Science Weekly Extra: The truth about the Climategate emails

Filed Under Uncategorized | Comments Off on Science Weekly Extra: The truth about the Climategate emails

Fred Pearce discusses his new book about the University of East Anglia hacked climate emails saga

DIA 2010 and BIOMED 2010

Target Health is pleased to announce that it will be attending and have a booth # 2534, at DIA being held in Washington, DC (June 14-17). In addition, we will be attending BioMed in Tel Aviv, Israel (June 14-16). Please let us know if you will be attending so we can say hello.

For more information about Target Health contact Warren Pearlson (212-681-2100 ext 104). For additional information about software tools for paperless clinical trials, please also feel free to contact Dr. Jules T. Mitchel 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:

www.targethealth.com

Polyphenols in Red Wine and Green Tea Halt Prostate Cancer Growth

In what could lead to a major advance in the treatment of prostate cancer, scientists now know exactly why polyphenols in red wine and green 1) ___ inhibit cancer growth. This new discovery, published online in The FASEB Journal, explains how antioxidants in red wine and green tea produce a combined effect to disrupt an important cell signaling pathway necessary for 2) ___ cancer growth. This finding is important because it may lead to the development of drugs that could stop or slow cancer progression, or improve current treatments.

“Not only does SphK1/S1P signaling pathway play a role in prostate cancer, but it also plays a role in other cancers, such as colon cancer, breast cancer, and gastric cancers,” said Gerald Weissmann, MD, editor-in-chief of The FASEB Journal. “Even if future studies show that drinking red wine and green tea isn’t as effective in humans as we hope, knowing that the compounds in those drinks disrupts this pathway is an important step toward developing 3) ___ that hit the same target.” Scientists conducted in vitro experiments which showed that the inhibition of the sphingosine kinase-1/sphingosine 1-phosphate (SphK1/S1P) pathway was essential for green tea and wine polyphenols to kill prostate cancer 4) ___. Next, mice genetically altered to develop a human prostate cancer tumor were either treated or not treated with green tea and wine polyphenols. The treated mice showed reduced 5) ___ growth as a result of the inhibited SphK1/S1P pathway. To mimic the preventive effects of 6) ___, another experiment used three groups of mice given drinking water, drinking water with a green tea compound known as EGCg, or drinking water with a different green tea compound, polyphenon E. Human prostate cancer cells were implanted in the mice and results showed a dramatic decrease in tumor size in the mice drinking the EGCg or polyphenon E mixtures. “The profound impact that the 7) ___ in red wine and green tea have on our bodies is more than anyone would have dreamt just 25 years ago,” Weissmann added. As long as they are taken in moderation, all signs show that red wine and green tea may be ranked among the most potent health foods we know.

ANSWERS: 1) tea; 2) prostate; 3) drugs; 4) cells; 5) tumor; 6) polyphenols; 7) antioxidants

A Royal Viking Maternity Case and Forensic Medicine

The last of the Danish Viking Kings, Sven Estridsen, died in A.D. 1074 and is entombed in Roskilde Cathedral with other Danish kings and queens. Sven’s mother, Estrid, is entombed in a pillar across the chancel. However, while there is no reasonable doubt about the identity of Sven, there have been doubts among historians whether the woman entombed was indeed Estrid. To shed light on this problem, we have extracted and analyzed mitochondrial DNA (mtDNA) from pulp of teeth from each of the two royals. Four overlapping DNA-fragments covering about 400 bp of hypervariable region 1 (HVR-1) of the D-loop were PCR amplified, cloned and a number of clones with each segment were sequenced. Also a segment containing the H/non-H specific nucleotide 7028 was sequenced. Consensus sequences were determined and D-loop results were replicated in an independent laboratory. This allowed the assignment of King Sven Estridsen to haplogroup H; Estrid’s sequence differed from that of Sven at two positions in HVR-1, 16093T —- C and 16304T —- C, indicating that she belongs to subgroup H5a. Given the maternal inheritance of mtDNA, offspring will have the same mtDNA sequence as their mother with the exception of rare cases where the sequence has been altered by a germ line mutation. Therefore, the observation of two sequence differences makes it highly unlikely that the entombed woman was the mother of Sven. In addition, physical examination of the skeleton and the teeth strongly indicated that this woman was much younger (approximately 35 years) at the time of death than the 70 years history records tell. Although the entombed woman cannot be the Estrid, she may well be one of Sven’s two daughters-in-law who were also called Estrid and who both became queens.

Novel Therapeutic Approach Shows Promise Against Multiple Bacterial Pathogens

 

A team of scientists from government, academia and private industry has developed a novel treatment that protects mice from infection with the bacterium that causes tularemia, a highly infectious disease of rodents, sometimes transmitted to people, and also known as rabbit fever. In experiments with human immune cells, the treatment also demonstrated protection against three other types of disease-causing bacteria that, like the tularemia bacteria, occur naturally, can be highly virulent, and are considered possible agents of bioterrorism. The experimental therapeutic works by stimulating the host immune system to destroy invading microbes. In contrast, antibiotics work by directly attacking invading bacteria, which often develop resistance to these medications. The therapeutic has the potential to enhance the action of antibiotics and provide an alternative to them. The study is available online in the open-access journal PLoS Pathogens. In the study, the researchers combined components isolated from the membrane of a weakened strain of Francisella tularensis, the agent of tularemia, with the Juvaris product CLDC (cationic liposome DNA complexes). The combination stimulated a natural antibacterial mechanism, called reactive oxygen species (ROS) and reactive nitrogen species (RNS), in immune cells that ingest bacteria. ROS and RNS attack and kill invading bacteria, preventing replication and spread of the pathogens to other cells. Sixty percent of mice in the study survived lethal pulmonary infection with virulent F. tularensis when treated with the therapeutic intravenously three days before the bacterial challenge. No mice survived when given the bacterial components or the CLDC alone, demonstrating the importance of combining both to maximize protection in mouse and human cells. The treatment also showed broad usage, protecting human immune cells from bacteria that cause plague, melioidosis and brucellosis as well as tularemia. Melioidosis is primarily a tropical disease spread to humans and animals through contaminated soil and water. Brucellosis is a disease that primarily affects animals, including humans who come in contact with infected animals or animal products, such as contaminated milk. According to the authors, the three-day advance treatment appears crucial to providing enough time to stimulate the immune system. Any treatment less than three days in advance failed to protect the mice.

Deep Brain Stimulation at Two Different Targets Produces Similar Motor Improvements in Parkinson’s Disease

Motor control problems such as shaking, rigidity, slowed movement and poor balance are often the first and most troubling symptoms of Parkinson’s disease (PD). In later stages, patients tend to develop a variety of cognitive and mood problems, including depression, apathy, slowed thinking, confusion, impaired memory and trouble sleeping. Medications such as L-dopa can control the motor symptoms of PD early in its course. The drugs alleviate some non-motor symptoms, but can worsen others. For patients with advanced disease, the drugs become less effective and more likely to cause side effects. Deep Brain Stimulation (DBS) is a surgical intervention that can help restore the control of motor symptoms for these patients. It does not help the non-motor symptoms of PD, and may even aggravate them. Most patients continue to take carefully balanced medications after they start DBS. When patients receive DBS for PD, a neurosurgeon precisely guides a very fine wire into one of two deep brain regions involved in motor control, the subthalamic nucleus (STN) or the globus pallidus interna (GPi). An implantable battery is used to send a finely tuned electrical current to stimulate the brain. Often, dramatic improvement of motor symptoms can be observed in the operating room when the wire is properly placed and the stimulator turned on. Stimulation on both sides of the brain, or bilaterally, is considered most effective. There is a widely held view that of the two techniques, STN DBS is more effective at controlling motor symptoms but more likely to aggravate non-motor symptoms. A new study, reported in the New England Journal of Medicine (2010;362:2077-2091), is the largest most comprehensive study ever done of patients receiving bilateral STN DBS or GPi DBS challenges these ideas. In the study, investigators compared how individuals with PD respond to deep brain stimulation (DBS) at two different sites in the brain. Contrary to current belief, patients who received DBS at either site in the brain experienced comparable benefits for the motor symptoms of PD. As reported in 2009, the first part of the study compared bilateral DBS to best medical therapy, including medication adjustment and physical therapy. Bilateral DBS showed overall superiority to best medical therapy at improving motor symptoms and quality of life. In the second part of the study, which is the subject of this report, 299 patients, including those who initially received best medical therapy, were randomly assigned to receive either bilateral STN DBS or GPi DBS. Over a two-year period, the two groups experienced similar improvements in scores on the Unified PD Rating Scale, which measures motor function. The two groups also reported similar improvements in quality of life. On a variety of neuropsychological tests, there were no significant differences between the two groups. However, the STN DBS group experienced a greater decline on a test of visuomotor processing speed, which measures how quickly someone thinks and acts on information. Also, the STN DBS group had slight worsening on a standard assessment of depression, while the GPi DBS group had slight improvement on the same test. The importance of these two differences is not clear, and will be scrutinized in follow-up research. In practice, after DBS surgery, the dosage of L-dopa and related medications is often reduced to prevent side effects such as dyskinesias, which are uncontrolled movements. In this study, medication use decreased more for the STN DBS group than for the GPi DBS group. For some patients, medications can cause unwanted side effects and a drop in medication may be favorable for them. For others a drop in medication could unmask symptoms related to cognition or mood that were previously under control. About half of all patients in both DBS treatment groups had serious adverse events, the most common being surgical site infection. By the end of the two-year study period, 99% of all serious adverse events were resolved. Lower levels of electrical stimulation were needed for STN DBS, suggesting that over the long term, this procedure might be associated with lower costs and less need for replacing the pulse generator.

Science Weekly: The man behind the Large Hadron Collider

Filed Under Uncategorized | Comments Off on Science Weekly: The man behind the Large Hadron Collider

The former director general of Cern reveals how the decision to build the Large Hadron Collider was made

Immune Cell’s Role in Lupus Nephritis Demonstrated, Paves Way for Safety Testing of Potential New Use for Asthma Drug

National Institutes of Health scientists have discovered that the activation of immune cells called basophils causes kidney damage in a mouse model of lupus nephritis. These findings and the team’s associated research in humans may lead to new treatments for this serious disease, a severe form of systemic lupus erythematosus (SLE) that affects the kidneys and is difficult to treat. In earlier research, the team found that mice engineered to be deficient in a protein called Lyn kinase had exaggerated responses to allergens in early life and developed a lupus-nephritis-like disease in later life. This was determined by monitoring the increase of immunoglobulin E (IgE) responses to normally harmless substances. The new study, published online in Nature Medicine (30 May 2010), demonstrates for the first time, in the context of this mouse model, how basophils activated by self-reactive IgE antibodies (antibodies that attack the self instead of germs) might contribute to the kidney damage associated with SLE. Specifically, the team showed that self-reactive IgEs attached to the surface of basophils, causing them to home to the mouse’s spleen and lymph nodes, where they promoted a cascade of cellular events that enhanced the production of more self-reactive antibodies. These antibodies are already known to cause kidney damage by binding with other proteins to form immune complexes that are deposited in the kidneys. Here, they caused inflammation, damage and progressive loss of kidney function. Furthermore, the study demonstrated that inducing the absence of self-reactive IgEs or depleting the population of basophils relieved many of the kidney disease features seen in the mouse model. To explore the implications of their results in humans, the study examined blood samples from 44 people with SLE and found the presence of self-reactive IgEs, as well as an increase in activated basophils, features not seen in healthy controls. Both factors were strongly associated with disease activity and lupus nephritis in the people with SLE, suggesting a potential therapeutic benefit in reducing the levels of self-reactive IgE or of activated basophils. One such potential treatment, the asthma medicine omalizumab, is already on the market. It blocks IgE from binding to the surface, and potential activation, of basophil cells, which might prevent basophils from promoting kidney inflammation. The NIH team is currently planning a safety study of omalizumab in people with SLE. In addition to testing omalizumab’s potential and safety for treating lupus nephritis, future research will explore other ways that IgEs can be prevented from binding with basophils. They will also attempt to determine whether or not depleting or inactivating the basophil population might reduce the production of self-reactive antibodies that can lead to kidney damage in SLE.

TARGET HEALTH excels in Regulatory Affairs and Public Policy issues.

 

Each week we highlight new information in these challenging areas.

FDA Approves New Injectable Osteoporosis Treatment for Postmenopausal Women

Osteoporosis is a disease in which the bones become weak and are more likely to break. According to the National Institute of Arthritis and Musculoskeletal and Skin Diseases, 80% of the people in the US with osteoporosis are women. One out of every two women over age 50 will break a bone in their lifetime due to osteoporosis. People with osteoporosis at high risk for fracture include those that have had an osteoporotic fracture, or have multiple risk factors for fracture; or those who have failed or are intolerant to other available osteoporosis therapy. The U.S. Food and Drug Administration today approved Prolia, an injectable treatment for postmenopausal women with osteoporosis who are at high risk for fractures. Prolia works to decrease the destruction of bone and increase bone mass and strength. An injection of Prolia is recommended once every six months. The safety and efficacy of Prolia in the treatment of postmenopausal osteoporosis was demonstrated in a three-year, randomized, double-blind, placebo-controlled trial of 7,808 postmenopausal women ages 60 to 91 years. In the study, Prolia reduced the incidence of vertebral, non-vertebral, and hip fractures in postmenopausal women with osteoporosis. The most common side effects reported with Prolia include back pain, pain in the extremities, musculoskeletal pain, high cholesterol levels, and urinary bladder infections. Serious adverse reactions include hypocalcaemia (low calcium levels in the blood), serious infections, including infections of the skin, and dermatologic reactions such as dermatitis, rashes, and eczema. Prolia causes significant suppression of bone turnover and this suppression may contribute to the occurrence of osteonecrosis of the jaw, a severe bone disease that affects the jaw, atypical fractures, and delayed fracture healing. Prolia was approved with a risk evaluation and mitigation strategy (REMS) that includes a Medication Guide for patients and communications to health care providers that explains the risks and benefits of the drug. Prolia is manufactured by Amgen Manufacturing Limited, a subsidiary of Thousand Oaks, CA-based Amgen Inc.

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

 

 

Target Health Inc.

261 Madison Avenue

24th Floor

New York, NY 10016

Joyce Hays CEO

Jules Mitchel President

www.targethealth.com