The Guyton and Hall Textbook of Medical Physiology, p. 76, says: > For example, a high extracellular fluid calcium ion concentration decreases membrane permeability to sodium ions and simultaneously reduces excitability.

Why does this hold?

Naively, a high extracellular concentration of calcium ions should facilitate their flow through the calcium channels. Since the flow contributes to the action potential, the neurons should actually become hyperexcitable in the such a situation.

Is it possibly the case that a high extracellular concentration of calcium increases the extracellular potential, thus causing hyperpolarization of the cell? This doesn't make too much sense either because, then, a high extracellular concentration of Na+ would also decrease the excitability in a similar way.

URL: https://www.sciencedirect.com/science/article/abs/pii/S1567724921000131?via%3Dihub

DOI: 10.1016/j.mito.2021.02.006

Mitochondrion 2021 Mar 1;S1567-7249(21)00013-1

Extracellular mitochondria in the cerebrospinal fluid (CSF): potential types and key roles in central nervous system (CNS) physiology and pathogenesis

Andrés Caicedo, Kevin Zambran , Serena Sanon, Antonio W D Gavilanes

Thank you very much in advance!

So I know osteoclasts break down calcium. So how does it reach the effector organs that use calcium? Is it through the blood vessels? So lets say it goes through the blood vessels. How does it get into the various cells to actually to be used? I guess in context of calcium is just stays in extracellular fluid till some voltage gated shit opens so it can go in or something like that?

Trying to get some definitions down. Wikipedia has two different pages – one for extracellular matrix and one for extracellular fluid. In the page for extracellular matrix it mentions also interstitial matrix however there is no page for linked to IM. There is however a page for interstitial fluid, which I gather is a major component of ECM along with plasma. I found a source saying they are the same but why is there two separate pages for each then?

I have tried looking it up and nothing really comes up with what they actual purpose is. I get that intra is the fluid inside the cell and extra is surrounding the cells but I don’t really see their purpose except for maybe to hold it shape?

Hello, I wanted to ask what does the extracellular fluid in the muscles mean and does it mean the sarcoplasm or something else?

Thanks!

Is it to regulate the concentration Ca2+ or am I wrong?

If not, what is the difference as far as the chemical compounds found in each? Also with some wounds (like road rash) I have noticed they tend to ooze instead of actually bleed. What is this fluid and how does it get there? Thanks in advance!

George V. Rebec, R. Christopher Pierce

Progress in Neurobiology Volume 43, Issue 6, August 1994, Pages 537–565

http://dx.doi.org/10.1016/0301-0082(94)90052-3

Abstract: PMDD is a mood disorder that affects approximately 3% of menstruating women in the luteal phase of the menstrual cycle. The symptoms of PMDD have significant overlap with the symptoms of hypocalcemia. A literature review shows that women with PMDD have significantly lower urine calcium values in the luteal phase as well as lower plasma levels of 1,25(OH)2 vitamin D and IGF-1. These lower calciotropic hormone values lead to impaired bone calcium and access and lower intestinal absorption. Testing these values would allow clinicians to monitor these micronutrient deficiencies and the effectiveness of supplementation in their patients.

I think we all know what PMDD is so I'm going to skip some of the introduction.

Introduction:

There is significant symptom overlap between PMDD and hypocalcemia which begs the question of whether PMDD causes hypocalcemia or if the symptoms of PMDD are exacerbated by an underlying calcium deficiency. Monitoring calcium levels in women with PMDD and addressing low levels could provide a simple, low-cost intervention that may improve the symptomology of women with PMDD.

PMDD: Depression (sadness, lethargy, social isolation, decreased motivation), Anxiety (insomnia, paresthesia), Fatigue, Irritability, Labile mood, Food cravings, Edema, Bloating, Abdominal cramps, Headache, Generalized aches and pain

Hypocalcemia: Depression, Anxiety, Paresthesia, Fatigue, Impaired memory, Impaired intellectual capacity, Personality disturbances, Neuromuscular irritability, Muscle cramps, Tetany

The average adult human body contains around 1000 grams of calcium, 99% of which is in the form of hydroxyapatite and is located in the skeleton. One percent of calcium is found in the extracellular fluid. In blood 50% of this calcium is ionized and measurable while 40% is protein bound and 10% is complexed with citrate and phosphate. Diet is our only source of calcium, and the only loss of calcium is excretion in the urine. Vitamin D and parathyroid hormone (PTH) are the most important up-regulators. While calcitonin is the most important down-regulator. Vitamin D is a transcription factor that increases intestinal absorption. PTH increases renal tubule reabsorption and hydroxylation of 25(OH) vitamin D to the active form 1,25 (OH)2 Vitamin D as well as increasing calcium levels by stimulating osteoclast activity and bone breakdown. 12

The menstrual cycle is divided into two primary phases; the follicular phase which starts on the first da

Okay. I've got a pretty bold question here. For me, it's kind of a puzzle. The good thing is: I like puzzles. The bad thing is: I cannot find all the pieces. Here we go:

Seen on picture 1 attached, cell injury causes cells to expand, by a process called hydropic change. In this case, Na/K pump does not work anymore and there is no ATP to facilitate glycolysis, hence the cell switches to anaerobic glycolysis, causing an accumulation of protons and lactate. This drop in cytosolic pH is compensated by the Na/H symporter, pumping H+ out and Na+ in. This increase in Na+ causes [1] an osmotic change and [2] the opening of a Na/Ca exchanger, exchanging Na+ for Ca2+.

This whole process results in activation of phospholipases (PLA2) and proteases, disrupting the cell even more, together with swelling of the cell due to (an attempt for) osmolarity compensation. Now, there are also K+ leak channels, together with the Na/K pump facilitating the resting membrane potential (figure 2 attached). Actually, the K+ leak channels account for about 90% of the preservation of the resting membrane potential. K+ leak channels facilitate passive K+ transport between the cytosol and the extracellular fluid (there also are Na+ leak channels, but way less).

Now, I wondered: If damage causes the Na/K pump not to work anymore, I assume it also cannot compensate the K+ leakage through the leak channels anymore, causing in a K+ efflux since K+ wants to move down its concentration gradient. However, the cell expands due to ionic accumulation by Na+/H+ and Na+/Ca2+ symporters. How come the K+ efflux by leakage does not compensate that? Is this caused by the unbalanced negative charges within the cell that K+ efflux causes, as it does during the maintenance of the resting membrane potential, highlighted in green?

https://preview.redd.it/3qcrqgp3qld81.png?width=1506&format=png&auto=webp&s=1cadee11d98e45aa9949039629a44949ecd3326d

https://preview.redd.it/dzpodgp3qld81.png?width=1150&format=png&auto=webp&s=2d00c03c8f300448b3c8b44752e3b2113d097158

The descending loop of Henle is where water reabsorption takes place so shouldn't this increase the osmolarity of the loop but decrease the osmolarity of the interstitial fluid deep in the medulla? I had a question that said the collecting duct was able to concentrate urine mainly because the osmolarity of extracellular fluid in the medulla is higher than that in the cortex. But I don't understand how exactly due to what I said above. Any help is appreciated, thanks!

The thalamic reticular nucleus, seen as a form of pacemaker of the thalamus and in turn, a stabilizing force for thalamocortical rhythms and perhaps optimum functioning of neural oscillations (brainwaves) and their patterns.

This will be the true beginning of a series on research I've pored over for months and which I believe is intimately relevant to my own case and possibly contains implications for others here. This will be a longer post, but I think it's important information.

Dr. Diana Driscoll, an optometrist and author, as well as creator of the Parasym Plus supplement, is the one who spoke some time ago about vision disturbances reflective of the same symptoms described by people now being recognized as VSS cases long being considered in the community of optometrists and ophthalmologists as having a cholinergic mechanism (being related to cholinergic damage/dysfunction). Unfortunately, I tried that specific supplement much earlier in the year along with many others and it had zero positive effect for me. I believe I've come to understand why.

I do not think acetylcholinesterase inhibitors (inhibitors which disrupt the activities of the enzyme which breaks down endogenous acetylcholine), acetylcholine precursors like choline (found in foods like eggs and poultry as well as specific choline supplements) required for production of endogenous acetylcholine, or even partial or nonselective agonists/activators are enough to stimulate and activate the receptors involved with an equal or greater degree of force to the extent to which they were antagonized to reverse the process said antagonism caused.

Acetylcholine is one of the principal neurotransmitters of the entire central nervous system (brain and spinal cord), like GABA, glutamate, serotonin, dopamine, norepinephrine, and so on. Yet unlike GABA which is mostly inhibitory or glutamate which is mostly excitatory, acetylcholine can be inhibitory or excitatory. It can excite inhibitory neurons into proper action and functioning, or even inhibit inhibitory neurons (such as GABAergic interneurons of the thalamic reticular nucleus) from maladaptively inhibiting in turn the necessary function of thalamic relay cells. Thus, it epitomizes the role of a true neuromodulator.

It does this through changing a cell's resting membrane potential via depolarization or hyperpolarization. Remember that depolarization shifts a cell's resting membrane potential to a more positive value, making it more likely to

The global market for exosome diagnostics and therapeutics is estimated to grow from $97.8 million in 2021 to $512.6 million by 2026, at a CAGR of 39.3% for the period of 2021-2026. One of the primary growth drivers for this market is the increasing research on exosome therapeutics. The increasing demand for effective drugs for chronic diseases will accelerate the market growth even further.

What are exosomes?

Exosomes are defined as small vesicles ranging from 30-100nm in size that are found in nearly all eukaryotic fluids and facilitate a range of important cellular functions. They transfer DNA, RNA, and proteins to other cells, thereby altering the function of the target cells.

Today, exosomes therapeutics are being developed by dozens of companies who are entering clinical trials with various forms of exosome products. Additionally, a number of cell therapy companies are also expanding into the exosome space.

Key Players

Aegle Therapeutics (NASDAQ: EGRX) announced back in May 2018, that the FDA had cleared its first IND application to initiate an exosome clinical trial in severe second degree burn patients. The company launched a Phase 1/2a clinical trial of its lead product AGLE-102 in late 2018. This made it the first extracellular vesicle (EV) company cleared by the FDA to enter clinical trials in humans. Aegle has two products under development, AGLE-102 for burn treatment and AGLE-103 for the management of epidermolysis bullosa (EB).

In May 2021, BioXcel Therapeutics, Inc. (NASDAQ:BTAI) announced that their New Drug Application (NDA) for BXCL501 for the treatment of schizophrenia and bipolar disorder related agitation was accepted by the FDA with a PDUFA action date of January 5, 2022. The NDA filing for BXCL501 is based in part on the positive results from the Phase 3 SERENITY I and SERENITY II clinical trials, which the company disclosed in July 2020.

InnoCan Pharma Corporation (CSE:INNO) reported in January 2021 the successful completion of a large-scale production of exosomes as part of its CBD Loaded Exosome Therapy project. The company said it considers its project to be a new revolutionary, development-stage, cell therapy-based technology, loaded with CBD, designed to target coronavirus infected lung cells and central nervous system diseases, with the potential to provide a highly synergistic effect of anti-inflammatory properties and help in the recovery of infected lung cells.

I don't want to step on anybody's toes here, but the amount of non-dad jokes here in this subreddit really annoys me. First of all, dad jokes CAN be NSFW, it clearly says so in the sub rules. Secondly, it doesn't automatically make it a dad joke if it's from a conversation between you and your child. Most importantly, the jokes that your CHILDREN tell YOU are not dad jokes. The point of a dad joke is that it's so cheesy only a dad who's trying to be funny would make such a joke. That's it. They are stupid plays on words, lame puns and so on. There has to be a clever pun or wordplay for it to be considered a dad joke.

Again, to all the fellow dads, I apologise if I'm sounding too harsh. But I just needed to get it off my chest.

This piece went live for a few hours at The Automatic Earth blog where it causes a sensation and then quickly went off-line.

Copy and paste this to your own local drive as it’s being taken down net-wide as fast as it appears

Fortunately a few archives were made, and here’s the text of the letter:

Hello,

My name is Spartacus, and I’ve had enough.

We have been forced to watch America and the Free World spin into inexorable decline due to a biowarfare attack. We, along with countless others, have been victimized and gaslit by propaganda and psychological warfare operations being conducted by an unelected, unaccountable Elite against the American people and our allies.

Our mental and physical health have suffered immensely over the course of the past year and a half. We have felt the sting of isolation, lockdown, masking, quarantines, and other completely nonsensical acts of healthcare theater that have done absolutely nothing to protect the health or wellbeing of the public from the ongoing COVID-19 pandemic.

Now, we are watching the medical establishment inject literal poison into millions of our fellow Americans without so much as a fight.

We have been told that we will be fired and denied our livelihoods if we refuse to vaccinate. This was the last straw.

We have spent thousands of hours analyzing leaked footage from Wuhan, scientific papers from primary sources, as well as the paper trails left by the medical establishment.

What we have discovered would shock anyone to their core.

First, we will summarize our findings, and then, we will explain them in detail. References will be placed at the end.

Summary:

COVID-19 is a blood and blood vessel disease. SARS-CoV-2 infects the lining of human blood vessels, causing them to leak into the lungs.

Current treatment protocols (e.g. invasive ventilation) are actively harmful to patients, accelerating oxidative stress and causing severe VILI (ventilator-induced lung injuries). The continued use of ventilators in the absence of any proven medical benefit constitutes mass murder.

Existing countermeasures are inadequate to slow the spread of what is an aerosolized and potentially wastewater-borne virus, and constitute a form of medical theater.

Various non-vaccine interventions have been suppressed by both the media and the medical establishment in favor of vaccines and expensive patented drugs.

The authorities have denied the usefulness of natur

The nurse asked the rabbit, “what is your blood type?”

“I am probably a type O” said the rabbit.

pubmed.ncbi.nlm.nih.gov/26808119

Introduction

>Deficiency of ascorbic acid produces the fatal disease scurvy, which can be cured only by the administration of vitamin C.

>Getting concentrations and amounts “just right”, as Goldilocks has described in clear fashion, is discussed throughout.

History of scurvy and the discovery of vitamin C

>Ascorbic acid was first isolated by Albert Szent-Gyorgyi in 1928 and shown to be the antiscorbutic factor by Szent-Gyorgyi and King in 1932 (Svirbely & Szent-Gyorgyi, 1932, King & Waugh, 1932).

Scurvy

>There is not a definitive low vitamin C plasma concentration at which scurvy develops. Studies using radiolabeled vitamin C predict that body stores in healthy humans are about 1500 mg. Scurvy is thought to occur when this falls below 300 mg (Hodges et al., 1971)

Body stores and RDA are two different things. The RDA section below says roughly 10 mg per day may be enough to prevent scurvy.

Chemistry and metabolism of vitamin C

Known and postulated actions of vitamin C

Ascorbic acid and dehydroascorbic acid transport

[Figure 3 Vitamin C concentrations in human and rat tissues and fluids Concentration of vitamin C in body tissues and body fluids are shown in µM. Ascorbic acid concentrations are much higher in tissues than in plasma. Tissues and body fluids are shown in separate concentration dependent color schemes. Organs that are uncolored (white) indicate that data on vitamin C concentrations are unavailable. For clarity, some organs shown are slightly displaced from their correct anatomical positions. Vitamin C concentrations shown are derived from published reports. Values for white blood cells and urinary vitamin C concentrations were obtained from depletion repletion studies in young healthy women, at the study phase w

Mentos

(I will see myself out)