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A ROSE or LaVENDER is NOT a FART -- Hydrogen Sulfide Heart Fiend-LY? PLC to GUT RESCUE? WILL BLOCK-> Propionyl L-Carnitine & IBD -- Liar on Fire -- Ei24 and ER with P53 (cancer skew Th2 inside of YOU?)
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randall
Aug 7, 2012, 2:36:26 PM8/7/12
to
hi
OK so i went looking to find the CURE of the gut without lavender you
EAT?
Whoever heard of that?
Maybe scurfy master Ben Franklin?
OK and who else?
Anyone who red the last thread:
last thread today:
Tues, Aug 7 2012 10:00 am
Subject: Gi TRACT & Psor ->GUT ->Causation -- Citrobacter Rodentium -
Lavender (Medicinal )-->MicroFLORA -- IL-22 -NAC - Nrf2 - Card14
Mutation Speculations - StuPidly time -- Higgs Field -- Hold EM?
Doctor Corsi - RiboCeine
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/msg/368e3dd41dd750fe
If i didn't read the pubmed on it i would NOT have believed it, right?
[...] http://www.ncbi.nlm.nih.gov/pubmed/22821949
Am J Physiol Gastrointest Liver Physiol. 2012 Jul 19.
Medicinal lavender modulates the enteric microflora to protect
against
Citrobacter rodentium-induced colitis.
[...] PMID: 22821949
I dunno you're fairly gullible on your travels tar baby.
And what about colitis caused by some other buggy agent?
Right id squid and it's the path and not the GOAL..... goal!
But in soccer it's the Goals due to the path then?
You got me.... Score!
So this is about fixing the gut, what?
With this Propionyl L-Carnitine according to will block of LE fame.
Is that his real name tar baby?
I dunno id squid...
What's in a name?
Well if it's rose or lavender you do have an expectation, right?
I guess... so will, WILL wait till i do these farty smelly abstracts/
links... i think!
9 results for fart gas hydrogen - p ng:
https://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?q=fart+gas+hydrogen&start=0&
#1 is Durk and Sandy Pearson (Shaw)--> hydrogen as a Selective
Antioxidant.
And durk and sandy are very LE-ish... so that is GOOD. I bet they
live to 122 and 3/4's?
Or maybe 86 for durk and 93 for sandy?
Hey... just guessing..i'm not a wizard on this health stuff btw...
what whey?
why whey in then tar baby?
For fun id squid...
ok...
Thurs, May 31 2012 1:29 pm
Subject: Anti-ROS -->Hydrogen From your Gut Flora --Durk/Sandy Pearson
--> LCFOS --> Don't SMELL or BE Dum Dum chewing Gum Gum - Ben Franklin
on Fartology -->Chessypoofs
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/msg/345d76bc71274827
Can FART GAS save the hearts of psoriatics which we KNOW are at risk?
Randall tar baby you give your heart to every tart that is merely an
idea!
Hey id squid that isn't true.... i think first and step on it
second.... and then like barney formula i take it and fake it and
them make up my mind and then don't take it and try xyz and decide.
It's science id squid!
Yeah anecdotally testing for one canary who sings like his beak is on
psor fire... LOL
FART on you id squid.
Hey your still me if you didn't KNOW tar blabby juan....
OK... but but but er er er...
I'm having a heart attack yack yack!
Quick.... FART produly...or hold it so the gas permeates your brains?
ER heart tissue.. Sorry rat baby.... i mean eR eR eR tar baby...
http://www.ncbi.nlm.nih.gov/pubmed/22815945
PLoS One. 2012;7(7):e41147. Epub 2012 Jul 18.
Hydrogen Sulfide Inhibits the Development of Atherosclerosis with
Suppressing CX3CR1 and CX3CL1 Expression.
Zhang H, Guo C, Wu D, Zhang A, Gu T, Wang L, Wang C.
Source
Department of Cardiology, Shanghai Ninth People's Hospital, Shanghai
JiaoTong University School of Medicine, Shanghai, China.
Abstract
Hydrogen sulfide, as a novel gaseous mediator, has been suggested to
play a key role in atherogenesis. However, the precise mechanisms by
which H(2)S affects atherosclerosis remain unclear. Therefore, the
present study aimed to investigate the potential role of H(2)S in
atherosclerosis and the underlying mechanism with respect to
chemokines (CCL2, CCL5 and CX3CL1) and chemokine receptors (CCR2,
CCR5, and CX3CR1) in macrophages. Mouse macrophage cell line RAW 264.7
or mouse peritoneal macrophages were pre-incubated with saline or NaHS
(50 µM, 100 µM, 200 µM), an H(2)S donor, and then stimulated with
interferon-γ (IFN-γ) or lipopolysaccharide (LPS). It was found that
NaHS dose-dependently inhibited IFN-γ or LPS-induced CX3CR1 and CX3CL1
expression, as well as CX3CR1-mediated chemotaxis in macrophages.
Overexpression of cystathionine γ-lyase (CSE), an enzyme that
catalyzes H(2)S biosynthesis resulted in a significant reduction in
CX3CR1 and CX3CL1 expression as well as CX3CR1-mediated chemotaxis in
stimulated macrophages. The inhibitory effect of H(2)S on CX3CR1 and
CX3CL1 expression was mediated by modulation of proliferators-
activated receptor-γ (PPAR-γ) and NF-κB pathway. Furthermore, male
apoE(-/-) mice were fed a high-fat diet and then randomly given NaHS
(1 mg/kg, i.p., daily) or DL-propargylglycine (PAG, 10 mg/kg, i.p.,
daily). NaHS significantly inhibited aortic CX3CR1 and CX3CL1
expression and impeded aortic plaque development. NaHS had a better
anti-atherogenic benefit when it was applied at the early stage of
atherosclerosis. However, inhibition of H(2)S formation by PAG
increased aortic CX3CR1 and CX3CL1 expression and exacerbated the
extent of atherosclerosis. In addition, H(2)S had minimal effect on
the expression of CCL2, CCL5, CCR2 and CCR5 in vitro and in vivo. In
conclusion, these data indicate that H(2)S hampers the progression of
atherosclerosis in fat-fed apoE(-/-) mice and downregulates CX3CR1 and
CX3CL1 expression on macrophages and in lesion plaques.
PMID: 22815945
Free PMC Article
http://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22815945/?tool=pubmed
---------------
http://en.wikipedia.org/wiki/NaHS
Sodium hydrosulfide is the chemical compound with the formula NaHS.
This compound is the product of the half neutralization of hydrogen
sulfide with sodium hydroxide. NaHS is a useful reagent for the
synthesis of organic and inorganic sulfur compounds. It is a colorless
solid that typically smells like H2S due to hydrolysis by atmospheric
moisture. In contrast with sodium sulfide, Na2S, which is insoluble in
organic solvents, NaHS, being a 1:1 electrolyte, is more soluble.
Alternatively, in place of NaHS, H2S can be treated with an organic
amine to generate an ammonium salt. Solutions of HS− are sensitive to
oxygen, converting mainly to polysulfides, indicated by the appearance
of yellow.
----------------
http://atvb.ahajournals.org/content/29/2/156.full
Is H2S a Stinky Remedy for Atherosclerosis?
Rui Wang
From Department of Biology &
Correspondence to Rui Wang, Lakehead University, Thunder Bay, 955
Oliver Rd, Ontario P7B5E1, Canada. E-mail rw...@lakeheadu.ca
Atherosclerosis is a complex and chronic pathological state that
adversely affects the structure of blood vessels. Vascular
inflammation, endothelial damage, smooth muscle cell migration, foam
cell accumulation, and lipid and cholesterol deposition contribute to
different stages of plaque formation in large and medium-sized blood
vessels. The consequential narrowing and stiffening of blood vessels
restricts blood circulation and increases plaque thrombogenicity.
Pathogenic causes that lead to these pathological changes in
atherosclerosis have always been the center of attention, but we have
not yet cleared the cloud on this issue.
See accompanying article on page 173
http://atvb.ahajournals.org/lookup/volpage/29/173
An ancient problem may have an ancient solution. A disease older than
the history of mankind, atherosclerosis affects the health of various
species in a much more profound fashion than other types of
cardiovascular problems. Taking the fish as a case in point, whereas
heart failure and hypertension are nonissues with them, fishes
spontaneously develop atherosclerosis in their natural habitat
regardless of what are on their menu. Even more ancient than the
origin of atherosclerosis, production of hydrogen sulfide (H2S) gas by
living organisms can be traced far back before the evolvement of the
vascular system. Bacteria and archaea produce and use H2S as the
essential element for their survival and proliferation. In eukaryotes,
H2S is produced under the enzymatic actions of 2 pyridoxal-5′-
phosphate-dependent enzymes, cystathionine beta–synthase (CBS) and
cystathionine γ-lyase (CSE).1 Importantly, CSE is a major H2S-
producing enzyme in the cardiovascular system.2
Recent advance in our understanding of the biological importance of
endogenous H2S has shed light on the potential use of this ancient
gasotransmitter to deal with atherosclerosis. First, H2S inhibits
smooth muscle cell proliferation, one major event in atherosclerosis.
Yang et al2 previously reported that, after inhibiting endogenous H2S
production by DL-propargyglycine (PPG) pretreatment or knocking down
endogenous CSE gene by short interfering RNA approach, H2S at 50 to
100 μmol/L induces apoptosis of human aorta smooth muscle cells (SMCs).
3 Without inhibiting endogenous H2S production, exogenously applied
H2S at 100 μmol/L had little effect on SMC apoptosis. The importance
of the interaction between exogenous and endogenous H2S is thus
indicated. Second, H2S inhibits homocysteine-induced vascular damage.
Homocysteine is a key amino acid in regulating cellular levels of
cysteine, methionine, and sulfur. Accumulation of homocysteine in the
plasma, termed hyperhomocysteinemia, is considered to be an
established risk factor for atherosclerosis. Dietary supplementation
with methionine and homocysteine induced hyperhomocysteinemia which
promoted early atherosclerosis in apolipoprotein E–deficient (apoE−/−)
mice.4 The development of hyperhomocysteinemia in CSE gene knockout
mice has been recently shown.5 It has also been demonstrated that low
levels of NaHS (30 or 50 μmol/L) protected rat aortic SMCs from
homocysteine-induced cytoxicity and reactive oxygen species, leading
to improved cell viability.6 Third, H2S reduces atherogenesis. H2S
inhibited atherogenic modification of purified LDL induced by
hypochlorite in vitro, as measured by apolipoprotein alterations.7
Meng et al reported that during neointimal formation induced by
balloon injury in rats,8 CSE expression was reduced and endogenous
production of H2S decreased. Rescue of the injured artery with NaHS
not only reversed the reduced endothelium-dependent vasorelaxation,
but also significantly inhibited neointima formation of the balloon-
injured carotid arteries.8
The report by Wang et al in this issue of Arteriosclerosis,
Thrombosis, and Vascular Biology adds a new twist in searching for the
direct correlation of H2S and atherosclerosis.9 They found that
treatment of apoE−/− mice with NaHS resulted in reduced
atherosclerotic plaque, whereas inhibition of CSE activity in apoE−/−
mice with PPG enlarged plaque size. By promoting adhesion of
inflammatory cells to the endothelium, intracellular adhesion
molecule-1 (ICAM-1) may be one of the causative factors for
atherosclerosis as its level is significantly higher in human
atherosclerotic plaques. Wang et al attributed the antiatherosclerotic
effect of NaHS on apoE−/− mice to the reduced ICAM-1 level in
circulation and lowered expression of ICAM-1 in aortic endothelial
cells.9
The excitement brought by the observation of Wang et al9 is beyond the
therapeutic value of NaHS in atherosclerosis, which can be traced back
to previous reports.3,8 It also proposes challenges and questions.
Essential and curious enough for the root of pathogenesis of
atherosclerosis is whether abnormality of CSE/H2S system is the cause
or consequence of the disease. While showing a marginal decrease in
H2S level in plasma from apoE−/− mice having advanced atherosclerosis,
basal levels of H2S and CSE protein expression before the
manifestation of atherosclerosis in apoE−/− mice were not determined.9
What is even more perplexing is the aortic production rate of H2S and
aortic CSE expression level in apoE−/− mice.9 Decreased H2S production
rate should reflect decreased CSE activity or expression. The
decreased H2S production rate, however, as reported by Wang et al,
contradicts with the increased CSE mRNA expression in aortic
atherosclerotic tissues,9 which cannot be readily explained by an
assumed “positive feedback” mechanism.
Interactions between SMCs and endothelial cells are key to
atherosclerosis development. Wang et al proposed that H2S produced by
SMCs may carry a signal to endothelial cells, thereby altering the
production of ICAM-1 and affecting endothelial integrity.9 This is an
interesting concept and worth further comment. Expression of CSE mRNA
was initially localized in vascular SMCs, not endothelial cells2;
however, immunoblot analysis had not been done to detect CSE protein
in endothelial cells in earlier studies. As our understanding of the
tissue- and species-specific expression of CSE mRNA and proteins
deepened, as well as the availability of more specific and sensitive
antibodies against CSE that target different CSE protein epitopes, the
cellular location of CSE in blood vessel has been better resolved. A
recent study by Yang et al presented clear evidence that mouse blood
vessels express CSE protein both in vascular smooth muscle and
endothelium layers.5 Cultured HUVECs also express CSE protein and
produce H2S.5 Even in the report by Wang et al, immunopositive
staining for CSE seems also obvious in the endothelial layer of mouse
aortic tissues from wild-type and apoE−/− mice (see Wang et al,9
Figure 2). It is therefore likely that H2S produced by endothelial
cells has a direct autocrinal effect on endothelial cells to regulate
ICAM-1 production.
Although a causative role of H2S in the pathogenesis of
atherosclerosis is still open for debate and inconsistencies have been
encountered, it is clear from this novel study by Wang et al that H2S
can be used as an effective therapeutic intervention for
atherosclerosis in apoE−/− mice.9 Stinky but healthy, H2S therapy
appears to be a good trade-off. Consumption of garlic, preserved bean
curd (stinky tofu), or preserved egg (thousand year’s egg) all
increase the production of H2S. But before you put these on the dinner
table, pause a while to hold your breath. If there were a “positive
feedback” mechanism between H2S and CSE expression as proposed by Wang
et al in this issue, application of exogenous H2S to atherosclerotic
patients would lead to inhibited CSE expression and decreased
endogenous H2S level. Would be this a good news for the prognosis of
atherosclerotic patients? Let’s pause even longer and investigate
further the correlation between H2S and atherosclerosis.
It ain’t done till it’s done.
<snip>
I bet Benjamin Franklin with psoriasis called scurffy back (?) then
would FART proudly NOW.
Ben and 13 hits for : scurf - p ng
https://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?q=scurf&start=0&scoring=d&
So when Big BEN went to FRANCE with ants in his pants and scurf on his
turf did he eat lavendar?
I wonder?
So how does Will Block treat the GUT?
He uses Propionyl L-Carnitine and i bet it isn't in the Barney
Formula?
WELL?
Seeing we have zero hits for Propionyl L-Carnitine you would be RIGHT
unless
barney is using things that make it inside of your liver... and you're
living it uP...
http://www.life-enhancement.com/article.aspx?id=2594
Propionyl L-Carnitine
Dispatches Ulcerative Colitis
PLC may be sequestered from circulating in ulcerative colitis
to serve as a source of L-carnitine and propionyl-coenzyme-A in the
colon
By Will Block
Inflammatory bowel disease is thought to be caused by the chronic or
recurring immune response and inflammation of the gastrointestinal
tract. The most common inflammatory bowel diseases are Crohn’s disease
and ulcerative colitis (UC).
Colitis is inflammation of the colon. It is also called colonitis. No
matter what you call it, it’s a miserable condition, and it’s likely
to hang on unless you do something about it. Colitis should not be
confused with irritable bowel syndrome (spastic colon), a different
and much less serious condition that is aggravating and a disorder
that affects the motility (muscle contractions) of the colon. But it
does not entail inflammation. In colitis, furthermore, inflammation is
typically accompanied by ulceration, which damages or destroys patches
of the mucosal lining of the colon or rectum. UC—the standard term for
the most common form of the disease—causes bloody diarrhea, and stools
may contain mucus and pus. There may also be fever and abdominal pain.
One thing more—patients with UC are at increased risk of colon cancer.
Patients with ulcerative colitis are at increased risk of colon
cancer.
Prevalence and Toll
Inflammatory bowel disease is one of the five most prevalent
gastrointestinal disease burdens in the United States, with an overall
health care cost exceeding $1.7 billion. Currently, there is no
medical cure. Thus care is commonly a life-long endeavor. Every year
in the United States, inflammatory bowel disease accounts for more
than 700,000 physician visits, 100,000 hospitalizations, and
disability in 119,000 patients.1 Up to 75% of patients with Crohn’s
disease and 25% of those with UC will require surgery.
Ulcerative colitis is regarded as an impaired fatty-acid oxidation
disease.
The Many Adversities of Drugs
So what can you do about all this? Well, there are the drugs of
course, and they can be quite effective, although you may have to pay
a price beyond mere money to obtain their benefits (see the sidebar
“Drug Side Effects—A Cascade of Adversities”). If the condition
affects just the rectum and lower part of the colon, the drugs of
choice are aminosalicylates or corticosteroids, administered rectally.
But if the condition goes farther up the pipeline, so to speak, oral
medication is indicated, and the drug of first choice is usually a
thiopurine (both drugs are in the sidebar).
Drug Side Effects—A Cascade of Adversities
Aminosalicylate and thiopurine are two of the drugs used to treat the
inflammatory bowel disease ulcerative colitis. Aminosalicylate belongs
to the family of medicines called anti-infectives. Thiopurine is an
immune system suppressant.
The common side effects of aminosalicylate include gastrointestinal
problems (nausea, vomiting, diarrhea, abdominal pain) Then, by
category: Cardiovascular; Central Nervous System [including headache
(35%), dizziness (8%), asthenia (7%), weakness (6%); hypertonia (5%)];
Dermatologic; Eye-Ear-Nose-Throat; GI [including abdominal pain (18%);
eructation (16%); nausea (13%); abdominal cramps/discomfort (8%);
diarrhea (7%); dyspepsia, flatulence (6%); vomiting (5%)]; Genito
urinary; Hematologic-Lymphatic; Hepatic; Lab Tests; Local; Metabolic-
Nutritional; Musculoskeletal; Respiratory; Dyspnea; Miscellaneous
[Pain (14%); fever (6%); flu syndrome (5%)]. In each category, only
those adverse effects greater than 5% are listed. There are a great
many more, and some are quite serious.
Thiopurine drugs can also cause side effects. The most common side
effects are stomach related problems (such as nausea, vomiting,
diarrhea, abdominal pain) and bone marrow problems. Also there may be
severe allergic reactions (rash; itching; hives; difficulty breathing;
tightness in the chest; swelling of the mouth, face, lips, or tongue);
chest pain or tightness; dizziness; fatty stools; fever, chills, or
persistent sore throat; increased or painful urination; muscle pain or
aches; painful, red bumps or blisters on the arms, face, neck, or
back; severe or persistent nausea, vomiting, or diarrhea; shortness of
breath; stomach pain; symptoms of liver problems (e.g., dark urine,
loss of appetite, pale stools, right-sided stomach pain, yellowing of
the eyes or skin); unusual bleeding or bruising; unusual growths or
lumps; unusual weakness or tiredness. And this is not a complete list.
Either way, this is one rough road to travel, so any new prospects of
treatment should be welcome, especially when there is virtually no
adversity.
References
Drugs.com www.drugs.com/ppa/mesalamine-5-aminosalicylic-acid-5-asa.html.
Accessed February 19, 2012.
Drugs.com www.drugs.com/sfx/azathioprine-side-effects.htm . Accessed
February 19, 2012.
A Disease of Fatty Acid Oxidation
UC is regarded as an impaired fatty-acid oxidation disease. Short-
chain fatty acids are produced in the lumen of the colon by bacterial
fermentation of consumed complex carbohydrates. These fatty acids—and
butyrate in particular—are the primary metabolic fuel of colonocytes
(epithelial cells of the colon). As well, short-chain fatty acids
affect colonic blood flow, motility, and mucus secretion. And while
the pathogenesis (cause) of UC is not yet fully understood, there is a
growing amount of evidence suggesting that a deficiency of these short-
chain fatty acids in the colon lining’s colonocytes may provide an
answer.
(click on thumbnail for full sized image)
In fact, several studies suggest that impaired beta-oxidation of short-
chain fatty acids may lead to colonic mucosal damage due to an energy
deficiency that can only partly be compensated for by the oxidation of
other substrates.2–4 Unfortunately, treatment of UC with fatty acid
enemas has not produced definitive results.
Carnitine Helps Feed Mitochondria
L-Carnitine is needed for the transport of activated fatty acids into
the mitochondria for beta-oxidation in order to generate Acetyl-CoA,
the entry molecule for the citric acid cycle. As at least one study
has shown, while plasma levels of free L-carnitine are similar in
patients with UC and matched healthy controls, plasma levels of the
ester propionyl L-carnitine (PLC) are lower in patients with UC.5 This
suggests that PLC may be sequestered from circulating in UC patients,
thus inhibiting its service as a source of L-carnitine and propionyl-
coenzyme-A in the colon.
Higher L-carnitine levels, in turn, facilitate energy release through
beta-oxidation of fatty acids, while propionyl-coenzyme-A—an efficient
energy source—enters the citric acid cycle as succinate.6 PLC
supplementation has the potential to improve cellular energy levels,
and is able to stimulate energy production in ischemic skeletal
muscles, and increases maximum walking distance in patients with
peripheral arterial obstructive disease.7
New Study Finds PLC Can Co-Treat Mild UC
Taking the above into consideration, a team of multinational
researchers set out to evaluate efficacy and safety of PLC in patients
with mild-to-moderate UC who were employing oral aminosalicylate or
thiopurine therapy.8 In a multicenter study, straddling five European
nations, the study was double-blinded, placebo-controlled, and
randomized. Each of three different groups of 40, 41, and 40 patients
respectively received PLC at 1 g/day, PLC at 2 g/day, or placebo.
In the PLC 1 g/day group,
30 of 40 (75%) patients had a
clinical/endoscopic response and
27 of 39 (69%) in the
PLC 2 g/day group.
All of the patients were between the ages of 18–75 with disease
activity index (DAI) scores of 3–10 (mild UC is 3–6 and moderate UC is
6–10). Of the 121 patients who were randomized, 57 of 79 (72%)
receiving PLC (combined 1 g and 2 g cohort) had a clinical/endoscopic
response vs. 20 of 40 (50%) compared to a clinical/endoscopic response
for those receiving placebo. Clinical/endoscopic response was defined
as a decrease in DAI score = 3 points or as remission, defined as a
DAI score = 2. Clinical/endoscopic response findings for the stratum
of patients in the combined PLC cohort who had mild disease were also
significantly different from placebo. Due to the small number of
patients with moderate disease, no statistical conclusions can be made
for this stratum.
The patients were not permitted to change their stable oral
concomitant aminosalicylate or thiopurine therapy during the trial.
Very few patients (n = 4) received stable oral thiopurine therapy; and
thus stratification was limited to disease severity only (rather than
for the drug used). Furthermore, the use of systemic or topical
corticosteroids, rectal therapies, NSAIDs, probiotics or antibiotics
was not allowed.
In the PLC 1 g/day group, 30 of 40 (75%) patients had a clinical/
endoscopic response and in the PLC 2 g/day group the response was 27
of 39 (69%). PLC 1 g/ day treatment was significantly superior
compared with placebo. Results for the stratum of patients in the PLC
1 g / day arm with mild disease were similarly significant compared to
placebo. Results for the PLC 2 g / day arm were not statistically
significantly different to the placebo arm.
Remission Analysis
Rates of disease absence (remission) were 22/40 (55%), 19/39 (49%),
14/40 (35%) in the PLC 1 g, PLC 2 g, and placebo groups, respectively
[41 / 79 (52%) patients in the combined PLC cohort]. However, none of
the remission rates for patients receiving PLC were significantly
greater than that for patients receiving placebo. When considering
data stratified by disease severity, only PLC 1 g/day in patients with
mild disease significantly increased the probability of remission
compared to corresponding placebo.
When the response rates for each of the four items (rectal bleeding,
stool frequency, mucosal appearance and physician global assessment)
of the DAI was analyzed—for each item, response was defined as a
lowering of at least 1 point of the score over baseline—the group
receiving PLC 1 g /day had a rate of response for rectal bleeding that
was significantly improved compared to the group receiving placebo.
PLC, as a group, had a similar safety profile to placebo; the most
common adverse events were gastrointestinal. This phase II trial
confirmed that PLC is a potential treatment for the management of mild-
to-moderate UC. Patients receiving PLC were more likely to have a
clinical/endoscopic response than those receiving placebo.
As there is no statistically significant clinical difference between
the two PLC doses investigated, the lower dose of PLC 1 g/day should
be used in future studies. When separated into layers for disease
severity, clinical/endoscopic response rates for the combined PLC
cohort and the PLC 1 g/ day arm were statistically significant vs.
placebo in patients with mild UC.
When considering data
stratified by disease severity,
only PLC 1 g/day in patients with
mild disease significantly increased
the probability of remission
compared to corresponding placebo.
Patients with mild disease receiving PLC 1 g /day were more likely to
achieve remission than those taking placebo. Because there were a
relatively small number of patients with moderate UC, no conclusions
could be drawn. Further studies are therefore needed to confirm the
effectiveness of PLC in patients with moderate and severe UC.
Maximizing Colonocyte Uptake Through PLC
PLC was administered in an oral colon-release formulation that allows
the active ingredient to be released directly into the colon lumen,
facilitating maximum uptake by colonocytes. This may explain why a low
1 g /day dose is effective and that the lack of additional benefit
with a 2 g/day dose may be due to saturation at the site of uptake.
As there is no statistically significant
clinical difference between the two
PLC doses investigated,
the lower dose of PLC 1 g/day
should be used in future studies.
Assessment of remission induction did not yield significant data. But
future studies with more patients or of longer duration may further
clarify the positive remission trends shown for PLC treatment in this
trial and even evaluate the role of PLC in maintaining remission.
PLC could provide an alternative treatment for patients with
aminosalicylate or thiopurine intolerance, or for those wanting to
avoid their adverse effects (see sidebar) and corticosteroids.
Certainly, data from this trial, where patients were already receiving
stable oral treatment, suggest a role for PLC as an adjunctive therapy
for the induction of remission.
As PLC was well tolerated, long-term therapy for remission maintenance
is plausible, and might reduce the risk of colon cancer, which is the
case with regular aminosalicylate treatment. In conclusion, this trial
has provided proof of concept for the use of PLC in the treatment of
mild-to-moderate UC. PLC 1 g /day appears to be well tolerated with a
favorable safety profile and should be further investigated as a
treatment for mild-to-moderate UC.
Carnitines for Energy, Muscle Strength, and Sex
Recent findings have shown that acetyl-L-carnitine (ALC) and PLC are
beneficial in other ways. ALC is thought to proffer benefits for
memory and for various neurological disorders: such as Alzheimer’s
dementia, depression in the elderly, chronic fatigue syndrome,
peripheral neuropathies, ischemia and reperfusion of the brain, and
cognitive impairment associated with various conditions.
PLC has also been shown to replenish the intermediates of the citric
acid cycle via propionyl-CoA moiety (boosting energy levels),
strengthen muscle cells, and assist peripheral vasodilator activity,
including the enhancement of sexual prowess. As well, PLC has been
found to help prevent and treat ischemic heart disease, congestive
heart failure, hypertrophic heart disease, and peripheral arterial
disease. It might be a good idea to add this supplement to your
program, if you are not already taking it.
Possible Parkinson’s Neuroprotection
Lastly, there is new evidence to indicate that ALC, along with α-
lipoic acid, may inhibit bradykinesia (slowed ability to start and
continue movement) and motor impairment in rats when given at a human
dose equivalent of 1215 mg/day of ALC and 608 mg/day of α-lipoic acid.
9 In this study, ALC also enhanced ATP production. According to the
researchers, “Taken together, our study reinforces the view that
acetyl-L-carnitine and α-lipoic acid are promising candidates for
neuroprotection in Parkinson’s disease.”
References
<snip>
342 hits : Propionyl L-Carnitine - pubmed
http://www.ncbi.nlm.nih.gov/pubmed?term=Propionyl%20L-Carnitine
Does it have barney?
I don't know... maybe FRED Flinstone ate it?
Wilma bring me some PLC please... this caveman is gonna swing.
Did gay cavemen set up their own cave's and pledge .... like a
marriage type of thing?
I bet thy did but then again they didn't worry about another ICE AGE
or global warming right? LOL
And the poopulation BOMB of those breeder's wasn't for another 69,000
years or so?
LOL
#1 of 347
http://www.ncbi.nlm.nih.gov/pubmed/22743351
Ther Drug Monit. 2012 Aug;34(4):406-14.
Effect of short- and long-term treatment with valproate on carnitine
homeostasis in humans.
Morand R, Todesco L, Donzelli M, Fischer-Barnicol D, Mullen PJ,
Krähenbühl S.
Source
*Division of Clinical Pharmacology and Toxicology, University Hospital
Basel †Department of Biomedicine, University of Basel ‡Psychiatric
University Hospital, University of Basel §Swiss Center of Human
Applied Toxicology (SCAHT), University of Basel, Basel, Switzerland.
Abstract
AIMS:
: The aim of this study was to identify the mechanisms of
hypocarnitinemia in patients treated with valproate.
METHODS:
: Plasma concentrations and urinary excretion of carnitine,
acetylcarnitine, propionylcarnitine, valproylcarnitine, and
butyrobetaine were determined in a patient starting valproate
treatment and in 10 patients on long-term valproate treatment.
Transport of carnitine and valproylcarnitine by the proximal tubular
carnitine transporter OCTN2 was assessed in vitro.
RESULTS:
: In the patient starting valproate, the plasma carnitine and
acetylcarnitine levels dropped for 1-3 weeks and had recovered after
3-5 weeks, whereas the plasma levels of propionyl and
valproylcarnitine increased steadily over 5 weeks. The renal excretion
and excretion fractions (EFs) of carnitine, acetylcarnitine,
propionylcarnitine, and butyrobetaine decreased substantially after
starting valproate. Compared with controls, patients on long-term
valproate treatment had similar plasma levels of carnitine,
acetylcarnitine, and propionylcarnitine, whereas valproylcarnitine was
found only in patients. Urinary excretion and renal clearance of
carnitine, acetylcarnitine, propionylcarnitine, and butyrobetaine were
decreased in valproate-treated compared with that in control patients,
reaching statistical significance for carnitine. The EFs of carnitine,
acetylcarnitine, and propionylcarnitine were <5% of the filtered load
in controls and were lower in valproate-treated patients. In contrast,
the EF for valproylcarnitine approached 100%, resulting from a low
affinity of valproylcarnitine for the carnitine transporter OCTN2 and
competition with concomitantly filtered carnitine.
CONCLUSIONS:
: The initial drop in plasma carnitine levels of valproate-treated
patients is most likely due to impaired carnitine biosynthesis,
whereas the recovery of the plasma carnitine levels is explainable by
an increased renal expression of OCTN2. Renally excreted
valproylcarnitine does not affect renal handling of carnitine in vivo.
PMID: 22743351
we have two hits for : valproate - p ng
https://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?q=valproate&start=0&
And one is kofi.... he's hot kofi... where is he these days?
I dunno tar baby... maybe his hair grew back and he's RICH now?
I hope so id squid..
SCORE...
Depakote is (Valproic Acid)
http://en.wikipedia.org/wiki/Valproate_semisodium
Valproate semisodium (INN) or divalproex sodium (USAN) consists of a
compound of sodium valproate and valproic acid in a 1:1 molar
relationship in an enteric coated form. It is used in the United
Kingdom, Canada, and United States for the treatment of the manic
episodes of bipolar disorder. In rare cases, it is also used as a
treatment for major depressive disorder, and increasingly taken long-
term for prevention of both manic and depressive phases of bipolar
disorder, especially the rapid-cycling variant. It is also used in the
US for the treatment of epilepsy, certain side effects of autism,
chronic pain associated with neuropathy, and migraine headaches. Its
chemical name is sodium hydrogen bis(2-propylpentanoate). The extended
release formulation allows for a single daily dose.
In the UK semisodium valproate has been sold for a few years as the
proprietary drug Depakote and marketed for psychiatric conditions
only. It is about five times the price of sodium valproate,[citation
needed] which has been marketed for around 30 years as Epilim by the
same company for epilepsy and is also available from other
manufacturers as a generic product.
<snip>
4 hits: depakote - p ng
https://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?q=Depakote&start=0&scoring=d&
#2 of 342
http://www.ncbi.nlm.nih.gov/pubmed/22593918
Propionic Acidemia.
Authors
Carrillo-Carrasco N, Venditti C.
EditorsIn: Pagon RA, Bird TD, Dolan CR, Stephens K, Adam MP, editors.
SourceGeneReviews™ [Internet]. Seattle (WA): University of Washington,
Seattle; 1993-.
2012 May 17.
Excerpt
DISEASE CHARACTERISTICS:
The spectrum of propionic acidemia (PA) ranges from neonatal-onset to
late-onset disease. Manifestations of neonatal and late-onset PA over
time can include growth impairment, intellectual disability, seizures,
basal ganglia lesions, pancreatitis, and cardiomyopathy. Other rarely
reported complications include optic atrophy, hearing loss, premature
ovarian insufficiency (POI), and chronic renal failure.
DIAGNOSIS/TESTING:
PA is caused by deficiency of propionyl-CoA carboxylase (PCC), the
enzyme that catalyzes the conversion of propionyl-CoA to methylmalonyl-
CoA. Newborns with PA tested by expanded newborn screening have
elevated C3 (propionylcarnitine). Testing of urine organic acids in
persons who are symptomatic or those detected by newborn screening
reveals elevated 3-hydroxypropionate and the presence of
methylcitrate, tiglylglycine, and propionylglycine, which are normally
not observed in the urine. Testing of plasma amino acids reveals
elevated glycine. Confirmation of the diagnosis relies on detection of
either deficient PCC enzymatic activity or biallelic mutations in PCCA
or PCCB.
MANAGEMENT:
Treatment of manifestations: The treatment of persons with acutely
decompensated PA is a medical emergency: treat precipitating factors
such as infection; arrest catabolism by providing high calorie and
fluid intake; minimize protein intake to reduce propiogenic
precursors; give intravenous carnitine; correct hypoglycemia and
metabolic acidosis; and care for the patient in a center with
biochemical genetics expertise and the ability to support urgent
hemodialysis, especially if hyperammonemia is present. Prevention of
primary manifestations: Individualized dietary management to restrict
propiogenic substrates; nasogastric or gastrostomy feeding as needed;
increased caloric intake during illness to prevent catabolism; and
continued multidisciplinary care with metabolic specialists.
Medications may include: L-carnitine supplementation; oral
metronidazole to reduce propionate production by gut bacteria; and/or
N-carbamoylglutamate. Orthotopic liver transplantation (OLT) may be
indicated in those with frequent metabolic decompensations,
uncontrollable hyperammonemia, and/or restricted growth. Prevention of
secondary complications: Consistent evaluation of the protein intake,
depending on age, gender, severity of disease and presence of other
factors such as growth spurts, can avoid insufficient or excessive
protein restriction. The latter can result in deficiency of essential
amino acids and impaired growth, as well as catabolism-induced
metabolic decompensation. Surveillance: Monitor closely patients with
a catabolic stressor (fasting, fever, illness, injury, and surgery) to
prevent and/or detect and manage metabolic decompensations early.
Regularly assess: (1) growth, nutritional status, feeding ability,
psychomotor development; (2) metabolic status by monitoring urine
organic acids and plasma amino acids; (3) renal function; (4) complete
blood count. At intervals not yet determined, screen for:
cardiomyopathy and arrhythmias; optic atrophy; and premature ovarian
insufficiency in females. Agents/circumstances to avoid: Prolonged
fasting; catabolic stressors. Evaluation of relatives at risk: Testing
of at-risk sibs of a patient is warranted to allow for early diagnosis
and treatment.
GENETIC COUNSELING:
Propionic acidemia is inherited in an autosomal recessive manner. At
conception, each sib of an affected individual has a 25% chance of
being affected, a 50% chance of being an asymptomatic carrier, and a
25% chance of being unaffected and not a carrier. Carrier testing for
at-risk relatives and prenatal diagnosis for pregnancies at increased
risk are possible if the disease-causing mutations in the family are
known.
PMID: 22593918
full text
http://www.ncbi.nlm.nih.gov/books/NBK92946/
zzzzzzzzzzzzzzzzzzzzzzzzzzzzzzz
OK fun stuff TIME... man does not live by bread alone..
he needs mirth and some red wine?
Right id squid!
Liar liar pants on FIRE?
Right and you AGE quicker to BOOT!
http://www.usatoday.com/news/health/story/2012-08-04/honesty-beneficial-to-health/56782648/1
Study finds that avoiding lies can improve your health
By Sharon Jayson, USA TODAY
ORLANDO – Honesty may boost your health, suggests a study that found
telling fewer lies benefits people physically and mentally.
Each week for 10 weeks, 110 individuals, ages 18-71, took a lie
detector test and completed health and relationship measures assessing
the number of major and minor lies they told that week, says lead
author Anita Kelly, a psychology professor at the University of Notre
Dame in Indiana. She presented findings at the annual meeting of the
American Psychological Association, which ended Sunday.
"When they went up in their lies, their health went down," says Kelly.
"When their lies went down, their health improved."
Researchers instructed half the participants to "refrain from telling
any lies for any reason to anyone. You may omit truths, refuse to
answer questions, and keep secrets, but you cannot say anything that
you know to be false." The other half received no such instructions.
Over the study period, the link between less lying and improved health
was significantly stronger for participants in the no-lie group, the
study found. When participants in the no-lie group told three fewer
minor lies than they did in other weeks, for example, they
experienced, on average, four fewer mental-health complaints and three
fewer physical complaints. Mental health complaints included feeling
tense or melancholy; physical complaints included sore throats and
headaches.
Linda Stroh, a professor emeritus of organizational behavior at Loyola
University in Chicago, says findings are consistent with her own
research on trust. "When you find that you don't lie, you have less
stress," she says. "Being very conflicted adds an inordinate amount of
stress to your life."
Evidence from past research suggests that Americans average about 11
lies a week. Kelly says the no-lie group participants were down to one
lie, on average, per week. For both groups, when participants lied
less in a given week, they reported their physical health and mental
health to be significantly better that week.
"It's certainly a worthy goal to have people be more honest and more
genuine and interact with others in a more honest way," says
psychologist Robert Feldman of the University of Massachusetts,
Amherst. "That would be ultimately beneficial. I'm a little skeptical
that it makes us all healthier, but it may make us healthier in a
psychological way."
<snip>
Wonder how democraps do it?
Like pelosi, obama and reed for instance?
Eggzactly... LOL
http://en.wikipedia.org/wiki/Pseudologia_fantastica
or
http://en.wikipedia.org/wiki/Pathological_liar
Pseudologia fantastica, mythomania, or pathological lying are three of
several terms applied by psychiatrists to the behavior of habitual or
compulsive lying.[1][2] It was first described in the medical
literature in 1891 by Anton Delbrueck.[2] Although it is a
controversial topic,[2] pathological lying has been defined as
"falsification entirely disproportionate to any discernible end in
view, may be extensive and very complicated, and may manifest over a
period of years or even a lifetime".[1]
[...] Pathological liars
Lying is the act of both knowingly and intentionally/willfully making
a false statement.[4] Most people do so out of fear.[5] Pathological
lying is considered a mental illness, because it takes over rational
judgement and progresses into the fantasy world and back.[6]
Excessive lying is a common symptom of several mental illnesses. For
instance people who suffer from antisocial personality disorder use
lying to benefit from others. Some individuals with borderline
personality disorder lie for attention by claiming they’ve been
treated poorly.[7] Pathological lying, on the other hand, can be
described as an addiction to lying. It is when an individual
consistently lies for no personal gain. The lies are commonly
transparent and often seem rather pointless.[8]
There are many consequences of being a pathological liar. Due to lack
of trust, most pathological liars' relationships and friendships fail.
If the disease continues to progress, lying could become so severe as
to cause legal problems, including but not limited to fraud.[9]
Psychotherapy appears to be one of the only methods to treat a person
suffering from pathological lying. There has been no research done
regarding the use of pharmaceutical medication to treat pathological
liars.[10] Some research suggests that certain people may have a
“predisposition to lying”.[11]
<snip>
yyyyyyyyyyyyyyyyyyyyyyyyyyyy
Oh oh... this looked interesting to me.
http://www.ncbi.nlm.nih.gov/pubmed/22771957
Int J Biochem Cell Biol. 2012 Jul 6;44(11):1887-1896.
Ei24-deficiency attenuates protein kinase Cα signaling and skin
carcinogenesis in mice.
Devkota S, Sung YH, Choi JM, Lee J, Ha NY, Kim H, Cho BC, Song J, Lee
HW.
Source
Department of Biochemistry, College of Life Science and Biotechnology,
Yonsei University, Seoul 120-749, Republic of Korea.
Abstract
Etoposide-induced gene 24 (Ei24) is a p53 target gene that inhibits
growth, induces apoptosis and autophagy, as well as suppresses breast
cancer. To evaluate the role of Ei24 in in vivo tumorigenesis, we
generated an Ei24-deficient mouse model. Here, we report that,
although Ei24 homozygous knockout mice are embryonic lethal, Ei24
heterozygous null mice are attenuated to DMBA/TPA-induced
carcinogenesis with regard to the number and size of tumors but not
the incidence. Ei24 contains a functional consensus motif, named as an
R motif that is highly analogous to amino acids 105-110 of RINCK1, an
E3 ligase for protein kinase C (PKC) proteins. We found that Ei24
stabilizes PKCαvia RINCK degradation and competition with RINCK for
binding with the C1a domain of PKCα. We also found that Ei24
contributes to PKCα-mediated transactivation of EGFR by promoting PKCα
membrane localization and interaction with EGFR. Finally, using
Oncomine database we show that Ei24 and EGFR are upregulated in some
subsets of human HNSCC. These results suggest that Ei24 is a regulator
of the RINCK1-PKCα-EGFR signaling pathway in the development of skin-
cancer.
PMID: 22771957
p53 + Ei24 - 15 hits -pubmed
http://www.ncbi.nlm.nih.gov/pubmed?term=p53%20Ei24
------------------
http://en.wikipedia.org/wiki/EI24
Symbols EI24; EPG4; PIG8; TP53I8
Etoposide-induced protein 2.4 homolog is a protein that in humans is
encoded by the EI24 gene.[1][2][3]
This gene has higher expression in p53-expressing cells than in
control cells and is an immediate-early induction target of p53-
mediated apoptosis. The protein encoded by this gene contains six
putative transmembrane domains and may suppress cell growth by
inducing apoptotic cell death through the caspase 9 and mitochondrial
pathways. This gene is located on human chromosome 11q24, a region
frequently altered in cancers. Alternative splicing results in two
transcript variants encoding different isoforms.[3]
<snip>
STAT to the ER?
NOPe... STRESS to the ER, er ER, ER....& then p53 will hang your
cancer out to dry?
http://www.ncbi.nlm.nih.gov/pubmed/22859938
Endoplasmic Reticulum Stress Stimulates p53 Expression through NF-κB
Activation.
Lin WC, Chuang YC, Chang YS, Lai MD, Teng YN, Su IJ, Wang CC, Lee KH,
Hung JH.
PLoS One. 2012;7(7):e39120. Epub 2012 Jul 30.
Source
Eppley Institute for Research in Cancer and Allied Diseases,
University of Nebraska Medical Center, Omaha, Nebraska, United States
of America.
Abstract
BACKGROUND:
Induction of apoptosis by endoplasmic reticulum (ER) stress is
implicated as the major factor in the development of multiple
diseases. ER stress also appears to be a potentially useful major
response to many chemotherapeutic drugs and environmental chemical
compounds. A previous study has indicated that one major apoptotic
regulator, p53, is significantly increased in response to ER stress,
and participates in ER stress-induced apoptosis. However, the
regulators of p53 expression during ER stress are still not fully
understood.
PRINCIPAL FINDINGS:
In this report, we demonstrate that induction of p53 expression is
mediated through NF-κB signaling pathways during ER stress in MCF-7
cells. Tunicamycin or brefeldin A, two ER stress inducers, increased
p53 expression in MCF-7 and Hela cells. We found p53 nuclear
localization, activity, and phosphorylation at serine 15 on p53
increased during ER stress. Nuclear translocation of NF-κB and
activity of NF-κB were also observed during ER stress. ER stress-
induced p53 expression was significantly inhibited by coincubation
with the NF-κB inhibitor, Bay 11-7082 and downregulation of NF-κB p65
expression. The role of p53 in mediating Brefeldin A-induced apoptosis
was also investigated. Induction of p53 expression by Brefeldin A was
correlated to Brefeldin A-induced apoptosis. Furthermore,
downregulation of p53 expression by p53 siRNA significantly reduced
Brefeldin A-induced apoptosis in MCF-7 cells.
SIGNIFICANCE:
Taken together, NF-κB activation and induction of p53 expression is
essential for ER stress-induced cell death which is important for
therapeutic effects of clinical cancer drugs. Our results may provide
insight into the mechanism of cancer chemotherapy efficacy that is
associated with induction of ER stress.
PMID: 22859938
but it should be in another thread tar baby?
yep..oh well...
*****************************************************
randall...
OK so i went looking to find the CURE of the gut without lavender you
EAT?
Whoever heard of that?
Maybe scurfy master Ben Franklin?
OK and who else?
Anyone who red the last thread:
last thread today:
Tues, Aug 7 2012 10:00 am
Subject: Gi TRACT & Psor ->GUT ->Causation -- Citrobacter Rodentium -
Lavender (Medicinal )-->MicroFLORA -- IL-22 -NAC - Nrf2 - Card14
Mutation Speculations - StuPidly time -- Higgs Field -- Hold EM?
Doctor Corsi - RiboCeine
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/msg/368e3dd41dd750fe
If i didn't read the pubmed on it i would NOT have believed it, right?
[...] http://www.ncbi.nlm.nih.gov/pubmed/22821949
Am J Physiol Gastrointest Liver Physiol. 2012 Jul 19.
Medicinal lavender modulates the enteric microflora to protect
against
Citrobacter rodentium-induced colitis.
[...] PMID: 22821949
I dunno you're fairly gullible on your travels tar baby.
And what about colitis caused by some other buggy agent?
Right id squid and it's the path and not the GOAL..... goal!
But in soccer it's the Goals due to the path then?
You got me.... Score!
So this is about fixing the gut, what?
With this Propionyl L-Carnitine according to will block of LE fame.
Is that his real name tar baby?
I dunno id squid...
What's in a name?
Well if it's rose or lavender you do have an expectation, right?
I guess... so will, WILL wait till i do these farty smelly abstracts/
links... i think!
9 results for fart gas hydrogen - p ng:
https://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?q=fart+gas+hydrogen&start=0&
#1 is Durk and Sandy Pearson (Shaw)--> hydrogen as a Selective
Antioxidant.
And durk and sandy are very LE-ish... so that is GOOD. I bet they
live to 122 and 3/4's?
Or maybe 86 for durk and 93 for sandy?
Hey... just guessing..i'm not a wizard on this health stuff btw...
what whey?
why whey in then tar baby?
For fun id squid...
ok...
Thurs, May 31 2012 1:29 pm
Subject: Anti-ROS -->Hydrogen From your Gut Flora --Durk/Sandy Pearson
--> LCFOS --> Don't SMELL or BE Dum Dum chewing Gum Gum - Ben Franklin
on Fartology -->Chessypoofs
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/msg/345d76bc71274827
Can FART GAS save the hearts of psoriatics which we KNOW are at risk?
Randall tar baby you give your heart to every tart that is merely an
idea!
Hey id squid that isn't true.... i think first and step on it
second.... and then like barney formula i take it and fake it and
them make up my mind and then don't take it and try xyz and decide.
It's science id squid!
Yeah anecdotally testing for one canary who sings like his beak is on
psor fire... LOL
FART on you id squid.
Hey your still me if you didn't KNOW tar blabby juan....
OK... but but but er er er...
I'm having a heart attack yack yack!
Quick.... FART produly...or hold it so the gas permeates your brains?
ER heart tissue.. Sorry rat baby.... i mean eR eR eR tar baby...
http://www.ncbi.nlm.nih.gov/pubmed/22815945
PLoS One. 2012;7(7):e41147. Epub 2012 Jul 18.
Hydrogen Sulfide Inhibits the Development of Atherosclerosis with
Suppressing CX3CR1 and CX3CL1 Expression.
Zhang H, Guo C, Wu D, Zhang A, Gu T, Wang L, Wang C.
Source
Department of Cardiology, Shanghai Ninth People's Hospital, Shanghai
JiaoTong University School of Medicine, Shanghai, China.
Abstract
Hydrogen sulfide, as a novel gaseous mediator, has been suggested to
play a key role in atherogenesis. However, the precise mechanisms by
which H(2)S affects atherosclerosis remain unclear. Therefore, the
present study aimed to investigate the potential role of H(2)S in
atherosclerosis and the underlying mechanism with respect to
chemokines (CCL2, CCL5 and CX3CL1) and chemokine receptors (CCR2,
CCR5, and CX3CR1) in macrophages. Mouse macrophage cell line RAW 264.7
or mouse peritoneal macrophages were pre-incubated with saline or NaHS
(50 µM, 100 µM, 200 µM), an H(2)S donor, and then stimulated with
interferon-γ (IFN-γ) or lipopolysaccharide (LPS). It was found that
NaHS dose-dependently inhibited IFN-γ or LPS-induced CX3CR1 and CX3CL1
expression, as well as CX3CR1-mediated chemotaxis in macrophages.
Overexpression of cystathionine γ-lyase (CSE), an enzyme that
catalyzes H(2)S biosynthesis resulted in a significant reduction in
CX3CR1 and CX3CL1 expression as well as CX3CR1-mediated chemotaxis in
stimulated macrophages. The inhibitory effect of H(2)S on CX3CR1 and
CX3CL1 expression was mediated by modulation of proliferators-
activated receptor-γ (PPAR-γ) and NF-κB pathway. Furthermore, male
apoE(-/-) mice were fed a high-fat diet and then randomly given NaHS
(1 mg/kg, i.p., daily) or DL-propargylglycine (PAG, 10 mg/kg, i.p.,
daily). NaHS significantly inhibited aortic CX3CR1 and CX3CL1
expression and impeded aortic plaque development. NaHS had a better
anti-atherogenic benefit when it was applied at the early stage of
atherosclerosis. However, inhibition of H(2)S formation by PAG
increased aortic CX3CR1 and CX3CL1 expression and exacerbated the
extent of atherosclerosis. In addition, H(2)S had minimal effect on
the expression of CCL2, CCL5, CCR2 and CCR5 in vitro and in vivo. In
conclusion, these data indicate that H(2)S hampers the progression of
atherosclerosis in fat-fed apoE(-/-) mice and downregulates CX3CR1 and
CX3CL1 expression on macrophages and in lesion plaques.
PMID: 22815945
Free PMC Article
http://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22815945/?tool=pubmed
---------------
http://en.wikipedia.org/wiki/NaHS
Sodium hydrosulfide is the chemical compound with the formula NaHS.
This compound is the product of the half neutralization of hydrogen
sulfide with sodium hydroxide. NaHS is a useful reagent for the
synthesis of organic and inorganic sulfur compounds. It is a colorless
solid that typically smells like H2S due to hydrolysis by atmospheric
moisture. In contrast with sodium sulfide, Na2S, which is insoluble in
organic solvents, NaHS, being a 1:1 electrolyte, is more soluble.
Alternatively, in place of NaHS, H2S can be treated with an organic
amine to generate an ammonium salt. Solutions of HS− are sensitive to
oxygen, converting mainly to polysulfides, indicated by the appearance
of yellow.
----------------
http://atvb.ahajournals.org/content/29/2/156.full
Is H2S a Stinky Remedy for Atherosclerosis?
Rui Wang
From Department of Biology &
Correspondence to Rui Wang, Lakehead University, Thunder Bay, 955
Oliver Rd, Ontario P7B5E1, Canada. E-mail rw...@lakeheadu.ca
Atherosclerosis is a complex and chronic pathological state that
adversely affects the structure of blood vessels. Vascular
inflammation, endothelial damage, smooth muscle cell migration, foam
cell accumulation, and lipid and cholesterol deposition contribute to
different stages of plaque formation in large and medium-sized blood
vessels. The consequential narrowing and stiffening of blood vessels
restricts blood circulation and increases plaque thrombogenicity.
Pathogenic causes that lead to these pathological changes in
atherosclerosis have always been the center of attention, but we have
not yet cleared the cloud on this issue.
See accompanying article on page 173
http://atvb.ahajournals.org/lookup/volpage/29/173
An ancient problem may have an ancient solution. A disease older than
the history of mankind, atherosclerosis affects the health of various
species in a much more profound fashion than other types of
cardiovascular problems. Taking the fish as a case in point, whereas
heart failure and hypertension are nonissues with them, fishes
spontaneously develop atherosclerosis in their natural habitat
regardless of what are on their menu. Even more ancient than the
origin of atherosclerosis, production of hydrogen sulfide (H2S) gas by
living organisms can be traced far back before the evolvement of the
vascular system. Bacteria and archaea produce and use H2S as the
essential element for their survival and proliferation. In eukaryotes,
H2S is produced under the enzymatic actions of 2 pyridoxal-5′-
phosphate-dependent enzymes, cystathionine beta–synthase (CBS) and
cystathionine γ-lyase (CSE).1 Importantly, CSE is a major H2S-
producing enzyme in the cardiovascular system.2
Recent advance in our understanding of the biological importance of
endogenous H2S has shed light on the potential use of this ancient
gasotransmitter to deal with atherosclerosis. First, H2S inhibits
smooth muscle cell proliferation, one major event in atherosclerosis.
Yang et al2 previously reported that, after inhibiting endogenous H2S
production by DL-propargyglycine (PPG) pretreatment or knocking down
endogenous CSE gene by short interfering RNA approach, H2S at 50 to
100 μmol/L induces apoptosis of human aorta smooth muscle cells (SMCs).
3 Without inhibiting endogenous H2S production, exogenously applied
H2S at 100 μmol/L had little effect on SMC apoptosis. The importance
of the interaction between exogenous and endogenous H2S is thus
indicated. Second, H2S inhibits homocysteine-induced vascular damage.
Homocysteine is a key amino acid in regulating cellular levels of
cysteine, methionine, and sulfur. Accumulation of homocysteine in the
plasma, termed hyperhomocysteinemia, is considered to be an
established risk factor for atherosclerosis. Dietary supplementation
with methionine and homocysteine induced hyperhomocysteinemia which
promoted early atherosclerosis in apolipoprotein E–deficient (apoE−/−)
mice.4 The development of hyperhomocysteinemia in CSE gene knockout
mice has been recently shown.5 It has also been demonstrated that low
levels of NaHS (30 or 50 μmol/L) protected rat aortic SMCs from
homocysteine-induced cytoxicity and reactive oxygen species, leading
to improved cell viability.6 Third, H2S reduces atherogenesis. H2S
inhibited atherogenic modification of purified LDL induced by
hypochlorite in vitro, as measured by apolipoprotein alterations.7
Meng et al reported that during neointimal formation induced by
balloon injury in rats,8 CSE expression was reduced and endogenous
production of H2S decreased. Rescue of the injured artery with NaHS
not only reversed the reduced endothelium-dependent vasorelaxation,
but also significantly inhibited neointima formation of the balloon-
injured carotid arteries.8
The report by Wang et al in this issue of Arteriosclerosis,
Thrombosis, and Vascular Biology adds a new twist in searching for the
direct correlation of H2S and atherosclerosis.9 They found that
treatment of apoE−/− mice with NaHS resulted in reduced
atherosclerotic plaque, whereas inhibition of CSE activity in apoE−/−
mice with PPG enlarged plaque size. By promoting adhesion of
inflammatory cells to the endothelium, intracellular adhesion
molecule-1 (ICAM-1) may be one of the causative factors for
atherosclerosis as its level is significantly higher in human
atherosclerotic plaques. Wang et al attributed the antiatherosclerotic
effect of NaHS on apoE−/− mice to the reduced ICAM-1 level in
circulation and lowered expression of ICAM-1 in aortic endothelial
cells.9
The excitement brought by the observation of Wang et al9 is beyond the
therapeutic value of NaHS in atherosclerosis, which can be traced back
to previous reports.3,8 It also proposes challenges and questions.
Essential and curious enough for the root of pathogenesis of
atherosclerosis is whether abnormality of CSE/H2S system is the cause
or consequence of the disease. While showing a marginal decrease in
H2S level in plasma from apoE−/− mice having advanced atherosclerosis,
basal levels of H2S and CSE protein expression before the
manifestation of atherosclerosis in apoE−/− mice were not determined.9
What is even more perplexing is the aortic production rate of H2S and
aortic CSE expression level in apoE−/− mice.9 Decreased H2S production
rate should reflect decreased CSE activity or expression. The
decreased H2S production rate, however, as reported by Wang et al,
contradicts with the increased CSE mRNA expression in aortic
atherosclerotic tissues,9 which cannot be readily explained by an
assumed “positive feedback” mechanism.
Interactions between SMCs and endothelial cells are key to
atherosclerosis development. Wang et al proposed that H2S produced by
SMCs may carry a signal to endothelial cells, thereby altering the
production of ICAM-1 and affecting endothelial integrity.9 This is an
interesting concept and worth further comment. Expression of CSE mRNA
was initially localized in vascular SMCs, not endothelial cells2;
however, immunoblot analysis had not been done to detect CSE protein
in endothelial cells in earlier studies. As our understanding of the
tissue- and species-specific expression of CSE mRNA and proteins
deepened, as well as the availability of more specific and sensitive
antibodies against CSE that target different CSE protein epitopes, the
cellular location of CSE in blood vessel has been better resolved. A
recent study by Yang et al presented clear evidence that mouse blood
vessels express CSE protein both in vascular smooth muscle and
endothelium layers.5 Cultured HUVECs also express CSE protein and
produce H2S.5 Even in the report by Wang et al, immunopositive
staining for CSE seems also obvious in the endothelial layer of mouse
aortic tissues from wild-type and apoE−/− mice (see Wang et al,9
Figure 2). It is therefore likely that H2S produced by endothelial
cells has a direct autocrinal effect on endothelial cells to regulate
ICAM-1 production.
Although a causative role of H2S in the pathogenesis of
atherosclerosis is still open for debate and inconsistencies have been
encountered, it is clear from this novel study by Wang et al that H2S
can be used as an effective therapeutic intervention for
atherosclerosis in apoE−/− mice.9 Stinky but healthy, H2S therapy
appears to be a good trade-off. Consumption of garlic, preserved bean
curd (stinky tofu), or preserved egg (thousand year’s egg) all
increase the production of H2S. But before you put these on the dinner
table, pause a while to hold your breath. If there were a “positive
feedback” mechanism between H2S and CSE expression as proposed by Wang
et al in this issue, application of exogenous H2S to atherosclerotic
patients would lead to inhibited CSE expression and decreased
endogenous H2S level. Would be this a good news for the prognosis of
atherosclerotic patients? Let’s pause even longer and investigate
further the correlation between H2S and atherosclerosis.
It ain’t done till it’s done.
<snip>
I bet Benjamin Franklin with psoriasis called scurffy back (?) then
would FART proudly NOW.
Ben and 13 hits for : scurf - p ng
https://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?q=scurf&start=0&scoring=d&
So when Big BEN went to FRANCE with ants in his pants and scurf on his
turf did he eat lavendar?
I wonder?
So how does Will Block treat the GUT?
He uses Propionyl L-Carnitine and i bet it isn't in the Barney
Formula?
WELL?
Seeing we have zero hits for Propionyl L-Carnitine you would be RIGHT
unless
barney is using things that make it inside of your liver... and you're
living it uP...
http://www.life-enhancement.com/article.aspx?id=2594
Propionyl L-Carnitine
Dispatches Ulcerative Colitis
PLC may be sequestered from circulating in ulcerative colitis
to serve as a source of L-carnitine and propionyl-coenzyme-A in the
colon
By Will Block
Inflammatory bowel disease is thought to be caused by the chronic or
recurring immune response and inflammation of the gastrointestinal
tract. The most common inflammatory bowel diseases are Crohn’s disease
and ulcerative colitis (UC).
Colitis is inflammation of the colon. It is also called colonitis. No
matter what you call it, it’s a miserable condition, and it’s likely
to hang on unless you do something about it. Colitis should not be
confused with irritable bowel syndrome (spastic colon), a different
and much less serious condition that is aggravating and a disorder
that affects the motility (muscle contractions) of the colon. But it
does not entail inflammation. In colitis, furthermore, inflammation is
typically accompanied by ulceration, which damages or destroys patches
of the mucosal lining of the colon or rectum. UC—the standard term for
the most common form of the disease—causes bloody diarrhea, and stools
may contain mucus and pus. There may also be fever and abdominal pain.
One thing more—patients with UC are at increased risk of colon cancer.
Patients with ulcerative colitis are at increased risk of colon
cancer.
Prevalence and Toll
Inflammatory bowel disease is one of the five most prevalent
gastrointestinal disease burdens in the United States, with an overall
health care cost exceeding $1.7 billion. Currently, there is no
medical cure. Thus care is commonly a life-long endeavor. Every year
in the United States, inflammatory bowel disease accounts for more
than 700,000 physician visits, 100,000 hospitalizations, and
disability in 119,000 patients.1 Up to 75% of patients with Crohn’s
disease and 25% of those with UC will require surgery.
Ulcerative colitis is regarded as an impaired fatty-acid oxidation
disease.
The Many Adversities of Drugs
So what can you do about all this? Well, there are the drugs of
course, and they can be quite effective, although you may have to pay
a price beyond mere money to obtain their benefits (see the sidebar
“Drug Side Effects—A Cascade of Adversities”). If the condition
affects just the rectum and lower part of the colon, the drugs of
choice are aminosalicylates or corticosteroids, administered rectally.
But if the condition goes farther up the pipeline, so to speak, oral
medication is indicated, and the drug of first choice is usually a
thiopurine (both drugs are in the sidebar).
Drug Side Effects—A Cascade of Adversities
Aminosalicylate and thiopurine are two of the drugs used to treat the
inflammatory bowel disease ulcerative colitis. Aminosalicylate belongs
to the family of medicines called anti-infectives. Thiopurine is an
immune system suppressant.
The common side effects of aminosalicylate include gastrointestinal
problems (nausea, vomiting, diarrhea, abdominal pain) Then, by
category: Cardiovascular; Central Nervous System [including headache
(35%), dizziness (8%), asthenia (7%), weakness (6%); hypertonia (5%)];
Dermatologic; Eye-Ear-Nose-Throat; GI [including abdominal pain (18%);
eructation (16%); nausea (13%); abdominal cramps/discomfort (8%);
diarrhea (7%); dyspepsia, flatulence (6%); vomiting (5%)]; Genito
urinary; Hematologic-Lymphatic; Hepatic; Lab Tests; Local; Metabolic-
Nutritional; Musculoskeletal; Respiratory; Dyspnea; Miscellaneous
[Pain (14%); fever (6%); flu syndrome (5%)]. In each category, only
those adverse effects greater than 5% are listed. There are a great
many more, and some are quite serious.
Thiopurine drugs can also cause side effects. The most common side
effects are stomach related problems (such as nausea, vomiting,
diarrhea, abdominal pain) and bone marrow problems. Also there may be
severe allergic reactions (rash; itching; hives; difficulty breathing;
tightness in the chest; swelling of the mouth, face, lips, or tongue);
chest pain or tightness; dizziness; fatty stools; fever, chills, or
persistent sore throat; increased or painful urination; muscle pain or
aches; painful, red bumps or blisters on the arms, face, neck, or
back; severe or persistent nausea, vomiting, or diarrhea; shortness of
breath; stomach pain; symptoms of liver problems (e.g., dark urine,
loss of appetite, pale stools, right-sided stomach pain, yellowing of
the eyes or skin); unusual bleeding or bruising; unusual growths or
lumps; unusual weakness or tiredness. And this is not a complete list.
Either way, this is one rough road to travel, so any new prospects of
treatment should be welcome, especially when there is virtually no
adversity.
References
Drugs.com www.drugs.com/ppa/mesalamine-5-aminosalicylic-acid-5-asa.html.
Accessed February 19, 2012.
Drugs.com www.drugs.com/sfx/azathioprine-side-effects.htm . Accessed
February 19, 2012.
A Disease of Fatty Acid Oxidation
UC is regarded as an impaired fatty-acid oxidation disease. Short-
chain fatty acids are produced in the lumen of the colon by bacterial
fermentation of consumed complex carbohydrates. These fatty acids—and
butyrate in particular—are the primary metabolic fuel of colonocytes
(epithelial cells of the colon). As well, short-chain fatty acids
affect colonic blood flow, motility, and mucus secretion. And while
the pathogenesis (cause) of UC is not yet fully understood, there is a
growing amount of evidence suggesting that a deficiency of these short-
chain fatty acids in the colon lining’s colonocytes may provide an
answer.
(click on thumbnail for full sized image)
In fact, several studies suggest that impaired beta-oxidation of short-
chain fatty acids may lead to colonic mucosal damage due to an energy
deficiency that can only partly be compensated for by the oxidation of
other substrates.2–4 Unfortunately, treatment of UC with fatty acid
enemas has not produced definitive results.
Carnitine Helps Feed Mitochondria
L-Carnitine is needed for the transport of activated fatty acids into
the mitochondria for beta-oxidation in order to generate Acetyl-CoA,
the entry molecule for the citric acid cycle. As at least one study
has shown, while plasma levels of free L-carnitine are similar in
patients with UC and matched healthy controls, plasma levels of the
ester propionyl L-carnitine (PLC) are lower in patients with UC.5 This
suggests that PLC may be sequestered from circulating in UC patients,
thus inhibiting its service as a source of L-carnitine and propionyl-
coenzyme-A in the colon.
Higher L-carnitine levels, in turn, facilitate energy release through
beta-oxidation of fatty acids, while propionyl-coenzyme-A—an efficient
energy source—enters the citric acid cycle as succinate.6 PLC
supplementation has the potential to improve cellular energy levels,
and is able to stimulate energy production in ischemic skeletal
muscles, and increases maximum walking distance in patients with
peripheral arterial obstructive disease.7
New Study Finds PLC Can Co-Treat Mild UC
Taking the above into consideration, a team of multinational
researchers set out to evaluate efficacy and safety of PLC in patients
with mild-to-moderate UC who were employing oral aminosalicylate or
thiopurine therapy.8 In a multicenter study, straddling five European
nations, the study was double-blinded, placebo-controlled, and
randomized. Each of three different groups of 40, 41, and 40 patients
respectively received PLC at 1 g/day, PLC at 2 g/day, or placebo.
In the PLC 1 g/day group,
30 of 40 (75%) patients had a
clinical/endoscopic response and
27 of 39 (69%) in the
PLC 2 g/day group.
All of the patients were between the ages of 18–75 with disease
activity index (DAI) scores of 3–10 (mild UC is 3–6 and moderate UC is
6–10). Of the 121 patients who were randomized, 57 of 79 (72%)
receiving PLC (combined 1 g and 2 g cohort) had a clinical/endoscopic
response vs. 20 of 40 (50%) compared to a clinical/endoscopic response
for those receiving placebo. Clinical/endoscopic response was defined
as a decrease in DAI score = 3 points or as remission, defined as a
DAI score = 2. Clinical/endoscopic response findings for the stratum
of patients in the combined PLC cohort who had mild disease were also
significantly different from placebo. Due to the small number of
patients with moderate disease, no statistical conclusions can be made
for this stratum.
The patients were not permitted to change their stable oral
concomitant aminosalicylate or thiopurine therapy during the trial.
Very few patients (n = 4) received stable oral thiopurine therapy; and
thus stratification was limited to disease severity only (rather than
for the drug used). Furthermore, the use of systemic or topical
corticosteroids, rectal therapies, NSAIDs, probiotics or antibiotics
was not allowed.
In the PLC 1 g/day group, 30 of 40 (75%) patients had a clinical/
endoscopic response and in the PLC 2 g/day group the response was 27
of 39 (69%). PLC 1 g/ day treatment was significantly superior
compared with placebo. Results for the stratum of patients in the PLC
1 g / day arm with mild disease were similarly significant compared to
placebo. Results for the PLC 2 g / day arm were not statistically
significantly different to the placebo arm.
Remission Analysis
Rates of disease absence (remission) were 22/40 (55%), 19/39 (49%),
14/40 (35%) in the PLC 1 g, PLC 2 g, and placebo groups, respectively
[41 / 79 (52%) patients in the combined PLC cohort]. However, none of
the remission rates for patients receiving PLC were significantly
greater than that for patients receiving placebo. When considering
data stratified by disease severity, only PLC 1 g/day in patients with
mild disease significantly increased the probability of remission
compared to corresponding placebo.
When the response rates for each of the four items (rectal bleeding,
stool frequency, mucosal appearance and physician global assessment)
of the DAI was analyzed—for each item, response was defined as a
lowering of at least 1 point of the score over baseline—the group
receiving PLC 1 g /day had a rate of response for rectal bleeding that
was significantly improved compared to the group receiving placebo.
PLC, as a group, had a similar safety profile to placebo; the most
common adverse events were gastrointestinal. This phase II trial
confirmed that PLC is a potential treatment for the management of mild-
to-moderate UC. Patients receiving PLC were more likely to have a
clinical/endoscopic response than those receiving placebo.
As there is no statistically significant clinical difference between
the two PLC doses investigated, the lower dose of PLC 1 g/day should
be used in future studies. When separated into layers for disease
severity, clinical/endoscopic response rates for the combined PLC
cohort and the PLC 1 g/ day arm were statistically significant vs.
placebo in patients with mild UC.
When considering data
stratified by disease severity,
only PLC 1 g/day in patients with
mild disease significantly increased
the probability of remission
compared to corresponding placebo.
Patients with mild disease receiving PLC 1 g /day were more likely to
achieve remission than those taking placebo. Because there were a
relatively small number of patients with moderate UC, no conclusions
could be drawn. Further studies are therefore needed to confirm the
effectiveness of PLC in patients with moderate and severe UC.
Maximizing Colonocyte Uptake Through PLC
PLC was administered in an oral colon-release formulation that allows
the active ingredient to be released directly into the colon lumen,
facilitating maximum uptake by colonocytes. This may explain why a low
1 g /day dose is effective and that the lack of additional benefit
with a 2 g/day dose may be due to saturation at the site of uptake.
As there is no statistically significant
clinical difference between the two
PLC doses investigated,
the lower dose of PLC 1 g/day
should be used in future studies.
Assessment of remission induction did not yield significant data. But
future studies with more patients or of longer duration may further
clarify the positive remission trends shown for PLC treatment in this
trial and even evaluate the role of PLC in maintaining remission.
PLC could provide an alternative treatment for patients with
aminosalicylate or thiopurine intolerance, or for those wanting to
avoid their adverse effects (see sidebar) and corticosteroids.
Certainly, data from this trial, where patients were already receiving
stable oral treatment, suggest a role for PLC as an adjunctive therapy
for the induction of remission.
As PLC was well tolerated, long-term therapy for remission maintenance
is plausible, and might reduce the risk of colon cancer, which is the
case with regular aminosalicylate treatment. In conclusion, this trial
has provided proof of concept for the use of PLC in the treatment of
mild-to-moderate UC. PLC 1 g /day appears to be well tolerated with a
favorable safety profile and should be further investigated as a
treatment for mild-to-moderate UC.
Carnitines for Energy, Muscle Strength, and Sex
Recent findings have shown that acetyl-L-carnitine (ALC) and PLC are
beneficial in other ways. ALC is thought to proffer benefits for
memory and for various neurological disorders: such as Alzheimer’s
dementia, depression in the elderly, chronic fatigue syndrome,
peripheral neuropathies, ischemia and reperfusion of the brain, and
cognitive impairment associated with various conditions.
PLC has also been shown to replenish the intermediates of the citric
acid cycle via propionyl-CoA moiety (boosting energy levels),
strengthen muscle cells, and assist peripheral vasodilator activity,
including the enhancement of sexual prowess. As well, PLC has been
found to help prevent and treat ischemic heart disease, congestive
heart failure, hypertrophic heart disease, and peripheral arterial
disease. It might be a good idea to add this supplement to your
program, if you are not already taking it.
Possible Parkinson’s Neuroprotection
Lastly, there is new evidence to indicate that ALC, along with α-
lipoic acid, may inhibit bradykinesia (slowed ability to start and
continue movement) and motor impairment in rats when given at a human
dose equivalent of 1215 mg/day of ALC and 608 mg/day of α-lipoic acid.
9 In this study, ALC also enhanced ATP production. According to the
researchers, “Taken together, our study reinforces the view that
acetyl-L-carnitine and α-lipoic acid are promising candidates for
neuroprotection in Parkinson’s disease.”
References
<snip>
342 hits : Propionyl L-Carnitine - pubmed
http://www.ncbi.nlm.nih.gov/pubmed?term=Propionyl%20L-Carnitine
Does it have barney?
I don't know... maybe FRED Flinstone ate it?
Wilma bring me some PLC please... this caveman is gonna swing.
Did gay cavemen set up their own cave's and pledge .... like a
marriage type of thing?
I bet thy did but then again they didn't worry about another ICE AGE
or global warming right? LOL
And the poopulation BOMB of those breeder's wasn't for another 69,000
years or so?
LOL
#1 of 347
http://www.ncbi.nlm.nih.gov/pubmed/22743351
Ther Drug Monit. 2012 Aug;34(4):406-14.
Effect of short- and long-term treatment with valproate on carnitine
homeostasis in humans.
Morand R, Todesco L, Donzelli M, Fischer-Barnicol D, Mullen PJ,
Krähenbühl S.
Source
*Division of Clinical Pharmacology and Toxicology, University Hospital
Basel †Department of Biomedicine, University of Basel ‡Psychiatric
University Hospital, University of Basel §Swiss Center of Human
Applied Toxicology (SCAHT), University of Basel, Basel, Switzerland.
Abstract
AIMS:
: The aim of this study was to identify the mechanisms of
hypocarnitinemia in patients treated with valproate.
METHODS:
: Plasma concentrations and urinary excretion of carnitine,
acetylcarnitine, propionylcarnitine, valproylcarnitine, and
butyrobetaine were determined in a patient starting valproate
treatment and in 10 patients on long-term valproate treatment.
Transport of carnitine and valproylcarnitine by the proximal tubular
carnitine transporter OCTN2 was assessed in vitro.
RESULTS:
: In the patient starting valproate, the plasma carnitine and
acetylcarnitine levels dropped for 1-3 weeks and had recovered after
3-5 weeks, whereas the plasma levels of propionyl and
valproylcarnitine increased steadily over 5 weeks. The renal excretion
and excretion fractions (EFs) of carnitine, acetylcarnitine,
propionylcarnitine, and butyrobetaine decreased substantially after
starting valproate. Compared with controls, patients on long-term
valproate treatment had similar plasma levels of carnitine,
acetylcarnitine, and propionylcarnitine, whereas valproylcarnitine was
found only in patients. Urinary excretion and renal clearance of
carnitine, acetylcarnitine, propionylcarnitine, and butyrobetaine were
decreased in valproate-treated compared with that in control patients,
reaching statistical significance for carnitine. The EFs of carnitine,
acetylcarnitine, and propionylcarnitine were <5% of the filtered load
in controls and were lower in valproate-treated patients. In contrast,
the EF for valproylcarnitine approached 100%, resulting from a low
affinity of valproylcarnitine for the carnitine transporter OCTN2 and
competition with concomitantly filtered carnitine.
CONCLUSIONS:
: The initial drop in plasma carnitine levels of valproate-treated
patients is most likely due to impaired carnitine biosynthesis,
whereas the recovery of the plasma carnitine levels is explainable by
an increased renal expression of OCTN2. Renally excreted
valproylcarnitine does not affect renal handling of carnitine in vivo.
PMID: 22743351
we have two hits for : valproate - p ng
https://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?q=valproate&start=0&
And one is kofi.... he's hot kofi... where is he these days?
I dunno tar baby... maybe his hair grew back and he's RICH now?
I hope so id squid..
SCORE...
Depakote is (Valproic Acid)
http://en.wikipedia.org/wiki/Valproate_semisodium
Valproate semisodium (INN) or divalproex sodium (USAN) consists of a
compound of sodium valproate and valproic acid in a 1:1 molar
relationship in an enteric coated form. It is used in the United
Kingdom, Canada, and United States for the treatment of the manic
episodes of bipolar disorder. In rare cases, it is also used as a
treatment for major depressive disorder, and increasingly taken long-
term for prevention of both manic and depressive phases of bipolar
disorder, especially the rapid-cycling variant. It is also used in the
US for the treatment of epilepsy, certain side effects of autism,
chronic pain associated with neuropathy, and migraine headaches. Its
chemical name is sodium hydrogen bis(2-propylpentanoate). The extended
release formulation allows for a single daily dose.
In the UK semisodium valproate has been sold for a few years as the
proprietary drug Depakote and marketed for psychiatric conditions
only. It is about five times the price of sodium valproate,[citation
needed] which has been marketed for around 30 years as Epilim by the
same company for epilepsy and is also available from other
manufacturers as a generic product.
<snip>
4 hits: depakote - p ng
https://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?q=Depakote&start=0&scoring=d&
#2 of 342
http://www.ncbi.nlm.nih.gov/pubmed/22593918
Propionic Acidemia.
Authors
Carrillo-Carrasco N, Venditti C.
EditorsIn: Pagon RA, Bird TD, Dolan CR, Stephens K, Adam MP, editors.
SourceGeneReviews™ [Internet]. Seattle (WA): University of Washington,
Seattle; 1993-.
2012 May 17.
Excerpt
DISEASE CHARACTERISTICS:
The spectrum of propionic acidemia (PA) ranges from neonatal-onset to
late-onset disease. Manifestations of neonatal and late-onset PA over
time can include growth impairment, intellectual disability, seizures,
basal ganglia lesions, pancreatitis, and cardiomyopathy. Other rarely
reported complications include optic atrophy, hearing loss, premature
ovarian insufficiency (POI), and chronic renal failure.
DIAGNOSIS/TESTING:
PA is caused by deficiency of propionyl-CoA carboxylase (PCC), the
enzyme that catalyzes the conversion of propionyl-CoA to methylmalonyl-
CoA. Newborns with PA tested by expanded newborn screening have
elevated C3 (propionylcarnitine). Testing of urine organic acids in
persons who are symptomatic or those detected by newborn screening
reveals elevated 3-hydroxypropionate and the presence of
methylcitrate, tiglylglycine, and propionylglycine, which are normally
not observed in the urine. Testing of plasma amino acids reveals
elevated glycine. Confirmation of the diagnosis relies on detection of
either deficient PCC enzymatic activity or biallelic mutations in PCCA
or PCCB.
MANAGEMENT:
Treatment of manifestations: The treatment of persons with acutely
decompensated PA is a medical emergency: treat precipitating factors
such as infection; arrest catabolism by providing high calorie and
fluid intake; minimize protein intake to reduce propiogenic
precursors; give intravenous carnitine; correct hypoglycemia and
metabolic acidosis; and care for the patient in a center with
biochemical genetics expertise and the ability to support urgent
hemodialysis, especially if hyperammonemia is present. Prevention of
primary manifestations: Individualized dietary management to restrict
propiogenic substrates; nasogastric or gastrostomy feeding as needed;
increased caloric intake during illness to prevent catabolism; and
continued multidisciplinary care with metabolic specialists.
Medications may include: L-carnitine supplementation; oral
metronidazole to reduce propionate production by gut bacteria; and/or
N-carbamoylglutamate. Orthotopic liver transplantation (OLT) may be
indicated in those with frequent metabolic decompensations,
uncontrollable hyperammonemia, and/or restricted growth. Prevention of
secondary complications: Consistent evaluation of the protein intake,
depending on age, gender, severity of disease and presence of other
factors such as growth spurts, can avoid insufficient or excessive
protein restriction. The latter can result in deficiency of essential
amino acids and impaired growth, as well as catabolism-induced
metabolic decompensation. Surveillance: Monitor closely patients with
a catabolic stressor (fasting, fever, illness, injury, and surgery) to
prevent and/or detect and manage metabolic decompensations early.
Regularly assess: (1) growth, nutritional status, feeding ability,
psychomotor development; (2) metabolic status by monitoring urine
organic acids and plasma amino acids; (3) renal function; (4) complete
blood count. At intervals not yet determined, screen for:
cardiomyopathy and arrhythmias; optic atrophy; and premature ovarian
insufficiency in females. Agents/circumstances to avoid: Prolonged
fasting; catabolic stressors. Evaluation of relatives at risk: Testing
of at-risk sibs of a patient is warranted to allow for early diagnosis
and treatment.
GENETIC COUNSELING:
Propionic acidemia is inherited in an autosomal recessive manner. At
conception, each sib of an affected individual has a 25% chance of
being affected, a 50% chance of being an asymptomatic carrier, and a
25% chance of being unaffected and not a carrier. Carrier testing for
at-risk relatives and prenatal diagnosis for pregnancies at increased
risk are possible if the disease-causing mutations in the family are
known.
PMID: 22593918
full text
http://www.ncbi.nlm.nih.gov/books/NBK92946/
zzzzzzzzzzzzzzzzzzzzzzzzzzzzzzz
OK fun stuff TIME... man does not live by bread alone..
he needs mirth and some red wine?
Right id squid!
Liar liar pants on FIRE?
Right and you AGE quicker to BOOT!
http://www.usatoday.com/news/health/story/2012-08-04/honesty-beneficial-to-health/56782648/1
Study finds that avoiding lies can improve your health
By Sharon Jayson, USA TODAY
ORLANDO – Honesty may boost your health, suggests a study that found
telling fewer lies benefits people physically and mentally.
Each week for 10 weeks, 110 individuals, ages 18-71, took a lie
detector test and completed health and relationship measures assessing
the number of major and minor lies they told that week, says lead
author Anita Kelly, a psychology professor at the University of Notre
Dame in Indiana. She presented findings at the annual meeting of the
American Psychological Association, which ended Sunday.
"When they went up in their lies, their health went down," says Kelly.
"When their lies went down, their health improved."
Researchers instructed half the participants to "refrain from telling
any lies for any reason to anyone. You may omit truths, refuse to
answer questions, and keep secrets, but you cannot say anything that
you know to be false." The other half received no such instructions.
Over the study period, the link between less lying and improved health
was significantly stronger for participants in the no-lie group, the
study found. When participants in the no-lie group told three fewer
minor lies than they did in other weeks, for example, they
experienced, on average, four fewer mental-health complaints and three
fewer physical complaints. Mental health complaints included feeling
tense or melancholy; physical complaints included sore throats and
headaches.
Linda Stroh, a professor emeritus of organizational behavior at Loyola
University in Chicago, says findings are consistent with her own
research on trust. "When you find that you don't lie, you have less
stress," she says. "Being very conflicted adds an inordinate amount of
stress to your life."
Evidence from past research suggests that Americans average about 11
lies a week. Kelly says the no-lie group participants were down to one
lie, on average, per week. For both groups, when participants lied
less in a given week, they reported their physical health and mental
health to be significantly better that week.
"It's certainly a worthy goal to have people be more honest and more
genuine and interact with others in a more honest way," says
psychologist Robert Feldman of the University of Massachusetts,
Amherst. "That would be ultimately beneficial. I'm a little skeptical
that it makes us all healthier, but it may make us healthier in a
psychological way."
<snip>
Wonder how democraps do it?
Like pelosi, obama and reed for instance?
Eggzactly... LOL
http://en.wikipedia.org/wiki/Pseudologia_fantastica
or
http://en.wikipedia.org/wiki/Pathological_liar
Pseudologia fantastica, mythomania, or pathological lying are three of
several terms applied by psychiatrists to the behavior of habitual or
compulsive lying.[1][2] It was first described in the medical
literature in 1891 by Anton Delbrueck.[2] Although it is a
controversial topic,[2] pathological lying has been defined as
"falsification entirely disproportionate to any discernible end in
view, may be extensive and very complicated, and may manifest over a
period of years or even a lifetime".[1]
[...] Pathological liars
Lying is the act of both knowingly and intentionally/willfully making
a false statement.[4] Most people do so out of fear.[5] Pathological
lying is considered a mental illness, because it takes over rational
judgement and progresses into the fantasy world and back.[6]
Excessive lying is a common symptom of several mental illnesses. For
instance people who suffer from antisocial personality disorder use
lying to benefit from others. Some individuals with borderline
personality disorder lie for attention by claiming they’ve been
treated poorly.[7] Pathological lying, on the other hand, can be
described as an addiction to lying. It is when an individual
consistently lies for no personal gain. The lies are commonly
transparent and often seem rather pointless.[8]
There are many consequences of being a pathological liar. Due to lack
of trust, most pathological liars' relationships and friendships fail.
If the disease continues to progress, lying could become so severe as
to cause legal problems, including but not limited to fraud.[9]
Psychotherapy appears to be one of the only methods to treat a person
suffering from pathological lying. There has been no research done
regarding the use of pharmaceutical medication to treat pathological
liars.[10] Some research suggests that certain people may have a
“predisposition to lying”.[11]
<snip>
yyyyyyyyyyyyyyyyyyyyyyyyyyyy
Oh oh... this looked interesting to me.
http://www.ncbi.nlm.nih.gov/pubmed/22771957
Int J Biochem Cell Biol. 2012 Jul 6;44(11):1887-1896.
Ei24-deficiency attenuates protein kinase Cα signaling and skin
carcinogenesis in mice.
Devkota S, Sung YH, Choi JM, Lee J, Ha NY, Kim H, Cho BC, Song J, Lee
HW.
Source
Department of Biochemistry, College of Life Science and Biotechnology,
Yonsei University, Seoul 120-749, Republic of Korea.
Abstract
Etoposide-induced gene 24 (Ei24) is a p53 target gene that inhibits
growth, induces apoptosis and autophagy, as well as suppresses breast
cancer. To evaluate the role of Ei24 in in vivo tumorigenesis, we
generated an Ei24-deficient mouse model. Here, we report that,
although Ei24 homozygous knockout mice are embryonic lethal, Ei24
heterozygous null mice are attenuated to DMBA/TPA-induced
carcinogenesis with regard to the number and size of tumors but not
the incidence. Ei24 contains a functional consensus motif, named as an
R motif that is highly analogous to amino acids 105-110 of RINCK1, an
E3 ligase for protein kinase C (PKC) proteins. We found that Ei24
stabilizes PKCαvia RINCK degradation and competition with RINCK for
binding with the C1a domain of PKCα. We also found that Ei24
contributes to PKCα-mediated transactivation of EGFR by promoting PKCα
membrane localization and interaction with EGFR. Finally, using
Oncomine database we show that Ei24 and EGFR are upregulated in some
subsets of human HNSCC. These results suggest that Ei24 is a regulator
of the RINCK1-PKCα-EGFR signaling pathway in the development of skin-
cancer.
PMID: 22771957
p53 + Ei24 - 15 hits -pubmed
http://www.ncbi.nlm.nih.gov/pubmed?term=p53%20Ei24
------------------
http://en.wikipedia.org/wiki/EI24
Symbols EI24; EPG4; PIG8; TP53I8
Etoposide-induced protein 2.4 homolog is a protein that in humans is
encoded by the EI24 gene.[1][2][3]
This gene has higher expression in p53-expressing cells than in
control cells and is an immediate-early induction target of p53-
mediated apoptosis. The protein encoded by this gene contains six
putative transmembrane domains and may suppress cell growth by
inducing apoptotic cell death through the caspase 9 and mitochondrial
pathways. This gene is located on human chromosome 11q24, a region
frequently altered in cancers. Alternative splicing results in two
transcript variants encoding different isoforms.[3]
<snip>
STAT to the ER?
NOPe... STRESS to the ER, er ER, ER....& then p53 will hang your
cancer out to dry?
http://www.ncbi.nlm.nih.gov/pubmed/22859938
Endoplasmic Reticulum Stress Stimulates p53 Expression through NF-κB
Activation.
Lin WC, Chuang YC, Chang YS, Lai MD, Teng YN, Su IJ, Wang CC, Lee KH,
Hung JH.
PLoS One. 2012;7(7):e39120. Epub 2012 Jul 30.
Source
Eppley Institute for Research in Cancer and Allied Diseases,
University of Nebraska Medical Center, Omaha, Nebraska, United States
of America.
Abstract
BACKGROUND:
Induction of apoptosis by endoplasmic reticulum (ER) stress is
implicated as the major factor in the development of multiple
diseases. ER stress also appears to be a potentially useful major
response to many chemotherapeutic drugs and environmental chemical
compounds. A previous study has indicated that one major apoptotic
regulator, p53, is significantly increased in response to ER stress,
and participates in ER stress-induced apoptosis. However, the
regulators of p53 expression during ER stress are still not fully
understood.
PRINCIPAL FINDINGS:
In this report, we demonstrate that induction of p53 expression is
mediated through NF-κB signaling pathways during ER stress in MCF-7
cells. Tunicamycin or brefeldin A, two ER stress inducers, increased
p53 expression in MCF-7 and Hela cells. We found p53 nuclear
localization, activity, and phosphorylation at serine 15 on p53
increased during ER stress. Nuclear translocation of NF-κB and
activity of NF-κB were also observed during ER stress. ER stress-
induced p53 expression was significantly inhibited by coincubation
with the NF-κB inhibitor, Bay 11-7082 and downregulation of NF-κB p65
expression. The role of p53 in mediating Brefeldin A-induced apoptosis
was also investigated. Induction of p53 expression by Brefeldin A was
correlated to Brefeldin A-induced apoptosis. Furthermore,
downregulation of p53 expression by p53 siRNA significantly reduced
Brefeldin A-induced apoptosis in MCF-7 cells.
SIGNIFICANCE:
Taken together, NF-κB activation and induction of p53 expression is
essential for ER stress-induced cell death which is important for
therapeutic effects of clinical cancer drugs. Our results may provide
insight into the mechanism of cancer chemotherapy efficacy that is
associated with induction of ER stress.
PMID: 22859938
but it should be in another thread tar baby?
yep..oh well...
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randall...
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