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Superbugs common in New Delhi
 Moderated by: Dr Trevor Marshall  

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Dr Trevor Marshall
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 Posted: Thu Apr 7th, 2011 10:55

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It seems that a gene thought to confer superbugs with the ability to evade beta-lactam antibiotics is common in New Delhi drinking water:

http://www.reuters.com/article/2011/04/07/us-bacteria-superbugs-india-idUSTRE7357W920110407

I am linking to this article as IMO it shows an incredible lack of competence and knowledge on the part of people whom we rely upon to understand pathogenic bacteria, and how antibiotics really work.

What do you think? Do they seem to be asking the questions a good scientist would ask? Such as "why aren't people dying from these superbugs, then?"

As food for thought, here is a slide from the presentation of Francisco Guamer, at the Vancouver Microbiome conference, contrasting UK and Indian demographics for ulcerative colitis:



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 Posted: Thu Apr 7th, 2011 12:10

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Is it possible the population in India hasn't been as subjected to Vitamin D supplementation or fortification?

Rico



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 Posted: Thu Apr 7th, 2011 12:25

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Unlikely, as powdered milk shipped from Europe to India has been fortified since the 1950's. Powdered milk is a staple of Indian cooking, I am told :(
 

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 Posted: Thu Apr 7th, 2011 12:46

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So, what is one to deduce from the graph, then? An increased microbiome for those moving to different parts of the world (e.g., people from India moving to Europe) or those experiencing greater exposure to people from other parts of the world (e.g., Europeans having greater exposure to immigrants) will likely result in increased disease? What was the context of the presentation?



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Dr Trevor Marshall
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 Posted: Thu Apr 7th, 2011 12:48

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The context was that more than one species was likely to be involved in  disease pathogenesis :)
 
The diet is very different in the UK, especially livestock handling...
 

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 Posted: Thu Apr 7th, 2011 16:48

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Vegetarian as of Dec 21st... :?



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findinganswers
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 Posted: Sat Apr 9th, 2011 02:27

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Dr Trevor Marshall wrote: The context was that more than one species was likely to be involved in  disease pathogenesis :)
 
The diet is very different in the UK, especially livestock handling...
 

I wonder if there is any difference in the amount of turmeric (the orange-colored spice in Indian cooking / curries) eaten by those in the UK. Turmeric contains a lot of curcumin, which you have said is a VDR agonist based on your own in-silico modelling (right?) I wonder if eating a lot of it would provide enough curcumin to the cells of the digestive tract to activate their VDR's enough to stave off bacterial infestation causing ulcerative colitis?



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 Posted: Sat Apr 9th, 2011 03:21

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I wonder if there is any difference in the amount of turmeric (the orange-colored spice in Indian cooking / curries) eaten by those in the UK. Turmeric contains a lot of curcumin, which you have said is a VDR agonist based on your own in-silico modelling (right?) I wonder if eating a lot of it would provide enough curcumin to the cells of the digestive tract to activate their VDR's enough to stave off bacterial infestation causing ulcerative colitis?
I think east Indians eat lots of turmeric in India as well.  They wouldn't just start eating more while in the U.K.

But I would believe that something in the food that is part of the problem. Like hormones in live stock, bpa, vit d supplementation. There are so many different chemical additives in food that it would be hard to find just one that is responsible for the disease.

I never been India but I imagine people buy every thing whole, straight from the farm. grown the old fashion way with out the use biotechnology to make quick bucks. But I bet that is probably changing exponentially too.



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findinganswers
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 Posted: Sat Apr 9th, 2011 05:38

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Marty.K wrote: I think east Indians eat lots of turmeric in India as well.  They wouldn't just start eating more while in the U.K.
I was suggesting eating turmeric might prevent ulcerative colitis, and that they might eat less of it in the UK. I should have worded the last sentence differently. "I wonder if eating a lot of it would provide enough curcumin to the cells of the digestive tract to activate their VDR's enough to stave off the bacterial infestation causing ulcerative colitis."

Last edited on Sat Apr 9th, 2011 05:59 by findinganswers



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 Posted: Sat Apr 9th, 2011 07:49

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I always thought curcumin was a vdr antagonist. :?

Last edited on Sat Apr 9th, 2011 07:50 by Marty.K



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Dr Trevor Marshall
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 Posted: Sat Apr 9th, 2011 11:18

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I am not sure what it is, agonist or antagonist, but I am sure its docking position in the VDR is very similar to 1,25-D and that it will displace 1,25-D as curcumin's dosage rises above a few hundred milligrams.

Here are the two molecules (1,25-D in green backbone) in their superimposed VDR docking configurations:


findinganswers
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 Posted: Sat Apr 9th, 2011 15:47

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Marty.K and Trevor,

Here are the posts I was making my assumptions from:

http://marshallprotocol.com/view_topic.php?id=12607&forum_id=39&highlight=curcumin#p192613

and

http://marshallprotocol.com/view_topic.php?id=12607&forum_id=39&highlight=circumin#p194318

Last edited on Sat Apr 9th, 2011 15:53 by findinganswers



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Dr Trevor Marshall
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 Posted: Sat Apr 9th, 2011 16:59

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I haven't looked into the actions of circumin in detail, as there is too little data on in-vivo concentration, etc. Also, it really is very difficult to discern antagonism from agonism using in-silico.

I just read (on slashdot) that "Curcumin and L-Carnitine lower TNF-alpha and C-reactive protein."  If that is true then circumin would likely be a VDR antagonist. Maybe somebody might take the time to pore through all the literature and check that statement, and also  the known transcriptomes for TNF-alpha and CRP. My mind is full of other things at the moment :X

..Trevor..

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 Posted: Sat Apr 9th, 2011 19:51

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I did a fast pass through Google Books and now quote:

Nutrition, Epigenetic Mechanisms, and Human Disease
 By Nilanjana Maulik, Gautam MaulikP

Many hits on curcumin.

Sherry



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 Posted: Sun Apr 10th, 2011 08:26

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I found this abstract at Pub Med. I hope it has some helpful info.....Terry

http://www.ncbi.nlm.nih.gov/pubmed/20153625

[url=javascript:AL_get(this, 'jour', 'J Nutr Biochem.');]J Nutr Biochem.[/url] 2010 Dec;21(12):1153-61. Epub 2010 Feb 12.

Curcumin: a novel nutritionally derived ligand of the vitamin D receptor with implications for colon cancer chemoprevention.
Bartik L, Whitfield GK, Kaczmarska M, Lowmiller CL, Moffet EW, Furmick JK, Hernandez Z, Haussler CA, Haussler MR, Jurutka PW.

Department of Biochemistry and Molecular Biophysics, College of Medicine, The University of Arizona, Tucson, AZ 85724, USA.


Abstract
The nuclear vitamin D receptor (VDR) mediates the actions of 1,25-dihydroxyvitamin D(3) (1,25D) to regulate gene transcription. Recently, the secondary bile acid, lithocholate (LCA), was recognized as a novel VDR ligand. Using reporter gene and mammalian two-hybrid systems, immunoblotting, competitive ligand displacement and quantitative real-time PCR, we identified curcumin (CM), a turmeric-derived bioactive polyphenol, as a likely additional novel ligand for VDR. CM (10(-5) M) activated transcription of a luciferase plasmid containing the distal vitamin D responsive element (VDRE) from the human CYP3A4 gene at levels comparable to 1,25D (10(-8) M) in transfected human colon cancer cells (Caco-2). While CM also activated transcription via a retinoid X receptor (RXR) responsive element, activation of the glucocorticoid receptor (GR) by CM was negligible. Competition binding assays with radiolabeled 1,25D confirmed that CM binds directly to VDR. In mammalian two-hybrid assays employing transfected Caco-2 cells, CM (10(-5) M) increased the ability of VDR to recruit its heterodimeric partner, RXR, and steroid receptor coactivator-1 (SRC-1). Real-time PCR studies revealed that CM-bound VDR can activate VDR target genes CYP3A4, CYP24, p21 and TRPV6 in Caco-2 cells. Numerous studies have shown chemoprotection by CM against intestinal cancers via a variety of mechanisms. Small intestine and colon are important VDR-expressing tissues where 1,25D has known anticancer properties that may, in part, be elicited by activation of CYP-mediated xenobiotic detoxification and/or up-regulation of the tumor suppressor p21. Our results suggest the novel hypothesis that nutritionally-derived CM facilitates chemoprevention via direct binding to, and activation of, VDR.
Copyright © 2010 Elsevier Inc. All rights reserved.
PMID: 20153625 [PubMed - indexed for MEDLINE]PMCID: PMC2891903 [Available on 2011/12/1



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 Posted: Sun Apr 10th, 2011 17:00

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Terry, it looks like in-vitro and in-silico agree again :) I would have guessed at agonist, based on the location of the oxygens, and the residues which circumin binds to (based on my Ligplot analyses, unpublished).

The in-vitro study notes it's profile in differing receptors is different from 1,25D, however, so it most probably would interfere with the way Olmesartan's receptor profile is 'just right'. In-silico indicates a concentration of several micromolar of circumin being needed, about 20 times higher than Olmesartan.

But it leads to an intriguing theory about disease  profiles in India, where Lupus is also low in incidence. I will float this concept during my Singapore presentation in November :)
 

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 Posted: Mon Apr 11th, 2011 08:22

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Dr Marshall in light of this discussion of curcumin .. should we avoid CM in our diets so as not to interfere with the actions of olmesartan?  

Last edited on Mon Apr 11th, 2011 08:28 by ChrisMavo



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Dr Trevor Marshall
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 Posted: Mon Apr 11th, 2011 15:09

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Dr Marshall in light of this discussion of curcumin .. should we avoid CM in our diets so as not to interfere with the actions of olmesartan?
The concentration needed to cause problems is about 10 times that of Olmesartan. Provided you keep the amount of circumin under 40 or 50milligrams you shouldn't experience too much trouble, and will be able to enjoy your curry :)
 
If the concentration is not under your control, then it is best to avoid, yes...
 

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 Posted: Tue Apr 12th, 2011 13:50

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PGA Terry,

Thanks for posting that study's complete abstract. sdcreacy referred to that study in the first post I referenced above about where I was making my assumptions from. :)

Also, further down in that same forum (http://marshallprotocol.com/view_topic.php?id=12607&forum_id=39&highlight=curcumin#p194310 - at the top of the page when you click the link), sdcreacy tells about a bad skin reaction after using a "preparation" of curcumin (related to its differing profile in other receptors?). I have not had problems with turmeric in my diet.

Last edited on Tue Apr 12th, 2011 15:30 by findinganswers



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