Anonymous ID: cc0194 March 23, 2020, 8:53 p.m. No.8542098   🗄️.is 🔗kun   >>2118 >>2121 >>2145 >>2152

>>8541728

Moar on Porphyria

https://www.scientificamerican.com/article/born-to-the-purple-the-st/

Porphyria is named from the ancient Greek word porphura, meaning purple. The Greeks borrowed the term from the Phoenicians, who extracted a purple pigment from purpura mollusks to dye the garments of their royal family. Later, in the Byzantine Empire, the term porphyrogenitos, or "born to the purple," literally meant that the imperial heir was born after the fathers accession to the throne, in a palace room draped in the color.

However, those with the misfortune to be born to the purple involved in porphyria–a group of diseases that result from abnormal accumulations of red and purple pigments produced by the body, called porphyrins–receive far less than royal treatment. There are at least eight types of porphyria, which vary substantially in their symptoms and severity. Historical victims of the worst, most disfiguring forms may have inspired tales of werewolves and vampires. Even today, managing the disease can be challenging.

 

Light-Activated Toxins

 

Hippocrates is often cited as the first to recognize porphyria (which was then referred to as blood/liver disease) but the causal role of porphyrin pigments was only established in 1871 by the great German pioneer of biochemistry Felix Hoppe-Seyer. In 1889, Dr. B.J. Stokvis described the clinical syndrome as "porphyria," and from then on more and more forms of the syndrome were discovered.

 

All the versions of porphyria have one thing in common: they each result from faults in the bodys heme-building machinery. Heme, a component of the oxygen transporter hemoglobin, is made in a sequence of eight steps, as in a factory assembly line. Each step is catalyzed by a separate enzyme. If any of these eight steps fails because of an inherited genetic mutation or an environmental toxin, then the whole assembly line gets jammed. The products of the earlier steps, porphyrin intermediates, may build up to toxic levels. These porphyrins accumulate in the skin and other organs before being excreted in feces and urine (which may turn a port-wine color). Exposed to light, the porphyrins can turn caustic and destroy surrounding tissue.

 

(Put to medical use, drugs containing porphyrins can attack tumors and other ailments. Unlike most natural porphyrins [but like chlorophyll] these drugs are not purple but green, as they have been modified chemically so that they absorb light at wavelengths that can penetrate into biological tissues. See "New Light on Medicine," by Nick Lane; Scientific American, January 2003.)

 

Exactly which porphyrins accumulate depends on the site of the jam, and it is this that gives porphyria such a wide range of symptoms. The severity of the jam also varies. In some cases the jam is total, preventing any heme synthesis at all. In others, it is only partial, permitting limited heme synthesis. The blockage of the assembly line also means that the body cannot make enough heme to produce normal red blood cells. Some of these abnormal red cells rupture, leading to hemolytic anemia, while the spleen detects abnormalities in other red cells and breaks them down, making matters worse.

 

Werewolves and Vampires

 

One of the more common types of the disease is acute intermittent porphyria (AIP), which famously afflicted the unfortunate King George III of Britain–the "mad king" of Alan Bennetts play. In AIP the most notable symptoms are neurological attacks, such as trances, seizures and hallucinations, which often persist over days or even weeks. Luckily, most people with AIP have a latent form, and never develop any symptoms.

 

Another relatively common form is porphyria cutanea tardea, which presents a very different spectrum of symptoms. In this case, the hallmark is photosensitivity (an excessive reaction to light), which causes chronic blistering and even burns on sun-exposed areas. Healing is slow and is associated with scarring and hair growth, especially on the face. Most of the time the facial hairs are fine, so the hirsutism is barely noticeable. Sometimes, however, the hair growth can give the appearance of a werewolf, leading to speculations that the myths may have had a medical basis.

 

In congenital erythropoietic porphyria (CEP), one of the rarest forms, 18 different mutations in the gene encoding the enzyme uroporphyrinogen III cosynthase have been reported in different families. These mutations obstruct heme synthesis to varying degrees, giving a spectrum of severity. At its worst, CEP causes appalling photomutilations from the light-activated porphyrins, including loss of facial features and fingers, scarring of the cornea and blindness. The condition may have been less rare in the past, especially in isolated pockets where inbreeding could occur such as the valleys of Transylvania–perhaps giving rise to tales of vampires.

Anonymous ID: cc0194 March 23, 2020, 8:54 p.m. No.8542118   🗄️.is 🔗kun   >>2152 >>2167

>>8542098

cont.

 

While the accumulation of porphyrins is usually caused by a genetic mutation, toxins (such as alcohol excess) and environmental contaminants can also cause the disease. The most notorious environmental episode happened in Turkey in the 1950s, when 4,000 people developed a form of porphyria after eating wheat seeds that had been sprayed with a fungicide, hexachlorobenzene. Hundreds died, and use of the fugicide was later banned around the world.

 

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Methods of Treatment

 

In most cases of porphyria, blood or heme transfusions can supply some relief from the symptoms, and this is still the mainstay of treatment. Interestingly, the heme pigment is robust enough to survive digestion, and is absorbed from the intestine (even though the protein parts of hemoglobin are broken down). This means that, in principle, it is possible to relieve the symptoms of porphyria by drinking blood–another possible link with the vampire stories.

 

Heme infusions help in the treatment of porphyria patients in two ways. First, they overcome the bodys shortage of heme, relieving anemia. Second, the extra heme suppresses further heme synthesis via a negative feedback loop. This effectively switches off the assembly line, bringing an end to the production of toxic porphyrin intermediates. Drawing blood (phlebotomy) can also help, because this quickly removes porphyrin intermediates from the circulation. In most cases, some degree of normality can be restored within a few days of an attack.

 

In the more serious forms of porphyria such as CEP, however, treatments are less effective. Sometimes the spleen must be removed in an attempt to treat the hemolytic anemia. In CEP, the genetic fault affects the stem cells in the bone marrow, which divide to produce new red blood cells. In principle, CEP can be cured by bone-marrow transplantation, which replaces the faulty stem cells with fully functional ones. Bone-marrow transplants have been carried out successfully in at least five children with CEP, usually within the first few years of life. The treatment apparently cures the disease over a period of years.

 

Future Therapies

 

But bone-marrow transplantation presents its own challenges, and is considered a last resort. In the longer term, hope to cure porphyria is invested in gene therapy, in which the faulty genes are replaced with functional ones using a virus as a vector (delivery method). The technique has been shown to be effective in cell culture, but there is still a long way to go before gene therapy for CEP can be used in clinical practice.

 

Other future treatments for porphyria will depend on the results obtained from research with experimental animal–and even plant–models. Some of these are improbable, to say the least. For example, all fox squirrels (Sciurus niger) have a gene defect that gives them a form of CEP, yet they do not suffer any adverse consequences, for unknown reasons. Studies of the animals could yield clues that would be useful in fighting CEP.

 

Surprisingly, even plants–which use the green porphyrin, chlorophyll, to absorb light energy–can suffer from a condition analogous to porphyria. Plants make chlorophyll via a pathway very similar to that for heme production in animals. Mutations in the gene for the final step in this pathway lead to a buildup of porphyrins in the leaves. On exposure to sunlight the leaves blister, and eventually wither and die. The process is so similar to human porphyria that some researchers hope to find a cure for the human condition by studying the properties of so-called "vampire plants," like maize.

 

 

Nick Lane studied biochemistry at Imperial College, University of London. His doctoral research, at the Royal Free Hospital, was on oxygen free radicals and metabolic function in organ transplants. Lane is an honorary senior research fellow at University College London and strategic director at Adelphi Medi Cine, a medical multimedia company based in London. His book, Oxygen: the Molecule That Made the World, is being published by Oxford University Press in the spring of 2003.