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wrotek
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Posted: Wed Mar 19th, 2008 21:36 |
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Very interesting...
I have been looking at Naltrexone(opioid antagonist) side effects http://www.minddisorders.com/Kau-Nu/Naltrexone.html
Side effects The following represents the most common side effects associated with naltrexone:- nausea, vomiting, diarrhea, cramps
- headache, insomnia, anxiety, irritability, depression, dizziness
- joint and muscle pain
- rash
Does not look like something Th1 person would want :]
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Lyme reflux chronic pain fatigue depression 125D36 Ph1Sep05 Ph2Oct06 Ph3Apr07 homebound in low lux NoIRs 25D<7 Oct06
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hullcrush
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Posted: Thu Mar 27th, 2008 06:03 |
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I'm confused by the mention of St. John's Wort being negative... It induces the metabolism of Vitamin D via increasing (<--- I guess this where I don't know) its respective hydroxylase, much like phenytoin and phenobarbitol.
"Here we show that these drugs lead to the upregulation of 25-hydroxyvitamin D(3)-24-hydroxylase (CYP24) gene expression through the activation of the nuclear receptor pregnane X receptor (PXR; NR1I2). CYP24 is a mitochondrial enzyme responsible for inactivating vitamin D metabolites. CYP24 mRNA is upregulated in vivo in mice by pregnenolone 16alpha-carbonitrile and dexamethasone, 2 murine PXR agonists, and in vitro in human hepatocytes by rifampicin and hyperforin, 2 human PXR agonists . Moreover, rifampicin increased 24-hydroxylase activity in these cells, while, in vivo in mice, pregnenolone 16alpha-carbonitrile increased the plasma concentration of 24,25-dihydroxyvitamin D(3)."
So is the paper simply illustrating the differences in cyp24 metabolism between mice and glass? I would not believe it be difficult to give rifampicin to a mouse, maybe they should have....
So if cyp3a4 induction is bad, would inhibition be positive. Or am I discussing an irrelevant biochemical pathway?
Last edited on Thu Mar 27th, 2008 06:33 by hullcrush
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Allergic fatigue, minimal sun exposure, no palliative medications. Start 05/07/08.
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wrotek
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Posted: Fri Mar 28th, 2008 18:35 |
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This paper has interesting graph showing how xenobiotics(for example cafestol or St. John's worth hyperforin, rifampicin) react with PXR which is compared how 1,25-D reacts with VDR.
Stay tuned to PXR: an orphan actor that may not be D-structive only to bone
http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=539210&blobtype=pdf
Figure 1 A schematic illustrating how xenobiotics and drugs that activate PXR can disrupt vitamin D metabolism and vitamin D function. The kidney is responsible for converting 25(OH)D to 1,25(OH)2D. Once formed, 1,25(OH)2D enters the blood and travels to its calcium-regulating target tissues, where it interacts with its specific nuclear VDR. This complex binds RXR, and the resulting heterodimeric complex binds to specific VDREs in the DNA, leading to regulation of gene expression responsible for calcium and bone metabolism. 25(OH)D can also be metabolized in a wide variety of tissues, including colon, prostate, breast, and skin, where it acts either as an autocrine or paracrine hormone to regulate cell growth and carry out other physiologic functions. Xenobiotics and drugs that activate PXR bind RXR. This heterodimeric complex is recognized by the VDRE of CYP24, which is responsible for the destruction of 1,25(OH)2D into a water-soluble, inactive metabolite. The activated PXR-RXR complex may also be able to alter other VDREs that have wide-ranging biologic functions in cell growth and maturation, immunomodulation, renin and insulin production, and osteoblast function. Understanding of the consequences of this potential interaction and alteration of VDRE gene expression on noncalcemic functions of vitamin D requires further investigation.
So, xenobiotics downregulate both 25-D and 1,25-d ?
Last edited on Fri Mar 28th, 2008 18:42 by wrotek
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Lyme reflux chronic pain fatigue depression 125D36 Ph1Sep05 Ph2Oct06 Ph3Apr07 homebound in low lux NoIRs 25D<7 Oct06
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Dr Trevor Marshall
Research Team
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Posted: Fri Mar 28th, 2008 18:43 |
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Except that PXR activation downregulates CYP24 and PXR antagonists upregulate CYP24 (see my latest paper, fig 1.). This is the danger of people who don't fully understand Molecular Biology trying to form hypotheses by groping about in the dark.
Michael Holick himself (the author) says he takes 11,000 IU of Vitamin D a day. No wonder his brain is oddled
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wrotek
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Posted: Fri Mar 28th, 2008 18:55 |
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I see, so it happens inversely Both 25-D an 1,25-D will increase upon PXR agonists ?
Last edited on Fri Mar 28th, 2008 18:56 by wrotek
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Lyme reflux chronic pain fatigue depression 125D36 Ph1Sep05 Ph2Oct06 Ph3Apr07 homebound in low lux NoIRs 25D<7 Oct06
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Dr Trevor Marshall
Research Team
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Posted: Fri Mar 28th, 2008 20:23 |
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Not necessarily, because 25-D and 1,25-D are themselves antagonists of PXR. There is a complex feedback loop set up. Look at Fig 1 of my latest paper. Carefully!
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wrotek
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Posted: Sat Mar 29th, 2008 01:20 |
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Is there a possibility that bugs also disable(act on) other nuclear receptors so 1,25-D cannot be dowregulated through them too, like PXR ?
Last edited on Sat Mar 29th, 2008 02:28 by wrotek
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Lyme reflux chronic pain fatigue depression 125D36 Ph1Sep05 Ph2Oct06 Ph3Apr07 homebound in low lux NoIRs 25D<7 Oct06
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wrotek
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Posted: Wed Apr 9th, 2008 04:17 |
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Nicotine is a PXR agonist ?
http://lib.bioinfo.pl/pmid:15364541
Nicotine, the psychoactive and addictive chemical in cigarettes, and a known inducer of brain CYP2B6, was an efficacious activator of PXR and inducer of CYP3A4 transcription. Because nicotine activation of PXR will enhance metabolism of nicotine to the non-psychoactive cotinine, these results provide one molecular mechanism for the development of tolerance to nicotine. Moreover, the identification of PXR in many human tissues, such as brain, and activation by tissue specific ligands (such as neurosteroids) suggests additional biological roles for this receptor in these tissues.
Last edited on Wed Apr 9th, 2008 04:17 by wrotek
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Lyme reflux chronic pain fatigue depression 125D36 Ph1Sep05 Ph2Oct06 Ph3Apr07 homebound in low lux NoIRs 25D<7 Oct06
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Dr Trevor Marshall
Research Team
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Posted: Wed Apr 9th, 2008 05:09 |
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Hmmm. That would make sense. I have often noted that smoking is reported to sometimes abate Th1 symptoms, and activation of PXR would be a loose enough perturbation to the D metabolism to correlate with the minor symptomatic observations that people have been recounting to me.
Thanks for this, Wrotek, it makes sense. It will take a lot of effort for me to confirm, however, as nicotine is rapidly metabolized in the body, and I don't know which of the intermediate compounds (or glycosylates) might be PXR-active. This is one time where wet biology has the experimental advantage (of simplicity) over molecular modeling
When I have some time spare I will check all the well-known metabolites:
http://tinyurl.com/5dd3vv
ps: the Danish study on smoking found that 25-D and 1,25-D levels were lower in smokers than in non-smokers. Which would correlate with PXR-agonism, as reported in the study you forwarded
http://www.ncbi.nlm.nih.gov/pubmed/10602348
Last edited on Wed Apr 9th, 2008 05:12 by Dr Trevor Marshall
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Markt9452
Member in Phase 3
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Posted: Wed Apr 9th, 2008 21:17 |
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Does that mean I should start smoking or stop smoking? 
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Th1 Lyme Symptoms 125D20 D2510 Ph1Feb08 Ph2Apr08 Ph3Oct08 daily med.exp covered up NoIRs| MyStory|
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Dr Trevor Marshall
Research Team
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Posted: Wed Apr 9th, 2008 22:53 |
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You should stop smoking, for all the reasons that smoking is regarded as being bad for you.
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wrotek
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Posted: Thu Apr 10th, 2008 00:41 |
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Coffee and cigarettes composition starts to be very interesting in regard to vitamin D metabolism
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Lyme reflux chronic pain fatigue depression 125D36 Ph1Sep05 Ph2Oct06 Ph3Apr07 homebound in low lux NoIRs 25D<7 Oct06
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wrotek
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Posted: Sat Apr 19th, 2008 23:11 |
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http://www.ncbi.nlm.nih.gov/pubmed/17053540
Association between coffee consumption and markers of inflammation and cardiovascular function during mental stress. Hamer M, Williams ED, Vuononvirta R, Gibson EL, Steptoe A. Department of Epidemiology and Public Health, University College London, London, UK. m.hamer@ucl.ac.uk BACKGROUND:
Coffee is widely consumed in the Western diet and therefore has important implications for public health. Research findings pertaining to the effects of coffee consumption on cardiovascular health are conflicting, and the role of caffeine is not clear. OBJECTIVE: To examine the relationship between coffee intake, inflammation and cardiovascular function at baseline and during mental stress, both cross-sectionally and after a 4-week period of withdrawal of coffee during which intake of caffeine was maintained. METHODS: Eighty-five healthy, non-smoking men with varying coffee-drinking habits were recruited. Blood pressure, heart rate, and markers of inflammation [C-reactive protein (CRP), von Willebrand factor antigen (vWF)], were measured at baseline and during mental stress. These measures were repeated after a 4-week period of withdrawal of coffee, during which intake of caffeine was maintained. Habitual levels of coffee and caffeine consumption were assessed from a self-reported questionnaire, and saliva samples for the analysis of caffeine concentrations were collected regularly throughout the period of withdrawal, to confirm compliance. RESULTS: Multiple linear regression analysis of pre-withdrawal data, adjusted for age, body mass index and intake of tea, red wine, fruit, vegetables, oily fish and dietary supplements revealed that coffee consumption was positively related to baseline systolic blood pressure, and increased heart rate and vWF responses to mental stress. Four weeks after withdrawal of coffee, the heightened vWF and heart rate responses to stress in habitual coffee drinkers persisted, whereas baseline systolic blood pressure had decreased. Total caffeine intake was unrelated to any measures of physiological function. CONCLUSIONS: Habitual coffee consumption is associated with heightened acute vascular inflammatory responses to mental stress, although these effects are not affected by short-term abstinence from coffee. These findings suggest that the relationship between coffee and markers of cardiovascular risk may be explained by residual or unmeasured confounding factors. PMID: 17053540 [PubMed - indexed for MEDLINE]
Very interesting, long lasting effects of coffee on inflammation(after abstinence even for 4 weeks), not caffeine related.
Last edited on Sun Apr 20th, 2008 04:09 by wrotek
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Lyme reflux chronic pain fatigue depression 125D36 Ph1Sep05 Ph2Oct06 Ph3Apr07 homebound in low lux NoIRs 25D<7 Oct06
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patsysweeney
Member in Phase 3
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Posted: Mon Apr 21st, 2008 01:13 |
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Toni,
I have written to Oprah 3 times to do a show about Sarcoidosis and the Marshall Protocol. Maybe we should all write and see if she wants to be instrumental in taking the blinders off the Medical World. What do you think?
Thank God for all of you!
Last edited on Mon Apr 21st, 2008 01:17 by patsysweeney
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Sarcoidosis/lungs/eyes/glands 125D63 25D10 19July06 MPh1Aug06 Ph2Dec06 Ph3Aug07 RsPh3Apr08 (Bells Palsy 2003) Daily atenenol zoloft diclofenac skelaxin advair synthroid NoIRs-Lowlux homebound.
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wrotek
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Posted: Sat Apr 26th, 2008 23:43 |
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Anecdotal story from oxyplus yahoo discussion group
Hi Laurie, There was a woman I know that suffered from fibro for years who recently found out it was the coffee bean that was causing her symptoms. She came off coffee and all the symptoms went away. She had her life back. But one cold winter day she thought she'd have some coffee and, low and behold, the pain came back. For her it was really significant and it took years to discover!
some quotes from our discussion
Hi Wrotek, The woman is a beautician and our conversation was over a hair cut so I don't have a lot of details. She mentioned once having had fibromyalgia, and yes, it did cause years of fatigue/pain. Her comment about it being the coffee bean (she specifically said coffee bean, not caffeine) that was the enemy for her.
Last edited on Sun Apr 27th, 2008 01:16 by wrotek
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Lyme reflux chronic pain fatigue depression 125D36 Ph1Sep05 Ph2Oct06 Ph3Apr07 homebound in low lux NoIRs 25D<7 Oct06
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Lottis
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Posted: Tue Apr 29th, 2008 13:44 |
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It has been said by a doctor at our hospital that we would not be able to run it without coffee, because coffee is the fuel to the complete machinery! 
Now if we combine the coffee, the cigarettes, the prions in the urine and all the L-form bacteria from the medications, the bio films on the tools and and all the blood from operations and lab tests, we have a deep understanding why coffee is so important and that many women working in hospitals have a problem stopping smoking!
Women working in hospitals are the most sick occupational unit, and now we can clearly see why. What an enormous sacrifice being done to nurse and help others! 
/Lottis
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HTN,LVH,CHF,arrhythmia,hypercholesterol,IBS? fibromyalgia?salivarystones,gallstones,ect...|15feb-07 init. 1,25D 37,5,|25-D 7,8(latest 15/2-07)| Ph1 29/7-08| Palliativ Meds. at the present; |Zoloft|NoIR's|covered up|disabled|
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mercuryspice
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Posted: Mon May 12th, 2008 07:46 |
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is it ok to have one cup a day?
thanks much
lisa
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Lyme 25d 11, 125D44 25D11 Ph1 Sep06 ModPh2Jan07 Ph2Oct 07 Ph3May08 motrin flexeril wellbutrin prozac ativan NoIRs lite exp r/t to school
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Deb Grabetz
Member in Phase 3
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Posted: Mon May 12th, 2008 15:47 |
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Hi Lisa,
I love my coffee...and have really had a tough time having to adjust to not having it....so I take 1/2 cup and add water to this to weaken it in the morning. I'm trying to wean off of it to completely to see how I react. I usually have to microwave my coffee/water mixture as it is not hot enough once I dilute!
Try it...it is 1/2 the coffee yet gives me the satisfaction I still need of that cup in the morning.
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Sarcoidosis/lungs, lymph,liver, GI, neuro, D125,42,D125,18 (5/09) Ph1,7/07, Ph2,3/08,cover up, NoIRs, low lux home,Back to work after 2 yrs; 4/07D25/11 1/08D25-0 Weaned Pred with MP/Massage
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schesche
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Posted: Wed May 14th, 2008 02:31 |
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does this mean--apples should be avoided?
i eat about 10 a week
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CFS, Lyme/neuro,joint pain,brain fog, insomnia,rage 125D56, MP 10/07, Triazep, zolpid, bvi, NoIRs, low lux home, lite exp. r/t work, covered up, 25D16
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Dr Trevor Marshall
Research Team
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Posted: Wed May 14th, 2008 02:40 |
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"An apple a day keeps the Doctor away"
but I am not sure about two...
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