Tag: Endocrinology

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New insights into how the mind influences the body

Post author By Vetscite
Post date September 13, 2016

Neuroscientists at the University of Pittsburgh have identified the neural networks that connect the cerebral cortex to the adrenal medulla, which is responsible for the body’s rapid response in stressful situations. These findings, reported in the online Early Edition of the journal Proceedings of the National Academy of Sciences (PNAS), provide evidence for the neural basis of a mind-body connection.

Specifically, the findings shed new light on how stress, depression and other mental states can alter organ function, and show that there is a real anatomical basis for psychosomatic illness. The research also provides a concrete neural substrate that may help explain why meditation and certain exercises such as yoga and Pilates can be so helpful in modulating the body’s responses to physical, mental and emotional stress.

“Our results turned out to be much more complex and interesting than we imagined before we began this study,” said senior author Peter L. Strick, Ph.D., Thomas Detre Chair of the Department of Neurobiology and scientific director of the University of Pittsburgh Brain Institute.

In their experiments, the scientists traced the neural circuitry that links areas of the cerebral cortex to the adrenal medulla (the inner part of the adrenal gland, which is located above each kidney). The scientific team included lead author Richard P. Dum, Ph.D., research associate professor in the Department of Neurobiology; David J. Levinthal, M.D., Ph.D., assistant professor in the Department of Medicine; and Dr. Strick.

The scientists were surprised by the sheer number of neural networks they uncovered. Other investigators had suspected that one or, perhaps, two cortical areas might be responsible for the control of the adrenal medulla. The actual number and location of the cortical areas were uncertain. In the PNAS study, the Strick laboratory used a unique tracing method that involves rabies virus. This approach is capable of revealing long chains of interconnected neurons. Using this approach, Dr. Strick and his colleagues demonstrated that the control of the adrenal medulla originates from multiple cortical areas. According to the new findings, the biggest influences arise from motor areas of the cerebral cortex and from other cortical areas involved in cognition and affect.

Why does it matter which cortical areas influence the adrenal medulla? Acute responses to stress include a wide variety of changes such as a pounding heart, sweating and dilated pupils. These responses help prepare the body for action and often are characterized as “fight or flight responses.” Many situations in modern life call for a more thought-out reaction than simple “fight or flight,” and it is clear that we have some cognitive control (or what neuroscientists call “top-down” control) over our responses to stress.

“Because we have a cortex, we have options,” said Dr. Strick. “If someone insults you, you don’t have to punch them or flee. You might have a more nuanced response and ignore the insult or make a witty comeback. These options are part of what the cerebral cortex provides.”

Another surprising result was that motor areas in the cerebral cortex, involved in the planning and performance of movement, provide a substantial input to the adrenal medulla. One of these areas is a portion of the primary motor cortex that is concerned with the control of axial body movement and posture. This input to the adrenal medulla may explain why core body exercises are so helpful in modulating responses to stress. Calming practices such as Pilates, yoga, tai chi and even dancing in a small space all require proper skeletal alignment, coordination and flexibility.

The PNAS study also revealed that the areas of the cortex that are active when we sense conflict, or are aware that we have made an error, are a source of influence over the adrenal medulla. “This observation,” said Dr. Strick, “raises the possibility that activity in these cortical areas when you re-imagine an error, or beat yourself up over a mistake, or think about a traumatic event, results in descending signals that influence the adrenal medulla in just the same way as the actual event.” These anatomical findings have relevance for therapies that deal with post-traumatic stress.

Additional links with the adrenal medulla were discovered in cortical areas that are active during mindful mediation and areas that show changes in bipolar familial depression. “One way of summarizing our results is that we may have uncovered the stress and depression connectome,” says Dr. Strick.

Overall, these results indicate that circuits exist to link movement, cognition and affect to the function of the adrenal medulla and the control of stress. This circuitry may mediate the effects of internal states like chronic stress and depression on organ function and, thus, provide a concrete neural substrate for psychosomatic illness.

https://www.sciencedaily.com/ Science Daily

https://www.sciencedaily.com/releases/2016/08/160815185555.htm Original web page at Science Daily

Tags Endocrinology, Human, Neurology

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Stress bites! Researchers study mosquito/bird interactions

Post author By Vetscite
Post date September 13, 2016

Research shows stressed-out birds more attractive to mosquitoes, raising fears birds exposed to stressors such as road noise, pesticides and light pollution, will be bitten more often and spread more West Nile virus

When researchers from the University of South Florida (USF) and colleagues investigated how the stress hormone, corticosterone, affects how birds cope with West Nile virus, they found that birds with higher levels of stress hormone were twice as likely to be bitten by mosquitoes that transmit the virus. Their studies have implications for the transmission of other viruses such as Eastern Equine Encephalitis, and perhaps even Zika, both known to be carried by the kind of mosquitoes used in this study. A paper describing their research was published in the Proceedings of the Royal Society B.

“Few studies have considered how stress hormone effects on individuals might influence population dynamics,” said study lead author Dr. Stephanie Gervasi, who conducted the studies while carrying out her postdoctoral work at USF and is now at the Monell Chemical Senses Center in Philadelphia. “For vector-borne diseases such as West Nile virus, the presence of corticosterone could influence pathogen spread through effects on contact rates with the mosquitoes that transmit it. In addition, stress hormones have negative effects on animals including immunosuppression and increased susceptibility to infections, which is why we are now also studying how corticosterone affects the birds’ immune response to the virus.”

According to the researchers, mosquitoes use a variety of cues to locate a target, including carbon dioxide output, body size and temperature. They hypothesized that these signals coming from a bird could convey information about stress hormones making the birds more appealing targets for the insects.

With the effects of corticosterone on mosquito feeding choices unknown, in a series of studies the researchers experimentally manipulated songbird stress hormones levels. Then they examined mosquito feeding preferences, feeding success and productivity as well as the defensive behaviors of birds trying to avoid being bitten.

In several phases of the study, zebra finches were treated with a low or high level of corticosterone and their caged light environment was altered to simulate dusk as the birds were made available to mosquitoes for measured periods of time. Bird and mosquito behavior was observed via video and the mosquitoes were later examined to determine if they had fed on the birds. The researchers also investigated the timing of subsequent mosquito egg-laying after the insects fed on the birds.

“Mosquitoes seem to be able to ‘sniff out’ the stress hormone and key in on individual birds,” said the study’s principal investigator Dr. Lynn Martin, associate professor in the USF Department of Integrative Biology. “The birds injected with higher levels of the hormone were twice as likely to be bitten by mosquitoes, even those hormone-treated birds were much more defensive than untreated ones. Corticosterone treatment increased tail flicks, and head shakes, and other defensive behaviors, but the mosquitoes managed to breach those defenses and feed more on stress hormone-treated birds.”

The study’s broader ecological implications suggest that an elevated stress hormone concentration raises the level of host attractiveness, potentially affecting the transmission of mosquito-borne diseases in a number of ways.

“Stress hormones also altered the relationship between the timing of laying and clutch size in mosquitoes,” said co-principal investigator Dr. Thomas Unnasch, chair and Distinguished USF Health Professor in the Department of Global Health, USF College of Public Health.

Mosquitoes that fed on birds with high stress hormone levels tended to lay different sized clutches of eggs at different rates than mosquitoes fed on control birds. These effects of bird stress on mosquito reproduction suggest that mosquito-feeding choice might also affect disease cycles in nature by changing the number of newborn mosquitoes that could be infected later by stressed birds.

The researchers concluded that the corticosterone levels in their test birds were within the range of normal for birds in the wild when exposed to stressors in natural their environments, such as road noise, pesticides and light pollution.

“Much more work is necessary to further understand on the interplay of host corticosterone, vector-feeding behavior, host defenses and mosquito productivity,” the researchers said.

https://www.sciencedaily.com/ Science Daily

https://www.sciencedaily.com/releases/2016/08/160810084631.htm Original web page at Science Daily

Tags Birds (pet; ornamental; prey e.g. falcons), Endocrinology, Virology

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More evidence that ‘healthy obesity’ may be a myth

Post author By Vetscite
Post date September 13, 2016

The term “healthy obesity” has gained traction over the past 15 years, but scientists have recently questioned its very existence. A study published August 18 in Cell Reports provides further evidence against the notion of a healthy obese state, revealing that white fat tissue samples from obese individuals classified as either metabolically healthy or unhealthy actually show nearly identical, abnormal changes in gene expression in response to insulin stimulation.

“The findings suggest that vigorous health interventions may be necessary for all obese individuals, even those previously considered to be metabolically healthy,” says first author Mikael Rydén of the Karolinska Institutet. “Since obesity is the major driver altering gene expression in fat tissue, we should continue to focus on preventing obesity.”

Obesity has reached epidemic proportions globally, affecting approximately 600 million people worldwide and significantly increasing the risk of heart disease, stroke, cancer, and type 2 diabetes. Since the 1940s, evidence supporting the link between obesity and metabolic and cardiovascular diseases has been steadily growing. But in the 1970s and 80s, experts began to question the extent to which obesity increases the risk for these disorders. Subsequent studies in the late 90s and early 2000s showed that some obese individuals display a relatively healthy metabolic and cardiovascular profile.

Recent estimates suggest that up to 30% of obese individuals are metabolically healthy and therefore may need less vigorous interventions to prevent obesity-related complications. A hallmark of metabolically healthy obesity is high sensitivity to the hormone insulin, which promotes the uptake of blood glucose into cells to be used for energy. However, there are currently no accepted criteria for identifying metabolically healthy obesity, and whether or not such a thing exists is now up for debate.

To address this controversy, Rydén, Carsten Daub, and Peter Arner of the Karolinska Institutet assessed responses to insulin in 15 healthy, never-obese participants and 50 obese subjects enrolled in a clinical study of gastric bypass surgery. The researchers took biopsies of abdominal white fat tissue before and at the end of a two-hour period of intravenous infusion of insulin and glucose. Based on the glucose uptake rate, the researchers classified 21 obese subjects as insulin sensitive and 29 as insulin resistant.

Surprisingly, mRNA sequencing of white fat tissue samples revealed a clear distinction between never-obese participants and both groups of obese individuals. White fat tissue from insulin-sensitive and insulin-resistant obese individuals showed nearly identical patterns of gene expression in response to insulin stimulation. These abnormal gene expression patterns were not influenced by cardiovascular or metabolic risk factors such as waist-to-hip ratio, heart rate, or blood pressure. The findings show that obesity rather than other common risk factors is likely the primary factor determining metabolic health.

“Our study suggests that the notion of metabolically healthy obesity may be more complicated than previously thought, at least in subcutaneous adipose tissue,” Rydén says. “There doesn’t appear to be a clear transcriptomic fingerprint that differentiates obese subjects with high or low insulin sensitivity, indicating that obesity per se is the major driver explaining the changes in gene expression.”

One limitation of the study is that it examined gene expression profiles only in subcutaneous white fat tissue, not other types of fat tissue or other organs. Moreover, all of the obese subjects were scheduled to undergo bariatric surgery, so the findings may only apply to individuals with severe obesity.

In future research, Rydén and his collaborators will track the study participants after bariatric surgery to determine whether weight loss normalizes gene expression responses to insulin. They will also look for specific genes linked to improved metabolic health in these individuals.

In the meantime, the study has an important take-home message. “Insulin-sensitive obese individuals may not be as metabolically healthy as previously believed,” Rydén says. “Therefore, more vigorous interventions may be necessary in these individuals to prevent cardiovascular and metabolic complications.”

https://www.sciencedaily.com/ Science Daily

https://www.sciencedaily.com/releases/2016/08/160818131127.htm Original web page web page at Science Daily

Tags Endocrinology, Genetics, Human

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* Common colon cancer tumor type blocked in mice

Post author By Vetscite
Post date August 30, 2016

A new scientific study has identified why colorectal cancer cells depend on a specific nutrient, and a way to starve them of it. Over one million men and women are living with colorectal cancer in the United States. The National Cancer Institute estimates 4.5% of all men and women will be diagnosed with the cancer during their lifetime, making it the third most common non-skin cancer.

In the study published online in Nature Communications, researchers showed how certain colorectal cancer cells reprogram their metabolism using glutamine, a non-essential amino acid. Many cancer cells rely on glutamine to survive. How they become so dependent on the molecule is hotly debated in the field.

Researchers studied a subset of colorectal cancer cells containing a genetic mutation called PIK3CA. This mutation is located in a gene critical for cell division and movement, and is found in approximately one third of all colorectal cancers. The mutation is also the most commonly identified genetic mutation across all cancers, making the results of the study universally appealing.

Researchers were interested in determining whether or not the common PIK3CA mutation contributes to changes in cancer cell metabolism, such as how nutrients like glutamine are processed. Normally, glutamine is broken down by cancer cells into several other molecules with the help of specific enzymes. This complicated system helps produce adenosine triphosphate, the energy currency of all cells, and other molecules critical for colorectal cancer cell growth.

The researchers found that colorectal cells with the PIK3CA mutation broke down significantly more glutamine than cells without the mutation. The researchers identified several enzymes involved in the process that are more active in the mutant cancer cells than in other cell types, explaining the increased need for glutamine. These enzymes become overactive in the mutant cancer cells due to a cascade of signals led by the protein encoded by mutant PIK3CA gene. This finding represents a novel and important link between the common PIK3CA mutation and altered glutamine metabolism in cancer cells.

Zhenghe John Wang, PhD, professor of genetics and genome sciences and co-leader of the Cancer Genetics Program at Case Western Reserve University School of Medicine helped lead the study. “In layman’s terms, we discovered that colon cancers with PIK3CA oncogenic mutations are addicted to glutamine, a particular nutrient for cancer cells. We also demonstrated that these cancers can be starved to death by depriving glutamine with drugs.”

When the researchers lowered the amount of glutamine available to mutant cancer cells growing in laboratory dishes, the cancer cells died. This discovery led the team to investigate the effects of blocking glutamine availability in mice with colorectal cancer tumors containing the common PIK3CA mutation. Wang and colleagues found that exposing these mice to a compound that blocks glutamine metabolism consistently suppressed tumor growth. They did not observe the same effect on tumors without the mutation. Together, these results provide a promising new therapeutic avenue to suppress growth of colorectal tumors with the PIK3CA mutation. The researchers have filed a patent application based on the unique mechanism of tumor suppression they have identified and the work is available for licensing.

“This study provides the basis for a colon cancer treatment clinical trial that will be started in the summer at the University Hospitals Seidman Cancer Center,” according to Neal Meropol, MD, Dr. Lester E. Coleman, Jr. Professor of Cancer Research and Therapeutics, chief of the division of hematology and oncology, and principal investigator for the trial. The phase I/II study will test the effects of a glutamine metabolism inhibitor in patients with advanced colorectal tumors.

https://www.sciencedaily.com/ Science Daily

https://www.sciencedaily.com/releases/2016/07/160720215322.htm Original web page at Science Daily

Tags Endocrinology, Pharmacology, Rodents/Lags

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* Happy cows make more nutritious milk

Post author By Vetscite
Post date August 10, 2016

Daily infusions with a chemical commonly associated with feelings of happiness were shown to increase calcium levels in the blood of Holstein cows and the milk of Jersey cows that had just given birth. The results, published in the Journal of Endocrinology, could lead to a better understanding of how to improve the health of dairy cows, and keep the milk flowing.

Demand is high for milk rich in calcium: there is more calcium in the human body than any other mineral, and in the West dairy products such as milk, cheese and yoghurt are primary sources of calcium. But this demand can take its toll on milk-producing cows: roughly 5-10% of the North American dairy cow population suffers from hypocalcaemia — in which calcium levels are low. The risk of this disease is particularly high immediately before and after cows give birth.

Hypocalcaemia is considered a major health event in the life of a cow. It is associated with immunological and digestive problems, decreased pregnancy rates and longer intervals between pregnancies. These all pose a problem for dairy farmers, whose profitability depends upon regular pregnancies and a high-yield of calcium-rich milk.

Whilst there has been research into the treatment of hypocalcaemia, little research has focused on prevention. In rodents it has been shown that serotonin (a naturally-occurring chemical commonly associated with feelings of happiness) plays a role in maintaining calcium levels; based on this, a team from the University of Wisconsin-Madison, led by Dr Laura Hernandez, investigated the potential for serotonin to increase calcium levels in both the milk and blood of dairy cows. The team infused a chemical that converts to serotonin into 24 dairy cows, in the run up to giving birth. Half the cows were Jersey and half were Holstein — two of the most common breeds. Calcium levels in both the milk and circulating blood were measured throughout the experiment.

Whilst serotonin improved the overall calcium status in both breeds, this was brought about in opposite ways. Treated Holstein cows had higher levels of calcium in their blood, but lower calcium in their milk (compared to controls). The reverse was true in treated Jersey cows and the higher milk calcium levels were particularly obvious in Jerseys at day 30 of lactation — suggesting a role for serotonin in maintaining levels throughout lactation.

“By studying two breeds we were able to see that regulation of calcium levels is different between the two,” says Laura Hernandez. “Serotonin raised blood calcium in the Holsteins, and milk calcium in the Jerseys. We should also note that serotonin treatment had no effect on milk yield, feed intake or on levels of hormones required for lactation.”

The next steps are to investigate the molecular mechanism by which serotonin regulates calcium levels, and how this varies between breeds.

“We would also like to work on the possibility of using serotonin as a preventative measure for hypocalcaemia in dairy cows,” continues Laura Hernandez, “That would allow dairy farmers to maintain the profitability of their businesses, whilst making sure their cows stay healthy and produce nutritious milk.”

https://www.sciencedaily.com/ Science Daily

https://www.sciencedaily.com/releases/2016/07/160715114108.htm. Original web page at Science Daily

Tags Bovine, Endocrinology, HerdHlth

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Pituitary tissue grown from human stem cells releases hormones in rats

Post author By Vetscite
Post date July 12, 2016

Researchers have successfully used human stem cells to generate functional pituitary tissue that secretes hormones important for the body’s stress response as well as for its growth and reproductive functions. When transplanted into rats with hypopituitarism–a disease linked to dwarfism and premature aging in humans–the lab-grown pituitary cells promoted normal hormone release. The study, which lays the foundation for future preclinical work, appears June 14 in Stem Cell Reports, a publication of the International Society for Stem Cell Researchers.

“The current treatment options for patients suffering from hypopituitarism, a dysfunction of the pituitary gland, are far from optimal,” says first study author Bastian Zimmer of the Sloan Kettering Institute for Cancer Research. “Cell replacement could offer a more permanent therapeutic option with pluripotent stem cell-derived hormone-producing cells that functionally integrate and respond to positive and negative feedback from the body. Achieving such a long-term goal may lead to a potential cure, not only a treatment, for those patients.”

The pituitary gland is the master regulator of hormone production in the body, releasing hormones that play a key role in bone and tissue growth, metabolism, reproductive functions, and the stress response. Hypopituitarism can be caused by tumors, genetic defects, brain trauma, immune and infectious diseases, or radiation therapy. The consequences of pituitary dysfunction are wide ranging and particularly serious in children, who can suffer severe learning disabilities, growth and skeletal problems, as well as effects on puberty and sexual function.

Currently, patients with hypopituitarism must take expensive, lifelong hormone replacement therapies that poorly mimic the body’s complex patterns of hormone secretion that fluctuates with circadian rhythms and responds to feedback from other organs. By contrast, cell replacement therapies hold promise for permanently restoring natural patterns of hormone secretion while avoiding the need for costly, lifelong treatments.

Recently, scientists developed a procedure for generating pituitary cells from human pluripotent stem cells–an unlimited cell source for regenerative medicine–using organoid cultures that mimic the 3D organization of the developing pituitary gland. However, this approach is inefficient and complicated, relies on ill-defined cellular signals, lacks reproducibility, and is not scalable or suitable for clinical-grade cell manufacturing.

To address these limitations, Zimmer and senior study author Lorenz Studer of the Sloan Kettering Institute for Cancer Research developed a simple, efficient, and robust stem cell-based strategy for reliably producing a large number of diverse, functional pituitary cell types suitable for therapeutic use. Instead of mimicking the complex 3D organization of the developing pituitary gland, this approach relies on the precisely timed exposure of human pluripotent stem cells to a few specific cellular signals that are known to play an important role during embryonic development.

Exposure to these proteins triggered the stem cells to turn into different types of functional pituitary cells that released hormones important for bone and tissue growth (i.e., growth hormone), the stress response (i.e., adrenocorticotropic hormone), and reproductive functions (i.e., prolactin, follicle-stimulating hormone, and luteinizing hormone). Moreover, these stem cell-derived cells released different amounts of hormone in response to known feedback signals generated by other organs in the body.

To test the therapeutic potential of this approach, the researchers transplanted the stem cell-derived pituitary cells under the skin of rats whose pituitary gland had been surgical removed. The cell grafts not only secreted adrenocorticotropic hormone, prolactin, and follicle-stimulating hormone, but they also triggered appropriate hormonal responses in the kidneys.

The researchers were also able to control the relative composition of different hormonal cell types simply by exposing human pluripotent stem cells to different ratios of two proteins: fibroblast growth factor 8 and bone morphogenetic protein 2. This finding suggests their approach could be tailored to generate specific cell types for patients with different types of hypopituitarism. “For the broad application of stem cell-derived pituitary cells in the future, cell replacement therapy may need to be customized to the specific needs of a given patient population,” Zimmer says.

In future studies, the researchers plan to further improve the protocol to generate pure populations of various hormone-releasing cell types, enabling the production of grafts that are tailored to the needs of individual patients. They will also test this approach on more clinically relevant animal models that have pituitary damage caused by radiation therapy and receive grafts in or near the pituitary gland rather than under the skin. This research could have important implications for cancer survivors, given that hypopituitarism is one of the main causes of poor quality of life after brain radiation therapy.

“Our findings represent a first step in treating hypopituitarism, but that does not mean the disease will be cured permanently within the near future,” Zimmer says. “However, our work illustrates the promise of human pluripotent stem cells as it presents a direct path toward realizing the promise of regenerative medicine for certain hormonal disorders.”

https://www.sciencedaily.com/ Science Daily

https://www.sciencedaily.com/releases/2016/06/160614133606.htm Original web page at Science Daily

Tags Cell Biology, Endocrinology, Rodents/Lags

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Shifting bird distribution indicates a changing Arctic

Post author By Vetscite
Post date June 28, 2016

Shifts in the distribution of Spectacled Eiders, a predatory bird at the top of the Bering Sea’s benthic food web, indicate possible changes in the Arctic’s marine ecosystem, according to new research in The Condor: Ornithological Applications.

Matt Sexson of the USGS Alaska Science Center and his colleagues compared recent satellite telemetry data from molting eiders with data from the mid-1990s. They found that in two of the species’ four primary molting areas, the birds have shifted their range significantly in the intervening decades, and the researchers interpret this as an indicator of ecosystem change–eiders go where their prey is, and their movements could indicate big changes in the community of bottom-dwelling, cold-water-dependent invertebrates they eat.

It’s easier to track marine predators than it is to track their prey, explains Sexson. “It’s tough to speculate on the connection with climate change because the data are so sparse, but we know that the north Pacific is changing,” he says. “There’s a lot of corresponding evidence that together all says something big is happening here, and eiders provide a readily available indicator that changes are occurring.”

Sexson and his colleagues spent months at a time in the remote Arctic to catch eiders on land during their breeding season, luring them into nets before making a two-hour trek back to base camp with each bird to surgically implant a satellite transmitter. “It’s a lot of hard work, but it’s a lot of fun,” Sexson says. “I used to just flip past the eiders in bird field guides, thinking I’d never see any of these. Now five years later I’m catching them and holding them. I’ve really developed a love for this group of birds–how unique they are, how beautiful they are. I’ve just become attached.”

According to the University of Maryland’s Jackie Grebmeier, an expert on Arctic marine ecosystems who was not involved with the new study, “The results of this research provide an important finding of biological response of an upper-trophic-level seabird to climate warming and sea ice retreat, another piece in the puzzle to address ecosystem change in the Pacific Arctic region.” As Arctic water warms, whole communities of animals are moving north–and there’s only so far they can go.

https://www.sciencedaily.com/ Science Daily

https://www.sciencedaily.com/releases/2016/06/160601082303.htm Original web page at Science Daily

Tags Birds (pet; ornamental; prey e.g. falcons), Dermatology, Endocrinology

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* First rodent found with a human-like menstrual cycle

Post author By Vetscite
Post date June 28, 2016

Mice are a mainstay of biomedical research laboratories. But the rodents are poor models for studying women’s reproductive health, because they don’t menstruate.

Now researchers at Monash University in Clayton, Australia, say that they have found a rodent that defies this conventional wisdom: the spiny mouse (Acomys cahirinus). If the finding holds up, the animal could one day be used to research women’s menstruation-related health conditions.

“When you do science you’re not surprised at anything — but wow, this was a really interesting finding,” says Francesco DeMayo, a reproductive biologist at the US National Institute of Environmental Health Sciences in Research Triangle Park, North Carolina, who was not involved in the work.

The study, which was posted to bioRxiv preprint server on 3 June1, involved 14 female spiny mice. The researchers found that the animals averaged a 9-day menstrual cycle and spent 3 days — or 20–40% of their cycle — bleeding. This ratio is similar to that in women, who typically bleed for 15–35% of their 28-day cycle.

To track the mice’s periods, the team flushed the animals’ vaginas with saline solution daily for 18 days. To ensure that the procedure itself did not cause the bleeding, the team treated five common lab mice in the same way. The scientists also dissected uteri taken from four spiny mice, each at a different stage of the menstrual cycle.

The team is continuing research into exactly how and when the mouse uterine lining breaks down and regrows. Jared Mamrot, a reproductive physiologist at Monash and a co-author of the study, has just sequenced the spiny mouse transcriptome — all of the RNA expressed by the animal’s genes at a given time. This could provide information on how genes regulate different stages of the spiny mouse’s menstrual cycle.

Warren Nothnick, a researcher at the University of Kansas in Kansas City who studies the uterine-lining disorder endometriosis, says that it will take a lot of work to prove that the spiny mouse is a good model for human menstruation. But he is intrigued.

“There’s some really simple studies that they could do to see if these animals would develop endometriosis spontaneously,” he says. A finding that the animals do develop the disease naturally would be a major breakthrough, Nothnick adds.

The current animal model for endometriosis is the baboon, and primate research is expensive and time-consuming. Laboratory mice can be induced to menstruate, but only if their ovaries are removed and they are given abnormally large doses of hormones. Only 1.5% of mammals menstruate naturally, and most of them are primates.

The spiny mouse could also help to shed light on healthy menstrual function, DeMayo says. Scientists don’t know the source of the cells that repopulate the uterine lining after each menstrual cycle, he notes.

But DeMayo cautions that there is more to learn about how similar menstruation is in spiny mice and women, including the patterns of gene expression involved and how the hormones oestrogen and progesterone regulate the process in the mouse.

Study co-author Hayley Dickinson., a reproductive physiologist at Monash University, says that the mouse discovery was hiding in plain sight. Monash established a breeding colony of spiny mice in 2003, and later transferred the animals to the nearby Hudson Institute for Medical Research. When Dickinson’s lab announced the menstruation discovery, several past students asked her how they could have missed it.

“The answer, as with many discoveries in science, is that no one really looked,” Dickinson says. “Everyone knew that rodents didn’t menstruate.”

Nature doi:10.1038/nature.2016.20072

http://www.nature.com/news/index.html Nature

http://www.nature.com/news/first-rodent-found-with-a-human-like-menstrual-cycle-1.20072 Original web page at Nature

Tags Endocrinology

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New guidelines explain how to monitor and treat hyperthyroid cats

Post author By Vetscite
Post date June 1, 2016

Over the last 30+ years, veterinary professionals’ understanding of clinical feline hyperthyroidism (FHT) has evolved tremendously. Initially FHT cats were referred to a specialist and now primary practitioners routinely manage these cases. The disease reportedly affects from 1.5-11.4% of cats around the world and is the most common endocrine disease of cats over 10 years of age in the US. The Guidelines for the Management of Feline Hyperthyroidism, from the American Association of Feline Practitioners (AAFP), are published today in the Journal of Feline Medicine and Surgery.

The new Guidelines explain FHT as a primary disease process with compounding factors and also provide a concise explanation of what veterinary professionals know to be true about the etiology and pathogenesis of the disease. Specifically, the Guidelines:

Distill the current research literature into simple recommendations for testing sequences that will avoid misdiagnosis and separate a FHT diagnosis into six clinical categories with associated management strategies.
Emphasize the importance of treating all hyperthyroid cats, regardless of comorbidities, and outline the currently available treatments for the disease.
Explain how to monitor the treated cat to help avoid exacerbating comorbid diseases.
Dispel some of the myths surrounding certain aspects of FHT and replace them with an evidence-based narrative that veterinarians and their practice teams can apply to feline patients and communicate to their owners.

“Our hope is that by using these Guidelines, veterinary professionals will be able to diagnose FHT long before the cat becomes the classic scrawny, unkempt patient with a mass on its neck,” said Cynthia Ward, VMD, PhD, DACVIM, and AAFP Advisory Panel Co-Chair. “With newer clinical presentations, the Guidelines explain how a cat can fall into one of six categories, and include a diagnostic and management strategy for each.”

“The Guidelines provide guidance on how to recognize the health significance of early presentations of the disease, how to treat the disease, and recommend treatment for all hyperthyroid cats with management of any comorbidity,” explains Hazel Carney, DVM, MS, DABVP (Canine & Feline), and AAFP Advisory Panel Co-Chair.

A client brochure outlining signs and symptoms of FHT, treatment options and management goals is also available, together with a chart comparing the four principal methods of FHT treatment.

https://www.sciencedaily.com/ Science Daily

https://www.sciencedaily.com/releases/2016/05/160503130346.htm Original web page at Science Daily

Tags Cats, Endocrinology

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* Hormones that are released during hunger affect decision making

Post author By Vetscite
Post date June 1, 2016

Never make a decision when you are hungry. The hormone ghrelin — that is released before meals and known to increase appetite — has a negative effect on both decision making and impulse control. Such were the results of a recently conducted study at Sahlgrenska University.

When hungry, the hormone ghrelin is produced in the stomach. In a new study conducted on rats at Sahlgrenska Academy, University of Gothenburg, the hormone has been shown to have a negative effect on decision making capabilities and impulse control.

“For the first time, we have been able to show that increasing ghrelin to levels that are seen prior to meals or during fasting, causes the brain to act impulsively and also affects the ability to make rational decisions,” says Karolina Skibicka, docent at Sahlgrenska Academy, University of Gothenburg.

Impulsivity is complex, but can be broken down into impulsive action (inability to resist a motoric response) and impulsive choice (inability to delay gratification).

Many have experienced the difficulty of resisting getting a sandwich or something else, even if we know that dinner will be served soon, and the same is true for the rats used in the study.

The rats can be trained to be rewarded (with sugar) when they execute an action such as pressing a lever (“go”) — or instead they can be rewarded only when they resist pressing the lever (“no-go”) when an appropriate learned signal is given. They learn this by repeatedly being given a signal, for example, a flash of light or a buzzing sound that tells them which action should be executed for them to receive their reward.

An inability to resist pressing the lever, when the “no-go” signal is given, is a sign of impulsivity. Researchers found that rats given ghrelin directly into the brain, which mimics how the stomach would notify us of a need to eat, were more likely to press the lever instead of waiting, despite it causing them loose their reward.

The ability to delay gratification in order to get a greater reward later is a comparable measure of impulsive choice (decision). It can be illustrated by options such as those between getting a single cookie now or several cookies if you wait a few minutes, or overeating high-calorie foods for immediate feeling of pleasure while disregarding the long term benefits of eating less or eating healthy.

The person who chooses immediate gratification even though waiting provides a greater reward, is characterized as being more impulsive and that implies a poorer ability to make rational decisions.

Researchers at Sahlgrenska Academy found that higher levels of ghrelin prevented the rats from being able to wait for the greater reward. They further evaluated where in the brain ghrelin acts to affect impulsivity.

“Our results showed that restricting ghrelin effects to the ventral tegmental area, the part of the brain that is a crucial component of the reward system, was sufficient to make the rats more impulsive. Importantly, when we blocked ghrelin, the impulsive behavior was greatly reduced,” says Karolina Skibicka. Even a short period of fasting, a more natural way of increasing the release of ghrelin, increased impulsive behavior.

Impulsivity is a distinctive feature of many neuropsychiatric disorders and behavior disorders such as ADHD, obsessive compulsive disorder (OCD), autism spectrum disorder (ASD), drug abuse and eating disorders.

The study also showed that increased levels of ghrelin even caused long-term genetic changes in the brain circuits that are linked to impulsivity and decision making. A ghrelin injection into the brain that resulted in impulsive behavior in rats, caused the same type of changes in dopamine related genes and enzymes as can be seen in ADHD and OCD.

“Our results indicate that the ghrelin receptors in the brain can be a possible target for future treatment of psychiatric disorders that are characterized by problems with impulsivity and even eating disorders,” says Karolina Skibicka.

https://www.sciencedaily.com/ Science Daily

https://www.sciencedaily.com/releases/2016/05/160509085807.htm Original web page at Science Daily

Tags Endocrinology, Human

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* Stem cells from diabetic patients coaxed to become insulin-secreting cells

Post author By Vetscite
Post date June 1, 2016

If damaged cells are replaceable, type 1 diabetics wouldn’t need insulin shots.

Signaling a potential new approach to treating diabetes, researchers at Washington University School of Medicine in St. Louis and Harvard University have produced insulin-secreting cells from stem cells derived from patients with type 1 diabetes.

People with this form of diabetes can’t make their own insulin and require regular insulin injections to control their blood sugar. The new discovery suggests a personalized treatment approach to diabetes may be on the horizon — one that relies on the patients’ own stem cells to manufacture new cells that make insulin.

The researchers showed that the new cells could produce insulin when they encountered sugar. The scientists tested the cells in culture and in mice, and in both cases found that the cells secreted insulin in response to glucose.

“In theory, if we could replace the damaged cells in these individuals with new pancreatic beta cells — whose primary function is to store and release insulin to control blood glucose — patients with type 1 diabetes wouldn’t need insulin shots anymore,” said first author Jeffrey R. Millman, PhD, an assistant professor of medicine and of biomedical engineering at Washington University School of Medicine. “The cells we’ve manufactured sense the presence of glucose and secrete insulin in response. And beta cells do a much better job controlling blood sugar than diabetic patients can.”

Millman, whose laboratory is in the Division of Endocrinology, Metabolism and Lipid Research, began his research while working in the laboratory of Douglas A. Melton, PhD, Howard Hughes Medical Institute investigator and a co-director of Harvard’s Stem Cell Institute. There, Millman had used similar techniques to make beta cells from stem cells derived from people who did not have diabetes. In these new experiments, the beta cells came from tissue taken from the skin of diabetes patients.

“There had been questions about whether we could make these cells from people with type 1 diabetes,” Millman explained. “Some scientists thought that because the tissue would be coming from diabetes patients, there might be defects to prevent us from helping the stem cells differentiate into beta cells. It turns out that’s not the case.”

Millman said more research is needed to make sure that the beta cells made from patient-derived stem cells don’t cause tumors to develop — a problem that has surfaced in some stem cell research — but there has been no evidence of tumors in the mouse studies, even up to a year after the cells were implanted.

He said the stem cell-derived beta cells could be ready for human research in three to five years. At that time, Millman expects the cells would be implanted under the skin of diabetes patients in a minimally invasive surgical procedure that would allow the beta cells access to a patient’s blood supply.

“What we’re envisioning is an outpatient procedure in which some sort of device filled with the cells would be placed just beneath the skin,” he said.

The idea of replacing beta cells isn’t new. More than two decades ago, Washington University researchers Paul E. Lacy, MD, PhD, now deceased, and David W. Scharp, MD, began transplanting such cells into patients with type 1 diabetes. Still today, patients in several clinical trials have been given beta cell transplants with some success. However, those cells come from pancreas tissue provided by organ donors. As with all types of organ donation, the need for islet beta cells for people with type 1 diabetes greatly exceeds their availability.

Millman said that the new technique also could be used in other ways. Since these experiments have proven it’s possible to make beta cells from the tissue of patients with type 1 diabetes, it’s likely the technique also would work in patients with other forms of the disease — including type 2 diabetes, neonatal diabetes and Wolfram syndrome. Then it would be possible to test the effects of diabetes drugs on the beta cells of patients with various forms of the disease.

https://www.sciencedaily.com/ Science Daily

https://www.sciencedaily.com/releases/2016/05/160510132809.htm Original web page at Science Daily

Tags Cell Biology, Endocrinology, Human

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Islet transplantation restores blood sugar awareness and control in type 1 diabetes

Post author By Vetscite
Post date May 17, 2016

New clinical trial results show that transplantation of pancreatic islets–cell clusters that contain insulin-producing cells–prevents severe, potentially life-threatening drops in blood sugar in people with type 1 diabetes. Researchers found that the treatment was effective for people who experienced episodes of severe hypoglycemia–low blood sugar levels that can lead to seizures, loss of consciousness and death–despite receiving expert care.

The Phase 3 trial was funded by the National Institute of Allergy and Infectious Diseases (NIAID) and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), both part of the National Institutes of Health, and was conducted by the NIH-sponsored Clinical Islet Transplantation (CIT) Consortium. The investigators designed the study in consultation with the U.S. Food and Drug Administration to enable potential future licensure of the manufacture of purified human pancreatic islets. The results appear online today in Diabetes Care.

“The findings suggest that for people who continue to have life-altering severe hypoglycemia despite optimal medical management, islet transplantation offers a potentially lifesaving treatment that in the majority of cases eliminates severe hypoglycemic events while conferring excellent control of blood sugar,” said NIAID Director Anthony S. Fauci, M.D.

As expected, the treatment carried risks, including infections and lowered kidney function as a result of people taking the immune-suppressing drugs needed to prevent rejection of the donor islets. Although some of the side effects were serious, none led to death or disability. In the United States, islet transplantation is currently available only in clinical trials.

“While still experimental, and with risks that must be weighed carefully, the promise of islet transplantation is undeniable and encouraging,” said NIDDK Director Griffin P. Rodgers, M.D. “Even with the best care, about 30 percent of people with type 1 diabetes aren’t aware of dangerous drops in blood glucose levels.”

In type 1 diabetes, the immune system attacks and destroys insulin-producing cells in the islets of the pancreas. People with type 1 diabetes need lifelong treatment with insulin, which helps transport the sugar glucose from the bloodstream into cells, where it serves as a key energy source. Even with insulin therapy, people with type 1 diabetes frequently experience fluctuations in blood sugar levels.

Hypoglycemia, or low blood sugar, typically is accompanied by symptoms such as tremors, sweating and heart palpitations that prompt people to eat or drink to raise their blood sugar levels. Those who do not experience these early warning signs–a condition called impaired awareness of hypoglycemia–are at increased risk for severe hypoglycemic events, during which the person is unable to treat himself or herself. Treatments such as behavioral therapies or continuous glucose-monitoring systems can prevent these events in many–but not all–people with this impaired awareness, leaving a substantial number of people at risk.

The current study enrolled 48 people who had persistent impaired awareness of hypoglycemia and experienced severe hypoglycemic events despite expert care by a diabetes specialist or endocrinologist. Investigators at eight study sites in North America used a standardized manufacturing protocol to prepare purified islets from the pancreases of deceased human donors. All study participants received at least one transplant of islets injected into the portal vein, the major vessel that carries blood from the intestine into the liver. Islet recipients currently must take immunosuppressive drugs for the rest of their lives to prevent their immune systems from rejecting the transplanted cells.

One year after the first transplant, 88 percent of study participants were free of severe hypoglycemic events, had established near-normal control of glucose levels, and had restored hypoglycemic awareness. After two years, 71 percent of participants continued to meet these criteria for transplant success.

Even a small number of functioning, insulin-producing cells can restore hypoglycemic awareness, although transplant recipients may need to continue taking insulin to fully regulate blood glucose levels. Participants who still needed insulin 75 days after transplant were eligible for another islet infusion. Twenty-five participants received a second transplant, and one received three. After one year, 52 percent of study participants no longer needed insulin therapy.

“This is the first license-enabling trial of a cellular product for treatment of type 1 diabetes,” said NIAID Transplantation Branch Chief Nancy D. Bridges, M.D., a co-author of the paper. “Licensure is critical because it will ensure the quality, consistency and safety of the islet product; provide greater patient access to islet transplantation; and accelerate continued research that we hope would make this procedure suitable for a broader population of people with type 1 diabetes.”

The researchers are continuing to follow participants to determine whether the benefits of restoring near-normal blood glucose control and protection from severe hypoglycemic events will outweigh the risks associated with chronic immunosuppression.

“For people unable to safely control type 1 diabetes, islet transplantation offers real hope for preventing severe, life-threatening hypoglycemia,” said study co-author Tom Eggerman, M.D., Ph.D., NIDDK scientific officer for the CIT Consortium. “However, as immunosuppression drugs required for transplantation can have significant adverse side effects, the treatment only makes sense for people who have frequent severe hypoglycemia despite optimal diabetes management, or for those already on immunosuppressant drugs for a kidney transplant, a group being studied in another Phase 3 trial.”

https://www.sciencedaily.com/ Science Daily

https://www.sciencedaily.com/releases/2016/04/160418120706.htm Original web page at Science Daily

Tags Endocrinology, Human

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* Scientists still fail to record age and sex of lab mice

Post author By Vetscite
Post date April 6, 2016

The largest-ever analysis of the quality of mouse studies reveals that as recently as 2014, only around 50% of research papers recorded both the sex and age of the animals used — key details needed for others to assess and reproduce the research.

The analysis, which used software to trawl through the text of more than 15,000 open-access papers published between 1994 and 2014, also reveals the preferences of different research fields. Cardiovascular research tends to use male mice, whereas research on infectious diseases such as HIV and tuberculosis favours female mice, for example.

The study is “the strongest evidence about sex and age bias through biomedical research to date”, say its authors.

Many researchers have pointed out that male and female mice — like men and women — can have different responses to drugs or different behaviours in laboratory experiments. One study last year, for instance, found that although inhibiting the function of immune cells called microglia helps to relieve pain in male mice, it doesn’t do so in female mice. The difference might explain why some clinical trials of pain drugs have failed.

Recognizing the problem, the US National Institutes of Health said in 2014 that it would require researchers to report their plans for the balance of male and female animals in preclinical studies. But even before that, scientists had been urged to report in more detail the strains, sexes and ages of the mice they experimented on.

“It’s useful to see what’s happening in a large-scale study — which has thrown up some things we weren’t expecting,” says Andrew Brass, a bioinformatician at the University of Manchester, UK, and a co-author of the study, which is published in eLife.

One surprise was that although recording of animal studies improved through the 1990s and 2000s, standards seem to have plateaued after 2010 — despite the introduction that year of a voluntary checklist to improve reporting, called the ARRIVE guideline.

The study shows the power of being able to mine the full text of research papers, says Malcolm Macleod, a stroke researcher and specialist in trial design at the University of Edinburgh, UK. But he notes that the fully open papers that can be mined may not be representative of the entire scientific literature: scientists who want to make their papers open may be “among the more enlightened”, he suggests.

Previous research has consistently suggested that researchers tend to use male mice in studies — but the eLife paper reports that, where the sex of animals is recorded, the mice are more likely to be female. That surprises Caroline Zeiss, a veterinary neuropathologist at Yale University in New Haven, Connecticut. The discrepancy might result from biases in the specific fields of research that the eLife paper examined, she says.

The sex bias varied according to the type of biomedical study, and even between studies of the same disease. Diabetes research, for example, was found to be male-biased overall — but studies on the immunology of the condition tended to use female mice. There was no correlation between reporting standards and the impact factor of the journal in which the studies were published, the researchers found.

Nature doi:10.1038/nature.2016.19500

http://www.nature.com/news/index.html Nature

http://www.nature.com/news/scientists-still-fail-to-record-age-and-sex-of-lab-mice-1.19500 Original web page at Nature

Tags Endocrinology, Laboratory Animal Science

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Link made between genetics, aging

Post author By Vetscite
Post date March 22, 2016

Scientists at the University of Georgia have shown that a hormone instrumental in the aging process is under genetic control, introducing a new pathway by which genetics regulates aging and disease.

Previous studies have found that blood levels of this hormone, growth differentiation factor 11, decrease over time. Restoration of GDF11 reverses cardiovascular aging in old mice and leads to muscle and brain rejuvenation, a discovery that was listed as one of the top 10 breakthroughs in science in 2014.

Scientists in the UGA College of Family and Consumer Sciences have now discovered that levels of this hormone are determined by genetics, representing another potential mechanism by which aging is encoded in the genome.

Future studies will seek to reveal why GDF11 levels decrease later in life and whether they can be sustained to prevent disease.

“Finding that GDF11 levels are under genetic control is of significant interest. Since it is under genetic control, we can find the genes responsible for GDF11 levels and its changes with age,” said the study’s senior author Rob Pazdro, an assistant professor in the college’s department of foods and nutrition.

The study confirmed results from previous experiments showing that GDF11 levels decrease over time and also showed that most of the depletion occurs by middle age.

In addition, the study examined the relationship between GDF11 levels and markers of aging such as lifespan in 22 genetically diverse inbred mice strains. Of note, the strains with the highest GDF11 levels tended to live the longest

Using gene mapping, Pazdro’s team then identified seven candidate genes that may determine blood GDF11 concentrations at middle age, demonstrating for the first time that GDF11 levels are highly heritable.

“Essentially, we found a missing piece of the aging/genetics puzzle,” Pazdro said. “Very generally, we’ve made an important step toward learning about aging and why we age and what are the pathways that drive it. It’s the first step down a long road, but it’s an important step.”

The study, “Circulating Concentrations of Growth Differentiation Factor 11 are heritable and correlate with life span,” was published in the Jan. 16 issue of the Journals of Gerontology Series A Biological Sciences and Medical Sciences.

https://www.sciencedaily.com/ Science Daily

https://www.sciencedaily.com/releases/2016/02/160219111513.htm Original web page at Science Daily

Tags Endocrinology, Genetics, Rodents/Lags

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The power of touch: Sex-changing snails switch sooner when together

Post author By Vetscite
Post date January 26, 2016

Many animals change sex at some point in their lives, often after reaching a certain size. Snails called slipper limpets begin life as males, and become female as they grow. A new Smithsonian study shows that when two males are kept together and can touch one another, the larger one changes to female sooner, and the smaller one later. Contact, rather than chemicals released into the water, is necessary for the effect.

“I was blown away by this result,” said co-author Rachel Collin, staff scientist at the Smithsonian Tropical Research Institute (STRI). “I fully expected that the snails would use waterborne cues to see their world.”

The article, co-authored by former STRI intern Allan Carrillo-Baltodano, now a pre-doctoral student at Clark University, was published in The Biological Bulletin.

Tropical slipper limpets, Crepidula cf. marginalis, live under rocks in intertidal areas along the shore, obtaining food by filtering plankton and other particles from the water. Their thin, flattened shells have a built-in shelf. When flipped over, they resemble men’s house slippers. Often found in clusters, they occur alone or as pairs or trios consisting of a large female with one or two smaller males riding piggyback on her shell.

A male limpet has a comparatively enormous penis–sometimes as long as his entire body–which rather incongruously emerges from the right side of his head. This elongated apparatus is necessary to extend around and under the female’s shell in order to reach her genital opening. When a snail changes sex, the penis gradually shrinks and then disappears at the same time that female organs develop. It is thought that this kind of sex change is advantageous because large animals are able to produce larger numbers of eggs as females, while small males can still produce plenty of sperm (which require much less energy to make than eggs).

In experiments, two males differing slightly in size were kept in small cups containing seawater. In some cups they were allowed to be in contact with one another, while in others a mesh barrier kept them apart while allowing water to pass through. The larger snails in the pairs in direct contact with their partners grew more quickly and changed into females sooner than those kept apart. Conversely, the smaller member of a pair that was in contact delayed sex change compared to ones separated by mesh.

In sex-changing coral-reef fishes, visual, behavioral and chemical cues may all influence switching by individuals that associate with each other. Slipper limpets, which are sedentary and have poor vision, were initially expected to depend more on waterborne chemical cues, already known to affect other aspects of their behavior. Surprisingly, slipper limpets turned out to be like fishes in showing a greater response to behavioral interactions or perhaps contact-based chemical cues, than waterborne signals. Slipper snails don’t move around much, so you don’t really think of them having complex reactions to each other,” Collin said. “But this study shows that there is more going on there than we thought.”

http://www.sciencedaily.com/ Science Daily

http://www.sciencedaily.com/releases/2015/12/151223130535.htm Original web page at Science Daily

Tags Biomedical, Endocrinology

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Gene controls stress hormone production in macaques

Post author By Vetscite
Post date January 26, 2016

Some people react more calmly in stressful situations than others. Certain genes, such as the so-called COMT gene, are thought to play a role in determining our stress response. Researchers from the Vetmeduni Vienna and the University of Vienna have now studied this gene in macaques, a genus of Old World monkeys, and for the first time have shown that a specific variant of the gene is associated with higher excretion of the stress hormone cortisol. The gene variant may also influence social rank among the animals. The results were published in the journal Hormones and Behavior.

Animals that live in groups face a variety of challenging social situations. The competition for food and mating partners as well as the establishment of the social hierarchy are potential stress factors. Ralf Steinborn, Head of the Genomics Unit of the VetCore Facility for Research at the Vetmeduni Vienna, and ethologist Lena Pflüger from the Department of Anthropology at the University of Vienna, studied Japanese macaques living at Affenberg Landskron in Carinthia, Austria, to investigate how their genetic make-up influences the excretion of the stress hormones and the behaviour of the animals.

“Japanese macaques live in strict hierarchy which entails a high level of aggressive interaction. This makes them ideally suited for a study on stress behaviour,” says Pflüger.

Pflüger, first author of the study and scientific director of the Affenberg facility, studied 26 sexually mature males during the mating season, a particularly stressful time for male animals as they must compete for females. She discovered that the amount of a metabolic product of the hormone cortisol in the animals’ faeces differed across individuals. “The macaques appear to handle stressful situations differently. Some are more courageous than others. We were interested to see whether there were genetic causes for this behaviour and how genetics affects the hormonal stress reaction and social rank,” says Pflüger.

The COMT gene is one of at least 18 genes in humans that control the dopamine system in the brain. Dopamine promotes skills such as planning, decision making and problem solving. Depending on its variant, more or less of the COMT enzyme is produced from the gene, resulting in a faster or slower dopamine metabolization in the brain. Higher amounts of dopamine in the brain increase various cognitive performances but are also associated with increased stress reactions.

Steinborn and Pflüger determined the different variants of the COMT gene in Japanese macaques. This revealed that macaques with high levels of the stress hormone also possess a certain COMT variant that presumably metabolizes dopamine in the brain more slowly. The functionality of this variant and the underlying mechanism resulting in higher stress hormone levels will be determined in further studies.

“Our results indicate that animals with stress-resilient COMT variants acquire higher rank positions in the group. But a direct correlation between COMT variant and social rank has to be investigated more closely in the future,” explains Steinborn.

“The dopamine level in the brain controls various behaviours in people. On the one hand, there are the so-called warrior types. In warriors, the dopamine in the brain is metabolized more quickly. Warriors possess lower cognitive skills and are less easily stressed. The second type are worriers, who score higher in cognitive performance tests but are more easily stressed. However, the dopamine system functions like an orchestra and is not dependent on just one factor,” says Steinborn.

In the future, Pflüger and Steinborn want to study other genes that play a role in the dopamine system of non-human primates. They aim to study a variety of primate species with different social styles. Another research focus will be the functionality of the newly discovered COMT gene variant at the RNA and protein levels.

http://www.sciencedaily.com/ Science Daily

http://www.sciencedaily.com/releases/2015/12/151218085455.htm Original web page at Science Daily

Tags Behaviour (Ethology), Endocrinology, Primates

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Articles examine relationship between skin, endocrine disorders

Post author By Vetscite
Post date January 26, 2016

Two studies and an editorial published online by JAMA Dermatology examine the relationship between skin disorders and endocrine diseases.

In the first study, Dipankar De, M.D., of the Postgraduate Institute of Medical Education and Research, Chandigarh, India, and coauthors looked at the association between insulin resistance and metabolic syndrome in male patients with acne (ages 20 to 32). The study included 100 men with acne and 100 men without.

The authors report the prevalence of insulin resistance was higher among the men with acne (22 percent) compared with the healthy control patients (11 percent). The prevalence of metabolic syndrome was not statistically significant between men with acne and without. The prevalence of insulin resistance and metabolic syndrome also did not differ significantly among men when they were grouped by the severity of their acne.

A limitation of the study is its cross-sectional design because it looks at a population at a moment in time.

“These patients should be followed up to determine whether they develop conditions associated with insulin resistance,” the authors conclude.

In a second study, Kanade Shinkai, M.D., Ph.D., of the University of California, San Francisco, and coauthors identified skin features of polycystic ovary syndrome (PCOS). The study included 401 women (median age 28) with suspected PCOS. Overall, 68.8 percent of women (276 of 401) met PCOS diagnostic criteria. Most women (91.7 percent [253 of 276]) who met the criteria for PCOS had at least one skin finding.

Women who met the criteria for PCOS were more likely than women who did not meet the criteria to have acne (61.2 percent vs. 40.4 percent); hirsutism or facial and trunk hair growth (53.3 percent vs. 31.2 percent); and acanthosis nigricans (AN) or dark areas on the skin (36.9 percent vs. 20 percent).

The authors note hirsutism affects 5 percent to 15 percent of women in the general population, while AN is estimated to affect 20 percent of the U.S. population. Also, while acne is a common skin feature in women with PCOS, it did not distinguish between women suspected of having PCOS and those meeting the diagnostic criteria.

The authors note limitations to their study including a comparison group not comprised of healthy controls but of women with suspected PCOS who did not meet the diagnostic criteria.

“This study demonstrates that hirsutism and AN are the most useful cutaneous indicators of PCOS to distinguish patients most at risk for having PCOS among a suspected population,” the authors conclude.

In a related editorial, Rachel V. Reynolds, M.D., of Beth Israel Deaconess Medical Center, Boston, writes: “The findings of these two studies remind us that as dermatologists, our detective work goes beyond identifying patterns on the surface to clinch a diagnosis. Thoughtful evaluation of even the most common of skin disorders provides the opportunity to take a deeper dive into the understanding of our patients’ general physical and emotional well-being.”

http://www.sciencedaily.com/ Science Daily

http://www.sciencedaily.com/releases/2015/12/151223130028.htm Original web page at Science Daily

Tags Dermatology, Endocrinology, Human

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Insulin-producing pancreatic cells created from human skin cells

Post author By Vetscite
Post date January 26, 2016

Scientists at the Gladstone Institutes and the University of California, San Francisco (UCSF) have successfully converted human skin cells into fully-functional pancreatic cells. The new cells produced insulin in response to changes in glucose levels, and, when transplanted into mice, the cells protected the animals from developing diabetes in a mouse model of the disease.

The new study, published in Nature Communications, also presents significant advancements in cellular reprogramming technology, which will allow scientists to efficiently scale up pancreatic cell production and manufacture trillions of the target cells in a step-wise, controlled manner. This accomplishment opens the door for disease modeling and drug screening and brings personalized cell therapy a step closer for patients with diabetes.

“Our results demonstrate for the first time that human adult skin cells can be used to efficiently and rapidly generate functional pancreatic cells that behave similar to human beta cells,” says Matthias Hebrok, PhD, director of the Diabetes Center at UCSF and a co-senior author on the study. “This finding opens up the opportunity for the analysis of patient-specific pancreatic beta cell properties and the optimization of cell therapy approaches.”

In the study, the scientists first used pharmaceutical and genetic molecules to reprogram skin cells into endoderm progenitor cells–early developmental cells that have already been designated to mature into one of a number of different types of organs. With this method, the cells don’t have to be taken all the way back to a pluripotent stem cell state, meaning the scientists can turn them into pancreatic cells faster. The researchers have used a similar procedure previously to create heart, brain, and liver cells.

After another four molecules were added, the endoderm cells divided rapidly, allowing more than a trillion-fold expansion. Critically, the cells did not display any evidence of tumor formation, and they maintained their identity as early organ-specific cells.

The scientists then progressed these endoderm cells two more steps, first into pancreatic precursor cells, and then into fully-functional pancreatic beta cells. Most importantly, these cells protected mice from developing diabetes in a model of disease, having the critical ability to produce insulin in response to changes in glucose levels.

“This study represents the first successful creation of human insulin-producing pancreatic beta cells using a direct cellular reprogramming method,” says first author Saiyong Zhu, PhD, a postdoctoral researcher at the Gladstone Institute of Cardiovascular Disease. “The final step was the most unique–and the most difficult–as molecules had not previously been identified that could take reprogrammed cells the final step to functional pancreatic cells in a dish.”

Sheng Ding, PhD, a senior investigator in the Roddenberry Stem Cell Center at Gladstone and co-senior author on the study, adds, “This new cellular reprogramming and expansion paradigm is more sustainable and scalable than previous methods. Using this approach, cell production can be massively increased while maintaining quality control at multiple steps. This development ensures much greater regulation in the manufacturing process of new cells. Now we can generate virtually unlimited numbers of patient-matched insulin-producing pancreatic cells.”

http://www.sciencedaily.com/ Science Daily

http://www.sciencedaily.com/releases/2016/01/160106091738.htm Original web page at Science Daily

Tags Cell Biology, Endocrinology, Human

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Tie between estrogen, memory explored by researchers

Post author By Vetscite
Post date January 13, 2016

A new study by University of Guelph researchers that narrows down where and how estrogens affect the brain may help in understanding how the hormones affect cognition and memory in women, says psychology professor Elena Choleris.

The team found that adding the hormone to female mouse brains helps boost short-term learning, likely through a ‘use-it-or-lose-it’ process, said Choleris, who co-authored the paper along with biomedical sciences professor Neil MacLusky. The paper was published recently in the Proceedings of the National Academy of Sciences.

Lead author Anna Phan, a recent PhD graduate who worked with both Guelph professors, is now a post-doc researcher at the Scripps Research Institute in Florida.

Researchers already knew that a region of the brain called the hippocampus responds to estrogens and is involved in cognition and memory. An earlier study led by Phan showed that mice given systemic injections of the hormone improved their learning.

For this new study, the researchers recorded learning improvements within 40 minutes of injecting an estrogen directly into specific regions of the hippocampus, said Choleris.

The team assessed learning in mice by testing how readily they recognized other mice or objects, or objects moved to unfamiliar locations.

Brain cells communicate by passing signals through long cell extensions called axons to tiny spines located on branches of adjacent neurons. Within minutes of adding more estrogen, the team saw huge numbers of spine synapses growing on those branches.

The researchers also expected to see greater electrical activity with more spines, but were surprised to find just the opposite in treated brain tissue alone.

Choleris said the scientists believe estrogens increase the number of synapses but that those potential connections remain silent unless they’re used for learning. Learning strengthens certain connections while others are pruned away.

“Use it or lose it,” said Choleris, adding that more research is needed to understand this mechanism.

She said studies have shown that post-menopausal women or women whose ovaries have been removed for medical reasons report problems with cognition and memory.

This new study suggests that boosting estrogen levels could help, although Choleris cautions that estrogen replacement therapy has been linked to greater cancer risk for some women.

“Ideally we would like to identify the estrogen mechanism to improve learning and not increase the risk of cancer.”

http://www.sciencedaily.com Science Daily

http://www.sciencedaily.com/releases/2015/12/151215134645.htm Orginal web page at Science Daily

Tags Endocrinology, Neurology, Rodents/Lags

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Salmon is first transgenic animal to win US approval for food

Post author By Vetscite
Post date December 15, 2015

Long-awaited decision authorizes a genetically engineered animal to grace US dinner tables for the first time. A fast-growing salmon has become the first genetically engineered animal to be approved for human consumption in the United States. The decision, issued by the US Food and Drug Administration (FDA) on 19 November, releases the salmon from two decades of regulatory limbo. The move was met with swift opposition from some environmental and food-safety groups.

But for advocates of the technology, the decision comes as a relief after a long and vexing wait. They say that it could spur the development of other genetically engineered animals. “It opens up the possibility of harnessing this technology,” says Alison Van Eenennaam, an animal geneticist at the University of California, Davis. “The regulatory roadblock had really been disincentivizing the world from using it.”

The genetically modified fish, called ‘AquAdvantage’ salmon, were engineered by AquaBounty Technologies of Maynard, Massachusetts, to express higher levels of a growth hormone than wild salmon. The fish grow to full size in 18 months rather than 3 years. According to proponents of the technology, these modifications mean that the fish require smaller amounts of food and other resources per kilogram of harvested fish, and that the modified salmon could ease pressure caused by heavy fishing of wild populations.

Opponents fear that engineered fish could escape from their farms and might alter natural ecosystems. They also criticize the lack of a requirement that the meat be labelled as genetically engineered.

“Huge numbers of people have said, ‘Yes, we want it labelled,’” says Jaydee Hanson, a senior policy analyst at the Center for Food Safety, an environmental-advocacy group in Washington DC. “If this is such a good product, the company itself should be saying it will label it.”

The FDA completed its food-safety assessment in 2010, and released its environmental-impact statement at the end of 2012. The long delay between the completion of those steps and a final decision led to rumours of political interference. But Laura Epstein, a senior policy analyst for the FDA’s Center for Veterinary Medicine, says that the approval took so long because it was the first of its kind. “With most products that are the first of its kind, we are very careful,” she says. The agency also had to wade through many public comments before it could issue a decision, she adds.

The FDA declined to comment on whether other applications for approval are in the regulatory pipeline. It is also unclear how the agency will handle animals that are genetically engineered using newer genome-editing technologies such as CRISPR, Van Eenennaam says

Nature doi:10.1038/nature.2015.18838

http://www.nature.com/news/index.html Nature

http://www.nature.com/news/salmon-is-first-transgenic-animal-to-win-us-approval-for-food-1.18838 Original web page at Nature

Tags Endocrinology, Fishes, Genetics

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Births down and deaths up in Gulf dolphins

Post author By Vetscite
Post date December 1, 2015

A NOAA-led team of scientists is reporting a high rate of reproductive failure in dolphins exposed to oil from the Deepwater Horizon spill. The team has monitored these bottlenose dolphins in heavily-oiled Barataria Bay for five years following the spill. Their findings, published in Proceedings of the Royal Society today, suggest that the effects of the Deepwater Horizon oil spill will be long-lasting.

The study assessed reproductive success and survival rate for Barataria Bay dolphins. These dolphins had been sampled for health assessments in 2011, and were found to have a high prevalence of lung disease and adrenal dysfunction. Now the team is reporting that only 20% of the sampled dolphins that were pregnant produced viable calves. This is compared to a previously-reported pregnancy success rate of 83% from a similar study in a dolphin population in Sarasota Bay, which was not affected by the spill.

After nearly four years of monitoring, scientists were also able to estimate the survival rate of the dolphins sampled in 2011. They found that only 86.8% of the dolphins survived each year, as compared to other populations where roughly 95% of the dolphins survived. The reduced reproductive potential, along with decreased survival, will have long-term consequences for the Barataria Bay dolphin population.

In August of 2011, a team of independent and NOAA scientists evaluating the health of bottlenose dolphins in Louisiana’s Barataria Bay gave dolphin Y35 a good health outlook. Based on the ultrasound, she was in the early stages of pregnancy, but unlike many of the other dolphins examined that summer day, Y35 was in pretty good shape. She wasn’t extremely underweight or suffering from moderate-to-severe lung disease, conditions connected to exposure to Deepwater Horizon oil in the heavily impacted Barataria Bay.

Veterinarians did note, however, that she had alarmingly low levels of important stress hormones responsible for behaviors such as the fight-or-flight response. Normal levels of these hormones help animals cope with stressful situations. This rare condition–known as hypoadrenocorticism–had never been reported before in dolphins, which is why it was not used for Y35 and the other dolphins’ health prognoses.

Less than six months later, researchers spotted Y35 for the last time. It was only 16 days before her expected due date. She and her calf are now both presumed dead, a disturbingly common trend among the bottlenose dolphins that call Barataria Bay their year-round home.

This trend of reproductive failure and death in Gulf dolphins over five years of monitoring after the 2010 Deepwater Horizon oil spill is outlined in a November 2015 study led by NOAA and published in the peer-reviewed journal Proceedings of the Royal Society.

Of the 10 Barataria Bay dolphins confirmed to be pregnant during the 2011 health assessment, only two successfully gave birth to calves that have survived. This unusually low rate of reproductive success–only 20%–stands in contrast to the 83% success rate in the generally healthier dolphins being studied in Florida’s Sarasota Bay, an area not affected by Deepwater Horizon oil.

While hypoadrenocorticism had not been documented previously in dolphins, it has been found in humans. In human mothers with this condition, pregnancy and birth–stressful and risky enough conditions on their own–can be life-threatening for both mother and child when left untreated. Wild dolphins with this condition would be in a similar situation.

Mink exposed to oil in an experiment ended up exhibiting very low levels of stress hormones, while sea otters exposed to the Exxon Valdez oil spill experienced high rates of failed pregnancies and pup death. These cases are akin to what scientists have observed in the dolphins of Barataria Bay after the Deepwater Horizon oil spill.

Among the pregnant dolphins being monitored in this study, at least two lost their calves before giving birth. Veterinarians confirmed with ultrasound that one of these dolphins, Y31, was carrying a dead calf in utero during her 2011 exam. Another pregnant dolphin, Y01, did not successfully give birth in 2012, and was then seen pushing a dead newborn calf in 2013. Given that dolphins have a gestation of over 12 months, this means Y01 had two failed pregnancies in a row.

The other five dolphins to lose their calves after the Deepwater Horizon oil spill, excluding Y35, survived pregnancy themselves but were seen again and again in the months after their due dates without any young. Dolphin calves stick close to their mothers’ sides in the first two or three months after birth, indicating that these pregnant dolphins also had calves that did not survive.

At least half of the dolphins with failed pregnancies also suffered from moderate-to-severe lung disease, a symptom associated with exposure to petroleum products. The only two dolphins to give birth to healthy calves had relatively minor lung conditions.

Dolphin Y35 wasn’t the only one of the 32 dolphins being monitored in Barataria Bay to disappear in the months following her 2011 examination. Three others were never sighted again in the 15 straight surveys tracking these dolphins. Or rather, they were never seen again alive. One of them, Y12, was a 16-year-old adult male whose emaciated carcass washed up in Louisiana only a few weeks before the pregnant Y35 was last seen. In fact, the number of dolphins washing up dead in Barataria Bay from August 2010 through 2011 was the highest ever recorded for that area.

Survival rate in this group of dolphins was estimated at only 86%, down from the 95-96% survival seen in dolphin populations not in contact with Deepwater Horizon oil. The marshy maze of Barataria Bay falls squarely inside the footprint of the Deepwater Horizon oil spill, and its dolphins and others along the northern Gulf Coast have repeatedly been found to be sick and dying in historically high numbers. Considering how deadly this oil spill has been for Gulf bottlenose dolphins and their young, researchers expect recovery for these marine mammals to be a long time coming.

http://www.sciencedaily.com/ Science Daily

http://www.sciencedaily.com/releases/2015/11/151104095227.htm Original web page at Science Daily

Tags Birds (pet; ornamental; prey e.g. falcons), Endocrinology, Toxicology

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Estrogen, shrubbery, and the sex ratio of suburban frogs

Post author By Vetscite
Post date October 20, 2015

A new Yale study shows that estrogen in suburban yards is changing the ratio of male and female green frogs at nearby ponds. Higher levels of estrogen in areas where there are shrubs, vegetable gardens, and manicured lawns are disrupting frogs’ endocrine systems, according to the study. That, in turn, is driving up the number of female frogs and lowering the number of male frogs.

The research appears in the journal Proceedings of the National Academy of Sciences. It is based on tests conducted at 21 ponds in southwestern Connecticut in 2012. Previous studies have shown similar effects caused by agricultural pesticides and wastewater effluent; the new study finds amphibian endocrine disruption also exists in suburban locales.

“In suburban ponds, the proportion of females born was almost twice that of frog populations in forested ponds,” said lead author Max Lambert, a doctoral student at the Yale School of Forestry & Environmental Studies. “The fact that we saw such clear evidence was astonishing.”

The researchers looked at ponds with varying degrees of suburban neighborhood impact — with entirely forested ponds at one end of the spectrum, and ponds that were heavily surrounded by suburbia at the other end. The sites included ponds linked to both septic systems and sewer lines. In many cases, the researchers needed to obtain permission from homeowners to survey their back yards.

“Our work shows that, for a frog, the suburbs are very similar to farms and sewage treatment plants,” Lambert said. “Our study didn’t look at the possible causes of this, partly because the potential relationship between lawns or ornamental plantings and endocrine disruption was unexpected.” Lambert noted that some plants commonly found in lawns, such as clovers, naturally produce phytoestrogens. The simple act of maintaining a lawn, in other words, may be one source of the contamination.

There also are possible implications for other species that use suburban ponds, note the researchers. Those species include other amphibians, such as wood frogs, spring peepers, gray tree frogs, and salamanders, as well as birds, turtles, and mammals. “Some of our lab’s current work is trying to understand how the suburbs influence sexual development in other species,” Lambert said.

http://www.sciencedaily.com/ Science Daily

http://www.sciencedaily.com/releases/2015/09/150907190643.htm Original web page at Science Daily

Tags Amphibians, Endocrinology

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Targeting glucose production in liver may lead to new diabetes therapies

Post author By Vetscite
Post date September 22, 2015

Disabling a critical checkpoint for controlling glucose production in the liver reduces blood sugar levels in mouse models of type 2 diabetes. High blood sugar is a defining characteristic of Type 2 diabetes and the cause of many of the condition’s complications, including kidney failure, heart disease, and blindness. Most diabetes medications aim to maintain normal blood sugar (glucose) levels and prevent high blood sugar by controlling insulin.

A new University of Iowa study shows that another biological checkpoint, known as the Mitochondrial Pyruvate Carrier (MPC), is critical for controlling glucose production in the liver and could potentially be a new target for drugs to treat diabetes. The study, led by Eric Taylor, PhD, UI assistant professor of biochemistry, and published Sept. 3 in the journal Cell Metabolism, shows that disabling MPC reduces blood sugar levels in mouse models of Type 2 diabetes.

Glucose is primarily made in the liver and requires the molecular building blocks to pass through specialized cellular compartments called mitochondria. Mitochondria use a small molecule called pyruvate as the starting point for synthesizing glucose, and the pyruvate is imported into the mitochondria through the MPC portal.

Taylor and his colleagues showed that disabling the MPC in mouse livers shuts down this major route of glucose production. However, because glucose is a critical cellular fuel, there are “back-up” mechanisms. When the MPC was disabled in mouse livers, another glucose-producing mechanism was activated to compensate. This alternative mechanism uses molecules from protein as the building blocks for glucose.

“Essentially, what we found is that disruption of the MPC makes the liver less efficient at making glucose and, as a result, the liver burns more fat for energy, makes less cholesterol, and makes less glucose in models of diabetes,” explains Taylor, who also is a member of the Fraternal Order of Eagles Diabetes Research Center at the UI. “This overall change in metabolism matches outcomes that would be therapeutically desirable for people with diabetes.”

The new research is based on earlier work by Taylor’s group and others, which identified the genes for MPC. In the new study, the UI researchers use this genetic information to specifically disrupt MPC activity in animal models. They found that disrupting MPC in normal mice doesn’t cause low blood sugar, or hypoglycemia, which would be important for the safety of any new treatment targeting MPC. In mouse models of Type 2 diabetes, however, loss of the MPC activity in the liver decreases high blood sugar and improves glucose tolerance. The study also suggests that MPC activity contributes to excess glucose production and high blood sugar levels in Type 2 diabetes.

The therapeutic potential of targeting glucose production in the liver is supported by the fact that metformin, the most widely used and staple treatment for Type 2 diabetes, also decreases glucose synthesis in the liver by disrupting mitochondrial metabolism, although the exact mechanisms underlying this drug’s action on mitochondria are controversial

However, Taylor cautions that additional research will be required to determine if inhibiting MPC activity might be a safe approach for human therapies, especially in people under high levels of physical stress or with other medical complications.

The team plans to extend their studies to cultured human liver cells to determine if disabling the MPC produces the same metabolic effects as seen in the mouse studies, and to make sure that inhibiting this checkpoint does not produce dangerous side effects

http://www.sciencedaily.com/ Science Daily

http://www.sciencedaily.com/releases/2015/09/150903131723.htm Original web page at

Tags Endocrinology, Rodents/Lags

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* Underlying cause of diabetes in dogs

Post author By Vetscite
Post date September 22, 2015

In a new effort, researchers from the University of Pennsylvania and Baylor College of Medicine have used advanced imaging technology to fill in details about the underlying cause of canine diabetes, which until now has been little understood. For the first time, they’ve precisely quantified the dramatic loss of insulin-producing beta cells in dogs with the disease and compared it to the loss observed in people with type I diabetes.

“The architecture of the canine pancreas has never been studied in the detail that we have done in this paper,” said Rebecka Hess, professor of internal medicine at Penn’s School of Veterinary Medicine and a study author.

Despite important differences between the disease in dogs and humans, the study also identified key similarities that suggest investigating diabetes in dogs may yield valuable insights into treating human.

The research was led by Emily Shields, currently a graduate student in Penn’s Perelman School of Medicine, who completed much of the work as a high school and then college student in labs at Penn and Baylor. Jake A. Kushner, formerly of Penn and now McNair Medical Institute Scholar and chief of pediatric diabetes and endocrinology at Baylor College of Medicine, was senior author. Together with Hess, they collaborated with Penn Vet’s Thomas J. Van Winkle, Matthew M. Rankin of Penn Medicine and Children’s Hospital of Philadelphia and Baylor’s Carol J. Lam and Aaron R. Cox. Their study was published in PLOS ONE.

Canine diabetes can be managed with insulin, similar to type I diabetes in humans. But, unlike the human version of the disease, dogs typically develop diabetes in middle or old age, while people with type 1 diabetes are typically diagnosed during childhood. In addition, while type 1 diabetes is known to be an autoimmune condition, researchers haven’t found conclusive evidence that the same is true in dogs.

To learn more about the factors that contribute to canine diabetes, the researchers made use of a repository of donated tissue samples from dogs — 23 with diabetes and 17 without — who had been treated at Penn Vet’s Ryan Hospital and later died. The team used robotic microscopes that can rapidly move around a slide taking images of pancreas tissue samples, which were analyzed by computer to determine the contents. “In a larger view we could look at the entire cross-section of pancreas to determine how many islets there were and how big they were,” Shields said. “Then we could zoom in to differentiate beta cells, which produce insulin, from alpha cells, which produce glucagon.”

They found that beta cells dropped off in dramatic fashion in diabetic dogs, reduced 13-fold compared to non-diabetic animals. They also found that non-diabetic canine islets contained a large percentage of beta cells, comprising about 80 percent of endocrine cells. In contrast, beta cells comprise slightly more than 50 percent of endocrine cells in non-diabetic human islets. The researchers noted that this may mean that dogs need to lose more beta cells before experiencing symptoms of diabetes. The observation could explain why dogs develop a form of diabetes that is similar to type 1 diabetes, but do so later in life, compared to humans.

They also identified features of the islets and pancreatic structures that were different in dogs than in humans. “In sharp contrast to human diabetes, in which there are a lot of islets still present but none contains insulin, we found in dogs that only a few beta cells were present and the islets were incredibly small,” Kushner said.

While the researchers had hoped to be able to visualize immune cells infiltrating the pancreas and attacking beta cells, they failed to do so. While other signs point to canine diabetes being an autoimmune condition, this study did not find a “smoking gun.

Though the work highlights differences between canine and human diabetes, it also points to a number of similarities that distinguish the two from diabetes in rodents, which are often used as models to study the disease. For example, the scientists observed that dogs’ beta cells were distributed throughout the islets, as beta cells in humans are. In rodents, beta cells are concentrated in the center of the islet. “Now that we know more about the disease in dogs and in particular how they are similar to humans in ways that rodents are not, it makes them more appealing as a model,” Kushner said.

At Penn, Hess is currently working to look for genetic markers in dogs that heighten a dog’s risk of developing diabetes. “My hope is that with genetic screening we can eventually identify pre-clinical diabetic dogs, potentially making breeding recommendations that could decrease the incidence and prevalence of the disease in dogs,” Hess said.

http://www.sciencedaily.com/ Science Daily

http://www.sciencedaily.com/releases/2015/08/150824140956.htm Original web page at Science Daily

Tags Dogs, Endocrinology

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Climate change could leave Pacific Northwest amphibians high and dry

Post author By Vetscite
Post date September 22, 2015

Far above the wildfires raging in Washington’s forests, a less noticeable consequence of this dry year is taking place in mountain ponds. The minimal snowpack and long summer drought that have left the Pacific Northwest lowlands parched also affect the region’s amphibians due to loss of mountain pond habitat. According to a new paper published Sept. 2 in the open-access journal PLOS ONE, this summer’s severe conditions may be the new normal within just a few decades.

“This year is an analog for the 2070s in terms of the conditions of the ponds in response to climate,” said Se-Yeun Lee, research scientist at University of Washington’s Climate Impacts Group and one of the lead authors of the study. We’ve seen that the lack of winter snowpack and high summer temperatures have resulted in massive breeding failures and the death of some adult frogs,” said co-author Wendy Palen, an associate professor at Canada’s Simon Fraser University who has for many years studied mountain amphibians in the Pacific Northwest. “More years like 2015 do not bode well for the frogs.”

Mountain ponds are oases in the otherwise harsh alpine environment. Brilliant green patches amid the rocks and heather, the ponds are breeding grounds for Cascades frogs, toads, newts and several other salamanders, and watering holes for species ranging from shrews to mountain lions. They are also the cafeterias of the alpine for birds, snakes and mammals that feed on the invertebrates and amphibians that breed in high-altitude ponds.

The authors developed a new model that forecasts changes to four different types of these ecosystems: ephemeral, intermediate, perennial and permanent wetlands. Results showed that climate-induced reductions in snowpack, increased evaporation rates, longer summer droughts and other factors will likely lead to the loss or rapid drying of many of these small but ecologically important wetlands.

According to the study, more than half of the intermediate wetlands are projected to convert to fast-drying ephemeral wetlands by the year 2080. These most vulnerable ponds are the same ones that now provide the best habitat for frogs and salamanders.

At risk are unique species such as the Cascades frog, which is currently being evaluated for listing under the Endangered Species Act. Found only at high elevations in Washington, Oregon and California, Cascades frogs can live for more than 20 years and can survive under tens of feet of snow. During the mating season, just after ponds thaw, the males make chuckling sounds to attract females.

“They are the natural jesters of the alpine, incredibly tough but incredibly funny and charismatic,” said Maureen Ryan, the other lead author, a former UW postdoctoral researcher who is now a senior scientist with Conservation Science Partners.

The team adapted methods developed for forecasting the effects of climate change on mountain streams. Wetlands usually receive little attention since they are smaller and often out of sight. Yet despite their hidden nature, ponds and wetlands are globally important ecosystems that help store water and carbon, filter pollution, convert nutrients and provide food and habitat to a huge range of migratory and resident species. Their sheer numbers — in the tens of thousands across the Pacific Northwest mountain ranges — make them ecologically significant.

“It’s hard to truly quantify the effects of losing these ponds because they provide so many services and resources to so many species, including us,” Ryan said. “Many people have predicted that they are especially vulnerable to climate change. Our study shows that these concerns are warranted.

Land managers can use the study’s maps to prepare for climate change. For example, Ryan and co-authors are working with North Cascades National Park, where park biologists are using the wetland projections to evaluate and update priorities for managing introduced fish and restoring natural alpine lake habitat.

http://www.sciencedaily.com/ Science Daily

http://www.sciencedaily.com/releases/2015/09/150904144459.htm Original web page at Science Daily

Tags Amphibians, Endocrinology

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Lipid enzyme heightens insulin sensitivity, potential therapy to treat Type 2 diabetes

Post author By Vetscite
Post date August 11, 2015

Reducing high concentrations of a fatty molecule that is commonly found in people with diabetes and nonalcoholic fatty liver disease rapidly improves insulin sensitivity, UT Southwestern Medical Center diabetes researchers have found.

Insulin is a crucial hormone that helps the body convert sugar into energy, absorb nutrients, and reduce the storage of sugars as fat. Poor insulin sensitivity reduces the effectiveness of these processes and results in diabetes and fatty liver disease. UT Southwestern researchers showed that introducing an enzyme called ceramidase in diabetic mice returned their insulin sensitivity to normal.

“Lowering ceramides may also make people more insulin-sensitive,” said study senior author Dr. Philipp Scherer, Director of the Touchstone Center for Diabetes Research at UT Southwestern. “Our findings suggest a new means to potentially treat Type 2 diabetes and nonalcoholic fatty liver disease.” Though no such therapy currently exists, Dr. Scherer said a drug form of the enzyme ceramidase likely could be developed. The findings are outlined in the journal Cell Metabolism.

When more fatty acids are consumed than the body burns off, some excess fat is converted to ceramide. When too much ceramide builds up, the lipid interferes with insulin signaling, resulting in insulin resistance and possibly diabetes or nonalcoholic fatty liver disease.

“It is a nasty lipid at times,” said Dr. Scherer, Professor of Internal Medicine and Cell Biology who holds the Gifford O. Touchstone, Jr. and Randolph G. Touchstone Distinguished Chair in Diabetes Research. “If we can lower ceramide, then we believe the body’s metabolism will return to normal.”

In their new study, the scientists showed that inducing ceramidase in the diabetic mice triggered degradation of ceramide in both fat tissue and the liver. This action then normalized insulin sensitivity and had the same beneficial effect when ceramidase was induced in the liver or fat cells. Excess ceramide was converted into sphingosine, another lipid byproduct. Both ceramide and sphingosine are energy sources, but the two lipids have contrary metabolic signaling power. Too much ceramide signals insulin resistance and inflammation, while more sphingosine does the opposite.

“This research suggests the existence of a rapidly acting “cross talk” between liver and adipose (fat) tissue in which ceramide and sphingosine critically regulate glucose metabolism and the uptake of lipids by the liver,” Dr. Scherer said.

http://www.sciencedaily.com/ Science Daily

http://www.sciencedaily.com/releases/2015/07/150716135229.htm Original web page at Science Daily

Tags Endocrinology, Rodents/Lags

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Neuroscience: The hard science of oxytocin

Post author By Vetscite
Post date July 28, 2015

As researchers work out how oxytocin affects the brain, the hormone is shedding its reputation as a simple cuddle chemical. In April 2011, Robert Froemke and his team were reprogramming the brains of virgin mice with a single hormone injection.

Before the treatment, the female mice were largely indifferent to the cries of a distressed baby, and were even known to trample over them. But after an injection of oxytocin, the mice started to respond more like mothers, picking up the mewling pup in their mouths. Froemke, a neuroscientist at New York University’s Langone Medical Center in New York City, was monitoring the animals’ brains to find out why that happened.

At first, the mice showed an irregular smattering of neural impulses when they heard the baby’s cries. Then, as the oxytocin kicked in, the signal evolved into a more orderly pattern typical of a maternal brain. The study showed in unusual detail how the hormone changed the behaviour of neurons. “Oxytocin is helping to transform the brain, to make it respond to those pup calls,” Froemke says.

Oxytocin has been of keen interest to neuroscientists since the 1970s, when studies started to show that it could drive maternal behaviour and social attachment in various species. Its involvement in a range of social behaviours, including monogamy in voles, mother–infant bonding in sheep, and even trust between humans, has earned it a reputation as the ‘hug hormone’. “People just concluded it was a bonding molecule, a cuddling hormone, and that’s the pervasive view in the popular press,” says Larry Young, a neuroscientist at Emory University in Atlanta, Georgia, who has been studying the molecule since the 1990s.

“What we need to start thinking about is the more fundamental role that oxytocin has in the brain.” That view has led some clinicians to try oxytocin as a treatment for psychiatric conditions such as autism spectrum disorder. But the early trials have had mixed results, and scientists are now seeking a deeper understanding of oxytocin and how it works in the brain. Researchers such as Froemke are showing that the hormone boosts neuronal signals in a way that could accentuate socially relevant input such as distress calls or possibly facial expressions. And clinical researchers are starting a wave of more ambitious trials to test whether oxytocin can help some types of autism.

The work is leading to a more sophisticated view of the hormone and its complex effects on behaviour — one that will take many types of expertise to refine. “The oxytocin field has just matured and ripened enough to draw in researchers from traditionally separate fields, catapulting this forward,” says Young.

Oxytocin’s story starts back in the early 1900s, when biochemists discovered that a substance from the posterior pituitary gland could promote labour contractions and lactation. When scientists later discovered the hormone responsible, they named it oxytocin after the Greek phrase meaning ‘rapid birth’. Oxytocin is produced mainly by the brain’s hypothalamus; in the 1970s, studies revealed that oxytocin-producing neurons send signals throughout the brain, suggesting that the hormone had a role in regulating behaviour.

http://www.nature.com/news/index.html Nature

http://www.nature.com/news/neuroscience-the-hard-science-of-oxytocin-1.17813 Original webpage at Nature

Tags Endocrinology, Neurology, Rodents/Lags

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* For black rhino, zoo diet might be too much of a good thing

Post author By Vetscite
Post date July 14, 2015

A new study shows that captive black rhinos — but not their wild counterparts — are at high risk for two common health problems suffered by millions of humans: inflammation and insulin resistance. The finding suggests captive black rhinos have metabolic problems. In humans, these same conditions can both result from a rich diet and sedentary lifestyle and contribute to obesity and other diseases.

To be clear, this study does not suggest that zoos cause health problems in black rhinos, said Pam Dennis, clinical assistant professor of veterinary preventive medicine at The Ohio State University and senior author of the study. Just as research in humans continues to shed new light on the metabolic complexities of obesity, she said veterinary research is “just scratching the surface” of the same kind of thinking about animal health.

“We now recognize that obesity in humans leads to increased inflammation and a whole cascade or problems ranging from heart disease to immune dysfunction,” Dennis said. “This is entering the vocabulary in zoo medicine, that obesity is much more than just a weight issue.”

Dennis, also a veterinary epidemiologist at Cleveland Metroparks Zoo, said a change in zoo diet management is the most feasible first step toward improving captive black rhinos’ health.

Worldwide, only about 5,000 black rhinos remain — a drop from an estimated 100,000 in the 1960s. Animals in the wild are threatened by poaching for their horns, and the roughly 250 captive black rhinos are at risk for a range of diseases. “Given their plight on the planet, we need to do something for each and every one of them. If we can help the ones we are caring for in zoos, that could make the difference for the species,” she said.

The research, co-led by first author Mandi Schook, associate research curator at Cleveland Metroparks Zoo, appears in the June-July issue of the journal General and Comparative Endocrinology. The African black rhinoceroses living in captivity are known to be at higher risk for a number of unusual diseases that include anemia, degraded muscle tissue, skin ulcers, liver disease, iron overload and low phosphate in the blood.

While some of these conditions can be treated, they often lead to death. In one large study of black rhinos living in North American zoos over a 70-year period, 73 percent of the captive-born animals died before reproducing. Reduced phosphate in the blood is common to most of the health problems observed in captive black rhinos. Because low phosphate has been linked to insulin resistance in humans, Dennis set out to see whether the same could be true in the black rhino species she has studied for some time.

The scientists analyzed biomarkers in blood samples from 86 captive and 120 free-ranging black rhinos of both sexes and various ages, measuring two proteins signaling the presence of inflammation, the ratio of insulin to glucose, phosphate levels and iron stores.

Because this is the first known comparison of disease markers in captive and wild animals, the researchers used markers from both sick and healthy animals to set reference points for the comparison. They also used data from horses, the closest domestic relative of the rhinoceros, to create reference points for normal and disease conditions.

In all cases, samples from the captive black rhinos contained more markers for disease. About 95 percent of captive black rhinos had significantly higher concentrations of iron in their blood than did wild rhinos, and a ninefold difference in the insulin-to-glucose ratio between wild and zoo animals suggested a much higher likelihood of insulin resistance in the captive rhinos. Consistently higher levels of pro-inflammatory proteins in the blood of zoo-dwelling rhinos also indicated chronic inflammation.

“We know in other species, including humans, how to address inflammation and insulin resistance, primarily with diet and exercise,” Dennis said. “Can we apply some of that knowledge from other species to black rhinos to improve their care?” Black rhinos are browsers that eat leaves, branches and parts of trees in the wild. Their zoo diets mainly consist of grass or hay, milled grains and fruits and vegetables.

“We are providing good, nutritious, high-quality food. And we may be overdoing it. We’re just learning that providing high-quality food in excess can cause problems,” Dennis said. “Knowing what we know now, how do we manage these animals in zoos in ways that decrease health risks? I think we’re going to have to manage their nutrition differently.”

Promoting exercise for these one-ton animals is another thing altogether. It’s not an issue of space, but of inclination, Dennis said. Adult rhinos tend to stand around or lie in the shade most of the time, and are motivated to move at mealtime to their feed locations. “We need to work harder to ensure that they move around just like we need to work harder to ensure we move around,” she said.

The finding can’t be extended to other species or even to other rhinos — the white rhino, for example, is a grazer with no known disease syndromes in captivity. However, insulin resistance and obesity, problems shared by humans and domestic animals, are becoming more common subjects of study among zoo veterinarians. “That’s the challenge when dealing with exotic species — figuring this out in the black rhino doesn’t at all mean it applies across the board,” Dennis said.

http://www.sciencedaily.com/ Science Daily

http://www.sciencedaily.com/releases/2015/06/150622150824.htm Original web page at Science Daily

Tags Endocrinology, Zoo/Wildlife

News

* Gold standard management of the diabetic cat

Post author By Vetscite
Post date July 14, 2015

An expert panel of veterinary clinicians and academics has been convened to produce practical guidance to help veterinary teams deliver optimal management for the increasing numbers of diabetic cats that are presenting to practices. The International Society of Feline Medicine (ISFM), the veterinary division of International Cat Care, has convened an expert panel of veterinary clinicians and academics to produce practical guidance to help veterinary teams deliver optimal management for the increasing numbers of diabetic cats that are presenting to practices.

Similar to type 2 (or adult-onset) diabetes in humans, there is thought to be a link between the increasing prevalence of diabetes mellitus in cats and rising levels of obesity, although other factors such as certain drug therapies and concurrent disease can also contribute to the problem of insulin resistance in cats. While generally straightforward to diagnose, feline diabetes can be challenging to manage.

The panel, which carefully reviewed clinical research studies to collate the best available evidence, has published its advice, ISFM Consensus Guidelines on the Practical Management of Diabetes Mellitus in Cats, in the March 2015 issue of the Journal of Feline Medicine and Surgery (JFMS).

The guidelines, which are free to access and download, focus on the most important aspects of managing diabetic cats including weight control, use of an appropriate diet, insulin therapy (highlighting the value of longer acting insulin preparations) and close monitoring of blood glucose concentrations (including in the home environment). Good diabetic control requires a long-term commitment and one of the keys to success is finding a treatment protocol that best fits in with owners’ daily lives. The panel recognises all too well that owners may give up on treatment, or even elect for euthanasia of the cat, if the disease impacts too negatively on them and their relationship with their cat. Moreover, with appropriate support and guidance from their veterinary practice, an owner can play an invaluable role in managing diabetes. A well-regulated cat will have a better prognosis and may also be more likely to go into diabetic remission, no longer requiring ongoing insulin therapy.

http://www.sciencedaily.com/ Science Daily

http://www.sciencedaily.com/releases/2015/03/150303105926.htm Original web page at Science Daily

Tags Cats, Endocrinology

News

* Environmental exposure to hormones used in animal agriculture greater than expected

Post author By Vetscite
Post date June 2, 2015

Research by an Indiana University environmental scientist and colleagues at universities in Iowa and Washington finds that potentially harmful growth-promoting hormones used in beef production are expected to persist in the environment at higher concentrations and for longer durations than previously thought. “What we release into the environment is just the starting point for a complex series of chemical reactions that can occur, sometimes with unintended consequences,” said Adam Ward, lead author of the study and assistant professor in the IU Bloomington School of Public and Environmental Affairs. “When compounds react in a way we don’t anticipate — when they convert between species, when they persist after we thought they were gone — this challenges our regulatory system.”

Numerical simulations performed in this study can help to predict the potential impact of environmental processes on contaminant fate to more effectively understand the potential for these unexpected effects. This study illustrates potential weaknesses in the U.S. system of regulating hazardous substances, which focuses on individual compounds and often fails to account for complex and sometimes surprising chemical reactions that occur in the environment. The publication, “Coupled reversion and stream-hyporheic exchange processes increase environmental persistence of trenbolone metabolites,” was published by Nature Communications and is now available online.

The study focuses on the environmental fate of trenbolone acetate, or TBA, a highly potent synthetic analogue of testosterone, used to promote weight gain in beef cattle. A majority of beef cattle produced in the U.S. are treated with TBA or one of five other growth hormones approved for use in animal agriculture. The compound and its byproducts are examples of contaminants of emerging concern called endocrine disruptors. In the environment they are capable of interfering with reproductive processes and behaviors in fish and other aquatic life.

TBA is implanted in the ears of beef cattle. The cattle metabolize the compound to produce 17-alpha-trenbolone, an endocrine disruptor that is chemically close to TBA. The metabolite makes its way to streams and rivers via manure that washes from feedlots or is applied to land as fertilizer. The compound breaks down rapidly when exposed to sunlight, and regulators once thought this attribute greatly reduced its environmental risk. But a 2013 study by Cwiertny, Kolodziej and others found that the breakdown products reverted back to 17-alpha-trenbolone in the dark. This means that, instead of permanent removal in sunlight, the compound would be expected to persist in stream environments, returning to its earlier form overnight in the dark, shallow streambed where stream water mixes with groundwater, known as the hyporheic zone.

Ward and his collaborators set out to learn how much longer trenbolone may persist in the environment because of its unique reactivity, and whether this added persistence matters for aquatic ecosystems. Using mathematical modeling techniques, they show that concentrations of TBA metabolites may be about 35 percent higher in streams than previously thought. And the compounds persist longer, resulting in 50 percent more biological exposure than anticipated. That’s a problem, Ward said, because even very low concentrations of these powerful endocrine disruptors have been shown to have significant effects on stream life.

“These compounds have the potential to disrupt entire ecosystems by altering reproductive cycles in many species, including fish,” Ward said. “We expect impacts that extend through the aquatic food web.” Studies by the U.S. Geological Survey and other agencies have found endocrine disruptors to be present in many streams, rivers and lakes, and several similar compounds have even been found in drinking water. While TBA and its metabolites are the focus of the study, Ward said those compounds are representative of many others — suggesting it may be time to update regulatory approaches to better include a wide range of findings from modern research.

“Our focus on individual compounds has been highly successful in getting us where we are today, which is some of the cleanest water in the world,” Ward said. “The next step is thinking about unexpected reactions that occur in the environment and how we can manage the diverse group of potential products and their joint effect on the environment and human health.”

http://www.sciencedaily.com/ Science Daily

http://www.sciencedaily.com/releases/2015/05/150508082829.htm Original web page at Science Daily

Tags Bovine, Endocrinology