18 replies to this topic

[tunt01]

This paper briefly mentions Cerebrolysin.  I've not fully digested it and prions is not an area I'm very fluid in, but I thought I might post it for all.

 

 

It mentions one known case of CJD in a recipient of a porcine dura graft in the UK.

 

 

  Porcine prion protein amyloid.

Hammarström P1, Nyström S.

Abstract

Mammalian prions are composed of misfolded aggregated prion protein (PrP) with amyloid-like features. Prions are zoonotic disease agents that infect a wide variety of mammalian species including humans. Mammals and by-products thereof which are frequently encountered in daily life are most important for human health. It is established that bovine prions (BSE) can infect humans while there is no such evidence for any other prionsusceptible species in the human food chain (sheep, goat, elk, deer) and largely prion resistant species (pig) or susceptible and resistant pets (cat and dogs, respectively). PrPs from these species have been characterized using biochemistry, biophysics and neurobiology. Recently we studied PrPs from several mammals in vitro and found evidence for generic amyloidogenicity as well as cross-seeding fibril formation activity of all PrPs on the human PrP sequence regardless if the original species was resistant or susceptible to prion disease. Porcine PrP amyloidogenicity was among the studied. Experimentally inoculated pigs as well as transgenic mouse lines overexpressing porcine PrP have, in the past, been used to investigate the possibility of prion transmission in pigs. The pig is a species with extraordinarily wide use within human daily life with over a billion pigs harvested for human consumption each year. Here we discuss the possibility that the largely prion disease resistant pig can be a clinically silent carrier of replicating prions.

 

Edited by prophets, 04 June 2016 - 11:43 AM.

[gamesguru]

Here we discuss the possibility that the largely prion disease resistant pig can be a clinically silent carrier of replicating prions.

I mean if that's the case, wouldnt a lot of cases be showing up already through consumption of infected meat?

[Kinesis]

Here we discuss the possibility that the largely prion disease resistant pig can be a clinically silent carrier of replicating prions.

I mean if that's the case, wouldnt a lot of cases be showing up already through consumption of infected meat?

Consider mode of ingestion. Are people injecting infected meat? I wouldn't worry about taking C orally.

[gamesguru]

agreed risk of transmission is tremendously higher with injections of brainstem products as compared with eating meat... but my understanding is if millions were eating tainted meat, thousands of cases of infection (through compromised intestinal walls or the likes) would be reported and scapegoated on cows (that shit spreads like wildfire, it goes into the oral nerves and even spreads by adherence to tartar scrapers. did i mention they are resistant to most chemicals and heat up to 2600F?). therefore, if this were the case, the public would be trying to expose a cattle scandal and undermine the beef industry. to the best of my knowledge, no such public reaction exists. i just really hope, for the benefit of us all, this study is mistaken and just using scare tactics.

[tunt01]

The paper is discussing the amyloid seeding potential of mammalian proteins, presumably like Cerebrolysin.  I don't think it's referring to prion disease in the classic sense of Bovine Spongiform Encephalopathy.  I think it's speaking to the possiblle amyloidogenic nature of Cerebrolysin that may not appear until years later after nucleation and formation of fibrils.  Where prion disease ends and beta-amyloid (protein aggregate) generated diseases like Alz/Parkinsons begin seems somewhat gray to me.

 

Maybe one counter to such an effect would be nilotinib.  Take cerebrolysin for the neurotrophic effects and then clean-up fibrils with nilotinib.  Just a thought, but I am not certain nor an expert in these matters and figured someone else might have a more expansive thought on the matter.

 

 

 

Edited by prophets, 05 June 2016 - 05:58 PM.

[gamesguru]

havent read anything about the fibrils popping up years later, interesting.

Nilotinib reverses loss of dopamine neurons and improves motor behavior via autophagic degradation of α-synuclein in Parkinson's disease models
Michaeline L. Hebron,† Irina Lonskaya,† and Charbel E.-H. Moussa (2013)

Parkinson's disease is a movement disorder characterized by death of dopaminergic substantia nigra (SN) neurons and brain accumulation of α-synuclein. The tyrosine kinase Abl is activated in neurodegeneration. Here, we show that lentiviral expression of α-synuclein in the mouse SN leads to Abl activation (phosphorylation) and lentiviral Abl expression increases α-synuclein levels, in agreement with Abl activation in PD brains. Administration of the tyrosine kinase inhibitor nilotinib decreases Abl activity and ameliorates autophagic clearance of α-synuclein in transgenic and lentiviral gene transfer models. Subcellular fractionation shows accumulation of α-synuclein and hyper-phosphorylated Tau (p-Tau) in autophagic vacuoles in α-synuclein expressing brains, but nilotinib enhances protein deposition into the lysosomes. Nilotinib is used for adult leukemia treatment and it enters the brain within US Food and Drug Administration approved doses, leading to autophagic degradation of α-synuclein, protection of SN neurons and amelioration of motor performance. These data suggest that nilotinib may be a therapeutic strategy to degrade α-synuclein in PD and other α-synucleinopathies.

=======================

Autophagy is activated by the STK11-PRKAA1 pathway.38 STK11 and PRKAA1 were activated in fAβ-treated microglia (Fig. 3A), which was also correlated with autophagosome formation. PRKAA1 activation by AICAR or metformin increased Aβ degradation, and PRKAA1 inhibition with compound C reduced Aβ degradation (Fig. 3C). This indicates that the autophagic degradation of Aβ fibrils by microglia is dependent on the PRKAA1 pathway. PRKAA1 activity has been reported to decrease with age,39 and PRKAA1 deficiency increases Aβ generation.40 Some molecules have been reported to decrease Aβ levels via the PRKAA1 pathway. Quercetin (HPD), a flavonoid found in green and black teas, decreases Aβ accumulation in murine brain tissue via the activation of PRKAA1.41 LEP (leptin), a metabolism-regulating hormone, reduces Aβ production in neuronal cultures in an PRKAA1-dependent manner.42 Our results also suggest that PRKAA1 activation in microglia could degrade Aβ fibrils via autophagic pathways. Recent studies have also reported that metformin induces not only PRKAA1-dependent autophagy but also the phagocytosis of Aβ fibrils by acidifying the lysosomal and endosomal compartments of microglia.7

Silibinin, a natural flavonoid, induces autophagy via ROS-dependent mitochondrial dysfunction and loss of ATP involving BNIP3 in human MCF7 breast cancer cells
KAI JIANG,1 WEI WANG,1 XIN JIN,1 ZHAOYANG WANG,2 ZHIWEI JI,3 and GUANMIN MENG1 (2015)
Silibinin, derived from the milk thistle plant (Silybum marianum), has anticancer and chemopreventive properties. Silibinin has been reported to inhibit the growth of various types of cancer cells. However, the mechanisms by which silibinin exerts an anticancer effect are poorly defined. The present study aimed to investigate whether silibinin-induced cell death might be attributed to autophagy and the underlying mechanisms in human MCF7 breast cancer cells. Our results showed that silibinin-induced cell death was greatly abrogated by two specific autophagy inhibitors, 3-methyladenine (3-MA) and bafilomycin-A1 (Baf-A1). In addition, silibinin triggered the conversion of light chain 3 (LC3)-I to LC3-II, promoted the upregulation of Atg12-Atg5 formation, increased Beclin-1 expression, and decreased the Bcl-2 level. Moreover, we noted elevated reactive oxygen species (ROS) generation, concomitant with the dissipation of mitochondrial transmembrane potential (ΔΨm) and a drastic decline in ATP levels following silibinin treatment, which were effectively prevented by the antioxidants, N-acetylcysteine and ascorbic acid. Silibinin stimulated the expression of Bcl-2 adenovirus E1B 19-kDa-interacting protein 3 (BNIP3), a pro-death Bcl-2 family member, and silencing of BNIP3 greatly inhibited silibinin-induced cell death, decreased ROS production, and sustained ΔΨm and ATP levels. Taken together, these findings revealed that silibinin induced autophagic cell death through ROS-dependent mitochondrial dysfunction and ATP depletion involving BNIP3 in MCF7 cells.

The Flavonoid Baicalein Inhibits Fibrillation of -Synuclein and Disaggregates Existing Fibrils
Article in Journal of Biological Chemistry 279(26):26846-57 · June 2004 with 35 Reads

The aggregation of alpha-synuclein has been implicated as a critical step in the development of Parkinson's disease. Parkinson's disease is a progressive neurodegenerative disorder caused by the loss of dopaminergic neurons from the substantia nigra; currently, no cure exists. Baicalein is a flavonoid with antioxidant properties; upon oxidation, it forms several products including quinones. We show here that low micromolar concentrations of baicalein, and especially its oxidized forms, inhibit the formation of alpha-synuclein fibrils. In addition, existing fibrils of alpha-synuclein are disaggregated by baicalein. The product of the inhibition reaction is predominantly a soluble oligomer of alpha-synuclein, in which the protein molecules have been covalently modified by baicalein quinone to form a Schiff base with a lysine side chain in alpha-synuclein. The binding of baicalein was abolished by conversion of the Tyr residues into Phe, demonstrating that Tyr is involved in the interaction of alpha-synuclein with baicalein. In disaggregation baicalein causes fragmentation throughout the length of the fibril. These observations suggest that baicalein and similar compounds may have potential as therapeutic leads in combating Parkinson's disease and that diets rich in flavonoids may be effective in preventing the disorder.

282200 Sigma
Galangin
autophagy inducing flavonoid
Synonym: 3,5,7-Trihydroxyflavone

[fairy]

Prions are scary: https://en.wikipedia...tional_concerns. That's why I don't plan on using Cerebrolysin.

 

[Kinesis]

agreed risk of transmission is tremendously higher with injections of brainstem products as compared with eating meat... but my understanding is if millions were eating tainted meat, thousands of cases of infection (through compromised intestinal walls or the likes) would be reported and scapegoated on cows (that shit spreads like wildfire, it goes into the oral nerves and even spreads by adherence to tartar scrapers. did i mention they are resistant to most chemicals and heat up to 2600F?). therefore, if this were the case, the public would be trying to expose a cattle scandal and undermine the beef industry. to the best of my knowledge, no such public reaction exists. i just really hope, for the benefit of us all, this study is mistaken and just using scare tactics.

Fair enough, gg. In the scheme of things, prions probably aren't the biggest risk associated with products like this. If anything though, this highlights the broader importance of using only scrupulously purified sources...

[tunt01]

This article at Scientific American briefly explains the issue of Beta Amyloid Seeding.

[NG_F]

Look this has been  posted numerous times and fine tooth combed to death; I'll make this short and sweet.......NO ! Even if deadly prions were generated, they would be too large to cross the BBB and 

 

B) I have regular ( like 4 a year regular ) MRI scans because of a small hemorrhage/cavernous malformation.  I am a long time user of cere with dosages between 5-20mls/day for as long as 160 days  during a few cycles. I have absolutely ZERO signs of Jakob creutzfeldt syndrome or ANY other abnormalities nor have I seen any negative functional changes. The small changes that have occurred from my Noot usage have all been positive.

 

End of story.......Next !! 

[gamesguru]

I am a long time user of cere with dosages between 5-20mls/day for as long as 160 days

 

watch out 4 dat beta amyloid seeding doe.

[fairy]

A ---

Explain this:

Between 1958 and 1985, a number of individuals with short stature received shots of human growth hormone extracted from the pituitary glands of cadavers. The gland is a pea-sized structure that sits at the base of the brain. Some of these samples were contaminated with prions that caused certain patients to develop Creutzfeldt-Jakob disease (CJD), a rare and fatal brain disorder. Treatments ceased once these reports came to light, but by that time an estimated 30,000 people had already received the injections. As of 2012, researchers have identified 450 cases of CJD worldwide that are the result of these growth hormone injections and other medical procedures, including neurosurgery and transplants.

Source: prophet's article.
 

B ---

 
Not all the HGH treated patients contracted the disease. But then, I can't find evidence of concrete risk associated with Cerebrolysin (which is pig derived) usage. CJD from MCD is still a thing though.

Mar 24, France confirms case of mad cow disease

2016OIE data showed just six cases of BSE worldwide in 2015, of which four were in the EU. That was down from 1,957 in 2000, 561 in 2005 and 125 in 2008.

Source: http://www.reuters.c...w-idUSKCN0WQ15S

Here http://goo.gl/ZeqK4T is reported one case of vCJD in the UK in 2016.

Bovine (Porcine) Spongiform Encephalopathy (BSE)

No naturally occurring cases of this have been identified in the pig. It has been produced experimentally by direct inoculation of infected bovine brain tissue into the brain. Feeding infected brain tissue however has not resulted in disease. The feeding of meat and bone meal to pigs is now banned in the UK but during its use no cases have been identified.

Source: http://www.thepigsit...phalopathy-bse/

Studies of the transmissibility of the agent of bovine spongiform encephalopathy to pigs

Studies to test the transmissibility of the bovine spongiform encephalopathy (BSE) agent to pigs began in 1989. Parenteral inoculation of the agent by three routes simultaneously (intracranially, intravenously and intraperitoneally) produced disease with an incubation period range of 69-150 weeks. Pre-clinical pathological changes were detected in two pigs killed electively at 105 and 106 weeks post-inoculation. Infectivity was detected by bioassay in inbred mice in the CNS of those pigs that developed spongiform encephalopathy. Infectivity was also found in the stomach, jejunum, distal ileum and pancreas of terminally affected pigs. These findings show that pigs are susceptible to BSE. In contrast, disease failed to occur in pigs retained for 7 years after exposure by feeding BSE-affected brain on three separate days, at 1-2 week intervals. The amounts fed each day were equivalent to the maximum daily intake of meat and bone meal in rations for pigs aged 8 weeks. No infectivity was found in tissues assayed from the pigs exposed orally. This included tissues of the alimentary tract. It is suggested that these pigs did not become infected. The relatively high oral exposure used in these experiments compared with feed-borne exposure in the field may explain the absence of an epidemic of spongiform encephalopathy in domestic pigs concurrent with the BSE epidemic in the UK.

Source: http://www.ncbi.nlm....pubmed/12655106

Further studies on the transmissibility of BSE to pigs

The results of this study indicate that the rostral colliculus vacuolation highlighted by previous studies is a normal, background pathological finding in the pig and is not caused by an endemic TSE-like agent.

Source: https://www.food.gov...research/m03010

Porcine prion protein amyloid

Source: http://www.ncbi.nlm....310/#s0006title

Thinking the unthinkable: Alzheimer's, Creutzfeldt-Jakob and Mad Cow disease: the age-related reemergence of virulent, foodborne, bovine tuberculosis or losing your mind for the sake of a shake or burger

In the opinion of experts, ample justification exists for considering a similar pathogenesis for Alzheimer's, Creutzfeldt-Jakob and the other spongiform encephalopathies such as Mad Cow disease. In fact, Creutzfeldt-Jakob and Alzheimer's often coexist and at this point are thought to differ merely by time-dependent physical changes. A recent study links up to 13% of all "Alzheimer's" victims as really having Creutzfeldt-Jakob disease.

Source: http://articles.merc...ease-cafos.aspx

[normalizing]

it says in reports it will take beyond normal human lifespan to generate such prions, about 100 years, is this really a concern guys considering if you live to 100 you will have way too many other problems to worry about

[tunt01]

it says in reports it will take beyond normal human lifespan to generate such prions, about 100 years, is this really a concern guys considering if you live to 100 you will have way too many other problems to worry about

 

Where does it say that?

[normalizing]

i watched that docu that was posted here and then i went and checked on wiki and found some there too

[fairy]

It says CJD, not vCJD; but you never now since the second is a subset of the first (https://en.wikipedia...#Classification). There is also this article
 
According to U.S. Government health officials, CJD is virtually nonexistent in North America though wild animals are increasingly developing TSEs. According to University of Pittsburgh researchers, however, 5.5 percent of Alzheimer's patients may have been misdiagnosed. A similar CJD study at Yale found more than twice that amount. Even at that small percentage rate, the authors concluded, with more than 2,000,000 Alzheimer's cases in the United States today, there is likely a "hidden CJD epidemic" of approximately 200,000 cases.
 
Source: http://articles.merc...ow-disease.aspx

 

but unfortunately there is no reference. There are a lot of results from PubMed though:

site:www.ncbi.nlm.nih.gov/pubmed Alzheimer's+Creutzfeldt-Jakob+variant OR Alzheimer's+Creutzfeldt-Jakob

[gamesguru]

there is likely a "hidden CJD epidemic" of approximately 200,000 cases.

 

i just have trouble believing Mercola's statistics. he really thinks 200,000 out of 300,000,000 million Americans has the thing?

CJD is very rare. It occurs in about 1 of every 1 million people.

There are several types of CJD. The classic types are:

• Sporadic CJD makes up most cases. It occurs for no known reason. The average age at which it starts is 65.
• Familial CJD occurs when a person inherits the abnormal prion from a parent (this form of CJD is rare).
• Acquired CJD includes variant CJD (vCJD), the form related to mad cow disease. Iatrogenic CJD is also an acquired form of the disease. Iatrogenic CJD is sometimes passed through a blood product transfusion, transplant, or contaminated surgical instruments.

---> https://www.nlm.nih....icle/000788.htm

 

About 15% of patients survive for two or more years.^[11] Some patients have been known to live four to five years with mostly psychological symptoms until the disease progresses causing more physical symptoms leading to a diagnosis and inevitable death usually within the first year of diagnosis.

---> Wikipedia

From 1958 until 1985, when the dangers were first realized, around 30,000 people worldwide had hGH injected into their muscles — mostly children who had not been growing at a normal rate. The preparations comprised pooled material extracted from thousands of cadavers. Some extracts turned out to have been contaminated with CJD prions, leading to 226 deadly infections by 2012, mostly in France (119 cases), Britain (65 cases) and the United States (29 cases). Numbers are still creeping up, because CJD has a long incubation period.

---> http://www.nature.co...atients-1.18331

[tunt01]

 

i just have trouble believing Mercola's statistics. he really thinks 200,000 out of 300,000,000 million Americans has the thing?

 

 

Who cares what Mercola thinks.  He's not a recognized expert on this matter.  He's a doctor pushing pills and youtube videos.

 

What's your expert opinion on the ultimate fate of 638 unidentified proteins, of porcine nature and where they ultimately end up?  You don't think any of them result in an immunogenic, amyloid-beta like response?  Are these protein fragments and smaller kda proteins ultimately the building blocks of larger fibrils?

Edited by prophets, 06 June 2016 - 05:11 PM.

[gamesguru]

it would have to come from a contaminated animal, either beta-amyloid or PrP^Sc. it's possible, the risk of transmission is just low, even injecting infected peptides.

peripheral beta-amyloid is called "inclusion body myositis", and usually does not progress to the CNS.

TSE  has  not  been  reported  in  natural  conditions  in pigs,  and  there  is  no  evidence  of  BSE  transmission between  pigs  fed  with  brain  material  from  cattle. However,  despite  the  existence  of  a  strong  transmission barrier,  signs  of  TSE  have  been  reported  in  pigs  challenged   simultaneously   with   BSE-derived   material   via  intraperitoneal,  intravenous  and  intracerebral  administration. Those studies demonstrated pathological changes  and  PrPSc deposition  in  the  CNS,  but  reported  no  evidence  of  PrPSc distribution  in  other  organs.