CPOX HCP And Mercury

Toooo many positives

CPOX is the gene location for Hereditary Coproporphyria and CPOX4 is located on that gene. Until now I had no idea there was a variation of HCP, just thought you either had gentic or acquired Porphyria and never had a clue there would be a twist like a mutation for Mercury. So if "genetic" Porphyria and Mercury caused Porphyria are on the same gene isn't it logical that BOTH are gentic? I dunno, I'm not a rocket scientist but if this isn't true I'm totally confused. Pentacarboxylporphyrin is a marker for Mercury. Again I bring up my mother. My mom had lots of Penta, Copro and Proto. My mother had Mercury poisoning. A mutation on CPOX4 causes one to possibly be more suseptable to Mercury exposure and a elevation in porphyrin. And Mercury causes a whole lot of stuff like immune problems, multiple symptoms and Porphyria. If there's a mutation called a polymorphism how is it acquired? And isn't Mercury implicated in MCS?



A cascade analysis of the interaction of mercury and coproporphyrinogen oxidase (CPOX) polymorphism on the heme biosynthetic pathway and porphyrin production.

Heyer NJ, Bittner AC Jr, Echeverria D, Woods JS.
Battelle Centers for Public Health Research and Evaluation, 1100 Dexter Avenue N, Suite 400, Seattle, WA 98109, USA.

Mercury (Hg) exposure in various forms remains a persistent public health concern in many parts of the world. In previous studies, we have described a biomarker of mercury exposure characterized by increased urinary concentrations of specific porphyrins, pentacarboxyporphyrin (5-CP) and coproporphyrin (4-CP), and the atypical keto-isocoproporphyrin (KICP), based on selective interference with the fifth (uroporphyrinogen decarboxylase, UROD) and sixth (coproporphyrinogen oxidase, CPOX) enzymes of the heme biosynthetic pathway. Whereas this response occurs in a predictable manner among approximately 85% of subjects with Hg exposure, an atypical porphyrinogenic response (APR) has been observed in approximately 15% of Hg-exposed persons, in which the three porphyrins that are affected by Hg, i.e., 5-CP, 4-CP and, KICP, are excreted in substantial excess of that predicted on the basis of Hg exposure alone. This APR has been attributed to a specific polymorphism in exon 4 of the CPOX gene (CPOX4). In the present study, we sought to further confirm the hypothesis that the observed changes in porphyrin excretion patterns might serve as a biomarker of Hg exposure and potential toxicity by statistically modeling the cascading effects on porphyrin concentrations within the heme biosynthetic pathway of Hg exposure and CPOX4 polymorphism in a human population with long-term occupational exposure to elemental mercury. Our results are highly consistent with this hypothesis. After controlling for precursor porphyrin concentrations, we demonstrated that 5-CP and 4-CP are independently associated with Hg concentration, while KICP is associated only with the CPOX4. An unpredicted association of Hg with heptacarboxyporphyrin (7-CP) may indicate a previously unidentified point of mercury inhibition of UROD. These findings lend further support to the proposed utility of urinary porphyrin changes as a biomarker of exposure and potential toxicity in subjects with mercury exposure. Additionally, these findings demonstrate the successful application of a computational model for characterizing complex metabolic responses and interactions associated with both toxicant exposure and genetic variation in human subjects.

PMID: 16214298 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/16214298?ordinalpos=15&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum

ROS Melatonin And Porphyria

Another interesting article I found just today confirming the ROS connection and Porphyria. Interesting that the study was done in 2001. Anybody out there on Melatonin? Ask your doctor if Melatonin is right for you.

Journal Molecular and Cellular Biochemistry
Publisher Springer Netherlands
ISSN 0300-8177 (Print) 1573-4919 (Online)
Issue Volume 218, Numbers 1-2 / February, 2001
DOI 10.1023/A:1007225809674
Pages 87-92
Subject Collection Biomedical and Life Sciences
SpringerLink Date Sunday, October 31, 2004


Wenbo Qi1, Russel J. Reiter1 , Dun-Xian Tan1, Lucien C. Manchester1 and Juan R. Calvo1

(1) Department of Cellular and Structural Biology, The University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA


Abstract -aminolevulinic acid (ALA), a heme precursor which accumulates during lead poisoning and acute intermittent porphyria, is reported to cause liver cancer. The carcinogenic mechanisms of ALA may relate to its ability to generate free radicals through metal-catalyzed oxidation which cause oxidative DNA damage. The aim of this study was to compare the efficacy of melatonin, trolox (vitamin E) and mannitol in altering DNA damage induced by ALA. Herein, we found, in the presence of Fe2+, that ALA-induced formation of 8-hydroxydeoxyguanosine in calf thymus DNA was dose and time-dependent. Melatonin, mannitol and trolox, all of which are free radical scavengers, inhibited the formation of 8-hydroxydeoxyguanosine in a concentration-dependent manner. The concentration of each (melatonin, mannitol and trolox) required to reduce DNA damage by 50%, i.e., the IC50, was 0.52, 0.84 and 0.90 mM, respectively.
-aminolevulinic acid - 8-hydroxydeoxyguanosine - melatonin - mannitol - vitamin E

http://www.springerlink.com/content/m366204481426129/

ROS And Porphyria

Many people wonder what the link could possibly be between Porphyria and Multiple Chemical Sensitivity. For you obnoxious people who insist MCS is all in people heads without walking in their shoes we will term it "multiple allergy" for you. ROS is Reactive Oxygen Species and I won't explain that because it would take a whole lot of explaining and technical language. There has been no dispute that porphyrins do increase in MCS and no dispute that many with Porphyria have a hypersensitivity to many things including chemicals. I have had advocates on both sides blast me for trying to link the two. Honestly it's a shame these heads don't pull together to find out why instead of having tunnel vision.

A quote:
Fernando G. Princa, Adela Ana Juknata, Adrian A. Amitranoa and Alcira Batllea, ,



1. δ-Aminolevulinic acid (ALA) has been reported to promote reactive oxygen species (ROS). Overproduction and accumulation of ALA, as it occurs in acute intermittent porphyria (AIP), can be the origin of an endogenous source of ROS, which can then exert their oxidative damage to cell structures.

2. To investigate the induction of lipid peroxidation by ALA, thiobarbituric acid reactive substances and conjugated diene formation were measured by using minimal tissue units (MTUs) obtained from rat cerebellum. Malondialdehyde levels increased with ALA concentration and incubation time (72% at 1.0 mM ALA and 127% at 4.0 mM ALA for 4 hr), and conjugated diene formation was enhanced 50% in incubations with 1.0 mM ALA for 4 hr.

3. ALA-promoted ROS by exposure of cerebellum MTUs to 1.0 mM ALA during different intervals (1–4 hr) was partly reduced by the addition of antioxidants such as superoxide dismutase (SOD; 50 U/ml), catalase (4.5 μM) and dimethylsulfoxide (150 mM), demonstrating the involvement of O2−., H2O2 and OH. in ALA autooxidation.

4. Porphobilinogen biosynthesis was 170% increased when cerebellum MTUs were incubated with 1.0 mM ALA for 4 hr in the presence of SOD, suggesting that protein damage was promoted by ALA autooxidation.

5. These findings provide the first experimental evidence of the involvement of ALA-promoted ROS in the damage of proteins related to porphyrin biosynthesis, specially ALA-D. Oxidation of this enzyme would lead to further accumulation of ALA in AIP patients, which may be the origin of the well-known neuropsychiatric manifestations.


A link to the article http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T71-3VPJ5XB-1T&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=bdd6c2425f23565cd907dc811814a2a2

So what does this mean? ROS has been studied extensively in relation to MCS but I've never seen a study that showed how the porphyrin could accumulate. I have lots of theories on all of it and speak my mind quite a bit but every so often I find a study like this that actually backs it up. More on ROS later. So my next question is what would happen if one were to have the genetic form of Porphyria but a deficiency of glycine and/or folate such as in pregnancy? A little technical but maybe someone will look into it and provide an answer. I suspect a lower level of porphyrin in a 24hr urine test. And that leads me to a whole lot of other "what ifs".

Porphyria Perfume And Pesticide

Why am I disabled? Well technically I wouldn't be if pesticide and perfume were outlawed. My doctor told me to quit my job or die. Finding a job that doesn't use pesticide in some form is impossible unless you work from home and even then you have to go out into the public sometime. Whether my Porphyria is genetic or acquired is a moot point when it comes to pesticide. Pesticide is a poison and raises the porphyrin of animals and people whether they have Porphyria or not. In some cases it raises it to the levels where symptoms occur which is pain in the gut, CNS (central nervous system)symptoms like peeing your pants in public, lack of oxygen which in my case is caused by the weak autonomic nervous system, and in short it does the same thing to my body that it does to a bug with the exception that it causes me to have Porphyria attacks. Time tested and true my levels spiked the day after my workplace was sprayed and took aproxamately two weeks to level down. Perfume does the same thing but not to the same extreme. Why? Perfume is unregulated and carries many of the same ingredients as pesticide but they are "trade secrets". Febreze is going to be the death of me and is also classified as a pesticide. There are alternatives to pesticide and nothing smells better than a freshly washed body. People with Porphyria need to do almost everything as natural as they can because alot of us are sensitive to almost everything synthetic or classified as a poison. Thus comes the Multiple Chemical Sensitivity controversy. More on that later. The mechanism of free radicals and NOS are the same in both Porphyria and MCS so why not quit arguing about it and figure out why?

Porphyria Genealogy and The Roots That Bind

If you think you couldn't possibly have document family history and connections to the Royal tree you need to read this book.


Gary Boyd Roberts, nationally renowned Senior Research Scholar emeritus at the New England Historic Genealogical Society (NEHGS) in Boston, Massachusetts, is well known for American Ancestors and Cousins of The Princess of Wales (1984), Ancestors of American Presidents (1989, 1995), Notable Kin, 2 vols. (1998-99), his Internet column on the NEHGS website, his introduction to C.A. Torrey's New England Marriages Prior to 1700, and his selections and introductions for fifteen volumes of journal articles reprinted by Genealogical Publishing Company. His 1993 compendium, The Royal Descents of 500 Immigrants, was an "instant classic," and became the springboard for much further research. He contributed to the last two or more editions of Ancestral Roots, Magna Charta Sureties, and The Plantagenet Ancestry of Seventeenth-Century Colonists. In addition, he has helped NEHGS patrons trace their royal descents and "notable kin" since 1974 and has lectured widely on various related topics.

Mr. Roberts' has written a twenty-three volume manuscript called "The Mowbray Connection," copies of which can be found at NEHGS, the New York Public Library, and the Society of Genealogists in London, is subtitled "An Analysis of the Genealogical Evolution of British, American, and Continental Nobilities, Gentries, and Upper Classes Since the End of the Middle Ages."
http://www.genealogical.com/products/The%20Royal%20Descents%20of%20600%20Immigrants/4963.html

Girl's Gone Child: SheNANNYgans: Introducing Lauren

Girl's Gone Child: SheNANNYgans: Introducing Lauren

Neurology Minutiae: Porphyria pearls

Neurology Minutiae: Porphyria pearls

Porphyria And Genealogy

It's very important when diagnosing to consider "family history" to determine whether your Porphyria is inherited or acquired. It also catches some people who may slip into the cracks of "further testing required". but not always. When moms diagnosis was reversed because of ignorance on her doctors part I became frustrated and decided to see whether people with Porphyria actually were related to each other. I can't go into detail about the project because of confidentiality but I can tell you it not only amazed the people involved but it amazed the geneticist to the point that he got involved and helped us immensley to get DNA done in Spain to determine if we had King Georges gene. The genes mutate alot so it was a long shot but it did diagnose someone who previously had been told she did not have Porphyria because her levels weren't high enough. Yay... one life saved but the rest are still waiting for that unknown mutation to appear. Literally everyone in the project so far has connected to each other in the family tree from the same lines that gave George his Porphyria. Dr Rushton has written a book on the Royals and their Porphyria going into detail about the medical history and the probability of Porphyria.

Royal Maladies was written by Alan Rushton M.D., PhD who has practiced Pediatrics and Medical Genetics at Hunterdon Medical Center in New Jersey since 1980. He attended the University of Chicago and Yale University, and served on the faculty of Princeton, University of Medicine and Dentistry of New Jersey and the Medical University of the Americas. In 1994 he published Genetics and Medicine in the United States 1800-1922 and soon a new book Genetics and Medicine in Great Britain from 1600 to 1939.

Dr Rushton helped to explain a whole lot of things the group had questions about and explained how intermarriage of the Royal Families of England, France, Russia, Spain and German carried the hereditary diseases from one end of Europe to the other.

So for three years I literally buried myself into geneology and there's really no easy explaination of how so many people can be weaved together like a tightly woven tapestry. We may not have had Georges mutation (with the exception of one) but we certainly share his Porphyria lines several times over. My data base is huge and if you have Porphyria I bet your lines are in it.

Homefront Hugs

My sister sent me this great link to send cards to soldiers overseas. This Christmas if you'd like to send a card check out this great organization.

http://homefronthugs.com/

APF Links And Other Stuff

There are a ton of links out there and articles leading back to the APF website and you may wonder why I don't have them. If I tried to explain you would be turned off by the first few sentences but the bottom line is if you need the information it's easier to find than my blog and if you ask I will direct you there. If you are denied help there do not give up until you have been proven to not have Porphyria. If your levels aren't high enough for diagnosis be sure you are in attack when testing and there have been people turned away who did in fact have Porphyria but the tests were done too late to be conclusive. With some types the porphyrin levels go down within days. The sooner you are dx'd the better and the less chance of developing peripheral neuropathy. Many stories out there about people who were tested many times before they fially got a positive test. There is huge controversy over what a "positive" test is. If you have a positive PBG you have to assume the life of a Porph until you can confirm you do not have it. A temporary dx won't kill you but an undiagnosed attack can. Avoidance of triggers is all that's needed until you are sure.

You may have seen a show on TV recently like CSI, House or Medical Mysteries where the patient was diagnosed with Porphyria. Most people will watch those shows and say "oh I don't have that" when in reality those shows take the worst cases and sensationalize them. If you have mysterious abdominal pains that cannot be explained by a doctor along with a checklist of various symptoms that may or may not manifest every time you have a possibility of having Porphyria especially if there is family history of the same unexplained symptoms. While it can affect you mentally it doesn't always and the most common mental symptom is depression. Sometimes it manifests as what we call a "fog" where you just aren't "with it" and get confused easily. I personally have trouble with my breathing and temporary incontinence because my muscles get weak. And the feeling of being wired... you are exhausted but just can't seem to get to sleep. That's when I start to carb load. Carbs don't have to be tons of sugars and cakes, it can be a baked potato or other complex carbs and most guidelines say you should eat carbs every three hours. Many people have to watch what they eat but aside from sulphites and MSG I've been pretty lucky. I don't take any prescriptions which I believe is why I'm able to tolerate more than alot of people as far as triggers. There is a long list of triggers and someone should avoid as many of them as possible but still live as normal a life as you can.

Eighteen years ago I was diagnosed with Acute Intermittent Porphyria after a phone call from my mother saying it could be the reason behind my mysterious illnesses.Mom had been diagnosed and when they tested me I had it too. Testing is difficult and some doctors aren't willing to diagnose unless the test is in the exceedingly high numbers which can be fatal if the doctor dismisses the thought totally. All it takes is one trigger too many. This blog is to reveal the complications with not only diagnosing but the ongoing struggle to live a normal life. I didn't realise it but I do have reactions to the sun which isn't typical for AIP but over the years I've noticed alot of things that I took for granted as being normal.

Stories

Today I am very discouraged reading some of the stories about Porphyria on the net. I have Porphyria and I have many online friends in my support group so have heard many many stories but the ones posted in blogs just seem so extreme when it comes to certain things. I welcome people to post their own story and you can do it annonymously. Don't ask for money and don't link back to a website that asks for donations. Don't claim that even the light from the computer causes attacks if you are known to be a regular in an online support group.