A research team in Israel has devised a novel approach to identifying the molecular basis for designing a drug that might one day decrease the risk diabetes patients face of developing Alzheimer's disease.
The team presented its work at the 57th annual meeting of the Biophysical Society, held Feb. 2-6 in Philadelphia, Pa.
A recent study suggests that people who suffer from type 2 diabetes face twice the risk of developing Alzheimer's disease later in life compared to those who do not have diabetes.
The link these diseases share relates to the formation of two types of peptide deposits that aggregate, or clump together.
Peptides are chains of amino acids; longer chains form proteins. One type of peptide, called amyloid beta, is found in Alzheimer plaques in neurons of the brain. The other type, amylin, is found in the pancreas and the brain.
Two years ago, researchers found both molecules in the pancreas of diabetic patients, and in both diseases their presence has been linked to the progression of the disease state.
To explore the hypothesis that interactions between the two molecules might play a critical role in the self-assembly of peptides that leads to protein aggregation, Yifat Miller, assistant professor from Ben-Gurion University of the Negev, Beer-Sheva, Israel, characterized the way the two protein molecules interact with each other through an examination of their structure. It was the first analysis of its kind.
“By identifying the specific 'hot regions' of these peptides that strongly interact with each other, our study may provide insight into the link between type 2 diabetes and Alzheimer's disease,” Miller said. “We believe that preventing these interactions by developing a drug will decrease the risk that type 2 diabetes patients face of developing Alzheimer's disease later life.”
Collaborator Aphrodite Kapurniotu of Technische Universität München, Freising-Weihenstephan, Germany, performed the molecular experimental examination of the interactions between these two peptides. Miller's research received funding from the European Union Seventh Framework Programme.
Three clinical trials that seek to find more effective treatments for influenza are enrolling volunteers with influenza at the National Institutes of Health’s Clinical Center in Bethesda, Md., and at several dozen other domestic and international sites.
One study examines whether treatment with a licensed influenza drug, oseltamivir, reduces the time that infected people continue to produce virus in the upper airway.
A second tests whether a combination of three licensed flu antiviral drugs works better than oseltamivir alone in people with influenza who have chronic health conditions, such as heart or lung disease, that put them at greater risk of severe illness.
The third tests whether treatment with plasma enriched with anti-influenza antibodies improves the condition of hospitalized influenza patients compared to standard antiviral treatment alone.
“This year’s flu season came earlier than usual and has been particularly hard on the elderly,” said Anthony S. Fauci, M.D., director of the National Institute of Allergy and Infectious diseases, part of the NIH. “Despite our best efforts to prevent influenza through vaccination, people still get sick every year with the flu. At best, influenza infection is a miserable experience. At worst, it can be a deadly one. We need better ways to treat people with influenza, which kills thousands of people in the United States each year, and clinical research supported by NIAID helps to address that need.”
The studies are sponsored by the NIAID Influenza Research Collaboration, a clinical research network funded by the NIAID Division of Clinical Research (DCR). Researchers at 36 sites in the United States and additional sites in Argentina, Australia, Mexico and Thailand participate.
Activities of the collaboration are coordinated under the leadership of Richard Davey, M.D., deputy clinical director, NIAID DCR, and John Beigel, M.D., medical affairs scientist on contract with NIAID.
Although oseltamivir has been approved for use in the United States since 1999, no studies have shown conclusively whether the drug significantly reduces the amount of virus produced (shed) by an infected person. Reduced shedding would likely lessen the chances of an infected person passing the virus to others.
The oseltamivir trial will enroll a total of approximately 560 people at 31 locations in the United States, Argentina and Thailand.
Enrollees must be between the ages of 18 and 65 years and have confirmed influenza virus infection but not be hospitalized or suffering from any other health conditions that would put them at risk of developing influenza complications.
The trial comparing oral oseltamivir alone to treatment with oseltamivir plus two other licensed antiviral drugs is enrolling a total of up to 720 adults at sites in the United States, Argentina, Australia, Mexico and Thailand.
In addition to having laboratory-confirmed influenza, enrollees must have at least one other characteristic that places them at higher risk of developing serious complications. Asthma and other lung disorders, heart disease, obesity, weakened immune function and being over age 65 are some of the conditions that place people at higher risk for serious disease.
The third trial is enrolling children as well as adults, including pregnant women, hospitalized with severe influenza.
This trial aims to enroll a total of approximately 100 people at approximately 20 sites in the United States.
All participants will receive standard drug treatment for influenza, and half will also receive two infusions of plasma enriched with antibodies against the virus. Antibodies are infection-fighting proteins produced by the immune system.
The antibodies used in the trial are derived from blood donated by volunteers who were recently vaccinated against flu or are recovered from a recent bout of flu.
“Anecdotal evidence suggests that the addition of plasma with high levels of antibody against the virus may confer additional benefit over drug treatment alone. This trial will be one of the first to examine that possibility in a scientifically rigorous fashion,” said Dr. Davey. “The outcome of this trial may provide valuable data on how best to treat patients hospitalized with severe influenza.”
Detailed information about each of the trials now enrolling volunteers is also available at http://www.clinicaltrials.gov .
SACRAMENTO – The California Department of Public Health (CDPH) issued 10 penalties to seven California hospitals and fines totaling $775,000 after investigations found the facilities’ noncompliance with licensing requirements caused, or was likely to cause, serious injury or death to patients.
The following hospitals received penalties:
– Adventist Medical Center, Hanford, Kings County: The hospital failed to ensure the health and safety of a patient when it did not follow established policies and procedures for safe distribution and administration of medication. The penalty is $50,000. This is the hospital’s third administrative penalty.
– Fresno Surgical Hospital, Fresno, Fresno County: The hospital failed to ensure the health and safety of a patient when it did not follow established surgical policies and procedures. The penalty is $75,000. This is the hospital’s second administrative penalty.
– Memorial Medical Center, Modesto, Stanislaus County: The hospital failed to ensure the health and safety of a patient when it did not follow established surgical policies and procedures related to patient care. The penalty is $50,000. This is the hospital’s first administrative penalty.
– Memorial Medical Center, Modesto, Stanislaus County: The hospital failed to ensure the health and safety of a patient when it did not follow established policies and procedures related to patient care. The penalty is $75,000. This is the hospital’s second administrative penalty.
– Placentia Linda Hospital, Placentia, Orange County: The hospital failed to ensure the health and safety of a patient when it did not follow established policies and procedures relating to patient protection. The penalty is $50,000. This is the hospital’s first administrative penalty.
– Santa Clara Valley Medical Center, San Jose, Santa Clara County: The hospital failed to ensure the health and safety of a patient when it did not follow established policies and procedures related to care in emergency situations. The penalty is $100,000. This is the hospital’s third administrative penalty.
– St. Mary’s Medical Center, San Francisco, San Francisco County: The hospital failed to ensure the health and safety of a patient when it did not follow surgical policies and procedures. This resulted in a patient having to undergo a second surgery to remove a retained foreign object. The penalty is $75,000. This is the hospital’s second administrative penalty.
– St. Mary’s Medical Center, San Francisco, San Francisco County: The hospital failed to ensure the health and safety of a patient when it did not follow established policies and procedures for safe distribution and administration of medication. The penalty is $100,000. This is the hospital’s third administrative penalty.
– UCSF Medical Center, San Francisco, San Francisco County: The hospital failed to ensure the health and safety of a patient when it did not follow surgical policies and procedures. This resulted in a patient having to undergo a second surgery to remove a retained foreign object. The penalty is $100,000. This is the hospital’s seventh administrative penalty.
– UCSF Medical Center, San Francisco, San Francisco County: The hospital failed to ensure the health and safety of a patient when it did not follow surgical policies and procedures. This resulted in a patient having to undergo a second surgery to remove a retained foreign object. The penalty is $100,000. This is the hospital’s eighth administrative penalty.
Administrative penalties are issued under authority granted by Health and Safety Code section 1280.1. Incidents that occurred prior to 2009 carry a fine of $25,000.
New legislation took effect Jan. 1, 2009, that increased fines for incidents that occurred in 2009 or later.
Under the new provisions, an administrative penalty carries a fine of $50,000 for the first violation, $75,000 for the second, and $100,000 for the third or subsequent violation by the licensee. Incidents that occurred prior to 2009 are not counted when determining the fine amounts.
When hospitals receive their survey findings, they are required to provide CDPH with a plan of correction to prevent future incidents.
Hospitals can appeal an administrative penalty by requesting a hearing within ten calendar days of notification. If a hearing is requested and the penalty upheld following an appeal, the penalties must be paid.
All hospitals in California are required to be in compliance with applicable state and federal laws and regulations governing general acute care hospitals, acute psychiatric hospitals, and special hospitals. The hospitals are required to comply with these standards to ensure quality of care.
A new computed tomography (CT) scanner substantially reduces potentially harmful radiation while still improving overall image quality.
National Institutes of Health researchers, along with engineers at Toshiba Medical Systems, worked on the scanner.
An analysis of data on 107 patients undergoing heart scans found that radiation exposure was reduced by as much as 95 percent compared to the range of current machines, while the resulting images showed less blurriness, reduced graininess, and greater visibility of fine details.
The machine recently received approval by the U.S. Food and Drug Administration, but more studies will be needed before it can be adopted for wide clinical use.
“CT scans are a great diagnostic tool for heart disease because we can obtain high-resolution 3-D images of the heart quickly and non-invasively,” said coauthor Andrew Arai, M.D., chief of the Cardiovascular and Pulmonary Branch at the NIH’s National Heart, Lung, and Blood Institute (NHLBI). “However, the benefits of CT have been tempered by concerns over the radiation required to achieve these images. With this next-generation device, we are close to achieving the best of both worlds.”
Most CT scanners available in clinics have 64 rows of X-ray detectors. The new scanner has 320 detector rows, which allow imaging of a larger area of the body at one time.
The new scanner also has a more powerful X-ray beam generator. And the gantry – the doughnut-shaped part of the CT machine – can complete a full rotation in 275 milliseconds. Current scanners top out at 350-millisecond rotations.
In addition to hardware advances, the NHLBI team worked on the device settings and features with Toshiba to optimize radiation usage and image quality.
“These multiple advancements work together to allow us to image the entire heart within one heartbeat about 93 percent of the time,” noted lead study author Marcus Chen, M.D., a clinician in the NHLBI’s Advanced Cardiovascular Imaging Laboratory.
“These improvements could help clinicians identify problems in even the smallest blood vessels or enable them to conduct complicated tests like measuring blood flow in the heart while limiting radiation exposure,” Chen added.
Between July and October 2012, Chen and colleagues used the new scanner to perform CT angiographies – which look for plaque buildup or other problems in the coronary arteries – on 107 adults of varied height and weight, between the ages of 27 and 82.
The research team then compared both the radiation dose and image quality of the new CT scans to 100 scans taken on a first-generation 320-detector row scanner at the NIH campus between January and April 2010.
The median effective radiation dose for the new scanner was 0.93 millisieverts (mSv), compared to 2.67 mSv for the first-generation scanner, and almost every patient (103 of 107) received less than 4 mSv of radiation. (millisieverts reflect how much radiation a body absorbs, so it can help determine potential health risks.
The average person receives about 2.4 mSv of background radiation each year.) Nationwide, coronary CT angiography typically involves effective radiation doses between 5 and 20 mSv, depending on the patient's body type and the quality of the machine.
The study, which was published Jan. 22 online in the journal Radiology, was funded by the NHLBI intramural research program.
The CT machine was provided to the NHLBI by Toshiba Medical Systems through a cooperative research agreement.