Talk:Mevalonate inhibition

Start

Statins are well established as the primary medication for the reduction of blood plasma cholesterol levels but they inhibit a primary step in the mevalonate pathway which has branches into some important biochemical product areas such as CoQ10, Dolichols (cell signalling - terpenoid anchored glycoproteins) and Steroids (via cholesterol).

Background

A 1997 a major paradigm shift in the function of cholesterol was under-way in the Biosciences. It was centred around the lipid raft hypothesis, which subsequently transformed our understanding of cholesterol function in cell membranes. Coincidentally the success of statin marketing took it beyond its undoubted cardiovascular uses into new areas of preventative and long term therapies. The clinical trials had not prepared the ground for this and it has been seen as controvertial. AT the same time F W Pfrieger was also publishing papers demonstrating the importance of freshly synthesised cholesterol and glial cell derived in synaptogenesis and maintenance of memory. A review of current research on the the impact of statins through their defined action on mevalonate derived product in non-cardiovascular areas is a major topic.

The issue of CoQ10 has and mitochondrial effects has a had a major review and we cite the Beatrice Golomb Review
Golomb, Beatrice A;Evans, Marcella A (2008). " Statin adverse effects : a review of the literature and evidence for a mitochondrial mechanism ". Am J Cardiovasc Drugs. 8: 373–418. PMID 19159124. {{cite journal}}: Cite has empty unknown parameter: |month= (help)CS1 maint: multiple names: authors list (link)
A review of the research and clinical implications of long-term statin use, particularly on the depletion of cholesterol in cell membranes is in press for Summer 2009
Wainwright; et al., Cholesterol-Lowering Therapies and Cell Membranes in press for 2009 {{citation}}: Explicit use of et al. in: |author= (help); Unknown parameter |PUBMED= ignored (help).
80.189.7.125 (talk) 11:30, 3 June 2009 (UTC)

Mevalonate Product Classification

Paradigm changes are threat to orthodoxy and the status quo - this means that this topic is very important right now and should be supported as a major topic for all Biosciences to share the fast moving implications of depletions of mevalonate dependent classes of biochemicals: CoQ10 Cholesterol dolichols that is all the Terpenoids and steroids Glynwiki (talk) 13:17, 26 May 2009 (UTC)

Declaration of NPOV Conformance

Realising this page has a way to go I will set about the re-edits required to ensure we get to the standard set by the medical sciences projects for wikipedia but independent advice is that it already complies with NPOV requirements and balances the implicit over-promotion of statin uses in other parts of this publication. Will all contributors and opponents please continue to make any personal and commercial interest clear on this matter. I have already done so on my page. 80.189.7.125 (talk) 11:30, 3 June 2009 (UTC)

Tau protein Synthesis

This page section seems to say statins cause AD. This is of course not supported by the evidence.--Doc James (talk · contribs · email) 15:41, 1 June 2009 (UTC)

Dolichol Inhibition

Implies that statins cause cancer. Also not supported.--Doc James (talk · contribs · email) 15:43, 1 June 2009 (UTC)
Hope the latest edit hold the position for clarification. We can make this much better, I agree. I'll do some more searches on this and make this issue a bit clearer for everyone.Glynwiki (talk) 10:58, 2 June 2009 (UTC)

References

The first ref Buhaescu I & Izzedine H. Mevalonate pathway: a review of clinical and therapeutical implications. Clin. Biochem. (2007) 40: pp. 575-584 is a decent review. It is taken out of context and than attempts to refute its conclusions take place using primary research. Fuzhen Xia, Li Xie, Anton Mihic, Xiaodong Gao, Yi Chen, Herbert Y. Gaisano and Robert G. Tsushima (2008). " Inhibition of Cholesterol Biosynthesis Impairs Insulin Secretion and Voltage-Gated Calcium Channel Function in Pancreatic β-Cells ". Endocrinology. 149 (10): 5136–5145. doi:10.1210/en.2008-0161.{{cite journal}}: CS1 maint: multiple names: authors list (link)--Doc James (talk · contribs · email) 15:55, 1 June 2009 (UTC)

Thanks - Its now been dealt with

There are a series of paper which followed this one but that would overload the page with citations. The squalene epoxidase inhibitors allowed the researchers to eliminate any confusion over CoQ10 depletions (covered in the paper above). There is much trial based evidence in the retrospective reviews. The hard in vitro evidence is there for both murine and human cells. The clinical trial data is strongly supportive (in so far as trials can be conclusive of anything). Glynwiki (talk) 15:59, 3 June 2009 (UTC)

Duane Graveline

This seems like nothing more than a promoting of the above authors work.--Doc James (talk · contribs · email) 15:59, 1 June 2009 (UTC)
Thanks Doc James, Have you read the books? The author has taken the trouble to cite in support and we could bring other citations forward eventually as the article develops a level of detail? Also.... Do feel free to contribute your citations on this matter as extra insight and factual content will help greatly. The influence and potential of 'inhibitors' in all parts of the mevalonate pathway for both research purposes and hopefully medications where appropriate. Have you looked at the field of squalene epoxidase inhibitors.
As a new comer I appreciate your help with specific issues you raise ith wiki compliance and procedure. Thanks for taking an interest in my topics Glynwiki (talk) 10:55, 2 June 2009 (UTC)

Article Assessment for WikiProject Medicine

Hello. I am a member of WikiProject Medicine, a Wikipedia wide project that maintains and improves articles that fall under the scope of medicine. Since your article has fallen under our scope, I have placed the correct template(s) on this talk page for verification. Upon reviewed of the article, I'd like to make a few points, as shown below:

• Assess article with class and importance factors
• Added Jargon template on page, please make sure you define medical and physic terms for us non-Mevalonate inhibition people. ;)

I'm glad this article could fall within our scope, and I hope to see it grow large! Many thanks! Renaissancee (talk) 21:50, 2 June 2009 (UTC)

Thanks - do you see any WP:SYN or NPOV problems here?
Any jargon busting issues and ideas are very welcome.
We do have a fight for survival going on but I'm sure this will help.
Glynwiki (talk) 06:28, 3 June 2009 (UTC)

To be honest, I really can't because of all the jargon in the article. It's quite hard to read, so I think you should clean up the jargon before doing anything else. If it's really bad you may need to rewrite it all over again. Renaissancee (talk) 21:54, 3 June 2009 (UTC)

More tau

So if you read the paper. It starts by saying that statins lead to a "decrease in beta-amyloid production, a major constituent of the plaques" then it goes on to say that in rat tissue culture "may evoke phosphorylation of tau". This is than written as "when normal phosphorylation is interfered with by mevalonate blockade, our cells increase the production of Tau protein"

This I will repeat is dishonest. Expecially when it goes on to say "Tau is the protein substance of the Neurofibrillary tangles common to Alzheimers and other neurodegenerative disease" why do we not say "Tau proteins are microtubule-associated proteins that are abundant in neurons in the central nervous system and are less common elsewhere"

What seems to me to be happening is that bits and pieces of primary sources are being used to create WP:OR to refute better quality research. Ideas are being inappropriately positioned to make what is written more significant than it actually is. Cheers--Doc James (talk · contribs · email) 20:27, 4 June 2009 (UTC)

To Doc James - I'm not disputing your correction at this point just your assertion of lack of good faith by the use of the word 'dishonest' over perhaps 'mistaken'. Which I understand to be very un-wikipedian as described in WP:AGF. I do not yet concede your interpretation of the paper but need to make checks as neither of us is infallible on this matter. I presume we can agree it is important that wikipedia is correct. Glynwiki (talk) 10:54, 6 June 2009 (UTC)

Please be careful using the word libelous. See WP:LEGAL.--Literaturegeek | T@1k? 11:16, 6 June 2009 (UTC)
Point taken and amended - I have assumed good faith and marked the section for improved references and verification.Glynwiki (talk) 13:46, 6 June 2009 (UTC)

I do not like the making of clinical claims on the basis of in vitro work. Expecially since in vivo work has been done and has shown the opposite of many of the conclusions of what is written here. The use of Statins for primary prevention is very controversial see http://www.ti.ubc.ca/node/52 but the evidence is good for secondary prevention http://www.ti.ubc.ca/node/51 --Doc James (talk · contribs · email) 16:49, 8 June 2009 (UTC)

I agree with you on that assessment of statins. That is why I am being careful about merge and redirect activity. The science of mevalonate metabolic blockade related but separate from clinical impact at present. In-vitro work represent what happens in cells, parameters are controlled and results are factual evidence. In-vivo work tends to be either anecdotal or based on trial statistics. In-vivo can produce strong associative signposts. Even with high confidence - probabilities are just that. Too much associative evidence from trials is treated as being causal. That is how we got the over-zealous application of the hmg-coa reductase inhibitors which are basically defensive plant toxins. Useful but risky!Glynwiki (talk) 20:43, 11 June 2009 (UTC)

'Tangled proteins may spread Alzheimer's through brain' Journal reference: Nature Cell Biology (DOI: 10.1038/ncb1901)91.125.48.147 (talk) 18:26, 12 June 2009 (UTC)

Attempted Merge aborted

As I am not very well versed with Mevalonate inhibition or Statin, is suggest that a qualified editor merge these two articles while maintaining the cause and effect hierarchy Wikishagnik (talk) 18:18, 11 March 2012 (UTC)