Research findings could pave way for a fructose tolerance test

 

October 13, 2014

Beth Israel Deaconess Medical Center

The FGF21 hormone may be a reliable predictor of altered fructose metabolism and provide the basis for a "fructose tolerance test," researchers report. Determining the body’s metabolic response to fructose has been a difficult task, researchers say and consequently, there is no equivalent test to warn of impaired or altered fructose metabolism. That may soon change, thanks to new research.

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Increased consumption of table sugar and high-fructose corn syrup has been linked to rising rates of obesity and type 2 diabetes in the United States and throughout the world. Both sweeteners are commonly found in processed foods and sugar-sweetened beverages, and both are made up of nearly equal amounts of two basic sugars, glucose and fructose.

The effects of glucose ingestion in humans are well understood, in part, because they are easily assessed by performing a Glucose Tolerance Test, which measures serum glucose levels after glucose ingestion and has become the diagnostic cornerstone for modern diabetes care. Furthermore, the hormone insulin can also be easily measured to assess the acute metabolic effects of glucose ingestion and evaluate a person's risk for developing diabetes and cardiovascular disease.

But determining the body's metabolic response to fructose has been much more difficult, and consequently, there is no equivalent test to warn of impaired or altered fructose metabolism.

That may soon change. A new study led by investigators at Beth Israel Deaconess Medical Center (BIDMC) now finds that blood levels of the hormone Fibroblast Growth Factor 21 (FGF21) increases rapidly acutely and robustly after fructose ingestion. Reported online in Molecular Metabolism, the new findings suggest that FGF21 is a reliable predictor of altered fructose metabolism and, in essence, provides the basis for a "fructose tolerance test."

"Accumulating evidence suggests that the fructose component of sugar may have a particularly deleterious effect on health," explains co-senior author Mark Herman, MD, of the Division of Endocrinology, Diabetes and Metabolism at BIDMC and Assistant Professor of Medicine at Harvard Medical School (HMS). "If you feed animals or people higher-than-normal amounts of fructose, they become obese, less responsive to the key actions of insulin, and develop fatty liver disease and abnormal blood lipid levels. All of these increase the risk of developing diabetes and cardiovascular disease." Fructose is a pervasive presence throughout our foods: high fructose corn syrup, for example, can be found in everything from processed cookies and sweets to seemingly healthy foods, such as yogurt.

"Fructose is taken up by the liver as soon as it's ingested and very little of it makes it to peripheral blood where it might be sampled and measured," adds co-senior author Eleftheria Maratos-Flier, MD, HMS Professor of Medicine in the Division of Endocrinology, Diabetes and Metabolism at BIDMC. "This makes it very hard to determine how an individual responds to fructose ingestion. Furthermore, there has, to date, been no known hormonal response to fructose in the way that the hormone insulin responds to glucose."

Maratos-Flier has been studying the FGF21 hormone for almost a decade and previously found that in both humans and animals, FGF21 levels are elevated in association with obesity, insulin resistance, and non-alcoholic fatty liver disease. Herman's work, meanwhile, had focused on a cellular factor, Carbohydrate Responsive-Element Binding Protein (ChREBP), which senses simple sugars and responds by activating cellular gene expression programs. Observations that fructose potently activates ChREBP in rodent livers and that ChREBP can regulate FGF21 expression suggested to Maratos-Flier and Herman the intriguing hypothesis that fructose ingestion might stimulate production of circulating FGF21 in people.

To test this hypothesis, the researchers, led by first author Jody Dushay, MD, HMS Instructor in Medicine, recruited 10 lean, healthy study subjects. They first tested the effect of glucose on FGF21 by giving volunteers a drink of 75 grams of glucose and measuring blood levels over the course of five hours. There was no immediate effect on FGF21 levels although modest changes in FGF21 were seen three to four hours later. In contrast, after ingesting 75 grams of fructose, FGF21 levels dramatically increased by an average of 400 percent -- within only two hours.

"This tells us that fructose actively regulates FGF21 in humans," says Maratos-Flier. "The hormone-like response of FGF21 to fructose ingestion suggests that FGF21 might play an unanticipated role in regulating fructose metabolism. We were totally surprised by this dramatic effect becausej, to date, there has been no way of assessing the body's acute metabolic response to fructose ingestion. We haven't had a simple quick test like we have for glucose."

Furthermore, she adds, the findings demonstrated that the FGF21 response was exaggerated in subjects with metabolic disease, suggesting that either some aspect of fructose metabolism changes during the development of metabolic syndrome and/or there are innate differences in fructose metabolism among individuals and those with an exaggerated FGF21 response to fructose are predisposed to developing disease.

"For the first time, this provides an avenue for labs everywhere to easily study fructose metabolism in people," adds Herman. "This study provides a foundational observation for further investigation into the genetic and environmental determinants of an individual's metabolic response to fructose and this type of knowledge will be essential to develop personalized dietary recommendations as well as pharmacological strategies to prevent and treat cardiometabolic disease."

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Story Source:

The above story is based on materials provided by Beth Israel Deaconess Medical Center. Note: Materials may be edited for content and length.

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Beth Israel Deaconess Medical Center. "Research findings could pave way for a fructose tolerance test." ScienceDaily. ScienceDaily, 13 October 2014. <www.sciencedaily.com/releases/2014/10/141013123018.htm>.

 

New cancer drug to begin trials in multiple myeloma patients

 

October 13, 2014

Imperial College London

A new cancer drug has been developed, which researchers plan to trial in multiple myeloma patients by the end of next year. The researchers report how the drug, known as DTP3, kills myeloma cells in laboratory tests in human cells and mice, without causing any toxic side effects, which is the main problem with most other cancer drugs. The new drug works by stopping a key process that allows cancer cells to multiply.

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Scientists at Imperial College London have developed a new cancer drug which they plan to trial in multiple myeloma patients by the end of next year.

In a paper published today in the journal Cancer Cell, the researchers report how the drug, known as DTP3, kills myeloma cells in laboratory tests in human cells and mice, without causing any toxic side effects, which is the main problem with most other cancer drugs. The new drug works by stopping a key process that allows cancer cells to multiply.

The team have been awarded Biomedical Catalyst funding from the Medical Research Council (MRC) to take the drug into a clinical trial in multiple myeloma patients, scheduled to begin in late 2015.

Multiple myeloma is an incurable cancer of the bone marrow, which accounts for nearly two per cent of all cancer deaths.

Professor Guido Franzoso, from the Department of Medicine at Imperial College London, who led the research, said: "Lab studies suggest that DTP3 could have therapeutic benefit for patients with multiple myeloma and potentially several other types of cancer, but we will need to confirm this in our clinical trials, the first of which will start next year."

The new drug was developed by studying the mechanisms that enable cancer cells to outlive their normal lifespan and carry on multiplying. In the 1990s, a protein called nuclear factor kappa B (NF-kB), which plays an important role in inflammation, and the immune and stress response systems, was discovered to be overactive in many types of cancer, and responsible for switching off the normal cellular mechanisms that naturally lead to cell death. This enables the cancer cells to survive.

The pharmaceutical industry and scientists around the world have invested heavily in research into NF-kB inhibitors, but such compounds have not been successfully developed as therapies because they also block the many important processes controlled by NF-kB in healthy cells, causing serious toxic side effects.

The Imperial researchers took a different approach, looking for target genes downstream of NF-kB that might be responsible for its role in cancer specifically.

By studying cells from multiple myeloma patients, they identified a protein complex, named GADD45β/MKK7, that appeared to play a critical role in allowing the cancer cells to survive.

Searching for a safe way to target the NF-kB pathway, they screened over 20,000 molecules and found two that disrupted the protein complex. Further refinements led to the experimental drug, DTP3, which tests showed kills cancer cells very effectively but appears to have no toxicity to normal cells at the doses that eradicate the tumours in mice.

"We had known for many years that NF-kB is very important for cancer cells, but because it is also needed by healthy cells, we did not know how to block it specifically. The discovery that blocking the GADD45β/MKK7 segment of the NF-κB pathway with our DTP3 peptide therapeutic selectively kills myeloma cells could offer a completely new approach to treating patients with certain cancers, such as multiple myeloma," Professor Franzoso said.

A spinout company, Kesios Therapeutics, was formed to commercialise DTP3 and other drug candidates based on Professor Franzoso's research, with support from Imperial Innovations, a technology commercialisation company focused on developing the most promising UK academic research.

"The significant progress made by Professor Franzoso in multiple myeloma is one of the many cancers we believe his signal transduction research could be applied to. To help develop this ground-breaking research further, Imperial Innovations created the spin out Kesios Therapeutics," explained Dayle Hogg from the Healthcare Ventures team at Imperial Innovations.

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Story Source:

The above story is based on materials provided by Imperial College London. Note: Materials may be edited for content and length.

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Journal Reference:

1. Laura Tornatore, Annamaria Sandomenico, Domenico Raimondo, Caroline Low, Alberto Rocci, Cathy Tralau-Stewart, Daria Capece, Daniel D’Andrea, Marco Bua, Eileen Boyle, Mark van Duin, Pietro Zoppoli, Albert Jaxa-Chamiec, Anil K. Thotakura, Julian Dyson, Brian A. Walker, Antonio Leonardi, Angela Chambery, Christoph Driessen, Pieter Sonneveld, Gareth Morgan, Antonio Palumbo, Anna Tramontano, Amin Rahemtulla, Menotti Ruvo, Guido Franzoso. Cancer-Selective Targeting of the NF-κB Survival Pathway with GADD45β/MKK7 Inhibitors. Cancer Cell, 2014; 26 (4): 495 DOI: 10.1016/j.ccr.2014.07.027

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Imperial College London. "New cancer drug to begin trials in multiple myeloma patients." ScienceDaily. ScienceDaily, 13 October 2014. <www.sciencedaily.com/releases/2014/10/141013123034.htm>.

 

Chemical derived from broccoli sprouts shows promise in treating autism

 

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Broccoli sprouts are shown.

Results of a small clinical trial suggest that a chemical derived from broccoli sprouts -- and best known for claims that it can help prevent certain cancers -- may ease classic behavioral symptoms in those with autism spectrum disorders (ASDs).

The study, a joint effort by scientists at MassGeneral Hospital for Children and the Johns Hopkins University School of Medicine, involved 40 teenage boys and young men, ages 13 to 27, with moderate to severe autism.

In a report published online in the journal Proceedings of the National Academy of Sciences during the week of Oct. 13, the researchers say that many of those who received a daily dose of the chemical sulforaphane experienced substantial improvements in their social interaction and verbal communication, along with decreases in repetitive, ritualistic behaviors, compared to those who received a placebo.

"We believe that this may be preliminary evidence for the first treatment for autism that improves symptoms by apparently correcting some of the underlying cellular problems," says Paul Talalay, M.D., professor of pharmacology and molecular sciences, who has researched these vegetable compounds for the past 25 years.

"We are far from being able to declare a victory over autism, but this gives us important insights into what might help," says co-investigator Andrew Zimmerman, M.D., now a professor of pediatric neurology at UMass Memorial Medical Center.

ASD experts estimate that the group of disorders affects 1 to 2 percent of the world's population, with a much higher incidence in boys than girls. Its behavioral symptoms, such as poor social interaction and verbal communication, are well known and were first described 70 years ago by Leo Kanner, M.D., the founder of pediatric psychiatry at The Johns Hopkins University.

Unfortunately, its root causes remain elusive, though progress has been made, Talalay says, in describing some of the biochemical and molecular abnormalities that tend to accompany ASD.

Many of these are related to the efficiency of energy generation in cells. He says that studies show that the cells of those with ASD often have high levels of oxidative stress, the buildup of harmful, unintended byproducts from the cell's use of oxygen that can cause inflammation, damage DNA, and lead to cancer and other chronic diseases.

In 1992, Talalay's research group discovered that sulforaphane has some ability to bolster the body's natural defenses against oxidative stress, inflammation and DNA damage. In addition, the chemical later turned out to improve the body's heat-shock response -- a cascade of events used to protect cells from the stress caused by high temperatures, including those experienced when people have fever.

Intriguingly, he says, about one-half of parents report that their children's autistic behavior improves noticeably when they have a fever, then reverts back when the fever is gone. In 2007, Zimmerman, a principal collaborator in the current study, tested this anecdotal trend clinically and found it to be true, though a mechanism for the fever effect was not identified.

Because fevers, like sulforaphane, initiate the body's heat-shock response, Zimmerman and Talalay wondered if sulforaphane could cause the same temporary improvement in autism that fevers do. The current study was designed to find out.

Before the start of the trial, the patients' caregivers and physicians filled out three standard behavioral assessments: the Aberrant Behavior Checklist (ABC), the Social Responsiveness Scale (SRS) and the Clinical Global Impressions-Improvement scale (CGI-I). The assessments measure sensory sensitivities, ability to relate to others, verbal communication skills, social interactions and other behaviors related to autism.

Twenty-six of the subjects were randomly selected to receive, based on their weight, 9 to 27 milligrams of sulforaphane daily, and 14 received placebos. Behavioral assessments were again completed at four, 10 and 18 weeks while treatment continued. A final assessment was completed for most of the participants four weeks after the treatment had stopped.

Most of those who responded to sulforaphane showed significant improvements by the first measurement at four weeks and continued to improve during the rest of the treatment. After 18 weeks of treatment, the average ABC and SRS scores of those who received sulforaphane had decreased 34 and 17 percent, respectively, with improvements in bouts of irritability, lethargy, repetitive movements, hyperactivity, awareness, communication, motivation and mannerisms.

After 18 weeks of treatment, according to the CGI-I scale, 46, 54 and 42 percent of sulforaphane recipients experienced noticeable improvements in social interaction, aberrant behaviors and verbal communication, respectively.

Talalay notes that the scores of those who took sulforaphane trended back toward their original values after they stopped taking the chemical, just like what happens to those who experience improvements during a fever. "It seems like sulforaphane is temporarily helping cells to cope with their handicaps," he says.

Zimmerman adds that before they learned which subjects got the sulforaphane or placebo, the impressions of the clinical team -- including parents -- were that 13 of the participants noticeably improved. For example, some treated subjects looked them in the eye and shook their hands, which they had not done before. They found out later that all 13 had been taking sulforaphane, which is half of the treatment group.

Talalay cautions that the levels of sulforaphane precursors present in different varieties of broccoli are highly variable. Furthermore, the capacity of individuals to convert these precursors to active sulforaphane also varies greatly. It would be very difficult to achieve the levels of sulforaphane used in this study by eating large amounts of broccoli or other cruciferous vegetables.

 

Story Source:

The above story is based on materials provided by Johns Hopkins Medicine. Note: Materials may be edited for content and length.

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Journal Reference:

1. Kanwaljit Singh, Susan L. Connors, Eric A. Macklin, Kirby D. Smith, Jed W. Fahey, Paul Talalay, and Andrew W. Zimmerman. Sulforaphane treatment of autism spectrum disorder (ASD). PNAS, October 13, 2014 DOI: 10.1073/pnas.1416940111

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Johns Hopkins Medicine. "Chemical derived from broccoli sprouts shows promise in treating autism." ScienceDaily. ScienceDaily, 13 October 2014. <www.sciencedaily.com/releases/2014/10/141013152608.htm>.

 

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Greater rates of mitochondrial mutations discovered in children born to older mothers

 

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The inner membrane of each mitochondrion contains distinctive folds known as cristae. In a normal mitochondrion (left) these folds fill the interior, but these folds are lost in damaged or dysfunctional mitochondria (right). Dozens of rare diseases have been shown to result from this type of mitochondrial dysfunction. Several others -- including Alzheimer disease, autism, cancer, cardiovascular disease, Parkinson disease, and type 2 diabetes -- are suspected to involve the mitochondria.

The discovery of a "maternal age effect" by a team of Penn State scientists that could be used to predict the accumulation of mitochondrial DNA mutations in maternal egg cells -- and the transmission of these mutations to children -- could provide valuable insights for genetic counseling. These mutations cause more than 200 diseases and contribute to others such as diabetes, cancer, Parkinson's disease, and Alzheimer's disease. The study found greater rates of the mitochondrial DNA variants in children born to older mothers, as well as in the mothers themselves. The research will be published in the early online edition of the Proceedings of the National Academy of Sciences on October 13, 2014.

Mitochondria are structures within cells that produce energy and that contain their own DNA. "Many mitochondrial diseases affect more than one system in the human body," said Kateryna Makova, professor of biology and one of the study's primary investigators. "They affect organs that require a lot of energy, including the heart, skeletal muscle, and brain. They are devastating diseases and there is no cure, so our findings about their transmission are very important."

The multidisciplinary research team set out to learn whether maternal age is important in the accumulation of mitochondrial DNA (mtDNA) mutations, both in the mother and in the child as a result of transmission. Collaborating with Ian Paul, a pediatrician at the Penn State Milton S. Hershey Medical Center, they took samples of blood and of cells inside the cheek from 39 healthy mother-child pairs. Because mtDNA is inherited only maternally, paternal mtDNA was not a factor in the study. Studying healthy individuals gave the researchers a baseline for future studies of disease-causing mutations.

Through DNA sequencing, they found more mutations in blood and cheek cells in the older mothers in the study. Maternal age of study participants ranged from 25 to 59. "This finding is not surprising," Makova said, "because as we age, cells keep dividing, and therefore we will have more mutant genes." But finding greater rates of mutations in children born to the older mothers did come as a surprise. The researchers believe a similar mutation process is occurring both in the cells of the mothers' bodies and in their germ lines.

The study led to another important discovery about egg-cell development. Although it was known that developing egg cells go through a "bottleneck" period that decreases the number of mtDNA molecules, scientists didn't know how small or large this bottleneck is. "If the bottleneck is large, the genetic makeup of the mother's mitochondria will be passed to her children," Makova explained. "However, if it is tiny -- if there is a severe decrease in mitochondrial molecules during the egg-cell development -- then the genetic makeup of the child might differ dramatically from that of the mother. What we discovered is that this bottleneck is indeed very small."

This finding is especially important for mothers who have a mitochondrial disease. For many mitochondrial diseases, 70 to 80 percent of molecules need to have the disease-causing variant for the disease to manifest itself. But for others, only 10 percent of the mtDNA molecules with the variant are needed to cause disease. "If the bottleneck is very small, as we've found in our study, these percentages can change dramatically," Makova said. "Knowing the size of the bottleneck allows us to predict, within a range, the percentage of disease-carrying molecules that will be passed on to the child."

Knowledge about both the maternal age effect and the bottleneck size is useful in family planning. "We have some predictive power now and can assist genetic counselors in advising couples about the chances of mitochondrial diseases being passed to the next generation," Makova said. "Everyone is concerned about Down syndrome because that is a common genetic problem. We have now added another set of genetic disorders that also might be affected by the age of the mother. It is good for couples to have this knowledge as they make family-planning decisions."

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Story Source:

The above story is based on materials provided by Penn State. The original article was written by Krista Weidner. Note: Materials may be edited for content and length.

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Journal Reference:

1. Boris Rebolledo-Jaramillo, Marcia Shu-Wei Su, Nicholas Stoler, Jennifer A. Mcelhoe, Benjamin Dickins, Daniel Blankenberg, Thorfinn S. Korneliussen, Francesca Chiaromonte, Rasmus Nielsen, Mitchell M. Holland, Ian M. Paul, Anton Nekrutenko, and Kateryna D. Makova. Maternal age effect and severe germ-line bottleneck in the inheritance of human mitochondrial DNA. PNAS, October 2014 DOI: 10.1073/pnas.1409328111

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About Discs and How They're Made

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How a CD is Made

CDs consist of 99% clear polycarbonate plastic. The reflective layer, protective layer and screen print comprise the remaining 1% of the disc.

1. A disc is created from molten polycarbonate and digital information is stamped on the top of the disc, while it is still near melting point, using a die with microscopic bumps. These bumps are known as "pits and lands".

2. After the information is molded into the poly- carbonate, a reflective foil layer is applied using a process called sputtering or wet silvering. This layer reflects the laser back to the player, so it's integrity is extremely important. The layer is usually silver, but can be made of gold or platinum..

3. A clear lacquer coating is applied to seal the reflective layer and prevent oxidation. This layer is very thin and offers little protection from top side scratches.

4. Finally the artwork is screen-printed on the top of the disc.

How a DVD is made

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DVDs are made in different ways depending on the amount of information that is recorded on the disc. DVDs may be single or double layered and single or double layered double sided. Single Layer DVDs (DVD-5 - 4.7GB). These DVDs are made the same way as a CD with one additional polycarbonate layer added between the label and the pits and lands.

Double Layered DVDs (DVD-9 - 8.5GB) Double layered DVDs have a semi reflective layer and a reflective layer giving two layers to store information.

Double Sided DVDs (DVD-10 - 9.4GB) Double sided DVDs consist of two discs bonded back to back with the reflective layers in the middle and both sides are repairable. Double sided DVDs use a different size of micro-abrasive polishing papers to prevent the manufacturer’s label area from being removed during the repair process.

Double Sided/Double Layered DVDs (DVD-18 - 17.1GB) Double sided/double layered DVDs are simply two double layered discs bonded back to back.

How A Blu-Ray is Made

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Unlike current DVDs, which use a red laser to read and write data, Blu-ray uses a blue laser (which is where the format gets its name). A blue laser has a shorter wavelength (405 nanometers) than a red laser (650 nanometers). The smaller beam focuses more precisely, enabling it to read information recorded in pits that are only 0.15 microns (µm) (1 micron = 10-6 meters) long -- this is more than twice as small as the pits on a DVD. Plus, Blu-ray has reduced the track pitch from 0.74 microns to 0.32 microns. The smaller pits, smaller beam and shorter track pitch together enable a single-layer Blu-ray disc to hold more than 25 GB of information -- about five times the amount of information that can be stored on a DVD.

Blu-ray discs not only have more storage capacity than traditional DVDs, but they also offer a new level of interactivity. Users will be able to connect to the Internet and instantly download subtitles and other interactive movie features. With Blu-ray, you can:

• Record high-definition television (HDTV) without any quality loss
• Instantly skip to any spot on the disc
• Record one program while watching another on the disc
• Create playlists
• Edit or reorder programs recorded on the disc
• Automatically search for an empty space on the disc to avoid recording over a program
• Access the Web to download subtitles and other extra features

Each Blu-ray disc is about the same thickness (1.2 millimeters) as a DVD. But the two types of discs store data differently. In a DVD, the data is sandwiched between two polycarbonate layers, each 0.6-mm thick. Having a polycarbonate layer on top of the data can cause a problem called birefringence, in which the substrate layer refracts the laser light into two separate beams. If the beam is split too widely, the disc cannot be read. Also, if the DVD surface is not exactly flat, and is therefore not exactly perpendicular to the beam, it can lead to a problem known as disc tilt, in which the laser beam is distorted. All of these issues lead to a very involved manufacturing process.

New Radio.cubo TS522D+ by Brionvega Collection

 

An icon of Italian design, updated with a more colorful cabinet design and technological heart, presents itself : bluetooth, DAB / DAB + , L-Band , Fm radio alarm clock and remote control. A timeless design, new colors and high-quality audio for a product that has revolutionized the way we listen to music.

New Radio.cubo TS522D+ by Brionvega

New Radio.cubo TS522D+ by Brionvega

New Radio.cubo TS522D+ by Brionvega

New Radio.cubo TS522D+ by Brionvega

New Radio.cubo by Brionvega

New Radio.cubo by Brionvega

New Radio.cubo by Brionvega

Play your favorite playlist by connecting radio.cubo to your smartphone , tablet or PC via Bluetooth or via aux input . Listen to radio stations in high sound quality through DAB+ digital technology and relish your wake-up with its alarmclock.

Try the audio quality and the exceptional power of radio.cubo, enhanced by a sealed-case bass reflex, deep and powerfull bass speaker, a 4″ loudspeaker, and a 9W amplifier! And if this is not enough … connect a second speaker to your radio.cubo through the appropriate output for an even more powerful and enveloping sound.

Radio.cubo has all the technology you may desire in a timeless design by Richard Sapper and Marco Zanuso.

More from Tododesign –http://www.arq4design.com 

21 Innovative Inventions

 

source : www.randompicdumps.com

Common anesthetic procedure dramatically improves well being of veterans with PTSD

 

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A single application of a common anesthetic procedure could be the answer to alleviating anxiety, depression and psychological pain in those suffering from chronic, extreme post-traumatic stress disorder (PTSD).

In a study presented at the ANESTHESIOLOGY™ 2014 annual meeting, researchers followed 12 patients with PTSD who had undergone a simple anesthetic procedure called a stellate ganglion block (SGB). This common procedure involves injecting a small amount of local anesthesia into the base of the neck. SGB is traditionally used to treat a variety of conditions, from pain syndromes to sleep disorders.

"While it doesn't cure the problem, we found that SGB appears to be a fast-acting and effective long-term treatment for chronic, extreme PTSD in veterans," said Michael T. Alkire, M.D., staff anesthesiologist at the Long Beach VA Healthcare System in California. "These improvements far outlasted what we would expect from SGB, which is usually used as a temporary nerve block and typically lasts three to five hours."

In the study, the patients each were given one SGB and followed closely with structured interviews and other psychological tests for six months after treatment. The positive effects of the SGB were evident often within minutes and resulted in significant improvement of scores for the Clinician Administered PTSD Score, or CAPS, the test used to measure the severity of PTSD.

Symptoms improved over time, and after one month, CAPS scores registered normal to mild PTSD levels for most of the patients. Positive effects were still seen at three months, but began fading and were generally gone by six months. Overall, 75 percent of the participants reported significant improvement of their PTSD symptoms after the SGB.

Data from the study further suggested that SGB might also be an effective initial treatment for depression and anxiety disorders.

"Further work is needed to identify which patients might respond best to this treatment as well as understand the mechanisms involved that produce such a rapid, dramatic and long-term change in psychological health for some patients," said Dr. Alkire, who also is a professor of anesthesiology at the University of California-Irvine.

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Story Source:

The above story is based on materials provided by American Society of Anesthesiologists (ASA). Note: Materials may be edited for content and length.

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Oral capsule as effective as invasive procedures for delivery of fecal transplant

 

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A noninvasive method of delivering a promising therapy for persistent Clostridium difficile (C. difficile) infection appears to be as effective as treatment via colonoscopy or through a nasogastric tube. In their JAMA report, receiving early online release to coincide with a presentation at the Infectious Diseases Society of America's ID Week conference, investigators from Massachusetts General Hospital (MGH) report that oral administration of the therapy called fecal microbiota transplant (FMT) in acid-resistant capsules was as successful as more invasive methods in eliminating recurrent diarrhea caused by C. difficile.

"Numerous reports have shown that FMT is effective in treating active C. difficile infection and preventing recurrences in patients whose infections failed to respond to standard treatments," says Ilan Youngster, MD, MMSc, a fellow in Pediatric Infectious Diseases at MGH and at Boston Children's Hospital, corresponding author of the JAMA report. "The procedures that have been used before -- colonoscopies, nasogastric tubes, even enemas -- all have potential risks and discomforts for patients. The use of capsules simplifies the procedure immensely, potentially making it accessible to a greater population."

Certain strains of C. difficile -- which currently causes about 250,000 hospitalizations and 14,000 deaths each year in the U.S. -- have become highly resistant to treatment, leading to a 30 percent treatment failure rate in patients infected with those strains. Since antibiotic therapy also kills off the normal population of beneficial intestinal microbes that can keep pathologic species in check, antibiotic therapy could actually make the situation worse. FMT is believed to restore the normal balance of beneficial microbes, and studies in animals and humans using fresh fecal material -- usually delivered by colonoscopy -- have had success rates around 90 percent.

Earlier this year the same MGH research team showed that delivering frozen fecal material for FMT either by colonoscopy or nasogastric tube was equally effective. Using frozen material offers the potential of maintaining a bank of frozen samples from donors prescreened for any health issues, reducing the risks of transmitting new infections and the need to recruit and screen donors for each patient. The current study was designed to investigate whether delivering FMT orally through capsules designed to open upon reaching the small intestine would be just as effective.

Conducted at MGH, the study enrolled 20 individuals ages 11 to 84 with persistent or recurrent C. difficile infection. Stool samples were gathered from healthy adult volunteers who had been comprehensively screened for infectious diseases and avoided eating common allergens for several days before donating. The samples were filtered, diluted, screened, placed into capsules and frozen for four weeks to enable retesting of donors for important viral infections. On two consecutive days each participant received 15 FMT capsules, which most of them ingested within a few minutes. If their symptoms did not improve within 72 hours, they were offered a second course of treatment with material from the same donor.

Of the 20 study participants, 14 had complete symptom resolution after a single treatment and no recurrence during the next eight weeks. The other 6 received a second treatment about a week after the first, and in 5 of them symptoms resolved. In addition to the single patient whose symptoms didn't respond to two courses of treatment, one of the participants whose infection responded to the second course had a recurrence within the eight-week follow-up period, resulting to an overall success rate of 90 percent for the study group. Participants who needed a second treatment were generally in poorer health -- including more serious C. difficile-associated symptoms -- than were those whose symptoms resolved after a single two-day treatment.

"This small investigation was designed to be a pilot study and provides preliminary data supporting the safety and effectiveness of this approach," says Elizabeth Hohmann, MD, of the MGH Infectious Diseases Division, senior author of the report and an associate professor of Medicine at Harvard Medical School. "More experience and larger studies are needed to determine the long-term safety and efficacy, and further investigation should help determine the most effective microbial mixes for either oral or procedural administration."

Youngster adds, "While we are striving to make this treatment more accessible to patients, it's important to remind people of the potential dangers of attempting 'home brew' FMT using fecal material from family members or friends. Many people can be carriers of bacteria, viruses, and parasites that are shed in their stools but have no symptoms. It's not enough to know your donor and just ask how he or she feels, as some websites suggest. In any form, this procedure should only be performed under strict medical supervision with material from thoroughly screened donors."

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Story Source:

The above story is based on materials provided by Massachusetts General Hospital. Note: Materials may be edited for content and length.

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Journal Reference:

1. Elizabeth L. Hohmann, MD et al. Oral, Capsulized, Frozen Fecal Microbiota Transplantation for Relapsing Clostridium difficile Infection. JAMA, October 2014 DOI: 10.1001/jama.2014.13875

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The dwindling stock of antibiotics, and what to do about it

 

A CDC microbiologist holds up a plate used to identify resistance in bacteria known as Enterobacteriaceae. Bacteria that are resistant to carbapenems, considered “last resort” antibiotics, produce a distinctive clover-leaf shape on the plate.

Credit: CDC

 

They soon learned his son's appendix had burst and he was septic. "Things moved so fast he was septic before he was symptomatic [for appendicitis]," Kinch said. His son was moved to an academic medical center where he had surgery and was put on four newer antibiotics.

When the lab tests for antibiotic susceptibility finally came in, they showed the pathogenic bacteria were susceptible to only two of the six antibiotics Kinch's son had been given. Stunningly, the two that worked were the older drugs he had been given at the clinic. "I can only assume that if we had gone straight to the academic medical center, he might not have survived," Kinch said.

"It's not that my son had had extensive exposure to antibiotics," Kinch explained carefully. "We're all just colonized by resistant bacteria now."

"Three weeks later I was asked to join a nonprofit organization working on new models for drug development, called the Institute for Life Sciences Collaboration," Kinch said. "The institute was picking the therapeutic areas that would be their focus. "They were considering various exotic diseases, and I said, 'Antibiotics.'"

Antibiotics are crashing

In his last position, as managing director of the Center for Molecular Discovery at Yale University, Kinch had assembled a huge database of information about drug discovery and development in the pharmaceutical industry.

He has been able to excavate story after story from this storehouse of data. The crash of antibiotics is one of the best known and scariest, since losing antibiotics would force changes in almost every area of medical practice.

In an article in Drug Discovery Today, Kinch summarized the financial constraints that have led to the current crisis in antibiotic supply. The number of antibiotics available for clinical use, Kinch said, has declined to 96 from a peak of 113 in 2000.

The rate of withdrawals is double the rate of new introductions, Kinch said. Antibiotics are being withdrawn because they don't work anymore, because they're too toxic or because they've been replaced by new versions of the same drug. Introductions are declining because pharmaceutical companies are leaving the business of antibiotic discovery and development.

Pfizer or its predecessors developed 40 of the 155 antibiotics ever sold in this country, Kinch said, but is no longer in the antibiotic space. Eli Lilly, AstraZeneca and Bristol-Myers Squibb have also left the antibiotic field, which is now dominated by small companies such as Cubist Pharmaceuticals, formed in 1992 specifically to focus on drugs for resistant bacterial infections that could have higher price points.

His count, Kinch said, if anything, overestimates the number of antibiotics still available, because some of the new drugs are not general-purpose antibiotics. They include, for example, an acne medication and a treatment for anthrax, developed for use in case of a bioterrorist attack.

One reason pharmaceutical companies are withdrawing, Kinch said, is that our patent law squeezes them for time. A patent gives a company 20 years of protection for a new drug, but it takes 11 years of clinical trial experience on average to get a drug approved. That means the typical company has nine years under patent to earn back the development costs before a generic comes in.

If the drug is an antibiotic, there is an additional catch. Because of rising resistance doctors hold new antibiotics in reserve, using them only in cases of dire need. This happened, for example, in the case of vancomycin, which has long been used as a drug of last resort. "When you hold a drug in reserve," Kinch said, "you're eating into the patent time a company has to recoup its development costs."

"If you've got this vancomycin-like situation, where the drug is sitting on a shelf -- quite literally sitting on a shelf -- how is a company going to make its money back? It can't price the drug at $10,000 a dose." Companies have consistently decided there is no exit from this trap -- as long as we hold to the current model for drug development.

What to do about it?

In the U.S., we're used to turning to the NIH to solve problems like this, but the NIH budget, which doubled in 2009, has fallen continuously ever since. It is now 30 percent below 2009 levels in constant dollars.

Since the NIH has fallen victim to congressional gridlock, people in the biomedical community are starting to organize on their own. The group Kinch helped found, the Institute for Life Sciences Collaboration, recently convened an expert panel at the United Nations to discuss the need for innovative partnerships and financing models to deal with antibiotic resistance.

One popular idea is "de-linkage," or finding a way to disconnect the costs of development from the sale of pills. Some have suggested that large prizes, of $1 billion or more, be offered for the development of new drugs, which would then be sold for modest prices by other companies.

The Infectious Diseases Society of America (ISDA) has launched a "10 x 20" initiative whose goal is to create global antibacterial drug research-and-development enterprise with the power in the short-term to develop 10 new, safe and effective antibiotics by 2020.

Britain is offering a prize of £10 million, called the Longitude Prize 2014 (after the prize once offered for an accurate way to determine the longitude of ships at sea), for a rapid test that would allow health professionals to identify bacteria quickly and so administer only the right antibiotics at the right time.

Newly arrived at Washington University in St. Louis, Kinch is just beginning to think about the role the university might play in redefining its role. He points out that the university excels in biomedical research, but is losing brilliant ideas in the Valley of Death between the lab and the market.

Led by Provost and Executive Vice Chancellor H. Holden Thorp, PhD, an enterpreneurship team has been convened to redefine what the university does with biomedical discoveries after the peer-reviewed articles are in print. In addition to Kinch, the team includes Dedric Carter, PhD, associate provost and vice chancellor for entrepreneurship and innovation; and Emre Toker, PhD, managing director of the Skandalaris Center for Entrepreneurial Studies.

One of the university's assets is School of Medicine research with the human microbiome, the trillions of organisms that live in our guts, many performing beneficial tasks such as digesting food and fighting off infections. Work the microbiome was pioneered by Washington University scientists led by Jeffrey Gordon, MD, the Dr. Robert J. Glaser Distinguished University Professor and director of the Center for Genome Sciences and Systems Biology.

Why is this relevant? In the past the hunting ground for new antibiotics was often the soil. Vancomycin, for example, was found in a soil sample from Borneo. But in the future, the hunting ground may become the natural products produced by the human microbiome.

Antibiotics are not the only drug class heading for trouble -- Kinch mentions that HIV/AIDs drugs are following a similar trajectory -- but they have become the poster child for the larger problem of drug discovery and development in part because they underpin every part of modern medical practice, from surgery to cancer treatment and pretty much everything in between.

Story Source:

The above story is based on materials provided by Washington University in St. Louis. The original article was written by Diana Lutz. Note: Materials may be edited for content and length.

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Journal Reference:

1. Michael S. Kinch, Eric Patridge, Mark Plummer, Denton Hoyer. An analysis of FDA-approved drugs for infectious disease: antibacterial agents. Drug Discovery Today, 2014; 19 (9): 1283 DOI: 10.1016/j.drudis.2014.07.005

Stunning finds from ancient Greek shipwreck

 

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Return to Antikythera project chief diver Philip Short inspects the bronze spear recovered from the Antikythera Shipwreck.

A Greek and international team of divers and archaeologists has retrieved stunning new finds from an ancient Greek ship that sank more than 2,000 years ago off the remote island of Antikythera. The rescued antiquities include tableware, ship components, and a giant bronze spear that would have belonged to a life-sized warrior statue.

The Antikythera wreck was first discovered in 1900 by sponge divers who were blown off course by a storm. They subsequently recovered a spectacular haul of ancient treasure including bronze and marble statues, jewellery, furniture, luxury glassware, and the surprisingly complex Antikythera Mechanism. But they were forced to end their mission at the 55-meter-deep site after one diver died of the bends and two were paralyzed. Ever since, archaeologists have wondered if more treasure remains buried beneath the sea bed.

Now a team of international archaeologists including Brendan Foley of the Woods Hole Oceanographic Institution and Theotokis Theodoulou of the Hellenic Ephorate of Underwater Antiquities have returned to the treacherous site using state-of-the-art technology. During their first excavation season, from September 15 to October 7, 2014, the researchers have created a high-resolution, 3D map of the site using stereo cameras mounted on an autonomous underwater vehicle (AUV). Divers then recovered a series of finds which prove that much of the ship's cargo is indeed still preserved beneath the sediment.

Components of the ship, including multiple lead anchors over a metre long and a bronze rigging ring with fragments of wood still attached, prove that much of the ship survives. The finds are also scattered over a much larger area than the sponge divers realized, covering 300 meters of the seafloor. This together with the huge size of the anchors and recovered hull planks proves that the Antikythera ship was much larger than previously thought, perhaps up to 50 meters long.

"The evidence shows this is the largest ancient shipwreck ever discovered," says Foley. "It's the Titanic of the ancient world."

The archaeologists also recovered a beautiful intact table jug, part of an ornate bed leg, and most impressive of all, a 2-meter-long bronze spear buried just beneath the surface of the sand. Too large and heavy to have been used as a weapon, it must have belonged to a giant statue, perhaps a warrior or the goddess Athena, says Foley. In 1901, four giant marble horses were discovered on the wreck by the sponge divers, so these could have formed part of a complex of statues involving a warrior in a chariot that was pulled by the four horses.

The shipwreck dates from 70 to 60 BC and is thought to have been carrying a luxury cargo of Greek treasures from the coast of Asia Minor west to Rome. Antikythera stands in the middle of this major shipping route and the ship probably sank when a violent storm smashed it against the island's sheer cliffs.

The wreck is too deep to dive safely using regular scuba equipment, so the divers had to use rebreather technology, in which carbon dioxide is scrubbed from the exhaled air while oxygen is introduced and recirculated. This allowed them to dive on the site for up to three hours at a time.

The archaeologists plan to return next year to excavate the site further and recover more of the ship's precious cargo. The finds, particularly the bronze spear, are "very promising," says Theodolou. "We have a lot of work to do at this site to uncover its secrets."

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Story Source:

The above story is based on materials provided by Woods Hole Oceanographic Institution. Note: Materials may be edited for content and length.

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Fast, simple diagnostic test specific to 2014 Ebola outbreak

 

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Primerdesign kit.

High-tech British company Primerdesign Ltd, a spin-off company from the University of Southampton, has developed a fast and simple diagnostic test solution specific to the 2014 Ebola outbreak.

With the current epidemic of Ebola virus in West Africa, Primerdesign are racing to provide an easy-to-use, affordable solution for screening suspect Ebola patients.

"Accurate diagnostics is essential in controlling an outbreak like Ebola. There is an urgent need for rapid testing to screen suspected patients and people travelling in and out of the region," explains Dr Jim Wicks, Managing Director of Primerdesign. "Our test is quick, affordable and easy to perform," he adds.

The kit detects the DNA finger print of the Ebola Virus. It means that even minute quantities of the disease can be detected in the early stages allowing for pre-emptive healthcare intervention.

Primerdesign Ltd, which is part of the university business incubator collaboration SETsquared, has finished development work in the last few days and is meeting with the World Health Organisation to discuss plans to possibly put large numbers of these tests in to the front line in West Africa as quickly as possible.

How the kit works

Viruses all have a unique genetic fingerprint the same as we do. Ours is encoded in DNA but the Ebola virus uses RNA (Ribonucleic acid). So the kit is designed to specifically detect the Ebola RNA in a patient blood sample.

Process:

1. Blood sample is taken from patient
2. RNA is extracted with a few simple steps
3. RNA is placed in a tube with our kit ingredients
4. Tube goes in to machine
5. Analysis complete within 90 minutes

Primerdesign is a spinoff company from the University of Southampton specialising in Real-Time PCR technology. Real-Time PCR, also known as 'qPCR' is a mature technology based on the same DNA testing technology of 'CSI' fame. Primerdesign deployed the same technology during the recent horsemeat scandal in the UK and famously developed the World's first Swine Flu detection kit in the 2009 outbreak.

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Story Source:

The above story is based on materials provided by University of Southampton. Note: Materials may be edited for content and length.

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