1230 replies to this topic

[Mian Ali Ismail]

Is it available subcutaneously ?

[albedo]

Not sure this fits in here but nevertheless I though useful to log it in this thread. I think previous work by some of the authors was discussed (and criticized) on LC, e.g. here, here.

 

A multi-ingredient dietary supplement abolishes large-scale brain cell loss, improves sensory function, and prevents neuronal atrophy in aging mice

http://onlinelibrary....22019/abstract

 

"Transgenic growth hormone mice (TGM) are a recognized model of accelerated aging with characteristics including chronic oxidative stress, reduced longevity, mitochondrial dysfunction, insulin resistance, muscle wasting, and elevated inflammatory processes. Growth hormone/IGF-1 activate the Target of Rapamycin known to promote aging. TGM particularly express severe cognitive decline. We previously reported that a multi-ingredient dietary supplement (MDS) designed to offset five mechanisms associated with aging extended longevity, ameliorated cognitive deterioration and significantly reduced age-related physical deterioration in both normal mice and TGM. Here we report that TGM lose more than 50% of cells in midbrain regions, including the cerebellum and olfactory bulb. This is comparable to severe Alzheimer's disease and likely explains their striking age-related cognitive impairment. We also demonstrate that the MDS completely abrogates this severe brain cell loss, reverses cognitive decline and augments sensory and motor function in aged mice. Additionally, histological examination of retinal structure revealed markers consistent with higher numbers of photoreceptor cells in aging and supplemented mice. We know of no other treatment with such efficacy, highlighting the potential for prevention or amelioration of human neuropathologies that are similarly associated with oxidative stress, inflammation and cellular dysfunction."

 

It is not open access but I included it in the list of readings, assuming it is worth, next time in the library.

[Der Springende Punkt]

I am also unable to find the oral version.

Might someone help out here? 

 

They used "40 mg of human recombinant DNase I (1500 KU/mg) given orally three times a day". Amazon.com has "Deoxyribonuclease I Human Recombinant, DNase": http://www.amazon.co...U/dp/B00KCV8DI8

[ceridwen]

Not available in the UK of course

[deetown]

That's a huge dose.  

[mag1]

Cystic fibrosis patients are treated with 2.5 mg inhaled doses (not sure of the KU/mg).

 

http://www.gene.com/...prescribing.pdf

 

Where did the researchers get the motivation to try this treatment at these much higher doses in an AD patient?

Is there any preclinical research for this?

[Mian Ali Ismail]

I couldnt find any data on preclinical research

[mag1]

Neither could I.

 

Did they really just roll the dice?

 

There is some research about cell free DNA.

http://www.clinchem..../51/8/1544.long

 

"a patient with severe end-stage AD who experienced significant symptomatic

improvement upon treatment with deoxyribonuclease I (DNase I), an enzyme

responsible for the cleavage of both human and microbial DNA, including cell-free DNA (cf-DNA)."

 

Would be interesting if they could find a DNase that only cleaved human DNA.

Perhaps DNase1 and the result with this AD patient is demonstrating the infection theory of AD?

Edited by mag1, 03 June 2016 - 02:53 AM.

[gamesguru]

ginger and chocolate lower BP.

 

Rutin reduces platelet aggregation and also appears to enhance capillary elasticity, through a secondary mechanism. it may also reduce blood pressure and LDL, although the effect is not as reliable or significant as its sister molecule, quercetin.

 

thining blood while decreasing capillary permeability does NOT carry the same increased risk of spontaneous bleeding (arterial or venous failure), which occurs in many old-age diseases and can be fatal. but it is much healthier inside the vein or artery to have thinner blood. the risk carried with the opposite, namely increased permeability and decreased elasticity, when combined with blood thinners... is grave.

An interesting development occurred in the treatment of hypertension. One of the best remedies for high blood pressure has an unfortunate tendency to weaken the capillaries of some patients. This fact forces the physician to use this powerful remedy with great caution in such cases. However, if the patient is given rutin, the tendency to weakening of the capillaries is counteracted, and the physician may proceed with his treatment. Similar effects have been noted in connection with the therapeutic use of salicylates and arsenicals, which also tend to weaken the capillary walls. Although rutin itself is not advocated as a cure for hypertension, a drop in the blood pressure has been noted in 36 percent of the cases under observation. In 6 percent, the decrease was marked; in the remainder, it was moderate. There is a possibility that rutin may be of value in the treatment of diabetic retinitis, a condition that frequently occurs in diabetes and involves bleeding in the retina.

 

 

though in terms of antidementia effect, research has yet to delineate the degrees of involvement of its antioxidative property versus its blood-thinning and artery-strengthen properties.

Quercetin reduces blood pressure in hypertensive subjects.
Edwards RL1, Lyon T, Litwin SE, Rabovsky A, Symons JD, Jalili T. (2007)
Epidemiological studies report that quercetin, an antioxidant flavonol found in apples, berries, and onions, is associated with reduced risk of coronary heart disease and stroke. Quercetin supplementation also reduces blood pressure in hypertensive rodents. The efficacy of quercetin supplementation to lower blood pressure in hypertensive humans has never been evaluated. We tested the hypothesis that quercetin supplementation reduces blood pressure in hypertensive patients. We then determined whether the antihypertensive effect of quercetin is associated with reductions in systemic oxidant stress.

 

those following a plant-based diet will already be enjoying the benefits of moderate rutin intake.

Rutin improves spatial memory in Alzheimer's disease transgenic mice by reducing Aβ oligomer level and attenuating oxidative stress and neuroinflammation.
Xu PX1, Wang SW2, Yu XL2, Su YJ1, Wang T2, Zhou WW2, Zhang H2, Wang YJ3, Liu RT4. (2014)
Alzheimer's disease (AD) is a progressive, neurodegenerative disease characterized by extracellular β-amyloid (Aβ) plaques and intracellular neurofibrillary tangles in the brain. Aβ aggregation is closely associated with neurotoxicity, oxidative stress, and neuronal inflammation. The soluble Aβ oligomers are believed to be the most neurotoxic form among all forms of Aβ aggregates. We have previously reported a polyphenol compound rutin that could inhibit Aβ aggregation and cytotoxicity, attenuate oxidative stress, and decrease the production of nitric oxide and proinflammatory cytokines in vitro. In the current study, we investigated the effect of rutin on APPswe/PS1dE9 transgenic mice. Results demonstrated that orally administered rutin significantly attenuated memory deficits in AD transgenic mice, decreased oligomeric Aβ level, increased super oxide dismutase (SOD) activity and glutathione (GSH)/glutathione disulfide (GSSG) ratio, reduced GSSG and malondialdehyde (MDA) levels, downregulated microgliosis and astrocytosis, and decreased interleukin (IL)-1β and IL-6 levels in the brain. These results indicated that rutin is a promising agent for AD treatment because of its antioxidant, anti-inflammatory, and reducing Aβ oligomer activities.

Rutin prevents cognitive impairments by ameliorating oxidative stress and neuroinflammation in rat model of sporadic dementia of Alzheimer type.
Javed H1, Khan MM, Ahmad A, Vaibhav K, Ahmad ME, Khan A, Ashafaq M, Islam F, Siddiqui MS, Safhi MM, Islam F. (2012)
The objective of the present study was to assess the neuroprotective role of rutin (vitamin P) and delineate the mechanism of action. Recent evidence indicates that rutin exhibits antioxidant potential and protects the brain against various oxidative stressors. More precisely, the aim of the present study was to examine the modulating impacts of rutin against cognitive deficits and oxidative damage in intracerebroventricular-streptozotocin (ICV-STZ)-infused rats. Rats were injected bilaterally with ICV-STZ (3 mg/kg), whereas sham rats received the same volume of vehicle. After 2 weeks of streptozotocin (STZ) infusion, rats were tested for cognitive performance using Morris water maze tasks and thereafter euthanized for further biochemical, histopathological, and immunohistochemical studies. Rutin pretreatment (25 mg/kg, orally, once daily for 3 weeks) significantly attenuated thiobarbituric acid reactive substances (TBARS), activity of poly ADP-ribosyl polymerase, and nitrite level and decreased level of reduced glutathione (GSH) and activities of its dependent enzymes (glutathione peroxidase [GPx] and glutathione reductase [GR]) and catalase in the hippocampus of ICV-STZ rats. ICV-STZ rats showed significant cognitive deficits, which was improved significantly by rutin supplementation. The results indicate that rutin attenuates STZ-induced inflammation by reducing the expression of cyclooxygenase-2 (COX-2), glial fibrillary acidic protein (GFAP), interleukin-8 (IL-8), inducible nitric oxide synthase (iNOS), nuclear factor-kB, and preventing the morphological changes in hippocampus. The study thereby suggests the effectiveness of rutin in preventing cognitive deficits and might be beneficial for the treatment of sporadic dementia of Alzheimer type (SDAT).

Edited by gamesguru, 03 June 2016 - 01:42 PM.

[Der Springende Punkt]

Not available in the UK of course

 

Yes, but as a research chemical for several hundreds of dollars each day it is unaffordable either way. If we would know more about the MoA and why a protein is working orally (how is it possible?) - there is always the possibility of a group buy - maybe via Logic's Nilo lab?

[Der Springende Punkt]

Perhaps DNase1 and the result with this AD patient is demonstrating the infection theory of AD?

 

Good point. The authors seem to work solely in the microbial field: http://www.ncbi.nlm....or_uid=27234814
 

[deetown]

Just in case you haven't seen this:

Thedistribution of deoxyribonuclease I (DNase I) in human and rat stomachs was examined by biochemical, molecular biological and immunohistochemical techniques. By the use of monoclonal anti-human DNase I and polyclonal anti-rat DNase I antibodies, we determined that strong immunoreactivity was present in the cytoplasm of chief cells of the human fundus and the rat pars glandularis, respectively. High DNase I enzyme activity was detected in tissue homogenates of both human fundus and rat pars glandularis. The presence of DNase I-specific mRNA was verified by reverse transcriptase-polymerase chain reaction analysis of the total RNAs extracted from human and rat stomachs. Immunoelectron microscopy revealed gold particles localized in the chief cells, with most labelling in exocrine secretory granules. These results show that the chief cells of human and rat stomach produce DNase I. This is the first report to demonstrate that secretion of DNase I is controlled by the chief cells in human and rat stomachs.

→ source (external link)

 

[deetown]

Interesting also.  I'd be interested in getting some Dnase.

[post='https://www.research...uman_Blood']Theconcentration of circulating DNA (cirDNA) and deoxyribonuclease activity in blood plasma of healthy donors and patients with colon or stomach cancer were analyzed. The concentration of DNA was measured using Hoechst 33258 fluorescent assay after the isolation by the glass-milk protocol. A 1-kbp PCR product labeled with biotinylated forward and fluorescein-labeled reverse primers was used as a substrate for DNase. DNase activity was estimated from the data of immunochemical detection of the nonhydrolyzed amplicon. The average concentration of cirDNA in the plasma of healthy donors was low (34 +/- 34 ng/mL), and was accompanied with high DNase activity (0.356 +/- 0.410 U/mL). The increased concentrations of cirDNA in blood plasma of patients with colon and stomach cancer were accompanied by a decrease in DNase activity below the detection level of the assay. The data obtained demonstrate that low DNase activity in blood plasma of cancer patients can cause an increase in the concentration of cirDNA.[/post]

[ceridwen]

I'm pretty sure it's an infection

[Mian Ali Ismail]

http://www.nature.co...ature01979.html

Much evidence supports the hypothesis that the infectious agents of prion diseases are devoid of nucleic acid, and instead are composed of a specific infectious protein¹. This protein, PrP^Sc, seems to be generated by template-induced conformational change of a normally expressed glycoprotein, PrP^C (ref. 2). Although numerous studies have established the conversion of PrP^C to PrP^Sc as the central pathogenic event of prion disease, it is unknown whether cellular factors other than PrP^C might be required to stimulate efficient PrP^Sc production. We investigated the biochemical amplification of protease-resistant PrP^Sc-like protein (PrPres) using a modified version³ of the protein-misfolding cyclic amplification method⁴. Here we report that stoichiometric transformation of PrP^C to PrPres in vitro requires specific RNA molecules. Notably, whereas mammalian RNA preparations stimulate in vitro amplification of PrPres, RNA preparations from invertebrate species do not. Our findings suggest that host-encoded stimulatory RNA molecules may have a role in the pathogenesis of prion disease. They also provide a practical approach to improve the sensitivity of diagnostic techniques based on PrPres amplification.

[Mian Ali Ismail]

What do you guies think about Ibudilast.Im confused about this tile .It says Ibudilast patients showed gains in study but I think that it slowed the rate of decline.Is the article title misleading ?

 

https://alsnewstoday...-in-orlando-fl/

[Der Springende Punkt]

There are now press releases about the deoxyribonuclease I case report:

 

http://www.prnewswir...-300280725.html

[Healthy Almonds]

To continue with the infection theory of Alzheimer's disease, I'd like to put forth a potential role Staphylococcus aureus has in the development of AD.

 

S. aureus can colonize the nostrils or ears and nasal carriage is associated with causing Staph infections. In the 2010 publication "The Alzheimer's Disease-Associated Amyloid β-Protein Is an Antimicrobial Peptide" the authors found that Aβ has antimicrobial properties against multiple infectious agents, including Staphylococcus aureus.

 

This AARP bulletin from 2011 "Minor Ailments Linked to Alzheimer's" discusses a study that finds having multiple, non-traditional ailments increases the risk of dementia. 

The 10-year study, launched in 1992, included more than 7,200 cognitively healthy 65-year-old Canadians who were asked questions regarding their overall health. While the questions included known risk factors for Alzheimer's, such as high blood pressure and diabetes, the thrust of the research was on 19 problems that seemingly have no connection with brain health – including vision and hearing, loose dentures, sinus congestion, arthritis, morning cough, and problems with the skin, stomach, kidneys or bowel.

While any healthy 65-year-old has an 18 percent chance of developing dementia in 10 years simply because they are aging, the study found that each health problem not traditionally associated with Alzheimer's increased that risk by 3.2 percent. The risk accelerated as more and more conditions were added, jumping to 40 percent among those in the study who reported as many as 12 conditions. 

 

 

 

Using the risk factors and ailments mentioned in the quote, there is research that shows Staphylococcus aureus or sinus problems as being associated with some of those conditions. 

 

1. Staphylococcus aureus may cause type 2 diabetes.

 

2. S. aureus was frequently found in patients suffering from chronic sinusitis and it is a major pathogen in acute bacterial rhinosinusitis.

 

3. Septic arthritis is most commonly caused by S. aureus.

 

4. S. aureus is linked to skin problems such as folliculitis, eczema, psoriasis, and rosacea.

 

5. S. aureus or sinus problems have been linked to bowel problems such as Crohn's disease, inflammatory bowel disease, and GERD.

 

 

If the infection theory for AD development is true, it is possible that a chronic Staph infection coupled with a compromised immune state is a contributing factor to AD development. 

[Mian Ali Ismail]

What mechanism of action might DNase1 have.Would it be symptomatic or disease reversing ?

[ceridwen]

Surely if the above is true all we need to do is treat staph to get it to stop?

[Der Springende Punkt]

Surely if the above is true all we need to do is treat staph to get it to stop?

 

No one knows, yet. The authors think it could be the amyloid beta that first fight infections and then is not removed completely with the result of dementia.

[Mian Ali Ismail]

http://www.scienceal...eimer-s-disease

 

Since the above blood test measures autoantibodies does this mean alzhimers is autoimmune disease ?

[ceridwen]

I looked at the wiki for staphylococcus Atreus. The alternative treatment for this is said to be honey and propolis from a South American bee,Tetragomisca Angustula. I have no idea how to get this on line. Does anyone have any idea if it would be possible to obtain this.

[ceridwen]

There have also been theories that AD is caused by HSV1 or some sort of an pneumonia or CSV or even chlamydia.
Maybe dementia can be caused by any of these but they all have the same result.

[Healthy Almonds]

Surely if the above is true all we need to do is treat staph to get it to stop?

 

If a chronic Staph infection is causing high levels of Aβ production, killing that bacteria where it lives should reduce future production. As for the amyloid plaques already in the brain, this article discusses a study that finds Vitamin D3 and omega 3 fatty acids may help clear those plaques. Interestingly, there may be an association between Vitamin D deficiency and Staph infections. The body may also be able to naturally remove plaques from the brain. 

 

 

I looked at the wiki for staphylococcus Atreus. The alternative treatment for this is said to be honey and propolis from a South American bee,Tetragomisca Angustula. I have no idea how to get this on line. Does anyone have any idea if it would be possible to obtain this.

 

A doctor can determine if you are a carrier of Staph in your nostrils and/or ears. If positive, your doctor may prescribe topical antibiotics to localize the attack to your nostrils/ears. Bactroban ointment is commonly prescribed to kill nasal Staph and it would be safe for the ears.

 

Alternatively, triple antibiotic ointment (Neosporin for example) has been shown to kill nasal Staph and it is available over the counter here in the US. I can personally speak for the effectiveness of triple antibiotic ointment. Staph in my nostrils and ears was responsible for my cystic acne, and TAO application keeps the Staph at bay and prevents cystic acne. Also, cleaning your ears with a paper towel and rubbing alcohol may help kill the bacteria.

Edited by Healthy Almonds, 09 June 2016 - 09:18 PM.

[deetown]

As a result of Biotoxin illness I have had a chronic nasal infection.  I am only now making progress on it using antibiotics to treat MARCONS and EDTA to break the biofilms.  It is possible the Dnase effectiveness was due to it's breaking down biofilms.  

[Mian Ali Ismail]

IS Dnase antibacterial ? and can it be taken orally? The ususal route is thru nebulization !

Edited by Mian Ali Ismail, 10 June 2016 - 05:52 AM.

[Adam1]

I looked at the wiki for staphylococcus Atreus. The alternative treatment for this is said to be honey and propolis from a South American bee,Tetragomisca Angustula. I have no idea how to get this on line. Does anyone have any idea if it would be possible to obtain this.

 

Ceridwen, I would not rush to get that specific propolis. The stingless Brazilian Tetragomisca Angustula has unique habits causing it to make its propolis largely from one tree, and that tree is toxic/irritating.

 

https://hal.archives...al-00892193.pdf

 

 

The constant chemical composition of  T. angustula  propolis is explained by the collection of resins preferentially from  Schinus  terebenthifolius , a plant  source  found  throughout  Brazil.

 

Wikipedia sheds some light on the Brazilian Pepper Tree, as it is commonly known:

 

 

Contact with the “sap” from a cut or bruised tree can result in rash, lesions, oozing sores, severe itching,reddening and swelling (especially of the eyes), and welts. The burning of plant matter releases many airborne irritants, so is not an effective means of control. It is said to have a "mace-like" effect upon nearby people and is highly advised against.

 

 

I recall some stingless bees drop propolis on attackers, and if this is true for Tetragomisca Angustula, it makes sense that the bee selects the Pepper Tree sap for its propolis. Yes, it would be a good anti-Staph agent, but theoretically it could damage mitochondria etc. along the way. I wonder if this particular propolis would eventually prove to be a candidate for the caveat emptor list, next to the tropical fruit sour sop (Annona Muricata) or A. Squamosa. If you are curious about the latter potentially neurotoxic foods, this is a good reference:

 

https://www.research...926eb45c358.pdf

Edited by Adam1, 12 June 2016 - 03:48 AM.

[Mian Ali Ismail]

Alzhimers patient cured in a case report.Please refer to this thread.Deoxyribose nuclease 1 was used

 

http://www.longecity...e1/#entry778257

Alzhimers patient cured in a case report.Please refer to this thread.Deoxyribose nuclease 1 was used

[ceridwen]

Can't get it anyway and there is probably a very good reason why it is unavailable