Re: Mechanism by which one stachybotrys mycotoxin can cause cholestasis (blockage of bile flow from liver to gallbladder)

[Guest guest]

I forgot to mention that cyclosporin in stachybotrys AMOUNTS are

unknown. Can any researcher who studies these things run some kind of

assay to tell us how much cyclosporin is in stachybotrys in home

environments and how often it is found in mold strains. Cyclosporin is

a drug with mulltiple effects and its EXTREMELY powerful. To have that

floating around in our homes might be very dangerous. We are not

transplant victims and we don't need immunosuppression.

It interrupts sleep. It causes lesions in the brain. It destroys

progenitor (stem) cells we need to repair ourselves.

Plus, its neurotoxic.

> J Antibiot (Tokyo). 1993 Dec;46(12):1788-98.Links

>

> Erratum in:

> J Antibiot (Tokyo) 1994 Feb;47(2):C-1.

>

> FR901459, a novel immunosuppressant isolated from Stachybotrys

> chartarum No. 19392. Taxonomy of the producing organism, fermentation,

> isolation, physico-chemical properties and biological activities.

> Sakamoto K, Tsujii E, Miyauchi M, Nakanishi T, Yamashita M,

> Shigematsu N, Tada T, Izumi S, Okuhara M.

>

> Exploratory Research Laboratories, Fujisawa Pharmaceutical Co.,

> Ltd., Ibaraki, Japan.

>

> FR901459, a novel immunosuppressant, has been isolated from the

> fermentation broth of Stachybotrys chartarum No. 19392. The molecular

> formula of FR901459 was determined as C62H111N11O13. FR901459 was

> found to be a member of the cyclosporin family. However, it is

> structurally distinct from any other cyclosporins discovered so far,

> in that Leu is present at position 5 instead of Val. FR901459 was

> capable of prolonging the survival time of skin allografts in rats

> with one third the potency of cyclosporin A.

>

> PMID: 8294235 [PubMed - indexed for MEDLINE]

>

>

> Yale J Biol Med. 1997 Jul-Aug;70(4):379-90.

> Mechanisms of hepatic transport of cyclosporin A: an explanation

> for its cholestatic action?

> Fricker G, Fahr A.

>

> Institut für pharmazeutische Technologie und Biopharmazie,

> Heidelberg, Germany. jw3@...

>

> The hepatic transport of the immunosuppressive Cyclosporin A (CyA)

> was studied using liposomal phospholipid membranes, freshly isolated

> rat hepatocytes and bile canalicular plasma membrane vesicles from rat

> liver. The Na(+)-dependent, saturable uptake of the bile acid

> 3H-taurocholate into isolated rat liver cells was apparently

> competitively inhibited by CyA. However, the uptake of CyA into the

> cells was neither saturable, nor temperature-dependent nor

> Na(+)-dependent, nor could it be inhibited by bile salts or

> CyA-derivatives, indicating passive diffusion. In steady state

> depolarization fluorescence studies, CyA caused a

> concentration-dependent decrease of anisotropy, indicating a membrane

> fluidizing effect. Ion flux experiments demonstrated that CyA

> dramatically increases the permeability of Na+ and Ca2+ across

> phospholipid membranes in a dose- and time-dependent manner,

> suggesting a iontophoretic activity that might have a direct impact on

> cellular ion homeostasis and regulation of bile acid uptake.

> Photoaffinity labeling with a [3H]-labeled photolabile CyA-derivative

> resulted in the predominant incorporation of radioactivity into a

> membrane polypeptide with an apparent molecular weight of 160,000 and

> a minor labeling of polypeptides with molecular weights of

> 85,000-90,000. In contrast, use of a photolabile bile acid resulted in

> the labeling of a membrane polypeptide with an apparent molecular

> weight of 110,000, representing the bile canalicular bile acid

> carrier. The photoaffinity labeling as well as CyA transport by

> canalicular membrane vesicles were inhibited by CyA and the

> p-glycoprotein substrates daunomycin and PSC-833, but not by

> taurocholate, indicating that CyA is excreted by p-glycoprotein. CyA

> uptake by bile canalicular membrane vesicles was ATP-dependent and

> could not be inhibited by taurocholate. CyA caused a decrease in the

> maximum amount of bile salt accumulated by the vesicles with time.

> However, initial rates of [3H]-taurocholate uptake within the first

> 2.5 min remained unchanged at increasing CyA concentrations. In

> summary, the data indicate that CyA does not directly interact with

> the hepatic bile acid transport systems. Its cholestatic action may

> rather be the result of alterations in membrane fluidity,

> intracellular effects and an interaction with p-glycoprotein.

>

> PMID: 9626758 [PubMed - indexed for MEDLINE]

>

>

>

[Guest guest]

thanks Live, thats pretty interesting.

[Guest guest]

I think so too, It seems to me that there are some similarities in

mycotoxin effects that can be used to examine the scientific

literature looking for things that can help figure out mold illnesses.

Things like knowing the amounts of cyclosporins and their relative

biological activity in different strains of stachybotrys would help a

lot.

On Jan 14, 2008 2:57 PM, who <jeaninem660@...> wrote:

>

>

>

>

>

>

> thanks Live, thats pretty interesting.

>

>