In the News

Gut Bacteria May Hold Key to Treating Autoimmune Disease

Klean Athlete® Launches NSF Certified for Sport® Klean Creatine and Targeted Product Bundles to Help Fuel Athletic Training and Recovery

Blood pressure lowering effect of melatonin: Study results presented at American Heart Association hypertension sessions

Link between Brain, Bone in Alzheimer's Disease Identified

CBD Oil May Reduce Frequency and Severity of Epileptic Seizures

Simple Walking Program Provides Physical and Mental Benefits to Dialysis Patients

Gut Bacteria May Hold Key to Treating Autoimmune Disease

Defects in the body’s regulatory T cells (T reg cells) cause inflammation and autoimmune disease by altering the type of bacteria living in the gut, researchers from The University of Texas Health Science Center at Houston have discovered. The study, “Resetting microbiota by Lactobacillus reuteri inhibits T reg deficiency–induced autoimmunity via adenosine A2A receptors,” published online in The Journal of Experimental Medicine, suggests that replacing the missing gut bacteria, or restoring a key metabolite called inosine, could help treat children with a rare and often fatal autoimmune disease called IPEX syndrome.

T reg cells suppress the immune system and prevent it from attacking the body’s own tissues by mistake. Defects in T reg cells therefore lead to various types of autoimmune disease. Mutations in the transcription factor Foxp3, for example, disrupt T reg function and cause IPEX syndrome. This inherited autoimmune disorder is characterized by a variety of inflammatory conditions including eczema, type I diabetes, and severe enteropathy. Without a stem cell transplant from a suitable donor, IPEX syndrome patients usually die before the age of two.

Autoimmune diseases can also be caused by changes in the gut microbiome, the population of bacteria that reside within the gastrointestinal tract. In the study, the team led by Yuying Liu and J. Marc Rhoads at The University of Texas Health Science Center at Houston McGovern Medical School find that mice carrying a mutant version of the Foxp3 gene show changes in their gut microbiome at around the same time that they develop autoimmune symptoms. In particular, the mice have lower levels of bacteria from the genus Lactobacillus. The researchers discovered that by feeding the mice with Lactobacillus reuteri, they could “reset” the gut bacterial community and reduce the levels of inflammation, significantly extending the animals’ survival.

Bacteria can secrete metabolic molecules that have large effects on their hosts. The levels of a metabolite called inosine were reduced in mice lacking Foxp3 but were restored to normal after resetting the gut microbiome with L. reuteri. The researchers found that, by binding to cell surface proteins called adenosine A2A receptors, inosine inhibits the production of Th1 and Th2 cells. These pro-inflammatory T cell types are elevated in Foxp3-deficient mice, but their numbers are diminished by treatment with either L. reuteri or inosine itself, reducing inflammation and extending the animals’ life span.

“Our findings suggest that probiotic L. reuteri, inosine, or other A2A receptor agonists could be used therapeutically to control T cell–mediated autoimmunity,” says Yuying Liu.

Conflict of interest statement: Some of the authors of this study, including Yuying Liu and J. Marc Rhoads, have a patent application pending on use of inosine and A2A agonists in IPEX syndrome.

He, B., et al. 2017. J. Exp. Med. https://doi.org/10.1084/jem.20160961

About The Journal of Experimental Medicine

The Journal of Experimental Medicine (JEM) features peer-reviewed research on immunology, cancer biology, stem cell biology, microbial pathogenesis, vascular biology, and neurobiology. All editorial decisions are made by research-active scientists in conjunction with in-house scientific editors. JEM provides free online access to many article types from the date of publication and to all archival content. Established in 1896, JEM is published by The Rockefeller University Press. For more information, visit jem.org.

SOURCE The Rockefeller University Press

Klean Athlete® Launches NSF Certified for Sport® Klean Creatine and Targeted Product Bundles to Help Fuel Athletic Training and Recovery

Klean Athlete, a line of science-based, NSF Certified for Sport^® nutritional supplements designed to give athletes a safe, effective nutritional foundation to fuel training and fortify performance, launched Klean Creatine to help athletes increase body strength, build muscle mass and recover more quickly from demanding exercise.* This latest addition to the Klean Athlete product line furthers the company's commitment to creating safe and effective supplements.

"For sprinters, stop-and-go sports and weight training, creatine may increase the hustle on the track or field and the muscle in the gym," said Leslie Bonci, a registered dietitian and sports nutrition expert. "Klean Athlete NSF Certified for Sport Creatine takes the guesswork out and puts the guarantee in to ensure the quality, safety and efficacy of the supplement."

The majority of sports injuries are the result of minor trauma to muscles, ligaments, and/or tendons. Creatine may increase strength, fat-free mass, and muscle morphology with concurrent heavy resistance training more than resistance training alone to help athletes develop strong, reliable muscles. The NSF Certified for Sport seal also means increased safety and confidence for elite athletes. Each product undergoes a meticulous testing and verification process, through which every product lot is screened for more than 245 athletic-banned substances based on the WADA list that could potentially compromise an athlete's career. This guarantees that when athletes see Klean Athlete products, they know they are consuming safer nutritional supplements and competing with the highest level of integrity and responsibility as an athlete.

"The USA Water Polo National Teams have worked with Klean Athlete throughout the 2016 season to ensure our athletes have regular access to safe, NSF Certified for Sport nutritional supplements so they can consistently compete at their best," explains John Abdou, USA Water Polo's high performance director. "We look forward to introducing Klean Creatine for the 2017 season."

Klean Athlete also announced new product bundles tailored to the type, intensity, frequency, and duration of athletic activity, making it easier than ever for athletes to optimize their nutritional protocol based on their targeted needs. New bundle offerings include:

• Starter Bundle — For individuals who engage in at least 30 minutes of both aerobic and resistance training, three or more days per week. Whether the goal is to improve one's physique or enhance one's competitive game with functional strength and stamina, this bundle will help athletes achieve their goals.*
• Foundation Bundle — For everyday use, to help athletes maintain optimal health and perform at their best. These are the basics.*
• The Strength & Conditioning I Bundle — For athletes who perform strength training two to four days per week at a moderate intensity.*
• Strength & Conditioning II Bundle — For highly committed elite or professional athletes looking to build strength, add lean muscle, and improve explosive power for a particular sport or athletic discipline.*
• Endurance I Bundle — For participatory and recreational athletes who engage in consistent and repetitive aerobic exercise two to four days a week, for at least 20 to 60 minutes per session and at a moderate intensity (steady but not to the point of maximal effort).*
• Endurance II Bundle — For committed endurance athletes who regularly train five to seven days a week, at a moderate to high intensity, for at least one hour per training session, race, or competition.*

Klean Athlete is a line of NSF Certified for Sport^® nutritional supplements. In addition to being formulated without wheat or gluten, all products are free of artificial coloring, flavoring, and sweeteners. The line was developed for athletes, by athletes, to provide a strong nutritional foundation to live healthy, train smart, and compete at the highest level, and also integrates seamlessly into an athlete's daily regimen. Athletes, coaches, and health care professionals know Klean Athlete products are safe sports supplements designed to help athletes reach optimal performance.*

For more information, visit http://www.kleanathlete.com/products/supplements/klean-creatine.html.

*These statements have not been evaluated by the Food and Drug Administration. These products are not intended to diagnose, treat, cure, or prevent any disease.

SOURCE Klean Athlete

Blood pressure lowering effect of melatonin: Study results presented at American Heart Association hypertension sessions

A study to determine the blood pressure lowering effect of melatonin in both younger and older normotensive and pre-hypertensive individuals was conducted at Thomas Jefferson University in Philadelphia, Pennsylvania, and presented as a poster presentation at the recent American Heart Association hypertension sessions.

The study, “Blood Pressure Lowering Effect of Melatonin in a Mixed Cohort of Younger and Older Non-Hypertensive Adults,” was conducted under the direction of Cynthia Cheng, MD, PhD, and Scott W. Keith, PhD, from the Departments of Family and Community Medicine/Biostatistics, Jefferson Medical College, and Nalaka S. Gooneratne, MD, MSc, of the Department of Medicine, University of Pennsylvania, Philadelphia.

Two successive blood pressure readings, with a one-minute interval between measurements, were taken from 23 participants in the seated position following 10 minutes of rest. A Dinamap ProCare 100 automatic blood pressure monitor with appropriate cuff size was used on the left arm of all study participants. All subjects had office and 24-hour ambulatory BP measured before and after dosing of 9 mg controlled release melatonin (melatonin group) or usual care (control group) for six weeks.

Mean systolic office pressure and 24-hour diastolic pressure were significantly lower following melatonin administration in both younger and older patients. Results were even more striking. The findings were of greater magnitude in the older patients.

The study concluded that these findings suggest possible future use of melatonin for lowering blood pressure in younger and older non-hypertensive individuals.

Support for the study was from a grant award provided by the National Heart, Lung and Blood Institute. The work was also supported by the Life Extension Foundation, Fort Lauderdale, Florida.

SOURCE Life Extension

Link between Brain, Bone in Alzheimer's Disease Identified

Researchers at NEOMED have just identified a major connection between areas of the brainstem—the ancient area that controls mood, sleep, and metabolism—and detrimental changes to bone in a preclinical model of Alzheimer's disease (AD). The study, titled "Early Evidence of Low Bone Density and Decreased Serotonergic Synthesis in the Dorsal Raphe of a Tauopathy Model of Alzheimer's Disease," is led by Christine Dengler-Crish, PhD, assistant professor of pharmaceutical sciences, and anatomy and neurobiology, and will be published in the upcoming issue of the Journal of Alzheimer's Disease, an international multidisciplinary journal that reports progress in understanding the causes, symptoms, and treatment of Alzheimer's.

More than five million Americans are living with Alzheimer's disease. Along with being the sixth leading cause of death in the U.S., Alzheimer's has major social, emotional, and financial consequences for patients and their families. Incurable and seemingly unstoppable, less than 5 percent of AD cases are due to a clear genetic reason, so it is hard to predict who will be at risk for acquiring this devastating disease.

Dr. Dengler-Crish and her research team that included graduate students Matthew Smith (NEOMED) and Gina Wilson (Kent State University) report that early reductions in bone mineral density (BMD) that occur in a preclinical model of AD are due to degeneration in an area of the brainstem that produces the majority of the brain's serotonin—a neurochemical that controls mood and sleep, which are two processes that are also affected early in AD.

One's bones may be one of the earliest indicators of brain degeneration in Alzheimer's disease

Reduced BMD, which sometimes leads to osteoporosis, translates to increased bone fracture risk, decreased quality of life, and increased mortality for AD patients. Furthermore, Dr. Dengler-Crish's research suggests that early bone loss and serotonin deficiency in AD may tell us something very important about how we approach diagnosing and treating this disease.

"Measurement of bone density, which is routinely performed in the clinic, could serve as a useful biomarker for assessing AD risk in our aging population," notes Dr. Dengler-Crish. "The findings of this study motivate us to explore the serotonin system as a potential new therapeutic target for this devastating disease."

Dengler-Crish, who received her bachelor's degree from Baldwin Wallace University, her master's in psychology from the University of Illinois at Chicago and her PhD in neuroscience from Vanderbilt University, has now been named an associate editor for the Journal of Alzheimer's Disease. She is excited to facilitate the work of other scientists in this important area. "I am thrilled to be able to assist the publication of researchers' innovative work, here and across the world, that is desperately needed to combat these currently incurable chronic diseases. Now more than ever, there is hope that we soon will be able to slow, stop or reverse the progression of these destructive neurodegenerative conditions."

"This is extremely exciting and has significant translational potential and relevance to early detection of the disease," noted Jason R Richardson, PhD, DABT, director for Neurodegenerative Disease and Aging Research at NEOMED.

SOURCE Northeast Ohio Medical University

Journal Reference:

Christine M. Dengler-Crish, Matthew A. Smith, Gina N. Wilson. Early Evidence of Low Bone Density and Decreased Serotonergic Synthesis in the Dorsal Raphe of a Tauopathy Model of Alzheimer’s Disease. Journal of Alzheimer's Disease, 2016

CBD Oil May Reduce Frequency and Severity of Epileptic Seizures

Cannabidiol oil, also known as CBD oil, reduces the frequency and severity of seizures in children and adults with severe, intractable epilepsy, according to findings presented by researchers from the University of Alabama at Birmingham at the American Epilepsy Society 70th Annual Meeting.

UAB researchers presented eleven abstracts, or research findings, at the meeting. A key finding was that CBD provided a significant reduction in frequency of seizures for a majority of the patients in the study, and that approximately two-thirds of patients saw a greater than 50 percent reduction in severity.

“It is encouraging that both frequency and severity of seizures appear to improve in the majority of patients in our study, patients who have limited treatment options,” said Jerzy P. Szaflarski, MD, PhD, professor in the Department of Neurology and director of the UAB Epilepsy Center. “Our research adds to the evidence that CBD may reduce frequency of seizures, but we also found that it appears to decrease the severity of seizures, which is a new finding.”

The results were based on an open-label study of 81 patients—42 children and 39 adults—who experienced four or more seizures per month. UAB launched the studies of CBD oil as a treatment for severe, intractable seizures in April 2015. The studies, an adult study at UAB and a pediatric study at Children’s of Alabama, were authorized by the Alabama Legislature in 2014 by legislation known as Carly’s Law.

After one month of beginning CBD therapy, 68 percent of the patients had experienced a greater than 25 percent reduction in seizure frequency, 58 percent had a greater than 50 percent reduction, 36 percent had a greater than 75 percent reduction, and 9 percent were seizure-free. Those results were maintained at three and six months.

To assess seizure severity, researchers led by Jenifer DeWolfe, MD, associate professor of neurology, used the Chalfont Seizure Severity Scale, a questionnaire given prior to therapy and re-administered at intervals throughout treatment. Fifty-seven patients were followed for three months: 67 percent experienced a more than 50 percent decrease in seizure severity, while 33 percent did not. Of 47 patients followed for six months, 64 percent had a greater than 50 percent decrease in seizure severity and 36 percent did not.

“These are encouraging results, but it is important to note that each patient may respond differently to CBD, and the dose for optimal seizures control varies,” said Martina Bebin, MD, professor of neurology and co-primary investigator of the CBD studies. “There appears to be an optimal CBD dose range where the patient achieves maximum benefit. If outside this CBD dosing range, the seizure frequency may not improve and may even increase. More research is needed, including determining why and how CBD helps some people with epilepsy but not others.”

Among the other UAB abstracts presented at the AES meetings:

·         CBD oil was associated with an improvement in mood, an effect independent of the extent of seizure reduction. Lead author Pongkiat Kankirawatana, MD, professor of pediatrics, says CBD oil may have overall positive effects on mood, which should be further investigated in patients with epilepsy and other chronic conditions in controlled studies. 

·         A study led by Szaflarski and Bebin found that the optimum dose in both children and adults was between 20 and 25 mg/kg/day. 

·         Jane Allendorfer, MD, assistant professor of neurology, found that CBD, in a selected group of patients with epilepsy who experienced overall improved seizure control, has the potential for positive cognitive effects that are associated with corresponding fMRI signal changes. 

·         One abstract reports on an interaction between warfarin, a drug used as an anticoagulant, and CBD. This underscores the importance of monitoring appropriate laboratory work in patients receiving CBD oil along with other medications, according to study lead Brannon Vines, MD, a clinical neurophysiology fellow.

·         Significant drug interactions were identified between CBD and commonly-used medications for epilepsy, including clobazam, rufinamide, topiramiate, zonisamide, and eslicarbazepine. This study, led by neurology fellow Tyler Gaston, MD, emphasizes the importance of monitoring anti-epilepsy drug levels during treatment with CBD.

·         Electrical discharges measured by EEG decreased significantly after initiation and maintenance of CBD, particularly in pediatric patients, according to a study led by Leslie Grayson, MD, a neurology fellow.

·         Using fMRI imaging, Amber Gregory, a graduate student in psychology, showed that persons with epilepsy showed gains in working memory that were associated with a shift in neural recruitment as examined with functional MRI.

·         An abstract aimed at examining associations between social determinants of health, such as age, gender and socioeconomic factors against health status, quality of life and mood states showed that higher age and low income were associated with lower health ratings among epilepsy patients, according to study led Magdalena Szaflarski, PhD, assistant professor of sociology.

The studies are designed to test the safety and tolerability of CBD oil in patients with intractable seizures. CBD oil, a derivative of the cannabis plant, is delivered orally as an oily liquid.

The oil used in the studies is produced under stringent requirements of the United States Food and Drug Administration by a licensed pharmaceutical company. It contains only traces of THC, the psychoactive component of marijuana. The process developed by GW Pharmaceuticals guarantees the consistency of the product that is provided to study participants.

About UAB

Known for its innovative and interdisciplinary approach to education at both the graduate and undergraduate levels, the University of Alabama at Birmingham is the state of Alabama’s largest employer and an internationally renowned research university and academic medical center; its professional schools and specialty patient-care programs are consistently ranked among the nation’s top 50. UAB’s Center for Clinical and Translational Science is advancing innovative discoveries for better health as a two-time recipient of the prestigious Center for Translational Science Award. Find more information at www.uab.edu and www.uabmedicine.org.

SOURCE The University of Alabama at Birmingham

Simple Walking Program Provides Physical and Mental Benefits to Dialysis Patients

In a recent study, a simple exercise program carried out at home improved dialysis patients’ walking performance and quality of life. The findings appear in an upcoming issue of the Journal of the American Society of Nephrology (JASN).

Studies have suggested that physical exercise can provide benefits for dialysis patients. To see if something as simple as walking may have positive effects, a team led by Carmine Zoccali, MD (CNR-IFC, Clinical Epidemiology and Physiopathology of Renal Diseases and Hypertension of Reggio Calabria, Italy), along with Fabio Manfredini, MD (University of Ferrara), and Francesca Mallamaci, MD (Reggio Cal Renal and Transplantation Unit and CNR), randomized 296 dialysis patients to normal physical activity or a low intensity exercise program—20 minutes of walking at low-moderate speed every second day—of gradually increasing intensity over 6 months (https://www.youtube.com/watch?v=ki8YX_t-0jA).

After 6 months, the distance covered during a 6-minute walking test improved in the exercise group (average distance: baseline 328 m; 6 months 367 m) but not in the control group (baseline 321 m; 6 months 324 m). Similarly, the 5 times sit-to-stand test time improved in the exercise group average time: baseline 20.5 seconds; 6 months 18.2 seconds) but not in the control group (baseline 20.9 seconds; 6 months 20.2 seconds). Cognitive function and quality of scores improved significantly in the exercise arm compared with the control arm.

“Poor physical functioning is perhaps the most pervasive and disabling disturbance in patients with advanced kidney disease who are on chronic dialysis,” said Dr. Zoccali. “While the effect of regular physical exercise training on physical performance in selected dialysis patients studied in standardized experimental settings in the laboratory is well documented, how exercise training should be articulated and implemented still remains an open problem. Our study shows that simple, home-based exercise programs hold potential for improving physical functioning in dialysis patients.”

Study co-authors include Graziella D’Arrigo, Rossella Baggetta, Davide Bolignano, Claudia Torino, Nicola Lamberti, Silvio Bertoli, Daniele Ciurlino, Lisa Rocca-Rey, Antonio Barill, Yuri Battaglia, Renato Rapanà, Alessandro Zuccalà, Graziella Bonanno, Pasquale Fatuzzo, Francesco Rapisarda, Stefania Rastelli, Fabrizio Fabrizi, Piergiorgio Messa Luciano De Paola, Luigi Lombardi, Adamasco Cupisti, Giorgio Fuiano, Gaetano Lucisano, Chiara Summaria, Michele Felisatti, Enrico Pozzato, Anna Maria Malagoni, Pietro Castellino, Filippo Aucella, Samar Abd ElHafeez, Pasquale Fabio Provenzano, Giovanni Tripepi, and Luigi Catizone.

Disclosures: The authors reported no financial disclosures.

The article, entitled “Exercise in Dialysis Patients: A Multi-Center, Randomized Clinical Trial,” is online at http://www.jasn.asnjournals.org/ on December 1, 2016; doi:10.1681/ASN.2016030378.

For more information, please visit http://www.asn-online.org or contact them at 202-640-4660.

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