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

Scientists have moved a step closer to being able to preserve fertility in young boys who undergo chemotherapy and radiation treatments for cancer. The new research addresses the safety of an option scientists are developing for boys who aren

Injured patients who have alcohol in their blood have a reduced risk for developing cardiac and renal complications, according to a study from the University of Illinois at Chicago School of Public Health. Among patients who did develop complications, those with alcohol in their blood were less likely to die.
‘After an injury, if you are intoxicated there seems to be a substantial protective effect,’ says UIC injury epidemiologist Lee Friedman, author of the study. ‘But we don

A study by researchers at Hospital for Special Surgery (HSS) finds that electromyography (EMG) testing to determine the quality of donor nerves can improve the outcome of nerve transfer surgery to restore function in patients with a brachial plexus injury. EMG is a sophisticated test used to objectively measure muscle and nerve function.
‘Our study found that pre-operative EMG evaluation should be considered a critical component of the donor nerve selection process when planning brachial plexus nerve transfer reconstruction,’ said Scott W. Wolfe, MD, senior investigator and Director of the Center for Brachial Plexus and Traumatic Nerve Injury at Hospital for Special Surgery in New York City.
The brachial plexus is a network of nerves that extends from the spinal cord in the neck, under the collarbone and down the arm. These nerves control the hand, wrist, elbow and shoulder. Injury to the brachial plexus can be devastating, and the most common cause is a serious accident or sports injury. Nerve reconstruction is considered when the nerves are so severely damaged they cannot recover on their own. These complex operations can take up to 12 hours.
One way surgeons can reconstruct nerves is by performing a nerve transfer to restore function. They carefully dissect out portions, or fascicles, of nearby functioning nerves (called ‘donor nerves’) and transfer these fascicles to the injured nerves to restore electrical connectivity and enable nerve regeneration to the paralysed muscle. ‘A nerve transfer takes a working nerve from one muscle and transfers part of that nerve to the injured, non-working nerve or another muscle, so the two muscles can share the nerve and regain function,’ Dr. Wolfe explained.
Electromyography is often used in the pre-operative assessment of brachial plexus injuries to estimate the degree of damage. However, the ability to predict surgical outcomes using pre-operative EMG to test donor nerves had not been previously evaluated. Researchers hypothesised that the health of the donor nerve and corresponding muscle, as assessed by EMG, could predict the outcome of nerve transfer surgery.
A retrospective review was conducted to investigate outcomes of nerve transfers for elbow flexion (ability to bend one’s elbow) and shoulder abduction (ability to lift arm away from the body). Muscle strength was graded both pre-operatively and at least one-year after surgery. Pre-operative EMG results for donor nerves were classified on a scale that rated their level of function and then compared with the patient’s muscle strength and range of motion after surgery.
Forty nerve transfers were identified. Twenty-seven were performed for elbow flexion and 13 for shoulder abduction. Overall, the 29 transfers using a normal donor nerve showed significantly greater post-operative improvement in muscle strength and function than the 11 transfers with the less robust donor nerve, as classified by EMG.
In the shoulder patients, the use of normal donor nerves resulted in greater strength and active motion compared to less robust donor nerves. In the elbow cohort, double nerve transfers with two normal donor nerves demonstrated improved strength compared to double nerve transfers when one of the donor nerves was affected by the injury.
Joseph Feinberg, MD, physiatrist-in-chief and co-medical director of the Brachial Plexus Center at HSS, has developed a system to classify potential donor nerves according to four levels of functioning: normal, moderately limited function, very limited function and no function.
‘Interestingly, we found that some of the donor nerves that were damaged and had some functional limitations were still healthy enough to do their job after the nerve transfer operation,’ Dr. Feinberg said. ‘On the flip side, if electromyography shows that a potential donor nerve is not at all functional, the surgeon may want to consider a different nerve donor, or potentially another solution such as nerve grafting or muscle transfer.’
‘Our findings demonstrate that a semi-quantitative EMG classification describing the quality of donor nerves can predict outcome as measured by post-operative muscle strength and range of motion,’ said Dr. Wolfe. ‘Despite the small numbers studied, we observed significantly greater gains in strength and range of motion in the normal donor nerve group as compared to the less robust donor nerves. EMG evaluation has value as a confirmatory component of the donor nerve selection process when planning brachial plexus surgery.’ EurekAlert