Science Weekly: Raising dead dogs and making indestructible sandwiches

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Mick O’Hare from New Scientist tells us about the strange things scientists do in their quest for knowledge

Target Health Chairs Basic and Applied Dermatology Forum

Dr. Jules Mitchel will be hosting a presentation by Dr. Yuval Cohen, President of Morria Biopharmaceuticals, on the topic of clinical data in patients with contact dermatitis treated with Multi-Functional Anti-Inflammatory Drugs (MFAIDs): a novel class of PLA2-targeting anti-inflammatory drugs. The presentation will be on:

Tuesday, January 19, 2010 – 12:30-2:30

At the NJ Center for BioMaterials

Rutgers Busch Campus

145 Bevier Road

Piscataway, NJ 08540

Dr. Cohen received his PhD (summa cum laude) from the Curie Institute in Paris in toxicology in 2002. He proceeded to co-found and head Morria Biopharmaceuticals – a drug discovery and development company focused on the development of novel, non-steroidal, anti-inflammatory drugs termed MFAIDs. These unique drugs target the PLA2 enzyme family, a sought-after pathway in the inflammation process upstream of current competitors. Morria has two lead products in clinical development: MRX-4 (allergic rhinitis) and MRX-6 (contact dermatitis) as well as a number of promising pre-clinical programs. 

There is no fee to attend but make sure you register and get instructions since it is a tricky place to get to once you are on the campus.

For more information about Target Health and our software tools for paperless clinical trials, please contact Dr. Jules T. Mitchel (212-681-2100 ext 0) or Ms. Joyce Hays. Target Health’s software tools are designed to partner with both CROs and Sponsors. Please visit the Target Health Website at:

Chemistry Provides Solution to Plug Pores in Teeth

We think of teeth as being the part visible above the 1) ___, but this is only the tip, or crown, of a tooth. There is also a neck that lies at the gum line, and a root, located below the gum. The crown of each tooth has an 2) ___ coating to protect the underlying dentine. Enamel is even harder than 3) ___, thanks to rows of tightly packed calcium and phosphorus crystals. The underlying dentine is slightly softer, and contains tiny tubules that connect with the central nerve of the tooth within the pulp. The pulp forms the central chamber of the tooth, and is made of soft tissue containing blood vessels that carry nutrients to the tooth. It also contains 4) ___ so teeth can sense hot and cold, as well as lymph vessels to carry white blood cells to fight bacteria. Sensitive teeth are a major problem for many people. More than 80% will experience pain from hot or cold liquids and foods at some point in their life, and about a quarter will experience this sensitivity frequently. The hypersensitivity arises when the 5) ___ of the tooth — which is normally covered by enamel or gum tissue — is exposed to the oral environment. Small “tubules” in the dentin can then transmit fluids that excite nerves in the pulp of the tooth, causing pain. Current toothpastes designed for sensitive teeth, like Sensodyne, use potassium nitrate compounds, which work by depolarizing nerves, which can mask more serious dental problems. A new toothpaste ingredient has been developed by scientists at the University of Maryland’s College of Dentristy. NovaMin is a material designed to relieve 6) ___ teeth, because it blocks the holes that open in the teeth as the ceramic wears down, causing the sensitivity. And it can also help teeth absorb minerals to make them stronger and more resistant to cavities. Additional research indicates that NovaMin could help prevent cavities, too. A recent study also showed that adding NovaMin to fluoride toothpaste provided just as much benefit as increasing fluoride levels by 400% — but without the toxicity concerns associated with too much fluoride. NovaMin does this by growing new tooth mineral crystals near tiny decay 7) ___ on the tooth surface. This new toothpaste, with NovaMin, is available through your dentist. The NovaMin compound spreads onto the tooth surface and blocks the dentin’s tubules, dramatically reducing sensitivity. This new chemical mix imitating the minerals found in 8) ___, but at higher concentrations, can be added to toothpaste to plug tiny pores that lead to nerves. Teeth become sensitive when gum tissue recedes, exposing a tooth’s 9) ___. Dentists also say that drinking too much fruit juice can cause teeth sensitivity. NovaMin is a compound made from elements naturally critical for bone and tooth mineralization: calcium, phosphorus, silica and sodium. In their common forms, these elements have very limited value in tooth health. But in their rare ionic form, they can renew 10) ___. Each microscopic NovaMin particle serves as a delivery system for these ionized bioactive particles. When the particle is exposed to water — whether it be saliva or tap water — it instantly reacts, releasing billions of mineral ions that augment the natural remineralization process that already occurs in the mouth. These ions combine with naturally occurring ones in the saliva to form hydroxyapatite crystals. No other manmade material is known to directly lead to the formation of these crystals in the body. Source: American Institute of Physics, The Materials Research Society, University of Maryland College of Dentistry

ANSWERS: 1) gum; 2) enamel; 3) bone; 4) nerves; 5) dentin; 6) sensitive; 7) cavities; 8) saliva; 9) roots; 10) teeth

Revisiting the Death of FDR

When President Franklin D. Roosevelt died unexpectedly on April 12, 1945, in Warm Springs, Ga., the White House announced the cause of death as a cerebral hemorrhage. (“Last Words,” read a front-page headline in The New York Times: “I Have a Terrific Headache.”). That Roosevelt died of a stroke is undisputed. But what caused it is a medical mystery that has persisted to this day, a mystery heightened by the secrecy in which he, his aides and his doctors always insisted on shrouding his health. Now a new book -“F.D.R.’s Deadly Secret,” by a neurologist, Dr. Steven Lomazow, and a journalist, Eric Fettmann (PublicAffairs) – revives an intriguing theory. Looking closely at Roosevelt’s portraits over his 12-year presidency, in his first two terms, there is a dark spot over his left eyebrow. It seems to grow and then mysteriously vanishes sometime around 1940, leaving a small scar. Was the spot a harmless mole or a cancerous melanoma? Melanomas are known for causing strokes from bleeding when they spread to the brain. In 1979, Dr. Harry S. Goldsmith, then a surgeon at Dartmouth, wrote a widely publicized medical journal article focusing attention on the possibility that the spot was a melanoma. In 2007, Dr. Goldsmith published a book, “A Conspiracy of Silence” (iUniverse). What is different in the new book is the categorical claim that the killer was melanoma that metastasized to his brain. Roosevelt’s death was shocking in part because the White House and his doctors had kept secret how sick he was. For example, though it was widely known that he had developed polio in 1921 at age 39, he and his aides disguised the fact that he could not walk unaided and used heavy metal braces to stand. He used a wheelchair and demanded that photographers not show his disabilities. His terminal illness came during wartime, and in an era when leaders’ health and other personal matters were considered strictly private. With rare exceptions, journalists were complicit. They did not probe the obvious clues they saw as the president’s appearance deteriorate over his last year, for instance, when FDR lost about 30 pounds. Dr. Lomazow and Mr. Fettmann point out that Turner Catledge, then a Washington correspondent for The New York Times and later its executive editor, did not report how awful Roosevelt looked during an interview at the White House in 1944, months before his nomination to an unprecedented fourth term. Roosevelt was gaunt and glassy-eyed, Catledge wrote many years later; his jaw drooped, and he lost his train of thought. Roosevelt’s cardiologist, Dr. Howard G. Bruenn, certified that he died of a cerebral hemorrhage from longstanding arteriosclerosis. Only in 1970 did Bruenn disclose in a medical journal article that for many years the president’s blood pressure was dangerously high. Available records show that it had risen to 230/126 in 1944, from 128/82 in 1930, which would have contributed to heart failure. A reading moments before he died was 300/190. Doctors knew that chronic high blood pressure and arteriosclerosis were a potentially lethal combination that could cause heart disease and strokes which became the standard and most plausible explanation for FDR’s stroke. The speculation about a melanoma cannot be verified because there was no autopsy and no known biopsy, and most of Roosevelt’s medical records disappeared shortly after his death from a safe in the United States Naval Hospital in Bethesda, Md. In their public accounts and the few surviving medical records, his doctors never suggested that they performed a biopsy to determine whether he had any form of cancer. (Even during his lifetime there were rumors that he had prostate cancer.) FDR was hardly the only president to bend the truth, if not lie, to hide his illnesses from the public. Thirteen years before Roosevelt took office, President Woodrow Wilson, in his second term, had a paralyzing stroke; Wilson’s wife and aides kept that fact hidden from the public while they took over the running of the government. Roosevelt’s ailments must still be viewed in the context of the times. In the 1930s and ’40s, doctors had none of the now-standard blood pressure drugs like strong diuretics, beta blockers and ACE inhibitors. They paid far less attention than they do now to moles suspected of being melanomas; even if they had such suspicions, it is inconceivable that the spot over Roosevelt’s eye would have drawn the kind of attention focused during the 2008 presidential campaign on the extensive surgery for the most serious of Senator John McCain’s four melanomas. Why did Roosevelt’s spot vanish after 1940? Melanomas rarely regress on their own. Was the spot removed for a biopsy or for cosmetic reasons? Even in the 1940s, some Washington insiders claimed that Roosevelt knew he was seriously ill, if not dying, when he ran for his final term, and that was one of the reasons he dumped his vice president, Henry A. Wallace, from the Democratic ticket in favor of Harry S. Truman. In July 1944, Dr. Frank H. Lahey, a nationally prominent surgeon in Boston, consulted in Roosevelt’s case. In a memorandum to the record that was made public largely through Dr. Goldsmith’s efforts, Dr. Lahey said he told Roosevelt’s White House physician, Adm. Ross T. McIntire, that he doubted Roosevelt’s capacity to survive another term. But the memorandum did not mention cancer: it focused on the president’s failing heart. The authors build on a 2007 paper by Dr. Barron H. Lerner that challenged a 1970 account by Bruenn, Roosevelt’s cardiologist, of the president’s illness and death. One reason is that Bruenn did not mention problems like the vanished eyebrow spot and the blood transfusions that Roosevelt needed to help correct a severe anemia in 1941. McIntire attributed the anemia to bleeding hemorrhoids; Dr. Lomazow contends it was something more serious. After McIntire’s death in 1959, Dr. Lomazow said, “it fell upon” Bruenn to protect Roosevelt’s wishes to keep his health problems secret. A British physician, Dr. Hugh L’Etang, was about to publish a paper suggesting that Roosevelt might have had melanoma, Dr. Lomazow said. Also, he said, the Roosevelt family wanted Bruenn’s cooperation in documenting that the president had been mentally capable during the Allies’ end-of-war conference at Yalta in February 1945. During the cold war, detractors had taken to calling him “the sick man at Yalta” and saying Stalin had taken advantage of him. The authors of “F.D.R.’s Deadly Secret” examined short film clips and deduced that he had a defect in his left visual fields known as a hemianopia. Although the authors say it is usually from a stroke, they state that the visual deficit was “caused by a metastatic brain tumor.” The book says the abdominal pains Roosevelt experienced in his last year were “caused by the cancer that had metastasized to his bowel.” Source: By Lawrence K. Altman MD, The New York Times, January 5, 2010

Preventing Surgical-Site Infections in Nasal Carriers of Staphylococcus aureus

Nasal carriers of Staphylococcus aureus are at increased risk for health care-associated infections with this organism. In order to evaluate the hypothesis that decolonization of nasal and extranasal sites on hospital admission may reduce risk of infection, a study published in the New England Journal of Medicine (2010; 362:9-17), was performed to assess whether rapid identification of S. aureus nasal carriers by means of a real-time polymerase-chain-reaction (PCR) assay, followed by treatment with mupirocin nasal ointment and chlorhexidine soap, reduces the risk of hospital-associated S. aureus infection. This randomized, double-blind, placebo-controlled, multicenter study screened a total of 6771 patients on hospital admission. A total of 1270 nasal swabs from 1251 patients were positive for S. aureus and all the strains identified on PCR assay were susceptible to methicillin and mupirocin. Of the 1251 patients, 917 were included in the intention-to-treat analysis and 808 (88.1%) underwent a surgical procedure. Results showed that the rate of S. aureus infection was 3.4% (17 of 504 patients) in the mupirocin-chlorhexidine group, as compared with 7.7% (32 of 413 patients) in the placebo group (relative risk of infection, 0.42. The effect of mupirocin-chlorhexidine treatment was most pronounced for deep surgical-site infections (relative risk, 0.21). There was no significant difference in all-cause in-hospital mortality between the two groups. The time to the onset of nosocomial infection was also shorter in the placebo group than in the mupirocin-chlorhexidine group (P=0.005). According to the authors, the number of surgical-site S. aureus infections acquired in the hospital can be reduced by rapid screening and decolonizing of nasal carriers of S. aureus on admission.

Small Changes in Protein Chemistry Play Large Role in Huntington’s Disease

Huntington’s disease is inherited, and usually strikes in middle age, producing uncontrollable movements of the legs and arms, a loss of muscle coordination, and changes in personality and intellect. It is inexorably progressive and leads to death of affected persons usually within 20 years after symptoms first appear. Individuals with the disease carry mutations that affect the huntingtin protein. The mutations involve a triple repeat DNA sequence, a type of genetic miscue similarly found in Friedreich’s ataxia, Kennedy’s disease, fragile X syndrome, and other neurodegenerative disorders. The normal huntingtin protein consists of about 3,150 amino acids (which are the building blocks for all proteins). In individuals with Huntington’s disease, the mutated protein contains an abnormally long string of a single amino acid repeat; lengthier chains are associated with worse symptoms and earlier onset of the disease. In recent years, however, researchers have begun looking at the effects of other, nearby amino acids in this large protein – and in particular, biochemical changes to those amino acids. According to two online studies published in the Journal of Cell Biology (21 December 2009) and Neuron (24 December 2009), a mutated protein can becomes toxic to brain cells and that very slight changes to this region can eliminate signs of Huntington’s disease in mice. It is not fully understand why the protein (called mutant huntingtin) is toxic, but one clue is that it accumulates in ordered clumps of fibrils, perhaps clogging up the cells’ internal machinery. The first study investigated how a process called phosphorylation affects huntingtin. Phosphorylation is the attachment of chemical tags, known as phosphates, onto the amino acids in a protein. The process occurs naturally and is a way of marking proteins for destruction by cellular waste handling systems. The investigators likened it to putting a sign on a pile of junk that tells the garbage collectors to take it away. The study results showed that phosphorylation of just two amino acids, located at one end of huntingtin, targets the protein for destruction and protects against the toxic effects of the mutant protein. In the parallel study, it was evaluated whether boosting phosphorylation of those two amino acids reduce the buildup of huntingtin and improve symptoms of the disease? Through further genetic engineering, the same two critical amino acids at the end of the mutant huntingtin protein to either mimic phosphorylation (phosphomimetic) or resist it (phosphoresistant) were altered. Results showed that mice with the phosphoresistant version of the protein developed symptoms of Huntington’s, but mice with the phosphomimetic version remained free of symptoms and huntingtin clumps up to one year. In addition, in vitro studies showed that phosphomimetic modification of a huntingtin fragment reduced its tendency to form clumps. Together, data from the mouse and test tube experiments provide strong support for the idea that phosphorylation acts as a molecular switch to alter clumping of the mutant protein. According to the authors, the nearly complete lack of any signs of disease in the phosphomimetic Huntington mice may point toward new strategies to treat the disorder and that drugs that enhance or mimic the effects of phosphorylation may help to detoxify the mutant huntingtin protein.

Effect of Music by Mozart on Energy Expenditure in Growing Preterm Infants

Previous reports have indicated that the rate of weight gain in preterm infants who are exposed to music seems to improve. A potential mechanism could be increased metabolic efficiency. Therefore, a study published in Pediatrics (2010;125:e24-e28) was performed to test the hypothesis that music by Mozart reduces resting energy expenditure (REE) in growing healthy preterm infants. REE is the rate at which one burns calories while at rest. REE accounts for 60%-75% of daily energy expenditure. The investigation was a prospective, crossover, randomized clinical trial in 20 healthy, appropriate-weight-for-gestational-age, gavage (tube)-fed preterm infants. Infants were randomly assigned to be exposed to a 30-minute period of Mozart music or no music on 2 consecutive days. Metabolic measurements were performed by indirect calorimetry. Results showed that REE was similar during the first 10-minute period of both randomization groups. However, during the next 10-minute period, infants who were exposed to music had a significantly lower REE than when not exposed to music (P = .028). This was also true during the third 10-minute period (P = .03). Thus, on average, the effect size of music on REE was a reduction of 10% to 13% from baseline, an effect obtained within 10 to 30 minutes. According to the authors, it is possible that this effect of music on REE might explain, in part, the improved weight gain that results from the “Mozart effect.”

FDA Awards Contract to Harvard Pilgrim to Develop Pilot for Safety Monitoring System

TARGET HEALTH excels in Regulatory Affairs and works closely with many of its clients performing all FDA submissions. TARGET HEALTH receives daily updates of new developments at FDA. Each week, highlights of what is going on at FDA are shared to assure that new information is expeditiously made available.


FDA Awards Contract to Harvard Pilgrim to Develop Pilot for Safety Monitoring System

The FDA has awarded a contract to Harvard Pilgrim Health Care Inc. to develop a pilot of the FDA’s Sentinel System, which will use automated health care data to evaluate medical product safety.

Reports filed by hospitals, health care professionals, and industry account for much of information that the FDA relies on regarding medical product safety. For a variety of reasons, these reports may be incomplete or not filed in a timely manner. The Sentinel System, once operational, will bolster the FDA’s efforts in monitoring product safety. Sentinel will provide FDA with the ability to analyze information collected during the course of routine health care, such as data from electronic health record systems, administrative and insurance claims databases and medical registries. The one-year contract with Harvard Pilgrim, based in Wellesley, Mass., includes four renewable years for a total of $72 million. Under the terms of the contract, Harvard Pilgrim will establish a coordinating center that will operate as a scaled down version of the Sentinel System. This center, or “mini-Sentinel,” will identify appropriate databases, develop a scientific framework for obtaining real-time data, and ensure data quality. To protect personal information, only summary results will be sent to the coordinating center. The data itself will remain within its database. The Sentinel System fulfills some requirements of the Food and Drug Administration Amendments Act of 2007 (FDAAA), which include provisions calling for the development of such a system. The Harvard Pilgrim contract is one of the many activities contributing to building the Sentinel System. The FDA already has awarded 10 small contracts addressing scientific operations, data and infrastructure, privacy, and stakeholder engagement. In addition, the FDA has awarded a cooperative agreement with the Brookings Institution to convene meetings and workshops on active medical product surveillance issues. The workshop on the Sentinel Initiative is scheduled for Jan. 11, 2010, in Washington, D.C.

For more information about our expertise in Regulatory Affairs, please contact Dr. Jules T. Mitchel or Dr. Glen Park.

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