Breakthrough antibacterial approach could resolve serious skin infections
Like a protective tent over a colony of harmful bacteria, biofilms make the treatment of skin infections especially difficult. Microorganisms protected in a biofilm pose a significant health risk due to their antibiotic resistance and recalcitrance to treatment, and biofilm-protected bacteria account for some 80 percent of total bacterial infections in humans and are 50 to 1,000 times more resistant to antibiotics than simpler bacterial infections.
"In essence, we may have stumbled onto a magic bullet," said David Fox, a Los Alamos National Laboratory (LANL) researcher on the project. "Through a robust screening strategy, our research team has identified a unique class of materials, known as ionic liquids, which both neutralize biofilm-forming pathogens and deliver drugs through the skin," he said.
"We extended our current capability in antimicrobial platforms with ionic liquids to new heights by partnering with Dr. Mitragotri at UCSB, who is an expert in transdermal drug delivery platforms. The merger made perfect sense," stated Fox.
"In several cases, we found the ionic liquid was more efficacious on a biofilm than a standard bleach treatment and exhibited minimal cytotoxicity effects on human cell lines (unlike bleach). This has excellent prospects for aiding antibiotic delivery to the pathogen through biofilm disruption but, most interestingly, the ionic liquids themselves are quite effective for pathogen neutralization," Fox said.
This work could have especially useful applications for military medical treatments, he noted, where soldiers in the field can be exposed to bacterial infections that are particularly difficult to treat.
Biofilms often persist in the periphery of an actual wound, beneath an intact, healthy skin layer and the difficulty of their treatment is largely due to the outermost layer of the skin, the stratum corneum, being a natural barrier for drug delivery.
"If the bacterial biofilm can be disrupted, delivery of antibiotics is greatly enhanced, and any dispersed pathogens are generally restored to normal antibiotic susceptibility," said Fox. "Further, many bacterial infestations in wounds penetrate under the outer skin layer, the stratum corneum, and deep into the tissue (epidermis and dermis). These materials are able to penetrate through the skin and effectively carry antibiotics to the deepest layers."
"Clearly, the ionic liquids would be of special benefit to our warfighters where exposure to biological agents in hostile environments is likely. Topical application as a prophylaxis or direct treatment to an open wound could buy enough time to reach the proper medical facilities when in an austere environment," he said. Importantly, ionic liquids can be derived from very cheap starting materials that are FDA approved and are extremely stable to high temperatures and pressures, which are necessary traits for commercialization in real-world applications.
In a groundbreaking manuscript appearing this week in the Proceedings of the National Academy of Science, as part of a multi-institutional effort between Los Alamos, University of California Santa Barbara, Dixie State University and Northern Arizona University, researchers explored exploiting ionic liquids both in a concerted effort to combat antibiotic-resistant bacterial biofilms in skin, as well as for topical transdermal drug delivery. The comprehensive strategy resulted in the identification of ionic liquids that are effective at disrupting biofilms, neutralizing pathogens, and enhancing delivery of antibiotic into skin.
Biofilms are a major cause of chronic wounds and wound degeneration. Wounds from infected surgical incisions result in 1 million additional hospital days. Additional causes of bacterial infected wounds include traumatic injuries, as well as diabetic foot ulcers, venous leg ulcers, and pressure ulcers.
The total economic burden of skin disease was estimated to be approximately $96 billion in 2004, and the prevalence and healthcare costs for skin disease have been increasing over the last three decades. Bacterial infections in the skin are among the most common diagnoses in hospital patients, accounting for some 10% of all hospital visits. Staphylococcus aureus infections acquired in hospitals, which account for only 16% of nosocomial infections, are estimated to result in $9.5 billion in extra patient costs and 12,000 deaths annually.
The comprehensive approach is unique in that the team examined a panel of in-house synthesized ionic liquids and enabled the discovery of one ionic liquid, choline-geranate, which showed excellent antimicrobial activity, minimal toxicity to epithelial cells as well as skin, and effective permeation enhancement for drug delivery. Specifically, choline-geranate was comparable with, or more effective than, bleach treatment against established biofilms of Salmonella enterica and Pseudomonas aeruginosa, respectively. In addition, choline-geranate increased delivery of cefadroxil, an antibiotic, by >16-fold into the deep tissue layers of the skin without inducing skin irritation.
Skin layer grown from human stem cells could replace animals in drug and cosmetics testing
An international team led by King's College London and the San Francisco Veteran Affairs Medical Center (SFVAMC) has developed the first lab-grown epidermis – the outermost skin layer - with a functional permeability barrier akin to real skin. The new epidermis, grown from human pluripotent stem cells, offers a cost-effective alternative lab model for testing drugs and cosmetics, and could also help to develop new therapies for rare and common skin disorders.
The epidermis, the outermost layer of human skin, forms a protective interface between the body and its external environment, preventing water from escaping and microbes and toxins from entering. Tissue engineers have been unable to grow epidermis with the functional barrier needed for drug testing, and have been further limited in producing an in vitro (lab) model for large-scale drug screening by the number of cells that can be grown from a single skin biopsy sample.
The new study, published in the journal Stem Cell Reports, describes the use of human induced pluripotent stem cells (iPSC) to produce an unlimited supply of pure keratinocytes – the predominant cell type in the outermost layer of skin - that closely match keratinocytes generated from human embryonic stem cells (hESC) and primary keratinocytes from skin biopsies. These keratinocytes were then used to manufacture 3D epidermal equivalents in a high-to-low humidity environment to build a functional permeability barrier, which is essential in protecting the body from losing moisture, and preventing the entry of chemicals, toxins and microbes.
A comparison of epidermal equivalents generated from iPSC, hESC and primary human keratinocytes (skin cells) from skin biopsies showed no significant difference in their structural or functional properties compared with the outermost layer of normal human skin.
Dr Theodora Mauro, leader of the SFVAMC team, says: "The ability to obtain an unlimited number of genetically identical units can be used to study a range of conditions where the skin's barrier is defective due to mutations in genes involved in skin barrier formation, such as ichthyosis (dry, flaky skin) or atopic dermatitis. We can use this model to study how the skin barrier develops normally, how the barrier is impaired in different diseases and how we can stimulate its repair and recovery."
Dr Dusko Ilic, leader of the team at King's College London, says: "Our new method can be used to grow much greater quantities of lab-grown human epidermal equivalents, and thus could be scaled up for commercial testing of drugs and cosmetics. Human epidermal equivalents representing different types of skin could also be grown, depending on the source of the stem cells used, and could thus be tailored to study a range of skin conditions and sensitivities in different populations."
- Skin disease takes emotional toll like chronic pain
- Hard to exercise because sweat triggers itch
- Diabetes, high blood pressure and insomnia add to eczema health woes
- Physicians need to treat cardiovascular risks as well as the itch
These behaviors give them a higher risk of cardiovascular disease, including high blood pressure and high cholesterol as well as diabetes. They also have higher rates of insomnia. About 10 percent of adults in the U.S. have eczema.
"This disease takes a huge emotional toll on its sufferers, like chronic pain," said lead study author Dr. Jonathan Silverberg. "Because eczema often starts in early childhood, people are affected all through their developmental years and adolescence. It hurts their self-esteem and identity. That's part of why we see all these negative behaviors."
Silverberg is an assistant professor of dermatology at Northwestern University Feinberg School of Medicine and a dermatologist at Northwestern Memorial Hospital. He also is director of the Northwestern Medicine Multidisciplinary Eczema Center.
Adding to eczema patients' health woes is difficulty exercising because sweat and heat aggravate the itching. "They will avoid anything that triggers the itch," Silverberg said. "Patients report their eczema flares during a workout."
"This opens our eyes in the world of dermatology that we're not just treating chronic inflammation of the skin but the behavioral, lifestyle side of things," Silverberg said. Dermatologists need to ask patients about their lifestyle habits such as smoking and physical activity so they can offer interventions.
The study analyzed data for 27,157 and 34,525 adults aged 18 to 85 years from the 2010 and 2012 National Health Interview Survey. The Northwestern study reported patients with eczema had 54 percent higher odds of being morbidly obese, 48 percent higher odds of hypertension, up to 93 percent higher odds of having pre-diabetes and up to 42 percent higher odds of having diabetes. They also had 36 percent higher odds of high cholesterol.
Silverberg said patients should be offered interventions for alcohol and smoking by their dermatologists. In addition, he is collaborating with colleagues in Northwestern's department of physical therapy and human movement sciences to figure out how patients with eczema can exercise to improve their health without worsening their skin flare-ups.
Researchers discover why Listeria bacterium is so hard to fight
Listeria is a dreaded bacterium that can be found in both unprocessed and processed foods. Over the last few weeks, 28 persons in Denmark have been infected with Listeria from processed food, sold in supermarkets. 13 have died.
The bacterium is notoriously difficult to fight because it has an almost uncanny ability to adapt to changes in its surroundings, says Associate Professor Birgitte Kallipolitis, University of Southern Denmark. Together with colleagues from the Department of Biochemistry and Molecular Biology, she has published a study, which in details reveals how this extreme ability to adapt takes place.
The researchers tested how Listeria reacts when it is exposed to a number of substances that can normally fight pathogenic bacteria. In the laboratory, Listeria was exposed to antibiotics, bile, salt, acid and ethanol, similar to what it often encounters in food, in the human body and during disinfection.
"We knew that Listeria can resist these substances, but we did not quite know how," says Birgitte Kallipolitis.
The researchers discovered that Listeria used a variety of strategies that enabled them to withstand the substances.
"Generally speaking, Listeria must be described as extremely adaptable. It is constantly aware of its surroundings and if the environment changes around it. It reacts instantly and has a number of strategies to withstand threats", says Birgitte Kallipolitis.
The researchers also discovered that Listeria is an expert at not attracting unwanted attention from the body's immune system.
"On the one hand, Listeria needs to produce some special proteins that enable it to infect the cells in our body. On the other hand, it must ensure that the body's immune system does not detect these proteins. It is vital for Listeria to keep a balance between producing enough of these proteins but not so many that they are detected by the immune system – and it masters just that", explains Birgitte Kallipolitis.
When in the lab, the researchers looked at what happened at the microbiological level. It turned out that Listeria started producing some special RNA molecules, when they were exposed to antibiotics, bile, salt, acid and ethanol.
"With these RNA molecules the bacteria can adjust how much or how little to produce of various proteins. For example it can downgrade the production of the protein LapB, which it uses to enter our cells. If this production is not downgraded, the bacterium will potentially be detected and fought by the immune system", says Birgitte Kallipolitis.
In other words: Listeria can fine-tune the production of the proteins needed to infect our cells to a point where there is exactly enough to sneak through the immune system's defense, but not so many that they are discovered.
The RNA molecules, produced when Listeria face dangerous environmental changes, also helps Listeria monitor its own cell wall. Antibiotics work by attacking the bacterial cell wall, and when exposed to antibiotics Listeria immediately detects that its cell wall is attacked. This enables it to quickly repair its cell wall - and thus become ready for combat again.
"We see this production of RNA molecules only when Listeria is exposed to threatening substances in the lab. When there are no threats, Listeria does not produce them. This reveals part of the mechanism behind Listeria´s extreme adaptability", concludes Birgitte Kallipolitis.
The understanding of how Listeria is able to survive antibiotics, the immune system and disinfecting agents is necessary in order to develop effective means against the life-threatening bacteria.
"Only by looking at what the bacteria themselves do to survive, we can become better at fighting their pathogenicity", says Birgitte Kallipolitis.
She and her colleagues are now investigating whether Listeria can be changed into harmless bacteria by removing the RNA molecules.
FLASHWHITE UNISPHERES®: INSTANT WHITENING BEADS
Induchem launches a new generation of active beads: they instantly whiten and smooth skin imperfections in 5 seconds. The Flashwhite Unispheres® are made of pure whitening pigment (Titanium dioxide) to offer this incredible instant effect, combined with two natural extracts (Vitamin C-rich cucumber and lemon extracts) to prolong the lightening action. With clinically proven results, these new generation of Unispheres® will not only enhance the visual attractiveness of your product, but they will also instantly brighten the complexion and even skin tone of your customers. Flashwhite Unispheres® have been selected as ingredient #1 for the whitening product trail at In Cosmetics Asia 2014.
PRICE INCREASE ON A RANGE OF ARKEMA'S ORGANIC PEROXIDES
Arkema has implemented from 1st of December 2014, or as contracts allow, a price increase on its Luperox® organic peroxides used in the unsaturated polyester resins segment and commercialized in Europe, Middle East and Africa. This is necessary to offset the raw material cost increases. The price increase will vary from 5 to 10% depending on the grade and will concern exclusively the range of the methyl-ethyl-keton peroxides and their blends. The methyl-ethyl-keton peroxides are used as curing agents in unsaturated polyester resins - or thermoset resins - very commonly used in the composite industry, mainly in the sectors of transport, sailing boats and in wind turbine blades.
SEPISUN FLASH is the natural "healthy glow" solution throughout the year. Its biological action naturally increases the production of melanin, thus maintaining the "sun-kissed" skin effect throughout the seasons. SEPISUN FLASH is not a UV filter (non absorption into UV range) and does not act like self-tanning agents.
In Spring, SEPISUN FLASH prepares for the sun and nicely pigments the skin. In just 15 days, it provides a "healthy glow effect without sun exposure.
In Summer, SEPISUN FLASH boosts the effects of the sun and helps tan twice as fast. The skin is protected from excessive UV exposure.
In Fall and Winter, SEPISUN FLASH prolongs the "sun-kissed" skin effect.
New molecule based on renewable resources and eco-designed
Ecocert process underway
Clinical efficacy compared to market benchmark
Clinical efficacy proven even without UV exposure
Liquid active, easy to formulate in hot or cold processes
Level of use: 1%
SYTHEON HAS RECEIVED A NEW US PATENT NO 8,859,021 ON SYTENOL® AS
Extensive research and clinical studies have confirmed that Sytenol® A is a true Retinol-like functional compound without having the negatives of Retinol. Sytenol® A is a well-defined natural compound, not an extract and has a purity of well over 95%. US patent # 8,859,021 relates to a method for treating, preventing and improving the condition and/or aesthetic appearance of aging skin, particularly, treating, preventing, ameliorating, reducing and/or eliminating fine lines and/or wrinkles of skin, using meroterpene- (more specifically, Bakuchiol). Issuance of this new patent along with an earlier US patent (No 8,529,967) on skin protective compositions of Sytenol® A, solidifies Sytheon's patent portfolio on Bakuchiol. Skin protective composition includes sunscreens and may optionally include one or more ingredients such as antioxidants, vitamins, anti-inflammatory agents, self-tanning agents and mixtures thereof. Anti-aging property of Sytenol® A is covered in a recent publication – "Bakuchiol: A retinol-like functional compound revealed by gene expression profiling and clinically proven to have anti-aging effects", International J of Cosmetic Science, 36(3):221-230, 2014.
DOLCÉVIA® EASING BEAUTY
Sinerga launches a surprising active ingredient: effective, 100% natural origin, in line with the latest trends of those who likes to take care of themselves: DOLCEVIA. Dolcévia® is the active ingredient for the new generation of cosmetic products claimed as "soft-aging" products: powerful and respectful allies of skin that aim at accompany at best our ages of life. Its tested action contrasts one of the main cause of the signs of aging: the involuntary muscle contractions caused by stress.
INDEPENDENT STUDIES PROVE BIODEGRADABILITY OF NEW EXFOLIATING BEADS
As plastic microbeads become restricted from use in cosmetics, formulators are urgently seeking natural, biodegradable alternatives. Floratech®, the world's first supplier of biodegradable, natural wax exfoliating beads, offers a variety of replacement options. Newly developed Ecobeads® are a low cost botanical scrubbing bead. Florabeads® provide gentle yet effective exfoliation. Both are available in a wide array of standard colours and both are proven biodegradable by independent studies.
LUBRIZOL ANNOUNCES MEMBERSHIP IN ROUNDTABLE ON SUSTAINABLE PALM OIL
The Lubrizol Corporation has announced the acceptance of Lubrizol Advanced Materials into the Roundtable on Sustainable Palm Oil (RSPO) association, a not-for-profit association that unites stakeholders from seven sectors of the palm oil industry - oil palm producers, palm oil processors or traders, consumer goods manufacturers, retailers, banks and investors, environmental or nature conservation non-governmental organizations (NGOs) and social or developmental NGOs - to develop and implement global standards for sustainable palm oil. Certification for membership is based on very stringent guidelines. "We are extremely proud of this achievement" said Jeff Carey, global product management director for Lubrizol personal and home care. "We are dedicated to helping our customers reach their sustainability goals and become RSPO compliant, and being a member of RSPO is consistent with our growth strategy to provide solutions to the personal and home care global market". Lubrizol has engaged all current suppliers of palm-oil derivatives and has determined that each is compliant with one of the RSPO supply chain models.
LIPOTEC DISTINGUISHED WITH THE SOCIETY OF COSMETIC CHEMISTS AWARD 2014
In a ceremony that took place on December 11th Lipotec was distinguished with the Society of Cosmetic Chemists Award for its presentation at the SCC 2013 "Counteracting circadian regulation of adipose tissue". This award recognizes the Best Paper presented at the SCC 2013 Annual Scientific Meeting and it has been an honour collecting it. The presentation awarded reflects the work and close cooperation of Dr. Cristina Carreño, Dr. Olga Laporta-Alcantara, Dr. Juan Cebrian, Dr. Nuria Almiñana, Dr. Raquel Delgado, Dr. Nuria Garcia-Sanz, Dr. Silvia Pastor, Dr. Albert Soley and Dr. Antonio Ferrer-Montiel. The paper explains the first studies and premises that led us to NOCTURSHAPE™ blue ingredient, launched in September of 2014. This innovative active, obtained through biotechnology from a planktonic microorganism of Fuente de Piedra, Spain, targets the expression of the circadian protein nocturnin in adipocytes, which peaks at early night.
HONEYWELL STARTS FULL-SCALE PRODUCTION OF LOW-GLOBAL-WARMING PROPELLANT, INSULATING AGENT, AND REFRIGERANT
Honeywell has announced that it has started full-scale commercial production of a low-global-warming-potential (GWP) material used as an aerosol propellant, insulating agent and refrigerant. The material, known by the industry designation HFO-1234ze and marketed by Honeywell under its Solstice® line of low-global-warming materials, is being produced at the Honeywell Fluorine Products facility in Baton Rouge, La. "Honeywell's Baton Rouge production facility is ready to serve customers around the world with this innovative material, which has an ultra-low GWP of less than 1" said Ken Gayer, vice president and general manager of Honeywell's Fluorine Products business. "We are seeing increasing demand for our entire Solstice line of low GWP materials, and this new product has already been adopted by a range of customers globally". Honeywell's Baton Rouge facility was built in 1945 and continues to serve as one of Honeywell's main manufacturing sites for its Performance Materials and Technologies business. The site employs more than 200 people. Louisiana Governor Bobby Jindal said: "Honeywell helps support hundreds of jobs in our state, and we're proud the company is expanding in Baton Rouge with a brand new product line. This project is a good example of how Louisiana's outstanding business climate is convincing companies like Honeywell to reinvest in our state, retain great existing jobs and create additional new career opportunities for our people
EVONIK INTRODUCES VARISOFT® EQ 100- THE HIGH PERFORMANCE LIQUID CONDITIONING AGENT WITH IMPROVED SUSTAINABILITY PROFILE
Evonik is now launching VARISOFT®EQ 100 (INCI proposed: Quaternium-98), a novel premium hair conditioning agent with exceptional performance and pronounced sustainability features. The 100% active esterquat provides superior manageability, lubricity and softness to the hair and outperforms leading market standards in both sensorial evaluations and technical measurements. The sustainability profile of VARISOFT® EQ 100, including its ready biodegradability, lower ecotox compared to common benchmark, cold-processability, and its primarily renewable, none palm-based feedstock, is supporting a more environmentally conscious approach in the cosmetic industry. Furthermore, VARISOFT® EQ 100 is a solvent-free and non-flammable liquid with reduced risk during transport or production, and, increased flexibility during processing. VARISOFT® EQ 100 is suitable for a broad range of application formats in the hair care market, including conditioning rinses, hair conditioning sprays and treatments, conditioning shampoos, styling products as well as hair dyes. With VARISOFT® EQ 100 Evonik introduces a high performance hair conditioning agent which helps to balance the consumers' desire for a beautiful appearance with the necessity to improve the sustainability profile of the hair care industry.