Ron Scott
you may find information here:
http://mp.medscape.com/cgi-bin1/DM/t/hDIhS0VoXWR0D2s0DUDl0Et&uac=126040DG
"In an interview with Medscape Medical News, Dr. Dandona explained that the literature shows a "clear epidemiological relationship" between obesity and type 2 diabetes and AD, with rates of AD twice as high in this population relative to the normal population. In addition, recent autopsy studies of AD patients have shown a lack of insulin and insulin signaling in the brain.
More recently, it was shown that adding β-amyloid to cultured neurons induces oxidative stress and inflammation, “but when you add insulin, this is neutralized. “The next question was can we marry these 2 findings in our work,” Dr. Dandona said."
One aspect that I think is missing in the "Insulin Model" of diabetes is that type II people aren't born with diabetes, they develop it as their pancreas fails. When we say a type II is insulin resistant that means either that their insulin is malformed, or that they quite literally have too much of it. But that for some reason it isn't working properly. I think this is a feedback problem, in essence, the cells produce a messenger that is sent to the pancreas to promote insulin production, but when the pancreas does, it can't achieve anything, because either the insulin can't enter the cell, or the result of it entering the cell is not what the cell expects.
What we get is the classic positive feedback loop, the pancreas reaches it's limit, and begins to fail.
For myself, I think that I have a very poorly tuned Kreb Cycle.
In essence, glucose comes into the cell, but about 1/4 of the way around the digestion cycle, first described by Kreb after the second world war, it needs a co-enzyme called co-enzyme CoA who's job it is to deposit an acetyl group on the chemical substrate, then go back to be recharged by some other metabolic process. The substrate is then allowed to combine with water which forms acetic acid, which quickly recombines and supplies Oxygen for Phosphate formulation. ATP, ADP or AMP.
Later this co-enzyme is also used to facilitate the generation of GTP, GDP, and GMP in the same cycle.
Without the enzyme or where the enzyme is malformed, the stereochemistry of the Acetyl group, is not as quick to cause a substitution, slowing down energy production for the cell.
Normally because the enzyme rate limits the reaction, All you really need to do is add glucose and a Kreb cycle will form around it, and energy will be produced in the form of phosphates. However in this case, even if you put more glucose into the cell, it is still going to take a long time to finish the digestive process, and during the process, just like in a car that has the wrong mixture, certain chemicals will form as a result of the substrate combining preferentially with other chemicals that pollute the cell, and in turn seem to lower the PH of the cell. Because this doesn't increase the energy in the cell, a signal is sent out for more glucose... etc.
The body in an attempt to manage the PH of the cell buffers it with calcium, which forms Calcium Carbonate and Calcium Oxcyiate Which are considered normal parts of the body, because there are mechanisms to recycle them if needed. The problem is that these calcium elements reach a volume high enough to plate out in the blood, and to precipitate within tissue and on bones, causing osteo-Arthritus, and possibly causing the calcification of the brain.
Now here is an interesting side effect, like muscles that give off Lactic Acid when they are overused, the acid in the diabetic muscle, results in pains reminiscent of fatigue. Over time the calcificiation of organs, and the chronic low-grade pain result in a gradual loss of function at the organic and muscular level, and this may also contribute to alzheimers if the glial model is at all correct.
Further, the failure of the glucose to meet the energy needs of the cell, has an added effect, in that it causes the appetite control mechanism to increase appetite, and instead of being hungry only when the blood sugar drops just before the regular mealtime, people with this version of diabetes can be hungry all the time, and in an attempt to get more glucose their diet will be skewed to the Carbohydrates because the body thinks that it has run out of glucose.
Normally the Fat Cells, would notice that they were filling up with glucose, (and therefore that it wasn't being cleaned up by the cells that demanded it,) but in some people the necessary chemical needed to make that signal is missing or malformed and fat cells do not signal a surfiet of fat. Those of us that have lived in Northern Climates think that perhaps this genetic change was brought about by the ICE age, in essence adding increased insulation and body storage of glucose, by sequestering more glucose in fat, in order to allow for longer times between meals.
Because fat cells absorb insulin, just like muscle cells, the more fat cells there are, the more demand there is on the pancreas and the more likely it is to fail. However, the chronic pain, and Insulin resistance, the skew of diet towards carbohydrates, and the plating of calcium in the organs probably increase the danger to the pancreas, causing it to fail earler in Insulin resistant people than in those that are merely obese.
no problem
I just have a few knowledge about some-insuline independents-glut transporters in the brain, so the relevance of insuline here was surprising to me.
One aspect that I think is missing in the "Insulin Model" of diabetes is that type II people aren't born with diabetes, they develop it as their pancreas fails. When we say a type II is insulin resistant that means either that their insulin is malformed, or that they quite literally have too much of it. But that for some reason it isn't working properly. I think this is a feedback problem, in essence, the cells produce a messenger that is sent to the pancreas to promote insulin production, but when the pancreas does, it can't achieve anything, because either the insulin can't enter the cell, or the result of it entering the cell is not what the cell expects.
What we get is the classic positive feedback loop, the pancreas reaches it's limit, and begins to fail.
For myself, I think that I have a very poorly tuned Kreb Cycle.
In essence, glucose comes into the cell, but about 1/4 of the way around the digestion cycle, first described by Kreb after the second world war, it needs a co-enzyme called co-enzyme CoA who's job it is to deposit an acetyl group on the chemical substrate, then go back to be recharged by some other metabolic process. The substrate is then allowed to combine with water which forms acetic acid, which quickly recombines and supplies Oxygen for Phosphate formulation. ATP, ADP or AMP.
Later this co-enzyme is also used to facilitate the generation of GTP, GDP, and GMP in the same cycle.
Without the enzyme or where the enzyme is malformed, the stereochemistry of the Acetyl group, is not as quick to cause a substitution, slowing down energy production for the cell.
Normally because the enzyme rate limits the reaction, All you really need to do is add glucose and a Kreb cycle will form around it, and energy will be produced in the form of phosphates. However in this case, even if you put more glucose into the cell, it is still going to take a long time to finish the digestive process, and during the process, just like in a car that has the wrong mixture, certain chemicals will form as a result of the substrate combining preferentially with other chemicals that pollute the cell, and in turn seem to lower the PH of the cell. Because this doesn't increase the energy in the cell, a signal is sent out for more glucose... etc.
The body in an attempt to manage the PH of the cell buffers it with calcium, which forms Calcium Carbonate and Calcium Oxcyiate Which are considered normal parts of the body, because there are mechanisms to recycle them if needed. The problem is that these calcium elements reach a volume high enough to plate out in the blood, and to precipitate within tissue and on bones, causing osteo-Arthritus, and possibly causing the calcification of the brain.
Now here is an interesting side effect, like muscles that give off Lactic Acid when they are overused, the acid in the diabetic muscle, results in pains reminiscent of fatigue. Over time the calcificiation of organs, and the chronic low-grade pain result in a gradual loss of function at the organic and muscular level, and this may also contribute to alzheimers if the glial model is at all correct.
Further, the failure of the glucose to meet the energy needs of the cell, has an added effect, in that it causes the appetite control mechanism to increase appetite, and instead of being hungry only when the blood sugar drops just before the regular mealtime, people with this version of diabetes can be hungry all the time, and in an attempt to get more glucose their diet will be skewed to the Carbohydrates because the body thinks that it has run out of glucose.
Normally the Fat Cells, would notice that they were filling up with glucose, (and therefore that it wasn't being cleaned up by the cells that demanded it,) but in some people the necessary chemical needed to make that signal is missing or malformed and fat cells do not signal a surfiet of fat. Those of us that have lived in Northern Climates think that perhaps this genetic change was brought about by the ICE age, in essence adding increased insulation and body storage of glucose, by sequestering more glucose in fat, in order to allow for longer times between meals.
Because fat cells absorb insulin, just like muscle cells, the more fat cells there are, the more demand there is on the pancreas and the more likely it is to fail. However, the chronic pain, and Insulin resistance, the skew of diet towards carbohydrates, and the plating of calcium in the organs probably increase the danger to the pancreas, causing it to fail earler in Insulin resistant people than in those that are merely obese.
Here we get into an interesting aspect again, the chemical that fat cells produce that is missing from some genetic variants, has shown that it can almost singlehandedly cure both obesity and diabetes in certain mouse models.
Certain mice, treated with this chemical, became more active, cut down their carbohydrate intake, lost weight and quit being diabetic, when given this one chemical. If it becomes popular it may well destroy the junk food market. The Diabetic community is guardedly optimistic that human trials will go well, since it is a natural part of the body, and seems to have few side effects in the Mouse population so treated.
It sounds as though the identity of this missing chemical is known. Are you working to market it? Curing obesity and diabetes II would be important advances. Would it work if people continued to eat junk food, or does it stop the cravings? I have read a lot about type II diabetes, and how exercise and diet changes can reverse it, but I had not heard of a "silver bullet" such as you mentioned.
Mahvish, Sorry, I have never heard that disease named. Am I right in thinking that you are talking about the gerontological onset of Diabetes?
Ron, Personally I have no stock in the product, and the Diabetes People are right to be skeptical until the human trials are completed, some time in the next 10-20 years. As I have suggested my own disease seems much more complex than the mouse models being investigated so I don't know if the supply of the drug will make a difference or not. I do have what many have called the "Thrifty Gene", where my body stores more fat than it needs to, but that is all I can say.
The link between diabetes tipus II and Alzheimer has been described, but the explanation is quite difficult. One aspect to solve is: all the people having diabetes II will they develop Alzheimer? If the answer is not, this menas that more factors are involved. One could be duabetes but it tis necessary other factors that in combination are the responsible. I do not know about the cell transport and about the physiology of the brain enough to discuss about these factors. However, I am very interested in the transport between the blood and the brain and also about the electro-magnetic fields into the brain. The molecules could be modified by the ionic strength changes in the intersticial liquids and intercellular liquid. The physico-chemical theories about the effects on thermodynamic and solution paramenters are not clear. The transpor could be affected by the solvatation and ion transfer in this liquids. But this is only a possibility. Is it possible to design experiments to determine the potential E in these liquids.
I think that it was a high co-morbidity rather than a guarantee. If my theory is correct, the "thickness" of the brain would be a good indicator of Alzheimers onset. of course you probably want a baseline around 20-40 years old, on which to base the measurements. The exact age might be dependent on the supply of growth factor to promote stem cell division, the reduction in thickness would therefore probably only start at about 22 years of age.
Wednesday, April 27, 2011
GENERATION ALZHEIMER'S: THE DEFINING DISEASE OF THE BABY BOOMERS
http://betaamyloidcjd.blogspot.com/2011/04/generation-alzheimers-defining-disease.html
Infectivity of bovine materials used in medicinal products and the importance of inoculation route
3.221 The risk from infectivity present in medicinal products was considered by the Southwood Working Party. They noted that ‘the greatest risk . . . would be from the parenteral injection of material derived from bovine brain or lymphoid tissue’.538 (As described previously, it was generally accepted that the oral route was considerably less efficient than the parenteral route.539)
3.222 In reality, different routes exist within the parenteral category – intracerebral, intraperitoneal, intramuscular, intravenous, intraspinal and subcutaneous. Experiments in 1978 looking at several of these routes found the efficiency between them to vary. Intracerebral and intraspinal were generally the most efficient, followed by intravenous, intraperitoneal and then subcutaneous.540 The fact that certain medicinal products could be injected directly into the body (most commonly intramuscularly) meant that in theory they would pose a greater risk than beef products in food.
3.223 Various cattle tissues were of relevance to medicinal products, including insulin, heparin, surgical catgut sutures and serum. The consideration given to these materials prior to March 1996 is addressed in vol. 7: Medicines and Cosmetics.
533 SEAC 22/5 534 Wells, G. (1998) Preliminary Observations on the Pathogenesis of Experimental Bovine Spongiform Encephalopathy (BSE): An Update, Veterinary Record, 142, 103 535 Wells, G., Hawkins, S., Green, P., Spencer, Y., Dexter, I. and Dawson, D. (1999) Limited Detection of Sternal Bone Marrow Infectivity in the Clinical Phase of Experimental Bovine Spongiform Encephalopathy (BSE), Veterinary Record, 144, 292–4 536 Scott, M.R., Will, R., Ironside, J., Nguyen, H.-O., Tremblay, P., DeArmond, S.J. and Prusiner, S.B. (1999) Compelling Transgenetic Evidence for Transmission of Bovine Spongiform Encephalopathy Prions to Humans, Proceedings of the National Academy of Sciences of the USA, 96, 15137–42 537 Scott, M.R., Safar, J., Telling, G., Nguyen, H.-O., Groth, D., Torchia, M., Kochler, R., Tremblay, P., Walther, D., Cohen, F., DeArmond, S. and Prusiner, S. (1997) Identification of a Prion Protein Epitope Modulating Transmission of Bovine Spongiform Encephalopathy Prions to Transgenic Mice, Proceedings of the National Academy of Sciences of the United States of America, 94, 14279–84 538 IBD1 tab 2 para. 5.3.3 539 Kimberlin, R. and Walker, C. (1989) Pathogenesis of Scrapie in Mice after Intragastric Infection, Virus Research, 12, 213–20; Diringer, H., Beekes, M. and Oberdieck, U. (1994) The Nature of the Scrapie Agent: The Virus Theory, Annals of The New York Academy of Science, 724, 246–58; Prusiner, S., Cochran, S. and Alpers, S. (1985) Transmission of Scrapie in Hamsters, Journal of Infectious Diseases, 152, 971–8 540 Kimberlin, R.H. and Walker, C.A. (1978) Pathogenesis of Mouse Scrapie: Effect of Route of Inoculation on Infectivity Titres and Dose-Response Curves, Journal of Comparative Pathology, 88, 39–47
http://collections.europarchive.org/tna/20080102110838/http://www.bseinquiry.gov.uk/pdf/volume2/chapter3.pdf
COMMERCIAL IN CONFIDENCE
NOT FOR PUBLICATION
COMMITTEE ON SAFETY OF MEDICINES
WORKING PARTY ON BOVINE SPONGIFORM ENCEPHALOPATHY
3. Products for injection using bovine tissue
This category includes tissue derived products, other than from brain or lymphoid tissue and excludes bovine blood.
3.1 Bovine Pancreas
3.1.1 Insulin
The following companies hold licences for bovine insulin.
Source Country
Denmark
USA
USA
Denmark, Sweden, USA, Italy, Canada, Portugal, Netherlands
In 1988 a sample consignment from UK was used. UK source material is no longer used.
Comment
There are no bovine insulins manufctured from UK sourced material.
Bovine insulin is not widely prescribed, but has a niche in the market for diabetics unable to tolerate other products.
3.1.2 Glucagon
bovine pancreas from USA.
as for insulin - Scandinavia, USA, Italy, Canada, Portugal and Netherlands.
3.1.3
Miscellaneous products containing Bovine Pancreas
3.1.3.1 Zonulysin (Chymotrypsin) - sourced from Canada
3.1.3.2 Streptokinase - culture medium, containing bovine muscle and pancreas are used in process - all sourced from Germany
3.1.3.3 Fibrinogen + Desoxyribonuclease - bovine pancreas sourced from Canada and S Africa.
3.2. Vaccines using Bovine Products in process
snip...see full text ;
http://classic-web.archive.org/web/20030704202503/http://www.bseinquiry.gov.uk/files/yb/1989/09/06011001.pdf
Sunday, May 18, 2008
MAD COW DISEASE BSE CJD CHILDREN VACCINES
http://bseinquiry.blogspot.com/2008/05/mad-cow-disease-bse-cjd-children.html
Sunday, May 1, 2011
W.H.O. T.S.E. PRION Blood products and related biologicals May 2011
http://transmissiblespongiformencephalopathy.blogspot.com/2011/05/who-tse-prion-blood-products-and.html
Subject: BSE--U.S. 50 STATE CONFERENCE CALL Jan. 9, 2001
Date: Tue, 9 Jan 2001 16:49:00 -0800
From: "Terry S. Singeltary Sr."
Reply-To: Bovine Spongiform Encephalopathy
[host Richard Barns] and now a question from Terry S. Singeltary of CJD Watch.
[TSS] yes, thank you, U.S. cattle, what kind of guarantee can you give for serum or tissue donor herds?
[no answer, you could hear in the back ground, mumbling and 'we can't. have him ask the question again.]
[host Richard] could you repeat the question?
[TSS] U.S. cattle, what kind of guarantee can you give for serum or tissue donor herds?
[not sure whom ask this] what group are you with?
[TSS] CJD Watch, my Mom died from hvCJD and we are tracking CJD world-wide.
[not sure who is speaking] could you please disconnect Mr. Singeltary
[TSS] you are not going to answer my question?
[not sure whom speaking] NO
from this point, i was still connected, got to listen and tape the whole conference. at one point someone came on, a woman, and ask again;
[unknown woman] what group are you with?
[TSS] CJD Watch and my Mom died from hvCJD we are trying to tract down CJD and other human TSE's world wide. i was invited to sit in on this from someone inside the USDA/APHIS and that is why i am here. do you intend on banning me from this conference now?
at this point the conference was turned back up, and i got to finish listening. They never answered or even addressed my one question, or even addressed the issue. BUT, i will try and give you a run-down for now, of the conference.
snip...full text ;
http://bse-atypical.blogspot.com/2010/01/14th-international-congress-on.html
Wednesday, April 27, 2011
GENERATION ALZHEIMER'S: THE DEFINING DISEASE OF THE BABY BOOMERS
http://betaamyloidcjd.blogspot.com/2011/04/generation-alzheimers-defining-disease.html
TSS
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