Men who develop prostate cancer, especially the more aggressive and dangerous forms that spread throughout the body, tend to retain denser bones as they age than men who stay free of the disease, suggests new research from Johns Hopkins and the National Institute on Aging (NIA), part of the National Institutes of Health.

The finding, published in the July British Journal of Urology International, could help scientists gain a better grasp on what causes prostate cancer and its spread.

Researchers have long known that prostate cancers that spread, or metastasize, often migrate to bone. That idea led Stacy Loeb, M.D., a resident in the Department of Urology at the Johns Hopkins University School of Medicine, and her colleagues to wonder whether there is a connection between bone characteristics and prostate cancer development and metastasis.

“We reasoned there may be some difference between men who develop prostate cancer, especially metastatic disease, and those who don’t, and it was logical to see if there was something different about their bones,” says Loeb.

To investigate, she and her colleagues used data from the NIA’s Baltimore Longitudinal Study of Aging , a long-term study that has tracked various health-related information for hundreds of Baltimore-area  participants since 1958. The researchers collected data on the bone mineral density of 519 men, measured from 1973 to 1984. They then used the same collection of data to see which men were eventually diagnosed with prostate cancer.

Typically, bone density declines with age in both men and women. However, Loeb and her colleagues found that the 76 men in their study who went on to develop prostate cancer had bone density that remained significantly higher as they aged, compared with those who remained cancer free. The findings held up even after the researchers accounted for lifestyle factors that might influence bone density, such as smoking, body mass index, and intake of dietary calcium and vitamin D.

Further examination showed that the 18 men who developed the high-risk form of the disease retained the highest bone density, but the researchers caution that the number of patients is too small to make any final conclusions about bone features and metastatic disease.

Loeb and her colleagues say that their findings don’t mean that bone density scans should be used as a screening tool for prostate cancer. Rather, their goal was to better understand the link between prostate cancer and bone. They say their results suggest that the same factors that influence bone density, such as sex hormones or growth factors in bone, may also be spurring prostate cancer to develop and metastasize. She and her colleagues plan to continue searching for what common factors connect bone density and prostate cancer in future studies.

“If we can elucidate the underlying pathways, we could develop strategies for preventing prostate cancer from occurring or spreading,” Loeb says.

Source:www.hopkinsmedicine.org
 
 
 
COLUMBUS, Ohio – Cancer researchers have discovered a previously unknown type of gene regulation and DNA behavior in breast cancer cells that may lead to better insight about environmental exposure to estrogen-like compounds. 

A new study, published in the journal Genome Research by researchers at The Ohio State University Comprehensive Cancer Center-Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC-James), provides the first evidence that cells can regulate many genes at once by looping their DNA, contributing to cancer when it goes awry. In this study, the gene regulation was discovered in breast cancer cells as a response to the hormone estrogen and resulted in the silencing of 14 genes at one time. 

Tim H.-M. Huang, professor of molecular virology, immunology and medical genetics in the OSUCCC-James human cancer genetics program, and Pei-Yin Hsu, a visiting scholar and researcher in Huang’s lab, discovered the DNA looping event in a breast cancer cell line gene cluster at chromosome region 16p11.2. They validated the finding using normal human breast epithelial cells and two animal models. 

In addition, they used the normal-cell model to determine if long-term exposure to nine estrogen-like chemicals can initiate gene silencing through this mechanism. These chemicals included diethylstilbestrol, two thalates and bisphenol A (BPA).

The suppressive effects varied in normal cells. When the investigators exposed a group of four rats to BPA for 21 days, however, they found concurrent suppression of ten genes comparable to those located at 16p11.2. These findings, says Huang, suggest that continuous exposure to estrogen-like compounds might lead to permanent silencing of genes located in this conserved cluster.

In healthy breast epithelial cells, 14 gene regulatory sites came together to form a single, temporary transcription site, Huang says. “But in breast cancer cells, there is no coordinated transcription site pairing, the DNA loops become tangled and the entire gene complex shuts down in a dead knot.” (For a demonstration of DNA looping, click here.)

In some cases, Huang says, this multi-gene regulatory mechanism can increase gene expression and oncogenic activity, and further contribute to cancer development.

“We offer a new concept in this paper for the collective regulation of gene transcription,” says first author Hsu, who identified the loop structures and their significance. “We found that in normal breast cells, DNA looping is more flexible and brings different promoters together temporarily. But in cancer, this complex just locks up and causes long-term suppression.”

Researchers generally believe that transcription factors bind to a site on a single gene, and then the gene is actively transcribed, according to Huang. The study’s findings show that this is not always the case. Sometimes the promoter is located far away, and it is remotely controlled.

"Overall, our study shows that certain regions of the genome are silenced because the DNA has lost flexibility, and that this inflexible DNA status might be a good marker for studying environmental exposure to estrogen-like compounds,” Hsu says.

Funding from the National Institute of Environmental Health Sciences and the National Cancer Institute supported this research.

Other researchers involved in this study were Hang-Kai Hsu, Gregory A.C. Singer, Pearlly S. Yan, Benjamin A.T. Rodriguez, Joseph C. Liu, Yu-I Weng, Daniel E. Deatherage, Zhong Chen and Qianben Wang of OSUCCC-James; Julia S. Pereira, Ricardo Lopez, and Jose Russo of Fox Chase Cancer Center; Coral A. Lamartiniere of the University of Alabama at Birmingham; and Kenneth P. Nephew of Indiana University.

The Ohio State University Comprehensive Cancer Center- Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (http://cancer.osu.edu) is one of only 40 Comprehensive Cancer Centers in the United States designated by the National Cancer Institute. Ranked by U.S. News & World Report among the top 20 cancer hospitals in the nation, The James is the 180-bed adult patient-care component of the cancer program at The Ohio State University. The OSUCCC-James is one of only seven funded programs in the country approved by the NCI to conduct both Phase I and Phase II clinical trials.

Source: medicalcenter.osu.edu
 
 
RIVERSIDE, Calif. – Vitamin D surfaces as a news topic every few months. How much daily vitamin D should a person get? Is it possible to have too much of it? Is exposure to the sun, which is the body's natural way of producing vitamin D, the best option? Or do supplements suffice?

In the July 2010 issue of Endocrine Today, a monthly newspaper published by SLACK, Inc., to disseminate information about diabetes and endocrine disorders, Anthony Norman, a distinguished professor emeritus of biochemistry and biomedical sciences and an international expert on vitamin D, notes that half the people in North America and Western Europe get insufficient amounts of vitamin D.

"Elsewhere, it is worse," he says, "given that two-thirds of the people are vitamin D-insufficient or deficient. It is clear that merely eating vitamin D-rich foods is not adequate to solve the problem for most adults."

Currently, the recommended daily intake of vitamin D is 200 international units (IU) for people up to 50 years old; 400 IU for people 51 to 70 years old; and 600 IU for people over 70 years old.

"There is a wide consensus among scientists that the relative daily intake of vitamin D should be increased to 2,000 to 4,000 IU for most adults," Norman says. "A 2000 IU daily intake can be achieved by a combination of sunshine, food, supplements, and possibly even limited tanning exposure."

While there is now abundant data on vitamin D and its benefits, Norman believes there is room for more study.

"The benefits of more research on the topic justifies why this field of research deserves additional governmental funding," he says. "Already, several studies have reported substantial reductions in incidence of breast cancer, colon cancer and type 1 diabetes in association with adequate intake of vitamin D, the positive effect generally occurring within five years of initiation of adequate vitamin D intake."

Because vitamin D is found in very few foods naturally (e.g. fish, eggs and cod liver oil) other foods such as milk, orange juice, some yogurts and some breakfast foods are fortified with it. The fortification levels aim at about 400 IU per day.

Norman, who holds the title of Presidential Chair in Biochemistry-Emeritus, has been researching vitamin D for nearly 50 years. In 1967, his laboratory discovered that the vitamin is converted into a steroid hormone by the body. Two years later, his laboratory discovered the vitamin D receptor (or VDR), an essential receptor for the steroid hormone form of vitamin D that is present in more than 37 target organs of the body that respond biologically to the vitamin.

"There is now irrevocable evidence that receptors in the immune, pancreas, heart-cardiovascular, muscle and brain systems in the body generate biological responses to the steroid hormone form of vitamin D," he says.

Source: EurekAlert
 
 
Many of us are simply overloaded with cholesterol, and now a report in the July issue of Cell Metabolism brings what might be good news: There is more than one way to get rid of that cholesterol, which can otherwise lead to atherosclerosis and heart disease.

"Cholesterol really can't be broken down," said Mark Brown of Wake Forest University School of Medicine. To get rid of it, it must be excreted, and now Brown and his colleagues have new evidence for an alternate way to deliver cholesterol into the feces. The findings revise scientific dogma about cholesterol loss that goes back almost 40 years.

Textbooks say that white blood cells known as macrophages gobble up cholesterol from artery walls. That cholesterol is then delivered to high-density lipoprotein [HDL, aka good cholesterol], which takes it back to the liver where it goes into bile.

"Bile is necessary under the model to deliver cholesterol to the intestine," Brown said.

There were some hints that might not be the whole story. A model of cholesterol loss first proposed way back in the 1920s suggested the existence of a route that didn't rely on bile. And indeed, studies in dogs unable to get cholesterol into bile showed that the animals actually experienced an increase in cholesterol loss. More recent studies in mice showed a similar thing.

Even so, the researchers said that an alternative pathway has largely been ignored. As a result, scientists have made very little progress in defining the molecular pathways and players involved.

Now, Brown and his colleagues offer new evidence that helps support and clarify this alternate path for cholesterol. They report that mice made unable to secrete cholesterol into bile through genetic manipulation or surgery still lose cholesterol through the feces at a normal rate. Macrophages in those animals also continued to take up cholesterol from blood vessels.

The researchers believe that alternate path delivers cholesterol from the liver to the intestine directly through the bloodstream.

"The classic view of reverse cholesterol transport involved the delivery of peripheral cholesterol via HDL to the liver for secretion into bile," the researchers wrote. "In parallel, we believe that the liver also plays a gatekeeper role for nonbiliary fecal sterol loss by repackaging peripheral cholesterol into nascent plasma lipoproteins that are destined for subsequent intestinal delivery."

For the purposes of cholesterol-lowering drug discovery, it may prove fruitful to consider those two pathways as "separate and complementary," Brown said.

There is some reason to think that drugs aimed to increase cholesterol loss without relying on bile might come with fewer side effects. That's because an excess of cholesterol in bile can lead to gallstones.

"You don't necessarily want to increase cholesterol in the bile," Brown said. And now it seems, there might be a way to get rid of cholesterol without having to.

Source: EurekAlert
 
 
Motivation doesn't have to be conscious; your brain can decide how much it wants something without input from your conscious mind. Now a new study shows that both halves of your brain don't even have to agree. Motivation can happen in one side of the brain at a time.

Psychologists used to think that motivation was a conscious process. You know you want something, so you try to get it. But a few years ago, Mathias Pessiglione, of the Brain & Spine Institute in Paris, and his colleagues showed that motivation could be subconscious; when people saw subliminal pictures of a reward, even if they didn't know what they'd seen, they would try harder for a bigger reward. In the earlier study, volunteers were shown pictures of either a one-euro coin or a one-cent coin for a tiny fraction of a second. Then they were told to squeeze a pressure-sensing handgrip; the harder they squeezed it, the more of the coin they would get. The image was subliminal, so volunteers didn't know how big a coin they were squeezing for, but they would still squeeze harder for one euro than one cent. That result showed that motivation didn't have to be conscious.

For the new study, in Psychological Science, a journal of the Association for Psychological Science, Pessiglione and his colleagues Liane Schmidt, Stefano Palminteri, and Gilles Lafargue wanted to know if they could dig even farther down and show that one side of the brain could be motivated at a time. The test started with having the subject focus on a cross in the middle of the computer screen. Then the motivational coin – one euro or one cent – was shown on one side of the visual field. People were only subliminally motivated when the coin appeared on the same side of the visual field as the squeezing hand. For example, if the coin was on the right and they were squeezing with the right hand, they would squeeze harder for a euro than for a cent. But if the subliminal coin appeared on the left and they were squeezing on the right, they wouldn't squeeze any harder for a euro.

The research shows that it's possible for only one side of the brain, and thus one side of the body, to be motivated at a time, says Pessiglione. "It changes the conception we have about motivation. It's a weird idea, that your left hand, for instance, could be more motivated than your right hand." He says this basic research helps scientists understand how the two sides of the brain get along to drive our behavior.

Resource: www.psychologicalscience.org
 
 
Los Angeles, CA (June 14, 2010) Apple juice can be a useful supplement for calming the declining moods that are part of the normal progression of moderate-to-severe Alzheimer's Disease (AD), according to a study in American Journal of Alzheimer's Disease and Other Dementias (AJADD), published by SAGE.

In the AJADD study, after institutionalized AD patients consumed two 4-oz glasses of apple juice a day for a month, their caregivers reported no change in the patients' Dementia Rating Scale or their day-to-day abilities. What did change, however, was the behavioral and psychotic symptoms associated with their dementia (as quantified by the Neuropsychiatric Inventory), with approximately 27% improvement, mostly in the areas related to anxiety, agitation, and delusion.

Alzheimer's disease is characterized by a progressive loss of memory, decline in cognitive function, behavioral changes, and the loss in ability to do daily activities, all of which causes a significant caregiver burden and increased health care costs. While pharmacological treatments can provide temporary reduction in AD symptoms, they're costly and cannot prevent the ultimate decline in cognitive and behavioral function. That's why the authors considered it important to discover any possible nutritional interventions.

"The modest, but statistically significant, impact of apple juice on the behavioral and psychological symptoms of dementia in this study adds to the body of evidence supporting the usefulness of nutritional approaches, including fruit and vegetable juices, in delaying the onset and progression of Alzheimer's Disease, even in the face of known genetic risk factors," write the authors, Ruth Remington, RN, PhD, Amy Chan, PhD, Alicia Lepore, MS, Elizabeth Kotlya, MS, and Thomas B. Shea, PhD, "As in prior studies with vitamin supplements, it indicates that nutritional supplementation can be effective even during the late stages of AD."

Resource: EurekAlert
 
 
TAU study confirms early detection tests are key for diabetic women

Type 2 adult-onset diabetes causes insulin-like hormones to circulate through the body. A new study finds this has a surprisingly positive effect on reducing the rate of prostate cancer in men, but is bad news for women: Type 2 diabetes may double the risk of female genital and other cancers.

The new study, led by Dr. Gabriel Chodickand Dr. Varda Shalev of Tel Aviv University's Department of Epidemiology and Preventive Medicine at the Sackler Faculty of Medicine, is not the first to report such a risk. But it's one of the largest to confirm these findings, and it's the first to determine the statistical differences in cancer risks for men and women.

Recently published in the journal Cancer Causes & Control, the Tel Aviv University study looked at 16,721 diabetics, differentiating between men and women and defining the relative cancer risks for each group. When the study began in 2000, none of the subjects had a history of cancer. Over the following eight years, the researchers documented 1,639 cases of different cancers among people with diabetes, and compared them to occurrences of the same cancers in the healthy non-diabetic population — a sample of 83,874 people.

Good news for men, bad news for women

"For men, this study is good news," says Dr. Chodick. The study demonstrates that diabetes actually appears to have a preventative effect on conditions like prostate cancer, reducing the risk of cancers associated with insulin-like hormones by a whopping 47 percent. But the opposite is true for women, he continues. "The interaction of diabetes and female hormones appears to exaggerate the risk, and make certain organs like the uterus and ovaries more receptive to certain kinds of cancer."

While the news is something for female diabetics and their practitioners to take into consideration, there's no cause for panic, Dr. Chodick notes. Although colon and ovarian cancers are serious, their overall risk in women is generally quite low. However, he stresses that physicians should take the research into account when assessing the long-term health histories of their patients.

An ounce of prevention still the best medicine

Dr. Chodick encourages diabetic women to be screened for colon cancer earlier and more often than those in the general population. As the occurrence of diabetes in America rises, primarily brought on by an unhealthy lifestyle, such screenings can save lives.

Type 2 diabetes, which is characterized by high blood glucose and an insulin deficiency, normally occurs in adulthood, and it can often be managed with a healthy diet, exercise, and oral medications. It affects more than 10% of all women in America over the age of 20, according to the American Diabetes Association.

Of course, wherever possible, the best approach is to avoid diabetes entirely, says Dr. Chodick, with the help of a high-fiber, low-carbohydrate diet combined with exercise.

Resource: www.aftau.org
 
 
Indiana U. research at the American College of Sports Medicine annual meeting

A twice weekly hip strengthening regimen performed for six weeks proved surprisingly effective at reducing -- and in some cases eliminating -- knee pain referred to as patellofemoral pain (PFP) in female runners.

The study by Tracy Dierks, assistant professor in the Department of Physical Therapy at Indiana University-Purdue University Indianapolis, was based on the theory that stronger hips would correct running form errors that contribute to PFP, even though study participants were given no instruction in gait training. The study used a pain scale of 0 to 10, with 3 representing the onset of pain and 7 representing very strong pain -- the point at which the runners normally stop running because the pain is too great. The injured runners began the six-week trial registering pain of 7 when they ran on a treadmill and finished the study period registering pain levels of 2 or lower; i.e. no onset of pain.

"I wasn't expecting such huge reductions, to be honest," Dierks said. "We've had a couple of runners who have been at level 2, but the overwhelming majority have been a 2 or below."

PFP, one of the most common running injuries, is caused when the thigh bone rubs against the back of the knee cap. Runners with PFP typically do not feel pain when they begin running, but once the pain begins, it gets increasingly worse. Once they stop running, the pain goes away almost immediately. Dierks said studies indicate PFP essentially wears away cartilage and can have the same effect as osteoarthritis. His study participants showed many of the classic signs of PFP, the most prominent being their knees collapsing inward when running or doing a squat exercise move.

The pilot study thus far involved five runners and a control group that comprised another four runners. Hip strength measurements were taken before and after the runners in the control group maintained their normal running schedule for six weeks. Hip strength measurements were taken for all of the runners before and after the next six-week period in which they all performed the hip-strengthening exercises. The exercises, performed twice a week for around 30 to 45 minutes, involved single-leg squats and exercises with a resistance band, all exercises that can be performed at home. This study is part of an ongoing study involving hip exercises and PFP pain, with 11 runners successfully using the intervention. Dierks said he plans to seek funding to test the exercises on a larger group of runners.

Earlier research had focused on the feet as a possible root of PFP, with studies only recently looking more closely at the hips. Dierks said studies have found an association between PFP in women and weak hips, but his study is the first to test a possible treatment. He noted that PFP is considered "multi-factorial," so his study is examining one of several possible causes of the pain.

Source: EurekAlert
 
 
Over-the-counter supplements can cause hypertension and kidney failure

Negative health effects linked to taking too much supplemental calcium are on the rise, according to a commentary appearing in an upcoming issue of the Journal of the American Society Nephrology (JASN). The incidence of the so-called milk-alkali or calcium-alkali syndrome is growing in large part because of widespread use of over-the-counter calcium and vitamin D supplements.

The milk-alkali syndrome arose in the early 1900s when patients ingested abundant amounts of milk and antacids to control their ulcers. This practice increased individuals' risk of developing dangerously high levels of calcium in the blood, which could cause high blood pressure and even kidney failure. The incidence of the milk-alkali syndrome declined when newer ulcer medications became available, but it appears to be on the rise again thanks to increased use of over-the-counter calcium and vitamin D supplements used mainly as preventive and treatment measures for osteoporosis. In many cases, patients with the syndrome require hospitalization.

Stanley Goldfarb, MD and Ami Patel, MD (University of Pennsylvania School of Medicine) recommend changing the name of the milk-alkali syndrome to the calcium-alkali syndrome because the condition is now associated with a large intake of calcium, not milk. Postmenopausal women, pregnant women, transplant recipients, patients with bulimia, and individuals who are on dialysis have the highest risks of developing the calcium-alkali syndrome due to various physiological reasons.

According to the authors, the obvious preventive strategy against the calcium-alkali syndrome is to limit the intake of calcium to no more than 1.2 to 1.5 grams per day. "Calcium supplements taken in the recommended amounts are not only safe but are quite beneficial. Taken to excess is the problem," said Dr. Goldfarb. "Even at the recommended dose, careful monitoring of any medication is wise and yearly determinations of blood calcium levels for those patients taking calcium supplements or vitamin D is a wise approach," he added.

Source: EurekAlert
 
 
USF researchers: Early clamping may interrupt humankind's first 'natural stem cell transplant'

Tampa, Fla. (May 24, 2010) – The timing of umbilical cord clamping at birth should be delayed just a few minutes longer, suggest researchers at the University of South Florida's Center of Excellence for Aging and Brain Repair.

Delaying clamping the umbilical cord for a slightly longer period of time allows more umbilical cord blood volume to transfer from mother to infant and, with that critical period extended, many good physiological "gifts" are transferred through 'nature's first stem cell transplant' occurring at birth.

The USF review is published in a recent issue of the Journal of Cellular and Molecular Medicine (14:3).

"Several clinical studies have shown that delaying clamping the umbilical cord not only allows more blood to be transferred but helps prevent anemia as well," said the paper's lead author Dr. Paul Sanberg, director of the Center. "Cord blood also contains many valuable stem cells, making this transfer of stem cells a process that might be considered 'the original stem cell transplant'."

At birth, the placenta and umbilical cord start contracting and pumping blood toward the newborn. After the blood equilibrates, the cord's pulse ceases and blood flow from mother to newborn stops. In recent Western medical practice, early clamping -- from 30 seconds to one minute after birth -- remains the most common practice among obstetricians and midwives, perhaps because the benefits of delaying clamping have not been clear. However, waiting for more than a minute, or until the cord stops pulsating, may be beneficial, the authors said.

Birthing methods have also changed over the last century. Throughout human history and currently in cultures and areas where delivering mothers squat to deliver, gravity helps speed the stem cell transfer. Today, the cord may be clamped early for a number of reasons, including the medical resuscitation and stabilizing of infants or the notion that delaying clamping might lead to adverse effects or, more recently, to quickly facilitate umbilical cord banking.

According to study co-author Dr. Dong-Hyuk Park, the relationship between cord clamping time and the transfer of stem cells needs to be understood through the early weeks of the perinatal period and the process of 'hematopoiesis,' the formation of blood cells that begins as early as two weeks into pregnancy. A transfer of pluripotent stems cells continues throughout pregnancy, however, and for a time through the umbilical cord following delivery.

"Several randomized, controlled trials, systematic reviews and meta-analyses have compared the effects of late versus early cord clamping," said Dr. Park. "In pre-term infants, delaying clamping the cord for at least 30 seconds reduced incidences of intraventricular hemorrhage, late on-set sepsis, anemia, and decreased the need for blood transfusions."

Another potential benefit of delayed cord clamping is to ensure that the baby can receive the complete retinue of clotting factors.

Yet, there is debate and disagreement on early versus later clamping. The side favoring delayed clamping, the authors noted, cite the value of the infant's receiving umbilical cord blood (UCB)-derived stem cells, known to be pluripotent.

"The virtue of the unique and immature features of cord blood, including their ability to differentiate, are well known," added Dr. Sanberg.

The researchers concluded that many common disorders in newborns related to the immaturity of organ systems may receive benefits from delayed clamping. These may include: respiratory distress; anemia; sepsis; intraventricular haemorrhage; and periventricular leukomalacia. They also speculate that other health problems, such as chronic lung disease, prematurity apneas and retinopathy of prematurity, may also be affected by a delay in cord blood clamping.

"There remains no consensus among scientists and clinicians on cord clamping and proper cord blood collection," concluded co-author and obstetrician Dr. Stephen Klasko, senior vice president of USF Health and dean of the USF College of Medicine. "The most important thing is to avoid losing valuable stems cells during and just after delivery."

The authors agreed that delaying cord clamping should appropriately be delayed for pre-term babies and babies born where there is no effort to bank umbilical cords, and for babies born where there is limited access to health care and where nutrition may be poor.

Resource: Eurekalert