Gut bacteria are protected by host during illness .


To protect their gut microbes during illness, sick mice produce specialized sugars in the gut that feed their microbiota and maintain a healthy microbial balance. This protective mechanism also appears to help resist or tolerate additional harmful pathogens, and its disruption may play a role in human diseases such as Crohn’s disease.
Laboratory mouse (stock image). To protect their gut microbes during illness, sick mice produce specialized sugars in the gut that feed their microbiota and maintain a healthy microbial balance.
To protect their gut microbes during illness, sick mice produce specialized sugars in the gut that feed their microbiota and maintain a healthy microbial balance. This protective mechanism also appears to help resist or tolerate additional harmful pathogens, and its disruption may play a role in human diseases such as Crohn’s disease, report scientists from the University of Chicago in Nature on Oct 1.

“Both hosts and their gut microbiota can suffer in the case of sickness, but this mutually beneficial relationship is guarded by the host,” said study senior author Alexander Chervonsky, MD, PhD, chairman of the Committee on Immunology at the University of Chicago.

When faced with systemic illness, animals eat less to conserve energy instead of foraging for food and to deprive pathogens of nutrients. However, this can harm beneficial gut bacteria, which have an important role in health and disease.

To investigate how microbiota might be supported during illness, Chervonsky and his team focused on a potential internal resource produced by the host — L-fucose, a sugar which has been shown to affect gut microbes. A host cannot use L-fucose for energy, but when bound to proteins, it can be used by microbes as a food source. Under normal conditions, however, the small intestine of mice produces almost no L-fucose.

The team exposed different types of mice to a molecule that mimicked a systemic infection. The mice became sick — eating less food, drinking less water and losing weight. Only a few hours after this induced sickness, the researchers observed that L-fucose was produced and present on almost every surface of the small intestine. This effect was seen only in response to illness.

The researchers then tested genetically engineered mice lacking Fut2, the gene responsible for L-fucose production. Healthy under normal conditions, mice without Fut2 regained weight after induced sickness — a measure of recovery — much slower than their normal counterparts. However, only mice with both intact gut microbiota and the ability to produce L-fucose recovered efficiently.

“Mice that can produce L-fucose recover better than those that can’t,” Chervonsky said. “If you remove bacteria the effect goes away.”

The team used genetic analyses to confirm that gut microbes were affected metabolically by the production of L-fucose. As part of this analysis, they noted that sick mice without Fut2 had significantly greater expression of harmful microbial genes than normal mice. Hypothesizing that L-fucose production was somehow preventing opportunistic bacteria from expressing virulent genes, they exposed mice to a mild bacterial pathogen and then four days later induced sickness. Under this condition, mice without Fut2 lost significantly more weight than normal, suggesting that the production of L-fucose helps the host tolerate or resist additional harmful pathogens.

Interestingly, around 20 percent of humans lack a functional gene to produce L-fucose, a problem that has been associated with the inflammatory bowel ailment known as Crohn’s disease.

“We speculate that without L-fucose, the activation of virulence genes cannot be blocked, and that’s why bacteria play a role in Crohn’s disease,” Chervonsky said. “Whether we can use this toward therapeutics in the future requires further study.”


Story Source:

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


Journal Reference:

  1. Joseph M. Pickard, Corinne F. Maurice, Melissa A. Kinnebrew, Michael C. Abt, Dominik Schenten, Tatyana V. Golovkina, Said R. Bogatyrev, Rustem F. Ismagilov, Eric G. Pamer, Peter J. Turnbaugh, Alexander V. Chervonsky. Rapid fucosylation of intestinal epithelium sustains host–commensal symbiosis in sickness.Nature, 2014; DOI: 10.1038/nature13823

This new material can suck all the oxygen out of a room


A new material has been invented by scientists in Denmark, and just a bucketful of the stuff could suck all the oxygen out of an entire room.

oxygen

Scientists from the University of Southern Denmark have developed a new form of crystalline cobalt salt that acts like a super-effective oxygen sponge. Once it sucks up oxygen, it will hold on to it indefinitely until it’s gently heated or exposed to low oxygen pressure, at which point it will quietly release its oxygen hoard back out into the atmosphere. About 10 litres of it would be needed to suck all of the oxygen out of an average-sized room.

“The material can absorb and release oxygen many times without losing the ability. It is like dipping a sponge in water, squeezing the water out of it and repeating the process over and over again,” said lead researcher and nanobioscience professor Christine McKenzie, in a press release. “When the substance is saturated with oxygen, it can be compared to an oxygen tank, containing pure oxygen under pressure. The difference is that this material can hold three times as much oxygen.”

The material works by forming a chemical bond with individual oxygen molecules, sort of how oxygen molecules bind with a blood protein called haemoglobin when we breathe, so the oxygen can be distributed around our bodies. Just like haemoglobin, this new material can both sense and contain oxygen, which means it can be used to bind, store and transport it for a range of different applications, from medical equipment to new scuba diving technology.

The key to the material’s success in trapping and holding such a large amount of oxygen molecules is its lattice crystalline structure, says Michael Byrne at Motherboard:

“Each single crystal structure features two nitrate ions bound to a metallic molecular substructure, like a nitrogen house built on a cobalt foundation. It’s really a nitrogen mobile home, however, as the introduction of oxygen to the neighbourhood means the nitrogen ions very quickly split town. The oxygen ions then set up shop themselves on the cobalt foundation.”

Once the material is heated up or the pressure in the environment is lowered just enough, the oxygen will move back out into the atmosphere and the nitrogen will move back into the lattice structure of cobalt material.

The team is hoping to use the new material to replace hefty oxygen tanks used by scuba divers and mountain climbers, plus it could have a huge effect on medical treatments, such as for patients with Chronic obstructive pulmonary disease (COPD), which right now requires them to be hooked up to a large oxygen tank 24 hours a day. What the researchers envision is a small, simple oxygen mask made from oxygen-packed cobalt material that constantly replenishes its supply.

Trial of the Route of Early Nutritional Support in Critically Ill Adults .


BACKGROUND

Uncertainty exists about the most effective route for delivery of early nutritional support in critically ill adults. We hypothesized that delivery through the parenteral route is superior to that through the enteral route.

METHODS

We conducted a pragmatic, randomized trial involving adults with an unplanned admission to one of 33 English intensive care units. We randomly assigned patients who could be fed through either the parenteral or the enteral route to a delivery route, with nutritional support initiated within 36 hours after admission and continued for up to 5 days. The primary outcome was all-cause mortality at 30 days.

RESULTS

We enrolled 2400 patients; 2388 (99.5%) were included in the analysis (1191 in the parenteral group and 1197 in the enteral group). By 30 days, 393 of 1188 patients (33.1%) in the parenteral group and 409 of 1195 patients (34.2%) in the enteral group had died (relative risk in parenteral group, 0.97; 95% confidence interval, 0.86 to 1.08; P=0.57). There were significant reductions in the parenteral group, as compared with the enteral group, in rates of hypoglycemia (44 patients [3.7%] vs. 74 patients [6.2%]; P=0.006) and vomiting (100 patients [8.4%] vs. 194 patients [16.2%]; P<0.001). There were no significant differences between the parenteral group and the enteral group in the mean number of treated infectious complications (0.22 vs. 0.21; P=0.72), 90-day mortality (442 of 1184 patients [37.3%] vs. 464 of 1188 patients [39.1%], P=0.40), in rates of 14 other secondary outcomes, or in rates of adverse events. Caloric intake was similar in the two groups, with the target intake not achieved in most patients.

CONCLUSIONS

We found no significant difference in 30-day mortality associated with the route of delivery of early nutritional support in critically ill adults.

Shocking statistic: 96% of pro football players suffered from brain disease before death.


Published time: October 01, 2014 20:38
Edited time: October 02, 2014 04:52

Reuters / David Stobbe

Nearly all of the former professional football players examined as part of a recent study were found to have had suffered from a degenerative brain disease that’s increasingly being linked to America’s favorite sport, a new report reveals.

According to the study — first reported on Tuesday this week by journalists at the PBS programFrontline — 96.2 percent of deceased pro footballers had the condition, chronic traumatic encephalopathy, or CTE, before dying.

Researchers at the United States Department of Veterans Affairs’ brain repository in Bedford, Massachusetts were limited with regards to the number of samples available, but nevertheless studied the brains of 79 ex-National Football League athletes and soon determined that all but three — 76 of the 79 — showed evidence of CTE.

Jason Breslow reported for Frontline that researchers studied the brain tissue of 128 footballers in all who played semiprofessionally, in college, in high school or for the NFL before dying and determined that 101 athletes, or 80 percent of the entire sample, tested positive for CTE. With respect to pro athletes, the statistic is closer to nine-out-of-ten.

Reuters

Reuters

“Obviously this high percentage of living individuals is not suffering from CTE,” Dr. Ann McKee of the Mass. brain bank told PBS. “Playing football, and the higher the level you play football and the longer you play football, the higher your risk.”

The latest report couldn’t have come at a worse time for the NFL, which is in the midst of responding to a lawsuit filed by more than 4,500 former players who say the league hid links between football and CTE. Those potential class-action plaintiffs have until October 14 to decide if they will agree to a settlement proposed by the NFL.

According to the Boston-based Sports Legacy Institute non-profit organization, athletes with a history of repetitive brain trauma are prone to being diagnosed with CTE, which involves the building-up on the brain tissue of an abnormal protein called tau. Although CTE can only be diagnosed with a post-mortem examination, athletes who lived with the disease can show symptoms that include memory loss, confusion, impaired judgment, paranoia, impulse control problems, aggression, depression, and progressive dementia before death.

A makeshift memorial for Kansas City Chiefs football player Jovan Belcher is seen outside his mother's home in West Babylon, New York December 4, 2012 (Reuters / Shannon Stapleton)

A makeshift memorial for Kansas City Chiefs football player Jovan Belcher is seen outside his mother’s home in West Babylon, New York December 4, 2012 (Reuters / Shannon Stapleton)

The release of the latest CTE report comes just as its being made public that Jovan Belcher, a former linebacker for the Kansas City Chiefs NFL team, suffered from the disease ahead of a December 2012 murder-suicide that claimed his life and his girlfriend’s.

“The Chiefs knew he and his significant other were having major domestic violence issues and he had a major concussion two weeks before this happened,” Ken McClain, an attorney who is suing the Chiefs over the incident, told Fox News.

Responding to requests for comment concerning the just released Belcher autopsy, the NFL told FX this week that the league “has a long history of a changing the rules of the game to make it safer on the field, providing players the best medical care, and updating protocols on diagnosing concussions, treating concussions and returning to play after a concussion.”

In January, ESPN reported that a Harris Poll found professional football to be the most popular sport in America among adult fans.

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Ebola worse than HIV, SARS .


The man leading the UN response to the Ebola epidemic, Dr. David Nabaro, says Ebola poses a worse threat to humanity than HIV or SARS and the global effort to combat it is woefully inefficient and that he needs $30 million now.

Nabaro was speaking after various presentations on how to combat the disease, including at the UN Security Council and General Assembly, before he returns to Europe and West Africa, reports the Sydney Morning Herald.

Ebola has so-far been centered on the West African countries of Guinea, Sierra Leone and Liberia, and has infected 6,553 people and killed 3,083. So far the outbreak looks like it’s been arrested in neighboring Senegal and Nigeria, but the US Centers for Disease Control (CDC) believes that if it is not contained Ebola may infect 1.4 million by January.

A burial team wearing protective clothes, remove a body from an isolated holding centre, for people waiting for laboratory results, at the Port Loko District Hospital September 27, 2014. (Reuters/Christopher Black/WHO)

Over a lifetime spent dealing with and leading international responses to epidemics and disasters, Nabaro said the current Ebola outbreak scares him more than any other.

“I can remember in Africa early on in HIV thinking ‘This is an unspeakably awful situation, but it will not decimate the population’…though we still lost millions. I watch this and I think it is much nastier than HIV. I remember working on SARS and being scared, but this is much worse than SARS. It is just spreading faster and faster and faster,” he told the paper.

A health worker in protective suit carries equipment on October 1, 2014 at MSF's (Doctors Without Borders) Ebola treatment center in Monrovia. (AFP Photo)

A health worker in protective suit carries equipment on October 1, 2014 at MSF’s (Doctors Without Borders) Ebola treatment center in Monrovia. (AFP Photo)

Put your money where your mouth is

Nabaro said his principle concern is that although world leaders say they appreciate the size and seriousness of the crisis, some countries are not yet contributing as much as they might, while others are dithering in a cloud of bureaucratic decision making.

“I don’t have time anymore for meetings or phone conferences in which decisions are not made. I need $30 million now, not in a month,” he said.

In fact the total that all the agencies dealing with the outbreak need is closer to $1 billion just to contain and control the outbreak in the foreseeable future. So far only 30 percent of this has been pledged.

But there are signs that countries are now starting to wake up and pull their weight in trying to provide the resources needed.

The US is sending soldiers to build field hospitals and training centers in Liberia, China a fully-equipped laboratory, Canada has promised $30 million and the Bridgestone tire company, which grows rubber in the affected West African areas, has pledged a million.

In an earlier interview with the UN news team, Nabaro was clear that he did not think restricting travel to countries affected by Ebola would have any effect on containing the outbreak and said that the virus can only be transmitted through bodily fluids and that if proper precautions are taken then there will not be cross infection between people.

Other people have voiced their concern about Ebola, including US President Obama, while the former commander of US Central Command, retired General Charlie Zinni, said he thinks Ebola is more dangerous to the world than the Islamic State (IS, formerly ISIS).

“I think ISIS certainly is a regional threat. I think its tentacles can reach out and create problems in our country and other countries, but it’s not an existential threat. Ebola can become an existential threat on a global level,” he said.

 

Pill coated with tiny needles can deliver drugs directly into the lining of the digestive tract


Given a choice, most patients would prefer to take a drug orally instead of getting an injection. Unfortunately, many drugs, especially those made from large proteins, cannot be given as a pill because they get broken down in the stomach before they can be absorbed.

To help overcome that obstacle, researchers at MIT and Massachusetts General Hospital (MGH) have devised a novel drug capsule coated with tiny needles that can inject drugs directly into the lining of the stomach after the capsule is swallowed. In animal studies, the team found that the capsule delivered insulin more efficiently than injection under the skin, and there were no harmful side effects as the capsule passed through the digestive system.

“This could be a way that the patient can circumvent the need to have an infusion or subcutaneous administration of a drug,” says Giovanni Traverso, a research fellow at MIT’s Koch Institute for Integrative Cancer Research, a gastroenterologist at MGH, and one of the lead authors of the paper, which appears in the Journal of Pharmaceutical Sciences.

Although the researchers tested their capsule with insulin, they anticipate that it would be most useful for delivering biopharmaceuticals such as antibodies, which are used to treat cancer and autoimmune disorders like arthritis and Crohn’s disease. This class of drugs, known as “biologics,” also includes vaccines, recombinant DNA, and RNA.

“The large size of these biologic drugs makes them nonabsorbable. And before they even would be absorbed, they’re degraded in your GI tract by acids and enzymes that just eat up the molecules and make them inactive,” says Carl Schoellhammer, a graduate student in chemical engineering and a lead author of the paper.

Safe and effective delivery

Scientists have tried designing microparticles and nanoparticles that can deliver biologics, but such particles are expensive to produce and require a new version to be engineered for each drug.

Schoellhammer, Traverso, and their colleagues set out to design a capsule that would serve as a platform for the delivery of a wide range of therapeutics, prevent degradation of the drugs, and inject the payload directly into the lining of the GI tract. Their prototype acrylic capsule, 2 centimeters long and 1 centimeter in diameter, includes a reservoir for the drug and is coated with hollow, stainless steel needles about 5 millimeters long.

Previous studies of accidental ingestion of sharp objects in human patients have suggested that it could be safe to swallow a capsule coated with short needles. Because there are no pain receptors in the GI tract, patients would not feel any pain from the drug injection.

To test whether this type of capsule could allow safe and effective drug delivery, the researchers tested it in pigs, with insulin as the drug payload. It took more than a week for the capsules to move through the entire , and the researchers found no traces of tissue damage, supporting the potential safety of this novel approach.

They also found that the microneedles successfully injected insulin into the lining of the stomach, small intestine, and colon, causing the animals’ to drop. This reduction in was faster and larger than the drop seen when the same amount of glucose was given by subcutaneous injection.

This therapeutic-use illustration of the microneedle pill shows the use of hollow needles and solid needles made from sugars or polymers. In both cases, the pill’s needles are initially coated by a pH-responsive coating to aid in ingestion (left). When the pill has reached the desired location in the GI tract, the coating dissolves, revealing the microneedles (middle). In the case of hollow microneedles (top right), the drug reservoir is compressed through peristalsis, releasing the drug through the needles. In the case of solid microneedles (bottom right), the drug is formulated into the microneedles. Credit: Carol Schoellhammer and Giovanni Traverso

“The kinetics are much better, and much faster-onset, than those seen with traditional under-the-skin administration,” Traverso says. “For molecules that are particularly difficult to absorb, this would be a way of actually administering them at much higher efficiency.”

“This is a very interesting approach,” says Samir Mitragotri, a professor of chemical engineering at the University of California at Santa Barbara who was not involved in the research. “Oral delivery of drugs is a major challenge, especially for protein drugs. There is tremendous motivation on various fronts for finding other ways to deliver drugs without using the standard needle and syringe.”

Further optimization

This approach could also be used to administer vaccines that normally have to be injected, the researchers say.

The team now plans to modify the capsule so that peristalsis, or contractions of the digestive tract, would slowly squeeze the drug out of the as it travels through the tract. They are also working on capsules with needles made of degradable polymers and sugar that would break off and become embedded in the gut lining, where they would slowly disintegrate and release the . This would further minimize any safety concern.

Omega-3 fatty acids may prevent some forms of depression


Patients with increased inflammation, including those receiving cytokines for medical treatment, have a greatly increased risk of depression. For example, a 6-month treatment course of interferon-alpha therapy for chronic hepatitis C virus infection causes depression in approximately 30% of patients.

Omega-3 fatty acids, more commonly known as fish oil, have a long list of health benefits, including lowering the risk of heart disease and reducing triglyceride levels. These nutritional compounds are also known to have anti-depressant and anti-inflammatory properties.

Despite some recent negative findings, as their tendency to increase the risk for prostate cancer was proven and some of the putative health benefits were not replicated in large trials, omega-3’s remain of high interest to the field, where several studies have suggested benefits for depression and other psychiatric disorders.

This led a group of international researchers, led by senior author Dr. Carmine Pariante, to conduct a randomized, double-blind, placebo-controlled study in order to carefully evaluate the effects of on -induced depression.

They recruited 152 patients with hepatitis C to participate, each of whom was randomized to receive two weeks of treatment with EPA, DHA, or placebo. EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) are the two main omega-3 fatty acids in fish oil supplements.

Following the two-week treatment, the patients received a 24-week course of interferon-alpha treatment and were evaluated repeatedly for depression.

The researchers found that treatment with EPA, but not DHA or placebo, decreased the incidence of interferon-alpha-induced depression in patients being treated for hepatitis C.

Pariante, a Professor at the Institute of Psychiatry, Psychology & Neuroscience at King’s College London, added, “The study shows that even a short course (two weeks) of a nutritional supplement containing one such omega-3 polyunsaturated fatty acid (EPA) reduced the rates of new-onset depression to 10%.”

In addition, both EPA and DHA delayed the onset of depression, and both treatments were well tolerated, with no serious side effects.

“These new data provide promising support for omega-3 fatty acids to prevent depression, complementing other studies where omega-3’s were found to enhance antidepressant treatment,” said Dr. John Krystal, Editor of Biological Psychiatry.

EPA is considered an “endogenous” anti-inflammatory, and in previous work, also published in Biological Psychiatry, these same authors found that subjects with low levels of endogenous EPA in the blood were at higher risk of developing depression. Therefore, the authors speculate that this nutritional intervention restores the natural protective anti-inflammatory capabilities of the body, and thus protects patients from new-onset depression when inflammation occurs.

Although further work is still necessary and the findings must be replicated, these data indicate that omega-3 polyunsaturated may be effective in preventing depression in a group of patients at high-risk of depression because of increased inflammation.

How dinosaur arms turned into bird wings


Although we now appreciate that birds evolved from a branch of the dinosaur family tree, a crucial adaptation for flight has continued to puzzle evolutionary biologists. During the millions of years that elapsed, wrists went from straight to bent and hyperflexible, allowing birds to fold their wings neatly against their bodies when not flying. A resolution to this impasse is now provided by an exciting new study.

(A) Whole-mount alcian blue staining confirms the ulnare is the first carpal formed in avian embryos, distal to the ulna. Thereafter, a distal carpal 3 (referred to as “element x” in previous embryological descriptions) is formed distal to the ulnare, coexisting with it. Finally, the ulnare disappears, whereas dc3 persists.
Credit: J. Botelho et al.; DOI: 10.1371/journal.pbio.1001957

Although we now appreciate that birds evolved from a branch of the dinosaur family tree, a crucial adaptation for flight has continued to puzzle evolutionary biologists. During the millions of years that elapsed, wrists went from straight to bent and hyperflexible, allowing birds to fold their wings neatly against their bodies when not flying.

How this happened has been the subject of much debate, with substantial disagreement between developmental biologists, who study how the wings of modern birds develop in the growing embryo, and palaeontologists who study the bones of dinosaurs and early birds. A resolution to this impasse is now provided by an exciting new study publishing on September 30 in PLOS Biology.

Underlying this striking evolutionary transformation change is a halving in the number of wrist bones, but developmental biologists and palaeontologists have different names for most of them, and seldom agree on the correspondence between specific dinosaur bones and those of their bird descendants. Indeed, each field has radically different data sources, methods, and research objectives, talking little to each other.

The critical advance made in the new study involved combining these two strands of research. Using an interdisciplinary approach, the lab run by Alexander Vargas at the University of Chile has re-examined fossils stored at several museum collections, while at the same time collecting new developmental data from seven different species of modern birds. Joao Botelho, a Brazilian student in Vargas’ lab, developed a revolutionary new technique that allows him to study specific proteins in 3D embryonic skeletons. By combining these data from both fossils and embryos, the research team has made a major step forward in clarifying how the bird wrist evolved.

From early dinosaur ancestors with as many as nine wrist bones, birds have only kept four during the course of evolution, but which of the original bones are they? The identity of each of these bones was debated. For instance, the late Yale professor John Ostrom famously pointed out in the 1970’s that the wrists of both birds and bird-like dinosaurs possess a very similar, half-moon shaped bone called the semilunate, and that this bone resulted from the merging of two bones present in dinosaurs. This formed part of Ostrom’s then-controversial argument that birds descended from dinosaurs. However, the failure of developmental biologists to confirm this raised doubts that it was the same bone, and even that birds came from dinosaurs.

Now, the new data obtained by the Vargas lab has revealed the first developmental evidence that the bird semilunate was formed by the fusion of the two dinosaur bones. They go on to show that another bone — the pisiform — was lost in bird-like dinosaurs, but then re-acquired in the early evolution of birds, probably as an adaptation for flight, where it allows transmission of force on the downstroke while restricting flexibility on the upstroke. Combined, the fossil and developmental data provide a compelling scenario for a rare case of evolutionary reversal.

The study by the Vargas lab also settled the identity of the other two bones of the bird wrist, which were commonly misidentified in both fields. This emphasizes the downsides of not integrating all data sources, and reveals a situation perhaps akin to that of astronomy and experimental physics in the pursuit of cosmology: Together, palaeontology and development can come much closer to telling the whole story of evolution — this integrative approach resolves previous disparities that have challenged the support for the dinosaur-bird link and reveals previously undetected processes, including loss of bones, fusion of bones, and re-evolution of a transiently lost bone.


Story Source:

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


Journal Reference:

  1. João Francisco Botelho, Luis Ossa-Fuentes, Sergio Soto-Acuña, Daniel Smith-Paredes, Daniel Nuñez-León, Miguel Salinas-Saavedra, Macarena Ruiz-Flores, Alexander O. Vargas. New Developmental Evidence Clarifies the Evolution of Wrist Bones in the Dinosaur–Bird Transition. PLoS Biology, 2014; 12 (9): e1001957 DOI: 10.1371/journal.pbio.1001957

Super-bacteria growing in space


Manned space missions bring with them a plethora of challenges to keep astronauts alive and healthy, especially on long-duration space missions. Astronauts need to breathe, eat, drink, excrete their food and drink, and be kept free of infections to stay healthy enough to do their job. The key to an astronauts’ wellbeing has been found, somewhat contradictorily, to be a group of tiny organisms — bacteria.

One challenge for astronauts is keeping well nourished and free of infection, especially on long-duration manned missions.

You might think of space as a germ-free environment, but microbes can be carried to space inside human gut flora as well as in food and water and once up there, can be expelled by humans in their breath.

According to NASA, immune systems weaken during space flight, making the impact of infection even greater.

What’s more, the weightless microgravity environment of space can alter bacteria as they grow. Recent work by Cheryl Nickerson and her team from Arizona State University and her NASA collaborators discovered that certain bacteria become more virulent in space, meaning they become better at causing disease.

Salmonella bacteria become more potent, virulent and are more able to cause disease.
Dr. Cheryl Nickerson, Arizona State University

“Salmonella bacteria become more potent, virulent and are more able to cause disease,” says Nickerson. “They also become more resistant to factors such as the acid in your stomach.” Nickerson’s group is investigating a range of bacteria found in food, water and our gut flora, including Salmonella typhimurium, a common cause of food poisoning and diarrhea, and Pseudomonas aeruginosa, which is a known water contaminant.

‘War with microorganisms’

As astronauts spend longer periods of time in space, their increased exposure to recycled air and water is likely to affect their risk of infection.

Mark Ott is one the people in charge of crew health at NASA and focuses on keeping microbes at bay. “We’re at a constant war with microorganisms because they adapt,” he says. “The stressful environment of spaceflight affects them and under stress your immune system also functions less effectively and we have to take precautions for this.” Reduced immunity can cause some bacteria, such as Pseudomonas aeruginosa, to cause illness despite normally being carried by many of us with no effect.

“However, not all microorganisms are bad and so the key is to understand how they change and impact us,” explains Ott, who also found that the infectious bacteria Staphylococcus aureus, which causes a range of symptoms from boils to food poisoning, may not increase in virulence like Salmonella in microgravity.

The microgravity environment on board the International Space Station (ISS) is useful to explore the inner workings of infectious bacteria.
NASA

By understanding the changes in Salmonella and other disease-causing bacteria in microgravity, Nickerson hopes to not only keep crew healthy but also help humans down on Earth through the development of drugs and vaccines.

“Infections are becoming harder to treat; we have no vaccine for Salmonella food poisoning and it remains [one of] the leading cause of bacterial food-borne illness worldwide,” states Nickerson.

Spaceflight opens up a new world of research that can’t take place on Earth and Nickerson has unmasked key changes in the behavior of genes in the bacteria which aren’t usually seen under gravity. “Vaccines are about identifying targets and in microgravity the bacteria have unmasked themselves and revealed secrets to help develop therapeutics.”

Sustaining life in space

For space missions the mass of oxygen, food, and water is high and not compatible with current launch technologies.
Dr. Christophe Lasseur, European Space Agency.

The research is in its early stages but it’s just one example of how bacteria are being investigated by space agencies. Far from just a health hazard, bacteria could be used to help sustain astronauts in space, as a source of food and oxygen.

“The major advantage to using bacteria is the size of them,” explains Christophe Lasseur, coordinator of life support research and development at the European Space Agency (ESA). “For space missions the mass of oxygen, food, and water is high and not compatible with current launch technologies. A crew of six to Mars would need over 30 tons.”

Lasseur directs the MELLiSSA programme at ESA, which aims to develop a regenerative life-support ecosystem for use on board spacecraft. “We need to recycle everything for an ecosystem that can sustain human life,” says Lasseur. The team wants to recycle 80% of all mass on board, including carbon dioxide, which can become toxic if allowed to build up.

Key algae and bacteria can mop up carbon dioxide and in turn release oxygen to enable astronauts to breathe. “We have approached this molecule by molecule, first oxygen, then water and now food, which is more complex,” says Lasseur.

The chosen range of bacteria not only utilize carbon dioxide but can also harness other human waste products, such as urine and feces — a win-win given their growth results in food for the astronauts.

Eating bacteria grown on urine may not sound like a delicacy, and it isn’t, which is why psychology also comes into play. “Our most advanced work is using spirulina as this has been used as a protein source for many centuries and in many countries, making it much more psychologically acceptable,” explains Lasseur. Spirulina is a cyanobacterium found in many salt water lakes and is consumed readily by lake communities. The edible bacterium is also marketed as a health supplement.

In the search for bacteria that feed on our food waste, Lasseur’s team discovered a hidden gem that has an additional medical benefit — helping to fight cholesterol.

“We were looking for bacteria which use a lot of carbon and nitrogen as there’s a lot of this in waste disposal,” states Lasseur. The resulting use of Rhodospirillum rubrum led to a nutritious product found to produce significantly lower levels of cholesterol in mice and will soon be marketed by spin-off company EzCOL BV, which is in talks with big pharma. This bacterium has been by-passed in favor of more nutritious alternatives for consumption by astronauts but the research to get there has borne beneficial fruit for those of us not venturing up into space.

As for the astronauts, Mars missions could be a reality in the, albeit distant, future. And when the day comes, crews could depart feeling confident of reaching the red planet well fed, watered and free of infection.

Bisphenol A (BPA): Use in Food Contact Application


Summary of FDA’s Current Perspective on BPA in Food Contact Applications

FDA’s current perspective is that BPA is safe at the current levels occurring in foods. Based on FDA’s ongoing safety review of scientific evidence, the available information continues to support the safety of BPA for the currently approved uses in food containers and packaging.

Overview of BPA Usage in Food Contact Applications

BPA is a structural component in polycarbonate beverage bottles. It is also a component in metal can coatings, which protect the food from directly contacting metal surfaces. BPA has been used in food packaging since the 1960s.

As is the case when foods are in direct contact with any packaging material, small, measurable amounts of the packaging materials may migrate into food and can be consumed with it. As part of its premarket review of food packaging materials, FDA’s food contact regulations and food contact notification program assesses the likely migration from the packaging material to assure that any migration to food occurs at safe levels.

Heightened interest in the safe use of BPA in food packaging has resulted in increased public awareness as well as scientific interest. As a result, many exploratory scientific studies have appeared in the public literature. Some of these studies have raised questions about the safety of ingesting the low levels of BPA that can migrate into food from food contact materials. To address these questions the National Toxicology Program, partnering with FDA’s National Center for Toxicological Research is carrying out in-depth studies to answer key questions and clarify uncertainties about BPA.

On the regulatory front, FDA’s regulations authorize FDA to amend its food additive regulations to reflect when certain uses of an additive have been abandoned. FDA can take this action on its own initiative or in response to a food additive petition that demonstrates that a use of a food additive has been permanently and completely abandoned. Recently, FDA granted two petitions requesting that FDA amend its food additive regulations to no longer provide for the use of certain BPA-based materials in baby bottles, sippy cups, and infant formula packaging because these uses have been abandoned. As a result, FDA amended its food additive regulations to no longer provide for these uses of BPA.

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Background

BPA is an industrial chemical used to make polycarbonate, a hard, clear plastic, which is used in many consumer products. BPA is also found in epoxy resins, which act as a protective lining on the inside of some metal-based food and beverage cans. Uses of all substances that migrate from packaging into food, including BPA, are subject to premarket approval by FDA as indirect food additives or food contact substances.  FDA can make regulatory changes based on new safety or usage information. The original approvals for BPA were issued under FDA’s food additive regulations and date from the 1960s.

In 2008 FDA released a document titled Draft Assessment of Bisphenol A for Use in Food Contact Applications.[1] This draft assessment was reviewed by a Subcommittee of FDA’s Science Board, which released its report at the end of October 2008.[2] Also in 2008, the National Toxicology Program Center for the Evaluation of Risks to Human Reproduction, part of the National Institutes of Health, released the Monograph on the Potential Human Reproductive and Developmental Effects of Bisphenol A.[3]

By 2009, FDA released reassessments of studies cited in the NTP Monograph in addition to other relevant studies that became available after the Monograph’s release. [4] The studies were evaluated for their relevance for regulatory hazard and/or risk assessment. In addition to the FDA review process, FDA’s Acting Chief Scientist asked five expert scientists from across the federal government to provide independent scientific review of these documents in the fall of 2009. The results of the independent evaluations were released in April 2010, as FDA made the CFSAN report and other relevant information available for public comment.[5] Although the reassessments indicated a need to further evaluate a number of endpoints or biological outcomes, the analyses did not recommend any adjustments to BPA levels reported in food at that time.

Since that time, the FDA has continued to review additional studies as they became available, including those addressing possible low-dose effects.

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Increasing Our Understanding about the Biology and Metabolism of BPA

Strong consumer and scientific interest in the safety of BPA has prompted FDA to support additional studies to provide further information and address apparent inconsistencies in the scientific literature about BPA. Many of these studies addressed how the body disposes of or metabolizes BPA. These studies also addressed questions about how long it takes for the body to dispose of BPA.

FDA’s Studies.  FDA’s regulatory Centers and FDA’s National Center for Toxicological Research continue to pursue a set of studies on the fate of BPA in the body from various routes of exposure and the safety of low doses of BPA, including assessing novel endpoints where questions have been raised.

Research studies pursued by FDA’s National Center for Toxicological Research have [6]:

  • Found evidence in rodent studies that the level of the active form of BPA passed from expectant mothers to their unborn offspring, following oral exposure, was so low it could not be measured. The study orally dosed pregnant rodents with 100-1000 times more BPA than people are exposed to through food, and could not detect the active form of BPA in the fetus 8 hours after the mother’s exposure.
  • Demonstrated that oral BPA administration results in rapid metabolism of BPA to an inactive form. This results in much lower internal exposure of BPA (i.e., the active form) than what occurs from other routes of exposure such as injection.
  • Found that primates (including humans) of all ages effectively metabolize and excrete BPA much more rapidly and efficiently than rodents.
  • Developed physiologically based pharmacokinetic models that can be used to predict the level of internal exposure to the active and inactive forms of BPA. Based on the effects of metabolism, internal exposures to the active form of BPA following oral administration are predicted to be below 1% or less of the total BPA level administered.
  • Recently completed a rodent subchronic study [7] intended to provide information that would help in designing a long-term study that is now underway (see below). The subchronic study was designed to characterize potential effects of BPA in a wide range of endpoints, including prostate and mammary glands, metabolic changes, and cardiovascular endpoints. The study included an in utero phase, direct dosing to pups to mimic bottle feeding in neonates, and employed a dose range covering the low doses where effects have been previously reported in some animal studies, as well as higher doses where estrogenic effects have been measured in guideline oral studies. The results of this study showed no effects of BPA at any dose in the low-dose range.

The FDA’s National Center for Toxicological Researchis continuing with an additional study:

  • Rodent chronic toxicity study, which is currently underway. Using the data and design from the rodent subchronic study, the National Toxicology Program/Food and Drug Administration (NTP/FDA) is conducting a long-term toxicity study of BPA in rodents to assess a variety of endpoints, including novel endpoints where questions have been raised. As an addition to this core study, FDA is providing extra animals and tissues to a consortium of grantees [8] selected and funded by the National Institute of Environmental Health Sciences to address other critical questions.

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Food Additive Regulations Amended to No Longer Provide for the Use of BPA-Based Materials in Baby Bottles, Sippy Cups, and Infant Formula Packaging

  • FDA has amended its regulations to no longer provide for the use of BPA-based polycarbonate resins in baby bottles and sippy cups. In July, 2012, FDA took this action in response to a food additive petition filed by the American Chemistry Council (ACC) [9]. The ACC petition demonstrated, from publicly available information and information collected from industry sources, that the use of polycarbonate resins in baby bottles and sippy cups had been abandoned.
  • FDA has amended its regulations to no longer provide for the use of BPA-based epoxy resins as coatings in packaging for infant formula.  In July, 2013, FDA took this action in response to a food additive petition filed by Congressman Edward Markey [10] of Massachusetts. This  petition demonstrated, from publicly available information and information collected from industry sources, that the use of BPA-based epoxy resins as coatings in packaging for infant formula had been abandoned.

An amendment of the food additive regulations based on abandonment is not based on safety, but is based on the fact that the regulatory authorization is no longer necessary for the specific use of the food additive because that use has been permanently and completely abandoned. The safety of a food additive is not relevant to FDA’s determination regarding whether a certain use of that food additive has been abandoned.

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Next Steps and Collaborations

FDA continues to review the available information and studies on BPA. FDA will update its assessment of BPA and will take additional action if warranted.  As the scientific field is evolving rapidly, FDA anticipates providing further updates on BPA to the public as significant new information becomes available. Based on FDA’s ongoing safety review of scientific evidence, the available information continues to support the safety of BPA for the currently approved uses in food containers and packaging.

FDA will also continue to consult with other expert agencies in the federal government, including the National Institutes of Health (and the National Toxicology Program), the Environmental Protection Agency, the Consumer Product Safety Commission, and the Centers for Disease Control and Prevention.

FDA will continue to participate in discussions with our international regulatory and public health counterparts who are also engaged in assessing the safety of BPA.

For example, FDA has participated with Health Canada in encouraging industry efforts to refine their manufacturing methods for the production of infant formula can linings to minimize migration of BPA into the formula.

In addition, FDA actively supported and participated in the Expert Consultation on BPA convened by World Health Organization and the Food and Agriculture Organization of the United Nations on November 2-5, 2010, in Ottawa, Canada. Information about this expert consultation and the report of the meeting is available from theWHO web site. [11]

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[1]U.S. Food and Drug Administration, Draft Assessment of Bisphenol A for Use in Food Contact Applications, 14 August 2008.

[2]FDA Science Board Subcommittee on Bisphenol A.  Scientific Peer-Review of the Draft Assessment of Bisphenol A for Use in Food Contact Applications, 31 October 2008.

[3]NTP-CERHR Monograph on the Potential Human Reproductive and Developmental Effects of Bisphenol A, NIH Publication No. 08-5994, September 2008.

[4] http://www.regulations.gov/#!documentDetail;D=FDA-2010-N-0100-0006.

[5] http://www.regulations.gov/#!docketDetail;D=FDA-2010-N-0100;dct=FR%252BPR%252BN%252BO%252BSR

[6]

a) Churchwell MI, Camacho L, Vanlandingham MM, Twaddle NC, Sepehr E, Delclos KB, Fisher JW, Doerge DR.Comparison of life-stage-dependent internal dosimetry for bisphenol a, ethinyl estradiol, a reference estrogen, and endogenous estradiol to test an estrogenic mode of action in Sprague Dawley rats. Toxicol Sci. 2014 May;139(1):4-20. doi: 10.1093/toxsci/kfu021. Epub 2014 Feb 4.

b) Delclos KB, Camacho L, Lewis SM, Vanlandingham MM, Latendresse JR, Olson GR, Davis KJ, Patton RE, Gamboa da Costa G, Woodling KA, Bryant MS, Chidambaram M, Trbojevich R, Juliar BE, Felton RP, Thorn BT.Toxicity evaluation of bisphenol a administered by gavage to sprague dawley rats from gestation day 6 through postnatal day 90. Toxicol Sci. 2014 May;139(1):174-97. doi: 10.1093/toxsci/kfu022. Epub 2014 Feb 4.

c) Doerge DR, Twaddle NC, Vanlandingham M, Fisher JW. Pharmacokinetics of bisphenol A in neonatal and adult Sprague-Dawley rats. Toxicol Appl Pharmacol. 2010 Sep 1;247(2):158-65.

d) Doerge DR, Twaddle NC, Vanlandingham M, Brown RP, Fisher JW. Distribution of bisphenol A into tissues of adult, neonatal, and fetal Sprague-Dawley rats. Toxicol Appl Pharmacol. 2011 Sep 15;255(3):261-70.

e) Doerge DR, Twaddle NC, Vanlandingham M, Fisher JW. Pharmacokinetics of bisphenol A in neonatal and adult CD-1 mice: inter-species comparisons with Sprague-Dawley rats and rhesus monkeys. Toxicol Lett. 2011 Dec 15;207(3):298-305.

f) Doerge DR, Twaddle NC, Vanlandingham M, Fisher JW. Pharmacokinetics of bisphenol A in serum and adipose tissue following intravenous administration to adult female CD-1 mice. Toxicol Lett. 2012 Jun 1;211(2):114-9.

g) Doerge DR, Twaddle NC, Woodling KA, Fisher JW. Pharmacokinetics of bisphenol A in neonatal and adult rhesus monkeys. Toxicol Appl Pharmacol. 2010 Oct 1;248(1):1-11.

h) Fisher JW, Twaddle NC, Vanlandingham M, Doerge DR. Pharmacokinetic modeling: prediction and evaluation of route dependent dosimetry of bisphenol A in monkeys with extrapolation to humans. Toxicol Appl Pharmacol. 2011 Nov 15;257(1):122-36.

i) Doerge DR, Vanlandingham M, Twaddle NC, Delclos KB. Lactational transfer of bisphenol A in Sprague-Dawley rats. Toxicol Lett. 2010 Dec 15;199(3):372-6.

j) Ferguson SA, Law CD Jr, Abshire JS. Developmental treatment with bisphenol A or ethinyl estradiol causes few alterations on early preweaning measures. Toxicol Sci. 2011 Nov;124(1):149-60.

k) He Z, Paule MG, Ferguson SA. Low oral doses of bisphenol A increase volume of the sexually dimorphic nucleus of the preoptic area in male, but not female, rats at postnatal day 21. Neurotoxicol Teratol. 2012 May-Jun;34(3):331-7.

l) Patterson TA, Twaddle NC, Roegge CS, Callicott RJ, Fisher JW, Doerge DR. Concurrent determination of bisphenol A pharmacokinetics in maternal and fetal rhesus monkeys. Toxicol Appl Pharmacol. 2013 Feb 15;267(1):41-8.

m) Twaddle NC, Churchwell MI, Vanlandingham M, Doerge DR. Quantification of deuterated bisphenol A in serum, tissues, and excreta from adult Sprague-Dawley rats using liquid chromatography with tandem mass spectrometry. Rapid Commun Mass Spectrom. 2010 Oct 30;24(20):3011-20.

n) Yang X, Doerge DR, Fisher JW. Prediction and evaluation of route dependent dosimetry of BPA in rats at different life stages using a physiologically based pharmacokinetic model. Toxicol Appl Pharmacol. 2013 Jul 1;270(1):45-59.

[7] Study available upon request.

[8] Schug et al. (2013) A new approach to synergize academic and guideline-compliant research: the CLARITY-BPA research program. Reprod Toxicol. 40:35-40.

[9] 77 Fed. Reg. 41,899

[10] 78 Fed. Reg. 41,840

[11] http://www.who.int/foodsafety/chem/chemicals/bisphenol/en/index2.html