ACS Chemistry for Life

New material for air cleaner filters that captures flu viruses
Biomacromolecules

Xuebing Li, Peixing Wu and colleagues are reporting development of a new material for the fiber in face masks, air conditioning filters and air cleaning filters that captures influenza viruses before they can get into people’s eyes, noses and mouths and cause infection. In an average year, influenza kills almost 300,000 people and sickens millions more worldwide. The constant emergence of new strains of virus that shrug off vaccines and anti-influenza medications has led to an urgent need for new ways of battling this modern-day scourge. So Li, Wu and colleagues sought a new approach, using a substance termed chitosan made from ground shrimp shells. The scientists combined chitosan with substances that the flu virus attaches to in order to infect cells. They found this new version of chitosan, ideal for attaching to fibers of face masks and air filters, was highly effective in capturing flu virus.

Advance toward a breath test to diagnose multiple sclerosis
ACS Chemical Neuroscience

Hossam Haick and colleagues are reporting the development and successful tests in humans of a sensor array that can diagnose multiple sclerosis (MS) from exhaled breath, an advance that they describe as a landmark in the long search for a fast, inexpensive and non-invasive test for MS – the most common neurological disease in young adults. Currently, doctors diagnose MS based on its characteristic symptoms, which include muscle spasms, numbness, coordination problems and slurred speech. Common tools for confirming the diagnosis and making informed decisions on treatment are magnetic resonance imaging (MRI) of the brain, or a lumbar puncture or “spinal tap” to analyze the fluid that bathes the brain and spinal cord. But MRI scans are costly, and lumbar punctures are invasive. To overcome these obstacles, the researchers have identified volatile organic compounds that can be associated with MS from exhaled breath, and developed a new sensor array that can diagnose MS. Using the developed sensors, the researchers carried out a proof-of-concept clinical study on 34 MS patients and 17 healthy volunteers and found that the developed sensors are just as accurate as a spinal tap but without the pain or the risk of side effects.

A better imaging agent for heart disease and breast cancer
Journal of the American Chemical Society

Taeghwan Hyeon, Seung Hong Choi, and colleagues are reporting development of a process for producing large quantities of tantalum oxide nanoparticles, a much-needed new imaging agent for computed tomography (CT) scans in heart disease, breast cancer and other diseases, and the first evidence that the material is safe for clinical use. Today’s imaging agents have many disadvantages. They don’t stay in the body for very long, for instance, limiting the types of images that physicians can obtain. Nanoparticles have been developed as imaging agents, but they have been made of either gold (very expensive) or bismuth (toxic). The researchers describe development and successful initial tests of large batches of tantalum oxide nanoparticles that exhibited “remarkable performances” in imaging tests of the heart, lymph nodes, kidneys, and other structures in laboratory rats, which are stand-ins for humans in such research. Regarding safety, they say, “The nanoparticles did not affect normal functioning of organs.”

New test shows promise for detecting warning signs of joint replacement failure
Molecular Pharmaceutics

A new test shows promise for detecting the early stages of a major cause of failure in joint replacement implants, so that patients can be treated and perhaps avoid additional surgery. Dong Wang and colleagues at University of Nebraska Medical Center and the Hospital for Special Surgery of New York explain that wear and tear in a joint replacement can create tiny bits of debris that cause local inflammation and lead to bone loss, eventually making the implant loose. Treatment usually comes too late, since it’s difficult to detect the problem in its early stages. To provide an early diagnostic tool for implant failure, the researchers developed a polymer-based system for imaging the inflammation that is associated with the wear debris. Their tests of the imaging agent in mouse bone suggest that it can help them detect the early stages of bone loss that might cause a joint implant to become loose. They also found that they could tether a powerful anti-inflammatory drug to the polymeric system, offering a way to treat inflammation and bone loss in these early stages of wear.

Toward a vaccine for methamphetamine abuse
Journal of the American Chemical Society

Kim Janda and colleagues are reporting development of three promising formulations that could be used in a vaccine to treat methamphetamine addiction – one of the most serious drug abuse problems in the U.S. Methamphetamine use and addiction cost the U.S. more than $23 billion annually due to medical and law enforcement expenses, as well as lost productivity. The drug, also called “meth” or “crystal meth,” can cause a variety of problems including cardiovascular damage and death. Meth is highly addictive, and users in conventional behavioral treatment programs often relapse. Previously tested meth vaccines either are not effective or are very expensive. To overcome these challenges, the researchers made and tested new vaccine formulations that could potentially be effective for long periods, which would drive down costs and help prevent relapse.

Natural protection against radiation
ACS Medicinal Chemistry Letters

In the midst of ongoing concerns about radiation exposure from the Fukushima nuclear power plant in Japan, scientists are reporting that a substance similar to resveratrol – an antioxidant found in red wine, grapes and nuts – could protect against radiation sickness. Michael Epperly, Kazunori Koide and colleagues explain that radiation exposure, either from accidents (like recent events in Japan) or from radiation therapy for cancer, can make people sick or die. The U.S. Food and Drug Administration is currently evaluating a drug for its ability to protect against radiation sickness, but it is difficult to make in large amounts, and the drug has side-effects that prevent its use for cancer patients. To overcome these disadvantages, the researchers studied whether resveratrol – a natural and healthful antioxidant found in many foods – could protect against radiation injuries. They found that resveratrol protected cells in flasks but did not protect mice (stand-ins for humans in the laboratory) from radiation damage. However, the similar natural product called acetyl resveratrol did protect the irradiated mice, and can be produced easily in large quantities and given orally. The authors caution that it has not yet been determined whether acetyl resveratrol is effective when orally administered.

Laser beam makes cells “breathe in” water and potentially anti-cancer drugs
The Journal of Physical Chemistry Letters

Shining a laser light on cells and then clicking off the light-makes the cells “breathe in” surrounding water, providing a potentially powerful delivery system for chemotherapy drugs, as well as a non-invasive way to target anti-Alzheimer’s medicines to the brain. Andrei Sommer’s group, with Emad Aziz and colleagues note using this technique before to force cancer cells to sip up anti-cancer drugs and fluorescent dyes. Using the so-called Liquidrom ambient approach, developed by Aziz’s group, the researchers combined for the first time laser irradiation with soft X-rays obtained from a cyclotron radiation source to explore the molecular structure of interfacial water layers under ambient conditions. The researchers showed that laser light aimed at a cell causes the water inside the cell to expand. When the light goes off, the volume of water collapses again, creating a strong pull that also sucks in the water surrounding the cell. This “breathing in and out” of the water molecules can pull chemotherapy drugs into a cell faster than they would normally penetrate, the researchers found.

Turning up the heat to kill cancer cells: “The Lance Armstrong effect”
Molecular Pharmaceutics

Robert Getzenberg and Donald Coffey note that patients with testicular cancer have a high survival rate – more than 70 percent – even if the cancer metastasizes, or spreads. For example, Lance Armstrong, the famous cyclist, beat metastatic testicular cancer that spread to his lungs and brain, and then went on to win the Tour de France a record seven consecutive times. But patients with pancreatic cancer have only a 25 percent survival rate in the first year and a 6 percent survival rate by the fifth year after diagnosis. Testicles are usually several degrees cooler than the rest of the body, owing to their position outside the body. When cancer cells from the testicles spread to other organs, such as the lungs or brain, they encounter a warmer environment. The researchers propose that this warmth shocks the tumor cells, making them more susceptible to conventional cancer therapies, which leads to a higher survival rate among testicular cancer patients, the so-called “Lance Armstrong effect.” The researchers describe tests now underway on nanoparticle therapies to specifically heat other types of tumors above their normal temperatures to see whether this effect holds true for non-testicular cancers.

New tool to help surgeons remove more cancer tissue during brain surgery
Analytical Chemistry

Zoltán Takáts and colleagues are reporting development and successful initial testing of a new tool that tells whether brain tissue is normal or cancerous while an operation is underway, so that surgeons can remove more of the tumor without removing healthy tissue, improving patients’ survival. Cancer can recur if tumor cells remain in the body after surgery, so as a precaution, surgeons typically remove extra tissue surrounding a breast, prostate and other tumors in the body. But neurosurgeons face severe limitations because removing extra tissue can impair the patient’s memory, mobility and other vital functions. Current methods to precisely identify tumor margins take too long and are unreliable. To overcome these challenges, the researchers developed a new tool that can identify the margin between cancerous and healthy tissue in half the time previously needed. They describe linking a mainstay surgical tool termed an ultrasonic aspirator – used to break up and suction tissue – to a modified version of a standard laboratory tool called a mass spectrometer.

Giant Fire-Bellied Toad’s brain brims with powerful germ-fighters
Journal of Proteome Research

Ren Lai and colleagues point out that scientists know little about the germ-fighting proteins in amphibian brains, despite many studies showing that amphibians synthesize and secrete a remarkably diverse array of antimicrobial substances in their skin. So they decided to begin filling that knowledge gap by analyzing brains from the Giant Fire-Bellied Toad and the Small-webbed Bell Toad. They discovered 79 different antimicrobial peptides, the components of proteins, including 59 that were totally new to scientists. Some of the peptides showed strong antimicrobial activity, crippling or killing strains of staph bacteria, E. coli, and the fungus that causes yeast infections in humans. These promising findings suggest that the toad brains might be a valuable source for developing new antibacterial and antiviral drugs.

Simple chemical cocktail shows first promise for limb re-growth in mammals
ACS Chemical Biology

Darren R. Williams and Da-Woon Jung are reporting that a simple chemical cocktail can coax mouse muscle fibers to become the kinds of cells found in the first stages of a regenerating limb. It is the first demonstration that mammal muscle can be turned into the biological raw material for a new limb. The scientists describe the chemical cocktail that they developed and used to turn mouse muscle fibers into muscle cells. Williams and Jung then converted the muscle cells into fat and bone cells. Those transformations were remarkably similar to the initial processes that occur in the tissue of newts and salamanders that are starting to regrow severed limbs. In the future, they suggest, the chemicals they use could speed wound healing by providing new cells at the injured site before the wound closes or becomes infected, and their methods might also shed light on new ways to switch adult cells into the all-purpose, so-called “pluripotent,” stem cells with the potential for growing into any type of tissue in the body.

Mussel adhesive inspires tough coating for living cells
Journal of the American Chemical Society

Inspired by Mother Nature, scientists are reporting development of a protective coating with the potential to enable living cells to survive in a dormant state for long periods despite intense heat, dryness and other hostile conditions. Insung S. Choi and colleagues liken the coating to the armor that encloses the spores that protect anthrax and certain other bacterial cells, making those microbes difficult to kill. They say their simple method for coating the yeast cells could “serve as a new strategy for controlling cell division and protection of artificial spore like structures in a designed way.” The new coating is an organic material called polydopamine, chemically similar to mussel adhesive. In laboratory experiments, the coating slowed down cell division in the yeast, while protecting them from cell-digesting chemicals. The technique could be used to encapsulate individual cells for a variety of purposes, including the creation of tiny chemical probes, single-cell chemical factories, and perhaps armor for transplanted cells used in anti-cancer therapies.

Polishing the apple’s popular image as a healthy food
Journal of Agricultural and Food Chemistry

Zhen-Yu Chen and colleagues are reporting the first evidence that consumption of a healthful antioxidant substance in apples extends the average lifespan of test animals, and does so by 10 percent. They note that damaging substances generated in the body, termed free radicals, cause undesirable changes believed to be involved in the aging process and some diseases. Substances known as antioxidants can combat this damage. Fruits and vegetables in the diet, especially brightly colored foods like tomatoes, broccoli, blueberries, and apples are excellent sources of antioxidants. The researchers found that apple polyphenols not only prolonged the average lifespan of fruit flies but helped preserve their ability to walk, climb and move about. In addition, apple polyphenols reversed the levels of various biochemical substances found in older fruit flies and used as markers for age-related deterioration and approaching death.

Blood protein in lung cancer could improve diagnosis and treatment
Journal of Proteome Research

Je-Yoel Cho and colleagues are reporting discovery of a protein in the blood of lung cancer patients that could be used in a test for the disease, which is difficult to diagnose in its earliest and most treatable stages. To find a better diagnostic tool, the researchers studied the proteins in the blood of lung cancer patients in search of red flags that could signal the disease’s presence. They focused on adenocarcinoma, which accounts for 1 in 3 cases and is the most rapidly increasing form of lung cancer in women. Cho and colleagues found elevated levels of a protein called serum amyloid A (SAA) in the blood and lung tissue of lung adenocarcinoma patients, compared to healthy people. Their work showed that high amounts of SAA were unique to lung cancers (compared with other lung diseases or other cancers) and that the protein was involved in metastasis of cancer cells from the original tumor site. The researchers say that the protein could be used as a diagnostic marker for lung cancer and as a target for developing drugs that stop metastasis.

New treaty on search for life-saving medicines in remote areas
Chemical & Engineering News

C&EN Associate Editor Carmen Drahl explains that environment ministers from 200 countries hammered out the Nagoya protocol, which extends a 1993 United Nations treaty declaring that nations have sovereign rights to the biological materials within their territory. Those materials – which include plants, microbes, and other living things – have been a rich source of so-called “natural products.” Almost 70 percent of today’s medicines are either natural products or are derived from natural products. The new treaty clarifies what agencies scientists who collect plant and other materials should approach for official clearance. It also requires countries that ratify the agreement to establish a “national focal point,” such as a university, government agency, or other contracting institution, for making such decisions. In addition, biodiversity-rich nations would receive compensation for medicines and other items commercialized from natural products discovered in their country.

An advance toward blood transfusions that require no typing
Biomacromolecules

Maryam Tabrizian and colleagues are reporting an “important step” toward development of a universal blood product that would eliminate the need to “type” blood to match donor and recipient before transfusions. The immunocamouflage technique hides blood cells from antibodies that could trigger a potentially fatal immune reaction that occurs when blood types do not match. A correct match between a donor and the recipient’s blood can be a tricky proposition given that there are 29 different red blood cells types, including the familiar ABO and Rh types. The wrong blood type can provoke serious immune reactions that result in organ failure or death, so scientists have long sought a way to create an all-purpose red blood cell for transfusions that doesn’t rely on costly blood typing or donations of a specific blood type. To develop this “universal” red blood cell, the scientists discovered a way to encase living, individual red blood cells within a multilayered polymer shell, making the cell invisible to a person’s immune system and able to evade detection and rejection. Oxygen can still penetrate the polymer shell, however, so the red blood cells can carry on their main business of supplying oxygen to the body.

Battling the bedbug epidemic
Chemical & Engineering News

C&EN News Editor William G. Schulz points out that bedbugs represent a growing epidemic that is difficult to control. Their bites can cause allergic skin reactions, mental anguish, and loss of sleep. Some chemicals that were once effective against the pests, such as DDT, have been banned due to threats to human health and the environment, leaving exterminators with few effective options for controlling the pests, which have developed the ability to shrug-off some pesticides. Scientists are looking for new substances to fight bedbugs that are safe and effective. Officials in Ohio – “bedbug ground zero” –are seeking Federal government permission to resume use of a pesticide called propoxur that can quickly halt infestations. Propoxur was pulled from the market by its manufacturer after EPA raised safety and efficacy concerns. For now, a combination of pesticides and preventive measures, such as regular inspection, laundering, vacuuming, removing clutter, and sealing up cracks in walls and baseboards, are among the best ways to control the bugs, the article notes.

New “dissolvable tobacco” products may increase risk of mouth disease
Journal of Agricultural and Food Chemistry

The first study to analyze the complex ingredients in the new genre of dissolvable tobacco products has concluded that these pop-into-the-mouth replacements for cigarettes in places where smoking is banned have the potential to cause mouth diseases and other problems. Dissolvable tobacco products contain finely-ground tobacco and other ingredients processed into pellet, stick, and strip forms that are advertised as smoke and spit-free. Health officials are concerned about whether the products, which dissolve inside the mouth near the lips and gums, are in fact a safer alternative to cigarette smoking. John V. Goodpaster and colleagues found that the products contain mainly nicotine and a variety of flavoring ingredients, sweeteners, and binders. They note abundant scientific evidence about the potential adverse health effects of nicotine, including those involving the teeth and gums. Other ingredients in dissolvables have the potential to increase the risk of tooth decay and one, coumarin, has been banned as a flavoring agent in food because of its link to a risk of liver damage.

Getting more anti-cancer medicine into the blood
Langmuir

Yuri M. Lvov and colleagues are reporting successful application of the technology used in home devices to clean jewelry, dentures, and other items to make anticancer drugs like tamoxifen and paclitaxel dissolve more easily in body fluids, so they can better fight the disease. Many drugs, including some of the most powerful anti-cancer medications, have low solubility in water, meaning they do not dissolve well. IV administration of large amounts can lead to clumping that blocks small blood vessels, so doses sometimes must be kept below the most effective level. The scientists describe using sonication, high-pitched sound waves like those in home ultrasonic jewelry and denture cleaners, to break anti-cancer drugs into particles so small that thousands would fit across the width of a human hair. Each particle then gets several coatings with natural polysaccharides that keep them from sticking together. The technique, termed nanoencapsulation, worked with several widely used anti-cancer drugs, raising the possibility that it could be used to administer more-effective doses of the medications.

Vegans’ elevated heart risk requires omega-3s and B12
Journal of Agricultural and Food Chemistry

People who follow a vegan lifestyle – strict vegetarians who try to eat no meat or animal products of any kind – may increase their risk of developing blood clots and atherosclerosis or “hardening of the arteries,” which are conditions that can lead to heart attacks and stroke. That’s the conclusion of a review by Duo Li of dozens of articles published on the biochemistry of vegetarianism during the past 30 years. Vegan diets tend to be lacking several key nutrients – including iron, zinc, vitamin B12, and omega-3 fatty acids. While a balanced vegetarian diet can provide enough protein, this isn’t always the case when it comes to fat and fatty acids. As a result, vegans tend to have elevated blood levels of homocysteine and decreased levels of HDL, the “good” form of cholesterol. Both are risk factors for heart disease. Dietary supplements can supply these nutrients.

New gift from Mother Nature’s medicine chest may help prevent and treat bone diseases
ACS Medicinal Chemistry Letters

One of Mother Nature’s latest gifts to medical science is stirring excitement with the discovery that the substance Largazole – obtained from a coral-reef inhabiting cyanobacterium – appears to be an ideal blueprint for developing new drugs for serious fractures, osteoporosis, and other bone diseases, and it already has attracted scientific attention for its ability to kill cancer cells in laboratory experiments. Jiyong Hong, Seong Hwan Kim, Hendrik Luesch and colleagues report that in laboratory dishes and test animals Largazole has an unusual dual action on injured or diseased bones. It stimulates a process in the body called osteogenesis, which involves the growth of new bone and the repair of damaged bone. Largazole also blocks the opposite process in which the body naturally breaks down and resorbs bone. Both of those benefits, the scientists found, come from Largazole’s effects on proteins called histone deacetylases, which are a sort of a master control switch for protein production. Drugs that block histone deacetylases are currently used to treat cancer, and they may have other health benefits as well. The researchers also showed that Largazole, when mixed with bone components collagen and calcium phosphate, helped heal fractured bones in laboratory mice and rabbits.

Toward a fast, simple test for detecting cholera rampaging in 40 countries
Bioconjugate Chemistry

With cholera on the rampage in Haiti and almost 40 other countries, J. Manuel Perez and colleagues are reporting the development of a key advance that could provide a fast, simple test to detect the toxin that causes the disease. The authors note that cholera is an intestinal infection from food or water contaminated with the bacterium Vibrio cholerae, which produces a toxin that can cause severe diarrhea, potentially leading to rapid dehydration and death. Prompt treatment thus is essential, and yet existing tests to diagnose cholera are time-consuming, expensive, and require the use of complex equipment. The new method uses specially prepared nanoparticles of iron oxide, each barely 1/50,000th the width of a single human hair, coated with a type of sugar called dextran. To achieve this, the researchers looked for specific characteristics of the cholera toxin receptor (GM1) found on cells’ surface in the victim’s gut, and then they introduced these features to their nanoparticles. When the magnetic nanoparticles are added to water, blood, or other fluids to be tested, the cholera toxin binds to the nanoparticles in a way that can be easily detected by instruments.

High vitamin-D bread could help solve widespread insufficiency problem
Journal of Agricultural and Food Chemistry

With most people unable to get enough vitamin D from sunlight or foods, Connie Weaver and colleagues are suggesting that a new vitamin D-fortified food – bread made with high-vitamin D yeast – could fill that gap. Connie Weaver and colleagues cite studies suggesting that up to 7 in 10 people in the United States may not get enough vitamin D, which enables the body to absorb calcium. Vitamin D insufficiency has been linked to an increased risk of heart disease, cancer, allergy in children, and other conditions. Scientists thus have been looking for new ways to add vitamin D to the diet. Weaver’s group did experiments with laboratory rats, a stand-in for humans in such research, that ease doubts over whether bread baked with high vitamin D yeast could be a solution. The doubts originated because yeast produces one form of the vitamin, termed vitamin D2, which has been thought to be not as biologically active as the form produced by sun, vitamin D3. They showed bread made with vitamin D2-rich yeast, fed to the laboratory rats, had effects that seemed just as beneficial as vitamin D3.

Needle-in-a-haystack search identifies potential brain disease drug
Journal of Medicinal Chemistry

Scientists who examined more than 10,000 chemical compounds during the last year in search of potential new drugs for a group of untreatable, and invariably fatal, brain diseases, are reporting that one substance shows unusual promise. Adam Renslo and colleagues, who include Nobel Laureate Stanley B. Prusiner, explain that prion diseases include conditions like mad cow disease in animals and Creutzfeldt-Jakob Disease in humans, and result from deposits of abnormal prion protein in brain tissue. The scientists describe narrowing their search among the 10,000 candidate drugs to a few dozen of the most promising and then synthesizing new variations of the compounds, termed aminothiazoles. Tests on laboratory mice showed that the new compounds can reach the brain in high concentrations when taken orally and do not appear toxic. Tests on prion-infected mouse brain cells showed that the compounds reduced the amount of the abnormal prion protein. The compounds appear to be among the most promising potential treatments for prion diseases yet discovered, the report suggests.

Probing the mysterious second-wave of damage in head injury patients
Chemical & Engineering News

Why do some of the one million people who sustain head injuries annually in United States experience a mysterious second wave of brain damage days after the initial injury – just when they appear to be recovering? C&EN Senior Editor Celia Henry Arnaud describes a phenomenon called depolarization, in which brain activity decreases in patients following initial trauma. The condition involves a wave of chemical changes that spread from the site of injury and inactivate nerve cells. Since reactivation of these cells requires large amounts of glucose, monitoring glucose levels in a patient’s brain can help doctors tell whether or not a patient is taking a turn for the worse. The article points out a promising new device, now in development at Imperial College London, that uses the new so-called “microfluidic method” to measure glucose quickly and continuously – in fractions of a second instead of hourly. The device is currently being tested in patients who have suffered trauma, stroke, or aneurysm (a balloon-like enlargement of a brain artery).

Built-in timer for improving accuracy of cost saving paper-strip medical tests
Analytical Chemistry

Scott Phillips and Hyeran Noh are reporting the development of a simple, built-in timer intended to improve the accuracy of paper tests and test strips for diagnosing diseases inexpensively at home and elsewhere. When fully developed, these low-cost paper tests may replace more expensive traditional tests for detecting biomarkers in urine, blood, and other body fluids, as well as for detecting pollution in water, but they require precise timing using a stopwatch to provide accurate results. For instance, the CHEMCARD diagnostic test for measuring blood sugar or cholesterol in a drop of blood, is almost 100 percent accurate when users view test results exactly 3 minutes after placing the drop of blood on the paper, but incorrect timing cuts accuracy nearly in half. Patients (particularly those in the developing world), they indicate, may not have stopwatches or other timing devices, or may not use external timing devices with enough accuracy to obtain meaningful results. The scientists describe the development of a built-in timer for paper-based diagnostic tests made from a dye and the paraffin wax used in some candles. Addition of water, blood, urine or other body fluids starts the timer, and a color change signals when the time is up. When used with a test similar to the CHEMCARD glucose test, the timer was 97 percent accurate, slightly better than when a stopwatch was used.

Scientific evidence supports effectiveness of Chinese drug for cataracts
Inorganic Chemistry

Tzu-Hua Wu, Fu-Yung Huang, Shih-Hsiung Wu and colleagues are reporting a scientific basis for the long-standing belief that a widely used non-prescription drug in China and certain other countries can prevent and treat cataracts, a clouding of the lens of the eye that is a leading cause of vision loss worldwide. Eye drops containing pirenoxine, or PRX, have been reputed as a cataract remedy for almost 60 years, but there have been few scientific studies on its actual effects. Currently, the only treatment for cataracts in Western medicine is surgical replacement of the lens, the clear disc-like structure inside the eye that focuses light onto the nerve tissue in the back of the eye. The scientists tested pirenoxine on cloudy solutions that mimic the chemical composition of the eye lens of cataract patients. The solutions contained crystallin – a common lens protein – combined with either calcium or selenite, two minerals whose increased levels appear to play key roles in the development of cataracts. Presence of PRX reduced the cloudiness of the lens solution containing calcium by 38 percent and reduced the cloudiness of the selenite solution by 11 percent.

Killer paper for next-generation food packaging
Langmuir

Aharon Gedanken and colleagues are reporting development and successful lab tests of “killer paper,” a material intended for use as a new food packaging material that helps preserve foods by fighting the bacteria that cause spoilage. The paper contains a coating of silver nanoparticles, which are powerful anti-bacterial agents. Nanoparticles, which have a longer-lasting effect than larger silver particles, could help overcome the growing problem of antibiotic resistance, in which bacteria develop the ability to shrug-off existing antibiotics. However, producing “killer paper” suitable for commercial use has proven difficult. The scientists describe development of an effective, long-lasting method for depositing silver nanoparticles on the surface of paper that involves ultrasound, or the use of high frequency sound waves. The coated paper showed potent antibacterial activity against E. coli and S. aureus, two causes of bacterial food poisoning, killing all of the bacteria in just three hours.

Forty-year-old test procedure finds modern niche in developing new medicines
Chemical & Engineering News

C&EN Senior Editor Celia Henry Arnaud notes that collecting drops of blood from patients and depositing the drops on special paper cards to dry has been used for decades to screen newborns for hereditary disorders and infectious disease. But the dried blood spot technology has found a new role at pharmaceutical companies in the development and testing of new drugs. The approach, possible now because modern lab instruments are more sensitive, has distinct advantages. The dried blood approach, for instance, involves taking only a few drops of blood from patients in clinical trials, and these can be stored and shipped more easily and inexpensively than liquid samples. Those advantages, alone, could cut the cost of introducing new drugs by millions of dollars, the article indicates.

Discovery of a biochemical basis for broccoli’s cancer-fighting ability
Journal of Medicinal Chemistry

Fung-Lung Chung and colleagues are reporting discovery of a potential biochemical basis for the apparent cancer-fighting ability of broccoli and its veggie cousins that targets and blocks a defective gene associated with cancer. They showed in previous experiments that substances called isothiocyanates (or ITCs) – found in broccoli, cauliflower, watercress, and other cruciferous vegetables – appear to stop the growth of cancer. But nobody knew exactly how these substances work, a key to developing improved strategies for fighting cancer in humans. The tumor suppressor gene p53 appears to play a key role in keeping cells healthy and preventing them from starting the abnormal growth that is a hallmark of cancer. When mutated, p53 does not offer that protection, and those mutations occur in half of all human cancers. The researchers found that ITCs are capable of removing the defective p53 protein but apparently leave the normal one alone. Drugs based on natural or custom-engineered ITCs could improve the effectiveness of current cancer treatments or lead to new strategies for treating and preventing cancer.

Secret funding fosters hope for new drugs for autism
Chemical & Engineering News

C&EN Senior Editor Lisa Jarvis notes that until recent interest from big pharmaceutical companies, a small drug company in Cambridge, Mass. named Seaside Therapeutics was virtually the only company trying to develop drugs for autism and fragile X syndrome. Fragile X syndrome, the most common known genetic cause of autism, results from mutation in a single gene with symptoms ranging from learning impairment to mental retardation. The article describes how Seaside, armed with funding from an anonymous wealthy family and new insights into the basic science behind these disorders, is making progress toward treating these much-neglected diseases. Two of the company’s potential drugs show promise in clinical trials as treatments for Fragile X syndrome. One appears to improve the behavior of children with severe social impairments. On the heels of Seaside’s encouraging results, big pharmaceutical companies that once showed little interest in tackling these diseases are now trying to develop their own new medications.

Toward the first nose drops to treat brain cancer
Molecular Pharmaceutics

Tomotaka Shingaki and colleagues report the development and successful initial testing of a new form of methotrexate – the mainstay anticancer drug – designed to be given as nose drops rather than injected. Brain cancer is difficult to treat, partly because current anticancer drugs have difficulty reaching the brain because the so-called blood-brain barrier (a protective layer of cells surrounding the brain) prevents medication in the blood from entering the brain. But new evidence indicates that some drugs administered through the nose, either as nose drops or nasal spray, can bypass this barrier and travel directly into the brain. The scientists tested methotrexate nose drops on laboratory rats with brain cancer. Compared to cancer treated with an injectable form of the drug, the nose drop drug reduced the weight of tumors by almost one-third, the scientists said. “The strategy to utilize the nose-brain direct transport can be applicable to a new therapeutic system not only for brain tumors but also for other central nervous system disorders such as neurodegenerative diseases,” the article noted.

Ingredient in soap points toward new drugs for infection that affects 2 billion
Journal of Medicinal Chemistry

Rima McLeod and colleagues report on the use of triclosan’s molecular structure as the model for developing other potential medications for toxoplasmosis. Toxoplasmosis is one of the world’s most common parasitic infections, affecting about one-third of the world population, including 80 percent of the population of Brazil. Many have no symptoms because their immune systems keep the infection under control and the parasite remains inactive, but it can cause eye damage and other problems. Most current treatments have some potentially harmful side effects and none of them attack the parasite in its inactive stage. The scientists knew from past research that triclosan has a powerful effect in blocking the action of a key enzyme that T. gondii uses to live. Triclosan, however, cannot be used as a medication because it does not dissolve in the blood.

Portable laser devices to improve disease diagnosis
Chemical & Engineering News

C&EN Senior Editor Celia Henry Arnaud notes potential diagnostic tools with the ability to see beneath the skin and detect disease, without exposing patients to X-rays. They embrace a technology that involves focusing a laser beam painlessly through the skin onto a bone or onto the surface of a tooth. After hitting its target, the beam returns to an electronic detector with imprinted information that can reveal whether disease is present. Called Raman spectroscopy, the technology is a mainstay tool in chemistry laboratories that is finding a new life in medicine. The article describes growing medical interest in Raman-based devices, especially for diagnosing osteoporosis and other bone diseases, and for tracking the effectiveness of treatment. Another application may be in very early detection of tooth decay, so that dentists can treat soft spots on tooth enamel before “drill-and-fill” becomes the only option, and blood tests conducted without taking blood samples.

Insights into environmental conditions that affect highly pathogenic bird flu virus survival
Environmental Science & Technology

Joseph Wood and colleagues note that the highly pathogenic (H5N1) avian influenza virus so far has been rare but dangerous in humans, with mortality rates of about 60 percent. On the eve of the 2010-11 influenza (flu) season, they have identified the environmental conditions and surfaces that could enable a highly pathogenic (H5N1) bird flu virus to survive for prolonged periods of time – cooler temperatures and low humidity. The study could lead to new strategies for preventing the flu virus from spreading. The scientists investigated the ability of a strain of highly pathogenic H5N1 originating from Vietnam to survive on a variety of materials under different environmental conditions, including changes in temperature, humidity, and simulated sunlight. They found that H5N1 survived longer (up to two weeks) at cooler temperatures – around 39 degrees Fahrenheit – but lasted only up to one day at room temperature. The virus also tends to persist at low humidity and no sunlight and on certain surfaces, including glass and steel.

Progress toward treating infections by silencing microbes’ “smart phones”
Chemical Reviews

Marvin Whiteley and Holly Huse point out that bacteria use chemical signals to communicate with each other to launch infections and monitor their environment. These signals can trigger infections when their numbers reach a certain threshold – a process known as “quorum sensing.” The “smart phones of the microbial world,” the authors describe progress toward understanding and blocking this biochemical chitchat, a development that could lead to new treatments for the growing problem of antibiotic-resistant infections. One prime target are the 4-quinolones, signaling molecules produced by Pseudomonas aeruginosa, a common disease-causing microbe. Their review of more than 60 years of research on 4-quinolones found promising indications that such a conversation-stopper will be developed. Scientists, for instance, now have evidence that a certain enzyme that modifies 4-quinolones can reduce infection.

New antibacterial material for bandages, food packaging, shoes
ACS Nano

Chunhai Fan, Qing Huang, and colleagues have developed a new form of paper with the built-in ability to fight disease-causing bacteria which could have applications that range from antibacterial bandages to food packaging that keeps food fresher longer to shoes that ward off foot odor. Scientists have tried to use graphene in solar cells, computer chips, and sensors. Fan and Huang decided to see how graphene affects living cells. So they made sheets of paper from graphene oxide, and then tried to grow bacteria and human cells on top. Bacteria were unable to grow on the paper, and it had little adverse effect on human cells.

Regrowing lost limbs
Chemical & Engineering News

C&EN Senior Editor Sophie Rovner notes that salamanders, flatworms, and certain other creatures can easily regrow lost body parts, including organs, nerves, and muscle, providing clues to regenerating human limbs. People can grow new skin and nerves, for instance, but regrowing an entire arm or leg seems like pure science fiction. Scientists have discovered certain proteins and genes with key roles in regenerating lost body parts. Certain chemicals in the amniotic fluid that cushions and protects fetuses prior to birth may help promote regeneration in adult mammals. There are other hints that electricity might be used to help jump-start regeneration.

Solving the mystery of bone loss from drug for epilepsy and bipolar disorder
Journal of Proteome Research

Glenn Morris and colleagues report a possible explanation for the bone loss that may occur following long-term use of a medicine widely used to treat epilepsy, bipolar disorder, and other conditions. The drug, valproate, appears to reduce the formation of two key proteins important for bone strength, they said. Valproate now is prescribed for mood disorders, migraine headache, and spinal muscular atrophy (SMA), a rare genetic disease that causes loss of muscle control and movement. Many SMA patients develop weak bones as a result of the disease itself, making further bone loss from valproate especially undesirable. The researchers found that valproate reduced production of collagen, the key protein that gives bone its strength, by almost 60 percent. The drug also reduced levels of osteonectin, which binds calcium and helps maintain bone mass, by 28 percent.

Deathstalker scorpion venom could improve gene therapy for brain cancer
ACS Nano

Miqin Zhang and colleagues note that chlorotoxin, an ingredient in the venom of the “deathstalker” scorpion, could help gene therapy become an effective treatment for brain cancer. Difficulties in getting genes to enter cancer cells and concerns over the safety and potential side effects of substances used to transport these genes have kept the approach from helping patients. Chlorotoxin allows therapeutic genes to reach more brain cancer cells and slow their spread better than current approaches. In tests on lab mice, the scientists demonstrated that their venom-based nanoparticles can induce nearly twice the amount of gene expression in brain cancer cells as nanoparticles that do not contain the venom ingredient.

Advance toward earlier detection of melanoma
ACS Nano

Lihong Wang, Younan Xia, and colleagues are reporting development of a substance to enhance the visibility of skin cancer cells during scans with an advanced medical imaging system that combines ultrasound and light. The five-year survival rate for melanoma is about 98 percent if detected early but can be as low as 15 percent when detected at an advanced stage. Existing imaging techniques for early detection of melanoma produce low-quality images, “seeing” only a fraction of an inch below the skin, and use potentially harmful radioactive materials. A promising new technique called photoacoustic tomography (PAT) can overcome these problems, but the PAT system lacks an optimal contrast agent that can easily enter skin cancer cells and make them visible. The scientists developed such an agent by attaching a peptide (one of the building blocks of proteins) that targets skin cancer cells to gold “nanocages.” When injected into mice with skin cancer, the nanocages improved the image quality of the cancer cells by three-fold compared to nanoparticles lacking the peptide. The gold nanocages also show promise as a way to kill skin cancer cells using heat or anti-cancer drugs, they add.

New evidence that fat cells are not just dormant storage depots for calories
Journal of Proteome Research

Anja Rosenow and colleagues are reporting new evidence that the fat tissue in those spare tires and lower belly pooches – far from being a dormant storage depot for surplus calories – is an active organ that sends chemical signals to other parts of the body, perhaps increasing the risk of heart attacks, cancer, and other diseases. They are reporting discovery of 20 new hormones and other substances not previously known to be secreted into the blood by human fat cells and verification that fat secretes dozens of hormones and other chemical messengers. Among those hormones is leptin, which controls appetite, and adiponectin, which makes the body more sensitive to insulin and controls blood sugar levels. However, little is known about most of the proteins produced by the billions of fat cells in the adult body. The scientists identified 80 different proteins produced by the fat cells, including six new proteins and 20 proteins that have not been previously detected in human fat cells. The findings could pave the way for a better understanding of the role that hormone-secreting fat cells play in heart disease, diabetes, and other diseases.

Preventing cancer, quite naturally
Chemical & Engineering News

Exciting headlines about the cancer-preventing potential of berries, red wine, and other foods are in the news almost every day. C&EN Associate Editor Carmen Drahl highlights researchers trying to make medicines based on substances in those foods and turn their potential into reality. She notes that scientists have tried for years to develop drugs that reduce the risk of cancer, with only a few successes. So-called “natural products” – chemicals derived from plants and other living organisms – are the basis for almost one-third of today’s prescription medicines. There are a variety of candidates, including resveratrol, a substance found in red wine; abyssinone, a substance found in a plant from traditional Chinese medicine; and potential cancer-preventing substances in deep-ocean microbes. Even though some natural products have failed to prevent cancer in human clinical trials, Drahl cites continued optimism that the search will pay off.

Toward making “extended blood group typing” more widely available
Analytical Chemistry

Christophe Marquette and colleagues are reporting an advance toward enabling more blood banks to adopt so-called “extended blood group typing,” which increases transfusion safety by better matching donors and recipients. Most blood banks still use a century-old blood approach to blood typing, which identifies blood group antigens on red blood cells – proteins that must match in donor and recipient to avoid potentially serious transfusion reactions. Most blood currently is typed for only a few of the 29 known human blood groups, even though some rare blood groups can affect outcomes. Commercial technology does exist for extended typing with DNA tests, but it is expensive, difficult to use, and suited more for research labs than high-volume blood centers. The study describes evaluation of the new more affordable method, called the HiFi Blood 96, which types blood with DNA testing in a high-speed automated procedure. Tests on 293 human blood samples demonstrated the performance and reliability of the new method.

Supercharged proteins enter biology’s forbidden zone
ACS Chemical Biology

David Liu and his colleagues are reporting discovery of a way to help proteins such as the new generation of protein-based drugs – sometimes heralded as tomorrow’s potential “miracle cures” – get past the biochemical “Entrance Forbidden” barrier that keeps them from entering cells and doing their work. Nearly all of the blockbuster drugs that are proteins must do their work on the exterior of cells, activating receptors that send signals to the interior. This constraint greatly limits the scope of protein-based drugs. Liu’s solution: Attaching proteins to molecules of “supercharged” green fluorescent protein, which they mutated to give it a very high positive charge. When the hybrid proteins bump into the surface of a cell, they get pulled inside by negatively charged molecules called proteoglycans. Liu and his team tested the hybrid proteins on five types of cells, and found that the supercharged protein was up to 100 times better at getting proteins into cells compared to other approaches. The delivered proteins were able to go to their target locations in the cell, such as the nucleus or cytoplasm, and perform their jobs.

New insights into link between anti-cholesterol statin drugs and depression
Biochemistry

Amitabha Chattopadhyay and colleagues note in the study that statins (anti-cholesterol drugs) work by blocking a key enzyme involved in the body’s production of cholesterol. Some studies link the drugs to an increased risk of anxiety and depression, but the reasons are unclear. The scientists previously showed that maintaining normal cholesterol levels is important for the function of cell receptors for serotonin, a brain hormone that influences mood and behavior. But the long-term effect of cholesterol depletion on these receptors, which can occur in patients taking anti-cholesterol drugs, is unknown. In lab tests using human serotonin receptors expressed in animal cells, they showed that long-term use of the statin medication mevastatin caused significant changes in the structure and function of serotonin cell receptors. Adding cholesterol to cells treated with mevastatin restored them to normal.

Nano-sized advance toward next big treatment era in dentistry
ACS Nano

Nadia Benkirane-Jessel and colleagues are reporting an advance toward the next big treatment revolution in dentistry – the era in which root canal therapy brings diseased teeth back to life, rather than leaving a “non-vital” or dead tooth in the mouth. They describe a first-of-its-kind, multilayered, nano-sized film – only 1/50,000th the thickness of a human hair containing a substance that could help regenerate dental pulp. Previous studies show that the substance, called alpha melanocyte stimulating hormone, or alpha-MSH, has anti-inflammatory properties. The scientists showed in laboratory tests that alpha-MSH combined with a widely-used polymer produced a material that fights inflammation in fibroblasts, the main type of cell found in dental pulp. Nano-films containing alpha-MSH also increased the number of these cells. This could help revitalize damaged teeth and reduce the need for a root canal procedure, the scientists suggest.

How safe and effective are herbal dietary supplements?
Chemical & Engineering News

Millions of people are taking herbs and other plant-based dietary supplements to improve their health, but they have precious little information on the actual effectiveness or potential ill effects of these products. C&EN Senior Editor Celia Henry Arnaud suggests that consumers are taking a gamble when it comes to the safety and effectiveness of hundreds of pills and potions cluttering store shelves. Scientists are concerned that some supplements, such as black cohosh and red clover, used by menopausal women to reduce hot flashes, and kava, which is used to treat anxiety and insomnia, may contain high levels of toxic metals, such as lead and mercury, or pesticides. There’s also the possibility that the plant itself might be toxic or that a supplement can cause harm by reacting with conventional drugs. The U.S. Food & Drug Administration, which regulates supplements as foods rather than drugs, recently took a step toward improving the situation by requiring all supplement manufacturers to test their products for contaminants. Ongoing research is providing new information that will help address these concerns in the future, including the long-term safety of these products for consumers.

New plastic-like materials may say “shhhh!” to hush disease-causing microbes
Biomacromolecules

Elena Piletska and colleagues are reporting success in a first attempt to silence the chemical signals bacteria use to launch infection. They describe use of specially designed plastic-like materials, similar to those dentists use to repair damaged teeth, to capture signaling molecules in laboratory experiments and thwart microbes’ attempts to start an infection. The increase in antibiotic resistant bacteria has led to a global scientific quest for new antibiotics, and totally new approaches for dealing with bacteria that have caused millions of deaths throughout human history. The developed materials also reduce the ability of the bacteria to form biofilms. Bacteria form these slimy layers inside medical tubing, water supply pipes, and other surfaces and use them as a refuge to grow and multiply.

Schizophrenia drugs raise the volume of a key signaling system in the brain
ACS Chemical Neuroscience

Eric J. Aamodt and colleagues report the first example of a specific molecular effect produced by all antipsychotic drugs in any biological system. Scientists know little about how antipsychotic drugs work, aside from the drugs’ effects on one signaling chemical called dopamine. But studies suggest that medications like olanzapine, quetiapine, and clozapine affect other signaling systems in the brain such as the Akt signaling pathway, which influences behavior by regulating communication between brain cells. Scientists tested 13 antipsychotic drugs on a genetically modified form of the worm, C. elegans, which were wired to glow green to show activity of Akt, a signal that is too quiet in schizophrenic brains. They found that all of the drugs tested, representative of all major categories of antipsychotic medications, helped the worms maintain their characteristic green glow. The results highlight the importance of Akt signaling in schizophrenia, suggesting that medications or other approaches that increase Akt signaling might help to alleviate the symptoms of schizophrenia.

Nanotech breath sensor detects diabetes and potentially serious complication
Analytical Chemistry

Professor Sotiris E. Pratsinis and colleagues are reporting development and successful testing of a sensor that can instantly tell whether someone has Type I diabetes. Type I diabetics release unusually high levels of acetone when they exhale. The sensor could also be used by emergency room doctors to determine whether a patient has developed diabetic ketoacidosis, a potentially serious complication that happens when diabetics do not take enough insulin. If they have diabetic ketoacidosis, a dangerous buildup of acetone in the blood, they exhale even-larger amounts of acetone. Pratsinis’ team built an extremely sensitive acetone detector by directly depositing from a flame plume a thin film of semiconducting, mixed ceramic nanoparticles between a set of gold electrodes. The device acts like an electrical resistor — when it gets hit with a puff of acetone-filled air, its resistance drops, allowing more electricity to pass between the electrodes. If a diabetic were to breathe on the sensor, its resistance would suddenly drop indicating high levels of acetone.

Nicer than needles: Insulin pills for diabetes finally in clinical trials
Chemical & Engineering News

C&EN Senior Correspondent Ann Thayer reports that insulin pills to manage diabetes are finally moving ahead in clinical trials and a step-closer to the medicine cabinet. Drug manufacturers have tried for years to develop oral insulin without much success. Insulin is a peptide hormone that people with diabetes currently take by injection to bring their blood sugar to within normal levels, but the discomfort and inconvenience can make patients reluctant to use the drug frequently enough to adequately control their blood sugar. An oral form of insulin could help solve this problem, but stomach acids and enzymes easily destroy insulin and other protein-based drugs. Scientists have responded to this challenge by developing special coatings for insulin pills that prevent stomach acid from destroying them, and using additives that make it easier for the intestine to absorb large molecules like insulin. Only time will tell, however, whether these much-anticipated pills will make it to the market.

First paper “dipstick” test for determining blood type
Analytical Chemistry

Gil Garnier and colleagues are reporting development of the first “dipstick” test for instantly determining a person’s blood type at a cost of just a few pennies. Current methods for determining blood type require the use of sophisticated instruments that are not available in many poor parts of the world. But this test involves placing a drop of blood on a paper strip impregnated with antibodies to the antigens on red blood cells that determine blood type; the strip changes color to indicate blood type. The authors say it could be a boon to health care in developing countries, allowing for successful blood transfusions, and for use in veterinary medicine, typing animals’ blood in the field.

Eyes of cattle may become new windows to detect Mad Cow Disease
Environmental Science & Technology

Jacob Petrich and colleagues report evidence that retinas of sheep infected with scrapie, a disease similar to Mad Cow Disease, emit a characteristic glow when examined with a beam of light from a special instrument. That test could help prevent the disease from spreading in the food supply. Past studies had suggested that chemical changes in an animal’s retina, the light sensitive nerve tissue in the back of the eye, may provide a basis for detecting prion diseases. They suggest that eye tests based on the finding could become important in the future for fast, inexpensive diagnosis of prion diseases and other neurological diseases such as Mad Cow Disease.

Evidence that nanoparticles in sunscreens could be toxic if accidentally eaten
Chemical Research in Toxicology

Philip Moos and colleagues note in a report in Chemical Research in Toxciology that zinc oxide particles smaller than 100 nanometers in size are slightly more toxic to colon cells than conventional zinc oxide, which is widely used in sunscreens. Their experiments with cell cultures of colon cells compared the effects of zinc oxide nanoparticles to zinc oxide sold as a conventional powder. They found that the nanoparticles were twice as toxic to the cells as the larger particles. The concentration of nanoparticles that was toxic to the colon cells was equivalent to eating 2 grams of sunscreen – about 0.1 ounce. This study used isolated cells to study biochemical effects and did not consider the changes to particles during passage through the digestive tract. The scientists say that further research should be done to determine whether zinc nanoparticle toxicity occurs in laboratory animals and people.

Potential new Alzheimer’s drugs advancing in clinical trials
Chemical & Engineering News

C&EN Senior Editor Lisa Jarvis assesses the scientific foundation and clinical landscape of abnormal clumps of protein in the brain called amyloid-beta. She notes that amyloid-beta is at the heart of a central hypothesis – and simmering controversy – about Alzheimer’s disease. Some scientists are convinced that amyloid-beta is the root cause of the nerve-cell death and subsequent mental decline in individuals with Alzheimer’s disease. Others think that something else, perhaps a still-unidentified environmental neurotoxin, is the real culprit. That mystery agent, they suspect, triggers formation of beta-amyloid. If clinical trials are successful, doctors within 5-10 years could have an arsenal of new drugs that can slow the progression of Alzheimer’s. If the trials fail, it’s back to the drawing board to find new hypothesis and drug targets for the disease, the article notes.

New advances in science of the ultra-small promise big benefits for cancer patients
ACS Nano

A $145-million Federal Government effort to harness the power of nanotechnology to improve the diagnosis, treatment, and prevention of cancer is producing innovations that will radically improve care for the disease. That’s the conclusion of an update on the status of the program, called the National Cancer Institute Alliance for Nanotechnology in Cancer. Piotr Grodzinski and colleagues note in the article that the alliance, launched in 2004, funds and coordinates research specifically intended to move knowledge about the small science out of laboratories and into hospitals and doctors’ offices in a big way. The article describes a range of potential advances, including earlier disease diagnosis, highly targeted treatments that kill cancer cells but leave normal cells alone, fewer side effects, and improved survival.

Toward simplifying treatment of a serious eye infection
Molecular Pharmaceutics

Howida Kamal Ibrahim and colleagues report the development of a potential new way of enabling patients with bacterial keratitis to stick with the extraordinarily intensive treatment needed for this potentially blinding eye infection. Bacterial keratitis is a rapidly-progressing infection of the cornea that affects more than half a million people each year worldwide. The treatment requires that patients frequently use antibiotic eye medicine – one drop every 5 minutes to start and then more drops every 15-30 minutes for up to 3 days – and daily use of anti-inflammatory drugs. This intensive treatment regimen is difficult for patients to follow and often requires putting them into a hospital to assure they get adequate treatment. The researchers describe the development of a new two-in-one formula that combines the antibiotic and anti-inflammatory drug into a single medication. In tests with lab animals, the drops delivered five times more medication to the eye and it remained there three times longer than existing medicine.

Prescription drug could boost effects of vaccines for HIV and other diseases
Molecular Pharmaceutics

John Pesce and colleagues at the Naval Medical Research Center and UC-Berkeley note that vaccines prepared from weakened or inactivated viruses or bacteria have had enormous success in preventing polio, influenza, and other diseases. However, vaccines containing living or weakened viruses cannot be used for HIV, hepatitis C, and other devastating diseases due to safety concerns. Scientists are instead trying to develop a new generation of vaccines, made with DNA or proteins from infectious agents that can prevent illness without carrying a risk of causing the diseases. These vaccines will be weaker than conventional vaccines and require a new generation of “adjuvants,” ingredients that boost a vaccine’s immunogenicity. The report identifies a promising candidate in the form of imiquimod, an immune-boosting drug already in general use to treat genital warts and skin cancer. The scientists coated imiquimod with dextran-based microparticles in hopes of increasing the efficiency of cellular uptake by cells associated with immune response initiation. The coated drug significantly boosted levels of inflammatory cytokines in laboratory cultures of immune cells from mice.

Real-world proof of hand washing’s effectiveness
Environmental Science & Technology

Alexandria Boehm, Jenna Davis, and their students note that almost half of the world’s population – over 3 billion people – have no access to municipal drinking water supply systems. They obtain drinking water from wells, springs, and other sources, and store it in jugs and other containers in their homes. Past research showed that this stored water contained nearly 100 times more fecal bacteria than the source where it was collected. The scientists found a strong link between fecal contamination on the hands of household residents and bacterial contamination in stored water in Dar es Salaam, Tanzania. “The results suggest that reducing fecal contamination on hands should be investigated as a strategy for improving stored drinking water quality and health among households using non-networked water supplies,” the report notes.

Toward reading your own personal “Book of Life”
Chemical & Engineering News

C&EN Senior Editor Celia Henry Arnaud notes that the first human genome sequence cost more than $2 billion and took about a decade to complete. Technological advances now have cut the time to as little as one week, and some companies are charging individuals $48,000 for the service, a cost that experts expect to drop sharply in the coming years. With their genomic sequence in hand, consumers and their physicians could map out strategies for the prevention, early diagnosis, and more effective treatment of diseases ranging from cancer to rare-genetic disorders. But the technology also raises important ethical and legal issues, including the possibility of discrimination on the basis of genetic information in the areas of employment and insurance coverage.

More evidence on benefits of high blood pressure drugs in diabetic eye disease
Journal of Proteome Research

Edward Feener and colleagues reported new evidence that certain high blood pressure drugs may be useful in preventing and treating diabetic retinopathy, the leading cause of vision loss in people with diabetes, which affects millions of people worldwide. It involves damage to blood vessels in the retina, the light sensitive tissue in the back of the eye. Previous studies suggested that drugs used to treat high blood pressure, including ACE inhibitors and angiotensin receptor blockers (ARBs), may help prevent the condition. The scientists analyzed proteins from the retinas of laboratory mice with normal blood pressure and diabetes and compared them to those of non-diabetic mice. They identified 65 abnormal proteins in the diabetic mice out of more than 1,700 proteins in the study. Treatment with the ARB medication, candesartan, prevented the abnormal changes in more than 70 percent of the proteins.

Nitric oxide-releasing wrap for donor organs and cloth for therapeutic socks
Chemistry of Materials

Researchers Kenneth Balkus and Harvey Liu are reporting development of a first-of-its-kind cloth that releases nitric oxide gas — an advance toward making therapeutic socks for people with diabetes and a wrap to help preserve organs harvested for transplantation. They note in the new study that nitric oxide (NO) helps increase blood flow and regulates a range of other body functions. Scientists have tried for years to find practical ways to store and deliver NO for use in medicine. However, they have had difficulty finding a suitable material that allows controlled delivery of NO. The scientists describe development of a new bandage composed of nitric oxide-absorbing zeolites embedded in a special water-repellant polymer. In experiments with laboratory rats, the bandage slowly released nitric oxide and increased blood flow.

Toward a less expensive version of the anti-flu drug Tamiflu®
Organic Letters

Anqi Chen, Christina Chai and colleagues have developed an alternative method for producing the active ingredient in Tamiflu®, the mainstay for fighting H1N1 and other forms of influenza. The new process could expand availability of the drug by reducing its cost, which now retails for about $8 per dose. Tamiflu®, also known as oseltamivir phosphate, remains the most widely used antiviral drug for the prevention and treatment of H1N1 infections as well as bird flu and seasonal influenzas. But growing demand for the drug has put pressure on the supply of shikimic acid, the raw material now used in making the drug. They found that D-ribose, a naturally-occurring sugar produced by fermentation in large scales, potentially provides an inexpensive and abundant substitute for shikimic acid at about one-sixth the cost.

New biomarkers for predicting the spread of colon cancer
Journal of Proteome Research

Maode Lai and colleagues report the discovery of two proteins present in the blood of people with colon cancer that may serve as the potential biomarkers for accurately predicting whether the disease will spread. Surgery is the main method of treating the disease. However, half of colon cancer patients undergoing surgery develop a recurrence of the disease within 5 years due to its spread, or metastasis, to other parts of the body. The spread of colon cancer can be difficult to detect and there are currently no reliable chemical markers in the body for predicting its spread, the scientists say. They identified two proteins that occurred at significantly higher levels in metastatic cells than in the primary cancer cells. The two proteins could serve as potential biomarkers in a blood test for predicting the spread of colon cancer, allowing earlier intervention and treatment, the scientists say.

First evidence that blueberry juice improves memory in older adults
Journal of Agricultural and Food Chemistry

Robert Krikorian and colleagues are reporting the first evidence from human research that blueberries — one of the richest sources of healthful antioxidants and other so-called phytochemicals — improve memory. Until now, however, there had been little scientific work aimed at testing the effect of blueberry supplementation on memory in people. In the study, one group of volunteers in their 70s with early memory decline drank the equivalent of 2-2 1/2 cups of a commercially available blueberry juice every day for two months, while a control group drank a beverage without blueberry juice. The blueberry juice group showed significant improvement on learning and memory tests, the scientists say. The report said, “These preliminary memory findings are encouraging and suggest that consistent supplementation with blueberries may offer an approach to forestall or mitigate neurodegeneration.”

Consumers over age 50 should consider steps to cut copper and iron intake
Chemical Research in Toxicology

Scientific evidence links high levels of copper and iron to Alzheimer’s disease, heart disease, and other age-related disorders. After age 50, high levels of these metals can damage cells in ways that may contribute to a range of age-related diseases. George J. Brewer and colleagues suggest those over age 50 avoid vitamin and mineral pills that contain copper and iron; lower meat intake: avoid drinking water from copper pipes; donate blood regularly to reduce iron levels; and take zinc supplements to lower copper levels.

Trojan Horse ploy to sneak protective drug into brains of stroke patients
Molecular Pharmaceutics

William Pardridge and colleagues are reporting the development of a long-sought method with the potential for getting medication through a biological barrier that surrounds the brain, where it may limit the brain damage caused by stroke. The researchers found an antibody that can go through the blood brain barrier and linked it to erythropoietin to make a hybrid protein. Tests showed that the approach worked in laboratory mice, with the hybrid protein successfully penetrating the blood-brain barrier. The advance will allow scientists to begin testing erythropoietin’s effects on mice with simulated stroke and other brain disorders such as Parkinson’s disease, so that scientists can establish the most effective dose and best timing for possible future tests in humans.

Firefly protein lights pathway to improved detection of blood clots
Bioconjugate Chemistry

The enzyme that makes fireflies glow is lighting up the scientific path toward a long-sought new medical imaging agent to better monitor treatment with heparin, the blood thinner that millions of people take to prevent or treat blood clots. Bruce Branchini and colleagues combined a protein obtained from firefly luciferase with a special dye that allows the protein to emit near-infrared light. In laboratory experiments, the new material successfully detected minute amounts of a specific blood protein, called factor Xa, which is used to monitor the effectiveness of heparin treatment.

Bacterial life on and in humans orchestrates health and disease
Chemical & Engineering News

C&EN Associate Editor Sarah Everts notes that the astonishing diversity of microbes inhabiting every inch of the skin and parts of the interior profoundly influences your quality of life — mostly for good — from cradle to grave. Microbes protect people from disease, make essential vitamins, and provide digestive enzymes needed to break down plant fibers for energy. Microbes also may have a say in whether people are skinny or fat and how they smell. In the past three years, scientists have begun several large projects to map the diversity and activities of these microbes in hopes of linking them to health and disease. These and other projects are starting to reveal that every part of the body has its own ecosystem, much like the diversity of landscapes on Earth.

The buzz on fruit flies: New role in the search for addiction treatments
ACS Chemical Neuroscience

Laboratory mice, rats, and monkeys have been mainstays in research with the ultimate goal of finding effective medicines for treating addiction. Although these mammals have helped establish the behavioral effects of cocaine on the body, they provide relatively complicated models to study the effects of cocaine and other illicit drugs on the brain and nerves. In the hope for a new simpler animal model they turned to fruit flies, which have many biological similarities to mammals, but are easier to study. Researchers confirmed those hopes in research that involved giving cocaine, amphetamine, methamphetamine, and methylphenidate to fruit flies and then studying brain chemistry with a microelectrode one-twentieth the diameter of a human hair. The results demonstrate that fruit flies are a valid model for studying drug addiction in humans, the scientists say.

Heart drugs show promise for fighting colon cancer
Journal of Natural Products

Jenny Felth, Joachim Gullbo, and colleagues note that cardiac glycosides, a family of naturally-derived drugs used to treat congestive heart failure and abnormal heart rhythms, show promise for fighting colon cancer. Colon cancer is the third most common cancer in the United States, with more than 150,000 cases diagnosed in the U.S. each year. Despite this, knowledge on effects in colon cancer or combination effects with other anti-cancer drugs is lacking. They selected five heart drugs to test against laboratory cultures of human colon cancer cells and found that they were all effective, to varying degrees, at killing the cancer cells. Several of the drugs showed increased anticancer activity when used alone or combined with certain drugs used for standard chemotherapy.