Age-related immune system decline slowed by antioxidants

The thymus is an organ that produces T lymphocytes – white blood cells that are crucial to the immune system.

New research has demonstrated how the aging process damages the immune system, while showing how antioxidants in the diet could slow the build-up of this damage.

Findings from the study, published in Cell Reports, also lend support to the “free-radical theory” of aging, whereby reactive oxygen species such as hydrogen peroxide that are produced by normal metabolism cause damage to cells. This damage contributes to both aging and age-related diseases.

The study was conducted by researchers from The Scripps Research Institute (TSRI) who focused their attention on an organ called the thymus that is responsible for the production of T lymphocytes – also referred to as T cells.

T cells are white blood cells that control the body’s immune response. These cells are continuously lost, and it is the job of the thymus – located between the lungs – to replenish them, enabling the body to respond to new infections. However, the thymus is unable to continuously produce high levels of T cells.

“The thymus begins to atrophy rapidly in very early adulthood, simultaneously losing its function,” explains study author Dr. Howard Petrie. “This new study shows for the first time a mechanism for the long-suspected connection between normal immune function and antioxidants.”

Antioxidants are substances that could prevent or delay damage to cells. Examples include beta-carotene, vitamin C and vitamin E. They can often be found in fruits and vegetables and are also available in the form of supplements.

The researchers set out to explore the mechanisms behind the connection by developing a computational approach they could use to assess gene activity in two types of thymus cell in mice – stromal cells and lymphoid cells.

In the stromal cells, they observed that a deficiency in an antioxidant enzyme called catalase led to the production of reactive oxygen species through metabolism, which in turn sped up the rate at which damage occurred.

COMMON DIETARY ANTIOXIDANTS FOUND TO PRESERVE SIZE OF THE THYMUS

The researchers then tested the role of this antioxidant by increasing catalase levels in genetically altered animal models. By doing this, they were able to maintain the size of the thymus for a longer period.

In addition, the researchers were also able to preserve the size of the thymus in animals by giving them two common dietary antioxidants – including vitamin C.

The question of why the thymus decreases in size more rapidly than other body tissues remains unanswered, however. Dr. Petrie says that while other research has demonstrated the thymus is responsive to sex hormones, their new study shows that its aging process is the same as in other tissues.

“However, the process is accelerated in the thymus by a deficiency in the essential protective effects of catalase, which is found at higher levels in almost all other body tissues,” he continues.

The researchers also point out that while increasing catalase levels in stromal cells preserved the size of the thymus for a longer period, it did not prevent it from atrophying – as yet, there is no way to completely halt metabolic damage accumulated over time.

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Commonly Used Drugs May Delay Brain Injury Recovery

New study shows that Anticholinergics, a category of drugs recommended to treat common problems which range from bladder issues, depression to insomnia, can in up to 50 percent of old age patients delay their recovery from brain injury.

Anticholinergics have in previous studies been identified to have side effects, such as short-term cognitive impairment, confusion and dizziness. But the new research lead by the University of East Anglia (UEA) in the UK is one of the first to examine their effects on people who have suffered from a brain injury.

The team of scientists, which includes researchers from Aston University, other UK research centers and the British National Health Service, presented their results in the journal Brain Injury. The study collected data from 52 subjects who had experienced brain or spinal cord injury and were undergoing treatment at a neuro-rehabilitation unit. Patients going through neuro-rehabilitation are usually given anticholinergics to reduce pain, bladder control and other problems. Researchers identified that the average length of stay among the subjects they examined was longer for those with greater levels of anticholinergic burden (ACB) in their system. The analysis of data revealed a direct connection between modifications in ACB and duration of hospital stay. Subjects whose ACB scores on discharge were greater than on admission remained longer in hospital compared to those whose ACB scores on discharge were reduced. However, the researchers point out their research was not developed to show cause and effect; it can only demonstrate that there is a link.

Anticholinergic medicines can conflict with rehabilitation

Senior author of the study Chris Fox, states that:

“This initial study shows the requirement for bigger studies to fully support the outcomes and calls for additional research into what long-term results these common drugs are having on the recovery of these patients.”

He describes that while it is usually essential to cure common problems of brain and spinal cord injuries with anticholinergic medicines, drugs side effects like cognitive impairment can get in the way of sufferers rehabilitation, causing in a longer hospital stay. Co-author Dr. Ian Maidment, says their results add to the proof that, where possible, anticholinergics must be prevented in a extensive range of populations.“Regular drugs review by a nurse, physician or pharmacist may be a way of guaranteeing that drugs with anticholinergic effects are used properly,” he suggests.

The research is significant not just for clinical reasons but also due to the fact one of the measures of hospital efficiency is length of stay, and there are financial rewards for discharging sufferers as soon as is safe.

Prof. Fox concludes:

“Determining things which might negatively affect the length of a patient’s stay can have significant financial along with quality of life implications.”

For that reason, he adds, the study’s results may help enhance the performance of health care by decreasing the time patients spend in rehabilitation.

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Roche Continues to be at the Top in Oncology Sales

Swiss drug maker Roche continues to be at the top of the heap in oncology sales for several years and it’s no wonder with its best selling drugs such as Avastin, Herceptin, Rituxan and Triumvirate. Roche generated revenue of over $25 billion via its cancer drugs in the previous year, which is more than twice the revenue generated by its nearest competitor Novartis.

But things are transforming. While Roche will not lose its top place in the near future, not with its well performing new products such as Perjeta and Gazyva, and a PD-L1 medicine on its way, however it is important to note that Roche’s cancer portfolio increased by just 2% in 2014, in comparison to double digit increases at US based drug makers such as Celgene, Johnson & Johnson and Bristol-Myers Squibb, which took the 3rd, 4th and 5th place in oncology sales respectively. Novartis with a larger baseline to begin with, saw its cancer medicines increase by 8% for the year reaching an estimated $10.2 billion.

And with the No. 2 Novartis taking on GlaxoSmithKline’s oncology portfolio, novel immuno-oncology drugs hitting the scene and other hot new oncology products on the prowl, competitor pharmaceutical companies are gaining.

Novartis definitely will add considerably to its total for 2015, with GSK’s medicines now the fold. Those medicines brought in some $1.8 billion in 2014, which would have increased Novartis past $12 billion previous year. If it can maintain the increasing sales of Tasigna and Afinitor as they have been, each delivered raises of a minimum of 20% last year – that’s one more big chunk.

Looking further ahead, the fight for second place could heat up. Estimations for 2020 sales put Clegene’s Revlimid (It is used in people with myelodysplastic syndrome triggered by an abnormal chromosome) at $10.1 billion all on its own, and the firm’s Abraxane is predicted to provide in over $2 billion. It also has Pomalyst, a novel multiple myeloma medicine, to play a crucial role with the $2.4 billion in its 2020 prediction. Clegene’s CEO Bob Hugin states that his organization can reach $20 billion in sales by then, though some of that predicted increase is pegged on an autoimmune disease candidate.

And then there’s immuno-oncology, which appears to be ready to take cancer therapy by surprise. How it will all play out is not clear at this point. US drug maker Bristol-Myers’ Opdivo data from ASCO put its long term  $6 billion prediction in question, for instance, but those medicines could change the cancer rankings significantly.

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FDA Awards $19 Million for 18 New Rare Disease Research Grants

The U.S. Food and Drug Administration (FDA) has awarded 18 new research grants totaling more than $19 million to enhance the development of orphan drugs for rare disease patients.

The grants are intended for clinical studies evaluating the safety and effectiveness of products that could either result in, or substantially contribute to, the FDA approval of products.

Since its creation in 1983, the Orphan Products Grants Program has provided more than $350 million to fund more than 570 new clinical studies and supported the marketing approval of more than 50 products.

Since many rare conditions are also pediatric conditions, it is no surprise that 10 of the 18 awards fund studies that enroll pediatric patients as young as newborns. Some of the rare conditions under investigation in the grants include sickle cell anemia, amyloidosis, autosomal dominant polycystic kidney disease, prader willi syndrome, as well as numerous rare cancers,

THE GRANT RECIPIENTS FOR FISCAL YEAR 2015 ARE:

• Albert Einstein College of Medicine (Bronx, New York), Deepa Manwani (principle investigator)
  • Phase 2 Study of Gamunex (Intravenous Gammaglobulin) for the Treatment of Sickle Cell Acute Pain
  • About $1.6 million over 4 years
• Baylor College of Medicine (Houston, Texas), Andrew Sikora
  • Phase 2 Study of ADXS11-001 Vaccine for the Treatment of HPV-Related Oropharyngeal Cancer
  • About $1.2 million over 3 years
• Beckman Research Institute of the City of Hope (Duarte, California), Behnam Badie
  • Phase 1 Study of Cellular Immunotherapy Using Optimized IL13Ra2 Specific CAR T Cells for the Treatment of Malignant Glioma
  • $600,000 over 3 years
• Columbia University (New York, New York), Suzanne Lentzsch
  • Phase 1A/B Study of 11-1F4 mAb for the Treatment of AL Amyloidosis
  • $600,000 over 3 years
• Edimer Pharmaceuticals Inc. (Cambridge, Massachusetts), Neil Kirby
  • Phase 2 Study of EDI200 for the Treatment of X-Linked Hypohidrotic Ectodermal Dysplasia
  • $1.6 million over 4 years
• Emory University (Atlanta, Georgia), Claudia Morris
  • Phase 2 Study of L-Arginine Therapy for the Treatment of Pediatric Sickle Cell Disease Pain
  • $1.6 million over 4 years
• Indiana University-Purdue University at Indianapolis (Indianapolis, Indiana), Kent Robertson
  • Phase 2 Study of Imatinib for the Treatment of Airway Tumors in Children with Neurofibromatosis Type 1
  • $1.6 million over 4 years
• Indiana University-Purdue University at Indianapolis (Indianapolis, Indiana), Sharon Moe
  • Phase 1 Study of Low Dose Pioglitazone for the Treatment of Autosomal Dominant Polycystic Kidney Disease
  • About $600,000 over 3 years
• New York University School of Medicine (New York, New York), Horacio Kaufmann
  • Phase 2 Study of Carbidopa for the Treatment of Familial Dysautonomia
  • About $1.1 million over 3 years
• Northshore University Healthsystem (Evanston, Illinois), Eli Ehrenpreis
  • Phase 1 Study of Naltrexone for the Treatment of Mesenteric Panniculitis
  • About $220,000 over 3 years
• Rhythm Metabolic Inc. (Boston, Massachusetts), Keith Gottesdiener
  • Phase 2 Study of the Melanocortin 4 Receptor Agonist RM-493 for the Treatment of Prader Willi Syndrome
  • About $1 million over 3 years
• Scioderm Inc. (Durham, North Carolina), Robert Ryan
  • Phase 2 Study of SD-101 for the Treatment of Epidermolysis Bullosa
  • $400,000 for 1 year
• Sloan-Kettering Institute Cancer Research (New York, New York), Mrinal Gounder
  • Phase 3 Study of Sorafenib for the Treatment of Desmoid Tumors or Aggressive Fibromatosis
  • About $900,000 over 4 years
• Transderm Inc. (Santa Cruz, California), Roger Kaspar
  • Phase 1 Study of Sirolimus for the Treatment of Pachyonychia Congenita
  • About $400,000 over 2 years
• University of California San Diego (La Jolla, California), Santosh Kesari
  • Phase 2 Study of Vascular-Targeted Prodrug (G-202) for the Treatment of Recurrent Glioblastoma
  • About $1.6 million over 4 years
• University of Kansas Medical Center (Kansas City, Kansas), Mazen Dimachkie
  • Phase 2 Study of Arimoclomol for the Treatment of Sporadic Inclusion Body Myositis
  • About $1.6 million over 4 years
• University of Michigan (Ann Arbor, Michigan), Meghan Arnold
  • Phase 3 Study of Standard vs Reduced IV Fat for the Prevention of Parenteral Nutrition-Associated Cholestasis (PNAC)
  • About $1.6 million over 4 years
• Innovative Biotherapies Inc. (Ann Arbor, Michigan), H. David Humes (medical device awardee)
  • Phase 2 Study of Selective Cytopheretic Device for the Treatment of Pediatric Patients with Acute Kidney Injury
  • About $1.6 million over 4 years

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Source

FDA awards 18 grants to stimulate product development for rare diseases [news release]. Washington, DC: US Food and Drug Administration; September 21, 2015.http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm463539.htm

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Sensitive Blood Test May Help Rule Out Heart Attack

WEDNESDAY Oct. 7, 2015, 2015 — A new, highly sensitive blood test may help doctors quickly rule out heart attack for almost two-thirds of people who seek emergency room treatment for chest pain, a new study suggests.

Researchers said their findings could potentially reduce unnecessary hospital admissions and substantially lower health-care costs. “Until now, there were no quick ways to rule out a heart attack within the emergency department,” said the study’s lead author, Dr. Anoop Shah, from the University of Edinburgh in Scotland.

“Over the last two decades, the number of hospital admissions due to chest pain has tripled. The overwhelming majority of these patients do not have a heart attack,” Shah said. Assessing a possible heart attack requires lengthy stays in the ER or hospitalization for repeat testing, the study authors pointed out.

The new test is more sensitive than the standard version, Shah’s team said. It can detect far lower blood levels of troponin, a protein released when heart muscle is damaged. The more damage that occurs, the higher blood levels of troponin will be. A slight increase in troponin suggests some damage has occurred, while very high levels indicate a person has had a heart attack, the researchers explained.

Using this new test, doctors could potentially double the number of low-risk patients able to be safely discharged from the emergency room, the researchers reported in the Oct. 8 issue ofThe Lancet.”Use of this approach is likely to have major benefits for both patients and health-care providers,” Shah said in a journal news release.

For the study, the researchers measured troponin levels in more than 6,000 patients admitted to the hospital with chest pain, and assessed their risk for heart attack and death from heart attack within 30 days.

The investigators found that 61 percent of the patients with a troponin level below 5 ng/L (nanograms per liter of blood) were at very low risk of heart attack and could have been discharged early, regardless of age, gender, and risk factors for heart disease. One year out, these patients had a three times lower risk of heart attack and cardiac death than those with higher troponin levels, the researchers said.

The authors of an accompanying editorial in the journal said patient follow-up will be needed to validate use of this test in routine practice.”Trials are needed to assess the safety and effectiveness of clinical pathways that involve no further testing for such patients,” wrote Martin Than from Christchurch Hospital, New Zealand, and colleagues.

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More information

The American Heart Association describes the symptoms of heart attack.

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Insight into cancer resistance in elephants could aid human treatment !!!!

They are the largest land animals in the world, weighing up to 14,000 pounds and standing up to 4 meters tall. Given their size, elephants should be highly susceptible to cancer – they have at least 100 times more cells than humans – but they rarely develop the disease. In a new study, researchers shed light on the mechanisms behind elephants’ resistance to cancer – information that could fuel knowledge on cancer resistance in humans.

Study leader Dr. Joshua D. Schiffman, of the University of Utah School of Medicine, and colleagues publish their findings in JAMA.

Theoretically, an animal’s cancer risk should increase with their size and lifespan; the bigger an animal is, the more cells they have, which should increase the rate of cell division and susceptibility to gene mutations.

In 1975, however, a study by Dr. Richard Peto, of the University of Oxford in the UK, challenged this notion. He observed that cancer incidence across species is not dependent on an animal’s size or lifespan – a theory that is now hailed “Peto’s Paradox.”

A good example of this theory is the disparity in cancer incidence between humans and elephants; despite elephants being significantly larger than humans, their risk for cancer is much lower.

Previous research has suggested that specific molecular mechanisms in elephants protect them against cancer, though Dr. Schiffman and colleagues note that such mechanisms are poorly understood.

For this latest study, the team set out to learn more about the disparities in cancer mortality rates across different mammals, with a specific focus on elephants, and to shed light on possible mechanisms that induce cancer resistance in different species.

ELEPHANTS HAVE MULTIPLE COPIES OF KEY TUMOR-SUPPRESSOR GENE

The researchers assessed information on disease and cause of death for 36 mammalian species, including African or Asian elephants.

The genomes of all species were assessed, as well as the activity of peripheral blood lymphocytes – a type of white blood cell – among elephants, healthy humans and patients with a disease called Li-Fraumeni syndrome (LFS), a rare inherited condition that greatly increases the risk for cancer. This was to assess response to DNA damage.

Overall, the researchers found that cancer mortality rates did not increase with the size or lifespan of a mammal. For example, the cancer mortality rate for elephants was only 4.8%, compared with an 11-25% cancer mortality rate in humans.

The team also revealed that elephants possess at least 20 copies of a major tumor-suppressor gene called TP53, while healthy humans only have one copy, with two alleles (gene variants) inherited from each parent. People with LFS only inherit one functioning allele of the TP53 gene, according to the team, putting them at a 90-100% lifetime risk for cancer.

The researchers explain that the TP53 gene plays a key role in the response to DNA damage by triggering a form of cell death called apoptosis via the p53 protein. Compared with human lymphocytes, the researchers found that elephant lymphocytes were subject to p53-induced apoptosis at higher rates.

Based on their findings, the team suggests the additional copies of the TP53 gene and increased p53-induced apoptosis in elephants have evolved to protect them against cancer.

The authors write:

“Compared with other mammalian species, elephants appeared to have a lower-than-expected rate of cancer, potentially related to multiple copies of TP53. Compared with human cells, elephant cells demonstrated increased apoptotic response following DNA damage.

These findings, if replicated, could represent an evolutionary-based approach for understanding mechanisms related to cancer suppression.”

HUMAN CANCER VULNERABILITY LIKELY DOWN TO MODERN LIFESTYLE FACTORS

In an editorial linked to the study, Mel Greaves, PhD, of the UK’s Institute of Cancer Research, says the theory that elephants may be protected against cancer due to the acquisition of multiple copies of the TP53 gene seems “plausible.”

However, Greaves notes that it is unclear what implications the findings have for cancer in humans. “Perhaps the main message from this innovative investigation is to bring into focus the question of why humans appear to be so ill-adapted to cancer, given the average size and life span,” he speculates.

“The human genome is replete with footprints of positive selection in the not-too-distant historical past. Humans may have acquired, in one particular respect, an extra cancer suppressor gene variant early on in evolutionary history approximately 1.8 million years ago,” Greaves continues.

He points out, however, that modern humans are particularly vulnerable to cancer, which is more down to lifestyle factors – such as smoking – that are not seen in other animals. “These behaviors are relatively recently acquired by humans, over a few hundred years, and the risks they impart far exceed prior and otherwise effective cancer suppressor mechanisms that were inherited from primate ancestors,” explains Greaves.

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