Water Structure, Osmolytes And Cancer

yerrag

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Hi @yerrag

Eating only sugar could clearly work :): Indeed, I think the part about fasting is more about protein restriction than the two other macros, but I may be wrong. Indeed, it is amino acid restriction that has been shown to promote NFAT5 expression (provided the study I saw could be extended to an in-vivo physiological amino acids restriction situation) in addition to dehydration. Moreover, If I'm not mistaken, dehydration deactivates mTor which has for effect to increase autophagy (don't quote me on that).

Sure, sugar is an osmolyte and could participate to the osmotic stress and the activation of the NFAT5 protein.

Currently, I'm not fasting but reducing the fluids I drink to a "minimum" ala @Scenes, 1L, which is not so much reduced after all if you add in the water that comes with food. For the moment, I plan to only drink along with my dinner.

I think that I'm experiencing in some extent the immunopathologies that are supposed to happen with the Marshall Protocol, if you had a look at this theory: except his stance on vitamin D which is controversial but central to his theory, his pathogenesis is quite interesting. I experience some fatigue and brainfog (there could be an adaptation period to fluid reduction, see citations below), some mild rosacea sometimes and some swollen lymph nodes in the armpit (I have mild CFS and I think it's a common symptom for CFS patients) that I normally never have in this area, or at all.

Note that, even while there seems to have a high cure rate for the type of diseases treated with the Marshall Protocol, i.e. especially autoimmune diseases, the Marshall Protocol could take more than 3 years on average. But if that's needed to heal...

However, dehydration seems to be a conserved way to activate the innate immune system, from Drosophila (Dehydration triggers ecdysone-mediated recognition-protein priming and elevated anti-bacterial immune responses in Drosophila Malpighian tubule renal cells), to snakes (When less means more: dehydration improves innate immunity in rattlesnakes, even if these snakes are adapted to aride environments), and to humans it seems, so it might (I hope) be more efficient than the treatment developed by the Professor Marshall. According to him, taking the drug he recommends (Olmesartan) activates the vitamin D receptor (while its activation was not possible without it, due to pathogens and imbalances of vitamin D metabolites) and allows the production of LL-37, which should be able in theory to neutralize LPS (provided there is enough of it and at the right place of course). So, if we follow the logic, immunopathologies might be reduced to a minimum. Yet, his patients report profound symptoms. Could also be Olmesartan side effects after all. Sorry for the digressions :stop:

Note that a dehydration treatment has already been studied regarding epilepsy, which has nothing to do with hypertension, but which could be considered to be caused by pathogens in the CNS according to Marshall. Some excerpts:

"This degree of fluid limitation is followed by some discomfort on the part of the patient for the first ten days, but in all cases where this initial period has been accomplished, they have maintained the restriction of fluids without difficulty and with no ill effects. It must be born in mind that: unless absolute fluid regulation is maintained, little or no results can be expected.
During the first few days of fluid limitation at this low level it is interesting to note the high output of urine in contrast to the intake. The accumulation of body fluids in excess, from former free intake of fluids, persists for about six days. Following this, there may be a drop in volume of urine passed to below the intake level; again a sharp rise above the intake point with fluctuation for several weeks may occur."

"It is of interest to note that there has never been any pathological urinary findings due to dehydration except, of course, high specific gravity."​

"Bauer pointed out that of 25 infants, maintained on a ketogenic diet, he had obtained symptomatic relief on approximatively 35%. When these same infants were placed on fluid limitation and dehydration for one year, he was able to establish 100% symptomatic relief in his group."

"In a later report, he mentions that he had observed 86-88 cases, with similar results."

"We believe that the effectiveness of fasting and the ketogenic diet is due not so much to the presence of ketosis per se as to the associated dehydrating effect."​

By the way, I think that NFAT5 expression could be increasing nitric oxide production, which is not something good if we listen to Ray Peat IIRC, which could be the reason why your hypertension is decreasing rapidly when you dry fast as nitric oxide is a vasodilator right? But nitric oxide also seems to be needed by the immune system as a signaling molecule and to kill cells or pathogens.

Thanks for this! It looks like I may be able to solve my blood sugar regulation after all, so that I won't have to resort to taking sugar while on a dry fast. It is probable that if I could manage to lower my monocyte levels that point to endotoxin levels being lower than a threshold, I would be able to restore my blood sugar regulation to where I could be able to fast for a day without my blood sugar levels dropping below 70, the point at which I would feel the effects of low blood sugar.

I will then be able to undergo dry fasts that would in time be longer in duration as I steadily increase the length of the fast. While the sugar idea may work also, I would still prefer to undergo a fast having my blood sugar regulation system in excellent condition.
 
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LLight

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Desmopressin stimulates bile secretion in anesthetized rats

"One of the synthetic analogues of antidiuretic hormone-desmopressin is used in patients with central diabetes insipidus and in those with coagulation disorders. However, its effects on bile secretion are not fully defined. We investigated the effect of desmopressin on bile formation and determined the role of V1a vasopressin receptors in the action of desmopressin on choleresis. Rats were injected intraportally with a bolus of desmopressin; the changes of bile flow, the content of free and conjugated cholates were compared with control animal group. Selective antagonist of V1a receptors was injected 10 minutes before desmopressin treatment and the findings were compared with the results after desmopressin injection alone. Desmopressin increased bile flow, secretion of total cholates like amino acids conjugated, while diminished free bile acids content. Secreted bile volume and conjugated bile acids content were reduced in V1a receptors antagonist+desmopressin-treated rats. In contrast, free bile acids content was more than the results in desmopressin-treated rats. Desmopressin at concentrations nearly equal to physiological concentrations of natural hormone in blood shows its choleretic effect. Antagonist of V1a vasopressin receptors modulates desmopressin action. This certifies the role of these receptors in the action of desmopressin on different processes of bile formation."

Thus, Vasopressin/ADH could be involved in bile secretion.

Interestingly, this hormone can be low for cancer or CFS:

Syndrome of Inappropriate Secretion of Antidiuretic Hormone (SIADH) in Malignant Disease - PubMed

"A broad spectrum of malignant tumours has been reported to cause SIADH; however, most of these observations have been in case reports including very few patients. This includes a number of primary brain tumours, haematologic malignancies, intrathoracic non-pulmonary cancers, skin tumours, gastrointestinal cancers, gynaecological cancer, breast-and prostatic cancer, and sarcomas."

Down-regulation of Renin-Aldosterone and Antidiuretic Hormone Systems in Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - PubMed

"Both the mean plasma aldosterone (104±37pg/ml vs. 157±67pg/ml, p=0.004) and antidiuretic hormone (ADH) (2.2±1.0pg/ml vs. 3.3±1.5pg/ml, p=0.02) concentrations were significantly lower in the ME group than in the Controls. Desmopressin (120μg), a synthetic version of arginine vasopressin, was orally administered for five successive days to 10 patients with ME. In five patients (50%), the symptoms of orthostatic intolerance during a 10min active standing test were ameliorated in association with a significant increase in urinary osmotic pressure and decrease in heart rate. Furthermore, in five patients (50%), the performance status scores for the activities of daily living were improved."
 
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LLight

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Putting these studies together, I think we have the beginning of a proof that boron promotes NFAT5 (and that boron could in counterpart be needed for the immune response that is promoted with NFAT5):

Boron Induces Lymphocyte Proliferation and Modulates the Priming Effects of Lipopolysaccharide on Macrophages
"The mediators of inflammation, TNF-α, IL-6, IL-1β and nitric oxide (NO), were measured in culture supernatant of LPS-primed macrophages isolated from borax treated mice."
"Results showed a significant increase in T and B cell populations, as indicated by an increase in CD4 and CD19, but not CD8, cells. Boron further stimulated the secretion of TNF-α, IL-6, IL-1β, NO and the expression of iNOS by the LPS-primed macrophages. The effect was dose dependent and most significant at a dose level of 4.6 mg/kg b. wt."​

Emerging New Role of NFAT5 in Inducible Nitric Oxide Synthase in Response to Hypoxia in Mouse Embryonic Fibroblast Cells - PubMed
"Some evidence indicates that NFAT5 is essential for the expression of iNOS in Toll-like receptor-stimulated macrophages and that iNOS inhibition increases NFAT5 expression in renal ischemia-reperfusion."

"Recent researchers have demonstrated that NFAT5 activation by tonicity-independent, isotonic stimuli is a key regulator of RA pathology. Masuda et al. first identified that NFAT5 mRNA is expressed in the RA synovia, particularly at sites of bone destruction (49)."​

So, boron promotes the expression of iNOS in macrophages stimulated by LPS, while NFAT5 seems to be essential for iNOS expression in them.

Also, NFAT5 seems to be expressed in synovial fluid of RA patients, and boron seems to be curative for RA.

In contrast, NFAT5 seems to upregulate CYP3A4, an enzyme which is involved in the catabolism of vitamin D, while boron could inhibit the 24-hydroxylase enzyme which is also involved in its catabolism.
 

yerrag

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@LLight I did a dry fast before Christmas for a day. I took a teaspoon of sugar every 2 hours and it's working. I'm able to keep my sugar levels high enough to keep from having low blood sugar - or at least not feel hungry, sleepy, or sick. My blood pressure went down from blood pressure went down from 219/129 to 179/129, and heart rate went up from 68 to 90. The most unexpected thing though, was that I hadn't slept so well for a while already. Before New Year, I can try a 2-day try fast to see how I respond

Ray Peat thinks lowered blood pressure has to do with lowered translocation of endotoxin from the gut due to fasting, but I'm not so sure in my case. The intake of sucrose could be feeding gut bacteria and increasing endotoxin translocation, but if this were true, my blood pressure won't go down. So maybe the NFAT5 and LL37 could be kicking in, and endotoxin is being destroyed, and this could be causing lowered bp. Even from a day of dry fasting only.

I'll have to do a 2-day dry fast (with sucrose assist) to see the effects on my blood pressure. This would be the longest dry fast so far. I'll also have to take my CBC blood test as well, to see my wbc, neutrophil, and monocyte levels primarily.

If I can associate lowered bp to lowered monocyte levels, it could strengthen the case that the dry fast is causing production of NFAT5 and LL37, and that they are responsible for lowering endotoxin.

I could then keep on increasing the length of my dry fasting and hope to achieve a certain reduced level of monocytes. I don't think dry fasting alone will permanently solve my hypertensive situation, as I am still dealing with a recurring low-grade infection which is evidenced by a wbc and neutrophil count that stays at a high level. I'll probably take about 2 x 25 mg doxycycline daily for a month, and during that time monitor my blood pressure. I expect it to increase as endotoxins increase from the die-off of bacteria from the antibiotic. During this time, I may go on dry fasts to keep the endotoxin levels down.

At the end of this period, I hope my wbc, neutrophils, and monocyte levels would be down, indicating a much lower level of low-grade infection. At this point, I could start to take proteolytic enzymes (3x ZymEssence/day) for a month. I expect the enzymes to lyse plaque, and in doing so, it will also release bacteria previously trapped by plaque. This would increase my low-grade infection, and I would then resume taking doxycyline. I would then incorporate fasting when I sense increased endotoxin levels from the bacteria die-off.

I hope this would enable me to permanently fix my high blood pressure condition.

This is the first time I've come to approach my problem as a process instead of seeing it as a silver bullet approach. Knowing about the mechanism of action involved, especially the NFAT5 and LL37 proteins involved, certainly helps.

I hope I have the big kahuna here down pat @ecstatichamster , and then I can get the role player substances such as progesterone, niacinamide, DHEA, etc. to render assistance in destroying an/or deactivating and/or transporting/excreting endotoxin out of my system.
 
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LLight

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I'm able to keep my sugar levels high enough to keep from having low blood sugar - or at least not feel hungry, sleepy, or sick. My blood pressure went down from blood pressure went down from 219/129 to 179/129, and heart rate went up from 68 to 90. The most unexpected thing though, was that I hadn't slept so well for a while already.

It's cool that it was as effective as the last time you dry fasted :):

I'm not sure what would be the exact mechanism for your decreased tension, there might be multiple explanations, causes.

I don't think dry fasting alone will permanently solve my hypertensive situation, as I am still dealing with a recurring low-grade infection

Maybe not, but short term improvements that it brings to your blood pressure could be not the only thing. I'm pretty convinced that it could help you, in the long term too, dealing with your infection: LL-37 binds to endotoxin but it also is an antibacterial (and it can be cut into sub-peptides having different mechanisms of action) and may be able to disrupt biolfilm.

Good luck with your 2 days dry fast!
 

yerrag

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It's cool that it was as effective as the last time you dry fasted :):

I'm not sure what would be the exact mechanism for your decreased tension, there might be multiple explanations, causes.



Maybe not, but short term improvements that it brings to your blood pressure could be not the only thing. I'm pretty convinced that it could help you, in the long term too, dealing with your infection: LL-37 binds to endotoxin but it also is an antibacterial (and it can be cut into sub-peptides having different mechanisms of action) and may be able to disrupt biolfilm.

Good luck with your 2 days dry fast!
Thanks!

I hope I can rely on less antibiotics as part of my healing protocol. Btw, I'm now my second 1 day fast now (more actually, since I get to skip 3 meals instead of 2) and my sleep is again so good.
 

yerrag

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If I understand well what the Randle cycle implies: if you eat fat and carbs at the same time, your body not being able to use it simultaneously should secrete insulin such that fat remains locked in adipocytes. When you're low in glucose, your insulin decreases so that free fatty acids replace carbs for fuel. So the Randle cycle is more about the body needing to use insulin to regulate between glucose and fat metabolism, because you should be burning one fuel at a time. Randle cycle is not really telling whether your insulin secretion will be problematic, which is governed more by your insulin sensitivity. Maybe if you are insulin sensitive, Randle cycle is not a problem in and of itself. Hyperinsulinemia/insulin resistance seem to be implied in all major diseases, and I don't know if too high levels of insulin is the real cause or just a correlation, but it's a fact, too much insulin is associated with major chronic diseases.
I don't really see it as a choice between running on fats or running on sugar for energy. They could be running in conjunction with each other. The problem would arise when fatty acid metabolism becomes predominant, for one reason or another, such that sugar metabolism comes crawling to a halt. This is where insulin comes in to correct the situation. At low or zero sugar metabolism, blood sugar will increase to a point where insulin is secreted. Insulin will inhibit lipolysis, and as a result inhibit fatty acid metabolism. It will also inhibit glycogenolysis (the turning of glycogen into glucose), as well as proteolysis and gluconeogensis. This will help boost sugar metabolism as the competing fatty acid metabolic pathway is suppressed. If this does not work, insulin will cause blood sugar to turn into fats so that blood sugar is lowered.

But insulin merely inhibits. People have very different responses to insulin inhibition, and this is where we talk about insulin sensitivity and insulin resistance. When insulin resistant, it takes a lot of insulin to inhibit lipolysis, glycogenolysis, proteolysis, and gluconeogenesis. Having difficulty suppressing these processes makes it harder to control blood sugar. The body still uses fatty acid oxidation, while it's unable to keep itself from supplying sugar endogenously, while the liver keeps on converting blood sugar to fat.

Low potassium stores, a high level of PUFA exposure in the form of PUFA fatty acids, endotoxemia, low tissue oxygenation, low oxygen supply (from bad lungs or from mercury toxicity), poor thyroid, vitamin deficiencies (thiamine) and enzyme deficiencies (cytochrome oxidase, PDH) all have a bearing on efficiency of sugar metabolism.
 
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LLight

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Thanks!

I hope I can rely on less antibiotics as part of my healing protocol. Btw, I'm now my second 1 day fast now (more actually, since I get to skip 3 meals instead of 2) and my sleep is again so good.

Cool :):

Is there a sort of compounding effect on your blood pressure or does it remain around 179/129?
 
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LLight

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Taxol the drug that l'm given weekly dries everything. I have to cover myself with cream and constantly drink because my mouth is dry.

Taxol/Paclitaxel seems to have a very dehydrating effect.

Osmotic stress can have damaging effect on DNA and it seems like TonEBP/NFAT5 is involved in the mechanism that protect against that.

TonEBP Regulates PCNA Polyubiquitination in Response to DNA Damage through Interaction with SHPRH and USP1:
"In the present study, we showed that TonEBP functions as an early sensor of the DNA damage response. TonEBP was found to be recruited to DNA damage sites with bulky adducts and to regulate PCNA polyubiquitination through sequential interactions with SHPRH and USP1. Accordingly, TonEBP suppressed cell death caused by mutagenesis in response to DNA damage."

Boron seems to be able to help with taxol genotoxicity: https://www.researchgate.net/public...s_a_protector_against_paclitaxel_genotoxicity

These elements suggest that boron could help with NFAT5 activation.
 

yerrag

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Cool :):

Is there a sort of compounding effect on your blood pressure or does it remain around 179/129?
It's staying put around this area. I'll see if I can do a 2-day fast before the New Year, hope I can see a larger dip.
 
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From this data, the aquaporin AQP4 seems to be involved in the clearance of brain lymph via the glymphatic system and its activation could be important regarding Alzheimer:

Astroglial water channel aquaporin 4-mediated glymphatic clearance function: A determined factor for time-sensitive treatment of aerobic exercise in patients with Alzheimer’s disease

"Further studies also show that the clearance function of the glymphatic system depends on astroglial water channel aquaporin 4 (AQP4) that lines the paravascular CSF pathways [28–30]. AQP4, the most abundant water channel in the brain, is crucial for maintaining brain water homeostasis [31,32]. We demonstrated that AQP4 gene knockout (AQP4-/-) in mice results in slightly increased brain water content, reduced CSF production rate, and delayed postnatal brain water uptake [33–34]. AQP4-/-mice exhibit slowed CSF influx from the subarachnoid space into the brain parenchyma, as well as ISF outflow into the subarachnoid space again [28]. Apart from maintaining brain water balance, AQP4 facilitates ISF entering into astrocyte processes surrounding the synapses, which might drive astrocyte Ca2+ signaling transduction and reuptake of K+ and glutamate, thus regulating synaptic plasticity [35,36]. AQP4 is also involved in the regulation of neurotrophic factordependent synaptic plasticity [37]. Adult AQP4-/-mice exhibit defects in consolidation memory and location-specific object memory [38,39]. Furthermore, AQP4 is necessary for the glymphatic system to clear Aβ and Tau [28–30]. Adult AQP4-/-mice show a ∼45% reduction in clearance of intrastriatal injected radio-labeled Aβ1-40, compared with aged-match wild-type (WT) mice [28]. In order to define the function of AQP4 in AD pathology, we successfully established AQP4-/-/APP/PS1 mice. Twelve-month-old AQP4-/-/APP/PS1 mice exhibit heightened spatial learning and memory impairment along with increased Aβ plaques deposition, amyloid angiopathy, synaptic protein loss and atrophy of astrocytes in the hippocampus and cortex [30]. This revealed a mitigating role of AQP4 in Aβ pathogenesis, suggesting that regulating the glymphatic system via targeting at AQP4 may be an effective therapeutic strategy for clearing soluble Aβ in the brain of patients with AD."
Interestingly, AQP4 seems to be activated by dehydration:

Water for Thought: Is There a Role for Aquaporin Channels in Delirium?

"The movement of water in and out of the neuropil occurs with the help of the glymphatic system via special molecular pumps, aquaporin water channels (AQP 4) located in astrocyte end-feet. Water circulation is enabled by the exchange between the cerebrospinal fluid (CSF) and interstitial fluid (ISF). The pressure gradient for this exchange is probably provided by pericytes’ contraction and arterial pulsations along with the suction, pump-like action of AQP 4 channels (4–6). This movement of water in and out of the neuropil enables both, clearance of molecular waste and volume transmission (VT) of chemical signals (7). Conversely, delayed water movement (glymphatic stasis) may predispose to the accumulation of misfolded proteins (4) and ultimately to neuroinflammation (8).

The relationship between water and delirium is complex. Both, brain edema and dehydration may predispose to delirium (9). Up-regulation of AQP 4 water channels seems to occur in both situations. In fact, a biphasic up-regulation was described in edema build-up and the resolution phase (10). Interestingly, AQP 4 receptors seem to be the common denominator between the neuropil water movement and neuroinflammation (10). Moreover, animal studies demonstrated that peripheral dehydration triggers central up-regulation of AQP 4 receptors (11–13). This in turn causes swelling and priming of astrocytes and microglia, predisposing to neuroinflammation (14)."
I wonder if hydration/dehydration cycles could be needed for a proper cleaning of brain's wastes and would advocate for intermittent dry fasting.
 
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TrpV1 receptor activation rescues neuronal function and network gamma oscillations from Aβ-induced impairment in mouse hippocampus in vitro. - PubMed - NCBI

"Amyloid-β peptide (Aβ) forms plaques in Alzheimer's disease (AD) and is responsible for early cognitive deficits in AD patients. Advancing cognitive decline is accompanied by progressive impairment of cognition-relevant EEG patterns such as gamma oscillations. The endocannabinoid anandamide, a TrpV1-receptor agonist, reverses hippocampal damage and memory impairment in rodents and protects neurons from Aβ-induced cytotoxic effects. Here, we investigate a restorative role of TrpV1-receptor activation against Aβ-induced degradation of hippocampal neuron function and gamma oscillations. We found that the TrpV1-receptor agonist capsaicin rescues Aβ-induced degradation of hippocampal gamma oscillations by reversing both the desynchronization of AP firing in CA3 pyramidal cells and the shift in excitatory/inhibitory current balance. This rescue effect is TrpV1-receptor-dependent since it was absent in TrpV1 knockout mice or in the presence of the TrpV1-receptor antagonist capsazepine. Our findings provide novel insight into the network mechanisms underlying cognitive decline in AD and suggest TrpV1 activation as a novel therapeutic target."

TRPV1 seems to be activated by osmotic stress too: Osmosensitivity of Transient Receptor Potential Vanilloid 1 Is Synergistically Enhanced by Distinct Activating Stimuli Such as Temperature and Protons

"Our findings thus indicate that TRPV1 integrates multiple different types of activating stimuli, and that TRPV1 is sensitive to hypertonic stimuli under physiologically relevant conditions."
 

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Water in malignant tissue, measured by cell refractometry and nuclear magnetic resonance. - PubMed - NCBI:

"Under these conditions the average water content of the cytoplasm of normal liver cells is calculated to be 87%. The cytoplasm of the liver tumour cells, on the other hand, have an average water content of over 92.5% and the cytoplasm of the cells of the ‘host liver tissue’ (tissue immediately adjacent to the tumour tissue) has an average water content of 89%."

"This meant that just over one third of all the intact living tumour cells examined had cytoplasmic refractive indices below 1.350, and consequently contained significantly more than 93% water. And as the cytoplasm of some of these cells appeared quite markedly bright in this mounting medium it seems likely that the upper end of the range of their water contents was at least 94% and probably nearer to 95%. This serves to indicate just how ‘watery’ these spherical cancer cells had become-very considerably more aqueous than any normal animal cells ever so far encountered. It also means that the averge refractive index of the cytoplasm of these cells is most unlikely to have been higher than 1.351, which implies that, at its very lowest, their average water content was in the region of 92.5%."

"One may legitimately ask, however, how much of the total water in the tissue is intracellular and how much is extracellular. In our present state of knowledge no answer is forthcoming. It could be that the NMR relaxation time measurements almost exclusively measure intracellular water; and the striking resemblance of Figs. 3A and 3B would seem to support this view; but this is in fact most unlikely because all the specimens removed from the livers for testing were ‘wet’ with extracellular fluid. Unquestionably some of their water was derived from the cellular environment. Extracellular liquid might be expected to be particularly in evidence in the tumour- bearing tissue since it always becomes to a greater or lesser degree inflamed. So probably both the cells comprising a tissue and their external environment become hydrated when a tumour develops in that tissue."

"What causes the increase in intracellular and extracellular water in these tumours and in the immediately adjacent tissues, which we have been able to demonstrate ? One possible cause can definitely be ruled out; it cannot be due to a change in the tonicity of the extracellular fluids causing the cells to swell and their contents to become more diluted. If this were so, removing the cells from the tissue and isolating them in isotonic media would cause them to contract again, and no difference between the refractive indices of the cytoplasm of the tumour cells and the normal cells from which they were ultimately derived would be apparent. Among the widely divergent views held on the aetiology of cancer there seems to be a certain measure of consensus that the cell membranes of malignant cells are probably abnormal with respect to their permeability properties, and the findings reported here could be interpreted as providing some additional support for this view."

So then you reccomend dry fasting repeatedly until the infection is completely eradicated?
 
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LLight

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So then you reccomend dry fasting repeatedly until the infection is completely eradicated?

That is the idea :):

But to be honest, I can't promise it will necessarily work for you and can't tell you how many times you would have to dry fast for you to have the results you expect, provided it's working in the first place. It's up to you to stop whenever you would feel like it does not good to you. Please always be cautious.
 

yerrag

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It's staying put around this area. I'll see if I can do a 2-day fast before the New Year, hope I can see a larger dip.
After a 2-day dry fast (sugar every few hours, when needed: in case my blood sugar falls low), my blood pressure only went down to 182/120. It wasn't a great improvement over the 179/129 a few days ago on a 1-day dry fast. I had a much higher heart rate, with heart rates ranging from 85-93, as in the two previous 1-day fasts.

I'll have to do another 2-day dry fast, but without sugar assist to see if that makes a big difference. I wonder how low blood sugar can get in a fast though, as it seems to me that in a fast, I can still carry on at a blood sugar of 60 (although I can sense it's low) while regularly (without a fast) I may have a harder time.

I wonder if hydration/dehydration cycles could be needed for a proper cleaning of brain's wastes and would advocate for intermittent dry fasting.
A good thing to try. I may try that in between dry fasts, just skipping breakfast and not drinking water until lunch. And during the other times, to drink only when I thirst.

It's the norm for people to keep drinking water throughout the day, and without ever dry fasting, the habit could be making thing worse for people.

I wonder how healthy and hardy wild animals are who go through the extreme seasons of water abundance and scarcity in some parts of Africa. There was a thread here about how animals who are less hydrated go to the watering holes being more peaceful. The idea was that this is an adaptation to make possible less conflicts given the proximity of animals sharing a space. Hard to know though if the lack of excessive hydration has anything to do with it, or that it was a survival adaptation to make animals co-exist and share a resource.


It's good to hear that you got some good results!

Regarding the question about the time needed to have increased LL-37 expression, I guess it happens gradually/increasingly when you are losing water / "dehydrating".

From the paper linking osmotic stress and the production of the LL-37 molecule:
"As shown in Figure 1A-C, hyperosmolality upregulated CAMP mRNA and protein expression in a dose-dependent manner."

Osmolality controls the expression of cathelicidin antimicrobial peptide in human macrophages

Regarding your sleep and your digestion, I wonder whether vasopressin could be involved as it seems to be linked with bile flow and circadian rythmes.

Not so sure on the role of vasopression. The stools could be "dehydrated" because the colon will tend to absorb more water from the colon wastes, leaving a smaller stool. And my sleep could be less interrupted by urination because water has to be conserved even more in a dry fast? But I'm still interested in knowing the effect of dry fasting on vasopressin as it relates to sleep and digestion.
 
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LLight

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I'll have to do another 2-day dry fast, but without sugar assist to see if that makes a big difference. I wonder how low blood sugar can get in a fast though, as it seems to me that in a fast, I can still carry on at a blood sugar of 60 (although I can sense it's low) while regularly (without a fast) I may have a harder time.
I would not be surprised if by 1 day of dry fasting you would already be in ketosis which is glucose sparing. In ketosis, glucose can be lower without you suffering symptoms of hypoglycemia.

It's the norm for people to keep drinking water throughout the day, and without ever dry fasting, the habit could be making thing worse for people.

I think you refer to this one: Intermittent Drinking, Oxytocin and Human Health - PubMed

Indeed, the author of this paper states that:
"This would mean that people would not drink less quantity but less frequently and that's how all animals, but also human newborns behave. It is the latter group, which is probably the only group of humans with a normal fluid homeostasis."
 
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Not so sure on the role of vasopression. The stools could be "dehydrated" because the colon will tend to absorb more water from the colon wastes, leaving a smaller stool. And my sleep could be less interrupted by urination because water has to be conserved even more in a dry fast? But I'm still interested in knowing the effect of dry fasting on vasopressin as it relates to sleep and digestion.

Not sure if the following could be relevant regarding your results:
Improvement of Sleep and Pituitary-Adrenal Inhibition After Subchronic Intranasal Vasopressin Treatment in Elderly Humans - PubMed

Vasopressin: more than just an output of the circadian pacemaker? Focus on “Vasopressin receptor V1a regulates circadian rhythms of locomotor activity and expression of clock-controlled genes in the suprachiasmatic nuclei”
"The versatility of vasopressin continues to astound physiologists. In addition to its importance in regulation of hydration, blood pressure, body temperature, corticotropin release, memory, and sociosexual behavior, we may find that its role in circadian timing is more than merely to serve as an output of the clock."
Also, vasopressin seems to be involved in bile flow (in rats) which could explain the results regarding digestion?
Desmopressin Stimulates Bile Secretion in Anesthetized Rats - PubMed
"Desmopressin increased bile flow, secretion of total cholates like amino acids conjugated, while diminished free bile acids content. Secreted bile volume and conjugated bile acids content were reduced in V1a receptors antagonist+desmopressin-treated rats. In contrast, free bile acids content was more than the results in desmopressin-treated rats. Desmopressin at concentrations nearly equal to physiological concentrations of natural hormone in blood shows its choleretic effect. Antagonist of V1a vasopressin receptors modulates desmopressin action. This certifies the role of these receptors in the action of desmopressin on different processes of bile formation."​

That being said, what you said is maybe more likely than these explanations.
 
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LLight

LLight

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NFAT5-sensitive Orai1 Expression and Store-Operated Ca 2+ Entry in Megakaryocytes

"The transcription factor nuclear factor of activated T cells 5 (NFAT5) is up-regulated in several clinical disorders, including dehydration."

"Platelets and megakaryocytes were isolated from wild-type mice with either access to water ad libitum or dehydration by 36 h of water deprivation."

"In the mice, dehydration increased NFAT5 and Orai1 protein abundance in megakaryocytes and NFAT5, Orai1, and Orai2 abundance in platelets. Dehydration further augmented the degranulation and integrin activation by thrombin and collagen-related peptide. In summary, NFAT5 is a powerful regulator of Orai1-expression and SOCE in megakaryocytes."

Emerging roles of store-operated Ca2+ entry through STIM and ORAI proteins in immunity, hemostasis and cancer

"The role of SOCE in immunity to infection is underlined by the severe, recurrent infections with viral, bacterial, and fungal pathogens affecting patients with mutations in ORAI1 and STIM1 genes that abolish SOCE.42,43 Patients are susceptible to chronic and recurrent viral infections, especially with herpes viruses such as cytomegalovirus (CMV), Epstein Barr virus (EBV) and human herpes virus (HHV) 8.44-46 SOCE is impaired in cells of both the innate and adaptive immune system in these patients, and defective immune responses by both systems are likely to contribute to their immunodeficiency."

"NK cells are cytotoxic lymphocytes that are essential for immune responses against many viral infections and antitumor immunity. Intriguingly, ORAI1- and STIM1-deficient NK cells from patients showed impaired cytokine production, failed to exocytose cytotoxic granules and were unable to lyse tumor target cells when coincubated in vitro.46,51 Consistent with these findings, NK cells from Orai1KI/KI mice also showed reduced degranulation and cytotoxic function in vitro (SF, unpublished data)."

"Pathogens sequestered within phagosomes of macrophages and neutrophils are killed following fusion of phagosomes with lysosomes. The phagosomal production of reactive oxygen species (ROS) by NADPH oxidase is dependent on SOCE."

Platelets: essential components of the immune system

"Platelets interact with bacteria, viruses, fungi and protozoa and demonstrate anti-microbial functions."

"Upon contact with certain bacteria, platelets can become activated, aggregate and degranulate. Activated platelets release over 300 known secretory products including anti-microbial products (collectively known as platelet microbicidal proteins (PMPs))."

"Recently, a study demonstrated the expression of β defensin 1 in human platelets and its novel antibacterial activity [21]. It was observed that activated platelets surround Staphylococcus aureus and force the pathogens into clusters which reduce growth rate. Platelet-derived β defensin 1 not only impaired the growth of S. aureus, but also triggered neutrophil extracellular trap (NET) formation."

"In addition to the anti-microbial mechanisms as discussed above, platelets can internalize bacteria and viruses. Specifically, platelets have been shown to engulf S. aureus and human immunodeficiency virus (HIV) thus promoting pathogen clearance from blood stream and tissues [22]. In fact, platelets are capable of not only internalizing targets but also the killing of various internalized bacterial species including Escherichia coli and S. aureus [23, 24]. Whether this entitles platelets a potential phagocytic role needs further investigation. Furthermore, platelets generate and release hydrogen peroxide and other reactive oxygen species to mediate other anti-microbial effects in response to stimuli."

From my limited understanding, these elements suggest that dehydration could increase NFAT5 in immune cells (at least platelets here) and then ORAI1 and SOCE which seem to be necessary for an efficient immune response. Platelets are recognized more and more for being able to fight pathogens directly or influencing the other immune cells.
 

yerrag

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AS10 is a peptide derived from cathelicidin-related antimicrobial peptide.

Derivatives of the Mouse Cathelicidin-Related Antimicrobial Peptide (CRAMP) Inhibit Fungal and Bacterial Biofilm Formation

ABSTRACT

We identified a 26-amino-acid truncated form of the 34-amino-acid cathelicidin-related antimicrobial peptide (CRAMP) in the islets of Langerhans of the murine pancreas. This peptide, P318, shares 67% identity with the LL-37 human antimicrobial peptide. As LL-37 displays antimicrobial and antibiofilm activity, we tested antifungal and antibiofilm activity of P318 against the fungal pathogen Candida albicans. P318 shows biofilm-specific activity as it inhibits C. albicans biofilm formation at 0.15 μM without affecting planktonic survival at that concentration. Next, we tested the C. albicans biofilm-inhibitory activity of a series of truncated and alanine-substituted derivatives of P318. Based on the biofilm-inhibitory activity of these derivatives and the length of the peptides, we decided to synthesize the shortened alanine-substituted peptide at position 10 (AS10; KLKKIAQKIKNFFQKLVP). AS10 inhibited C. albicans biofilm formation at 0.22 μM and acted synergistically with amphotericin B and caspofungin against mature biofilms. AS10 also inhibited biofilm formation of different bacteria as well as of fungi and bacteria in a mixed biofilm. In addition, AS10 does not affect the viability or functionality of different cell types involved in osseointegration of an implant, pointing to the potential of AS10 for further development as a lead peptide to coat implants.
 

yerrag

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@LLight I believe you're spot on with LL-37 having antibacterial effects, but not only that, it can be effective at busting biofilms effectively. I think AS10 peptide is a derivative of it, or something similar to it.

I can't find the AS10 on Google search, as I'd like to use it also.

I've been trying to fix my blood sugar issue so that I can go back to dry fasting for long periods. Right now, I can't do it unless I'm assisted by regular intakes of sugar during the fast, but I'd prefer fixing my blood sugar issue, of which I know is caused by p. gingivalis, a periodontal bacteria lurking in my vascular system.
 

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