbiome and Prostate Cancer

A recent article published in Science looked at the effect of gut microbiome and prostate cancer.  Obesity alters the gut flora.  It has been known for some time that obese men are more prone to prostate cancer.  Now, it seems there is a cause and effect. 

A current treatment for prostate cancer is castration (to remove the driving force of testosterone) either chemical via anti-androgens or surgical.  This almost uniformly leads to a very good clinical response.  But in some patients this response is short lived because their gut flora alters to bacteria that can produce androgens (testosterone).  This switch phenomenon is more likely to occur with obesity.  Currently research is ongoing to find an antibiotic therapy to eliminate these mischievous microbes or a form of probiotic to displace them. 

While that research is being completed another approach is via self-reliance.  It is known that even modest weight reduction (10 to 15 pounds) has a favorable impact on the gut microbiome.  In addition, adding a probiotic and selecting foods to support the probiotic (pre-biotics) can reduce the bad gut flora. 

Ivermectin for Covid

Ivermectin for Covid

Ivermectin in an FDA approved drug for the treatment of intestinal strongyloidiasis (round worm) and onchocerciasis (filarial worm).  It is also used in veterinary medicine to treat parasites in pets and in livestock. 

Because of significant use of Ivermectin off label to either try and prevent or to try and treat Covid, scientists have scrutinized its potential.  Of interest in vitro (in a test tube) Ivermectin does inhibit replication of the virus.  Unfortunately, in vivo (in actual patients) multiple studies have confirmed that it fails to either prevent Covid or treat Covid.  Despite these scientific facts, thousands of Americans have taken Ivermectin for Covid.  These individuals obtain either veterinary Ivermectin or prescription Ivermectin. 

This wouldn’t be a problem if Ivermectin were a perfectly safe drug.  Unfortunately, that isn’t the case.  Oregon Health and Science University recently reported in the New England Journal of Medicine a plethora of cases of Ivermectin toxicity.  

The usual treatment of Strongyloides is 12 to 14 mg either one time or twice.  But some individuals using the drug for Covid are using much larger doses and for longer periods of time.  The University of Oregon has compiled a study of Ivermectin toxicity.  To date no one has died, but there have been many patients hospitalized and many requiring ICU care for their toxicity.  The majority of these individuals were using veterinary products without prescription guidance.  Some were taking as much as 100 to 125 mg a day.  The main toxic effects were gastrointestinal, cardio vascular or neurologic.  The neurologic side effects included generalized weakness, ataxia and seizures. 

As the Covid pandemic continues it is critical that good scientific inquiry and open-mindedness prevail.  But at this point in time good science indicates that Ivermectin is not helpful and can be harmful. 

Transplant Immunology

Transplant Immunology

Since the first kidney transplant in 1950 and the first heart transplant in 1967 the field of transplant immunology has grown by leaps and bounds.  As successful as transplant medicine has become, there is still a major problem:  not enough donors.  This has led many scientists to explore the field of

xenotransplantation, using non-human animals as a source for organs. 

Other than the circumstance of receiving an organ from an identical twin, human to human transplants require immunosuppressive therapy to prevent immune rejection from occurring.  As good as this therapy has become, long-term rejection still occurs. 

Current research, therefore, centers on two areas:  genetics and immunology.  The genetic aspect involves genetically engineering the donor animal.  Two already successful inroads to this end are producing chimeras and immune cloaking.  A chimera is a genetically modified animal that expresses human antigens.  Immune cloaking involves a process that “hides” the animal antigens from immune scrutiny.  These techniques have been proven to work in animal models allowing rat pancreas to be transplanted into a mouse.  So, the future of human health may lie with our porcine and bovine brethren. 

New Covid Strategies

New Covid Strategies

The FDA has recently approved (emergency use authorization) two oral antivirals and a monoclonal antibody for Covid. 

The antivirals are designed for out patient use in mild to moderate Covid-19.  Both have proven to be active against the original Corona virus and its new variants. 

Paxlovid uses two agents:  nirmatrelvir (a viral protease inhibitor) and ritonavir (a CYP3a inhibitor).  The treatment is for 5 days and can be used down to the age of 12. 

Lagevrio contains molnupiravir a nucleoside analog that can be used down to 18-year-olds but not in pregnant women.  Again, it is a 5-day treatment. 

The monoclonal therapy is Evusheld and it contains two long lasting (6 months) antibodies:  tixagevimab and cilgavimab.  It is not a vaccine but a prophylaxis for people who are immune compromised (whether or not they have also been vaccinated) and for patients who can not receive one of the existing vaccines. 

Many immunocompromised individuals have a poor response to the vaccines and Evusheld provides an additional method of protection. 

Dear Dr. K;

Dear Dr. K;

My sister is on a JACK medicine for her ulcerative colitis but she said it may soon be used for allergies.  Is that true?

Well, kind of.  First of all, not to be too picky but there is a whole family of JAK drugs and the “JAK” refers to Janus kinase which is a pathway that transmits signals across cell membranes.  The JAK system plays important roles in embryonic development, stem cell development, blood cell production and inflammation signaling. 

This last role is why it can be targeted to prevent inflammation, because left to its own devices it transduces signals from cytokines (chemical messengers) into cells leading to inflammation.  I’m pretty sure your sister is taking tofacitinib which is also being used to treat rheumatoid arthritis and most recently Covid-19. 

You might have heard about a phenomenon in severely ill Covid patients called cytokine storm.  Basically, these particular individuals have an unbridled inflammatory response to Covid which causes the severe lung inflammation.  Tofacitinib has saved the lives of thousands of ICU hospitalized Covid patients by abrogating this “over the top” inflammation. 

But to get to the point of your question, the JAK system has great potential to help a myriad of allergic conditions.  Just as Covid related cytokine storm, and autoimmune diseases such as your sister’s rheumatoid arthritis are due to failure to properly regulate the immune system, so too is allergy. 

The currently available JAK drugs are taken orally and therefore work systemically.  Because of their systemic nature there is some potential for untoward side effects such as immune suppression.  The research on JAK’s for

allergy has focused on site delivery either by inhalation to treat asthma or by skin application to treat eczema.  Research on both of these applications is very promising.  In fact, the FDA just approved the first topical JAK for treating eczema: Opzelura (ruxolitinib cream).  For both asthma and eczema, the JAK drugs will provide an alternative to steroids to treat the inflammation that causes both conditions. 

Irisin

Irisin

Patients who come to this office know well the exercise sermon both doctors preach.  Exercise is one of the key foundational elements of general health and also allergic/immunologic health.  New research is adding cognitive health to the list of benefits.  

Recent journal articles in the Journal of Cellular Physiology and in Journal of Nature Metabolism contain new data on the fact that exercise leads to the production of a hormone irisin.  It has been known for some time that irisin transforms white fat cells (which store fat) into brown fat cells (which burn fat) and also improves insulin resistance (the cause of Type II diabetes). 

Now it seems that irisin enhances cognition in humans and in experimental mice.  Several experiments in mice were very compelling.  In one experiment either injecting irisin into mouse brains or increasing irisin production via gene therapy led to marked improvement in cognitive function in otherwise normal mice.  Then in two established mouse models of Alzheimer’s disease increasing irisin restored lost cognition.  It did so by reducing neuro inflammation which is the cause of Alzheimer’s disease. 

Lions and tigers and bears, oh my! Or polyomavirus…

Lions and tigers and bears, oh my! Or polyomavirus…

It has been known for quite a while that certain viruses such as respiratory syncytial virus (RSV) and rhinovirus (the common cold) have been associated with the development and/or worsening of asthma.  Both of these viruses are RNA viruses.  This fact led researchers to wonder about certain DNA viruses.  The one most recently studied is polyomavirus.  This virus is widespread and consists of 117 species.  Once thought to be totally innocuous, it is now understood that these viruses can cause clinical illness in people with compromised immune systems.  But people with normal immune systems don’t have a clinical illness.  However, now it seems that some of these asymptomatic infections can be either helpful or hurtful.  Two of the viruses: KIPyV and HPyV6 have been shown to confer protection from children developing eczema; whereas, a different virus WUPyV is associated with a strong proclivity for children to develop asthma. 

What is really weird is where these viruses infect a child.  The KIPyV and HPyV6 infect the skin while the WUPyV infects the lungs.  It seems that this is what makes the difference.  The immune response to the virus can either help or hurt.  So, even though healthy children exhibit absolutely no symptoms from these infections, their immune response to the viruses can have either a protective or harmful effect in terms of allergy.  Researchers want to extend these findings especially in terms of finding the “friendly and protective” viruses.