Hemochromatosis and Autoimmune Conditions

[Jacques]

Re: hematochrosis

Hello,

After searching for "hematochrosis" on the forum, only one result came back; but, something like two years ago there was much more, here, about it...

Would you know where it is?!

Thank you :)

Are you looking for that thread: Topic: Hemochromatosis and Autoimmune Conditions

https://cassiopaea.org/forum/index.php/topic,20265.0.html

 

[know_yourself_1234]

Re: hematochrosis

Yes that's it! Thank you very much (and sorry for the mistake )

 

[Persej]

I apologize if this is a stupid question, but I was wondering if this can be perhaps connected to hemochromatosis.

What is Secondary Porphyria?

Porphyrias are diseases in which the heme pathway has malfunctioned. They can be genetic or be secondary to another disease process. Part of what is so special about the thoroughness with which Dr. Charles Stratton and his colleagues have studied Chalmydial disease is their discovery that Cpn interferes with the heme pathway, and that many patients with chronic Cpn infections have secondary porphyria to start with, and that this is further exacerbated under treatment. When you understand more about porphyria, it can help you sort out "die-off" as well as chronic symptoms you have, which may be due to heme byproducts-- and how to treat for it.

Heme is a Fe2+ complex. A number of critical cellular functions rely on it and the biosynthesis of heme occurs in all human cells. Toxic compounds called porphyrinogens are formed in one transitional phase of the heme biosynthesis pathway but under normal circumstances are quickly transformed into heme which is not toxic.

The porphyrias are consequences of any impairment of the formation of porphyrinogens or in their transformation to heme. Chlamydiae interfere with this step. Porphyrins then accumulate in the cell itself, and then in the extracellular milieu. Within the mitochondrial matrix, the final steps in the biosynthesis of heme are halted. Depletion of host cell energy by the intracellular infection with Chlamydia species causes additional energy-related complications.

Highly simplified, heme synthesis should look like this:

Heme precursors >> porphrinogens>> transformation to heme >> increased cellular transport including ATP production.

Instead, Cpn interferes with this normal process, and this happens:

Heme precursors >> porphrinogens >> interference with transformation to heme >> build up of unstable heme precursors and porphyrins inside and outside cells >> free radical damage and reduced ATP (energy) synthesis.

http://www.cpnhelp.org/secondary_porphyria_what_

Perhaps if you don't produce enough of heme, your body thinks that it needs more iron, so it takes more iron from your food, but that doesn't help because the problem is not in lack of iron but in your cells which can't produce enough of heme. So over time you get both an iron overload and toxic porphyrins. And also low energy because you cannot produce enough of ATP.

 

[Voyageur]

I apologize if this is a stupid question, but I was wondering if this can be perhaps connected to hemochromatosis.

What is Secondary Porphyria?

[...]

Perhaps if you don't produce enough of heme, your body thinks that it needs more iron, so it takes more iron from your food, but that doesn't help because the problem is not in lack of iron but in your cells which can't produce enough of heme. So over time you get both an iron overload and toxic porphyrins. And also low energy because you cannot produce enough of ATP.

Just caught what you said here, I don't know, yet it's not a stupid question, osit. Something acts as a switch to bind more iron (which has been discussed here as per hemochromatosis), and yet perhaps their are other, or many influence that play on the cells message to attract iron.

Anyway, had another decant session this weekend, so that is the first since September of last year. All went well other than missing the vein in one arm and having to switch to the other arm. Recovered well and felt no ill effects. Having a problem getting my iron levels retested (Doc. related), yet hopefully will get that sorted out soon.

 

[Gaby]

Here is an interesting testimonial shared on my site:

http://health-matrix.net/2013/07/06/the-iron-elephant-the-dangers-of-iron-overload/

I went from a shockingly high Ferritin level of 1160 ng/mlat the end of August last year to a current level of 141 ng/ml(last Friday).
A single blood donation is good for about a 23.5% quick drop and I have made 2 blood donations in this period.
Most of the overall decrease however is the result of taking 2 level teaspoons of IP6(Inositol Hexaphosphate) first thing in the morning with water. (You have to understand “Water” and “Empty Stomach” or it will combine with other minerals and not work as an iron chelator.)
IP6 is on the FDA’s list of Iron Chelators, it is natural and safe unlike the pharmaceutical chelators which seem more dangerous than high plasma iron levels.
The iron Disorders institute recomends a ferritin level between 20 and 80, but my research indicates that indications of thyroid dysfunction begin to occur at levels below 50. Also it seems optimum thyroid function is maintained by a ferritin level between 90 and 105. So my conclusion is to strive for a long term ferritin level between 90 and 105.
The plan now is to continue with the IP6(currently dropping 5 points/day) and to do one last donation this coming Friday.
In about 1.5 weeks I will be at about 60 for ferritin, and the final donation will help lower my hemoglobin level which is quite high (the Iron Disorders Institute indicates this as a problem also).
After that I will allow the ferritin to climb back up to about 100 ng/ml(start eating oysters and red meat again…”Deliscious!”) and monitor and maintain that level for the long term.
It’s been a long haul dealing with Ferro-toxicity and I will be glad to have regained my health and lowered the oxidative stress and predictor of many inflammatory diseases!
I hope this info helps someone! :)

I thought it was pretty interesting because I had very low energy when my ferritin was the lowest. Last time I checked it was a little bit over 80 and I'll check again pretty soon. Iodine can lower ferritin levels as well, so perhaps some people with hypothyroidism on iodine therapy should consider checking out their ferritin levels and other iron overload markers (TIBC, Hb, Ht, iron, transferrin, ferritin and iron saturation).

FWIW.

 

[SeekinTruth]

Thanks for sharing the interesting testimonial, Gaby. I used IP6 as an iron chelator in the past (around 2013) and still have some - need to check if it's expired though.

 

[Voyageur]

Thanks for sharing the interesting testimonial, Gaby. I used IP6 as an iron chelator in the past (around 2013) and still have some - need to check if it's expired though.

I've never used IP6 and had noticed Gaby's post on this the other night. When reading about optimum ferritin levels > 50 for thyroid function (90 - 105), could not recall what Roberta Crawford (Iron Elephant) had said as I gave the book away to a physician friend. Anyway, looked it up in this article on SoTT which said (thanks Gaby):

Some researchers suggest that ferritin should fall between 20-80 ng/ml, with an ideal range being 40-60 ng/ml. If you are above those levels, but less than 150, consider donating at the blood bank. You can only benefit and at the same time, your blood will potentially go to someone who needs it more.

So this is lower than the Iron Disorders Institute's optimum marker of 90 - 105 ng/ml, interesting, as it say's optimum thyroid function is maintained at the latter higher values. Thanks for pointing that out.

 

[Ant22]

Here is an interesting testimonial shared on my site:

http://health-matrix.net/2013/07/06/the-iron-elephant-the-dangers-of-iron-overload/

I went from a shockingly high Ferritin level of 1160 ng/mlat the end of August last year to a current level of 141 ng/ml(last Friday).
A single blood donation is good for about a 23.5% quick drop and I have made 2 blood donations in this period.
Most of the overall decrease however is the result of taking 2 level teaspoons of IP6(Inositol Hexaphosphate) first thing in the morning with water. (You have to understand “Water” and “Empty Stomach” or it will combine with other minerals and not work as an iron chelator.)
IP6 is on the FDA’s list of Iron Chelators, it is natural and safe unlike the pharmaceutical chelators which seem more dangerous than high plasma iron levels.
The iron Disorders institute recomends a ferritin level between 20 and 80, but my research indicates that indications of thyroid dysfunction begin to occur at levels below 50. Also it seems optimum thyroid function is maintained by a ferritin level between 90 and 105. So my conclusion is to strive for a long term ferritin level between 90 and 105.
The plan now is to continue with the IP6(currently dropping 5 points/day) and to do one last donation this coming Friday.
In about 1.5 weeks I will be at about 60 for ferritin, and the final donation will help lower my hemoglobin level which is quite high (the Iron Disorders Institute indicates this as a problem also).
After that I will allow the ferritin to climb back up to about 100 ng/ml(start eating oysters and red meat again…”Deliscious!”) and monitor and maintain that level for the long term.
It’s been a long haul dealing with Ferro-toxicity and I will be glad to have regained my health and lowered the oxidative stress and predictor of many inflammatory diseases!
I hope this info helps someone! :)

I thought it was pretty interesting because I had very low energy when my ferritin was the lowest. Last time I checked it was a little bit over 80 and I'll check again pretty soon. Iodine can lower ferritin levels as well, so perhaps some people with hypothyroidism on iodine therapy should consider checking out their ferritin levels and other iron overload markers (TIBC, Hb, Ht, iron, transferrin, ferritin and iron saturation).

FWIW.

Thank you for posting this Gaby, I bought IP6 right after I read your post and I’ve already started taking it first thing in the morning on empty stomach. I was diagnosed with Hemochromatosis (among other issues) in September last year, after a lifetime of recurring tummy aches and fatigue that eventually led a lot of research since the only advice I ever got from doctors was that I was just stressed out and I needed to relax more.

Unfortunately I can’t just donate blood to keep the condition under control as there is a minimum body weight requirement I don’t meet. I’ve always wanted to put on weight but it never happened so there’s little chance it will change in the nearest future.

Upon diagnosis, my doctor sent me to do blood work for iron levels, which came back OK. Only after the test was done I came across information that iron levels can be low whilst ferritin levels can still be high.

I suffered through debilitating fatigue throughout my 20ies and the first time I noticed any improvement to my health was when I started the iodine protocol. Now that you said it lowers ferritin levels it makes sense to me why it helped. It was like waking up after all these years of sleepwalking through every single day.

I suspect DMSA helps lower iron and ferritin levels too because I tend to feel much more awake after each round. I finished a round earlier this week so hopefully this is going to be a productive weekend :)

That said my symptoms still come back out of the blue with the same old severity and stick around for days, weeks or months at a time. When this happens, nothing seems to help and I always try to do as much reading and ‘intellectual’ stuff as possible when I feel OK because when the fatigue is back brain fog gets the best of me.

I guess going forward I’ll get a private test for ferritin levels done and continue with IP6, iodine and DMSA.

 

[Nico]

A friend of mine, which study osteopathy asked his teacher about iodine and he said that studies about supplemental iodine after tchernobyl made some people hypothyroid and under medication for the rest of their life. I haven't yet research and came across such a point but my readings continue.

About iron load, I am giving chance to activated charcoal, as stated from Gaby's article :

Just an update for the data pool – After giving two pints of blood and drinking activated charcoal on average of every few days for the past 2 months (some days I’d drink it some days I would not), my Ferritin level dropped to 55 from 197, so I think the activated charcoal really played a part since giving a pint of blood should only drop it about 50 points from what I understand, so if the drop were just from the pints of blood, the reading should have been around 97. Of course there could be other factors at play of which I am unaware. Serum iron level dropped to 70, though that doesn’t tell us much.

Unfortunately, this doctor I had didn’t do either of the binding capacity tests so I have no idea of the saturation, logically, it should have improved (I think). So, I’m going to continue to give blood as often as the red cross allows me to and I think that should manage it. All my other blood tests were normal and she did an abdominal ultrasound to make sure I didn’t have liver enlargement or anything and that all looked normal as well. I did have one liver hemangioma, a benign mass but she said that’s no big deal.”

So, if anyone can’t do EDTA or doesn’t want to do EDTA, activated charcoal certainly appears to be an alternative.

When I take it I feel bubbling inside the body and light adrenal weakness, one drink out of two. So it's quite powerful.

 

[Ant22]

A friend of mine, which study osteopathy asked his teacher about iodine and he said that studies about supplemental iodine after tchernobyl made some people hypothyroid and under medication for the rest of their life. I haven't yet research and came across such a point but my readings continue.

About iron load, I am giving chance to activated charcoal, as stated from Gaby's article :

Just an update for the data pool – After giving two pints of blood and drinking activated charcoal on average of every few days for the past 2 months (some days I’d drink it some days I would not), my Ferritin level dropped to 55 from 197, so I think the activated charcoal really played a part since giving a pint of blood should only drop it about 50 points from what I understand, so if the drop were just from the pints of blood, the reading should have been around 97. Of course there could be other factors at play of which I am unaware. Serum iron level dropped to 70, though that doesn’t tell us much.

Unfortunately, this doctor I had didn’t do either of the binding capacity tests so I have no idea of the saturation, logically, it should have improved (I think). So, I’m going to continue to give blood as often as the red cross allows me to and I think that should manage it. All my other blood tests were normal and she did an abdominal ultrasound to make sure I didn’t have liver enlargement or anything and that all looked normal as well. I did have one liver hemangioma, a benign mass but she said that’s no big deal.”

So, if anyone can’t do EDTA or doesn’t want to do EDTA, activated charcoal certainly appears to be an alternative.

When I take it I feel bubbling inside the body and light adrenal weakness, one drink out of two. So it's quite powerful.

Thank you for posting this Nico, I've been reading about activated charcoal to get a clearer picture of what it does. What caught my attention is the fact that it can be used as an alternative for EDTA, I'm sorting out my hard metal tests at the moment and I will be looking to address any toxicity as soon as I know what to focus on. I had a really bad reaction to EDTA and I would like to avoid it. It's great to know there are alternatives.

Like I said above, I'm pretty sure DMSA does help with iron overload. I had a longer break before rounds and I started to have stomach aches that stopped right after the last round. Not to mention that I really do feel good after each round too.

 

[Nico]

EDTA really scared me off, it was too strong, the two one week cycle I tried it I have been so dry and exhausted, dizzy and sluggish, even in supplementing with minerals. The only other treatment that was worse was DMSO, I collapse one time, it literally flush everything inside of you => out. But there was no fear fortunately, so the experience was well accepted.

Since that time I seek slow and safe purifiers, the best being releasing emotional/mental issues, but it make take some time and being frustrating if you are ready to accelerate !
Besides coconut (apparently the best) based activated charcoal, there is microsilica from here. It's expensive and I have not tested it yet but it seems to have much more potency than chlorella or other "from the gut" chelators.
Note here that charcoal or microsilica don't go into the blood but help the intestines to release the toxicity, and it was the point of Dr Christopher Shade from QuickSilver (the releasing company of Microsilica), he was saying that EDTA and other chemical chelators were overwhelming the kidneys and detox pathways and he was promoting, instead, helping the natural pathway of detox. From my point of view there's less inconvenients, it's smoother, and it enhance gently your natural capacity to heal, so it build confidence more efficiently than using powerful EDTA.

I might be wrong, but now I've passed through this, last week I have engulfed a mix of DMSO, lugol's and liquid trace minerals (for maximal absorption), three times, and it did not make as much catastrophic effects as the last time, progress ?

Let us know about your journey with IP6 and DMSA !

 

[Regulattor]

Interesting testimony from Dr. Mercola in his article about iron overload:

I stopped the phlebotomy when I started a comprehensive detoxification strategy involving near and far infrared sauna, and interestingly, despite the fact I was no longer removing blood, my ferritin continued to drop over the next nine months. Now, it's down to 37 — far lower than I was ever able to get down to with therapeutic phlebotomies, and as I mentioned earlier I have a healthy GGT level of 17.

It looks like near/far infrared exposure can play significant role in bringing iron to healthy levels.

(_https://articles.mercola.com/sites/articles/archive/2017/09/20/monitoring-serum-ferritin-and-ggt.aspx?utm_source=facebook.com&utm_medium=referral&utm_content=facebookmercola_lead&utm_campaign=20170920_monitoring-serum-ferritin-and-ggt)

 

[Voyageur]

Something further on IP6 noted - I've not read this book mentioned and was not aware of these other aspects with only the focus on Iron overload that was cited above:

http://www.webmd.com/vitamins-supplements/ingredientmono-775-ip-6.aspx?activeingredientid=775&activeingredientname=ip-6

Overview

IP-6 Overview Information

IP-6, inositol hexaphosphate, is a vitamin-like substance. It is found in animals and many plants, especially cereals, nuts, and legumes. It can also be made in a laboratory.

Some people use IP-6 to treat and prevent cancer, including prostate cancer, breast cancer, colon cancer, liver cancer, and blood cancers. Researchers have been studying the role of IP-6 in cancer treatment and prevention since 1988. But, so far, there have been no studies in people with cancer. A book called "IP-6, Nature's Revolutionary Cancer-Fighter" by prominent IP-6 researcher Abulkalam M. Shamsuddin, MD, Ph.D, has popularized IP-6 as an anti-cancer tool.

IP-6 is also used for boosting the immune system, treating anemia, and preventing heart disease and kidney stones.

In manufacturing, IP-6 is added to food to keep it from spoiling.

How does it work?

IP-6 might help treat and prevent cancer by slowing down the production of cancer cells. It might also bind to certain minerals, decreasing the risk of colon cancer. IP-6 is also an antioxidant.

Interesting concerning "cereals, nuts and legumes" as these don't work well for some people.

Uses

Possibly Effective for:

Preventing kidney stones, when IP-6 is consumed in the diet.


Insufficient Evidence for:

Treating and preventing cancer.
Preventing heart attacks.
Other conditions.

More evidence is needed to rate the effectiveness of IP-6 for these uses.

Side effects

IP-6 is safe when used in amounts found in foods. There isn't enough information to know if it is safe when used in medicinal amounts.

Special Precautions & Warnings:
Pregnancy and breast-feeding: IP-6 is safe for pregnant and breast-feeding women when used in food amounts. But the safety of using IP-6 is larger medicinal amounts is unknown. It’s best to stick to food amounts if you are pregnant or breast-feeding.

Clotting disorders: Test tube studies suggest that IP-6 can slow blood clotting. Although this effect has not been shown in humans, experts recommend that people with clotting disorders avoid using IP-6.

Iron-deficiency anemia: IP-6 binds with iron in the gastrointestinal (GI) tract. This reduces the amount of iron that the body absorbs from food and supplements.

Weak bones (osteoporosis or osteopenia): IP-6 binds with calcium in the gastrointestinal (GI) tract. This reduces the amount of calcium that the body absorbs from food and supplements. Reduced calcium can affect bone strength.

Surgery: Since test tube research suggests that IP-6 might slow blood clotting, there is a concern that it might increase the risk of extra bleeding during and after surgery. Stop using IP-6 at least 2 weeks before a scheduled surgery.

Gaby spoke to the Iron issue and there is likely more going on with the calcium issue cited - from this article:

Bones are not made from calcium alone. They're an amalgam that includes various minerals such as zinc, boron and copper. Foremost of the additional minerals needed for healthy bones is magnesium, which is actually considered by health experts to be more important for bone health than calcium.

Have a look at Magnesium in this thread https://cassiopaea.org/forum/index.php/topic,2354.0.html

Interactions

Moderate Interaction Be cautious with this combination

Medications that slow blood clotting (Anticoagulant / Antiplatelet drugs) interacts with IP-6

IP-6 nicotinate might slow blood clotting. Taking IP-6 along with medications that also slow clotting might increase the chances of bruising and bleeding.
Some medications that slow blood clotting include aspirin, clopidogrel (Plavix), diclofenac (Voltaren, Cataflam, others), ibuprofen (Advil, Motrin, others), naproxen (Anaprox, Naprosyn, others), dalteparin (Fragmin), enoxaparin (Lovenox), heparin, warfarin (Coumadin), and others.

I think drugs like Plavix can cause much bruising and bleeding.

IP-6 Dosing

The appropriate dose of IP-6 depends on several factors such as the user's age, health, and several other conditions. At this time there is not enough scientific information to determine an appropriate range of doses for IP-6. Keep in mind that natural products are not always necessarily safe and dosages can be important. Be sure to follow relevant directions on product labels and consult your pharmacist or physician or other healthcare professional before using.

 

[RedFox]

Interesting testimony from Dr. Mercola in his article about iron overload:

I stopped the phlebotomy when I started a comprehensive detoxification strategy involving near and far infrared sauna, and interestingly, despite the fact I was no longer removing blood, my ferritin continued to drop over the next nine months. Now, it's down to 37 — far lower than I was ever able to get down to with therapeutic phlebotomies, and as I mentioned earlier I have a healthy GGT level of 17.

It looks like near/far infrared exposure can play significant role in bringing iron to healthy levels.

(_https://articles.mercola.com/sites/articles/archive/2017/09/20/monitoring-serum-ferritin-and-ggt.aspx?utm_source=facebook.com&utm_medium=referral&utm_content=facebookmercola_lead&utm_campaign=20170920_monitoring-serum-ferritin-and-ggt)

Wanted to see if I could find something to back this one up:

_https://www.ncbi.nlm.nih.gov/pubmed/10677564

Induction of the putative protective protein ferritin by infrared radiation: implications in skin repair.

Abstract

The modification of ferritin in human skin cells in vitro and in vivo following infrared-A [760-1400nm] irradiation by immunohistochemical analysis and ELISA were evaluated. In addition, we observed that IR-A is not capable of inducing frank damage to DNA (pyrimidine dimers, p53), induction of oxidative stress proteins (heme oxygenase, nitric oxide, superoxide dismutase, heat shock proteins) or proteases (collagenase, stromelysin, gelatinase) involved in carcinogenesis and photoaging of the skin. in vivo, basal levels of ferritin were heterogeneous for all individuals tested but all showed ferritin to stain precisely in the basal layer of unirradiated epidermis. Following IR-A radiation, the ferritin increase was localized to epidermal tissue and showed an increase from 120 to 220%. Parallel to the in vivo analysis, dermal fibroblasts were cultured from six individuals. Quantitative analysis for ferritin in cultured fibroblasts was assessed by ELISA and increases were seen to be dose-dependent and up to 130% of basal levels of ferritin following infrared-A. Our findings indicate that the putative defense system of ferritin that exists in human skin in vivo can be induced by infrared-A radiation and that these wavelengths may prove to be beneficial for human skin. Importantly, following the same doses of IR-A that induced ferritin levels, there was no alteration seen for nuclear DNA type damage, oxidative stress proteins or proteases involved in the degradation of skin. The increased concentrations of this antioxidant in human skin following acute UV radiation could afford increased protection against subsequent oxidative stress.

So it's possible that NIR could cause iron to be moved into the skin, which is then eventually shed.

 

[fabric]

Interesting testimony from Dr. Mercola in his article about iron overload:

I stopped the phlebotomy when I started a comprehensive detoxification strategy involving near and far infrared sauna, and interestingly, despite the fact I was no longer removing blood, my ferritin continued to drop over the next nine months. Now, it's down to 37 — far lower than I was ever able to get down to with therapeutic phlebotomies, and as I mentioned earlier I have a healthy GGT level of 17.

It looks like near/far infrared exposure can play significant role in bringing iron to healthy levels.

(_https://articles.mercola.com/sites/articles/archive/2017/09/20/monitoring-serum-ferritin-and-ggt.aspx?utm_source=facebook.com&utm_medium=referral&utm_content=facebookmercola_lead&utm_campaign=20170920_monitoring-serum-ferritin-and-ggt)

Wanted to see if I could find something to back this one up:

_https://www.ncbi.nlm.nih.gov/pubmed/10677564

Induction of the putative protective protein ferritin by infrared radiation: implications in skin repair.

Abstract

The modification of ferritin in human skin cells in vitro and in vivo following infrared-A [760-1400nm] irradiation by immunohistochemical analysis and ELISA were evaluated. In addition, we observed that IR-A is not capable of inducing frank damage to DNA (pyrimidine dimers, p53), induction of oxidative stress proteins (heme oxygenase, nitric oxide, superoxide dismutase, heat shock proteins) or proteases (collagenase, stromelysin, gelatinase) involved in carcinogenesis and photoaging of the skin. in vivo, basal levels of ferritin were heterogeneous for all individuals tested but all showed ferritin to stain precisely in the basal layer of unirradiated epidermis. Following IR-A radiation, the ferritin increase was localized to epidermal tissue and showed an increase from 120 to 220%. Parallel to the in vivo analysis, dermal fibroblasts were cultured from six individuals. Quantitative analysis for ferritin in cultured fibroblasts was assessed by ELISA and increases were seen to be dose-dependent and up to 130% of basal levels of ferritin following infrared-A. Our findings indicate that the putative defense system of ferritin that exists in human skin in vivo can be induced by infrared-A radiation and that these wavelengths may prove to be beneficial for human skin. Importantly, following the same doses of IR-A that induced ferritin levels, there was no alteration seen for nuclear DNA type damage, oxidative stress proteins or proteases involved in the degradation of skin. The increased concentrations of this antioxidant in human skin following acute UV radiation could afford increased protection against subsequent oxidative stress.

So it's possible that NIR could cause iron to be moved into the skin, which is then eventually shed.

That's very very interesting, and could open up another way to reduce one's iron loading without having to donate blood all the time to keep things in check. I'm not sure what my levels were but last time I checked they were in the 300 range which was a couple of years ago. I've donated blood a couple of times since then and was retested and got it down to 200ish but it's been a while and prob should go again. That said, if there is a connection to reduced iron levels and infrared, I wonder how much reduction does one get with each exposure.