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Author: Stephen J. Klemawesch, MD

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. 

Microbiome and Medicines

Microbiome and Medicines

Previous issues of the Allergic Reaction have had several articles about the human microbiome and its impact on health including its effects on the immune system and other systems.  Now, add an additional new finding to this list.   This research was recently published in Nature and it studied interactions of gut bacteria with oral drugs. 

Among people who have the same disease a particular medicine can vary greatly in its effectiveness and side effects.  Much of this variability has been attributed to genetic differences.  This new research indicates that some of the variability is also due to the patients’ gut flora. 

Scientists studied the effects of 15 drugs on 25 strains of human gut bacteria and found a remarkable variability in drug-bacteria interactions.  For a given medicine some bacteria stored it without modifying it; whereas, other bacteria modified it either to make it more or less bioactive.  Either way, the bacteria can lead to the patient receiving a bigger dose or a lower dose of the medicine than was intended. Getting a bigger dose than intended has potential to lead to greater incidence of side effects. 

The other side of the research coin showed that some of the drugs altered the growth rate and metabolism of the bacteria.  This in turn led to an increase or decrease in the molecules secreted by the gut bacteria including: hormones, neurotransmitters and inflammatory molecules. 

At first blush many people are going to feel frustrated by this new level of complexity in how medicines affect us, but scientists have known for a long time this variability in patient response and it was dealt with via “trial and error”.  Hopefully, this new research will lead to a scientific algorhythm for proper dosing based on individual microbiome. 

C- Tips: (Christmas Tips)

C- Tips: (Christmas Tips)

-Nuts (especially walnuts & chestnuts), chocolate, cinnamon and “re-gifted” fruit cake can be non-allergic irritants to the mouth and tongue even to the point of causing canker sores, so tread lightly

-Mistletoe can be a contact irritant similar to poison ivy so when kissing stand beneath it but don’t hold it

-“Fresh” Christmas trees are often not so fresh but are often harvested weeks beforehand and kept damp.  This in turn can lead to mold contamination which can be both an allergen and a respiratory irritant. 

-Sleepiness after eating turkey is caused by its high content of the amino acid L-tryptophan which is readily converted to the neurotransmitter serotonin. 

Dear Dr. K;

Dear Dr. K;

My husband and I are pre-planning for our first pregnancy.  I’ve had asthma since I was 11years old, can I stay on my asthma medications while pregnant? 

The short answer is yes.  The emphatic answer is yes, its vital.  The long answer comes next. 

Asthma affects 5 to 8% of women of childbearing age and is one of the most common underlying health conditions that can complicate pregnancy.  Poorly controlled asthma is associated with increased risk of maternal morbidity, spontaneous miscarriage, gestational diabetes, hypertension of pregnancy, pre-term delivery, fetal growth retardation, and congenital abnormalities. 

Therefore, the basic take home message is “control your asthma as well as you can during pregnancy”.  In 2019 the NIH (National Institute of Health) hosted a scientific workshop to better define the safety of asthma medications during pregnancy.  Based on their findings they recommended a six-step approach to treating pregnant asthmatics based on the severity of their condition. 

Step 1 for very mild intermittent asthma was to use a rescue inhaler as needed but no daily “controller” medicine. 

Step 2 for mild persistent asthma was to start a controller medication.  The preferred controller was low dose inhaled steroid but alternative controllers were theophylline, cromolyn, or a leukotriene antagonist (LTRA) such as Singular or Accolate.