Stem Cells Transplanted From Marrow Into Heart May Improve Heart's Performance

The Cardiology department and the Area of Cell Therapy of Cordoba hospital Reina Sofia are carrying out clinical tests with patients who have suffered from a severe heart attack. With the implantation of the patient's stem cells, the heart regenerates thus improving its wall motion, that is, its cardiac performance. Indeed for the last four years, the Area of Cell Therapy of Cordoba hospital, led by haematologist Dr. Concha Herrera, has been implementing a therapy program with adult stem cells in patients with heart-related problems. However, this therapy is not a service the hospital offers yet. More specifically, at the end of 2007 the hospital ended a clinical test with patients who had suffered a severe myocardial infarction, that is, an obstruction of one of the main coronary arteries that stops the blood pump to the heart.

The test consisted of treating 30 people split into three groups of ten each at random. The first group was the control group, where patients received standard treatment for acute myocardial infarction; the second group was treated with stem cells directly implanted into the coronary artery affected using a catheterization; the third group was treated with a medicine called G-CSF, which makes cells move from the marrow to the blood, so that they get to the heart in a natural way, without having to do so through a catheter.

At the end of the test, the results revealed that the two groups treated without cells improved slightly, whereas patients transplanted with stem cells through the coronary arteries (vessels which bring the blood to the Herat muscle) did improve their ventricular function much more. This was interpreted as a significant decrease of the cardiac failure symptoms such as pain, fatigue and breathlessness when making small efforts.

Moreover, with this process it is possible to prevent some acute arrhythmias (change or irregularity in the rhythm of the heartbeat), which in many cases could result in the patient's death. ‘However, it does not prevent a future heart attack', Dr. Herrera assures.

In short, the stem cells transplanted from the marrow into the heart muscle have a double function: on the one hand they regenerate the heart cells, the cardiomiocites. In addition to this, they segregate a series of proangiogenic factors that produce blood vessels (angiogenesis) and can also produce the recruitment of stem cells that are in the myocardium itself.

The Are of Cell Therapy, led by Dr. Herrera, is currently developing other trials in the cardiology department, both in patients with acute myocardial infarction (35) and in those with chronic ischemic cardiopathy, due to one or more heart attacks suffered in the past, either months or years ago (20 patients). Moreover, in the last few months a new clinical trial has been started - so far in eight patients- who suffer from a disease called Dilated Myocardiopathy. The origin of this disease is unknown but it causes a very severe cardiac failure which conditions the need for a heart transplant in many cases. So far, ‘the results in these first patients are very satisfactory'.

'We will start shortly a clinical test where we will use stem cells from the marrow in diabetic patients who have the artery taking the blood to the lower limbs blocked. This pathology, called peripheral ischemia, can result in a limb being amputated'.

This work, published in Revista Española de Cardiología journal, has been awarded with a prize by the Sociedad Española de Cardiología.

Stronger Material For Filling Dental Cavities Has Ingredients From Human Body

Scientists in Canada and China are reporting development of a new dental filling material that substitutes natural ingredients from the human body for controversial ingredients in existing "composite," or plastic, fillings. The new material appears stronger and longer lasting as well, with the potential for reducing painful filling cracks and emergency visits to the dentist, the scientists say. Julian X.X. Zhu and colleagues point out that dentists increasingly are using white fillings made from plastic, rather than "silver" dental fillings. Those traditional fillings contain mercury, which has raised health concerns among some consumers and environmental issues in its production. However, many plastic fillings contain controversial ingredients (such as BisGMA) linked to premature cracking of fillings and slowly release bisphenol A, a substance considered as potentially toxic to humans and to the environment.

The scientists developed a dental composite that does not contain these ingredients. Instead, it uses "bile acids," natural substances produced by the liver and stored in the gallbladder that help digest fats. The researchers showed in laboratory studies that the bile acid-derived resins form a hard, durable plastic that resists cracking better than existing composites.

Brain-behavior Disconnect In Cocaine Addiction

Parts of the brain involved in monitoring behaviors and emotions show different levels of activity in cocaine users relative to non-drug users, even when both groups perform equally well on a psychological test. These results — from a brain-imaging study conducted at the U.S. Department of Energy's Brookhaven National Laboratory and published online the week of May 25, 2009, by the Proceedings of the National Academy of Sciences — suggest that such impairments may underlie addictive vulnerability, and that treatments aimed at improving these functions could help addicted individuals resist drugs."Many studies have found decreased brain activity in drug-addicted individuals relative to healthy control subjects during psychological tests," said lead author Rita Goldstein, a psychologist at Brookhaven Lab. "But it's never been clear if these differences were due to varying levels of interest or ability between the two groups. This is the first study to look at two groups matched for performance and interest — and we still see dramatic differences in the brain regions that play a very significant role in the ability to monitor behavior and regulate emotion, which are both important to resisting drug use.

"Whether these brain differences are an underlying cause or a consequence of addiction, the brain regions involved should be considered targets for new kinds of treatments aimed at improving function and self-regulatory control," Goldstein said.

The researchers studied 17 active cocaine users and 17 demographically matched healthy control subjects. Both groups were trained to push one of four colored buttons corresponding to the color of type used to present words that were either related to drug use (e.g., crack, addict) or neutral household terms. Subjects were given monetary rewards for fast, accurate performance — up to 50 cents for each correct answer on some tests, for a maximum of $75.

After training, both groups performed equally well on this same test while lying in a magnetic resonance imaging (MRI) scanner, with performance improving when they knew they'd be earning the highest monetary reward. During the tests, the scientists used functional MRI (fMRI) to indirectly measure the amount of oxygen being used by specific regions of the brain, as an indicator of brain activity in those regions.

There were three main differences between the cocaine-addicted subjects and the healthy controls:

* The cocaine users had reduced activity in a portion of the anterior cingulate cortex that usually becomes more active (compared to a passive baseline) when monitoring behavior. Activity levels were lowest during the least "interesting," or salient, version of the test — when there was no monetary reward and the words shown were neutral household terms. Within the cocaine-user group, activity levels were lowest in the people who had used cocaine most frequently in the 30 days prior to the test.
* The cocaine users also had reduced activity in another part of the anterior cingulate cortex that usually becomes less active (compared to a passive baseline) when someone is successfully suppressing emotional feelings. Within the cocaine-user group, activity levels during the high-salience version of the test — when each fast, correct answer was rewarded with 50 cents and the words presented were drug-related — were lowest in the people who were most successful in suppressing the task-induced craving. In healthy controls, who did not report craving, activation in this region was not significantly different from baseline.
* The functions within the behavior-monitoring and emotion-monitoring brain regions were interconnected in the healthy control subjects but not in the addicted individuals. In all, these group differences in brain function and interconnectivity were quite robust and all the more meaningful in that there were no differences between the groups in performance on or interest ratings for the task.

"When you really have to suppress a powerful negative emotion, like sadness, anxiety or drug craving, activity in this brain region is supposed to decrease, possibly to tune out the background 'noise' of these emotions so you can focus on the task at hand," Goldstein said.

"Our results show that activity in this region indeed went down in the drug-using group, suggesting they were actively trying to suppress craving. Indeed subjects who reported the highest levels of task-induced craving were the least able to suppress activity in this particular brain region.

"This could be because these drug users were still being distracted by background 'noise' stimuli, like memories of having taken drugs or anticipation of further use," Goldstein said.

"This work gives us some clues as to what happens when drug users are unable to suppress craving — and how that might work together with a decreased ability to monitor behavior, even during neutral, non-emotional situations, to make some people more vulnerable to taking drugs," Goldstein said.

The findings point to the importance of improving activity in the behavior-monitoring brain region, possibly by using behavioral and pharmacological approaches to increase motivation and top-down monitoring. Treatments aimed at strengthening activity in the emotion-monitoring brain region may further help addicted individuals regain self-control, especially during hard to suppress highly emotional situations (e.g., during craving). Treatments aimed at strengthening the interconnectivity between these brain regions may decrease impulsivity.

This study was supported by grants from the National Institute on Drug Abuse and the General Clinical Research Center of Stony Brook University.