Daily Archives: January 13, 2017

Progesterone may be key to preventing recurrent miscarriage

For women who suffer multiple pregnancy losses in the first four to six weeks of gestation, the hormone progesterone could offer hope for a successful birth, according to a new study by Yale School of Medicine researchers and their colleagues at University of Illinois at Chicago.

The results are published in the current issue of Fertility Sterility, the international journal of the American Society for Reproductive Medicine.

Cyclin E staining of the endometrium from a patient’s with recurrent pregnancy loss. On the left her endometrial gland is markedly positive (the brown staining) for glandular nuclear cyclin E staining, which is abnormal and is associated with early recurrent pregnancy loss. On the right is cyclin E staining from the same patient after she was treated with vaginal progesterone suppositories. Her endometrial glands are now negative (no brown staining), which is a normal finding. After this successful treatment she went on to have a normal pregnancy. Image credit: Harvey J. Kliman / Yale School of Medicine

Fetal death, or intrauterine fetal demise (IUFD), affects 30,000 women each year in the United States. About 25% of all women who become pregnant have a first-trimester loss. But for some women, every pregnancy results in a loss. The researchers studied the effects of micronized plant-derived progesterone in 116 of these women who had experienced two or more pregnancy losses.

To determine whether a woman’s endometrium (uterine lining) is healthy and can sustain the embryo, the research team used the endometrial function test (EFT®), which was created by study co-author Dr. Harvey J. Kliman, director of the Reproductive and Placental Research Unit in the Department of Obstetrics, Gynecology and Reproductive Sciences at Yale School of Medicine. An abnormal EFT is associated with pregnancy failure, while a normal EFT is associated with pregnancy success. Kliman and the team focused on the ncyclinE molecular marker as a way to assess patients with recurrent pregnancy loss.

Women in the study with an abnormal nCyclinE level were prescribed progesterone two days after ovulation, when the uterine lining matures in preparation for a possible pregnancy.

The researchers believe that the progesterone caused the patients’ endometrium to produce more endometrial secretions. “The endometrium feeds the baby up until the eighth week of pregnancy. Then at 9 to 10 weeks the mother’s blood takes over to feed the embryo,” said Kliman.

“In this subset of women experiencing multiple early miscarriages, we assume that their embryos were literally starving to death,” Kliman added. “They attached, but they were not getting enough food. When we give progesterone back to these women, the endometrium makes more nutrients and prevents their pregnancy loss.

Kliman said he initially created the Endometrial Function Test (EFT®), which uses the nCyclinE marker, to identify women with infertility. “This study has shown that the EFT can also be an important tool for patients with recurrent pregnancy loss,” he said.

Kliman worked with lead author Dr. Mary Stephenson, the Dr. Theresa S. Falcon-Cullinan Professor of Obstetrics and Gynecology at the University of Illinois at Chicago and director of the University of Illinois Recurrent Pregnancy Loss Program.

“We are very pleased to find that these results reinforce the evidence that progesterone could be a very beneficial, inexpensive, and safe treatment for many women with a history of recurrent pregnancy loss,” said Stephenson. “The positive results show us that next we need to study progesterone as a treatment for recurrent pregnancy loss with a prospective randomized trial to validate the findings.”

Other authors on the study included Dr. Dana McQueen and Dr. Michelle Wintes.

Source: Yale University

Advertisements

Schizophrenia could directly increase risk of diabetes

People with early schizophrenia are at an increased risk of developing diabetes, even when the effects of antipsychotic drugs, diet and exercise are taken out of the equation, according to an analysis by researchers from King’s College London.

Schizophrenia is known to be associated with a reduced life expectancy of up to 30 years. This is largely due to physical health disorders such as heart attack or stroke, for which type 2 diabetes is a major risk factor.

People with long-term schizophrenia are three times more likely than the general population to have diabetes, something which has previously been attributed to poor diet and exercise habits in this group, as well as the use of antipsychotic medication.

Credit: King’s College London

Published in JAMA Psychiatry, this new study examined whether diabetes risk is already present in people at the onset of schizophrenia, before antipsychotics have been prescribed and before a prolonged period of illness that may be associated with poor lifestyle habits (such as poor diet and sedentary behaviour).

The researchers pooled data from 16 studies comprising 731 patients with a first episode of schizophrenia and 614 people from the general population. They analysed blood tests from these studies and found that patients with schizophrenia showed higher risk of developing type 2 diabetes compared with healthy controls.

Specifically, the patients had higher levels of fasting blood glucose, which is a clinical indicator of diabetes risk. The higher the glucose in your blood, the more likely you are to have diabetes as the body cannot efficiently remove glucose into cells where it can be used as fuel.

They also discovered that compared with healthy controls, patients with first episode schizophrenia had higher levels of insulin and increased levels of insulin resistance, again supporting the notion that this group are at higher risk of developing diabetes.

These results remained significant even when analyses were restricted to studies where patients and controls were matched for dietary intake, the amount of regular exercise they engaged in, and ethnic background. This suggests that the results were not wholly driven by differences in lifestyle factors or ethnicity between the two groups, and may therefore point towards schizophrenia’s direct role in increasing risk of diabetes.

The researchers highlight several factors that could increase the likelihood of developing both conditions, including shared genetic risk and evidence of shared developmental risk factors, such as premature birth and low birth-weight. It is also thought that the stress associated with developing schizophrenia, which sees levels of the stress hormone cortisol rise, may also contribute to a higher risk of diabetes.

Dr Toby Pillinger, first author of the study from the Institute of Psychiatry, Psychology Neuroscience (IoPPN) at King’s College London, said: ‘The mortality gap between people with schizophrenia and the general population is growing, and there is a need for novel approaches to halt this trend. Our study highlights the importance of considering physical health at the onset of schizophrenia, and calls for a more holistic approach to its management, combining physical and mental healthcare.

‘Our findings tell us that people with early schizophrenia have already started down the road to developing diabetes, even if they haven’t been diagnosed with diabetes yet.’

Dr Pillinger added: ‘Given that some antipsychotic drugs may increase the risk of diabetes further, clinicians have a responsibility to select an appropriate antipsychotic at an appropriate dose. Our results also suggest that patients should be given better education regarding diet and physical exercise, monitoring, and, where appropriate, early lifestyle changes and treatments to combat the risk of diabetes.’

Professor Oliver Howes, senior author of the study from the IoPPN at King’s College London, said: ‘These findings are a wake-up call that we need to rethink the link between diabetes and schizophrenia and start prevention right from the onset of schizophrenia. It is a case of thinking mind and body right from the start.’

Source: King’s College London

‘Housekeepers’ of the brain renew themselves more quickly than first thought

Cells in the brain responsible for detecting and fixing minor damage renew themselves more quickly than previously thought, new research has shown.

A study, led by the University of Southampton and published in Cell Reports, shows that the turnover of the cells, called Microglia, is 10 times faster, allowing the whole population of Microglia cells to be renewed several times during a lifetime.

Microglia cells (green spider shapes). Credit: University of Southampton

“Microglia are constantly scanning the brain to find and fix issues – you could call them the housekeepers of the brain,” said Dr Diego Gomez-Nicola, of the University of Southampton, who supervised the study. “We previously thought that microglia would renew themselves so slowly that a whole lifetime would not suffice to renew the whole population. But now we can talk about up to six renewal cycles in a lifetime. We now need to reinterpret how they interact and regulate the function of other brain cells to understand their full potential.”

The study, led by PhD student, Katharine Askew, assessed the proliferation of microglia, from both mouse and human brain, using staining of sections with specific antibodies alongside live imaging of the cells.

It also found that the number of microglial cells remains relatively unchanged from birth until ageing and is maintained by the spatial and temporal coupling of cell division and cell death.

The research was carried out in collaboration with researchers at the University of Tubingen (Germany), University of Oxford, University of Hamburg (Germany) and Achucarro Basque Center for Neuroscience (Spain).

The Southampton team believe this new research will help the understanding of Microglia’s behaviour in diseases like Alzheimer’s Disease. In Alzheimer’s microglia contribute to the person’s cognitive decline.

Dr Diego Gomez-Nicola added: “This finding provides a basic piece of cell biology, needed to understand the functions of microglia and their interaction with other cells in the brain. Understanding the clockwork of microglia will help understand their behaviour in psychiatric and neurodegenerative diseases of the brain like Alzheimer’s.”

Source: University of Southampton

Imperceptible electric stimulation produces lasting improvement in elderly body balance

A University of Tokyo research group has revealed that healthy elderly people who received weak electric stimulation through the ear saw their sense of balance, which tends to deteriorate with age, improve and last for several hours after discontinuing administering the electric current. The present study holds promise of becoming the cornerstone of new therapies to help patients regain their body balance function, the impairment of which has been difficult to treat until now.

Effect of nGVS in improving body balance. Subjects who received two 30-minute nGVS with a 4-hour interval in between showed improvement in their sense of body balance. The positive effect of the stimulation can be seen by the balance parameter following stimulation, represented by the blue line, falling below the value before the electric current was applied, represented by the dotted line. Image credit: Chisato Fujimoto.

The vestibular apparatus made up of structures in the inner ear enables the body to maintain a sense of equilibrium and plays a critical role in retaining balance. A decline in vestibular function causes deterioration in body balance, and existing therapies, for the most part, have not been successful in improving the condition especially for elderly patients suffering from vestibular disorders, with no effective treatment in sight.

The research group led by Assistant Professor Chisato Fujimoto, Associate Professor Shinichi Iwasaki, and Professor Tatsuya Yamasoba of the Department of Otolaryngology at the University of Tokyo Hospital has previously reported that healthy adults and patients with untreatable vestibular disorders showed improvement in their sense of balance when a weak, imperceptible electric current called noisy galvanic vestibular stimulation (nGVS), causing neither pain nor discomfort in the subjects, was administered through an electrode attached behind the ear. However, the improvement was seen only while the subjects were receiving the electric stimulation, which was applied for a relatively short period lasting just 30 seconds, and whether there were any long-term effects of nGVS on maintaining a steady balance remained unknown.

In the present study, the researchers applied 30-minute and 3-hour nGVS, respectively, to 30 healthy elderly participants, between 64 and 70 years old, and studied the stimulation’s effects on their sense of balance, and observed improved body balance lasting several hours after ceasing to apply the electric current in both cases. Furthermore, they found that a second 30-minute stimulation applied at an interval of 4-hours produced additional enhancement in body balance, as well as prolonging the period of balance improvement.

The current outcome revealed that nGVS could lead to improvement in individuals’ sense of balance that lasted several hours after ceasing the stimulation. The study showed that improved body balance can be sustained without continuous electric stimulation, and the findings may eventually find applications for the development of new treatments.

“The series of nGVS studies will be the cornerstone for development of new treatments for what has been considered an untreatable balance disorder,” says Fujimoto. He continues, “We will conduct a further clinical trial to determine the long-term effect of nGVS on balance improvement in patients with abnormalities in their vestibular apparatus. If we can prove the effect of nGVS through this trial, nGVS will be the world’s first treatment supported by highly reliable scientific evidence for persistent unsteadiness caused by a severe vestibular disorder.”

Source: University of Tokyo

Bacteria Recruit Other Species with Long-Range Electrical Signals

Biologists at UC San Diego who recently found that bacteria resolve social conflicts within their communities and communicate with one another like neurons in the brain have discovered another human-like trait in these apparently not-so-simple, single-celled creatures.

Bacteria living in diverse communities called “biofilms” create what are essentially electronic advertisements, the scientists report in a paper published in the journal Cell, by sending long-range electrical signals to other bacterial species that can lead to the recruitment of new members to their biofilm community.

“We’ve discovered that bacterial biofilm communities can actively modulate the motile behavior of diverse bacterial species through electrical signals,” said Gürol Süel, a professor of molecular biology, Associate Director of the San Diego Center for Systems Biology and Howard Hughes Medical Institute – Simons Faculty Scholar at UC San Diego, who headed the research effort. “In this way, bacteria within biofilms can exert long-range and dynamic control over the behavior of distant cells that are not part of their communities.”

Electrical messages sent by biofilms (in green, at left) recruit new members (in red, at right) to the microbial community. Photos by Suel Lab, UC San Diego

Biofilms are communities of bacteria and other microorganisms that form thin structures on surfaces—such as the tartar that develops on teeth—that are highly resistant to chemicals and antibiotics. Because not much is known about how they form, recruit other microorganisms and resist attack, such information about their behavior has practical applications—from preventing tartar formation on teeth to avoiding Staph infections in hospitals.

But the idea that bacteria ensconced in their protective biofilm villages behave like sophisticated marketing agents—advertising the presence of their communities by sending out electronic messages—overturns fundamental beliefs that both scientists and the general public have about these supposedly lowly creatures.

“Our study shows that bacteria living in biofilm communities do something similar to sending electronic messages to friends,” said Jacqueline Humphries, a doctoral student working in Süel’s laboratory and the first author of the paper. “In fact, the mechanism we discovered is general. We found that bacteria from one species can send long-range electrical signals that will lead to the recruitment of new members from another species. As a result, we’ve identified a new mechanism and paradigm for inter-species signaling.”

The UC San Diego biologists discovered in their laboratory work, which integrated experiments with mathematical modeling, that a biofilm composed of a single species of Bacillus subtilis bacteria was able to recruit bacteria of a different species—in this case, Pseudomonas aeruginosa—through electrical signaling.

Using microfluidic growth chambers, the biologists documented the process by which potassium ion electrical signaling generated by B. subtilis biofilms attracted distant cells within the chambers to the edge of electrically oscillating biofilms.

Süel and his team of graduate students and postdoctoral fellows discovered in the summer of 2015 that oscillations within biofilm communities resolved a social conflict between individual cells that were cooperating, but also had to compete for food.

Bacteria at the outer edge of the biofilm are closest to nutrients necessary for growth and could starve the sheltered interior cells. But the scientists discovered that oscillating biofilms develop what they call “metabolic codependence” by putting the brakes periodically on the outer cells’ growth to give the interior cells access to nutrients.

Not long after, Süel and his team discovered that bacteria living in biofilm communities communicate with one another electronically through proteins called “ion channels,” an electrical signaling method similar to that used by neurons in the human brain.

Their most recent discovery—that bacteria in biofilms can recruit other species with long-range electrical signals—could turn out to be not only the most surprising of the team’s findings, but perhaps the most significant for our understanding of how bacteria impact human health.

“Our latest discovery suggests that the composition of mixed species bacterial communities, such as our gut microbiome, could be regulated through electrical signaling,” said Süel. “It may even be possible that bacterial and human gut cells can interact electrically within the human gut. Our work may in the future even lead to new electrical-based biomedical approaches to control bacterial behavior and communities.”

Source: UC San Diego