Target Health Supports the Arts in NYC

 

As part of being a good corporate citizen, each year Target Health Inc. supports the Arts in NYC. Without this type of support from us and other generous supporters New York would lose its ability to be called the cultural capital of the world and the soul of humanity could disappear. The following is the list of organizations we support:

 

1. Atlantic Theatre Company

2. Irish Repertory Theatre

3. Manhattan Theatre Club

4. MCC Theater (Lucille Lortel Theater)

5. Metropolitan Opera

6. NY Theater Workshop

7. Pilobolus Dance Company

8. Playwrights Horizons

9. Roundabout Theatre Company

10. Signature Theatre

11. SITE Santa Fe (Art Museum)

 

Last week we had a big snow storm in NY. We were in the office at 7am at which time the sky lit up bright red. About 20 minutes later the sky opened up and the snow started. This was a true “Red Sky in Morning, Sailor’s Take Warning.“

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©Jules Mitchel, Target Health

 

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©Jules Mitchel, Target Health

ON TARGET is the newsletter of Target Health Inc., a NYC-based contract research organization (CRO), providing strategic planning, regulatory affairs, clinical research, data management, biostatistics, medical writing and software services, including the paperless clinical trial, to the pharmaceutical and device industries.

 

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. The Target Health software tools are designed to partner with both CROs and Sponsors. Please visit the Target Health Website.

 

Joyce Hays, Founder and Chief Editor of On Target

Jules Mitchel, Editor

Vanessa Hays, Editorial Contributor

Evolution in a Test Tube – Powerful Method to Find New Drug Therapies

 

In the RNA world, RNA evolved to perform all sorts of different jobs – that is what researchers are trying to do: evolve RNA molecules that perform useful jobs, such as binding to a tumor cell or stopping viral replication. This technique is called directed evolution.

How do biologists “evolve“ RNA in a test tube? The same way that a population of organisms evolves in the real world: natural selection. It works like this:

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Image credit: University of California Museum of Paleontology’s Understanding Evolution (http://evolution.berkeley.edu).

 

So natural selection can operate on any varying set of individuals that reproduces via genetic inheritance – even if an “individual“ is simply a molecule like RNA and is not technically alive (whatever “alive“ is)!

 

Scientists at The Scripps Research Institute (TSRI) have demonstrated the power of a new drug discovery technique, which allows them to find — relatively quickly and cheaply — antibodies that have a desired effect on 1) ___. The TSRI scientists used the technique to discover two antibodies that protect human cells from a cold virus. The finding includes the useful insight that the cold 2) ___ can be stopped by targeting a key viral enzyme in just the right way. More importantly, the study highlights the broad potential of this discovery method to find new ways to fight infections, cancers and other diseases, and perhaps even aging.

 

“This method allows you to find antibodies that prevent cell death — in this case virus-induced cell death, but potentially any kind of cell death,“ said Richard A. Lerner, Lita Annenberg Hazen Professor of Immunochemistry and Institute Professor at TSRI. Lerner was the senior author of the study, which is reported online ahead of print on January 16, 2014 by the Cell Press journal Chemistry & Biology.

 

For the past two decades, Lerner and his TSRI laboratory have helped pioneer techniques for discovering 3) ___ that can be used as therapies or scientific tools. Humira®, now among the world’s top-selling pharmaceuticals, is one of many products that have been discovered using such techniques. Recently, the Lerner laboratory developed an advanced technique in which hundreds of millions of distinct antibodies are produced artificially within very large 4) ___ of mammalian cells. Scientists can use such a system to swiftly find any antibodies that cause a desired outcome (“phenotype“) in the cells where they reside. Scientists for decades have applied similar “phenotypic selection“ methods to libraries of standard small-molecule compounds. But the antibody libraries that can be used with the new method are orders of magnitude larger, making them much more likely to contain members that can achieve a desired result in cells.

 

“Small-molecule libraries generally contain only tens to hundreds of thousands of 5) ___, whereas with this method we can use libraries with more than a billion distinct antibodies,“ said Jia Xie, a staff scientist in the Lerner laboratory who was first author of the new study. The new method gives scientists more power not only to find new antibody-based therapies, but also to discover the biological pathways through which they work — pathways that may turn out to be more easily and cheaply targeted by small-molecule drugs.

 

Earlier this year, Lerner, Xie and their colleagues reported using the new method to find an antibody that can perform the remarkable trick of turning bone marrow cells into young brain cells, via a previously unknown signaling mechanism. For the new study, the team set out to do a proof-of-principle selection of antibodies that can bring about a different effect: protecting cells against an otherwise certain death. In this case, the agent of death was a rhinovirus, a respiratory virus that is the most common cause of ordinary colds. This rhinovirus reliably kills HeLa cells, a line of human-derived cells that have long been used in studies of viral infection. To begin, the team used harmless lentiviruses to distribute the genes for about 100 million distinct antibodies among a similar number of HeLa cells, and later exposed the cells to the rhinovirus. So lethal was this virus to the HeLa cells that nearly every cell soon 6) ___, overwhelmed by the infection despite any protective effect from antibodies they harbored. To detect a protective effect, Xie and his colleagues knew that he would have to make the selection process less drastic. Thus, for the next test, instead of selecting cells that survived — for none would have survived — they selected cells that showed delayed signs of impending death. The researchers then harvested the antibody genes these cells contained, and distributed them among a fresh set of cells. In this way, they reasoned, the 7) ___ for the antibodies that had exerted a protective effect would become more abundant within the cells. Xie and his colleagues took the cells through three of these selection rounds — each requiring about ten days of working and waiting — but saw dismayingly few signs of progress. “The cells that had been infected with our antibody library still showed marginal to undetectable differences from the control cells,“ he said. Then in the fourth round, the protective antibodies became abundant enough to bring about a dramatic change: almost all the antibody-containing cells survived, whereas all the 8) ___ cells died.

 

The protection turned out to come from just two antibodies out of the original pool of roughly 100 million. The team determined that both these antibodies protected the cells by attaching to the 3C protease, a rhinovirus enzyme, in ways that hindered its infection-enabling activity. In principle, if further tests bear out the protective effects of the two antibodies, then optimized versions of them, or 9) ___-molecule drugs that hit the same target, could be developed as treatments for rhinovirus infections. But Xie noted that the study was mainly about demonstrating the usefulness of this broad new method. “It’s a fast, economical, multi-round selection scheme that enables scientists to identify functional antibodies from an unusually big library,“ he said. “As long as we have a way to detect and select a desired phenotype in the test cells, this method lets us fish out the antibodies that can make the phenotype happen.“ The study also shows the power of the new method to illuminate biological pathways that mediate disease — in this case the activity of the rhinovirus 3C protease. Moreover, it offers unprecedented insight into the selection process itself. “We were able to see at each round what antibodies were being selected and how abundant they were in cells,“ Lerner said. “It was like following 10) ___ in a test tube.“

 

Lerner emphasized that this was the first demonstration of screening for the prevention-of-cell-death phenotype using very large antibody libraries — but it won’t be the last. “People now can use this technique to find antibodies that prevent cell death in a wide variety of situations,“ he said.

 

Scripps Research Institute. “Preventing cell death from infection: Scientists demonstrate powerful method to find new therapies.“ ScienceDaily, 16 January 2014.

 

ANSWERS: 1) cells; 2) virus; 3) antibodies; 4) cultures; 5) compounds; 6) died; 7) genes; 8) control; 9) small; 10) evolution

Richard A. Lerner MD (1938 to Present)

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Richard A. Lerner (born 28 August 1938) is an American research chemist. Best known for his work on catalytic antibodies, Lerner served as President of The Scripps Research Institute (TSRI) until January 1, 2012, and is currently a member of its Skaggs Institute for Chemical Biology, in La Jolla, California. Lerner grew up in Chicago and excelled at chemistry and wrestling as a schoolboy. After attending Northwestern University as an undergraduate, Lerner obtained an MD from Stanford Medical School in 1964 then undertook postdoctoral training at Scripps Clinic and Research Foundation, an early incarnation of the institute he would eventually lead. In the 1970s Lerner carried out research at the Wistar Institute in Philadelphia then returned to La Jolla to the now renamed Research Institute of Scripps Clinic. In 1982 he was appointed chairman of the Department of Molecular Biology, then five years later assumed the directorship. In 1991, when the TSRI was established as a nonprofit entity, Lerner became its first president.

 

In addition to his research into catalytic antibodies, providing a method of catalyzing chemical reactions thought impossible using classical techniques, Lerner has led extensive studies into protein structure, characterized cis-9,10-octadecenoamide, a novel lipid hormone that induces sleep, and provided the first evidence of a role for ozone in human disease. In 1967 Lerner discovered the role of anti-GBM antibodies in the pathogenesis of Goodpasture’s disease.

 

Lerner is currently the Lita Annenberg Hazen Professor of Immunochemistry and Cecil H. and Ida M. Green Chair in Chemistry. He has been the recipient of over 29 honors and prizes. These include the Parke-Davis Award in 1978, the San Marino Prize in 1990, the Wolf Prize in Chemistry for 1994 (with Peter Schultz). He was the Myron L. Bender and Muriel S. Bender Summer Lecturer at Northwestern University in 1994 as well. Richard Lerner was awarded the California Scientist of the Year Award in 1996 and the University of California Presidential Medal in 2002. He has also been elected to the Royal Swedish Academy of Sciences and the United States National Academy of Sciences. In 2010 he was awarded an honorary degree from the University of Warwick to add to those he received from Technion – Israel Institute of Technology in 2001, Ben-Gurion University of the Negev in 2003 and Florida Atlantic University in 2004 and University of Oxford in 2007. Richard Lerner shared the 2012 Prince of Asturis award, that is often called the Spanish Nobel Prize, with Sir Gregory Winter for his conception and development of combinatorial antibody libraries.

 

Under Lerner’s leadership, The Scripps Research Institute grew threefold in terms of laboratory space and more than quadrupled its staff levels, making it among the largest nonprofit biomedical research organizations in the world. He also oversaw the establishment of a sister research campus, called Scripps Florida, in Palm Beach County. In 2006, Lerner announced that he intended to return to full-time research in his laboratory in five years. Lerner officially stepped down on January 1, 2012, having led the Institute for 25 years.

 

Lerner serves on the boards of six for-profit and nonprofit companies, including Kraft Foods, advises four other companies and two venture capital funds. He has declined to reveal the sum of his earnings, but acknowledged he earned $8.5 million for his part in the discovery of Humira.

NIH Research Network Finds Many Youth Have High Levels of HIV

 

According to an article published online in the journal AIDS (23 January 2014), more than 30% of young males who had intimate relationships with other males and who were subsequently enrolled in a government treatment and research network were found to have high levels of HIV. The health status of the study participants, who ranged in age from 12 to 24 years, was monitored as part of their participation in the Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN). The ATN provides medical care to youth with HIV and offers counseling and, medications, and other preventive measures to youth who are at risk of acquiring HIV. As part of their participation in the network, the youth have the option of taking part in research studies of the latest methods to prevent people from acquiring HIV and to treat those who have become infected.

 

To conduct the study, authors analyzed the health records of youth with HIV, soon after they enrolled in the ATN. The study authors noted that the high blood levels of the virus seen in the majority of study participants indicated that they were diagnosed early in the course of HIV infection, when the chances for minimizing the health consequences of HIV are greatest. The authors added, however, that the study results suggest that HIV is highly likely to be transmitted among members of this group.

 

According to the U.S. Centers for Disease Control and Prevention, 1 in 4 new HIV infections occur in young people from 13 to 24 years of age. About 60% of all youth with HIV do not know they are infected, are not getting treated, and can unknowingly pass the virus on to others. Among the groups that the CDC recommends get tested for HIV are those:

 

1. Who have injected drugs and shared needles and other equipment with others

2. Who have had unprotected relationships with men who have intimate realtionships with men, had multiple partners or anonymous partners

3. Have been diagnosed with hepatitis, tuberculosis, or a STD

4. Had unprotected relationships with someone in the above groups

 

To conduct the study, the authors measured the viral load and CD4 counts of 852 youth in 14 cities in the United States and Puerto Rico. Viral load is the amount of HIV in the blood. The authors explained that viral levels are highest very early in the course of an HIV infection. CD4 counts measure infection-fighting white blood cells known as T-cells. In the first few weeks, the viral load can be millions of copies, or higher. Then, over the ensuing months, it stabilizes at about 30,000 to 50,000 copies. Normal CD4 counts range from 500 to 1,000, but drop substantially during the infection.

 

Among the study participants, 34% had CD4+ counts of 350 or less, 27% had counts from 351 to 500, and 39% had counts greater than 500. Male youth who had reported intimate relationships with another male had the highest average viral load, in excess of 115,000. Among all males studied, the viral load averaged more than 106,000. For females, the average viral load count was roughly 48,000. Most of those diagnosed with HIV had been referred for medical care during the course of the study (79%.)

 

Because of the high viral loads they detected in their study, the authors concluded that efforts to diagnose and treat people with HIV should focus a large share of their efforts on youth, particularly young men who have intimate relationships with men.

Severe Mental Illness Tied to Higher Rates of Substance Use

 

Studies exploring the link between substance use disorders and other mental illnesses have typically not included people with severe psychotic illnesses.

 

According to a study published online in JAMA Psychiatry (01 January 2014), people with severe mental illness such as schizophrenia or bipolar disorder have a higher risk for substance use, especially cigarette smoking.  Protective factors usually associated with lower rates of substance use do not exist in severe mental illness. Protective factors are conditions or attributes in individuals, families, communities or the larger society that help people deal more effectively with stressful events and mitigate or eliminate risk in families and communities.

 

Estimates based on past studies suggest that people diagnosed with mood or anxiety disorders are about twice as likely as the general population to also suffer from a substance use disorder. Statistics from the 2012 National Survey on Drug Use and Health indicate close to 8.4 million adults in the United States have both a mental and substance use disorder. However, only 7.9% of people receive treatment for both conditions, and 53.7% receive no treatment at all, the statistics indicate.

 

In the current study, 9,142 people diagnosed with schizophrenia, schizoaffective disorder, or bipolar disorder with psychotic features, and 10,195 controls matched to participants according to geographic region, were selected using the Genomic Psychiatry Cohort program. Mental disorder diagnoses were confirmed using the Diagnostic Interview for Psychosis and Affective Disorder (DI-PAD), and controls were screened to verify the absence of schizophrenia or bipolar disorder in themselves or close family members. The DI-PAD was also used for all participants to determine substance use rates.

 

Results showed that compared to controls, people with severe mental illness were about 4 times more likely to be heavy alcohol users (four or more drinks per day); 3.5 times more likely to use marijuana regularly (21 times per year); and 4.6 times more likely to use other drugs at least 10 times in their lives. The greatest increases were seen with tobacco, with patients with severe mental illness 5.1 times more likely to be daily smokers. This is of concern because smoking is the leading cause of preventable death in the United States.

 

In addition, certain protective factors often associated with belonging to certain racial or ethnic groups — or being female — did not exist in participants with severe mental illness. According to the authors, in the general population, women have lower substance use rates than men, and Asian-Americans have lower substance use rates than white Americans. However, these differences were not seen among people with severe mental illness. The authors added that they also saw that among young people with severe mental illness, the smoking rates were as high as smoking rates in middle-aged adults, despite success in lowering smoking rates for young people in the general population.“

 

Previous research has shown that people with schizophrenia have a shorter life expectancy than the general population, and chronic cigarette smoking has been suggested as a major contributing factor to higher morbidity and mortality from malignancy as well as cardiovascular and respiratory diseases. These new findings indicate that the rates of substance use in people with severe psychosis may be underestimated, highlighting the need to improve the understanding of the association between substance use and psychotic disorders so that both conditions can be treated effectively.

TARGET HEALTH excels in Regulatory Affairs. Each week we highlight new information in this challenging area.

 

FDA Prohibits Ranbaxy’s Toansa, India Facility from Producing and Distributing Drugs for the U.S. Market

 

The U.S. FDA has notified Ranbaxy Laboratories, Ltd., that it is prohibited from manufacturing and distributing active pharmaceutical ingredients (APIs) from its facility in Toansa, India, for FDA-regulated drug products. The Toansa facility is now subject to certain terms of a consent decree of permanent injunction entered against Ranbaxy in January 2012. The decree contains, among other things, provisions to ensure compliance with current good manufacturing practice (CGMP) requirements at Ranbaxy facilities in Paonta Sahib and Dewas, India, as well as provisions to address data integrity issues at those facilities. In September 2013, the FDA added Ranbaxy’s Mohali facility to the CGMP provisions of the decree.

 

Under the decree, the FDA has issued an order prohibiting Ranbaxy from:

1. Distributing in the United States drugs manufactured using API from Toansa, including drugs made by Ranbaxy’s Ohm Laboratories facility in New Jersey;

2. Manufacturing API at its Toansa facility for FDA-regulated drug products;

3. Exporting API from Toansa to the United States for any purpose; and

4. Providing API from Toansa to other companies, including other Ranbaxy facilities, making products for American consumers.

 

The FDA exercised its authority under a provision in the consent decree which permits the agency to extend the decree’s terms to any Ranbaxy-owned or operated facility if an FDA inspection finds the facility in violation of the Federal Food, Drug, and Cosmetic Act or FDA regulations, including CGMP requirements. CGMP requirements serve as the primary regulatory safeguard over drug manufacturing and must be followed by companies to ensure manufacturing quality. The FDA also acted under a separate provision in the decree which permits the agency to order additional corrective actions that FDA determines are necessary to achieve compliance with the law or the decree.

 

The FDA’s inspection of the Toansa facility, which concluded on Jan. 11, 2014, identified significant CGMP violations. These included Toansa staff retesting raw materials, intermediate drug products, and finished API after those items failed analytical testing and specifications, in order to produce acceptable findings, and subsequently not reporting or investigating these failures.

 

The agency is evaluating potential drug shortage issues that may result from this action. If the FDA determines that a medically necessary drug is in shortage or at risk of shortage, the FDA may modify this order to preserve patient access to drugs manufactured under controls that are sufficient to assure quality, safety and effectiveness.

 

As a result of this action, Ranbaxy is now prohibited from manufacturing API for FDA-regulated drugs at the Toansa facility and from introducing API from that facility into interstate commerce, including into the United States, until the firm’s methods and controls used to manufacture drugs at the Toansa facility are established, operated and administered in compliance with CGMP.

 

Ranbaxy is required to hire a third-party expert to thoroughly inspect the Toansa facility and certify to the FDA that the facility and its methods and controls are adequate to ensure continuous compliance with CGMP. Ranbaxy will not be permitted to resume manufacturing and distributing API for FDA-regulated drugs from the Toansa facility until the agency is satisfied that Ranbaxy has addressed its manufacturing quality issues at that facility.

 

The FDA recommends that patients not disrupt their drug therapy because this could jeopardize their health. Patients who are concerned about their medications should talk with their health care professional before discontinuing treatment.

Shredded Cabbage with Cilantro, Sour Cream (low-fat) Cashews & Raisins

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©Joyce Hays, Target Health

 

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©Joyce Hays, Target Health – Line up all the ingredients, near the stove, so you can add them easily.

 

Ingredients

 

2 Tablespoons peanut oil or canola oil

2 teaspoons black mustard seeds

2 teaspoons urad dal (optional), or 1 teaspoon each urad dal and channa dal (optional)

Pinch cayenne (or to your taste)

2 teaspoons ground coriander seeds

1 teaspoon turmeric

1/2 teaspoon cumin

2 garlic cloves, minced

2/3 cup cilantro, chopped

1 onion, cut in half root to stem, then thinly sliced across the grain

1 small cabbage (or 1/2 large), cored and shredded

1 cup cashews, toasted

Pinch black pepper (grind to your taste)

4 Tablespoons grated coconut (to taste)

1 cup golden raisins

1 pint low-fat sour cream

 

Directions

 

1. Clean the cabbage and cut into thirds or quarters. Slice it thinly with a mandolin and set aside in bowl.

2. Line up all the ingredients near the stove, so that you can add them quickly.

3. Heat the oil over medium heat in a 14-inch wok or 12-inch skillet, and add the mustard seeds (and dal if using). As soon as the mustard seeds begin to pop, add the cumin, cayenne, coriander seeds and turmeric.

4. Stir together, and add the onion and garlic. Cook, stirring, until onion begins to soften, about three minutes.

5. Add the cabbage. Cook, stirring, for one minute until it begins to wilt. Add the golden raisins and cashews, salt (optional), stir together, cover and turn the heat to low. Cook for about eight minutes until the cabbage is just tender.

6. Stir in the coconut, taste and adjust seasoning. Keep warm.

Taste, and decide if you want to add the sour cream or not. The photo, above, has no sour cream added and tastes wonderful. The spices are stronger without the sour cream.

 

The photo, below, has sour cream added. I would say, that after experimenting with this recipe several times, I prefer not adding the sour cream. Without adding sour cream, the wonderful spices can be experienced much better. I love this recipe because of the mild spicy-ness. You could simply serve sour cream at the table and let people add what they want. You might also like to serve some chutney at the table.

 

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 ©Joyce Hays, Target Health

 

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©Joyce Hays, Target Health Inc.

 

Serve warm with basmati (above) or jasmine rice. Instead of water, make the rice in chicken stock or chicken broth.

It’s fun to take a common veggie, like cabbage, and turn it into a really interesting and delicious meal or side dish. The first time I served this, it was a side dish with rice, fish and icy white wine. The meal began with another kale salad, I’d been experimenting with. (recipe next time). We smacked our lips. Last night, it was equally good, but I would recommend not mixing sour cream into this recipe because it dulls the spices, and they’re so good, you really want them to explode in your mouth.

 

Bon Appetit!