Molecule of the day – Fucnose – any carbohydrate of indeterminate structure. These sugar molecules are so tough to crack that you may hear chemistry professors shout its name from the top of their voice in exasperation at just how hard it is to identify. Fucnose is loosely related in structure to godnose (an early name for vitamin C, having originally been known as ignose!). Check out Paul May’s silly molecules site for more (genuine) molecules with (you guessed it) silly names and to read the complete tale of godnose and ignose.
Category: Science
Red meat linked to increased risk of bowel cancer
The UK media today reported that red meat increases the risk of bowel cancer: e.g. Telegraph
35% increased risk screamed the headlines. But, as fascinating as the finding is none of the reports I saw mentioned the incidence rate and how low that actually is compared to, say, deaths from road accidents or obesity-related heart disease. No absolute risk was mentioned. If it’s 100Â in a ten-thousand, then a 35% increase would then be 135 in 10000…
So, a 35% increased risk of something not very risky is not necessarily as significant as the cancer research organisations are claiming. Moreover, just one portion of any fish once a week can reduce the risk by 30%. So, presumably you can eat bacon, burgers and bangers 5 days a week and fish at weekends to almost cancel the positive effect with a negative.
Do you want Rosemary with that?
It’s not the most likely request you’ll hear at your local flame-grilled burger joint, but according to (KSU researchers, antioxidants in rosemary could help reduce the potentially harmful formation of heterocyclic amines during the “barbecuing” process. That’s all well and good, but who wants a burger tasting of rosemary, now if they could demonstrate the same benefits with onions, and a six-pack of beer, that would be a different matter.
Genetic Orgasm
It’s no surprise that one of the most widely repeated news items this week is the finding that genetics is involved in a woman’s ability to achieve an orgasm: Google Search: orgasm genetics. But, does this give men a sexual get out clause? Probably not, the research suggests that couples may simply have to “work” harder. One thing that is missing from all the discussion in the news is how a particular gene package actually precludes orgasm. They talk about women who can orgasm through masturbation but not intercourse, and emphasise that environmental and psychological factors are also involved, but is it a brain chemistry effect (genetically speaking) or perhaps just a matter of anatomy?
Anyway, how would you like to have beaucoup des petit morts? Killer orgasms, in other words.
Fearing Fat, Airbag Atrocities
According to the June issue of Scientific American, a growing number of dissenting researchers are accusing the US government and medical authorities – as well as the media – of misleading the public about the health consequences of rising body weights. These researchers suggest that excess body weight may not be the serious health risk it is claimed (by others) to be.
As with the anti-antismoking lobby, there are always going to be dissenters in any argument concerning health and safety, who can cite examples of overweight smokers living healthy lives into their 90s. Anyway, if the fat and smoke don’t kill you, the airbag just might. At least according to a statistical analysis that is yet to be reported widely in the mainstream media.
Apparently, the National Highway Traffic Safety Administration (NHTSA) has reported that airbags saved some 10000 lives as of January 2004. But, statistician Mary Meyer of the University of Georgia, has carried out an analysis of the data to demonstrate that airbags actually increase the risk of death (when other factors are controlled for).
“NHTSA recorded 238 deaths due to airbags between 1990 and 2002, according to information about these deaths on their Web site,” said Meyer. “They all occurred at very low speeds, with injuries that could not have been caused by anything else. But is it reasonable to conclude that airbags cause death only at very low speeds? It seems more likely that they also cause deaths at high speeds, but these are attributed to the crash.
“For any given crash at high speed, we can’t know what would have happened if there had been no airbag; however, statistical models allow us to look at patterns in the data, and compare risks in populations, in a variety of situations.” The study was published this week in Chance (2005, 18(2), pp 3-16).
The new analysis directly contradicts earlier studies about the effectiveness of airbags, which have been required for drivers and front-seat passengers in all cars since the 1998 model year in the United States.
While the value of airbags seems dubious in the new study, the value of seatbelts is not. The analysis found that proper use of a seatbelt reduces the odds of death by 67 percent for any given speed category and airbag availability. Airbags, however, cause no statistical difference in car-crash deaths, except for unseatbelted occupants at low speeds, where the odds of death are estimated to be more than four times higher with an airbag than without.
It has been known for some time that airbags pose special risks to children and small women. Auto manuals routinely say young children, especially those in car seats, should not be put in front seats where they might be injured or killed by an inflating airbag.
The reason earlier studies have found that airbags save lives is that they used only a special subset of the available data, said Meyer. The Fatality Analysis and Reporting System (FARS) is a high-quality compilation of information about every highway accident for which a death occurred. The Crashworthiness Data System (CDS) is another high-quality dataset, containing random samples of all accidents. The previous studies used FARS, and Meyer’s study used CDS.
“When we look at the random sample of all accidents, we find that airbags are associated with increased risk of death,” she said, “and this increase is due to more deaths with airbags in low-speed crashes and no seatbelts. However, if we limit the dataset to include only collisions in which a fatality occurred, we get a significantly reduced risk of death due to airbags.”
By way of analogy, Meyer explained it this way: “If you look at people who have some types of cancer, you will see that those who get radiation treatment have a better chance of surviving than those who don’t. However, radiation is inherently dangerous and could actually cause cancer. If you give everyone radiation treatment, whether they have cancer or not, you will probably find an increased risk of death in the general population.
“Making everyone have airbags and then verifying the effectiveness using only fatal crashes in FARS is like making everyone get radiation and then estimating the lives saved by looking only at people who have cancer. Overall, there will be more deaths if everyone is given radiation, but in the cancer subset, radiation will be effective.”
The new study directly contradicts assertions about airbag safety on the NHTSA Web site, said Meyer. The correct analysis is important to obtain now, because in only a few years, there will be virtually no cars on the road without airbags.
“We are confident that our analyses better reflect the actual effectiveness of airbags in the general population [than earlier studies],” said Meyer. “The evidence shows that airbags do more harm than good.”
Antiwrinkle System
A Sciencebase reader emailed to ask where they could find more information on Isolagen and its research into a system for eradicating wrinkles and facial scars. So here’s what we found:
Isolagen specializes in the development and commercialization of autologous cellular therapies for tissue regeneration and on May 23rd unveiled a design for an automated system to propagate and harvest cells more efficiently and cost effectively than other cell harvesting systems currently available. The ACE system could be used by cell and tissue companies worldwide and a successfully implemented ACE system would dramatically improve the time and cost of propagating and harvesting cells.
“We’ve invested significant resources to make the cell propagation process scalable, consistent and cost-efficient,” said Isolagen’s Chairman and interim CEO Frank DeLape. “The Automated Cellular Expansion (ACE) System is a simple solution that should enable us to introduce the Isolagen Process on a global scale, and will allow us to pursue licensing opportunities with organizations engaged in cell propagation and harvesting.”
Experts in the cell biology field acknowledge the potential significance of the ACE technology. “This system could significantly reduce the time and resources needed by any research or commercial lab that grows cells, while ensuring the consistency of cell growth and reducing the potential for culture contamination,” said Dr. Mark P. Lewis, Director of Research Operations and Senior Lecturer at Eastman Dental Institute of University College London.
Isolagen is best known for its patented Isolagen Process in which a patient’s own cells are used to correct and reduce the normal effects of aging and replenish deficiencies caused by the loss of fibroblast cells as a person ages. An aesthetic dermal application is currently available in the UK and is in Phase III pivotal clinical trials in the US. A Biologics License Application is expected to be filed with the FDA in late 2005. In addition to dermal indications, Isolagen is researching the use of autologous cellular therapies to treat gum recession, acne scarring and wound healing among other indications.
Growing Cells: Effective But Not Efficient
Cell propagation in Isolagen’s London and Houston laboratories is effective, but labor-intensive and time consuming. The Isolagen Process begins when a physician takes a small tissue sample from which millions of fibroblast cells are extracted and allowed to multiply in the laboratory. The regenerated fibroblast cells are then injected into the patient’s wrinkles when the cells reach a target quantity.
In preparing for its global market launch, Isolagen devoted significant resources to create a system that would make cell propagation and harvesting scalable and more efficient. Several years ago, a team of Isolagen scientists and engineers set out to design an automated cellular expansion (ACE) system that would substantially improve capacity and operating margins.
“The original business plan for Isolagen called for a single lab in every country, so the concept of scalability was not a priority,” said Mr. DeLape. “Our science has advanced to the point that we now envision a single laboratory serving multiple continents utilizing an efficient method of cell propagation and harvesting on a commercial scale.” Mr. DeLape noted the company recently announced the acquisition of a facility in Neuchatel, Switzerland intended to service Europe, Asia and Africa, and the purchase of a lab in Exton, PA to service the Central and South America and the United States once FDA approval is obtained.
ACE Advances Cell Propagation
The ACE unit consists of two separate and distinct parts. The first is a permanent unit, housing circuitry, pumps and a thermo-electric heater. The second part is the disposable unit, which contains a “cell tower,” media bags, cell separator and a sterile tubing for media flow. Cells are placed within the cell tower, which is designed to accommodate the growth of the cells, eliminating the time-consuming transfer of growing cells into new flasks. Every step, from feeding the cells to the harvesting of the injection syringes, will be executed in a sterile, closed-loop system.
The design eliminates nearly all human intervention, dramatically reducing the chance of contamination and the technical labor and monitoring associated with the process. And, the footprint of the Isolagen ACE unit as designed is small, allowing for modular stacking and maximum space efficiency.
“We are confident that we can maintain the quality and consistency of cell production, realize substantial savings and gain tremendous efficiencies through the use of the ACE System,” said Mr. DeLape. “Although ACE was developed to provide large-scale improvements in capacity and operating margins for the production of the Isolagen Process, we believe that ACE represents substantial improvements in cell propagation and harvesting for many other applications. Following the anticipated successful implementation of ACE for the Isolagen Process, we intend to seek licensing opportunities with other cell-based companies thereby creating a new revenue stream for our shareholders.”
The Isolagen ACE system was designed in collaboration with Fairway Medical Technologies and International Biophysics Corporation, leaders in medical device and equipment technology.
Logistical Advances Inherent with ACE
This fully automated, sterile closed-loop system is designed to offer enhanced benefits for other aspects of the Isolagen Process. The ACE design secures and records the identification of each patient’s cells through every step of the process — from biopsy to injection — creating a clear electronic chain of custody. Cells will be contained in a cell tower, which is designed to accommodate the expansion and growth of the cells and monitor cell growth and cell count to effectively predict when the target number of cells will be reached. In addition, Isolagen intends to utilize cryogenic preservation and freezing technology to allow maximum flexibility in scheduling treatments.
Next Steps
Isolagen intends to introduce ACE technology in the UK and its new Swiss facility during 2006.
About Isolagen
Isolagen specializes in the development and commercialization of autologous cellular therapies for soft and hard tissue regeneration. The company’s product candidates are based on its proprietary Isolagen Process and are directed toward dermatology — facial rejuvenation, gingival disease — gum disease, vocal cord lesions, and wound treatment. Based on the accumulated experience of the company through its pre-clinical studies, clinical trials and treatment of patients in the United Kingdom, the company believes that the Isolagen Process utilizing a patient’s own cells creates a safe and effective therapy for facial rejuvenation. Pre-clinical and clinical studies for future autologous therapies are ongoing. Autologous cellular therapy is the process whereby a patient’s own cells are extracted, allowed to multiply and then injected into the patient. Isogalen’s product candidates are designed to be minimally invasive and nonsurgical.
For additional information, please visit: http://www.isolagen.com .
Horseradish Down on the Farm – How Saucy
A mixture of horseradish and peroxide can (apparently) dampen swine farm odours.
According to news from the American Chemical Society, as cities expand, encroaching suburbanites are raising a stink about unpleasant odors emanating from neighbouring hog farms. But a simple, inexpensive concoction of horseradish root and hydrogen peroxide developed by Pennsylvania State University researchers could help deodorize swine and other animal manure, perhaps putting an end to a festering war of the noses.
“The problem of odors from farm manure has never been solved. Yet it is a problem that needs to be addressed given the strain it puts on the increasing number of people living nearby,” says Jerzy Dec, “Our new approach is a very simple method that doesn’t really take a lot of time, money or effort to do.”
In laboratory studies, Dec and his colleagues mixed horseradish root – purchased at a vegetable market – with hydrogen peroxide. Horseradish root contains large amounts of peroxidase, an enzyme that when combined with peroxide neutralizes phenols. Phenols are chemical compounds that are a common source of odors in manure.
A panel of six trained odor evaluators randomly sniffed treated and untreated manure samples. Overall, the panelists found the samples treated with the horseradish mixture had odors about 50 percent less intense than untreated ones. Chemical analysis indicated the deodorizing effects lasted for at least 72 hours.
In pilot-scale tests, the horseradish mixture effectively deodorized more than 50 gallons of hog manure, Dec says. Larger tests are planned.
I was going to say this has got to be hogwash…but then that’s exactly what it is!
Registered Drug Trials
The editors of eleven major medical journals have repeated their call to have clinical drug trials added to a public registry.
In a joint editorial, the members of the International Committee of Medical Journal Editors (ICMJE), said they will consider publishing results of clinical trials that begin enrolment on or after July 1, 2005, only if the trial has been entered in a registry that is electronically searchable and publicly accessible at no charge before the first patient is enrolled. The journals will accept retrospective registration of trials that began enrollment before July 2005 as long as registration is complete by Sept. 13, 2005.
The editorial, “Is This Trial Fully Registered?: A Statement from the International Committee of Medical Journal Editors,” will be released on www.ICMJE.org and on individual journal Web sites on May 23 at 5 p.m. EDT.
“Our first editorial [in September 2004] was a wake-up call for researchers, trial authors and sponsors,” said Harold Sox, MD, editor of Annals of Internal Medicine, “This editorial reaffirms our intent and tells researchers what they must do to meet our requirements for editorial review and subsequent publication.”
The ICMJE editorial tells researchers that they must not leave out key information when they register a trial. Specifically, ICJME says that researchers must name the treatment in a meaningful way so that patients and others know what intervention is under study.
The editorial also advises authors not to “use meaningless phrases to describe key information.”
Cut the bull in other words!
Structure of morphine
On 21st May 2005, medicine celebrated the bicentenary of the crystallization of morphine
Since 1805, morphine and its derivatives have become the most widely used treatment for severe pain. Now more than 230 tons of morphine is used each year for medical purposes including pain relief for patients with chronic pain or advanced medical illness and post-operative analgesia. By the way, if you’re looking for a chemical structure for opium, you’re out of luck. Opium is not a single compound but an extract of the immature seeds of the opium poppy, Papaver somniferum. This extract contains up to 10% morphine, the opiate alkaloid, which is processed to produce diamorphine, better known as heroin. The resin also includes codeine and non-narcotic alkaloids, such as papaverine and noscapine.
 Although many new pain relievers have been synthesized since the crystallization of morphine from opium almost 200 years ago, “morphine remains the standard against which all new medications for postoperative pain relief are compared,” notes Jonathan Moss, M.D., Ph.D., professor of anaesthesia and critical care at the University of Chicago.
Despite 200 years of increasingly frequent use, however, even the medical uses of morphine still present problems, such as severe nausea, itching, and constipation.
Moss has been invited to speak at the Einbeck morphine-commemorative conference in May on the relationship between morphine and a drug known as methylnaltrexone — a peripheral opiate antagonist developed at the University of Chicago — which can prevent many of these troubling side effects.
Moss’s lecture, “Morphine’s secrets revealed,” will focus on how methylnaltrexone enables scientists to distinguish between the central analgesic effects of morphine and its peripheral side effects. Check out the Chemspider page for morphine.
Discovery of morphine
Morphine was discovered by Freidrich Wilhelm Adam Serturner (1783-1841), an obscure, uneducated, 21-year-old pharmacist’s assistant with little equipment but loads of curiosity.
Serturner wondered about the medicinal properties of opium, which was widely used by 18th-century physicians. In a series of experiments, performed in his spare time and published in 1806, he managed to isolate an organic alkaloid compound from the resinous gum secreted by Papaver somniferum — the opium poppy.
Serturner found that opium with the alkaloid removed had no effect on animals, but the alkaloid itself had ten times the power of processed opium. He named that substance morphine, after Morpheus, the Greek god of dreams, for its tendency to cause sleep. He spent several years experimenting with morphine, often on himself, learning its therapeutic effects as well as its considerable dangers. Although his work was initially ignored, he recognized its significance. “I flatter myself,” he wrote in 1816, that “my observations have explained to a considerable extent the constitution of opium, and that I have enriched chemistry with a new acid (meconic) and with a new alkaline base (morphium), a remarkable substance.”
As he predicted, chemists and physicians soon grew interested in his discoveries. Serturner’s crystallization of morphine was the first isolation of a natural plant alkaloid. It sparked the study of alkaloid chemistry and hastened the emergence of the modern pharmaceutical industry.
Other researchers soon began to isolate similar alkaloids from organic substances, such as strychnine in 1817, caffeine in 1820 and nicotine in 1828. In 1831, Serturner won a lucrative prize for the discovery.
In 1818, French physician Francois Magendie published a paper that described how morphine brought pain relief and much-needed sleep to an ailing young girl. This stimulated widespread medical interest. By the mid-1820s morphine was widely available in Western Europe in standardized doses from several sources, including the Darmstadt chemical company started by Heinrich Emanuel Merck.
By the 1850s the first reliable syringes were developed and injected morphine became a standard method of reducing pain during and after surgery. Since then, various delivery systems for morphine have been developed, including epidural injection and pumps that allow patient-controlled analgesia.
Although morphine was originally touted as a cure for many maladies, even for opium addiction, by the 1870s physicians had become increasingly aware of its own addictive properties. Ironically, C.R. Alder Wright, a chemist at a London hospital who was searching for a non-addictive alternative to morphine, came up with a more potent narcotic, diacetylmorphine, in 1874.
Heinrich Dreser, a chemist at Bayer Laboratories developed and tested Wright’s new semi-synthetic drug on animals, humans, and most notably himself. Finding that it was a powerful painkiller and appeared effective for a variety of respiratory ailments, Bayer began producing and marketing this drug as an analgesic and a “sedative for coughs” in 1898. Because of its “heroic” ability to relieve pain, they called it heroin.
The medical profession initially welcomed the new drug but soon recognized it’s addictive potential. In 1913, Bayer halted production, edited the drug out of their official company history and focused instead on marketing their second blockbuster drug, aspirin.
Discovery of Methylnaltrexone
Yearly, more than 500,000 patients with advanced cancer depend on powerful opioid-based pain relievers such as morphine, or its derivatives OxyContin or Percocet, for pain relief. One side effect of all narcotic pain relievers is severe constipation, which can be so distressing that many patients discontinue their pain medication.
To solve this problem, the late Leon Goldberg, a University of Chicago pharmacologist, developed methylnaltrexone (MNTX). In order to help a friend with morphine-induced constipation, Goldberg modified naltrexone, an established drug that blocks the effects of morphine, so that it could no longer cross the protective barrier that surrounds the brain. Consequently, it did not interfere with morphine’s effect on pain, which is centred in the brain, but it did block morphine’s effects on gut motility, which are mediated by receptors in the gastrointestinal tract.
Goldberg’s university colleagues continued to develop the compound, testing it in animals and performing the initial human safety trials and clinical studies in volunteers and patients.
The University of Chicago licensed the MNTX technology to UR Labs, Inc. and in 2001, Progenics Pharmaceuticals of Tarrytown, NY, sub-licensed the worldwide exclusive rights to develop MNTX from UR Labs. One phase 3 trial of MNTX for treatment of opioid-induced constipation in patients with advanced medical illness has been completed and results from a second trial were reported May 17 at the American Society of Clinical Oncology annual meeting. Progenix has a target date of New Drug Application submission in late 2005.
Meanwhile, Moss and his University colleagues have identified multiple uses of MNTX, beyond the original discovery by Goldberg. Some of these additional uses of MNTX include treatment of post-operative bowel dysfunction (a serious impairment of the gastrointestinal tract following surgery), opioid-induced itching, urinary retention, and possibly HIV.
Opiates appear to increase the ability of HIV to infect certain immune system cells. In 2003, Moss reported that very small amounts of methylnaltrexone blocked these increases. “If our studies are borne out in future clinical trials, methylnaltrexone may improve the care of patients who take opioids for pain caused by AIDS,” he said.
“Two hundred years after Serturner’s work, we continue to learn a great deal about morphine,” Moss said. “The ability to facilitate pain relief while minimizing side effects is both conceptually important and very relevant to patient care.”
Barry Sharpless Lab
Scroll down to the members page for Nobel chemist Barry Sharpless and you’ll see not only is his team cross-cultural and international but trans-species too…
…meanwhile, watch out for the latest word on purity from the Sharpless lab in David Bradley’s Resonants webzine, coming soon.