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Topical treatment on hand for liver spots

first_imgAn investigation into the molecular mechanisms responsible for the most common type of benign skin lesion may lead to the first nonsurgical treatment for the growths called seborrheic keratoses (SKs), which can be cosmetically unattractive and often worrisome to patients. A paper by researchers at Harvard-affiliated Massachusetts General Hospital (MGH), published online in the Journal of Investigative Dermatology, reports that blocking the action of a specific signaling enzyme leads to the death of cultured SK cells and the breakdown of SK lesions.“Our paper is the first to show that SKs are dependent on an enzyme called Akt for survival,” said Victor Neel, director of dermatologic surgery at MGH and lead author of the paper. “Inhibition of this enzyme in SK cells causes rapid cell death while having no effect on normal skin cells. We are confident that this paper heralds the development of an effective, topical treatment for SKs.”Sometimes called senile warts, barnacles, or liver spots, SKs vary in color from tan to black, can be flat or raised, and range in size from quite small to an inch or more across. They become more common with aging; most individuals over 40 are likely to have a few, and some have hundreds scattered across the torso and face. While SKs have some microscopic features in common with their malignant counterpart squamous cell carcinoma and most have mutations in genes known to be involved in cancer, SKs never become malignant.Previous research by members of the MGH team identified increased expression in SKs of growth factor receptors and other genes thought to be involved in skin cell differentiation and in skin cancer development. Neel explained, “We still don’t know why SKs resist malignant transformation, but we think studying SKs will help us identify factors that prevent benign lesions from becoming malignant.”The two genes that are most frequently mutated in SKs — called PI3K and FGFR3 –— code for proteins that affect the activation of the Akt kinase enzyme, which is known to block several cell-death related pathways. Although previous studies have reported higher levels of activated Akt in SKs than in normal skin, determining the significance of that finding was hampered by the inability to grow SK cells in the laboratory. Through trial and error and a bit of luck, the MGH team identified conditions that permit SK cells to be cultured, opening up an array of opportunities for studying their biology.Cultured SK cells were exposed to a panel of specific kinase inhibitors, confirming that the development and maintenance of SK cells requires the presence of activated Akt. One particular Akt inhibitor, called A44 (A-443654, produced by Abbvie Pharmaceuticals), was by far the most efficient at inducing the death of cultured SK cells. Small doses of A44 initiated a cell-death program called apoptosis. The researchers also found that applying A44 to intact SK lesions that had been excised from patients’ skin and maintained in culture caused the lesions to die through apoptosis.“Within 48 hours of exposure to A44, the SK lesions from patients completely disintegrated,” said co-author Anna Mandinova of MGH’s Cutaneous Research Biology Center. “This effect was very specific to SK lesions, as A44 was harmless both to normal skin cells and to malignant squamous cell carcinoma cells.”The MGH team is continuing to investigate the potential of A44 and several other compounds to identify the best candidate for clinical trials of a topical treatment for SKs. A patent application based on the study findings has been filed, and the team is continuing to pursue what SKs can reveal about the molecular differences between benign and malignant tumors.“Understanding why SKs never become malignant, even though they have mutations in classic oncogenes, was the primary question we wanted to address when we started studying this skin lesion. Finding a novel inhibitor of SKs was a serendipitous byproduct of that inquiry,” says Neel, who is an assistant professor of dermatology at Harvard Medical School. “We suspect that other, yet-to-be-determined mutations in SKs are incompatible with the mutations that lead to malignancy. For example, p53 is commonly mutated both in sun-damaged skin and in cancers like squamous cell carcinoma, but is never mutated in SKs.“We hope that pinpointing other mutations underlying SK development will help us understand how they resist becoming malignant, which could inform us of new ways of treating more dangerous tumors.”last_img read more


Kazeem shocks Camelot for Gold

first_imgAl Kazeem produced a tremendous performance to lower the colours of hot favourite Camelot in the Tattersalls Gold Cup at the Curragh. Roger Charlton’s British raider was settled in last place of the four runners, just behind Camelot, as the market leader’s stablemate Windsor Palace took them along in single file. All looked to be going well enough for triple Classic winner Camelot but James Doyle ranged upsides at the quarter-mile pole on the lightly-raced Al Kazeem (9-4) and it soon became apparent he had his rival’s measure. Press Associationcenter_img Quickening in great style, Charlton’s five-year-old claimed the Group One prize with something in hand. A length and a half was the winning margin for Al Kazeem, who was having just his second start since victory in the Jockey Club Stakes at Newmarket last May. Charlton said: “He’s been a slow maturing horse. Last year he came home with a stress fracture of his pelvis in the Jockey Club Stakes. His work has been really impressive and James said the ground was a bit lively for him there. He’s a good horse and he rode him confidently. The plan was to drop in behind Camelot and he rode a good race. “We can look at all the top races over a mile and a quarter and we also know he stays a mile and a half very well. I’d like to think maybe the Arc at the end of the season. Ascot is an obvious possibility, we’ve also got the Eclipse – there’s lots of lovely races there for him.” Doyle was riding his first winner in Ireland and was recording his second Group One winner after the Charlton-trained Cityscape in Dubai last year. He added: “All credit to Mr Charlton – he’s done a fantastic job with the horse and he’s done a fantastic job with me as well. He took me on – I’d never even ridden in a Group One race before and he gave me a massive opportunity in Dubai and it paid off. “Without people like him I’d probably be doing OK but I wouldn’t be here today in these type of races. He’s a great boss and a great person to work for. He gives me great confidence. My grand-father is from Monasterevin. He’s 75 now and he’ll be at home watching. My mother used to train and right from an early age I had ponies and stuff. I started riding out when I was about 12 years of age. I’m 5ft 10, it’s not easy but as I’ve got older I’ve become more disciplined. I can comfortably do 8st 10 so it’s grand.” Aidan O’Brien admitted he has had to tread carefully with Camelot after the horse had surgery for colic late last year, saying: “They say it usually takes six months to get over an anaesthetic as big as he had, so we are taking him along gently. He ran a very good race. Obviously we are disappointed he got beat, but that’s the way it is and it’s a stepping stone on the way.The plan was to go here and then go to Ascot and I think that is still the plan at the moment.” last_img read more


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Oceania Cruises continues to earn its reputation a

first_imgOceania Cruises continues to earn its reputation as the world’s leading culinary and destination-focused cruise line with the most sought-after dining experience at sea: modern Asian restaurant, Red Ginger.“Oceania Cruises is renowned for its culinary excellence and has a reputation for delivering The Finest Cuisine At Sea,” explained Steve Odell, senior vice president and managing director Asia Pacific for Oceania Cruises.“Red Ginger is particularly popular with our Australian guests who, given our multiculturalism, are used to enjoying Asian-inspired meals regularly. Red Ginger, along with other onboard restaurants like Toscana, Polo Grill, Jacques Bistro and Waves Grill, allows guests to take their taste buds on a global culinary tour while they sail the world.”Designed with a mix of contemporary Asian style and feng shui principles, the restaurant’s interior features ebony timbers, golden walls, rich red furnishings, striking modern Asian art, a waterfall wall and glowing lighting.Red Ginger’s cuisine is as bold as the décor, with presentation to match. Guests can select chopsticks from a fascinating array of options, varying in length, material and colour from stainless steel to wood, on a dedicated tray.With a focus on fresh interpretations of Asian classics, dishes include a salad of spicy roast duck and watermelon with cashews, mint and Thai basil, a Malaysian beef Penang with coconut Rice and paratha roti, or caramelised tiger prawns, miso-glazed sea bass or lobster pad thai.Representing a blend of the best of Vietnamese, Thai and Japanese cuisine, the chefs at Red Ginger, under the leadership of Master Chef and Executive Culinary Director for Oceania Cruises. Jacques Pépin, have developed their own unique techniques to present dishes in an innovative fashion, without compromising the authentic Asian flavours.The dessert menu features delights such as steamed ginger cake, yuzu citrus sorbet and matcha green tea ice-cream, and special attention has been given to the Asian tradition of serving tea, with a dedicated menu and server on hand to help diners choose, sample and enjoy a raft of loose leaf teas. The extensive wine and sake list with food pairing recommendations complements the Asian-inspired cuisine of the restaurant.“Although the food in Red Ginger is pan-Asian, this is not a ‘fusion’ restaurant. Rather, the culinary team did hands-on research throughout Asia and worked with chefs all over the world to find recipes and techniques that represent the best of Vietnamese, Thai, and Japanese cooking – and spent months mastering their preparation. The presentation is refined in a way that is exciting and modern, but the dishes themselves, like all of our food, are firmly grounded in authentic recipes, traditions, and ingredients,” writes Jacques Pepin in ‘Taste the World: The Food and Flavors of Oceania Cruises’.Red Ginger is open for dinner bookings every night. Reservations are required to secure a table in this popular onboard specialty restaurant. Onboard Marina, Riviera and Sirena and dishes from Red Ginger are featured nightly in The Grand Dining Room.last_img read more


Irregular metabolism of branchedchain amino acids may cause progression of type 2

first_img Source:https://www.brighamandwomens.org/ Jul 6 2018In the U.S., about five out of 100 expectant mothers develop gestational diabetes mellitus (GDM), a temporary form of diabetes in which hormonal changes disrupt insulin function. Although GDM is often symptomless and subsides after delivery, women with a history of it face a seven-fold risk for developing type 2 diabetes.The biological mechanisms underlying this rise in type 2 diabetes risk are mysterious. But a new study in Clinical Chemistry led by Deirdre Tobias, DSc., associate epidemiologist at Brigham and Women’s Hospital and Assistant Professor at Harvard Medical School, suggests that the irregular metabolism of branched-chain amino acids – components of proteins found in many foods – may be partially to blame for progression to type 2 diabetes.Tobias and her team of researchers assessed reported diets and blood samples collected during the Nurses’ Health Study II, an investigation of chronic disease risk in women that was carried out from 1989 and continues today. They looked at the data from 347 women with histories of GDM, roughly half of whom later developed type 2 diabetes. The researchers calculated the women’s levels of branched-chain amino acid intake using published guidelines for nutrient content. Using mass spectrometry, they also measured the levels of branched-chain amino acids in the blood samples that were collected prior to type 2 diabetes development during the period of 1996-1999.The researchers found that women with a history of GDM who later developed type 2 diabetes had higher levels of branched-chain amino acids in their blood, regardless of their dietary intake. That suggests that greater consumption of branched-chain amino acids may increase the risk for type 2 diabetes, but only if an individual’s ability to properly metabolize them is impaired.Related StoriesDiet and physical exercise do not reduce risk of gestational diabetesUranium toxicity might have caused obesity and diabetes in Kuwait, finds new studyMothers with gestational diabetes transferring harmful ‘forever chemicals’ to their fetus”If your dietary intake is high, but you can clear these normally from circulation, then you don’t seem to be at a higher type 2 diabetes risk,” said Tobias.Researchers cannot yet fully characterize the specific pathway of this impaired metabolism, but the abnormality seems to result in a buildup of circulating branched-chain amino acids, which have a detrimental downstream effect on insulin function.Branched-chain amino acids are essential amino acids, meaning that they can only be obtained from food. They play important roles in immune and neurological function, and they exist in a wide variety of foods. Tobias emphasized that branched-chain amino acids are not necessarily unhealthy. More research is needed to determine whether lowering dietary intake of them can lower type 2 diabetes risk in people with abnormal metabolism.”From a practical point of view, branched-chain amino acids are difficult to avoid,” said Tobias. “They are found in so many protein sources, both healthy and less healthy.”Tobias and her team hope that early detection of abnormally high branched-chain amino acid blood concentrations may one day enable earlier interventions for those at risk for type 2 diabetes. They suggest it will take further research to determine if tests to detect these levels should become standard procedures during doctor’s appointments.last_img read more