> I would point to a nexus of factors like cathelicidin, HIF-1a and
> metallothionein at work in the sebaceous glands. It's been shown that
> in common acne you've got defective innate antimicrobial production
> and it's not too many jumps down a few pathways from there until
> you get to MT.
Per wiki, Cathelicidins found in neutrophils, epithelial cells,
macrophages, etc are activated by bacteria, viruses, fungi, etc.
HIF-1a plays an essential role in cellular and systemic responses to
hypoxia. Metallothionein have the capacity to bind both physiological
(Zn, Cu, Se,...) and xenobiotic (Cd, Hg, Ag,...) heavy metals.
I would agree that sunlight exposure and butyrate produced from a
health flora are im****tant.
> I think you're inclined to filter everything through the lens of dioxin.
I am guilty of that. I am overly suspicious of POPs such as PCBs,
dioxins, pesticides, plasticizers and heavy metal. Combined with
genetic susceptibility, POPs could be signicant triggers for IBD.
> The simple fact is the body tries to get rid of toxins. First it tries
> to send them out the G.I. tract or through the kidneys. If that doesn't
> work, it tries to put the toxins on slow-growing hairs to move them out
> that way and if all else fails, the body can stick it in fat cells or
> bone for long-term storage where it will do the least harm. Of course,
> you also have specific issues with specific toxins like dioxin but I'm
> trying to think generally about how the body's detox system is tied up
> in all this.
I am particularly concerned about TCDD, the most potent dioxin.
TCDD concentrates in fatty tissues (ie adipose, bone marrow, nervous
system) because it is highly lipophilic and difficult to detox. In
such tissue, TCDD will cause long-term stress/inflammation due to
hyperactivated detox and damage to mitochondria. PMID: 2540069
Below related info from California Environmental Protection Agency's
http://oehha.ca.gov/water/phg/pdf/PHGDioxin062907.pdf
The metabolism of TCDD in humans is very slow and the half-life of
TCDD in humans is much longer than has been do***ented in any other
animal species.
Poiger and Schlatter (1986) estimated that the half-life for
elimination of TCDD in humans was 2,120 days (5.8 yrs) based on fecal
excretion over a 125-day period following a single exposure of 1.4 ng/
kg TCDD3H in a 42-year old male volunteer. Elimination rates for TCDD,
with estimates of half-life ranging from 5-12 years, have also been
have been estimated from epidemiologic studies (Hooiveld et al., 1998;
Michalek et al., 2002; Steenland et al., 2001). Median TCDD half-lives
of 8.7 years (95 percent confidence interval 8.0-9.5 years) and 7.2
years have been calculated in blood fat from 213 Ranch Hand veterans
(Michalek et al., 1996) and 43 Boehringer workers (Flesch-Janys et
al., 1996), respectively. A median half-life of 7.8 years (95 percent
confidence interval 7.2-9.7 years) was calculated in 27 adults from
Seveso, Italy with initial TCDD concentrations between 130 and 3,830
pg/g; a faster decline of TCDD concentrations in blood fat was
re****ted for a few of the Seveso children with a very high exposure
(Needham et al., 1997).
The U.S. EPA, in its most recent *****sment of 2,3,7,8-TCDD (U.S. EPA,
2000), utilized an elimination rate constant (i.e., half-life) for
TCDD in humans of 7.1 years.
------------
Recent trend of polychlorinated dibenzo-p-dioxins and their related
compounds in the blood and sebum of Yusho and Yu Cheng patients.
We investigated the levels of polychlorinated dibenzo-p-dioxins
(PCDDs) and their related compounds in blood and sebum from Yusho and
Yu-Cheng patients and findings compared with those of normal subjects.
Concentrations of these compounds in blood and sebum still were
obviously reflected the chemical concentration in the causal rice oil
ingested 17 or 26 years since the outbreak. In addition, sebum form
the body surface was the most useful sample for monitoring the amount
of chemicals contaminating the human body. PMID: 10028655
Levels of PCDDs, PCDFs and coplanar PCBs in sebum and blood of Yusho
patients:
Polychlorinated dibenzo-p-dioxins (PCDDs) and it's related compounds
such as polychlorinated dibenzofurans (PCDFs) can be detected in the
body in Yusho patients, a condition caused by ingestion of
contaminated rice oil with these compounds... We concluded that
dioxins and it's related compounds in Yusho patients and normal
subjects were excreted not only in the feces but also in the sebum.
PMID: 9194338
Dioxin TCDD induces hyperplasia in confluent cultures of human
keratinocytes.
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is the prototype for a
group of halogenated aromatic hydrocarbons which can be potent
modulators of growth and differentiation of epithelial tissues. TCDD
causes chloracne and can act as a skin tumor promoter, but these
actions have been demonstrated only in animals in which TCDD causes
epidermal hyperplasia. Study of the hyperplastic response to TCDD has
been hampered by lack of an in vitro model; all previous
investigations indicated that TCDD had no in vitro effect on cell
growth. We show here that nanomolar concentrations of TCDD cause
hyperplasia in confluent cultures of human keratinocytes and suggest
that this model system will be useful for analyzing mechanisms of TCDD-
induced epithelial hyperplasia and genetic differences in
responsiveness to TCDD. PMID: 6210328
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