Wednesday, July 27, 2016

An end to Alzheimer’s disease, TSE Prion Research, and the Honorable Hillary Clinton

An end to Alzheimer’s disease

 

We can prevent, effectively treat, and make an Alzheimer’s cure possible by 2025.

 

An end to Alzheimer’s disease

 

“If we’re the kind of nation that cares for its citizens and supports families, respects our elders, and takes care of our neighbors, then we’ve got work to do. And we need to do better when it comes to diseases like Alzheimer’s.”

 

Hillary, December 22, 2015

 

Alzheimer’s disease is the sixth leading cause of death in the United States. It’s the only cause of death in the top 10 that we can’t prevent, cure, or even delay.

 

As the population of our country ages, the number of people suffering from Alzheimer’s is expected to grow to nearly 15 million Americans—and could cost more than $1 trillion per year—by 2050.

 

As president, Hillary will: Commit to preventing, effectively treating, and making a cure possible for Alzheimer’s disease by 2025. Invest $2 billion per year in research for Alzheimer’s and related disorders, the level leading researchers have determined necessary to prevent and effectively treat Alzheimer’s and make a cure possible by 2025. Make sure that funding is reliable and consistent so researchers can work steadily toward effective treatment. Put the best and brightest on the case. Hillary will appoint a top-flight team of research and health experts to oversee this ambitious initiative.

 

Alzheimer’s disease affects a growing number of Americans and their families. To support those families, Hillary will: Make it easier for families and individuals with Alzheimer’s to get the care they need. Medicare should cover comprehensive Alzheimer’s care-planning sessions and the cost of properly documenting every diagnosis and care plan. Help protect loved ones who wander. Hillary will work with Congress to reauthorize the Missing Alzheimer’s Disease Patient Alert Program to help find individuals who are reported missing. Ensure our seniors are aware and can take advantage of their Medicare benefits. Hillary will direct the Social Security Administration to raise awareness about the wellness visits, cognitive screenings, and other preventive benefits covered by Medicare.

 

Hillary’s plan builds on her long record of working across the aisle on behalf of patients and families dealing with Alzheimer’s disease: In the U.S. Senate, she consistently pushed for greater funding for Alzheimer’s research, including federally funded stem cell research. She also co-chaired the Congressional Task Force on Alzheimer’s Disease and introduced legislation to restore funding for the Alzheimer’s Association 24/7 Contact Center and for Alzheimer’s disease demonstration grants.

 


 

Greetings Madam Secretary Clinton et al,

 

I WOULD KINDLY LIKE TO ANALYZE THIS STATEMENT MA’AM ;

 

>>> We can prevent, effectively treat, and make an Alzheimer’s cure possible by 2025.

 

PREVENT

 

this must be on the forefront of research i.e. ‘iatrogenic’ transmission.

 

Alzheimer’s disease, iatrogenic, and Transmissible Spongiform Encephalopathy TSE Prion disease, that is the question ???

 

>>> The only tenable public line will be that "more research is required’’ <<<

 

>>> possibility on a transmissible prion remains open<<<

 

O.K., so it’s about 23 years later, so somebody please tell me, when is "more research is required’’ enough time for evaluation ?

 


 


 

SWISS MEDICAL WEEKLY

 

Alzheimer-type brain pathology may be transmitted by grafts of dura mater 26/01/2016 Singeltary comment ;

 


 

re-Evidence for human transmission of amyloid-β pathology and cerebral amyloid angiopathy

 

Nature 525, 247?250 (10 September 2015) doi:10.1038/nature15369 Received 26 April 2015 Accepted 14 August 2015 Published online 09 September 2015 Updated online 11 September 2015 Erratum (October, 2015)

 

snip...see full Singeltary Nature comment here;

 


 

Self-Propagative Replication of Ab Oligomers Suggests Potential Transmissibility in Alzheimer Disease

 

*** Singeltary comment PLoS ***

 

Alzheimer’s disease and Transmissible Spongiform Encephalopathy prion disease, Iatrogenic, what if ?

 

Posted by flounder on 05 Nov 2014 at 21:27 GMT

 


 

Sunday, November 22, 2015

 

*** Effect of heating on the stability of amyloid A (AA) fibrils and the intra- and cross-species transmission of AA amyloidosis Abstract

 

Amyloid A (AA) amyloidosis is a protein misfolding disease characterized by extracellular deposition of AA fibrils. AA fibrils are found in several tissues from food animals with AA amyloidosis. For hygienic purposes, heating is widely used to inactivate microbes in food, but it is uncertain whether heating is sufficient to inactivate AA fibrils and prevent intra- or cross-species transmission. We examined the effect of heating (at 60 °C or 100 °C) and autoclaving (at 121 °C or 135 °C) on murine and bovine AA fibrils using Western blot analysis, transmission electron microscopy (TEM), and mouse model transmission experiments. TEM revealed that a mixture of AA fibrils and amorphous aggregates appeared after heating at 100 °C, whereas autoclaving at 135 °C produced large amorphous aggregates. AA fibrils retained antigen specificity in Western blot analysis when heated at 100 °C or autoclaved at 121 °C, but not when autoclaved at 135 °C. Transmissible pathogenicity of murine and bovine AA fibrils subjected to heating (at 60 °C or 100 °C) was significantly stimulated and resulted in amyloid deposition in mice. Autoclaving of murine AA fibrils at 121 °C or 135 °C significantly decreased amyloid deposition. Moreover, amyloid deposition in mice injected with murine AA fibrils was more severe than that in mice injected with bovine AA fibrils. Bovine AA fibrils autoclaved at 121 °C or 135 °C did not induce amyloid deposition in mice. These results suggest that AA fibrils are relatively heat stable and that similar to prions, autoclaving at 135 °C is required to destroy the pathogenicity of AA fibrils. These findings may contribute to the prevention of AA fibril transmission through food materials to different animals and especially to humans.

 

Purchase options Price * Issue Purchase USD 511.00 Article Purchase USD 54.00

 


 


 

*** Transmission of Creutzfeldt-Jakob disease to a chimpanzee by electrodes contaminated during neurosurgery ***

 

Gibbs CJ Jr, Asher DM, Kobrine A, Amyx HL, Sulima MP, Gajdusek DC. Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.

 

Stereotactic multicontact electrodes used to probe the cerebral cortex of a middle aged woman with progressive dementia were previously implicated in the accidental transmission of Creutzfeldt-Jakob disease (CJD) to two younger patients. The diagnoses of CJD have been confirmed for all three cases. More than two years after their last use in humans, after three cleanings and repeated sterilisation in ethanol and formaldehyde vapour, the electrodes were implanted in the cortex of a chimpanzee. Eighteen months later the animal became ill with CJD. This finding serves to re-emphasise the potential danger posed by reuse of instruments contaminated with the agents of spongiform encephalopathies, even after scrupulous attempts to clean them.

 


 

Diagnosis and Reporting of Creutzfeldt-Jakob Disease

 

Singeltary, Sr et al. JAMA.2001; 285: 733-734. Vol. 285 No. 6, February 14, 2001 JAMA

 

Diagnosis and Reporting of Creutzfeldt-Jakob Disease

 

To the Editor: In their Research Letter, Dr Gibbons and colleagues1 reported that the annual US death rate due to Creutzfeldt-Jakob disease (CJD) has been stable since 1985. These estimates, however, are based only on reported cases, and do not include misdiagnosed or preclinical cases. It seems to me that misdiagnosis alone would drastically change these figures. An unknown number of persons with a diagnosis of Alzheimer disease in fact may have CJD, although only a small number of these patients receive the postmortem examination necessary to make this diagnosis. Furthermore, only a few states have made CJD reportable. Human and animal transmissible spongiform encephalopathies should be reportable nationwide and internationally.

 

Terry S. Singeltary, Sr Bacliff, Tex

 

1. Gibbons RV, Holman RC, Belay ED, Schonberger LB. Creutzfeldt-Jakob disease in the United States: 1979-1998. JAMA. 2000;284:2322-2323.

 


 

Transmissible Spongiform Encephalopathy TSE PRION UPDATE

 

Saturday, July 23, 2016

 

BOVINE SPONGIFORM ENCEPHALOPATHY BSE TSE PRION SURVEILLANCE, TESTING, AND SRM REMOVAL UNITED STATE OF AMERICA UPDATE JULY 2016

 


 

Tuesday, July 26, 2016

 

Atypical Bovine Spongiform Encephalopathy BSE TSE Prion UPDATE JULY 2016

 


 

Sunday, July 17, 2016

 

CHRONIC WASTING DISEASE CWD TSE PRION GLOBAL REPORT UPDATE JULY 17 2016

 


 

Monday, May 02, 2016

 

*** Zoonotic Potential of CWD Prions: An Update Prion 2016 Tokyo ***

 


 

*** NIH awards $11 million to UTHealth researchers to study deadly CWD prion diseases Claudio Soto, Ph.D. ***

 

Public Release: 29-Jun-2016

 


 

Tuesday, July 12, 2016

 

Chronic Wasting Disease CWD, Scrapie, Bovine Spongiform Encephalopathy BSE, TSE, Prion Zoonosis Science History

 

see history of NIH may destroy human brain collection

 


 

I urge everyone to watch this video closely...terry

 

*** you can see video here and interview with Jeff's Mom, and scientist telling you to test everything and potential risk factors for humans ***

 


 

Sunday, July 24, 2016

 

Chronic Wasting Disease Prions in Elk Antler Velvet and Marketing of this Product in Nutritional Supplements for Humans?

 

Research Project: TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES: THE ROLE OF GENETICS, STRAIN VARIATION, AND ENVIRONMENTAL CONTAMINATION IN DISEASE CONTROL

 


 

Saturday, April 23, 2016

 

SCRAPIE WS-01: Prion diseases in animals and zoonotic potential 2016

 

Prion. 10:S15-S21. 2016 ISSN: 1933-6896 printl 1933-690X

 


 

Saturday, July 16, 2016

 

Importation of Sheep, Goats, and Certain Other Ruminants [Docket No. APHIS-2009-0095]RIN 0579-AD10

 

WITH great disgust and concern, I report to you that the OIE, USDA, APHIS, are working to further legalize the trading of Transmissible Spongiform Encephalopathy TSE Pion disease around the globe.

 

THIS is absolutely insane. it’s USDA INC.

 


 

Saturday, May 28, 2016

 

*** Infection and detection of PrPCWD in soil from CWD infected farm in Korea Prion 2016 Tokyo ***

 


 

Thursday, June 9, 2016

 

Advisory Committee; Transmissible Spongiform Encephalopathies Advisory Committee; Termination

 


 

TREATMENT

 

However, this is where Confucius is confused Ma’am, see my letter to President Clinton and his response back in 1997 ;

 

THE WHITE HOUSE

 

WASHINGTON

 

July 3, 1997

 

Mr. Terry S. Singletary, Sr.

 

xxx

 

Bacliff, Texas 77518

 

Dear Terry:

 

Thank you for writing to me regarding the use of marijuana for medical purposes. I appreciate knowing your views. My Administration has worked very hard to ensure that Americans have access to safe and effective medicine.

 

My Administration strongly opposes the California and Arizona drug legalization measures because they contradict our federal law and our national drug control strategy. They disregard the medical and scientific process by which our nation evaluates and approves safe and effective medicines. And, most important, they send the wrong message to our children -- undermining the efforts of parents, educators, elected leaders, and countless others who are working to ensure a healthy, drug-free society.

 

However, in response to anecdotal claims about marijuana's medical benefits, the Office of National Drug Control Policy is funding a comprehensive research review by the National Academy of Science's Institute of Medicine. The purpose of this study is to ensure that good science remains the basis of our drug control policy.

 

As we work to protect the health of children and our nation, I appreciate your interest in this issue.

 

Sincerely,

 

Bill Clinton

 

end

 

1-7-97

 

Mr. President,

 

Hello, I’m writing in concern with the issues around the use of Medical Marijuana for people suffering from Aids, Cancer, Glaucoma, Chronic Pain, Muscle Spasms, and Multiple Sclerosis, and also Spinal Cord Injury.

 

I’m very concerned about the stance you and your...my administration has taken against this. Somebody needs to wake up and read the medical findings over the past years. Look at how it has helped people. ...

 

snip...(I get a bit long winded here)...snip

 

But what has disturbed me the most, is what happened in California and Arizona, how our appointed federal government bureaucrats and law enforcement agencies openly and actively engaged in a campaign to undermine, subvert and ultimately destroy the voters decision to enact laws of their choosing.

 

If this keeps happening, you will destroy the voters hope of ever changing anything. You will destroy the Democratic process.

 

Come on Bill, we all know you inhaled and I still voted for you twice. Change this Refer Madness. We don’t need the politicians writing prescriptions...

 

P.S. just think of the jail space you could use for murderers and rapist.

 

Very Sincere,

 

Terry S. Singeltary Sr.

 

END

 

ALZHEIMER’S TREATMENT SEE UPDATED SCIENCE 2016

 

Public Release: 28-Jun-2016 Cannabinoids remove plaque-forming Alzheimer's proteins from brain cells

 

Salk Institute

 

IMAGE: Preliminary lab studies by Salk Professor David Schubert suggest that the molecule THC reduces beta amyloid proteins in human neurons. view more

 

Credit: Salk Institute

 

LA JOLLA -- Salk Institute scientists have found preliminary evidence that tetrahydrocannabinol (THC) and other compounds found in marijuana can promote the cellular removal of amyloid beta, a toxic protein associated with Alzheimer's disease.

 

While these exploratory studies were conducted in neurons grown in the laboratory, they may offer insight into the role of inflammation in Alzheimer's disease and could provide clues to developing novel therapeutics for the disorder.

 

"Although other studies have offered evidence that cannabinoids might be neuroprotective against the symptoms of Alzheimer's, we believe our study is the first to demonstrate that cannabinoids affect both inflammation and amyloid beta accumulation in nerve cells," says Salk Professor David Schubert, the senior author of the paper.

 

Alzheimer's disease is a progressive brain disorder that leads to memory loss and can seriously impair a person's ability to carry out daily tasks. It affects more than five million Americans according to the National Institutes of Health, and is a leading cause of death. It is also the most common cause of dementia and its incidence is expected to triple during the next 50 years.

 

It has long been known that amyloid beta accumulates within the nerve cells of the aging brain well before the appearance of Alzheimer's disease symptoms and plaques. Amyloid beta is a major component of the plaque deposits that are a hallmark of the disease. But the precise role of amyloid beta and the plaques it forms in the disease process remains unclear.

 

In a manuscript published in June 2016's Aging and Mechanisms of Disease, Salk team studied nerve cells altered to produce high levels of amyloid beta to mimic aspects of Alzheimer's disease.

 

The researchers found that high levels of amyloid beta were associated with cellular inflammation and higher rates of neuron death. They demonstrated that exposing the cells to THC reduced amyloid beta protein levels and eliminated the inflammatory response from the nerve cells caused by the protein, thereby allowing the nerve cells to survive.

 

"Inflammation within the brain is a major component of the damage associated with Alzheimer's disease, but it has always been assumed that this response was coming from immune-like cells in the brain, not the nerve cells themselves," says Antonio Currais, a postdoctoral researcher in Schubert's laboratory and first author of the paper. "When we were able to identify the molecular basis of the inflammatory response to amyloid beta, it became clear that THC-like compounds that the nerve cells make themselves may be involved in protecting the cells from dying."

 

Brain cells have switches known as receptors that can be activated by endocannabinoids, a class of lipid molecules made by the body that are used for intercellular signaling in the brain. The psychoactive effects of marijuana are caused by THC, a molecule similar in activity to endocannabinoids that can activate the same receptors. Physical activity results in the production of endocannabinoids and some studies have shown that exercise may slow the progression of Alzheimer's disease.

 

Schubert emphasized that his team's findings were conducted in exploratory laboratory models, and that the use of THC-like compounds as a therapy would need to be tested in clinical trials.

 

In separate but related research, his lab found an Alzheimer's drug candidate called J147 that also removes amyloid beta from nerve cells and reduces the inflammatory response in both nerve cells and the brain. It was the study of J147 that led the scientists to discover that endocannabinoids are involved in the removal of amyloid beta and the reduction of inflammation.

 

###

 

Other authors on the paper include Oswald Quehenberger and Aaron Armando at the University of California, San Diego; and Pamela Maher and Daniel Daughtery at the Salk Institute.

 

The study was supported by the National Institutes of Health, The Burns Foundation and The Bundy Foundation.

 

About Salk Institute:

 

Every cure has a starting point. The Salk Institute embodies Jonas Salk's mission to dare to make dreams into reality. Its internationally renowned and award-winning scientists explore the very foundations of life, seeking new understandings in neuroscience, genetics, immunology and more. The Institute is an independent nonprofit organization and architectural landmark: small by choice, intimate by nature and fearless in the face of any challenge. Be it cancer or Alzheimer's, aging or diabetes, Salk is where cures begin. Learn more at: salk.edu.

 

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

 


 

*** National Cancer Institute at the National Institutes of Health ***

 

Cannabis and Cannabinoids (PDQ®), Cancer Antitumor Effects, Prion prevention, Pain management, muscle relaxer, and Palliative Medicine

 

Cannabis and Cannabinoids (PDQ®)

 

Laboratory/Animal/Preclinical Studies

 

Antitumor Effects Appetite Stimulation Analgesia

 

Laboratory/Animal/Preclinical Studies

 

Antitumor Effects

 

Appetite Stimulation

 

Analgesia

 

Cannabinoids are a group of 21-carbon–containing terpenophenolic compounds produced uniquely by Cannabis sativa and Cannabis indica species.[1,2] These plant-derived compounds may be referred to as phytocannabinoids. Although delta-9-tetrahydrocannabinol (THC) is the primary psychoactive ingredient, other known compounds with biologic activity are cannabinol, cannabidiol (CBD), cannabichromene, cannabigerol, tetrahydrocannabivarin, and delta-8-THC. CBD, in particular, is thought to have significant analgesic and anti-inflammatory activity without the psychoactive effect (high) of delta-9-THC.

 

Antitumor Effects One study in mice and rats suggested that cannabinoids may have a protective effect against the development of certain types of tumors.[3] During this 2-year study, groups of mice and rats were given various doses of THC by gavage. A dose-related decrease in the incidence of hepatic adenoma tumors and hepatocellular carcinoma was observed in the mice. Decreased incidences of benign tumors (polyps and adenomas) in other organs (mammary gland, uterus, pituitary, testis, and pancreas) were also noted in the rats. In another study, delta-9-THC, delta-8-THC, and cannabinol were found to inhibit the growth of Lewis lung adenocarcinoma cells in vitro and in vivo .[4] In addition, other tumors have been shown to be sensitive to cannabinoid-induced growth inhibition.[5-8]

 

Cannabinoids may cause antitumor effects by various mechanisms, including induction of cell death, inhibition of cell growth, and inhibition of tumor angiogenesis invasion and metastasis.[9-12] One review summarizes the molecular mechanisms of action of cannabinoids as antitumor agents.[13] Cannabinoids appear to kill tumor cells but do not affect their nontransformed counterparts and may even protect them from cell death. These compounds have been shown to induce apoptosis in glioma cells in culture and induce regression of glioma tumors in mice and rats. Cannabinoids protect normal glial cells of astroglial and oligodendroglial lineages from apoptosis mediated by the CB1 receptor.[14]

 

The effects of delta-9-THC and a synthetic agonist of the CB2 receptor were investigated in hepatocellular carcinoma (HCC).[15] Both agents reduced the viability of hepatocellular carcinoma cells in vitro and demonstrated antitumor effects in hepatocellular carcinoma subcutaneous xenografts in nude mice. The investigations documented that the anti-HCC effects are mediated by way of the CB2 receptor. Similar to findings in glioma cells, the cannabinoids were shown to trigger cell death through stimulation of an endoplasmic reticulum stress pathway that activates autophagy and promotes apoptosis. Other investigations have confirmed that CB1 and CB2 receptors may be potential targets in non-small cell lung carcinoma [16] and breast cancer.[17]

 

An in vitro study of the effect of CBD on programmed cell death in breast cancer cell lines found that CBD induced programmed cell death, independent of the CB1, CB2, or vanilloid receptors. CBD inhibited the survival of both estrogen receptor–positive and estrogen receptor–negative breast cancer cell lines, inducing apoptosis in a concentration-dependent manner while having little effect on nontumorigenic, mammary cells.[18]

 

CBD has also been demonstrated to exert a chemopreventive effect in a mouse model of colon cancer.[19] In the experimental system, azoxymethane increased premalignant and malignant lesions in the mouse colon. Animals treated with azoxymethane and CBD concurrently were protected from developing premalignant and malignant lesions. In in vitro experiments involving colorectal cancer cell lines, the investigators found that CBD protected DNA from oxidative damage, increased endocannabinoid levels, and reduced cell proliferation.

 

Another investigation into the antitumor effects of CBD examined the role of intercellular adhesion molecule-1 (ICAM-1).[12] ICAM-1 expression has been reported to be negatively correlated with cancer metastasis. In lung cancer cell lines, CBD upregulated ICAM-1, leading to decreased cancer cell invasiveness.

 

In an in vivo model using severe combined immunodeficient mice, subcutaneous tumors were generated by inoculating the animals with cells from human non-small cell lung carcinoma cell lines.[20] Tumor growth was inhibited by 60% in THC-treated mice compared with vehicle-treated control mice. Tumor specimens revealed that THC had antiangiogenic and antiproliferative effects. However, research with immunocompetent murine tumor models has demonstrated immunosuppression and enhanced tumor growth in mice treated with THC.[21,22]

 

In addition, both plant-derived and endogenous cannabinoids have been studied for anti-inflammatory effects. A mouse study demonstrated that endogenous cannabinoid system signaling is likely to provide intrinsic protection against colonic inflammation.[23] As a result, a hypothesis that phytocannabinoids and endocannabinoids may be useful in the risk reduction and treatment of colorectal cancer has been developed.[24-27]

 

Appetite Stimulation Many animal studies have previously demonstrated that delta-9-THC and other cannabinoids have a stimulatory effect on appetite and increase food intake. It is believed that the endogenous cannabinoid system may serve as a regulator of feeding behavior. The endogenous cannabinoid anandamide potently enhances appetite in mice.[28] Moreover, CB1 receptors in the hypothalamus may be involved in the motivational or reward aspects of eating.[29]

 

Analgesia Understanding the mechanism of cannabinoid-induced analgesia has been increased through the study of cannabinoid receptors, endocannabinoids, and synthetic agonists and antagonists. The CB1 receptor is found in both the central nervous system (CNS) and in peripheral nerve terminals. Similar to opioid receptors, increased levels of the CB1 receptor are found in regions of the brain that regulate nociceptive processing.[30] CB2 receptors, located predominantly in peripheral tissue, exist at very low levels in the CNS. With the development of receptor-specific antagonists, additional information about the roles of the receptors and endogenous cannabinoids in the modulation of pain has been obtained.[31,32]

 

Cannabinoids may also contribute to pain modulation through an anti-inflammatory mechanism; a CB2 effect with cannabinoids acting on mast cell receptors to attenuate the release of inflammatory agents, such as histamine and serotonin, and on keratinocytes to enhance the release of analgesic opioids has been described.[33-35] One study reported that the efficacy of synthetic CB1- and CB2-receptor agonists were comparable with the efficacy of morphine in a murine model of tumor pain.[36]

 

References

 

snip...

 


 

J Neurosci. 2007 Sep 5;27(36):9­537-44.

 

Nonpsychoa­ctive cannabidio­l prevents prion accumulati­on and protects neurons against ***prion*** toxicity.

 

*** Our results suggest that CBD may protect neurons against the multiple molecular and cellular factors involved in the different steps of the neurodegenerative process, which takes place during prion infection. When combined with its ability to target the brain and its lack of toxic side effects, CBD may represent a promising new anti-prion drug.

 


 

Report of a parent survey of cannabidiol-enriched cannabis use in pediatric treatment-resistant epilepsy

 

Brenda E. Porter x Brenda E. Porter Search for articles by this author , Catherine Jacobson x Catherine Jacobson Search for articles by this author Correspondence Corresponding author. email Received: May 24, 2013; Received in revised form: July 23, 2013; Accepted: August 30, 2013; DOI: http://dx.doi.org/10.1016/j.yebeh.2013.08.037 Abstract Full Text Images/Data References Related Articles To view the full text, please login as a subscribed user or purchase a subscription. Click here to view the full text on ScienceDirect.

 

Abstract

 

Severe childhood epilepsies are characterized by frequent seizures, neurodevelopmental delays, and impaired quality of life. In these treatment-resistant epilepsies, families often seek alternative treatments. This survey explored the use of cannabidiol-enriched cannabis in children with treatment-resistant epilepsy. The survey was presented to parents belonging to a Facebook group dedicated to sharing information about the use of cannabidiol-enriched cannabis to treat their child's seizures. Nineteen responses met the following inclusion criteria for the study: a diagnosis of epilepsy and current use of cannabidiol-enriched cannabis. Thirteen children had Dravet syndrome, four had Doose syndrome, and one each had Lennox–Gastaut syndrome and idiopathic epilepsy. The average number of antiepileptic drugs (AEDs) tried before using cannabidiol-enriched cannabis was 12. Sixteen (84%) of the 19 parents reported a reduction in their child's seizure frequency while taking cannabidiol-enriched cannabis. Of these, two (11%) reported complete seizure freedom, eight (42%) reported a greater than 80% reduction in seizure frequency, and six (32%) reported a 25–60% seizure reduction. Other beneficial effects included increased alertness, better mood, and improved sleep. Side effects included drowsiness and fatigue. Our survey shows that parents are using cannabidiol-enriched cannabis as a treatment for their children with treatment-resistant epilepsy. Because of the increasing number of states that allow access to medical cannabis, its use will likely be a growing concern for the epilepsy community. Safety and tolerability data for cannabidiol-enriched cannabis use among children are not available. Objective measurements of a standardized preparation of pure cannabidiol are needed to determine whether it is safe, well tolerated, and efficacious at controlling seizures in this pediatric population with difficult-to-treat seizures.

 


 

Marijuana and Epilepsy

 


 

Original Contribution| January 11, 2012 Association Between Marijuana Exposure and Pulmonary Function Over 20 Years

 

Conclusion Occasional and low cumulative marijuana use was not associated with adverse effects on pulmonary function.

 


 

Cannabidiol inhibits lung cancer cell invasion and metastasis via intercellular adhesion molecule-1

 

Cannabinoids inhibit cancer cell invasion via increasing tissue inhibitor of matrix metalloproteinases-1 (TIMP-1).

 


 


 

Cannabis in Palliative Medicine: Improving Care and Reducing Opioid-Rel­ated Morbidity

 

Published online before print March 28, 2011, J HOSP PALLIAT CARE August 2011 vol. 28 no. 5 297-303

 


 

Published online ahead of print August 30, 2010 CMAJ 10.1503/cm­aj.091414

 

Smoked cannabis for chronic neuropathi­c pain: a randomized controlled trial

 

Conclusion

 

Our results support the claim that smoked cannabis reduces pain, improves mood and helps sleep. We believe that our trial provides a methodological approach that may be considered for further research. Clinical studies using inhaled delivery systems, such as vaporizers,32,33 are needed.

 


 

Cases J. 2009; 2: 7487.

 

Published online 2009 May 18

 

Standardiz­ed natural product cannabis in pain management and observatio­ns at a Canadian compassion society: a case report

 

The roughly 4000 members of the Green Cross Society find similar benefit from standardized natural product cannabis medicine. To follow, will be publication of the Society's demographic data regarding use for various conditions such as arthritis, fybromyalgia, HIV/AIDS, and chronic pain, to name a few. A breakdown of the illnesses, what strains (cannabinoid profiles) is most effective, and at what dosages will be published at a later time.

 


 

Effect of D9-tetrahydrocannabinol, a cannabinoid receptor agonist, on the triggering of transient lower oesophageal sphincter relaxations in dogs and humans

 

These findings confirm previous findings in dogs and indicate that CB receptors are also involved in the triggering of TLESRs in humans.

 


 

Drugs: 9 July 2010 - Volume 70 - Issue 10 - pp 1245-1254

 

Pharmacological Management of Pain in Patients with Multiple Sclerosis

 

Cannabinoids have been among the few treatments studied in well designed, randomized, placebo-controlled trials for central neuropathic pain. In the largest of these trials, which included 630 subjects, a 15-week comparison between Δ9-tetrahydrocannabinol and placebo was performed. More patients receiving active treatment perceived an improvement in pain than those receiving placebo, although approximately 20% of subjects reported worsening of pain while on active treatment.

 


 

Cannabinoids control spasticity and tremor in a multiple sclerosis model

 

The exacerbation of these signs after antagonism of the CB1 and CB2 receptors, notably the CB1 receptor, using SR141716A and SR144528 (ref. 8) indicate that the endogenous cannabinoid system may be tonically active in the control of tremor and spasticity. This provides a rationale for patients' indications of the therapeutic potential of cannabis in the control of the symptoms of multiple sclerosis2, and provides a means of evaluating more selective cannabinoids in the future.

 


 


 

Thursday, June 30, 2016 Cannabinoids remove plaque-forming Alzheimer's proteins from brain cells

 


 


 

CURE?

 

we will never cure anything if we can never see the forest for the trees $$$

 

we must get corporate political science, god save the industry at all cost mentality, out of sound scientific policy making.

 

NEEDLESS CONFLICT

 


 


 


 

Evidence That Transmissible Mink Encephalopathy Results from Feeding Infected Cattle

 

Over the next 8-10 weeks, approximately 40% of all the adult mink on the farm died from TME.

 

snip...

 

The rancher was a ''dead stock'' feeder using mostly (>95%) downer or dead dairy cattle...

 


 


 


 

In Confidence - Perceptions of unconventional slow virus diseases of animals in the USA - APRIL-MAY 1989 - G A H Wells

 

3. Prof. A. Robertson gave a brief account of BSE. The US approach was to accord it a very low profile indeed. Dr. A Thiermann showed the picture in the ''Independent'' with cattle being incinerated and thought this was a fanatical incident to be avoided in the US at all costs. ...

 


 

”The occurrence of CWD must be viewed against the contest of the locations in which it occurred. It was an incidental and unwelcome complication of the respective wildlife research programmes. Despite it’s subsequent recognition as a new disease of cervids, therefore justifying direct investigation, no specific research funding was forthcoming. The USDA veiwed it as a wildlife problem and consequently not their province!” ...page 26.

 


 

*** Spraker suggested an interesting explanation for the occurrence of CWD. The deer pens at the Foot Hills Campus were built some 30-40 years ago by a Dr. Bob Davis. At or abut that time, allegedly, some scrapie work was conducted at this site. When deer were introduced to the pens they occupied ground that had previously been occupied by sheep.

 


 

2016

 

What say ye Ma’am ?

 

Terry S. Singeltary Sr. Bacliff, Texas USA 77518 flounder9@verizon.net
Posted by at No comments:

Thursday, June 30, 2016

Cannabinoids remove plaque-forming Alzheimer's proteins from brain cells

Cannabinoids remove plaque-forming Alzheimer's proteins from brain cells
 
 
Public Release: 28-Jun-2016 Cannabinoids remove plaque-forming Alzheimer's proteins from brain cells
 
Salk Institute
 
IMAGE: Preliminary lab studies by Salk Professor David Schubert suggest that the molecule THC reduces beta amyloid proteins in human neurons. view more
 
Credit: Salk Institute
 
LA JOLLA -- Salk Institute scientists have found preliminary evidence that tetrahydrocannabinol (THC) and other compounds found in marijuana can promote the cellular removal of amyloid beta, a toxic protein associated with Alzheimer's disease.
 
While these exploratory studies were conducted in neurons grown in the laboratory, they may offer insight into the role of inflammation in Alzheimer's disease and could provide clues to developing novel therapeutics for the disorder.
 
"Although other studies have offered evidence that cannabinoids might be neuroprotective against the symptoms of Alzheimer's, we believe our study is the first to demonstrate that cannabinoids affect both inflammation and amyloid beta accumulation in nerve cells," says Salk Professor David Schubert, the senior author of the paper.
 
Alzheimer's disease is a progressive brain disorder that leads to memory loss and can seriously impair a person's ability to carry out daily tasks. It affects more than five million Americans according to the National Institutes of Health, and is a leading cause of death. It is also the most common cause of dementia and its incidence is expected to triple during the next 50 years.
 
It has long been known that amyloid beta accumulates within the nerve cells of the aging brain well before the appearance of Alzheimer's disease symptoms and plaques. Amyloid beta is a major component of the plaque deposits that are a hallmark of the disease. But the precise role of amyloid beta and the plaques it forms in the disease process remains unclear.
 
In a manuscript published in June 2016's Aging and Mechanisms of Disease, Salk team studied nerve cells altered to produce high levels of amyloid beta to mimic aspects of Alzheimer's disease.
 
The researchers found that high levels of amyloid beta were associated with cellular inflammation and higher rates of neuron death. They demonstrated that exposing the cells to THC reduced amyloid beta protein levels and eliminated the inflammatory response from the nerve cells caused by the protein, thereby allowing the nerve cells to survive.
 
"Inflammation within the brain is a major component of the damage associated with Alzheimer's disease, but it has always been assumed that this response was coming from immune-like cells in the brain, not the nerve cells themselves," says Antonio Currais, a postdoctoral researcher in Schubert's laboratory and first author of the paper. "When we were able to identify the molecular basis of the inflammatory response to amyloid beta, it became clear that THC-like compounds that the nerve cells make themselves may be involved in protecting the cells from dying."
 
Brain cells have switches known as receptors that can be activated by endocannabinoids, a class of lipid molecules made by the body that are used for intercellular signaling in the brain. The psychoactive effects of marijuana are caused by THC, a molecule similar in activity to endocannabinoids that can activate the same receptors. Physical activity results in the production of endocannabinoids and some studies have shown that exercise may slow the progression of Alzheimer's disease.
 
Schubert emphasized that his team's findings were conducted in exploratory laboratory models, and that the use of THC-like compounds as a therapy would need to be tested in clinical trials.
 
In separate but related research, his lab found an Alzheimer's drug candidate called J147 that also removes amyloid beta from nerve cells and reduces the inflammatory response in both nerve cells and the brain. It was the study of J147 that led the scientists to discover that endocannabinoids are involved in the removal of amyloid beta and the reduction of inflammation.
 
###
 
Other authors on the paper include Oswald Quehenberger and Aaron Armando at the University of California, San Diego; and Pamela Maher and Daniel Daughtery at the Salk Institute.
 
The study was supported by the National Institutes of Health, The Burns Foundation and The Bundy Foundation.
 
About Salk Institute:
 
Every cure has a starting point. The Salk Institute embodies Jonas Salk's mission to dare to make dreams into reality. Its internationally renowned and award-winning scientists explore the very foundations of life, seeking new understandings in neuroscience, genetics, immunology and more. The Institute is an independent nonprofit organization and architectural landmark: small by choice, intimate by nature and fearless in the face of any challenge. Be it cancer or Alzheimer's, aging or diabetes, Salk is where cures begin. Learn more at: salk.edu.
 
Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.
 
 
*** National Cancer Institute at the National Institutes of Health ***
 
Cannabis and Cannabinoids (PDQ®), Cancer Antitumor Effects, Prion prevention, Pain management, muscle relaxer, and Palliative Medicine
 
Cannabis and Cannabinoids (PDQ®)
 
Laboratory/Animal/Preclinical Studies
 
Antitumor Effects Appetite Stimulation Analgesia
 
Laboratory/Animal/Preclinical Studies
 
Antitumor Effects
 
Appetite Stimulation
 
Analgesia
 
Cannabinoids are a group of 21-carbon–containing terpenophenolic compounds produced uniquely by Cannabis sativa and Cannabis indica species.[1,2] These plant-derived compounds may be referred to as phytocannabinoids. Although delta-9-tetrahydrocannabinol (THC) is the primary psychoactive ingredient, other known compounds with biologic activity are cannabinol, cannabidiol (CBD), cannabichromene, cannabigerol, tetrahydrocannabivarin, and delta-8-THC. CBD, in particular, is thought to have significant analgesic and anti-inflammatory activity without the psychoactive effect (high) of delta-9-THC.
 
Antitumor Effects One study in mice and rats suggested that cannabinoids may have a protective effect against the development of certain types of tumors.[3] During this 2-year study, groups of mice and rats were given various doses of THC by gavage. A dose-related decrease in the incidence of hepatic adenoma tumors and hepatocellular carcinoma was observed in the mice. Decreased incidences of benign tumors (polyps and adenomas) in other organs (mammary gland, uterus, pituitary, testis, and pancreas) were also noted in the rats. In another study, delta-9-THC, delta-8-THC, and cannabinol were found to inhibit the growth of Lewis lung adenocarcinoma cells in vitro and in vivo .[4] In addition, other tumors have been shown to be sensitive to cannabinoid-induced growth inhibition.[5-8]
 
Cannabinoids may cause antitumor effects by various mechanisms, including induction of cell death, inhibition of cell growth, and inhibition of tumor angiogenesis invasion and metastasis.[9-12] One review summarizes the molecular mechanisms of action of cannabinoids as antitumor agents.[13] Cannabinoids appear to kill tumor cells but do not affect their nontransformed counterparts and may even protect them from cell death. These compounds have been shown to induce apoptosis in glioma cells in culture and induce regression of glioma tumors in mice and rats. Cannabinoids protect normal glial cells of astroglial and oligodendroglial lineages from apoptosis mediated by the CB1 receptor.[14]
 
The effects of delta-9-THC and a synthetic agonist of the CB2 receptor were investigated in hepatocellular carcinoma (HCC).[15] Both agents reduced the viability of hepatocellular carcinoma cells in vitro and demonstrated antitumor effects in hepatocellular carcinoma subcutaneous xenografts in nude mice. The investigations documented that the anti-HCC effects are mediated by way of the CB2 receptor. Similar to findings in glioma cells, the cannabinoids were shown to trigger cell death through stimulation of an endoplasmic reticulum stress pathway that activates autophagy and promotes apoptosis. Other investigations have confirmed that CB1 and CB2 receptors may be potential targets in non-small cell lung carcinoma [16] and breast cancer.[17]
 
An in vitro study of the effect of CBD on programmed cell death in breast cancer cell lines found that CBD induced programmed cell death, independent of the CB1, CB2, or vanilloid receptors. CBD inhibited the survival of both estrogen receptor–positive and estrogen receptor–negative breast cancer cell lines, inducing apoptosis in a concentration-dependent manner while having little effect on nontumorigenic, mammary cells.[18]
 
CBD has also been demonstrated to exert a chemopreventive effect in a mouse model of colon cancer.[19] In the experimental system, azoxymethane increased premalignant and malignant lesions in the mouse colon. Animals treated with azoxymethane and CBD concurrently were protected from developing premalignant and malignant lesions. In in vitro experiments involving colorectal cancer cell lines, the investigators found that CBD protected DNA from oxidative damage, increased endocannabinoid levels, and reduced cell proliferation.
 
Another investigation into the antitumor effects of CBD examined the role of intercellular adhesion molecule-1 (ICAM-1).[12] ICAM-1 expression has been reported to be negatively correlated with cancer metastasis. In lung cancer cell lines, CBD upregulated ICAM-1, leading to decreased cancer cell invasiveness.
 
In an in vivo model using severe combined immunodeficient mice, subcutaneous tumors were generated by inoculating the animals with cells from human non-small cell lung carcinoma cell lines.[20] Tumor growth was inhibited by 60% in THC-treated mice compared with vehicle-treated control mice. Tumor specimens revealed that THC had antiangiogenic and antiproliferative effects. However, research with immunocompetent murine tumor models has demonstrated immunosuppression and enhanced tumor growth in mice treated with THC.[21,22]
 
In addition, both plant-derived and endogenous cannabinoids have been studied for anti-inflammatory effects. A mouse study demonstrated that endogenous cannabinoid system signaling is likely to provide intrinsic protection against colonic inflammation.[23] As a result, a hypothesis that phytocannabinoids and endocannabinoids may be useful in the risk reduction and treatment of colorectal cancer has been developed.[24-27]
 
Appetite Stimulation Many animal studies have previously demonstrated that delta-9-THC and other cannabinoids have a stimulatory effect on appetite and increase food intake. It is believed that the endogenous cannabinoid system may serve as a regulator of feeding behavior. The endogenous cannabinoid anandamide potently enhances appetite in mice.[28] Moreover, CB1 receptors in the hypothalamus may be involved in the motivational or reward aspects of eating.[29]
 
Analgesia Understanding the mechanism of cannabinoid-induced analgesia has been increased through the study of cannabinoid receptors, endocannabinoids, and synthetic agonists and antagonists. The CB1 receptor is found in both the central nervous system (CNS) and in peripheral nerve terminals. Similar to opioid receptors, increased levels of the CB1 receptor are found in regions of the brain that regulate nociceptive processing.[30] CB2 receptors, located predominantly in peripheral tissue, exist at very low levels in the CNS. With the development of receptor-specific antagonists, additional information about the roles of the receptors and endogenous cannabinoids in the modulation of pain has been obtained.[31,32]
 
Cannabinoids may also contribute to pain modulation through an anti-inflammatory mechanism; a CB2 effect with cannabinoids acting on mast cell receptors to attenuate the release of inflammatory agents, such as histamine and serotonin, and on keratinocytes to enhance the release of analgesic opioids has been described.[33-35] One study reported that the efficacy of synthetic CB1- and CB2-receptor agonists were comparable with the efficacy of morphine in a murine model of tumor pain.[36]
 
References
 
snip...
 
 
J Neurosci. 2007 Sep 5;27(36):9­537-44.
 
Nonpsychoa­ctive cannabidio­l prevents prion accumulati­on and protects neurons against ***prion*** toxicity.
 
*** Our results suggest that CBD may protect neurons against the multiple molecular and cellular factors involved in the different steps of the neurodegenerative process, which takes place during prion infection. When combined with its ability to target the brain and its lack of toxic side effects, CBD may represent a promising new anti-prion drug.
 
 
Report of a parent survey of cannabidiol-enriched cannabis use in pediatric treatment-resistant epilepsy
 
Brenda E. Porter x Brenda E. Porter Search for articles by this author , Catherine Jacobson x Catherine Jacobson Search for articles by this author Correspondence Corresponding author. email Received: May 24, 2013; Received in revised form: July 23, 2013; Accepted: August 30, 2013; DOI: http://dx.doi.org/10.1016/j.yebeh.2013.08.037 Abstract Full Text Images/Data References Related Articles To view the full text, please login as a subscribed user or purchase a subscription. Click here to view the full text on ScienceDirect.
 
Abstract
 
Severe childhood epilepsies are characterized by frequent seizures, neurodevelopmental delays, and impaired quality of life. In these treatment-resistant epilepsies, families often seek alternative treatments. This survey explored the use of cannabidiol-enriched cannabis in children with treatment-resistant epilepsy. The survey was presented to parents belonging to a Facebook group dedicated to sharing information about the use of cannabidiol-enriched cannabis to treat their child's seizures. Nineteen responses met the following inclusion criteria for the study: a diagnosis of epilepsy and current use of cannabidiol-enriched cannabis. Thirteen children had Dravet syndrome, four had Doose syndrome, and one each had Lennox–Gastaut syndrome and idiopathic epilepsy. The average number of antiepileptic drugs (AEDs) tried before using cannabidiol-enriched cannabis was 12. Sixteen (84%) of the 19 parents reported a reduction in their child's seizure frequency while taking cannabidiol-enriched cannabis. Of these, two (11%) reported complete seizure freedom, eight (42%) reported a greater than 80% reduction in seizure frequency, and six (32%) reported a 25–60% seizure reduction. Other beneficial effects included increased alertness, better mood, and improved sleep. Side effects included drowsiness and fatigue. Our survey shows that parents are using cannabidiol-enriched cannabis as a treatment for their children with treatment-resistant epilepsy. Because of the increasing number of states that allow access to medical cannabis, its use will likely be a growing concern for the epilepsy community. Safety and tolerability data for cannabidiol-enriched cannabis use among children are not available. Objective measurements of a standardized preparation of pure cannabidiol are needed to determine whether it is safe, well tolerated, and efficacious at controlling seizures in this pediatric population with difficult-to-treat seizures.
 
 
Marijuana and Epilepsy
 
 
Original Contribution| January 11, 2012 Association Between Marijuana Exposure and Pulmonary Function Over 20 Years
 
Conclusion Occasional and low cumulative marijuana use was not associated with adverse effects on pulmonary function.
 
 
Cannabidiol inhibits lung cancer cell invasion and metastasis via intercellular adhesion molecule-1
 
Cannabinoids inhibit cancer cell invasion via increasing tissue inhibitor of matrix metalloproteinases-1 (TIMP-1).
 
 
 
Cannabis in Palliative Medicine: Improving Care and Reducing Opioid-Rel­ated Morbidity
 
Published online before print March 28, 2011, J HOSP PALLIAT CARE August 2011 vol. 28 no. 5 297-303
 
 
Published online ahead of print August 30, 2010 CMAJ 10.1503/cm­aj.091414
 
Smoked cannabis for chronic neuropathi­c pain: a randomized controlled trial
 
Conclusion
 
Our results support the claim that smoked cannabis reduces pain, improves mood and helps sleep. We believe that our trial provides a methodological approach that may be considered for further research. Clinical studies using inhaled delivery systems, such as vaporizers,32,33 are needed.
 
 
Cases J. 2009; 2: 7487.
 
Published online 2009 May 18
 
Standardiz­ed natural product cannabis in pain management and observatio­ns at a Canadian compassion society: a case report
 
The roughly 4000 members of the Green Cross Society find similar benefit from standardized natural product cannabis medicine. To follow, will be publication of the Society's demographic data regarding use for various conditions such as arthritis, fybromyalgia, HIV/AIDS, and chronic pain, to name a few. A breakdown of the illnesses, what strains (cannabinoid profiles) is most effective, and at what dosages will be published at a later time.
 
 
Effect of D9-tetrahydrocannabinol, a cannabinoid receptor agonist, on the triggering of transient lower oesophageal sphincter relaxations in dogs and humans
 
These findings confirm previous findings in dogs and indicate that CB receptors are also involved in the triggering of TLESRs in humans.
 
 
Drugs: 9 July 2010 - Volume 70 - Issue 10 - pp 1245-1254
 
Pharmacological Management of Pain in Patients with Multiple Sclerosis
 
Cannabinoids have been among the few treatments studied in well designed, randomized, placebo-controlled trials for central neuropathic pain. In the largest of these trials, which included 630 subjects, a 15-week comparison between Δ9-tetrahydrocannabinol and placebo was performed. More patients receiving active treatment perceived an improvement in pain than those receiving placebo, although approximately 20% of subjects reported worsening of pain while on active treatment.
 
 
Cannabinoids control spasticity and tremor in a multiple sclerosis model
 
The exacerbation of these signs after antagonism of the CB1 and CB2 receptors, notably the CB1 receptor, using SR141716A and SR144528 (ref. 8) indicate that the endogenous cannabinoid system may be tonically active in the control of tremor and spasticity. This provides a rationale for patients' indications of the therapeutic potential of cannabis in the control of the symptoms of multiple sclerosis2, and provides a means of evaluating more selective cannabinoids in the future.
 
 
 
 
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Tuesday, January 26, 2016

Amyloid-β pathology and cerebral amyloid angiopathy are frequent in iatrogenic Creutzfeldt-Jakob disease after dural grafting

Alzheimer-type brain pathology may be transmitted by grafts of dura mater

 

26/01/2016 By Karl Frontzek, et al.: Alzheimer’s disease is characterized by progressive dementia and brain plaques consisting of the Aβ protein. Conventional wisdom has it that Alzheimer’s disease is not a transmissible disease. However, plaques recovered from brains of Alzheimer’s disease patients were repeatedly found to induce further plaques when injected into the brains of laboratory mice, suggesting that transmission may actually occur.

 

Reporting in today’s Swiss Medical Weekly, Karl Frontzek and colleagues (University of Zurich and Vienna Medical University) have investigated individuals who received brain grafts of dura mater during neurosurgery. The dura mater (“tough mother”) is the leathery membrane covering the brain and spinal cord. Such grafts were necessary to allow the brain to heal after surgery. Tragically, some of the dura mater donors were infected with prions (the agents causing the fatal Creutzfeldt-Jakob disease), and the grafting procedure transmitted the disease to the recipients.

 

Frontzek and colleagues now report the presence of Aβ plaques in 5 of 7 brains of relatively young recipients of dura mater grafts who succumbed to Creutzfeldt-Jakob disease. Aβ plaques were detected much more frequently than in brains of people who did not receive any dura mater grafts. Aβ plaques are highly unusual in young individuals and may have been caused by the dural grafts. This study adds to the evidence that the hallmarks of Alzheimer’s disease may indeed be transmissible under certain circumstances, and calls for heightened attention to an unexpected, potentially very serious problem of transplantation medicine.

 

>> Read the article

 

This is a summary of a paper that was published on www.smw.ch. Must be cited as: Frontzek K, Lutz MI, Aguzzi A, Kovacs GG, Budka H. Amyloid-β pathology and cerebral amyloid angiopathy are frequent in iatrogenic Creutzfeldt-Jakob disease after dural grafting. Swiss Med Wkly. 2016;146:w14287.

 


 

Original article | Published 26 January 2016, doi:10.4414/smw.2016.14287

 

Cite this as: Swiss Med Wkly. 2016;146:w14287

 

Amyloid-β pathology and cerebral amyloid angiopathy are frequent in iatrogenic Creutzfeldt-Jakob disease after dural grafting

 

Karl Frontzeka, Mirjam I. Lutzb, Adriano Aguzzia, Gabor G. Kovacsb *, Herbert Budkaa,b *

 

a Institute of Neuropathology, University Hospital Zurich, Switzerland b Institute of Neurology, Medical University Vienna, Austria * These authors contributed equally

 

 Summary

 

QUESTIONS UNDER STUDY: Alzheimer-type amyloid-β (Aβ) pathology was reported in brains of individuals developing iatrogenic Creutzfeldt-Jakob disease (iCJD) after treatment with human cadaveric growth hormone, and interpreted as evidence of human transmission of Aβ by the treatment. Here we investigated the prevalence of Aβ pathology in other instances of iCJD related to dura mater grafts.

 

 METHODS: By use of immunohistochemistry for Aβ, we investigated seven brains of patients (age range 28–63) who succumbed to iCJD after dural grafting, which had been applied by means of neurosurgery between 11 and 25 years before death. For control, we examined a series of 21 brains of age-matched (40–63 years) patients with sporadic CJD (sCJD) and an additional series of 81 sCJD cases (55–85 years) with the same methods.

 

 RESULTS: In five of seven iCJD brains, Aβ was deposited in meningeal vessels as congophilic amyloid angiopathy and brain parenchymal plaques. This was significantly (p <0 .001="" age-matched="" and="" controls="" div="" frequent="" in="" more="" scjd="" series.="" than="" the="" usual="">
 

 CONCLUSIONS: We conclude that congophilic amyloid angiopathy and brain parenchymal Aβ plaques are frequent in iCJD after dural grafting. The presence of Aβ pathology in young individuals is highly unusual and suggests a causal relationship to the dural grafts. Further studies will be needed to elucidate whether such pathology resulted from the seeding of Aβ aggregates from the grafts to host tissues.

 

 Key words: prion; iatrogenic Creutzfeldt-Jakob disease; amyloid-beta; Alzheimer pathology; prion-like propagation; dural grafting

 

Introduction...

 

snip...

 

Discussion We report here that CAA and brain parenchymal Aβ plaques are frequent in iCJD after dural grafting, even in young individuals. Similarly to what was previously reported in iCJD after hGH treatment [15], we failed to detect any marked tau pathology in our series after dural grafting. The presence of Aβ pathology in young individuals who present with neither a family history of early-onset dementia or prominent AD-related tau pathology is highly unusual and suggests a causal relationship to the dural grafts [19]. It is plausible that such pathology may have resulted from the seeding of Aβ aggregates from the grafts to host tissues, yet alternative explanations are also possible.

 

The Aβ pathology was observed many years after neurosurgery that applied a graft of dura mater. It is intriguing that all cases with particularly long intervals after dural grafting (more than 20 years) were the five who had Aβ pathology, whereas the two brains without Aβ had much shorter intervals of 11 and 12 years, respectively. This does not seem to be a function of age, as both cases without Aβ had ages in the 50s, whereas Aβ brains included three cases younger than 50. Such prolonged incubation over decades would be another striking similarity with prion diseases. As data on the site of the applied dural graft were not available for all cases, we were unable to investigate conclusively whether the severity of the induced Aβ pathology had a topographic relationship to the site of grafting. For the same reason, it was not possible to assert any local difference between meningeal vs parenchymal Aβ according to graft site.

 

The clinical signs and symptoms in all patients reported here were typical of CJD [3]; there was no report of previous mild or slowly progressive cognitive impairment that might have been the result of Aβ pathology prior to the onset of rapidly progressive iCJD. All brains had prominent and widespread deposition of PrPSc; in comparison, Aβ was less prominent. Thus, any striking local co-occurrence suggestive of potential cross-seeding was not discernible.

 

The findings reported here extend a previous study of iCJD after hGH treatment [15] and suggest that both human dural tissue grafts and pituitary extracts are able to elicit Aβ pathology decades later. This would be in agreement with ample evidence of prion-like propagation of aggregated proteins in animal models of neurodegeneration [8]. However, as discussed previously [16], it is currently impossible to eliminate the possibility that head trauma or the underlying conditions which had led to dural grafting, or neurosurgery, may have contributed to the induction of Aβ pathology.

 

A previous study [20] demonstrated the presence of Aβ in human pituitary tissue, the source of prion-contaminated hGH preparations. However, no clinically manifest cases of AD or PD were identified among recipients of pituitary-derived hGH in review of the large US National Hormone and Pituitary Program cohort database [20]. Hence, further studies are needed to elucidate whether potential transmission and propagation of Aβ – and of other neurodegeneration-related proteins – from external sources is indeed able to induce a clinically manifest human disease.

 

Whilst the iatrogenic transmission of aggregated Aβ is one of several possible explanations for the findings reported here, the growing circumstantial evidence for such transmission should prompt a critical re-evaluation of the decontamination procedures for surgical instruments and drugs of biological origin, with the goal to ensure the complete absence of potentially transmissible contaminants.

 

Disclosure statement: We declare no competing interests.This research received no specific grant from any funding agency in the commercial or not-for-profit sectors. The national CJD surveillance in Switzerland and Austria, as performed by the respective National Reference Centres for Human Prion Diseases (NRPE, located at the Institute of Neuropathology, University Hospital Zurich, and ÖRPE, located at the Institute of Neurology, Medical University Vienna) is supported by the Federal Office of Public Health in Berne, Switzerland, and the Federal Ministry of Health in Vienna, Austria, respectively.

 

Correspondence: Herbert Budka, Institute of Neuropathology, University Hospital Zurich, Schmelzbergstr. 12, CH-8091 Zurich, Switzerland, herbert.budka[at]usz.ch

 

References snip...end

 


 

Evidence for human transmission of amyloid-? pathology and cerebral amyloid angiopathy

 

07 02:27 AM

 

Terry S. Singeltary Sr. said:

 

re-Evidence for human transmission of amyloid-? pathology and cerebral amyloid angiopathy

 

2015-12-07 02:27 AM

 

Terry S. Singeltary Sr. said: re-Evidence for human transmission of amyloid-? pathology and cerebral amyloid angiopathy Nature 525, 247?250 (10 September 2015) doi:10.1038/nature15369 Received 26 April 2015 Accepted 14 August 2015 Published online 09 September 2015 Updated online 11 September 2015 Erratum (October, 2015)

 


 

I would kindly like to comment on the Nature Paper, the Lancet reply, and the newspaper articles.

 

First, I applaud Nature, the Scientist and Authors of the Nature paper, for bringing this important finding to the attention of the public domain, and the media for printing said findings.

 

Secondly, it seems once again, politics is getting in the way possibly of more important Transmissible Spongiform Encephalopathy TSE Prion scientific findings. findings that could have great implications for human health, and great implications for the medical surgical arena. but apparently, the government peer review process, of the peer review science, tries to intervene again to water down said disturbing findings.

 

where have we all heard this before? its been well documented via the BSE Inquiry. have they not learned a lesson from the last time?

 

we have seen this time and time again in England (and other Countrys) with the BSE mad cow TSE Prion debacle.

 

That ?anonymous' Lancet editorial was disgraceful. The editor, Dick Horton is not a scientist.

 

The pituitary cadavers were very likely elderly and among them some were on their way to CJD or Alzheimer's. Not a bit unusual. Then the recipients ? who got pooled extracts injected from thousands of cadavers ? were 100% certain to have been injected with both seeds. No surprise that they got both diseases going after thirty year incubations.

 

That the UK has a "system in place to assist science journalists" to squash embargoed science reports they find ?alarming? is pathetic.

 

Sounds like the journalists had it right in the first place: ?Alzheimers may be a transmissible infection? in The Independent to ?You can catch Alzheimers? in The Daily Mirror or ?Alzheimers bombshell" in The Daily Express

 

if not for the journalist, the layperson would not know about these important findings.

 

where would we be today with sound science, from where we were 30 years ago, if not for the cloak of secrecy and save the industry at all cost mentality?

 

when you have a peer review system for science, from which a government constantly circumvents, then you have a problem with science, and humans die.

 

to date, as far as documented body bag count, with all TSE prion named to date, that count is still relatively low (one was too many in my case, Mom hvCJD), however that changes drastically once the TSE Prion link is made with Alzheimers, the price of poker goes up drastically.

 

so, who makes that final decision, and how many more decades do we have to wait?

 

the iatrogenic mode of transmission of TSE prion, the many routes there from, load factor, threshold from said load factor to sub-clinical disease, to clinical disease, to death, much time is there to spread a TSE Prion to anywhere, but whom, by whom, and when, do we make that final decision to do something about it globally? how many documented body bags does it take? how many more decades do we wait? how many names can we make up for one disease, TSE prion?

 

Professor Collinge et al, and others, have had troubles in the past with the Government meddling in scientific findings, that might in some way involve industry, never mind human and or animal health.

 

FOR any government to continue to circumvent science for monetary gain, fear factor, or any reason, shame, shame on you.

 

in my opinion, it?s one of the reasons we are at where we are at to date, with regards to the TSE Prion disease science i.e. money, industry, politics, then comes science, in that order.

 

greed, corporate, lobbyist there from, and government, must be removed from the peer review process of sound science, its bad enough having them in the pharmaceutical aspect of healthcare policy making, in my opinion.

 

my mother died from confirmed hvCJD, and her brother (my uncle) Alzheimers of some type (no autopsy?). just made a promise, never forget, and never let them forget, before I do.

 

I kindly wish to remind the public of the past, and a possible future we all hopes never happens again. ...

 

[9. Whilst this matter is not at the moment directly concerned with the iatrogenic CJD cases from hgH, there remains a possibility of litigation here, and this presents an added complication. There are also results to be made available shortly (1) concerning a farmer with CJD who had BSE animals, (2) on the possible transmissibility of Alzheimers and (3) a CMO letter on prevention of iatrogenic CJD transmission in neurosurgery, all of which will serve to increase media interest.]

 


 


 


 

Terry S. Singeltary Sr. Bacliff, Texas USA 77518

 

snip...see Singeltary comment ;

 


 

Subject: 1992 IN CONFIDENCE TRANSMISSION OF ALZHEIMER TYPE PLAQUES TO PRIMATES POSSIBILITY ON A TRANSMISSIBLE PRION REMAINS OPEN

 

BSE101/1 0136

 

IN CONFIDENCE

 

CMO

 

From: . Dr J S Metiers DCMO

 

4 November 1992

 

TRANSMISSION OF ALZHEIMER TYPE PLAQUES TO PRIMATES

 

1. Thank you for showing me Diana Dunstan's letter. I am glad that MRC have recognised the public sensitivity of these findings and intend to report them in their proper context. 'This hopefully will avoid misunderstanding and possible distortion by the media to portray the results as having more greater significance than the findings so far justify.

 

2. Using a highly unusual route of transmission (intra-cerebral injection) the researchers have demonstrated the transmission of a pathological process from two cases one of severe Alzheimer's disease the other of Gerstmann-Straussler disease to marmosets. However they have not demonstrated the transmission of either clinical condition as the "animals were behaving normally when killed". As the report emphasises the unanswered question is whether the disease condition would have revealed itself if the marmosets had lived longer. They are planning further research to see if the conditions, as opposed to the partial pathological process, is transmissible.

 

what are the implications for public health?

 

3. The route 'of transmission is very specific and in the natural state of things highly unusual. However it could be argued that the results reveal a potential risk, in that brain tissue from these two patients has been shown to transmit a pathological process. Should therefore brain tissue from such cases be regarded as potentially infective? Pathologists, morticians, neuro surgeons and those assisting at neuro surgical procedures and others coming into contact with "raw" human brain tissue could in theory be at risk. However, on a priori grounds given the highly specific route of transmission in these experiments that risk must be negligible if the usual precautions for handling brain tissue are observed.

 

1

 

92/11.4/1.1

 

BSE101/1 0137

 

4. The other dimension to consider is the public reaction. To some extent the GSS case demonstrates little more than the transmission of BSE to a pig by intra-cerebral injection. If other prion diseases can be transmitted in this way it is little surprise that some pathological findings observed in GSS were also transmissible to a marmoset. But the transmission of features of Alzheimer's pathology is a different matter, given the much greater frequency of this disease and raises the unanswered question whether some cases are the result of a transmissible prion. The only tenable public line will be that "more research is required’’ before that hypothesis could be evaluated. The possibility on a transmissible prion remains open. In the meantime MRC needs carefully to consider the range and sequence of studies needed to follow through from the preliminary observations in these two cases. Not a particularly comfortable message, but until we know more about the causation of Alzheimer's disease the total reassurance is not practical.

 

J S METTERS Room 509 Richmond House Pager No: 081-884 3344 Callsign: DOH 832 llllYc!eS 2 92/11.4/1.2

 


 

>>> The only tenable public line will be that "more research is required’’ <<<

 

>>> possibility on a transmissible prion remains open<<<

 

O.K., so it’s about 23 years later, so somebody please tell me, when is "more research is required’’ enough time for evaluation ?

 

Self-Propagative Replication of Ab Oligomers Suggests Potential Transmissibility in Alzheimer Disease

 

*** Singeltary comment PLoS ***

 

Alzheimer’s disease and Transmissible Spongiform Encephalopathy prion disease, Iatrogenic, what if ?

 

Posted by flounder on 05 Nov 2014 at 21:27 GMT

 


 

Sunday, November 22, 2015

 

*** Effect of heating on the stability of amyloid A (AA) fibrils and the intra- and cross-species transmission of AA amyloidosis Abstract

 

 Amyloid A (AA) amyloidosis is a protein misfolding disease characterized by extracellular deposition of AA fibrils. AA fibrils are found in several tissues from food animals with AA amyloidosis. For hygienic purposes, heating is widely used to inactivate microbes in food, but it is uncertain whether heating is sufficient to inactivate AA fibrils and prevent intra- or cross-species transmission. We examined the effect of heating (at 60 °C or 100 °C) and autoclaving (at 121 °C or 135 °C) on murine and bovine AA fibrils using Western blot analysis, transmission electron microscopy (TEM), and mouse model transmission experiments. TEM revealed that a mixture of AA fibrils and amorphous aggregates appeared after heating at 100 °C, whereas autoclaving at 135 °C produced large amorphous aggregates. AA fibrils retained antigen specificity in Western blot analysis when heated at 100 °C or autoclaved at 121 °C, but not when autoclaved at 135 °C. Transmissible pathogenicity of murine and bovine AA fibrils subjected to heating (at 60 °C or 100 °C) was significantly stimulated and resulted in amyloid deposition in mice. Autoclaving of murine AA fibrils at 121 °C or 135 °C significantly decreased amyloid deposition. Moreover, amyloid deposition in mice injected with murine AA fibrils was more severe than that in mice injected with bovine AA fibrils. Bovine AA fibrils autoclaved at 121 °C or 135 °C did not induce amyloid deposition in mice. These results suggest that AA fibrils are relatively heat stable and that similar to prions, autoclaving at 135 °C is required to destroy the pathogenicity of AA fibrils. These findings may contribute to the prevention of AA fibril transmission through food materials to different animals and especially to humans.

 

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Transmission of Creutzfeldt-Jakob disease to a chimpanzee by electrodes contaminated during neurosurgery.

 

Gibbs CJ Jr, Asher DM, Kobrine A, Amyx HL, Sulima MP, Gajdusek DC. Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.

 

Stereotactic multicontact electrodes used to probe the cerebral cortex of a middle aged woman with progressive dementia were previously implicated in the accidental transmission of Creutzfeldt-Jakob disease (CJD) to two younger patients. The diagnoses of CJD have been confirmed for all three cases. More than two years after their last use in humans, after three cleanings and repeated sterilisation in ethanol and formaldehyde vapour, the electrodes were implanted in the cortex of a chimpanzee. Eighteen months later the animal became ill with CJD. This finding serves to re-emphasise the potential danger posed by reuse of instruments contaminated with the agents of spongiform encephalopathies, even after scrupulous attempts to clean them.

 


 

Friday, January 10, 2014

 

vpspr, sgss, sffi, TSE, an iatrogenic by-product of gss, ffi, familial type prion disease, what it ???

 

Greetings Friends, Neighbors, and Colleagues,

 


 

Thursday, January 14, 2016

 

Preventable Tragedies: Superbugs and How Ineffective Monitoring of Medical Device Safety Fails Patients REPORT

 

how can it be, HOW CAN IT BE $$$ not a word about CJD GSS FFI VPSPR TSE Prions that I saw...absolutely crazy, WE ARE MISSING THE BIGGER PICTURE!

 

how many victims that will never be reported ???

 


 

Sunday, January 17, 2016

 

Of Grave Concern Heidenhain Variant Creutzfeldt Jakob Disease

 


 

kind regards, terry

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