Common ingredient in shampoo causes eczema

Considerably more people than previously believed are allergic to the most common fragrance ingredient used in shampoos, conditioners and soap. A thesis presented at the Sahlgrenska Academy, University of Gothenburg, Sweden found that over 5% of those who underwent patch testing were allergic to the airoxidised form of the fragrance ingredient linalool.

“I would suspect that about 2% of the complete population of Sweden are allergic to airoxidised linalool. That may not sound very much, but it is serious since linalool is so widely used as a fragrance ingredient. Linalool is found in 60-80% of the perfumed hygiene products, washing up liquids and household cleaning agents that can be bought in the nearest supermarket, and it can be difficult for people who are allergic to avoid these products”, says dermatologist Johanna Bråred Christensson, author of the thesis.

Around one person in five in Sweden has some form of contact allergy. Nickel is by far the most common substance that causes eczema, but the thesis shows that oxidised linalool occupies third place in the list, after nickel and cobalt.

In the study, oxidised linalool was added at patch testing for more than 3,000 patients who wanted to find out what was causing their eczema. Between 5% and 7% proved to be allergic to the oxidised form of the fragrance ingredient.

Linalool is a fragrance ingredient found naturally in lavender, mint, and other plants. Linalool breaks down when it comes into contact with oxygen, it becomes oxidised and can cause allergy. Manufacturers do include other substances in the products to delay this oxidation process, but allergenic substances can still be formed from linalool when it is stored.

“One way of trying to minimise exposure to oxidised linalool is to avoid buying large packs of soap and shower cream, and always to replace the top after using a bottle,” says Johanna Bråred Christensson.

Alternative to biopsy may improve cancer treatment

A drop of blood or a bit of tissue smaller than the period at the end of this sentence may one day be all that is necessary to diagnose cancers and assess their response to treatment, say researchers at the Stanford University School of Medicine in the US.

In a study published 12 April in the online version of Nature Medicine, the scientists used a specialised machine capable of analysing whether individual cancer-associated proteins were present in the tiny samples and even whether modifications of the proteins varied in response to cancer treatments. Although the study focuses on blood cancers, the hope is that the technique might also provide a faster, less invasive way to track solid tumours.

“Currently we don’t know what’s going on in a patient’s actual tumour cells when a treatment is given,” said oncologist Alice Fan, MD, a clinical instructor in the division of oncology at the medical school. “The standard way we measure if a treatment is working is to wait several weeks to see if the tumour mass shrinks. It would really be a leap forward if we could detect what is happening at a cellular level.”

Dean Felsher, MD, PhD, senior author of the study and associate professor of medicine and of pathology and the leader of the Stanford Molecular Therapeutics Program said: “This technology allows us to analyse cancer-associated proteins on a very small scale. Not only can we detect picogram levels – one-trillionth of a gramme – of protein, but we can also see very subtle changes in the ways the protein is modified.”

Variations in the way a protein is modified can affect how it functions in tumour progression. Analysing repeated small samples from a tumour undergoing treatment may allow doctors to stop proliferation of cells that would make the tumour more resistant to treatment or to identify patients likely to fail standard approaches to treatment.

“With this technology we can see changes that occur in as little as 10% of the total protein pool. Now we have a tool that will really help us look at what’s happening in cells over time,” said Dr Felsher. By extracting just a few cells, as opposed to the traditional large tissue biopsy, frequent assessments could be made of the tumour to check its progress.

New findings could lead to culturing blood cells

Researchers at the US National Institutes of Health (NIH) have deciphered a key sequence of events governing whether the stem cells that produce red and white blood cells remain anchored to the bone marrow, or migrate into the circulatory system.

An understanding of the factors that govern migration of blood stem cells might lead to improved treatment of leukaemia. The findings also have implications for culturing infection-fighting immune cells outside the body, where they could be temporarily held in storage during chemotherapy and other treatments which suppress the immune system. Moreover, the findings could contribute to a strategy for growing large quantities of red blood cells in laboratory dishes outside the body, to reduce the need for blood donations.

Previously, researchers thought that the cellular environment in which the stem cells reside produced the chemical signals that determined whether the cells would be stationary or freefloating. The current study provides evidence that the stem cells produce chemical signals of their own that may, in turn, influence the chemical signals they receive from their environment.

“This important discovery will advance our understanding of how blood cells and immune cells are generated,” said Duane Alexander, MD, director of the NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). The findings were published online in Nature Cell Biology.

Bio-engineered Proteins: Trial confirms new way to tackle cancer

Re-engineering a protein that helps prevent tumours spreading and growing has created a potentially powerful therapy for people with many different types of cancer. In a study published in the first issue of EMBO Molecular Medicine, Canadian researchers modified the tumour inhibiting protein, von Hippel-Lindau (VHL), and demonstrated that it could suppress tumour growth in mice.

When solid tumours grow they often have relatively poor and disorganised blood supplies. As a result, various regions including the centre of the tumour have low levels of oxygen and are said to be hypoxic. Cells in these hypoxic areas produce hypoxia-inducible factor (HIF) that helps them carry on growing. Consequently HIF is associated with aggressiveness in some of the most common types of cancer, including prostate, breast, colon and lung cancer. Under normal conditions VHL degrades HIF, but VHL is deactivated when oxygen levels are low. So, in hypoxic regions of a tumour, just where VHL is needed to inhibit cancer, it is ineffective.

The researchers, therefore, created a new version of VHL that does not stop working when oxygen is scarce. Introducing this newly engineered version of VHL into mice that had kidney tumours dramatically reduced levels of HIF, caused tumours to regress and limited the formation of new blood vessels within the tumours. “

We have genetically removed the Achilles’ heel of VHL to permit unrestricted destruction of HIF,” says lead researcher Professor Michael Ohh, who works in the Faculty of Medicine at the University of Toronto. “The level of HIF is usually very high under conditions of low oxygen, but when we put in our bioengineered VHL its levels go right down to a level that would be comparable to that in normal oxygen levels.”

Their findings could have implications for any type of cancer in which HIF plays a role. “We used kidney cancer as a model because it is one of the most resistant tumours to conventional radiation and chemotherapy, but our findings provide a novel concept that could potentially serve as a foundation for smarter anti-cancer strategy for a wide variety of cancers,” says Prof Ohh.

First patient receives treatment in study for beta islet transplant

Swedish company TikoMed announced in March that the first patient has been treated in a phase II study evaluating its product IBsolvMIR. If the study is successful, and IBsolvMIR is ultimately approved, it could transform beta cell islet transplantation into a widely used cure for diabetes type 1 patients with unstable diabetic conditions.

“Results from previous studies with IBsolvMIR indicate that the ongoing clinical trial will be successful,” said Anders Milton, MD, aboard member at TikoMed.

IBsolvMIR is a Low Molecular Weight Dextran Sulfate (LMW-DS) with an efficient inhibitor of Instant Blood-Mediated Inflammatory Reaction (IBMIR). The product has the potential to improve the survival of the transplanted islets. The IBMIR reaction plays a key role as it reduces the survival of the islet cells, thereby limiting the benefit of the transplantation. In a previous phase I study, IBsolvMIR was generally well tolerated by healthy volunteers, with no dose-limiting adverse effects documented.

The CIT-01A study is a multi-national, open, randomised (1:1), parallel-group clinical trial designed to evaluate the efficacy and safety of IBsolvMIR added to standard care in up to 72 patients undergoing beta cell islet transplantations. The multicenter study, which now enters phase II, is conducted by the Nordic Network for Clinical Islet Transplantation and The Clinical Islet Transplantation Consortium (CITC), under the direction of Professor Olle Korsgren, MD.

“The start of patient enrolment in the study marks an important milestone,” said Professor Olle Korsgren, MD, lead trial investigator, Uppsala University. “It brings us closer to the ultimate goal of improving outcomes for patients suffering from severe, hypoglycaemic episodes.”

The primary efficacy endpoint in the study is the level of C-peptide derived from the mixed-meal tolerance test at 75 days following the first islet infusion. The study also evaluates the safety and longterm effects of treatment with IBsolvMIR compared to standard care and the survival of islet cells through the use of PET/CT.

Non-alcoholic fatty liver disease linked to poor aerobic fitness

Poor aerobic fitness is strongly associated with obesity and its consequent risks of heart disease, strokes and diabetes – now considered worldwide epidemics. But the underlying link has long puzzled scientists. New research in The Journal of Physiology connects low aerobic capacity to another serious condition – non-alcoholic fatty liver disease (NAFLD) – and suggests that the resulting liver problems play a crucial step developing obesity-related illnesses.

Sufferers of NAFLD accumulate fat in their livers and have high levels of fat in their blood, amplifying the riskfactors of obesity. The disease leads to a form of liver damage called fibrosis, similar to the results of alcohol abuse. “Fatty liver disease will be the next big metabolic disorder associated with obesity and inactivity,” said the study’s lead author John Thyfault of the University of Missouri. “It also is a significant contributor to type 2 diabetes.”

To test the link between fitness and fatty liver disease, Dr Thyfault’s team selectively bred two groups of rats with very different levels of intrinsic aerobic capacity. After 17 generations of careful breeding, their ‘unfit’ rats could run an average of just 200m compared to over 1,500m achieved by the average ‘fit’ rat.

The effect on the rats’ livers was devastating. At 25 weeks old, the unfit group were displaying clear symptoms of NAFLD – weakened mitochondria, poor fat processing power, high fat retention and other abnormalities. By the end of their natural lives, the rats’ livers had sustained damage including fibrosis (the precursor to cirrhosis) and unexpected cell death.

In contrast, the ‘fit’ group enjoyed healthy livers throughout their lifespans – despite the fact that neither group was getting any real exercise.

The team’s findings provide the first biochemical links between low aerobic fitness and fatty liver disease, and have lead the authors to suggest that NAFLD could potentially be treated or prevented by a suitable exercise programme.

● Citation: John P. Thyfault, et al. Rats selectively bred for low aerobic capacity have reduced hepatic mitochondrial oxidative capacity and susceptibility to hepatic steatosis and injury. The Journal of Physiology, 15 April 2009. DOI: 10.1113/jphysiol.2009.169060

Source of health benefits in olive oil revealed

Scientists have pinned down the constituent of olive oil that gives greatest protection from heart attack and stroke. In a study of the major antioxidants in olive oil, Portuguese researchers showed that one, DHPEA-EDA, protects red blood cells from damage more than any other part of olive oil.

“These findings provide the scientific basis for the clear health benefits that have been seen in people who have olive oil in their diet,” says lead researcher Fatima Paiva- Martins, who works at the University of Porto.

Heart disease is caused partly by reactive oxygen, including free radicals, acting on LDL or “bad” cholesterol and resulting in hardening of the arteries. Red blood cells are particularly susceptible to oxidative damage because they are the body’s oxygen carriers.

In the study, published in Molecular Nutrition & Food Research, Paiva-Martins and colleagues compared the effects of four related polyphenolic compounds on red blood cells subjected to oxidative stress by a known free radical generating chemical.

DHPEA-EDA was the most effective and protected red blood cells even at low concentrations. The researchers say the study provides the first evidence that this compound is the major source of the health benefit associated with virgin olive oils, which contain increased levels of DHPEAEDA compared to other oils. In virgin olive oils, DHPEAEDA may make up as much as half the total antioxidant component of the oil.

Paiva-Martins says the findings could lead to the production of “functional” olive oils specifically designed to reduce the risk of heart disease. “Now we have identified the importance of these compounds, producers can start to care more about the polyphenolic composition of their oils,” she says.

● Citation: Paiva-Martins, et al. (2009), Effects of olive oil polyphenols on erythrocyte oxidative damage, Mol. Nutr. Food Res. 2009, Vol. 53, DOI: 10.1002/mnfr.200800276.

Scientists unlock secrets of superbug’s protective shell

The detailed structure of a protective ‘jacket’ that surrounds cells of the Clostridium difficile superbug, and which helps the dangerous pathogen stick to human host cells and tissues, is revealed in part in the 1 March issue of Molecular Microbiology.

Scientists hope that unravelling the secrets of this protective layer’s molecular structure might reveal possible targets for new drugs to treat C. difficile infections.

The ‘jacket’ is a surface layer, or ‘S-layer’, made of two different proteins, with half a million of each covering every C. difficile cell. The S-layer is believed to help C. difficile cells colonise the human gut, where they release sickness-causing toxins.

The new research was led by scientists from Imperial College London, funded by the European Union Seventh Framework Programme and the Medical Research Council. They used X-ray crystallography techniques to produce the first ever high-resolution images of the structure of LMW-SLP, one of the two proteins that make up C. difficile’s S-layer. The team also produced lower resolution images of the two S-layer proteins linked together into the ‘building block’, which makes up the layer over all.

Understanding exactly how the S-layer is formed, and how it works, could reveal new ways of fighting C. difficile infections, because without the S-layer, the pathogen cells cannot function, and die. The team behind the new study say that the long term aim is to use this structural knowledge to design a drug that will target the S-layer, leading to cell death, and the defeat of infection.

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