Marshaling the body’s own weapons against psoriasis

Immunotherapy with natural signaling substance relieves skin condition.A three-character code brings relief to patients with psoriasis and sheds light on complex immunoregulation processes: IL-4, an abbreviation for the endogenous signaling molecule Interleukin 4. The substance’s ability to inhibitinflammation is well known, but its mechanism of action was not fully understood. Scientists from the Technische Universität München (TUM) and the University of Tübingen have now shown in an animal model and in a study on patients exactly how IL-4 helps against psoriasis at the molecular level and the important role it plays in our immune system.Inflammation is a defense strategy of the body against invaders. Increased amounts of blood and fluid flow into the infected areas, and the release of signaling molecules summon immune cells to the site of infection to effectively neutralize the pathogens. However, poorly coordinated or misdirected immune reactions can trigger inflammation even in the absence of external agents, thus causing undue tissue damage. This is the case in psoriasis and other autoimmune diseases, such as multiple sclerosis and rheumatoid arthritis.

Read the rest of the article at http://www.medicalnewstoday.com/releases/290084.php.

Sunlight continues to damage skin in the dark

Much of the damage that ultraviolet radiation (UV) does to skin occurs hours after sun exposure, a team of Yale-led researchers concluded in a study that was published online by the journal Science.Exposure to UV light from the sun or from tanning beds can damage the DNA in melanocytes, the cells that make the melanin that gives skin its color. This damage is a major cause of skin cancer, the most common form of cancer in the United States. In the past, experts believed that melanin protected the skin by blocking harmful UV light. But there was also evidence from studies suggesting that melanin was associated with skin cell damage.In the current study, Douglas E. Brash, clinical professor of therapeutic radiology and dermatology at Yale School of Medical, and his co-authors first exposed mouse and human melanocyte cells to radiation from a UV lamp. The radiation caused a type of DNA damage known as a cyclobutane dimer (CPD), in which two DNA “letters” attach and bend the DNA, preventing the information it contains from being read correctly. To the researchers’ surprise, the melanocytes not only generated CPDs immediately but continued to do so hours after UV exposure ended. Cells without melanin generated CPDs only during the UV exposure.

Read the rest of the article at http://www.medicalnewstoday.com/releases/289728.php.

Text messages a new tool in the fight to prevent skin cancer, Australia

Australians’ love affair with mobile phones could save their life according to a joint QUT, Cancer Council Queensland and University of Queensland study using text messages to improve skin cancer prevention and promote sun protection.Funded by Cancer Australia, the 12-month trial targeted individuals aged between 18 and 42 – an age group in which mobile phone use is almost universal – and the results have just been published in international journal international journal Preventative Medicine.A Queensland-first, the Healthy Text trial tested the impact and value of SMS-delivered messages promoting sun protection along with skin self-examination for early detection of skin cancer, while a third group received texts encouraging physical activity.Weekly texts for the first 12 weeks were followed by monthly text messages for another nine months and a final in-depth telephone interview was conducted.Lead investigator Associate Professor Monika Janda from QUT’s Institute of Health and Biomedical Innovation said the study involved more than 500 participants and concluded that SMS-delivered intervention was effective, far-reaching, flexible and individualised.

Read the rest of the article at  http://www.medicalnewstoday.com/releases/289067.php.

Gene may open door for improved keloid, scar treatment

Researchers at Henry Ford Hospital in Detroit have identified a gene that may offer a better understanding of how keloid scars develop and potentially open the door to improved treatment for the often painful, itchy and tender scars.

The study is the first to demonstrate that an altered AHNAK gene may have a significant biological role in keloid development.

“This finding has great promise for better understanding how keloids function and offer a potential target for improved and novel treatments,” says study lead author Lamont R. Jones, M.D., Vice Chair, Department of Otolaryngology-Head and Neck Surgery at Henry Ford.

“We now have a better understanding of how this gene fits in the broader picture of the wound healing process, which may be important in preventing scars in general.”

Study results were presented at the 2015 Triological Combined Sections Meeting in San Diego.

Keloid scars form raised, firm skin areas and most often occur on the chest, shoulders, earlobes (following ear piercing), upper arms and cheeks. Unlike regular scars, keloids do not subside over time and often extend outside the wound site.

The lowest rates of keloid formation have been documented in albinos and the highest seen in dark skinned individuals, especially in the African-American population.

Treatment for keloids includes cortisone injections, pressure dressings, silicone gels, surgery, cryosurgery (freezing), laser treatment, or radiation therapy. A combination of treatments may be used, depending on the individual. In some cases, keloids return after treatment, up to 50 to 100 percent of the time.

AHNAK is a 700 kDa protein located on the cell membrane in epithelial cells and in the nucleus and cytoplasm of other cell types such as fibroblasts. AHNAK has been suspected to contribute to cell-cell adhesion or exocytosis.

For their study, Dr. Jones and his colleges investigated AHNAK as a potential biomarker in keloids through the integration of methylation and gene expression.

To do so, the Henry Ford team examined samples of fresh keloid tissue and fresh normal tissue for AHNAK expression.

Three of the five keloid samples showed a large reduction in expression as compared to the normal tissue.

In this small sample, gene expression was consistent with methylation, a process that allows the researchers to look for genetic abnormalities within tumor samples.

“Identifying AHNAK puts our translational research one step closer to moving from the bench to the bedside,” says Dr. Jones.

Adapted by MNT from original media release

http://www.medicalnewstoday.com/releases/288491.php

 

Sun risk for children of melanoma survivors

New study has found that children whose parents are melanoma survivors are not receiving the best possible protection from the sun and ultraviolet radiation.

 

This lack of protection can lead to sunburn, increasing the risk of melanoma for the children, who already face a substantially higher risk of developing the skin cancerdue to their family history.

Melanoma is the most serious form of skin cancer as well as one of the most common. In the US, in 2014, it was estimated that 76,100 new melanomas would be diagnosed with around 9,710 people dying from the disease. According to the American Cancer Society, melanoma rates have been rising for the past 30 years.

The authors of the study, published in Cancer Epidemiology, Biomarkers & Prevention, state that childhood is estimated to be one of the most critical exposure periods for conferring risk.

Individuals with a family history of melanoma can faced an increased risk of melanoma due to an inherited disposition to the disease, shared phenotypic characteristics (such as pale skin) and common high risk exposure patterns, explain the authors.

Experts recommend the following measures to prevent ultraviolet (UV) radiation exposure in children:

• Wearing protective clothing, such as hats and sunglasses
• Using sunscreen with a sun protection factor (SPF) greater than 30
• Limiting time spent in the sun, particularly during the peak sun hours of 10am to 4pm.

Sunburns were ‘common’, despite elevated risk

Researchers from the University of California, Los Angeles (UCLA), led by Dr. Beth Glenn, identified 300 melanoma survivors from the California Cancer Registry with children aged 17 and below. The participants were surveyed on their attitudes to melanoma prevention for 3 years.

The study specifically targeted Latino melanoma survivors and non-Latino white melanoma survivors due to melanoma rates being most prevalent among these groups. Previous studies have often left out Latino people from skin cancer prevention research due to a misconception that sun protection is not as important for this group.

Dr. Glenn and her team asked the study participants how at risk they felt their children from melanoma and what sun protection strategies they used for them. The majority relied on sunscreen as protection from sun exposure, with 79% of children “often or always” using sunscreen.

However, far fewer children “often or always” wore a hat (30%), stayed in the shade (23%) or wore sunglasses (8%).

In addition, the researchers found that 43% of parents reported their child being sunburned at some point over the past year.

“Sunburns were common among the children in our study despite their elevated risk for skin cancer. Also, children of Latino survivors were just as likely as children of non-Latino white survivors to have experienced a recent sunburn, which highlights the importance of including this group in our work,” says Dr. Glenn.

Over-reliance on sunscreen may be ‘problematic’

“Although sunscreen is an important tool in sun protection, over-reliance on this method may be problematic,” write the authors. “Prior studies have found sunscreen use to be positively correlated with UV exposure in adults, potentially due to a false sense of security.”

The study is limited by the use of self-reporting for sun exposure and a lack of in-person contact with participants. The authors suggest that future research might consider using more refined measures of sun protection knowledge to better identify targets for intervention.

The team will use their findings to apply for further funding with the aim of developing a new intervention program to help melanoma survivors monitor their children and protect them properly from UV radiation. The program will combine text message reminders with educational materials and activities.

“Protecting kids against the sun’s harmful rays at an early age is vitally important. Our goal is to develop an intervention that will help parents protect their children today and help children develop sun safe habits that will reduce their risk for skin cancer in the future,” Dr. Glenn concludes.

Recently, Medical News Today reported on a study suggesting that exposure to UV radiation from the sun could negatively affect fertility and lifespan.

Written by James McIntosh

http://www.medicalnewstoday.com/articles/287925.php

What is a dermatologist? What do dermatologists do?

Dermatologists are specially trained doctors who diagnose and treat conditions of the skin, hair, nails and mucous membranes, such as the eyelids and the lining of the mouth. They see patients at every stage of life, from newborn infants to the elderly.

According to the American Academy of Dermatology (AAD), they deal with more than 3,000 different diseases, ranging from acne toskin cancer. They can also give aid and assistance with more cosmetic issues, helping patients to revitalize the appearance of their skin, hair and nails.1

The Centers for Disease Control and Prevention (CDC), report that in 2010, there were an estimated 39 million visits to nonfederal employed, office-based dermatologists in the US.2 There are approximately 700,000 practicing physicians in the US; of this number, an estimated 8,050-8,500 (1.2%) are dermatologists.3

In a 2012 survey of 29,025 physicians representing 25 different medical specialties, dermatologists were found to be the second happiest with their lives outside of work, behind physicians practicing rheumatology. Dermatologists reported an average happiness rating of 4.05 on a scale of 1-5, with 1 meaning “very unhappy” and 5 meaning “very happy.”4

Contents of article:

• What is dermatology?
• Dermatologist qualifications
• Common conditions treated
• Common procedures performed
• When to see a dermatologist

What is dermatology?5

Dermatology is an area of medicine concerned with the skin, keeping it healthy and treating the diseases that afflict it. This also incorporates the diagnosis, maintenance and treatment of diseases of the hair, nails and mucous membranes.

The skin is the largest organ of the body, covering a total area or around 20 square feet.6 It is the first line of defense against bacteria and injury, and often reflects the overall health of the body. A study conducted by the Mayo Clinic, published in 2013, reported that 42.7% of patients visited their doctors at some point due to a skin disorder.7

Disorders of the skin, hair, nails and mucous membranes are managed through investigations and therapies that include histopathology, immunotherapy, laser therapy, medication, phototherapy, radiotherapy and surgery (including cosmetic procedures).

Dermatologist qualifications1,8

To become a dermatologist in the US, candidates have to complete at least four separate steps. First and foremost, they must earn a college degree and go on to graduate from medical school, either becoming a medical doctor (MD) or doctor of osteopathic medicine (DO).

Following this, the doctor must complete an internship – the first year of medical training which can take place in hospitals and clinics. Dermatologists-to-be will commonly intern in an associated field, such as general surgery, internal medicine, family medicine, emergency medicine or pediatrics.

The doctor can enter into a dermatology residency program once they have completed their internship. They are then known as a dermatology resident and receive training in surgical procedures, diagnosis and treatment for the vast array of conditions that they will go on to face, all while seeing patients. Residency programs run for at least 3 years.

Once this is completed, dermatology board exams can be taken. These exams are now required to be taken every 10 years, reflecting the advances that are made within the specialty over time.

If a dermatologist wishes to specialize in a particular subspecialty of dermatology, such as cosmetic dermatology or Mohs surgery (a form of skin cancer treatment), they can continue their studies and take a fellowship, commencing extensive medical study into one particular area.

Some dermatologists may have the initials FAAD listed after their name. This stands for “Fellow of the American Academy of Dermatology.” The initials indicate the following:

• They are licensed to practice medicine
• They have passed exams given by either the American Board of Dermatology or the Royal College of Physicians and Surgeons of Canada
• They are a member of the AAD.

Common conditions treated5

Dermatologists need to have a vast wealth of clinical knowledge at their disposal, including knowledge of the basic sciences and all other medical specialties; many skin diseases are associated with internal conditions which they need to be aware of.

Even without being presented with conditions that could be categorized within other specialties, dermatologists have a great deal to contend with that specifically belongs to their field. Here are some examples of the more common conditions dermatologists treat:

Vitiligo is a condition in which the skin loses melanin, leading to the development of patches of lighter colored skin.

• Acne: a disease affecting the skin’s oil glands, acne is the most common skin condition in the US. It causes the formation of many different kinds ofpimples which can lead to depression, low self-esteem, and scarring. 9,10
• Dermatitis and eczema: inflammation of the skin, typically involving swelling with an itchy rash. Dermatitis comes in many different forms, including the atopic dermatitis – often referred to as eczema – contact dermatitis and seborrheic dermatitis.11,12
• Fungal infections: affecting the skin, nails, and hair, these infections are common and normally mild in effect. However, in people with weakened immune systems they can be more serious. A group of yeasts called candida can cause a wide range of infections, including oral thrush and balanitis.13,14
• Hair disorders: both males and females can experience hair loss. This can be due to an underlying condition or a stand alone one, such as hereditary hair loss – affecting 80 million men and women in the US – or a form of alopecia. The hair can also be affected by head lice – around 6-12 million children aged 3-12 years get head lice in the US every year.15-17
• Nail problems: nails often reflect the body’s overall health and conditions affecting them make up around 10% of all dermatological conditions. Approximately half of these are fungal infections, while ingrown nails are also common. Nail problems can be indicative of other underlying conditions.18,19
• Psoriasis: a chronic, autoimmune skin disorder that speeds up the growth of skin cells, resulting in thick red skin and silvery scales. There are several different types of psoriasis and sometimes it can be similar in appearance to eczema. As a result, it is important that a dermatologist makes the diagnosis.20,21
• Rosacea: a skin condition that causes redness in the face, akin to blushing or flushing. It often causes small, pus-filled bumps to appear, and can also lead to visible blood vessels and swollen eyelids. Rosacea can spread from the nose and cheeks to the forehead, chin, ears, chest and back, and is most often experienced by fair-skinned middle-aged women.22,23
• Skin cancer: each year, almost 5 million people receive treatment for skin cancer in the US. One in five Americans will develop a form of this disease at some point in their lifetime. The most common forms of skin cancer are basal cell carcinoma (BCC), melanoma, and squamous cell carcinoma (SCC). Most skin cancers can be treated if they are treated early.24,25
• Shingles (herpes zoster): a viral infection causing a painful rash. Although the condition clears without treatment after a few weeks, treatment is recommended to speed up recovery and to prevent long-lasting pain, numbness and itching after the disease has gone. Shingles can also potentially damage the eyes. 26,27
• Vitiligo: a condition whereby the skin loses melanin – the pigment that determines eye, hair and skin color. Vitiligotypically leads to the development of patches of lighter skin. Although there is no cure for the condition, treatments are available for the symptoms, such as mini skin grafts. The condition can have a strong social and psychological impact on patients that develop it.28,29
• Warts: contagious benign skin growths that appear when a virus infects the top layer of skin. Warts frequently go away without treatment, though dermatologists are also able to remove any that persist with a variety of different techniques to suit all patients.

Common procedures performed

Although many of the conditions seen by dermatologists can be treated with medication and therapy, there are still a wide range of procedures that these physicians can perform. Below is a list that includes some of the most common procedures that urologists perform, either in an outpatient or inpatient settings:

In dermabrasion, dermatologists use a high-speed rotating brush to surgically remove the very top layer of skin.

• Biopsies: skin biopsies are primarily carried out to diagnose or rule out certain skin conditions. There are three main types of skin biopsy that are commonly performed: shave biopsies remove small sections of the top layer of skin, punch biopsies remove small circular section including deeper layers, and excision biopsies remove entire areas of abnormal-looking skin.33,34
• Chemical peels: a chemical solution is applied to the skin. It causes a layer of skin to separate and peel off over the course of up to two weeks, leaving a layer of regenerated skin underneath that is typically smoother. Dermatologists can use this procedure to treat sun-damaged skin and some types of acne, as well as more cosmetic complaints, such as age spots and lines under the eyes.35,36
• Cosmetic injections: wrinkles, scarring and lost facial fullness can be temporarily treated with injections to diminish the signs of aging. Botulinum toxin therapy or fillers such as collagen and fat can be injected by dermatologists during office visits. Results of this treatment tend to last for a few months, and so injections need to be repeated periodically.37,38
• Cryotherapy: a quick and common form of treatment for many benign skin conditions such as warts. Skin lesions are frozen, often using liquid nitrogen, in order to destroy affected skin cells. Dermatologists can perform cryotherapy in their offices.39
• Dermabrasion: another procedure to change the appearance of the skin. Using a high-speed rotating brush, a dermatologist removes the top layer of skin, surgically sloughing scars, fine wrinkles, tattoos and potentially precancerous skin patches.40,41
• Excisions of lesions: skin lesions can be excised for several reasons; to prevent disease from spreading, for cosmetic reasons, to prevent repeat infection, to alleviate symptoms and for diagnosis. Depending on the size of the lesion, local or general anesthetic can be used to numb the area.42
• Hair removal and restoration: Hair loss can be treated with hair transplantation or surgery to the scalp. Unwanted body hair can be removed with laser hair epilation or electrolysis to destroy hair follicles. 43,44
• Laser surgery: dermatologists can use special light beams to remove a variety of skin complaints. These include and are not limited to tumors, warts, moles, tattoos, birthmarks, scars, wrinkles and unwanted hair.45
• Mohs surgery: a specific type of surgery for the treatment of skin cancer. Layers of skin are removed and examined under microscope in order to get rid of cancerous cells. Successive layers are removed until the surgeon is unable to find any cancer cells. Mohs surgery is only performed by Mohs surgeons – dermatologists who have completed specific additional medical training.46
• PUVA: an abbreviation of psoralen combined with ultraviolet A (UVA) treatment. Psoralen is a drug that is administered to make the skin more receptive to radiation treatment. PUVA is used to treat severe skin diseases such as psoriasis, dermatitis, and vitiligo.3,47
• Skin grafts and flaps: dermatologists can repair parts of the body where skin is missing, possibly due to other surgery or an injury, using skin from elsewhere on the body. Skin can either be grafted, using a free piece of tissue without its own blood supply, or a skin flap can be created from skin tissue adjacent to the area of skin loss.48
• Tumescent liposuction: Liposuction is the removal of excess fat from the body. Dermatologists typically use a process called tumescent liposuction to do this, whereby large volumes of local anesthetic are injected into the fatty tissue being removed. The tissue is then sucked out of the body. Tumescent liposuction should not be considered a treatment for obesity, rather a procedure for body contouring. The process can be aided further with the use of lasers to selectively melt fat and help remove tumescent fluid.49,50
• Vein therapy: superficial leg veins – also known as spider veins – are small, dilated surface veins that may look unsightly. Sclerotherapy is a minimally invasive procedure that is usually the preferred treatment for spider veins. Dermatologists insert either foam or a solution into the vein which irritates the lining and causes it to shut. The vein becomes less distinct or disappears completely.51,52

When to see a dermatologist1

Dermatologists should be consulted when the symptoms of a disease affecting the skin, hair, nails or mucous membranes appear. They can also be consulted if a patient has any concerns about the appearance of their skin, hair and nails – in this instance, a cosmetic dermatologist may be ideal.

Specific types of dermatologist should be sought for particular conditions. Cosmetic dermatologists specialize in treatment to improve appearances; dermatopathologists specialize in diagnosing disease of the skin, hair, and nails by examining samples under a microscope; and Mohs surgeons specialize in treating skin cancer with Mohs surgery.

Written by James McIntosh

http://www.medicalnewstoday.com/articles/286743.php

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UV tanning dependence: some people may be genetically susceptible

Researchers have found a possible underlying genetic susceptibility to being dependent on UV tanning.

After interviewing young people about their indoor and outdoor tanning history and using questionnaires to classify people as being dependent on UV tanning or not, the investigators conducted a large scale scan of approximately 319,000 rare and common genetic variants in the participants’ genomes.

“We observed that inherited variation in one gene – known as patched domain containing 2 (PTCHD2) – was significantly associated with whether or not young people, all of whom had previously sunbathed or indoor tanned, exhibited symptoms of tanning dependence,” said Dr. Brenda Cartmel, lead author of the Experimental Dermatology study.

Cartmel, B., Dewan, A., Ferrucci, L. M., Gelernter, J., Stapleton, J., Leffell, D. J., Mayne, S. T. and Bale, A. E. (2014), Novel gene identified in an exome-wide association study of tanning dependence. Experimental Dermatology, 23: 757?”759. doi: 10.1111/exd.12503

http://www.medicalnewstoday.com/releases/286367.php

 

 

Few adverse events found in noninvasive, minimally invasive cosmetic procedures

A tiny fraction of adverse events occurred after dermatologists performed more than 20,000 noninvasive and minimally invasive cosmetic procedures, according to a study published online by JAMA Dermatology.

Cosmetic dermatology is a well-developed field and data suggest the procedures are associated with a low rate of adverse events, according to background information in the study.

Researcher Murad Alam, M.D., M.S.C.I., of the Feinberg School of Medicine at Northwestern University, Chicago, and co-authors characterized the incidence of adverse events associated with a subset of common cosmetic dermatologic procedures that utilized laser and energy devices, as well as injectable neurotoxins and fillers.

Data was collected for 13 weeks at eight centers for cosmetic dermatology between March and December 2011 from 23 dermatologists. A total of 20,399 procedures were studied and 48 adverse events were reported, for an adverse event rate of 0.24 percent, according to study results. Overall, 36 procedures resulted in at least one adverse event for a rate of 0.18 percent. Adverse events most commonly happened after procedures on the cheeks, followed by nasolabial (the so-called smile lines) and eyelid procedures. Adverse events were most commonly lumps or nodules, persistent redness or bruising, skin darkening, or erosions or ulcerations. No serious adverse events were reported.

“In the hands of well-trained dermatologists, these procedures are safe, with aggregate adverse event rates of well under 1 percent. Moreover, most adverse events are minor and rapidly remitting, and serious adverse events were not seen. Patients seeking such procedures can be reassured that, at least in the hands of trained board-certified dermatologists, they pose minimal risk,” the study concludes.

http://www.medicalnewstoday.com/releases/284887.php

 

 

New patent for method to establish whether a person will suffer from burns when he or she is submitted to laser hair removal treatments

Researchers at the U. of Granada have developed an innovative technique which facilitates the preventive identification of potential damage in the skin of a patient before he or she is submitted to a dermatological treatment by pulsed light, such as IPL (Intense Pulsed Light). These systems are frequently used in dermatological treatments such as photoepilation, skin rejuvenation, the elimination of acne or vascular injuries.

In spite of the fact that the manufacturing and maintenance of IPL equipment have grown dramatically due to its frequent use in dermatological clinics, there is not an exhaustive and reliable method that can determine the susceptibility of a patient for skin burns due to an excess in the absorption of radiation during the treatment.

So far, only the skill of the operator of this equipment was used to adapt the power and the type of pulse to a given patient’s skin type. The operator must also rely on the information provided by the patient as regards, for instance, whether he or she has been sunbathing recently or not. The application of laser pulsed light on suntanned skin can provoke serious burns which do not become visible at the moment of the treatment, but manifest themselves serveral days afterwards. This has resulted in frequent legal disputes between patients and the dermatological centres that applied the treatment.

An OTRI (Knowledge Transfer Office, U. of Granada) patent

The new method, designed at the U. of Granada, has been patented through its Knowledge Transfer Office. It can determine the sensitivity of the skin to radiation immediately before the dermatological treatment. By means of the application of pulsed light in different skin areas, the system analyses the temporal evolution of the thermic response of the patient’s skin, and provides information on the potential risk that the subject might suffer burns during and after the treatment.

According to PI of the team that has patented this new device, prof. Andrés Roldán Aranda from the Electronics and Computing Technologies Department, “this method works through an electronic device that can be incorporated to pre-existing pulsed light equipment, and of course it can also be integrated within new devices.”

Researchers have also developed a new electronic device capable of monitoring a patient’s skin temperature as he or she receives the effects of pulsed light radiation generated by IPL equipment.

“A device like this one provides a competitive advantage for dermatological clinics, in particular as regards photoepilation, since it can avoid the most potentially risky cases of skin burns, and thus avoid the legal disputes originated by injuries of this type”, profesor Roldán emphasised.

This research team at the U. of Granada is currently looking for business partners in the field who might be interested in reaching a licencing agreement and in establishing joint projects for the further development of this new invention.

The research team responsible for this new device includes Andrés Roldán Aranda, Francisco Javier Arrebola Vargas, Pedro Ortuño Cañizares and Juan Bautista Roldán Aranda.

Adapted by MNT from original media release

http://www.medicalnewstoday.com/releases/285132.php

 

Scientists unravel the mystery of rare sweating disorder anhidrosis

An international research team discovered that mutation of a single gene blocks sweat production, a dangerous condition due to an increased risk of hyperthermia, also known as heatstroke. The gene, ITPR2, controls a basic cellular process in sweat glands, promoting the release of calcium necessary for normal sweat production, and its loss results in impaired sweat secretion.

The study, published on October 20, in the Journal of Clinical Investigation, was led by Katsuhiko Mikoshiba, a molecular cell biologist from the RIKEN Brain Science Institute in Japan and Niklas Dahl, a genetics expert at Uppsala University in Sweden.

Dr. Dahl’s group studies rare single-gene diseases, also known as Mendelian disorders, with the goal of identifying causative genes to develop diagnostic or treatment tools. Working with collaborators in Pakistan, they identified a family with several children who could not sweat, a rare condition called anhidrosis.

Sweating serves to regulate body temperature and keeps animals from overheating. Although excessive sweating is an embarrassing problem, an inability to sweat is potentially lethal, as it impairs the body’s ability to regulate temperature and increases susceptibility to heatstroke.

Anhidrosis can have several causes, including genetic, in which case the sweat glands are either deformed or missing. In contrast, the sweat glands of the individuals examined in this study appeared visually normal and no other physical problems were reported.

Analysis of the patients’ genomes revealed a mutation in a gene called ITPR2, which encodes IP3 receptor type 2 (IP3R2), a protein that forms a channel in the membrane of the endoplasmic reticulum, an organelle within cells that stores an ion called calcium. Opening of the IP3R channel releases calcium, triggering essential cell behaviors such as movement, shape changes, or secretion.

In order to understand how the mutation caused a lack of sweat production, Dr. Dahl sought collaboration with Dr. Mikoshiba, who discovered the IP3 receptor. “This is the first report of IP3 receptor type 2 mutation in human disease,” said Dr. Mikoshiba. “The surprise was that a point mutation, not a large deletion was enough to cause the human disorder.”

Dr. Mikoshiba’s group examined the function of the mutated IP3R2 protein in cultured cells and found that a single nucleotide change in the DNA code resulted in a change in protein structure impeding the ability of the channel to release calcium. The team then examined sweat production in mice with a genetic loss of the IP3R2 protein and found that they had reduced sweating.

Calcium release is a potent signal within cells and some animals have several IP3 receptor types to compensate for each other if one is not functioning properly. The researchers found that human sweat glands mainly have IP3R2. However, in mouse, sweat glands also have R1 that may partially make up for the lack of R2, explaining why the mutant mice were still able to produce some sweat.

“Although anhidrosis is quite a rare condition, the ‘opposite’ phenotype, excess sweating or hyperhidrosis, is a common problem affecting 2% of the population” said Dr. Dahl. “Such symptoms may be alleviated by a drug that inhibits IP3R2. However,” he cautions, “IP3R2 is expressed in many tissues, and compounds must first be carefully evaluated in experimental models.” Efforts to develop drugs to regulate the IP3R are currently underway.

http://www.medicalnewstoday.com/releases/284224.php