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A Randomized Trial of Protocol-Based Care for Early Septic Shock
The ProCESS Investigators, N Engl J Med 2014; 370:1683-1693May 1, 2014
Excerpts:
"BACKGROUND
In a single-center study published more than a decade ago involving patients presenting to the emergency department with severe sepsis and septic shock, mortality was markedly lower among those who were treated according to a 6-hour protocol of early goal-directed therapy (EGDT), in which intravenous fluids, vasopressors, inotropes, and blood transfusions were adjusted to reach central hemodynamic targets, than among those receiving usual care. We conducted a trial to determine whether these findings were generalizable and whether all aspects of the protocol were necessary.
METHODS
In 31 emergency departments in the United States, we randomly assigned patients with septic shock to one of three groups for 6 hours of resuscitation: protocol-based EGDT; protocol-based standard therapy that did not require the placement of a central venous catheter, administration of inotropes, or blood transfusions; or usual care. The primary end point was 60-day in-hospital mortality. We tested sequentially whether protocol-based care (EGDT and standard-therapy groups combined) was superior to usual care and whether protocol-based EGDT was superior to protocol-based standard therapy. Secondary outcomes included longer-term mortality and the need for organ support.
RESULTS
We enrolled 1341 patients, of whom 439 were randomly assigned to protocol-based EGDT, 446 to protocol-based standard therapy, and 456 to usual care. Resuscitation strategies differed significantly with respect to the monitoring of central venous pressure and oxygen and the use of intravenous fluids, vasopressors, inotropes, and blood transfusions. By 60 days, there were 92 deaths in the protocol-based EGDT group (21.0%), 81 in the protocol-based standard-therapy group (18.2%), and 86 in the usual-care group (18.9%) (relative risk with protocol-based therapy vs. usual care, 1.04; 95% confidence interval [CI], 0.82 to 1.31; P=0.83; relative risk with protocol-based EGDT vs. protocol-based standard therapy, 1.15; 95% CI, 0.88 to 1.51; P=0.31). There were no significant differences in 90-day mortality, 1-year mortality, or the need for organ support.
CONCLUSIONS
In a multicenter trial conducted in the tertiary care setting, protocol-based resuscitation of patients in whom septic shock was diagnosed in the emergency department did not improve outcomes. (Funded by the National Institute of General Medical Sciences; ProCESS ClinicalTrials.gov number, NCT00510835.)"
Article at:
http://www.nejm.org/doi/full/10.1056/NEJMoa1401602
List of countries by total health expenditure (PPP) per capita at Wikipedia
List at:
http://en.wikipedia.org/wiki/List_of_countries_by_total_health_expenditure_(PPP)_per_capita
List of countries by life expectancy at Wikipedia
List at:
http://en.wikipedia.org/wiki/List_of_countries_by_life_expectancy
My comments:
Yikes! We are number one!---in cost and number 35 in life expectancy. Doesn't look like we're getting out bang for the bucks. Or is it the Big Mac?
Large Study Reveals Important New Information About Hypertension in Forbes Health, Larry Husten, 5/30/2014
Article:
"Although high blood pressure has long been recognized and studied as a cardiovascular risk factor, a large new study published in the Lancet provides a more detailed, granular view of the specific role of different forms of hypertension.
Eleni Rapsomaniki and colleagues in the U.K. analyzed data from 1.25 million people without existing cardiovascular disease age 30 and older. An important, and perhaps surprising, new finding is that high blood pressure was not a simple monolithic cardiovascular risk factor. Instead, the researchers found that different types of hypertension at different stages of life had different cardiovascular effects.
“Our findings do not support the widely held assumptions that systolic and diastolic pressure have similar strong associations with the occurrence of all cardiovascular diseases across a wide age range,” said Rapsomaniki, in a Lancet press release.
An elevated systolic BP was strongly linked to intracerebral hemorrhage, subarachnoid hemorrhage, and stable angina, but had only a weak association with abdominal aortic aneurysm (AAA). Pulse pressure (systolic pressure minus diastolic pressure), by contrast, had an inverse correlation with AAA but was a strong predictor of peripheral arterial disease. In accord with many studies over the last few decades, diastolic blood pressure was a less powerful predictor of most cardiovascular diseases than systolic pressure, though it was also a strong predictor of AAA. The results, the authors write, “support the shift in guideline focus in recent years from the importance of diastolic towards the greater importance of systolic pressure in people aged 60 years and older.”
The researchers found no evidence for a J-shaped curve found in some previous studies showing that the lowest blood pressure levels were associated with increased risk. Instead, people in the new study with the lowest blood pressure levels (90-114 mm Hg systolic and 60-74 mm Hg diastolic) had the lowest risk for cardiovascular disease.
For younger patients, the negative effects of hypertension were largely due to an increased risk for coronary artery disease. For older patients, heart failure was the bigger risk.
The findings may also support the early use of antihypertensive treatment in younger people with mild blood pressure elevations. This topic has provoked “substantial debate,” but, the authors write, “in the absence of long-term randomized trials, our estimates of lifetime risk and cardiovascular disease-free years of life lost provide epidemiological evidence of substantial morbidity associated with raised blood pressure, irrespective of the starting baseline risk.”
Although current therapies have helped blunt the impact of hypertension, the authors note that a 30-year-old with hypertension has a 63% lifetime risk of developing cardiovascular disease, compared with 46% in a person without high blood pressure."
Article at:
http://www.forbes.com/sites/larryhusten/2014/05/30/large-study-reveals-important-new-information-about-hypertension/?ss=pharma
NEW TOBACCO DERIVED SUPPLEMENT THAT REDUCES HASHIMOTO'S ANTIBODIES in Thyroid Pharmacist Blog, 11/17/2013
Excerpts:
"Hot off the presses, released on October 31st!
A brand new randomized, double-blind and placebo controlled study (this time in humans) followed a total of 146 patients with Hashimoto's for 3 months. Seventy of those patients were treated with Anatabine at a dose of 9-24mg per day, while the rest were treated with placebo.
The results showed a statistically significant reduction in Thyroglobulin antibodies (TgAb's) at weeks 4, 8, and 12. TgAb's reduced by an average of 46 points in the treatment group compared to a reduction by 4 points in the placebo group. 50% of patients reduced their antibodies by at least 25 points, while 25% reduced their TG antibodies by at least 100 points.
All of the patients in the study were euthyroid, meaning their TSH, T4, T3 were within range, either because they were taking levothyroxine or because they were in the early stages of Hashimoto's. Anatabine did not affect the levels of TSH, T4 or T3, but the patients who were taking levothyroxine seemed to have a greater reduction in antibodies that patients that were not.
Dizziness, nausea, tingling and headaches were some of the more common side effects."
"Surprisingly, the study did not find a statistically significant reduction in TPO antibodies. The authors of the study noted that TG antibodies are often the first antibodies to come down, followed by TPO antibodies and thought that perhaps more time was needed to see a statistically significant drop in TPO antibodies.
I found the same to be true in my case as well. My TG antibodies completely went away after my first lifestyle changes, but the TPO antibodies were slower to budge and took a longer time to reduce.
Additionally, while this was not shared in the study results, the manufacturer did share some preliminary results on TPO levels last January on their healthcare professional portal. One patient who was studied had an enormous drop in antibody levels after she took a dose of 0.12 mg/kg per day of anatabine for sixteen days. Her TPO antibodies reduced from 3655 IU to 300 IU.
I personally tried Anatabine for three months last year when I was in the middle of my root cause search and it actually lowered my TPO antibodies by about 50% (I didn't have anymore TG antibodies at the time).
What I found particularly interesting is that not everyone responds the same to Anatabine, the study noted that not everyone had a drop in TG antibodies, and some had a greater drop than others did. Of course, this makes sense as not everyone has the same root cause.
Article at:
http://www.thyroidpharmacist.com/blog/category/rock-creek-pharmaceuticals
Top GSK exec faces life in Chinese prison for alleged 'massive bribery network' in Fierce Pharma Marketing, May 14, 2014 | By Tracy Staton
Excerpts:
"China is coming down hard on GlaxoSmithKline's ($GSK) local operation. After a months-long bribery probe, Chinese police have charged Glaxo's former country chief and two other top execs with several counts of bribery. All could face life in prison.
Mark Reilly, who headed up the China office when the initial bribery allegations emerged, is accused of masterminding an elaborate scheme to bribe doctors to prescribe GSK products. According to police, Reilly created a "massive bribery network" that funneled secret payments to doctors, hospital staffers and government officials, the London Evening Standard reports."
"The charges are much harsher than industry executives and Chinese insiders had expected. And the potential penalties are equally harsh. The maximum sentence for a bribery charge in China is life in prison.
"It is an extremely serious accusation that they are making here," a lawyer close to the case told the Financial Times. "They are looking at corporate liability. Mark has really been singled out as being responsible for creating a corrupt organization."
"Other Glaxo comments suggested that it's afraid China will bar the company from the country. The company certainly could be forced to pay fines and disgorge profits tainted by corruption, the FT reports. Officials said the bribery generated "illegal revenue worth billions of renminbi"; 1 billion is worth about $160 million."
"Corruption allegations against Glaxo have spread since the China scandal broke. The company is investigating potential bribery in 9 Middle Eastern countries, plus Poland."
Article at:
http://www.fiercepharmamarketing.com/story/top-gsk-exec-faces-life-chinese-prison-alleged-massive-bribery-network/2014-05-14#ixzz33Ii95hbH
Carl Icahn, Phil Mickelson 'in insider trading probe' in BBC News, 31 May 2014
Excerpt:
"The FBI is investigating possible insider trading involving billionaire investor Carl Icahn, golfer Phil Mickelson and Las Vegas gambler William Walters, reports say.
The inquiry is reportedly examining whether Mr Mickelson and Mr Walters may have traded shares illegally, based on information provided by Mr Icahn.
Mr Mickelson's lawyers say he is not the target of an investigation. Mr Icahn denies giving out insider information."
"Mr Icahn, a billionaire investor and prominent activist, was mounting a takeover bid for Clorox around the time that Mr Mickelson and Mr Walters placed their trades, the New York Times reports."
Article at:
http://www.bbc.com/news/world-us-canada-27647437
Global population of obese and overweight tops 2.1bn in BBC Health News, By Pippa Stephens, Health reporter, BBC News, 28 May 2014
My comments:
More autoimmune diseases, cardiovascular problems, cancers, and obviously diabetes. So what part does Anatabine Citrate play?
Article:
"The number of people in the world who are obese or overweight has topped 2.1 billion, up from 875 million in 1980, the latest figures published in the Lancet show.
And not one country is succeeding in treating it, said the research.
US, China and Russia had the highest rates and the UK was third in Western Europe, the 188-country study said.
Experts said the rise was due to the "modernisation of our world", causing "physical inactivity on all levels".
“It takes a little bit of time to see success stories”
Prof Ali Mokdad
Institute for Health Metrics and Evaluation
Gender split
Researchers across the world were led by the Institute for Health Metrics and Evaluation (IHME) in Washington, in a study they said is the most comprehensive to date.
Scientists analysed data from surveys, such as from the World Health Organization, government websites, and reviewed "all articles" about the numbers of obese or overweight people in the world.
The study said rates of obesity were rising across the world, although the rates in developed countries remain the highest.
More than half of the world's 671 million obese people live in 10 countries, ranked in order:
US
China
India
Russia
Brazil
Mexico
Egypt
Germany
Pakistan
Indonesia
Source: The Lancet
The UK has the third highest rates in Western Europe, with 67% of men and 57% of women overweight or obese, it said.
The study called for "urgent global leadership" to combat risk factors such as excessive calorie intake, inactivity, and "active promotion of food consumption by industry".
Prof Ali Mokdad, of the IHME, said no country was beating obesity as it was a relatively new problem.
“Obesity is a complex issue that requires action at national, local, family and individual level”
Prof John Newton
Public Health England
"It takes a little bit of time to see success stories," he said.
The study reported more obese women than men living in developing countries.
Rates tended to be higher for women in developing countries as they were multi-tasking, looking after the family and working, said Prof Mokdad, so did not have the time to dedicate to managing their weight.
But more obese men than women lived in developed countries, said the study.
'Classical eating' loss
Prof Mokdad said rates were higher for men in developed countries because of longer commutes to work, fuelled by a move to the suburbs, and spending more time inactive, using computers, he said.
Prof Hermann Toplak, at the University of Graz, in Austria, said: "Over the past decades the modernisation of our world, with all the technology around us, has led to physical inactivity on all levels."
Inactivity caused self-control to spiral, he said.
Children and adults were not building up enough functioning muscle mass, and "classical eating" had been replaced by "uncontrolled food intake" spread over the day. he said.
Britain's action
Prof John Newton, chief knowledge officer at Public Health England, said poor nutrition and lack of exercise were a big risk factor in Britain's most deprived areas.
PHE ran campaigns to help families be healthy, more active, and cut down on fat and sugar, he said.
He added: "Obesity is a complex issue that requires action at national, local, family and individual level; everyone has a role to play in improving the health and well-being of the public, and children in particular.""
Article at:
http://www.bbc.com/news/health-27586365
Globesity: Fat's New Frontier at YouTube
Published on Jul 24, 2012
Obesity is no longer just a rich country's problem. It's now taken hold in poor and emerging countries and is rapidly developing into an insurmountable health crisis. Type 2 diabetes, heart disease and some cancers are on the march in nation's ill equipped to treat sufferers or educate others about the dangers of getting too fat. It's predicted that by 2030 one billion people will be obese, so how will the world cope with its ever expanding waistline?
My comments:
The death spiral to health. Refined carbohydrates, processed foods, processed seed oils, fast foods, and sugar are the developed worlds latest lifestyle export to solve malnutrition and it's killing the world. The video is an hour long but if you want an overview of today's world of health and where it is headed, well worth the time to view it.
Video at:
Immune Therapy’s Cancer Promise Creates Research Rush in Bloomberg
By Naomi Kresge and Robert Langreth May 29, 2014
Excerpt:
"A new class of medicines that help the body’s own immune cells fight tumors could target a wide set of cancers, opening a $35 billion market for Merck (MRK) & Co., Bristol-Myers Squibb Co., AstraZeneca Plc and Roche (ROG) Holding AG.
The drugmakers will use the world’s largest meeting of cancer doctors, the American Society of Clinical Oncology, to stake their claim on the new technology, which aims to interrupt cancer’s ability to switch off immune system cells that might otherwise attack it.
For years, the idea was only seen as usable against a handful of uncommon tumors. Now, new evidence the drugs may work in a wider range of malignancies, advanced in just the last two years, has spurred Merck, Bristol-Myers, AstraZeneca and Roche to begin at least 78 clinical trials. While the research, with more than 19,000 patients, could cost the four companies as much as $1.3 billion, the payoff would be the creation of a new market that Citigroup Inc. (C) analysts have predicted could reach $35 billion a year."
Article at:
http://www.bloomberg.com/news/2014-05-29/immune-therapy-s-cancer-promise-creates-research-rush.html
Rheumatoid Arthritis video collage on CNN, Healthmakers Series, no date
My comments:
Easy to understand series of videos on RA with references to chronic inflammation. Dialog is similar to discussions with your doctor and your doctor explaining, cause, effect, and treatment.
Video at:
http://healthmakers.cnn.com/rheumatoid-arthritis?videoId=2572941283001&hpt=he_bn7#cmpid=p1rss12
If All Roads Lead to Inflammation, How Do We Get to Health? in Forbes, Alice G. Walton, PhD in Biopsychology and Behavioral Neuroscience at CUNY's Graduate Center in New York City, 10/19/2011
Excerpts:
"Inflammation is a major buzzword in the health industry these days. It seems like all bad lifestyle choices lead to inflammation, and most inflammation leads to bad health outcomes. Eating too much, being sedentary, stressing out, and lacking sleep all apparently make one inflamed and more prone to disease. What, though, does inflammation actually mean, why is it bad for us, and how do we escape it?"
"The problems arise in the aftermath of inflammation – especially chronic inflammation – and our healthy cells can take the brunt. When the immune system kicks into gear, white blood cells and their byproducts can saturate a region and leave healthy tissue overwrought and stressed. Katz says that “our healthy tissues are potential collateral damage – victims of friendly fire – as the immune system does its job defending us from pathogens, and rogue cells. The term is descriptive, and derives more from observation than any genuine insights about physiology.”
In other words, it is difficult to know all the myriad events that are occurring in previously healthy tissue that has suffered the aftermath of inflammation, but the end product is not good.
To put it plainly, chronic inflammation can provide the framework for, if not outright cause, a lot of the major chronic disease states. Katz says that “inflammation – the actions of white blood cells, and the molecules they produce (including oxygen free radicals) – is directly implicated in the progression of most chronic diseases.” This isn’t dramatic, it’s intuitive, he says, because “the process is fundamental, just like oxidation. There are ‘final common pathways’ that unify all of the ways we, and our parts, can fail.”
So what are the diseases that all stem from inflammation? Some of the ones most people are aware are linked are heart disease, type 2 diabetes, and stroke. These diseases are all strongly connected to metabolic syndrome, a pesky intermingling of risk factors like being overweight (particularly having belly fat), being sedentary, and having high blood fats, blood pressure, and cholesterol. Inflammation seems to be the common denominator, possibly the result of the body being subject to these variables over many years.
Other diseases linked to inflammation are less obvious, but just as disturbing – like cancer, Alzheimer’s disease, and, oddly, depression."
"While one’s risk for cancer comes in part from the genes, there is, for better or for worse, more to the picture than genes. The inflammatory status in the body, which can be the result of various lifestyle factors, has a lot to do with cancer risk. The cancer-inflammation connection could work in a variety of ways: one possibility is that an inflamed environment presents the opportunity for potentially cancerous cells to take root and grow. Some evidence has shown that certain immune cells are actually hijacked by cancer cells to become their partners in crime. Other studies have shown bacterial and viral infections are strongly linked to cancer; certain inflammatory diseases like crohn’s disease, also linked to bacterial infection, are known to increase one’s risk for cancer.
Not surprisingly, but unfortunately, inflammation can also affect the brain, and when it does, it seems to lead to some dire consequences. For example, Alzheimer’s disease develops when plaques accumulate in the brain and cannot be cleared away efficiently: it’s thought that the particles that are byproducts of inflammation are at least in part responsible for the formation of these plaques, and studies have shown that the markers of inflammation pepper the brains of Alzheimer’s patients.
Depression is another disorder that has recently been connected with brain inflammation. Some researchers have suggested that depression in an adaptive mechanism to address severe psychological stress. The brain responds to serious psychological assaults with inflammation, say the researchers, and depression becomes the brain’s ineffective, pathological attempt to quell it. Other studies have found that markers of inflammation are actually present more often in the brains of depressed people."
Article at:
http://www.forbes.com/sites/alicegwalton/2011/10/19/all-roads-lead-to-inflammation-so-can-we-ever-get-healthy/
CHRONIC INFLAMMATION AND PATHOGENESIS OF GI AND PANCREATIC
CANCERS, Lindsey Jackson^ and B. Mark Evers, Department of Surgery and ^The Sealy Center for Cancer Cell Biology, The University of Texas Medical Branch Galveston, Texas, source unknown, date unknown
Abstract:
"The pathogenesis of cancer represents a complex and multifactorial process requiring a number of acquired and genetic defects. It is becoming increasingly apparent that many cancers originate from a chronic inflammatory process. The topic of this review is the inflammatory response and development of gastrointestinal (GI) and pancreatic cancers. Here, we describe
the development of various gastric colorectal and pancreatic cancers through an inflammatory process. The tumor microenvironment which predisposes to tissue destruction, subsequent attempts at healing and accumulation of cellular
damage with loss of cell cycle control mechanisms is discussed. Components of the tumor microenvironment that are important in the final common pathway leading to cancer include the tumor stroma, tumor-associated macrophages, cytokines and chemokines and reactive oxygen and nitrogen species. Common signaling pathways that link inflammation with cancer are described and include the COX-2, NF-KB and phosphatidyl inositol 3-kinase
(PI3K) pathways. Finally, therapies that can be directed to the inflammatory process as either treatment or prevention of these cancers will be discussed including novel inhibitors of signaling pathways which are currently in development.
Link Unknown
Obesity and Cancer Risk in National Cancer Institute Fact Sheet, no author, January 2012
Excerpts:
"Keypoints:
During the past several decades, the percentage of overweight and obese adults and children has increased markedly.
Obesity is associated with increased risks of cancers of the esophagus, breast (postmenopausal), endometrium (the lining of the uterus), colon and rectum, kidney, pancreas, thyroid, gallbladder, and possibly other cancer types.
Obese people are also at higher risk of coronary heart disease, stroke, high blood pressure, diabetes, and a number of other chronic diseases."
"Obesity is associated with increased risks of the following cancer types, and possibly others as well:
Esophagus
Pancreas
Colon and rectum
Breast (after menopause)
Endometrium (lining of the uterus)
Kidney
Thyroid
Gallbladder"
"Obese people often have chronic low-level, or “subacute,” inflammation, which has been associated with increased cancer risk.
Other possible mechanisms include altered immune responses, effects on the nuclear factor kappa beta system, and oxidative stress."
Article at:
http://www.cancer.gov/cancertopics/factsheet/Risk/obesity
Inflammation-Associated Cancer Development in Digestive Organs: Mechanisms and Roles for Genetic and Epigenetic Modulation in Gastroenterology, Tsutomu Chibaemail, Hiroyuki Marusawa, Toshikazu Ushijima, Kyoto University, Kyoto, Japan, Received: March 5, 2012; Accepted: July 3, 2012; Published Online: July 16, 2012, Robert F. Schwabe and John W. Wiley, Section Editors
Abstract:
"Chronic inflammation, regardless of infectious agents, plays important roles in the development of various cancers, particularly in digestive organs, including Helicobacter pylori–associated gastric cancer, hepatitis C virus–positive hepatocellular carcinoma, and colitis-associated colon cancers. Cancer development is characterized by stepwise accumulation of genetic and epigenetic alterations of various proto-oncogenes and tumor-suppressor genes. During chronic inflammation, infectious agents such as H pylori and hepatitis C virus as well as intrinsic mediators of inflammatory responses, including proinflammatory cytokines and reactive oxygen and nitrogen species, can induce genetic and epigenetic changes, including point mutations, deletions, duplications, recombinations, and methylation of various tumor-related genes through various mechanisms. Furthermore, inflammation also modulates the expressions of microRNAs that influence the production of several tumor-related messenger RNAs or proteins. These molecular events induced by chronic inflammation work in concert to alter important pathways involved in normal cellular function, and hence accelerate inflammation-associated cancer development. Among these, recent studies highlighted an important role of activation-induced cytidine deaminase, a nucleotide-editing enzyme essential for somatic hypermutation and class-switch recombination of the immunoglobulin gene, as a genomic modulator in inflammation-associated cancer development."
Article at:
http://www.gastrojournal.org/article/S0016-5085(12)00957-2/abstract
Chronic Inflammation and Cancer: The Role of the Mitochondria in in Defeat Osteosarcoma, 27 Apr 2011 in Carcinogens, Educational, Etiology and cause of osteosarcoma, Inflamation, MicroRNA, Understanding Cancer, ONCOLOGY. Vol. 25 No. 5
By David W. Kamp, MD1,2,Emily Shacter, PhD3, Sigmund A. Weitzman, MD2 | April 22, 2011, 1 Jesse Brown VA Medical Center, Chicago, Illinois, 2 Northwestern University Feinberg School of Medicine, Chicago, Illinois, 3 Center for Drug Evaluation and Research, Food and Drug Administration, Bethesda, Maryland
ABSTRACT:
"Accumulating evidence shows that chronic inflammation can promote all stages of tumorigenesis, including DNA damage, limitless replication, apoptosis evasion, sustained angiogenesis, self-sufficiency in growth signaling, insensitivity to anti-growth signaling, and tissue invasion/metastasis. Chronic inflammation is triggered by environmental (extrinsic) factors (eg, infection, tobacco, asbestos) and host mutations (intrinsic) factors (eg, Ras, Myc, p53). Extensive investigations over the past decade have uncovered many of the important mechanistic pathways underlying cancer-related inflammation. However, the precise molecular mechanisms involved and the interconnecting crosstalk between pathways remain incompletely understood. We review the evidence implicating a strong association between chronic inflammation and cancer, with an emphasis on colorectal and lung cancer. We summarize the current knowledge of the important molecular and cellular pathways linking chronic inflammation to tumorigenesis. Specifically, we focus on the role of the mitochondria in coordinating life- and death-signaling pathways crucial in cancer- related inflammation. Activation of Ras, Myc, and p53 cause mitochondrial dysfunction, resulting in mitochondrial reactive oxygen species (ROS) production and downstream signaling (eg, NF?B, STAT3, etc.) that promote inflammation- associated cancer. A recent murine transgenic study established that mitochondrial metabolism and ROS production are necessary for K-Ras–induced tumorigenicity. Collectively, inflammation-associated cancers resulting from signaling pathways coordinated at the mitochondrial level are being identified that may prove useful for developing innovative strategies for both cancer prevention and cancer treatment.
Article at:
http://defeatosteosarcoma.org/2011/04/chronic-inflammation-and-cancer-the-role-of-the-mitochondria/
Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability in Carcinogenesis, Italian Association for Cancer Research; Italian Ministry of Health; Project Oncology 2006 and Alleanza Contro il Cancro, University and Research; European FP6 Programme (LSHB-CT-2005-518167) Project Innochem; NOBEL project, Fondazione Cariplo., Francesco Colotta1, Paola Allavena2, Antonio Sica2,3, Cecilia Garlanda2 and Alberto Mantovani2,4,*
1Nerviano Medical Sciences, Nerviano, 20014 Nerviano, Milan, Italy
2Department of Immunology and Inflammation, Istituto Clinico Humanitas IRCCS, Via Manzoni 56, 20089 Rozzano, Milan, Italy
3Institute of Pathology, University of Piemonte Orientale, 28100 Novara, Italy, 4Department of Translational Medicine, University of Milan, 20121 Milan, Italy, May 2009
Abstract:
"Inflammatory conditions in selected organs increase the risk of cancer. An inflammatory component is present also in the microenvironment of tumors that are not epidemiologically related to inflammation. Recent studies have begun to unravel molecular pathways linking inflammation and cancer. In the tumor microenvironment, smoldering inflammation contributes to proliferation and survival of malignant cells, angiogenesis, metastasis, subversion of adaptive immunity, reduced response to hormones and chemotherapeutic agents. Recent data suggest that an additional mechanism involved in cancer-related inflammation (CRI) is induction of genetic instability by inflammatory mediators, leading to accumulation of random genetic alterations in cancer cells. In a seminal contribution, Hanahan and Weinberg [(2000) Cell, 100, 57–70] identified the six hallmarks of cancer. We surmise that CRI represents the seventh hallmark."
Article at:
http://carcin.oxfordjournals.org/content/30/7/1073.full
Targeting chronic inflammation in cerebral aneurysms: focusing on NF-?B as a putative target of medical therapy
March 2010, Vol. 14, No. 3 , Pages 265-273, Tomohiro Aoki1 & M Nishimura†2, 1Kyoto University, Pharmacology, Kyoto, Japan
2Kyoto University, Neurosurgery, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan
Article Summary:
"Importance of the field: Cerebral aneurysms (CAs) are the main cause of life-threatening subarachnoid hemorrhage. Given its prevalence and endpoint, CA treatment is a public health issue. Effective medical treatment of CAs is lacking because the detailed mechanisms of CA formation are incompletely understood.
Areas covered in this review: The aim of this contribution is to review recent articles about CA formation, to suggest the underlying mechanisms of CA formation, and to discuss potential therapeutic targets for treatment. Articles were collected by an internet search of PubMed using the keywords ‘intracranial’ or ‘cerebral aneurysm’.
What the readers will gain: A review of articles about the pathogenesis of CA formation focusing on inflammation. Recent articles demonstrate that inflammation-related-molecule induction and inflammatory cell infiltration in CA walls and the close relationship between inflammatory responses and CA formation. From studies in experimental models, chronic inflammation triggered primarily by NF-?B activation in endothelial cells and subsequent macrophage infiltration have critical roles in CA formation. Inhibition of inflammation-related molecules in CA walls results in the decreased incidence of CA formation.
Take-home message: Agents with anti-inflammatory activity (particularly anti- NF-?B effects) have potential as therapeutic drugs for CAs."
Article at: http://informahealthcare.com/doi/abs/10.1517/14728221003586836
Re your commentary:
"This is a REAL study not STSI garbage...
Notice how the results are talking about improving symptoms.
The STSI studies don't study symptoms... because they know those studies would expose anatabloc as a scam. JMHO"
The facts:
Anatabloc is a neutracutical that underwent a small clinical trial no different than a prescription drug would during phase 3 trials. Please tell me the names of other neutracuticals that have done the same? Anatabloc blocks the stimulation of NF-B, the cause of chronic inflammation. ("Thyroiditis is an inflammation (not an infection) of the thyroid gland." (from EndoCrine Web)) So, in fact, Anatabloc's mode of efficacy treats the cause rather than symptoms as you state. From the article: "The Bristol Myers drug clazakizumb in concert with another drug methotrexate showed efficacies equal to an existing drug by Humira." Please reread the excerpt again, carefully. The article shows that their drug treated improvement in symptoms, not cause. From the article:
"Bristol-Myers’s clazakizumab with methotrexate reduced their symptoms by at least 20 percent, the company said. That was twice the rate of patients who took only methotrexate, a generic treatment for the disease. Of patients taking methotrexate and Humira, AbbVie’s injectable drug that sold $9.27 billion last year, 76 percent had symptoms fall by at least 20 percent. " So Bristol Myer's drug just equaled an existing drug by AbbVie.
It is unusual that a neutracutical would take on a clinical trial, especially in an area where few drugs provide a reduction in anti-bodies. The clincal trials also state that: "Long-term studies are warranted to confirm these results"
You can reread the facts about the trial here:
ASAP trial: Anatabine decreased thyroid autoimmunity in Endocronology Today, Schmeltz LR. J ClinEndocrinolMetab.,November 6, 2013 at:
http://www.healio.com/endocrinology/thyroid/news/online/%7B288199cd-9fb4-46e7-8240-9de6a1346786%7D/asap-trial-anatabine-decreased-thyroid-autoimmunity
Your negative commentaries, while appreciated, should be based on facts and not on false assertations that are misleading. You should read a book: "Merchants of Doubt", it pretty much sums up your modus-operandi: "The U.S. scientific community has long led the world in research on such areas as public health, environmental science, and issues affecting quality of life. Our scientists have produced landmark studies on the dangers of DDT, tobacco smoke, acid rain, and global warming. But at the same time, a small yet potent subset of this community leads the world in vehement denial of these dangers. Merchants of Doubt tells the story of how a loose-knit group of high-level scientists and scientific advisers, with deep connections in politics and industry, ran effective campaigns to mislead the public and deny well-established scientific knowledge over four decades. Remarkably, the same individuals surface repeatedly-some of the same figures who have claimed that the science of global warming is "not settled" denied the truth of studies linking smoking to lung cancer, coal smoke to acid rain, and CFCs to the ozone hole. "Doubt is our product," wrote one tobacco executive. These "experts" supplied it. Naomi Oreskes and Erik M. Conway, historians of science, roll back the rug on this dark corner of the American scientific community, showing how ideology and corporate interests, aided by a too-compliant media, have skewed public understanding of some of the most pressing issues of our era." Your character description is similar to 'Fred Singer'
I recommend this book highly, you might get some ideas from it to improve your editorial skills.
BTW, you apparently did not read the posting #19261. I bring this to your attention-- "Calling all Cynics" at: http://investorshub.advfn.com/boards/read_msg.aspx?message_id=102589698
Biochemistry Brings Health Management Up Close And Personal in Forbes, Robert Szczerba, 5/29/2014
Excerpts:
"We’re all painfully aware that, despite the abundance of data supporting the benefits of a healthy diet, regular exercise, and moderate alcohol consumption, Americans are increasingly challenged by excess weight, limited physical activity, and bad eating habits. These risk factors routinely lead to such conditions as cardiovascular disease, diabetes, osteoporosis, depression, and cancer. Exercise and diet are critical parts of an individual’s lifestyle, but attempts to change lifestyle are notoriously problematic in terms of compliance.
Next generation blood analysis can help
For many people, having more information about the state of their health can motivate them to make lifestyle changes and empower them to maintain those changes over time. One innovative company that aims to provide that motivating data is InsideTracker. Their next-generation health management tools are tailored to the biochemistry of an individual. We had the opportunity to speak with InsideTracker’s founder and Chief Scientific Officer, Gil Blander, about how detailed information on key blood biomarkers can be used by individuals to manage and optimize their own health.
“Blood analysis is a powerful indicator of your current health condition,” Blander explains, “but most people don’t get the full benefits of testing that they’ve already done. Do you have an annual blood test at your doctor’s office? If you do, then you’re probably used to getting a follow-up postcard in the mail that says your blood test was ‘normal.’ You may not know which blood tests your doctor ordered, let alone what your results actually were.”
"Go beyond “normal” to “optimal”
The “normal” range for a biomarker typically applies to all adults. That means “normal” may be the same for everyone from a 22-year-old who regularly competes in triathlons to an inactive, 78-year-old retiree. “Why do we accept ‘normal’ for our health results,” asks Blander, “when in all other aspects of our professional and personal lives we want to be the best we possibly can be?”
To make meaningful changes to your health risk behaviors you need to know not just your “normal” range for each biomarker, but also your personal “optimal” range, based on your unique characteristics, including age, gender, ethnicity, height, weight, activity level, and lifestyle goals.
Research has shown that improving your biomarkers into your optimal zone can increase your well-being, performance, and, in some cases, longevity. Knowing your optimized level gives you data to identify which behavioral changes can decrease your long-term risk for chronic health conditions. For example, your glucose may be “normal,” but higher than optimal. Lowering your glucose level to your optimal zone can improve your longevity and reduce your risk of developing diabetes."
"Focus on health, not on sickness
Blood work, and healthcare in general, has traditionally focused on identifying and treating current illnesses, rather than prevention and overall wellness. Some important biomarkers that are not typically tested during yearly physicals include C-reactive protein (CRP), vitamin D, and testosterone. CRP can indicate low levels of chronic inflammation, which has been linked to a variety of conditions, such as cardiovascular disease and diabetes. Your CRP levels may rise before you have any visible symptoms. Low levels of vitamin D are associated with low energy, poor immune system function, and difficulty in losing weight. Low testosterone can affect your overall energy and muscle development, making it harder to increase your physical activity."
"Retest regularly
Your annual blood test isn’t enough to support an effort to change your health risk behaviors. With appropriate modifications, some biomarkers may change in just 2 months, while others may take 3-4 months. Blander suggests “to stay on track, to fine-tune your program, and to continue to make progress, you should have your blood tested 2-4 times a year.”
Article at:
http://www.forbes.com/sites/robertszczerba/2014/05/29/biochemistry-brings-health-management-up-close-and-personal/
Obama Vs. Concussions: Why The White House Made Head Injuries A Presidential Issue in Forbes Pharma and Healthcare, Dan Diamond, 5/29/2014
Excerpts:
"There are many reasons why President Obama might have decided to host the first-ever White House summit on concussions. He’s a sports fan. He’s a parent.
And he’s a lifelong athlete who likely had a couple concussions of his own, Obama acknowledged on Thursday. (An admission that I don’t believe he’s made before.)"
“When I was young and played football briefly, there were a couple of times where I’m sure that that ringing sensation in my head and the need to sit down for a while might have been a mild concussion,” the president said at Thursday’s White House Healthy Kids & Safe Sports Concussion Summit.
“At the time you didn’t think anything of it. [And] the awareness is improved today, but not by much.”
The presidential summit brings together sports officials, researchers, parents, and athletes. And the day is packed with a mix of activities. In the morning, Obama gave his most extensive remarks yet on concussions; in the afternoon, the president will participate in drills with local youth athletes. FOX Sports reporter Pam Oliver—who suffered her own high-profile concussion—will moderate a panel with General Ray Odierno, the Army’s chief of staff. Academics will be on hand to discuss their latest findings.
As Sean Gregory writes at TIME, it’s unclear exactly how much the summit will actually accomplish—although it’s already served to boost awareness and gin up more research dollars.
The president announced a $30 million joint study between the NCAA and the Pentagon that purports to be “the most comprehensive clinical study of concussion and head impact exposure ever conducted.” The NFL and NIH have announced significant new research efforts, too."
"At Thursday’s summit, Obama stressed that while many young athletes experience head injuries, the sheer volume of concussions remains little-understood. “The fact is, we don’t have solid numbers, and that tells me that at every level we’re all still trying to fully grasp what’s going on with this issue,” he said.
But the president shared his hope that by finding out more data on head injuries, and changing awareness, more youth athletes will ultimately be protected.
According to Obama, “we have to change a culture that says ‘you suck it up’” and try to play through head injuries.
“It doesn’t make you weak” to admit that you’ve had a concussion, the president added. “It means you’re strong.”
Article at:
http://www.forbes.com/sites/dandiamond/2014/05/29/obama-vs-concussions-why-the-white-house-made-head-injuries-a-presidential-issue/?ss=pharma
Bristo-Myers Shares Rise on Drug Trial Results in Bloomberg, By Drew Armstrong Oct 28, 2013
Excerpt:
"Bristol-Myers Squibb Co. (BMY) rose to its highest closing price since 2001 after releasing trial results that showed its experimental drugs for lung cancer and rheumatoid arthritis helped patients.
Bristol-Myers rose 6.7 percent to $52.02 at 4 p.m. New York time, the highest closing value since December 2001 and the biggest one-day gain since March 2009. The New York-based company released data over the weekend that showed its top pipeline project, an immune-system based cancer treatment, extended the lives of lung cancer patients. The company’s experimental rheumatoid arthritis treatment was found to be about as effective as a current standard treatment sold by AbbVie Inc. (ABBV), a study found.
In a trial of 418 rheumatoid arthritis patients, 78 percent of those who took Bristol-Myers’s clazakizumab with methotrexate reduced their symptoms by at least 20 percent, the company said. That was twice the rate of patients who took only methotrexate, a generic treatment for the disease. Of patients taking methotrexate and Humira, AbbVie’s injectable drug that sold $9.27 billion last year, 76 percent had symptoms fall by at least 20 percent.
“It’s encouraging, especially since they had a comparator arm there with Humira plus methotrexate,” said Grant Louie, a rheumatologist and professor of medicine at Johns Hopkins University School of Medicine. “It does appear to be comparable.”
Article at:
http://www.bloomberg.com/news/2013-10-28/bristo-myers-shares-rise-on-drug-trial-results.html
Down-regulation of NF-?B transcriptional activity in HIV-associated kidney disease by BRD4 inhibition in The Journal of Biological Chemistry, Guangtao Zhang, Ruijie Liu, Yifei Zhong, Alexander N. Plotnikov, Weijia Zhang, Lei Zeng, Elena Rusinova, Guillermo Gerona-Nevarro, Natasha Moshkina, Jennifer Joshua, Peter Y. Chuang, Michael Ohlmeyer, John Cijiang He and Ming-Ming Zhou*, Mount Sinai School of Medicine, United States, May 2012
Abstract:
"NF-kB-mediated inflammation is the major pathology in chronic diseases including HIV-associated kidney disease (HIVAN) that ultimately progresses to end stage renal disease. HIV infection in kidney induces NF-kB activation leading to the production of pro-inflammatory chemokines, cytokines, and adhesion molecules. In this study, we explored selective inhibition of NF-kB transcriptional activity by pharmacological blocking NF-kB binding to the transcriptional cofactor BRD4 that is required for the assembly of the productive transcriptional complex comprising p-TEFb and RNA Polymerase II. We showed that our BET-specific bromodomain inhibitor MS417, designed to block BRD4 binding to the acetylated NF-kB, effectively attenuates NF-kB transcriptional activation of pro-inflammatory genes in kidney cells treated with TNFa or infected by HIV. MS417 ameliorates inflammation and kidney injury in HIV-1 transgenic mice, an animal model for HIVAN. Our study suggests that BET bromodomain inhibition, targeting at NF-kB pro-inflammatory activity, represents a new therapeutic approach for treating NF-?B-mediated inflammation and kidney injury in HIVAN.
Article at:
http://www.jbc.org/content/early/2012/05/29/jbc.M112.359505
NF-kB as target for Parkinson's Disease Therapy at Michael J. Fox Foundation For Parkinson's Research, Therapeutics Development Initiative, 2007
Objective/Rationale:
"Chronic inflammation mediated by microglial cells is the fundamental process contributing to the death of dopamine producing neurons in the brain. Production of inflammatory products by these microglial cells characterizes the slow destructive process in Parkinson’s disease. NF-?B is a protein which controls the expression of over 200 genes critical in inflammation and the immune response within the microglial cell, and we believe that therapies aimed at inhibiting the expression of NF-kB will be successful in reversing or slowing the progression of Parkinson’s disease. "
Webpage at:
https://www.michaeljfox.org/foundation/grant-detail.php?grant_id=394
European NF-kappaB Subunit Workshop, 6-8 October 2014, Atholl Palace Spa Hotel, Pitlochry, Scotland
Public Notice:
"On behalf of the Organizing Committee, we are delighted to invite you to participate in the second European NF-kappaB Subunit Workshop, to be held at Atholl Palace Spa Hotel in Pitlochry, Scotland from 6th to 8th October 2014.
The NF-kappaB transcription factor is essential for immune development and homeostasis, but is also a broad regulator of fundamental cellular processes that control the cell cycle, proliferation, differentiation and autophagy. NF-kappaB also has a central role in many important human diseases including chronic inflammation, cancer and atherosclerosis. There are five subunits within the NF-kappaB family, each of which can have independent or combined functions. Although the NF-kappaB pathway is the subject of intensive research, the function of these independent subunits has traditionally been overlooked. The objective of this workshop is to increase our understanding of these subunits and their role in disease.
The first European NF-kappaB Subunit Workshop was held in Germany in 2012 and was considered a tremendous success. The outcomes from this meeting were increased collaboration, sharing of reagents/biological tools and more coherence within the community. With the 2014 meeting, we aim to continue to build our knowledge in this subject area and increase relations between researchers across Europe, with thoughts of collaborative proposals for Horizon 2020.
The workshop will be held in beautiful Pitlochry, in the heart of Scotland. In addition to the scientific programme, we will also ensure that delegates have the opportunity to experience Scottish hospitality and culture through the conference dinner and ceilidh.
We look forward to welcoming you to Scotland in 2014!
The Scientific Organising Committee
Dr Kirsteen Campbell, The Beatson Institute, Glasgow
Dr Ruaidhri Carmody, Institute of Infection Immunity and Inflammation, University of Glasgow
Professor Neil Perkins, Institute for Cell and Molecular Biosciences (ICaMB), Newcastle University
Dr Sonia Rocha (Chair SOC), The Centre for Gene Regulation and Expression, University of Dundee
Dr Lesley Stark, Medical Research Council, Human Genetics Unit, The University of Edinburgh
Dr Simon Wilkinson, Edinburgh Cancer Research UK Centre, University of Edinburgh"
Website at:
http://nf-kappab.eu/
A Third of the World is Now Obese or Overweight in Time Magazine,
Denver Nicks @DenverNicks May 28, 2014
Article:
"No country on earth has reduced obesity rates in more than three decades
Almost 30 percent of the earth’s population is obese or overweight, a new study reports, estimating that this affects about 2.1 billion people.
Obesity rates have increased in countries all over the world, but it’s not an evenly distributed health problem, the Institute for Health Metrics and Evaluation reported on Wednesday.
In the developed world, adult men have higher rates of obesity (defined as having a Body Mass Index of 30 or more) than adult women. In the developing world, the opposite is true.
The prevalence of overweight and obese children and adolescents worldwide has increased by nearly 50 percent since 1980, the study says, and no country on Earth has successfully reduced obesity rates in the last 33 years.
Childhood obesity rates are notably higher in the Middle East and North Africa, particularly among girls.
[b]Though the rate of increase in obesity has slowed in the developed world, in the developing world, home to two-thirds of the world’s obese people, obesity rates are projected to continue their climb."
Article at:
http://time.com/134206/a-third-of-the-world-is-now-obese-or-overweight/
NF-?B pathway activators as potential ageing biomarkers: targets for new therapeutic strategies in Immunity and Aging, Carmela R Balistreri*, Giuseppina Candore, Giulia Accardi, Giuseppina Colonna-Romano and Domenico Lio, Corresponding author: Carmela R Balistreri, Department of Pathobiology and Medical and Forensic Biotechnologies, University of Palermo, Corso Tukory 211, Palermo 90134, Italy, October 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.
Article at:
http://www.immunityageing.com/content/10/1/24
NF-?B pathway in colitis-associated cancers in Translational Gastrointestinal Cancer, Emilie Viennois1, Fengyuan Chen1, Didier Merlin1, Department of Biology, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA, USA; 2Department of Gastroenterology, Shanghai Fifth People’s Hospital, Fudan University, Shanghai 200240, People’s Republic of China; 3Veterans Affairs Medical Center, Decatur, GA, USA
Corresponding to: Emilie Viennois, Ph.D. Department of Biology, Center for Diagnostics and Therapeutics, Po Box 5090, Georgia State University, Atlanta, GA, 30303, USA., January 2013
Abstract:
Colitis-associated cancer is the subtype of colorectal cancer that is associated with inflammatory bowel diseases including ulcerative colitis and Crohn’s disease. Colorectal cancer is one of the most commonly diagnosed cancers, and is the third leading cause of cancer death in developed countries. Of the signaling pathways involved in colonic inflammation, that triggered by NF-?B plays a key role. A relationship between inflammation and cancer is now well documented. Moreover, the association between NF-?B activity and cancer development has been intensively investigated. The present review focuses on the activity of the NF-?B signaling pathway in colitis-associated carcinogenesis. The pivotal roles played by this pathway in apoptosis, tumor promotion, and tumor maintenance strongly suggest that inhibitors of the pathway would be powerful anti-cancer agents.
Article at:
http://www.amepc.org/tgc/article/view/1254/1878
NF-kB mediated inflammation in tobacco-induced lung cancer in Tobacco Related Disease Research Program, Institution: University of California, San Diego, Investigator(s): Michael Karin, Ph.D., Award Cycle: 2006 (Cycle 15) Grant #: 15RT-0197, Award: $420,000, Subject Area: Cancer, Award Type: Research Project Awards
Abstracts:
Initial Award Abstract
Chronic exposure to tobacco smoke leads to a large increase in the risk of development of lung cancer. It is well established that tobacco smoke contains chemicals that cause cancer, called carcinogens. Carcinogens act by causing damage to DNA and consequently a variety of genetic alterations. However, not every individual that has been exposed to the same amount of carcinogens through tobacco smoking develop lung cancer. Also some people suffer from lung cancer after a few years of smoking, while others develop cancer only after many years of heavy smoking. Thus additional factors, other than exposure to carcinogens, strongly modulate and affect the development of lung cancer. Based on previous work done in our laboratory we propose that one such additional factor is inflammation. We have shown that activation of inflammatory cells (such as macrophages and other phagocytes) makes an important and considerable contribution to the development of chemically-induced colon cancer and liver cancer. It is well established that tobacco smoke is full of irritants and various particles that can trigger an inflammatory response. Indeed, prolonged cigarette consumption results in chronic airway and lung inflammation. This inflammation can activate a regulatory protein called NF-?B that promotes the production of various growth factors and protects pre-malignant cells from surveillance mechanisms that keep the incidence of cancer low by killing cells that suffered DNA damage as a result of carcinogen exposure. We have previously shown that NF-?B plays a critical role in the development of colon and liver cancer and now we propose to examine its role in the development of lung cancer. We will use a mouse model of lung cancer in which cancer is induced by exposure to carcinogens and tobacco smoke. Genetic technology will be used to prevent the activation of NF-?B in either the epithelial cells of the lung or in inflammatory cells and the consequences of these manipulations on the development of lung cancer will be determined. We will also investigate the molecular mechanisms through which NF-?B contributes to cancer development in this model. These studies will provide us with critical and important information on the role of inflammation in lung cancer and should lay the foundations for new interventional strategies.
Article at:
http://www.trdrp.org/fundedresearch/grant_page.php?grant_id=4758
NF-kappaB as a therapeutic target in chronic inflammation: recent advances in Research Gate, S S Makarov, Thurston Arthritis Research Center, Center for Inflammatory Disorders, and Department of Endodontics, University of North Carolina at Chapel Hill, 27599-7280, USA., Source: PubMed, no date
ABSTRACT:
" The family of nuclear factor kappaB (NF-kappaB) transcription factors is a topic of intense interest in the biomedical community stemming from the role NF-kappaB plays in almost every aspect of cell regulation: stress responses, immune cell activation, apoptosis, proliferation, differentiation and oncogenic transformation. The objective of this article is to provide an overview of recent developments in the field with an emphasis on the role of NF-kappaB in chronic inflammation, and to discuss the feasibility of therapeutic approaches based on the specific suppression of the NF-kappaB pathway."
Article at:
http://www.researchgate.net/publication/12254037_NF-kappaB_as_a_therapeutic_target_in_chronic_inflammation_recent_advances
The Inflammation Link: NF-?B Remains a Difficult but Intriguing Target in OncLive, Jane de Lartigue, PhD, Published Online: Friday, June 28, 2013
Excerpt:
"While anticancer therapies aimed at particular pathways have mushroomed in recent years, one crucial target has remained elusive: nuclear factor kappa-light-chain-enhancer of activated B cells (NF-?B). The pathway is constitutively active in the majority of cancers and provides a mechanistic link between chronic inflammation and tumorigenesis. As such, it represents an important target for anticancer therapy. The complex regulation of NF-?B activation has presented significant challenges for the development of such agents, but researchers are now beginning to better understand and embrace this complexity to drive development of a variety of novel NF-?B-targeting strategies."
Article at:
http://www.onclive.com/publications/oncology-live/2013/june-2013/the-inflammation-link-nf-b-remains-a-difficult-but-intriguing-target/1#sthash.vBupZeXI.dpuf
Secrets From the Longest-Living Place on Earth in AARP Health,
A healthy diet, among other things, contribute to town's remarkable turnaround, by Kirk Spitzer, AARP Bulletin, May 2014
Excerpts:
"A focus on diet
The first step in boosting Nagano's life span was a campaign to reduce salt consumption and promote a healthier diet and lifestyle. Miso soup, served three times a day in many homes, became a prime target of health officials. Cases of hypertension and related illnesses began to decline shortly after, Sonohara says. The region of 2.1 million people now has some 4,500 volunteers who host seminars and clinics at supermarkets, shopping malls and community centers. They also conduct regular home visits to measure the salt content in daily meals and make dietary recommendations. "Our goal and our motives had nothing to do with becoming number one in life expectancy," said Sonohara. "[But] individual efforts and local initiatives gradually changed the lifestyle, and that in turn lengthened the life expectancy for the region as a whole."
"The efforts paid off with surprising speed. By 1990, life expectancy for men had risen three years in a decade in Nagano prefecture, and 3.5 years for women. Nagano life spans continued to climb until they topped all of Japan by 2010. Rates of deaths due to cancer, heart and liver disease, and pneumonia now rank well below the national average."
"Those preventive care efforts contributed to lower health care costs in Nagano, which came to about $2,488 per person in 2009. The per capita average in Japan was $3,120, according to a survey by the Kaiser Family Foundation. That compares with $8,233 in the United States. Japan's national health insurance program, which covers virtually all residents, including those in intensive nursing care, is funded in part by local contributions. "Preventive medicine is much less costly than having to put people in the hospital," Sugenoya says."
Article at:
http://www.aarp.org/health/healthy-living/info-2014/longevity-secrets-from-japan.2.html
Chronic inflammation: The new science behind America's deadliest diseases in Fox News, Published July 17, 2012, The Wall Street Journal, no author cited
Article:
"What do heart disease, diabetes, Alzheimer's, stroke and cancer have in common? Scientists have linked each of these to a condition known as chronic inflammation, and they are studying how high-fat foods and excess body weight may increase the risk for fatal disorders.
Inflammation is the body's natural response to injury and outside irritants. But when the irritants don't let up, because of a diet of high-fat foods, too much body fat and smoking, for example, the immune system can spiral out of control and increase the risk for disease. Experts say when inflammation becomes chronic it can damage heart valves and brain cells, trigger strokes, and promote resistance to insulin, which leads to diabetes. It also is associated with the development of cancer.
Much of the research on chronic inflammation has focused on fighting it with drugs, such as cholesterol-lowering statins for heart disease. A growing body of research is revealing how abdominal fat and an unhealthy diet can lead to inflammation. Some scientists are investigating how certain components in foods might help. Dietary fiber from whole grains, for instance, may play a protective role against inflammation, a recent study found. And dairy foods may help ease inflammation in patients with a combination of risk factors.
Chronic inflammation is perhaps best understood in its relation to cardiovascular disease. The immune system's white blood cells rush to the arteries when the blood vessels are besieged by low density lipoprotein, or LDL—the "bad" cholesterol. The cells embed themselves in the artery wall and gobble up the invading cholesterol, causing damage to the arteries that can lead to heart attack or stroke.
"You need to have inflammation when you have a wound and the immune system goes in to heal it. Yet we don't want too much inflammation in our system causing damage to our arteries" and other harm, says Wendy Weber, a program director at the National Center for Complementary and Alternative Medicine, part of the National Institutes of Health.
One significant discovery concerns obesity and the ways it promotes inflammation. Fat cells, particularly those in the visceral fat that settles in the belly and around organs, were long thought merely to store excess weight. Instead, fat cells act like small factories to churn out molecules known as cytokines, which set inflammation in motion, says Peter Libby, chief of the division of cardiovascular medicine at Brigham and Women's Hospital in Boston and a professor at Harvard Medical School."
Article at:
http://www.foxnews.com/health/2012/07/17/chronic-inflammation-new-science-behind-america-deadliest-diseases/
Can Young Blood Reverse Aging in Older Brains? in AARP Health,
Posted on 05/6/2014 by Elizabeth Agnvall |AARP Blog Author |
Article:
"What’s the secret of youth? It may be all in the blood.
labmouse
Three new studies published Sunday showed that when the blood of young mice was put into the systems of older mice, the effects of aging were reversed, improving both muscles and brains. Researchers will now race to find practical implications for older human brains. One of the study authors plans to start a trial this year, giving young blood to Alzheimer’s patients to see if it can reverse effects of the disease.
“These findings could be a game changer,” Rudolph Tanzi, a professor of neurology at Harvard Medical School, told the New York Times.
Scientists at Stanford University joined mice by stitching together their skin. The blood from the young mouse flowed into the system of the older mouse and vice versa. The scientists found that the older mice benefited from the merging. Not only did they produce more blood vessels and neurons, they had an enhanced ability to strengthen connections between nerve cells. Researchers then discovered that injecting a protein found in blood had the same benefits as sharing the blood supply.
“It was as if these old brains were recharged by young blood,” said Tony Wyss-Coray, lead author of the study published in Nature Medicine and a professor of neurology and neurological sciences at Stanford. If the same goes for humans, it could mean new new therapeutic approaches for treating dementias such as Alzheimer’s disease. Wyss-Coray has launched a start-up company, Alkahest, and is planning to start the first young blood trial this year on Alzheimer’s patients, according to the Washington Post.
Two studies out of Harvard, both released online in the journal Science, tested a protein that is more plentiful in the blood of younger mice than older ones. They found that giving older mice the protein, called GDF11, caused them to grow new blood and brain cells, leading to better brain function.
>> Get discounts on health services with your AARP Member Advantages.
“There seems to be little question that, at least in animals, GDF11 has an amazing capacity to restore aging muscle and brain function,” said Doug Melton, co-chair of Harvard’s Department of Stem Cell and Regenerative Biology.
Some scientists are urging caution, however, warning that no one knows what might happen with efforts to rejuvenate older human brains. Irina Conboy, a professor of bioengineering at the University of California, Berkeley, told the New York Times that waking up stem cells could dramatically increase the incidence of cancer. “You have to be careful about overselling it,” she said."
Article at:
http://blog.aarp.org/2014/05/06/can-young-blood-reverse-aging-in-older-brains/
Calling All Cynics: Your Mistrust Is Bad for Your Brain in AARP Brain Health, Posted on 05/28/2014 by Elizabeth Agnvall |AARP Blog Author
Excerpt:
"If you’re a cynic you’ll probably disregard this, but researchers say that cynical mistrust will triple your risk of developing dementia.
Scoff all you want, but researchers in Finland who tested 1,449 older adults (average age 71) found that highly cynical people were three times more likely to develop dementia than those with a more trusting, optimistic personality, according to a study published today in the journal Neurology.
In other words, “your personality may affect your brain health,” explained lead author Anna-Maija Tolppanen, of the University of Eastern Finland in Kuopio."
"But there may be more to it than that. Tolppanen’s study made adjustments for smoking and general health, so she said cynicism may cause chemical or structural changes in the brain. Cynical people may have higher levels of inflammation, a weakened immune system and higher stress levels, she said.
It also could be because highly cynical people border on being paranoid. To be judged highly cynical in this study, people had to wholeheartedly agree with statements like: “I think most people would lie to get ahead,” “It is safer to trust nobody” and “I commonly wonder what hidden reasons another person may have for doing something nice to me.” Paranoia is a common symptom of dementia.
Thomas Wisniewski, M.D., director of the Center for Cognitive Neurology at NYU Langone Medical Center, says that the study results make sense, because cynicism is a risk factor for poor heart health, which is strongly linked to poor brain health. He also said that even though Americans have the reputation for being eternally optimistic, he’d be surprised if a similar study in the United States didn’t produce the same results."
"Social interaction is a key to maintaining cognitive health, for example, and cynics tend to not socialize much. That’s something people can work to change.
“Being socially active is good for your brain, so if the decrease in cynicism would lead to increased social interactions, this would be good for brain health,” Tolppanen said."
Article at:
http://blog.aarp.org/2014/05/28/calling-all-cynics-your-mistrust-is-bad-for-your-brain/
10 Drugs That May Cause Memory Loss in AARP Health, Are you having trouble remembering things? One of these meds may be the problem
by Dr. Armon B. Neel Jr., AARP, May 10, 2013
Excerpts:
"For a long time doctors dismissed forgetfulness and mental confusion as a normal part of aging. But scientists now know that memory loss as you get older is by no means inevitable. Indeed, the brain can grow new brain cells and reshape their connections throughout life.
Most people are familiar with at least some of the things that can impair memory, including alcohol and drug abuse, heavy cigarette smoking, head injuries, stroke, sleep deprivation, severe stress, vitamin B12 deficiency, and illnesses such as Alzheimer's disease and depression
But what many people don't realize is that many commonly prescribed drugs also can interfere with memory. Here are 10 of the top types of offenders"
1. Antianxiety drugs (Benzodiazepines)
2. Cholesterol-lowering drugs (Statins)
3. Antiseizure drugs
4. Antidepressant drugs (Tricyclic antidepressants)
5. Narcotic painkillers
6. Parkinson's drugs (Dopamine agonists)
7. Hypertension drugs (Beta-blockers)
8. Sleeping aids (Nonbenzodiazepine sedative-hypnotics)
9. Incontinence drugs (Anticholinergics)
10. Antihistamines (First-generation)
My comments, the article describes the use, examples, action of memory loss, and alternates that could be used. Maybe you don't have dementia.
Article at:
http://www.aarp.org/health/brain-health/info-05-2013/drugs-that-may-cause-memory-loss.4.html
Lasers Used to Treat Some Rosacea Signs in ROSACEA REVIEW, Lynn Drake MD, no date
Excerpts:
"In today's high-tech world, powerful and nearly painless beams of light are increasingly used to treat components of rosacea that were once considered difficult or even impossible to correct.
"Laser therapy is now widely considered the primary treatment for telangiectasia (visible blood vessels) and rhinophyma (enlarged nose), and may also be very effective for reducing extensive redness," said Dr. Philip Bailin, chairman of Dermatology at the Cleveland Clinic Foundation. "At the same time, medications must continue to be used to manage the papules (bumps) and pustules (pimples) that often go along with rosacea, and to help maintain remission."
""Laser treatment is by far more elegant, more refined and less painful than previous treatment options for these conditions," Dr. Bailin said. He noted that in mild cases each treatment session may cost from $150 to $300, while more extensive sessions may run up to $500 or more. Laser treatment for rhinophyma is a one-time procedure that may cost between $1,500 and $3,000."
"He emphasized that, because of the chronic and relapsing nature of rosacea, patients should be given a proper perspective on their condition, including the need for continuing preventive therapy and avoidance of lifestyle and environmental factors that may trigger flare-ups.2
"The underlying cause of rosacea will still be there, and further laser treatment may again be required at a later time," he said. "There are no cures for rosacea, only good treatments."
My comments:
Anatabloc face cream at GNC is about $240 with their Gold Card. Worth trying first before lasers? Looks like a 5 star rating by seven users at GNC.
Article at:
http://www.rosacea.org/rr/2001/summer/article_2.php
Valeant offloads aesthetic treatments to Nestlé's derm unit in $1.4B deal in Fierce Pharma, May 28, 2014 | By Carly Helfand
My comments: Hmmmm-Anatabloc face cream anyone?
Article:
"Valeant Pharmaceuticals ($VRX) CEO J. Michael Pearson is an aggressive buyer, especially when it comes to the fast-growing skincare field. Just Wednesday morning his company upped its bid for Botox-maker Allergan ($AGN). But Pearson was also a seller on Wednesday, shipping off rights to a handful of cosmetic products to Nestlé as the Swiss food group looks to expand into the dermatology space.
In exchange for $1.4 billion in cash, Nestlé will grab North American rights for antiwrinkle treatments Restylane, Perlane, Emervel and Dysport. The company already claims the ex-North American rights to those treatments, thanks to its March move to take full ownership of Galderma, a dermatology venture with L'Oreal. As part of the Valeant deal, Nestlé will also gain worldwide rights to another aesthetic med, Sculptra.
Galderma "not only has a history of building strong businesses, but is firmly committed to the aesthetic dermatology," Pearson said in a statement. "Galderma has already built a strong franchise with Restylane, Perlane, Dysport and Emervel outside North America and, with the addition of Sculptra, will now have the ability to bring their expertise to the U.S. and Canada."
For Nestlé, the pickup is part of an attempt to diversify beyond its signature food products. While it isn't a huge deal, in combination with the $3.6 billion Galderma buyout, it's a signal that "they are serious about expanding their business into the health sphere," Kepler Cheuvreux analyst Jon Cox told the Financial Times. "I would expect to see more acquisitions from them as they move further into the medical and health spectrum," he said.
While Valeant said the deal is not contingent on its wooing of Allergan, it could be just the beginning of a larger role reversal if the Canadian pharma is successful in that pursuit. As Reuters reported earlier this week, Valeant would consider a breakup if its serial acquisition strategy makes the company unwieldy.
And this deal may just help it get there, potentially clearing some antitrust hurdles that stand in the way of an Allergan merger. It "eliminated one more roadblock in terms of our integration with Allergan," Pearson said on a conference call Wednesday, as quoted by Bloomberg."
Article at:
http://www.fiercepharma.com/story/valeant-offloads-aesthetic-treatments-nestl-s-derm-unit-14b-deal/2014-05-28#ixzz332m0zZi5
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Analysis: A weakened Pfizer signals that it's prepped to wheel and deal in Fierce Biotech, May 27, 2014 | By John Carroll
Excerpt:
"Now that the deadline for any quick deal to acquire AstraZeneca ($AZN) has passed, about the only certainty to emerge from the wrecked takeover is that the last thing Pfizer ($PFE) can do now is go back to business as usual.
AstraZeneca has already been doing deals, and more than likely will continue to look at new ways it can partner up with other companies. But the bottom line assertion at the U.K. pharma giant is that the company has turned the corner and positioned itself for a comeback over the next three years, supremely confident that it has enough would-be blockbusters in the pipeline to overcome a brutal onslaught of generics. And it's done enough in recent years to gain significant support for its position among some top analysts and investors.
Pfizer, while it sounds optimistic about its pipeline, does not have what it takes to make that argument stick. Pfizer was not well positioned to be spurned by the likes of AstraZeneca, especially not with the stinging assertion that a Pfizer takeover could wind up killing patients by delaying R&D. The new offer focused ample attention on Pfizer's value-destroying tactics in M&A. And it came out looking weak after the rejection."
"But M&A remains the simplest direct route to changing its near-term financial future, which is bleak. So you can expect the focus at Pfizer will stay focused on the bargaining table, though probably not with the same big figures as the ones tied to a potential megamerger.
In a post-deal collapse interview with the Wall Street Journal, Pfizer CEO Ian Read continued to talk deals, saying that he will look for new pacts that stay focused on core areas: vaccines, cancer, inflammation, heart disease and pain. And he's opened to all deals of every shape and size, ranging from new medicines to older therapies."
Article at:
http://www.fiercebiotech.com/story/analysis-weakened-pfizer-signals-its-prepped-wheel-and-deal/2014-05-27#ixzz332Z8zptq
Antisense compound may provide new Alzheimer's treatment in Fierce Biotech Research, May 27, 2014 | By Emily Mullin
Excerpt:
"A new antisense compound developed by Saint Louis University scientists restored learning, memory and other behaviors in mice genetically engineered to have Alzheimer's disease.
The compound, antisense oligonucleotide (OL-1), also reduced inflammation in the part of the brain responsible for learning and memory. The finding, which appears in the May issue of the Journal of Alzheimer's Disease, is the second mouse study published by the team that supports the potential therapeutic value of an antisense compound in treating Alzheimer's disease in humans.
Many antisense therapies are approved to treat certain genetic disorders and infections, such as familial hypercholesterolemia, cancer and HIV/AIDS. Antisense is a strand of molecules that bind to messenger RNA, triggering a sequence of cellular events that turn off a certain gene"
Article at:
http://www.fiercebiotechresearch.com/story/antisense-compound-may-provide-new-alzheimers-treatment/2014-05-27
My comments:
Isn't that what Anatabine Citrate does?
Excerpt from PubMed:
"Anatabine lowers Alzheimer's Aß production in vitro and in vivo.
Paris D1, Beaulieu-Abdelahad D, Bachmeier C, Reed J, Ait-Ghezala G, Bishop A, Chao J, Mathura V, Crawford F, Mullan M.
Author information
1Roskamp Institute, 2040 Whit?eld Avenue, Sarasota, FL 34243, USA. dparis@rfdn.org
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."
Article at:
http://www.ncbi.nlm.nih.gov/pubmed/21958873
Peptides genetically selected for NF-?B activation cooperate with oncogene Ras and model carcinogenic role of inflammation in the Proceedings of the National Academy of Science of the United States of America, Venkatesh Natarajana,1,2, Andrei P. Komarovb,1, Thomas Ippolitoa, Kyle Bonneaub, Alex A. Chenchikb, and Andrei V. Gudkova, Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY
Abstract
"Chronic inflammation is associated with increased cancer risk. Furthermore, the transcription factor NF-?B, a central regulator of inflammatory responses, is constitutively active in most tumors. To determine whether active NF-?B inherently contributes to malignant transformation, we isolated a set of NF-?B–activating genetic elements and tested their oncogenic potential in rodent cell transformation models. Genetic elements with desired properties were isolated using biologically active selectable peptide technology, which involves functional screening of lentiviral libraries encoding 20 or 50 amino acid-long polypeptides supplemented with endoplasmic reticulum-targeting and oligomerization domains. Twelve NF-?B–activating selectable peptides (NASPs) representing specific fragments of six proteins, none of which was previously associated with NF-?B activation, were isolated from libraries of 200,000 peptides derived from 500 human extracellular proteins. Using selective knockdown of distinct components of the NF-?B pathway, we showed that the isolated NASPs act either via or upstream of TNF receptor-associated factor 6. Transduction of NASPs into mouse and rat embryo fibroblasts did not, in itself, alter their growth. However, when coexpressed with oncogenic Ras (H-RasV12), NASPs allowed rodent fibroblasts to overcome H-RasV12–mediated p53-dependent senescence and acquire a transformed tumorigenic phenotype. Consistent with their ability to cooperate with oncogenic Ras in cell transformation, NASP expression reduced the transactivation activity of p53. This system provides an in vitro model of NF-?B–driven carcinogenesis and suggests that the known carcinogenic effects of inflammation may be at least partially due to NF-?B–mediated abrogation of oncogene-induced senescence."
Significance:
Despite general acceptance of the link between chronic inflammation and cancer, the precise molecular mechanisms underlying the cancer-promoting effects of inflammation remain undefined. Inducible transcription factor NF-?B is the key regulator of inflammation, which is commonly deregulated in cancer cells to become constitutively active. Whether this deregulation contributes to malignant transformation was the main question addressed in this study. We isolated a series of genetic elements encoding artificial intracellular proteins capable of constitutive activation of NF-?B, named NF-?B–activating selectable peptides (NASPs), and demonstrated that all of them had carcinogenic activity in conventional cellular models. Specifically, NASPs made normal rodent cells susceptible to malignant transformation by oncogene Ras, which cannot do it on its own. This result defines chronically active NF-?B as an oncogene."
Article at:
http://www.pnas.org/content/early/2014/01/09/1311945111