Sunday, February 2, 2014

Philip Seymour Hoffman's Drug Overdose

Sources: Philip Seymour Hoffman dead of apparent drug overdose

By Shimon Prokupecz, Todd Leopold and Steve Almasy, CNN

updated 4:25 PM EST, Sun February 2, 2014

Hoffman played the slightly creepy production assistant Scotty in 1997's "Boogie Nights," with Mark Wahlberg and John C. Reilly.

HIDE CAPTION

Philip Seymour Hoffman: Master of film

STORY HIGHLIGHTS

NEW: Sources: Investigators found empty bags stamped with street names for heroin
Police are investigating the scene; an autopsy is scheduled for Monday
Law enforcement sources tell CNN that a needle was found in Hoffman's arm
He won an Oscar for the film "Capote"

(CNN) -- Oscar-winning actor Philip Seymour Hoffman has been found dead of an apparent drug overdose in his Manhattan apartment, law enforcement sources said Sunday.

Police said Hoffman, 46, was found on the bathroom floor and pronounced dead at the scene.

Investigators found two bags of what is believed to be heroin inside the fourth-floor apartment, law enforcement officials said.

Police are investigating to determine whether anyone was with the actor when he died, the officials said.

$Philip Seymour Hoffman arrives for the Los Angeles premiere of \'The Hunger Games: Catching Fire\' at the Nokia Theatre LA Live in Los Angeles, California, on November 18.$

Philip Seymour Hoffman arrives for the Los Angeles premiere of 'The Hunger Games: Catching Fire' at the Nokia Theatre LA Live in Los Angeles, California, on November 18.

Photos: People we lost in 2014

"We are devastated by the loss of our beloved Phil and appreciate the outpouring of love and support we have received from everyone. This is a tragic and sudden loss and we ask that you respect our privacy during this time of grieving," Hoffman's family said in a statement. "Please keep Phil in your thoughts and prayers."

Hoffman was last seen alive at 8 p.m. Saturday, a law enforcement official said. He was expected to get his kids on Sunday, but didn't show up, the official said. Playwright David Katz and another person went to the apartment and found him dead, the official said.

A needle was in the actor's left arm, and eight empty glassine-type bags that usually contain heroin were found in the apartment, law enforcement sources told CNN.

The bags were stamped with "Ace of Hearts" and "Ace of Spades" -- street names for the heroin, the sources said.

An autopsy will be conducted on Hoffman's body Monday, said Julie Blocker, a spokeswoman for New York City's Office of Chief Medical Examiner.

Hoffman won an Academy Award for best actor for the 2005 biopic "Capote."

He was a beefy 5-foot-10-inch man, but was convincing as the slight, 5-foot-3-inch Truman Capote. He had a booming voice like a deity's but often played shlubby, conflicted characters.

He could be heartfelt and giving, as with his male nurse in "Magnolia" or rock critic in "Almost Famous," or creepily Machiavellian, like the gamemaster in the latest "Hunger Games" movie or a "Mission: Impossible" movie villain.

He also appeared in "Charlie Wilson's War," "Doubt," and "The Master," for which he was nominated as best supporting actor.

According to a biography of the actor posted on the Turner Classic Movies website, last year Hoffman revealed he was seeking treatment for drug abuse, and "seemed to be confident that he was getting a handle on the situation."

Hoffman's father was a salesman and his mother was a family court judge, the biography says.

He landed his first professional stage role before graduating from high school and went on to study acting at New York University.

In Hollywood, his big break came with a small role as Chris O'Donnell's classmate in the 1992 film "Scent of a Woman."

For years, Hoffman was the kind of anonymous character actor who earned critical raves but was often unnoticed by the general public. He used his abilities to take chances with such directors as a then-unknown Paul Thomas Anderson, with whom he worked in "Hard Eight" (and several ensuing films, as both became better known) and Todd Solondz ("Happiness").

"I think about that a lot," he told Esquire in 2012 of his anonymity. "I feel it cracking lately, the older I'm getting. I think I'm less anonymous than I was."

Even after winning the Academy Award, he took challenging roles. He was an L. Ron Hubbard-style leader in "The Master" and an intense theater director in "Synecdoche, New York." Neither lit up the box office, but Hoffman's performances earned wide praise for their immersiveness.

Hoffman appeared last month at the Sundance Film Festival, where a movie he starred in, "God's Pocket," premiered.

After his Oscar win at the Academy Awards in 2006, Hoffman thanked his mother for taking him to his first play.

"She brought up four kids alone and she deserves a congratulations for that. Ah, we're at the party, Ma, you know? And she took me to my first play and she stayed up with me and watched the NCAA Final Four, and my passions, her passions became my passions. And, you know, be proud, Mom, because I'm proud of you and we're here tonight and it's so good," he said in his acceptance speech.

Hoffman stayed active on stage even as his star rose in Hollywood. He starred in a Broadway production of "Death of a Salesman" in 2012 and was co-artistic director of the Labyrinth Theater Company in New York.

He is survived by three children and his longtime partner, Mimi O'Donnell.

Saturday, February 1, 2014

Molecules

This morning this episode of Radiolab reran on WNYC. This is the "shorts" version of a longer episode all about symmetry. The first 8 minutes or so of the short is about chirality and talks a little about a drug called thalidomide. It's old news (1950s), but I thought it was interesting.

Thursday, January 30, 2014

Psychobiotics: How gut bacteria mess with your mind

Gut bugs can change the way our brains work, offering new ways to relieve problems like stress, anxiety and depression, say two leading professors

WE HAVE all experienced the influence of gut bacteria on our emotions. Just think how you felt the last time you had a stomach bug. Now it is becoming clear that certain gut bacteria can positively influence our mood and behaviour. The way they achieve this is gradually being uncovered, raising the possibility of unlocking new ways to treat neurobehavioural disorders such as depression and obsessive-compulsive disorder (OCD).

We acquire our intestinal microbes immediately after birth, and live in an important symbiotic relationship with them. There are far more bacteria in your gut than cells in your body, and their weight roughly equals that of your brain. These bacteria have a vast array of genes, capable of producing hundreds if not thousands of chemicals, many of which influence your brain. In fact, bacteria produce some of the same molecules as those used in brain signalling, such as dopamine, serotonin and gamma-aminobutyric acid (GABA). Furthermore, the brain is predominantly made of fats, and many of these fats are also produced by the metabolic activity of bacteria.

In the absence of gut bacteria, brain structure and function are altered. Studies of mice reared in a germ-free environment, with no exposure to bacteria, show that such mice have alterations in memory, emotional state and behaviour. They show autistic patterns of behaviour, spending as much time focusing on inanimate objects as on other mice. This behavioural change is driven by alterations in the underlying brain chemistry. For example, dramatic changes in serotonin transmission are seen, together with changes in key molecules such as brain-derived neurotrophic factor, which plays a fundamental role in forming new synapses.

Cancer Painkiller Blamed for 22 Pennsylvania Deaths

Cancer painkiller mixed with heroin blamed for 22 Pennsylvania deaths

From Lorenzo Ferrigno and Kevin Conlon, CNN

updated 12:32 PM EST, Tue January 28, 2014

A deadly mix of heroin and fentanyl has led to a rise in drug overdoses in Pennsylvania.

STORY HIGHLIGHTS

"This is not accidental," Pittsburgh medical examiner says
Fentanyl is used to treat pain in cancer patients
Mixing it with heroin is "extremely dangerous" mix, prosecutor warns

(CNN) -- Dr. Karl Williams says he normally sees three or four deaths from drug overdoses in a typical week as the chief medical examiner in Pennsylvania's Allegheny County, which includes Pittsburgh.

In the past week, he saw 15 -- men and women, of various ethnicities, ranging in age from 22 to 53. All of them appear to have been heroin users who instead received a mix of heroin andfentanyl, a powerful narcotic used to treat cancer patients' pain, Williams told CNN.

"This is pretty clearly somebody manufacturing fentanyl and selling it as heroin," Williams said.

The deaths Williams has recorded are among nearly two dozen in western Pennsylvania linked to a heroin-fentanyl mix, state Attorney General Kathleen Kane said Monday. The "extremely dangerous and potentially lethal" combination has killed 22 people in six counties, Kane said in a written statement.

Heroin use soaring in U.S.

Heroin and its devastating toll

"We are working with the Allegheny County Police Department, the Pittsburgh Police, and their counterparts in the region to get this deadly mix of heroin off the streets of Western Pennsylvania, and to arrest and prosecute anyone caught selling, distributing, and producing these drugs," her statement said.

Williams said fentanyl can be 10-100 times more potent than morphine, the base molecule in heroin, and it's only distributed as a powder when someone is manufacturing it illegally. The drug is being distributed in bags marked "Income Tax," "Bud Ice" and "Theraflu, Williams said.

"This is not accidental. Somebody is deliberately trying to make a big batch of fentanyl," he said. "It is not an extraordinarily complex molecule to synthesize, and you can find instructions on the Internet. It does not take a sophisticated chemist to do this."

It's not the first time that fentanyl has turned up on the streets of Pittsburgh. In 1988, Williams said, 17 people died when a chemist distributed fentanyl as heroin.

And in 2006, in Philadelphia, 269 people were killed by fentanyl overdoses, the state Department of Drug and Alcohol Programs said. The agency raised new alarms about fentanyl in July, blaming it for 50 deaths in Pennsylvania by mid-2013.

Russia's drug-resistant TB spreading more easily

NATURE | NEWS
Newly discovered mutations help tuberculosis to stay infectious while evolving resistance to multiple drugs.

ZUMA Press, Inc. / Alamy

A patient undergoing chest X-rays at an anti-tubercular clinic in St. Petersburg.

Bacterial 'superbugs' are getting ever more potent. Tuberculosis (TB) strains in Russia carry mutations that not only make them resistant to antibiotics but also help them to spread more effectively, according to an analysis of 1,000 genomes from different TB isolates — one of the largest whole-genome study of a single bacterial species so far.

TB, which is caused by the bacterium Mycobacterium tuberculosis, exploded in Russia and other former Soviet nations in the early 1990s, after the collapse of the Soviet Union and its health system. The incomplete antibiotic regimens some patients received, meanwhile, sparked rampant drug resistance. But the latest study of TB cases in Russia, published today in Nature Genetics¹, indicates that such ‘programmatic’ failures may not be the only explanation for the rise of drug-resistant TB in the region — biological factors also play a big part.

As part of a long-standing effort to study the rampant drug-resistant TB in Samara, a region of Russia about 1,000 kilometres southeast of Moscow, researchers collected TB isolates from 2,348 patients and sequenced the entire genomes of 1,000 of them. This enabled the team to identify previously unknown mutations linked to antibiotic resistance, as well as 'compensatory mutations' that improve the ability of drug-resistant TB to spread.

Nearly half of the TB isolates were multi-drug resistant, which means that they were impervious to the two common first-line antibiotics that cure most TB infections, while 16% of these isolates also harboured mutations that made them impervious to ‘second-line’ drugs. These infections are more expensive to treat, and patients who receive ineffective drugs are more likely to spread TB.

Antibiotics in Animals Tied to Risk of Human Infection

A federal analysis of 30 antibiotics used in animal feed found that the majority of them were likely to be contributing to the growing problem of bacterial infections that are resistant to treatment in people, according to documents released Monday by a health advocacy group.

... scientists from the F.D.A. studied 30 penicillin and tetracycline additives in animal feed. They found that 18 of them posed a high risk of exposing humans to antibiotic-resistant bacteria through food.

Resistant bacteria make it difficult and sometimes impossible to treat infections with ordinary antibiotics. The scientists did not have enough data to judge the other 12 drugs.

At least two million Americans fall sick every year and about 23,000 die from antibiotic-resistant infections, the Centers for Disease Control and Prevention estimates. Representatives of the food industry largely blame hospitals and treatments given to people for the rise of deadly superbugs. But many scientists believe that indiscriminate use of antibiotics in animal feed is a major contributor.

Farmers and ranchers feed small amounts of the drugs to animals over their lifetimes to keep them healthy in crowded conditions, causing bacteria to develop a resistance passed on to people through the environment and eating meat from the animals.

The F.D.A. has tried repeatedly to rein in the use of the drugs in animals. It adopted regulations in 1973 that required companies to submit studies showing that a drug’s use in animal feed did not promote resistance in people.

In 1977, the agency proposed withdrawing approvals for animal feed additives containing penicillin and most tetracyclines, but it never followed through, said Avinash Kar, a lawyer for the Natural Resources Defense Council. The group sued the agency in 2012 to try to force it to carry out the 1977 proposal.

“This is an agency that has repeatedly found, since the 1970s, that these drugs pose a risk to human health, but it has not done anything meaningful with those conclusions,” Mr. Kar said.

Obama Interview about Marijuana

ANNALS OF THE PRESIDENCY

GOING THE DISTANCE

On and off the road with Barack Obama.

BY DAVID REMNICK

When I asked Obama about another area of shifting public opinion—the legalization of marijuana—he seemed even less eager to evolve with any dispatch and get in front of the issue. “As has been well documented, I smoked pot as a kid, and I view it as a bad habit and a vice, not very different from the cigarettes that I smoked as a young person up through a big chunk of my adult life. I don’t think it is more dangerous than alcohol.”

Is it less dangerous? I asked.

Obama leaned back and let a moment go by. That’s one of his moves. When he is interviewed, particularly for print, he has the habit of slowing himself down, and the result is a spool of cautious lucidity. He speaks in paragraphs and with moments of revision. Sometimes he will stop in the middle of a sentence and say, “Scratch that,” or, “I think the grammar was all screwed up in that sentence, so let me start again.”

Less dangerous, he said, “in terms of its impact on the individual consumer. It’s not something I encourage, and I’ve told my daughters I think it’s a bad idea, a waste of time, not very healthy.” What clearly does trouble him is the radically disproportionate arrests and incarcerations for marijuana among minorities. “Middle-class kids don’t get locked up for smoking pot, and poor kids do,” he said. “And African-American kids and Latino kids are more likely to be poor and less likely to have the resources and the support to avoid unduly harsh penalties.” But, he said, “we should not be locking up kids or individual users for long stretches of jail time when some of the folks who are writing those laws have probably done the same thing.” Accordingly, he said of the legalization of marijuana in Colorado and Washington that “it’s important for it to go forward because it’s important for society not to have a situation in which a large portion of people have at one time or another broken the law and only a select few get punished.”

As is his habit, he nimbly argued the other side. “Having said all that, those who argue that legalizing marijuana is a panacea and it solves all these social problems I think are probably overstating the case. There is a lot of hair on that policy. And the experiment that’s going to be taking place in Colorado and Washington is going to be, I think, a challenge.” He noted the slippery-slope arguments that might arise. “I also think that, when it comes to harder drugs, the harm done to the user is profound and the social costs are profound. And you do start getting into some difficult line-drawing issues. If marijuana is fully legalized and at some point folks say, Well, we can come up with a negotiated dose of cocaine that we can show is not any more harmful than vodka, are we open to that? If somebody says, We’ve got a finely calibrated dose of meth, it isn’t going to kill you or rot your teeth, are we O.K. with that?”

Drug helps to clear traumatic memories

NATURE | NEWS

Medication removes markers from brain’s DNA to increase effectiveness of existing treatment.

Traumatic experiences leave a signature in the brain that is hard to erase. Painflul memories of war or child abuse are recorded in DNA as chemical marks in the genome, which makes conditions such as post-traumatic stress disorder (PTSD) difficult to treat with behavioural approaches.

Now, researchers report¹ that in mice, clearing these epigenetic markers with a drug can dramatically improve the effectiveness of a common behavioural treatment for PTSD, allowing the brain to dissociate a specific memory from the emotion associated with it.

In people with PTSD or other anxiety disorders, the pain associated with a specific memory fails to subside over time, as it usually would. “Every day they’re reliving it,” says Li-Huei Tsai, a neuroscientist at the Massachusetts Institute of Technology in Cambridge, and a co-author of the study. Exposure to the memory through photos or virtual reality simulations of the traumatic event in a safe environment — part of a technique known as extinction therapy — can help to dull the pain, but people with severe PTSD tend to relapse.

To simulate the disorder, Tsai and her colleagues delivered electrical shocks to the feet of mice while playing a loud sound. When the mice had learned to associate the sound with the painful stimulus, they would freeze whenever they heard it, even if they did not receive another shock. A day after the fear-conditioning, the researchers repeatedly played the sound in a safe environment, and made the mice forget the fearful association. But when the extinction therapy was started a month after the fear-conditioning, it did not work — in part because the bad memory had become epigenetically engrained.

Combined treatment

In rodents, Tsai says, it seems to take about a week for a memory to be permanently written into the epigenome. But her work suggests that a class of drugs called histone deacetylase inhibitors (HDACis), which clear epigenetic marks from DNA, can lengthen that window.

When researchers gave the mice an HDACi before they began the extinction therapy, the drug seemed to 'prime' the epigenome, creating a brief period in which memories could be reconsolidated, or modified. The HDACi alone had no effect on the mice’s memories, but just one dose combined with extinction therapy made the mice stop freezing when they heard the traumatic sound.

Drugs in the News