Breakthrough vitiligo treatment offers longer-lasting results

Longer-lasting treatment for vitiligo could be available within the next few years.

According to John Harris, M.D., Ph.D., director of the Vitiligo Clinic and Research Center at the University of Massachusetts Medical School, a new treatment targets and removes the cells responsible for developing the condition.

He discussed this research at the American Academy of Dermatology Annual Meeting in Washington, D.C.

“Compared to treating psoriasis, we’re in the Dark Ages when it comes to treating vitiligo,” he said. “We hope to be able to give vitiligo patients the treatment they deserve.”

CURRENT TREATMENT

JAK inhibitors, such as tofacitinib, are among the standard vitiligo treatments, targeting the cytokine interferon gamma. The treatment is available both orally or topically, and it blocks interferon gamma signaling. The problem, Harris said, is that the effect is temporary.

“JAK inhibitors and other more conventional treatments work, but when you stop them, the disease comes right back,” he said. “And, it doesn’t just relapse. It returns in the exact same places as before.”

WHAT’S HAPPENING

Harris and other researchers have determined autoimmune memory cells, specifically resident memory T cells, are responsible for vitiligo relapses. These cells attack viral infections on the skin, and several cells linger to ward off future outbreaks. Current treatments turn these cells off, but they re-activate when medication use stops.

“These cells wake back up, and they’re right there waiting,” he said. “And, the white spots return.”

NEW THERAPY

To offer longer-lasting therapy, the new treatment-in-testing targets the cytokine interleukin (IL)-15. It’s an antibody blockade that blocks IL-15 signaling. Results of a mouse study reveal that not only did the antibody turn off the signaling, but it also removed the resident memory T cells from the skin, eliminating the possibility of future relapse.

“This is a drug that you’re, hopefully, going to see in the clinic within the next 5 years. It’s different from psoriasis and TNF inhibitors that were discovered to work by accident. We’re actually going to be able to tell you exactly how it’s working,” he said. “We’re hoping the IL-15 biologic will provide long-lasting results typically not seen in dermatology.”

Ultimately, Harris said, this drug could fundamentally alter how dermatologists treat vitiligo patients. It could give them a tool designed to combat this specific condition.

“The future is bright for vitiligo,” he said. “I like comparing it to other disease like atopic dermatitis and psoriasis because both of those diseases have targeted therapies that really have changed what it means to manage difficult patients. Vitiligo is next in line.”

Reference:
S011 - Inflammatory Skin Diseases: The Translational Revolution. “New Developments in Vitiligo.” John Harris, M.D. 2:15 PM, March 1, American Academy of Dermatology annual meeting.

JAK inhibitors offer hope for vitiligo patients

With several Janus kinase (JAK) inhibitors undergoing clinical trials for vitiligo, their potential approvals will deliver new hope and an entirely new treatment strategy, said an expert at the American Academy of Dermatology annual meeting in Washington, D.C.

"JAK inhibitors are exciting. They're probably going to be the first FDA-approved treatment for vitiligo. We don't have any FDA-approved drugs right now that reverse disease," said John Harris, M.D., Ph.D. He is an associate professor of dermatology at the University of Massachusetts Medical School.

Although JAK inhibitors likely will be the first generation of FDA-approved drugs for vitiligo, he added, researchers are hoping that over time, they will be able to refine this approach to produce even more targeted treatments that are safe and beneficial.

Over the past 10 to 15 years, said Dr. Harris, vitiligo has undergone a surge in research that has outlined the central pathways that drive the disease. "One of those pathways is the interferon gamma (IFN-ƴ) signaling pathway. It seems to be very important for the progression of vitiligo." IFN-ƴ signals through the IFN-ƴ receptor and JAK1 and JAK2, then through STAT1. The discovery that IFN-ƴ drives vitiligo in part came from a mouse model developed by Dr. Harris and colleagues. "We found that the spots appearing in the skin of mice and in people expressed the same IFN-ƴ gene signature."2

More specifically, he said, the researchers used IFN-ƴ knockout mice and IFN-ƴ receptor knockout mice. "And we were able to target IFN-ƴ with an antibody. All these approaches have shown us that the mouse disease is prevented and reversed by blocking the pathway. This finding laid out the rationale for testing drugs that target IFN-ƴ signaling."

Dr. Harris and others hypothesized that blocking JAK1/2 signaling with JAK inhibitors could be an effective treatment for vitiligo. The first case report, published by Brett King, M.D., Ph.D., of Yale University School of Medicine, featured a patient treated with the JAK1/3 inhibitor tofacitinib.3Subsequently, Dr. Harris and colleagues published a case report of a patient treated with the JAK1/2 inhibitor ruxolitinib.4

Additional research with the mouse model showed that when IFN-ƴ is produced in the skin, it activates the chemokines CXCL9 and CXCL10 within the epidermis. These proteins use a positive feedback loop (through the signaling of the CXCL10 receptor, CXCR3) to recruit T cells to the skin. "Essentially, T cells go to the skin, and make IFN-ƴ when they see their target melanocytes. The keratinocytes sense IFN-ƴ and make CXCL9 and CXCL10, and that recruits more T cells. We believe that's what's being inhibited by the JAK inhibitors."

He likens the positive feedback loop to the way ants would find a drop of melted ice cream on a sidewalk. "An ant eventually will stumble across one of those drops and very quickly will lay a trail back to the nest. Soon you'll have 1,000 ants on that spot, devouring it. That's what's happening here — the first T cell is the scout ant, but then it lays a trail for all the other ones to follow. That's where disease occurs." Blocking IFN-ƴ signaling and CXCL10 production inhibits the entire cycle, preventing or possibly even reversing disease, he said.

Because Dr. Harris and colleagues were able to show the key role played by keratinocytes in responding to IFN-ƴ, they hypothesized that topical JAK inhibitors could also be effective because topical agents can target keratinocytes. An 11-patient study showed that topical ruxolitinib was effective for vitiligo.5

Taken together, said Dr. Harris, the above findings all provide rationale for three ongoing clinical trials of JAK inhibitors in vitiligo. Aclaris and Incyte Pharmaceuticals are testing topical ATI-502 and INCB018424, respectively, in phase 2. Pfizer is testing two oral JAK inhibitors, he said. "The Incyte study is the furthest along. It's a two-year study with a six-month primary endpoint. There should be interim data soon." The entire study is scheduled for completion in July 2020.

Other researchers led by Dr. King have also observed that patients whose vitiligo improved with tofacitinib did so on areas of exposed skin.6 "So he hypothesized that this was due to exposure to light. Whether it's sunlight or visible light, it's hard to know. But exposed skin seems to do better with JAK inhibitors, suggesting that light was also beneficial in promoting the reversal of disease."

As part of the same analysis, Drs. Harris and King sampled the skin of a tofacitinib-treated patient. "We found that treatment with a JAK inhibitor actually removed the autoimmune cells from all of her skin, including the (light-exposed) skin that got better and the skin that did not. That suggested to us that the JAK inhibitor is sufficient to remove autoimmunity, the autoimmune cells driving the disease. The possible reason why light is helpful is because it stimulates the melanocytes to regrow."

Resources: https://www.dermatologytimes.com/aad-psoriasis/jak-inhibitors-offer-hope-vitiligo-patients

HSP70i Heat Protein Vitiligo Treatment

‘Temprian’ is an old English word that means ‘to restrain within due limits, to moderate’. At Temprian Therapeutics, we are passionate about finding an efficient treatment for Vitiligo. The company focuses on getting the mutant HSP70i-based drug subject to clinical trials. We will do this by partnering with patients, clinicians, investors, and the pharmaceutical industry. Here is how we look at the challenge: What is Vitiligo? Vitiligo is typically induced by a variety of stress factors ranging from exposure to harmful chemicals, intense sunlight, scrapes and bruises or emotionally draining conditions. The stress results in an immune response, where the body’s own T cells erroneously attack pigment cells (also called ‘melanocytes’) in the skin. Melanocytes are in charge of producing melanin, the pigment that gives the skin its color. Vitiligo tends to be progressive and evolves in stress induced bursts. The rate of pigment loss varies widely between individuals and may in due time result in complete depigmentation.

Why does vitiligo occur? When subject to stress, cells in the skin start producing the heat shock protein HSP70i. This protein acts as a messenger that is crucial for maintaining the viability of the cell during stressful conditions, by shielding cellular molecules. Some heat shock proteins are transported out of the cell, from where they get taken up by so called dendritic cells and transported to local lymph nodes. Here the dendritic cells signal that something is wrong in the skin. This triggers the activation and recruitment of a variety of T cells, reactive with proteins transported by HSP70i. Such target proteins include melanocyte proteins. That leads to vitiligo in patients with pre-existing T cells that carry receptors aimed at recognizing and killing pigment cells. 

Why do T cells attack the body’s own cells?   Activation of melanocyte reactive T cells is based on the T cells responding to a very specific protein transported to dendritic cells by the heat shock protein. The heat shock protein sounds the alarm, and the protein it carries is digested into peptides to form a “key”, that fits into a “lock” on the T cell. The chaperone function of HSP70 is thought to be very important, as it is very well preserved throughout evolution, and can be found in stressed cells from organisms ranging from bacteria to plants and mammals.  

How would the therapy work? The heat shock protein-based vitiligo treatment is based on introducing a slightly modified version of HSP70i into the skin, where the alarm region has been re-engineered. The resulting heat shock protein scientifically named HSP70iQ435A now has the opposite effect on dendritic cells as compared to its natural counter-part.  The modified heat shock protein actually acts as an immuno-suppressant, stalling the release of T cells. The lack of killer T cells in the skin now allows new pigment cells to occupy the skin, reversing the progression of vitiligo. The non-pigmented lesions start filling in with pigmentation. 

How will the drug be induced? The modified protein will be introduced into the skin by a series of DNA injections. Laboratory research with vitiligo disease models show that mice and swine respond well to four weekly treatments, to initiate the path to recovery.

Twice-Daily 2% Tofacitinib Cream Plus UVB Improves Facial Vitiligo Symptoms

A twice-daily 2% tofacitinib cream in addition to narrow-band ultraviolet B (NBUVB) administration has shown promise for improving the symptoms of facial vitiligo, according to the results of a small pilot study published in the Journal of the American Academy of Dermatology.

Patients with vitiligo of the face were recruited from the Pigmentary Disorders Clinic at The University of Texas Southwestern Medical Center (n=11, mean age, 44 years). Only patients who had not received benefit with topical corticosteroids or calcineurin-inhibitors in addition to thrice weekly NBUVB phototherapy or sunlight exposure were enrolled in the study. Treatment consisted of twice-daily 2% tofacitinib cream in addition to thrice-weekly NBUVB over a period of approximately 3 months. At 3-month follow-up, the researchers measured the amount of depigmentation in each participant with the facial Vitiligo Area Severity Index.

The mean time to follow-up was 112 (range, 84 to 154) days. There was a 70% (range, 50% to 87%) mean improvement in the facial Vitiligo Area Severity Index from baseline to 3-month follow-up (0.8 [range, 0.1 to 2.25] vs 0.23 [range, 0.03 to 0.75], respectively). The 30-g tube of tofacitinib costs $320, but because of its small application area, the medication lasted each patient an average of 90 days. No adverse effects were reported.

Study limitations included its small sample size, its use on only the face, and the lack of control groups.

“Future controlled studies with larger sample sizes and long-term follow up should be performed,” the researchers wrote. “If they are confirmatory, topical tofacitinib may become a useful addition to our therapeutic armamentarium for vitiligo.”

Çernobil felaketi: Küba nükleer kazadan etkilenen binlerce çocuğu nasıl tedavi etti?

"Hastanedeymişiz gibi gelmiyordu. Benden daha hasta olan çocuklar bile burada olmaktan memnundu."

Ukraynalı Roman Gerus, bir felaketle başlayan çocukluk anılarını çok iyi hatırlıyor: 26 Nisan 1986'da Çernobil nükleer santralinde bir reaktörün patlaması ile yaşanan ve popüler dizi 'Çernobil'de anlatılan felaket sonrası Gerus'un da aralarında olduğu 23 binden fazla çocuk, Küba'ya tedavi görmeye gitti.

Küba Sağlık Bakanlığı'nın sponsor olduğu tedavi programı, 1990-2011 yılları arasında devam etti.

Mayıs ayında Kübalı ve Ukraynalı yetkililer, o yıllardaki ortaklığı daha küçük çaplı da olsa devam ettirmek istediklerini duyurdu.

Küba'da tedavi gören 'Çernobil çocukları' yaşadıklarını BBC'ye anlattı:

BBC'ye konuşan Roman Gerus, Küba'ya 3 kez gittiğini söylüyor. Tedavi için ilk kez 12 yaşında gittiği ve 6 ay kaldığı Küba'ya, 14 yaşında geri dönüp 3 ay kaldığını, son olarak da 15 yaşındayken gidip 45 günü burada geçirdiğini belirtiyor.

Gerus, "Her gidişim, diğerlerinden farklıydı ama her seferinde çok keyif almıştım. O günleri sevgi ile hatırlıyorum ve aileme gösterebilmek için Küba'ya geri dönmeyi istiyorum" diyor.

Beyaz lekeler

Şimdi 27 yaşında olan Gerus, Çernobil'deki kaza olduğunda henüz doğmamıştı bile. Ancak ailesi nükleer santrale çok yakın yaşadığı için, 10 yaşlarındayken Vitiligo (akderi) hastalığı baş gösterdi.

Vücudunda beyaz noktalar çıkmaya başlayan Gerus'un ailesi onu Ukrayna'da tedavi etmeye çalıştı ama doktorlar ilaçların çok pahalı olduğunu, yardımcı olacaklarına söz veremeyeceklerini söyledi.

Annesi Küba'daki tedavi programından haberdar olduğunda, yaşamı değişti:

"Biri anneme programdan bahsetmiş. Bedava olduğunu söylediklerinde annem inanamamış. 6 aya yakın bekledikten sonra aniden bir telefon almıştık. Karşıdaki ses iki hafta için yola çıkacağımızı söylüyordu. Annem ve babam, Küba çok uzak, ben de çok genç olduğunu için kaygılıydı ama bunu yapmaya karar verdik."

25 binden fazla hasta

Gerus başkent Havana'nın 30 km doğusunda bulunan sahil kasabası Tarara'ya geldi.

Eskiden varlıklı Kübalıların rağbet ettiği Tarara'da 1959 Küba devriminden sonra çocuk ve gençler için kamplar yapılmıştı.

Mart 1990 ve Kasım 2011 tarihleri arasında ise kasaba 'Çernobil çocukları' olarak bilinen program kapsamında, felaketten etkilenen çocukların evi oldu.

Küba resmi istatistiklerine göre bu dönemde programa katılan 26 bin 114 kişiden yüzde 84'ü çocuklardı ve önemli bir bölümü Ukrayna, Rusya ve Beyaz Rusya'dan geliyordu.

Tedavi programı, Küba'nın 1990'larda baş müttefiği Sovyetler Birliği'nin dağılması ile yaşadığı zorluklar da dahil, pek çok engele rağmen ayakta kaldı.

Farklı hastalıklar

Tarara'daki bu tesiste hem çocuklar hem de refakatçilerine ayrılan evlerin yanında, iki hastane, bir klinik, okullar, parklar ve bir tiyatro salonu da vardı. Tesis, sahile de yalnızca 15 km uzaklıktaydı.

Kanserden beyin felcine, sindirim bozukluklarından psikolojik rahatsızlıklara pek çok farklı şikayetle gelen hastalar burada tedavi görüyordu.

Doktorlar Julio Medina ve Omar Garcia, programda çocukların dört gruba ayrıldığını söylüyor:

• Hastaneye yatırılması gereken ve iyileşene kadar adada kalması gerekenler
• Ciddi sayılmayan ama doktorların gözetimi altında olması gereken sağlık sorunları olup, 60 ve daha fazla gün kalanlar
• Ayakta tedavi edilen ve 45 ila 60 gün kalanlar
• Sağlığı görece daha iyi olan ve 45 ila 60 gün kalanlar

1991 ve 1992 yıllarında, 12-13 yaşlarındayken tesiste tedavi gören Ukraynalı Khrystyna Kostenetska, dördüncü gruptandı.

"İki gidişimde de 40'ar gün kaldım. Bu, alçak dozda radyasyon olan insan vücudunun iyileşmesi için gereken süreçti" diyen Kostenetska, çok ciddi sağlık sorunları olanlar ile daha iyi durumda olanlar için iki ayrı alan bulunduğunu söylüyor:

"Her birinde 15 çocuğun kaldığı küçük evlerdeydik. Bizim bulunduğumuz yerde özel bir tedavi yoktu ama göz ve diş muayeneleri oluyordu. Muhteşem denizi, gün batımını ve dondurmalarını hatırlıyorum.

"Ancak ciddi sağlık sorunları olan çocuklar da vardı. Bazılarının vitiligo deri hastalığı olduğu için güneşin altında uzun kollu giyiyorlardı. Küba'nın havası bazılarını tedavi ederken, bazılarının iyileşme sürecini hızlandırmıştı."

Güneşin altında

Roman Gerus, burada iyileşen çocuklardandı.

Küba'ya ikinci gidişinde derisindeki beyaz plakların tamamının kaybolduğunu söyleyen Gerus, "Bazı ilaçlar aldım ama güneş, en iyi ilaçtı. Çok yüzüyorduk. Sahilde olmak tedavinin bir parçasıydı. Hep gitmek istiyorduk" diyor.

Çocukların nasıl seçildiği tartışması

Bazı gazeteciler ise, Ukrayna'nın derin krizde olduğu bir dönemde yaşanan felaketten etkilenen çoğu ailenin çocuklarını tedavi için başka ülkelere gönderecek maddi durumu olmadığına dikkat çekiyor.

BBC Ukrayna Servisi'nden Diana Kuryshko da, çocukların seçilmesi sürecinin tartışmalı yanları olduğunu söylüyor:

"Küba hükümetinin programı duyurulduğunda insanlar çocuklarını oraya gönderebileceklerini düşündüler. Ancak çocuğunuzu gönderebiliyorsanız, çok şanslıydınız. Programa katılan çocukların nasıl seçildiği konusu belirsizdi. Çocukların çoğunun en mütevazi ailelerden seçildiğini söyleyemeyiz."

Buna rağmen Ukrayna'da ve diğer Sovyetler Birliği cumhuriyetlerinde programa bakış olumluydu.

Gerus, "O dönem Küba halkının durumunun ne kadar kötü olduğunu anlayabilmiştim. Yoksulluk yaygındı ama bize karşı, mutfakta çalışanlardan doktorlara kadar herkes çok nazikti" diyor.

Kaynak: https://www.bbc.com/turkce/haberler-dunya-48721120

Chernobyl heals in Havana: The episode that didn’t count HBO

Thousands of children were cared for in Cuba after the Chernobyl explosion.

The beaches of Tarará are all you can expect from the Cuban Caribbean. Warm turquoise blue sea, idyllic palm trees on fine sand and ochre, soft breeze. A handful of low houses with gardens are arranged on a perfect grid just 30 kilometers east of Havana. In the center, a crude building with red paint stripped by saltpeter hides one of the lesser-known episodes of the Chernobyl disaster.

Built in the 1950s, the Tarará urbanization served as a summer neighborhood for the country’s bourgeois and military elite during Fulgencio Batista’s dictatorship and later became a giant children’s sports camp for the José Martí Organization of Pioneers. But as of March 29, 1990, this paradisiacal resort would become the largest health program for children affected by the accident at the Chernobyl nuclear plant four years earlier.

Between 1990 and 2011, the Tarará pediatric hospital treated more than 25,000 children who were victims of radiation in Ukraine, Russia and Belarus, most of them affected by cancer, deformities, muscular atrophy, dermatological problems and stomach problems. And many with high levels of post-traumatic stress for having experienced the nuclear horror.

In addition to the clinical facilities for those affected – which included two hospitals and some 20 medical branches in the professional category – the small city had a theatre, several schools and recreational areas stretching over almost two kilometres of crystal-clear beaches.

“Fidel told me ‘I don’t want you to be going to the press, nor do I want the press to be going to the consulate. This is an elementary duty that we are doing with the Soviet people, with a brother people. We’re not doing it for publicity,'” says Cuban ex-consul Sergio Lopez in the documentary ‘Chernobyl in us.

Almost 30 years after Fidel Castro himself received the first contingent of 139 children at the foot of the plane’s steps, a recent agreement signed between the Cuban Ministry of Health and the Ukrainian government opens the door to a possible re-edition of the program coinciding with the attention aroused by the HBO series on Chernobyl.

The Cuban News Agency announced that a new group of 50 Ukrainian children, many of them children of those who in the early 1990s lived the same experience in the Caribbean nation, will travel to Havana in 2019 to treat their ailments.

The ‘anti-radiation’ beach.

For years, the beaches of Tarará were populated by rubicundas girls and pale boys that habaneros became accustomed to seeing sunbathing on the beach outside the summer season.

On the morning of April 26, 1986, a series of fatal errors affected the reactor number 4 of the Vladimir Ilyich Lenin atomic power plant, whose core of the reactor was exposed throwing a large amount of radioactive material in the middle of several explosions and an intense fire that lasted ten days.

Pripyat, a city of 50,000 people built to house the facility’s workers and their families, was not evacuated until 36 hours after the explosion. Hundreds of thousands of adults and children were exposed to the contamination. Many of the children then developed thyroid cancer and leukaemia, probably through inhalation or ingestion of iodine 131 or celsium 173.

The patients used to be “carriers of more than one chronic disease,” accompanied by severe psychological alterations, according to a study conducted by Cuban doctors Julio Medina, coordinator for years of the Program; and Omar Garcia, researcher at the Center for Radiation Protection and Hygiene. That is why they classified the affected in four groups, from the most serious, which could stay for months on the island, to the “relatively healthy” of group IV, which stayed between 45 and 60 days.

For years, the beaches of Tarará were populated by rubicundas girls and pale boys that habaneros became accustomed to seeing sunbathing on the beach outside the summer season. Tanning and submerging in seawater was a complementary part of the melagenin and pilotrophin treatment they received to improve skin pigmentation and hair growth.

“I can say, without exaggeration, that for us Cuba has been the salvation,” says young mother Natasha Salimova while rocking her child with cerebral palsy in a trolley, in a piece of the Associated Press of 1999, where you can see the Cuban clinic in operation.
Miracle in Special Period

Source :http://www.rguama.icrt.cu/en/chernobyl-heals-in-havana-the-episode-that-didnt-count-hbo/

Man who was bullied for vitiligo is now a model who sees his skin as art

Growing up, Mahmoud Hassan was bullied for his vitiligo, a skin condition that caused patches of pale skin on his face and body. At school he would be called ‘cow’ or ‘zebra’. Now, at 25, he’s a model. Mahmoud has learned to love his skin, and views his patches as a work of art. Mahmoud, from Helwan in Egypt, developed vitiligo when he was just 13. When he noticed the loss of pigment in his skin he found it difficult to deal with, worrying he would no longer fit in with his peers. Mahmoud spent years trying to cover up his differences. ‘It was a really difficult time for me,’ he says. ‘I was embarrassed about it and did everything I could to hide it from my friends.

‘People around me at school and in public would shout ‘cow’ or ‘zebra’ at me because my condition causes light skin coloured patches around my body. I guess they think my skin looks the same as those animals.’ It took Mahmoud years to overcome his insecurities. Being given the opportunity to model made a huge change. Now, he shares photos of his skin to inspire others to embrace what makes them different.

‘I now treat my body as if it’s a work of art,’ he explains. ‘Showing it to the public in a beautiful and creative way and stepping away from being that insecure ‘cow’. ‘I adore sports and I used to work as a sports advisor and parkour trainer for teenagers and now I’m a ski and snowboard instructor.

‘My vitiligo gave me the opportunity to become a fashion model and that has made me feel the strongest I have ever been before.

Source: https://metro.co.uk/2019/07/06/man-bullied-vitiligo-now-model-sees-skin-art-10125140/

Treatment responses in patients with vitiligo to very potent topical corticosteroids combined with vitaminotherapy in Madagascar

In the management of nonsegmental vitiligo in Madagascar, researchers evaluated outcomes obtained 10 years after the initiation of a therapeutic protocol which combines very potent topical corticosteroids (TCS), vitaminotherapy (B12 and C), and suppression of microtraumas. Included in the research were patients who agreed to follow the treatment protocol, which combined very potent TCS (two applications/day for 10 days, and then one application/day for the following 10 days), oral vitamin C 500 mg/day for 20 days, and oral vitamin B12 100 mg/day for 20 days. 

Details were evaluated for 308 patients (mean age was 33.3 years) with vitiligo. According to this prospective and descriptive study, 239 patients had excellent therapeutic compliance and attended regular follow-up. In 50 patients less than 14 years of age, excellent repigmentation was noted. In 31 patients, lesions that developed in less than 1 year had excellent treatment response. With outstanding repigmentation in 108 patients, localized lesions responded favorably to treatment. These findings indicate that therapeutic response is better for youth, lesions of less than 1 year of evolution, and for facial and neck localization of vitiligo.

The endocannabinoid system and skin conditions

Although most of the research on the endocannabinoid system focuses on its involvement in the CNS and immune systems, a significant amount of research over the past 20 years has demonstrated that this system also plays a role in maintaining several important functions of the skin. This article will examine the functions of the endocannabinoid system on the skin and its involvement in several skin conditions.

Functions of the endocannabinoid system

The endocannabinoid system is comprised of various endogenous ligands, their receptors, and a complex enzyme and transporter apparatus. Each of the components of the endocannabinoid system is involved in either synthesizing, releasing, transporting and/or degrading various endocannabinoid molecules throughout the body. Furthermore, molecules that have been recognized as exhibiting “cannabinoid-like” roles can also be involved in the endocannabinoid system pathway.

In addition to endogenous cannabinoids that naturally exist throughout our body is a second class of cannabinoids known as phytocannabinoids. To date, more than 100 different phytocannabinoids have been identified from the Cannabis genus, most notable of which include the main active compounds of tetrahydrocannabinol (THC) and cannabidiol (CBD).

Both endocannabinoids and phytocannabinoids have been shown to either activate, antagonize or inhibit a wide variety of different cellular targets in the human body.

The endocannabinoid system in the skin

An extensive amount of research over the past two decades has demonstrated that both endocannabinoids and phytocannabinoids exert various biological effects in the skin homeostasis.

Numerous cell types of the skin, some of which include epidermal keratinocytes, melanocytes, mast cells, fibroblasts, sebocytes, sweat gland cells and certain populations of hair follicles have been shown to host different endocannabinoid molecules and receptors.

With this information in mind, researchers have focused their endeavors on understanding how these endocannabinoid ligands and receptors play a role in skin-related disorders.

Endocannabinoids and skin conditions

The influence of the endocannabinoid system on a wide variety of skin conditions is well-documented. In addition to the skin conditions discussed below, endocannabinoid signaling has also been associated with atopic dermatitis, melanoma, systemic sclerosis, wound healing processes, non-melanoma skin cancers and much more.

Numerous cell types of the skin, some of which include epidermal keratinocytes, melanocytes, mast cells, fibroblasts, sebocytes, sweat gland cells and certain populations of hair follicles have been shown to host different endocannabinoid molecules and receptors.

With this information in mind, researchers have focused their endeavors on understanding how these endocannabinoid ligands and receptors play a role in skin-related disorders.

Endocannabinoids and skin conditions

The influence of the endocannabinoid system on a wide variety of skin conditions is well-documented. In addition to the skin conditions discussed below, endocannabinoid signaling has also been associated with atopic dermatitis, melanoma, systemic sclerosis, wound healing processes, non-melanoma skin cancers and much more.

Acne

One of the most established side effects of cannabinoid abuse is acne, which clearly demonstrates the ability of the phytocannabinoids of this substance to have an effect on human sebaceous glands present within the skin.

Researchers have found that both CB1 and CB2, which are two predominant endocannabinoid-responsive receptors, are expressed in human sebaceous glands. The discovery of CB2 in human sebaceous glands led to researchers uncovering a role for this receptor in maintaining homeostatic sebaceous lipogenesis (the formation of fats within sebaceous glands). Any dysregulation to the endogenous sebaceous pathway, such as the overstimulation of these receptors, can therefore promote the development of both seborrhea and acne.

Pigmentation disorders

In vitro studies on primary human melanocytes have shown that these cells express various endocannabinoid receptors including CB1 and CB2, endocannabinoid target, GPR119 and the cannabinoid-responsive calcium channel TRPV1.

When exposed to CBD, human epidermal melanocytes were found to exhibit enhanced melanogenesis and tyrosinase activity. The ability to activate this CB1-coupled signaling pathway indicates that this type of treatment could be used to better understand chronic depigmentation conditions like vitiligo.

Psoriasis

Psoriasis is a chronic inflammatory skin disorder. The pathogenesis of psoriasis, while poorly understood, has been associated with both genetic and epigenetic abnormalities, as well as changes in the microbiota and pH of the skin.

Understanding the anti-proliferative and anti-inflammatory properties of various endocannabinoids, such as those involved in the CB1 and CB2 pathways in the skin, has led to the suggestion that targeting these pathways could assist in the development of more effect psoriasis treatments.

In fact, the relationship between the dysregulation of endocannabinoid pathways and psoriasis development has been demonstrated by several different studies. For example, elevated levels of anandamide in the plasma, increased activity levels of fatty acid amide hydrolase and monoacylglycerol lipase in granulocytes and upregulation of GPR55 has been associated with potential involvement in endocannabinoid dysregulation of psoriasis patients.

Source:

Toth, K. F., Adam, D., Biro, T., & Olah, A. (2019). Cannabinoid Signaling in the Skin: Therapeutic Potential of the “C(ut)annabinoid” System. Molecules. 24(918). DOI: 10.3390/molecules24050918.

Kim Kardashian sedef için geliştirdiği fondötenini önce kendi daha sonra büyükannesinin üzerinde denedi

Kurucusu olduğu KKW Beauty sayesinde ciddi bir başarı sağlayan ve markasının reklamlarını sadece Instagram hesabından yapan reality şov yıldızı Kim Kardashian yeni vücut ürünüyle yine tüm dikkati üzerine çekti. Sedef rahatsızlığı ile mücadele eden Kim, ürünü önce kendi daha sonra da büyükannesinin üzerinde denedi.

Sedef lekelerini bile gizleyecek bir vücut fondöteni piyasaya süren Kim Kardashian yeni ürününe çok güveniyor.

Fondötenin ne kadar etkili olduğunu göstermek için oldukça etkili örneklerde bulunan Kardashian ürünü önce sedef hastalığı nedeniyle vücudundaki izleri gidermek için denedi. Daha sonra ailesini dahil ederek büyükannesinin ellerinde denedi.

Son olaraksa ürünü, antrenörünün bacaklarında deneyen Kardashian, tüm bunları 142 milyon takipçisi bulunan Instagram hesabından paylaştı.

kaynak: https://www.mynet.com/kim-kardashian-yeni-vucut-fondotenini-once-kendi-daha-sonra-buyukannesinin-uzerinde-denedi-1236654-mykadin