Effect Of Miglustat On Bone Disease In Adult Type 1 Gaucher Disease (GD1): Results Of Apooleda Pooled Analysis

Effect Of Miglustat On Bone Disease In Adult Type 1 Gaucher Disease (GD1): Results Of Apooleda Pooled AnalysisActelion Ltd (SWX: ATLN) announced the publication of "Effect of miglustat on bone disease in adult type 1 Gaucher disease: a pooled analysis of three multinational open label studies" (Pastores et Al) in Clinical Therapeutics, vol 29, number 8, 2007. This pooled analysis investigates the efficacy of Zavesca® (miglustat) in controlling bone manifestations, such as bone pain, osteopenia and osteoporosis, bone crisis and fractures, in Gaucher Disease type 1 patients. The data in this analysis is drawn from the Zavesca pivotal studies OGT 918 - 001, 004, 005. Bone manifestations are considered among the most painful and debilitating components of Gaucher Disease type 1 highly impacting on patients' quality of life. It has been estimated that bone pain occurs in more than half of GD1 patients and that 26% will develop bone crisis (1); in addition GD1 has been shown to effect affect bone metabolism leading to an increase in bone resorption, which causes a decrease in bone mineral density (BMD), osteopenia and osteoporosis in the majority of the GD patients. Furthermore, the current standard treatment, enzyme replacement therapy (ERT), has shown only limited efficacy in GD1 related bone disease (2) (3) (4). The analysis involved 72 patients, including 41 (57%) who had received previous ERT and 20 (28%) who had undergone splenectomy. Patients' mean (SD) age was 41.2 (13.1) years. The most frequent bone related manifestations at study entry were osteoporosis (43/63 [68%] patients) and bone pain (41/65 [63%] patients). This paper, led by Dr. Gregory Pastores, associate professor of neurology and pediatrics at the New York University School of Medicine, has shown that at two years 83% (54/65) of the patients reported no bone pain compared to baseline data. The reductions in bone pain were comparable among all subgroups, including high-risk patients (i.e. splenectomized). Moreover, there were no new cases of "bone crisis", osteonecrosis or fracture; BMD Z-scores were improved from baseline at both the lumbar spine and femoral neck at each time point (months 6, 12, and 24) (P < 0.001). As early as 6 months after the initiation of miglustat monotherapy, significant increases from baseline in the BMD Z-score were observed at both the lumbar spine (mean, 0.15; P = 0.022) and femoral neck (0.23; P < 0.001); the increases remained significant at 12 months (0.19 [P = 0.012] and 0.21 [P = 0.017], respectively) and 24 months (0.21 [P = 0.015] and 0.18 [P = 0.039]). Significant increases in BMD Z-scores were observed at the femoral neck in splenectomized patients (P < 0.001) and at both sites in osteoporotic patients (lumbar spine: P < 0.001; femoral neck: P = 0.006). Lead investigator Dr Gregory Pastores commented: "Bone disease in patients with Gaucher Disease can be a source of severe debilitation and remains a major management issue. The beneficial effect of miglustat on bone manifestations and especially on bone pain in these patients might be explained by its wide tissue distribution even in deep organs such as bone and by a direct effect on bone cells." Zavesca is currently not approved for the treatment of bone manifestations in Gaucher disease type 1. About Gaucher's diseaseGaucher's disease is a rare genetic disorder, which results from reduced activity of glucocerebrosidase, a key enzyme responsible for the metabolism of glycosphingolipids (GSL - a subclass of fats). Symptoms include enlargement of spleen and liver, bone disease, anaemia, intense fatigue, and in some cases lung involvement. About Zavesca® in type 1 Gaucher DiseaseZavesca® (Miglustat) is the only oral treatment option approved for adults with type 1 Gaucher disease for whom enzyme replacement therapy is not a therapeutic option. It is the first in a class of drugs known as substrate reduction therapy. Zavesca® reduces the rate of formation of glucosylceramide, a glycosphingolipid that accumulates in Gaucher disease, to a level that can be cleared by the remaining enzyme, thus preventing the build up of excess glucosylceramide in the macrophage cells. Zavesca® is approved and available in the European Union, United States, Canada, Switzerland, Brazil, Australia and Israel. Zavesca is currently not approved for the treatment of bone manifestations in Gaucher disease type 1. Zavesca® safety informationMild-to-moderate tremor was reported in approximately 30% of patients in all Zavesca trials combined. Many cases were resolved spontaneously within 1 to 3 months; dose reduction may ameliorate tremor within days;3 patients claimed tremor as one of the reasons for withdrawal from the clinical trials although 1 of these was considered unrelated to Zavesca. The most common adverse reactions in all Zavesca trials combined were diarrhoea and weight loss. Gastrointestinal events, mainly diarrhoea, have been observed in more than 80% of patients treated with Zavesca®, either at the outset of treatment or intermittently during treatment. The majority of cases are mild and are expected to resolve spontaneously on therapy. In clinical practice, diarrhoea has been observed to respond to diet modification (reduction of lactose and other carbohydrate intake), to taking Zavesca® away from meals, and/or to anti-diarrhoeal medication such as loperamide. In some patients, temporary dose reduction may be necessary. Patients with chronic diarrhoea or other persistent gastrointestinal events that do not respond to these interventions should be investigated according to clinical practice. Zavesca® has not been evaluated in patients with a history of significant gastrointestinal disease, including inflammatory bowel disease. Weight loss was mild (6% - 7% of total body weight); most prevalent in the first year of treatment and stabilized thereafter; no patients claimed weight loss as a reason for withdrawal from the clinical trials.Peripheral neuropathy has been reported in type 1 Gaucher patients treated with Zavesca®. Patients should undergo a neurological exam at the start of treatment and regularly thereafter. Zavesca® should be reassessed in patients who develop symptoms of peripheral neuropathy. Zavesca® may cause fetal harm if administered to a pregnant woman and is contraindicated in women who are or who may become pregnant; patients should be apprised of the potential hazard to the foetus. There is a risk of impaired fertility in men. Men should maintain reliable contraceptive methods and not plan to conceive while taking Zavesca® and for three months thereafter. References- Mankin et al. Clin Genet 2006- Charrow et Al, 2007. - Mankin et al. Clin Genet 2006 - Pastores et al. Semin Hematol 2004Actelion Ltd Actelion Ltd is a biopharmaceutical company with its corporate headquarter in Allschwil/Basel, Switzerland. Actelion's first drug, Tracleer®, an orally available dual endothelin receptor antagonist, has been approved as a therapy for pulmonary arterial hypertension. Actelion markets Tracleer® through its own subsidiaries in key markets worldwide, including the United States (based in South San Francisco), the European Union, Japan as well as Canada, Australia and Switzerland. Actelion, founded in late 1997, is a leading player in innovative science related to the endothelium - the single layer of cells separating every blood vessel from the blood stream. Actelion focuses on the discovery, development and marketing of innovative drugs for significant unmet medical needs. Actelion shares are traded on the SWX Swiss Exchange (ticker symbol: ATLN).

GetABI Study Finds That Even Mild Atherosclerosis In The Legs Increases Mortality Substantially

GetABI Study Finds That Even Mild Atherosclerosis In The Legs Increases Mortality SubstantiallyPatients with atherosclerosis in the leg arteries face a substantially increased all cause and cardiovascular mortality risk, according to a large study presented at the European Society of Cardiology Congress in Vienna.Heart attacks and strokes as a result of atherosclerosis have been ranked for years among the most common causes of deaths in Europe. Another previously underestimated manifestation of atherosclerosis is peripheral arterial disease (PAD), which is closely associated with heart attack or a stroke.The German epidemiological study on Ankle Brachial Index (getABI) was initiated in 2001 to answer questions about whether a simple screening test on atherosclerosis can be applied to identify it at an early stage, and if so, what risk such patients carry in the future. Professor Curt Diehm from the Clinic Karlsbad-Langensteinbach, an affiliated teaching hospital of the University in Heidelberg, and his co workers from various renowned medical institutions in Germany presented a 5 year study follow-up.Professor Diehm explained: "We used the ankle brachial-index (ABI), which is simple to understand and to apply by physicians and nurses. In an individual in the supine position, the blood pressure in the leg arteries is equal to or a little higher than in the arm arteries. If atherosclerotic stenoses in the legs manifests (termed PAD), blood flow after the obstruction decreases, and the pressure in the leg artery is lower than in the arm. This sign is almost and reliable as angiography to identify your atherosclerotic risk patient."The study included a total of 6,880 unselected patients in primary care, which underwent ABI testing by their primary care physician. Mean age of the patients was 72.5 years, 58% were females, 46% were past or current smokers, 74% had hypertension, 24% diabetes mellitus and 52% lipid disorders. Of all patients, 18.0% in the total cohort had a pathological ABI test, but the majority of these patients had no clinical signs or complaints.After a 5 year observation period, all cause mortality was 24% in patients with symptomatic PAD, 19% with asymptomatic PAD (i.e., pathological ABI but no complaints), and 9% in patients without PAD. Even when all other known risk factors for cardiovascular death were accounted for by statistical means, PAD had the best ability to predict future death, stroke or myocardial infarction.Professor Diehm said, "The bad news is: we showed that in primary care every fifth patient aged 65 years or older has atherosclerosis in the leg arteries. Because atherosclerosis is not a local process but at the same time progresses in the heart and brain vessels, such patients usually die from heart attacks or stroke. The good news is that the ABI test is not limited to expert use but can be performed in general practice. Thus, family physicians can identify high risk patients and initiate and maintain effective treatment in this large group."The study also showed that the extent of the blood pressure difference between legs and arms matters: the higher the spread between both pressures is (in other words: the lower the ABI), the higher is the mortality of patients.Professsor Diehm said that every effort should be made to implement the ABI screening in standard programs for elderly patients and patients with cardiac risk factors such as diabetes or hypertension. "A huge number of lives could be saved if patients with atherosclerosis would be identified with the ABI, and treated timely."

The Goals Of Platelet Inhibition In Acute Coronary Syndromes

The Goals Of Platelet Inhibition In Acute Coronary SyndromesPlatelet activation and aggregation play important roles in the pathogenesis of cardiac ischemic events after either spontaneous plaque disruption in acute coronary syndromes or mechanical disruption of coronary artery plaques caused by percutaneous coronary intervention (PCI), which could be considered an artificially induced acute coronary syndrome.Standard therapy for the prevention of thrombotic events after acute coronary syndromes and coronary stenting involves dual antiplatelet therapy with aspirin plus a thienopyridine, already established in European and American guidelines years ago. Thienopyridines, like clopidogrel and prasugrel, block platelet activation and aggregation by inhibiting the P2Y12 ADP receptor. Most clinical trials supporting the use of thienopyridines plus aspirin in PCI compared with aspirin alone were originally conducted with ticlopidine. However, clopidogrel has largely replaced ticlopidine for use in PCI because of better tolerability and a lower risk of hematologic abnormalities compared with ticlopidine.Despite the widespread use of clopidogrel in patients undergoing PCI with currently available thienopyridines, several important issues remain. Data from the Clopidogrel to Reduce Events During Observation (CREDO) trial suggest that most of the acute effect seen in reducing periprocedural events with clopidogrel was limited to patients who received the drug at least 6 hours, and perhaps as many as 15 hours, before the procedure.As irreversible inhibitors of platelet function, the effects of thienopyridines are long-lasting, and therefore seem to carry a more or less inherent risk of bleeding complications, also resulting in a reluctance in current clinical practice to give these agents before determining whether a patient is likely to need coronary bypass surgery or using it over very long periods. This balance in efficacy/side-effects may be especially important for patients that receive a drug-eluting stent, which may require prolonged powerful antiplateletherapy to avoid the recently reported very late (>1 year after drug eluting stent implantation) stent thrombosis, a serious an possibly life threatening conditition.Finally, a significant variability in the response to clopidogrel among healthy subjects and patients undergoing PCI or suffering from ACS has been observed, with some individuals having minimal inhibition of ADP-induced platelet aggregation.This concept of clopidogrel resistance led to the concern that some patients may not be adequately protected from the intense platelet activation and aggregation that occur after ACS with or without PCI and are therefore at increased risk for thrombotic events. Because of all of these issues, an improved antiplatelet regimen for the treatment of ACS and to support PCI still seems desirable.Promising results with Prasugrel (CS-747, LY640315) a novel thienopyridine antiplatelet agent that has been shown in preclinical studies and in the JUMBO TIMI 26 trial to be possibly more potent and to have a more rapid onset of action than clopidogrel.ConclusionsThe currently most used thienopyridine antiplatelet agent clopidogrel is an important component of the adjunctive therapy in ACS and PCI with (drug eluting) stenting. However since on one hand not all thrombotic complications are avoided and on the other hand still bleeding complications do occur, there seems to be room for improvement with new and hopefully better (thienopyridine) antiplatelet agents, especially since patients with drug eluting stents implanted may require prolonged treatment with this class of drugs.

Imaging And Percutaneous Valve Therapy

Imaging And Percutaneous Valve TherapyThe scope of percutaneous cardiac therapy has expanded from percutaneous coronary and peripheral intervention to percutaneous valve intervention, first used in the mid eighties. Today mitral regurgitation represents the second most important native valve disease in Europe (30%) as shown by the Euro Heart Survey.When patients present with symptoms, or when there are objective signs of poor tolerance in patients without symptoms, surgery should be performed using as often as possible surgical mitral valve repair, as this treatment has shown safety, efficacy and good long-term results.However, real life observation, once again from the Euro Heart Survey, has shown that mitral valve repair is performed only 50% of the time. This shortfall is mostly due to a lack of expertise in performing the procedure. Finally, observations from the Euro Heart Survey also stress the fact that half of the patients, despite the presence of severe symptoms and severe mitral regurgitation, are not considered for surgery by their practising physicians. Thus, there is a need for treatment, other than surgery, for high-risk patients or those denied surgery.Percutaneous mitral valve repair was introduced only a few years ago. There are two different approaches to percutaneous mitral valve repair.The first approach is the edge to edge technique, which creates a double mitral valve orifice replicating the surgical intervention pioneered by Professor Alfieri. This technique is very demanding since it requires transseptal catheterisation and sophisticated collaboration between the echocardiographist and interventionist to catch the valve at the appropriate moment and location. Preliminary clinical results obtained in over 100 patients suggest that in expert hands the feasibility of the technique is high (80-90%) and the degree of mitral regurgitation can be reduced to mild in two-thirds of cases. In addition, the risk is low, once again, in experienced centres. In patients where the procedure was successful, two-thirds of the cases remained event free after three years. Thus these data, even if only preliminary, are encouraging.The second possible approach is mitral annuloplasty, which is achieved by introducing a constraining device in the coronary sinus located in the vicinity of the mitral annulus. The rationale here is that ring annuloplasty is almost always combined with other procedures during surgical interventions on the mitral valve. More than ten devices have been designed and three are currently being studied. They share common technical features: distal fixation and proximal fixation in the coronary sinus and a bridge between these two fixating elements. Here the procedure is easier since it only requires a catheterisation of the coronary sinus. Preliminary results from the EVOLUTION study in 60 patients show here again high feasibility (90%) and good safety profiles since almost 80% of the patients experienced no complications within 90 days. Very preliminary efficacy data suggest a reduction in the degree of regurgitation.Clearly at the present stage these two approaches do not yet reach the standard of the multiple surgical techniques that make the success of surgical mitral valve repair.The annuloplasty technique could be potentially used in patients with functional mitral regurgitation, while the edge to edge technique could be used in selected patients with degenerative mitral regurgitation.The potential clinical indications of the new percutaneous techniques are represented by the vast group of patients with contraindications or judged to be at very high risk for surgery. Before considering extending the application of these techniques to other patients, trials should be performed in order to answer 3 major questions: how much are we ready to lose in terms of efficacy by going percutaneously as opposed to surgically? Secondly, how much are we ready to risk in patients who have not yet reached surgical indication? And finally, will the performance of this percutaneous intervention compromise subsequent treatment possibilities?Many devices are currently being studied or are at the experimental stage: suture based direct annuloplasty, percutaneous mitral valve replacement, or transpericardial left ventricular remodelling.In conclusion, the first steps of percutaneous mitral valve repair have been taken in almost 300 patients and show the feasibility of this technique suggesting also a reduction in the degree of mitral regurgitation.Today, we are at the stage of evaluation and the research should be carefully evaluated in comparison with surgery and standard contemporary medical treatment including cardiac resynchronisation. Trials such as EVEREST II, EVOLUTION II, and AMADEUS are underway.The development of these new techniques will require close collaboration between engineers, interventionalists, imaging specialists, and surgeons.

Plague Suspected In Death Of Man In Arizona

Eric York, a 37 year old wildlife biologist who worked at the Grand Canyon National Park who was found dead at his home on the South Rim of the Canyon in Arizona on November 2nd, probably died of the plague caught while carrying out an autopsy on a mountain lion that had probably died of the disease a week earlier.Plague, due to the bacterium Yersinia pestis, was confirmed as the likely cause of death following preliminary laboratory tests at the Arizona Department of Health Services (ADHS) and the Centers for Disease Control and Prevention (CDC).York had been treated at a local clinic for flu like symptoms that started three days after he did the autopsy, but nothing more serious than that was diagnosed at the time. When he was found dead health officials suspected either plague or hantavirus that causes a type of hemorrhagic fever, and immediately tracked down 49 people who had been in recent contact with him so they could have aggressive antibiotic treatment. None of them has become ill.Plague is primarily a disease of animals and rarely infects humans, who can catch it from being bitten by rodent fleas or, as is suspected in the case of York, from direct contact with infected animals. York' symptoms were similar to those of pneumonic plague, the most serious, but least common form of plague.Plague can be passed on from one human to another, and from animals to humans, through coughing and sneezing, which thrusts infected droplets into the air that is then breathed in by others. However, according to the CDC, human to human infection is rare, and their records show the last time this happened in the US was in 1924.Symptoms of pneumonic plague include: high fever, chills, nausea, chest pain, cough, headache, and blood in the saliva. Symptoms are often accompanied by a painful, enlarged lymph node in the groin or armpit. If treated early with antibiotics, the chances of survival are very high.Anyone who has these symptoms, particularly if they have been exposed to fleas, sick cats, rodents or rabbits in areas where plague may be active, should seek medical attention immediately. Plague is considered endemic high in the mountains of northern Arizona (above 4,500 feet). 48 cases of plague have been reported in the state since 1977, eight of which were fatal. Not one was reported between 2001 and 2007, which officials put down to drought conditions and high summer temperatures.In September 2007, Arizona health officials released news of the state's first human infection since 2000, a woman in Apache County, who became ill following a flea bite at her home in the northern part of the state. She was given antibiotics and is now recovering, they said.Craig Levy, head of Arizona's Vector Borne and Zoonotic Disease Program, said at the time that:"The recent appearance of plague activity in two northern counties has us concerned that we may see plague in other areas as well." Animal cases of plague in Arizona in 2007 include prairie dog colony die-offs in two separate neighbourhoods in Flagstaff in Coconino County, and a pet cat in Prescott in Yavapai County.Arizona state health officials warned campers, hunters, hikers and others who live at 4,500 feet or higher or are visiting the area, to take the following precautions to avoid being exposed to the plague: Do not handle sick or dead animals.Don't go near rodent burrows. Avoid exposure to fleas. Stop your dog or cat from roaming as they can bring home plague infected fleas. Use flea control products on your dog or cat, ask your veterinarian about the best ones. Wear protective gloves when cleaining or skinning wild animals, for instance for cooking. If cooking game meat, do so at 180 degrees, until the juices run clear. If you get start getting symptoms like those listed above, within 6 days of a potential exposure, seek medical help at once. If your cat falls ill, get it checked by a veterinarian. For more information call the Grand Canyon National Park Incident Information Center at (928) 638-7922 or (928) 638-7688.

CDC: New respiratory bug has killed 10

ATLANTA - A mutated version of a common cold virus has caused 10 deaths in the last 18 months, U.S. health officials said Thursday. Adenoviruses usually cause respiratory infections that aren't considered lethal. But a new variant has caused at least 140 illnesses in New York, Oregon, Washington and Texas, according to a report issued Thursday by the U.S. Centers for Disease Control and Prevention.
CDC officials don't consider the mutation to be a cause for alarm for most people, and they're not recommending any new precautions for the general public.
"It's an uncommon infection," said Dr. Larry Anderson, a CDC epidemiologist.
The illness made headlines in Texas earlier this year, when a so-called boot camp flu sickened hundreds at Lackland Air Force Base in San Antonio. The most serious cases were blamed on the emerging virus and one 19-year-old trainee died.
"What really got people's attention is these are healthy young adults landing in the hospital and, in some cases, the ICU," said Dr. John Su, an infectious diseases investigator with the CDC.
There are more than 50 distinct types of adenoviruses tied to human illnesses. They are one cause of the common cold, and also trigger pneumonia and bronchitis. Severe illnesses are more likely in people with weaker immune systems.
Some adenoviruses have also been blamed for gastroenteritis, conjunctivitis and cystitis.
There are no good antiviral medications for adenoviruses. Patients usually are treated with aspirin, liquids and bed rest.
Some people who get infected by the new bug probably would not suffer symptoms, and some may just feel a common cold. Sick people should see a doctor if they suffer a high fever or have trouble breathing, Anderson said.
In the CDC report, the earliest case of the mutated virus was found in an infant girl in New York City, who died last year. The child seemed healthy right after birth, but then became dehydrated and lost appetite. She died 12 days after she was born.
Tests found that she been infected with a form of adenovirus, called Ad14, but with some little differences, Su said.
It's not clear how the changes made it more lethal, said Linda Gooding, an Emory University researcher who specializes in adenoviruses.
Earlier this year, hundreds of trainees at Lackland became ill with respiratory infections. Tests showed a variety of adenoviruses in the trainees, but at least 106 — and probably more — had the mutated form of Ad14, including five who ended up in an intensive care unit
In April, Oregon health officials learned of a cluster of cases at a Portland-area hospital. They ultimately counted 31 cases, including seven who died with severe pneumonia. The next month, Washington state officials reported four hospitalized patients had the same mutated virus. One, who also had AIDS, died.
The Ad14 form of adenovirus was first identified in 1955. In 1969, it was blamed for a rash of illnesses in military recruits stationed in Europe, but it's been detected rarely since then. But it seems to growing more common.
The strain accounted for 6 percent of adenovirus samples collected in 22 medical facilities in 2006, while none was seen the previous two years, according to a study published this month in the medical journal Clinical Infectious Diseases.
The new bug could have implications for the military. Other forms of adenoviruses have been a common cause of illness in recruits. Military officials are bringing back an adenovirus vaccine — administered as a pill — that was given to recruits from 1971 to 1999, CDC officials said.
A Barr Pharmaceuticals vaccine for the military, currently being tested, is expected to be licensed in 2009. Like the old pill, it focuses on adenovirus serotypes 4 and 7, because those bugs have been persistent problems, said Col. Art Brown, an Army physician involved in the product's development.
Some CDC officials said a vaccination against the mutant Ad14 might be needed. Brown said it isn't clear if the mutant Ad14 will be an enduring threat, but the military will monitor illness reports.
"If it persists, then we'd consider if the vaccine needs to be modified further," said Brown, of the U.S. Army Medical Materiel Development Activity.

Musculoskeletal Regeneration Research Receives First-Of-A Knd ' Emerging Frontiers' NSF Grant

Musculoskeletal Regeneration Research Receives First-Of-A Knd ' Emerging Frontiers' NSF GrantA research group led by Dr. Cato T. Laurencin, with faculty representing five departments at the University of Virginia, will work on a first-of-its kind, $2 million grant project as they explore novel methods for the regeneration of musculoskeletal tissues. The grant from the National Science Foundation is known as an EFRI grant -- Emerging Frontiers in Research and Innovation. The group, led by Dr. Laurencin, with faculty in orthopaedic surgery, chemical engineering, biomedical engineering, electrical engineering and materials science, will investigate several innovative ways to engineer new material surfaces that will allow a range of musculoskeletal tissues to grow. "These studies should give us important fundamental information that will be broadly applicable in tissue engineering and regenerative medicine," said Dr. Laurencin, principal investigator (PI) for the studies and Professor of Orthopaedic Surgery, Biomedical Engineering and Chemical Engineering at the University of Virginia. "This grant complements my recently awarded Department of Defense grant aimed at exploring new strategies for limb regeneration." Laurencin said that a team approach is needed to tackle such a great problem. "The National Science Foundation Grant allows for a broad team that will explore important material surface cues to permit optimum cellular interactions. Learning how best to design materials, create artificial tissues and understand their healing abilities -- ultimately, for the successful treatment of our patients -- is what this translational research program aims to do," Laurencin said.

Musculoskeletal Regeneration Research Receives First-Of-A Knd ' Emerging Frontiers' NSF Grant

Musculoskeletal Regeneration Research Receives First-Of-A Knd ' Emerging Frontiers' NSF GrantA research group led by Dr. Cato T. Laurencin, with faculty representing five departments at the University of Virginia, will work on a first-of-its kind, $2 million grant project as they explore novel methods for the regeneration of musculoskeletal tissues. The grant from the National Science Foundation is known as an EFRI grant -- Emerging Frontiers in Research and Innovation. The group, led by Dr. Laurencin, with faculty in orthopaedic surgery, chemical engineering, biomedical engineering, electrical engineering and materials science, will investigate several innovative ways to engineer new material surfaces that will allow a range of musculoskeletal tissues to grow. "These studies should give us important fundamental information that will be broadly applicable in tissue engineering and regenerative medicine," said Dr. Laurencin, principal investigator (PI) for the studies and Professor of Orthopaedic Surgery, Biomedical Engineering and Chemical Engineering at the University of Virginia. "This grant complements my recently awarded Department of Defense grant aimed at exploring new strategies for limb regeneration." Laurencin said that a team approach is needed to tackle such a great problem. "The National Science Foundation Grant allows for a broad team that will explore important material surface cues to permit optimum cellular interactions. Learning how best to design materials, create artificial tissues and understand their healing abilities -- ultimately, for the successful treatment of our patients -- is what this translational research program aims to do," Laurencin said.

Diesel Air Pollution Linked To Heart Attack And Stroke In Healthy Men

Diesel Air Pollution Linked To Heart Attack And Stroke In Healthy MenUK and Swedish researchers found that diesel fumes from road vehicles increased blood clots and platelets in healthy volunteers. These are symptoms closely linked to increased risk of heart attack and stroke.The researchers reported the results of a small study to a meeting of the American Heart Association's Scientific Sessions 2007 held in Orlando, Florida, earlier this week.Previous observational and epidemiological studies have also shown a close link between exposure to traffic pollution and heart attack, said study lead author Dr Andrew Lucking, who is a cardiology fellow at the University of Edinburgh in Scotland, UK."This study shows that when a person is exposed to relatively high levels of diesel exhaust for a short time, the blood is more likely to clot. This could lead to a blocked vessel resulting in heart attack or stroke," said Lucking.Lucking and colleague carried out a double blind, randomized cross-over study on 20 healthy male participatns aged from 21 to 44. Using a specially designed exposure chamber, the men were separately exposed to filtered air (this was the control) and then to 300 mg per cubic metre (mcg/m3) of diesel exhaust fumes, which is roughly the concentration you breathe in while standing by a busy street.The researchers measured clot formation, blood coagulation, platelet activity and markers of inflammation by attaching each participant to a perfusion chamber and allowing a small amount of blood to pass through it. This was done 2 hours after exposure and then again 6 hours after exposure.Clot formation was assessed by passing the blood through a special shear chamber that simulates the types of pressure the blood would be under in blood vessels. The researchers tested the blood at high shear and low shear.Platelet activation was assessed by measuring the number of platelets associated with white blood cells. When platelets are activated they stick to white blood cells like neutrophils and monocytes and form clumps, thereby playing a key role in the formation of blood clots.The results showed that: Breathing diesel fumes increased clot formation in the low shear chamber by 24.2 per cent compared to breathing filtered air.In the high shear chamber the increase in clot formation from diesel fumes was 19.1 per cent.These effects were observed at both 2 and 6 hours after exposure to diesel fumes.Breathing diesel fumes increased platelet-neutrophil aggregates from 6.5 to 9.2 per cent 2 hours after exposure.It also increased platelet-monocyte aggregates from 21 per cent to 25 per cent 2 hours after exposure.But at 6 hours after exposure the platelet activation increases due to diesel fumes were not statistically significant.Lucking said: "High levels of traffic pollution are known to increase the risk of heart attack in the immediate hours or days after exposure."He said this study showed a "potential mechanism that could link exposure to traffic-derived air pollution with acute heart attack."Although these results apply to diesel engine fumes, it's not clear whether gasoline powered engines would have the same effect, said the researchers. Diesel fumes contain a much higher concentration of very fine particles, they said.Diesel engines are on the rise because they offer superior fuel economy, but, as Lucking explained:"While diesel engines burn more efficiently, they also put more fine particulate matter into the air."The researchers said while exercise was good for people with cardiovascular disease, they would not recommend they exercise near traffic congestion.The UK and Swedish team will be working together on the next step, which is to test the effectiveness of the particle traps fitted to diesel engines to reduce exhaust particles."Exposure to air pollution clearly is detrimental and we must look at ways to reduce pollution in the environment," said Lucking.An earlier study published in the 13th September issue of the NEJM , also by UK and Swedish researchers, showed that men with coronary heart disease who inhaled diesel fumes experienced a three fold increase in stress on the heart.

工作

昨天上班的时候有两间事,都是属于口误造成的.
第一件是一个学生寄信,就问同事(杀鸟那个),请问信交在哪里?结果他回了一句,交信在类边,啥子信交哦,表乱说.第二件是外面的人用特快专递寄了一个篮球到学校,一起上班的阿姨说了一句话，把我恩笑到了住,拉说:硬是钱多了索,寄个球!