A recent discovery has provided an insight into the mechanical factors that play a critical role in the differentiation and function of fibroblasts, which will aid in our understanding of wound healing and scar tissue formation.
When the skin is wounded fibroblasts emerge from beneath the surface of the skin and infiltrate the soft, provisional wound matrix to begin secreting collagen, which rapidly cover and close the wound.
Researchers from the Ecole Polytechnique Fédérale de Lausanne (EPFL), Switzerland, have revealed how the fibroblasts transform into contractile cells. It was previously suggested that the fibroblasts digested the matrix in order for this process to occur.
EPFL scientist Boris Hinz and his colleagues have discovered that the fibroblasts release their growth factor by a mechanical process rather than digestion. They found that when the wound matrix achieves a certain rigidity the growth factors emerge or ‘pop out’ of the matrix of their own accord owing to cell-exerted force.
The availability of the growth factor converts the fibroblasts who adhere to the matrix, contract and liberate more growth factor in the process. More fibroblasts then express the contractile process and contraction is increased. As the entire process can only begin when the matrix has reached a certain rigidity, this acts as a signal that ensures that contraction occurs only at the point when the rigidity is sufficient to maintain the integrity of the wound surface while contraction takes place.
Problems in this process can occur if there is a buildup of fibrous tissue. This can be potentially fatal following trauma to organs such as the heart and lungs. If fibroblasts overproduce fibrous strands, fibrosis can ensue, where a scar tissue buildup impairs the organ’s function. It can also cause a problem following plastic surgery in the form of excessive scar tissue. Furthermore, fibrosis can also be a problem in mesenchymal stem cell cultures when the culture’s substrate is stiff. The stem cells often turn into fibroblasts instead of the intended cell type owing to the rigidity of the substrate. It is therefore essential that cell culture’s rigidity is controlled.
It is hoped that fibrosis can now be prevented, with this new understanding of the mechanism, without growth factor inhibition, which is essential for other bodily functions. Hinz suggests the possible ways that you could manipulate this process, “you could interfere with the way the cells grab onto the growth factor complex, you could interfere with their attachment points on the matrix and you could interfere with their contractile forces so that the matrix never gets stiff enough to liberate the growth factor”.
Source: Wipff PJ, Rifkin DB, Meister JJ, Hinz B. Myofibroblast contraction activates latent TGF-1 from the extracellular matrix. J. Cell. Biol. 179(6), 1311–1323 (2007).
Steroids found in body lotion in UK
An intensive body lotion sold in the UK, which claims to contain natural ingredients, has been found to contain steroids. The Medicines and Healthcare products Regulatory agency made the discovery in the unlicensed product named ‘OSAS’, which claimed to treat eczema and psoriasis.
The product has been on sale in Asian and African beauty shops throughout London and the West Midlands, UK, and has also been available over the internet. The lotion was tested after a pediatric dermatologist observed the effects of the lotion on a baby he was treating for eczema. He then alerted the MRHA to the product who tested it and revealed that it contained betamethasone dipropionate and clotrimazole.
Betamethasone should only be available on prescription as careful supervision of this treatment is necessary. Complications, such as skin thinning, can be caused by long-term use of the product, which may occur when there has been insufficient application advice before administering the product.
The Medicines and Healthcare products Regulatory agency have since advised that anyone who is currently using the product to stop, especially if it is being used on children or babies, and to seek medical advice on cessation of treatment in case a rebound effect is observed.
The Medicines and Healthcare products Regulatory agency are also advising that anyone who is selling this product should stop immediately and remove the product from their stock. They have warned that action will be taken against retailers found selling the product.
Source: www.mhra.gov.uk
University hospital researchers enroll on gene therapy trial for late-stage skin cancer
A gene therapy trial to assess the effectiveness of the therapy Allovectin-7® for advanced skin cancer has recently been joined by researchers at the Ireland Cancer Center of University Hospitals Case Medical Center (OH, USA). They are the first in the region to join the nationwide clinical trial.
Allovectin-7 works by initiating the patient’s immune system into fighting the cancer. The treatment is injected directly into the cancer in the hope that it will appear foreign to the immune system, which should then begin to attack it. Previously, gene therapy has been demonstrated to launch the immune system into attacking cancer at other sites of the body following a single injection at an initial cancer site.
Julian Kim, Chief of Surgical Oncology and lead investigator of the study, explains that the main hurdle with treating advanced melanoma is to train the body into recognizing the cancer as foreign, which will help to eliminate them.
Kim explains, “The concept of injecting a gene into a cancer to make it appear as a foreign tissue essentially creates a personalized vaccine for each individual patient’s cancer. The hope is that the newly formed cancer vaccine will trigger several of the body’s natural immune response mechanisms to recognize and attack the cancer, both within the injected cancer and throughout the body”.
The study of this gene therapy focuses on those with advanced melanoma. Nationwide, 40 melanoma centers are participating in the Allovectin-7 trial, which is now joined by University Hospitals Case Medical Center – the only regional center participating in the gene therapy trial.
“The Ireland Cancer Center aims to bring the newest therapies to our patients and this new study is a prime example of bringing the latest research into our clinical practice”, explains Stanton Gerson, Director of the Ireland Cancer Center. He goes on to add that he is delighted to be able to offer this innovative gene therapy trial to patients in the Northeast Ohio region.
Sources: www.melanomatrial.com; www.irelandcancercenter.org
License for adalimumab to treat chronic plaque psoriasis in the UK
Drug: Adalimumab
Tradename: HUMIRA®
Manufacturer: Abbott Laboratories
Indication: Moderate-to-severe chronic plaque psoriasis
A license has been granted to Abbott laboratories for HUMIRA® (adalimumab) to treat moderate-to-severe chronic plaque psoriasis in the UK. Chronic plaque psoriasis results in silvery plaques on the skin and raised red lesions. It affects approximately 2% of the population in the UK.
Adalimumab is a fully human anti- TNF monoclonal antibody and works by binding to TNF, blocking its interaction with cell surface TNF receptors, hence neutralizing it.
Christopher Griffiths (The University of Manchester, UK) explains that “Psoriasis is a disease that causes great distress physically and emotionally to patients”. He adds, “anti-TNF treatments are a promising development for those with moderate-to-severe disease and the availability of a new treatment option is a big step forward. The licensing of adalimumab is a welcome announcement and provides an additional tool for physicians to treat those who are seriously affected by the disease”.
Adalimumab comes in the form of a subcutaneous injection in a prefilled pen. Patients, following suitable training, can administer the drugs themselves at home.
The efficacy and safety of the drug in moderate-to-severe psoriasis patient have been demonstrated in clinical trials by Abbott. They conducted two Phase III randomized, controlled, multicenter trials. The first, REVEAL3, looked at 1212 patients over the course of 52 weeks. In this time they were administered either adalimumab or a placebo drug every 2 weeks for 15 weeks. The second trial, CHAMPION, compared methotrexate with a biologic medication.
“The licensing of adalimumab offers a valuable new treatment option for people living with moderate-to-severe psoriasis, a very difficult and often isolating condition”, explains Gladys Edwards from the Psoriasis Association, UK”. We welcome the approval of new therapies, such as adalimumab, that can significantly improve the quality of life of patients and expand the options available to those who are most in need of treatment”.
Source: http://www.abbott.com/
Honey probably does not benefit venous leg ulcer treatment
Honey has been found to be of no benefit and, in fact, a significant increase in adverse events was observed following the treatment of leg ulcers with dressings soaked in honey, as reported in the British Journal of Surgery.
Leg ulcers form when there is a breakdown in skin tissue below the knee. Treatment involves application of compression bandages, which help the leg to cope with the hydrostatic pressure. Due to current interest in alternative and natural remedies, honey has been suggested to aid in wound healing when added to compression bandages.
A trial was conducted in four centers in New Zealand and consisted of 368 patients. These patients were randomly assigned to two groups. Patients in one group received conventional compression bandages, while the other was treated with bandages soaked in honey. No significant difference in the rate of healing was observed after 12 weeks between the two groups. The only difference between the two groups was that the treatment of the patients who received the honey bandages was more expensive and those patients reported more adverse side effects compared to those treated with normal bandages (111 vs 84; p = 0.013).
“In our trial the honey dressing did not significantly improve healing, time to healing, change in ulcer area, incidence of infection or quality of life”, Andrew Jull (Clinical Trials Research Unit at the University of Auckland, New Zealand) advises.
He concludes, “the current focus of venous ulcer management should remain on compression and other treatments that have demonstrated that they improve compression’s ability to work or prevent ulcer recurrence”.
Source: Jull A, Walker N, Parag V, Molan P, Rodgers A; on behalf of the Honey as Adjuvant Leg Ulcer Therapy trial collaborators. Randomized clinical trial of honey-impregnated dressings for venous leg ulcers. Br. J. Surg. 95(2), 175–182 (2007).
Breakthrough into the cause of itchy skin
New genetic mutations have been discovered that could be the cause of itching and, in particular, familial primary localized cutaneous amyloidosis (PCLA). The breakthrough was made by ‘Action Medical Research’, a UK charity, and was published in the American Journal of Human Genetics.
To date there has been little understanding regarding itch mediators, receptors and pathways in the skin, despite the itch being a common occurrence in most people. This has resulted in limited availability of treatments. This recent development is the first time that a gene abnormality has been discovered that is directly linked with itchy skin.
PCLA is an itch disorder commonly observed by dermatologists. The research team, based at King’s College London, UK, investigated the inherited form of PCLA, known as familial PCLA. They found that mutations in the oncostatin M receptor-β gene (OSMR) are the cause of this disorder.
In response to cytokines, skin cells with a mutant copy of the OSMR gene failed to activate certain anti-inflammatory genes that are activated in normal skin cells, with no defective gene. This resulted in itchy skin.
John McGrath, lead researcher of the study, believes that this is a very exciting discovery. He explains, “We have shown that inherited abnormalities in a particular part of a cell signaling receptor directly lead to a specific form of itchy skin”. McGarth believes that this work provides a new insight into what can cause itchy skin.
The team now intend to look into other itchy skin disorders, such as lichen simplex or lichen planus, and find if abnormalities of this signaling pathway exist in these similar diseases. They will also then examine how a potential treatment might be developed that could control the symptoms of itching using their findings.
Source: Arita K, South AP, Hans-Filho G et al. Oncostatin M receptor-β mutations underlie familial primary localized cutaneous amyloidosis. Am. J. Hum. Genet. 82(1), 73–80 (2008).