heard of (auto) "urine therapy" ?

Erach

Dioxin are pervasive, persistent, potent, slow-acting toxins. The most
potent form is TCDD. World Health Organization currently suggests a
limit of 1 to 4 parts per trillion (1,000,000,000,000). Dioxins are by
products of city and hospital waste incineration of chloronated
products (ie PVC), various manufacturing processes and natural causes
(fires). Because dioxins are lipophillic (fat loving), after being
released into the atmosphere, underground, rivers, lakes and oceans,
dioxins biomagnify as they move up the food chain. Infants have the
highest dioxin intake by weight. Because almost every cell has an Ah
Receptor, dioxins alters gene expression and effects are quite diverse
including cellular stress, wasting, liver damage, high cholesterol,
immune dysfunction, neuropathy, endometriosis, reduced fertility,
chloracne, etc. Below are some abstracts from www.pubmed.com related
to TCDD and PCT:

[Essential role of the AH receptor in the dysfunction of heme
metabolism induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin.]
The dysfunction of hepatic heme synthesis by 2,3,7,8-
tetrachlordibenzo- p-dioxin (TCDD) in mice, enhanced by iron, leads to
accumulation of uroporphyrins I and III (uroporphyria) and resembles
the human disorder porphyria cutanea tarda (PCT) precipitated by
alcohol and estrogenic drugs. Although consequences of TCDD are
considered entirely dependent on the aryl hydrocarbon receptor (AHR),
this is not proven for uroporphyria. Administration of TCDD (75 microg/
kg) caused uroporphyria in susceptible C57BL/6J mice with high-
affinity AHR after 5 weeks (>600-fold increase in hepatic
uroporphyrins). Transcriptomics showed significant modified gene
expressions for intermediary, heme, and iron metabolism as well as for
oxidative stress and cell injury. Resistant low-affinity AHR DBA/2
mice (no increase in porphyrins) showed far fewer changes. At this
dose of TCDD, persistent up-regulation of some traditional AH battery
genes occurred in both strains. Essentiality of AHR was demonstrated
with C57BL/6 Ahr knockout mice. Elevation of hepatic uroporphyrins was
964-fold in Ahr (+/+) mice, lower in Ahr (+/-) (60-fold), but
undetectable with Ahr (-/-) . Consistent with an oxidative mechanism,
iron overload enhanced porphyria as well as general liver injury in
Ahr (+/+) and Ahr (+/-) mice but had no interactive effect in Ahr
(-/-) . In contrast, when iron-treated mice received, instead of TCDD,
the heme precursor 5-aminolevulinic acid (ALA), causing uroporphyia in
Ahr (+/+) mice (242-fold rise in uroporphyrins), elevation of
uroporphyrins I and III (42-fold) also occurred in Ahr (-/-) mice and
was seemingly associated with AHR-independent expression of Cyp1a2.
The findings prove that AHR is a key factor in porphyria induced in
mice by TCDD. However, in other models of human PCT, participation of
AHR may not be an essential requirement. PMID: 18163543

[Synergistic effect of 2,2',4,4',5,5'-hexachlorobiphenyl and 2,3,7,8-
tetrachlorodibenzo-p-dioxin on hepatic porphyrin levels in the rat.]
We studied the effect of polychlorinated biphenyls (PCBs) on hepatic
porphyrin accumulation in female Sprague-Dawley rats by feeding them
diets containing 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 2,2',4,4',
5,5'-hexachlorobiphenyl (PCB 153), 2,3,3',4,4',5-hexachlorobiphenyl
(PCB 156), 3,3',4,4',5-pentachlorobiphenyl (PCB 126), or combinations
of the single PCB congeners with TCDD for 13 weeks. A dose-dependent
increase in hepatic porphyrin accumulation occurred after TCDD, PCB
126, or PCB 156 administration, reaching maximal levels of about twice
control values. The lowest dose levels for which a significant
increase in hepatic porphyrin accumulation was found were 0.7
microgram TCDD/kg diet, 50 micrograms PCB 126/kg diet, or 6 mg PCB 156/
kg diet. These doses are equivalent to 47 ng TCDD/kg/day, 3.2
micrograms PCB 126/kg/day, and 365 micrograms PCB 156/kg/day. Relative
potencies for hepatic porphyrin accumulation, using TCDD as a
reference, ranged from 0.015 to 0.06 for PCB 126 and from 0.0001 to
0.0003 for PCB 156. CYP1A2 activities significantly correlated with
hepatic porphyrin levels, with coefficients of 0.629, 0.483, or 0.808
for TCDD, PCB 126, or PCB 156, respectively. Administration of PCB 153
alone did not result in hepatic porphyrin accumulation. Co-
administration of PCB 153 and TCDD revealed a strong synergistic
effect on porphyrin accumulation (about 800 times control levels).
This synergistic effect was significant in rats fed diets containing
any combination of PCB 153 with TCDD. Uroporphyrin III and
heptacarboxylic porphyrin were accumulated in porphyrinogenic livers.
These results suggest that TCDD induction of CYP1A2 may be involved,
leading to oxidation of uroporphyrinogen III to uroporphyrin III, in
combination with an increase in delta-aminolevulinic acid synthetase
induced by PCB 153. Under porphyrinogenic conditions, an inhibitor of
CYP1A2 activity may also be formed. The interactive effects on
porphyrin accumulation after co-administration of dioxinlike and non-
dioxinlike compounds may have significant implications for the risk
assessment of these chemicals. PMID: 8743444

[Angiosarcoma, porphyria cutanea tarda, and probable chloracne in a
worker exposed to waste oil contaminated with 2,3,7,8-
tetrachlorodibenzo-p-dioxin.]
A worker developed angiosarcoma, porphyria cutanea tarda, and skin
lesions characteristic of mild chloracne. About 10 years earlier he
had been employed at a truck terminal in Saint Louis, Missouri, at a
time when it was sprayed with waste oil contaminated with 2,3,7,8-
tetrachlorodibenzo-p-dioxin (TCDD). The occurrence of these three rare
conditions in a single exposed worker supports the aetiological
relation between environmental exposure to TCDD and the subsequent
development of soft tissue sarcoma and porphyria cutanea tarda.PMID:
8104464

[Effects of chlorinated organics on intermediates in the heme pathway
and on uroporphyrinogen decarboxylase.]
Experimental porphyria induced by PHAHs is characterized by a
progressive reduction in the activity of UROD. After intoxication with
TCDD, the most porphyrogenic compound known to date, the liver was the
principal site of action, as regards both porphyrin accumulation
(mostly uroporphyrin) and the degree of enzyme impairment; the kidney
was the site of the second greatest accumulation; the brain and
erythrocytes were unaffected. Additional modifications of the heme
pathway involved induction of the activity of ALAS and, at least in
HCB-induced porphyria after iron pretreatment, may have involved
reduced activity of uroporphyrinogen III cosynthetase. These changes
can alter the amount and the isomeric composition of uroporphyrinogens
and uroporphyrins present in the liver in a way that is likely to help
reduce formation of coproporphyrinogen III in porphyric animals. As in
the human syndrome porphyria cutanea tarda, iron administration
increased porphyrin accumulation and the degree of reduction of UROD
activity in mice fed HCB. Mice fed HCB also presented an activation of
the type O form of XO. This activation was independent of tissue
injury derived from the lipid peroxidation that was concomitant with
iron administration. The increase in activity of the type O form of XO
may be a characteristic feature of the liver damage found in PHAH
intoxication and, in intoxicated animals, could be a source in the
liver of oxidant species involved in the mechanism of UROD
inactivation--if this inactivation is in fact due to an oxidative
reaction. PMID: 3442377

[Different susceptibility of mouse tissues to porphyrogenic effect of
2,3,7,8-tetrachlorodibenzo-p-dioxin.]
The porphyrogenic effect of chronic administration of 2,3,7,8-
tetrachlorodibenzo-p-dioxin (TCDD) (25 micrograms/kg/week) to male
C57BL/6 mice was evaluated through quantitative and qualitative
analysis of the porphyrins accumulated and of porphyrinogen
carboxylase activity in liver, kidney, spleen, brain and erythrocytes.
The liver was the principal site of action, both for porphyrin
accumulation and for enzyme inhibition, with kidney next, whereas
brain and erythrocytes were unaffected. In the spleen, despite
unchanged formation of total products of uroporphyrinogen III
decarboxylation, both an increase and a decrease of coproporphyrinogen
formation were observed, the decrease being concomitant with a higher
accumulation of tissue porphyrins. When a response to TCDD was found,
the formation of the products of decarboxylaction of uroporphyrinogen
III were affected to different extents. The pattern of enzyme
inhibition paralleled data reported in the literature regarding tissue
distribution of TCDD and indicated that TCDD porphyria is a suitable
experimental model for the human 'sporadic' type of porphyria cutanea
tarda (PCT).
PMID: 6695411

[Development of chronic hepatic porphyria (porphyria cutanea tarda)
with inherited uroporphyrinogen decarboxylase deficiency under
exposure to dioxin.]
Exposure to dioxin triggered a clinically manifest chronic hepatic
porphyria (porphyria cutanea tarda) in two patients (brother and
sister) with hereditary uroporphyrinogen decarboxylase deficiency. The
patients showed a decrease of erythrocyte uroporphyrinogen
decarboxylase activity to approximately 50% of controls even in
reinvestigations after three years, whereas clinical symptoms and
porphyrinuria had improved considerably. Only a subclinical phase of
chronic hepatic porphyria persisted. Subnormal uroporphyrinogen
decarboxylase activity could be determined in altogether nine family
members. The remission of porphyria cutanea tarda into a subclinical
phase occurred after chloroquine therapy. Subclinical phases of
chronic hepatic porphyria (type A) in other family members remitted
without special therapy. Among the 60 persons dioxin-exposed by the
Seveso accident, a secondary coproporphyrinuria was found in 22% of
examined patients with transition to a subclinical chronic hepatic
porphyria in 5 cases. The changes had subsided completely after one
year. A persistence of the transition state in 3 cases is probably due
to alcohol influence. None of these cases developed a porphyria
cutanea tarda. The investigations showed that a hereditary disposition
is necessary for biochemical and clinical expression of chronic
hepatic porphyria after a unique dioxin exposure. This is not given in
the sporadic cases: after a unique dioxin exposure they indeed develop
a symptomatic disturbance of porphyrin metabolism but not a clinically
relevant chronic hepatic porphyria. We conclude that a unique acute
exposure to dioxin can trigger the chronic hepatic porphyria disease
process in persons with an underlying genetic abnormality of
uroporphyrinogen decarboxylase. PMID: 6714509

[Effects of polychlorinated biphenyl compounds, 2,3,7,8-
tetrachlorodibenzo-p-dioxin, phenobarbital and iron on hepatic
uroporphyrinogen decarboxylase.]
Treatment of cultured chick embryo hepatocytes with phenobarbital,
polychlorinated biphenyl compounds and 2,3,7,8-tetrachlorodibenzo-p-
dioxin resulted in increased delta-aminolaevulinate synthase and
decreased uroporphyrinogen decarboxylase activities and porphyrin
accumulation; uroporphyrin and heptacarboxyporphyrin predominated.
Iron had no effect on these changes. Simultaneous treatment of
cultures with dioxin and phenobarbital produced a synergistic response
in delta-aminolaevulinate synthase induction, uroporphyrinogen
decarboxylase inhibition and porphyrin accumulation. These data
suggest that an inhibitor of uroporphyrinogen decarboxylase may be
generated in the liver from polychlorinated biphenyl compounds or
dioxin by metabolic activation. Additionally these findings bear on
the postulated role of these and related chemicals in determining the
low levels of uroporphyrinogen decarboxylase activity in porphyria
cutanea tarda patients. PMID: 6412692

[Chloracne, porphyria cutanea tarda, and other poisonings due to the
herbicides]
In 80 industrial workers producing herbicides (2,4,5-
trichlorphenoxyaceticacidsodium and sodiumpentachlorphenolate) in
Czechoslovakia the following signs of intoxication caused by 2,3,6,7-
tetrachlordibenzodioxin were found: Dermatological: Chloracne and
Porphyria cutanea tarda. Internal: Disorders of the metabolism of
porphyrins, fats, carbohydrates, plasmaproteins. Neurological: Mainly
lesions of the peripheral neurone. Psychiatric: Neurasthenic syndrome
and organic lesions. Differences from the usual course of chloracne
were observed. Porphyria cutanea tarda acquisita was most obvious, one
patient suffered and died from severe atherosclerosis, hypertension
and diabetes. Many patients developed polyneuropathy, as verified both
by EMG and autopsy. Two patients died from bronchogenic carcinoma.
PMID: 134006