Health,Stem Cells, and Technology

Friday, October 29, 2010

BPA Linked To Sperm Dysfunction

Dr De-Kun Li, a reproductive and perinatal epidemiologist at Kaiser Permanente's Division of Research in Oakland, California and colleagues, found that over 500 factory workers with higher urine levels of BPA had between two and four times the risk of having poor semen quality, including low sperm count, motility, vitality and concentration, compared with those who had low urine BPA. Previous animal studies have also shown a link between BPA and adverse effects in male reproductive systems in mice and rats.


These findings may also point to problems beyond the male reproductive system: semen quality and male sexual dysfunction could be early signs of diseases that are harder to study, such as cancer or metabolic diseases. Future diagnostic tests for a variety of indications could incorporate an analysis of sperm.

BPA (Bisphenol-A) is found in food and drink cans, plastic bottles, and many other everyday products. Thus, environmental exposure to BPA may be linked to an increase in infertility.

Saturday, October 23, 2010

DHEAS Associated With Wealth And Health

Professor Sir Michael Marmot has published a study on the hormone called DHEAS, and found that higher blood levels of DHEAS is associated with incresed lifespan and with improved memory. Increased levels of DHEAS were also associated with increased wealth. Higher levels of this hormone, secreted by the adrenal glands, are associated with both greater amounts of exercise and an active life with lots of interests, friends and family – all of which tend to come with wealth.

The rate of production of the hormone is greatest in childhood and teenage years, before gradually declining through adult life. Having more DHEAS in the body is linked to a better memory and ability to cope with mental tasks, particularly in men. Along with another insulin-like growth factor I (IGF-I), DHEAS helps control reactions to stress and regulate various body processes including digestion, the immune system, mood and energy usage.

Dehydroepiandrosterone (5-DHEA) is an endogenous natural steroid hormone that is the major secretory steroidal product of the adrenal glands, and is also produced by the gonads and the brain. Dehydroepiandrosterone sulfate (DHEAS) is the sulfated version of DHEA. This conversion is reversibly catalyzed primarily in the adrenals, the liver, and small intestine. In the blood, most DHEA is found as DHEAS with levels that are about 300 times higher than those of free DHEA. Orally ingested DHEA is converted to a sulfate when passing through intestines and liver.

Although supplementation of DHEA in humans has proven variable in various studies, there is good evidence that it can improve memory function as a supplement. Further research is needed to determine whether supplementation of DHEA can be a significant benefit to human health.

Wednesday, October 20, 2010

Epigenetics: Metabolic Disorders Resulting From Fathers' Nutritional State

A female can develop a diabetes-like disease due to a high fat content in her father's diet before she was conceived. Epigenetic modifications of the father's sperm DNA resulting from his diet may underlie this observation.

Published today in Nature, Ng et al. in Dr. Margaret Morris' laboratory in Sydney, Australia report one of the early observations that a father's diet can affect his daughters' health. When the authors fed male rats a high-fat diet, the outcome was not surprising: the animals' body weight and body fat increased, and they exhibited glucose intolerance and resistance to the hormone insulin. Additionally, and this is the important part, a chronic high fat diet in Sprague–Dawley fathers induced increased body weight, adiposity, impaired glucose tolerance, and insulin sensitivity in the daughter. Relative to controls, the father's female offspring had an early onset of impaired insulin secretion and glucose tolerance that worsened with time, and normal adiposity.

This is further evidence that epigenetics, that is, environmental control of gene expression, can afflict not only the host, in this case the father, but also effect the host's offspring, in this case the daughter. Thus it may be that genes are not the immutable code that we once thought they were.

Tuesday, October 19, 2010

SLS-Based Creams Can Make Eczema Worse

For years people in the UK with eczema have been advised by physicians to use an inexpensive emollient cream to soothe their irritated skin. But researchers have now discovered that emollients containing sodium lauryl sulphate (SLS) can make the condition worse. Tests show that SLS, a detergent contained in the cream, thins the skin and actually causes irritation.

Dr. Richard Guy, Professor of Pharmaceutical Sciences at the University and Project Supervisor, along with postgraduate researcher Manda Tsang will publish a study in the British Journal of Dermatology showing that aqueous cream BP reduces the thickness of healthy skin over a period of four weeks, calling into question whether the cream should be used for treating eczema.

Originally used as a wash product in the UK, aqueous cream BP is currently the most widely prescribed emollient for the treatment of dry skin conditions in the UK, and is used to moisturize the skin, improving flexibility and preventing cracking in the protective outer layer, called the stratum corneum.

However, the cream contains the detergent SLS that can increase the permeability of the skin barrier and cause irritation. The study found that when healthy volunteers applied the cream to their forearms daily for a period of four weeks, the thickness of the stratum corneum was reduced by more than ten per cent. The researchers anticipate that using this cream would have an even more dramatic effect on damaged skin such as that found in eczema.

SLS is a detergent used to mix oils into water-based moisturization creams to yield a creamy texture. SLS is also used widely in shower gels and other cosmetics. The skin has a protective barrier layer of lipids that stops chemicals from entering into the body and to retain moisture. Professor Guy’s study has found that rubbing aqueous cream containing SLS into the skin thins this protective barrier, making the skin more susceptible to irritation. Therefore to use such creams on eczemous skin, which is already thin and vulnerable to irritation, is likely to make the condition even worse.

Eczema affects around 30 per cent of the population, an increase from around five per cent a generation ago. The increased incidence is likely due to a combination of genetic and environmental factors, such as central heating, exposure to pollutants and toxins, and carpets that can encourage dust mites, and using more creams and cosmetics that can thin the skin if used too frequently.

Dr. Guy’s study suggests that it is better for eczema patients to use oil-based ointments, instead of paraffin-based ointments that contain SLS, on damaged skin. This recommendation may be true in general to prevent thinning of the skin and therefore decrease the likelihood of inducing irritating skin conditions in normal or at risk skin.

Monday, October 18, 2010

Stem Cells: Systems Biology-Based Therapeutics

In response to a question last week, here is a short description of the relationship between stem cells and systems biology.

First, systems biology is a relatively new branch of science that is based on inter-disciplinary study of complex interactions in biological systems. Instead of only understanding biology at a reductionist level, i.e. the pieces of the system, the Systems Biology approach also seeks to understand how the pieces are joined together, and how the conjoined pieces serve to create function.

While a number of analytical approaches have been developed to understand biology at the systems level, including matematical modeling, genomics, metabolomics, proteomics, new imaging methodologies, and multi-dimensional recording to name a few, few therapeutics are in development to treat the human using a systems approach.

One method to develop a system biology approach to therapeutics involves the use of stem cells. As an example, our work at BioRegenerative Sciences, Inc.(BRS) uses stem cells and the molecules that the stem cells release (SRM) to treat degenerative or traumatized tissue with a multitude of molecules to mimic what normally occurs in the human body. Thus, when the body normally heals, a system of mechanisms operate in time and space, doing so in parallel and and in sequence to initiate and maintain the healing process. At BRS, we use the SRM methodology to develop therapeutics that mimic the healing processes that are occuring in parallel and in sequence.

The systems biology-based therapeutics (SRM Technology) that we develop at BRS are in contradisctinction to those therapeutics that are normally developed using a reductionist approach. Thus, the reductionist approach uses one molecule to treat one particular mechanism underlying the disease. But as we know, biology is not a reductionist system, and neither are disease states. Disease states involve multiple pathways. Thus treating a disease state with one molecule will only serve to partially treat the disease.

In contrast, the system biology-based approach using SRM Technology treats the disease at multiple points using multiple molecules and thus treats all, or many, of the mechanisms underlying the disease. In this way, a more efficacious and safer therapeutic is developed compared to the classic reductionist based therapeutics.

Taiwan Team Develops New Stem Cell Therapy For Heart Repair

Dr. Patrick C. H. Hsieh of Institute of Nanotechnology and Microsystems Engineering, College of Medicine, National Cheng Kung University (NCKU), Tainan, Taiwan, has published an important new study on myocardial regeneration in pigs, which is a common animal model for human heart disease. Prof. Hsieh and team have shown that by combining self-assembling peptide nanofiber hydrogel with autologous bone marrow stem cell, myocardial protection, including vascular regeneration and heart function, can be improved after acute myocardial infarction.

These data were published in Circulation, an important international journal in the cardiovascular field, in September, 2010, and the technology is currently under the applications of domestic and foreign patents.

Each year, 17,000,000 people die from heart disease worldwide. The most common cause for the heart disease is coronary occlusion or myocardial infarction, preventing blood from reaching the heart and thus leading to myocardial necrosis and apoptosis. The mortality rate is estimated to be as high as 30%.

Even if the patients survive, their heart cells lack the ability to regenerate. The remaining myocardial cells cannot withstand intraventricular pressure and thus they will thin due to gradual expansion. As a result, the patients will have heart failure and face death.

The current best clinical treatment is heart transplant. However, due to limited heart donors and risks such as immune rejection and infection, it is not in common use. The most common clinical treatment is drug control, including ACE inhibitors, β-blockers, digitalis glycosides and diuretics. However, these drugs simply slow down disease progression, and they normally have side-effects. Thus, stem cell therapy for heart repair, has become the solution to one of the most urgent medical problems.

Prof. Hsieh’s method is one way to bolster the positive effects of stem cells on the heart by using a new bioengineering technology that allows the stem cells to remain in place at the site of the damaged tissue in the heart. Thus, by combining self-assembling peptide nanofiber hydrogel with stems cells and injecting the mixture into cardiac muscle, the stem cells will not be easily carried away from the heart by the blood and therefore act to remain in place at the heart where they can then regenerate the heart tissue.

Saturday, October 16, 2010

New National "Systems Biology" Centers Created at UCSD and UCSF

The National Institute of Health has awarded $15.4 million to UCSD and $15.4 million to UCSF to establish two National Centers for Systems Biology. Systems biology, is a relatively new branch of science that is based on inter-disciplinary study of complex interactions in biological systems. Instead of only understanding biology at a reductionist level, i.e. the pieces of the system, the Systems Biology approach also seeks to understand how the pieces are joined together, and how the conjoined pieces serve to create function.

The UCSD Center for Systems Biology will work on maping interactions between regulatory molecules in order to understand how complex biological systems work, with one focus on interactions involved in cells’ responses to stress .

Researchers at the UCSD center will analyze interactions among all of the genes (genomics) and proteins (proteomics) within a cell in response to potentially harmful changes in the environment, then test the functions of specific genetic “circuits” involved in the response by re-creating them in isolation using synthesized genes.

The new UCSF center, named The UCSF Center for Systems and Synthetic Biology, is heralded as a center to develop the possible means of engineering a patient's own cells for therapeutic uses. By developing an understanding of the design rules that govern biological circuits, particularly those involved in adaptation, the UCSF center could help steer a revolutionary direction in medicine, namely the engineering of 'smart cells' that can carry out therapeutic or biotechnologically useful tasks.

This engineering-inspired approach at UCSF has the potential to transform medicine. The fundamental understanding of circuit structure and function that emerges from studies at center will allow definition of core circuit architectures in natural systems, how these circuits are perturbed in disease states, and how the circuit can be engineered to carry out therapeutic or biotechnologically useful target functions.

An example of the early success of systems biology includes the Nobel Prize winning work of Alan Hodgkin and Andrew Huxley in England who in 1952 developed the seminal Hodgkin–Huxley model, a mathematical model that describes how action potentials in neurons are initiated and propagated. The model is a set of nonlinear ordinary differential equations that approximates the electrical characteristics of excitable cells such as neurons and cardiac myocytes. The model is based on experimental data that were collected by the then revolutionary means of “voltage-clamp” techniques developed by Hodgkin, Huxley, and K.C. Cole at the Marine Biological Laboratory in Woods Hole, MA. This systems biological approach led to an understanding of the basis of nervous system function.

The two new national centers at UCSD and UCSF should promote equally significant advances as those by Hodgkin and Huxley in our understanding of man at the systems level.

Tuesday, October 12, 2010

Folic Acid Supplementation Does Not Show Heart Benefits

Dr. Robert Clarke of the University of Oxford performed a meta analysis of 8 large trials concluding that the use of folic acid supplements does not appear to be linked to reduced rates of cardiovascular events, despite folic acid’s ability to lower blood levels of homocysteine, an amino acid thought to be a risk factor for diseases of the heart and blood vessels (11 October 1 issue of Archives of Internal Medicine).

Dr. Clarke and colleagues pooled the results of 8 large randomized, placebo-controlled trials of folic acid supplementation involving over 37,000 participants at increased risk of cardiovascular disease. Altogether, 18,723 of the participants were randomly assigned to take a daily dose of folic acid ranging from 0.8 milligrams per day to 40 milligrams, while the other 18,762 took placebo or an equivalently small dose of folic acid. The trials lasted for a median of 5 years.

The results showed that those in the active folic acid groups experienced an average 25 per cent reduction in homocysteine levels, but there were no significant differences between active folic acid and placebo for overall vascular mortality, overall cancer incidence, cancer mortality, or deaths from all causes, either during the whole scheduled treatment period or during the later period of it.

Monday, October 11, 2010

Culturing Adult Stem Cells That Do Not Age

Biomedical researcher, Dr. Techung Lee at the University at Buffalo in New York has engineered adult stem cells that scientists can grow continuously in culture, a discovery that could speed development of cost-effective treatments for diseases including heart disease, diabetes, immune disorders and neurodegenerative diseases

The research breakthroughs a frustrating barrier to progress in the field of regenerative medicine: The difficulty of growing adult stem cells for clinical applications. Because mesenchymal stem cells have a limited life span in laboratory cultures, scientists and physicians who use the cells in research and treatments must continuously obtain fresh samples from bone marrow donors or other tissues, a process both expensive and time-consuming.

Stem cells help regenerate or repair damaged tissues, primarily by releasing growth factors, cytokines and other factors that encourage existing cells in the human body to function and grow. Dr Lee's ongoing work indicates that this feature makes it feasible to repair tissue damage by injecting mesenchymal stem cells into skeletal muscle, a less invasive procedure than injecting the cells directly into an organ requiring repair. In a rodent model of heart failure, Lee and collaborators showed that intramuscular delivery of mesenchymal stem cells improved heart chamber function and reduced scar tissue formation.

Geron Initiates Clinical Trial of Human Embryonic Stem Cell-Based Therapy

In a landmark study, the Geron Corporation of Menlo Park, CA today announced the enrollment of the first patient in the company's clinical trial of human embryonic stem cell (hESC)-derived oligodendrocyte progenitor cells; proprietary designation GRNOPC1. For the first time ever in the United States, a patient has been treated with embryonic stem cells under FDA approval. Experimental stem cell treatments have already taken place in China under their government auspices.

The primary objective of this FDA approved Phase I study is to assess the safety and tolerability of GRNOPC1 in patients with complete American Spinal Injury Association (ASIA) Impairment Scale grade A thoracic spinal cord injuries. Participants in the study must be newly injured and receive GRNOPC1 within 14 days of the injury.

The patient was enrolled at Shepherd Center, a 132-bed spinal cord and brain injury rehabilitation hospital and clinical research center in Atlanta, GA. Shepherd Center is one of seven potential sites in the United States that may enroll patients in the clinical trial.

In addition to Shepherd Center, Northwestern Medicine in Chicago, IL is also open for patient enrollment. As additional trial sites come online and are ready to enroll patients, they will be listed on the Patient Information pages of Geron's website and on the NIH clinical trials registry, ClinicalTrials.gov.

This clinical trial follows years of non-clinical laboratory work and many millions of dollars invested by Geron in their spinal cord-stem cell research program. Despite an unhealthy climate in the USA for embryonic stem cell research, Geron has steadily worked on this program through private financing. Two weeks ago Senators Tom Harkin and Arlen Specter (and others) held a subcommittee meeting in support of embryonic stem cell research, which is hoped to propel the US to support embryonic stem cell research and better enable the development of stem cell therapeutics by Geron and other companies in the USA.

Further information on the criteria for patient eligibility for the study is also available on ClinicalTrials.gov.

High BPA Exposure: Canned Vegetables, Cigarettes and Cashier Receipts

According to new studies cited in "Variability and Predictors of Urinary Bisphenol A Concentrations During Pregnancy,” Environmental Health Perspectives, Oct. 8, 2010, more than 90 percent of pregnant women had detectable levels of BPA from a variety of sources. Pregnant women who eat canned vegetables daily have elevated levels of bisphenol A, and pregnant women who were exposed to tobacco smoke or worked as cashiers also had above-average concentrations in their bodies.

Bisphenol A, or BPA, is an estrogen-mimicking chemical used in food and beverage can linings, polycarbonate plastic and cash register receipts. Lab animals exposed in the womb to low amounts of BPA develop prostate and mammary gland cancers, obesity and reproductive problems. Recent studies in lab animals also show that BPA profoundly changes epigenetics such that obesity can be passed to the mother's offspring.  In humans, BPA has been linked to heart disease and diabetes.

A few years ago, many mothers reacted strongly to protect their infants from BPA by pressuring retailers and manufacturers to offer BPA-free baby bottles. But the new study shows that pregnant women are still unwittingly exposing their infants during fetal development, which is an even more vulnerable time for the child.

While vegetables and fruit are an important part of nutrition for pregnant women, given these data, I recommend  best to choose fresh produce instead of canned.

Friday, October 8, 2010

Insoluble Drugs In Nano Crystal Form Can Be Made Orally Available

Dr. R. Ravichandran of the Regional Institute of Education (NCERT), in Bhopal, India, has published results in the International Journal of Nanoparticles (2010, 3, 280-296) demonstrating that producing nanoscopic crystals of a pharmaceutical product can allow the medication to be absorbed by the gut even if the drug is not soluble in water.

Data suggest that about half of the medicinal drugs being developed by the pharmaceutical industry either don’t dissolve, or do so only very weakly in water. This is a major problem for administering such drugs because they cannot be taken orally. The industry has developed many approaches to addressing this problem by using a number of different additives, however such approaches can be time consuming and costly to manufacture.
During the last decade, scientists have discovered that producing microscopic crystals of a pharmaceutical product can make it soluble in water even if the original compound is not. The mechanism for solubility is that the tiny size of the particle yields a much greater surface area to volume ratio giving the particle access to more water molecules that can surround the particles; hence the compound dissolves and is able across the lining of the gut wall and becomes bioavailable.

Thursday, October 7, 2010

Improved HSC Stem Cell Grafts: Inhibition of EGFR signaling enhances G-CSF–induced hematopoietic stem cell mobilization

Dr Marnie Ryan and research team at the Cincinnati Children's Hospital Medical Center have published in Nature Medicine this week a new method for mobilization of hematopoietic stem cells (HSCs) from the bone marrow.  Using cytokine granulocyte colony–stimulating factor (G-CSF) is the standard method to collect HSC grafts for stem cell transplants, however, G-CSF fails to mobilize sufficient numbers of stem cells in up to 10% of donors, precluding autologous transplantation in those donors or substantially delaying transplant recovery time. These new data suggests that epidermal growth factor receptor (EGFR) inhibition can augment HSC mobilization, bringing us one step closer to an universal method to obtain HSCs for transplantation. These studies were performed in mice and will need to be replicated in humans before we can assess the value of the procedure for human transplantations.

Vitamin D Deficiency Rampant And Diminishes Orthopedic Surgery Recovery

Nearly 50 percent of patients undergoing orthopedic surgery have vitamin D deficiency that should be corrected before surgery to improve patient recovery, based on a study by Dr. Joseph Lane and colleagues at the Hospital for Special Surgery (HSS) in New York City. Vitamin D is essential for bone healing and muscle function and is critical for a patient's recovery. The study appears in the October 2010 issue of The Journal of Bone and Joint Surgery.

The study suggests that 2,000-4,000 milligrams of vitamin D per day, based on what their deficient value was,  can correct their deficiency. Usually the deficiency can be corrected in four to six weeks. According to Dr. Lane an aggressive vitamin D regimen just before surgery can correct deficient levels quickly, but needs to be monitored very carefully. Vitamin D levels are critical to the surgical outcome because bone remodeling or bone tissue formation, a critical part of the healing process, occurs about two to four weeks after surgery. This is the critical period when the body needs vitamin D for healing.

The take home message of this study is that vitamin D is important for muscle and fracture healing, and about 50 percent of people coming in for orthopedic surgery will not heal properly because of insufficient vitamin D levels. This problem is easily correctable. Patients undergoing a procedure that involves the bone or the muscle should correct their vitamin D levels if they want to have an earlier, faster, and improved recovery.
In recent years, vitamin D deficiency has been recognized as a widespread and caused by a number of factors. First, Vitamin D is difficult to attain from foods, except, for example, cod liver oil and fish. Second, until recently the recommended daily allowance of vitamin D was set too low and therefore foods were inadequately supplemented. And third, while people can absorb vitamin D from sunlight, people these days often work long hours indoors and have been made scarred of overexposure to the sun for fear of cancer so that they often use sunscreen that impedes vitamin D intake.

Wednesday, October 6, 2010

Link Between X-Rays And Increased Childhood Leukemia Risk

Diagnostic X-rays may increase the risk of developing childhood leukemia, according to a new study by Dr. Patricia Buffler and her research team at the University of California, Berkeley's School of Public Health.

Specifically, the researchers found that children with acute lymphoid leukemia (ALL) had almost twice the chance of having been exposed to three or more X-rays compared with those who did not have leukemia. Surprisingly, just one X-ray was enough to moderately increase the risk. Chest X-rays resulted in a slightly increased risk compared to other regions of the body.

Published in the October 2010 issue of the International Journal of Epidemiology, these data come from the Northern California Childhood Leukemia Study, a population-based case-control study that includes 35 counties in the northern and central regions of the California.

The relationship between high doses of radiation and
cancer has been well known, but significant debate still surrounds the health impacts from low dose diagnostic radiation typical of conventional X-rays, or radiographs. Both are forms of ionizing radiation.

Natural sources of ionizing radiation are ubiquitous, from the air we breathe to the soil we walk on. Unlike ionizing radiation which is known to cause cancer in humans, non-ionizing radiation, such as exposures associated with radio signals, microwaves and electric power lines, does not cause cancer. The dose of ionizing radiation from a single chest X-ray is roughly equivalent to the amount one would receive from natural surroundings in 10 days, a dose that until now has been considered low. Dr. Buffler said that the results of her study were not expected.
I believe the take home message here is that although X-rays are important part of diagnosing many maladies, when X-rays are not an important part of the diagnosis, they should not be used.

Light Drinking In Pregnancy Does Not Harm Children's Development

In a UK study of over 11,000 children, Dr. Yvonne Kelly has found that children of mothers who drank heavily during pregnancy were more likely to be hyperactive, and have behavioral and emotional problems than those whose mothers abstained during pregnancy.

 
But in the case of children whose mothers drank only one or two units of alcohol a week, or per occasion, during pregnancy, there was no evidence of this being linked to their behavioral or intellectual development.

Interestingly, some benefit to light drinking was observed: The researchers found that children born to mothers who drank one or two units a week, or per occasion, during pregnancy were 30 per cent less likely to have behavioral problems than children born to mothers who did not drink during pregnancy. The abstract of the original research is shown below:



J Epidemiol Community Health doi:10.1136/jech.2009.103002

Light drinking during pregnancy: still no increased risk for socioemotional difficulties or cognitive deficits at 5 years of age?

Press Release
  1. Yvonne J Kelly1,
  2. Amanda Sacker2,
  3. Ron Gray3,
  4. John Kelly1,
  5. Dieter Wolke4,
  6. Jenny Head1,
  7. Maria A Quigley3
+ Author Affiliations
  1. 1Department of Epidemiology and Public Health, University College London, London, UK
  2. 2Institute for Social and Economic Research (ISER), University of Essex, Colchester, UK
  3. 3National Perinatal Epidemiology Unit, University of Oxford, Headington, Oxford, UK
  4. 4Department of Psychology and Health Sciences Research Institute, Warwick Medical School, The University of Warwick, Coventry, UK
  1. Correspondence to Dr Yvonne Kelly, Department of Epidemiology and Public Health, 1–19 Torrington Place, University College London, London WC1E 6BT, UK; y.kelly@ucl.ac.uk
  • Accepted 25 June 2010
  • Published Online First 5 October 2010

Abstract

Background This study examines the relationship between light drinking during pregnancy and the risk of socioemotional problems and cognitive deficits at age 5 years.
Methods Data from the nationally representative prospective UK Millennium Cohort Study (N=11 513) were used. Participants were grouped according to mothers' reported alcohol consumption during pregnancy: never drinker; not in pregnancy; light; moderate; heavy/binge. At age 5 years the strengths and difficulties questionnaire (SDQ) and British ability scales (BAS) tests were administered during home interviews. Defined clinically relevant cut-offs on the SDQ and standardised scores for the BAS subscales were used.
Results Boys and girls born to light drinkers were less likely to have high total difficulties (for boys 6.6% vs 9.6%, OR=0.67, for girls 4.3% vs 6.2%, OR=0.69) and hyperactivity (for boys 10.1% vs 13.4%, OR=0.73, for girls 5.5% vs 7.6%, OR=0.71) scores compared with those born to mothers in the not-in-pregnancy group. These differences were attenuated on adjustment for confounding and mediating factors. Boys and girls born to light drinkers had higher mean cognitive test scores compared with those born to mothers in the not-in-pregnancy group: for boys, naming vocabulary (58 vs 55), picture similarities (56 vs 55) and pattern construction (52 vs 50), for girls naming vocabulary (58 vs 56) and pattern construction (53 vs 52). Differences remained statistically significant for boys in naming vocabulary and picture similarities.
Conclusions At age 5 years cohort members born to mothers who drank up to 1–2 drinks per week or per occasion during pregnancy were not at increased risk of clinically relevant behavioural difficulties or cognitive deficits compared with children of mothers in the not-in-pregnancy group.

Tuesday, October 5, 2010

A New Method to Make Pluripotent Stem Cells

An NIH-funded Harvard researcher has developed a way to make pluripotent stem cells from skin cells that solves several of the major impediments to using iPSCs to treat human diseases. Dr. Derrick Rossi, an assistant professor at Harvard Medical School, created pluripotent stem cells, which can turn into almost any other type of cell in the body, from non-stem cells without using viruses to modify a cell's genome, as conventional methods do. This means that Rossi's new method could be substantially safer for treating disease. The work is published this month in the journal Cell - Stem Cell.

Dr. Rossi's innovation, which has not yet been tested in humans, was to use messenger RNA instead of DNA to produce the four proteins needed to reprogram the cell. He has started a company called ModeRNA to commercialize this use of messenger RNA. The new approach may also have potential in gene therapy, which also relies on viruses to deliver treatment.

Improving the usability of man-made stem cells instead of using embryonic stem cells is one method under investigation for helping patients and avoiding the political controversy that has slowed government funded embryonic stem-cell research. In late September, a U.S. federal appeals court allowed federal funding of embryonic stem-cell research to continue while a legal case against such funding proceeds. The human embryonic stem cells (hESC) used in research were mostly derived from embryonic tissue grown more than a decade ago. hESCs are the most versatile cells in the body, and the gold standard by which iPSCs are judged.

Four years ago, University of California San Francisco researcher Dr.Shinya Yamanaka showed that adult cells could be turned into induced pluripotent stem  cells (iPSC) through the introduction of four specific proteins. Theoretically, this means that physcians can remove skin cells from a sick or disabled person, transform them into iPSCs, and then inject the iPSC into the patient for treatment. Using iPSCs avoids the need to destroy embryos and, because they can be derived from the patient's own cells, may mean less risk of rejection. 

Dr. Rossi successfully differentiated his stem cells into muscle cells using RNA, a process that may offer promise in gene therapy and other treatments. Although the new  method does not alter the cell's underlying genome, the effects on the cells epigenome, which controls expression of genes, is not yet known. The new cells are termed "RNA Induced Pluripotent Stem Cells."

California Board of Regents Announces New Hospital at UCSF

After nearly a decade of planning, site preparations are underway at the Mission Bay Campus on a 14.5-acre parcel of land. Construction of the 878,000-gross-square-foot hospital complex is scheduled to begin in December 2010, after required state permits are expected to be issued. Upon completion in 2014, the 289-bed facility will set a new standard for patient- and family-centered health care, safety, sustainability and translational medicine.
The Regents arrived at this point in significant measure because of a generous, visionary group of donors who believe in biomedical research.  In June, the second $100 million plus gift to this project was announced.  It was from Lynne and Marc Benioff to name the UCSF Benioff Children’s Hospital.  This gift followed a 25 million gift in 2007 latered bolstered by a $125 million matching challenge gift from Charles “Chuck” Feeney's Atlantic Philanthropies in 2008. The hospital joins an ongoing world-class biomedical and biotechnology research center at the UCSF Mission Bay Campus.

Leadership That Money Can’t Buy

Few of us Californians doubt the importance of the gubernatorial race between Jerry Brown and Meg Whitman, two remarkable and highly accomplished individuals. Our great state has seen times of boom and bust, and now in our current crisis the time has come for another boom. Who will best lead us into our next boom? History may be instructive here. In recent times, California has enjoyed two great booms and, interestingly, both were realized when the governor’s last name was Brown. Jerry Brown’s father, Edmund G. "Pat" Brown, whose two-term governorship (1959-1967) is remembered as the apogee of California's emergence as a nation state, in which Brown's leadership led to California’s construction of the largest water aqueduct in the world, created the world’s best university system (UC), expanded the state college system, and built more freeways than any state has done before or since.  Pat Brown sponsored about forty major proposals, only five of which failed to pass in the Legislature. As Tom Brokaw has said, “I believe he is the godfather of modern California.”  A second boom occurred when Jerry Brown was governor (1975-1983). This period saw a great expansion of innovation and technology, with the rise of the computer business in Silicon Valley and biotech in the San Francisco Area. Amongst others, Steve Jobs, co-founder of Apple, and Bob Noyce, co-founder of Intel,  two of the most important and enduring high tech companies in the world, were an important part of Brown’s administration. Jobs, a personal friend of Jerry Brown, served on the state's Commission on Industrial Innovation, and Noyce, inventor of the microchip, was a member of the University of California Board of Regents. Brown’s period of governorship also saw the incubation of the biotech industry from our great universities; thus a whole new industry was born up and down the California Coast from San Francisco to San Diego. During this period Jerry Brown was dubbed "Governor Moonbeam" by his critics because of his proposal that the State of California purchase its own space satellite that would provide intra-state and emergency communications for California; a prophetic idea that was later realized through a similar program of leasing satellites by the state.
During this period Brown also led the way to California’s energy efficiency and renewable resources programs. This vision not only served the environment of California very well, but also saved California millions of dollars and paved the way  for a generation of new industries. Jerry’s ideas of the 70s and 80s have now provided a  policy model for farsighted people around the world, including our competitors in Asia, such as China, who is now developing industry based on those ideas.
Indeed Brown's original policies of environmental stewardship and technological innovation are fusing into the makings of the greentech economic boom. Brown says that he wants to spur a new wave of technological innovation and create new industries and jobs, that will reduce our dependency on imported oil, reduce our skyrocketing debt, and build a sustainable future. Brown is planning the creation of 20,000 megawatts of new renewable power, of which 12,000 will be distributed and 8,000 centrally based, that will be generated in the desert. These plans will create 500,000 jobs. Brown has also pushed hard to build California’s infrastructure, arguing for high-speed rail, and for stem cell research, so that California can continue to lead the way in biotech and biomedicine.
Now, more than ever before, California needs the leadership to continue our creative spirit and translate our great ideas into marketplace realities. Such leadership will need to foster our great university system, especially our great research universities in order to maintain the flow of new ideas. Our leadership will also need to embrace the new technologies, such as greentech, just as California did in the past with the then new semiconductor and biotech industries. Leadership will also mean working with disparate groups across the state to inform, engage in rational dialogue as opposed to demagoguery, and draw reasonable compromises across the groups in order to push meaningful legislative, policy, and executive actions forward.  Is there hope for our state? Given that California’s budget deficit is only 1% of the gross state product (GSP), compared to Greece’s deficit, which stands at about 14% of their GDP, or the US deficit, which stands at about 11% of GDP, we can see that our crisis is not insurmountable and that with proper leadership, the state of California can emerge from our current economic crisis stronger, and with sustainable plans for our next boom.