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Depression with diabetes may speed mental decline BY VERONICA HACKETHAL, MD, NEW YORK Fri Aug 23, 2013
My comments: Anatabloc is a monoamine oxidase inhibitor. "Monoamine oxidase inhibitors (MAOIs) are chemicals which inhibit the activity of the monoamine oxidase enzyme family. They have a long history of use as medications prescribed for the treatment of depression. They are particularly effective in treating atypical depression.[1] They are also used in the treatment of Parkinson's Disease and several other disorders." (Wikipedia)
Excerpts:
"(Reuters Health) - In a study of middle-aged and older people with type 2 diabetes, declines in thinking and memory that are often linked to later dementia happened faster in those who were depressed compared to those who were not.
Over less than four years, U.S. and Canadian researchers saw significant differences between depressed and non-depressed diabetes patients in the erosion of a wide range of cognitive abilities.
"Depression appears to be an important risk factor for dementia and cognitive decline among patients with diabetes," Dr. Mark Sullivan, professor of psychiatry at the University of Washington and lead author of the study, told Reuters Health in an email.
Both diabetes and depression have been found to raise the risk of Alzheimer's disease and other forms of dementia later in life. But whether depression is a cause or an effect of cognitive decline remains unclear.
Diabetes can damage organs, especially the kidneys, eyes, nervous system and brain. The disease also raises a person's risk for having a cardiovascular "event" such as a heart attack or stroke.
More than one-quarter of Americans older than age 65 have diabetes, according to the Centers for Disease Control and Prevention. An estimated 6.5 million Americans in this age group suffer from depression, according to the National Alliance for Mental Illness."
"Depression itself is associated with increases in stress hormones, inflammation and other processes that could directly contribute to cognitive decline, Sullivan said. But the array of other diseases that often go along with diabetes may also harm cognition and promote depression.
People with diabetes are at higher risk for vascular dementia, for example, which develops when blood supply to parts of the brain is cut off, often during a series of unnoticed "mini-strokes" that cause brain cells to die. Depression might be an early symptom of vascular disease in the brain, which later develops into dementia.
"My clinical experience is that dementing illness like Alzheimer's disease and vascular dementia commonly present to the primary care clinician and mental health professional with depressive symptoms," Nathanson, who is also a clinical assistant professor of psychiatry, wrote in an email.
Vascular dementia is different from Alzheimer's disease, which causes the majority of dementia cases in the U.S. and forms characteristic plaques in the brain.
One implication of this study, Nathanson said, is that primary care physicians would do well to pay attention to and treat depression in people with chronic illnesses like diabetes."
Article at:
http://www.reuters.com/article/2013/08/23/us-health-depression-diabetes-dementia-idUSBRE97M0KQ20130823
Intercept liver drug meets main goal in study, shares quadruple
BY VRINDA MANOCHA, Thu Jan 9, 2014 in Reuters News
Excerpt:
"Intercept Pharmaceuticals Inc's drug to treat liver disease caused by fat buildup was found effective in a trial, paving the way for it to become the first approved treatment for the chronic condition.
The company's shares nearly quadrupled to a life high of $305 on Thursday morning on the Nasdaq, valuing the company at about $6 billion.
Intercept said it had stopped the trial after the drug showed statistically significant improvement in patients, compared with a placebo, in a review by an independent safety committee.
The trial tested the drug, obeticholic acid, in patients with non-alcoholic steatohepatitis (NASH), a form of liver inflammation."
Article at:
http://www.reuters.com/article/2014/01/09/us-intercept-study-liverdiseasedrug-idUSBREA080ME20140109
50% of Americans take prescription drugs by Nadia Kounang - CNN Medical Producer, May 14th, 2014 at CNN Health
About half of all Americans take at least one prescription drug each month, and 10% take more than four, according to a new government report.
"Health, United States, 2013" is an annual report on the nation’s health prepared by the Centers for Disease Control and Prevention's National Center for Health Statistics. This year’s report includes a special section on prescription drugs.
Here are a few key facts from that section:
We spend a lot on prescription drugs. In 2011, Americans spent $263 billion on prescription drugs, which accounts for 9.7% of all national health expenditures (up from 5.6% in 1990).
Pharmaceutical companies aren't relying on doctors to sell their pills. Spending on direct-to-consumer advertising for all drugs more than tripled between 1996 and 2005 to $4.2 billion, according to the report.
Americans are depressed. Adults' use of antidepressants increased more than fourfold between the years of 1988-94 and 2007-10, from 2.4% to 10.8%.
Doctors are prescribing fewer useless antibiotics. Antibiotics prescribed during medical visits for cold symptoms declined 39% between 1995-96 and 2009-10. That's good news, as the overuse and misuse of antibiotics is contributing to antibiotic resistance worldwide and limiting our arsenal to fight infections.
Sinus infection? Antibiotics won't help
The prescription drug death epidemic is a big problem. Consumption of pain medications called opioid analgesics increased 300% between 1999 and 2010, and death rates in people age 15 and older involving these drugs more than tripled between 2000 and 2010.
Article at:
http://thechart.blogs.cnn.com/2014/05/14/50-of-americans-take-prescription-drugs/?iref=allsearch
Follow the money---Nutraceuticals vs Prescription drugs (no article)
Nutraceuticals Market to Reach $204.8 Billion by 2017 - See more at: http://www.nutraceuticalsworld.com/issues/2013-09/view_industry-news/nutraceuticals-market-to-reach-2048-billion-by-2017/#sthash.ChKg2bDr.dpuf
The worldwide market for prescription drugs is forecast to reach almost $900 billion by 2015, according to research from Global Industry Analysts.
(in Report Linker at: http://www.reportlinker.com/ci02264/Prescription-Drug.html)
AstraZeneca trumpets diabetes duo's victory in Phase III, May 13, 2014 | By Tracy Staton in FiercePharma
My comments:
Amazing what they say is great news on new diabetes drugs. Improvements is about 1.5% and improvements in fractions of percent deemed good news----grasping for straws? (non-diabetics <5.7, pre-diabetic 5.7 to 6.4, diabetic greater than 6.5) Are they cherry-picking the data? <7.0 is good?
Excerpts:
"While its top executives were prepping for a hearing on Pfizer's ($PFE) megamerger offer, AstraZeneca ($AZN) rolled out new data from a diabetes trial. The verdict? A combination of the company's two diabetes pills, Onglyza and Farxiga, bested either drug alone.
The three-arm, 534-patient trial compared metformin plus the duo against metformin plus Farxiga (dapagliflozin) and metformin plus Onglyza (saxagliptin), in patients who weren't getting adequate blood sugar control from metformin alone.
After 24 weeks of therapy, a key measure of blood glucose, HbA1c, fell an average of 1.47% in patients who took both drugs, compared with 1.2% in the Farxiga group and less than 1% in the Onglyza group. Plus, more patients in the combo group hit their blood sugar goal of less than 7% HbA1c: 41%, compared with 18% in the Onglyza group and 22% in the Farxiga group."
"the company is depending on diabetes to help fuel growth as it fights back from the loss of patent protection on its blockbuster antipsychotic Seroquel and braces for generic rivals to the big-selling stomach drug Nexium, set to appear this month. Another of its top sellers, the cholesterol fighter Crestor, faces generic competitors in 2016 under a patent settlement.
Article at:
http://www.fiercepharma.com/story/astrazeneca-trumpets-diabetes-duos-victory-phase-iii/2014-05-13#ixzz31z9ZvBEe
Toxic Sugar?---Inflammation in spades! YOU MUST WATCH THIS 20 MINUTE VIDEO, for the sake of your health and life.
Video at:
Diets rich in antioxidant resveratrol fail to reduce deaths, heart disease or cancer, May 13, 2014 in Fierce Biotech Research
Excerpts:
"A study of Italians who consume a diet rich in resveratrol -- the compound found in red wine, dark chocolate and berries -- finds they live no longer than and are just as likely to develop cardiovascular disease or cancer as those who eat or drink smaller amounts of the antioxidant."The story of resveratrol turns out to be another case where you get a lot of hype about health benefits that doesn't stand the test of time," says Richard D. Semba, M.D., M.P.H., a professor of ophthalmology at the Johns Hopkins University School of Medicine and leader of the study described May 12 in JAMA Internal Medicine. "The thinking was that certain foods are good for you because they contain resveratrol. We didn't find that at all."
"Despite the negative results, Semba says, studies have shown that consumption of red wine, dark chocolate and berries does reduce inflammation in some people and still appears to protect the heart. "It's just that the benefits, if they are there, must come from other polyphenols or substances found in those foodstuffs," he says. "These are complex foods, and all we really know from our study is that the benefits are probably not due to resveratrol."
Article at:
http://www.fiercebiotechresearch.com/press-releases/diets-rich-antioxidant-resveratrol-fail-reduce-deaths-heart-disease-or-canc#ixzz31trJbApk
U.S. regulator rejects Novartis heart failure drug in Reuters News
ZURICH Fri May 16, 2014 8:34am EDT, Reporting by Caroline Copley; Editing by Mark Potter
Article:
"(Reuters) - U.S. health regulators turned down an application to approve Novartis' experimental heart failure drug due to insufficient evidence that it improves symptoms, the Swiss drugmaker said on Friday.
Novartis said in a statement the Food and Drug Administration (FDA) had asked for further evidence to determine the efficacy of serelaxin, also known as RLX030.
The decision follows a unanimous recommendation from a panel of advisers in March against approving the drug.
Serelaxin is one of several potential "blockbuster" drugs the Basel-based pharmaceutical company is looking to as it bets on cancer, heart and respiratory treatments to fill the gaps left by patent expiries on drugs such as Diovan, which lost U.S. patent rights and faces generic competition.
Tim Wright, global head of development at Novartis, said Novartis still believed serelaxin had the potential to become "an important treatment" for acute heart failure.
Novartis is continuing with its clinical trial programme in order to build up a further body of evidence and plans to enrol over 6,300 patients in a second late-stage trial, the company said.
About five million people in the United States are living with chronic heart failure, a progressive weakening of the heart, according to Novartis. About one million are hospitalized with episodes of acute heart failure, and about 22 percent of patients who are hospitalized die within a year."
Article at:
http://www.reuters.com/article/2014/05/16/us-novartis-serelaxin-idUSKBN0DW0YM20140516?feedType=RSS&feedName=healthNews
RAGE (receptor)From Wikipedia, the free encyclopedia, no author, no date
Excerpts:
"RAGE, the Receptor for Advanced Glycation Endproducts is a 35kD transmembrane receptor of the immunoglobulin super family which was first characterized in 1992 by Neeper et al.[1] It is also called "AGER". Its name comes from its ability to bind advanced glycation endproducts (AGE), which include chiefly glycoproteins, the glycans of which have been modified non-enzymatically through the Maillard reaction. In view of its inflammatory function in innate immunity and its ability to detect a class of ligands through a common motif, RAGE is often referred to as a pattern recognition receptor. RAGE also has at least one other agonistic ligand: high mobility group protein B1 (HMGB1). HMGB1 is an intracellular DNA-binding protein important in chromatin remodeling which can be released by necrotic cells passively and by active secretion from macrophages, natural killer (NK) cells and dendritic cells.
The interaction between RAGE and its ligands is thought to result in pro-inflammatory gene activation.[2] Due to an enhanced level of RAGE ligands in diabetes or other chronic disorders, this receptor is hypothesised to have a causative effect in a range of inflammatory diseases such as diabetic complications, Alzheimer's disease and even some tumors."
"RAGE and disease[edit]
RAGE has been linked to several chronic diseases, which are thought to result from vascular damage. The pathogenesis is hypothesized to include ligand binding, upon which RAGE signals activation of nuclear factor kappa B (NF-?B). NF-?B controls several genes involved in inflammation. RAGE itself is upregulated by NF-?B. Given a condition in which there is a large amount of RAGE ligands (e.g. AGE in diabetes or amyloid-ß-protein in Alzheimer's disease) this establishes a positive feed-back cycle, which leads to chronic inflammation. This chronic condition is then believed to alter the micro- and macrovasculature, resulting in organ damage or even organ failure. Diseases that have been linked to RAGE are:[citation needed]
Atherosclerosis
Peripheral vascular disease
Myocardial infarction
Congestive heart failure
Diabetic retinopathy
Diabetic neuropathy
Diabetic nephropathy
Alzheimer's disease
Psoriasis"
Article at:
http://en.wikipedia.org/wiki/RAGE_(receptor)
Role of NF-kappa B in the pathogenesis of diabetes and its associated complications. in PubMed, Patel S1, Santani D. Department of Pharmacology, Indukaka Ipcowala College of Pharmacy, August 2009
Abstract"
"The nuclear factor-kappaB (NF-kappaB) family is comprised of DNA-binding protein factors that are required for the transcription of most proinflammatory molecules, including adhesion molecules, enzymes, cytokines, and chemokines. [b]Studies performed in a variety of cell and animal based experimental systems suggest that NF-kappaB activation is a key event early in the pathobiology of diabetes[/b]. The purpose of this review is to summarize the current knowledge about the molecular biology of NF-kappaB and to review evidence that implicates NF-kappaB in the pathogenesis of diabetes and its associated complications.
Multiple Facets of NF-?B in the Heart To Be or Not to NF-?B,in Circulation Research, Joseph W. Gordon, James A. Shaw, Lorrie A. Kirshenbaum From the Institute of Cardiovascular Sciences, St Boniface General Hospital Research Centre (J.W.G., J.A.S., L.A.K.) and Departments of Physiology (L.A.K.) and Pharmacology & Therapeutics (L.A.K.), Faculty of Medicine University of Manitoba, Winnipeg, Canada.
Abstract:
"The progression from cardiac injury to symptomatic heart failure has been intensely studied over the last decade, and is largely attributable to a loss of functional cardiac myocytes through necrosis, intrinsic and extrinsic apoptosis pathways and autophagy. Therefore, the molecular regulation of these cellular programs has been rigorously investigated in the hopes of identifying a potential cell target that could promote cell survival and/or inhibit cell death to avert, or at least prolong, the degeneration toward symptomatic heart failure. The nuclear factor (NF)-?B super family of transcription factors has been implicated in the regulation of immune cell maturation, cell survival, and inflammation in many cell types, including cardiac myocytes. Recent studies have shown that NF-?B is cardioprotective during acute hypoxia and reperfusion injury. However, prolonged activation of NF-?B appears to be detrimental and promotes heart failure by eliciting signals that trigger chronic inflammation through enhanced elaboration of cytokines including tumor necrosis factor a, interleukin-1, and interleukin-6, leading to endoplasmic reticulum stress responses and cell death. The underlying mechanisms that account for the multifaceted and differential outcomes of NF-?B on cardiac cell fate are presently unknown. Herein, we posit a novel paradigm in which the timing, duration of activation, and cellular context may explain mechanistically the differential outcomes of NF-?B signaling in the heart that may be essential for future development of novel therapeutic interventions designed to target NF-?B responses and heart failure following myocardial injury."
Article at:
http://circres.ahajournals.org/content/108/9/1122.full
Oncogenic activation of NF-kappaB, Staudt LM, Metabolism Branch, Center for Cancer Research, National Cancer Institute/NIH, Bethesda, MD
Abstract:
Recent genetic evidence has established a pathogenetic role for NF-kappaB signaling in cancer. NF-kappaB signaling is engaged transiently when normal B lymphocytes respond to antigens, but lymphomas derived from these cells accumulate genetic lesions that constitutively activate NF-kappaB signaling. Many genetic aberrations in lymphomas alter CARD11, MALT1, or BCL10, which constitute a signaling complex that is intermediate between the B-cell receptor and IkappaB kinase. The activated B-cell-like subtype of diffuse large B-cell lymphoma activates NF-kappaB by a variety of mechanisms including oncogenic mutations in CARD11 and a chronic active form of B-cell receptor signaling. Normal plasma cells activate NF-kappaB in response to ligands in the bone marrow microenvironment, but their malignant counterpart, multiple myeloma, sustains a variety of genetic hits that stabilize the kinase NIK, leading to constitutive activation of the classical and alternative NF-kappaB pathways. Various oncogenic abnormalities in epithelial cancers, including mutant K-ras, engage unconventional IkappaB kinases to activate NF-kappaB. Inhibition of constitutive NF-kappaB signaling in each of these cancer types induces apoptosis, providing a rationale for the development of NF-kappaB pathway inhibitors for the treatment of cancer.
NF-kB Transcription Factor, Dr. Thomas Gilmore, Biology Department, Boston University, no date
Excerpts:
"Rel or NF-kappaB (NF-kB) proteins comprise a family of structurally-related eukaryotic transcription factors that are involved in the control of a large number of normal cellular and organismal processes, such as immune and inflammatory responses, developmental processes, cellular growth, and apoptosis. In addition, these transcription factors are persistently active in a number of disease states, including cancer, arthritis, chronic inflammation, asthma, neurodegenerative diseases, and heart disease (see DISEASES link)."
Article at:
http://www.bu.edu/nf-kb/
Video on JAK/STAT Signaling Pathway
Understandable description on how the JAK/STAT works at:
Heart Disease Facts at Center for Disease Control (CDC), no date, no author
America's Heart Disease Burden
About 600,000 people die of heart disease in the United States every year–that’s 1 in every 4 deaths.1
n. More than half of the deaths due to heart disease in 2009 were in men.1Heart disease is the leading cause of death for both men and women
Coronary heart disease is the most common type of heart disease, killing nearly 380,000 people annually.1
Every year about 720,000 Americans have a heart attack. Of these, 515,000 are a first heart attack and 205,000 happen in people who have already had a heart attack.2
Coronary heart disease alone costs the United States $108.9 billion each year.3 This total includes the cost of health care services, medications, and lost productivity.
Very important link. Great post! Makes Anatabine Citrate a very important anti-inflammatory for the brain.
Cancer Facts & Figures 2014
Excerpts:
"Who Is at Risk of Developing Cancer?
Anyone can develop cancer. Since the risk of being diagnosed
with cancer increases with age, most cases occur in adults who
are middle aged or older. About 77% of all cancers are diagnosed
in people 55 years of age and older. "
" How Many People Alive Today Have Ever Had Cancer?
Approximately 13.7 million Americans with a history of cancer
were alive on January 1, 2012. Some of these individuals were
cancer free, while others still had evidence of cancer and may
have been undergoing treatment.
How Many New Cases Are Expected to Occur This Year?
About 1,665,540 new cancer cases are expected to be diagnosed
in 2014."
"How Many People Are Expected to Die of
Cancer This Year?
In 2014, about 585,720 Americans are expected to die of cancer,
almost 1,600 people per day. Cancer is the second most common
cause of death in the US, exceeded only by heart disease,
accounting for nearly 1 of every 4 deaths."
Article at:
http://www.cancer.org/acs/groups/content/@research/documents/webcontent/acspc-042151.pdf
World Cancer Day 2014 Press Release, Tuesday 4 February 2014 –
Crisis of cancer impact worldwide exposed
New UN Agency report shows cancer is now the world’s biggest killer – with the number of cases set to explode in coming years
World Cancer Day: Geneva, Switzerland – On World Cancer Day 2014, a new global cancer report compiled by UN Agency, The International Agency for Research on Cancer (IARC) shows1:
As a single entity, cancer is the biggest cause of mortality worldwide2 - there were an estimated 8.2 million deaths from cancer in 2012
Global cancer incidence over four years increased by 11%* to an estimated 14.1 million cases in 2012 – equal to the population of India’s largest city (Mumbai)3
Cancer cases worldwide are forecast to rise by 75% and reach close to 25 million over the next two decades
Press Release at:
http://www.worldcancerday.org/cancer-myths
2014 Alzheimer’s Disease Facts and Figures in Alz.org March 2014
Women are at the epicenter of the
Alzheimer’s crisis.
• Nearly two-thirds of those with Alzheimer’s
disease – 3.2 million – are women.
• Women in their 60s are about twice as likely to
develop Alzheimer’s disease over the rest of their
lives as they are to develop breast cancer.
• More than 3 in 5 unpaid Alzheimer’s caregivers
are women – and there are 2.5 more women than
men who provide on-duty care 24-hours a day for
someone with Alzheimer’s.
• Among women caregivers who also work,
20 percent have gone from working full time to
part time because of their caregiving duties.
All caregivers of people with Alzheimer’s
– both women and men – face a
devastating toll.
• In 2013, 15.5 million family and friends provided
17.7 billion hours of unpaid care to those with
Alzheimer’s and other dementias – care valued at
$220.2 billion.
• Nearly 60 percent of Alzheimer’s and dementia
caregivers rate the emotional stress of caregiving
as high or very high; more than one-third report
symptoms of depression.
• Due to the physical and emotional toll of
caregiving, Alzheimer’s and dementia caregivers
had $9.3 billion in additional health care costs of
their own in 2013.
The number of Americans with
Alzheimer’s disease is growing – and
growing fast.
• Today, over 5 million Americans are living with
Alzheimer’s disease, including an estimated
200,000 under the age of 65. By 2050, up to
16 million will have the disease.
• Of Americans aged 65 and older, 1 in 9 has
Alzheimer’s; 1 in 3 people aged 85 and older has
the disease.
• Another American develops Alzheimer’s disease
every 67 seconds. In 2050, an American will
develop the disease every 33 seconds.
2014 Costs of Alzheimer's = $214 Billion
The growing Alzheimer’s crisis is helping
to bankrupt America.
• In 2014, the direct costs to American society of
caring for those with Alzheimer’s will total an
estimated $214 billion, including $150 billion in
costs to Medicare and Medicaid.
• Nearly one in every five dollars of Medicare
spending is spent on people with Alzheimer’s and
other dementias.
• Average per-person Medicare spending for those
with Alzheimer’s and other dementias is three
times higher than for those without these
conditions.
• Average per-person Medicaid spending for
seniors with Alzheimer’s and other dementias is
19 times higher than average per-person
Medicaid spending for all other seniors.
• Unless something is done, Alzheimer’s will cost
an estimated $1.2 trillion (in today’s dollars) in
2050. Costs to Medicare and Medicaid will
increase nearly 500 percent.
Alzheimer’s is not just memory loss –
Alzheimer’s kills.
• In 2010, 83,494 Americans died from Alzheimer’s,
according to the official cause of death listed on
death certificates. This makes Alzheimer’s
disease the 6th leading cause of death in the
United States.
• In addition, in 2010, Alzheimer’s played some role
in the deaths of 500,000 Americans. And, in 2014,
an estimated 700,000 people will die with the
disease, meaning they will die after having
developed it.
• Deaths from Alzheimer’s increased 68 percent
between 2000 and 2010, while deaths from other
major diseases decreased
Article at:
http://www.alz.org/documents_custom/2014_facts_figures_fact_sheet.pdf
Health Care Crisis Looms as China Faces Elderly Dementia Upsurge
A growing population of elderly people with Alzheimer’s and other forms of dementia in China threatens to overwhelm the country’s social support systems
May 12, 2014 |By Sandra Upson
China's elderly population
China’s one-child policy throttled population growth so successfully that the proportion of elderly Chinese is now soaring., in Scientific American, May 12, 2014 |By Sandra Upson
Excerpt:
"In little more than half a century the average Chinese life span has almost doubled. Life expectancy in China is now 76 years, nearly on par with the U.S.’s 79 years. Yet this tremendous boon comes with a dark side: an aging population.
China’s one-child policy throttled population growth so successfully that the proportion of elderly Chinese is now soaring. A 2011 report from the Chinese Academy of Social Sciences predicts that the percentage of the population that is 65 or older will triple between 2000 and 2050. With an aging population comes a greater burden of diseases, chief among them neurodegeneration. Already China has more than nine million people with some form of dementia and more cases of Alzheimer’s disease than any other country, according to a 2013 paper in The Lancet. Its authors dubbed dementia “the single largest challenge to health and social care systems” in China."
Article at:
http://www.scientificamerican.com/article/health-care-crisis-looms-as-china-faces-elderly-dementia-upsurge/?&WT.mc_id=SA_MB_20140514
A Generation Loses Consciousness, and Grows More Conscious of Headbanging in Scientific American, May 13, 2014 |By Dina Fine Maron
Excerpts:
"New work published in the May 13 issue of JAMA The Journal of the American Medical Association finds that head injuries led an estimated 2.5 million people to visit a U.S. emergency room in 2010. About one third of the cases were children, with most ER visits sparked by falls or some collision involving the head. The study adds to a growing body of data that suggests mild traumatic brain injury (TBI) is a larger public health problem than physicians previously knew.
U.S. emergency room visits for TBIs shot upward by almost 30 percent between 2006 and 2010. The majority of these incidents were coded in medical records as either concussion or unspecified head injury. The incidence of these TBIs climbed upward in every age group but children under three years old and adults over 60 showed the largest increases in TBI rates during that period, according to the study."
"Still, it’s clear that none of this is good news. At the hospital, Marin says, “we stabilize patients but then they go home and a lot of them will experience complications down the line.”
Article at:
http://www.scientificamerican.com/article/a-generation-loses-consciousness-and-grows-more-conscious-of-headbanging/?&WT.mc_id=SA_MB_20140514
Top 10 Drugs for 2013 in Fierce Pharma. I put in spreadsheet form so you can summarily look at these drugs to see where Anatabloc might fit. Looks like quite a few to me, some with another drug. What do you think?
RANK DRUG WORLD SALES FOR PATENT EXPIRE
1 Humira $11.02 B anti-inflammatory 2016
2 Enbrel $8.776 B TNF inhibition 2012
3 Remicade $8.386 B RA, Crohn's disease 2018
4 Advair/Seretide $8.25 B Asthma Inhaler none
5 Lantus $7.59 B diabetes 2015
6 Rituxan/MabThera$7.50 B cancer 2018
7 Avastin $6.751 B colon cancer 2019
8 Herceptin $6.56 B breast cancer 2033
9 Crestor $6.044 B cholesterol 2016
10 Abilify $5.501 B schizophrenia 2015
11 ? ? Alzheimers ?
Remicade, The 10 best-selling drugs of 2013, March 25, 2014
in Fierce Pharma
Excerpt:
"3. Remicade
The companies: Janssen (Johnson & Johnson), Merck, Mitsubishi Tanabe Pharma
[b]Worldwide sales: $8.386 billion
Janssen's monoclonal antibody (mAb) therapy for rheumatoid arthritis (RA), Crohn's disease and other conditions is Johnson & Johnson's ($JNJ) best-selling drug by far. It generated more than $5.2 billion in sales for J&J last year. Its next best-selling product is oncology drug Zytiga, at about $1.698 billion.
Remicade is no slouch for Merck ($MRK), either, which has rights to the drug throughout Europe, Russia and Turkey. It generated $2.271 billion for Merck last year. The rest goes to Mitsubishi Tanabe Pharma, which sells it in Japan and parts of Asia.
While Remicade continues to grow, up 8.7% in 2013, the extent of its potential growth has been put into question by the approval of biosimilars last year by the European Commission. U.S. generic drugmaker Hospira ($HSP) and its biosimilar partner South Korea-based Celltrion got their versions, Inflectra and Remsima, approved for treating many of the same inflammatory diseases for which Remicade is used. It may take time to get physician buy-in for the biosimilars, but that could be helped by a comparison study being conducted by Norway for Remicade and the new biosimilars.
Merck will be the first to feel that pain because it sells Remicade in Europe, but the clock is ticking for J&J as well, with the U.S. patent set to go off in 2018. By then, it may be facing biosimilars from a host of makers who want a piece of the action. While biosimilars are not expected to undercut drug sales like small-molecule generics, Celltrion has said it will price its biosimilar at a 30% discount to Remicade. You can expect payers to jump on that bandwagon as soon as they feel justified in moving patients to a copy."
Article at:
http://www.fiercepharma.com/special-reports/remicade-best-selling-drugs-2013#ixzz31iHjeBfN
Subscribe at FiercePharma
Humira, The 10 best-selling drugs of 2013, March 25, 2014 in Fierce Pharma
Excerpt:
1. Humira
The companies: AbbVie, Eisai
[b]Worldwide sales: $11.02 billion
AbbVie ($ABBV) rides Humira sales hard; the anti-inflammatory drug has churned out the majority of the company's revenue since Abbott Laboratories ($ABT) spun it off last January. In AbbVie's first full year on its own, its $10.7 billion from Humira made up 57% of overall sales, which tallied $18.8 billion.
Luckily for AbbVie, Humira's growth has shown no signs of slowing. Thanks to a score of additional indications as a treatment for ailments the likes of plaque psoriasis, Crohn's disease and ulcerative colitis, sales have nearly doubled since 2010's $5.5 billion haul. And in 2013 alone, Humira posted double-digit gains each quarter for AbbVie, with revenue increases from the year-ago period coming in at 16%, 13%, 19% and 13% in Q1, Q2, Q3 and Q4, respectively.
But no drug can stay at the top forever; Humira's patent protection is set to expire in 2016. And somewhat unsurprisingly, Humira's success has put a target on its back for biosimilar developers hungry for a piece of its revenues. A recent report from Moody's named AbbVie's drug as among the most sought-after prototypes for biosimilar copies; Novartis' ($NVS) Sandoz, for one, is well on its way with a version, starting Phase III trials in mid-December.
But until copycats hit, AbbVie plans to keep things going in the same direction. The company expects $19 billion in 2014 revenue, with Humira sales figuring in heavily.
Article at:
http://www.fiercepharma.com/special-reports/humira-best-selling-drugs-2013#ixzz31iEwpq1V
Humira Adverse Effects:
Common side effects of Humira subcutaneous:
Bacterial Infection of Blood or Tissues affecting the Whole Body Severe
Cellulitis Severe
Acute Infection of the Nose, Throat or Sinus Severe
Lupus-Like Syndrome Severe
Fever Severe
Rash Severe
Infection Severe
Extreme Loss of Body Water Severe
Sinus Irritation and Congestion Less Severe
Head Pain Less Severe
Feel Like Throwing Up Less Severe
Stomach Cramps Less Severe
Signs and Symptoms at Injection Site Less Severe
Infrequent side effects of Humira subcutaneous:
Multiple Sclerosis Severe
Cataracts Severe
Abnormal Increase in Red Blood Cells Severe
High Blood Pressure Severe
Extremely High Blood Pressure Severe
Heart Attack Severe
Inflammation of the Covering of the Heart or Pericardium Severe
Fluid in the Covering of the Heart or Pericardium Severe
Atrial Fibrillation Severe
Complete Stoppage of the Heart Severe
Abnormal Heart Rhythm Severe
Chronic Heart Failure Severe
Accumulation of Blood in Subdural Space Under Skull Bone Severe
Formation of Blood Clots in the Leg Veins Severe
Shingles Severe
Pneumonia Severe
Asthma Severe
Bronchospasm Severe
Liver Tissue Death Severe
Gallstones Severe
Bleeding of the Stomach or Intestines Severe
Bacterial Infection of the Kidney and Renal Pelvis Severe
Kidney Stone Severe
Inflammation of the Bladder Severe
Urinary Tract Infection Severe
Feeling Faint Severe
Flu-Like Symptoms Severe
Fluid Retention in the Legs, Feet, Arms or Hands Severe
Fast Heartbeat Severe
Heart Throbbing or Pounding Severe
Trouble Breathing Severe
Chest Pain Severe
Broken Bone Severe
Infection caused by a Fungus Severe
Reactivated Tuberculosis Severe
A Malignant Pigmented Mole or Tumor Severe
Malignant Lymphoma Severe
Breast Cancer Severe
Tumor of the Skin Severe
Decreased Function of the Parathyroid Gland Severe
Increased Antibody Proteins in the Blood Severe
Accumulation of Ketones from Abnormal Metabolism Severe
Red Lesions of Skin caused by Group A Streptococcus Severe
Deficiency of Granulocytes a Type of White Blood Cell Severe
Decreased White Blood Cells Severe
Acquired Increase of Red Blood Cells Severe
Escape of Fluid into the Lungs Less Severe
Inflammation of the Esophagus Less Severe
Inflammation of the Lining of the Stomach and Intestines Less Severe
Bloody Urine Less Severe
Irregular Periods Less Severe
Bacteria causing an Infection in the Joints Less Severe
Arthritis Less Severe
Backache Less Severe
Muscle Weakness Less Severe
Pain in Arms or Legs Less Severe
Cramps Less Severe
Bone Disease Less Severe
Involuntary Quivering Less Severe
Throwing Up Less Severe
Pelvic Pain Less Severe
Impaired Wound Healing Less Severe
Numbness and Tingling Less Severe
Inflammation of the Lining of a Joint Less Severe
High Cholesterol Less Severe
High Amount of Fats in the Blood Less Severe
Confused Less Severe
Rare side effects of Humira subcutaneous:
Demyelinating Disease Severe
Guillain-Barre Syndrome Severe
Sudden Blindness and Pain Upon Moving the Eye Severe
Relapse of Hepatitis B Infection Symptoms Severe
Drug Therapy that Worsens or Flares Psoriasis Severe
Pancreatitis Severe
Hepatosplenic T-cell Lymphoma Severe
Worsening of Chronic Heart Failure Severe
Blood Clot in Lung Severe
Heart Failure Severe
Stroke Severe
Vasculitis Severe
Inflammation of Blood Vessels in the Skin Severe
Blood Clot in a Deep Vein Severe
Legionnaire's Disease Severe
Lung Fibrosis Severe
Appendicitis Severe
Diverticulitis Severe
Hole in the Intestine Severe
Liver Failure Severe
Inflammation of the Gallbladder Severe
Erythema Multiforme Severe
Stevens-Johnson Syndrome Severe
Abnormal Liver Function Tests Severe
Infection caused by Coccidioides Fungus Severe
Type of Infection caused by Histoplasmosis Fungus Severe
Infection caused by Blastomyces Dermatitidis Fungus Severe
Life Threatening Allergic Reaction Severe
Giant Hives Severe
Reaction due to an Allergy Severe
A Fungal Infection that Occurs Under Certain Circumstances Severe
Active Tuberculosis Severe
Sarcoidosis Severe
Infection caused by a Protozoa Organism Severe
Malignant Tumor or Cancer Severe
Leukemia Severe
Infection caused by the Bacteria Listeria Monocytogenes Severe
Acquired Decrease of All Cells in the Blood Severe
Low Blood Counts due to Bone Marrow Failure Severe
Decreased Blood Platelets Severe
Hair Loss Less Severe
Humira Side Effects list at:
http://www.webmd.com/drugs/drug-64713-Humira+SubQ.aspx?drugid=64713&drugname=Humira+SubQ&pagenumber=6
College football players have visible brain changes BY ANDREW M. SEAMAN, NEW YORK Tue May 13, 2014 7:22pm EDT in Reuters News
Excerpts:
"(Reuters Health) - The brains of college football players may already display the effects of years of taking hits, according to a new brain imaging study.
Players who had been diagnosed with concussions and those who had been playing for years had smaller hippocampuses - a brain structure critical to memory - compared to those who never played football or played for fewer years, researchers found."
"Between June 2011 and August 2013 the researchers recruited 25 college football players who had been diagnosed with a concussion, 25 players without a history of diagnosed concussion and 25 similar young men who had never played.
The participants had magnetic resonance imaging (MRI) of their brains and researchers used the images to measure the volume of certain brain regions. The athletes also took a computerized test to assess their cognitive abilities.
The researchers found that college athletes had hippocampuses between 17 percent and 26 percent smaller than non-athletes. Those who had been diagnosed with concussions also had smaller hippocampuses than the players without past concussions.
The longer the young men had played football, the smaller their hippocampuses were and the slower their reaction time on one of the tests.
“People try to understand why some NFL players have what looks like Alzheimer’s in their forties,” Dr. Jeffrey Bazarian said. “How did they get there? I think this study points out the early stages of that.”
Article at:
http://www.reuters.com/article/2014/05/13/us-brain-health-football-idUSKBN0DT24720140513?feedType=RSS&feedName=healthNews
10 big brands keep pumping out big bucks, with a little help from price hikes May 7, 2014 | By Tracy Staton in Fierce Pharma Marketing
Excerpt:
"Drugmakers raise U.S. prices to make more money. This isn't a surprise to anyone. It's a basic business strategy, and the U.S. market is among the few where pharma companies still have considerable pricing power. But thanks to a steady flow of expensive new cancer therapies--and a public brouhaha over the cost of next-gen treatments for hepatitis C--drug prices are on center stage.
Prominent cancer doctors have balked at adopting a new Sanofi ($SNY) drug, Zaltrap, because they decided its benefits weren't worth the cost. Pharmacy benefits managers, notably Express Scripts, have nixed drugs from their formularies in favor of competing--and less expensive--options. And Gilead Sciences' ($GILD) pricing poster child Sovaldi has private payers and government programs so spooked, they're considering limiting its use to the sickest patients, at least until they can use soon-to-be-approved rivals to negotiate better pricing.
Though the spotlight has picked out these few prominent cases, price hikes are happening all over. Drugmakers hike prices to offset patent losses on other meds. To milk an aging product for all it's worth before its patent expires. Or simply because they can: Last year, as U.S. drug spending dropped a couple of percentage points, Novo Nordisk ($NVO) and Sanofi--among others--raised prices on some products, thinking the market could bear it.
But which price tags are changing most? Bloomberg enlisted DRX, a drug-data firm, to find out; you can read the news service's coverage here. We thought we'd look into the products at the top of the list, to see how and why their prices are leaping. Some of the biggest hikes are for products you don't hear much about--specialty meds, such as Jazz Pharmaceuticals' ($JAZZ) narcolepsy treatment Xyrem. Others are mass-market, primary care products, such as Daiichi Sankyo's blood pressure pill Benicar. Any pricing examples you find most egregious--or most justified? Let us know. --Tracy Staton (email | Twitter) | Carly Helfand (email | Twitter) | Emily Wasserman (email | Twitter)
1. Xyrem (narcolepsy symptoms) -- Jazz Pharmaceuticals
2. Humulin (diabetes) -- Eli Lilly
3. Premarin (menopause symptoms) -- Pfizer
4. EpiPen (anaphylaxis) -- Mylan
5. Lunesta (sleep disorders) -- Sunovion
6. Benicar (high blood pressure) -- Daiichi Sankyo
7. Lantus (diabetes) -- Sanofi
8. Viagra (erectile dysfunction) -- Pfizer
9. Gleevec (leukemia) -- Novartis
10. Copaxone (MS) -- Teva
Article at:
http://www.fiercepharmamarketing.com/story/10-big-brands-keep-pumping-out-big-bucks-little-help-price-hikes/2014-05-07#ixzz31i7uySIA
Biogen Idec preps for a big leap into the anti-TNF blockbuster biosimilars market, December 17, 2013 | By John Carroll
Article:
"Biogen Idec ($BIIB) is taking its supporting role in a big biosimilars development venture with Korea's Samsung one giant leap forward. The Big Biotech spread the word this morning that it will take the lead on commercializing their anti-TNF knockoffs for some big inflammatory targets--including rheumatoid arthritis and Crohn's disease--in Europe, where they plan to follow a regulatory trail that's already been clearly marked out.
Biogen originally inked its JV deal with Samsung--dubbed Samsung Bioepis--two years ago as CEO George Scangos kept a commitment to find a practical way to capitalize on the new market by leveraging the company's manufacturing and development know-how. The two companies have emerged as key players in the advancement of biologic follow-on products, though they have been quiet on exactly which drugs are in their sights.
The Korean conglomerate said initially that it planned to invest $2 billion in its new biosimilars venture, with Biogen Idec contributing a minority share of the initial $300 million down payment. Merck later jumped into the venture after experiencing some big setbacks in the field.
There's no word in the joint announcement today on exactly which anti-inflammatory blockbusters are on the table, but ClinicalTrials.gov flags a trial for SB2 from Samsung Bioepis in comparison with J&J's ($JNJ) Remicade along with another study of SB4 against Amgen's ($AMGN) Enbrel.
Europe has approved a number of biosimilars over recent years, but the market took a big step forward a few months ago when regulators on the continent approved Inflectra, a copycat of Remicade from Hospira ($HSP) and Celltrion. The pioneering move marked the entry of the first discounted biologic to go head-to-head with the original. Europe has moved well ahead of the U.S. on biosimilars, as the FDA has yet to fully clarify the regulatory pathway that will be established for approving biosimilars in the giant North American market. Nevertheless, Novartis ($NVS), Amgen and others have been advancing their own biosimilars in anticipation of creating a valuable new market for generic biologics.
"This is a unique opportunity for us to leverage our experience in developing and manufacturing high-quality biologics in therapeutic areas where we are deeply focused, and provide medicines to patients where there is a significant societal need," said Tony Kingsley, executive vice president of global commercial operations for Biogen Idec. "As a company that aims to make a difference in the lives of patients with serious diseases, we are excited by the potential to offer additional highly effective therapies in critical areas where there is growing demand."
Article at:
http://www.fiercebiotech.com/story/biogen-idec-preps-big-leap-anti-tnf-blockbuster-biosimilars-market/2013-12-17#ixzz31i4C7ELY
Subscribe at FierceBiotech
The 10 best-selling drugs of 2013, March 25, 2014
Enbrel, The companies: Amgen, Pfizer, Takeda, Worldwide sales: $8.776 billion
Excerpt:
Enbrel was the first of its kind, a TNF (tumor necrosis factor) inhibitor to treat autoimmune diseases, and its distinction allowed it to become one of the best-selling drugs in the world. It was first approved by the FDA more than 15 years ago in 1998 for treating moderate to severe rheumatoid arthritis, but it has racked up four more approvals in the U.S. since then and the revenues to go with it. Amgen bought its developer, Immunex, in 2002 for about $16 billion, a deal that seemed incredible to some at the time, but that in retrospect was a bargain.
Article at:
http://www.fiercepharma.com/special-reports/enbrel-best-selling-drugs-2013#ixzz31i0Trg4K
Serious side effects of Embrel at Embrel website:
Serious side effects of ENBREL
Risk of infection. ENBREL can lower the ability of your immune system to fight infections. Some people have serious infections while taking ENBREL. These infections include tuberculosis (TB), and infections caused by viruses, fungi or bacteria that spread throughout their body. Some people have died from these infections.
Risk of cancer.
There have been cases of unusual cancers in children and teenage patients who started using TNF-blocking agents at less than 18 years of age.
For children, teenagers, and adults taking TNF-blocker medicines, including ENBREL, the chances of getting lymphoma or other cancers may increase.
People with rheumatoid arthritis or psoriasis, especially those with very active disease, may be more likely to get lymphoma.
Previous Hepatitis B infection. If you have been previously infected with the hepatitis B virus (a virus that affects the liver), the virus can become active while you use ENBREL.
Nervous system problems. Rarely, people who use TNF blocker medicines have developed nervous system problems such as multiple sclerosis, seizures, or inflammation of the nerves of the eyes.
Blood problems. Low blood counts have been seen with other TNF blocker medicines. Your body may not make enough of the blood cells that help fight infections or help stop bleeding. Symptoms include fever, bruising or bleeding very easily, or looking pale.
Heart failure including new heart failure or worsening of heart failure you already have. New or worse heart failure can happen in people who use TNF blocker medicines, like ENBREL.
Psoriasis. Some people using ENBREL developed new psoriasis or worsening of psoriasis they already had.
Allergic reactions. Allergic reactions can happen to people who use TNF blocker medicines.
Autoimmune reactions, including:
Lupus-like syndrome. Symptoms include a rash on your face and arms that gets worse in the sun.
Autoimmune hepatitis. Liver problems can happen in people who use TNF blocker medicines, including ENBREL. These problems can lead to liver failure and death.
Embrel webpage:
http://www.enbrel.com/possible-side-effects.jspx?WT.z_co=A&WT.z_in=OTH&WT.z_ch=PDS&WT.z_se=G&WT.srch=1&WT.mc_id=A_OTH_PDS_G
Tomorrow's cardio blockbusters: Inside 'the next big leap' in controlling cholesterol, March 31, 2014 | By Damian Garde in Fierce Biotech
Excerpts:
"A new era for cardiology---Whether PCSK9 drugs can live up to their billing likely won't be decided for at least three years, but their short-term promise heralds the grand entry of biologics into the cardiology world, Libby said. As anyone inundated with TV ads for Enbrel and Humira can attest, TNF-blocking biotech drugs have revolutionized rheumatology, according to Libby, and the same thing has taken place in cancer. But for cardiology, an area long focused on small-molecule therapies with varying rates of success, drugs like evolocumab, alirocumab and bococizumab signal a new way forward.
Article at:
http://www.fiercebiotech.com/story/tomorrows-cardio-blockbusters-inside-next-big-leap-controlling-cholesterol/2014-03-31#ixzz31hyggeRA
Big Pharma Hiding Dangers of Cholesterol-lowering Statin Drugs, May 14, 2014, by by Jerome Burne, HealthinsightUK.org
Excerpts:
"Are statin drugs the biggest fraud in the history of medicine? Consider the evidence:
“Bad” cholesterol is actually a myth, as cholesterol is essential to life.
The brain contains only 2% of the body’s mass, but 25% of the total cholesterol. Lowering cholesterol by drugs may be contributing to Alzheimer’s.
Lipitor, the best selling-drug in the history of medicine, at one time outsold every other drug on the market with no serious competitors.
[b]Statin drugs are known to have serious side effects, including these that the FDA warns against: liver damage, memory loss and confusion, type 2 diabetes, and muscle weakness.
Now, a group in the U.K. is reporting that the Cholesterol Treatment Trialists’ (CTT) Collaboration in Oxford has an agreement to keep secret much of the information contained in its huge database which holds results from 27 trials of these drugs, nearly all of which were run by a drug company (story below).
This follows the publication last year (2013) of a study published in the Journal of Endocrine and Metabolic Diseases: The Ugly Side of Statins. Systemic Appraisal of the Contemporary Un-Known Unknowns which concluded: “These finding on statin major adverse effects had been under-reported and the way in which they withheld from the public, and even concealed, is a scientific farce.”
And now, in both the USA and the UK, doctors are being encouraged to prescribe even more statin drugs. Fortunately, many doctors are now stepping forward and speaking out against this biggest medical fraud of all time."
Excerpts:
"
Should a professional body, however eminent, be allowed to keep information about the safety of products they are supplying to public hidden so no one else can run tests on them?
That is the question raised by HealthInsightUK’s finding that a large and respected organisation whose job it is to analyses the findings of statin trials – The Cholesterol Treatment Trialists’ (CTT) Collaboration in Oxford – has an agreement to keep secret much of the information contained in its huge database which holds results from 27 trials of these drugs, nearly all of which were run by a drug company.
Questions about the secrecy of the CTT have been put in the spotlight following the recent recommendation by NICE to change the guidelines on statins. If the proposals are accepted, millions more healthy people in the UK who have no sign of heart disease will be prescribed these drugs.
HealthInsightUK has also established that the CTT do not hold data on the side-effects of statins. A spokesman confirmed that they base their estimate of risk on the published results of trials conducted by the drug companies. He dismissed claims that side-effects such as muscle pain and depression were wide spread, saying they were only “hypotheses”.
"A number of senior researchers approached by HealthInsight have supported Dr Wright’s claim that the data held by CTT hasn’t been available. Professor Rita Redberg cardiologist and editor of the journal JAMA Internal Medicine, has stated in an email that: “CTT will not make their data available to any colleagues and other researchers who wish to study risks and benefits of statins. The CTT data is not accessible publicly.”
"Professor Harriet Rosenberg of the Health and Society Program at York University in Toronto commented that: “many scholars have asked the CTT for data without success” in a formal reply to the Cochrane review last year.
So there seems a pretty strong case for saying that for all practical purposes the drug company trials held by the CTT are not available for independent scrutiny."
SOS: Sanity over Statins – CTT the house of statin secrets
Article at:
http://healthimpactnews.com/2014/big-pharma-hiding-dangers-of-cholesterol-lowering-statin-drugs/
The Ugly Side of Statins. Systemic Appraisal of the Contemporary Un-Known Unknowns, Sherif Sultan, Niamh Hynes, July 2013 in Scientific Research
My Comments: Statins are being touted as an excellent anti-inflammatory for the fight against auto-immune disorders and other related diseases.
Abstract:
"Cardio-vascular specialists have witnessed and actively participated in the revolutionary developments that have occurred in their field of specialization over the last few years. Cutting-edge technologies have led to dramatic improvements in life-expectancy and quality of life. An open-mind and pioneering attitude are necessary when exploring new frontiers to improve our patients’ health. However, naive indiscriminate acceptance of novel mainstream therapies is not always advisable and prudence is required in unearthing harmful, covert side effects. An objective review of contemporary vascular research was performed and industrial bias was sifted out for a fresh prospective on how to promote primary cardiovascular prevention with attainable lifestyle adjustments [1]. A comprehensive review of Pubmed, EM-BASE and Cochrane review databases was undertaken for articles relating to cardiovascular primary prevention and statin side effects with the aim of harmonising their roles within contemporary clinic practice. Particular attention was paid to large-scale randomised controlled trials on contemporary cardiovascular pharmacotherapies and their specific adverse effects on metabolic pathways which feature prominently in cardiovascular primary prevention and regenerative programmes. There is a categorical lack of clinical evidence to support the use of statin therapy in primary prevention. Not only is there a dearth of evidence for primary cardiovascular protection, there is ample evidence to show that statins actually augment cardiovascular risk in women, patients with Diabetes Mellitus and in the young. Furthermore statins are associated with triple the risk of coronary artery and aortic artery calcification. Cardiovascular primary prevention and regeneration programmes, through life style changes and abstaining from tobacco use have enhanced clinical efficacy and quality of life over any pharmaceutical or other conventional intervention."
Article at:
http://www.scirp.org/journal/PaperInformation.aspx?PaperID=34065#.U3OBzYFdXTp
NF-?B pathway activators as potential ageing biomarkers: targets for new therapeutic strategies, Carmela R Balistreri*, Giuseppina Candore, Giulia Accardi, Giuseppina Colonna-Romano and Domenico Lio
Department of Pathobiology and Medical and Forensic Biotechnologies, University of Palermo, Corso Tukory 211, Palermo 90134, Italy, Published: 20 June 2013
Abstract:
"Chronic inflammation is a major biological mechanism underpinning biological ageing process and age-related diseases. Inflammation is also the key response of host defense against pathogens and tissue injury. Current opinion sustains that during evolution the host defense and ageing process have become linked together. Thus, the large array of defense factors and mechanisms linked to the NF-?B system seem to be involved in ageing process. This concept leads us in proposing inductors of NF-?B signaling pathway as potential ageing biomarkers. On the other hand, ageing biomarkers, represented by biological indicators and selected through apposite criteria, should help to characterize biological age and, since age is a major risk factor in many degenerative diseases, could be subsequently used to identify individuals at high risk of developing age-associated diseases or disabilities. In this report, some inflammatory biomarkers will be discussed for a better understanding of the concept of biological ageing, providing ideas on eventual working hypothesis about potential targets for the development of new therapeutic strategies and improving, as consequence, the quality of life of elderly population."
Chronic Inflammation at Depke Wellness, no date, no author
Chronic inflammation is much different though.
First of let me define chronic inflammation as a NF-kB state. This actually stands for nuclear factor kappa beta. In essence NF-kB is a protein complex that controls the transcription of DNA. If this sounds like an impact on your health and happiness, you are absolutely correct.
This NF-kB state is due to the long term chronic inflammatory states. This factors that typically trigger this are:
Gluten intolerance
Gluten cross reactive intolerance
Standard American diet or (SAD) which is high in sugar and processed foods
Chronic mental/emotional stress
Chronic infection (very often undiagnosed gut infections)
Obesity
Addiction
Chemotherapy
When any of these factors trigger this NF-kB state, this is when the “you know what” hits the fan.
Once the NF-kB state is now a factor in your health, the real challenges begin. This is due to the fact that the NF-kB has its own feedback loops that continually recycle your inflammatory condition.
The NF-kB leads to an increase in fat cell production, which in turn leads to insulin resistance and insulin surges. This than leads to further inflammation.
The NF-kB state leads to challenges with biotransformation in the liver, challenges with liver detoxification and ultimately, further inflammation.
The NF-kB leads to an increase in cytokine production, which leads to autoimmunity and ultimately, more inflammation.
The NF-kB state leads to a leaky gut condition, which in turn leads to an autoimmune reaction with the end result of, you guessed it, more inflammation.
Another factor to recognize is the fact that the NF-kB state can lead to immune system dysregulation. From this dysregulation, chemical intolerance is often a challenge. You may recognize somebody with this or perhaps even yourself. Recognized by the inability to be around new paint, new carpeting, perfumes, ect..
One more significant factor with immune dysregulation caused by NF-kB is the fact that this shuts down apoptosis. Apoptosis is basically cellular suicide. Understand that when a cell in your body becomes “broken”, this broken cell is designed to destroy itself. This is important because you do not want a broken cell becoming another broken cell and so on. When you get too many of these “broken” cells replicating themselves, this is the opportunity for cancer to develop.
One more point to make though. Even if you rid yourself of all the triggers of the chronic inflammation or NF-kB state, due to the feedback loops mentioned above, this condition continues. Yikes!
NF-kB DISEASES list at Boston University Biology website, no date, no author
Excerpt:
On this page are listed several diseases in which activation of NF-kB has been implicated. For general reviews on the role of NF-kB in disease, see Aradhya & Nelson (2001), Kumar et al (2004), Yamamoto & Gaynor (2002) or Baldwin (2001). For specific diseases see the listed references, which can be found either on this site (under References) or at PubMed (through the linked references).
My comments: There are 79 general diseases listed in Table 1, of which, cancer is one item. Table 2 lists 43 cancers related to NF-kB transcription.
Article at:
http://www.bu.edu/nf-kb/physiological-mediators/diseases/
Chronic Diseases and Health Promotion from the CDC, no date
Article:
"Chronic Diseases: The Leading Causes of Death and Disability in the United States
Chronic diseases and conditions—such as heart disease, stroke, cancer, diabetes, obesity, and arthritis—are among the most common, costly, and preventable of all health problems.
As of 2012, about half of all adults—117 million people—have one or more chronic health conditions. One of four adults has two or more chronic health conditions.1
Seven of the top 10 causes of death in 2010 were chronic diseases. Two of these chronic diseases—heart disease and cancer—together accounted for nearly 48% of all deaths.2
Obesity is a serious health concern. During 2009–2010, more than one-third of adults, or about 78 million people, were obese (defined as body mass index [BMI] =30 kg/m2). Nearly one of five youths aged 2–19 years was obese (BMI =95th percentile).3
Arthritis is the most common cause of disability.4 Of the 53 million adults with a doctor diagnosis of arthritis, more than 22 million say arthritis causes them to have trouble with their usual activities.5
Diabetes is the leading cause of kidney failure, lower limb amputations other than those caused by injury, and new cases of [color=red]blindness among adults.6
Health Risk Behaviors that Cause Chronic Diseases
Health risk behaviors are unhealthy behaviors you can change. Four of these health risk behaviors—lack of exercise or physical activity, poor nutrition, tobacco use, and drinking too much alcohol—cause much of the illness, suffering, and early death related to chronic diseases and conditions.
In 2011, more than half (52%) of adults aged 18 years or older did not meet recommendations for aerobic exercise or physical activity. In addition, 76% did not meet recommendations for muscle-strengthening physical activity.7
About half of US adults (47%) have at least one of the following major risk factors for heart disease or stroke: uncontrolled high blood pressure, uncontrolled high LDL cholesterol, or are current smokers.8 Ninety percent of Americans consume too much sodium, increasing their risk of high blood pressure.9
In 2011, more than one-third (36%) of adolescents said they ate fruit less than once a day, and 38% said they ate vegetables less than once a day. In addition, 38% of adults said they ate fruit less than once a day, and 23% said they ate vegetables less than once a day.10
More than 42 million adults—close to 1 of every 5—said they currently smoked cigarettes in 2012.11 Cigarette smoking accounts for more than 480,000 deaths each year.11 Each day, more than 3,200 youth aged 18 years or younger smoke their first cigarette, and another 2,100 youth and young adults who smoke every now and then become daily smokers.11
Drinking too much alcohol is responsible for 88,000 deaths each year, more than half of which are due to binge drinking.12, 13 About 38 million US adults report binge drinking an average of 4 times a month, and have an average of 8 drinks per binge, yet most binge drinkers are not alcohol dependent.14
Top of page
The Cost of Chronic Diseases and Health Risk Behaviors
The majority of US health care and economic costs associated with medical conditions are for the costs of chronic diseases and conditions and associated health risk behaviors.
Eighty-four percent of all health care spending in 2006 was for the 50% of the population who have one or more chronic medical conditions.15
The total costs of heart disease and stroke in 2010 were estimated to be $315.4 billion. Of this amount, $193.4 billion was for direct medical costs, not including costs of nursing home care.16
Cancer care cost $157 billion in 2010 dollars.17
The total estimated cost of diagnosed diabetes in 2012 was $245 billion, including $176 billion in direct medical costs and $69 billion in decreased productivity. Decreased productivity includes costs associated with people being absent from work, being less productive while at work, or not being able to work at all because of diabetes.18
The total cost of arthritis and related conditions was about $128 billion in 2003. Of this amount, nearly $81 billion was for direct medical costs and $47 billion was for indirect costs associated with lost earnings.19
Medical costs linked to obesity were estimated to be $147 billion in 2008. Annual medical costs for people who are obese were $1,429 higher than those for people of normal weight in 2006.20
For the years 2009–2012, economic cost due to smoking is estimated to be more than $289 billion a year. This cost includes at least $133 billion in direct medical care for adults and more than $156 billion for lost productivity from premature death estimated from 2005 through 2009.11
The economic costs of drinking too much alcohol were estimated to be $223.5 billion, or $1.90 a drink, in 2006. Most of these costs were due to binge drinking, and resulted from losses in workplace productivity, health care expenses, and crimes related to excessive drinking.21
Article at:
http://www.cdc.gov/chronicdisease/overview/index.htm?s_cid=ostltsdyk_govd_203
Worms or Anatabloc?--Parasitic Worms Wiggle into ModernMedicine By Julia Calderone | May 12, 2014 in Scientific American.
Excerpt:
"In 2006, a man named Jasper Lawrence travelled to Africa to infect himself with hookworm by walking barefoot in a steaming mound of human excrement. He and other proponents of so-called helminthic therapy say that industrialized societies have become too clean, and in the process of sterilizing our homes and bodies, we’ve eradicated an essential piece of our biology: intestinal worms.
Hookworms attached to the intestinal mucosa. (Source: CDC)
The therapy requires the deliberate infection with helminths, or parasitic worms, by swallowing them or letting them crawl through the skin. It claims to alleviate a range of autoimmune and inflammatory diseases like allergies, inflammatory bowel diseases (IBD) and multiple sclerosis (MS). The Food and Drug Administration has not approved helminthic therapy. Nonetheless, Lawrence formed an online business in 2007 selling homegrown worms to autoimmune disease suffers around the world; he now operates out of the U.K."
"Helminthic therapy is mainly used to treat IBD, like ulcerative colitis and Crohn’s disease. Can you describe any particularly compelling evidence of its success with these diseases?
There was an individual in California who had severe IBD. The standard treatment of steroids wasn’t effective for him, so he went to Thailand and got a doctor to infect him with human Trichuris trichiura [whipworm] and he got better right away, which is kind of amazing.
The parasite only stays in the body for a few years, so when it disappeared, he started to come down with IBD again. He went to UC San Francisco and they offered him treatments, but he wasn’t getting better. So they said if you go back to Thailand and get infected again, we’ll track you. Of course this is all anecdotal, but sure enough, after he got infected, he got better again."
"Helminthic therapy claims to treat a wide variety of diseases like MS, IBD, diabetes, allergies and even autism. Are all of these diseases related?
Yes, they are. All of those diseases have an immune response that’s gone awry, resulting in harmful inflammation. What really stands out in diseases like MS, Type I diabetes and IBD is the Th1 immune response. It’s a common thread that seams throughout all these different diseases."
Article at:
http://blogs.scientificamerican.com/guest-blog/2014/05/12/parasitic-worms-wiggle-into-modern-medicine-qa/
Mechanisms and consequences of constitutive NF-?B activation in B-cell lymphoid malignancies. on Pubmed, in Oncogene advance online publication, 27 January 2014 Nagel D, Vincendeau M, Eitelhuber AC, Krappmann D., Research Unit Cellular Signal Integration, Institute of Molecular Toxicology and Pharmacology, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Neuherberg, Germany.
Abstract:
The discovery of constitutive nuclear factor-?B (NF-?B) activation in Hodgkin's lymphoma tumor cells almost two decades ago was one of the first reports that directly connected deregulated NF-?B signaling to human cancer. Subsequent studies demonstrated that enhanced NF-?B signaling is a common hallmark of many lymphoid malignancies, including Hodgkin lymphoma, mucosa-associated lymphoid tissue lymphoma, diffuse large B-cell lymphoma and multiple myeloma. By inducing an anti-apoptotic and pro-proliferative gene program, NF-?B is involved in lymphoma survival and growth. Identification of somatic mutations that led to activation of oncogenes and inactivation of tumor suppressor genes in the pathway revealed that specific pathogenic mechanisms are responsible for constitutive NF-?B activation in different lymphoma entities. Thus, the identification of distinct oncogenic events is reflecting the diverse cellular origins of the different lymphomas. Further, elucidation of the mechanisms that drive NF-?B in lymphoma is of high clinical relevance as it will allow the design of target-directed precision therapy. Indeed, a number of drugs that impair constitutive NF-?B activation in lymphoid malignancies are currently in preclinical or clinical development.
Article at:
http://www.ncbi.nlm.nih.gov/pubmed/24469030
Anatabine lowers Alzheimer's Aß production in vitro and in vivo. published in NCBI Pubmed.com US National Library of Medicine National Institutes of Health, Paris D1, Beaulieu-Abdelahad D, Bachmeier C, Reed J, Ait-Ghezala G, Bishop A, Chao J, Mathura V, Crawford F, Mullan M. Roskamp Institute, 2040 Whit?eld Avenue, Sarasota, FL 34243, USA
Abstract:
Brain Aß accumulation represents a key pathological hallmark in Alzheimer's disease. In this study, we investigated the impact of anatabine, a minor alkaloid present in plants of the Solanacea family on Aß production in vitro using a cell line overexpressing the human amyloid precursor protein (APP) and in vivo using a transgenic mouse model of Alzheimer's disease. In vitro, anatabine lowers Aß1?40 and Aß1?42 levels in a dose dependent manner and reduces sAPPß production without impacting sAPPa levels suggesting that anatabine lowers Aß production by mainly impacting the ß-cleavage of APP. Additionally, we show that anatabine lowers NF?B activation at doses that inhibit Aß production in vitro. Since NF?B is known to regulate BACE-1 expression (the rate limiting enzyme responsible for Aß production), we determined the impact of anatabine on BACE-1 transcription. We show that anatabine inhibits BACE-1 transcription and reduces BACE-1 protein levels in human neuronal like SHSY-5Y cells suggesting that the Aß lowering properties of anatabine are mediated via a regulation of BACE-1 expression. In vivo, we show that an acute treatment with anatabine for four days significantly lowers brain soluble Aß1?40 and Aß1?42 levels in a transgenic mouse model of Alzheimer's disease. Altogether our data suggest that anatabine may represent an interesting compound for regulating brain Aß accumulation.
Published before at Investohub but noted again.
Article at:
http://www.ncbi.nlm.nih.gov/pubmed/21958873
Inflammation, a Key Event in Cancer Development in Cancer Stem Cell Conference, Case Western University
Haitian Lu, Weiming Ouyang and Chuanshu Huang, Nelson Institute of Environmental Medicine, New York University School of Medicine, Tuxedo, New York
Abstract:
"Several recent studies have identified nuclear factor-?B as a key modulator in driving inflammation to cancers. Besides this transcription factor, essential in regulating inflammation and cancer development, an inflammatory microenvironment inhabiting various inflammatory cells and a network of signaling molecules are also indispensable for the malignant progression of transformed cells, which is attributed to the mutagenic predisposition of persistent infection-fighting agents at sites of chronic inflammation. As a subverted host response to inflammation-induced tumors, the inflammatory cells and regulators may facilitate angiogenesis and promote the growth, invasion, and metastasis of tumor cells. Thus far, research regarding inflammation-associated cancer development has focused on cytokines and chemokines as well as their downstream targets in linking inflammation and cancer. Moreover, other proteins with extensive roles in inflammation and cancer, such as signal transducers and activators of transcription, Nrf2, and nuclear factor of activated T cells, are also proposed to be promising targets for future studies. The elucidation of their specific effects and interactions will accelerate the development of novel therapeutic interventions against cancer development triggered by inflammation
Article at:
http://mcr.aacrjournals.org/content/4/4/221.full
COPD, INFLAMMATION, AND LUNG CANCER Jerome S Brody, M.D., Professor of Medicine and Avrum Spira, M.D., Assistant Professor of Medicine, Pulmonary Center and Department of Medicine
Boston University School of Medicine, no date
Abstract:
"Both lung cancer and COPD are associated with cigarette smoking, which by generating reactive oxidant species, induces a chronic inflammatory state in the lung. Activation, particularly of NF-kB occurs in both cancer and COPD,[/b] and expression of a number of genes is altered in both diseases. In lung cancer DNA damage, lack of DNA repair and genomic instability predominate whereas matrix degradation, lack of repair and an intense immune response predominate in COPD. The reasons for the different responses to a common inflammatory response induced by smoking remain to be determined, but likely lie in genetic polymorphisms in genes that regulate genome integrity in cancer and that regulate the immune response to tissue destruction in COPD. "
Other excerpts:
"Cigarette smoke contains an extremely high concentration of oxidants along with a number of known carcinogens 4
. The reactive oxidant species (ROS) generated by smoking induce inflammation in the lung and its airways as well as
causing mutations in airway epithelial cell DNA. The risk of developing lung cancer does not disappear after smoking has been discontinued. In the United States lung cancer now occurs in as many former smokers as current smokers 5"
"Chronic inflammation has been shown to lead to cancer in a number of organs. Reflux esophagitis, H.pylori gastric inflammation, viral hepatitis, ulcerative colitis, and cigarette smoking are all associated with chronic inflammation and an increased incidence of local cancers 8
. In ulcerative colitis, DNA mutational “fingerprints” of dysplastic and normal colonic crypts show that
DNA mutations spread by clonal expansion of proliferating cells and by fusion of adjacent crypts moderated in part by crypt cell turnover and cell death 9
. The clonal expansion of crypt cells occurs because of the growth advantage and apoptosis resistance of cells that has been induced by continued inflammation
and generation of ROS"
"There is considerable evidence that links chronic inflammation, the transcription factor NF-kB, and cancer 10. Recent studies have also demonstrated the synergistic interaction of the classic mediator of inflammation, NFkB, and the classic tumor suppressor gene, p53, which acts as a general inhibitor of inflammation "
"As noted earlier, NF-kB activation and subsequent
transactivation of inflammation-related genes appears to play a central role in both COPD and cancer. These events occur to some extent in all smokers, even those without evident lung disease. Which genes are activated and which are suppressed in smokers may be a major determinant of whether a smoker remains disease free, or develops cancer or COPD."
"The recent focus on smoking-related lung disease and on COPD and lung cancer, and the advances that have been made in defining important pathogenetic mechanisms hold promise for clarifying the relation between inflammation, cancer, and COPD, and for identifying potential therapeutic targets in the next decade."
Article at:
http://www.bumc.bu.edu/pulmonary/files/PDFs/Faculty/brody1.pdf