Potassium supplements may increase survival in patients taking diuretics for heart failure
July 16, 2014
Perelman School of Medicine at the University of Pennsylvania
Researchers from the Perelman School of Medicine at the University of Pennsylvania found that patients taking prescription potassium supplements together with loop diuretics for heart failure have better survival rates than patients taking diuretics without the potassium. Moreover, the degree of benefit increases with higher diuretic doses. The team, including senior author Sean Hennessy, PharmD, PhD, associate professor of epidemiology in Penn’s Center for Clinical Epidemiology and Biostatistics (CCEB), report their findings in a study published online July 16 in PLOS ONE.–Loop diuretics — one type of diuretic or “water pill” named after the part of the kidney it acts on — are commonly used in the treatment of heart failure (and associated lower-limb edema or swelling) to help push out extra fluid that can accumulate when the heart is not working properly. But they also flush out needed potassium, causing many doctors, but not all, to prescribe the supplements. However, its survival benefit has never been studied, and because of this lack of evidence, there is controversy about whether potassium should be prescribed to all patients receiving loop diuretics.–In a retrospective study, the researchers examined existing health care data from Medicaid between 1999 and 2007 to study approximately 180,000 new starters of loop diuretics who were prescribed supplemental potassium and an equal number of people who started a loop diuretic without the potassium supplement. The researchers found that in patients receiving at least 40 mg/day of furosemide (one form of loop diuretic), adding supplemental potassium appeared to reduce mortality by 16 percent, a large and statistically significant reduction.—“Our findings provide evidence that adding potassium supplementation may increase survival rates among patients taking loop diuretics,” said the study’s lead author, Charles E. Leonard, PharmD, MSCE, a senior research investigator in the CCEB and senior manager of the Ambulatory Drug Use & Effects Program at Penn. “Nonetheless, because this is the first such study of this question, we hope that others confirm these results in independent studies.”–They also found that in patients receiving less than 40 mg/day of furosemide, potassium appeared to reduce the mortality rate by seven percent, a suggestive but statistically non-significant finding. (The overall mortality rate was about nine percent per year in the population under examination.)–The use of potassium supplementation under investigation was preventive, as opposed to being prescribed to patients who already had measured reductions in potassium. Only patients receiving supplemental potassium in solid, not liquid form, were studied[F4], the latter possibly being indicative of an inability to swallow and therefore a marker for a possibly complicating corollary medical impairment.–Loop diuretics act at the ascending loop of Henle in the kidney and help the body push out extra fluid that could accumulate in the lungs or legs and ankles when the heart is unable to completely pump blood throughout the body. But they may also cause the body to eliminate excessive amounts of potassium, which might be expected to increase mortality from heart arrhythmias. As a precaution therefore, many doctors prescribe potassium supplements to their patients receiving loop diuretics.–These results appear to support the common (but not universal) practice of using potassium together with loop diuretics. Today, nearly 5.8 million Americans suffer from heart failure.–“Using potassium supplementation for patients receiving loop diuretic therapy may be a relatively inexpensive way to save lives,” said Hennessy. “In today’s climate of seeking cost-effective measures to keep patients healthy, this is a therapy that certainly merits additional consideration.” Story Source-The above story is based on materials provided by Perelman School of Medicine at the University of Pennsylvania. Note: Materials may be edited for content and length. Journal Reference–Charles E. Leonard, Hanieh Razzaghi, Cristin P. Freeman, Jason A. Roy, Craig W. Newcomb, Sean Hennessy. Empiric Potassium Supplementation and Increased Survival in Users of Loop Diuretics. PLoS ONE, 2014; 9 (7): e102279 DOI: 10.1371/journal.pone.0102279
Recipe—instead of using a Diuretic from a Doctor Utilize Nettle and Dandelion Root to accomplish the same thing—Herbalist have known that Dandelion Puts Back in Potassium when used to accomplish the diuretic effect and as well regulates liver and insulin in the system further reducing any unwanted imbalance
Gut microbes turn carbs into colorectal cancer
July 17, 2014
Colorectal cancer has been linked to carbohydrate-rich western diets[F5], but the underlying mechanisms have been unclear. A study published by Cell Press July 17th in the journal Cell shows that gut microbes metabolize carbohydrates in the diet, causing intestinal cells to proliferate and form tumors in mice that are genetically predisposed to colorectal cancer. Treatment with antibiotics or a low-carbohydrate diet significantly reduced tumors in these mice, suggesting that these easy interventions could prevent a common type of colorectal cancer in humans.–“Because hereditary colorectal cancer is associated with aggressive and rapid tumor development, it is critical to understand how major environmental factors such as microbes and diet interact with genetic factors to potentially affect disease progression[F6],” says senior study author Alberto Martin of the University of Toronto. “Our study provides novel insights into this question by showing that gut bacteria interact with a carbohydrate-rich diet to stimulate a prevalent type of hereditary colon cancer[F7].” –Carbohydrates account for about half of the daily caloric intake of adults on a western-style diet, and previous studies have linked carbohydrate-rich diets to colorectal cancer in humans. [F8]This type of cancer is also frequently associated with mutations in a tumor suppressor gene called APC as well as the MSH2 gene, which plays a critical role in repairing DNA damage[F9]. However, it has been unclear why mutations affecting the DNA repair pathway are much more common in colorectal cancer compared with other cancers. Because gut microbes also contribute to the development of colorectal cancer, Martin and his team suspected that they could interact with diet to explain how the mutations could cause this type of cancer.–To explore this question in the new study, Martin and his collaborators used mice that had APC and MSH2 mutations and thus were predisposed to develop colorectal cancer. Treatment with either antibiotics or a low-carbohydrate diet reduced cell proliferation as well as the number of tumors in the small intestines and colons of these mice. These two treatments also reduced levels of certain gut microbes that metabolize carbohydrates to produce a fatty acid called butyrate. When the researchers increased butyrate levels in the antibiotic-treated mice, cell proliferation and the number of tumors increased in the small intestines.[F10]–Taken together, the findings suggest that carbohydrate-derived metabolites produced by gut microbes drive abnormal cell proliferation and tumor development in mice genetically predisposed to colorectal cancer. “By providing a direct link between genetics and gut microbes, our findings suggest that a diet reduced in carbohydrates as well as alterations in the intestinal microbial community could be beneficial to those individuals that are genetically predisposed to colorectal cancer,” Martin says.–Story Source-The above story is based on materials provided by Cell Press. Note: Materials may be edited for content and length.–Journal Reference-Antoaneta Belcheva, Thergiory Irrazabal, Susan J. Robertson, Catherine Streutker, Heather Maughan, Stephen Rubino, Eduardo H. Moriyama, Julia K. Copeland, Sachin Kumar, Blerta Green, Kaoru Geddes, Rossanna C. Pezo, William W. Navarre, Michael Milosevic, Brian C. Wilson, Stephen E. Girardin, Thomas M.S. Wolever, Winfried Edelmann, David S. Guttman, Dana J. Philpott, Alberto Martin. Gut Microbial Metabolism Drives Transformation of Msh2-Deficient Colon Epithelial Cells. Cell, 2014; 158 (2): 288 DOI: 10.1016/j.cell.2014.04.051
Acute glaucoma discovered to be an inflammatory disease
July 14, 2014
University of California, San Diego Health Sciences
Researchers at the University of California, San Diego School of Medicine and Sun Yat-sen University in China have shown that acute glaucoma in mice is largely an inflammatory disease and that high pressure in the eye causes vision loss by setting in motion an inflammatory response similar to that evoked by bacterial infections.—The study, published in this week’s issue of the Proceedings of the National Academy of Sciences, has immediate clinical relevance in treating the tens of millions of people worldwide from what is known as acute closed-angle glaucoma.–“Our research is the first to show an inflammatory mechanism by which high ocular pressure causes vision loss in acute glaucoma patients,” said co-senior author Kang Zhang, MD, PhD and professor of ophthalmology.–The second leading cause of irreversible blindness globally, glaucoma refers to a group of eye diseases associated with elevated intraocular pressure broadly classified as either open-angle or closed-angle. Open-angle is sometimes called the silent thief of sight because of its slow, often overlooked progression. By contrast, acute closed-angle glaucoma often is a painful ophthalmologic emergency in which there is a sudden rise in eye pressure and immediate damage to eyesight.–Less than 10 percent of glaucoma patients in America have the closed-angle form, but in parts of Asia it accounts for almost half of all cases. The higher prevalence of closed-angle glaucoma in Asians and women is believed to be due to a shallower anterior (frontal) eye chamber. –In the study, researchers showed that a rapid, sustained large increase in eye pressure in mice turns on a gene (TLR4) that activates a protein known as caspase-8. This signaling protein in turn triggers the production of inflammatory proteins that normally help mammals fight microbial infections.–“This immune response is a double-edge sword because, while these proteins protect us from infection in a normal situation, they stimulate apoptosis (programmed cell death) in retinal cells in cases of acute glaucoma[F11],” said Zhang, who is also a staff physician at the Veterans Affairs San Diego Healthcare System.–To further confirm the mechanism linking high eye pressure to retinal damage, researchers showed that they could slow retinal cell death in mice with acute glaucoma by suppressing either the TLR4 gene or caspace-8 protein.–The latter is particularly significant because caspace-8 inhibitors are currently in clinical trials for treating cancer and stroke. “By injecting these inhibitors into the eyes of acute glaucoma patients, it may be possible to evaluate and bring them vision-sparing treatments more quickly,” said co-author Robert N. Weinreb, MD, chairman and Distinguished Professor of Ophthalmology.-Story Source-The above story is based on materials provided by University of California, San Diego Health Sciences. Note: Materials may be edited for content and length.-Journal Reference-W. Chi, F. Li, H. Chen, Y. Wang, Y. Zhu, X. Yang, J. Zhu, F. Wu, H. Ouyang, J. Ge, R. N. Weinreb, K. Zhang, Y. Zhuo. Caspase-8 promotes NLRP1/NLRP3 inflammasome activation and IL-1 production in acute glaucoma. Proceedings of the National Academy of Sciences, 2014; DOI: 10.1073/pnas.1402819111
EYE-Occular Support and Prevention
Choline deficiency may cause degeneration of the Eyes. [more info]
Inositol may stimulate the growth of Eye membranes. [more info]
Vitamin A may improve the structural integrity of the Mucous Membranes that line the Eyes and may maintain the health of the Cornea of the Eyes: [more info]
11-cis Retinal (an endogenous isomer of the Retinal form of Vitamin A) is essential to Eyesight – it combines with Opsin to form the visual Pigment – Rhodopsin.
Vitamin B2 may improve the function of the Eyes (it is a component of Visual Pigments in the Retina). references
Vitamin C concentrates in the Eyes. [more info]
The Retina of the eye may be prone to degeneration when a Vitamin E deficiency exists. [more info]
Taurine concentrates in the Retina of the Eyes and may be essential for optimal Sight
Selenium may help to maintain the health of the Eyes. references
Zinc concentrates in the Retina of the Eye.
Anthocyanosides may strengthen the lens of the Eye (by improving blood supply to the eyes). [more info]
Kaempferol may be beneficial for the health of the Eyes. [more info]
Myricetin may improve the health of the Eyes. [more info]
Oligomeric Proanthocyanidins (OPCs) may enhance the health of the Eyes and significantly improve Sight. references
Collagen is an important structural component of the Eyes.
Rosemary—Goji berry –Marigold—Nettle—Parsely—Head of the carrot( part where the leaf and the top part of the carrot are connected–
Rosemary—Goji berry –Marigold—Nettle—Parsely—Head of the carrot( part where the leaf and the top part of the carrot are connected
Methylsulfonylmethane (MSM) – applied topically as eyedrops – may reduce intraocular pressure in persons afflicted with Glaucoma. [more info]
Folic Acid may help to prevent Glaucoma (by counteracting the toxicity of Glutamic Acid, a suspected cause of Glaucoma). references
Lipoic Acid may alleviate Glaucoma. references
Glaucoma patients are often found to be deficient in Vitamin B1 (indicating that restoring Vitamin B1 levels to normal via supplementation may be beneficial for Glaucoma patients). references
Coenzyme Q10 may help to prevent Glaucoma (by counteracting the toxicity of Glutamic Acid, a suspected cause of Glaucoma). references
Coenzyme Q10 may help to prevent Glaucoma (by counteracting the toxicity of Glutamic Acid, a suspected cause of Glaucoma)
CDP-Choline (1,000 mg per day) may alleviate (chronic simple) Glaucoma. references
Hydergine (5 – 20 mg per day) may lower intraocular pressure in Glaucoma patients. references
Picamilon may improve Eyesight in (chronic simple) Glaucoma patients. references
Vinpocetine may help to stabilize the condition of Glaucoma patients. references
THE SECRET COVENANT
An illusion it will be, so large, so vast it will escape their
Those who will see it will be thought of as insane.
We will create separate fronts to prevent them from seeing the
connection between us.
ØØØWe will behave as if we are not connected to keep the illusion alive.
Our goal will be accomplished one drop at a time so as to never bring
suspicion upon ourselves. This will also prevent them from seeing
the changes as they occur.
We will always stand above the relative field of their experience
for we know the secrets of the absolute.
We will work together always and will remain bound by blood and
secrecy. Death will come to he who speaks.
ØØØWe will keep their lifespan short and their minds weak while
pretending to do the opposite.
We will use our knowledge of science and technology in subtle
ways so they will never see what is happening.
ØØØWe will use soft metals, aging accelerators and sedatives in
food and water, also in the air. ( sounds like Chem. Trails …fluoride…chlorine….hormone additives ( will age you exponentially)
They will be blanketed by poisons everywhere they turn.
The soft metals will cause them to lose their minds. We will
promise to find a cure from our many fronts, yet we will
feed them more poison. ØØØ ( Sounds to me like the medical field and the the pharmaceutical Industry, and the agro fields eh!!)
The poisons will be absorbed trough their skin and mouths, ØØØ ( Chem Trails….Plastic Particulates….Hormones in water)
they will destroy their minds and reproductive systems.
ØØØFrom all this, their children will be born dead, and we will conceal
this information. ( Genetic programmed death…)
The poisons will be hidden in everything that surrounds them,
in what they drink, eat, breathe and wear. ØØØ ( Synthetics that use toxic SOY and other Genetically Modifed Organisms )….We must be ingenious in dispensing the poisons for they
can see far.
We will teach them that the poisons are good, with fun images
and musical tones. ØØØ ( tech toys and TV)
Those they look up to will help. We will enlist them to
push our poisons. ØØØ ( Medical industry….Pharmaceutical Industry…Religious Institutions…Agencies of the global gov’t )
They will see our products being used in film and
will grow accustomed to them and will never know
their true effect. ØØØ ( Bloody TV and Videos and Music Videos and radio )
When they give birth we will inject poisons into the blood
of their children and convince them its for their help. ØØØ ( Bloody Injections )
We will start early on, when their minds are young, we will
target their children with what children love most, sweet
things. ØØØ ( Addiction to junk )
When their teeth decay we will fill them with metals
that will kill their mind and steal their futureØØØ( Mercury…. Plastics … Braces ) When their ability to learn has been affected,
we will create medicine that will make them sicker and cause other
diseases for which we will create yet more medicine.
We will render them docile and weak before us by our power. ØØØ ( Estrogenic Foods and Flouride-Nanoparticle/biofilm-Vaccines-Smart Meter Freq-ELF-EMF- )
ØØØThey will grow depressed, slow and obese, and when they
come to us for help, we will give them more poison.
ØØØWe will focus their attention toward money and material goods
so they many never connect with their inner self. We will distract
them with fornication, external pleasures and games so they may
never be one with the oneness of it all. ØØØ ( Lust…. Distractions through debt and Slavery not thinking in any other term but of going in the circle ) Their minds will belong to us and they will do as we say.
If they refuse we shall find ways to implement mind-altering technology
into their lives. We will use fear as our weapon.
ØØØWe will establish their governments and establish opposites within. We will own both sides.
We will always hide our objective but carry out our plan.
ØØØThey will perform the labor for us and we shall prosper from their toil.
Our families will never mix with theirs. Our blood must be pure
always, for it is the way.
ØØØWe will make them kill each other when it suits us.
ØØØWe will keep them separated from the oneness by dogma and religion. ( The Illusion of God through Religion…this is Why I hate all religions…it does nothing but enslave and bring us against the truth…which is we are all Created in the Image of God….and the way to God is By God not through Religion!!!!!!!!!! )
We will control all aspects of their lives and tell them what to think and how.
We will guide them kindly and gently letting them think they are guiding
We will foment animosity between them through our factions. ØØØ ( Team Concept ..remember when they wanted everyone to be on a Team at the job site breeding competition to keep everyone against each other so they would be distracted to what management was doing….this is why a lot of those who were free thinkers never got the jobs they should have ….)
When a light shall shine among them, we shall extinguish it by ridicule,
or death, whichever suits us best.
We will make them rip each other’s hearts apart and kill their own children. ØØØ ( Abortions ….Genetic experimentation with human and animal genetics)
We will accomplish this by using hate as our ally, anger as our friend. ØØØ ( Ever wonder why you feel so miserable all the time or aggressive for no reason or agitated )… ØØØ
The hate will blind them totally, and never shall they see that from their
conflicts we emerge as their rulers. They will be busy killing each other. ( Divide and Conquer) They will bathe in their own blood and kill their neighbors for as long as we see fit. ØØØWe will benefit greatly from this, for they will not see us, for they cannot see us. ( we will be to busy fearing the other Guy or Gal …Anarchy is the objective so they can re implement there hold of power Continuing this Bloody cycle for another millennium ) We will continue to prosper from their wars and their deaths.
We shall repeat this over and over until our ultimate goal is accomplished.
We will continue to make them live in fear and anger though images and sounds. We will use all the tools we have to accomplish this.
The tools will be provided by their labor. ØØØ ( imagine that you digging your own grave for them so then when you are ready you can drop in the Hole you dug )
We will make them hate themselves and their neighbors.
We will always hide the divine truth from them, that we are all one.
This they must never know! They must never know that color is an illusion, they must always think they are not equal.
Drop by drop, drop by drop we will advance our goal.
We will take over their land, resources and wealth to exercise total
control over them.
We will deceive them into accepting laws that will steal the little
freedom they will have.
We will establish a money system that will imprison them forever,
keeping them and their children in debt.
When they shall ban together, we shall accuse them of crimes and present a
different story to the world for we shall own all the media.
We will use our media to control the flow of information and their sentiment
in our favor.
When they shall rise up against us we will crush them like insects, for
they are less than that.
They will be helpless to do anything for they will have no weapons.
We will recruit some of their own to carry out our plans, we will promise them eternal life, but eternal life they will never have for they are not of us. ØØØ ( this is the way to use those who seek power and then when the agenda is completed destroy those who aided in there rise…Hussein was installed by the US cia and when gotten in Power Murdered all those who were at the top who got him to that point!!! Hitler did this so did Marxs…..)
The recruits will be called “initiates” and will be indoctrinated to believe
false rites of passage to higher realms. Members of these groups will think they are one with us never knowing the truth. They must never learn this truth for they will turn against us. ØØØ ( the special forces who get this training eventually are exterminated by there own respective gov’ts this is the show of appreciation that these gov’ts have )
For their work they will be rewarded with earthly things and great titles,
but never will they become immortal and join us, never will they receive
the light and travel the stars. They will never reach the higher realms, for the killing of their own kind will prevent passage to the realm of enlightenment. This they will never know.
The truth will be hidden in their face, so close they will not be able to focus
on it until its too late.
Oh yes, so grand the illusion of freedom will be, that they will never know they are our slaves. ØØØ ( The financial institutions have given out money for next to nothing and as a result the sheep or cattle have laid themselves to sleep thinking they are secure and settled in there homes…when in fact they have made there own prisons and pastures for entrapment ) When all is in place, the reality we will have created for them will own them.This reality will be their prison. They will live in self-delusion.
ØØØWhen our goal is accomplished a new era of domination will begin.
Their minds will be bound by their beliefs, the beliefs we have established
from time immemorial.
But if they ever find out they are our equal, we shall perish then. THIS THEY MUST NEVER KNOW.
ØØØIf they ever find out that together they can vanquish us, they will take action.
They must never, ever find out what we have done, for if they do, we shall
have no place to run, for it will be easy to see who we are once the veil has
fallen. Our actions will have revealed who we are and they will hunt us down and no person shall give us shelter.
This is the secret covenant by which we shall live the rest of our present
and future lives, for this reality will transcend many generations and life
spans. This covenant is sealed by blood, our blood. We, the ones who from
heaven to earth came. This covenant must NEVER, EVER be known to exist. It must NEVER, EVER be written or spoken of for if it is, the consciousness it will spawn will release the fury of the PRIME CREATOR upon us and we shall be cast to the depths from whence we came and remain there until the end time of infinity itself.
Chronic central cholesterol treatment enhances spatial learning and memory
The clear effect of cholesterol replenishment in rescuing impaired LTD in old animals prompted us to test whether the infusion of cholesterol into the brain of old rats would improve some of the cognitive deficits typical of this stage of life. Therefore, 19 month old rats were perfused in the lateral ventricle for 1 month with a cholesterol replenishment solution (containing the 300 μM cholesterol MβCD complex + 5 μM free cholesterol dissolved in artificial cerebrospinal fluid – aCSF). Subsequently, the spatial learning ability of the animals was evaluated in the reference version of the Morris water maze, an established hippocampal dependent task (see Materials and Methods) where aged animals typically exhibit impaired learning of the location of the hidden escape platform (Gallagher et al, 1993).
Post hoc statistical comparison of the learning curves demonstrated significant differences for the two groups of rats (repeated measure ANOVA, F1,11 = 5.848, P = 0.016: Fig 8A). A more detailed analysis of each training day indicated that cholesterol treated rats outperformed their controls in the water maze on day 4 (F1,2 = 7,707; P = 0.008). The Bonferroni post hoc test indicated significant differences to find the hidden platform between cholesterol treated rats and controls in trial 11 (P = 0.019). One day after the acquisition of spatial learning, the strength of long term spatial memory was evaluated in a probe trial (i.e., free swimming without platform). During the probe trial, rats that received cholesterol spent more time swimming in the quadrant of the pool that contained the platform during training (target quadrant) than those that did not (t18 = 2.659, P = 0.016: Fig 8B and C). No differences in swim speed or thigmotactic behavior were found during spatial training or in the probe trial. These results show that cholesterol perfusion can rescue learning and memory in old rats.
Cholesterol improves learning and memory in old rats
· A. The spatial abilities of 20M rats subjected to intraventricular infusion of control or cholesterol solution were evaluated in the Morris water maze. The animals were trained three times each day over 4 days, and the learning curves were plotted for the two groups. Average group distance (cm) to find the hidden platform across trials is shown, whereby cholesterol treated rats (n = 9) outperformed their controls (n = 11) in the water maze on day 4 (repeated‐measure ANOVA, F1,2 = 7,707; P = 0.008), and significant differences were found in trial 11 (Bonferroni post hoc test, P = 0.019).
Constitutive hippocampal cholesterol loss underlies poor cognition in old rodents
Mauricio G Martin, Tariq Ahmed, Alejandra Korovaichuk, Cesar Venero, Silvia A Menchón, Isabel Salas, Sebastian Munck, Oscar Herreras, Detlef Balschun, Carlos G Dotti
DOI: 10.15252/emmm.201303711 |Published 30.05.2014
Cognitive decline is one of the many characteristics of aging. Reduced longterm potentiation (LTP) and longterm depression (LTD) are thought to be responsible for this decline, although the precise mechanisms underlying LTP and LTD dampening in the old remain unclear. We previously showed that aging is accompanied by the loss of cholesterol from the hippocampus, which leads to PI3K/Akt phosphorylation. Given that Akt dephosphorylation is required for glutamate receptor internalization and LTD, we hypothesized that the decrease in cholesterol in neuronal membranes may contribute to the deficits in LTD typical of aging. Here, we show that cholesterol loss triggers pAkt accumulation, which in turn perturbs the normal cellular and molecular responses induced by LTD, such as impaired AMPA receptor internalization and its reduced lateral diffusion. Electrophysiology recordings in brain slices of old mice and in anesthetized elderly rats demonstrate that the reduced hippocampal LTD associated with age can be rescued by cholesterol perfusion. Accordingly, cholesterol replenishment in aging animals improves hippocampal dependent learning and memory in the water maze test.[F12]
It is well established that cognitive deficits go hand in hand with aging. Restoring cholesterol levels in the aged hippocampus to values found in the young can rescue learning and memory in the old, linking age dependent cholesterol decline with synaptic plasticity and neuronal function.
· A mild yet significant reduction in membrane cholesterol characterizes the aging rodent hippocampus.
· Low synaptic hippocampal cholesterol determines reduced Akt dephosphorylation after NMDA induced LTD, together with reduced glutamate (AMPA) receptor lateral diffusion and endocytosis.
· Low synaptic hippocampal cholesterol plays a role in the poor LTD of old mice and rats, in ex vivo and in vivo paradigms.
· Normal levels of pAkt after NMDA, proper receptor lateral diffusion, and internalization and normal (young animals‐like) LTD in the old can be rescued by membrane cholesterol replenishment.
· Cholesterol replenishment in living old rats improves learning and memory.
EMBO Mol Med (2014) 6: 902–917Abstract/FREE Full Text
Aging is associated with cognitive decline, such that individuals older than 65 develop cognitive deficits or age associated memory impairments. The hippocampus, a brain structure that is central to the formation of declarative and other types of memory, is particularly sensitive to aging. However, these impairments are not paralleled by an increase in neuronal death (Burke & Barnes, 2006), indicative that more subtle mechanisms must be affected by aging to produce memory decline.
We previously showed that the phosphorylated form of the serine–threonine kinase Akt (pAkt) accumulates in old hippocampal neurons, both in vivo and in vitro (Martin et al, 2008, 2011; Trovò et al, 2013), which probably reflects the strong need for survival signaling. Nevertheless, the counter effect of robust survival might be reduced performance. In fact, pAkt phosphorylation negatively regulates long term depression (LTD), a key process in learning and memory (see below and Peineau et al, 2007).
The accumulation of pAkt[F13] with age may be the result of different processes. We previously observed that the increase with age of the cholesterol hydroxylating enzyme cholesterol 24hydroxylase (CYP46A1), the major catabolic enzyme of cholesterol in the brain (Lund et al, 2003), triggers cholesterol loss dependent, ligand independent, activation of the TrkB receptor and, consequently, Akt phosphorylation (Martin et al, 2008, 2011; Sodero et al, 2011a,b). A second mechanism driving the increase in pAkt with age is also linked to cholesterol loss, and it involves the increase in plasma membrane sphingomyelin, similarly contributing to ligand independent TrkB phosphorylation and PI3K/Akt activation (Trovò et al, 2011). Increased PI3K/Akt activity in old neurons also seems to arise from the constitutive increase with age of interleukin 1B (IL 1B) activity and from the age associated detachment from the plasma membrane of the PIP2 binding protein, myristoylated alanine rich C kinase substrate (MARCKS: Trovò et al, 2013). Altered binding of MARCKS to the membrane favors the accumulation of PIP3 in the synaptic fraction of old mice, with the subsequent increase in Akt phosphorylation (Trovò et al, 2013).
Activity dependent changes in synaptic strength, such as long term potentiation (LTP) and long term depression (LTD) of synaptic transmission, are considered to be the cellular substrates of learning and memory (Neves et al, 2008; Collingridge et al, 2010). Competitive interactions between these forms of synaptic plasticity have been proposed to participate in memory storage (Diamond et al, 2005; Nicholls et al, 2008; Ge et al, 2010). Indeed, glycogen synthase kinase 3 beta (GSK3β) determines whether NMDA receptor activation induces or inhibits LTD (Peineau et al, 2007). Moreover, the activation of protein phosphatase 1 (PP1) during LTD dephosphorylates GSK3β at Ser9, resulting in its activation and receptor internalization. Since pAkt is a GSK3β inhibitor, PP1 mediated Akt dephosphorylation further contributes to the enhancement of GSK3β activity. Significantly, GSK3β and Akt dephosphorylation are impaired by okadaic acid, a compound that also blocks LTD by inhibiting PP1 (Peineau et al, 2007). Conversely, activation of NMDA receptors leads to the stimulation of PI3K/Akt pathway during LTP, provoking the phosphorylation of GSK3β at Ser9 to prevent LTD. Thus, it appears reasonable to assume that the loss of cholesterol and the consequent enhancement of PI3K/Akt activity that occurs in the hippocampus during aging will have a detrimental effect on LTD and, consequently, on cognition. Since most studies coincide that aging is accompanied by a decreased propensity to develop LTD (Lee et al, 2005; Billard & Rouaud, 2007; Ahmed et al, 2011), we investigated here whether and how this is related to age‐associated constitutive cholesterol loss
[F1]Hyperammonemia (or hyperammonaemia) is a metabolic disturbance characterised by an excess of ammonia in the blood. It is a dangerous condition that may lead to encephalopathy and death. It may be primary or secondary.
[F2]But this is still effective—you would need to take somethingwith the cinnamon to block that coumarin—which in minutia amounts can have an actual benefit as well
[F3] indigenous or endemic to a region
[F4]Capsule-powder or tablet
[F5]What is in the carbs?
[F6]Read Carefully here “genetic factors” not necessary about YOUR genetics—look at this closely the mice are genetically engineered—if the carb they are using as well genetically modified your bacteria in the colon is going react negatively with these genetics and these probiotics are going to cause a biological reaction to generate something that would not be there normally and cause a over growth and promote tumours—because the chemistry in these genes are designed to form this type activity
[F7]Hereditary—is a cover word for GMO
[F8]Question here should be asked what type of carbohydrate are we referring to
[F9]These will as well stops or blocks the immune response to protecting the RNA-DNA
[F10]This would be a result again from the genetic interaction—normally butyric acid protects the body’s system
[F11]What is actually going on here is the immune response is doing what it is supposed to be doing but the programmed response is attaching itself to something that is causing it to be overly responsive-over activating the immune system causing it to become self destructive—nanoparticulates would in deed cause this response
[F12]Welll what do you know an increase in fat can restore learning
[F13]phosphorylated form of the serine–threonine kinase Akt (pAkt)