tag:blogger.com,1999:blog-655962722302095847.post3082753562295095213..comments2024-03-27T20:20:54.505+01:00Comments on Epiphany: The Purkinje-RORa-Estradiol-Neuroligin-KCC2 axis in AutismPeter Lloyd-Thomashttp://www.blogger.com/profile/10173383229834614994noreply@blogger.comBlogger100125tag:blogger.com,1999:blog-655962722302095847.post-47102644354499368152017-02-07T03:19:14.496+01:002017-02-07T03:19:14.496+01:00Hi Peter
Thanks for quick reply
I will check about...Hi Peter<br />Thanks for quick reply<br />I will check about IV ALA but my DAN uses EDTA iv not sure if you heard about it<br />Thanks <br />BKAnonymousnoreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-64065524372038238302017-02-07T00:10:16.184+01:002017-02-07T00:10:16.184+01:00BK, my son has not used IV antioxidants, but his G...BK, my son has not used IV antioxidants, but his Grandfather has been using IVA ALA for several years to treat diabetic neuropathy and finds is very effective and free of side effects. Chelation is no more than treatment with antioxidants. <br /><br />IV ALA should give an improvement, if oral ALA gave an improvement, and should be more effective as with neuropathy treatment.<br /><br />Leucoverin (calcium folinate)in addition to helping people with genetic folic acid deficiency is effective in treating nitrosative stress.<br /><br />People with autism usually have oxidative stress and may also have nitrosative stress.<br /><br />HBOT does not seem to help most people. There have been numerous clinical trials. I think there is a big parental placebo effect, because of the cost.Peter Lloyd-Thomashttps://www.blogger.com/profile/10173383229834614994noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-39490446847976491882017-02-06T22:33:26.678+01:002017-02-06T22:33:26.678+01:00Hi Peter,
My son who is 4.5 years old now recently...Hi Peter,<br />My son who is 4.5 years old now recently had some very good gains( He is flying through ABA programs he was stuck on for months - his main issue is lack of attention & lack of speech).<br />What we tried new is: Leucovorin which I beleive is folinic acid (Not Methyl folate - this I think is what DAN doctors suggest), and we tried low dose AC Chelation for around 5 weeks - with ALA & DMSA (micro doses). Cant say for sure which helped.<br />Question is : Our DAN was suggesting HBOT and may be IV chelation, wanted to check if you or any other readers have tried these, IV chelation seems a little risky, so not sure about it. And HBOT will probably be one of the most expensive ones we try, but we are ok with the expense part.<br />For other readers: I just wanted to share that some parents found folinic acid (Leucovorin) more helpful than Methly Folate (Deplin in US).<br />Thanks<br />BKAnonymousnoreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-28771309868952127602017-02-05T14:02:59.998+01:002017-02-05T14:02:59.998+01:00AJ, an alternative to synitrol/naringin capsules c...AJ, an alternative to synitrol/naringin capsules could be this old-folk home-made cholesterol remedy drink. It is very popular in certain parts of Europe, where many people swear by it, including some doctors. I now believe that the supposed effects are due to naringin that gets extracted in the process. <br /><br />There are many versions of the recipe and they all involve about a kilo of either whole lemons or whole oranges, washed well and chopped up in pieces or thin slices, which are then brought to boil in about 1-2 litres of water and left to cool, then sieved. Some recipes recommend simmering oranges/lemons on a very low heat for a couple of hours (in which case you would need 2 litres of water per kilo of citrus fruit) and some say to add the fruit to boiling water and take the pot off heat as soon as it reaches the boiling point again (in which case you only 1 litre of water, as it won’t evaporate). Some say boil for 20 min, but don’t let temp of water go over 60 degrees celsius. Once cooled, the mixture is sieved by pressing hard to squeeze out as much as possible, leaving only dry pulp, and put in a fridge. <br /><br />Each recipe always has something else added to the mix, either a large bunch of rosemary, or parsley, celery root, or loads of garlic cloves, even ginger. This add-on ingredient largely determines the taste of the drink, ½ glass of which should be taken first thing in the morning, and one later in the day. I have tried both the rosemary and garlic versions, and both taste fine from an adult perspective :) but I guess even if only citrus fruits are used you would get the benefit of naringin. Worth a try?<br /><br />I could not find any recipes in English but these pics could give you an idea of the process: <br /><br />http://www.coolinarika.com/recept/napitak-od-limuna-i-cesnjaka-za-snizavanje-masnoce-u-krvi/<br /><br />http://www.coolinarika.com/recept/anti-trigliceridi-limun-i-celer/ <br />Natnoreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-12197204609813293992017-02-05T00:22:51.741+01:002017-02-05T00:22:51.741+01:00RG, more recent papers suggest things rather diffe...RG, more recent papers suggest things rather differently. Quite often things seem to work in reverse. The more recent paper suggests that less RORα is good for heart disease.<br /><br />Inhibition of RORα/γ suppresses atherosclerosis via inhibition of both cholesterol absorption and inflammation<br />https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5034492/<br /><br />So in this study they are doing the opposite of what was done in the study in my post where they used an RORα agonist in the animal model of autism with a good effect.<br /><br />I think they will have to trial things in humans to see what actually happens.<br /><br />So the conclusion is that statins are good but when it comes to RORα it is unclear whether your daughter needs more or less, because that data is contradictory, but she is unlikely to be at optimal point now.Peter Lloyd-Thomashttps://www.blogger.com/profile/10173383229834614994noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-60083571353132939272017-02-05T00:03:01.165+01:002017-02-05T00:03:01.165+01:00"However, this apparent contradiction can be ..."However, this apparent contradiction can be accounted for by the in vitro model used. The modulation of the RORα transcriptional activity by statins has been assessed in in vitro studies with LDL serum-free medium.1 However, total depletion in intracellular cholesterol has detrimental effects, leading to cell death. In vivo inhibition of cellular synthesis of cholesterol by statins results in increased uptake of circulating LDL cholesterol, leading to a compensation of decreased intracellular cholesterol synthesis. Therefore, it is most likely that in vivo statin treatment does not result in total depletion of cellular cholesterol, allowing RORα to be active. Thereby, in vivo statin treatment is unlikely to impair the protective effects of RORα in the vascular system."<br /><br />Your daughter probably needs more RORα, because she has high levels of cholesterol and inflammation. The paper is saying that the theoretical effect of the statin reducing cholesterol and so reducing RORα activity does not occur in the real world. So in effect though the statin reduces cholesterol there is still plenty left to maintain RORα activity.<br /><br />So statins should still be good for your daughter. More RORα activity would also be good.Peter Lloyd-Thomashttps://www.blogger.com/profile/10173383229834614994noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-31401666170329497202017-02-04T23:18:12.563+01:002017-02-04T23:18:12.563+01:00Hi Peter,
Please help me understand this better....Hi Peter, <br /><br />Please help me understand this better. I have been reading about RORs and there is a lot written about cholesterol binding of these receptors and the use of statins. I am unable to really understand the conclusion, do statins upregulate the activity or vice versa? I am especially keen on figuring this out as they seem to play a role in regulation of lipoprotein A, which my daughter has been shown to have very high levels of. <br /><br />http://atvb.ahajournals.org/content/24/4/637.fullRGhttps://www.blogger.com/profile/07458829468580940361noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-77647321137972455672017-02-04T08:22:55.236+01:002017-02-04T08:22:55.236+01:00Tanya, I absolutely get it. Will contact you hopin...Tanya, I absolutely get it. Will contact you hoping its not too much of a trouble. As a parent, maintaing propriety is the last thing on my mind when it comes to seeking help from someone whom I find to be really wise, but still did not want to be a pest.<br /><br />Warm regardsKritikanoreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-79243364175327673972017-02-03T23:26:08.928+01:002017-02-03T23:26:08.928+01:00Kritika! I had a long paragraph typed in this litt...Kritika! I had a long paragraph typed in this little box, went to copy and paste a link, and returned to find my comments vanished. arrgh. Maybe this is a sign. haha<br />Please feel free to email me and I will gladly share tanyastatum@gmail.comTanyahttps://www.blogger.com/profile/01489962611979985947noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-45921214191617294292017-02-03T23:07:55.988+01:002017-02-03T23:07:55.988+01:00Agnieszka and Peter, have wondered about neuropath...Agnieszka and Peter, have wondered about neuropathic pain as well in my son - but not sure. When he is having a fit reaction, in the past he has pinched himself down his legs. I am looking more in to histamine intolerance because we still have lingering issues in spite of verapamil and using anti histamines and other measures. So if there is an inability to degrade histamine, and h1 and/h2 blockers used, wpuld all that histamine overwhelm the other histamine receptors and intensify pain?? I found this information that h3 blockers used for neuropathic pain treatment. Interesting. excuse amateur questions - still learning. <br />http://onlinelibrary.wiley.com/store/10.1111/cns.12279/asset/cns12279.pdf;jsessionid=27BE51016CB7C3EAB159BE96E03AE189.f01t04?v=1&t=iyqbvhso&s=ff9615752ab2558824835c8d0383f5b67f33b7c2Tanyahttps://www.blogger.com/profile/01489962611979985947noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-31783766093010398122017-02-03T21:20:19.521+01:002017-02-03T21:20:19.521+01:00Agnieszka, before finding an efficient therapy in ...Agnieszka, before finding an efficient therapy in the form of verapamil, during allergy driven self-injury my son would always hit the upper part of his right leg. Maybe this was just a convenient part of the body, but maybe he actually felt pain there. <br /><br />I think most SIB that is reported is directed at the head. It was suggested that degranulation of mast cells might cause pain. <br /><br />There is some logic in hitting the part of your body that hurts. <br /><br />I expect the explanation will vary somewhat from case to case and that channelopathies, mast cells etc will all play a role. If you could correlate a positive behavioral response to bumetanide to the existence of self-injury then you could make a good case for the involvement of neuropathic pain driving the SIB.<br /><br />A problem with SIB is that once it becomes established, it just becomes an acquired behavior that then reoccur for other unrelated and possibly quite minor reasons. It is hard to lose this behavior once it has been discovered.<br /> Peter Lloyd-Thomashttps://www.blogger.com/profile/10173383229834614994noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-22349289628597790152017-02-03T18:46:03.285+01:002017-02-03T18:46:03.285+01:00It is well established that epilepsy rate is high ...It is well established that epilepsy rate is high in people with severe autism and chloride neuronal regulation may at least partially contribute to this. From what is known about neuropathic pain and KCC2/NKCC1 involvement, I would suspect that many people with severe autism may suffer from neuropathic pain, just as from epilepsy. It might affect those with the most impaired communication skills and while it is hardly possible not to recognize grand mal seizure, pain presentation in autism may be atypical. I mean, it does not look like what doctors and caregivers expect from a person affected by pain. “Challenging behaviours” can be the only visible sign. Thinking how many people can’t communicate the pain and are given neuroleptics or behavioural therapy is really scary to me. <br /><br />“Autism”+”neuropathic pain” search in PubMed brings you null with regard to clinical papers. <br /><br />I once had a thought that my son suffers from periodic neuropathic pain. I haven’t fully explained his recurrent episodes, but maybe it is periodic calcium channelopathy that comes with massive mast cells degranulation and inflammatory mediators release, this via further KCC2/NKCC1 dysregulation can lead to peripheral neuropathic pain and headache. Do you think it is plausible?Agnieszka Wroczyńskahttps://www.blogger.com/profile/04738535364585304041noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-21108032498612817112017-02-03T17:11:27.652+01:002017-02-03T17:11:27.652+01:00Tyler, very funny! I assumed that if you liked foo...Tyler, very funny! I assumed that if you liked football you would get it right away. Sometimes it complicates me a bit to understand complex ideas and translate them at the same time, I miss things. <br />ValentinaAnonymousnoreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-43594513704863255472017-02-03T16:09:03.612+01:002017-02-03T16:09:03.612+01:00Kritika, my son did not tolerate Biogaia Gastrus b...Kritika, my son did not tolerate Biogaia Gastrus but responds well to Biogaia Protectis. The second bacteria in Gastrus was also not tolerated by some other commenters. It can take 10 days to get back to normal.<br /><br />So better not to use Gastrus. I think your Bioamicus is very similar to Protectis.Peter Lloyd-Thomashttps://www.blogger.com/profile/10173383229834614994noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-86664479202922041252017-02-03T15:36:36.428+01:002017-02-03T15:36:36.428+01:00Tanya,
How did you zero in on histamine intoleran...Tanya,<br /><br />How did you zero in on histamine intolerance issues in your son? I understand there are no reliable tests available..the most reliable biopsy being a very expensive one and mostly it is through following an elimination diet to see if it helps. Then there is the confusion between food allergy and histamine intolerance. In fact, some opine that its not even a real medical condition but sychosomatic in nature. My son does not have any problem whatsoever with histaminey foods but as you said, once you breach a threshold, that is when the problem starts appearing. Then there is something called sensitivity to vasoactive amines. My head is spinning. Gluten, caesin sensitivity, sensitivity to tannins, flavonoids..should I teach my child photosynthesis now!!!<br /><br />I will be mindful about what to give to my son but if you can suggest anything I would be grateful.<br /><br />Warm regardsKritikanoreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-59473430543234519652017-02-03T14:49:06.733+01:002017-02-03T14:49:06.733+01:00So, allergic reactions produce histamine and in s...So, allergic reactions produce histamine and in some histamine produces an allergic reaction or sort of because it can't be degraded. Actually my son started the disruptive behavior this time after the first half a tab of gastrus. I do not know whether he is allergic to it or intolerant to histamine production involved with gastrus... And this histamine intolerance behavior got accentuated with the seasonal allergy? Could be be having both? And the behavioral manifestations of both could be same? Tanya was suggesting histamine intolerance. There must be tests available to find out if one is histamine intolerant. I am just doing loud thinking.. will look up. <br /><br />Thanks Peter Kritikanoreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-76094492730065707242017-02-03T12:41:39.223+01:002017-02-03T12:41:39.223+01:00Kritika, it seems that any inflammatory condition ...Kritika, it seems that any inflammatory condition may block the effect of bumetanide, the inflammation itself leads to higher intracellular chloride.<br /><br />You need to differentiate between histamine intolerance, when you cannot degrade histamine, and just allergic reactions that cause histamine to be released from mast cells. If he has allergies you need to treat these first and do your bumetanide trial when he is allergy free. <br /><br />Clonazepam is different and the effect should be there regardless of allergy. It takes 3 days to show effect, if he is a responder. So this might be best to try first.Peter Lloyd-Thomashttps://www.blogger.com/profile/10173383229834614994noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-23317460738549049952017-02-03T12:27:15.089+01:002017-02-03T12:27:15.089+01:00I would try one quarter of a tablet, once a day. ...I would try one quarter of a tablet, once a day. Try it for a few days and then decide if it is helpful.<br /><br />I would continue with his other treatments.Peter Lloyd-Thomashttps://www.blogger.com/profile/10173383229834614994noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-55408261143923557892017-02-03T11:28:36.433+01:002017-02-03T11:28:36.433+01:00Hello Peter,
I have stopped everything (bioray ...Hello Peter, <br /><br />I have stopped everything (bioray products, Biogaia gastrus, carnosine) and my son is still displaying the pinching, flopping himself impact fully on the bed repeatedly. But doing well with learning and awareness. This almost looks cute but I know my child is uncomfortable and this could in all probability turn into a major crisis. It's spring here. In India, specially in Delhi we have six major seasons, ranging from 'brain freezing' cold to vaporizing heat. With each turn of weather, my son used to display sensory behavior without the cognitive loss, rather a little enhancement. His therapist advised to wait it out. I knew seasonal changes trigger allergies, seasonal changes trigger sensitivities in my son, allergies involve histamine production but it was actually Tanya who made me sort of compose the sentence... My son displays sensory issues and sometimes deteriorating behavior as and histamine is the cause for this. This is so helpful and probably I might stock on some very verapamil as a contingency measure. And probably try and manage it through CAM therapies. And evaluate drug reactions in that light too. Moderation, thresholds, total load and the works. <br /><br />I presume some of the strategies like bumetanide and clonazepam can be tried out irrespective of histamine status. <br /><br />Regards Kritikanoreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-72239757145172094112017-02-03T11:12:47.632+01:002017-02-03T11:12:47.632+01:00Ok, I have found acetazolamide 250mg. How much sho...Ok, I have found acetazolamide 250mg. How much should I start with? Give it with or without the rest of treatment?Anonymoushttps://www.blogger.com/profile/16138974464162606874noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-55653065072042520342017-02-03T10:10:36.812+01:002017-02-03T10:10:36.812+01:00Petra, I am no expert on neuropathic pain, but I d...Petra, I am no expert on neuropathic pain, but I do not think where he feels the pain is necessarily the location of the problem. <br /><br />I was thinking that if your son responds to bumetanide, it is just a case of the NKCC1/KCC2 imbalance having effects elsewhere in the body. As you reduce intracellular chloride, by whatever means, you should improve both his Asperger's and any neuropathic pain. <br /><br />So you might look at Acetazolamide/Diamox, even Dr Frye in the US is using smallish doses (60mg) doses. <br /><br />If nicotine is effective, you could try small pieces of a nicotine patch to give a small continuous dose.Peter Lloyd-Thomashttps://www.blogger.com/profile/10173383229834614994noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-6951493358608764172017-02-03T10:05:04.841+01:002017-02-03T10:05:04.841+01:00Tyler, I had quitted smoking about one year before...Tyler, I had quitted smoking about one year before my pregnancy with the idea of protecting my fetus from nicotine exposure. Now we are challenged with a paradox outcome.Anonymoushttps://www.blogger.com/profile/16138974464162606874noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-57114249138822952342017-02-03T09:55:27.244+01:002017-02-03T09:55:27.244+01:00Thanks Tyler, it does get complicated. Another po...Thanks Tyler, it does get complicated. Another point to remember is that inflammation affects neuroligin-2 and KCC2. This helps explain why allergy and hence more IL-6 reduces cognitive function in my son, even though I am blocking some Cl- entry with bumetanide, I then have more NKCC1 transporters and less KCC2 transporters, so Cl- concentration goes up. <br /><br />So for multiple reasons too much inflammatory signaling of any kind is bad for autism, SIB and cognitive function. <br /><br />This also might explain why some people's severe SIB goes away with nicotine patches. It is neuropathic pain that prompts the SIB and nicotine is lowering the Cl- level and halting the pain.Peter Lloyd-Thomashttps://www.blogger.com/profile/10173383229834614994noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-37454636068639219032017-02-03T09:45:27.527+01:002017-02-03T09:45:27.527+01:00Peter, thank you very much. I am going to work on ...Peter, thank you very much. I am going to work on that direction.<br /><br />This may sound strange, Asperger's can sense things differently, but before I got back your reply, my son had started complaining about his spinal cord, saying that there may be something connected to pain there.<br />In the past he said that many times before and we visited the doctor to see if there is scoliosis or something like that. Doctor said there is no scoliosis but when he had an operation and needed local anesthesia, the anesthesiologist said that there must be something wrong with his spinal cord because he had trouble doing his job, but didn't explain further.<br />I saw him many times press his side parts of spinal cord seeking relief and it cracks there. <br />He also finds relief when he is not in "freezing" mode and can do some exercises that seem to address to his spinal cord, such as stretching, push ups, sit ups and back exercises.<br />Do you think this may be relevant to spinal cord neuropathic pain?Anonymoushttps://www.blogger.com/profile/16138974464162606874noreply@blogger.comtag:blogger.com,1999:blog-655962722302095847.post-85593984193929723552017-02-03T09:40:38.214+01:002017-02-03T09:40:38.214+01:00AJ, this is what I came up with:-
https://epiphan...AJ, this is what I came up with:-<br /><br />https://epiphanyasd.blogspot.com/2015/10/is-dysregulated-ip3r-calcium-signaling.htmlPeter Lloyd-Thomashttps://www.blogger.com/profile/10173383229834614994noreply@blogger.com