السلام عليكم


Malaria Drug Slows Pancreatic Cancer Growth in Mouse Models


Newswise — BOSTON--Dana-Farber Cancer Institute scientists report they have shrunk or slowed the growth of notoriously resistant pancreatic tumors in mice, using a drug routinely prescribed for malaria and rheumatoid arthritis.

The pre-clinical results, which will appear in the April issue of the journal Genes & Development and is currently published on its web site, have already prompted the opening of a small clinical trial in patients with advanced pancreatic cancer, one of the deadliest and hardest-to-treat forms of cancer, said the investigators, led by Alec Kimmelman, MD, PhD, a radiation oncologist at Dana-Farber.

"We are seeing robust and impressive responses in pancreatic cancer mouse models," said Kimmelman, whose laboratory specializes in studies of pancreatic cancer, the fourth-leading cause of cancer death in the United States. The oral drug, hydroxychloroquine, is inexpensive, widely available, and causes relatively mild side effects, he said. A second, planned clinical trial will combine the drug with radiation.

"While these findings are indeed exciting and a cause for optimism, one needs to be mindful that so far the effects, while impressive, have only been shown in mice," said Ronald DePinho, MD, director of the Belfer Institute for Applied Cancer Science at Dana-Farber. "I eagerly await to see how the human studies will progress."

A new treatment avenue would be extremely welcome in pancreatic cancer. The National Cancer Institute estimates that 43,140 people were diagnosed in 2010 and 36,800 died. Despite some recent gains with targeted molecular agents and combination regimens, only about 6 percent of patients live five years, and the median survival is less than six months.

Hydroxychloroquine is a form of the drug chloroquine, which is used to prevent and treat malaria and also prescribed for autoimmune diseases, including lupus and rheumatoid arthritis. These compounds have recently stirred much interest in cancer research, because they inhibit a process called autophagy (from the Greek for "self-eating") that is elevated in cancer cells.

Autophagy is present in normal cells as well, but at a much lower level. The process enables cells to break down and eliminate proteins, such as damaged cell membranes and worn-out organelles like mitochondria. But it is also a survival strategy. When nutrients are scarce, cells can digest and feed on their own non-critical proteins to avoid starvation.

Cancer cells also use autophagy to outwit chemotherapy treatment. Research has shown that cancer cells can activate this process in response to a variety of cancer treatments, allowing them to survive during the stress of therapy. But, as Kimmelman noted, autophagy can also be a cell-death mechanism. Cancer researchers are intensely studying – and debating – how to manipulate autophagy as a potential method to slow tumors’ growth or make them more sensitive to other therapies.

In their research reported in Genes & Development, Kimmelman and colleagues were stunned to find that autophagy was turned on at all times in pancreatic cancer cell lines – not just under conditions of stress, treatment or starvation. "This was a big surprise," he said. "These cells weren't deprived of nutrients; they were swimming in all the nutrients they could ever want." This suggested that for some unknown reason, pancreas tumors are highly dependent on autophagy, and therefore potentially uniquely good candidates for autophagy-inhibiting treatment.

In their next experiments, the team administered chloroquine to several different pancreatic cancer cell cultures, and also tested its effects in three types of mouse models. In the laboratory cultures, they reported, the drug "markedly decreased" the growth of the tumor cells, showing that the cells were heavily dependent on autophagy to for continued growth.

In vivo testing involved three types of mouse models – human pancreatic cancer cells placed under the rodents' skin (xenografts); human cells injected into the animals' pancreases (orthotopic transplants); and a genetic model (mice bioengineered to develop native pancreatic tumors).

The response to chloroquine was "profound" in the xenograft models, Kimmelman said: All eight untreated mice died of their cancer within 140 days, while only one of eight treated mice had died by 180 days.

The drug's effects were less dramatic but still impressive in the orthotopic and genetic mouse models, the researchers said. The tumors that developed in the genetically pancreatic cancer-prone mice were, like their equivalent in human patients, extremely resistant to all treatments. Among other properties, these tumors were embedded in tough, fibrous tissue that is difficult for drugs to penetrate.

Nevertheless, the scientists reported that chloroquine treatment as a single agent increased the rodents' survival by 27 days compared with untreated control mice. This is encouraging, Kimmelman commented, because even the newest targeted drugs aimed at pancreatic cancer "don't have much effect in this genetic mouse model."

The Dana-Farber trial of hydroxychloroquine, led by Kimmelman and oncologist Brian Wolpin, MD, is designed to enroll 36 pancreatic cancer patients in whom first- or second-line treatments have failed. The drug is taken in pill form twice a day. Results won't become available for at least a year, said Kimmelman.

Kimmelman said the next step will be to investigate the combination of hydroxychloroquine with radiation in patients with operable pancreatic cancer.

"This is a very interesting and promising approach, attacking the Achilles' heel in pancreatic cancer's defenses," commented Robert Mayer, MD, of Dana-Farber’s Center for Gastrointestinal Oncology. "But it's too early to say whether hydroxychloroquine should be added to chemotherapy, and what the risks and benefits might be, so we want to examine it in a clinical trial."

Kimmelman's lab is also investigating other forms of cancer that might be good candidates for inhibition of autophagy by the drug. He said that their work, as well as recent findings from other labs, suggests that those cancers may be ones that are primarily driven by the KRAS oncogene – as nearly all pancreatic tumors are.

Kimmelman, who also is an assistant professor of radiation oncology at Harvard Medical School, is the senior author of the publication. First author is Shenghong Yang, PhD, a member of the Kimmelman lab. Other authors are from Dana-Farber, Massachusetts General Hospital, Harvard Medical School, Boston University, and scientists from Italy and Germany.

Funding was provided by Dana-Farber, the Friends of Dana-Farber Cancer Institute, the Sidney Kimmel Foundation, and the AACR-Pancreatic Cancer Action Network.

Dana-Farber Cancer Institute (www.dana-farber.org) is a principal teaching affiliate of the Harvard Medical School and is among the leading cancer research and care centers in the United States. It is a founding member of the Dana-Farber/Harvard Cancer Center (DF/HCC), designated a comprehensive cancer center by the National Cancer Institute. It provides adult cancer care with Brigham and Women's Hospital as Dana-Farber/Brigham and Women's Cancer Center and it provides pediatric care with Children's Hospital Boston as Dana-Farber/Children's Hospital Cancer Center. Dana-Farber is the top ranked cancer center in New England, according to U.S. News & World Report, and one of the largest recipients among independent hospitals of National Cancer Institute and National Institutes of Health grant funding

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Insulin-Releasing Switch Discovered

Newswise — Johns Hopkins researchers believe they have uncovered the molecular switch for the secretion of insulin — the hormone that regulates blood sugar — providing for the first time an explanation of this process. In a report published online March 1 in Cell Metabolism, the researchers say the work solves a longtime mystery and may lead to better treatments for type 2 diabetes, the most common form of the disease.

“Before our discovery, the mechanism behind how exactly the insulin-producing beta cells in the islet of Langerhans of the pancreas fail in type 2 diabetes was incompletely understood, making it difficult to design new and better therapies, says Mehboob Hussain, M.D., associate professor of pediatrics, medicine and biological chemistry. “Our research cracks open a decades-long mystery.”

After a meal, the pancreas produces insulin to move glucose from the blood into cells for fuel. People with type 2 diabetes either don’t secrete enough insulin or their cells are resistant to its effects.

In a study designed to figure out more precisely how the pancreas releases insulin, Hussain’s group looked at how other cells in the body release chemicals. One particular protein, Snapin, found in nerve cells, caught their eye because it‘s used by nerve cells to release chemicals necessary for cell communication. Snapin also is found in the insulin-secreting pancreatic beta cells.

To test the role of Snapin, researchers engineered a change to the Snapin gene in mice to keep Snapin permanently “on” in the pancreas. Researchers removed the pancreas cells and grew them in a dish for a day, then added glucose to the cells and took samples to measure how much insulin was released.

When the scientists compared that measurement to what was released by pancreas cells in normal mice, they found that normal mice released about 2.8 billionths of a gram of insulin per cell, whereas the cells from “Snapin-on” mice released 7.3 billionths of a gram of insulin per cell — about three times the normal amount.

“We were surprised to find that the Snapin-on mice didn’t have more or bigger pancreas cells, they just made more insulin naturally,” says Hussain. “This means all our insulin-secreting cells have this amazing reserve of insulin that we didn’t really know existed and a switch that controls it.”

To see if permanently turning off Snapin would reduce insulin release and further demonstrate that Snapin controls the process, the researchers first grew normal mouse pancreas cells in a dish, and treated them with a chemical that stopped them from making the Snapin protein. They again bathed the cells in glucose and measured how much insulin was released by the cells. Normal cells released 5.8 billionths of a gram of insulin, whereas cells with no Snapin only released 1.1 billionths of a gram of insulin — about 80 percent less.

“These results convinced us that Snapin is indeed the switch that releases insulin from the pancreas,” says Hussain.

Normally, according to Hussain, when we ingest glucose, the pancreatic beta cells release an initial burst of insulin almost immediately, then gradually release more insulin about 15 minutes later. However, people with type 2 diabetes and mice engineered to react metabolically like people with type 2 diabetes don’t release this initial spurt of insulin when fed glucose, but still have the later gradual insulin release.

“We knew how important the first burst of insulin is for controlling our blood sugar, but we did not know what really went wrong in our beta cells in people with type 2 diabetes,” says Hussain. “We have drugs that restore the first burst of insulin and yet we did not completely understand how they work.”

Hussain then questioned whether Snapin could be used to fix the defects in cells from a diabetic animal.

Since the cells with Snapin on made too much insulin, researchers wanted to see if they could use this to restore these mice’s ability to secrete the initial burst of insulin. After growing pancreatic beta cells from type 2 diabetes mice in a dish and engineering them to make the Snapin-on protein, the researchers fed the cells glucose and found that they did indeed regain the ability to release that initial insulin burst.

“While keeping Snapin on in these mouse cells corrects the problem in this animal model of type 2 diabetes, we’re still a long way from knowing if the same mechanism will work in people, but this gives us an encouraging start,” says Hussain.

This study was funded by the National Institutes of Health.

Other authors on the paper are Woo-Jin Song, Madhav Seshadri, Uzair Ashraf, Thembi Mdluli and Prosenjit Mondal of the Johns Hopkins University School of Medicine; Meg Keil and Monalisa Azevedo and Constantine Stratakis of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH; and Lawrence Kirschner of Ohio State University.

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Methodist Neurosurgeon First in World to Implant Next Generation Device for Deep Brain Stimulation Therapy
Newswise — A 65-year-old woman with Parkinson’s disease became the first patient in the United States to receive a new device for deep brain stimulation (DBS) therapy.

Dr. Richard Simpson, neurosurgeon at the Methodist Neurological Institute in Houston, Texas, was the first physician to implant Medtronic’s Activa® SC neurostimulator. The single-channel Activa SC is the latest addition to the Medtronic’s Activa® portfolio of DBS systems, which treat the symptoms of advanced Parkinson’s disease and essential tremor in the United States and Europe. The device is also approved for dystonia in Europe.

“We are excited to be the first institution in the United States to offer Activa SC, an important new technology that greatly enhances our ability to treat and customize therapy for a large group of our patients,” said Simpson. “We have a greater ability to fine-tune stimulation and customize our patients’ therapy, which may help us treat their disease more efficiently and in a shorter amount of time.”

The Activa SC system is comprised of an implantable neurostimulator; a thin, insulated lead that is placed in a specific target within the brain; and an extension to connect the neurostimulator and the lead. The new device is powered by a non-rechargeable battery that does not require maintenance from the patient to provide continuous stimulation for multiple years. Once implanted, a neurologist can program the device, adjusting stimulation based on that patient’s needs.

More than 80,000 patients worldwide have received Medtronic DBS Therapy, which delivers mild, continuous electrical stimulation from a surgically implanted neurostimulator to precisely targeted areas within the brain. Stimulation of these areas interrupts the brain signals that cause motor symptoms associated with common movement disorders, allowing many individuals to achieve greater control over their body movements.

شكرا عالمعلومات الغاية في الروعة ..............

السلام عليكم


خبراء "الشاي الأخضر والأسود يحافظان على صحة الأسنان" 


وجد خبراء في مركز "وسترن دنتل" للأسنان الذي يقدم خدمات طبية في كاليفورنيا وأريزونا

ونيفادا إن الشاي الأخضر والأسود يمكن أن تساعد في تحسّن صحّة الأسنان.

ونقلت وكالة الأنباء الأمريكية (ي ب ا) يوم الأربعاء عن لويس أمندولا مدير مركز وسترن دنتل

إن "البكتيريا التي تساهم في تسوّس الأسنان والتي تسمّى ستريبتوكوكوس تتغذّى على

السكّر الذي نتناوله ومع تكاثرها تطلق هذه البكتيريا أسيداً يؤدي إلى تسوّس الأسنان".

حيث أن الشاي الأسود والأخضر يحميان الأسنان لما يتضمنّاه من فلورايد إضافة إلى أنزيم

يساعد في عدم تشكّل الجير.

كما أشار الخبراء إلى أن هناك بعض الأطعمة الأخرى التي تساعد في حماية ووقاية الأسنان

من التسوس وتساعد في تحسن صحتها.

وقال الخبراء أن "من بين هذه المواد العلكة الخالية من السكّر والتي تتضمن

المحلّي "كزيليتول"، وينصح الأطباء أيضاً "بشرب الماء المدعّم بالفلورايد ومن الحنفية وليس

المياه المعبّأة، وكذلك تناول الجبنة بعد الغداء".

سيريانيوز

بس سلام في مشكلة التصبغات يللي بيسببها الشاي الأسود...... خاصة أنو غالباً بمنطقتنا منشرب الشاي أكرك عجم وحلو متل القطر.....فهذا شو بدو يحمي ليحمي


وموضوع شرب المياه من الحنفية برأيي غلط لأنو مو أي مياه حنفية بتنشرب ببلدنا وبغير بلدان


وموضوع المياه المدعمة بالفلور فكمان فيه مخاطرة إذا كانت مياه المنطقة فيها نسبة جيدة من الفلور.......لأنو بيعمل أعراض تسمم


فالشغلة مو عشوائية

السلام عليكم


إي هنن لو ساووا الدراسة عنا أكيد كانوا غيروا رأيهم

           


                                                                                                                                           

السلام عليكم


إشعاعات الشمس تؤثر في مدى فعالية الأدوية التي يتناولها المرضى   

براغ-سانا

كشفت دراسة سويدية حديثة أن كمية إشعاعات الشمس التي يتعرض لها الإنسان تؤثر في

مدى فعالية الأدوية المقدمة للمرضى بمعنى أنه كلما زاد تعرض الإنسان للشمس زادت

الحاجة إلى منحه كمية أكبر من الأدوية.

ونقلت مجلة تيدين التشيكية عن ايريك ايلياسون رئيس الفريق الذي قام بالبحث قوله إن فعالية

الأدوية التي تؤثر عليها الأنزيمات الكبدية ينخفض خلال الأيام المشمسة بمقدار يصل إلى 17

بالمئة أما المواد الضاغطة على مناعة الانسان والتي تلعب آليات أخرى دورا فيها فإنها تبقى

دون تغييرات.

وأكد أن كمية الأشعة الشمسية تؤثر على عمل جهاز الاستقلاب وجهاز المناعة وأن الجسم

يتعرض في الصيف إلى خطر اكبر لأن البكتريا تدخله أكثر ولذلك فان ما يحدث هو بمثابة رد فعل

يقوم به جهاز المناعة لدى الانسان.

وأشار إلى أن الاختبارات الخاصة بهذه الدراسة استغرقت عشرة أعوام وشملت أكثر من

سبعين ألف عينة دم ظهر بنتيجتها أن كمية إشعاعات الشمس توءثر في مدى فعالية الأدوية.

السلام عليكم


استخدام الخلايا الجذعية يقلص حجم القلوب المتضخمة   

واشنطن-سانا

أعلن باحثون أميركيون عن استخدامهم الخلايا الجذعية للمساعدة في تقليص قلوب تضخمت

بشكل خطير بعد التعرض لأزمات قلبية ما يدل على ان العلاج بالخلايا الجذعية يحرز تقدماً

ملحوظاً ويصبح أكثر واقعية .

وذكرت وكالة يو بي أي ان الباحثين يعتبرون هذه المقاربة الطبية تقضي بأخذ خلايا جذعية من

النخاع العظمي لمرضى القلب وحقنها في قلوبهم المتضررة ما يوءدي بالنتيجة إلى تحسن

ملحوظ في أداء القلب خلال أشهر وتقلص واضح في حجم القلب والندبة الناجمة عن الجراحة

التي خضعوا لها بعد سنة واحدة من العلاج.

وقال الدكتور جوشوا هاير أحد معدي الدراسة من كلية الطب في جامعة ميامي ميلر ان النتائج

مشجعة جداً مضيفاً ان العلاج قيد التطوير منذ قرابة عشر سنوات .

لكن الباحثين أوضحوا ان الدراسة شملت 8 مرضى فقط ولا بد من إجراء مزيد من التجارب للتأكد

من نتائجها لذا ما زالت تعتبر في إطار التجربة.

يشار إلى ان نحو 5 ملايين أميركي يشكون حالياً من تضخم القلب نتيجة التعرض لأزمة قلبية.