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28 abril 2015
Tiny vehicles deliver more medication to tumors and reduce side...
Tiny vehicles deliver more medication to tumors and reduce side effects
Cancer plays a deadly game of hide-and-seek in the body, and the drugs sent to treat it are often the losers—as is the cancer patient. The drugs have trouble distinguishing between tumor cells and healthy ones and may drop their payload on the normal cells, causing miserable side effects and leaving nearby cancer cells untouched. Malignancies may also get a helping hand from the body’s own leading defense weapon, the immune system. It often mistakes anticancer drugs for harmful bacteria or other foreign invaders and breaks them down. The shattered pieces are conveyed to the body’s trash receptacles in the liver, kidneys and spleen, again, before they reach their intended target. Even when the drugs do manage to arrive at a tumor, many of them become entangled in the dense undergrowth of the malignant mass—unable to penetrate it completely.
Recent advances in nanomedicine are now allowing drugs to better traverse this fraught landscape and hit tumors where they live. The key is a uniquely crafted drug vehicle, wrapped in a protective outer shell, that shuttles the chemotherapy drugs through the body. Fine-grained control over the components from which the vehicles are built, which can be just a few billionths of a meter across, has let scientists create a specialized architecture that, among other things, does not trip immune system alarms. Researchers such as Kazunori Kataoka of the University of Tokyo and his colleagues have tucked potent chemotherapy drugs inside sheaths the size of a hepatitis C virus— some 200 times as small as a red blood cell. On a molecular level, those drugs look a lot more like something the body makes. These compounds also have the advantage of being able to slip into tumors and steer clear of healthy cells.
Several versions of nanodrug vehicles from Kataoka’s team, each holding different medications and aimed at different types of tumors, are now wending their way through the final stages of clinical trials in Asia. Drugs in these new carriers have slowed or reversed disease progression in people with breast or pancreatic cancer. Still another nanoparticle is in the second stage of clinical trials in the U.S. “With science like this, the initial stages take time, but I believe the field is starting to show promise,” Kataoka says. “The development speed will be much faster in the coming five years.”
DRUGS IN DISGUISE
Employing nanotechnology for chemotherapy drugs is not a brand-new idea. Medications such as Abraxane for metastatic breast cancer and Eligard for advanced prostate cancer, which are already on the market, are nanodrugs. But these pharmaceuticals attack only certain tumors, so more therapies are needed. Subsequent advances in engineering have allowed scientists to tweak the structure of nanocarriers so they work against a wider array of cancers with even greater precision. The nanotherapies now being tested—administered via an intravenous injection—seem to be more effective at eliminating tumors.
Most of these newer nanomedicines encase a drug-containing core in a soft sheath dotted with polyethylene glycol, a synthetic material that acts as a cloaking agent. That cloak is a covering of water molecules, which are attracted by the sheath material and thus surround it with a common body liquid. Water helps to block electrical charges from the particle that would otherwise alert the immune system to the presence of a foreign substance.
The liquid buffer also covers the nanoparticle’s edges, making it too smooth to provide purchase for any passing sentries from the immune system, such as antibodies. The size of the nanoparticle—somewhat larger than a traditional chemotherapy drug—also helps to ensure that it is not broken down too quickly by the body’s enzymes. That resistance to degradation gives the drug more time to reach a tumor and do its job. For example, the first approved nanotherapy for cancer, called Doxil, has a half-life in the bloodstream that allows it to survive much longer than its conventional chemotherapy cousin, doxorubicin. (Both drugs are used to treat ovarian cancer.) With its design and protective coating, the nanoscale version is better poised to get to tumors without being destroyed by the body. The soft, flexible texture of the newest nanoshell-type drugs also allows them to skip through one of their final obstacles: the dense, irregular ecosystem of the malig- nant tissue that could snag something more rigid.
The final weapon of the new nanoparticles lies within their inner depths. The drug-containing core can be broken down by acid, so it will readily disintegrate and shed its drug cargo only after it leaves the neutral environment of the blood and arrives at its tumor destination, which has much higher acid levels.
To better steer the nanocarriers toward cancers and away from healthy cells, other scientists are trying to dot their exteriors with selected antibody molecules that are attracted to proteins that are particularly abundant on cancer cells. Proteins such as EGFR are one such example, and University of California, Los Angeles, bioengineer Dean Ho has done preliminary experiments, published in Advanced Materials in 2013, showing that nanoparticles can be layered with antibodies that link to those proteins.
Nanoparticles can also be built to serve as actual medicines, not just the delivery vehicles. Scientists at Northwestern University created nanoparticles made from bits of gold and laced with genetic material—RNA—selected for its ability to silence cancer-causing genes. Because of the particles’ small size and other yet to be determined factors, gold nanoparticles studded with RNA can penetrate one of the hardest places to reach with a drug: the brain. In October 2013 researchers reported that, in animals, the nanoparticles can cross the blood-brain barrier—a tight mesh of small blood vessels—to help combat brain tumors. The approach caused overall tumor size to shrink in rodents, but ultimately the creatures still died from the cancer, says researcher Alexander Stegh of Northwestern. Exactly how this technique managed to clear the blood-brain barrier is still being explored, he notes. It is possible that the particles’ structure binds to receptor molecules on the surfaces of blood vessel cells, and the receptors help to pull them in.
Still other types of nanoparticles made from nucleic acids are being studied as probes to detect cancer cells that circulate through human blood. Chad A. Mirkin, a Northwestern chemist leading the project, says the research may lead to nanoparticles that carry both diagnostic chemicals and medicine—a formidable package that could eliminate hard-to-find cancerous cells before they spread to new places in the body. Devising that kind of tiny powerhouse would be no small feat.
Dementia ‘halted in mice brains’The team at Duke University, in...
Dementia ‘halted in mice brains’
The team at Duke University, in the US, showed immune cells which start attacking nutrients in the brain may be a trigger for the disease.
They say their findings could open up new avenues of research for a field that has not developed a single drug to slow the progression of the disease.
Experts said the findings offered new hope of a treatment.
The researchers indentified microglia - normally the first line of defence against infection in the brain - as major players in the development of dementia.
They found some microglia changed to become exceptionally adept at breaking down a component of protein, an amino acid called arginine, in the early stages of the disease.
As arginine levels plummeted, the immune cells appeared to dampened the immune system in the brain.
Stopping dementia
In mouse experiments, a chemical was used to block the enzymes that break down arginine.
They showed fewer of the characteristics of dementia such as damaged proteins collecting in the brain and the animals performed better in memory tests.
One of the researchers, Dr Matthew Kan, said: “All of this suggests to us that if you can block this local process of amino acid deprivation, then you can protect the mouse, at least from Alzheimer’s disease.
“We see this study opening the doors to thinking about Alzheimer’s in a completely different way, to break the stalemate of ideas in Alzheimer’s disease.”
However, the findings do not suggest that arginine supplements could combat dementia as the boosted levels would still be broken down.
‘Hope’
Dr James Pickett, from the Alzheimer’s Society said the study was “offering hope that these findings could lead to new treatments for dementia”.
He added: “This study in animals joins some of the dots in our incomplete understanding of the processes that cause Alzheimer’s disease, in particular around the role played by the immune system.”
Dr Laura Phipps, from Alzheimer’s Research UK, said the study was “interesting” and shed “more light on the mechanisms of immune system involvement in Alzheimer’s”.
But she cautioned clinical trials in people were still needed and that “the findings do not suggest that supplementation of the amino acid could mirror the benefits seen in these mice”.
Can humans hibernate in space? What better way to pass a long...
Can humans hibernate in space?
What better way to pass a long stretch of time than by entering a deep sleep to shut down some bodily functions and conserve energy? Bears do it to get through cold winters. So do many smaller mammals, including squirrels and hedgehogs. Even the fat-tailed lemur (a primate cousin ofHomo sapiens), living in warm Madagascar, slows down for months when its food supply runs low. But for us humans, hibernation has been an unnecessary and impossible goal. Until now.
Taking lessons from animal hibernators, scientists are using their tricks for medical therapies and may some day adopt them for space travel. Some physicians are employing therapeutic hypothermia – a lowering of the body temperature by a few degrees for several days at a time – to help treat patients with traumatic brain injuries or conditions such as epilepsy. And trials are under way to see if there is a way to lower the body temperature of people, keep them in a sleep-like state for days or weeks and then revive them with no ill effects, something that astronauts may have to do to travel deep into space.
“We see the science has advanced enough to put some of the science fiction into the realm of science reality,” says Leopold Summerer, head of the advanced concepts team of the European Space Agency, one of the operators of the International Space Station. “It doesn’t mean we will have hibernating astronauts any time soon, but we are learning from nature how to understand some of the things that happen to animals during hibernation, such as preventing bone loss or preventing muscle loss.”
A panel of European biomedical researchers, biologists and neuroscientists is expected to deliver recommendations for future lines of human hibernation research and funding soon, according to Summerer. One Italian scientist says he is conducting an experiment to test an animal’s body thermostat for a six-hour period as a precursor to human trials.
Nasa funded a preliminary study that looked at the idea of putting astronauts into a state of torpor, or hibernation, for weeks at a time. The prospective benefits that were reported last year included a cut in the food and water required on their spacecraft, a reduction in waste products, smaller living quarters and less space needed for supplies, exercise and entertainment. And putting the crew to sleep might minimise their psychological challenges.The idea, however, didn’t make it to a second round of funding. John Bradford, head of the company that proposed the human hibernation, says he’s hoping to get funding elsewhere. Nasa says it will be using the year-long sojourn US astronaut Scott Kelly just started at the International Space Station, combined with medical monitoring of his Earthbound twin brother, retired astronaut Mark Kelly, to collect clues about protecting humans who leave Earth’s orbit for months or years at a time.
Biologists aren’t waiting for results from space. They are busy dissecting the neurological and biochemical pathways of such hibernating animals as the Arctic ground squirrel, which sets its internal body temperature at freezing point during the winter, and several kinds of bears that slumber six months at a time without awakening as puny weaklings. “We think that if we understand how they do it, we can replicate it in humans,” said Kelly Drew, a biochemist at the University of Alaska at Fairbanks. Drew and her colleagues at the university’s Institute of Arctic Biology are looking at how the Arctic ground squirrel can get so cold without dying. She believes she has found the molecule that does the job, the A1 adenosine receptor. While she has learned that stimulating this receptor makes the animal get cold, she hasn’t found what triggers it.
“We don’t know what the natural signal is for torpor,” she said. “We don’t know where the signal occurs in the brain – it could be in the brain stem or the hypothalamus.” The next step is to learn how to safely use drugs that stimulate the A1 adenosine receptor and then induce animals that do not normally hibernate to enter and stay in a state of torpor for two to three weeks at a time.
A shorter period of human deep sleep, induced by cooling the body, isalready used to help brain-injury patients at the Johns Hopkins University and many other hospitals. Romergryko Geocadin, a Hopkins professor of neurology and anaesthesiology, has used the treatment, known as therapeutic hypothermia, to help patients with severe epilepsy or brain trauma. “We don’t know why it works,” Geocadin said, “but we know it slows down metabolism and the inflammation” that occurs in the brain with epilepsy. Cooling the body gives the brain a chance to repair itself. “You actually lower the need for energy for the entire body,” he said. “So you give it time to catch up.”
Using ice packs, liquid-filled blankets, caps and even cooling IV fluids, Geocadin lowers a patient’s body temperature from its ordinary level of about 37C to about 33-34C for up to three days at a time. (This involves a handful of patients each month who are comatose because of cardiac arrest or who are experiencing seizures or brain swelling.) Longer than that, “and the whole house of cards starts to fall apart”, increasing the risk of blood clots, pneumonia and other complications.
Scientists in Italy have started a clinical trial to lower a pig’s temperature by inhibiting a part of the hypothalamus that controls energy levels, in effect inducing hypothermia.It’s a proof-of-concept trial that could lead to longer durations of torpor for an animal that doesn’t normally hibernate. Inhibiting this region of the brain “seems to work the same way in several different species”, said Matteo Cerri, an assistant professor of physiology at the University of Bologna, who is leading the work. “There is some wishful thinking that the same [areas of the brain] could work across all mammals.” Cerri and other researchers hope to apply some of these new medical and pharmaceutical approaches to healthy human volunteers. But that could be a way off, scientists say, given the moral issues. What if something goes wrong? It’s an ethical gulf that perhaps is just as great as the challenge of sending a rocket to Mars. “If you are not conscious, how are we going to know what to do if something goes wrong?” Cerri asks. Still, he says he’d be happy to be a volunteer. “I would love to try it.”
Yet there are sceptics who doubt that any of this will lead toward human hibernation useful for space travel. Stanford University neurobiologist Craig Heller has studied black bears and northern brown bears. Lowering their body temperature by only a few degrees, they curl up for months without urinating or defecating. Because bears recycle the nitrogen from their waste products, going for months without moving doesn’t seem to affect their bones or muscles. Astronauts can barely walk after returning from a few weeks or months in zero gravity, and have to keep up rigorous exerciseprogrammes to maintain bones and muscles while in orbit. So while it might be possible to induce humans into deep sleep by cooling the body, Heller said, a months-long spaceflight under such conditions is likely to be too damaging.
“I think it’s probably not doable,” he said. “The hibernator [animal] has evolved so that all the enzymes and biochemical systems are adapted to run at low temperature. That is not true of animals that don’t experience it. We can lower body temperature and survive that for a short period of time; it’s unlikely we can allow all of our systems to go to a much lower temperature and continue to function.”
April 28th 1908: Oskar Schindler bornOn this day in 1908, the...
Oskar Schindler (1908 - 1974)
Schindler's grave covered in small stones left by Jewish visitors
April 28th 1908: Oskar Schindler born
On this day in 1908, the famous German industrialist Oskar Schindler was born. Hailing from Zwittau, Austria-Hungary - which is now Svitavy, Czech Republic - he had a variety of jobs, including farming and driving instruction, before finding success in industry. In the 1930s, Schindler began working as a spy for the German intelligence agency, which resulted to his arrest for espionage. However, he escaped the death penalty when the Sudetenland was annexed by Germany from Czechoslovakia. He quickly rose through the ranks of the German administration, and joined the Nazi Party in 1939. Through his black market connections, he leased an enamelware factory, eventually employing hundreds of employees, many of whom were Jewish. Schindler is most famous for saving the lives of 1,100 Jews during the Holocaust by employing them in his factories. Due to his efforts to save people from extermination, Schindler has been hailed as a hero. He was the subject of the 1982 novel ‘Schindler’s Ark’ and the 1993 film ‘Schindler’s List’.
stars & saturn’s rings, photographed by cassini, 25th april...
stars & saturn’s rings, photographed by cassini, 25th april 2015.
12 images. the background stars appear to move because of the motion of cassini relative to the rings.
image credit: nasa/jpl/ssi. animation: ageofdestruction.
ageGo Here –> http://bit.ly/EmbCognition to read an...
Go Here –> http://bit.ly/EmbCognition to read an excellent full-text article by Dr. Andrew Wilson and Dr. Sabrina Golonka on embodied cognition.
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New Research Shows Early Humans Had Wide Range Of Body Types
Actually, we always knew that – look at the wide range of body types you see today. What’s interesting about the latest study is how early the variety appeared. This study, using tiny fragments to estimate body masses of homo erectus and other early homo species, points to a variety of heights living around the same times. It was previously believed that homo erectus developed longer legs and greater body mass, and this pushed the species to spread into Eurasia. But if there was a variety of heights and body masses, that could not have been why the species began to move into new continents.
The study looked around 2.5 and 1.5 million years ago, when homo species shared the earth with mammoths and sabre-toothed tigers. Comparing measurements of fossils from sites in Kenya, Tanzania, South Africa, and Georgia, the researchers found that there was significant regional variation in the size of early humans during the Pleistocene. And they found that there were a great variety in “average” heights of populations. This suggested local conditions, versus species’ overall evolution, dictated body size. In short, there was great diversity among early homos. According to one of the researchers, “It’s possible to interpret our findings as showing that there were either multiple species of early human, such as Homo habilis, Homo ergaster and Homo rudolfensis, or one highly diverse species. This fits well with recent cranial evidence for tremendous diversity among early members of the genus Homo.“
Astronaut Scott Kelly Speaks at Shuttle Enterprise Dedication Ceremony
NASA astronaut Scott Kelly delivers remarks from onboard the International Space Station during the Space Shuttle Enterprise dedication ceremony Monday, April 27, 2015, at the Intrepid Sea, Air & Space Museum in New York City. Enterprise was dedicated to the fallen crews who gave their lives in pursuit of space exploration.
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Tu casa es mi casa AMERICA is a country built by immigration,...
AMERICA is a country built by immigration, but nothing in its history compares to the rise in its Hispanic population. Changes to immigration law in the 1960s triggered a decades-long surge in arrivals, taking the Hispanic population from just 7m in 1970 to 57m today, a number that is set to double by mid-century. At that point one in four Americans will be of Latino descent. In relation to the population of the day, there have been proportionally larger surges in the past, notably involving European migrations in the 19th and early 20th centuries.
Two factors make the rise of Hispanic America different. Never before has such a large group of new arrivals lived so close to their ancestral homelands, linked to grandparents in the same time zone by cheap flights and Skype. Secondly, America is entering an era of white decline. For almost two centuries, from the time of George Washington’s presidency to the election of Ronald Reagan, whites of European descent made up at least 80% of the population. That share is below two-thirds now, and the white majority is set to become a minority by 2044. That brings both challenges and opportunities. Today’s Hispanics lag behind whites when it comes to education and wealth. But they are strikingly young, lowering America’s median age and offering workers to fill the labour market when other rich countries face greying decline. Politicians too often discuss Hispanics as almost a single-issue group, as victims or villains of immigration. But five-sixths are legal residents and recent Latino growth has been mostly from births, not new arrivals. Hispanics are dispersing across the country and their political clout will only grow: nearly 1m US-born Latinos reach voting age annually.
(From The Economist)
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