Vermont_Lymie
Frequent Contributor (1K+ posts)
Member # 9780
posted
From today's paper:
Extract May Help Treat Bladder Infection
By THE ASSOCIATED PRESS Published: April 8, 2007 Filed at 1:26 p.m. ET
WASHINGTON (AP) -- An herbal extract that is sold in health food stores and promoted as an allergy and fat loss aid may improve treatment of bladder infections when it is taken with antibiotics, research suggests.
Some 90 percent of bladder infections are caused by E. coli bacteria. They affect women four times more often than men, sometimes recurring over and over.
The bladder is lined with small pouches that allow it to stretch as it fills. Researchers at Duke University reported in Sunday's online edition of Nature Medicine that some bacteria were able to hide in those pouches, escaping the antibiotics used to treat the infection.
In tests in mice, the extract forskolin can cause the pouches to kick out the bacteria, allowing antibiotics to kill them, said the lead researcher, microbiologist Soman N. Abraham. Forskolin is derived from the Indian coleus plant.
''If we combine this with antibiotics we would be in a very good position to eradicate urinary tract infection,'' he said in a telephone interview.
In the experiments, forskolin was injected into some mice and placed directly into the bladders in others, Abraham said.
The extract is available in health food stores and some people take it by mouth as a supplement, he said. It is promoted as a treatment for allergies, breathing problems and even fat loss.
That availability does ''absolutely not'' mean people should attempt to treat themselves for bladder infections, Abraham said.
Urinary tract infections must be treated with antibiotics because they can quickly spread to the kidneys, so infected people needed to see their doctor, he said.
But the fact that forskolin is being used by some people does help indicate it is safe, he said.
Abraham said the next step for the researchers is to experiment in larger animals to see if they can completely eliminate a bladder infection.
''If we can show an impact in combination with antibiotics it should not be too long before we can go to clinical trials'' in people, he said.
Extracts from the Indian coleus were used in ancient Asia to treat a variety of diseases including urinary tract infections, Abraham said. ''So, we have come full circle,'' he said.
Walter Hopkins, a scientist in the Division of Urology at the University of Wisconsin School of Medicine and Public Health, said the research shows ''forskolin may provide a means to interrupt the infection-reinfection cycle'' and lead to a quicker resolution of the illness.
''If these results could be duplicated in human studies, forskolin could offer a new treatment option for recurrent'' urinary tract infection said Hopkins, who was not part of the research team.
Dr. Gregor Reid of the Lawson Health Research Institute in London, Ontario, said the research was interesting.
''In some patients, such augmentation may be beneficial. Once human studies are done, we'll have a better idea,'' he said. ''For now, this concept is a long way from being used in patients,'' said Reid, who was not part of the research team.
The research was funded by the National Institutes of Health. ^------
A hopeful sign that NIH is funding research looking into herbal and antibiotics combinations?? Where is the research on lyme disease alternatives??
And gee, if this bacteria can hide in the bladder, would they think that perhaps borrelia can hide in the body as well? And perhaps devise research similarly aimed to impact that hidden reservoir of borrelia? Can we get so lucky?
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treepatrol
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1. What is it and where does it come from?
A plant used since antiquity in Hindu and Ayurvedic traditional medicine is the source of an amazing compound of unique biological importance. The plant, Coleus forskohlii, is where the compound forskolin comes from.
Forskolin has started showing up in many of the most advanced thermogenics and fat burners on the market due to it natural fat-loss-enhancing properties. Forskolin has also been touted as a life extension/longevity/anti-aging health product due to studies showing it's positive effects on the heart, lungs, and blood pressure.
2. What does it do and what scientific studies give evidence to support this?
Forskolin has been shown to increase thyroid hormone production as well as stimulate thyroid hormone release. As we know, the thyroid is responsible for metabolic rate via the hormones it releases. Therefore, increasing production of the thyroid results in an increase in metabolism. But, that's not all forskolin is good for!
Over the centuries, Coleus has been used for a wide range of conditions such as cardiovascular disease, eczema, colic, insomnia, convulsions, painful urination and respiratory problems. It turns out that the active ingredient in this herb, Forskolin, is capable of beneficial action against a wide range of conditions. This is because it affects one of the most basic and important cell regulating compounds in the body: cyclic adenosine monophosphate (cAMP.)
Cyclic AMP is perhaps the most important cell-regulating compound. Once formed it activates many other enzymes involved in diverse cellular functions. Under normal situations cAMP is formed when a stimulatory hormone (e.g., epinephrine) binds to a receptor site on the cell membrane and stimulates the activation of adenylate cyclase. This enzyme is incorporated into all cellular membranes and only the specificity of the receptor determines which hormone will activate it in a particular cell. In the case of forskolin, it can aide in a number of biological processes, explained in further detail below.
Forskolin appears to bypass this need for direct hormonal activation of adenylate cyclase via transmembrane activation. As a result of this activation of adenylate cyclase intracellular cAMP levels rise. The physiological and biochemical effects of a raised intracellular cAMP level include: inhibition of platelet activation and degranulation; inhibition of mast cell degranulation and histamine release; increased force of contraction of heart muscle; relaxation of the arteries and other smooth muscles; increased insulin secretion; increased thyroid function; and increased lipolysis (fat destruction). Recent studies have found forskolin to possess additional mechanisms of action independent of its ability to directly stimulate adenylate cyclase and cAMP dependent physiological responses.
Specifically forskolin has been shown to inhibit a number of membrane transport proteins and channel proteins through a mechanism that does not involve the production of cAMP. The result is again a transmembrane signaling that results in activation of other cellular enzymes.
Research is underway in the attempt to determine the exact receptors to which the forskolin is binding. Another action of forskolin is on antagonizing the action of platelet-activating factor (PAF) by interfering with PAF binding to receptor sites.
PAF plays a central role in many inflammatory and allergic processes including neutrophil activation, increasing vascular permeability, smooth muscles contraction including bronchoconstriction, and reduction in coronary blood flow. After treatment of platelets with forskolin prior to PAF binding, a 30% to 40% decrease in PAF binding was observed. The decrease in PAF binding caused by forskolin was concomitant with a decrease in the physiological responses of platelets induced by PAF.
However, this forskolin-induced decrease in PAF binding was not a consequence of cAMP formation as the addition of a cAMP analog could not mimic the action of forskolin.
By raising cAMP, forskolin is responsible for:
Inhibition of platelet activation factor (PAF) and degranulation. Inhibition of mast cell degranulation and histamine release. Increased force of contraction of heart muscle. Relaxation of the arteries and other smooth muscle.
Increased insulin secretion. Increased thyroid function. Increased lipolysis (breakdown of fat) Additionally, the inactive analog of forskolin, dideoxyforskolin, which does not activate adenylyl cyclase, also reduced PAF binding was due to a direct effect of this molecule and its analog on the PAF receptor itself or to components of the post receptor signaling for PAF.
The therapeutic ramifications of c. forskohlii based on the pharmacology of forskolin are immense. There are many conditions where a decreased intracellular cAMP level is thought to be a major factor in the development of the disease process.
At present C. forskohlii appears to be extremely well indicated in these types of conditions which include: eczema (atopic dermatitis), asthma, psoriasis, angina, and hypertension, as well as obesity. Forskolin works well as a fat-loss-aide stacked with ephedra because it counteracts the age-related decrease in response of fat cells to thermogenic (heat producing and calorie burning) agents like ephedrine.
3. Who needs it and what are some symptoms of deficiency?
Allergic conditions such as asthma and eczema are characterized by a relative decrease in cAMP in the bronchial smooth muscle and skin respectively.
As a result of this derangement, mast cells degranulate and smooth muscle cells contract. In addition, these allergic conditions are also characterized by excessive levels of PAF. Current drug therapy for allergic conditions like asthma and eczema is largely designed to increase cAMP levels by using substances which either bind to receptors to stimulate adenylate cyclase (e.g., corticosteroids) or inhibit the enzyme phosphodiesterase which break down cAMP once it I formed (e.g., methyxanthines).
These actions are different then forskolin's ability to increase the initial production of cAMP via a transmembrane activation of adenylate cyclase. The cAMP elevating action of forskolin supports the use of C. forskohlii extracts used alone or in combination with standard drug therapy in the treatment of virtually all allergic conditions.
Coleus forskohlii extracts may be particularly useful in asthma as increasing cellular levels of cAMP results in relaxation of bronchial muscles and relief of symptoms in asthma. Forskolin has been shown to have remarkable effects in relaxing constricted bronchial muscles in asthmatics.
The bronchials are composed of what is known as smooth muscle. This type of muscle is also found in the gastrointestinal tract, uterus, bladder, and arteries.
Forskolin has been shown to have tremendous antispasmodic action on these various smooth muscles. This antispasmodic action of forskolin supports the long time use of C. forskohlii in the treatment of not only asthma, but also intestinal colic, uterine cramps (menstrual cramps), painful urination, angina, and hypertension.
Forskolin's ability to relax smooth muscle in bronchial asthma is most probably due to an increase in cAMP, although forskolin has other anti-allergic activities such as inhibiting the release of histamine and the synthesis of allergic compounds.
The ancient medicinal plant Coleus forskohlii is the source of the compound forskolin which possesses unique biological activity. While clinical results are thought to be better obtained using the whole plant versus the isolated constituent forskolin, research on forskolin is upholding the traditional uses of the plant.
Due to the unique pharmacology of forskolin, C. forskohlii may prove to be useful in a wide range of clinical conditions. Presently, it appears C. forskohlii is best suited for asthma, eczema, psoriasis, hypertension, congestive heart failure, and angina. It can be used alone, but it may prove to be most useful when combined with other botanicals and/or other measures in the treatment of these disorders.
4. How much should be taken? Are there any side effects?
The forskolin content of Coleus root is typically 0.2% to 0.3%, therefore the forskolin content of crude Coleus products may not be sufficient to produce a pharmacological effect. It is best to use standardized extracts which have concentrated the forskolin content. The recommended dosage should be based upon the level of forskolin. Future studies will undoubtedly produce more precise dosage recommendations of a Coleus forskohlii.
The current recommendation for Coleus forskohlii extract, standardized to contain 185 forskolin, is 50 mg (9 mg of forskolin) two to three times daily. The animal studies on forskolin indicate an extremely low order of toxicity for forskolin. Based on the pharmacology of forskolin, it may be wide to restrict the use of C. forskohlii preparations in cases of low blood pressure and peptic ulcers.
Furthermore, C. forskohlii preparations should be used with caution in patients on presription medications especially anti-asthmatics and anti-hypertensives due to its ability to possibly potentiate the drug's effect.
-------------------- Do unto others as you would have them do unto you. Remember Iam not a Doctor Just someone struggling like you with Tick Borne Diseases.
posted
I saw this article as well! I am amazed at how many health issues this herb helps. Particularly thryoid production which is a problem I have in addition to lyme.
I also thought if it can help bring out hidden bacteria in the bladder, why wouldn't it do so for bacteria anywhere in the body that initial antibiotics don't reach? (Like our spiro cysts?)
I went and ordered some as it felt right to do so. I have to say, I said a prayer last night for help to cure myself....saw this article and the amazing thing is how close it is to my last name pronunciation!!
So I took it as a sign from above to look into it. Posts: 867 | From PA | Registered: Jan 2006
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cantgiveupyet
Frequent Contributor (1K+ posts)
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Do you think it would be helpful to take this without abx? And take it with something like cats claw or olive leaf?
Where did you order it from Tothepoorhouse?
-------------------- "Say it straight simple and with a smile."
"Thus the task is, not so much to see what no one has seen yet, But to think what nobody has thought yet, About what everybody sees."
-Schopenhauer
pos babs, bart, igenex WB igm/igg Posts: 3156 | From Lyme limbo | Registered: Oct 2005
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GiGi
Frequent Contributor (5K+ posts)
Member # 259
I looked here, iHerb.com doesn't have this in stock right now.
Also, the warnings should be read ... just in case you fit in the group of people who need to be careful.
quote:If you want to use forskolin to replace antihypertensive drugs, extreme caution is mandatory and physician cooperation is essential. Reduce the dosage of your antihypertensive drugs slowly, while increasing your intake of forskolin and monitor your blood pressure on a daily basis, otherwise an acute hypertensive event could occur, resulting in a stroke.
If you want to use forskolin to replace drugs that strengthen heart muscle contraction, extreme caution is also mandatory and physician cooperation essential. Numerous cardiac test should be conducted to make sure forskolin is helping to maintain adequate cardiac output.
-------------------- When I lost my grip on Faith in the maze of illness, Hope gently clasped my hand and led on.
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Vermont_Lymie
Frequent Contributor (1K+ posts)
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Thanks for all the great information Treepatrol! Hope you are well.
I have never taken this herb, although it sounds like a powerful medicine. I was interested in this article especially for the type of research it represents -- studying the effects of herbal supplements in combination with antibiotics to deal with pathogenic bacteria that have ways of hiding in the human body. Sound familiar?? Why is no research going on like this regarding borrelia?
To the poor house -- Please keep us posted on your experience, and I hope that you are well and speak to your llmd about this! Sounds like a powerful supplement...though I have no personal experience with it. Take care.
And thanks to Gigi, as always, for information!
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Marnie
Frequent Contributor (5K+ posts)
Member # 773
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I saw it too!
Inhibit PDE4.
Ultimately INactivate PFK1.
Careful.
As the pathogen/cells containing them are destroyed, "toxins" are released...
The kidneys can take a hit trying to maintain the pH. It logically will use the most abundant mineral to counter. Not esp. a good thing.
Personally, I'd go with lactoferrin instead while keeping my electrolyte levels up...
This is curious:
"When aerobic metabolism fails to provide enough energy, extra ATP is produced during the anaerobic breakdown of glucose to lactic acid."
Fails to provide enough ENERGY...
As in hydrogen electrons released?
Raise the pH (availabiltiy of hydrogen) and glucose won't be broken down?
" Blood must always remain at an alkaline pH 7.4 so that it can retain its oxygen."
This surprised me:
"forskolin increased sodium channel density up to 125%." PMID: 2409245
But...
Na is needed to transport choline...
But...somewhere waaaaaaaaay back in my research, I remember sodium "opens" cells to receive Mg.
The above maybe WHY my son benefitted from Na Bicarb. (baking soda) TOGETHER WITH Mg sulfate (epsom salt) baths. He used a 1# box of baking soda and a full 4# bag of epsom salts in the bath which he took for TWENTY minutes. (He was recovering from what I suspect was a salmonella infection.)
It made a HUGE difference immediately. His "spirits" were "lifted" TREMENDOUSLY.
What appears to be happening, is our body is using the most abundant mineral, Calcium. Good and bad (too much = thyroid problems, off the bat. We don't want the thyroid cells to "calcify".)
"However when insufficient mineral consumption is in the diet, the body is forced to rob Peter (other body fluids) to pay Paul (the blood). In doing so, it removes crucial minerals, such as calcium, from the saliva, spinal fluids, kidneys, liver, etc., in order to maintain the blood at pH 7.4.
This causes the de-mineralized fluids and organs to become acidic and therefore anaerobic, thus inducing not only cancer, but a host of other degenerative diseases, such as heart disease, diabetes, arthritis, lupus, etc..
Everyone knows that the human body is made up of 78% water by weight, and that water is hydrogen and oxygen gases.
When nitrogen gas and carbon in the form of carbon dioxide and methane gases are added, the total gas in the body by weight becomes over 95%.
Almost half of the remaining 5% that makes up the human body and controls all biological functions is the mineral calcium.
No other mineral is capable of performing as many biological functions as is calcium. Calcium is involved in almost every biological function.
This amazing mineral provides the electrical energy for the heart to beat and for all muscle movement.
It is the calcium ion that is responsible for feeding every cell. It does this by latching on to seven nutrient molecules and one water molecule and pulls them through the nutrient channel.
It then detaches its load and returns to repeat the process. Another important biological job for calcium is DNA replication, which is crucial for maintaining youth and a healthy body. DNA replication is the basis for all body repair and can only occur on a substrate of calcium.
Thus, low calcium means low body repair and premature aging.
As important as all these and hundreds of other biological functions of calcium are to human health, none is more important than the job of pH control.
Calcium to acid, is like water to a fire.
Calcium quickly destroys oxygen robbing acid in the body fluids.
Thus, the more calcium, the more oxygen, and therefore, the less cancer and other degenerative disease.
"-- studying the effects of herbal supplements in combination with antibiotics to deal with pathogenic bacteria that have ways of hiding in the human body. Sound familiar?? Why is no research going on like this regarding borrelia?"
we should all be paying attention to CODEX regarding this kind of work. if the FDA and others succeed in restricting use and access to herbs, it will squash promising studies like these and result in almost total pharmaceutical control over health care.
anyone know where the CODEX thread went?
mo
Posts: 8337 | From the other shore | Registered: Jul 2002
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Marnie, Kind of off topic, but your post makes me wonder... if my pH is good (alkaline), that means I'm doing something right I guess. Does it also mean I'm getting enough oxygen? Or can you be needing more oxygen and still have an alkaline pH?
-------------------- When I lost my grip on Faith in the maze of illness, Hope gently clasped my hand and led on.
RuthRuth Posts: 478 | From California | Registered: Jan 2007
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Mo, I don't know what is going on with the Codex, but if it is like many other shady pieces of law, someone has it waiting in the wings until no one is looking and then, bam, they try to punch it through again. Be vigilant.
-------------------- When I lost my grip on Faith in the maze of illness, Hope gently clasped my hand and led on.
RuthRuth Posts: 478 | From California | Registered: Jan 2007
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Marnie
Frequent Contributor (5K+ posts)
Member # 773
posted
AND MORE!!!
The transient increase in AChE synthesis was also induced by direct activation of AC with
forskolin,
a natural diterpene extracted from Coleus forskolii, indicating that mechanisms downstream the AC activation might be responsible for the attenuation of cellular response."
WHAT... increase the enzyme that breaks down acetylcholine?
That seems contrary since many drugs (for AD, etc.) are intended to INhibit the enzyme acetylcholinesterase and PREVENT the breakdown = more acetylcholine available for a longer period of time.
But...
"IL-1 can induce neuronal acetylcholinesterase expression and increase the enzyme's activity,
thus promoting a cholinergic deficit.79
In addition, direct inhibition by IL-1 of acetylcholine release from hippocampal neurons has been documented.
Injection of IL-1_ into the basal forebrain of rats led to an increase in cortical release of the neurotransmitter gamma amino butyric acid (GABA)."
Looks like (to me) the body is trying to make the "right" choice.
Now...the "flip" of lyme looks to be Myasthenia Gravis (extreme muscle RELAXATION). In this disease, the patient should NEVER take Mg!
But look at how MG is treated:
"Treatment usually consists of medical management with acetylcholinesterase (AChE) inhibitors , plasma exchange for the elimination of autoantibodies, immunosuppression, and occasionally surgical intervention by means of a thymectomy."
If we are to "flip" the treatment, it would appear we should consider NOT inhibiting acetylcholinesterase, but instead "promote" it.
Is it LOGICAL to INhibit acetylcholinesterase (AChE)? in Alzheimer's when...
"An obvious starting point for any investigation with CSF in AD (Alzheimer's Disease) would be with markers of the cholinergic system.
Postmortem studies uniformly reveal decreases in cholinergic indices, including choline acetyl transferase (CAT), acetylcholinesterase (AChE), and the number of cholinergic neurons.
may result in poor reflexes, nervous disorders, respiratory failure, cardiac arrest, ear noises, muscle damage.
IF we can get K back IN the cells (where it belongs), this is a good thing...a very good thing.
HOWEVER...K (potassium) is tricky!!! VERY. The hypo and hyper symptoms are almost identical and dangerous (both situations) to the heart especially.
Be careful. Really careful.
Note: cancer cells follow the glycolysis pathway, are loaded with lactic acid and are hypomethylated.
Food for thought!
Re: lactic acid:
Lactate and pyruvate productions (indicators of glycolysis) were diminished by
glucagon in livers from normal rats;
in the arthritic condition an initial stimulation was found, followed by a slow decay, which did not result in significant inhibition at the end of the glucagon infusion period (20 min).
The actions of cAMP and dibutyryl-cAMP were similar to those of glucagon.
It was concluded that livers from arthritic rats show an impaired capacity of releasing glucose under the stimulus of glucagon.
This can be partly due to the lower glycogen levels and partly to
a smaller capacity of inhibiting glycolysis.
(My note: Mg-ATP is one thing that INhibits PFK...the rate limiting enzyme for glycolysis. Bb is PFK dependent. We have lost control of that enzyme.)
Reduction in glycogen levels was not associated with reduction in food intake or failure in the energetic state of the hepatic cells.
These changes in glycogen metabolism may be related to reduced gluconeogenic capacity of the livers and/ or to production of inflammatory mediators observed in the arthritis disease .
TNF/NO look to cause INCREASED lactic acid production.(linked elsewhere).
As a defense mechanism? Make the system very acidic to destroy the pathogen?
Also:
Since the demonstration by Levine et al. (1969) that rat liver rapidly destroyed cAMP during per- fusion, a number of tissues/cells such as thymic lymphocytes (Macmanus et al., 1971)(Those are T cells),
slime mould (Riedel and Gerisch, 1971),
avian erythrocytes (Aurbach et al. 1975),
frog skeletal muscle (Woo and Manery, 1973),
adrenal tumor cells (Wolff and Hope-Cook, 1977),
isolated rat kidney (Coulson, 1976), and cultured hepatoma cells (Grenner et al., 1975),
were shown to degrade exogenously added cAMP extracellularly.
More recently, Gorin and Brenner (1976) showed that in the rat, intravenously administered cAMP was metabolised to ATP, ADP, AMP and IMP by kidney, liver and muscles.
Since it is well known that plasma membrane is permeable to adenosine (Murray, 1971) it was suggested that the physiological effects attributed to exogenously added cAMP in in vitro systems, may well be due to the adenosine formed from cAMP or some of its metabolites.
Following the demonstration by Tepperman and Tepperman (1972)
that lipo-genesis in animal liver is tinder hormonal regulation,
***hepatic synthesis of fatty acids was shown to be inhibited by cAMP or dibutyryl cAMP in vivo***
(Tous, 1970) or in vitro with tissue slices (Allred and Roehrig, 1973; Akhtar and Bloxham, 1970; Bricker and Levey, 1972; Bhat et al., 1978) or isolated cells (Goodridge, 1973; Capuzzi et al., 1974; Harris, 1975).
It is interesting to note here that Gorin and Brenner (1976)
had shown ATP to be one of the main products of the metabolism of exogenously administered cAMP in liver and adipocytes and that adenosine is an intermediate in this process.
Further, Lund et al (1975) and Rapaport and Zamecnik; (1976)had reported that incubation of cultured rat liver cells with adenosine led to
(cAMP up -> more ATP? A lot more info. in the above link.)
Alanine <- pyruvate -> lactic acid...somewhere buried in my files.
The effects of vasoactive intestinal polypeptide (VIP) and of
forskolin on alanine metabolism in hepatocytes isolated from fed and fasted rats were examined.
VIP and 17 microM forskolin stimulated glucose production, gluconeogenesis from alanine, and ureagenesis, and inhibited glyconeogenesis to comparable degrees.
(Definition here: "Gluconeogenesis, ultimately, is the generation of glucose from noncarbohydrate sources like lactate, glycerol, and amino acids." )
However, combination of 17 microM forskolin with a maximal dose of VIP significantly augmented only the inhibition of glyconeogenesis.
At 100 microM, forskolin induced metabolic responses comparable to those induced by glucagon, but similarly, in combination with maximal doses of VIP or glucagon, augmented only inhibition of glycogen synthesis.
In addition to demonstrating modulation of alanine metabolism by VIP and forskolin , these results raise questions about the nature of the coupling between VIP receptor occupancy and metabolic response.
PMID: 6540208
Alanine deficiency or too much expressed/used?
Alanine is a non-essential amino acid that is involved in the metabolism of tryptophan and the vitamin pyridoxine (B6).
The alpha-carbon in alanine is substituted with a levorotatory (l)-methyl group, making it one of the simplest amino acids with respect to molecular structure.
This amino acid is one of the most widely used in protein construction, averaging about 9 percent of average protein composition on a per-mole basis when compared with the other amino acids.
Alanine has little therapeutic role in humans, although it has been demonstrated to display a cholesterol-reducing effect in rats."
"An especially rich source of a-alanine is silk fibroin, from which the amino acid was first isolated in 1879. Alanine is one of several so-called nonessential amino acids for birds and mammals; i.e., they can synthesize it from pyruvic acid (formed in the breakdown of carbohydrates)..."
"We report on a patient, now 17 year old, in whom lactic acidosis was detected at the age of 7 while attempting to diagnose the causes of increasing weakness.
The laboratory examinations revealed elevated pyruvate, alanine and oxaloacetate levels in serum and also a lowered citrate level.
This led us to suspect a disturbance of the pyruvate dehydrogenase complex.
Reduced pyruvate dehydrogenase activation in leucocytes and muscle tissue was indeed found.
This article reports on the 10 year history of this case and attempts to establish a connection between the various symptoms observed and the underlying metabolic defect."
PMID: 3919358
More:
Microglia are immune cells in the brain; their activation, migration, and proliferation have pivotal roles in brain injuries and diseases.
Microglia are known to attach firmly to fibronectin, the upregulation of which is associated with several pathological conditions in the CNS, through β1 integrin and become activated.
Extracellular nucleotides can serve as potent signaling molecules.
Recently, ATP and ADP were revealed to possess chemoattractive properties to microglia via Gi-coupled P2Y receptors.
In the present study, we report that the ADP-induced chemotaxis of microglia is mediated by P2Y12/13 receptors and is β1 integrin-dependent in the presence of fibronectin.
Signals from P2Y12/13 receptors also cause β1 integrin translocation to the membrane ruffle regions,
but this redistribution was lost when the intracellular cyclic AMP (cAMP) was increased by
Not a good idea to reduce ATP synthesis...right? Those of us here for years are aware of the danger of DNP. It is an acid in a class with cyanide and causes glycolysis to be GREATLY speeded up.
More:
Short-term feeding of fish oil down-regulates the expression of pyruvate dehydrogenase E1 alpha subunit in a mouse brain,
Pyruvate Dehydrogenase catalyzes oxidative decarboxylation of pyruvate, to form acetyl-CoA.
The resulting inhibition of Pyruvate Dehydrogenase prevents muscle and other tissues
from catabolizing glucose and gluconeogenesis precursors.
Metabolism shifts toward fat utilization, while muscle protein breakdown to supply gluconeogenesis precursors is minimized, and available glucose is spared for use by the brain."
"Pyruvate dehydrogenase complex deficiency (PDCD) is one of the most common neurodegenerative disorders associated with abnormal mitochondrial metabolism.
The citric acid cycle is a major biochemical process that derives energy from carbohydrates.
Malfunction of this cycle deprives the body of energy.
An abnormal lactate buildup results in nonspecific symptoms (eg, severe lethargy, poor feeding, tachypnea), especially during times of illness, stress, or high carbohydrate intake.
Pyruvate dehydrogenase complex (PDC) converts pyruvate to acetyl-CoA, which is one of the two essential substrates needed to produce citrate (see Image 1).
A deficiency in this enzymatic complex limits the production of citrate.
Because citrate is the first substrate in the citric acid cycle, the cycle cannot proceed. Alternate metabolic pathways are stimulated in an attempt to produce acetyl-CoA; however, an energy deficit remains, especially in the central nervous system.
The magnitude of the energy deficit depends on the residual activity of the enzyme."
"The pyruvic acid to lactic acid ratio is increased as in thiamine deficiency produced with diets low in thiamine.
The changes are reversed by thiamine.
The symptoms of rats suffering from the functional thiamine deficiency include
extreme irritability
and a tendency for the animals to scratch themselves vigorously."
"Reduced plasma levels of lactic acid levels following L-carnitine treatment may be related with both improved insulin resistance and increased oxidative glucose use by
activating pyruvate dehydrogenase
and decraesing intra mithochondrial Acetyl CoA / CoA ratio.
L-carnitine promotes mitochondrial beta oxidation of long-chain fatty acids by facilitating their transfer across the inner mitochondrial membrane."
"Lactic acid is an end product of anaerobic metabolism.
Under conditions of anaerobic metabolism
or inflammation ,
lactate levels become elevated and a characteristic peak at 1.3 ppm is detected on MR.
Brain lesions with elevated lactic acid peaks on magnetic resonance spectroscopy - Volume 33, Issue 2, Pages 85-95 (March 2004)
"A remarkable, intermittent sudden-onset vigilance and movement disorder in an exclusively breast-fed infant is reported, which was caused by
cobalamin depletion due to maternal vitamin B12 malabsorption.
The lack of cobalamin caused a severe encephalopathy in the infant, whose brain displayed a striking loss of volume and a
delay of myelination.
Proton magnetic resonance spectroscopy revealed
an accumulation of lactate
in the gray and white matter of the brain
and a sustained depletion of choline-containing compounds in the white matter,
reflecting a reversible disturbance of oxidative energy metabolism in brain cells and a long-lasting
hypomyelination disorder.
The clinical picture in conjunction with MRI and spectroscopic data of this case study yields more insight into the functions of cobalamin in the cerebral metabolism.
PMID: 14598232
"Lactic acid is an organic acid typically derived from sugar through a process known asfermentation.
This is a process in which microorganisms convert carbohydrates, like sugar,
into alcohol
and then an acid."
"The purpose of lactate production is to regenerate nicotinamide adenine dinucleotide (NAD+) needed for glycolysis and thus allow adenosine triphosphate (ATP) production to continue."
"Lactic acid is utilized for the reformation of glucose in the process of gluconeogenesis and this occurs in the liver.
There, lactic acid is converted first back to pyruvate and then through the
reverse steps of glycolysis back to glucose.
The events encompassing the production of lactic acid in the muscle, its conversion to glucose in the liver and the return of the glucose to the muscle with the eventual reformation of lactic acid constitutes the Cori cycle."
But...once again, buried in my files...the liver will not release glucose UNTIL it finishes breaking down ethanol/alcohol.
Glucose stimulates the release of serotonin! This is WHY alcoholics suffer from depression. The liver is too busy processing the alcohol and won't release the sugar needed to trigger serotonin, it appears.
Note to others who maybe reading...alcoholics suffer from a serotonin AND dopamine problem (deficiencies).
It takes restoring BOTH to prevent relapses. Obsession -> anxiety. Compulsion (to drink) -> LESS anxiety.
Believe it or not...strep infections leading to DNA genetic damage have been linked to alcoholic "tendencies".
Re: alcohol and lyme:
These results support the concept that acute exposure to high levels of ethanol can impair host defense mechanisms, especially those expressed at the cellular level, which could lead to
increased susceptibility to certain types of infections.
For example, an alcohol-related decrease of protection has been reported to occur in response to viral infection (4) and to listerial infection in mice (24) and during salmonellosis in mice (25).
To understand further the mechanisms by which ethanol limits cell-mediated immunity's participation in destroying microorganisms (primarily through spontaneous activity), we established an in vitro system in which spleen cells kill bacteria and combined this finding with a well-established animal model for measuring direct in vivo effects of ethanol intoxication on host resistance to bacterial infection.
Accordingly , we used this combined in vitro-in vivo infectivity model to test the effect of ethanol on cellular immune responses against two genera of bacteria (Listeria monocytogenes and Burrelia burgdorferi).
Clinical and Diagnostic Laboratory Immunology, March 2002, p. 282-286, Vol. 9, No. 2
Past studies from our laboratory (21, 23) and those from others (6, 13, 15, 20) have shown the importance of both humoral and cellular immunity in the host defense against the Lyme disease spirochete, B. burgdorferi, and against the causative agent of listeriosis.
In other related studies (21), members of our group have shown that ethanol interferes with the ability of rats to mount optimal humoral and cellular immune responses against borrelial antigens.
Because ethanol-associated immunosuppression closely resembles short-term immune system impairment (induced by certain types of drugs), it was therefore of interest to explore further the impact that ethanol might have on two diverse bacterial pathogens.
CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY, Mar. 2002, p. 282-286
The following is from a microbiology book online:
``Spirochetes have a limited metabolism and can only ferment a few types of organic molecules.
They ferment carbohydrates to acetate, ethanol, CO2, and H2 as major end products.
All spirochetes so far examined use the Embden-Meyerhoff-Parnas pathway to take glucose to pyruvate.
Under anaerobic conditions this is converted to acetate and ethanol using common fermentative pathways.
Interestingly, the facultative anaerobes in the group use both oxidative phosphorylation and substrate level phosphorylation in the presence of air and seem to be dependent on at least some fermentation. The TCA cycle has not been detected in these microbes, and it is unclear how they get their ATP by oxidative phosphorylation.''
"The "hydroxy" portion of the name tells chemists that there is an alcohol (OH) group in the molecule, and the "alpha" part of the name means that the alcohol is attached to the carbon atom adjacent to the acid (COOH) group. The "prop" portion of the name indicates that there are three carbon atoms. Lactic acid can also be called 2-hydroxypropanoic acid.
"Natural lactic acid is used to lower pH in the manufacturing of dairy products.
Its presence in dairy products , combined with its natural dairy flavor, makes it a good choice for acidification"
Anyone here off dairy products to avoid ADDITIONAL lactic acid?
To Ruth: It appears our blood pH is supposed to be slightly alkaline in order for us to be able to utilize oxygen. But...there is a iron problem happening too...heme. Bb looks to use a Fe transporter.
Remember zinc fingers...histidine?
A zinc finger is a structure that occurs in proteins (those that bind to DNA and RNA).
A string of amino acids folds back on itself and forms a ``finger-shaped'' bit of protein.
At the base of the ``finger'' are two cysteine and two histidine amino acids which bind with a single zinc ion to hold the structure together.
posted
On potassium: mine tends to run low (especially when I used to sauna). It's hard to get potassium in amounts greater than 99mg.
I understand that we need amounts in the range of grams per day which is best sourced from fruit. But I usually don't eat fruit, because I don't want to feed yeast or skeets.
You can get from it from Environmental Health in Dallas in powder form: Trisalts, potassium chloride or potassium becarbonate.
And yes Marnie too much does feel like too little: weakness.
I took at the same time 2 teaspoons each of Trisalts and potassium bicarbonate in an attempt to get my ph up, and I was not a happy camper.
Of course, getting into the mouth and into the cells and other places where it is needed is not necessarily the same thing.
Thanks Marnie for another helpful post.
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Vermont_Lymie
Frequent Contributor (1K+ posts)
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posted
Thanks Marnie for the fascinating posts -- alot of material to think about here. I cannot claim that my brain is up to understanding all these points yet, but it provokes alot of questions, and I am going to print it out and keep reading until I do understand! (after I finish my taxes, that is).
Thanks for your research, and it is always great to 'see' you here on lymnet! Hope all is good for you and your family.
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Marnie
Frequent Contributor (5K+ posts)
Member # 773
posted
Up for Tree and others who might be accummulating a file on this PDE4 inhibitor and cAMP.
It sure looks promising.
Posts: 9481 | From Sunshine State | Registered: Mar 2001
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posted
Cool link for the structure Marnie! Thanks.
-------------------- When I lost my grip on Faith in the maze of illness, Hope gently clasped my hand and led on.
RuthRuth Posts: 478 | From California | Registered: Jan 2007
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Marnie
Frequent Contributor (5K+ posts)
Member # 773
posted
For Ruth (and interested) others. Lots of info. follows...as I try to "talk" you thru this.
I'm glad you liked the animated link with re: to oxygen binding to heme.
I wish I had a copy of a TV program I caught months ago that "animated" how the neurotransmitters work. It made it much easier to understand!
Bb is impacting acetylcholine which impacts all the other neurotransmitters.
Re: alkaline urine.
With lactic acidosis (and perhaps ketoacidosis on top of that), the body will buffer the system to keep the fluid(s) pH at the right levels.
Bicarbonates play a huge part, but also...
This is where the primary electrolytes come into play. The kidneys are responsible for this...maintaining the pH balance...keeping the levels of K,Na,Ca, and Mg in balance...our major electrolytes. It does so within a 2 hour time frame.
Eventually...with ongoing metabolic acidosis, the body WILL use our most abundant mineral...calcium. It will come FROM the bones if not enough is available from the diet.
Hello osteoporosis.
But...before that...
Bones need Mg, Ca, P, boron and vitamin D to be healthy. All in balance. (Estrogen helps keep Ca in the bones.)
When Mg and P levels drop, the bones can become "brittle" and break easily. Bone health is not about Ca levels ALONE! Too much Ca in relationship to the other nutrients = brittle bones.
Babies are a good example. The % of Mg/Ca in their bones is much greater. This makes their bones "softer" - they can't support their body weight (stand). Calcium hardens the bones...so they can stand and walk.
In a way, Mother Nature protects us...the softness of the bones as well as the "gaps" in the skull bones prevent the bones from breaking when they go thru the birth canal.
It is fairly easy to dislocate an infant's shoulder for delivery if the baby is really big (over 12#) and has to go thru that relatively small way out.
I've seen it done...intentionally dislocate the shoulder to deliver a big baby.
The greater % of Mg in an infant may be helping in another way.
Babies NEVER EVER are "diabetic". They NEVER need insulin.
Food for thought!
What is it that triggers the "genetic" code to develop diabetes? More importantly, what is it that can PREVENT this gene from activating/emerging if it is "recessive"?
Babies born to diabetic moms are often really "fat newborns". Where is excess glycogen stored...fat cells. What happens when those stores are utilized and the fat cells are destroyed...too acidic -> DNA damage/recessive gene emerges?
I suspect colostrum (lactoferrin in it) plays a HUGE part in protecting infants which is why breast feeding (esp. the initial feedings to transport antibodies) is so important.
Infants are also born with STERILE bowels. Did you know that? No lactobacillus, and the other friendly bacteria which just happen to produce...lactic acid to control OTHER pathogens.
If you type in "Mg diabetes" into a search engine, you will get over 2000 hits to read about that link.
Chromium can help in a pinch.
The reason why I am so insistent on putting the brakes back on the glycolysis pathway is this:
Cancer cells follow the glycolysis pathway. They contain lactic acid, and are undermethylated. Many are/were epithelial/endothelial cells (line the blood vessels).
That should send up a "red flag"! Sound familiar?
The underlying basis of cancer is a triggering INFECTION OR bad choices/exposure to other toxins (diet, environmental factors - including ongoing stress - do play a part). I believe MORESO than "genetics".
Even identical twins do not get identical diseases. Heredity does play a part, but environmental factors are really key.
Bb is NOT the ONLY pathogen capable of triggering DNA damage...and starting the premature aging and disease (cancer esp.) process.
We have lots of backup protective help, but if our immune system is overwhelmed and we don't support it, cancer can develop over time.
It does NOT, I repeat, it does NOT happen overnight!
But...having lyme is bad enough. I do NOT want to see this trigger cancer, so...
Once again:
Cancer cells:
1. Follow the glycolysis pathway. These cells function on sugar alone to make ATP (too little). ATP drives Mg INTO the cells. Then Mg-ATP can control glycolysis via INactivating PFK.
2. Have very few mitochondria (powerhouses) left. As cells die off and new ones are made (timing varies with what kind of cell), the % of mitochondria in the new cells drops. Liver cells contain 4000 mitochondria PER CELL. Muscle cells also contain a LOT. Wherever we need a LOT of energy = lots of mitochondria in those cells.
3. Are high in lactic acid as a result of anaerobic fermentation.
4. Are undermethylated.
5. Many originate as epithelial/endothelial cells (line the blood vessels).
So...how to address this?
1. Glycolysis:
A. Try to follow a low glycemic index diet. Complex carbs are okay and are needed! Avoid foods that are really high in processed (not natural) sugars. We do NOT want to trigger insulin SPIKES.
Avoiding eating fruit is stupid, IMO. Apples contain a natural sugar AND vitamins as well as pectin (fiber) in the skin. They are "electromagnetically" already in balance. Think of them as HYDROGEN (energy) bombs. Same with veggies...already in BALANCE for us. We DO need several portions of fruits and veggies per day which most of us are NOT eating.
Here is what a banana contains (also the link is really fascinating!):
A banana contains:
1 gram of protein 3 grams of dietary fiber, 467 mg Potassium 43 mg Magnesium 27 mg Phosphorus 7 mg Calcium 1.3 mg Selenium .4 mg Iron Also trace amounts of zinc, manganese and copper 95 IU Vitamin A 11 mg Vitamin C 22.5 mcg Folate (important during pregnancy) .7mcg Vitamin B6 .6 mg Niacin .31 mg Pantothenic Acid .67 IU Vitamin E
Vitamins and amino acids (protein building blocks) are ACIDIC. Minerals and sugar are alkaline. Do you see the "balance"? Proteins and fats are acidic. So...we need more acids than alkaline things, but we need BOTH.
B. Mg with B vitamins. Because Mg-ATP is one thing that INactivates PFK. Most of our foods are very high in Ca, which is good, but...we must have Mg too which "competes". Years ago, the ratio of Ca:Mg was 1:1. Now, most sources say 2:1. We don't even follow that! Many foods that are high in Mg, we deem as "fattening" (like nuts). Eat a handful of nuts per day...esp. almonds with the brown (tannin) skin on.
C. Chromium can help. I will talk about it later, but Gluco Reg by Solaray CAN help reduce blood sugar levels. It is chromium AND acids. Hydrogen. If the blood pH is not acidic, pancreas isn't signaled to release (acidic) insulin to counter an overly alkaline (sugar) system.
D. It appears the PDE4 inhibitors (which is what this thread is about) help to inhibit glycolysis via ultimately putting the brakes on PFK...the "rate limiting" enzyme for glycolysis...the MAJOR controlling enzyme.
Forskolin and lactoferrin (in colostrum) as well as the Omega 3s look to impact PDE4. This gets tricky because as I have said before...we need glycogen! Our WBCs and especially our brain cells MUST have glycogen. SOME...ongoing.
2. The mitochondria. To "heal" the mitochondria, I know of 2 plans:
A. The "Perricone Prescription" (book by a Harvard dermatologist and professor). He uses chromium and a LOT of acids as well as a low glycemic index diet to actually "reverse aging".
You see...both aging and disease damage the mitochondria via ongoing "oxidative stress". We must protect these powerhouses by providing...HYDROGEN to react WITH those free oxygen "radicals".
B. The supplement called Juvenon by Professor (and brillant) Bruce Ames. It is: biotin, Ca, Acetyl L-carnitine HCL and alpha lipoic acid.
Once again...Ca (+) and lots of "selective" (-) charges. Hydrogen.
Hydrogen goes right INTO the cells. To get it INTO the mitochondria = CoQ10 (enzyme) which we MAKE when we...exercise! To make it we need several nutrients, but primarily B6 which works WITH Mg.
There has been a LOT of research on using CoQ10 too (to treat Parkinson's). VERY HIGH doses. What I think "they" don't "get" is the need for this ONGOING... smaller doses more often for many months to reverse the damage.
Normally testing only lasts a short time...relatively speaking.
It takes TIME...MANY months for the body to heal.
3. Lactic acid.
A. If you are paying attention ;-) you might have "caught" the L-carnitine (in Juvenon) which works with the Omega 3s, reduces lactic acid and looks to INhibit PDE4!
B. Bicarbonate support. Melatonin triggers bicarbonate release. Is it any wonder your body is making you "sleepy"? (Melatonin triggers sleep.) Your defense mechanisms are working! Serotonin is converting to melatonin. Unfortunately, we apparently make LESS of this hormone as we age. It is a POWERFUL anti-oxidant.
Glycogen triggers serotonin release! If glycogen is low (like a pathogen using it), it should come as no surprise that many here become "depressed".
In extreme cases of lactic acidosis, bicarbonates are given IV.
"Large doses of NaHCO2 (up to 2,500mMol) have been given."
Na bicarb. was even given to dogs with neurobabesia and they RECOVERED! (Germany, 1970s).
Bicarbonates are often mentioned on cancer boards as well as lactic acid! If you go to pubmed and type in "melatonin cancer" you will find a LOT of research is underway looking at this hormone to see if it will help.
(Now the focus is on PDE4.)
You see...
K is supposed to be IN the cells and Na outside. They are supposed to be able to flow in and out, but that pump (Na-K) gets "broken" (via a pathogen triggering this).
When our K levels (very reactive mineral, just below Li) drop:
"Hypokalemia induces cellular acidosis this stimulates H secretion ."
Hydrogen leaves the cells. NOT GOOD. Need it IN the cell, in the mitochondria, to react with the free oxygen radicals. To prevent DNA damage.
4. Undermethylated.
This is tricky...and potentially dangerous . Some diseases cause us to be UNDERmethylated and some cause us to be OVERmethylated. There are a list of indicators. Folic acid level is one.
Many of you already know that SAMe can help, but it canNOT be taken with drugs you maybe already on!
Here is a good easy to understand website for a starting point to learn about this:
They lack cell wall protection. Nutrients must be able to flow into them to be delivered to the other cells that make up the tissues which make up organs throughout the body. This makes them esp. vulnerable to attack by pathogens, but makes our Langerhans cells (first line of defense) really vital. They are our "police" cruising the body on the "look out".
It is CRITICAL to keep our blood vessels "elastic" (able to expand and contract as needed) as well as keeping our blood SLIGHTLY "thin".
This is where heparin therapy for lyme entered in. It works to not only keep the blood "thin", but apparently can destroy SOME strains of Bb (but not all).
This is where a baby ASA a day plays a part. Notice I said a baby ASA dose. Some acid, not a lot!
Balance.
The dilation of vessels happens when we...exercise!
NO..nitric oxide dilates the vessels. Understanding this led to the development of Viagra which happens to work on another PDE (5, I think it is, not 4). It is very specific for "certain" blood vessels. NO is also a powerful pathogen killer.
Cancer cells often (usually) develop their own blood supply. Additional vessels (collateral circulation) develop around cancer tumors.
Now...the thought was...block these vessels and "starve" the cancer tumor.
But...there is another viewpoint:
Perhaps the body has triggered the development of these vessels to help deliver...OXYGEN...to destroy those cells.
Remember, these cells don't need oxygen, they use SUGAR.
We need oxygen to survive, but it also leads to our demise. The "free radicals" that happen are very damaging to many pathogens, but to us too.
Which is why we have a backup system to help.
Hydrogen. Our pH is the most important.
Anti-oxidants and the anti-oxidant enzymes.
Bb has developed ways to protect itself from the powerful superoxide free radical as well as from H2O2 (which is what NORMALLY) destroys many pathogens every split second of our lives.
We MAKE H2O2 inside our cells. It only is there for a very short time because if the cells STAY acidic, they die. H2O2 (hydrogen peroxide) is a mild acid. We make H2O2, break it down, make it.... To breakdown H2O2 into H2O and O...we use a very abundant enzyme called catalase. It works in 1/400,000th of a SECOND!
You maybe familiar with the other 2 anti-oxidant enzymes also...glutathione peroxidase and superoxide dismutase. Glutathione should ring a bell...this drops in lyme as our defense system is overwhelmed.
These enzymes are available as a supp. called SOD by Solaray. Do they work? I don't know. Are they destroyed by our really strong stomach acid? I don't know.
Now...as I have said...cells that are "upregulating" glycolysis are vulnerable to oxygen therapies...such as trivalent O3...ozone. We canNOT breathe ozone (!!!), but some is actually necessary for life. It is when it combines with "fossil fuels" (auto exhaust) that the real problems are compounded.
This is also where hyperbaric chambers enter into the picture...increasing oxygen...a LOT.
Really $$$.
Okay, enough for now. I'm sure you are overwhelmed with information.
I am not a doctor, but just someone who loves to learn and am trying hard to do this on my own...to understand the enormous complexity of the body. Like everyone else , I do make mistakes along the way (misinterpret).
There is so much we don't yet know and so much we do...it is mind-boggling.
Ancora Imparo (I am still learning). I hope you are too.
We are "exercising" our brains! We actually MAKE more neuro receptors when we LEARN.
So, keep trying.
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