11 November 2007
I. WHAT'S NEW?
Target e*CRF® Accomplishments
II. QUIZ - (Fill In The Blanks)
Stem Cell Technology, Seaweed and Regenerative Medicine
III. HISTORY OF MEDICINE
The Bunsen Burner
IV. BASIC SCIENCE
Fly Consortium Uncovers Swarm of Novel Findings
V. IMMUNOLOGY
Abnormal Immune Cells May Cause Unprovoked Anaphylaxis
VI. PEDIATRIC CARDIOLOGY
Brain Development in Newborns with Congenital Heart Disease
VII.
REGULATORY AFFAIRS
Food Safety Initiative
VIII. TARGET HEALTH
II. QUIZ
(Fill
In The Blanks)
Stem Cell Technology, Seaweed and Regenerative Medicine
Engineers at New York's Rensselaer Polytechnic Institute have transformed a 1) ___ found in common brown seaweed into a device that can support the growth and release of stem cells at the site of a bodily injury or at the source of a disease. The findings mark an important step in efforts to develop new medical therapies using stem cells. A 2) ___ has been developed for stem cell culture that can degrade in the body at a controlled rate. With this level of control, the growth of stem cells can be controlled in the scaffold as to how, when, and where to release them into the body. This device is created from a material known as alginate. Alginate is a complex 3) ___ found naturally in brown seaweed. When mixed with calcium, alginate gels into a rigid, three-dimensional 4) ___. The device has a wide-ranging potential for use in regenerative medicine. For example, the scaffolds could one day be used in the human body to release stem cells directly into injured tissue. The scaffold could eventually be used for medical therapies such as releasing healthy bone stem cells right at the site of a broken bone, or releasing neural stem cells in the brain where cells have been killed by diseases such as 5) ___. The research team encapsulated healthy neural stem cells in the alginate mesh, producing a three-dimensional scaffold that degrades at a controlled rate. Once the scaffold was implanted, an enzyme called alginate lyase was used, which eats away at alginate, to release the stem cells. Alginate lyase is naturally produced in some marine animals and bacterial strains, but not in humans. In order to control the degradation of the alginate scaffold, varying amounts of alginate lyase were encapsulated into microscale beads, called 6) ___. The microspheres containing the alginate lyase were then encapsulated into the larger alginate scaffolds along with the stem cells. As the microspheres degraded, the alginate lyase enzyme was released into the larger alginate scaffold and slowly began to eat away at its surface, releasing the healthy 7) ___ cells in a controlled fashion. The microspheres also can be filled with more than just alginate lyase. Drug or proteins can be added to the microspheres along with the alginate lyase that, when released into the larger alginate scaffold, could influence the fate of the encapsulated stem cells. By adding these materials to the larger scaffold, the stem cells can be directed to become the type of mature, differentiated cell that is desired, such as a neuron. This will prove very valuable for applications of stem cells in 8) ___ medicine. The findings are detailed in the December 2007 edition of Biomaterials.IV. BASIC SCIENCE
Fly Consortium Uncovers Swarm of Novel Findings
The fruit fly is one of the most important model organisms in genetic research. In studies dating back nearly a century, researchers used fruit flies to discover the basic rules of inheritance and to study how a single cell, the fertilized egg, develops into a whole animal. Because fruit flies are easy to work with in laboratory settings, they continue to be used as a model to study fundamental biological processes that occur in many living things, including humans. Although fruit flies have a genome that is 25 times smaller than the human genome, many of the flies' genes correspond to those in humans and control the same biological functions. In recent years, fruit fly research has led to discoveries related to the influence of genes on diseases, animal development, population genetics, cell biology, neurobiology, behavior, physiology and evolution. An international research consortium of scientists, supported by the National Human Genome Research Institute (NHGRI),have announced publications comparing the genome sequences of 12 closely related fruit fly species, 10 of which were sequenced for the first time. The analyses identify thousands of novel genes and other functional elements in the insects' genomes, and describe how evolution has shaped the genomes of these important models for genetic research. The work was carried out by hundreds of scientists from more than 100 institutions in 16 countries. The sequencing of the 10 new genomes was led by Agencourt Bioscience Corp., Beverly, Mass. Other sequencing centers contributing to the sequencing were Washington University School of Medicine, St. Louis, Mo., the Broad Institute of MIT and Harvard, Cambridge, Mass., and the J. Craig Venter Institute, Rockville, Md. At first glance, the genomes of the various types of fruit flies appeared quite similar. However, a more detailed examination revealed that only 77% of the approximately 13,700 protein-coding genes in Drosophila melanogaster (reference species) are shared with all of the other 11 species. It was found that different regions of the fruit fly genomes, including protein-coding genes and gene families, are evolving at different rates. For example, genes involved in taste and smell, detoxification and metabolism, gender and reproduction, and immunity and defense appear to be the most rapidly evolving in the fruit fly genomes. The findings suggest that these particular protein-coding genes likely evolve in the fruit fly genome as a result of adaptation to changing environments and gender selection. For instance, the fruit fly species D. sechellia, whose population lives on the Seychelles islands in the Indian Ocean, is losing gustatory (taste) receptors approximately five times faster than other fruit fly species that generally encounter a more diverse set of foods than those available on an island.V. IMMUNOLOGY
Abnormal Immune Cells May Cause Unprovoked Anaphylaxis
Anaphylaxis occurs when mast cells release large quantities of chemicals (histamines, prostaglandins and leukotrienes) that cause blood vessels to leak, bronchial tissues to swell and blood pressure to drop. Resulting conditions such as shock and unconsciousness usually resolve in most people treated with epinephrine (adrenaline) and first aid measures. In rare cases, however, death may occur. While some people suffer anaphylaxis as part of a serious allergic reaction, in two out of three people, anaphylaxis has no known cause and thus the anaphylactic reaction is called idiopathic. In some of these individuals, it has been found that mast cells (a type of immune cell involved in allergic reactions) have a mutated cell surface receptor that disturbs normal processes within the cell. The association of this mutation with unprovoked anaphylaxis is striking. From the therapeutic perspective, the hope is that these individuals may respond to inhibitors targeting the mutated cell surface receptor. Abnormally low blood pressure and fainting episodes are also features of mastocytosis-a disease in which people have an excessive number of mast cells. Interestingly, it is known that systemic mastocytosis in adults often results from a mutation in the Kit receptor found on the surface of mast cells. The mutation causes an abnormal growth of mast cells, as is observed in bone marrow biopsies of patients with mastocytosis. As a result, a study published online in Blood (2007; DOI: 10.1182/blood-2006-06-028100), was performed to see if the Kit mutation could make mast cells grow and cause mastocytosis, and if this was associated with anaphylactic reactions, could the same mutation predispose mast cells to release chemicals responsible for idiopathic anaphylaxis. A two-year study conducted at the NIH Clinical Center, evaluated 48 patients diagnosed with mastocytosis with or without associated anaphylaxis, 12 patients with idiopathic anaphylaxis, and 12 patients with neither disease. Within the group of 12 patients who had idiopathic anaphylaxis, five were found with evidence of a disorder in a line of mast cells (clonal mast cell disorder). The study looked for evidence of a Kit mutation in three patients by analyzing bone marrow samples, and all three samples yielded a positive result. The findings demonstrated that some patients with idiopathic anaphylaxis have an aberrant population of mast cells with mutated Kit. According to the authors, both Kit and the IgE receptor responsible for allergic reactions use a common molecule, a protein, inside the cell for mast cell activation, and that the mutated Kit markedly elevates the function of the protein which results in increased cell signaling.VI. PEDIATRIC CARDIOLOGY
Brain Development in Newborns with Congenital Heart Disease
Congenital heart disease in newborns is associated with global impairment in development. As a result, a study published in New England journal of Medicine (2007; 357:1928-1938), was performed to characterize brain metabolism and microstructure, as measures of brain maturation, in newborns with congenital heart disease before they underwent heart surgery. Forty one term newborns with congenital heart disease, 29 with transposition of the great arteries and 12 who had single-ventricle physiology were studied. Magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), and diffusion tensor imaging (DTI) were used to diagnose the extent of the cardiac abnormality before cardiac surgery. In addition, the following were calculated: the ratio of N-acetylaspartate to choline (which increases with brain maturation), the ratio of lactate to choline (which decreases with maturation), average diffusivity (which decreases with maturation), and fractional anisotropy of white-matter tracts (which increases with maturation). These findings were compared with those in 16 control newborns of a similar gestational age. Compared with control newborns, those with congenital heart disease had a decrease of 10% in the ratio of N-acetylaspartate to choline (P=0.003), an increase of 28% in the ratio of lactate to choline (P=0.08), an increase of 4% in average diffusivity (P<0.001), and a decrease of 12% in white-matter fractional anisotropy (P<0.001). Preoperative brain injury, as seen on MRI, was not significantly associated with findings on MRS or DTI. White-matter injury was observed in 13 newborns with congenital heart disease (32%) and in no control newborns. The authors concluded that term newborns with congenital heart disease have widespread brain abnormalities before they undergo cardiac surgery, and that the imaging findings in such newborns are similar to those in premature newborns and may reflect abnormal brain development in utero.VII. REGULATORY AFFAIRS
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.Food Safety Initiative
This year, $2 trillion worth of goods will be imported into the U.S., and this may triple by 2015. Advances in food production technology, rapid methods of food distribution, and globalization have transformed supermarket shelves and restaurant menus, broadened the tastes of consumers, and challenged the existing food protection framework. HHS Secretary Mike Leavitt has announced a comprehensive initiative by the FDA designed to bolster efforts to better protect the nation's food supply. The Food Protection Plan (FPP) proposes the use of science and a risk-based approach to ensure the safety of domestic and imported foods. The FPP, focuses on both domestic and imported food, and complements the Import Safety Action Plan. The Import Safety Action Plan lays out a road map with short- and long-term recommendations to enhance product safety at every step of the import life cycle. Taken together, the two plans should improve efforts by the public and private sector to enhance the safety of a wide array of products used by American consumers. The plan is premised on preventing harm before it can occur, intervening at key points in the food production system, and responding immediately when problems are identified. Within these three overarching areas of protection, the plan contains a number of action steps as well as a set of legislative proposals. The FDA will work with industry, state, local, and foreign governments to identify vulnerabilities and will look to industry to mitigate those vulnerabilities, using effective methods such as preventive controls. The plan's intervention element emphasizes focusing inspections and sampling based on risk at the manufacturer and processor level, for both domestic and imported products, that will help verify the preventive controls. This approach is complemented by targeted, risk-based inspections at the points where foreign food products enter the United States, including ports. The plan calls for enhancing FDA's information systems related to both domestic and imported foods to better respond to food safety threats and communicate during an emergency. The Food Protection Plan's three core elements--prevention, intervention, and response, incorporate four cross-cutting principles for comprehensive food protection along the entire production chain:VIII. TARGET HEALTH
TARGET HEALTH INC. (www.targethealth.com) is a full service eCRO with full-time staff dedicated to all aspects of drug and device development. Areas of expertise include Regulatory Affairs, comprising, but not limited to, IND, IDE, NDA, PMA and 510(k) submissions, execution of Clinical Trials, Project Management, Biostatistics and Data Management, Web Trials, utilizing Target e*CRF®, our proprietary Internet-based Clinical Trial System, and Medical Writing. TARGET HEALTH's Pharmaceutical Advisory Dream Team assists companies in strategic planning from Discovery to Market Launch. Let us help you on your next project.TARGET
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