This blog is a way of sharing the information and resources that have helped me to recover my son Roo from an Autism Spectrum Disorder. What I have learned is to view our symptoms as the results of underlying biological cause, which can be identified and healed. I say "our symptoms" because I also have a neuro-immune disorder called Myalgic Encephalomyelitis.

And, of course, I am not a doctor (although I have been known to impersonate one while doing imaginative play with my son)- this is just our story and information that has been helpful or interesting to us. I hope it is helpful and interesting to you!


Monday, March 4, 2024

Harm Caused by Prescription Medications

There are many drugs and categories of drugs that can cause harm.  Here are some of the more common ones:

EpiPen maker failed to investigate product flaws associated with patient deaths, FDA says
"The FDA said Meridian Medical Technologies, a Pfizer company that manufactures the auto-injectors used to treat life-threatening allergic reactions, had detected faults in some units of the EpiPen and failed to adequately respond. In addition, the company received "hundreds of complaints" that the drug did not function properly -- "including some situations in which patients subsequently died."

Prescription Drugs Now Kill More People In The US Than Heroin And Cocaine Combined
When Half a Million Americans Died and Nobody Noticed (Vioxx) 

Not Good: Nearly 1 in 3 Drugs Have Safety Issues Even After FDA Approval
"New research has shown that, even after drugs are approved by the US Food and Drug Administration (FDA), nearly one in three of them go on to have safety issues. That's not necessarily as bad as it sounds - the good news is that this shows the FDA is taking lifetime monitoring of its approved drugs seriously. But perhaps more concerning is the fact that so many drugs with safety issues are getting approved in the first place."

Fluoroquinolones are a class of antibiotics, ciprofloxin is probably the most widely recognized.  Other drugs in this category, sometimes called "floxies" have names ending in -floxin.  In 2016 the FDA put out a warning saying that these drugs should be used as a last line of defense and generally avoided for common, non-serious infections because they cause serious side effects.  These side effects can be disabling and permanent and include tendon rupture, central nervous system damage, and heart damage.

FDA Drug Safety Communication: FDA advises restricting fluoroquinolone antibiotic use for certain uncomplicated infections; warns about disabling side effects that can occur together
"The U.S. Food and Drug Administration is advising that the serious side effects associated with fluoroquinolone antibacterial drugs generally outweigh the benefits for patients with acute sinusitis, acute bronchitis, and uncomplicated urinary tract infections who have other treatment options. For patients with these conditions, fluoroquinolones should be reserved for those who do not have alternative treatment options.

An FDA safety review has shown that fluoroquinolones when used systemically (i.e. tablets, capsules, and injectable) are associated with disabling and potentially permanent serious side effects that can occur together. These side effects can involve the tendons, muscles, joints, nerves, and central nervous system."

FDA updates warnings for fluoroquinolone antibiotics on risks of mental health and low blood sugar adverse reactions
"Across the fluoroquinolone antibiotic class, a range of mental health side effects are already described in the Warnings and Precautions section of the drug labeling, but differed by individual drug. The new class-wide labeling changes will require that the mental health side effects be listed separately from other central nervous system side effects and be consistent across the labeling of the fluoroquinolone class. The mental health side effects to be included in the labeling across all the fluoroquinolones are disturbances in attention, disorientation, agitation, nervousness, memory impairment and delirium."

"Additionally, the recent FDA review found instances of hypoglycemic coma where users of fluoroquinolones experienced hypoglycemia. As a result, the Blood Glucose Disturbances subsection of the labeling for all systemic fluoroquinolones will now be required to explicitly reflect the potential risk of coma with hypoglycemia."

Specific cases and stories
Paralyzed By A Prescription: Doctor 'Poisoned' By Common Antibiotic
A doctor who once prescribed these meds became paralyzed after taking them.  He recovered after a stem cell transplant, and now raises awareness among other doctors about the risks they pose.  He says the experience taught him about what patients go through.

‘I can’t walk today:’ 25 Investigates finds millions still prescribed risky antibiotic
In 2023 over 3,000 adverse reactions to fluoroquinolones were reported to the FDA.  These drugs continue to be used with relative frequency despite the FDA's warning that the risks generally outweigh the benefits.  

Southland Firefighter Says Popular Antibiotic Poisoned His Body, His Life
The prescribing doctor told him that only elderly people or those with existing health problems get the side effects, and another doctor told him it was fine and to stay off the internet.  Doctors are generally unaware of the dangers of this drug.

Popular antibiotics linked to growing number of suicide deaths, patients unaware of side effects
FDA reports tie over 200 suicides to cipro and levaquin.  The FDA estimates that only between 1 and 10% of adverse drug reactions are reported.


Tuesday, October 17, 2023

Metabolic and Mental Health

 What are Metabolism and Metabolic Health, and How Do They Impact Mental Health?
"Metabolism is the set of life-sustaining chemical reactions in organisms.  The three main things that metabolism does is convert the energy in food to energy that is available to power the cell and therefore the organism, the conversion of elements in food into the building blocks to make proteins, lipids, nucleic acids and carbohydrates, and the elimination of metabolic waste.   Another definition of metabolism is "all the physical and chemical processes in the body that convert or use energy".  Metabolism is how we use our food to create energy.  If we consume more calories then we need we need to store the excess energy.  We store some as glycogen in the liver, but most is stored in our fat cells.  It makes sense that our bodies would have evolved with uncertainty about when we would have food and how much we would have, so we would have needed to store up excess for times when we didn't have enough.  

Metabolic dysfunction usually results from too much food intake or eating foods with a poor ratio of nutrients to calories.  If we consistently eat more calories/energy than we need, our bodies first store the excess in our fat cells but they eventually get full, and then we store fat in our organs, called visceral fat (such as fatty liver). Visceral fat interferes with the function of the organ in question and leads to disease states such as type 2 diabetes.  We need to have low levels of insulin in order to access and use the energy stored in fat.  Insulin levels rise when we eat, especially if we eat sugars and simple carbs.  When our insulin levels are high this signals our body to store energy because we have plenty for now.  The state of having high insulin levels from frequent eating is called hyperinsulinemia.  If the state of hyperinsulinemia persists our cells become less responsive to insulin, producing a state called insulin resistance.  This means too much sugar stays in the blood and not enough is available for energy use.

Mitochondria and Mental Health

Brain Energy, Mitochondria, and Mental Health
Dr Chris Palmer, MD, Harvard Psychiatrist

A major change in psychiatry has been going on for awhile now in which more and more clinicians and researchers are recognizing mental health disorders as related to, and sometimes caused by, physical states in the body and therefore using therapies that are meant to address these states.  A primary example of this is looking at brain metabolism (mitochondrial function in the brain).

The Keto diet is a 100 year old, evidence based therapy that can stop seizures that medication can't stop.  This is evidence of how powerful nutrition and diet can be in treating and altering brain function.  Psychiatrists use epilepsy medications to treat people with other mental mental health conditions often, usually off-label, so there's nothing new about using the ketogenic diet to treat other mental health conditions.  Seizure meds are used to treat dementia, eating disorders, anxiety, psychosis, mood disorders, substance use disorders, and others.  

The Brain Energy Theory- Mitochondria do more than just produce energy for cells "mitochondria play a role in directing and allocating resources for cells".  Not all of the food that mitochondria in the brain process is turned into ATP- some is turned into serotonin, dopamine, or cortisol, and they also play a part in regulating those molecules.  Mitochondrial function is one way of understanding the imbalances of the neurotransmitters and hormones in the brain.  They are also involved in regulating inflammation (turning it both on and off) and epigenetics by signaling the nucleus of the cell to regulate the transcription of gene.  They monitor our outer and inner environment; sensing stress levels, food intake, blood sugar levels, and oxygen levels.  

"Mitochondria play a role in our response to trauma- psychological and social stressors."  Trauma and stressors play a role in mental illness, so this connection could be very significant, because while people have known that there is a connection they haven't known exactly what that connection is on a biological level.  He points out that mitochondria seem to be a way to "connect the dots" in the mental health puzzle between factors like trauma, neurotransmitters, sleep, substances like drugs and alcohol (I would add exercise and sunlight too).  These are all things that affect mitochondrial and metabolic health or are affected by it or both.  People with mental health conditions have higher rates of many physical disorders including diabetes, obesity, heart attacks, strokes, and generally have a shorter life expectancy.  This connection also opens up the possibility of more and better treatments.

For people who struggle to believe this connection is real, he explains that mitochondria are what drives metabolism, which is how we take food and oxygen and transform them to keep ourselves alive.  If these processes are disturbed it means illness, and if they are disturbed enough or stop, we die.  Most poisons work by harming mitochondria- that's how they harm or kill you.  Other cellular components can be harmed without nearly as much danger to the organism.  It makes sense that since mitochondria are the most important part of the cell and what keeps it able to perform its function, if they aren't functioning right the cell won't be able to function right.  

Mitochondria can become both under-active AND overactive.  This makes sense because there are mental health disorders involving areas of the brain becoming overactive as well as areas becoming under-active.  If the health of mitochondria impacting the cell's functioning is the cause or major contributing factor to many mental health disorders that would explain why they can be better or worse at different times of day (or different seasons), why they can be worsened by stress and sleep deprivation.  A lot of the details aren't known yet but already the basic insight that mitochondria are central to mental health is transformative of the fields of psychiatry and psychology.

What options are available to support mitochondrial functioning?

There are a huge variety of things available to help mito function including sun exposure, red light therapy, various supplements, glutathione, methylene blue, and more, but these can only help so much if core lifestyle issues aren't addressed.  For example, alcohol is a potent mito toxin so a person drinking a large amount daily is poisoning their mitochondria far beyond what those things can help.  Having healthy mitochondria requires lifestyle changes- eating well and avoiding highly processed foods, sleeping well, exercising, and avoiding excess stress.  

The ketogenic diet and its effect on brain function has been studied for a long time, its known to change neurotransmitter levels, inflammation, the gut microbiome, but Dr Palmer says that he believes the impact it has on mitochondria is its most important therapeutic effect.  The keto diet creates a state in the body similar to fasting, which is known to trigger mitophagy (when the cell breaks down old and defective mitochondria that are replaced by new, healthy ones) and mitogenesis (which is the production of new, healthy mitochondria).  Dr Palmer suggests that these two processes that remove old, defective mitochondria and replace them with more and healthier ones, might lead to long-term healing where a person could potentially go off the keto diet and remain healthy.  People who are on the diet to control seizures will usually be kept on the diet for 2 to 5 years after the point at which their seizures completely stop (some people with seizures must stay on keto for life).  People can experience improvement of mental health symptoms, even very significant improvement or remission in weeks or months.  Psychotic symptoms tend to take weeks if not months to improve especially if severe.  People often wonder if making some changes in their diet, such as eating more fatty fish, will be enough.  Dr Palmer says maybe for people with relatively mild symptoms or conditions, some changes such as eating more fatty fish can help, but he points out that those changes don't stop seizures but the keto diet does, he says  "ketogenic therapy is a unique and powerful intervention".

What about other interventions to support mito health?

Exercise is a really important factor also and should be part of a treatment plan.  The two types of exercise for which there is the most evidence of benefit for mito health are strength training (aka lifting weights, working out to build muscle) and level 2 cardio (which he defines as 3-60 minutes of running, cycling, etc that gets you breathing hard but not out of breath).  Those types of exercise increase the number and health of mitochondria in muscles which then send endocrine signals to your brain that improve brain function.  Exercise alone isn't enough to heal mito, lose weight, or heal type 2 diabetes.  If people exercise more but don't change how they eat they don't get significant or sustained weight loss.  There has been one very well-done study of middle-aged adults who were prescribed exercise.  In addition, half were given the drug metformin to take and the other half were given a placebo.  The group that got metformin didn't get the mito and metabolic benefits of exercise the way the other group did, which is evidence that metformin interferes somehow with mitochondrial biogenesis.  Many other medications, including many psych meds, are known to interfere in mito function and biogenesis, so this should be considered.  Lifestyle behaviors such as drinking alcohol and smoking cigarettes and marijuana are also mito toxins.  

The psych drugs that can do this are mostly the anti-psychotics, which have been known to have metabolic side-effects and neurological side effects.  They can cause significant weight gain (he has seen people gain as much as 100 pounds in 6 months), they can cause type 2 diabetes, they worsen every known risk factor for cardiovascular disease (raise blood pressure, raise triglycerides, worsen LDL levels), and increase inflammatory biomarkers.  

This represents a new way to understand mental illness and what might be happening in the brain, and a new way to treat it.  This is especially important as mental health remains highly stigmatized in the US and research around it receives very little funding in comparison to disorders considered to be physical.  Many mentally ill people are in prisons, shelters, or even on the street.  "There is tremendous injustice, in my mind, in how we treat people with mental illness".  Dr Palmer points out that while psychological and social factors play a role in mental illness, it's no less physical and "real" in that way.  People with mental illness "deserve medically necessary treatment".  If we can get needed care to people in prison or who are homeless and who have mental illness, they won't be in prison or homeless anymore, they can live enjoyable, productive lives. 


 

 

 

 

 

 

Thursday, September 7, 2023

Some Antihistamines Found to Treat Cancer

Desloratadine and loratadine stand out among common H1-antihistamines for association with improved breast cancer survival
"As tumors maintain an inflammatory microenvironment, anti-inflammatory medication can be useful in cancer therapy. We have previously shown an association with improved survival in melanoma for use of the H1-antihistamines desloratadine and loratadine, and here we examine use of H1-antihistamines and breast cancer mortality.  We investigated use of the six major H1-antihistamines (cetirizine, clemastine, desloratadine, ebastine, fexofenadine and loratadine) and breast cancer-specific and overall mortality in a nation-wide register-based study of all 61,627 Swedish women diagnosed with breast cancer 2006–2013.  

We found a consistently improved survival of desloratadine users, as well as of loratadine users, relative to nonusers, regardless of patient age, menopause, estrogen receptor status or stage of the tumor, or whether breast cancer-specific or overall survival was analyzed. The survival of users of other antihistamines varied relative to non-users.

Based on their safety and current use within the patient population, together with our observations, we suggest the initiation of trials of desloratadine and loratadine as treatment of breast cancer as well as studies of the mechanism behind their possible effect. Further studies on any effects of other H1-antihistamines may also be merited, as well as of H1-antihistamine use and survival in other malignancies."

Histamine receptor 1 inhibition enhances antitumor therapeutic responses through extracellular signal-regulated kinase (ERK) activation in breast cancer

Repurposing Cationic Amphiphilic Antihistamines for Cancer Treatment
"Non-small cell lung cancer (NSCLC) is one of the deadliest cancers worldwide. In search for new NSCLC treatment options, we screened a cationic amphiphilic drug (CAD) library for cytotoxicity against NSCLC cells and identified several CAD antihistamines as inducers of lysosomal cell death. We then performed a cohort study on the effect of CAD antihistamine use on mortality of patients diagnosed with non-localized cancer in Denmark between 1995 and 2011. The use of the most commonly prescribed CAD antihistamine, loratadine, was associated with significantly reduced all-cause mortality among patients with non-localized NSCLC or any non-localized cancer when compared with use of non-CAD antihistamines and adjusted for potential confounders. Of the less frequently described CAD antihistamines, astemizole showed a similar significant association with reduced mortality as loratadine among patients with any non-localized cancer, and ebastine use showed a similar tendency."

H1-Antihistamines Reduce the Risk of Hepatocellular Carcinoma in Patients With Hepatitis B Virus, Hepatitis C Virus, or Dual Hepatitis B Virus-Hepatitis C Virus Infection
"AH use may reduce the risk for HCC among patients with HBV, HCV, or dual infection in a dose-dependent manner. Further mechanistic research is needed."

Sunday, August 27, 2023

Mast Cell Activation Syndrome and the Vagus Nerve

These are my notes from the article "Mast cell activation syndrome and the vagus nerve"
written by Ross Hauser, MD of Caring Medical on February 4, 2023 

Many patients diagnosed with MCAS (Mast Cell Activation Syndrome) also have neck pain that is diagnosed as (or can be described as) upper cervical instability or cervical spine instability.  It is generally assumed that this pain is part of the existing illness, but in this article Dr Hauser explains that the causality could be going the other way.  Many of these patients are also diagnosed with  Chronic Fatigue Syndrome, Myalgic Encephalomyelitis (ME/CFS), POTS, or some other form of Dysautonomia.  When these patients see specialists to see if the neck pain and problems could be causing some of their symptoms, some are then diagnosed with "degenerative disc disease in their cervical spine and a loss of the cervical curve contributing to kyphosis".Dr Hauser explains that:

"Which brings us to an important question, which came first? Autonomic nervous dysfunction or immune-mediated allergy?  At a minimum, we know they are interconnected. A lot of antigen-antibody immune complexes and a host of histamine releases are going to excite the autonomic nervous system throughout and likewise, autonomic nervous system dysfunction makes antigen-antibody reactions more likely. The patient has the symptoms, is it the neck causing them? Is it the allergies?"

He explains that the way cervical instability could lead to symptoms of MCAS, etc, is because it may be causing the vagus nerve to be pinched or compressed in the neck or: "damaged cervical ligaments’ inability to hold the “wandering” vertebrae in place."  The vagus nerve is how signals from the brain reach the viscera (the organs in your torso) in order to control them, so anything that impedes its function can have major consequences:

"When the vagal nerve sensory afferents are dysfunctional, the important body sensors for homeostasis are switched off. Cervicovagopthy or vagus nerve disorder brought on by cervical spine instability, has wide-ranging negative effects on mucosal barriers in the intestines and lungs, producing a large number of inflammatory mediators, including histamine."

Dr Hauser explains that many patients who fit this profile- having MCAS along with many of the following additional diagnoses- EDS (Ehlers-Danlos Syndrome, POTS (Postural Orthostatic Tachycardia Syndrome), Gastroparesis, Fibromyalgia, sleep disturbances, low blood pressure, serious gastrointestinal pain and dysfunction, "When someone has a myriad of symptoms like this, it is of course difficult to believe they all start spontaneously without a common thread linking them together. In a person like this, when all is a mystery, we follow the neurology, we look for short-circuiting messages between brain and body being caused by compression of the arteries, veins, and the nerves that travel through the cervical spine."

Dr Hauser notes that many of the different disorders and symptoms experienced by these patients Do have established connections and that these connections are further evidence of vagus nerve involvement.  A key example of this is the interconnection between the immune system and the gut, mediated by the vagus nerve, in which modulating signals are sent both ways.  Also, regulating signals and neurotransmitters in this system are part of the mechanism that the body uses to turn inflammation on and off.  To explain this he quotes a may 2021 study in the journal Frontiers in Pharmacology:

“Inflammatory bowel disease, irritable bowel syndrome, and severe central nervous system injury (of which the vagus nerve plays a dominant role) can lead to intestinal mucosal barrier damage, which can cause endotoxin/enterobacteria translocation (movement, or better thought of as escaping to other parts of the body) to induce infection and is closely related to the progression of metabolic diseases, cardiovascular and cerebrovascular diseases, tumors and other diseases.”

"The researchers add that repairing the intestinal barrier represents a potential therapeutic target for many diseases. Repair means addressing the dysfunction of enteral afferent nerves, efferent nerves, and the intrinsic enteric nervous system that play key roles in regulating intestinal physiological homeostasis and coping with acute stress. Furthermore, innervation actively regulates immunity and induces inherent and adaptive immune responses through complex processes, such as secreting neurotransmitters or hormones and regulating their corresponding receptors."

"Histamine is synthesized by mast cells, basophils, platelets, histaminergic neurons, and enterochromaffin cells, where it is stored intracellularly and released upon stimulation. It can be found basically everywhere in the body, including the spinal cord and brain. Histamine causes smooth muscle cell contraction, vasodilation, increased vascular permeability and mucus secretion, tachycardia, alterations of blood pressure, and arrhythmias, while it stimulates gastric secretion and nociceptive nerve fibers. Histamine increases secretions such as hydrochloric acid in the stomach and is vital to protecting the lungs and gastrointestinal tract from infections. When histamine levels are high, increased secretions in the lungs, therefore, cause coughing, phlegm production, sneezing, and diarrhea occur in the digestive tract in an attempt by the body to rid itself of an infectious agent or toxin."

When the transmission of nerve impulses along the vagus nerve from the brain are interrupted or stopped, this can limit the body's ability to regulate and maintain homeostasis (balance of systems), which can keep the body from appropriately limiting the inflammatory response.  It also results in higher histamine content of mast cells, mast cells being more responsive to nerve signals to react, which ultimately means a higher level of histamine in the organs systems.  

"The GI tract harbors the largest population of mast cells in the body and is thus the main reservoir of the body’s histamine. The mast cells’ job is to maintain intestinal permeability and make sure that no microorganisms or antigens enter the body. (A dysfunction of this system can lead to Leaky Gut Syndrome and inflammation of the intestines.) The neurological control over mast cells and their various digestive functions is via the vagal influences on the enteric nervous system.  Elevated histamine levels in the body occur when there is an increase in intestinal permeability (regardless of the cause), including that from synthetic foods (industrial food additives, chemicals in food, genetically modified foods), Ehlers-Danlos syndrome (EDS), and cervical spine instability induced cervicovagopathy."

The effects of histamine on gut function, and how this impacts other disease processes especially autoimmune, has been well-studied.  Some common industrial food additives are known to trigger mast cells to make the gut more permeable (increase the amount of space between cells that line the gut and regulate what gets into the bloodstream and what doesn't), allowing larger proteins than usual into the bloodstream.  Once there, these proteins can trigger allergic and other inflammatory responses and are especially associated with autoimmune disease.  

"Histamine intolerance results from excessive histamine and a decreased ability to absorb or neutralize it.  Elevated levels of histamine give symptoms that mimic allergic reactions, and these include diarrhea, headache, rhinoconjunctival symptoms, asthma, hypotension, arrhythmia, urticaria, pruritis, flushing, and skin lesions. A true allergy is tied to IgE-mediated histamine release, which is to be differentiated from histamine intolerance. The latter is associated with some forms of urticaria, eczema, asthma, food sensitivity, migraines, and chronic GI and neurological ailments, including inflammatory and irritable bowel syndromes."

"The reservoir of histamine in the body originates in the gut and comes from the breakdown of food that is ingested or the microbiota-generated histamine. Histamine intolerance is akin to lactose intolerance in that the body is missing a key enzyme to digest a food substance. In histamine intolerance, it is DAO in the digestive tract, a deficiency of which leads to elevated histamine levels in the body. DAO is synthesized by the intestinal villi (enterocytes) and is constantly released from the intestinal mucosa into the gut, as well as the blood circulation, during eating and digestion."

Mast cell dysfunction is also being increasingly recognized as a major part of many neurological and psychiatric disorders, especially neurodegenerative disease.  "What is being suggested is that the Mast cells are causing runaway neurological inflammation by excerpting a disruptive influence (bad messages) on the central nervous system and brain and this is leading to neurodegenerative disorders such as Parkinson’s disease and Alzheimer’s disease for example." 

"vagal activity, partially driven by gastric mast cells, induces long-lasting changes in corticotrophin-releasing factor signaling in the amygdala that may be responsible for enhanced pain and enhanced anxiety- and depression-like behaviors."

"What they found was vagus nerve stimulation resulted in a significant reduction of the different inflammatory parameters assessed. They said their results underscore the anti-inflammatory properties of the vagus nerve and the potential of neuro-immune interactions in the intestine.  In other words, if the vagus nerve is working correctly, anti-inflammatory and mast cell activation could be suppressed."

Further Information from Dr Hauser:
Can Chronic fatigue syndrome and Myalgic encephalomyelitis be caused by cervical stenosis and cervical spine instability? 

Postural Orthostatic Tachycardia Syndrome (POTS), the Vagus Nerve and Cervical Spine instability

Treatments for Neck Pain and Cervical Instability: A review of upper cervical instability and symptom treatment with Ross Hauser, MD

Cervical Curve Correction – Caring Cervical Realignment Therapy

Research Articles Cited in this Article (not all):
How to evaluate the patient with a suspected mast cell disorder and how/when to manage symptoms

Diagnosis of mast cell activation syndrome: a global "consensus-2"

Global Classification of Mast Cell Activation Disorders: An ICD-10-CM-Adjusted Proposal of the ECNM-AIM Consortium

Evaluation and Classification of Mast Cell Disorders: A Difficult to Manage Pathology in Clinical Practice

Intestinal Mucosal Barrier Is Regulated by Intestinal Tract Neuro-Immune Interplay

The Gut's Little Brain in Control of Intestinal Immunity

Vagal gut-brain signaling mediates amygdaloid plasticity, affect, and pain in a functional dyspepsia model

Vagus nerve stimulation dampens intestinal inflammation in a murine model of experimental food allergy






Wednesday, August 23, 2023

Toxicity From Plastics and Endocrine Disruption

Uterine fibroid growth activated by chemicals found in everyday products
"“These toxic pollutants are everywhere, including food packaging, hair and makeup products, and more, and their usage is not banned,” said corresponding study author Dr. Serdar Bulun, chair of the department of obstetrics and gynecology at Northwestern University Feinberg School of Medicine and a Northwestern Medicine physician. “These are more than simply environmental pollutants. They can cause specific harm to human tissues.”

 "Up to 80% of all women may develop a fibroid tumor during their lifetime, Bulun said. One-quarter of these women become symptomatic with excessive and uncontrolled uterine bleeding, anemia, miscarriages, infertility and large abdominal tumors necessitating technically difficult surgeries."

"Prior epidemiological studies have consistently indicated an association between phthalate exposure and uterine fibroid growth, but this study explains the mechanisms behind that link. The scientists discovered exposure to DEHP may activate a hormonal pathway that activates an environmentally responsive receptor (AHR) to bind to DNA and cause increased growth of fibroid tumors."

Critical Overview on Endocrine Disruptors in Diabetes Mellitus
"Diabetes mellitus is a major public health problem in all countries due to its high human and economic burden. Major metabolic alterations are associated with the chronic hyperglycemia that characterizes diabetes and causes devastating complications, including retinopathy, kidney failure, coronary disease and increased cardiovascular mortality."

Endocrine disruptors in plastics alter β-cell physiology and increase the risk of diabetes mellitus
"Here we review epidemiological, animal, and cellular studies linking exposure to BPs and phthalates to altered glucose regulation, with emphasis on the role of pancreatic β-cells. Epidemiological studies indicate that exposure to BPs and phthalates is associated with diabetes mellitus. Studies in animal models indicate that treatment with doses within the range of human exposure decreases insulin sensitivity and glucose tolerance, induces dyslipidemia, and modifies functional β-cell mass and serum levels of insulin, leptin, and adiponectin. These studies reveal that disruption of β-cell physiology by EDCs plays a key role in impairing glucose homeostasis by altering the mechanisms used by β-cells to adapt to metabolic stress such as chronic nutrient excess. Studies at the cellular level demonstrate that BPs and phthalates modify the same biochemical pathways involved in adaptation to chronic excess fuel. These include changes in insulin biosynthesis and secretion, electrical activity, expression of key genes, and mitochondrial function. The data summarized here indicate that BPs and phthalates are important risk factors for diabetes mellitus and support a global effort to decrease plastic pollution and human exposure to EDCs."

Phthalate exposure and risk of diabetes mellitus: Implications from a systematic review and meta-analysis
"Our results showed that urinary concentrations of phthalates were positively associated with risk of DM.  In literature review, most studies showed positive correlations of phthalates, especially ∑DEHP, with homeostasis model assessment of insulin resistance and fasting glucose."

Association between phthalate exposure and insulin resistance: a systematic review and meta-analysis update
"The majority of included studies revealed positive relationships of insulin resistance with different phthalate metabolites exposure.  The results of sensitivity analyses stratified by age, sex, and site of study remained stable, suggesting the robustness of these meta-analyses."

Urinary phthalate metabolites and metabolic syndrome in U.S. adolescents: Cross-sectional results from the National Health and Nutrition Examination Survey (2003-2014) data
"Relationships between MiBP concentrations and odds of MetS varied by sex. Males with higher concentrations of MnBP and MiBP had greater odds of having a higher number of MetS components. Relationships between phthalate metabolites and MetS did not vary by economic adversity." (MetS is metabolic syndrome, and MnBP and MiBP are types of phthalates)

Association of Early Life Exposure to Phthalates With Obesity and Cardiometabolic Traits in Childhood: Sex Specific Associations
"Prenatal phthalate exposure was not consistently associated with child adiposity and cardiometabolic measures. Our findings suggest that early life phthalate exposure may affect child growth and adiposity in a sex-specific manner and depends on the timing of exposure."

Exposure to endocrine-disrupting compounds such as phthalates and bisphenol A is associated with an increased risk for obesity
"Increasing evidence from epidemiological, animal and in vitro studies suggests that the increased production of synthetic chemicals that interfere with the proper functioning of the hormonal system, so-called endocrine-disrupting compounds (EDCs), might be involved in the development and rapid spread of obesity, coined the obesity epidemic. Recent findings have demonstrated that EDCs may interfere with hormonal receptors that regulate adipogenesis and metabolic pathways. Furthermore, prenatal exposure to EDCs has been shown to influence the metabolism of the developing embryo through epigenetic mechanisms and to promote obesity in subsequent generations."

Diabetes mellitus: Plasticizers and nanomaterials acting as endocrine-disrupting chemicals (Review)
"Various plasticizers and nanomaterials have been linked to endocrine disruptors or endocrine-disrupting chemicals (EDCs) which represent a large, heterogeneous, yet incompletely understood group of structures acting on normal and pathological body pathways such as hormonal production, secretion, transport and receptor binding."

Bisphenol A and Phthalates in Diet: An Emerging Link with Pregnancy Complications
"Bisphenol A (BPA) and phthalates contaminate food and water and have been largely studied as obesogenic agents. They might contribute to weight gain, insulin resistance and pancreatic β-cell dysfunction in pregnancy, potentially playing a role in the development of pregnancy complications, such as gestational diabetes mellitus (GDM), and adverse outcomes. Pregnancy and childhood are sensitive windows of susceptibility, and, although with not univocal results, preclinical and clinical studies have suggested that exposure to BPA and phthalates at these stages of life might have an impact on the development of metabolic diseases even many years later. The molecular mechanisms underlying this association are largely unknown, but adipocyte and pancreatic β-cell dysfunction are suspected to be involved. Remarkably, transgenerational damage has been observed, which might be explained by epigenetic changes."

Bisphenol A is a carcinogen that induces lipid accumulation, peroxisome proliferator‑activated receptor‑γ expression and liver disease
"Bisphenol (BP) A is an exogenous endocrine disruptor that mimics hormones closely associated with health complications, e.g., obesity and cancers."

"The present study revealed that BPA served as a carcinogen, enhanced tumorigenesis susceptibility and may induce other types of liver disease."

Bisphenol S in Food Causes Hormonal and Obesogenic Effects Comparable to or Worse than Bisphenol A: A Literature Review

Pathogenesis of Male Reproductive Tract Lesions from Gestation ThroughAdulthood Following in Utero Exposure to Di(n-butyl) Phthalate

Human 'testicular dysgenesis syndrome': a possible model using in-utero exposure of the rat to dibutyl phthalate
" Abnormal development of Sertoli cells, leading to abnormalities in other cell types, is our hypothesized explanation for the abnormal changes in DBP-exposed animals. As the testicular and other changes in DBP-exposed rats have all been reported in human TDS, DBP exposure in utero may provide a useful model for defining the cellular pathways in TDS."

Disruption of reproductive development in male rat offspring following in utero exposure to phthalate esters
"Certain Phthalate esters have been shown to produce reproductive toxicity in male rodents with an age dependent sensitivity in effects with foetal animals being more sensitive than neonates which are in turn more sensitive than pubertal and adult animals. While the testicular effects of phthalates in rats have been known for more than 30 years, recent attention has been focused on the ability of these agents to produce effects on reproductive development in male offspring after in utero exposure. These esters and in particular di-butyl, di-(2-ethylhexyl) and butyl benzyl phthalates have been shown to produce a syndrome of reproductive abnormalities characterized by malformations of the epididymis, vas deferens, seminal vesicles, prostate, external genitalia (hypospadias), cryptorchidism and testicular injury together with permanent changes (feminization) in the retention of nipples/areolae (sexually dimorphic structures in rodents) and demasculinization of the growth of the perineum resulting in a reduced anogenital distance (AGD). Critical to the induction of these effects is a marked reduction in foetal testicular testosterone production at the critical window for the development of the reproductive tract normally under androgen control. A second Leydig cell product, insl3, is also significantly down regulated and is likely responsible for the cryptorchidism commonly seen in these phthalate-treated animals. The testosterone decrease is mediated by changes in gene expression of a number of enzymes and transport proteins involved in normal testosterone biosynthesis and transport in the foetal Leydig cell. Alterations in the foetal seminiferous cords are also noted after in utero phthalate treatment with the induction of multinucleate gonocytes that contribute to lowered spermatocyte numbers in postnatal animals. The phthalate syndrome of effects on reproductive development has parallels with the reported human testicular dysgenesis syndrome, although no cause and effect relationship exists after exposure of humans to phthalate esters. However humans are exposed to and produce the critical phthalate metabolites that have been detected in blood of the general population, in children and also human amniotic fluid."

Friday, July 14, 2023

Anaphylaxis

International consensus on (ICON) anaphylaxis

Emergency treatment of anaphylaxis: concise clinical guidance
"Anaphylaxis is a serious systemic hypersensitivity reaction that is usually rapid in onset and may cause death. It is characterised by the rapid development of airway and/or breathing and/or circulation problems. Intramuscular adrenaline is the most important treatment, although, even in healthcare settings, many patients do not receive this intervention contrary to guidelines. The Resuscitation Council UK published an updated guideline in 2021 with some significant changes in recognition, management, observation and follow-up of patients with anaphylaxis. This is a concise version of the updated guideline."

Lessons for management of anaphylaxis from a study of fatal reactions
"The unpredictability of anaphylactic reactions and the need for immediate, often improvised treatment will make controlled trials impracticable; other means must therefore be used to determine optimal management.  This study aimed to investigate the circumstances leading to fatal anaphylaxis.  Immediate recognition of anaphylaxis, early use of adrenaline, inhaled beta agonists and other measures are crucial for successful treatment. Nevertheless, a few reactions will be fatal whatever treatment is given; optimal management of anaphylaxis is therefore avoidance of the cause whenever this is possible. Predictable cross-reactivity between the cause of the fatal reaction and that of previous reactions had been overlooked. Adrenaline overdose caused at least three deaths and must be avoided."

Food-induced anaphylaxis
"In the UK register of fatal anaphylactic reactions, all food-induced fatalities have been accompanied by respiratory problems with respiratory arrest. Atopic individuals with bronchial asthma and prior allergic reactions to the same food are at a particularly high risk. Not only peanuts, seafood and milk can induce severe, potentially lethal, anaphylaxis, but indeed a wide spectrum of foods, according to the different patterns of food sensitivity in different countries. Foods with "hidden" allergens and meals at restaurants are particularly dangerous for patients with food allergies. Similarly, schools, public places and restaurants are the major places of risk. However, the main factor contributing to a fatal outcome is the fact that the victims did not carry their emergency kit with adrenaline (epinephrine) with them. Therefore, we suggest that the pharmaceutical industry should reintroduce an adrenaline inhaler that is more effective, especially in asthmatic reactions."

A guide for the management of post vaccination allergy and anaphylaxis in a pharmacy clinic
"Vaccination falls within the scope of practice of a pharmacist and the coronavirus disease 2019 pandemic has seen an increase in pharmacies providing vaccination services. These vaccines are not without risk of allergic reactions and anaphylaxis. The available guidelines for the management of anaphylaxis include the administration of intravenous (IV) fluids. However, IV administration does not fall within the scope of practice of a pharmacist. A gap was identified in the availability of guidelines for the management of anaphylaxis without the use of IV fluid administration."

Presentations of Anaphylaxis
NOT THE VACCINE, BUT ANAPHYLAXIS TO THE COVID-19 VIRUS ITSELF
A patient developed systemic allergic symptoms including fatigue, rash, rhinitis, and lip swelling after exposure to the COVID 19 virus (most likely omicron variant).  She had a history of chronic idiopathic urticaria and dermatographism, so her mast cells may have already been disordered.  Her symptoms lasted for 4 days, during which time she required a continuous IV benadryl infusion as well as remdesivir, Solu-Medrol, loratadine, and famotidine.  Testing showed that she had an elevated level of IL10.