Archive for November 8th, 2006
Babies can be exposed to methamphetamine or “crystal meth” while in the womb, reveals an analysis
of hair samples, published ahead of print in the Fetal and Neonatal Edition of Archives of Disease in Childhood.
Unlike hair, the most commonly used detection methods (blood and urine), cannot register long term use, nor can they always distinguish among different drugs, say the authors. Bleaching or straightening the hair will not erase the chemical evidence it holds.
Crystal meth boosts alertness and promotes a sense of wellbeing, euphoria, and exhilaration. It also curbs appetite and enhances sexual arousal. But long term abuse damages nerves in the brain and can lead to psychotic behaviour and aggression.
The drug is very easy to manufacture in home laboratories, and global use has soared, particularly among young women, say the authors. An estimated half a million Americans alone are thought to use it every week, including 5% of pregnant women.
The authors carried out hair sample analysis on more than 8,000 people, totalling more than 34,000 test results between 1997 and 2005.
In all, 396 samples tested positive for crystal meth, accounting for 8% of the total during this period. This number included 11 mother and baby pairs.
All but 14 of the samples testing positive for crystal meth had been sent for analysis in 2005. The first positive cases dated from 2003.
Wide ranging levels of the drug were found in both the mothers’ and the newborns’ hair samples. But the levels matched, indicating that the drug is able to cross the placenta directly to the developing fetus, say the authors.
Only one newborn had no evidence of the drug in its hair. Fetal hair starts to grow at about 20 weeks.
The authors say that the precise effects of crystal meth on a fetus are not fully known, but the evidence to date points to restricted fetal growth and developmental problems.
Crystal meth users were also significantly more likely to use other drugs, the results showed. Most (85%) of the 396 samples positive for crystal meth also tested positive for at least one other illegal drug, predominantly cocaine. .
Drug abuse increases complications of pregnancy and triples the likelihood of serious medical problems among the babies born, say the authors.
November 8th, 2006
Women with eating disorders often cannot recognise their problem, or attempt to disguise it. This makes
diagnosis and treatment very difficult. But newly published research from Rapid Communications in Mass Spectrometry shows that analysing the carbon and nitrogen bound into hair fibres can determine whether a person does indeed have an eating disorder.
Hair grows by adding new proteins to the base of the strand, and pushing the strand up out of the hair follicle. The make-up of these proteins will be influenced by the nutritional state of the person at that moment. This nutritional state is in turn subtly affected by eating patterns associated with eating disorders. Because hair grows all the time, each strand consequently becomes a chemical diary, recording an individual’s day-by-day nutrition.
Research published this week by a multidisciplinary team of researchers at the Brigham Young University, Provo, Utah, USA, set out to analyse the pattern of carbon and nitrogen molecules in strands of hair.
The aim was to see if this pattern varied between people with eating disorders and others with normal eating behaviours. Careful statistical analysis of the data enabled them to give an 80% accurate prediction about whether a person had anorexia or bulimia — the two most common eating disorders. The test was so powerful that it required only five stands of hair.
“The test needs further validation before it will be ready for routine clinical use, but we believe that the current work shows that the method is already quite robust,” says lead author Kent Hatch of Brigham Young University’s Department of Integrative Biology.
“While some objective measures, such as low weight for age and height, aid in diagnosis of eating disorders, up until now doctors and researchers have had to rely heavily on self-reported information and qualitative interviews with patients. Data collected this way is often highly subjective and demands honesty from the patient. This test has the potential of providing an objective, biological measure for diagnosing eating disorders,” says Kent.
November 8th, 2006
Oregon Health & Science University researchers have uncovered a pathway through which a gene’s over-
expression causes skin stem cells to switch from creating hair follicles to creating sebaceous glands.
The discovery by the laboratory of Xiao-Jing Wang, M.D., Ph.D., professor of otolaryngology/head and neck surgery, OHSU School of Medicine, and member of the OHSU Cancer Institute, points to a new pathway that could some day be used as a therapeutic target for not only treating hair loss and oily skin, but prevent and treat cancer.
The study’s results are published in the current issue of the journal Developmental Cell.
Epidermal stem cells give rise to the outer layer of the skin that serves as a barrier for the body, as well as follicles that produce hairs and sebaceous glands that produce lipid oil to lubricate the skin. In aged skin, a protein called Smad7 is overproduced, which triggers hair loss and sebaceous gland growth.
The Developmental Cell study is the first to definitively link Smad7 over-expression and the pathological changes that occur in aged skin.
“In humans, scientists and medical doctors documented the aging skin phenotype a long time ago, and the Smad7 over-expression in aged skin was reported a few years ago, but nobody knew whether these two events had any link,” said Wang, who also serves in the OHSU departments of Cell and Developmental Biology, and Dermatology. “We found the mechanism that links these two together.”
For their study, the researchers created genetically engineered mice in which Smad7 is expressed in the skin, including epidermal stem cells, with the expression level comparable to aged skin. They found that Smad7 over-expression shifts the epidermal stem cell differentiation program from forming hair follicles to sebaceous glands, causing the mice to exhibit balding and oily skin.
Surprising to the researchers was that, independent of its normal role in blocking signaling from a group of genes called Smad, Smad7 shuts down signaling of another group of genes called Wnt, by binding to a Wnt signaling protein known as Beta-catenin and degrading it with an enzyme called Smurf2. Wnt signaling is critical for organ development, but if Wnt signaling is too active, it also causes cancer.
“Our study identifies a new Beta-catenin degradation pathway,” the scientists said in the study. “This finding has a significant impact not only on skin development and diseases, but also on diseases and cancers in other organs.”
For example, enhanced Beta-catenin signaling contributes to many cancer types, including those of the colon, lung and brain. The researchers believe inducing over-expression of Smad7 or delivery of Smad7 directly to tumor cells would provide a therapeutic approach because of the boost in Beta-catenin degradation.
However, impaired Beta-catenin signaling contributes to neurodegeneration, such as that caused by Alzheimer’s disease, retina degeneration, bone density defect and aging. For these diseases, blocking Smad7-mediated Beta-catenin degradation may offer a therapeutic approach.
The Developmental Cell study was supported by grants from the National Institutes of Health.
November 8th, 2006
Using an animal model, a research team ledby Yann Barrandon at the EPFL (Ecole Polytechnique Federale
deLausanne) and the CHUV (Lausanne University Hospital) has discoveredthat certain cells inside the hair follicle are true multipotent stemcells, capable of developing into the many different cell types neededfor hair growth and follicle replacement. In an article appearing inthe Oct 3 advance online edition of the Proceedings of the NationalAcademy of Sciences, they demonstrate that these holoclones can be usedfor long-term follicle renewal.
In 2001, Barrandon was part of aFrench research team who reported in the scientific journal Cell thatstem cells could be used to generate skin containing hair and sebaceousglands in mice. But at that time it was unclear whether the stem cellsin hair follicles were true stem cells, capable of long-term renewal,or multipotent progenitor cells that would not permanently engraft inthe follicle.
In the current PNAS study, the Swiss researchershave answered that question, using rat whisker hair follicles todemonstrate that the clonogenic keratinocytes in hair follicles aretrue stem cells.
Barrandon’s group isolated stem cells from ratwhisker follicles, labelled them, and grew them in culture for 140generations. They then implanted progeny cells into the skin of newbornmice whose hair follicles were just being formed. This skin was thengrafted onto athymic (nude) mice. Some cells were incorporated intodeveloping follicles, but other follicles were completely made up oflabelled cells. Each progeny cell contributed to the formation of eightdifferent types of cell in the follicle, including those of the outerroot sheath, inner root sheath, the hair shaft, the sebaceous gland andthe epidermis.
After 125 days, a biopsy was taken from the graft,and labelled stem cells were isolated, subcloned, cultivated and thenonce again transplanted. The rat whisker stem cells participated againin forming all the cell types needed to form the hair follicle andsebaceous glands, resulting in hair bulbs that underwent repeatednormal phases of growth, rest and regeneration. The fact that thetransplanted cells participate in the hair cycle over long periods oftime shows that they are true multipotent stem cells and notprogeniture cells.
“With the progeny of a single stem cell, itwould be theoretically possible to generate the complete hair bulb of ahuman being, and one that would last for years,” explains Barrandon.
Theability of the stem cells in hair follicles to repeatedly regenerateall the different cell types of the follicle and sebaceous glands hasimportant implications for regenerative medicine. The method could oneday be used to regenerate hair on patients with severe burns. Thisstudy is a logical complement to other work in Barrandon’s Laboratoryof Stem Cell Dynamics, recognized for research into the reconstructionof injured tissues and organs.
November 8th, 2006
Finding advances understanding of skin wounds and skin cancer
In a study that has implications for understanding the way skin wounds heal and some skin cancers develop, researchers at the University of Pennsylvania Medical Center and New York University School of Medicine have found compelling evidence that the hair follicle and the epidermis may originate from the same cache of cells.
The researchers have traced the earliest daughters of the stem cells (primitive cells not yet committed to a specific developmental pattern) to the section of the upper follicle adjacent to the region where the stem cells reside.
The finding shows clearly for the first time how cells from the hair follicle can directly influence the epidermis.
“Our results suggest that in normal newborns, and in healing wounds throughout life, it is the daughter cells in the upper follicle that migrate upward to form and maintain the new epidermis. The daughter cells of the stem cells also migrate downward to form the hairshaft,” said Robert M. Lavker, PhD., professor of dermatology at the University of Pennsylvania School of Medicine.
Lavker has been investigating stem cell systems for nearly 20 years in collaboration with Tung-Tien Sun, PhD, of the NYU School of Medicine. Their current work identifies the upper follicle as the site of young transient amplyfying (TA) cells — which are the early offspring of stem cells — and follows the TA cells’migration into the epidermis and into the bulb, or root, of the hair where the TA cells differentiate into components of the hair shaft.
The current study, which will be published in the August 18 issue of Cell, builds on the 1990 research of Lavker and his coworkers, in which they located stem cells at the bulge of the follicle (the point where the outer root sheath attaches to the arrector pili muscle).
The new study furnishes evidence that these researchers were correct at the time when they also postulated that the bulge stem cells are bipotent capable of generating TA cells that develop along two distinct paths.
Lavker and Sun had proposed that the stem cells were bipotent in order to explain a phenomenon that scientists had been aware of for years, but had never been able to understand: Healthy skin seems capable of self-regeneration. But when a severe burn destroys the skin, epidermal cells are found to emerge from any remaining hair follicles to re-establish the outer skin in circles of re-growth. The precise origin of those new epidermal cells had never been established.
Lavker and Sun’s theory that bulge stem cells were the source of both epidermal cells and hair cells became the basis of their current research. Using young and adult mice, Lavker, Sun and their colleagues devised a double-labeling technique in which they could follow the division of the stem cells, and then observe the trafficking patterns of the early-offspring TA cells.
Results from the study “strongly suggest that the bulge stem cell is bipotent, and that the daughter (TA) cells migrate up to the epidermis and down to the root,” Lavker said.
Added Sun: “There’s been a termendous controversy as to where the epidermal stem cells are. We are proposing that there is just one entity — an ultimate epidermal stem cell — located in the bulge area of the hair follicle, that is capable of forming skin or hair.”
A major “take home message” of the research, Lavker said, is the pivotal importance of the upper follicle in the healing process of the skin: “It places the upper follicle directly in the center, for wound repair.”
The work also paves the way for designing effective skin cancer treatment, by explaining why skin tumors that are produced for the purpose of research frequently originate in the upper follicle.
“In addition to wanting to target stem cells in the bulge for skin cancer (stem cells are the prime source of abnormal growth and mutation), now you also have to consider targeting the upper follicle where the TA cells retain most characteristics of the stem cells,” Lavker said.
Participating with Lavker and Sun in the research were Michael Lehrer, MD., and Pamela Jensen, PhD., of Penn, and Gina Taylor, MD., of Presbyterian Hospital. The work was funded by the National Institutes of Health.
November 8th, 2006