Estrogen Activates Critical Lung Genes To Improve Lung Function Following Preterm Birth

Estrogen may be a new postnatal therapy to improve lung function and other outcomes in preterm infants, researchers at UT Southwestern Medical Center have found in an animal study.



"Ironically, a hormone that has received great attention as a potential means to optimize the health of older women may be a beneficial treatment for humans during the earliest stages of life," said Dr. Philip Shaul, professor of pediatrics at UT Southwestern and the study's senior author.



The study, conducted in preterm primates, appears in the March issue of the American Journal of Respiratory and Critical Care Medicine. The study was performed at the Southwest Foundation for Biomedical Research Primate Center in San Antonio as part of a National Institutes of Health-funded consortium investigating causes and treatments for bronchopulmonary dysplasia (BPD), a devastating primary complication of premature birth that develops in the preterm lung following ventilation and oxygen support.



Sufficient production of nitric oxide in fetal and newborn lungs is necessary for the lungs to develop and function properly. During the latter part of pregnancy the placenta produces large amounts of estrogen that enters the fetal circulation. Another spike of estrogen occurs during labor. In prior studies in cultured cells the investigators found that estrogen activates the genes in lung cells encoding nitric oxide synthases, enzymes that produce nitric oxide. That research suggested treatment with the hormone may achieve the same results in the intact lung. Premature infants - nearly 50,000 are born in the U.S. each year - miss out on this exposure to estrogen in the womb and, as a consequence, may experience respiratory problems because they lack nitric oxide.



Dr. Shaul and his colleagues found that administering estrogen to premature primates accomplished several things.



First, the treated animals had greater abundance of nitric oxide synthases in their lungs, resulting in markedly enhanced lung function and a significantly reduced need for ventilation support. This represents an important step in lessening the lung injury that causes BPD in humans, Dr. Shaul said. It also prevented low blood pressure, which is a common problem in preterm infants.



Estrogen also caused the closure of the ductus arteriosus, a shunt that connects the pulmonary artery to the aorta during the primates' fetal development to allow blood flow to bypass the fetus' fluid-filled lungs. In the case of full-term infants, the ductus arteriosus normally closes at the time of birth once breathing is established. In premature infants, however, it frequently fails to close resulting in further impairment in lung and heart function.



"With just one therapeutic intervention multiple benefits occurred in the lungs and the circulation," Dr. Shaul said. "Estrogen-based therapies to prevent BPD and other complications of prematurity should be further developed, and it is our hope to begin clinical trials in the near future."



Dr. Shaul said that future studies also would need to evaluate other potential targets of estrogen in the lung in addition to nitric oxide synthases and possible effects of postnatal estrogen treatment on nonpulmonary development, including those related to the later reproductive health of the child.



Notes:



Other UT Southwestern researchers involved in the study were the lead author Dr. Donald McCurnin, professor of pediatrics and medical director of the neonatal intensive care unit at Children's Medical Center Dallas; Dr. Brigham Willis, a former assistant professor of pediatrics; and Ivan Yuhanna, senior research associate in pediatrics.



Also participating were researchers from UT Health Science Center at San Antonio; the Southwest Foundation for Biomedical Research; Washington University School of Medicine; National Jewish Medical and Research Center, the University of Utah School of Medicine, the University of California, San Francisco, School of Medicine; SRI International, the University of Rochester School of Medicine and Dentistry; and Vanderbilt University School of Medicine.



Visit utsouthwestern/pediatrics to learn more about UT Southwestern's clinical services in pediatrics.



Dr. Philip Shaul -- utsouthwestern.edu/findfac/professional/0,2356,16558,00.html



Source: Erin Prather Stafford


UT Southwestern Medical Center

Recommendations:


•   Buy Maxaman without Prescription
•   Buy Excel (Herbal Viagra) without Prescription

What Decides Neural Stem Cell Fate?

Early in embryonic development, the neural crest - a transient group of stem cells - gives rise to parts of the nervous system and several other tissues. But little is known about what determines which cells become neurons and which become other cell types. A team led by Dr. Alexey Terskikh at Sanford-Burnham Medical Research Institute (Sanford-Burnham) recently found that expression of a gene called SOX2 maintains the potential for neural crest stem cells to become neurons in the peripheral nervous system, where they interface with muscles and other organs. Their results, published online May 5 by the journal Cell Stem Cell, could help better inform therapies aimed at neurocristopathies, diseases caused by defects in the neural crest or neurons, which include microphthamia and CHARGE syndrome.



The SOX2 gene encodes a transcription factor, a type of protein that switches other genes on or off. SOX2 is one of two key genes researchers use to generate induced pluripotent stem cells (iPSCs), which are capable of differentiating into all cell types for research and potential therapeutic applications.



"In this study, we looked at SOX2's role in cells of the peripheral nervous system and discovered that it's required to sustain multipotency - the ability to differentiate into several cell types in the peripheral nervous system, including neurons and glia," explained Dr. Terskikh, assistant professor in Sanford-Burnham's Del E. Webb Neuroscience, Aging and Stem Cell Research Center.



Using an embryonic stem cell model, Dr. Terskikh and colleagues showed that stem cells in the developing nervous system start out with SOX2, but lose it at the stage when they are considered migratory neural crest cells. Later, as neural crest stem cells aggregate at a subsequent point in development, SOX2 is regained only by those cells fated to become neurons. Neural crest stem cells that remain SOX2-free differentiate into other cell types, but never become neurons.



To determine how SOX2 controls this stage in nervous system development, the researchers looked at the genes it acts upon. They found that SOX2 switches on neurogenin-1 and Mash-1, two genes that support neuronal survival in both the central and peripheral nervous systems.



"If we prevent neural crest stem cells from re-expressing SOX2, we don't get neurons. If we try to push these SOX2-deficient cells to become neurons, they die, but they can readily give rise to glia or smooth muscle cells," Dr. Terskikh said. "We think that one function of SOX2 is to keep cells multipotent or pluripotent for one reason - if they need to become a neuron later in development. We hope this finding will be useful to researchers studying neural crest development and stem cell differentiation."


Notes:


Dr. Terskikh is supported by the California Institute for Regenerative Medicine (CIRM). Co-authors of this study include Flavio Cimadamore, Elena Giusto, Ksenia Gnedeva, Giulio Cattarossi, Amber Miller and Laurence M. Brill at Sanford-Burnham, Katherine Fishwick and Marianne Bronner-Fraser at the California Institute of Technology and Stefano Pluchino from the Institute of Experimental Neurology, IRCCS, in Italy.



Original paper:


Cimadamore F, Fishwick K, Giusto, Gnedeva K, Cattarossi G, Miller A, Pluchino S, Brill LM, Bronner-Fraser M, Terskikh AV. Human ESC-Derived Neural Crest Model Reveals A Key Role For SOX2 In Sensory Neurogenesis. Cell Stem Cell. May 5, 2011.



Source:

Heather Buschman, Ph.D.

Sanford-Burnham Medical Research Institute

Recommendations:


•   Buy Penis Growth Oil without Prescription

Eiken Chemical to Release New Avian Flu Virus Detection Reagent Kit

Tokyo (JCNN) - Eiken Chemical (TSE:4549) announced December 21 that it will begin marketing Loopamp Primer Set for Avian
Flu H5, a reagent kit to identify the A/H5 avian flu virus (Flu A/H5) designed for academic research, on December 24.



In combination with its proprietary kit Loopamp RNA Amplification Kit (RT-LAMP), the new product detects the amplification or
presence of Flu A/H5 through either a real-time turbidimeter or fluorescent visualization.


The product will be available through WebSERVE/e Genome Order (genome.e-mp.jp/), an online shop run by Fujitsu System
Solutions.


View Eiken Chemical Co., Ltd. company profile
here


japancorp/Article.Asp?Art_ID=9061

Recommendations:


•   Buy Caverta without Prescription

How Ion Channels Are Organized To Control Nerve Cell Communication

The messages passed in a neuronal network can target something like 100 billion nerve cells in the brain alone. These, in turn communicate with millions of other cells and organs in the body. How, then, do whole cascades of events trigger responses that are highly specific, quick and precisely timed? A team at the Weizmann Institute of Science has now shed light on this mysterious mechanism. Their discovery could have important implications for the future development of drugs for epilepsy and other nervous system diseases. These findings were recently published in the journal Neuron.



The secret is in the control over electrical signals generated by cells. These signals depend on ion channels - membrane proteins found in excitable cells, such as nerve cells - that allow them to generate electrical signals, depending on whether the channels are opened or closed. Prof. Eitan Reuveny, together with Ph.D. students Inbal Riven and Shachar Iwanir of the Weizmann Institute's Biological Chemistry Department, studied channels that work on potassium ions and are coupled to a protein called the G protein, which when activated, causes the channel to open. Opening the channel inhibits the conductance of electrical signals, a fact that might be relevant, for example, in the control of seizures.



The G protein itself is activated by another protein, a receptor, which gets its cue to carry out its task from chemical messengers known as neurotransmitters. But neurotransmitters are general messengers - they can inhibit as well as excite, and the receptors can respond to either message. How, the scientists wanted to know, is the G protein targeted so quickly and precisely to activate the channel?



Reuveny and his team found that the receptor and G protein are physically bound together in a complex, allowing the process to be finely tuned. When the receptor receives a chemical message from the neurotransmitter, it is already hooked up to the correct G protein. After being activated by the receptor, the G protein changes shape, opening the ion channel. The evidence for this complex structure came from special technique called FRET (Fluorescence Resonance Energy Transfer) that can measure the distance between two molecules. The scientists observed that even without stimulation, there is a lot of energy transfer between the G protein and the potassium channel, suggesting that they are very close together.



Mutations in ion channels are likely to be involved in epilepsy, chronic pain, neurodegenerative diseases and muscular diseases, and ion channels are the target of many drugs. Understanding the basic biological phenomena behind the way proteins organize themselves and orchestrate biological processes may allow scientists to design better or more efficient drugs.







Prof. Eitan Reuveny's research is supported by the Y. Leon Benoziyo Institute for Molecular Medicine; the Clore Center for Biological Physics; and the Dr. Josef Cohn Minerva Center for Biomembrane Research.



The Weizmann Institute of Science in Rehovot, Israel, is one of the world's top-ranking multidisciplinary research institutions. Noted for its wide-ranging exploration of the natural and exact sciences, the Institute is home to 2,500 scientists, students, technicians and supporting staff. Institute research efforts include the search for new ways of fighting disease and hunger, examining leading questions in mathematics and computer science, probing the physics of matter and the universe, creating novel materials and developing new strategies for protecting the environment.



Contact: Jennifer Manning


American Committee for the Weizmann Institute of Science

Recommendations:


•   Buy Urimax F without Prescription

Sciele Pharma And Plethora Solutions Announce That PSD502 Demonstrates Substantial Benefit In The Treatment Of Premature Ejaculation

Sciele Pharma, Inc. a Shiongi Company, and Plethora Solutions Holdings PLC ("Plethora" - AME:PLE) today presented highly encouraging results from a European Phase III randomized, double-blind, placebo-controlled study of PSD502 for the treatment of premature ejaculation (PE). In this study, men treated with PSD502 five minutes before intercourse were able to delay ejaculation up to six times longer than those who used a placebo. Additionally, patients and their partners reported significant improvements in overall sexual satisfaction scores when using PSD502. The results were presented today at the American Urological Association Annual Meeting.


"Premature ejaculation is a very distressing condition that can have a devastating impact on the intimate relationship between men and their partners," said Professor Wallace Dinsmore, Royal Victoria Hospital, Belfast, UK, and lead study investigator. "The data suggest that PSD502 is effective in delaying ejaculation for several minutes, significantly improving the overall sexual experience. Equally important is the fact that in this trial PSD502 was shown to be well tolerated and well accepted by patients."


The European Phase III study, one of two major international trials, was designed to determine whether PSD502, a metered-dose aerosol formulation of lidocaine and prilocaine, would result in longer intravaginal ejaculatory latency time (IELT) in men who suffer from PE. The study also assessed the safety and tolerability of the therapy.


"Premature ejaculation is experienced by up to 30 percent of the adult male population at some time in their lives, yet there is no FDA-approved prescription product to treat this sexual dysfunction," said Ira D. Sharlip, M.D., clinical professor of urology, University of California, San Francisco. "The significant improvement in ejaculatory control and overall sexual satisfaction reported by men using PSD502 in this study is very encouraging news for physicians who treat these patients."


"PSD502 may represent a promising new therapy in the management of premature ejaculation, meeting an unmet medical need in a condition that affects millions of men," said Ed Schutter, President and Chief Operating Officer of Sciele Pharma. "We look forward to completing the North American Phase III study in the second half of this year, with an anticipated filing with the FDA in the first half of 2010."


European Phase III Study


The European study was conducted with 300 randomized patients across 32 investigational centers in four countries across Europe. Of these, 268 patients have now been entered into the optional nine-month open-label study.


Final analyses confirmed that PSD502 produced a highly clinically and statistically significant increase from baseline in all three co-primary study endpoints, and also in all secondary endpoints. The IELT for PSD502 was four minutes compared with one minute in placebo (p

Of patients who received PSD502, 91% achieved an IELT of greater than one minute and 75% achieved an IELT of greater than two minutes following treatment. This compared with only 54% and 22% of placebo patients, respectively. Both endpoints were highly clinically and statistically significant (p

Recommendations:


•   Buy VP-RX Oil without Prescription

Federal Appeals Court Upholds Ruling That Colorado Right To Life Exempted From State Campaign Finance Amendment

The 10th U.S. Circuit Court of Appeals in Denver on Tuesday upheld a lower court ruling that the Colorado Right to Life Committee is exempted from a state constitutional amendment that requires some advocacy groups to file financial disclosure papers, the AP/Frisco Summit Daily News reports (AP/Frisco Summit Daily News, 8/21). Amendment 27, which was approved by Colorado voters in November 2002, bans direct corporate campaign contributions, limits contributions from political action committees to candidates and political parties, and restricts how much an individual or company can contribute to a candidate.

CRLC and the Colorado Citizens for Responsible Government in August 2003 filed a lawsuit in federal court challenging the amendment. The groups claimed that the amendment is unconstitutional because it regulates issue advocacy (Kaiser Daily Women's Health Policy Report, 8/4/03). Colorado Secretary of State Mike Coffman (R) argued that CRLC had to register as a political action committee and was subject to financial disclosure requirements.

The appellate court in its ruling said that CRLC qualified as an exception because it was not formed for business activities, did not have shareholders and received less than 1% of its annual gross income from business corporations. The court added that CRLC did not qualify because its main purpose is not to promote the defeat or election of candidates but rather to promote respect for human life. A spokesperson for Coffman said the secretary could not comment because he had not seen the ruling (AP/Frisco Summit Daily News, 8/21).

"Reprinted with permission from kaisernetwork. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at kaisernetwork/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork, a free service of The Henry J. Kaiser Family Foundation . © 2005 Advisory Board Company and Kaiser Family Foundation. All rights reserved.

Recommendations:


•   Buy Tentex Royal without Prescription

Key Protein In Energy Regulation Identified By Gladstone Scientists

With obesity and obesity-related diseases epidemic in the developed world, a clear understanding of how metabolism is regulated is crucial. One of the key metabolic pathways involves the oxidation of fat. In the current edition of the journal Nature, scientists at the Gladstone Institute of Virology and Immunology report on a new mechanism that governs this pathway and in the process identified a novel potential therapeutic target for controlling fat metabolism. The target is a protein from the mitochondria, or the "power plants" of every cell that are responsible for processing oxygen and converting substances from the foods we eat into energy for essential cell functions.



"Many mitochondrial proteins undergo a small chemical modification known as acetylation, which varies during feeding and fasting conditions," said Eric Verdin, MD, senior investigator and senior author of the study. "From our previous studies, we knew that the enzyme SIRT3 is involved in removing these modifications, and we speculated that SIRT3 might have a role in regulating metabolism and looked for how it might do this."



To study the enzyme's role in mice, the researchers used mice in which both copies of the gene had been deleted. Interestingly, mice that lost both copies of the SIRT3 gene appeared to be completely normal. However, the investigators then tested the mice under fasting conditions. During fasting, expression of SIRT3 was increased in the liver, an organ that helps maintain the body's energy balance. The livers of mice without SIRT3 had higher levels of fat and triglycerides than normal mice, because the mice could not burn fat.



To determine how SIRT3 controls fat burning, the researchers looked at the mitochondrial proteins. They found that the enzyme called LCAD was "hyperacetylated" and contained even more acetyl groups than usual and the enzyme had reduced activity.



The mice that lacked SIRT3 also had many of the key markers of fat oxidation disorders, low energy levels and low tolerance to cold. Further investigation showed that higher levels of SIRT3 expression and activity increase the activity of this key enzyme in fat oxidation. However, a number of other proteins are acetylated in the mitochondria, an observation which suggests that other proteins may be involved.



"We conclude that acetylation is a new mechanism for regulating fatty acid oxidation in mitochondria and that SIRT3 mediates the acetylation state," said Matthew Hirschey, postdoctoral fellow and lead author of the study. "The implication is that SIRT3 may have a pathologic role in some metabolic disorders, such as diabetes, cardiovascular disease, or fatty liver disease. We are excited about exploring these possibilities."



Additional contributors to the research include C. Ron Kahn of the Joslin Diabetes Center at Harvard Medical School, Robert V. Farese, Jr. of the Gladstone Institute of Cardiovascular Disease, and Chris Newgard of Duke University Medical Center. The work was supported in part by a Senior Scholarship in Aging from the Ellison Medical Foundation and by institutional support from The J. David Gladstone Institutes.



Dr. Verdin's primary affiliation is with the Gladstone Institute of Virology and Immunology where he is associate director and where his laboratory is located and his research is conducted. He is also professor of medicine at UCSF.



Source:

Valerie Tucker

Gladstone Institutes

Recommendations:


•   Buy Himcolin without Prescription