Pyroluria—A Hidden Disorder
What Is Pyroluria?
Pyroluria is a genetic blood disorder and chemical imbalance, involving an abnormality in haemoglobin synthesis. Haemoglobin is a protein that holds iron in the red blood cell. During the production of haemoglobin a seemingly harmless byproduct is created called Kryptopyrrole, or what is now more specifically and accurately known as OHHPL, or HPL (hydroxyhemoppyrrolin-2-one). HPL is a chemical substance involved in the formation of heme, which makes blood red. In most individuals this by-product is harmless and excreted in the urine. For people with Pyroluria, levels of HPL multiply too rapidly and systemically bind and block receptor sites to the nutrients Zinc and Vitamin B6.
Kryptopyrroles (HPL) specifically seek out aldehydes to bind to, in this case Pyridoxine (vitamin B6). This duo does further damage by attaching itself to Zinc, forming a complex which is then eliminated via urine. The result is major deficiency in Vitamin B6 and Zinc. This presents a wide spectrum of mental/physical symptoms. The extent of the deficits are so large, they cannot be counterbalanced by foods high in these particular nutrients.
What This Article Will Cover
• Pyroluria Etiology and History
• Signs, Symptoms, and Associated Conditions
• An Inspiring True Story
Aetiology and History
A familial condition caused by poor genetics (such as familial alcoholism) and/or by environmental toxicity, Pyroluia can be induced by childhood trauma or chronic infection early in life. The onset commonly occurs during the late teens and continues throughout a person's life. It may be triggered by a traumatic incident, such as the death of a loved one, a parental divorce, or moving away to college. The disorder is highly aggravated by prolonged stress, for instance during injury, oxidative stress, or chronic or debilitating illness.
It is estimated that approximately 10% of the population have Pyroluria, with estimates as high as 20% of all psychiatric patients and 40% of all schizophrenic patients, with a higher prevalence in women than men.
Pyroluria was first discovered in the late 1950s in relation to schizophrenia by a Canadian research team led by psychiatrist Dr. Abram Hoffer. Hoffer was a pioneer of Orthomolecular Psychiatry and Orthomolecular Medicine, and became editor of the Journal of Orthomolecular Medicine. This was the first medical journal to bring attention to many important new treatments in medicine such as the yeast syndrome, the toxicity of mercury from amalgams, and the orthomolecular treatment of the schizophrenias.
In his research, Hoffer discovered a clear relationship between elevated urinary HPL, or as they called it then "the mauve factor," and patients with schizophrenic symptoms. According to Hoffer, 25% of nonpsychotic psychiatric patients, 50% of chronic schizophrenics, and 75% of acute (sudden-onset) schizophrenics exhibited "the mauve factor" in their urine, with 0% in the control group. They called it "mauve" due to the mauve colour that was observed on the paper chromatograms. All patients within the schizophrenic subgroup that were administered high dose niacinamide (Vitamin B3) converted from Mauve positive to Mauve negative. Discontinuation of the niacinamide was associated with the reappearance of Mauve. The researchers called this condition "Malvaria."
Malvaria was later renamed "Pyrolleuria" by Dr. Carl Pfeiffer of an American research team and later, for no obvious reason, consistently spelled "Pyrroluria" in later publications. It is also known as Kryptopyrroluria (KPU) and Haemopyrrollactamuria (HPU). In the 1970s Pfeiffer created a relatively simple, quantitative, colorimetric assay for the condition and was the first to show clinical improvement in positive patients using high doses of Vitamin B6 and Zinc.
The following statistics were obtained from the publication Discerning the Mauve Factor - Part 1 , by Woody R. McGinnis MD; Tapan Audhya PhD; William J. Walsh, PhD; James A. Jackson PhD; John McLaren-Howard, DSc, FACN; Allen Lewis, MD; Peter H. Lauda, MD; Douglas M. Bibus, PhD; Frances Jurnak, PhD; Roman Lietha, MD; Abram Hoffer, MD, PhD.
Neurobehavioral Disorders Associated with Elevated HPL:
- Latent AIP 70%
- Acute Intermittent Porphyria (AIP) 100%
- Down Syndrome 71%
- Schizophrenia (Acute) 59-80%
- Schizophrenia (Chronic) 40-50%
- Manic Depression 47-50%
- Depression, non Schizophrenic 12-46%
- Criminal Behaviour - Adults (Sudden deviance) - 71%; Youths (Violent Offenders) - 33%
- Autism - 46-48%
- Epilepsy 44%
- Learning Disability/ADHD 40-47%
- Neuroses 20%
- Alcoholism 20-84%
In 1977, Irvine demonstrated the correlation between high HPL levels in urine and symptoms such as emotional withdrawal, motor retardation and severe depression in schizophrenia. He also experimented on rats by administering HPL resulting in hypothermia, locomotor aberration and ptosis (drooping eyelid). In 1990, Cutler and Graham reported an increase in head twitching and backward locomotion in mice after HPL administration. Graham suggested that HPL appears to exhibit excitotoxic properties, but it's yet to be investigated. There is a need for controlled therapeutic trials of existing treatments and potential new interventions, particularly anti-oxidants. The origin and genetics of HPL are important areas of inquiry.
Many great people in history have shown the signs of pyroluria. Among them are the poet Emily Dickinson and the scientific philosopher and discoverer Charles Darwin. Their life stories reflect many of the character traits associated with this condition. Pyroluria—the reason for adult withdrawal and seclusion? Reflections on the meaning of life and death were the two major influences in the life works of both Emily Dickinson and Charles Darwin.— Dr. Carl C. Pfeiffer
Signs, Symptoms, and Associated Conditions
Characteristics commonly seen include white spots on fingernails, unusual fat distribution (larger mid section), increased incidence of stretch marks, pale skin that burns easily, sweet and fruity breath and body odour, overcrowded teeth, coarse eyebrows, poor appearance of tooth enamel, creaking knees, cold hands and feet, and stunted growth.
Anxiety, nervousness, pronounced mood swings, low stress tolerance, depression, panic attacks, motion sickness, general loss of appetite, social withdrawal, memory loss, episodic anger/temper outbursts, severe inner tension, insomnia, seizures, tremors, migraines, acne, irregular menstruation, impotence in males, disordered perception, eosinophilia, dyslexia, hallucinations, delusions, paranoia, loss of reality, increased sensitivity/intolerance to sound, light, smell and touch, frequent unexplained nausea, joint pain (specifically in the knee and leg), restless leg syndrome, fatigue, poor dream recall, stitch in side, digestive disturbances (abdominal tenderness, constipation), Irritable bowel syndrome, gluten intolerance, glucose intolerance/hypoglycaemia, anaemia, food/environmental allergies, delayed onset of puberty, suicidal tendencies, sensitivity to medications, pessimism, hyperactivity, emotional lability.
Schizophrenia, bipolar disorder, ADHD, alcoholism, autism, Dissociative Identity Disorder, epilepsy, Asperger Syndrome, Obsessive-Compulsive Disorder, Multiple Sclerosis, Parkinson's disease, and Lyme disease.
There are varying degrees of Pyroluria. Expression of this condition can be mild, severe, or borderline, depending on genotypes, level of toxic environmental exposure, and complicated by the presence of other genetic defects such as Histadelia, Histapenia and Hypercupremia. Signs and symptoms will vary between individuals.
Upon consultation with a qualified practitioner, a thorough investigation into patient history coupled with a simple urine test for HPL will form the basis for diagnosis of Pyroluria.
The presence of HPL can be established using a colorimetric biochemical screening test adapted from Dr. Carl Pfeiffer’s method. Urine is collected in a vial containing ascorbic acid, wrapped in aluminium foil then frozen immediately for transport. The HPL molecule is unstable and will disappear rapidly at room temperature or if exposed to bright light.
Laboratory investigations including plasma zinc, serum copper, and ceruloplasmin (copper binding protein), along with HPL level and symptom picture, will be key in determining an individualised nutritional treatment regime.
Differential diagnosis is vitally important as many of the symptoms of Pyroluria present similarly to those of Histadelia (high histamine), Histapenia (low histamine) and Hypercupremia (high copper). The similar and also very severe, rare genetic condition known as, Acute Intermittent Porphyria (AIP) is commonly associated with Pyroluria with 100% of AIP patients tested exhibiting positive results for Pyroluria.
The first line of treatment is to supplement with higher than the recommended daily average requirement of Zinc and Vitamin B6 to compensate for the deficits caused by the condition. These essential nutrients will reduce the excretion of HPL, improving all neurobehavioral symptoms associated with these deficits.
The favoured forms of these nutrients are Zinc picolinate and Pyridoxal-5-phosphate (P5P).
Not all Zinc supplements have equal bioavailability. Picolinic acid for example is a natural mineral chelate produced in the body from tryptophan. It makes its way to the pancreas where it is secreted during digestion into the small intestine, binding to minerals and facilitating their absorption. This makes Zinc picolinate the preferred supplement of choice.
There are three natural forms of Vitamin B6 found in food: Pyridoxine, Pyridoxine, and Pyridoxal. Pyridoxal joined with a phosphate is the metabolically active coenzyme form used within our bodies, also known as P5P. Pyridoxine hydrochloride is the more commonly used form of supplement for vitamin B6, and is well utilised in most individuals. However the body is then required to convert the pyridoxine into P5P in the small intestine so it can be utilised. The pyridoxine can not be used by the body directly. Two metabolic steps must first be performed: phosphorylation and oxidation. These processes require nutrients like Zinc, Magnesium and Riboflavin (Vitamin B2). If Riboflavin is low, P5P production can be reduced by up to 60%. For this reason in the treatment of Pyroluria it is important to administer the P5P form, as deficiencies in Zinc, Magnesium and B2 are most likely to be present.
Suggested Daily Dosage:
- Vitamin B6 - 200mg Pyridoxine hydrochloride and 50mg P5P. I personally find taking smaller doses of P5P (20mg) every 3-4 hours throughout the day to be most affective. P5P is a water soluble vitamin that is not stored in the body and easily depleted, particularly if you drink tea/coffee or consume anything with a diuretic effect.
- Zinc picolinate - anywhere from approximately 50 - 100mg for severe adult cases, taken in the morning after food. Zinc dosages are to be built up slowly in accordance with blood labs results for Zinc/Copper/Ceruloplasmin levels, HPL results, and general vitality/adaptive ability to cope with chelation.
NOTE: All supplements should be titrated to the individuals age, body weight, laboratory results, severity of symptoms and ability to absorb supplements, i.e. underlying digestive malabsorptive disorders such as Crohn's disease, Irritable Bowel Syndrome, Inflammatory Bowel Disease, Coeliac disease, Leaky gut syndrome, Intestinal dysbiosis (an imbalance of bowel flora), GIT infections (parasites, yeast, clostridia, H. pylori), Gastritis, Peptic ulcer, and food allergies/intolerances.
Secondary deficiencies will also need to be addressed as a result of pre-existing deficiencies of B6 and Zinc. These nutrients are crucial for the production of other nutrients, neurotransmitters, hormones, and over 100 enzymes in the body: Manganese, Magnesium, Biotin, Vitamin B complex, Omega 6 essential fatty acids (EFA) in particular Arachidonic acid, 5 Hydroxy Tryptophan (5HTP), Vitamins A, C, E, Glutamine, Gamma Amino Butyric Acid (GABA), Inositol, Taurine, and Glycine are some examples of nutrients that may need to be included in your initial treatment regime. Due to alterations in the fatty acid pathways, deficiency in arachidonic acid (Omega 6) is most common. It is important to note that omega 3 EFA's (EPA/DHA) must also be avoided, as they compete with omega 6 in enzymatic pathways. In this case it is the enzyme delta 5,6 desaturase that is required to convert omega 6 to arachidonic acid.
Chelation therapy may also be necessary for those with long standing Pyroluria who exhibit high copper levels. Copper levels can be tested utilising hair and blood analysis. Copper and Zinc compete for cellular uptake on receptor sites, so when Zinc levels are low, Copper will be high. Copper is neurotoxic to the body in higher than normal amounts, exhibiting similar chemical behaviour as an equivalent dose of the psycho-stimulant drug D-amphetamine. High copper levels can also be initiated by long term stress, a common state for the Pyroluric.
During emotional, mental or physical stress the body releases Aldosterone, Cortisol and Adrenaline. Aldosterone, in particular increases the retention of copper and sodium to protect us from the perceived threat, producing a neuro-excitatory effect and simultaneously releases Zinc and Magnesium (our calming nutrients). The body retains excess copper causing further neurotoxicity. Chelation therapy involves the use of high dose Vitamin C, Zeolite (Volcanic ash), Copper antagonists such as Zinc, Manganese and Molybdenum. Nutrients that encourage the formation of Metallothionein (Copper binding protein) such as Selenium, Vitamin B6, Zinc and Folinic acid will further assist in balancing copper levels in the body. Chelation must be taken slowly to prevent exacerbation of symptoms. Copper removal commonly creates an initial aggravation of copper related symptoms, so care must be taken during this process.
Diet and Digestion
It's vitally important to treat Pyroluria from a holistic standpoint. Addressing only the nutrient deficiencies, and copper chelation, may not be enough. Long standing deficiency, chronic adrenal stress, high copper, and poor diet can contribute to digestive disorders and intestinal dysbiosis that may further affect absorption of the nutrients required to reestablish optimum health. Investigations and corrections of diet and digestion form an important part of long term treatment success.
Diet has a profound effect and behave. There is a tendency in Pyroluria towards high consumption of sugar/refined carbohydrate foods and alcohol, to compensate for low serotonin levels. Serotonin is the body's natural anti-depressant, inducing a sense of well-being, calm, and confidence. Low serotonin levels are comomonly seen in Pyroluria due to the Vitamin B6 deficiency. Vitamin B6 (P5P) is a necessary coenzyme in the conversion of tryptophan to serotonin. Eating foods like cakes, chocolate, potato chips or ice-cream and drinking alcohol, are usually the first things we reach for when we are anxious, depressed, or sad. These high sugar substances increase insulin production in order to lower our blood sugar levels. The high levels of insulin produced, flush out competing amino acids, allowing higher levels of the amino acid tryptophan to reach the brain. The end result is a boost of serotonin to elevate mood and reduce anxiety. There is some therapeutic benefit in treating Pyroluria with Tryptophan or 5HTP supplementation, especially if the patient suffers from depression and insomnia and craves sweets and carbohydrates.
Marked improvements have been seen in pyroluric patients embracing gluten free and low- no-grain and no-sugar diets. Decreasing sugar and refined carbohydrates and opting for gluten free wholegrains can further improve recovery when an underlying digestive disorder is present. Some interesting insights have been discovered by British neurologist and nutritionist Dr Natasha Campbell-McBride who developed the GAPS diet, Gut and Psychology Syndrome. Her book outlines the relationship and importance between our mental and gastrointestinal health. There is an emphasis on maintaining the intricate balance of our intestinal flora, without which we can not digest food or absorb nutrients. When we consume large amounts of sugar, refined carbohydrates, alcohol, yeast containing foods, or food we are allergic/intolerant to (gluten, dairy, wheat, fructose, salicylates, yeasts, sulfur, caffeine etc) we provide the perfect breeding ground for opportunistic organisms. Intestinal dysbiosis will develop with the most common culprits being yeast (candida) and the Clostridia family. These organisms produce their own toxins. Yeasts create acetaldehyde and alcohol, causing liver damage, with an inability to remove old neurotransmitters, hormones and other byproducts of normal metabolism from the body. These substances accumulate in the body causing behavioural abnormalities. Pancreatic damage with a reduced ability to produce pancreatic enzymes; brain damage with loss of memory, impaired coordination, stupor, mental retardation, are also side effects of these yeast producing toxins. Clostridia produces neurotoxins which have been seen in patients with Schizophrenia, Autism, and severe depression.
When there is evidence of digestive abnormalities, with symptoms such as constipation, excessive flatulence, diarrhoea, intestinal cramps, epigastric pain, irregular bowel motions, reflux, heartburn, nausea and vomiting, a comprehensive Gastrointestinal profile via DNA stool analysis can be utilised to investigate the presence of digestive disease, yeast, parasites, bacteria, intestinal dysbiosis or leaky gut syndrome. Any of these conditions can further complicate and slow recovery in Pyroluria. Treatment may include high dose probiotics, glutamine, deglycyrrhizinated licorice (DGL), hydrochloric acid, pancreatic enzymes, anti-parasitic and anti-fungal herbs/nutrients - Black Walnut, Pau d'arco, Saccharomyces boulardii, Methylsulfonylmethane for those who are not sulfur sensitive (CBS, SUOX polymorphisms), Wormwood, Caprylic acid, Cloves, Goldenseal, Oregon grape and Citrus seed extract. Diet change will be at the core of treatment success in these cases.
Hormonal balance is another aspect worth mentioning. It is intricately tied into digestive and neurobehavioral health and heavily influenced by deficiencies of Zinc, B6 and high copper levels. High oestrogen levels overstimulate aldosterone receptors, which in turn leads to copper retention, similarly to the stress response. Symptoms of high blood pressure, fluid retention through an increase in blood volume may be evident; common side effects seen in those taking the Oral Contraceptive Pill (OCP). Interestingly the OCP has been associated with exacerbation in patients suffering from Schizophrenia, with complete remission of their schizophrenic symptoms once the OCP was stopped.
Conditions that may ensue from estrogen imbalance/dominance include PMS, ovarian cysts, miscarriage, Polycystic Ovarian Syndrome (PCOS), Uterine fibroids, sexual dysfunction. High oestrogen levels can occur as a result of toxic exposure to xeno-estrogens within the environment/food. Xeno-estrogens chemically mimic our natural estrogen hormones and replace them on receptor sites within our cells. This unnatural replacement creates imbalance within estrogen levels and ratios between other hormones within the body - progesterone, thyroid hormones etc. Xeno-estrogen's can be avoided; they are present in pesticides, plastics - especially soft plastics (food wrap), volatile organic compounds (VOC's), growth hormones used in animals, and all petrochemical waste products used in the manufacture of plastics, gasoline and petrochemical derivatives. Estrogen imbalance can also occur from inside the body; this is where hormones and digestion are intricately involved. When our digestive processes slow down, and we adopt unhealthy dietary principles, or ones that do not suit our genotype/constitution, our intestines can become a compost heap and putrefaction/fermentation ensues. Bacterial imbalance within our intestinal microbiota leads to production of toxic metabolites and a great deal of metabolic activity that is detrimental to our health. During putrefaction, the bacterial enzyme beta-glucuronidase is produced, causing an enterohepatic recirculation of estrogen, rather than elimination of excess levels, placing extra strain on the liver's role of conjugating and eliminating oestrogen. This disease causing biochemical pathway, induced by poor diet, creates a state of oestrogen dominance within the body, increasing the risk of hormonally dependant cancers, hormonal disease, obesity, diabetes, circulatory disorders and much more. Supplementation with Calcium d-glucarate can support oestrogen reduction through inhibition of beta-glucuronidase activity. Diindolylmethane (DIM) is another natural compound obtained from the Brassica family, which can be used to inhibit oestrogen's dominant effect in the body. It works by adjusting the pathways of oestrogen metabolism in favour of 2-hydroxy oestrone production, whilst simultaneously decreasing 16-alpha hydroxy oestrone levels. 2-hydroxy oestrone has been indicated through clinical studies as a protective biomarker against hormonally dependant cancers.
Symptoms of hypothyroidism; fatigue, depression, brain fog, constipation, dry skin, dry, thinning hair, weight gain, intolerance to cold, excessive menstrual flow, can also be seen in oestrogen dominant states. Estrogen has a similar chemical structure to the active thyroid hormone Triiodothyronine (T3) and can block receptors sites on the cell membrane, inducing a hypothyroid state. Copper also plays a part by disrupting the conversion of Thyroxine (T4) to T3. Addressing Copper, Oestrogen and stress levels can have a positive impact on regulating metabolic activity of the thyroid gland.
Treatment for hormonal balancing will focus largely on correcting nutritional imbalances and dietary change; reduction and in some cases elimination of sugar, grains, alcohol, excessive fat/protein intake from animal sources (meat, dairy). Simultaneously increasing fibre and vegetable content and shaping your diet around vegetables/fruits/nuts/seeds/lean meat as your core will provide the quickest results to eliminate the state of putrefaction. Diet coaching with an understanding of how to eat; being in a relaxed, present state, no fluids with meals, small portion sizes, chewing well, and possible use of aperitifs, will improve hormonal balance. Increasing transit time of stool is vitally important with the concurrent use of probiotics, certain fibres and cultured foods.
Treatment will always vary depending on the individual. We are biochemically and genetically unique. No treatment would be complete without addressing one's lifestyle and the need to discover and implement stress reducing strategies. And these strategies will indeed be different for everyone. Some people will find exercise helpful: yoga, swimming, kick boxing, martial arts, pilates, dance, gym. Other's may find relaxation in practices like meditation, breathing techniques (Uijayi breathing), sound healing and music. Other ideas include support/social groups, emWave (biofeedback personal stress reducer), retreats, massage, emotional freedom technique (EFT), neuro-emotional technique (NET), neurolink. Lifestyle changes and stress reducing activities will help you develop internal resources and healthier coping mechanisms, that you can incorporate into your daily life. Balancing your daily stress levels is key to keeping copper levels down, and maximising the calming benefits of zinc supplementation.
The encouraging part about Pyroluria treatment is that in patients with uncomplicated Pyroluria (no food allergy/digestive disorder/methylation issues), improvement can be seen within a few days, with only taking Zinc and Vitamin B6. In more complicated cases, where diet and digestion need addressing, it may take 3-6 months to reach a consistently stable level. This will be dependant on patient compliance with new diet change, and also allowing for an adjustment period of learning new information, new ways of cooking, techniques for stress reduction etc. Because of the varying presentations and severities of pyroluria, each person does best with a treatment plan specifically tailored to them. It is important to note that discontinuation of a treatment regime may result in deterioration of the patient within as little as 48 hours.
Pyroluria has only begun to be recognised as a medical condition for about 10 years now and many health practitioners are still not taught about it in school. Due to a lack of knowledge, awareness, research, and complete acceptance within the mainstream medical profession, unfortunately most people with Pyroluria go undiagnosed. On a positive note, I am continuously becoming aware of more and more doctors and psychiatrists worldwide accepting the validity of Pyroluria and changing the lives of those suffering from mental illness. Though without proper identification and treatment, those affected tend to become loners in order to avoid stressful situations in life. Their lives become an ongoing struggle to protect themselves from too much emotional and physical stress. Let's spread the word and openly share our experiences with others, and start support groups within our communities. Let us find ways for Pyroluria to become known and accepted within our society, so we are no longer hiding behind a veil.
An Inspiring True Story
Extracted from Direct Health Care Access Laboratory website:
A classic case involved an 11 year old girl diagnosed with Schizophrenia. Her history included chronic insomnia, loss of reality, attempted suicide, amnesia, seizures, nausea, vomiting and debilitating pain in her extremeties. She was misdiagnosed by a series of physicians, labelled as "schizophrenic," "paranoid" and "schizophrenic with convulsive disorder." Psychotherapy and medications were ineffective. Her physical debilitation was almost total.
Everything changed when a Kryptopyrrole Quantitative Urine Test, demonstrated that her symptoms were consistent with elevated kyptopyrrole levels. Indeed, her urinary kryptopyrrole level was at times as high as 1,000mcg (the normal range is less that 15mcg). She was diagnosed as vitamin B6 and zinc deficient and treatment commenced immediately.
In just three months her pain disappeared, the depression subsided and the seizures and nausea vanished. In effect, all of her symptoms were gone! Since then, she has experienced no recurrence of her grave illness. She has finished college and now works in New York. She takes zinc and B6 daily. When under stress of any kind, she increases her intake of vitamin B6. All indications are that she has been completely cured as a direct result of correct diagnosis and proper treatment.
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- Great Plains Laboratory - USA
Testing for Pyroluria
- Biolab Medical Unit - UK
A nutritional biochemistry medical laboratory measuring trace metals/minerals & toxic metals, vitamins, pesticides and levels of biochemical markers related to exposure to environmental contaminants. Pyrrole Testing.
- KEAC - Klinisch Ecologisch Allergie Centrum - Netherlands
Testing for Pyroluria
- Direct Health Care Access Laboratory - USA
Lab testing for kryptopyrrole, pyrroles, hpl, pyroluria, histamine, copper, zinc, identified in autism, aspergers, add/hd, bipolar, anxiety, depression, stress, aggression.
- Pfeiffer Treatment Center - USA
Treatment and assessment of Pyroluria and other biochemical imbalances
- Safe Analytical Laboratories - Australia
Testing for Pyroluria
- Applied Analytical Laboratories - Australia
Specialist analytical service for urinary pyrrole analysis. At the forefront of cutting edge research into more effective methods of pyrrole testing
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