Vitamin D -- IL-12p40 - Mycobacterium SPP -- Paratuberculosis - LDN to CURE?
randall
OK, this was unexpected to start with D in the gut and end up with LDN
again.
See how I got there.
This was a FUN post/thread for me. :)
http://www.ncbi.nlm.nih.gov/pubmed/19450178
Regulation of the colonic vitamin D system for prevention of tumor
progression: an update.
Cross HS, Kallay E.
Department of Pathophysiology, Medical University of Vienna,
Waehringerguertel 18-20, A-1090 Vienna, Austria.
heide...@meduniwien.ac.at
A compromised vitamin D status and nutritional calcium deficit are
linked with sporadic colorectal cancer incidence. 25(OH)D(3) serum
concentration is a major determinant of 1,25-dihydroxyvitamin D3 (1,25
[OH](2)D(3)) synthesis in colonic mucosa, which expresses the vitamin
D receptor and both the synthesizing (CYP27B1) and catabolic (CYP24A1)
hydroxylases. Receptor-bound, 1,25(OH)(2)D(3) regulates proliferation,
differentiation and apoptosis in an autocrine/paracrine manner. During
early malignancy 1,25(OH)(2)D(3) synthesis is often enhanced to
counteract hyperproliferation. In many advanced tumors, vitamin D
catabolism surpasses synthesis. In vivo, expression and activity of
CYP27B1 and vitamin D receptor are stimulated by (phyto)estrogens.
Conversely, low nutritional calcium and folate enhance vitamin D
catabolism. These insights could explain the lower colorectal cancer
incidence in females, the chemopreventive potency of vitamin D and
calcium against colorectal cancer, and the benefit of nutritional
folate as a methyl donor for epigenetic regulation of the vitamin D
system.
PMID: 19450178
CYP* + psoria* [19 hits on pubmed]
http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=DetailsSearch&term=cyp*+AND+psoria*&log$=activity
CYP-450
http://en.wikipedia.org/wiki/Cytochrome_P450
==============
The abstract for___ exercise/supplements___ today's last thread.
Found here:
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/msg/bae4329081339b74
Called:
FLAKE GENEs --- TOPICALs - Stress -- Lithium -- ___EXERCISE vs
Supplements___... Options
http://www.ncbi.nlm.nih.gov/pubmed/19433800
Antioxidants prevent health-promoting effects of physical exercise in
humans.
Ristow M, Zarse K, Oberbach A, Klöting N, Birringer M, Kiehntopf M,
Stumvoll M, Kahn CR, Blüher M.
Department of Human Nutrition, Institute of Nutrition, University of
Jena, Jena D-07743, Germany;
Exercise promotes longevity and ameliorates type 2 diabetes mellitus
and insulin resistance. However, exercise also increases mitochondrial
formation of presumably harmful reactive oxygen species (ROS).
Antioxidants are widely used as supplements but whether they affect
the health-promoting effects of exercise is unknown. We evaluated the
effects of a combination of vitamin C (1000 mg/day) and vitamin E (400
IU/day) on insulin sensitivity as measured by glucose infusion rates
(GIR) during a hyperinsulinemic, euglycemic clamp in previously
untrained (n = 19) and pretrained (n = 20) healthy young men. Before
and after a 4 week intervention of physical exercise, GIR was
determined, and muscle biopsies for gene expression analyses as well
as plasma samples were obtained to compare changes over baseline and
potential influences of vitamins on exercise effects. Exercise
increased parameters of insulin sensitivity (GIR and plasma
adiponectin) only in the absence of antioxidants in both previously
untrained (P < 0.001) and pretrained (P < 0.001) individuals. This was
paralleled by increased expression of ROS-sensitive transcriptional
regulators of insulin sensitivity and ROS defense capacity, peroxisome-
proliferator-activated receptor gamma (PPARgamma), and PPARgamma
coactivators PGC1alpha and PGC1beta only in the absence of
antioxidants (P < 0.001 for all). Molecular mediators of endogenous
ROS defense (superoxide dismutases 1 and 2; glutathione peroxidase)
were also induced by exercise, and this effect too was blocked by
antioxidant supplementation. Consistent with the concept of
mitohormesis, exercise-induced oxidative stress ameliorates insulin
resistance and causes an adaptive response promoting endogenous
antioxidant defense capacity. Supplementation with antioxidants may
preclude these health-promoting effects of exercise in humans.
PMID: 19433800
---------------
http://www.ncbi.nlm.nih.gov/pubmed/19454718
Differential role for c-Rel and C/EBPbeta/delta in TLR-mediated
induction of proinflammatory cytokines.
Lu YC, Kim I, Lye E, Shen F, Suzuki N, Suzuki S, Gerondakis S, Akira
S, Gaffen SL, Yeh WC, Ohashi PS.
The Campbell Family Institute for Breast Cancer Research, Ontario
Cancer Institute, Ontario, Canada.
TLR stimulation triggers a signaling pathway via MyD88 and IL-1R-
associated kinase 4 that is essential for proinflammatory cytokine
induction. Although NF-kappaB has been shown to be one of the key
transcriptional regulators of these cytokines, evidence suggests that
other factors may also be important. In this study, we showed that
MyD88-deficient macrophages have defective c-Rel activation, which has
been linked to IL-12p40 induction, but not IL-6 or TNF-alpha. We also
investigated other transcription factors and showed that C/EBPbeta and
C/EBPdelta expression was limited in MyD88- or IL-1R-associated kinase
4-deficient macrophages treated with LPS. Importantly, the absence of
both C/EBPbeta and C/EBPdelta resulted in the impaired induction of
proinflammatory cytokines stimulated by several TLR ligands. Our
results identify c-Rel and C/EBPbeta/delta as important transcription
factors in a MyD88-dependent pathway that regulate the induction of
proinflammatory cytokines.
PMID: 19454718
For IL-12p40 see pmid # 15251981
http://www.copewithcytokines.de/cope.cgi?key=IL12-p40
IL12 P40 subunit + psoria* (40 hits)
-----------------------
Oh man! Bret would be proud of me right now...
I'm like having a myco nano bac OH! moment iirc. LOL
http://www.ncbi.nlm.nih.gov/pubmed/19454688
In situ IL-12/23p40 production during mycobacterial infection is
sustained by CD11bhigh dendritic cells localized in tissue sites
distinct from those harboring bacilli.
Rothfuchs AG, Egen JG, Feng CG, Antonelli LR, Bafica A, Winter N,
Locksley RM, Sher A.
Immunobiology Section, Laboratory of Parasitic Diseases, National
Institute of Allergy and Infectious Diseases, National Institutes of
Health, Bethesda, MD 20892, USA.
Although IL-12/23p40 is known to play a major role in host resistance
to Mycobacterium spp, the cellular source, tissue localization, and
regulation of p40 production during mycobacterial infection in vivo
has been unclear. In this study, we used IL-12/23p40eYFP (yet40)
reporter mice to track expression of the cytokine following
Mycobacterium bovis bacillus Calmette-Guérin (BCG) infection. We found
that in spleens of these mice, p40 production is initiated by a
transient burst from CD11b(low)CD11c(+) dendritic cells (DC) which are
later replaced at the onset of granuloma formation by CD11b(high)CD11c
(+) DC as the major source of the cytokine. The latter subset was also
found to be the key producer of DC-derived p40 in nonlymphoid tissue
and in both spleen and liver optimal production of the cytokine was
regulated by endogenous TNF-alpha. Although BCG and p40-expressing DC
were both observed in splenic white pulp, p40(+) DC rarely colocalized
with bacilli. Indeed, in vitro flow cytometry and confocal microscopy
indicated that the presence of intracellular bacteria is not required
for p40 production by DC and Transwell experiments confirmed that
soluble mycobacterial components are sufficient for inducing cytokine
expression by these cells. Moreover, when stimulated with LPS, DC
directly infected with BCG showed impaired IL-12p40 production in
vitro. Together, our findings establish CD11b(high) DC as a major
source of IL-12/23p40 during mycobacterial infection in situ and
implicate both soluble mycobacterial products and TNF-alpha in
stimulating sustained production of p40 by these cells.
PMID: 19454688
IL-12 p40 or IL12p40
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?hl=en&q=IL-12+p40+&start=0&scoring=d&hl=en&
or [13 hits
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?hl=en&q=IL-12p40+&start=0&scoring=d&hl=en&
http://en.wikipedia.org/wiki/Mycobacterium
Mycobacterium is a genus of Actinobacteria, given its own family, the
Mycobacteriaceae. The genus includes pathogens known to cause serious
diseases in mammals, including tuberculosis and leprosy.[1] The Latin
prefix "myco—" means both fungus and wax; its use here relates to the
"waxy" compounds in the cell wall.
[...]
http://en.wikipedia.org/wiki/Mycobacterium#Microbiologic_characteristics
-------
H'm maybe not if your a FISH. LOL
http://www.holar.is/aquafarmer/node151.html
Right a fish who doesn't get TB or drink milk. <g>
-------------
Unless we're allergic to our own skin? Then?
http://en.wikipedia.org/wiki/List_of_Normal_Flora_species
http://en.wikipedia.org/wiki/Actinobacteria
Actinobacteria or actinomycetes are a group of Gram-positive bacteria
with high G+C ratio
<sniP>
to guano time:
http://en.wikipedia.org/wiki/G%2BC_ratio
GC-content (or guanine-cytosine content), in molecular biology, is the
percentage of nitrogenous bases on a DNA molecule which are either
guanine or cytosine (from a possibility of four different ones, also
including adenine and thymine).
=================
So we look at cow's milk for Mycobacterium. Did that before i'm
thinking. Better check.
Six hits for randall mycobacterium dairy and seven for randall
mycobacterium milk on
the P ng
============
Only 461 hits:
http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=DetailsSearch&term=Mycobacterium+milk&log$=activity
17 hits for [Mycobacterium milk spp]
http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=DetailsSearch&term=Mycobacterium+milk+spp&log$=activity
Nothing is jumPing outa the milk and kicking me in the face.
Can't be TB in cow's milk as we'd know:
http://biblioteca.universia.net/ficha.do?id=626484
Is it an unKNOWable bug in milk?
Does it hook up with D3 or the lack of it during the winter?
Or paraTB?
http://www.ncbi.nlm.nih.gov/pubmed/9436127
-----
But 99.99% of milk is KILLED by heating right?
http://www.ncbi.nlm.nih.gov/pubmed/8852355
Thermal inactivation of several Mycobacterium spp. in milk by
pasteurization.
Grant IR, Ball HJ, Rowe MT.
Department of Food Science (Food Microbiology), Queen's University of
Belfast, Northern Ireland, UK.
The thermal inactivation of Mycobacterium avium, Myco. bovis, Myco.
fortuitum, Myco. intracellulare and Myco. kansaii in milk at 63.5
degrees C was investigated. Survivors were enumerated after heating
for 0, 5, 10, 15, 20 and 30 min and thermal death curves were
constructed for each species. Mycobacterium bovis and Myco. fortuitum
were found to exhibit linear thermal death curves and neither species
demonstrated any survival after heating at 63.5 degrees C for 30 min
(equivalent to holder pasteurization). In contrast, Myco. avium, Myco.
intracellulare and Myco. kansasii yielded thermal death curves which
exhibited significant 'tailing' and all three strains survived holder
pasteurization.
PMID: 8852355
--------------------
So we look at paratuberculosis in the P NG 12---> hits
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?hl=en&q=paratuberculosis+&start=0&scoring=d&hl=en&
Then look at MAP, Mycobacterium avium subspecies paratuberculosis
(MAP) on pubmed?
Only 1543 hits with the proverbial crohns hit right up top:
http://www.ncbi.nlm.nih.gov/pubmed/19457586
+++++++++++++++++++++++++
So the cow get's it and then someone get's crohns? We know that.
So we wiki it again. :)
http://en.wikipedia.org/wiki/Mycobacterium_avium_subspecies_paratuberculosis
Mycobacterium avium subspecies paratuberculosis is an obligate
pathogenic bacteria in the genus Mycobacteria.[1] It is often
abbreviated Map, M. paratuberculosis, or M. avium sub.
paratuberculosis. The type strain is ATCC 19698 (equivalent to CIP
103963 or DSM 44133).[2]
Pathophysiology
Map causes Johne's disease in cattle and other ruminants, and it has
long been suspected as a causative agent in Crohn's disease in humans;
this connection is controversial.[3]
Recent studies have shown that Map present in milk can survive
pasteurization, which has raised human health concerns due to the
widespread nature of Map in modern dairy herds. Map is heat resistant
and it is capable of sequestering itself inside white blood cells,
which may contribute to its persistence in milk. It has also been
reported to survive chlorination in municipal water supplies.
Even though Map is hardy, it is slow growing and fastidious, which
means it is difficult to culture. Many negative studies for Map
presence in living tissue, food, and water have used culture methods
to determine whether the bacteria is present. Due to recent advances
in our knowledge of the bacterium, some or all of these studies may
need to be re-evaluated on the basis of culture methodology.
Map, like most mycobacteria, is difficult to treat. It is not
susceptible to anti-tuberculosis drugs (which can generally kill
Mycobacterium tuberculosis), but can only be treated with a
combination of antibiotics such as Rifabutin and a macrolide such as
Clarithromycin. Treatment regimes can last years.[4][5]
Crohn's disease
MAP is recognized as a multi-host mycobacterial pathogen with a proven
specific ability to initiate and maintain systemic infection and
chronic inflammation of the intestine of a range of histopathological
types in many animal species including primates.[6]
On the assumption that Map is a causative agent in Crohn's disease,
the Australian biotechnology company Giaconda is seeking to
commercialize a combination of Rifabutin, clarithromycin, and
clofazimine as a potential drug therapy for Crohn's. As of April 2007,
Giaconda received United States FDA IND approval for this medication,
now called Myoconda[7]. With a clinical response of almost 95%, the
results of Phase II clinical trial of Myoconda are among the most
promising to date[8].
Anti-MAP treatments have been used successfully in the past[9][10] to
treat Crohn's disease. MAP has been found in larger numbers within the
intestines of Crohn's disease patients[11] than those with Ulcerative
Colitis and healthy controls.
======================
And guess what's going to be used for this.
Guess?
OK, LDN?
BinGO..
They boost the immune system with LDN
But rememeber to use ALA, aLc, nac and what ever suPPlements as
needed. :)
But don't exercise and take huge amounts of anti-ROS supplements.
Duh.. read the abstract up TOP.
http://en.wikipedia.org/wiki/Low_dose_naltrexone
[...]
She concluded that "LDN therapy appears effective and safe in subjects
with active Crohn’s disease."[1] Smith and her colleagues have since
received a substantial NIH grant and are proceeding with a definitive
Phase II placebo-controlled clinical trial.
In addition, there is some in vitro data that indirectly suggest the
potential benefits of LDN therapy. Many anecdotal accounts and case
reports have also been cited in favor of LDN therapy. Some of the many
conditions for which LDN has been reported as beneficial include
multiple sclerosis (in particular, the primary progressive variant
[2]), Crohn's disease, HIV/AIDS, chronic fatigue syndrome, irritable
bowel syndrome, psoriasis, fibromyalgia, ALS, autism in children, and
cancer. Several clinical trials have been planned and a few are
currently taking place.
<sniP>
There we go again.
All the same old players dressed uP with a new little factoid here and
there...
And it never stoPs....
And their controversy remains for us as well:
http://en.wikipedia.org/wiki/Low_dose_naltrexone#Controversy
Critics point out that the drug companies and doctors refuse to test
LDN on multiple sclerosis patients, as LDN boosts the immune system.
As a prevailing theory is that MS patients have over-active immune
systems, many do not feel that LDN is a safe drug for those with MS.
Critics also point to the fact that doctors who prescribe LDN to MS
patients tend to do it via a telephone conversation, without even
seeing the patients or their medical records, for which they receive a
payment from the person that they prescribed to. Many who use LDN for
multiple sclerosis can also suffer from side effects, including
stiffness, and the long term effects of using the drug are still
unknown.
<sniP>
=========================
So LDN will cure Farrah Fawcett's cancer and a half dozen other deals.
If you game it with ALA, ALC, NAC and some other supplements as
needed.
Let's run it on pumbed:
Dumb bed then... LOL
Ok, got one. No, two. Ok got three:
http://www.ncbi.nlm.nih.gov/pubmed/17222320
Low-dose naltrexone therapy improves active Crohn's disease.
Smith JP, Stock H, Bingaman S, Mauger D, Rogosnitzky M, Zagon IS.
Department of Medicine, Pennsylvania State University College of
Medicine, Hershey, Pennsylvania 17033, USA.
OBJECTIVES: Endogenous opioids and opioid antagonists have been shown
to play a role in healing and repair of tissues. In an open-labeled
pilot prospective trial, the safety and efficacy of low-dose
naltrexone (LDN), an opioid antagonist, were tested in patients with
active Crohn's disease. METHODS: Eligible subjects with histologically
and endoscopically confirmed active Crohn's disease activity index
(CDAI) score of 220-450 were enrolled in a study using 4.5 mg
naltrexone/day. Infliximab was not allowed for a minimum of 8 wk prior
to study initiation. Other therapy for Crohn's disease that was at a
stable dose for 4 wk prior to enrollment was continued at the same
doses. Patients completed the inflammatory bowel disease questionnaire
(IBDQ) and the short-form (SF-36) quality of life surveys and CDAI
scores were assessed pretreatment, every 4 wk on therapy and 4 wk
after completion of the study drug. Drug was administered by mouth
each evening for a 12-wk period. RESULTS: Seventeen patients with a
mean CDAI score of 356 +/- 27 were enrolled. CDAI scores decreased
significantly (P= 0.01) with LDN, and remained lower than baseline 4
wk after completing therapy. Eighty-nine percent of patients exhibited
a response to therapy and 67% achieved a remission (P < 0.001).
Improvement was recorded in both quality of life surveys with LDN
compared with baseline. No laboratory abnormalities were noted. The
most common side effect was sleep disturbances, occurring in seven
patients. CONCLUSIONS: LDN therapy appears effective and safe in
subjects with active Crohn's disease. Further studies are needed to
explore the use of this compound.
PMID: 17222320
---------------
http://www.ncbi.nlm.nih.gov/pubmed/19041189
Low-dose naltrexone for disease prevention and quality of life.
Brown N, Panksepp J.
Department of Humanities and Social Sciences, Embry-Riddle
Aeronautical University, Daytona Beach, FL 32114, United States.
NPHb...@aol.com
The use of low-dose naltrexone (LDN) for the treatment and prophylaxis
of various bodily disorders is discussed. Accumulating evidence
suggests that LDN can promote health supporting immune-modulation
which may reduce various oncogenic and inflammatory autoimmune
processes. Since LDN can upregulate endogenous opioid activity, it may
also have a role in promoting stress resilience, exercise, social
bonding, and emotional well-being, as well as amelioration of
psychiatric problems such a autism and depression. It is proposed that
LDN can be used effectively as a buffer for a large variety of bodily
and mental ailments through its ability to beneficially modulate both
the immune system and the brain neurochemistries that regulate
positive affect.
PMID: 19041189
LDN in a MS trial:
A pilot trial of low-dose naltrexone in primary progressive multiple
sclerosis.
Gironi M, Martinelli-Boneschi F, Sacerdote P, Solaro C, Zaffaroni M,
Cavarretta R, Moiola L, Bucello S, Radaelli M, Pilato V, Rodegher M,
Cursi M, Franchi S, Martinelli V, Nemni R, Comi G, Martino G.
Institute of Experimental Neurology (INSPE) and Department of
Neurology, San Raffaele Scientific Institute, Via Olgettina 58, Milan,
Italy.
A sixth month phase II multicenter-pilot trial with a low dose of the
opiate antagonist Naltrexone (LDN) has been carried out in 40 patients
with primary progressive multiple sclerosis (PPMS). The primary end
points were safety and tolerability. Secondary outcomes were efficacy
on spasticity, pain, fatigue, depression, and quality of life.
Clinical and biochemical evaluations were serially performed. Protein
concentration of beta-endorphins (BE) and mRNA levels and allelic
variants of the mu-opiod receptor gene (OPRM1) were analyzed. Five
dropouts and two major adverse events occurred. The remaining adverse
events did not interfere with daily living. Neurological disability
progressed in only one patient. A significant reduction of spasticity
was measured at the end of the trial. BE concentration increased
during the trial, but no association was found between OPRM1 variants
and improvement of spasticity. Our data clearly indicate that LDN is
safe and well tolerated in patients with PPMS.
PMID: 18728058
+++++++++++++++++++++++++++++
Five hits for :: NALTREXONE + psoria* [on pubmed]
This one says it could stoP the itch. LOL
http://www.ncbi.nlm.nih.gov/pubmed/10495371
H'm they all deal with pruitus. Oh well.
But i don't itch... what a bi itch...
==============
But still, if it works for crohn's then it may be an UN-heartbreaker
for those milky PSOR cases.
Did watch the film milk the other day.
So i'm all milked up, not that THAT's my bag. <w> <g>
-------------
http://www.ncbi.nlm.nih.gov/pubmed/17222320
Low-dose naltrexone therapy improves active Crohn's disease.
Smith JP, Stock H, Bingaman S, Mauger D, Rogosnitzky M, Zagon IS.
Department of Medicine, Pennsylvania State University College of
Medicine, Hershey, Pennsylvania 17033, USA.
OBJECTIVES: Endogenous opioids and opioid antagonists have been shown
to play a role in healing and repair of tissues. In an open-labeled
pilot prospective trial, the safety and efficacy of low-dose
naltrexone (LDN), an opioid antagonist, were tested in patients with
active Crohn's disease. METHODS: Eligible subjects with histologically
and endoscopically confirmed active Crohn's disease activity index
(CDAI) score of 220-450 were enrolled in a study using 4.5 mg
naltrexone/day. Infliximab was not allowed for a minimum of 8 wk prior
to study initiation. Other therapy for Crohn's disease that was at a
stable dose for 4 wk prior to enrollment was continued at the same
doses. Patients completed the inflammatory bowel disease questionnaire
(IBDQ) and the short-form (SF-36) quality of life surveys and CDAI
scores were assessed pretreatment, every 4 wk on therapy and 4 wk
after completion of the study drug. Drug was administered by mouth
each evening for a 12-wk period. RESULTS: Seventeen patients with a
mean CDAI score of 356 +/- 27 were enrolled. CDAI scores decreased
significantly (P= 0.01) with LDN, and remained lower than baseline 4
wk after completing therapy. Eighty-nine percent of patients exhibited
a response to therapy and 67% achieved a remission (P < 0.001).
Improvement was recorded in both quality of life surveys with LDN
compared with baseline. No laboratory abnormalities were noted. The
most common side effect was sleep disturbances, occurring in seven
patients. CONCLUSIONS: LDN therapy appears effective and safe in
subjects with active Crohn's disease. Further studies are needed to
explore the use of this compound.
PMID: 17222320
============================================
randall..