A new methodology for rapidly measuring the level of antibiotic drug molecules in human blood serum has been developed, paving the way to applications within drug development and personalised medicine.
The study, describes the exploitation of a sensor for measuring the concentration of effective antibiotics in blood, giving an indication of their efficiency against disease causing pathogens, for instance multidrug resistant hospital ‘superbugs’.
This development could potentially give a far greater understanding of the effectiveness of drug dosages required for different individuals, reducing potential toxic effects, allowing personalised treatment for patients and leading to new insights into optimal clinical regimes, such as combination therapies.
When effective, antibiotic molecules impose cellular stress on a pathogen’s cell wall target, such as a bacterium, which contributes to its breakdown. However, competing molecules in solution, for example serum proteins, can affect the binding of the antibiotic to the bacterium, reducing the efficacy of the drug. Serum proteins bind to drugs in blood and, in doing so, reduce the amount of a drug present and its penetration into cell tissues.
As the amount of antibiotics that bind to serum proteins will vary between individuals, it is extremely valuable to be able to determine the precise amount of the drug that is bound to serum proteins, and how much is free in the blood, in order to be able to accurately calculate the optimum dosage.
Existing biosensors on the market do not measure cellular stress, however, the nanomechanical sensor exploited by a group of researchers from the London Centre for Nanotechnology (LCN) at UCL, the University of Cambridge, the University of Queensland and Jomo Kenyatta University of Agriculture and Technology, can accurately measure this important information even when antibiotic drug molecules are only present at very low concentrations.
The researchers coated the surface of a nanomechanical cantilever array with a model bacterial membrane and used this as a surface stress sensor. The sensor is extremely sensitive to tiny bending signals caused by its interactions with the antibiotics, in this case, the FDA-approved vancomycin and the yet to be approved oritavancin, which appears to deal with certain vancomycin-resistant bacteria, in the blood serum.
This investigation has yielded the first experimental evidence that drug-serum complexes (the antibiotics bound to the competing serum proteins) do not induce stress on the bacteria and so could provide realistic in-vitro susceptibility tests for drugs and to define effective doses which are effective enough but less toxic to patients.
In the future, the researchers believe that with a suitably engineered surface probe, this sensor could be paired with customised drug delivery for anaesthetics, anti-cancer, anti-HIV and antibacterial therapies.
The lead author of the study, Dr. Joseph W. Ndieyira of the LCN, said ‘This discovery represents a major advance in our fundamental understanding of the pathways between chemical and mechanical signals in a complex media, such as blood serum, and how this information can be used to tune the efficacy of drugs and to minimise the potential toxic side effects.’ EurekAlert

Pain from inflammation sidelines thousands of Americans each year. Many face a tough choice: deal with the pain, take a potentially addictive opioid or use a non-steroidal anti-inflammatory drug that may increase risk for cardiovascular disease or gastrointestinal bleeding.

Now, researchers at the Stanford University School of Medicine have discovered a compound thought to be non-addictive and safe for the heart and gastrointestinal system that reduces inflammatory pain in mice and rats. They call the compound Alda-1.

The researchers have been working with Alda-1 for more than five years. They discovered it while searching for the reason that moderate drinkers have less-severe heart attacks than non-drinkers or heavy alcohol drinkers. They found that alcohol increases the activity of an enzyme called aldehyde dehydrogenase 2. This enzyme breaks down a by-product of alcohol called acetaldehyde, forming free radicals that can damage cells. The enzyme also breaks down additional toxic aldehydes that are formed in the body because of oxidative stress, such as that occurring during a heart attack. Alda-1, an abbreviation for aldehyde dehydrogenase activator 1, kicks the enzyme into high gear, allowing it to break down toxic aldehydes more quickly and leaving less time for them to cause damage. (Coincidentally, Alda is also the name of Mochly-Rosen

In a study that included long-term follow-up of obese patients with type 2 diabetes, bariatric surgery was associated with more frequent diabetes remission and fewer complications than patients who received usual care.

Obesity and diabetes have reached epidemic proportions and constitute major health and economic burdens. Worldwide, 347 million adults are estimated to live with diabetes and half of them are undiagnosed.

Studies show that type 2 diabetes is preventable. The incidence of diabetes can be reduced by as much as 50 percent by lifestyle and pharmacological interventions, according to background information in the article.

Short-term studies show that bariatric surgery results in remission of diabetes. The long-term outcomes for bariatric surgery and diabetes remission and diabetes-related complications have not been known.

Lars Sjostrom, M.D., Ph.D., of the University of Gothenburg, Sweden, and colleagues performed a follow-up of the Swedish Obese Subjects (SOS) study, conducted at 25 surgical departments and 480 primary health care centres in Sweden. Of patients recruited between September 1987 and January 2001, 260 of 2,037 control patients and 343 of 2,010 bariatric surgery patients had type 2 diabetes at baseline.

For the current analysis, the presence of diabetes was determined at SOS health examinations and information on diabetes complications was obtained from national health registers. For diabetes complications, the median follow-up time was 17.6 years in the control group, and 18.1 years in the surgery group.

The proportion of patients in remission (defined as blood glucose <110 mg/dL and no diabetes medication) after 2 years was 72.3 percent in the surgery group and 16.4 percent in the control group. At 15 years, the diabetes remission rates decreased to 30.4 percent for bariatric surgery patients and 6.5 percent for control patients. All types of bariatric surgery (adjustable or nonadjustable banding, vertical banded gastroplasty, or gastric bypass) were associated with higher remission rates compared with usual care. In addition, bariatric surgery was associated with a decreased incidence of microvascular and macrovascular complications.

A new generation of coronary artery stent that combines a biodegradable component with an ultrathin scaffold showed promising results compared with the current gold standard, in a large population of coronary artery disease patients, according to a new study.

The experimental stent

Researchers from Penn Medicine have developed a safe and effective technique for inducing sleep in patients with severe obstructive sleep apnea. The new procedure, known as drug-induced sleep endoscopy (DISE), uses progressive doses of anesthesia to pharmacologically induce sleep to the point of the obstruction-causing apnea in a short time frame without a dip in blood oxygen level and with few side effects.
The Penn team recently tested the procedure in 97 patients with severe sleep apnea who were candidates for transoral robotic resection of the tongue, the removal of a section of the tongue where it meets the epiglottis to prevent the tongue from obstructing the airway during sleep, the most common surgical procedure for the treatment of severe sleep apnea.
TransOral Robotic Surgery (TORS) was originally developed by Penn head and neck surgeons for the removal of benign and malignant tumours of the mouth and throat.