August 3, 2011

4 Unintended Consequences of Seroquel's Adjunct to Antidepressants Indication

prozac.jpg

cutting edge research on this drug should be coming any day now


Part 3 here-- short refresher.


In 1998, I discover something is red.  "It's red."  Sweet.

In 2010, I discover that same thing is also hard.  "It's hard."  Nice.

The question is: what is its primary attribute?  Is it a Red thing that's hard, or a Hard thing that's red? 

II.

Imagine you did it the other way around: in 1998 you discover it is hard, then in 2010 it's found to be red.  Does that change things?  Is the primary attribute based on history, or something else?

"I guess it all depends on what you use it for."  You guess?

III.

Seroquel is that thing, discovered first to be efficacious in schizophrenia (translation: "antipsychotic") and now found to be efficacious in depression ("antidepressant").

So is it an antipsychotic that treats depression, or an antidepressant that treats psychosis?

"I guess it all depends--"  Shut it.  Scientists are talking.


IV.

You might think it doesn't much matter what you call it but rather how you use it, but it matters.  If you call it an antidepressant, regardless of mechanism of action, price, or data it gets slapped with a suicide warning.  If you call it an antipsychotic you forever battle a diabetes warning regardless of the truth of it (see Geodon, Latuda.)  And call it the wrong thing, or the right thing at the wrong time, and your company gets to pay $1B to the government.


V.

Seroquel is a special case study in the semiotics of psychiatry, because much of the naming was intentional.


1.  Excessively high dosing.

One can't fault the FDA for striking a balance between safety and efficacy.  They voted nearly unanimously "Yes" on its monotherapy efficacy in GAD and MDD-- they agreed it worked; but they didn't want it being used as commonly as Prozac, so voted unanimously "No" on safety.  So no monotherapy approval. 

Recall that one of the monotherapy trials of Seroquel showed efficacy at 50mg.   However, because the FDA chose to go with the adjunct indication for safety reasons, it can only approve the doses used in those adjunct trials: 150mg.  Three times higher than the "minimally" efficacious dose in a monotherapy trial.

So in choosing an indication out of safety concerns, it tripled the doses used.

The reps are not allowed to suggest you use 50mg, or tell you that those studies exist; indeed, they aren't told about those studies themselves.

2.  Reinforcement of an erroneous mechanism of action.

The FDA wants to "protect the public". They know docs will generalize the indication of one drug to others in the class.  Hence, the FDA's and AZ's interests run in parallel: not all antipsychotics are antidepressants.

So AZ avoids all talk about mechanisms of action which are shared by all atypicals (dopamine or serotonin antagonism) and settles on a mechanism which is specific to
Seroquel-- the NET inhibition.

However, as I hope is clear, from part 3, the NET probably has nothing to do with it.

3. Reinforcement of the cult of polypharmacy.

It worked fine as monotherapy; but it's indicated as an add on to drugs (SSRIs/SNRIs) that failed for over 100 days at high doses.

If the combination works, what then?  Was it the Seroquel alone that did it?  Was it the SSRI just taking longer to kick in? Or some kind of synergy?  The FDA answer is that since you don't know,  you use both.

But you do know: Seroquel worked as monotherapy in at least two FDA trials.  Given this, it would be most logical to taper off the SSRI after a while, because you don't know two drugs are better than one drug, but I can promise they are twice as toxic and twice as expensive. But you won't find that recommendation in the PI or any academic journal.   The FDA is causing psychiatry to move backwards: more polypharmacy; less safety; greater costs. 

4. Pharma/academic focus on "bipolar depression."


Seroquel isn't indicated as monotherapy for MDD, but it is indicated as monotherapy for bipolar depression.  Fortunately, 1) bipolar depression looks exactly like major depression during the episode; 2) it's indicated at 300mg, so you can be guaranteed to get heavier.

From the company perspective, the obvious marketing strategy is to push for "awareness and detection of bipolar depression" (read: "recurrent major depression is probably bipolar disorder"), and "incentivize" the reps to have their scripts skew towards 300mg.  Farewell, depression, again.

For example, if Seroquel is truly an "antidepressant" then the competition would be Prozac.  But it isn't; it's Geodon.  Reps aren't measured against SSRIs, only against atypicals, which, in theory, they're not really competing against.


VI.  Should we worry about any of this?


Nope.  Once Seroquel goes generic, the impact of all of this nonsense will be minimal.  Then no one will care how you use it, at what dose; whether you use it monotherapy or in combination with nine other drugs none of which anyone cares about either.  Do a Pubmed search on Zyprexa research in the last year.  Anything?

Granted, there's probably patients who do care.  But.






Comments

If I were cynical, I'd say ... (Below threshold)

August 3, 2011 10:21 PM | Posted by Adam: | Reply

If I were cynical, I'd say that once seroquel goes generic, all of the attention will be on Seroquel XR. And if I knew more about the chemical composition, I might say all the attention will be on a new compound containing only the active dextrorotary isomer of quetiapine. But that's just me.

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I have a non-trivial questi... (Below threshold)

August 3, 2011 11:20 PM | Posted by elitegarbageman: | Reply

I have a non-trivial question:

How many psychiatrist use / have used the psychiatric drugs they prescribe? Does a psychiatrist ever just pop a ritalin to see what it's actually like before they prescribe it to a patient? Maybe this doesn't work with drugs that take longer to take effect... but still?

How many docs try the meds they dole out?

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Maybe I misunderstand your ... (Below threshold)

August 4, 2011 2:21 AM | Posted, in reply to elitegarbageman's comment, by Nik: | Reply

Maybe I misunderstand your post and you're just wondering about the statistical data, but even if it's just for arguments sake I'm assuming you think a psychiatrist should "try" some/all the medications they prescribe.
Would you ask an Oncologist to "try" chemo therapy to see what it's like before prescribing it for a patient? No, because that would be insane. While the negative side effects of most psychiatric drugs are not as lethal, they still exist. When a doctor prescribes a drug, it is with the belief that the health benefit outweighs the (potential) side effects.
Even if we don't take side effects into consideration, Ritalin does not have the same effect on the cognitive abilities of those who need it/would benefit from it and those who don't. So to your point of "seeing what it's like", unless the doctor suffered from the same condition as his patient he wouldn't know what it was like.

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Call me old-fashioned, but ... (Below threshold)

August 4, 2011 6:41 AM | Posted by robotslave: | Reply

Call me old-fashioned, but I've got this unshakable feeling that everything would be a lot clearer if we were to mention, at least in passing, the olde-tymes classification of a given "don't stab people" drug as "major tranquilizer" or "minor tranquilizer".

Or is that word not allowed in psycho-pharmacology anymore?

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After it's generic, they mi... (Below threshold)

August 4, 2011 7:52 AM | Posted by wilyliam: | Reply

After it's generic, they might not care about Seroquel, but they'll care plenty about SeroquelXR!! :-)

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"Even if we don't take side... (Below threshold)

August 4, 2011 3:57 PM | Posted by elitegarbageman: | Reply

"Even if we don't take side effects into consideration, Ritalin does not have the same effect on the cognitive abilities of those who need it/would benefit from it and those who don't. So to your point of 'seeing what it's like', unless the doctor suffered from the same condition as his patient he wouldn't know what it was like."

Don't beg the question. Why does you assume it effects people differently? This is why I'm starting to think piechiatry/piechology is a pseudoscience.

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I'm taking Seroquel 100 mg/... (Below threshold)

August 4, 2011 8:28 PM | Posted by FSK: | Reply

I'm taking Seroquel 100 mg/day, and no other drugs. It's been very effective for me as a monotherapy, even though everything else I tried was horrible (Lithium, Risperdal, Geodon, Abilify). For all the other drugs, they were so horrible that I refused to take them.

I had a bizarre unusual side-effect for Seroquel. It partially cured my color blindness! That's an incredible side-effect. I E-Mailed AstraZeneca, and they didn't respond.

I'd like to see a proper experiment, on a possible connection between Seroquel and color blindness.

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Do you understand the words... (Below threshold)

August 4, 2011 8:52 PM | Posted, in reply to elitegarbageman's comment, by Nik: | Reply

Do you understand the words that you're using? I'm not "begging-the-question". Why are MAOIs, SSRIs, SNRIs, all used to treat depression if one pill effects everyone the same way? Why have all these different types if Prozac worked for everyone? Adderall and Ritalin have different chemical compositions, again not equally effective for everyone with ADHD, one works better than the other for some. The same pill will not effect every individual the same way.
And again, let's assume I'm not right about how the same medication having different effects on different people (even though I am correct), there's still that pesky issue about side effects and benefit outweighing risk. And then there's simply a time issue. How could one doctor possibly conceive of and try all the different combinations of medications he might prescribe for differing lengths of time in his limited career? Just think of how many new combinations there would be each time a new drug entered the market!

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A psychiatrist with such a ... (Below threshold)

August 5, 2011 12:16 AM | Posted by Sfon: | Reply

A psychiatrist with such a casual attitude toward drugs that he pops them to see what they are like would be even more reckless than usual, and that is saying a lot.

As for being pseudoscience, it is rather bad. But that is because the tools to help people mentally are not very well developed, not because we've got great tools laying around we cannot be bothered to use. So the current tools are used even if they are largely broken, simply due to a lack of reliable options when trying to help people who cannot wait 200 years for the science to develop.

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No, actually Ritalin has th... (Below threshold)

August 5, 2011 2:53 AM | Posted, in reply to Nik's comment, by Ed: | Reply

No, actually Ritalin has the same effects on people with or without a medical indication, just as anabolic steroids have the same effects on people with or without a medical indication. Both are performance-enhancing drugs.

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> I'd like to see a proper ... (Below threshold)

August 5, 2011 1:06 PM | Posted, in reply to FSK's comment, by Rooster: | Reply

> I'd like to see a proper experiment, on a possible connection between Seroquel and color blindness.

The PI sheet for Seroquel, at the time I took it, mentioned that some animal trials caused blindness in beagles -- there might really be something going on between it and the vision thingamajigs.

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Well, statins probably prod... (Below threshold)

August 5, 2011 1:12 PM | Posted, in reply to Ed's comment, by Rooster: | Reply

Well, statins probably produce the same effects on people with slightly elevated cholesterol and people with major heart problems. As a matter of fact, antibiotics also have the same effects on sick and healthy persons (i.e. they kill small bugs).

Maybe Ritalin is really watered-down cocaine. Why does it matter?

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Semiotics is some heady stu... (Below threshold)

August 6, 2011 9:57 PM | Posted by Anonymous: | Reply

Semiotics is some heady stuff. Would a guy in a band who wears his own band's tshirt be an example of recursion?

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Only if that tshirt had a p... (Below threshold)

August 7, 2011 3:05 AM | Posted, in reply to Anonymous's comment, by Rookie: | Reply

Only if that tshirt had a picture of him on it wearing a tshirt of the band with him on it wearing a tshirt of the band... Dammit, weren't we talking about psychiatry here?

TLP: This astounds me, it's ludicrous to make a more unsafe indication in the name of safety. Surely its an example of why limiting information, any information, is a bad idea even with the best of intentions?

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>>As for being pseudoscienc... (Below threshold)

August 7, 2011 1:45 PM | Posted, in reply to Sfon's comment, by Anonymous: | Reply

>>As for being pseudoscience, it is rather bad. But that is because the tools to help people mentally are not very well developed, not because we've got great tools laying around we cannot be bothered to use. So the current tools are used even if they are largely broken, simply due to a lack of reliable options when trying to help people who cannot wait 200 years for the science to develop.

The problem most people have with psychiatrists is that most will not tell you their tools are largely broken but indeed the opposite, i.e. they are extremely effective and all but necessary to deal with any mental problems, it's only a matter of finding the right combination/dose. What's more, most experts, e.g. lawyers, accountants, financial advisors, even medical doctors in other fields, are willing to entertain informed opinions or questions from their clients. This is almost never the case with psychs. IMO as long as a significant proportion of psychiatrists continue to be downright frauds or quacks and many of the remaining treat their patients as infants (partial objects?), there will continue to be much well deserved skepticism of psychiatry.

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50 mg. of Seroquel (taken a... (Below threshold)

August 8, 2011 8:28 AM | Posted by JMS: | Reply

50 mg. of Seroquel (taken at bedtime) will knock you out for the night. Never underestimate the healing power of sleep: "Sleep that knits up the ravell'd sleeve of care/ The death of each day's life, sore labour's bath/ Balm of hurt minds, great nature's second course/ Chief nourisher in life's feast."

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Because of the antagonist h... (Below threshold)

August 8, 2011 8:40 AM | Posted, in reply to JMS's comment, by Rookie: | Reply

Because of the antagonist hystamine effect? Isn't that the second part of the story according to TLP? That because of the way depressive symptoms are measured (including insomnia) then a sedating effect, which is all such a low dose will give, makes it an effective 'antidepressant' despite the fact its reducing sleeplessness not low mood?

I mean it's just a cake of stupidity, layers and layers deep.

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Layers of stupidity? You b... (Below threshold)

August 8, 2011 10:51 AM | Posted, in reply to Rookie's comment, by JMS: | Reply

Layers of stupidity? You betcha! BOM does a great job at slicing and dicing: http://1boringoldman.com/index.php/2011/03/21/abilify-meets-depression/ (he includes a comparison with Seroquel) and http://1boringoldman.com/index.php/2011/03/21/atypical-augmentation-statistical-but-irrelevant/

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Then again, the Seroquel sl... (Below threshold)

August 9, 2011 10:25 AM | Posted, in reply to JMS's comment, by Rooster: | Reply

Then again, the Seroquel sleepiness @ 50mg happens through the same mechanism prn allergy drugs make you sleepy -- it's an antihystamine, dude. There are reasons to prescribe low-dose Seroquel, though, particularly now that it's coming generic and shouldn't be expensive anymore -- but I'm not sure there's a clear case for low-dose Serocool over trazodone. Then again, I'm just a patient.

"Sleep that knits up the ravell'd sleeve of care/ The death of each day's life, sore labour's bath/ Balm of hurt minds, great nature's second course/ Chief nourisher in life's feast."

My anecdotal experience -- although at 150-200ish mg -- is that Seroquel knocks you the fuck out, and you could choke on your own vomit or have the ceiling collapse over you without waking up. Sleep was restful in the sense that your brain is not processing a clusterfuck of incoming information, but I'm not sure I was ever alert enough during sleep to reach REM and have dreams. Significantly, I've always waked up with a vague notion of my last dream, even on benzos, but not on Seroquel.

Is it healthy to go through 18+ months without dreaming? Me, I don't have any complaints. But I think such comatose kind of sleep hardly agrees with your poem.

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The problem most p... (Below threshold)

August 9, 2011 11:02 AM | Posted, in reply to Anonymous's comment, by Rooster: | Reply

The problem most people have with psychiatrists is that most will not tell you their tools are largely broken but indeed the opposite, i.e. they are extremely effective and all but necessary to deal with any mental problems, it's only a matter of finding the right combination/dose.
I don't think that's really the problem, although I'm sure there's always some psycho trying to foist Abilify on a borderliner. Then again, I was once saw a dude with a MD in psychiatry that showed me pictures of flowers and prescribed floral medicines based on my favorites. Then you have the cardiologists who will prescribe statins because they don't have the talk therapy chops to get people to cut the meat and go ride bikes.

Hell, this is not restricted to medicine. As an economist/consultant, I face this problem all the time -- tell the client we really can't tell far enough into the future to answer his pointed question and should work in building institutional frameworks that are more resilient and quicker to respond to radical change, or make statistical assumptions over parameters we know nothing about and run Monte Carlo computations to find a probability distribution for the thing they're asking us about.

This is the problem:

What's more, most experts, e.g. lawyers, accountants, financial advisors, even medical doctors in other fields, are willing to entertain informed opinions or questions from their clients. This is almost never the case with psychs. IMO as long as a significant proportion of psychiatrists continue to be downright frauds or quacks and many of the remaining treat their patients as infants

This will vary in degree from place to place, school of origin, etc., but this is a mental framework inherited from the days of large-scale institutionalization. Although large inpatient facilities are far and between these days, residency in such a hospital is part of the MD in psych education here in Brazil. And this presents with an even harsher contrast, because the only people left in institutions are total basket cases -- with Geodon and clozapine, there's no reason a schizophrenic couldn't run for POTUS.

And while I haven't been a MD, I've been a young professional and I know hubris. "These are the mathematical tools that will rock your world". 4-5 years in the workforce mollified me, but that's because I've had credible feedback from clients (that would be "patients" for MDs) and superiors.

Is peer review happening at the clinician level? Couldn't case reports be sent to the local university so med students can have a first look at thug life and find the bigger problems while their textbooks are fresh inside their heads?

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REM sleep is not restorativ... (Below threshold)

August 9, 2011 11:26 AM | Posted, in reply to Rooster's comment, by JMS: | Reply

REM sleep is not restorative sleep (stage 3 and 4 sleep),and I don't think that your failure to remember dreaming is proof positive evidence that you aren't dreaming. As I've aged, I've noticed that the only dreams I remember are the unpleasant ones that I experience when I'm going through a period of extreme stress - the acute illness and death of a parent, for example.

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"Would you ask an Oncologis... (Below threshold)

August 9, 2011 11:57 AM | Posted, in reply to Nik's comment, by Anonymous: | Reply

"Would you ask an Oncologist to "try" chemo therapy to see what it's like before prescribing it for a patient?"
The treatment for cancer chemo therapy, hurts both the patient and the disease. The patient is usually stronger than the disease, so lives. What is mental illness? Where is the disease? Lobotomy said the disease was here at this spot in the brain. E.C.T. says the disease is everywhere in the brain. Emotions and thoughts are not diseases , never were and never will be.

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Ritalin doesn't "help" some... (Below threshold)

August 9, 2011 2:12 PM | Posted, in reply to Nik's comment, by JMS: | Reply

Ritalin doesn't "help" someone who doesn't have ADHD? Well, you could have fooled me - when I was an undergraduate, I "mastered" (P/F) a semester's worth of German (never went to that 8 AM class)in two days with a little help from some "Black Beauties". I'm sure this assertion of yours also comes as a big surprise to those combat pilots who fly the long missions that require mid-air refueling. Not all psychiatrists are reluctant to sample their wares - what follows is a description (provided in Moncrieff's "the Myth of the Chemical Cure") by two Israeli doctors who decided to give Haldol a whirl: "The effect was marked and very similar in both of us. Within ten minutes a marked slowing of thinking and movement developed, along with a profound inner restlessness. Neither subject could continue work, and each left for over 36 hours. Each subject complained of a lack of volition, a lack of physical and psychic energy. The subjects felt unable to read, telephone or perform household tasks of their own will, but could perform these tasks if demanded to do so. There was no sleepiness or sedation; on the contrary, both subjects complained of severe anxiety." Surprise, surprise - psychotic patients complain about the same effects and generally require sedation (back in the day, it was chloral hydrate) for sleep.

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I've heard many patients sa... (Below threshold)

August 13, 2011 1:11 PM | Posted by Anonymous: | Reply

I've heard many patients say they liked Seroquel because it numbed them out, and they didn't have to feel anything. I'm not sure that's much of a success story.

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Eli Lilly Zyprexa,Ri... (Below threshold)

August 13, 2011 5:23 PM | Posted by Daniel Haszard: | Reply


Eli Lilly Zyprexa,Risperdal and Seroquel same saga

The use of powerful antipsychotic drugs has increased in children as young as three years old. Weight gain, increases in triglyceride levels and associated risks for diabetes and cardiovascular disease.
The average weight gain (adults) over the 12 week study period was the highest for Zyprexa—17 pounds. You’d be hard pressed to gain that kind of weight sport-eating your way through the holidays.
One in 145 adults died in clinical trials of those taking the antipsychotic drugs Zyprexa. This is Lilly's # 1 product over $ 4 billion year sales,moreover Lilly also make billions on drugs that treat the diabetes often that has been caused by the zyprexa!
---
Daniel Haszard Zyprexa victim activist and patient who got diabetes from it. http://www.zyprexa-victims.com

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FSK, you might want to get ... (Below threshold)

August 21, 2011 3:53 AM | Posted by Meat Robot: | Reply

FSK, you might want to get yourself in to an optometrist/ophthalmologist.

The beagle blindness is due to the formation of cataracts. As it turns out, the particular enzyme activated in the beagle lens by Seroquel is essentially absent in humans, though I've heard of rare cases of some patients reporting a bluish tinge to their vision.

Good pro-tip on the 50 mg dosing. I hadn't run across that. That seems to be mercifully below the intense sugar-cravings that kick in around 150 to 200.

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Hopefully you really are th... (Below threshold)

August 29, 2011 11:22 AM | Posted by Scott : | Reply

Hopefully you really are the last psychiatrist because this criminal organization needs to be stopped. And as per any criticism of establishment psychiatry, no, i am not a scientologist. Also, these drugs shrink your brain. Whatayaknow, now psychiatry can lobotomize people with chemicals. You frauds make the bankers blush. You want to know why? They are doing damage in the abstract, you can see your patients become fat, trempling messes when you give these drugs.

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I know a psychiatrist who h... (Below threshold)

August 31, 2011 11:03 AM | Posted, in reply to elitegarbageman's comment, by Jam: | Reply

I know a psychiatrist who has tried drugs from every class he prescribes. He said he did it to be able to prescribe in good faith. He is one helluva guy.

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This article is a nightmare... (Below threshold)

October 8, 2011 8:14 PM | Posted, in reply to Sfon's comment, by Altostrata: | Reply

This article is a nightmare, but it explains plenty why psychiatric treatment seems arbitrary. It is arbitrary, when the doctor is informed, and worse when the doctor is not -- which is most of the time.

Blaming the FDA? Excuse me, who do you think is making decisions for the FDA? And how did Alan Schatzberg get elected president of APA, anyhow?

Note: No psychiatric drugs have been tested for long-term safety over years, yet that's how they're prescribed, and that includes a supposedly low dose of 50mg Seroquel. Post-marketing monitoring is a joke.

Sfon -- You're working on people's brains with those broken tools. Perhaps okay if the person has some extreme condition, has exhausted all other options, and is in extreme distress. Not okay for the other 90% of the 30 million people in the US who are taking psychiatric medication.

I'm really sorry I've had any exposure the inner workings of psychiatry, but I've had no choice having been severely injured by it, for no good reason. Pseudoscience is a euphemism. It disgusts me to the bottom of my soul, as do the so-called medical doctors who practice it with arrogance and complacency.

(No, Rooster, there is no peer review in psychiatry, at any level.)

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Would you ask an Oncologist... (Below threshold)

October 10, 2011 9:36 AM | Posted, in reply to Nik's comment, by john: | Reply

Would you ask an Oncologist to "try" chemo therapy to see what it's like before prescribing it for a patient? No, because that would be insane. Would you ask an emotionally troubled or drug effected person, to try insanity in a pill or an injection,on top of their troubles, before trying a non invasive natural medicinal gentle approach first, no, because that would be insane. Same deal, different story.

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when i was in residency, a ... (Below threshold)

November 13, 2011 3:36 PM | Posted by jk: | Reply

when i was in residency, a colleague took pephenazine 8mg to see what it was like. he stayed in bed for 3 days. otoh, i saw some patients take 32mg and not bat an eye. something about individual differences and the disease state....

the field is hampered by its lack of understanding of the pathophysiology of what it treats. i tell medical students that psychiatry has a 19th century nosology [diagnosis by checklist], 20th century treatment, and some 21st century science. i suspect that between micro-array genetic scans on the one hand, and fmri's on the other, we may get some more insight into what we're treating.

in the 19th century, if you had fevers, night sweats, coughed up blood and lost weight, you were said to have "consumption." [diagnosis by checklist.] if we had a time machine and a boatload of streptomycin and rifampin, we could help a lot of those sufferers, even if they'd never heard of tuberculosis.

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If seroquel acts as just an... (Below threshold)

December 9, 2011 10:18 AM | Posted by susan: | Reply

If seroquel acts as just an antihistamine at 175mg, should someone be able to just stop taking it? Or would this be bad to do, possibly causing bad withdrawl side effects?

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You have no medical trainin... (Below threshold)

December 12, 2011 12:29 PM | Posted by You're insane: | Reply

You have no medical training. You are a fraud. You don't have a clue about what you're talking about as evidenced by your comic opinions on the uses and mechanism of action regarding seroquel. Don't bother writing back, I wont be reading what you have to say.

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This isn't as stupid a post... (Below threshold)

January 9, 2012 2:33 AM | Posted, in reply to elitegarbageman's comment, by Anonymous: | Reply

This isn't as stupid a post as you might suppose.

My mother was forced by her dental school to try the drugs involved on herself so that she would have a better understanding of what they did to patients.

Personally I think that psychiatrists, and maybe also psychologists and social workers, should be required to pop double-blind doses of psychotropic drugs, then be told what they took.

Just so they develop some empathy.

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The first poster might not ... (Below threshold)

January 9, 2012 2:38 AM | Posted, in reply to Nik's comment, by Anonymous: | Reply

The first poster might not have known about large-scale studies, and therefore have thought that you were either question-begging or doing something akin to question-begging by denying (to phrase it in an overly rough way) the idea of professionals learning experientially about the effects of various drugs because of the drugs' possible effects.

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i do so shut up.... (Below threshold)

March 28, 2012 4:04 AM | Posted, in reply to elitegarbageman's comment, by Anonymous: | Reply

i do so shut up.

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Big words, buddy. If you ar... (Below threshold)

April 15, 2012 9:55 PM | Posted, in reply to You're insane's comment, by Anonymous: | Reply

Big words, buddy. If you are so much smarter I'd looove to hear all about it. I have an interest in this neuroleptic shit. Enlighten me, it might help. I am all ears.

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You are certain the author ... (Below threshold)

April 16, 2012 12:56 PM | Posted, in reply to You're insane's comment, by T'ion: | Reply

You are certain the author has no medical training? What do you expect to achieve by using such an abrasive tone? I find seroquel to be a confusing drug..... If you can refute or add to the author's analysis, it would be a big help. How, in your opinion does this med work, its indications, and pharmacodynamics? Thanks.

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This drug is a Godsend! My ... (Below threshold)

April 24, 2012 3:59 PM | Posted by NAMI Mom: | Reply

This drug is a Godsend! My 21yr son has been taking Seroquel 400XR at bedtime and 450mg Lithium twice a day and it has worked beautifully for his schizoaffective disorder! I'm very excited to hear from this blog that it may be going generic soon.

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So, who's that idiot that s... (Below threshold)

October 13, 2012 10:00 AM | Posted by Charles Ferdinand: | Reply

So, who's that idiot that suggests psychiatrists try the meds they prescribe and then goes on to say that ritalin affects everyone the same?
Hahahaha! Fucking asshole doesn't know shit about psychopharmacology or medicine, and even if he does, he sucks at it:
Ritalin, and any other psychiatric medication, wouldn't affect everyone the same way simply because every brain is different, otherwise, everyone would have the EXACT same side-effects and there would be only ONE type of medication for everything.
Idiot.

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I found these two article... (Below threshold)

November 28, 2012 2:30 PM | Posted by Harry Horton: | Reply

I found these two articles off the internet: "How to let go of the past" - Squidoo - Beginning a new life. Carl Jung material amongst others in the article. "Ten quotes on stop living in the past and letting go past...". Thus a person suffering neurosis lives in the past, in regards to their psychology and mental currents.
Interestingly enough, one with schizophrenia or bi polar, that eventually develops diabetes---such persons have a medical condition that lives in the past. Such a person would find themselves senstive to seasonal light and temperature changes. For example the glucose and a1c numbers are more sensitive to darkness and cold temps in winter. Thus with this situation, schizo and bi polar people are something of amphibians, an energy and metabolic status of the past of a prehistoric amphibian that was predecessor of the current day evolved human---a past when the schizo and bi polar were once amphbians before they evolved into present day humans. Thus the sensitivity to environmental temperature changes are an expression of the ---past---type of metabolic status of an amphibian. A schizo and bi polar person is something of an amphibian and as such because of this regressive metabolic status lives in the past even metabolically.

The Atypical antipsychotics that created diabetes and metabolic inflexability of the fat burning channel coming first for fat burning and the carbohydrates being secondary as an energy burning channel---this situation found in hibernation states----this situation once again is the schizophrenic person and bipolar person whose metabolism is living in the past. That is a past when such persons were once burrowing hibernating animals during winter. The atypical antipsychotics thus have createded an original state of living in the past, in neurotic people and psychotic people who uses these agents.Since one burns fat initially like a hibernating aninal, a schizophernic and bi polar person with this AAP induced metabolic inflexability condition is now a hibernating animal, like his ancestors so many millions of years ago before evolving into present day humans. Being an amphibian and a hibernating mamammal, is what a diabetes of hyperglycemia possessing--that is what a schizophrenic and bi polar person has become. THus such a person lives in the past in regressed metabolic state of being along with the concommitant psychological energies of neurosis and psychosis, that keeps one in the past psychologically. Thus the AAps have created anew metabolic state of living in the past, with a hibernating status along with more pronounced depression tendacies since depression is a state of mind of the hibernating and burrowing animal.

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The mitochonrial energy d... (Below threshold)

December 3, 2012 1:47 PM | Posted by Harry Horton: | Reply

The mitochonrial energy deficit is a good hallmark symptom for understanding how the AAP's create the metabolic disturbances of hyperglycemia, diabetes, increase in insulin resistance and changes in lipid metabolism ect.. THe central element is ATP hydrolysis exceeding ATP resynthesis, as the embodiment of the mitochonrial energy deficit, as the British Docotr R.F. Green has noted in his rapid response pieces on psychiatric disorders. THe central significant fact of the mitochondrial energy deficit is that it occurs in an energy homeostasis system that came late in the pathway towards human evolution. THe mitochondria is "an oxygen era" energy powerhouse organelle that came into being in the evolutionary history of human celluar life---that is the mitochondria came into being only very roughly 400-450 millions years ago, when most improtantly the earth's atmosphere went through some salient changes with the oxygen appearing within the atmosphere. Most singificantly the circadian rhythm, the anaerobic glycolysis and vitamin D energy homeostasis energy systems originated with the non oxygenated era, with the roots of these three energy systems being traced well back to 3.8 billion years ago. These energy homeostasis systems are much older than the the mitochondrial system and they functioned for over 3 billion years ago in the early precursor human cells in the nonoxygenated realms of the earth's geological history.

The authors of the medical study: Atypical antipsychotics
rapidly and inappropriately switch fuel untilization....noted that the dark cycle RER number is altered and lowered with AAP usage as the central detrimental dysfunction within the cells for inclining the AAP user to developing metabolic syndrome features: hyperglycemia, diabetes ect. Thus what one should note about this RER number alteration is the following significant two charactersitcs that embody the RER dysfunction. The RER alteration occurs within the mitchondria that is an oxygen later evolved organelle compared to the earlier aforementioned nonoxygenated era energy homeostasis systems. Even more specifically the RER is a function utlizing oxygen predominantly in itself, since respiration involves oxygen utilization. THis feature once again is an expression of the latest functions of energy homeostasis in human cells since oxygen came fairly late in the human cell's evolution----only 400-450 million years ago. THe second feature though is much more interesting: (2) The nonoxygenated era circadian rhythm of sunlight and darkness alternation, and its essence is embodied too in the RER cycle functions. Since the light cycle and the dark cycle are two facets of the RER metabolism in general, and this circadian rhythm energy homeostasis function is the oldest energy homeostasis process in the human cell----dating back well to 3.8 billion years ago if not earlier when the first biological cells came into being ---most importantly---in the nonoxygenated era. And yet it is involved when going dysfunctional---- by AAP detrimental influences on its metabolism. And RER metabolism being embodied by the nonoygenated era energy homeostasis system dark and light cycle characterstics, and this circadian rhythm characteristic being a metabolic regulator as a co joint feature to its presence with the RER metabolism over all metabolism itself--such other feature of such over all metabolism being simply: "the oxygen utilization within the RER"---this being the much later evolved feature of the oxygen era for the overall RER function.

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The following medical and... (Below threshold)

December 4, 2012 3:56 PM | Posted by Harry Horton: | Reply

The following medical and scientific studies centering on the circadian rhythms is detailed below. The studies center in large part on the circadian rhythm's strong regulation of metabolism in the human body. Psychiatric disorders are well interwoven within disruptions of the circadian rhythm's normal processes and functions in the body. THe studies are:

(1) Circadian RHythm - Science Daily: News & Articles in Science - www.sciencedaily.com/articles/c/circadian_rhythm.htm.
(2) Circadian rhythms, sleep, and metabolism - www.ncbi.nlm.nih.gov/pmc/articles/PMC3104765
quote: "disruption of clock genes results in metabolic dysregulation have revealed interactions between metabolism and circadian rhythm at neural, molecular, and cellular levels. Amajor challenge remains in understanding the interplay between brain & peripheral clocks and in deteermining how these interactions promote energy homeostasis across the sleep-wake cycle." end quote.

An study that is not about circadian rhythm:
"Quetiapine, an atypical antipsychoitc, is prtoetective against auto-immune - mediated demylineation by inhibiting effector T cell proliferation."

"Circadian rhythms in the development of obesity: potential role for the circadian clock within the sdipocyte" MS Bray and ME Young.
"Metabolism and circadian rhythm - implications for obeisty" Quote:
"The circadian rhythm has been rewported to regulate metabolism & energy homeostasis in the liver & peripheral tissues." --One observation on this article. With AAP usage AMPK has been shown to be perturbed with AAP usage resulting in liver located hepatic insulin resistance ---these dysfunctions are central for bringing on AAP induced metabolic syndrome disturbances.

With the above content in mind, the mitochondria energy deficit has been noted to be present and influential as an energy disturbance in psychiatric disorders as well as other diseases such as diabetes. One major facet of the mitochondira energy deficit is the fact that the electron transport chain in a healthy manner occasionally shifts its nature of operation from the familiar oxidative phosphorylation to a second separate condition:the uncoupling mode of operation. This is normal for mitochondrial functions. However when the rhythm of this shift becomes irregular and dysfunctional a mitochondrial energy deficit occurs. That is the uncoupling protein presence and operations stay on longer than they should.Most, most significantly Richard Fiddian Green has noted that this normal shift is expressive of a light to dark cycle that embodies the mitochondrial shift from oxidative phsopshorylation to th euncoupling protein mode. THis is another way of saying the shift is embodied as the circadian rhythm function. And the circadian rhythm nature within the mictochondria ETC chain is regulatory of the whole mitochondrial shift process itself.
What is significant about this information, is that there is a good chance that this mitochondria energy deficit is already present in psychiatric patients that start to take the AAPs. And thus this mitochondria energy deficit, particular its severity, puts them at risk for developing metabolic syndrome side effects of the AAPs. Couple that fact in that the dark cycle of the RER has a low number and is detrimentally altered by AAPs, and like the mitochondria energy deficit, this RER disturbance is circadian rhythm comprised. So the RER disturbance is basically a further extension and aggravation of the mitochondrial energy deficit that is present in psychiatirc patients themselves and since both areas are heavily comprised of the circadian rhythm presence intrinsic to both metabolic areas. AAp usage evidentaly just further develops another extended disturbance in the circadian rhythm comprised RER metabolism.

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A little more clarificati... (Below threshold)

December 4, 2012 7:24 PM | Posted by Harry Horton: | Reply

A little more clarification on the concluding sentence: When a psychiatric patient has a mitochondrial energy deficit situation, and such a patient is given an AAP, the AAP usage further develops a second and separate circadian rhythm disturbance in the mitochondria, that is' the altered RER dark cycle number'---this latter disturbance is an extended disturbance from the previously present mitochondrial energy deficit. The mitochondrial energy deficit has' a dysfunctional regulatory circadian rhythm presence' within its deleterious nature, and likewise the newly emergent AAP induced RER dark cycle lower number also is expressive of a circadian rhythm dysfunctionality in is nature likewise.

Note in the Zyprexa makes you fat article, I posted a comment that included a'Science Daily article information': that the Liver carries a gene that converts the body's use of fat burning first and carbohydrates and sugars burning second, a gene that goes into action with darkness. Darkness thus throws a switch for the body to go into fat burning mode initially ---the gene I beleive was called proclipase. And it is found in the liver. Most fascinating to add into that fact is the previous comment posts' article: "Metabolism and Circadian ryhthm: implications for obesity" - the regulation of metabolism and energy homeostasis is in the liver and most fascinating, the circadian rhythm is doing the regulation in the liver---particularly regulating energy homeostasis. The same organ, the liver that is, that in the Science Daily article on proclipase stated: that the molecular switch called darkness can convert the body's fuel channel utilization to fat burning mode initially---this condition additionally occurs in 'AAP usage hyperglycemic conditions' with the lower RER dark cycle number emergence in AAP deleterious usage.

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"Inhibition of cancer growt... (Below threshold)

December 5, 2012 2:59 PM | Posted by Harry Horton: | Reply

"Inhibition of cancer growth and induction of apoptosis by BGP-13 and BGP-15, new calcipotriene-derived vitamin D 3 analogs, in vitro and in-vivo stuides"
Medline Literature Alert Gene-Disease Link
One of the most innovative approaches to the treatment of cancer entails the use of 1 alpha, 25,-dihydroxyvitamin D(3) (calcitrol) analogs to inhibit cancer cell growth. We deomnstrate here that BGP-13, a new calcipotirene based 1 alpha, 25-dihydroxyvitamin D(3) analog that we synthesized in our laboratory, inhibits the growth of prostate cancer (LNCaP), breast cancer (MCF-7), and colon cancer (HT-29) cell lines. Moreover, we also show that BGP-13 causes cells both to accumulate in G(0) - G (1) and to activate caspase - 3 and undergo apoptosis. In addition, we observed elevated vitamin D receptor (VDR) mRNA and protein levels in both LNCaP and MCF-7 cells following exposure of the two cell lines to BGP-13. Importantly, we found that both the new analog BGP-13 and also BGP-15 another calcipotriene based analog we synthesized previously and about which we published recently, inhibit the growth of HT-29 tumor xenografts in nude mice; read more on this story here.

----The above study interestingly relates the BGP-15 drug's favourable effects on arresting cancer growth in several cancers. The vitamin D item, the vitamin that is synthesized by the sunlight is also central to the therapeutic effects of the anti- cancer properties of BGP-13 and 15. Sunlight is a central feature of the circadian rhythm in that sunlight alternates with darkness to form the essence of the circadian rhythm. And vitamin D synthesis is stimulated by sunlight also places the vitamin D creation within the circadian rhythm mechanics. Since sunllight is a part of the circadian rhythm and stimulates vitamin D synthesis in the body. Cancer too is characterized by a loss of metabolic regulation of cell growth and the circadian rhythm is a regulator of healthy cell growth.

BGp-15 has been shown to prevent metabolic syndrome side effects in atypical antipsychotic usage. weight gain, insulin resistance and hyperglycemia were abolished in mice with clozaril by the application of BGP-15 to the clozaril dosed mice.

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Psychosis has always been... (Below threshold)

December 7, 2012 1:56 PM | Posted by Harry Horton: | Reply

Psychosis has always been characterized a demonism or a mind that lives in the dark. Its sort of like Dracula, a vampire like being that was created by Brom Stoker, who would come to life during the night and its darkness and he would go prey on women for blood ---something like a bat. Behaviour that is psychosis comprised and such behaviour and actions occuring in the dark.
Such is the same for the mitochondrial energy deficit--because the circadian rhythm dictated shifting of oxidative phosphorylation to uncoupling protein processes in the ETC becomes dysregulated, and if the uncoupling protein operations of the mitochondrial ETC become more prolonged and predominant in existance, more so than what should be normal, the mind and body metabolism spends more time in the darkness cycle and areas. Its interesting that psychosis has been characterized as being dark and chaotic like thinking---as Shakespeare says the actions of psychotic people are like disasters in the sun. And the mitochondrial ETC dysfunctions with uncoupling protein processes are darkness comprised functions that underlie neuro psychiatric disorders, and the dark abberant hallucinatory thinking of psychosis is found in the regions of uncoupling protein predominance in the mtiochondria ETC. Most notably along these lines, the mitochondria ETC uncoupling protein predominance, is the primary mode of energy homeostasis in action with the hibernation states of animals---that is such a mode in action totally in the environment of darkness, when an animal is burrowed away in a hole from sunlight during the dark winter months. Months of continual darkness in the environment without a trace of sunlight is what comrpises the hibernating animal's existence in his wintertime burrow, and that is the hibernating animals mind and environemntal existence and uncoupling protein predominated mitochndrial status. An existence like Darcula. In fact there has been an interesting discovery of late in Burma of a fish called the Dracula fish. It lost alot of its bones and teeth over the past 50 million years and has grown fangs in place of its teeth. It can be found only in a small stream in Burma and has been claimed to be one of the most extroidinary vertebrate finds in the world over the past decade or so. An amphibian it is thus has the metabolism of a lot of diabetics---being sensitive to temperature and seasonal sunlight variations like a diabetic. Images of the fish can be found on google and yahoo images section for the entry Dracula Fish.

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In regards to the Decembe... (Below threshold)

January 29, 2013 2:32 PM | Posted by Harry Horton: | Reply

In regards to the December 4 2012, correspondences on diabetes and hyperglycemia conditions especially the role that the circadian rhythm plays in creating AAP induced hyperglycemia and diabetes. The following two articles are helpful in possibly shedding more light on the underlying mechanisms for hyperglycemia and diabetes development in AAP usage. The histamine 1 receptor is known to be involved in regulating the circadian rhythm and also activating PLC and hence the PIP2 pathway that contains the important signal transductors: DAG and IP3. These two items have been shown to play a central role in diabetes development.

From "wikipedia: H1 receptor", quote: "The histamine 1 receptor is an important target for clinically important drugs, and is likely one of the most important receptors for modulating mammalian circadian cycles.

Histamine H1 receptor are metabotropic G-protein coupled receptors expressed throughout the body, specifically in smooth muscles, on vascular endothelial cells, in the heart, and in the central nervous system. The H1 receptor is linked to an intracellular G-protein (gq) which activates phospholipase C and the phsophoatidylinositol (PIP2) signalling pathway." end quote.

Second medical study: "Diacylglycerol activation of protein kinase C and Hepatic Insulin resistance." Gerald Shulman.

Quote: "Although the cellular mecahnism underlying the relationship are unknown, hepatic accumulation of diacylglycerol (DAG) in both animals and humans has been linked to hepatic insulin resistance. In this perspective we discuss the role of DAG activation of protein kinase C as the mechanism..." end quote.

Second study: "Signalling via plasma membrance inositides IP3 mobilizes Ca2+ from intracellular stores and DAG is important for activation of protein kinase C."

The atypical antipsychotics fairly thoroughly blockade the histamine receptor 1, and in the above two articles, the histamine 1 receptor is involved with maintaining the central circadian rhythm metabolism in the body. If the AAP's disrupt the regulatory H1 receptor metabolism then the circadian rhythm metabolism is further disrupted and dysregulated by AAP blockading of the H 1 receptor. The circadian rhythm could play an improtant foundation role in regulating all the other subequent evolutionary evolved energy homeostasis systems of anaerobic glycolysis, and mitochondrial ETC functins as well as krebs cycle functions. The energy deficit in the mitochondiral could easily be an expression of a substantial circadian rhtyhm disturbance and dysregulation in itself. If the AAPS disturb this already present mitochondrial energy deficit even more so in an increased aggravative fashion, hyperglycemia, diabetes and the hibernating like fuel channel inflexability that is found in AAP users could emerge more easily.

Furthermore an increase in hepatic insulin resistance too occurs with AAP usage. And the DAG protein which is most improtantly to note its presence and function in the cell's membrane functions is too involved with a preceding activation of Histamine 1 receptor functioning. If the AAPs dysrupt the histamine 1 functions actions then DAG likewise, its metabolism and presence will be affected most notably in a negative manner. And such a neagtive affectation could bring on liver based hepatic insulin resistance. The other study that is introduced in other posts on the Last psychiatirst comment sections, within this stypical antipsychotics category is the fact that a study that went roughly like: AMPK perturbed by AAP'..." This study did find increased hepatic insulin resistance, and as such this condition did paly a central role in bringing on the metabolic side effects such as hyperglycemia, weigth gain, lipid abnormalities, ect. found in AAP usage. THis article read in coordiantion with the above two diacylglycerol articles and their content seeing the correlations and similarites would be interesting to investigate. The liver plays a central role in obseity and weight gain development as an early circadian rhythm posts of December 4 2012 has related.


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The R.F. Green rapid resp... (Below threshold)

February 25, 2013 1:36 PM | Posted by HARRY hORTON: | Reply

The R.F. Green rapid response piece: Schizophrenia and the adverse effects of its treatments on mitochonrial metabolism relates the central significant subject matter. That psychiatirc patients suffer froma--mitochondrial energy deficit---in their cellular functions, especially the ETC area of the mitochondria. The hallmark dysfunction of the mitochondrial energy deficit is the dysfunction: ATP hydrolysis exceeding ATP resynthesis. That is another way of saying that intramitochodnrial ATP sotres are low. ANd because the low and inadequate amount of ATP in the intramitochondrial stores as an already present malady riven condition---the result of this is that there is not enough ATP untits to meet 'the ATP hydrolysis functions demands for ATP' in the mitochondiral ATP hydrolysis processes.

What is known from the Penn State Study found in Schizophrenia Bulletin about two ro three years ago--that is the Fuel consumption inflexability amongst the fat burning and the carbohydrate fuel consumption channel ----the major finding is that with AAP induced metabolic syndrome condition appearance there is no malonly CoA sysnthesis going on and this too affects the KReb Cycle functions. The central function of Malonoyl CoA is that it inhibits fatty acid oxidation. And this is important and has a lot to do with the previously mentioned R.F. Green observation that aggravation of the mitochondrial energy deficit is a real and valid facet of what occurs with APP administration. The real issue is once malonyl CoA is diminished to evidently a nonexistant point in AAP usage, the inhibition of fatty acid synthese disappears along with it. Thus the highly significant fact occurs: Its well known in biology that the disappearance of malonyl CoA brings on fatty acid oxidation preminence and increase in the cells functions--and this being a condition that occurs when ATP is low in the cell. THus if R.F. Greens energy deficit is already present in psychiatric patients and this means ATP is low already to begin with before AAP adminstration. The AAPs further aggravate this already precedent 'low ATP amount presence situation', and such a deleterious situation strains the energy homesostasis systems to produce enough adequate ATP, that is figuring out a way to adequately increase ATP amounts. One response to this AAP induced strain is simply ridding the fatty oxidation inhibitor: malonly CoA. And once this is done Fatty synthesis moves to the forefront to attempt to produce the adequate amounts of ATP. Since removal of malonyl CoA in normal energy homeostasis functions occurs when the condition of low ATP is present in the cells mitochondrial areas. And removal of malonyl CoA results in producing and increasing ATP amounts. Via fatty oxidation. ANd fatty oxidation that is full throttle without its natural inhibitor intact: malonyl CoA, sinc Malonyl Coa is dimiinished off with AAP usage. This is the condition in the psychiatric patient's cellular energy homeostasis functions when such patients possess the inital already present mitochondrial energy deficit as the starter point for all the rest to follow into action upon. Richard Fiddian Green writes about this in his above rapid response piece.

Hence the significant fact> The disappearance of malonyl CoA with AAP usage is an extension and further aggravation of the mitochondrial energy deficit of R.F. Greens: That is the original condition of ATP hydrolysis exceeding ATP resynthesis as a dysfunction of mitochondrial ETC functions. Low ATP in the mitochoindrial energy deficit situaiton, and thus with AAP usage such low ATP amount presence could conceivably even go lower and diminish off in a worsened status with even lesser amounts of availbale ATP. This as a result of AAP administration. When this occurs the cell's energy processes have to take drastic action by simply ridding the malonyl coA this biological entity being the fatty acid inhibitor so ATP can be produced in adequate amounts as an attempt of overcome low ATP store amounts in the energy homeostasis areas of the cells.

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In regards to previous po... (Below threshold)

February 26, 2013 1:20 PM | Posted by Harry Horton: | Reply

In regards to previous post on the mitochondrial energy deficit, the malonyl coA diminishment leads to a full prominence of fatty acid synthesis in order to raise ATP amount levels. What is interesting about this process is that it has two dimensions to it. The malonyl CoA diminshment with AAP application simply comes into being as an energy homeostasis process to raise the ATP levels in the psychiatric patient's energy homeostasis systems. Tha seems simply enough in its seemingly sole apparency. (2) But interestingly the raising of ATP amount with this above process also simultaneously sends the overall metabolic functioning of the AAP user into the past. That is returning the metabolic functions into the evolutionary past at earlier points in time when the human's biological and evoultionary ancestors were hibernating animals and amphibians. The appearance of the fat burning channel being used initially and carbohydrates and sugars production going on in the human metabolism with AAP usage and this carb sugar channel being
unused, that drives the hyperglycemia in AAP user patients. This return to the past is rather important, because with the original mitochondrial energy deficit present in psychiatric patients and a biological phenomena that plays a role in substantiating their neuropsychiatric disorders, the main energy homeostasis dysfunction could be the circadian rhythm is out of rhythm and healthy processing in the psychiatric patient, that is the alternation in the mtochondrial ETC areas between oxidative phosphorylation and its alternate function, uncoupling protein emergence---this alternation could basically be in fairly extensive nature, regulated and comprised by the circadian rhythm functions. The significant aspect of this is that the circadian rhythm originates well way back in the nonoxygenated era's existence, 3.8 billion years ago. Yet it is well present and ingrained in the mitochondria's ETC operations that is ingrained within the alternation of the oxidative phsophorylation and the second uncoupling protein expression in the ETC operations. The mitochondrial energy deficit thus is an expression of this highly evolutionary earlier circadian rhythm ingrainment in the mitochondrial operations----such ingrainment sets the stage for the return to the past for the metabolic syndrome sufferer's energy homeostasis functioning. THe earliest energy homeostasis facet in biological cells certainly would be the circadian rhythm, the circadian rhythm that originated in the earliest stretches of the nonoxgentaed era of earth's history. Because when the mitochondrial energy deficit shows up the circadian rhythm dysfunction shows up within such energy deficit. And in order to correct the ATP energy production with the mitochondria energy deficit, one has to center the focus and basis of correction back in the earliest stretches of the biological cell's history, in the non oxygenated era's circadian rhythm processes, because the circadian rhythm is involved in creation of the mitochondrial energy deficit situation. Which is another way of saying the ancient 3.8 billion years old environs of the earth's non oxygenated era is primary and involved in the creation of the mitochondria energy deficit. So with the mitochondria energy deficit emergence and presence, one will see the present day evolved human metabolic status return back through various earlier geohistorical evolutionary points in time until arrival at the earliest ciracdian rhythm's time in the earliest nonoxygenated time period of the earth's history. Circadian rhythm dysfunction is central and involved in creating the energy deficit to begin with. The human metabolism functioning more on the order of a hibernating animal or na amphibian, these two example evolutionary functioning points of earlier time---appear with the energy deficit possessing diabetic patient and AAP usaer hyperglycemia patient. The hibernating animal and amphibian status of functioning in these patients is an expression of zooming back to these earliest points of evolutionary history and stopping at these points and using these early energy hoemostasis functions for present day diabetic human patient metabolic functioning--this phenomena as a continuance of the of the travelling back through time of the diabetic patient's metabolic functions towards the non oxygenated era where the circadian rhythm emerged from and stems back to even with today's present day human metabolism.

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In regards to previous tw... (Below threshold)

February 26, 2013 4:34 PM | Posted by Harry Horton: | Reply

In regards to previous two posts content. The insulin sensitizer drug BGP-15 has been shown to prevent AAP side effects such as weight gain, glucose problems, insulin resistance, lipid metabolism deleterious problems ect. A central finding with the BGp-15 administration to AAP usage patients, is the disappearance of heat shock proteins in monnuclear cells. With BGP-15 adminstration heat shock proteins reappear evidently to their full healthy presnece in number and function in mononuclear cells. With this occurrence the AAP metabolic syndrome side effects too, disappear. And a healthy status re emerges in these cellular areas in AAp patients that suffered the destructive side effect pattern.

There are several feature of heat shock proteins that hold significance. The most significant one is heat shock proteins have been around since---ancient evolutionary times---easily way back in the non oxygenated era, over 3 billion years ago most liklely. Thus the heat shock protein shares the same ancient evolutionary historical presence of the circadian rhythm since this metabolic function is rooted too in the earliest stretches of the earth's history. (2) the article heat shock protein wikipedia relates: HSPs are found in virtually all living organisms, from bacteria to humans. This omnipresence of heat shock proteins from the smallest bacteria to the ever complex multi organ human and other animals is a testment to its long presence and central function in evolutionary history. THe wikipedia article went on to note more importantly, the following quote: "Heat Shock Proteins (HSP) are a class of functionally related proteins involved in the folding and unfolding of other proteins. Their expression is increased when cells are exposed to elevated temperatures or other stress. This increase is transcriptionally regulated. The dramatic upregulation of the heat shock proteins is a key part of the heat shock response and is induced primarily by Heat shock factor (HSF)." end quote.

Once again the Heat Shock Protein participation with unfolding and folding of other proteins, in normal biological life of current status,--- such process obviously has ancient evoltionary roots back in biological life's history since the continued evolvement of proteins in the cell occurs from earlierest times ---if this was not true or did not happen evolution would not take place, because there woulkd be no mechanism for cells proteins to unfold and fold in their pattern. So heat shock proteins in this regards is most likely tied to circadian rhythm processes in a rather intimate manner since circadian rhythm and heat shock protein metabolism orignated in the earliest times of earth's history---that is the non oxygenated era time period.

(2) the second most fascinating prospect of heat shock proteins functions is their expression is increased when cells are exposed to elevated temperatures. The non oxygenated period fo earth's history definitely housed high elevated temperatures in the environs of this period of time. So interestingly the sensitivity of heat shock proteins to high elevated temperatures is a statement of heat shock protein existance during the high temperatures of earth's environments back in the ancient non oxygenated era. Thus heat shock proteins are a major biological entity of R.F. Greens temperature principle in understanding metabolic syndrome conditions. That is pH and temperature being made new Gods to keep in balance and function for preventing metabolic syndrome conditions and energy deficit phenomena in pateints such as diabetics--this fact as R.F. Green has related in his rapid repsonse pieces. So the reinstatement of BGP-15 of heat shock proteins is a reinstatement of directing the human metabolism towards a healthy present ph and temperature status, both these features in coordination and participation with each other since HSP's are so intimately tied into biologically functioning with high sensitivity to temperature variances, especially elevated temperatures, and such elevated temperatures omnipresent in earth's ancient evolutionary days of the nonoxygenated eras. ALong with this important fact is the second important realization. The first realization: the mitochondrial energy deficit is embodied most likely with the dysfunctional regulatory role of the circadian rhythm. And such energy deficit is omnipresent in metabolic syndrome conditions, like diabetics. But most significantly the circadian rhythm has an ancient evolutionary history and presence in the mitochondrial ETC functions and such a presence, thus, in the mitochondrial energy deficit processes. Heat Shock PRoteins too have roots back to the ancient evolutionary times and thus heat shock proteins are embodied with this same ancient evolutionary geohistorical span as the circadian rhythm, and such embodiment within the circadian rhythm presence and pariticpation in mitochondrial energy deficit conditions. And temperature, whether elevated or not, is part of the circadian rhythm essence and such elevated temperature presence is also evident and present with the heat shock protein metabolism. Thus these just delineated features and characteristics of substantial similarity between the heat shock protein and the circadian rhythm, are thus given and appatent. And in AAp usage metabolic syndrome side effect emergence---- its interesting that both circadian rhtythm process and HSP metabolism go awry in dysfunctional manner and proceses. Whether it be the circadian rhythm embodied mitochondrial energy deficit becoming more worsened or aggravated with AAP application ---or the reduction of HSP number in mononulcear cells with AAP application also.

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Some further illustration ... (Below threshold)

March 1, 2013 11:49 AM | Posted by Harry Horton: | Reply

Some further illustration on how intertwined the circadian rhythm and the heat shock protein phenomena is within the context of mitochondrial energy deficits ---these facets could be illustrated by the following three phenomenon.
One can take the human being in regards to his evolutionary past--taking such an evolutionary past and dividing into three past sections. (1) Section 1 is the human being once being a unicellular organism back 3.8 billion years ago. The unicellular organism inhabits a starkly hostile earth environment that is non oxgenated and the daylight temperatures ranging well into the upper hundreds if not higher. The unicelluar organism is moving through time into the future with its replicating DNA and processing protein structures folding and unfolding, creating the basic metabolic essence of the organism, with the presence of these extremely heated environmental conditions. The heat shock protein presence is extant with it participation with the extreme hot earth temperatures and also the heat shock protein participation is present with the unfolding and folding of proteins and its chaperone functions within the unicellular organism of this non oxgenated region. (b.) Part b. of section 1: Along with this heat shock illustration is the fact that the hot temperature extremes of this harsh volatile nonoxgenated earth environment, is an expression of one facet of the circadian rhythm. The daylight period of day and night cycle is the light cycle of the circadian rhythm. With this cycle, the high temperatures of eath's environment are contained within and with such containment is the heat shock phenomena' s presence and functions since heat shock proteins functions operate with the protein's sensitivity to high elevated temperatures. The high temperatures of the ciracadian rhythm's existence within the earth's early evoutionary days in the
nonoxygenated days of earth's existence. (2) section 2- The prededecossor species of humans in the oygenated era, within the past 400 million years was once an amphibian. This amphibian's internal metabolic functions would be sensitive to earth's seasonal temperature variations and the night and day cycle of the circadian rhtyhm. With this fact involved, a metabolic syndrome sufferer such as a diabetic would be sensitive to tempreature variations. Also a diabetic suffere would be sensitive to variations of season's temperatures. There are features of an amphibian's metabolism present with the diabetic. (3) Section 3 - A more recent ancestor of humans in the human evolutionary past tens of millions of years ago was a predecessor species that hibernated. Such a human ancestor would burn fat initially for its fuel consumption to maintain it energy homeostasis systems while in the hibernation state. AAp usage creates this ancetral energy homeostasis condition with the fact that some AAP users burn fat initially and with that development shifts the carb and sugar burning back to a secondary fucntioning. When in current human metabolic funcitoning carb and sugar burning should come first and fat burning should come second. In AAP usage the order of these two fuel consumption processes are reversed.

With the three above sections in mind, if one considered a current metabolic syndrome sufferer, such a sufferer or patient would possess a mitochondrial energy deficit. The chief dysfunction of regulation that comprises the mitochindrial energy deficit nature is ciracdian rhythm dysregulation. ATP amounts are not getting adequately produced with a patient with mitochondrial energy deficit conditions. And the fact that one phase of the mitochondria's oprations such as uncoupling protein phneomenon could be staying on or present for longer periods of time in the rhythm and metabolic functions of the mitochondria's ETC functions. This means that the section 1 metabolic functions in the unicellular organisms is dysfucntional--that is the circadian rhythm functions are dysfunctional--in present day human mitochondrial operations. Thus the main circadian rhythm dysfunction is the primary early evolutionary process of the ---past---in the hman ancestral evolutionary line, that comes to the fore front as a dysfunctional process in AAp users and diabetics.
When AAPs are given to psychiatric patients this mitochondrial enregy deficit is already present and with it the AAP user is living in the past with the circadian rhythm in dysfunctional ryhthm. And when the AAP is given to the patient the patient further moves back into the past if the patient develops diabetes. He develops secion 2 --- the amphibian metabolism features of sensitivity to enviornmental temperatures. And most interestingly deveops a condition that is not usually found in regular diabetics, that is, the hibernating animals' initial fat burning fuel consumption process- a process found in hibernating animals during their winter time existence. Yet like the circadian rhythm dysfunction, the amphibian temperature sensitivity and the hibnernating animal intitial fat burning channel, are all returns to the past for the diabetic and the AAP users metabolism. And the mitochondrial energy deficit is central indicator of the these earlier states of evolution coming into more participatory existenece within the present human's metabolic functions in order to produce the adequate ATP amount levels to keep the current human energy homeostaiss functioning on somehat of a normal basis according to current evolutionary status.

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March 1, 2013 12:59 PM | Posted by Harry Horton: | Reply

The use of BGP-15 to restore the nromal healthy status of heat shock proteins could be a significant facet of how to treat the side effects disturbances of AAP usage when metabolic syndrome conditions develop. Heat Shock proteins and their functions of normal healthy status is diminished off in mononuclear cells with AAP usage. The return of mononuclear cell's heat shock proteins to normal healthy status via BGP-15 application in metabolic syndrome suffering AAP patients means the earliest evolutionary period of time, the nonoxygenated period of earth's existence, this earliest metabolic dysfunction of 'circadian rhythm essence containing heat shock protein fucntions' is being corrected and returned to normal health status. The non oxgenated era unicellular organisms metabolic processes are being corrected with heat shock protein re-emergence in the mononuclear cells. And with this early non oxgenated era correction the later evolutionary metabolic disturbances and weight gain and insulin resistance are abolished. Insulin sensitivity returns to normal health functioning and status. One highly important recognition involving weight gain and insulin resistance along with lipid metabolism abnormalities---these abnormalities are expressions of the -----oxgenated---era of human evolutionary history. Humans are multi organ beings of the oxygenated era, and the weight gain and insulin functions in humans along with lipid metabolism are primarily evolutionary travelled metabolic functions, that is functions whose structure and functioning developed and evolved within the confines of 'the oxgen replete atmosphere of earth' over the past 400 million years. They are not metabolic processes of dysfunctional essence of the much earlier non oxygenated era. And such a nonoxygenated era that came---before and earlier---than 'the subsequent oxygen replete atmosphere era of earth's past' 400 million years ago or so. The heat shock proteins thus are representative of an earlier precursor and foundation function which the later secondary metabolic processes of dysfunction--weight gain, insulin resistance and lipid abnormalities are based upon. Weight gain, insulin resistnace and lipid abnormalities that is, that are found in diabetics and AAP users. The oxygenated era associated dysfunctions of metabolic dysfunctions these functions are.
Thus an interesting issue to consider in treating a diabetic's features and conditions. Mitigating temperature sensitivity would be a partial therapeutic achievement. If the carb and sugar channel functions as initial fuel consumption processes could be returned to normal in AAP user metabolic syndrome status--that too would be a secondary and partial therapeutic achievement. The partial and secondary nature of such a therapeutic accomplishment would be based on the fact that the temperature sensitivity and fat channel burning mode as initial mode of fuel consumption--that being a netabolic disturbance--- are dysfuntions of the oxygenated era. The oxygenated era that came later than the nonoxgenated era , and the nonoxygenated era is where the real originating disturbances can be found with the circadian rhythm irregularities and the heat shock deleterious alterations as found in mononuclear cells with AAp application. So returning the heat shock protein status and functions to normal is thus an assertion of making a major correction in the circadian rhythm disturnaces of the early evolutionary non oxygenated era epriod of time. And this nonoxygenated period of time being the time period that contains the first and original dysfunctions in human metabolism---particularly in the comprisement of the circadian rhtyhm and its dysfunctions that arise and are expressed in metabolic syndrome conditions. Especially the circadian rhythm dysfunction comprisement of 'the later oxgenated era mitchondrial energy deficit.'

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In regards to the BGP-15 ... (Below threshold)

March 1, 2013 5:21 PM | Posted by Harry Horton: | Reply

In regards to the BGP-15 heat shock protein reinstatement there are the following other therapeutic area: TRPV1 nerve hypofunctional type in pancreatic TRPV1 nerve presence in diabetes. THe journal Cell December 15, 2006 a Toronto Sick Childrens Hospital study found that diabetes 1 and 2 were cured in obese rats by altering hypofunctional mutant TRPV1 pancreatic nerves. TRPV1 is well known for modulating temperature in the body and temperature extremes. THus it is a nerve most intimately associated with circadian rhythm processes too and TRPV1 as a temperature oriented biological entity too puts it in the same neighborhood as Heat Shock proteins. The heat shock proteins functions are oriented around elevated temperatures. If one reconstituted the heat shock status in mononuclear cells, then the elevated temperature function modulating biological entity, namely heat shock proteins, is restored. With this function, weight loss and insulin resistance disappear. IT has been shown with TRPV1 that alteration of the TRPV1 nerve too, also reduces weight. An article called the Skinny of TRPV1 goes into that phenomena with more detail.
Thus TRPV1 the temperature oriented nerve once altered in its functions reduces weight in obese rats rather profusely. Heat SHock protein reconstitution with BGP-15 also accomplishes the same feat. And heat shock protein reconstitution also conveys the temperature associated weight loss gain in AAP usage.
Weight gain is intimately associated with temperature status in the body, and thus metabolic syndrome features are too associated with temperature status.Heat shock proteins and TRPV1 functions and treatment in diabetes cases, once again reaffirm the dynamics of harsh elevated temperatures of the sunlight created domains of
nonoxygenated era of earth's earliest evolutionary regions, say 3.8 billion years ago. Sunlight in day time periods in the earliest ancient regions of earth's evolutionary nonoxygenated history, say 3.8 billion years ago, creates the extreme elevated temperatures that heat shock proteins deal with---and with such daylight created elevated temperatures the sunlight that creates the extreme high temperatures is a central feature of the natural circadian rhythm present on earth and its environment in these earliest days.

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The BGP-15 drug that abol... (Below threshold)

March 4, 2013 1:22 PM | Posted by Harry Horton: | Reply

The BGP-15 drug that abolishes side effects of AAPs in AAP users, is interestingly a "1 alpha, 25-dihydroxyvitamin D(3) (calcitrol) analog. The central biological component of BGP-15 is thus a sunlight associated entity and furthermore since it is a sunlight associated entity it is an expression of the circadian rhythm, since sunlight is the central feature of the circadian rhythm. And hence the circadian rhythm has been around well since the ancient evolutionary days of the non oxygenated eras of earth's primitive history, that is 3.8 billion years ago if not more. Sunlight stimulates vitamin D metabolism. And BGP-15 as a vitamin D analog is biological component that is stimulated by sunlight. Vitamin D once stimulated as such then goes on to synthesize calcium in the body.

TRPV1 and heat shock proteins thus like the circadian rhythm have internal biological functions that span present day evolved functions back through time to the earlist days of evolutionary history, the ancient domains of evolution, millions of years ago. The TRPV1's modulation of temperature has a span that originated in the ancient evolutonary days of unicellular life. That is TRPV1 functions traverse this wide history of functions since the nerve handled temperautre variances of the non oxygenated era. Heat shock proteins and their functions as responders to temperature conditions, also originated in the earliest evolutionary days too. The circadian thyrhm also originated in the ancient domains of evolutonary history in the nonoxygenated era. So all three of these areas where metabolic syndrome features of AAPs are involved in, these three areas give rise to the metabolic feature side effects and the three areas are involved in abolishing the side effects also. Histamine 1 receptors are intimately involved in modulating circadian rhthym functions. And the histamine 1 recpetor also is blcokaded by the AAP. This area ostensibly gives rise to metabolic side effects in the AAP user.

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March 4, 2013 1:35 PM | Posted by Harry Horton: | Reply

One additional note on the above TRPV1. TRPV! evolved 420 million years ago when oxygen was coming into the atmosphere. A good deal of its range of tempertaure modulation would occur within the past 420 million year period, not the 3.8 million year period. However the 420 year period is so close to the non oxygenated era that could have spanned 3.8 billion years ago to the 420 million years ago period that TRPV1 could have developed senistivity to temperatures at this earlier nonoxygenated era period of time.

The following is s study: "Analysis of Transient Receptor Potential Ankyrin 1 (TRPA1) in frogs and lizards illuminates both nocireceptive heatand chemical sensitivites and (expression with TRP vanilloid 1 (TRPV1) in ancestral vertebrates" the study relates a variant of TRPV1 TRPA1.

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March 5, 2013 3:03 PM | Posted by Harry Horton: | Reply

In regards to the previous 5 or more posts, regarding the circaidian rhythm as the major energy homeostasis sytem that goes awry and dysregulated and plays a role in the development of AAP side effects. A few more studies apparently clarify this issue more accurately. One is from a geologist, a German scientist at Darmstadt UNiversity; Stephan Kempe. He spent a good deal of his professional life investigating the conditions leading for the origins of biological life in the world. One of his studies cited alkaline pH conditions and calcium for initiating the evolutionary trek for all subsequent biological life, particularly his studies of soda lake phenomena and the genesis of calcium pumps in early non oxygenated unicellular life. The sunlight and nightime darkness cycle, that is the essential embodiment of the, circadian rhythm was also a very substantial process interwoven too in the genesis of unicellular life, but most improtantly the presence of the circadian rhythm for constituting the nature of the earliest evolutionary homeostasis systems to arrive in actualization 3.8 billion years ago in the non oxygenated unicellular organisms.
And lo and behold BGP-15 is a vitamin D analog. Vitamin D is the earliest direct biological entity to enter into the circadian rhythm at he earliest points in biological life's evolutionary history 3.8 billion years ago---(it actually may be 3.2 billion years ago but I forgot but I'll stick with 3.8 billion years ago though the 3.8 billions years ago could easily be 3.2 billion years ago. BGP - 15 the vitamin D compound restores heat shock proteins in mono nuclear cells, the restoration occurs within the dynamics and strucutre of the circadian rhythm since vitamin D came into being as particpant with sunlight, sunlight being a component feature of the circadian rhythm. And as one moves down the line in the vitamin D homeostasis system products---calcium is synthesized and its metabolism started by preceding initial vitamin D synthesizing and initiating biological activity. Which is another way of saying that sunlight initiates the calcium metabolism. And in the Kempe study calcium is a major biological compound from the most historical ancient evolutionary grounds for commencing biological life's start (along with alklaine pH conditions) in the non oxygenated era of earth's geohistory. And the circadian rhythm with its temperature facet is present in the Kempe calcium recognition for calcium presence for starting life since calcium has to depend upon sunlight and vitamin D for its presence in biological life's functions. And here with BGP-15 a vitamin D compound ---the compound being the earliest of all biological phenomena for commencing biological life in total as well as creating and initiating the earliest evoltionary energy homeostasis systems.

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Further studies on the at... (Below threshold)

March 6, 2013 2:01 PM | Posted by Harry Horton: | Reply

Further studies on the atypical antipsychotics and their effects on RER and metabolic infleibility.

"Second Generation antipsychotics cause rapid switch to fat oxidation that is reqired for survival in C57BL - 163 Mice"
Schizophrenia Bulletin C201.3 January 17, 2013 Pennstate University of School of Medicine.

quotes: "some seond generation antipsychotics (SGAs) increase insulin resistance and fat oxidation, but counter intuitively they do not activate lipolysis." end quotes. "Olanzapine, risperidone, and clozapine (2.5-10mg/kg) elicited rapid drops in dark cycle RER (-0.7) within minutes whereas apripiprazole exerted only modest changes." end quote. "VO2 and RER effects appear independent of sedation/physical activity and H1 receptors."

(2) "Atypical antipsychotics rapidly and inappropriately switch peripheral fuel utilization to lipids, impairing metabolic flexibility in rodents" Schizophrenia Bulletin.

quote: "Clozapine which along with olanzapine has a high incidence of metabolic side effects caused a rapid and efficacious lowering of RER in mice (figure 5B). Risperidone and ziprasidone, which have a lower incidence of metabolic side effects showed a reduced efficacy on rapid RER lowering..." end quote. Once again the finding that risperidone has a lower and weaker ability to lower RER values, especially the dark cycle level, indicates the primacy of the histamine 1 receptor blocking that creates this RER disturbance in AAPusage. That is most likely, H1 receptor blocking by AAps ceates this RER disturbance. SImply because olanzapine and clozapine block the histamine receptor at 0.1 strength. Risperidone blocks the histamine 1 receptor at weaker 0.19 level. The smaller number indicates the stronger the blocking ability. And clozaril and olanzapine possess this smaller number of 0.1 and hence stronger H1R blocking strength. WIthin the above quote, since risperidone has a---lower incidence and propensity---for creating RER lowering,(in comparison to the clozapine and olanzapine) it seems the obvious reason for this is simply because risperidone blocks the H1R with more weaker strength than the clozapine and olanzapine therapeutics. Risperidone is much weaker at the 0.19 that the 0.1's of clozapine and olanzapine. The differences in the magnitude of RER lowering between "Olanzapine and clozapine' with and relationship to ripseridone, follows the H1R blockading propensities of 'the olanzapine -clozapine' in contrast to risperidone.

further quoted material:"As confirmed here, the chronic effects of atypical antipsychotics on insulin sensitivity in rats can also be onserved rapidly, supporting the conclusion that insulin resistance rise acutely in this model and not simply secondary changes in body composition or weight gain observed with chronic treatment. The same could be said for lipid effects diminished in new link between lipid and glucose metabolism in the development of the metabolic side effcts of atypical antipsychotics." end quote.

New quote: "After clozapine and olanzapine gavage in mice, RER dropped as low as 0.63 in the main chambers. If RER is a true reflection of the combined respiratory quotients of all tissues, it would not be expected to drop below 0.7" End quote.

One more study from the internet: "Mecahnisms of the metabolic side effects of atypical antipsychotic drugs" Albaugh, Vance L, Phd Pennsylvania State University.

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Thus, more studies off th... (Below threshold)

March 6, 2013 4:45 PM | Posted by Harry Horton: | Reply

Thus, more studies off the internet conveying information on RER reespiratory ration and its interwoven nature to the circadian Rhythm.

"The Genetic Chroeography of Circadian Rhythm" Science Blog.

A quote: "The researchers uncovered the new information using a series of mouse models, one of which was described as an inducible double knockout, since treatment of the mice with the drug tamoxifen resulted in deactivation of both REv-erb genes. In wheel running tests in darkness(a method assessing circadian behaviour in mice) tamoxifen-treated mice ran on their wheels for much shorter preiods of time compared with normal mice. They also suffered from metabolic abnormalities, such as increased levels of sugars and triglycerides in their blood.

Under dark conditions the mice expeirenced a drop in their respiratory exchange ratio (the ratio of CO2 exhales to O2 inhaled in a breath), which was suggestive of significant metabolic dysregulation. THis conclusion was supported by further genomic investigation, which revealed that the Rev-erb genes work in tandem to regulate hundreds of genes that influence metabolism, including those that govern cholesterol levels and the metabolism of bile acids.

The study is not the first to reveal a link between circadian clock regulation and metabolism. In 2008, for instance, scientists reported that a protein known as CLOCK regulates circadian activity as well as cellular energy consumption, performing the latter task in cooperation with SIRT1, a protein that earlier work had indicated was involved in intracellular regulation." End quote.

The above study relates the same areas of RER phenomena that appear with AAP induced RER disurbances. ALso the study backs up the substantial intertwining of the two metabolic areas of the cell---circadian rhythm and cell metabolism with its cellular energy consumption. Fuel consumption inflexibility with fat burning modes and the carb-sugar mode is a disturbance created in AAP usage related metabolic syndrome conditions as the previous post's content has detailed.

Other studies from the internet: "A novel inverse relationship between metformin triggered AMPK-SIRT1 signaling and p53 protein abundance in high glucose - expresed Hep62 cells" Cell Physiology Lauren E. Nelson

"An endogenous circadian rhythm of repsiratory control in humans" Journal of Physiology Splenger et al.
"Time of Feeding and the intrinsic circadian rhythms in hepatic gene expression"
"AMPK regulates circadian rhythm in a tissue"
"Temporally consolidated feeding generates rhythm in the Respiratory Exchange Ratio independent of the circadian clock"

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Some internet studies on ... (Below threshold)

March 8, 2013 1:58 PM | Posted by Harry Horton: | Reply

Some internet studies on the circadian clock genes Rev-erb genes and its relationship to weight gain, bi polar disorder and other disorders:

1. The clock gene Rev-erb regulates pancreatic - cell function
2. Rev-ErbA aplha wikipedia
quote: "it has been shown that lithium which inhibits GSK-3B can destabilize Rev-erba protein and affect its function in the circadian clock. This may partly explain lithium's therapeutic effect on circadian rhtym diesases such as bi polar." end quote.

3. "Rev-erb-a an integrator of circadian rhythms and metabolism"
4. "Body clock linked to weight gain"
5."How nuclear recptors tell time"
6."Clock molecules's sensitivity to lithium sheds light on bi polar disorder" February 21, 2006 Science Daily.
7."Faulty Body clock may make kids bi polar" Nov 13, 2009 Science Daily.
8. "Body clocks may hold key for treamtent of bi polar. March 13, 2012. Science Daily.

Thr RER ration dark cycle phase lower number is lowered with AAP usage from 0.7 to 0.63 - in some cases, and with this lowering the circadian rhtyhm is further disturbed and with such RER number lowering metabolic syndrome features and conditions actualize themselves in AAP users. This phenomena is directly linked most likely to the mitochondrial energy deficit and its aggravation by AAPs and such deficit embodied with circadian rhthym dysregulation for its creation. In any case the REv-erb gene covers a lot ofterrain where weight gain, bi polar and RER ratio health are all integrated and connected amongst other metabolic fucntions with Rev-erb processes and connections to other genes.

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Additional internet studi... (Below threshold)

March 9, 2013 1:34 PM | Posted by Harry Horton: | Reply

Additional internet studies on the RER, atypical antipsychotics SIRT1 gene, and their role in metabolism and metabolic syndrome conditions.

"Association study between variants of AMP- activated protein kinase catalytic & regulatory subunit genes with antipsychotic induced weight gain." Psychiatry.
"Study provides clues about how cancer cells develop resistance to chemotherapy drug."
"AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity." Nature.
"Reservatrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC- alpha.
"A Review of the Sirtuin system, its clinical implications, and the potential role of Dietary activators like reservatrol: Part 2"
Also there is a part 1 to this series of articles.
"Assessing mitochondrial dysfunction in cell." Martin D. Brad Biochemical journal.

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The recent observations ... (Below threshold)

March 14, 2013 6:36 PM | Posted by Harry Horton: | Reply

The recent observations of AAP induced deleterious side effects involving mitochondrial energy deficits, lowered dark cycle RER numbers and the omnipresent circadian rhythm and its metabolism central in elucidating the metabolism of the metabolic syndrome of AAP usage. One interesting area that many psychiatrists and diabetologists over look is the earth's early evolution and the original conditions that give rise to biological life in the far away nonoxygenated realms of earth's existance, over 3.0 billion years ago. Here one finds the circadian rhythm in full force, alkaline oceans and calcium metabolism, extant and participatory with the most ancient evolutionary origins actualizing itself in all mysterious harmony amongst each other. THe following studies off the internet are an exploration of these ancient early nonoxygenated areas that gave rise to biological life. THe German scientist Stephan Kempe is the author and conveyor of a lot of the ideas. The scientific studies are as follows:

(1) Hydrochemical key to the Genesis of Calcareous nonlaminated and laminated cynobacterial microbiolites"
A quote: "...Single most important factor for short term modification of Phanerozoic ocean chemistry. Sudden, in geological terms, export of alkalinity from over turning anaerobic basins could cause high pH and Ca2+ stress upon marine biota." end quote.
(2) "Modelling in Natural Sciences: Design, Validation and Case studies - P"
(3) "Modern Soda lakes: Model Environments for an early alkaline ocean." Stephan Kempe.
(4) "Genuine modern analogues of PreCambrian Stromatalites from caldera lakes of Niuafo'ou Island, Tonga"

BGP_15 is a therapeutic agent that is vitamin D comprised. Vitamin D in connected substantially for the present day evolved calium metabolism to take place in human cells. And here in these studies calicum pumps and calcium itself is investigated as a central biological entity for starting biological life in the earliest stretches of ancient evolutionary time domains. Also the mitochondrial energy deficit is intimately tied to the circadian rhythm for its comprisement and the alternation of sunlight and darkness of night too are present in these early ancient evolutionary days the above studies delve into. The centrality that R.F> Green gives to alkaline conditions in human energy homeostasis systems for relating the dynamics of metabolic syndrome condition development in today's patients----alkaline pH conditions also are given central primacy for commencing biological life in these earliest days of evolution as the above studies relates. As the scientist Stephan Kempe has made note of in the above studies.

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The Soda Lake phenomena o... (Below threshold)

March 21, 2013 4:18 PM | Posted by Harry Horton: | Reply

The Soda Lake phenomena of Stephan Kempe and its importance in originating and forwarding calcium metabolim through evolution and more on BGP-15 are some areas the following post centers on.
The internet study: "BGP-15 --- a novel poly(ADP-ribose) polymerase inhibitor - protects against nephrotoxicity of cisplatin without compromising its anti tumor activity" quote: "BGP-15 either blocked or significantly reduced (60-90% in 100-200mgkg oral doe) cisplatin induced increase in serum urea and creatinine level in mice and rats and prevented the structural degeneration of the kidney, as well. The nephroprotectitive effect was accompanied by inhibition of cisplatin-induced ROS production in rat kidney mitochondria and improved the antioxidant status of the kidney in mice with cisplatin-induced retinopathy. In rat kidney, cisplatin caused a decrease in the level of Bcl-x, a mitochondrial protective protein, and this was normalized by BGP-15 treatment." end quote. The substantial chemoprtoective qualities of BGP-15 thus are related in the above study.

"Cynobacterial key to the genesis of micrtic and peloidal limestones in ancient seas" Stephan kempe et al. A survey of cyanobacteria in ancient seas bottom floors where calicification of these ancient microroganism is investigated. The origins of calcium pumps and areas for developing future skeletal features of later evolved organisms and animals is implied within the study's surveyance. Modern Soda lakes are referred to in the article. Diabetes, schizophrenia and bi polar disorders all involve calcium metabolism and its dysfunction in substantial part for determining the nature and existance of such disorders. The above Kempe study explores the genesis of these area.

(2) Calcium pumps in the Central Nervous System" A study on exploring current day evolved calcium pumps inthe cells that play a large role in maintaining normal health of current day evolved neurological signaling. Tw types of calcium pumps are addressed in this article.

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More internet studies on ... (Below threshold)

March 22, 2013 12:41 PM | Posted by Harry Horton: | Reply

More internet studies on BGP-15:

"Membrane - Lipid Therapy in Operation: THe HSP co-Inducer BGP-15 activates stress signal transduction pathways by Remodeling Plasma Membrane Rafts."
"Influence of BGP-15 a Nicotinic Amidoxime Derivative, on the Vascularization and Growth of Murine Hepatoma Xwnografts"
"Allos THerapeutics hopes BGP-15 drug beats the Odds" May 6, 2002 Biotech Rod Franklin.
"BGP-15, a hydroximic acid derivative, protects against cisplatin - or taxol induced periphereal neuropathy in rats."
"The effect of insulin sensitizer BGP-15 on alanzapine induced metabolic disorders."
"HSP72 protects against obesity - induced insulin resistance."
"Inhibition of cancer growth and induction of apoptosis by BGP-13 and BGP-15, new calcipotriene - derived vitamin D3 analogs, in-vitro and in vivo studies"
"Heat shcok proteins may be new approach to DMD treatment."
"News Article BGP-15's potential in treating DMD came as a surprise, says Kalman..." www.drugsdiscoverynews.com

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Further thoughts on BGP-1... (Below threshold)

March 27, 2013 4:25 PM | Posted by Harry Horton: | Reply

Further thoughts on BGP-15 and its mechanisms of action. As an earlier scientific study related, the heat shock protein status and function in mononuclear cells were returned to normal in AAP usage psychiatric patients with BGP-15 application. With this occurrence weight gain was abolished, insulin resistance also was eradicated and the glucose status normalized in Wistar rats. The study that related these accomplishments is in one of the previous comment postings on this comment section centering on Seroquel.
THere are some interesting facets to consider with the above. That is the area of cancer and rapid tumour cell growth that basically suctions off the nutrient supply in the cells. The rapid cells growth that is mitotic division that is greatly accelerated amongst cancer cells in comparison to regular human cells----the more rapid cell division is interesting. Because in physics any or at least a vast majority of type of chemical reactions is speeded up when heat is increased and applied to the chemical reaction. With cancer the cell division is rapidly accelerated and the cancerous condition onsets in with such circumstances.
According to the wikipedia article on Heat shock Proteins:the following quote comes: "Heat Shock Factor 1 (HSF1) is a transcription factor that is involved in the upregulation of HSP70 protein expression. Recently it was discovered that HSF1 is a powerful multifaceted modifier of carcinogenesis. HSF1 knockout mice show significantly decreased incidence of skin tumour after topical application of DMBA, a mutagen." End of quote.
In the above quote its interesting that heat shock factors and proteins are effective in mediating cancer development and treating the cancer itself. And the one central issue with this phenomena is heat shock proteins are centered within the factors of increased heat that in turn increases the activity, of,unfolding of proteins and the protein development as well as chaperoning such proteins to other sites in the cells. With that issue, heat as an instigator of more rapid development of the cell's functions is apparent with heat shock proteins, since heat shock proteins increase their number and function with heat presence and application. And cancer is a disease in which rapid cellular growth also is apparent, like a process, cancer is, as if it were a disease responsive to heat application. Like heat shock protein increase in number and development resulting from elevated temperatures-heat.
Another interesting area with all of this is the metabolic status and physiology of sharks. Sharks have been around for over 240 million years and interestingly their cell growth is more rapid than humans. A tooth of a shark if broken or lost can regrow back in a matter of hours, just to give an idea how rapid the cellular growth within the sharks physiology is. But most significantly along with that factor is the shark has no known experiences with cancer or heart disease. One reason could be that the shark's cells are more ancient and thus evolved within or near an earlier era of nonoygenated age when heat temperatures were higher and the high heat temperatures caused more rapid cell divsion. So the shark kept more rapid cell division within its constitution that has not changed since 240 million years ago. The significant fact of that is that the cells are more expressive of cancer cell's mechanisms of rapid growth, yet such rapidity is normal for the prehistoric creature the shark is, since its cells have more rapid cell division as a normal natural phenomena indigenous to the shark's metabolism and biology, than present day human cells. And cancer cells share too this more rapid cell division phenomena as with the shark, yet when the rapid cell division appears within 'recently evolved vertbrate humans' human cells become diseased and deleterious. Thus no cancer or heart disease has ever been found in sharks, since whatever rapid cell growth one would find in cancer as an abnormal rapidity of cell division, in sharks such a rapiditiy of cell division is more aligned and expressed with the normal shark cell of cellular division. A cellular division that is more rapid. And elevated temperatures that one would find in the non oxygenated era is thus a causative factor for any rapid growth of any bio chemical reaction whether biological or otherwise. The shark thus still could incoporate a lot of the energy homeostasis functions from this nonoxygenated era where elevated temperatures shaped its internal cell division speed---a speed of rapid mitosis. and thus the shark still could incorporate a lot of its energy homeostasis functions, too, of whatever predecessor species came before it, such predecessor species inhabiting the nonoxygenated eras of biological life roughly extant about 500 million years ago. Note the shark never advanced evolutionary wise over the past 240 million years and carries no evolutionary trek of any real substantial mutative development and evolutionary advancement within the bulk of the oxygenated era of biological life' march and advancemnet in evolution. Thus the shark's cell division and bilogical status is more relative to the nonxygenated era's preence with such elevated temperatures shaping the shark's metabolic status, more so than the oxygenated era's presence.

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Some recent internet art... (Below threshold)

April 1, 2013 3:54 PM | Posted by Harry Horton: | Reply

Some recent internet articles on progress on the war against HIV and AIDS. Advances made in treatments for combatting the virus.

(1) "Study: bee venom kills HIV" US News and Report. Jason Koebler.
(2) "Early HIV drugs "cure 1 in 10" BBC NEws.
(3)"Researchers report on first infant with "functional HIV cure". April 1, 2013. Ekaterina Pesheva.
(4) "innate immune system can kill HIV when a viral gene is deactivated." Science Daily March 30, 2013.

(5) "AIDs Breakthrough: Melbourne researchers uncover HIV's genetic hiding place." "Australian News" March 04, 2013.

(6) " Scientists reprogram body's own cells to kill cancer, HIV"
2013.03.26. A pair of papers published in the journal Stem Cell, from two separate Japanese universites. A successful technique to reprogram the boy's own immune cells to seek out and destroy cancer cells and HIV cells."

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HIV Cure: ... (Below threshold)

May 2, 2013 9:51 AM | Posted by Harry Horton: | Reply

HIV Cure:


May 2, 2013 - THe following internet articles convey what appears to be a fairly optmisitc view HIV will finally be cured in th4 scant few months ahead. The cure is a result of research efforts from Danish scientists. The articles are:

"HIV Cure on the Brink" -I4U-
"HIV 'cure' looks promising Danish scientists" medicinenet.com
"Scientists on brink of HIV cure" - Telegraph.

There are other articles that relate this scientific discovery for curing HIV. I found one article that was skeptical.

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I'm on 25 mg of quetiapine ... (Below threshold)

July 5, 2013 10:41 AM | Posted by Egnarts: | Reply

I'm on 25 mg of quetiapine at bedtime for over two years. It is the only med that allows me to sleep and Ive been given at least 10 other anti psych Rx. I was diagnosed bi polar when I hit menopause and lost touch with reality after five days of no sleep. My sister has FMD and Celiacs disease and we both have MTHFR defects. She is homozygous c677t and I am homozygous MTRR A664a and VDR Taq++, along with heterozygous defects of bhmt, CBS and COMT function. ( I thought epigenetics was bogus, except my homocysteine was at 17 and went down to 6 on methyl folate and methyl b12 ). What are your thoughts on deplin? Like Prozac, antihistamines increase my racing thoughts. Seroquel makes me fat, sluggish, joyless, apathetic, asexual and unfocused, but at least I sleep. (and I miss Grapefruit.)

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Why not? Shrink doesn't kno... (Below threshold)

July 26, 2013 3:03 AM | Posted, in reply to Nik's comment, by J: | Reply

Why not? Shrink doesn't know if his patient is ADHD any better than he knows he himself isn't ADHD. What if he took an anti-psychotic and realized, "Oh my god, I have no emotions, I can't partake in these crimes any longer..." or took a stimulant and said "Holy shit, I'm dealing meth to inattentive C students!"

Your analogy to chemotherapy is stupid. Cost/benefit my ass, let the shrink take a Lexapro and keep telling his patients "You need to continue your regimen a little while longer, I don't think you're well yet..."

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I used to be on 50mg of ser... (Below threshold)

September 27, 2013 2:20 PM | Posted by Anonymous: | Reply

I used to be on 50mg of seroquel, jumped to 100, then 200mg. I don't take any seroquel today at all because it is bad for you, makes you gain weight, and sleep too much. When i did take it i was only using it to treat my insomnia. I feel horrible without it, being a couple years later, ever since i stopped taking it it feels as if i am just slipping farther and farther into depression, i am losing touch with reality. I am starting to wonder if seroquel caused me to slip into a depression. I honestly don't know what i should do, I'm only 20 years old i shouldn't have to deal with this, seriously thinking about getting it prescribed again because i felt great with it.

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Hello 20 year old. So, hati... (Below threshold)

September 28, 2013 8:00 AM | Posted by Egnarts: | Reply

Hello 20 year old. So, hating the drugged feeling of seroquel, but fearing that you may need it to sleep? Have your MTHFR status checked. You might be surprised how much more energy and less brain fog you have when you switch to methyl folate and methyl b12 and avoid folic acid. Also, go Gluten free for a month and see how you feel. Deplin, although available by prescription is not a drug, it's a "food", nothing but pure methyl folate. Which you can get cheaply, over the counter. Seroquel inhibits dopamine and seratonin receptors in your brain. It changes the way your brain breaks them down. You actually need the by products of broken down dopamine to produce more dopamine. I'm trying to get off of them for sleep myself. My A4m doc said I should be off in three months, but that it may take another three months afterwards for my body to adjust. ( i also have hormone issues that you may not have.)

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Why? Psychiatrists so casua... (Below threshold)

October 5, 2013 11:12 AM | Posted, in reply to Sfon's comment, by Sirene: | Reply

Why? Psychiatrists so casually hand out drugs to patients.

I think it shows a little bit of curiosity and dare I say authenticity. Of course its not acceptable for a psychiatrist to test the drugs they prescribe on themselves, its more "acceptable" for psychiatrists to mindlessly repeat the line they are fed from the pharm companies who supply them with a drug.

What kind of scientist mindlessly passes out serious drugs to people who may (or may not!) have serious illnesses when they themselves can't answer the simple question of "How does this drug work?" THAT'S a careless attitude.

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<a href="http://www.hospita... (Below threshold)

July 26, 2014 1:25 AM | Posted by hospitalkhoj: | Reply

Top 10 Hospitals in India has witness to held a lot of expansion in the medical humanity. Not only Indian doctors are now leading practitioners in the grassland of medicine across the world, but also patients from extraordinary parts of the world are approaching to India for treatment.

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