On Target

ON TARGET
COMPLIMENTARY NEWS LETTER OF TARGET HEALTH® INC.

01 July 2007

I. WHAT'S NEW?
Welcome New Readers From DIA 2007
II. QUIZ - (Fill In The Blanks)
New Species Discovered
III. HISTORY OF MEDICINE
World's First Isolation Hospital
IV. OPHTHALMOLOGY
Omega 3 Fatty Acids Protect Against Retinopathy in Mice
V. SURGERY
Psychological Performance in Children Undergoing Cardiac Surgery
VI. NEUROLOGY
Gene Variant Increases Risk For Alcoholism Following Childhood Abuse
VII. REGULATORY AFFAIRS
FDA Approves Rapid Test For Malaria
VIII. TARGET HEALTH

I. WHAT'S NEW

Welcome New Readers From DIA 2007

We would like to thank the many visitors who stopped by our booth at the annual DIA meeting in Atlanta. We met many new colleagues and also had a chance to renew acquaintances. We were able to demo Target e*CRF®, Target Document® and Target Encoder™ and received rave reviews. Our goal is to provide high quality, and fairly priced software tools to the pharmaceutical industry in order to facilitate the drug, biologic and device development process. We will also partner with CROs and allow for technology transfers of all of our products. We also only sell what we fully test and use ourselves. This year an NDA, BLA and PMA have already been submitted which used Target e*CRF for all of the clinical trials. A 4th submission (NDA) is due in November.

For more information about Target Health, please contact Dr. Jules T. Mitchel. Visit our Blog and Website.

II. QUIZ (Fill In The Blanks)

New Species Discovered

Extremophiles are 1) ___ that have adapted to extreme environments, such as Utah's Great Salt Lake. Because of advances in computer technology and 2) __ testing, researchers are identifying new species faster than ever. Among the latest discoveries are tiny microorganisms, one hundred, of which, fit on the head of a pin. Scientists have discovered a new species of microbe living in Utah's Great Salt Lake. The new species is part of a group of organisms called 3) ___ because they can survive in extreme environments that would kill a human being in mere seconds: extreme heat or cold, for example. The new organism is classified as a "halophile," or 4) ___-loving micro-organism, because it thrives in water that is ten times saltier than the sea. The new microbe is rod-shaped and orange-red in color, and measures only 1.5 microns long. Among its most interesting features is its abundance of 5) ___ pigments, which makes it completely resistant to damaging UV rays from the sun. Studying the microbe's unique properties could lead to new ways to protect humans from UV 6) ___. The newly discovered microbe belongs to the Halorubrum ("salt red") genus. Some 1.7 million species have been identified on earth, but scientists believe the total number is between 5 million and 10 million. Scientists discover thousands of new species every year.

ANSWERS: 1) microbes; 2) DNA; 3) extremophiles; 4) salt; 5) carotenoid; 6) damage

III. HISTORY OF MEDICINE

World's First Isolation Hospital

Venetians who lived during the Fourteenth Century, were, on average, five feet five inches in height. They were well nourished, and if they lacked sugar and fat, the result was excellent teeth with no cavities. These are among the first findings of a group of archaeologists exploring a treasure trove of Venetian history that has been locked away in graves and forgotten for centuries. Lazzaretto, an island in the Venetian lagoon, became the world's first isolation hospital following an outbreak of the plague in 1348. Click on this map for the route of the plague epidemic. At the time of the outbreak, the Doge and his advisers put their minds to thinking up a way to prevent a recurrence. The upshot, at the beginning of the 15th century, was the world's first isolation hospital occupying the entire small island. In 1630 the hospital was dissolved and the island taken over by a military garrison; later it was used to hold stray dogs. In the 1960s it was abandoned altogether. Recently, archaeologists have uncovered more than 1,500 skeletons of Lazzaretto patients. The first grave was found when the excavators began clearing away rubble for the rebuilding of one of the sheds. Since then more than 240 have come to light, some crowded with skeletons, some housing only a few. To date 1,560 individual skeletons have been found, dating from four, five and six centuries ago, most of them in perfect condition. Already a picture of the harsh lives of some of those confined here is beginning to emerge. A number of the patients were afflicted with a disease called Schmorl's Node, a type of hernia caused by heavy stress on the back - probably the occupational hazard of the porters who lugged Venice's merchandise around on their backs. Yet although these skeletons by definition belonged to people who were extremely sick, they were remarkably fit. Some had arthritis, some tuberculosis, some had fractures that had healed badly, but in general they seem to have enjoyed a nutritious diet and a healthy lifestyle. Source: The Independent, UK, June 2007

IV. OPHTHALMOLOGY

Omega 3 Fatty Acids Protect Against Retinopathy in Mice

Omega-3 fatty acids create chemical compounds known as bioactive mediators, which protect against the growth of abnormal blood vessels, a condition that characterizes some forms of retinopathy. In part, this occurs because these mediators suppress a type of inflammatory protein called tumor necrosis factor alpha (TNF-alpha). TNF-alpha is found in one type of cell, called microglia, that can be closely associated with retinal blood vessels. According to an article published in Nature Medicine (July 2007), omega-3 polyunsaturated fatty acids protect against the development and progression of oxygen-induced retinopathy of retinopathy (a deterioration of the retina) in a mouse model. The study evaluated the effect of the omega-3 fatty acids EPA and DHA, derived from fish, and the omega-6 fatty acid arachidonic acid, on the 1) loss of blood vessels, 2) re-growth of healthy vessels, and 3) growth of destructive abnormal vessels. Omega-6 is derived from grains and soybeans and is found in many of the foods we consume which contain soy oil. . The retinopathy in the mouse shares many characteristics with retinopathy of prematurity (ROP) in humans. ROP is a disease of the eyes of prematurely born infants in which the retinal blood vessels increase in number and branch excessively, sometimes leading to bleeding or scarring. Infants who progress to a severe form of ROP are in danger of becoming permanently blind. There are also aspects of the disease process that may apply to diabetic retinopathy (a disease in which blood vessels swell and leak fluid or grow abnormally on the surface of the retina), and age-related macular degeneration (AMD), (a disease of the macula, the part of the retina responsible for central vision). AMD is a leading cause of vision loss in Americans 60 years of age and older. Results showed that increasing omega-3 fatty acids and decreasing omega-6 fatty acids in the diet reduced the area of vessel loss that ultimately causes the growth of the abnormal vessels and blindness. In contrast, omega-6 fatty acid contributed to the growth of abnormal blood vessels in the retina. To further test the apparent beneficial effect of omega-3 fatty acids, the investigators studied mice fed a diet modeled after a traditional Japanese diet (more omega-3 than omega-6 fatty acids), and mice fed a diet modeled after a traditional Western diet (lower amounts of omega-3 fatty acids). In addition, they studied mice genetically altered with a gene which mammals normally lack that converts omega-6 into omega-3 fatty acids. Results showed that the mice with higher amounts of omega-3 had a nearly 50% decrease in retinopathy. According to the authors, the findings represent new evidence suggesting the possibility that omega-3 fatty acids act as protective factors in diseases that affect retinal blood vessels.

V. SURGERY

Psychological Performance in Children Undergoing Cardiac Surgery

As surgical management of children with congenital heart disease (CHD) becomes more advanced, developmental outcome has become a main focus. According to an article published in the Journal of Pediatrics (2007;151:73-78), a study was performed to specify the cognitive profile of children with CHD, 6 to 12 years postoperatively. The study included patients with CHD (n = 43, mean age 8 years, 8 months) and healthy controls (n = 43, mean age 8 years, 11 months). All patients were examined with an abbreviated intelligence scale (Wechsler Intelligence Scale for Children-3rd edition, Dutch version) and a developmental neuropsychological assessment battery (NEPSY [a developmental NEuroPSYchological assessment]). Results showed significantly lower scores for the CHD group on Estimated Full Scale IQ (P < .01). Neuropsychological assessment revealed lower scores for the CHD group on the cognitive domains of Sensorimotor Functioning (P < .001), Language (P < .001), Attention and Executive Functioning (P < .05), and Memory (P < .05). Children with CHD displayed more impulsive test behavior than healthy peers. No differences on IQ or cognitive domains were found between the cyanotic and the acyanotic CHD group. According to the authors, 6 to 12 years postoperatively, children with CHD display a neuropsychological profile with mainly mild motor deficits and subtle difficulties with language tasks. Attention/executive functioning and memory also appear involved but to a lesser degree. Long-term follow-up of children with surgically corrected CHD, even when hemodynamically successful, is warranted, as they are at risk for neurodevelopmental delay at school age.

VI. NEUROLOGY

Gene Variant Increases Risk For Alcoholism Following Childhood Abuse

according to a new study published online on June 26, 2007 in Molecular Psychiatry, has shown that women who suffered childhood abuse are more likely to develop alcoholism later in life if they possess a particular variant of a gene involved in the body's response to stress, The new finding could help explain why some individuals are more resilient to profound childhood trauma than others.
Previous studies have shown that childhood abuse increases the risk for numerous mental health problems in adulthood. However not all abused children develop such problems, a likely indication that genetic factors also play a role. Recent studies have linked the monoamine oxidase A (MAOA) gene with adverse behavioral outcomes stemming from childhood mistreatment. MAOA is an enzyme that metabolizes various neurotransmitters that regulate the body's response to stress. DNA variations occur within a regulatory area -- the MAOA-linked polymorphic region (MAOA-LPR) -- of the MAOA gene. Two such MAOA-LPR variants occur most frequently and result in high or low MAOA enzyme activity. In a recent study, it was found that maltreated boys who possessed the low activity MAOA-LPR variant were more likely to develop behavior problems than boys with the high activity variant. The goal of the study was to test whether this low activity variant influences the impact of childhood abuse on alcoholism and antisocial personality disorder (ASPD) in women. For the study, DNA samples were analyzed from a group of American Indian women living in a community in which rates of alcoholism and ASPD are about six times higher than the average rates among all U.S. women. Childhood abuse is also prevalent in this population, reported by about half of the women in the community, compared with a U.S. average of 13%. Analyses of MAOA-LPR genotypes in this study revealed that women who had been abused in childhood were much more likely to develop alcoholism and antisocial behavior if they had the low activity variant whereas the high activity variant was protective. In contrast, there was no relationship between alcoholism, antisocial behavior and MAOA-LPR genotype among non-abused women. According to the authors, the findings show that MAOA seems to moderate the impact of childhood trauma on adult psychopathology in females in the same way as previously shown among males, and that the MAOA-LPR low activity allele appears to confer increased vulnerability to the adverse psychosocial consequences of childhood abuse. The authors added that the hippocampus, a brain region which is involved in the processing of emotional experience, may underlie the interaction between MAOA and childhood trauma.

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.

FDA Approves Rapid Test For Malaria

People infected with malarial parasites often experience a high fever, chills, and flu-like illness. Left untreated, they may develop severe complications and die. Although malaria has been eliminated from the United States since the 1950s, it can still affect U.S. residents who travel or who work in other countries. According to the Centers for Disease Control and Prevention, there were 1,528 newly-reported cases of malaria in the United States in 2005, including seven deaths. Nearly all deaths can be prevented if the infection is diagnosed and treated early. Standard laboratory tests for malaria require identifying parasites in a blood sample under a microscope, a difficult task that requires training and experience. The FDA has recently cleared for marketing the Binax NOW Malaria Test, the first authorized U.S. rapid test for malaria. The test is intended for laboratory use. The Binax NOW test is significantly faster and easier to use than current laboratory tests. Results are available in 15 minutes after a few drops of whole blood are placed on a dipstick. The test can also differentiate the most dangerous malaria parasite, Plasmodium falciparum, from less virulent malaria parasites. Results still need to be confirmed using standard microscopic evaluation. The Binax NOW test was 95% accurate compared with standard microscopic diagnosis in a multi-center study outside the United States in areas where malaria is prevalent. The Binax NOW test is manufactured by Binax Inc., a subsidiary of Inverness Medical Innovations Inc. of Scarborough, Me.

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

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 (PADT) assists companies in strategic planning from Discovery to Market Launch. Let us help you on your next project.

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Dr. Jules T. Mitchel, President
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