Porphyria human

Although normally present in normal human plasma in abundance ( 0.6 mg/ml, 10 pM) (27-30), concentrations ofhemopexin are sensitive to a variety of pathological conditions. Decreased levels have been noted in chronic and severe hemolytic states (31) and in heme infusion of acute intermittent porphyria patients (32). On the other hand, hemopexin levels increase in the acute-phase response (33-36), and hemopexin has been designated as a type II acute-phase reactant. Plasma hemopexin also increases in certain conditions of muscle breakdown and neuromuscular disease (37). 

It is possible that the medieval legends about human vampires ( Dracula ) originated in the behavior of porphyria sufferers (avoidance of light, behavioral disturbances, and drinking of blood in order to obtain heme— which markedly improves some forms of porphyria). 

Most, if not all, occupational illnesses associated with 2,4,5-T (such as chloracne) have been found to be the result of product contamination with TCDD. TCDD is extremely toxic to animals, and exposure has also been associated with liver function impairment, peripheral neuropathy, personality changes, porphyria cutanea, hypertrichosis, and hyperpigmentation in humans. TCDD is a chlorinated dioxin, one of a large number of related compounds referred to as dioxins it has no functional use and is not intentionally produced. It has been identified as the responsible toxic agent in several industrial disasters, such as accidental releases at Nitro, WV in 1949, and at Seveso, Italy in 1976. " The role of dioxin contaminants must also be considered in the discussion of 2,4,5-T toxicology. 

The porphyrias. The human body does not use all of the porphobilinogen produced, and a small amount is normally excreted in the urine, principally as coproporpyrins (Fig. 16-5). In a number of hereditary and acquired conditions blood porphyrin levels are elevated and enhanced urinary excretion (porphy-... 

Photoprotection is an inhibition of heme photosensitization via the quenching of photoreactive intermediates ( 02) by orally administrated P-carotene. Photoprotection concerns some kinds of porphyrias (the hereditary or chemically induced production of excessive amount of porphyrins in human and animals). Similarly as in photodynamic therapy, a raised concentration of porphyrins (Mb, Hg, cytochromes) causes the destruction of cells in the presence... 

It may be noted that although the human organism is capable of degrading metal-containing porphyrins such as heme, it has no means of degrading porphyrins containing no metal, for example coproporphyrins and uroporphyrins. These must be excreted as such. The latter two are water-soluble and are thus found in urine and to some extent in the feces. Protoporphyrins, however, are largely water-insoluble and are excreted in the feces. Finally, it may be mentioned that porphyrias make their appearance after puberty. This has been associated with the appearance of 5/3-steroid reductases, as discussed above. 

Bonkowsky HL, Bloomer JR, Ebert PS, Mahoney MJ (1975) Heme synthetase deficiency in human protoporhyria Demonstration of the deficit in liver and cultured skin fibroblasts. J Clin Invest 56 1139-1148 De Vemeuil H, Aitken G, Nordmann Y (1978) Familial and sporadic porphyria cutanea two different diseases. Hum Genet 44 145-151... 

Hexachlorobenzene (a fungicide) has caused porphyria cutanea tarda in humans. It does not cause convulsions. Lindane, chlordane, and dieldrin have been associated anecdotally with certain rare hematologic disorders, including aplastic anemia the incidence of these effects appears to be extremely low. 

The complex tetrapyrrole ring structure of heme is built up in a stepwise fashion from the very simple precursors sue-cinyl-CoA and glycine (Figure 32-2). The pathway is present in all nucleated cells. From measurements of total bilirubin production, it has been estimated that daily synthesis of heme in humans is 5 to 8mmol/kg body weight. Of this, 70% to 80% occurs in the bone marrow and is used for hemoglobin synthesis. Approximately 15% is synthesized in the liver and is used to produce cytochrome P-450, mitochondrial cytochromes, and other hemoproteins. The pathway is compartmentalized, with some steps occurring in the mitochondrion and others in the cytoplasm. Little is known about the transport of intermediates across the mitochondrial membrane, and no transport defect has yet been reported in the porphyrias. 

Jacob K, Doss M. Excretion pattern of faecal copro-porphyrm isomers I-IV in human porphyrias. Eur J Chn Chem Clin Biochem 1995 33 893-901. 

The chemical is banned. PBBs may not be used for the production of textile articles (clothes, underwear, bedclothes, etc.) to come into contact with human skin. All other uses than the use in textile articles intended to come in contact with the skin are continued. PBBs cause weight loss, liver damage, porphyria, effects on the central nervous system, skin, eyes and the immune system, effects on reproduction, they are weakly teratogenic (embryotoxic) in cattle and laboratory animals. 

We wondered therefore whether, under appropriate conditions, it might be possible to induce a transient state of porphyria in cells and tissues other than liver and bone marrow. Experiments which were carried out in mice and subsequently on human volunteers confirmed that it was in fact possible. 

In 1956, it was reported that of four volunteers who ingested ALA as part of a study of porphyrin metabolism, those who took the largest doses experienced transient photosensitization of the skin [105,106]. These experiments took place at a time when it was generally believed that the capacity for excessive synthesis of porphyrins was restricted to the liver and the bone marrow, because it was these organs which produced the porphyrins responsible for the skin photosensitization associated with certain types of porphyria [107]. Consequently, the skin photosensitization induced by ingestion of ALA was interpreted in similar terms. Despite this erroneous assumption about the mechanism involved, these researchers had established that systemic administration of ALA to humans could cause skin photosensitization. We verified these observations in mice given ALA... 

R.L.P. Lindberg, C. Procher, B. Grandchamp, B. Lederman, K. Burki, S. Aguzzi, U.A. Meyer (1996). Porphobilinogen deaminase deficiency in mice causes a neuropathy resembling that of human hepatic porphyria. Nat. Gen., 12, 195-199. 

B.C. Shanley, V.A. Percy, A.C. Neethling (1976). Neurochemistry of acute porphyria. Experimental studies on delta-aminolaevulinic acid and porphobilinogen. In M. Doss (Ed.), Porphyrins in Human Diseases (pp. 156-162). Karger, Basel. 

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