Researchers investigate more accurate method to predict preeclampsia risk

Researchers have found a new marker that predicts the risk of developing preeclampsia during pregnancy. According to these findings, women who have a reduced number of capillaries under the skin during pregnancy are more likely to develop this complication that can be life-threatening. It seems that measuring skin capillary density is a better predictor than Doppler ultrasound to identify the risk of preeclampsia. The results of this study are presented at the American College of Cardiology’s 62nd Annual Scientific Session.

British researchers conducted a study to determine the number of capillaries from 305 patients in the first trimester of pregnancy. A similar study was conducted in 2001 by the same research team but included women with preeclampsia in late pregnancy. Then it was noted that women who had fewer capillaries had a higher risk of preeclampsia. It was found that women who developed preeclampsia later in pregnancy have a decreased number of capillaries since 20 weeks of pregnancy.

The study showed that test accuracy is 87% which is a significant improvement over the current screening test. Furthermore it seems that repeating the test at 27 weeks of pregnancy, the  risk of preeclampsia is identified in 75% of cases and the risk of false positive results is much lower. Tarek Antonios, MD, St. George’s, University of London, and the study’s lead investigator, said that the predictive value of the test far exceeds that of Doppler ultrasound, which is currently used to detect preeclampsia. He added that if further studies confirm the results in the future, this new technique could change clinical practice and thus thousands of women could benefit from early medical care to prevent the newborns from dying because of the disease. “We found that if we examine the microcirculation and measure the changes in capillaries we can predict preeclampsia in a more accurate way and this is exciting news,” Dr. Antonios said.

Preeclampsia is a life-threatening obstetrical condition that occurs after 20 weeks and is manifested by hypertension, proteinuria (protein in urine) and edema of lower limbs. Preeclampsia may leads to eclampsia, which is a condition that, in addition to the ones listed, also includes seizures. Nobody knows exactly why it occurs, but there are several assumptions. There seems to be some abnormal blood vessels in the placenta that causes vasoconstriction and thus on the one hand hypertension occurs, and on the other hand there is a restriction of blood flow to the fetus. Preeclampsia is diagnosed at present with Doppler ultrasound ( which investigates uterine artery), but it appears that the accuracy of the  technique is 50%.

Autologous cell-based therapies for Duchenne muscular dystrophy is under investigation

Researchers at the University of Minnesota’s Lillehei Heart Institute are about to discover a cure for Duchenne muscular dystrophy with the use of stem cells. The results of serial experiments on rats conducted so far are promising and it is likely that in the future this debilitating, lethal, muscle disease be cured.

First, scientists have turned skin cells into pluripotent cells, that is cells that can differentiate into any cell in the body. Researchers create pluripotent cells from the skin of rats carrying mutations in the dystrophin and utrophin gene to create a model as close to Duchenne muscular dystrophy in humans. The resulting disease in rats practically mimicked muscle dystrophy in humans. The next step was to send a gene called “micro-utrophin” to the pluripotent cells that the researchers intend to differentiate. They have done this with ‘Sleeping Beauty transposon’, which is a tool for genetic correction, which means it can introduce certain genes in the human genome.

stem cell

These two components, dystrophin and utrophin, are similar in many ways because both have a role in supporting muscle fibers and in muscle force generation. In Duchenne muscular dystrophy, which is a genetic disease, dystrophin is absent so the body gradually becomes weaker as the muscles begin to atrophy. Because it is a genetic disorder characterized by a mutation in the dystrophin gene, Duchenne muscular dystrophy is incurable and treatment is only supportive. However, the researchers found that utrophin is active and functional in these patients and that can take dystrophin function.

The next experiment was conducted by Rita Perlingeiro, Ph.D. who generated skeletal muscle stem cells from pluripotent cells. The experiment consisted in stimulating muscle cells to become pluripotent cells with a protein called Pax3. The Pax3-induced muscle stem cells were then transplanted into the same rats from which were taken the  pluripotent stem cells. In this way they were created muscle-generating stem cells without the body to trigger an immune reaction.

Perlingeiro, the Lillehei Endowed Scholar within the Lillehei Heart Institute and an associate professor in the University of Minnesota Medical School, said she is excited to see that the newly formed myofibers expressed correction biomarkers including utrophin. She added that it is very interesting to find out if these cells, after transplantation, would self-renew and would give rise to new muscle stem cells in addition to the new muscle fibers. Antonio Filareto, Ph.D., a postdoctoral fellow in Perlingeiro’s laboratory and the lead author on the study, said: “Utilizing corrected induced pluripotent stem cells to target this specific genetic disease proved effective in restoring function.”

Lymphoma Cells Shown to be Destroyed by Experimental Drug Combination

A new laboratory experiment reveals that if the drugs ibrutinib and bortezomib (two experimental drugs used to treat different types of cancer) are combined, it could lead to a new, potentially potent, therapy for numerous types of blood cancer. The current targets for this novel therapy scheme are DLBCL (diffuse large B–cell lymphoma) and MCL (mantle cell lymphoma). The study was recently published in the journal British Journal of Hematology.

According to the reports, the experimental combination between the two drugs was able to kill cancerous cells by inducing apoptosis. Furthermore, researchers reveal that the combination wasn’t as toxic on normal cells, when compared to other marketed drugs. The first drug, ibrutinib, has been recently developed as an inhibitor of the B-cell receptor complex. The BCR complex plays a major role in the survival of malignant B-cells. So far, the results of initial trials with ibrutinib show promise for patients suffering from diffuse large B-cell lymphoma, mantle cell lymphoma and chronic lymphocytic leukemia. The combination proved to be a very potent against lymphoma cells that developed resistance against bortezomib.

bortezomib

“Bortezomib is currently used to treat MCL and multiple myeloma, but, unfortunately, many patients develop resistance to the drug”, said the main author of the study, Steven Grant, whilst adding that such a potent drug is required in order to address the need for effective medication for patients suffering from these rare medical conditions. The research team conducted their tests on specially cultivated DLBCL and MCL cells and discovered that ibrutinib is responsible for blocking certain molecular pathways that are used by the cancerous cells. When combined with bortezomib, an elevated level of synergy was observed. The synergy between the two drugs is responsible for inducing apoptosis in the cancerous cells. According to the researchers, some of the pathways blocked by ibrutinib are related to the pathways that are used by cancerous cells to survive the action of bortezomib.

Further studies reveal that the pathways blocked by the action of ibrutinib are NF-?B, ERK1/2 and AKT. These three pathways are responsible for the cellular ability to adapt to various harmful environmental stimuli. Precedent studies have shown that these three pathways are responsible for the biological processes that are needed for the survival and proliferation on cancerous cells. The research team managed to show that a chemical such as ibrutinib is able to aid the action of a proteasome inhibitors, thus making it a potential combination for new, future cancer therapies.

The Amygdala Isn’t Always Linked to Fear

According to a new paper published in the journal Natural Neuroscience, researchers discovered that patients with deficient or damaged amygdalas can experience internal fear, contrary to previous knowledge. The research team reports that they managed to induce internal fear into three volunteering women, in spite of the fact that they were all suffering from a degenerative disease which caused them to be immune to fear.

It took the medical researchers several years in order to reach a consensus regarding the connection between the human brain and the fear sensation. The majority of researchers agreed that the amygdala was the primary region of the brain that was involved in the fear sensation. Without the amygdala, scientists concluded that humans would not be able to sense fear. However, this new study reveals that fact that this theory might not be correct due to the fact that three women who participated in the study were able to sense internal fear despite the fact that they suffered from a genetic disease responsible for the degeneration of the amygdala.

fear

According to the research team, all three women suffer from a genetic condition called Urbach-Wiethe disease. This disease causes both dermatological and neurological changes. About 50“75% of the patients that are diagnosed with Urbach“Wiethe disease suffer from bilateral symmetrical calcifications of the amygdala and the periamygdaloid gyri. Two of the three patients are identical twins. All three women volunteered to undergo thorough tests over a span of multiple years. The various tests included both laboratory tests (which included various experiments with scary movies, spiders, snakes, etc.) and real life threats. However, these types of threats that are capable of inducing fear are known as external threats.

The current study tried to determine whether internal threats can cause fear in these three patients. The internal type of threats include suffocating and even heart attacks. In order to simulate suffocation, patients were put to breathe through a mask which delivered air with high levels of carbon dioxide. This causes an abnormal rise in the carbon dioxide levels from the blood, thus causing panic in some patients. All three patients experienced a sense of fear during the examination, reporting that they felt a sensation of panic they hadn’t felt in a very long time.

Researchers concluded that despite the fact that all three women had a dysfunctional amygdala, they were able to fear internal fear, even though external threats had no effect on them. This discovery led scientists to suggest that perhaps other parts of the brain are also connected to the expression of fear. Another suggestion was that the amygdala only plays a role in the expression of fear caused by external threats.

New Information on Alzheimer’s Disease Being Linked to Type 2 Diabetes

A new study that will be presented at the 57th Annual Meeting of the BPS (Biophysical Society) at the beginning of February 2013 reveals a novel approach by a team of scientists from Israel towards a drug that could be capable of lowering the risk of diabetes patients to develop Alzheimer’s disease. The researchers are trying to identify the molecular basis for the design of such drug.

A precedent study shows that patients suffering from type 2 diabetes are more predisposed to the development of Alzheimer’s disease than patients without diabetes. Their risk is almost doubled. According to researchers, these two diseases are related because they both form a type of peptide deposits that either aggregate or for clusters together. Peptides are short chains of amino acid monomers that are linked together by amide (peptide) bonds. These bonds are formed when the amino group of one amino acid reacts with the carboxyl group of another. Compared to proteins, peptides are smaller in size, containing, on average, 50 amino acids or less. The peptide formed in Alzheimer’s disease is called amyloid beta and is foun the plaques formed in the brain’s neurons. The second type of peptide, called amylin, is linked to type 2 diabetes and can be found in the pancreas and in the brain. A couple of years ago, scientists discovered that both peptide molecules are found in the in the pancreas of patients suffering from diabetes. Furthermore, the presence of these peptides has been linked in both diseases to their progression rate.

Neuron

Assistant Professor Yifat Miller, from the Ben-Gurion University in Israel, with the help of his research team, managed to examine the structure of these molecules and they way they interact. His study reveals the fact that interactions between these two molecules are responsible for the self-assembly of peptides which will further lead to the aggregation of proteins. It is the first paper to have shown this connection.

“By identifying the specific ‘hot regions’ of these peptides that strongly interact with each other, our study may provide insight into the link between type 2 diabetes and Alzheimer’s disease”, said Yifat Miller, whilst adding that “We believe that preventing these interactions by developing a drug will decrease the risk that type 2 diabetes patients face of developing Alzheimer’s disease later life”. The research team from Israel collaborated with Aphrodite Kapurnitou from the Technische Universität München, from Germany. Professor Kapurnitou is responsible for the experimental studies of the peptide interactions.

Obesity and Type 2 Diabetes

According to a study published in Nature Medicine, researchers from UT Southwestern Medical Center have made new discoveries about the link between obesity and diabetes. The team led by Dr. Philipp Scherer, director of the Touchstone Center for Diabetes Research at UT Southwestern, found that MitoNEET protein, that is a key component of a cell’s mitochondrion, is involved in the pathology of obesity.

The body stores the excess energy in adipose tissue and these deposits may disappear if one exercise and eat healthy. Now researchers have shown that by manipulating the components of mitochondria, can influence storing excess calories into “good” locations.

Obesity and Diabetes

Experiments conducted on laboratory animals have shown that when the MitoNEET is elevated in rodents, the deposition of fat in the tissue adipos increases. Researchers showed that this mechanism can result in morbid obesity in rodents but this metabolic imbalance  does not lead to diabetes mellitus. In other words, rodents , even obese, they were healthy. However, if MitoNEET protein level is low, the rats were lean but unhealthy as diabetes began to settle. Obese mice used in the study had about 120 to 130 grams (4.23 to 4.58 ounces), while  healthy mice does not exceed 25 to 30 grams.

Dr. Scherer, senior author of the three-year study and Professor of Internal Medicine and Cell Biology at UTSW, said that handling some components of mitochondria can be extremely helpful in manipulating adipose tissue and the use of fat. He added that it was underestimated the importance of mitochondrial pathway in the metabolism and weight loss management.

The researchers mentioned that the study does not promotes the idea that obesity is a good thing but it shows the importance of mitochondrial pathways and the link between diabetes and obesity. Dr. Christine Kusminski, a postdoctoral researcher in Internal Medicine who served as the study’s first author, said she hoped the further understanding of the mechanisms underlying obesity and diabetes can help to develop targeted therapies in the future.

Obesity and diabetes are strongly interconnetected. It seems that obesity contributes to the onset of diabetes by several mechanisms: excess free fatty acids, leptin, adiponectin, inflammatory cytokines (interleukin-1, interleukin-6, TNF-alpha), etc.. In addition, studies have shown that diabetes is 4-5 times more common in obese people aged between 20 and 40 years, and that there is a high risk of cardiovascular disease among these individuals. Obesity and diabetes are among the criteria of the metabolic syndrome, along with hypertension, high triglycerides, low HDL cholesterol.

A new pharmacotherapy for Cocaine Addiction

New FDA approved treatment is now available for cocaine addiction. According to a study published in Biological Psychiatry, researchers at Columbia University and New York State Psychiatric Institute, are confident that the new treatment regimen that includes amphetamine and topiramate, may help cocaine addicts. Cocaine addiction refers to the psychological need to consume the drug. Although initially is associated with pleasure and euphoria, regular consumption of cocaine has devastating effects on the body. Cocaine addicts have behavioral disorders, tachycardia, hypertension, paranoia, insomnia. Finally, there is psychological dependence and the entire behavior will focus on drug procurement. There are a number of symptoms for those  who seek treatment also, such as depression, fatigue, irritability, insomnia, all part of the abstinence syndrome.

Cocaine

Over time many pharmacotherapies have been tested, but none seems to have good results. Cocaine addiction likely require a multidisciplinary approach and a combination of several drugs as it is in cancer, heart disease or AIDS treatment.
The researchers assumed that stimulants like amphetamine, methylphenidate, and modafinil, are able to reduce the reward and cognitive deficits that occur in addiction. This assumption confirms the concept of self medication which is used in the treatment of addiction and which says that there can be used drugs to treat addiction effects.

Topiramate, included in the new drug regimen, is considered the most effective in the treatment of alcohol dependence. Originally used as an anticonvulsant (Lennox Gastaut syndrome), topiramate has been investigated and used for other conditions such as drug addiction, alcohol, obesity, migraine, binge eating. It is not clear how this drug works in treating alcohol dependence, but experiments in laboratory animals gave positive results. Recent studies have shown that it can reduce the intensity of methamphetamine use.

Researchers have mixed amphetamine salts and topiramate for treating cocaine addiction. Then they tested to see if this combination is effective in adults who wanted to cure their drug addiction. A double-bind study was conducted in which participants received either the combination treatment or a placebo for twelve weeks. It was found that this combination treatment had the greatest effect on those who used to consume large doses of cocaine. The researchers noted that amphetamine and topiramate combination helped the patients to get three weeks of continuous abstinence from cocaine. Although the results of this study were encouraging, researchers now believe that this treatment regimen needs to be tested in a larger, multicenter clinical trial.

New enzyme contributes to Preeclampsia

Preeclampsia is one of the most feared complications that can occur during pregnancy and can affect both the mother and child ‘s health. Although many studies have been performed on this condition, the  causes of this disease could not be clearly identified. But now researchers at the Experimental and Clinical Research Center (ECRC) of the Max Delbrück Center have made new discoveries on the triggers of preeclampsia.
Preeclampsia consists of hypertension (that is blood pressure values above 140/90 mmHg) and proteinuria, which means proteins in the urine. Although this condition can be controlled with antihypertensive medications, there are emergency situations where the only solution is Cesarean section.

Preeclampsia Treatment

The researchers found that an enzyme called CYP2J2 is high in women with preeclampsia and that this enzyme is the basis of this condition. This idea is supported by the fact that experiments on animals have shown that by inhibiting this enzyme, preeclampsia symptoms are relieved.
To reach these conclusions, the researchers conducted a study that included 48 women: 25 women diagnosed with preeclampsia and 23 healthy women from Finland, Norway, Austria, and the U.S.

After approximately 40,000 genes analyzed, it was found that expression of CYP2J2 enzyme is found in high levels in placental cells and the uterine lining (decidua) of women with preeclampsia. It seems that this enzyme is involved in the production of specific metabolites called EETs (epoxyeicosatrienoic acids), which leads to hypertension. In addition to hypertension, these metabolites play a role in inflammatory processes and vascular growth.

In addition, the team of researchers led by Dr. Herse  and Dr. Dechend found that the cells that produce this enzyme are the trophoblasts. Trophoblasts, fetal cells that migrate from the placenta in maternal decidua, contribute to the remodeling of spiral-arteries that nourish the fetus with nutrients. But if these trophoblasts are not well implanted into the decidua, then blood flow is disturbed and so preeclampsia occurs. According to the findings so far, EETs prevent normal implantation of  trophoblasts in decidua.

Previous studies done on rats have shown that in healthy pregnant mice, inhibiting the enzyme and the EET leads to hypertension and kidney failure. What is interesting is that in mice with preeclampsia, by inhibiting the same enzyme, there are adverse effects. In other words, CYP2J2 enzyme inhibition causes a  decrease in blood pressure. The explanation is that EETs are converted to other metabolites. Also an increasingly important role in this mechanism is played by TNF-alpha that promotes the production of CYP2J2 and EET in the placenta.

Study Reveals Connection Between Physical Activity and Longevivity

A new study led by researchers from the Brigham and Woman’s Hospital and the National Cancer Institute manages to quantify the years of life gained through different levels of physical activity. The study was conducted on various individuals, with different BMIs and lifestyles.

The study answers the question “How good is exercise for you?”. Precedent studies only show that there is a connection between physical activity and mortality. However, this is the first study to reveal the link between life expectancy and the level of physical activity. This new research collaboration manages to quantify the amount of life years gained through physical activity. The paper is published in the journal PLOS Medicine.

Physical Activity

According to Dr I-Min Lee, the senior author of the study, the study shows that 75 minutes of brisk walking every week can increase the life expectancy over 40 by almost 2 years. “Physical activity above this minimal level was associated with additional gains in longevity”, noted Dr Lee. In comparison, 450 minutes of brisk walking every week increases the life expectancy over 40 by almost 5 years. Researchers also studied the differences that appear between subjects of different BMI values. Data for the study was gathered from 6 prospective cohort studies, amassing over 650 thousand patients. Patients were followed over an average of 10 years. More than 80 thousand deaths were also analyzed during the study. Due to the large number of patients, researchers were able to analyze and estimate the increase in life expectancy based on each patients’ BMI and weekly physical activity.

According to the researchers, their findings show that the increase in life expectancy was seen in all patients, varying through different BMIs and different levels of physical activity. Patients who were doing physical activity comparable to 75 minutes of brisk walking per week were seen to have a decreased risk of mortality by almost 20%. The equivalent of 150 minutes of brisk walking per week was shown to increase life expectancy by almost 3.5 years. This amount of weekly physical activity is currently recommended by the Government.

Physical Activity

The benefits of weekly physical activity were seen in men and women, no matter the race. Notably, these benefits were also observed in normal, overweight and obese patients. However, the subjects which showed the highest benefits were those that were both physically active and had a normal weight. An increase in life expectancy of more than 7 years was seen in normal weight subjects which had an equivalent physical activity to 150 minutes of brisk walking per week.

“Our findings reinforce prevailing public health messages promoting both a physically active lifestyle and a normal body weight”, concluded Dr Steven C. Moore, the lead author of this study. According to the research team, their findings might convince inactive people to start being physically active, even if they wouldn’t start various weight control programs.

Study abstract here.