NF-kB Signalling and Chronic Inflammatory Diseases: Exploring the potential of Natural Products to Drive New Therapeutic Opportunities in Drug Discovery Today, Matthew J. Killeen, Nov 2013

Abstract Excerpt:
"Chronic inflammation has a key role in the pathogenesis of multiple diseases that represents major public health and financial concerns; including heart failure, Alzheimer's Disease, and arthritis. Nuclear Factor kappa beta (NF-kB) is a central component of inflammation. Owing to it's upstream signalling position, it is considered an attractive target for new anti-inflammatory therapeutics.

Article at:
https://www.facebook.com/137874126245637/photos/a.695406507159060.1073741826.137874126245637/695406510492393/?type=3&theater

Inflammation 101: The Fuel That Feeds Cancer in Integrative Oncology Essentials, Published November 11, 2012 by Brian D. Lawenda, I am an integrative oncologist. I trained at Massachusetts General Hospital (Harvard Medical School) in radiation oncology and through Stanford-UCLA (Helms Medical Institute) in medical acupuncture. I am the founder of IntegrativeOncology-Essentials.

Excerpts:
"Chronic Inflammation: Whereas acute inflammation protects us from our hostile environment, “chronic” inflammation (a prolonged state of low-level, smoldering inflammation, lasting months-to-years) can hurt or even kill us. This difference is one of the most important discoveries of modern medicine. We now recognize that chronic inflammation is involved in the development and progression of almost every chronic disease…including cancer. The role of chronic inflammation is particularly poignant in the autoimmune and chronic infectious diseases, where the involved tissues are flooded with persistent chemical and protein signaling to repair and grow. Chronic inflammation can also significantly reduce your body’s sensitivity to insulin, leading to persistently elevated levels of blood sugar, increased production of insulin and insulin-like growth factor 1 (IGF-1), metabolic syndrome, type 2 diabetes and obesity. All of these factors have been shown to increase the risk of cancer development, progression and recurrence. "

"The Role of Nuclear Factor Kappa-B (NF-kB) in Cancer When immune cells first detect any signs of tissue injury or stress, they activate a cellular protein, called nuclear factor kappa-B (or NF-kB.) This protein is the main ‘switch’ that turns on the inflammation in the tissues. Activated NF-kB signals the cell (via many pathways, including through the activation of inflammasomes) to begin to produce numerous proteins involved in inflammation and tissue repair. So far so good, as long as the growth signals are not happening in precancerous or cancerous tissues… During chronic inflammatory conditions, inflamed tissues are predisposed to developing and accumulating DNA damage at a greater rate than non-inflamed tissues. This is due to the production of large amounts of free radicals in inflamed tissues [in fact, billions of DNA mutations develop in our cells each day as a result of free radical injury and toxic exposures.] When these highly-reactive chemicals interact with DNA, they can create DNA mutations. As long as the cell is able to either repair these DNA mutations (most cells have built-in DNA repair mechanisms) or signal the cell to undergo a process of cell suicide (“apoptosis”), precancerous cells will not develop. However, during constant exposure to NF-kB directed signals (which happens during chronic inflammation), both apoptosis and DNA repair mechanisms are shut down. This leads to an accumulation of cells with genetic mutations. If these cells develop enough mutations, they can transform into precancerous cells and, eventually, cancer cells. In the presence of chronic inflammation, precancerous and cancerous tissues are signaled to divide, grow and even invade into surrounding tissues (including blood and lymph vessels, which gives them access to the rest of the body; this is referred to as “metastatic” spread.) These inflammatory signals also inactivate immune cells in the area, preventing them from being able to identify and attack the newly formed cancer cells. One of the sneaky things that cancer cells learn to do to ensure their own growth and survival, is that they can activate their own NF-kB. This enables them to turn on all of the same inflammatory proteins in the surrounding tissues, thereby hijacking the body’s tissue repair and growth mechanisms."

Article at:
http://www.integrativeoncology-essentials.com/2012/11/inflammation-101-the-fuel-that-feeds-cancer/#sthash.oQhXGIzl.dpuf

Chronic Inflammation, NF-kB, and Cancer in Science and Medicine, M. Bokulich, Science & Medicine: Volume 10 Number 3: Page 180 (June 2005)

Abstract:
"The inflammatory microenvironment is characterized by the presence of activated macrophages and other immune cell types, which secrete a host of proinflammatory factors, such as cytokines, chemokines, and proteases. In chronic inflammation, this unabated immune response stimulates the proliferation of mutated cells, enhances their survival, and promotes angiogenesis, invasion, and metastasis. By regulating the expression of various factors that modulate the inflammatory processes, the transcription factor NF-kB appears to play a central role. Blocking NF-kB may offer a therapeutic option against cancer."

Book Excerpt at:
http://www.sciandmed.com/sm/journalviewer.aspx?issue=1171&article=1701

The Most Important Thing You May Not Know About Hypothyroidism at Chris Kresser's HEALTH for the 21ST CENTURY website, by CHRIS KRESSER, no date

Article:
"An estimated 20 million Americans have some form of thyroid disease. Up to 60 percent of these people are unaware of their condition. One in eight women will develop a thyroid disorder during her lifetime. Levothyroxine, a synthetic form of thyroid hormone, is the 4th highest selling drug in the U.S. 13 of the top 50 selling drugs are either directly or indirectly related to hypothyroidism. The number of people suffering from thyroid disorders continues to rise each year.

Hypothyroidism is one of the most common thyroid disorders. One recent analysis suggested up to 10% of women over 60 have clinical or subclinical hypothyroidism. It is characterized by mental slowing, depression, dementia, weight gain, constipation, dry skin, hair loss, cold intolerance, hoarse voice, irregular menstruation, infertility, muscle stiffness and pain, and a wide range of other not-so-fun symptoms.

Every cell in the body has receptors for thyroid hormone. These hormones are responsible for the most basic aspects of body function, impacting all major systems of the body.

Thyroid hormone directly acts on the brain, the G.I. tract, the cardiovascular system, bone metabolism, red blood cell metabolism, gall bladder and liver function, steroid hormone production, glucose metabolism, lipid and cholesterol metabolism, protein metabolism and body temperature regulation. For starters.

You can think of the thyroid as the central gear in a sophisticated engine. If that gear breaks, the entire engine goes down with it.

That’s why people with hypothyroidism experience everything from weight gain and depression to infertility, bone fractures and hair loss.

One of the biggest challenges facing those with hypothyroidism is that the standard of care for thyroid disorders in both conventional and alternative medicine is hopelessly inadequate.

The dream of patients with thyroid disorders and the practitioners who treat them is to find that single substance that will magically reverse the course of the disease. For doctors, this is either synthetic or bio-identical thyroid hormone. For the alternative types, this is iodine.

Unfortunately, in the vast majority of cases neither approach is effective. Patients may get relief for a short period of time, but inevitably symptoms return or the disease progresses.

So what’s the problem? Why have replacement hormones and supplemental iodine been such dismal failures?

Because hypothyroidism is caused by an autoimmune disease.
Studies show that 90% of people with hypothyroidism are producing antibodies to thyroid tissue. This causes the immune system to attack and destroy the thyroid, which over time causes a decline in thyroid hormone levels.

This autoimmune form of hypothyroidism is called Hashimoto’s disease. Hashimoto’s is the most common autoimmune disorder in the U.S., affecting between 7-8% of the population. While not all people with Hashimoto’s have hypothyroid symptoms, thyroid antibodies have been found to be a marker for future thyroid disease.

Most doctors know hypothyroidism is an autoimmune disease. But most patients don’t. The reason doctors don’t tell their patients is simple: it doesn’t affect their treatment plan.

Conventional medicine doesn’t have effective treatments for autoimmune disease. They use steroids and other medications to suppress the immune system in certain conditions with more potentially damaging effects, such as multiple sclerosis, rheumatoid arthritis and Crohn’s disease.

But in the case of Hashimoto’s, the consequences – i.e. side effects and complications – of using immunosuppressive drugs are believed to outweigh the potential benefits. (Thanks to conventional medicine for a relative moment of sanity here.)

So the standard of care for a Hashimoto’s patient is to simply wait until the immune system has destroyed enough thyroid tissue to classify them as hypothyroid, and then give them thyroid hormone replacement. If they start to exhibit other symptoms commonly associated with their condition, like depression or insulin resistance, they’ll get additional drugs for those problems.

The obvious shortcoming of this approach is that it doesn’t address the underlying cause of the problem, which is the immune system attacking the thyroid gland. And if the underlying cause isn’t addressed, the treatment isn’t going to work very well – or for very long.

If you’re in a leaky rowboat, bailing water will only get you so far. If you want to stop the boat from sinking, you’ve got to plug the leaks.

Extending this metaphor to Hashimoto’s disease, thyroid hormones are like bailing water. They may be a necessary part of the treatment. But unless the immune dysregulation is addressed (plugging the leaks), whoever is in that boat will be fighting a losing battle to keep it from sinking.

What the vast majority of hypothyroidism patients need to understand is that they don’t have a problem with their thyroid, they have a problem with their immune system attacking the thyroid. This is crucial to understand, because when the immune system is out of control, it’s not only the thyroid that will be affected.

Hashimoto’s often manifests as a “polyendocrine autoimmune pattern”. This means that in addition to having antibodies to thyroid tissue, it’s not uncommon for Hashimoto’s patients to have antibodies to other tissues or enzymes as well. The most common are transglutaminase (Celiac disease), the cerebellum (neurological disorders), intrinsic factor (pernicious anemia), glutamic acid decarboxylase (anxiety/panic attacks and late onset type 1 diabetes).

In the next post we’ll look more closely at why Hashimoto’s can’t be treated successfully without addressing the autoimmune component, and why both the conventional and alternative approaches to treating hypothyroidism are destined to fail from the start."

Article at:
http://chriskresser.com/the-most-important-thing-you-may-not-know-about-hypothyroidism

Diabetes and Inflammation at WebMD, Diabetes Health Center, no author, no date

Article:
"Inactivity and obesity increase the risk for diabetes, but exactly how is unclear. Recent research suggests that inflammation inside the body plays a role in the development of type 2 diabetes.

The good news: An "anti-inflammatory" diet and exercise plan can help prevent and treat type 2 diabetes.

The effects of inflammation are familiar to anyone who has experienced a bug bite, rash, skin infection, or ankle sprain. In those situations, you will see swelling in the affected area.

With type 2 diabetes, inflammation is internal.

Slideshow: Type 2 Diabetes Overview
How Inflammation Develops

People with type 2 diabetes don't produce enough insulin or their bodies can't use the insulin adequately. Insulin is a hormone that is made by cells in the pancreas. It controls the amount of sugar in the blood.

Insulin may also have an impact on tissue in the body. Its effects on tissue are influenced by many factors, including obesity and the accumulation of fat around the belly and on major organs in the abdomen. The fat cells can produce chemicals that lead to inflammation.


Scientists are only beginning to understand the role this form of internal inflammation may play in the development of chronic diseases like diabetes.

The Role of Inflammatory Chemicals

Decades ago, researchers identified higher levels of inflammation in the bodies of people with type 2 diabetes. The levels of certain inflammatory chemicals called cytokines are often higher in people with type 2 diabetes compared to people without diabetes.

Obesity and inactivity have long been known to be the most important risk factors that drive the development of type 2 diabetes.

How could carrying extra weight and sofa-sitting be connected to higher levels of inflammatory chemicals in the body and the development of diabetes?

Researchers discovered that in people with type 2 diabetes, cytokine levels are elevated inside fat tissue. Their conclusion: Fat causes continuous (chronic), low levels of abnormal inflammation that alters insulin's action and contributes to the disease.

As type 2 diabetes starts to develop, the body becomes less sensitive to insulin and the resulting insulin resistance also leads to inflammation. A vicious cycle can result, with more inflammation causing more insulin resistance and vice versa. Blood sugar levels creep higher and higher, eventually resulting in type 2 diabetes.

Emotional stress can also increase levels of the chemicals of inflammation. It's unknown whether stress by itself can contribute to the development of diabetes, though.

Does inflammation cause diabetes? It's not as simple as that. All researchers know for sure is that inflammation is somehow involved in the development of type 2 diabetes."

Article at:
http://www.webmd.com/diabetes/guide/inflammation-and-diabetes

Novo Nordisk's Medical Miracle in Forbes, Robert Langreth, Forbes Staff, 2/09/2011

My comments, this is the story of insulin. Could Anatabine Citrate follow a similar path? Anatabine with it's multitude of potential applications might grow into a plethora of uses by itself or in combination with other drugs. Anatabine also has the potential to quell chronic inflammation as a preventative agent to slow or stop autoimmune diseases, cardiovascular diseases, cancers, and depression.


Excerpts:
"Novo Nordisk Chief Executive Lars Rebien Sørensen made a bold decision four years ago. His company had made its name selling one 90-year-old miracle drug–insulin for diabetes. Rival drug companies were testing new diabetes pills that threatened to cut into insulin’s market share. One such pill from Merck had just been approved in the U.S. Others seemed imminent. Worse, Novo Nordisk had spent $1 billion to come up with its own diabetes pills with limited success.

The Danish company could have licensed a product from another company to keep pace. Instead, Sørensen shut down Novo’s pill research. He poured the savings into the company’s core competency–insulin and other injected diabetes meds–betting that their sales would continue to grow in the wake of a global diabetes epidemic. “It was a calculated risk,” says Sørensen. “We could see that there was a declining return on investment in [diabetes pills] and pulled our resources earlier than most.”

It turned out to be a brilliant move. In an era when markets for many pills are shrinking thanks to patent expirations and safety worries, insulin has emerged as an unlikely growth story. It remains the most potent drug for a disease that is on the rise around the world. No pill has come close to displacing it. Because diabetes is a progressive disease, many, if not most, patients end up on it eventually. Unlike newfangled drugs that turn out to have unexpected side effects–like the heart risk problems that hobbled GlaxoSmithKline’s Avandia–insulin has a safety profile that is well understood. Doctors are used to managing its main side effect, dangerously low blood sugar.

Worldwide insulin sales have quadrupled in the last decade to $15.4 billion, according to IMS Health. Novo, the world’s largest insulin maker, sold $7.1 billion of insulin last year in a hard-to-penetrate oligopoly that also includes Sanofi-aventis and Eli Lilly. The company’s overall sales ($11.25 billion; it also sells hemophilia drugs) were up 13% in 2010. They are projected to grow at an 8% to 10% clip for years to come. Its stock has quintupled in the last decade. Novo’s $64 billion market cap is bigger than biotech stalwart Amgen ($52 billion) and its rival Lilly ($39 billion).

A big part of Novo’s success is that the patient pool is growing every year. Some 26 million Americans have diabetes and another 79 million–a third of the adult population–have prediabetes, the CDC says. At the current rate, one in three American adults will have diabetes by 2050. As India, China and other emerging economies become wealthier and adopt Western diets, the diabetes rate is surging in those places as well. The most common form of the disease, type 2 diabetes, starts in adulthood and is closely linked to obesity and inactivity; it is a progressive disease in which the body loses the ability to make enough insulin or use it properly. Patients with type 1 (juvenile) diabetes can’t make insulin at all and need to inject it their whole lives.

“The market for insulin is almost endless. It is going up and up and up. It is not even close to the peak,” says diabetes specialist David Nathan of Massachusetts General Hospital. “There is no cure in sight, and insulin is extraordinarily effective,” says David Kliff, a diabetes sufferer who runs the e-newsletter Diabetic Investor. “Talk about being in the right place at the right time with the right thing.”

Some of Novo Nordisk’s success has come at the expense of its competitors. Eli Lilly started producing insulin in 1923 and long dominated the U.S. market. Under Sørensen Novo expanded its U.S. sales force and overtook Lilly. Novo’s $2.9 billion in U.S. insulin sales easily outpace Lilly’s $2.1 billion, according to IMS Health. “They brought in a full portfolio of modern insulins and caught Eli Lilly on the back foot,” says Morgan Stanley analyst Peter Verdult. Says Sørensen: “Lilly was off focus for a period of time. That led to an opening for us.”

Article at:
http://www.forbes.com/forbes/2011/0228/features-lars-sorensen-novo-nordisk-medical-miracle.html

FDA MedWatch Alerts at Drugs.com, current issue, 5/28/14

My comments: ( Last 30 day postings) Looks like the FDA is attacking neutraceuticals using "undeclared drug ingredient' to hinder their business.

Postings:

Asset Bold: Public Notification - Undeclared Drug Ingredient
MAY 16, 2014

MV5 Days: Public Notification - Undeclared Drug Ingredient
MAY 16, 2014

Asset Bee Pollen: Public Notification - Undeclared Drug Ingredient

Natural Body Solution: Public Notification - Undeclared Drug Ingredient
MAY 6, 2014

Slim Trim U: Public Notification - Undeclared Drug Ingredient
MAY 6, 2014

African Black Ant, Black Ant, and Mojo Risen by Eugene Oregon, Inc: Recall - Undeclared Drug Ingredient MAY 6, 2014

Flawless Beauty and Skin Products: Recall - Unapproved Drugs
APRIL 30, 2014

Super Arthgold by Nano Well-being Health: Recall - Undeclared Drug Ingredients APRIL 24, 2014

S.W.A.G: Public Notification - Undeclared Drug Ingredient
APRIL 18, 2014

Postings at:
http://www.drugs.com/fda_alerts.html

The most important lesson from 83,000 brain scans at TEDx Talks, Daniel Amen, October 2013 (15 minute video)

Video at:

Insulin and Alzheimer's video, HBO Documentary at Alzheimer's Association Research(approx. 22 min.) Video at:

http://www.alz.org/research/video/video_pages/insulin_and_alz.html

Most people don't know that diabetes may contribute to Alzheimer's. Suzanne Craft, Ph.D., discusses the role insulin plays in the brain, the benefits of diet and exercise in improving insulin metabolism, and investigational treatment based on intranasal insulin.

My comments:
A must watch, Alzheimer connection with insulin and insulin resistance process becomes an important marker and maybe delaying Alzheimer.

Inflammation, the immune system and Alzheimer's video(approx. 29 min.) by HBO Documentary at Alzheimer's Association, Joseph Rogers, PhD, describes the role of inflammation in the body and its possible role in Alzheimer's. Dale Schenk, PhD, recounts his quest to bring an anti-Alzheimer's vaccine to market.

Video at:
http://www.alz.org/research/video/video_pages/inflammation.html

Alzheimer Treatment Horizon at Alzheimer's Association Science and Progress website, no date, no author

Excerpt:
"The hope for future drugs
Currently, there are five FDA-approved Alzheimer's drugs that treat the symptoms of Alzheimer's — temporarily helping memory and thinking problems in about half of the people who take them. But these medications do not treat the underlying causes of Alzheimer's.

In contrast, many of the new drugs in development aim to modify the disease process itself, by impacting one or more of the many wide-ranging brain changes that Alzheimer's causes. These changes offer potential "targets" for new drugs to stop or slow the progress of the disease. Many researchers believe successful treatment will eventually involve a "cocktail" of medications aimed at several targets, similar to current state-of-the-art treatments for many cancers and AIDS.

"Targets for future drugs
Beta-amyloid
Tau protein
Inflammation
Insulin resistance"

Article at:
http://www.alz.org/research/science/alzheimers_treatment_horizon.asp

Women are hit especially hard by Alzheimer’s at Alzheimer's Association Alzheimers and Dementia eLetter, no author, March 26, 2014

Excerpt:
"The Alzheimer’s Association’s new 2014 Alzheimer’s Disease Facts and Figures report shows women have a 1 in 6 chance of developing Alzheimer’s, while men have a 1 in 11 chance. Not only are 3.2 million women living with Alzheimer’s, women are also at the epicenter of caregiving for someone with the disease."

Article and video link at:
http://act.alz.org/site/MessageViewer?em_id=146641.0&_ga=1.99246998.944720949.1400630412

Clinical Trials on Alzheimers Disease Conference:


Presentation:
"Dear Colleague,
You can now register for the 7th Clinical Trials on Alzheimer’s Disease (CtaD) to be held in Philadelphia, November 20-22, 2014.

Alzheimer’s disease is one of the most important health challenges facing aging populations worldwide. The development of the next generation of Alzheimer’s disease drugs is becoming essential to face up to this challenge. We learned in San Diego of new pathways identified with biomarkers, facilitating novel trial designs for studies of tau-based therapies and other disease-modifying drugs including immunotherapy.

We are looking forward to making CtaD 2014 scientifically and clinically challenging, be part of this exciting program submit today your abstract for a symposium, oral communication or poster presentation! Deadline is June 10th."

Website at:
http://www.ctad.fr/01-presentation/presentation.asp

FDA Approves Entyvio in Drugs.com, Entyvio, Generic Name: vedolizumab, Date of Approval: May 19, 2014
Company: Takeda Pharmaceutical Company Limited

Excerpt:
The United States Food and Drug Administration (FDA) has approved Entyvio (vedolizumab), a new biologic therapy for the treatment of adults with moderately to severely active ulcerative colitis and Crohn’s disease, conditions marked by inflammation in the lining of the gastrointestinal tract.

Vedolizumab, an integrin receptor antagonist, is a humanized monoclonal antibody that works as a selective adhesion molecule blocker - blocking the interaction of a specific integrin receptor (a4ß7 which is expressed on circulating inflammatory cells) with a specific protein (MAdCAM-1 which is expressed on cells in the interior wall of blood vessels), and thereby blocking the migration of those circulating inflammatory cells across those blood vessels and into areas of inflammation in the gastrointestinal tract. The interaction of the a4ß7 integrin with MAdCAM-1 has been implicated as an important contributor to the chronic inflammation that is a hallmark of ulcerative colitis and Crohn’s disease."

"Important information
Entyvio may cause serious side effects: (see article)


Article at:
http://www.drugs.com/entyvio.html

Elevated levels of tumor necrosis factor alpha and mortality in centenarians in The American Journal of Medicine, Helle Bruunsgaard, MD, PhDemail, Karen Andersen-Ranberg, MD, PhD, Jacob v.B Hjelmborg, MS, PhD, Bente Klarlund Pedersen, DMSc, Bernard Jeune, MD
Received: October 30, 2002; Accepted: April 29, 2003

Abstract"

Background
Aging is accompanied by low-grade inflammation. Tumor necrosis factor (TNF) a initiates the cytokine cascade, and high levels are associated with dementia and atherosclerosis in persons aged 100 years. We hypothesized that TNF-a was also a prognostic marker for all-cause mortality in these persons.

Methods
We enrolled 126 subjects at or around the time of their 100th birthday. Plasma levels of TNF-a, interleukin (IL)-6, IL-8, and C-reactive protein were measured at baseline, and we determined the associations between the markers of inflammation and mortality during the subsequent 5 years.

Results
Only 9 subjects were alive after 5 years. Elevated levels of TNF-a were associated with mortality in both men and women (hazard ratio = 1.34 per SD of 2.81 pg/mL; 95% confidence interval: 1.12 to 1.60, P = 0.001). Levels of IL-6 and IL-8 did not affect survival; levels of C-reactive protein were not associated with mortality when levels of TNF-a were included in the analysis. Dementia and cardiovascular diseases represented the major causes of comorbid conditions at baseline. TNF-a was still associated with mortality in multivariate models that included these parameters as confounders.

Conclusion
TNF-a was an independent prognostic marker for mortality in persons aged 100 years, suggesting that it has specific biological effects and is a marker of frailty in the very elderly.

Article at:
http://www.amjmed.com/article/S0002-9343(03)00329-2/abstract

Bristol-Myers adds a $1.24B deal plus partnership in immuno-oncology deal frenzy in Fierce Biotech, May 27, 2014 | By John Carroll

Excerpt:
"Following fast on the heels of two earlier immuno-oncology partnerships, Incyte has agreed to partner its prolific IDO inhibitor INCB24360 with Bristol-Myers Squibb's marquee PD-1 program for nivolumab. And with just days to go before the start of ASCO, Bristol-Myers ($BMY) also inked a biobucks-packed $1.24 billion deal with South San Francisco-based CytomX to broaden its pipeline of immuno-oncology drugs with up to four new clinical candidates spawned by its next-gen antibody development platform.

The pair of deals highlights how leaders in this field, which includes Bristol-Myers, Merck ($MRK), Roche ($RHHBY) and evidently AstraZeneca ($AZN), are expanding their work in the immuno-oncology arena through a frenzy of new discovery and development deals. Incyte ($INCY) has already partnered INCB24360 with Merck's MK-3475, with AstraZeneca following up just days ago with a deal on MEDI4736, which has only recently entered the spotlight.

With analysts painting cheery pictures of the blockbuster future that awaits the successful survivors of these fast-tracked development programs, the emphasis now is on gearing up as quickly as possible, while proliferizing cancer targets in an industry gold rush.

Like Merck and AstraZeneca, Bristol-Myers is fascinated by the therapeutic potential of marrying an immune checkpoint drug with a therapy--INCB24360--that is designed to spur an immune system attack on cancer cells. Their Phase I/II study, which will explore the combos impact on multiple tumor types, is being co-funded by the two companies with Incyte taking the lead on the work.

"Given the encouraging data for Incyte's IDO1 inhibitor and our current understanding of nivolumab's anti-tumor immune response, we see this as an important area of study to add to our broad clinical development program," said Bristol's Michael Giordano in a statement.



Article at:
http://www.fiercebiotech.com/story/bristol-myers-adds-348m-deal-plus-partnership-immuno-oncology-deal-frenzy/2014-05-27#ixzz32vOufdJI

Mechanisms and secrets of Alzheimer's disease: exploring the brain video at:

Chronic inflammation: An important factor in the pathogenesis of oral cancer in Dentistry IQ, no author, no date


Inflammation and cancer: historical overview:
The association between chronic inflammation with a variety of epithelial malignancies has been recognized since the observation of Virchow,1 who attributed tumor formation to chronic irritation in the 19th century. Examples of inflammatory processes linked with an increased cancer risk include inflammatory bowel diseases and colorectal adenocarcinoma, atrophic gastritis and gastric cancer, cholangiocarcinoma related to chronic cholecystitis, and esophageal carcinoma following reflux esophagitis.2-4 As the concept of inflammation involves reaction to microbial agents, cancers caused by chronic infection, causing chronic inflammation, can be added to this list of examples. These infectious agents include Helicobacter pylori (chronic gastritis linked with adenocarcinoma of stomach and B-cell lymphoma), Epstein-Barr virus (non-Hodgkin lymphoma, Hodgkin lymphoma, nasopharyngeal carcinoma, and natural killer-T cell lymphoma), human papillomavirus (anogenital carcinoma and perhaps oropharyngeal carcinoma), hepatitis B or C virus (hepatocellular carcinoma), human herpesvirus 8 (Kaposi sarcoma), and schistosoma haematobium (squamous carcinoma of urinary bladder).5,6

Article at:
http://www.dentistryiq.com/articles/gr/print/volume-2/issue-1/original-article/chronic-inflammation-an-important-factor-in-the-pathogenesis-of-oral-cancer.html

INFLAMMATION AND BREAST CANCER Breast Cancer Conqueror, no author cited, April 3, 2012

Excerpt:
"The role of Inflammation and Breast Cancer has become abundantly clearer. It has been estimated that 95% of all cancers have a common factor: Inflammation and a protein complex involved in cellular stress called NF-kB.
Think of inflammation in the body as a slow burning fire that is fueled by chronic injuries, stress, toxins and auto immune responses. When this alarm reaction is not slowed down or stopped, the terrain of the body becomes overloaded which creates an environment that supports cancer.
“Interestingly, inflammation functions at all 3 stages of tumor development: initiation, progression and metastasis. Inflammation contributes to initiation. Chronic inflammation appears to contribute to tumor progression by establishing a milieu conducive to development of different cancers.”
-National Cancer Institute (NCI) Inflammation and Cancer Think Tank
A STUDY SPONSORED BY THE NATIONAL CANCER INSTITUTE FOUND THAT WOMEN WHO HAD ELEVATED INFLAMMATORY MARKERS IN THEIR BLOOD, HAD A MUCH POORER PROGNOSIS THAN WOMEN WHO DID NOT HAVE THIS MARKER.
So what causes inflammation that may increase your risk for Breast Cancer?
Smoking and Alcohol
Sleep deficit
Environmental toxins, both in and out of the home
Unhealthy saturated fats, trans fats and too many Omega 6’s
Chronic elevated blood sugar and insulin resistance
Chronic stress
Emotional wounds"

Article at:
http://breastcancerconqueror.com/inflammation-and-breast-cancer/

New Revolutionary Alzheimer Treatment video at:

Bill to put warning label on sugary drinks advances in California in Reuters, BY JENNIFER CHAUSSEE, SACRAMENTO Calif. Fri May 23, 2014

Excerpt:
"(Reuters) - A measure to require sugary soft drinks to carry labels warning of obesity, diabetes and tooth decay advanced in the California state legislature on Friday, the latest move by lawmakers nationwide aimed at persuading people to drink less soda.

The legislation, if enacted, would put California, which banned sodas and junk food from public schools in 2005, in the vanguard of a growing national movement to curb the consumption of high-calorie beverages medical experts say are largely to blame for an epidemic of childhood obesity.

"This is a major victory for public health advocates, community groups, physicians, and dentists,” said Democratic state senator Bill Monning, author of the bill. "By informing consumer choice, we can improve the health of Californians.”

"Efforts to curtail consumption of sugary drinks through taxes and other efforts have met fierce resistance from the U.S. food and beverage industry, which opposes the labeling bill.

Lisa Katic, who testified on behalf of the California Nevada Soft Drink Association in April, said the proposal, while well intentioned, "will do nothing to prevent obesity, diabetes or tooth decay, and may even make problems worse."

According to Katic, the main source of added sugars in American diets are sandwiches and hamburgers, and not sodas or other soft drinks."

My comments:
White bread sandwiches/hamburger buns contain about 30 to 40 grams of sugar (about 7 to 10 teaspoons) and a 12 oz coke contains 39 grams, a 20 oz coke contains 65 grams.---both are bad news for obesity! It's the fructose in sugar and HFCS that metabilizes into fat that is making us fat. Read Fast Food Nation: The Dark Side of the All-American Meal available at Amazon, link is: http://www.amazon.com/Fast-Food-Nation-All-American-Doing-ebook/dp/B003G83UI2/ref=sr_1_2?s=books&ie=UTF8&qid=1401121026&sr=1-2&keywords=fast+foods


Article at:
http://www.reuters.com/article/2014/05/23/us-usa-beverages-california-idUSKBN0E321Z20140523?feedType=RSS&feedName=healthNews

The Role of Chronic Inflammation in Obesity-Associated Cancers in ISRN Oncology, Maria E. Ramos-Nino, Department of Pathology and Department of Medical Laboratory Sciences, University of Vermont, Burlington, VT, USA, 17 April 2013; Accepted 12 May 2013


Abstract:
There is a strong relationship between metabolism and immunity, which can become deleterious under conditions of metabolic stress. Obesity, considered a chronic inflammatory disease, is one example of this link. Chronic inflammation is increasingly being recognized as an etiology in several cancers, particularly those of epithelial origin, and therefore a potential link between obesity and cancer. In this review, the connection between the different factors that can lead to the chronic inflammatory state in the obese individual, as well as their effect in tumorigenesis, is addressed. Furthermore, the association between obesity, inflammation, and esophageal, liver, colon, postmenopausal breast, and endometrial cancers is discussed.

Article at:
http://www.hindawi.com/journals/isrn.oncology/2013/697521/

Alzheimer's Disease: Overview and Current Research video by Allan Levey, MD, PhD, professor and chair of the Department of Neurology at the School of Medicine and director of Emory's Alzheimer's Disease Research Center, talks about the latest research on this crippling disease (April 23, 2013). (one hour video)

Video at:

Obesity and Inflammation: New Insights into Breast Cancer Development and Progression at ASCO University, Neil M. Iyengar, MD, Clifford A. Hudis, MD, and Andrew J. Dannenberg, MD, the Memorial Sloan-Kettering Cancer Center, New York, NY; Weill Cornell Medical College, New York, NY., 2013

Overview:
The importance of inflammation in promoting carcinogenesis and tumor progression is well recognized. Chronic inflammation caused by a variety of infectious agents can lead to the development of several common malignancies. Similarly, inflammatory bowel disease is a well-known risk factor for colorectal cancer. Much less is known about the link between inflammation and the development of breast cancer. Recent data suggest that obesity causes both in-breast and systemic inflammation that contribute to the development and progression of breast cancer. This observation has potentially important implications in terms of prevention and treatment of breast cancer, especially given the rising worldwide overweight and obesity rates. Inflamed white adipose tissue (WAT) within the breast is associated with elevated levels of proinflammatory mediators, enhanced expression of aromatase (the rate-limiting enzyme for estrogen biosynthesis), and increased estrogen receptor-a (ER-a)-dependent gene expression. Systemic consequences of obesity including altered adipokine levels, elevated circulating estrogen levels, and insulin resistance are also believed to play a role in the pathogenesis of breast cancer. Collectively, these findings suggest a significant role for inflammation in the pathogenesis of breast cancer in obese and overweight patients.

Article at:
http://meetinglibrary.asco.org/content/143-132

Inflammation and breast cancer survival at Inflammation and breast cancer survival, no author, no date


Excerpt:
Chronic, low-grade inflammation drives the progression of many cancers, including breast cancer. Researchers observing breast cancer patients in a lifestyle study thus measured biochemical markers of inflammation and correlated it with survival times, to see if the markers could be used to predict disease outcomes. They took blood samples from 734 patients with non-invasive and invasive (stages I-III) breast cancer and measured two proteins, C-reactive protein (CRP) and serum amyloid A (SAA). These proteins were measured approximately 30 months after breast cancer diagnosis. The patients were then observed. Regardless of tumor
stage, age, race, cardiovascular disease or body mass index, high levels of the inflammatory markers were significantly linked with shorter survival. Specifically, the patients with the
highest SAA levels were 3 times as likely to die as patients with lowest SAA, and those with the highest CRP levels were twice as likely to die (hazard ratios were 3.15 and 2.27 respectively).
Thus, these markers of chronic inflammation may be good prognostic predictors in breast cancer. Pierce BL et al. Elevated biomarkers of inflammation are associated with reduced survival among breast cancer patients. J Clin Oncol. 2009, May 26. Epublication.

To summarize: Breast cancer patients with the most elevated levels of blood proteins indicating chronic, low-grade inflammation were 2-3 times more likely to die than those with the low levels.

Globalization of Diabetes, The role of diet, lifestyle, and genes
Frank B. Hu, MD, PHD, Departments of Nutrition and Epidemiology, Harvard School of Public Health, Boston, Massachusetts, and the Department of Medicine, Channing Laboratory, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, June 2011

Abstract:
"Type 2 diabetes is a global public health crisis that threatens the economies of all nations, particularly developing countries. Fueled by rapid urbanization, nutrition transition, and increasingly sedentary lifestyles, the epidemic has grown in parallel with the worldwide rise in obesity. Asia's large population and rapid economic development have made it an epicenter of the epidemic. Asian populations tend to develop diabetes at younger ages and lower BMI levels than Caucasians. Several factors contribute to accelerated diabetes epidemic in Asians, including the “normal-weight metabolically obese” phenotype; high prevalence of smoking and heavy alcohol use; high intake of refined carbohydrates (e.g., white rice); and dramatically decreased physical activity levels. Poor nutrition in utero and in early life combined with overnutrition in later life may also play a role in Asia's diabetes epidemic. Recent advances in genome-wide association studies have contributed substantially to our understanding of diabetes pathophysiology, but currently identified genetic loci are insufficient to explain ethnic differences in diabetes risk. Nonetheless, interactions between Westernized diet and lifestyle and genetic background may accelerate the growth of diabetes in the context of rapid nutrition transition. Epidemiologic studies and randomized clinical trials show that type 2 diabetes is largely preventable through diet and lifestyle modifications. Translating these findings into practice, however, requires fundamental changes in public policies, the food and built environments, and health systems. To curb the escalating diabetes epidemic, primary prevention through promotion of a healthy diet and lifestyle should be a global public policy priority."

Article at:
http://care.diabetesjournals.org/content/34/6/1249.full

Link between inflammation and breast cancer metastases identified, may be treatable in Science Daily, April 1, 2012, Source: American Association for Cancer Research (AACR)

Excerpt:
"The incidence of breast cancer-associated metastasis was increased in animal models of the chronic inflammatory condition arthritis, according to results of a preclinical study presented at the AACR Annual Meeting 2012, held in Chicago March 31 -- April 4. The results indicate that inflammatory cells known as mast cells play a key role in this increase and that interfering with mast cells reduces the occurrence of bone and lung metastases.


"The most devastating aspect of breast cancer is the emergence of tumor cells that grow to distant organs," said Lopamudra Das Roy, Ph.D., research assistant professor at the University of North Carolina in Charlotte, N.C. "It has been reported that sites of chronic inflammation are associated with the establishment and growth of tumor cells.""

Article at:
http://www.sciencedaily.com/releases/2012/04/120401134939.htm

Inflammatory Bowel Disease (IBD) Video (<7 minutes) by Mike Evans MD, June 2013

Excellent cartoon video describing inflammatory IBD ala Chrohn's disease and Ulcerative Colitis (UC)


Video at:

Inflammation in aging processes: an integrative and ecological perspective at Rand.org, Caleb E Finch,
Davis school of Gerontology and Dept Biological Sciences USC College
University of Southern California, 3/19/2010


Introduction:
" This review surveys inflammation during aging and chronic disease in an integrative and ecological perspective that emphasizes generalizable changes, interactions of inflammation with oxidative damage, and environmental influences. Inflammation may be considered a core process of human aging because of its involvement in baseline aging and in the major
degenerative diseases of later life, atherosclerosis, Alzheimer disease, and cancer. Blood levels of C-reactive protein (CRP), IL-6, and other proinflammatory cytokines are risk indicators of
cardiovascular events and mortality. Even in the absence of specific pathological lesions, inflammatory gene expression increases during aging in humans and animal models, in
mammals and in several invertebrate models. Nonetheless, inflammatory mediators are essential to normal function and health, as illustrated by the importance of IL-6 secretion to normal metabolic activities, e.g. IL-6 is released by skeletal muscle in proportion to exercise intensity, while IL-6 also regulates insulin sensitivity of adipocytes (Finch 2007, p. 58).
Many inflammatory changes are highly plastic and influenced by nutrition and physical activity. Inflammation may prove central to therapeutic interventions for specific diseases as
well as to general anti-aging strategies. Moreover, the global spread of obesity and the increasing inflammatory load from polluted air and water may be a limiting factor in future increases in life expectancy. This integrative perspective on inflammation in aging considers all levels of function and causality, from the atomic to cellular to environmental. A leading question is the role of endogenous vs extrinsic factors in the perpetuation of chronic elevations of acute phase
innate immune responses. Outlining these broad domains and links in a concise review necessarily precludes in depth review of most topics and neglects mention of a great amount of excellent relevant science.

Global cost of chronic disease treatment to top $47 trillion by 2030, more than triple current US national debt by: Ethan A. Huff, staff writer (this was written in 2011)

Excerpt:
"NaturalNews) Between now and 2030, the aggregate global cost of treating the five most common, non-infectious diseases -- cancer, diabetes, heart disease, lung disease, and mental health disorders -- will top $47 trillion, according to a new report released by the World Economic Forum (WEF). And experts warn that if nothing is done to curb this escalating healthcare crisis, the global economy will most certainly collapse due to insurmountable financial insolvency.

To put this astronomical $47 trillion figure into perspective, consider the fact that the current US national debt is just under $15 trillion -- this means that at the current rate of growth, global healthcare costs associated with treating just these five diseases will exceed the US national debt by more than 300 percent in less than 20 years.

Put another way, the entire global gross domestic product (GDP), which represents the final value of all goods and services produced, was $63 trillion in 2010. Based on WEF figures, global treatment costs for the "big five" non-communicable diseases will represent a shocking 75 percent of the current global GDP by 2030."



Article at: http://www.naturalnews.com/033651_chronic_disease_expenditures.html#ixzz32lxwBJqA

The Cost of Chronic Diseases On Healthcare at the GSK sponsored website, no date, no author

Article:
"The Financial Cost
"The crisis is clear. Chronic diseases are crushing healthcare.

Our healthcare system is good at treating short-term problems, such as broken bones and infections. Medical advances are helping people live longer. But obesity is reaching epidemic proportions. The population is aging. We need to do a much better job managing chronic diseases.

Chronic conditions such as diabetes, heart disease, lung disease, and Alzheimer’s disease take a heavy toll on health. Chronic conditions also cost vast amounts of money. The trends are going in the wrong direction:

Obesity increases the risk of developing conditions, such as diabetes and heart disease. The rate of obesity in adults has doubled in the last 20 years. It has almost tripled in kids ages 2-11. It has more than tripled in children ages 12-19.2
Without big changes, 1 in 3 babies born today will develop diabetes in their lifetime.3
Average healthcare costs for someone who has one or more chronic conditions is 5 times greater than for someone without any chronic conditions.4
Chronic diseases account for $3 of every $4 spent on healthcare. That’s nearly $7,900 for every American with a chronic disease.1
These chronic diseases drive healthcare costs at an alarming annual rate:

Heart Disease and Stroke: $432 billion/year.5
Diabetes: $174 billion/year.6
Lung Disease: $154 billion/year.8
Alzheimer’s Disease: $148 billion/year.7
The Human Cost
The human cost of chronic diseases cannot be ignored:

Chronic diseases cause 7 out of every 10 deaths.1
Chronic diseases such as diabetes, cancer, and heart disease are the leading causes of disability and death in the US.
About 25% of people with chronic diseases have some type of activity limitation. This includes difficulty or needing help with personal tasks such as dressing or bathing. It may also mean being restricted from work or attending school.9
Today, Americans suffering from chronic diseases face rising healthcare costs. They also receive lower quality care and have fewer options.
Health insurance co-pays and out-of-pocket expenses continue to rise. In many cases, choices and care are limited.
The disabling and long-term symptoms that often come with chronic diseases add to extended pain and suffering. This decreases the overall quality of life.
We must face the epidemic of chronic diseases. If we don’t, the human costs will continue to soar. We might even face a lack of available or affordable care when it is needed most.

The financial and human costs of chronic diseases can no longer be ignored."



Article at:
http://www.forahealthieramerica.com/ds/impact-of-chronic-disease.html

Making Prevention Popular at TEDMED, January 17 2013 (One hr video)

Excerpt:
"America spends $2 trillion a year on healthcare — mostly treating people after they become sick. How can we unlock prevention as a trillion-dollar business in America so we spend less on “sick care” and get Americans to “buy” healthy lifestyles?"

Video at:
http://www.tedmed.com/greatchallenges/liveevent/277479


My comments:
Some excellent and interesting ideas proposed and occurring today (Especially watch the last 5 minutes-incentives) Though the focus is on 'lifestyle' changes, is Anatabine part of the 'prevention'? Is it part of the 'upstream' solution?---knowing the reality of our current condition.(ie keeping chronic inflammation in check) Could Anatabine be part of the solution to prevent autoimmune disorders, cardiovascular disease, cancers, and aging. So, what's that worth? Shouldn't insurance companies focus more on promoting the reduction of the chronic inflammatory conditions? ie 'reward' for staying healthy. With insurance and medical costs continuing to spiral upwards for 'sick care' at an alarming rate, when do we reach the 'unaffordable' point? Maybe we are already there? We need to take back our health!

The Next Big Thing? Medicine! in MedCrunch by LUKAS ZINNAGL on Mar 7, 2011

Article:
"Have you ever heard of a person that goes by the name of Nikolai Kondratiev? If you are not into macro economic theories and global economics then you probably have never heard about him. You actually also don’t need to, but let us give you a quick overview of Kondratiev’s primary research interest.

In economics there is a phenomenon that has been described as the Kondratiev wave. Those are “long waves” that last for around sixty years and describe the future and past economical changes for capitalistic structures in a sinusidial way. Those superficial waves are the combined output of several decades of resarch and economic shifts in a certain economic market. In economics these waves are also predictable to a certain extent and have proven to be correct when looking into the past of recent decades. A rough chronolocial order of these types of market segments is

1800 – steam, cotton, engine

1850 – railway, steel

1900 – electrical, chemical, engineering

1950 – petrochemicals, automobiles

1990 – information, technology

As you can see these vast correlations do make sense and at least for the 1990s we can say that it’s absolutely correct. The biggest thing that happened to the world starting in the 90s has been the arrival of the personal computer and bits and bytes as our mode of work and life. It changed everything and it is still ongoing with the internet as the most recent addition to 1990's Kondratiev wave transforming industries and lives.

Now there are a lot of smart people out there, from philosophers to economists, who are trying to understand the mechanisms of these long sinusoidal “K-waves” by looking at the data and extrapolating it for future industries. Many researchers and also Team MedCrunch are pretty sure that the industry, which will be next in this cycles is medicine. Medicine has been practiced the way it is now for hundreds of years. Elements that have transformed medicine are all part of former K-waves such as chemical and engineering in the 1950s or with information technology in the 1990s. Medicine itself has not transformed. It’s underlying principles remain untouched and whereas the surroundings we act in change, healthcare and medicine are pretty old-fashioned.

If medicine happens to be what information technology has been for the last decades – transformative, disruptive and powerful – then we, as physicians and medical thinkers, should be happy to live in these times. At the same time it should be an endavour and personal venture to actively shape this economic wave and truly bring medicine to a completely new level and significance for the world."

Article at:
http://www.medcrunch.net/big-medicine/

Pharmaceuticals: Companies Will Focus On External Partnerships To Improve Productivity in Chemical and Engineering News, By Lisa M. Jarvis, January 14, 2013

Article:
"If the buzzword for the pharmaceutical industry in 2012 was “patent cliff,” the key theme for 2013 is “partnership.” With smaller R&D organizations and budgets, drug companies are putting more emphasis on working relationships with biotech firms or with academia.
“Everything we hear, everyone we talk to, has one word. It’s ‘collaboration',?” says Patrick Flochel, global pharmaceutical leader for the consulting firm Ernst & Young. The urge to partner is driven by a desire to share risk and lower research costs while at the same time improving productivity.
Partnerships are extending across the entire life cycle of a drug, Flochel notes, from precompetitive collaborations related to elucidating targets all the way to commercial relationships that leverage a partner’s marketing network. They run the gamut from deeper ties with academic institutions—such as Biogen Idec’s new academic consortium to identify treatments for amyotrophic lateral sclerosis—to more pacts with biotech companies and consortia with governments, nonprofits, and other drug firms.
The focus on collaboration comes as drug companies try to move beyond several years of patent expirations on some of their biggest selling products. Along with the patent losses came overhauls to drug company R&D organizations and painful job cuts. In 2013, industry observers expect, companies will focus on executing new R&D strategies. They say the worst of the pharma layoffs is likely over.
While trying to make their own research efforts more productive, companies are filling gaps in their drug pipelines through acquisitions. Merger and acquisition activity in 2013 should keep to the tone set last year: modest purchases and an emphasis on mitigating risk. Transactions will be creative, with drug firms offering less money up front but promising bigger benefits as a project reaches key milestones, notes Michael Latwis, an analyst with the health care consultancy Decision Resources.
Industry experts say big pharma companies will continue to shun megamergers like those seen in 2009. An exception may be AstraZeneca, which lost its patent for the antipsychotic drug Seroquel and was hit hard by generics competition. “AstraZeneca is in a pretty dire situation,” Latwis says. Last year, Pascal Soriot, former chief operating officer of Roche’s pharmaceutical business, took on the unenviable task of turning AstraZeneca around after the ouster in March of CEO David Brennan. Soriot “hasn’t ruled anything out yet,” Latwis notes, and industry watchers are awaiting an update on the company’s strategy that’s expected at the end of January."

Article at:
http://cen.acs.org/articles/91/i2/Pharmaceuticals-Companies-focus-external-partnerships.html

Experimental autoimmune encephalomyelitis (EAE) as a model for multiple sclerosis (MS) in PubMed, Constantinescu CS1, Farooqi N, O'Brien K, Gran B., Division of Clinical Neurology, School of Clinical Sciences, University of Nottingham, Queen's Medical Centre, Nottingham, UK.

Abstract:
"Experimental autoimmune encephalomyelitis (EAE) is the most commonly used experimental model for the human inflammatory demyelinating disease, multiple sclerosis (MS). EAE is a complex condition in which the interaction between a variety of immunopathological and neuropathological mechanisms leads to an approximation of the key pathological features of MS: inflammation, demyelination, axonal loss and gliosis. The counter-regulatory mechanisms of resolution of inflammation and remyelination also occur in EAE, which, therefore can also serve as a model for these processes. Moreover, EAE is often used as a model of cell-mediated organ-specific autoimmune conditions in general. EAE has a complex neuropharmacology, and many of the drugs that are in current or imminent use in MS have been developed, tested or validated on the basis of EAE studies. There is great heterogeneity in the susceptibility to the induction, the method of induction and the response to various immunological or neuropharmacological interventions, many of which are reviewed here. This makes EAE a very versatile system to use in translational neuro- and immunopharmacology, but the model needs to be tailored to the scientific question being asked. While creating difficulties and underscoring the inherent weaknesses of this model of MS in straightforward translation from EAE to the human disease, this variability also creates an opportunity to explore multiple facets of the immune and neural mechanisms of immune-mediated neuroinflammation and demyelination as well as intrinsic protective mechanisms. This allows the eventual development and preclinical testing of a wide range of potential therapeutic interventions."

Article at:
http://www.ncbi.nlm.nih.gov/pubmed/21371012



Amelioration of experimental autoimmune encephalomyelitis by anatabine.
Paris D1, Beaulieu-Abdelahad D, Mullan M, Ait-Ghezala G, Mathura V, Bachmeier C, Crawford F, Mullan MJ.
Author information
1Roskamp Institute, Sarasota, Florida, United States of America.

Abstract:
"Anatabine, a naturally occurring alkaloid, is becoming a commonly used human food supplement, taken for its claimed anti-inflammatory properties although this has not yet been reported in human clinical trials. We have previously shown that anatabine does display certain anti-inflammatory properties and readily crosses the blood-brain barrier suggesting it could represent an important compound for mitigating neuro-inflammatory conditions. The present study was designed to determine whether anatabine had beneficial effects on the development of experimental autoimmune encephalomyelitis (EAE) in mice and to precisely determine its underlying mechanism of action in this mouse model of multiple sclerosis (MS). We found that orally administered anatabine markedly suppressed neurological deficits associated with EAE. Analyses of cytokine production in the periphery of the animals revealed that anatabine significantly reduced Th1 and Th17 cytokines known to contribute to the development of EAE. Anatabine appears to significantly suppress STAT3 and p65 NF?B phosphorylation in the spleen and the brain of EAE mice. These two transcription factors regulate a large array of inflammatory genes including cytokines suggesting a mechanism by which anatabine antagonizes pro-inflammatory cytokine production. Additionally, we found that anatabine alleviated the infiltration of macrophages/microglia and astrogliosis and significantly prevented demyelination in the spinal cord of EAE mice. Altogether our data suggest that anatabine may be effective in the treatment of MS and should be piloted in clinical trials."


Article at:
http://www.ncbi.nlm.nih.gov/pubmed/23383175

My comments:
These article suggest that a clinical trial for MS could be coming.

BTW, I took your advice and e-mailed the following to STSI:

http://grants.nih.gov/grants/guide/pa-files/PAR-13-233.html

Chronic Inflammation and Age-related Disease (R01), Funding Opportunity Announcement (FOA) Number: PAR-13-233 Funding Application by Department of Health and Human Services, Posting date: May 30, 2013, Start submission date: September 5, 2013, Expiration date: September 8, 2014

FUNDING OPPORTUNITY PURPOSE:
"The participating NIH Institutes and Centers invite applications to address both the origins and the effects of low level chronic inflammation in the onset and progression of age-related diseases and conditions. Chronic inflammation, as defined by elevated levels of both local and systemic cytokines and other pro-inflammatory factors, is a hallmark of aging in virtually all higher animals including humans and is recognized as a major risk factor for developing age-associated diseases. The spectra of phenotypes capable of generating low-level chronic inflammation and their defining mediators are not clear. Further, a clear understanding of how chronic inflammation compromises the integrity of cells or tissues leading to disease progression is lacking. The role of dietary supplements and/or nutritional status in chronic inflammation in age-related disease is also poorly studied. Thus, there is a critical need to establish the knowledge base that will allow a better understanding of the complex interplay between inflammation and age-related diseases. Applications submitted to this FOA should aim to clarify the molecular and cellular basis for the increase in circulating inflammatory factors with aging, and/or shed light on the cause-effect relationship between inflammation and disease, using pre-clinical (animal or cellular based) models."

"Background
A central molecular feature of acute inflammation is the production, primarily by innate immune cells, of cytokines, chemokines, and other inflammatory molecules that often expand the response from its tissue of origin to a systemic level. There is considerable epidemiological evidence indicating that aging is associated with a chronic increase in circulating levels of several of these same effectors, including IL-6, TNF-alpha and CRP. The age-related increase in circulating levels of these mediators is generally several orders of magnitude lower than that observed during the classical acute inflammation that occurs in response to injury or infection. In contrast, however, it is significantly longer in duration, often measured in years rather than hours.

Chronic inflammation has been linked to major age-related changes including physical frailty, energy imbalance, homeostatic dysregulation, and changes in body composition which in turn are believed to underlie many of the chronic diseases and conditions affecting the elderly. Indeed, chronic inflammation has been linked to many age-related chronic diseases including neurodegeneration, Alzheimer’s disease, atherosclerosis, cancer, sarcopenia, kidney and lung diseases, metabolic syndrome, diabetes and many others.

Several critical questions remain unanswered, including the cellular origin of the inflammatory mediators and their role in age-related disease, either as causative agents or as a consequence of tissue damage, or whether both are interconnected by a more complex linkage. The role of dietary supplements and/or nutritional status on chronic inflammation is also of interest but poorly studied. It has been proposed that poor immune function, persistent infections (e.g., by CMV or HIV), and breakdown of the intestinal barrier during aging could lead to chronic activation of the innate immune system. In addition, research has shown that pro-inflammatory cytokines can be produced both by senescent cells present in many tissues (and often in higher abundance at sites of injury) and by pre-adipocytes present in fat depots, which also tend to increase with age. At the sub-cellular level, several potential drivers should be examined, including the NF-kB pathway, free radicals, or autophagy. The degree to which each cell type contributes to chronic inflammation at different sites and in relation to different chronic diseases is another open question. Similarly, the role of inflammatory mediators might vary with each specific chronic disease and this also needs to be addressed.

Perhaps the most critical need is to fully understand the potential effects, both positive and negative, of blocking the inflammatory state on different age-related diseases and conditions. While there is epidemiological evidence suggesting a causative role for chronic inflammation in age-associated disease onset and progression, the evidence is still inconclusive. Several clinical trials are currently in progress that will address whether reducing the inflammatory state can affect outcomes (cardiovascular, diabetes and others) in individuals with otherwise comparable classical risk factors for those diseases, yet even the necessary basic understanding of the biology behind these approaches is incomplete.

Purpose
This FOA aims to clarify the molecular and cellular basis for the increase in circulating inflammatory factors with aging, and to shed light on the cause-effect relationship between inflammation and disease, using pre-clinical (animal or cellular-based) models.

Areas of Research Interest
The focus of this FOA is on understanding the basic molecular and cellular mechanisms that link aging with inflammation and chronic diseases. The long term view is to better inform clinical trials and eventually interventions that will directly benefit humankind, but clinical trials are not the focus of this FOA. Experimental approaches might include ablation of relevant aspects of the chronic inflammatory state, comparative biology, expression profiles, or others. Examples of responsive areas of research include, but are not limited to:

Develop novel technologies and/or approaches that increase the ability to measure low level inflammation in the context of aging organisms.
Identification of the origin of the pro-inflammatory state associated with aging.
Further definition of the signature of chronic (as opposed to acute) inflammation in humans or animal models.
Investigations on the role of chronic inflammation in immune-privileged tissues such as the brain.
Studies on the role of inflammation on general conditions of aging (frailty, resilience) that predispose to diseases or conditions.
Studies on the crosstalk between inflammation and tissue metabolic or physiological function.
Identification of feedback loops and cross-talk between disease and inflammation.
Possible trade-offs involved in approaches that diminish or eliminate the pro-inflammatory state of aging.
In animal models, testing the effect of anti-inflammatory interventions on the development of age-related diseases and conditions.
In addition to these common areas of interests, the participating Institutes and Centers (ICs) are interested in the following areas of research:

Office of Dietary Supplements (ODS):

Studies on the role of dietary supplements and/or nutritional status in the chronic inflammation and age related diseases.

National Institute on Alcohol Abuse and Alcoholism (NIAAA):

Many diseases associated with chronic alcohol consumption overlap with those associated with aging, including neurodegeneration, lung infection, muscle wasting, cardiovascular diseases, diabetes, and some cancers. Chronic alcohol consumption leads to chronic elevation of inflammatory markers in circulation. Therefore, NIAAA proposes the following topic areas:

Characterization of inflammatory mediator profiles associated with aging in the presence and absence of chronic alcohol consumption and expansion of this profile to include more specific and stable markers in the general population. Examination of the relationship between aging and excessive alcohol on chronic inflammatory markers and whether these effects are additive or synergistic would be of interest.
Investigations on the cellular origin of the inflammatory mediators in age-related inflammation, compared and contrasted with alcohol-related inflammation.
Comparisons between mechanisms associated with the increased susceptibility to pneumonia due to aging or as a consequence of chronic alcohol intake.
The role of subclinical inflammation and oxidative stress in muscle wasting and comparisons between age-related vs alcohol-related sarcopenia.

National Institute of Allergy and Infectious Diseases (NIAID):

Studies to understand the links between age-related adiposity, low-level chronic inflammation, and immune system dysfunction in the elderly.
Mechanisms by which incomplete resolution of an immune response to infection contributes to age-related chronic inflammation.
Effects of increased levels of reactive oxygen species, declines in anti-oxidant capacity, and/or activation of the innate immune response on age-associated chronic inflammation.
Determine the mechanisms by which chronic inflammation contributes to immune system dysfunction associated with aging, such as poor immune responses to infections and/or vaccines, and increased incidence of immune-mediated disease.
Identification of mechanisms or pathways that could be targeted to prevent or reverse chronic immune activation in HIV-infected individuals on suppressive antiretroviral therapy.
National Institute of Environmental Health Science (NIEHS):

Studies that identify the role of environmental exposures in initiating and/or sustaining a chronic inflammatory state.
Studies that focus on genetic susceptibility to chronic inflammation and its interaction with environmental exposure in determining risk or protection from age-related diseases or disorders.
National Center for Complementary and Alternative Medicine (NCCAM):

Studies to elucidate molecular targets using non-nutritional natural products that likely modulate the effects of inflammation-induced pain in the elderly. With NCCAM has a special interest in projects that address the following program areas:

Natural product modulators of inflammation-induced pain that elucidate novel mechanisms of action, including analgesic or noxious stimuli (plant derived analgesics, marine neurotoxins, venoms).
Anti-inflammatory properties of probiotics in immunosenescence and pain in the elderly.
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS):

The role of chronic inflammation in the pathophysiology, etiology and progression of diseases or conditions in the NIAMS mission area, including (and not limited to) osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, systemic lupus erythematosus, scleroderma, psoriasis, alopecia areata, wound healing. (NIAMS webpage/long range plan: http://www.niams.nih.gov/About_Us/Mission_and_Purpose/long_range.asp)

National Institute of Child Health and Human Development (NICHD):

NICHD is interested in how the inflammatory cytokines generated by adipocytes and by macrophages embedded in the fat mass as a result of childhood obesity can accelerate the appearance of diseases associated with aging, especially T2DM, now commonly seen in adolescence, and atherosclerotic plaques in the third decade.

National Heart, Lung, and Blood Institute (NHLBI):

Investigation into the influence of chronic inflammation associated with aging on the development, etiology and progression of diseases within the NHLBI mission, including (and not limited to) hypertension, aneurysm, lymphatic disease, peripheral vascular disease, atherothrombosis, coronary artery disease, heart failure, idiopathic pulmonary fibrosis (IPF), asthma, chronic obstructive pulmonary disease (COPD), lung vascular disease, anemia, venous thromboembolism (VTE), and chronic inflammatory complications as a function of age that develop in patients following blood transfusion or hematopoietic stem cell transplantation (HSCT), or with hemoglobinopathies.

National Cancer Institute (NCI):

Studies that define mechanistically how aging-associated inflammation causes cancer initiation, progression, or affects the tumor microenvironment.
Studies that identify or characterize how etiological factors such as viruses, the microbiota, or chemical exposures influence inflammation-mediated tumorigenesis in aging individuals or models."

Application Guide/Instructions at:
http://grants.nih.gov/grants/guide/pa-files/PAR-13-233.html

Key to extending human lifespans lies in preventing chronic inflammation, research suggests, Dr. James Aw | February 26, 2014 Dr. James Aw is the medical director of the Medcan Clinic, a leading private health clinic in Toronto|

Excerpts:
"Why can some people smoke a pack a day and never get lung cancer? Why do 50% of the people who get heart attacks have normal levels of cholesterol? The emerging field of epigenomics is at the heart of the biggest mysteries in medicine."

"Last week, I was at a medical conference in New Orleans when I heard a talk by Dr. Muin J. Khoury, the director of public health genomics at the U.S. Centers for Disease Control and Prevention in the United States. Part of Khoury’s work involves epigenomics, or the interplay between environment and the body’s genes — why some people’s genes turn on in certain situations, while others do not.

Dr. Khoury’s research got me thinking about one of epigenomic’s most exciting frontiers: why some people are able to stay healthy until the age of 100 — and why others die of old age in their eighties.

Many researchers now believe the answer involves the body’s inflammatory response. Inflammation is one of the processes that is key to the body’s healing cycle. Think of what happens when a puck hits you in the face during a game of shinny. Your eye swells shut, and the tissue around it gets swollen and hot as the body goes into overdrive to repair the damage. Many things besides a hockey puck can trigger this inflammatory response — often it’s an infection. And once the body has fought off the infection, or repaired the damage, the inflammatory response is supposed to turn off."

"Research is showing that maintaining control over the body’s inflammatory response can help us to live longer"

"But as we get older, most of us grow worse at regulating the inflammatory response. We lapse into a state of chronic inflammation, or “inflamm-aging,” that isn’t precipitated by injury or disease. The body persists in an ongoing state of high alert, a bit like the multicoloured terrorist attack threat levels instituted by the U.S. Homeland Security Department. The inflamm-aging process sees cytokines, proteins the immune system typically uses to protect the body from harm, actually damaging the body’s ability to stay healthy — triggering aging"

"Removing ‘deadbeat’ cells that stop functioning but nevertheless continue to live may open the door to future treatments that extend lifespans in humans"


"Could a customized diet help regulate the chronic inflammatory response? And would that, in turn, help more people to live well to the age of 100?"

"Today, clinical medicine is beginning to harness and control the chronic inflammatory process. By testing levels in the blood of a substance called hsCRP, we can now assess whether a given patient is experiencing acute inflammation — and the future is likely to bring us more sophisticated testing of chronic inflammation with such biomarkers as interleukin, insulin growth factor and tumour necrosis factor."

Article at:
http://life.nationalpost.com/2014/02/26/dr-aw-key-to-extending-human-lifespans-and-slowing-aging-lies-in-preventing-treating-chronic-inflammation-in-the-body-research-suggests/

How we grow old_How to prevent growing old, Published on Apr 1, 2013
(BBC Documentary) One hour video at:

Chronic Inflammation Could Hinder Your Chances Of Healthy Aging in HuffPost Healthy Living, Posted: 09/19/2013 , no author

Article:
"Chronic inflammation lowers your chances of aging disease-free, a new study suggests.

European researchers found that people who had higher levels of interleukin-6, a marker of inflammation, were less like to stay disease-free 10 years later.

"Chronically high levels of interleukin-6 halved the odds of successful aging 10 years later and was associated with increased odds of future cardiovascular disease and death from noncardiovascular causes in a dose–response fashion," researchers wrote in the study. "These associations were independent of socioeconomic factors, health behaviors (smoking, physical activity), conditions such as obesity, acute inflammation and use of anti-inflammatory drugs."

The study, published in the Canadian Medical Association Journal, included 3,044 people ages 35 to 55 who worked in government service in London, who were part of the Whitehall II study. The researchers measured their interleukin-6 levels about five years apart, and analyzed the potential association these levels had on heart disease, non-heart-related deaths, and healthful aging over the next 10 years.

By the end of the 10-year follow-up period, 24 percent of the participants had experienced healthy aging (without any diseases or disability), 11 percent experienced heart disease (fatal and nonfatal), 5 percent died from another kind of disease, and 61 percent experienced normal aging (which consisted of everyone else who didn't fall under these three other categories).

Indeed, researchers found associations between having low interleukin-6 levels at the start of the study and having better odds of experiencing healthy aging 10 years later.

It should be noted that not all inflammation is bad; it is, after all, our body's natural defense against infection and injury. Chronic inflammation, on the other hand, has been tied to a whole host of health problems, including diabetes, cancer and depression."

Article at:
http://www.huffingtonpost.com/2013/09/19/chronic-inflammation-aging-healthy-disease_n_3922967.html