A centuries-old herbal medicine, discovered by Chinese scientists and used to effectively treat malaria, has been found to potentially aid in the treatment of tuberculosis and may slow the evolution of drug resistance.

In a promising study led by Robert Abramovitch, a Michigan State University microbiologist and TB expert, the ancient remedy artemisinin stopped the ability of TB-causing bacteria, known as Mycobacterium tuberculosis, to become dormant. This stage of the disease often makes the use of antibiotics ineffective.

‘When TB bacteria are dormant, they become highly tolerant to antibiotics,’ Abramovitch said, an assistant professor in the College of Veterinary Medicine. ‘Blocking dormancy makes the TB bacteria more sensitive to these drugs and could shorten treatment times.’

One-third of the world’s population is infected with TB and the disease killed 1.8 million people in 2015, according to the Centers for Disease Control and Prevention.

Mycobacterium tuberculosis, or Mtb, needs oxygen to thrive in the body. The immune system starves this bacterium of oxygen to control the infection. Abramovitch and his team found that artemisinin attacks a molecule called heme, which is found in the Mtb oxygen sensor. By disrupting this sensor and essentially turning it off, the artemisinin stopped the disease’s ability to sense how much oxygen it was getting.

‘When the Mtb is starved of oxygen, it goes into a dormant state, which protects it from the stress of low-oxygen environments,’ Abramovitch said. ‘If Mtb can’t sense low oxygen, then it can’t become dormant and will die.’

Abramovitch indicated that dormant TB can remain inactive for decades in the body. But if the immune system weakens at some point, it can wake back up and spread. Whether it wakes up or stays asleep’ though, he said TB can take up to six months to treat and is one of the main reasons the disease is so difficult to control.

‘Patients often don’t stick to the treatment regimen because of the length of time it takes to cure the disease,’ he said. ‘Incomplete therapy plays an important role in the evolution and spread of multi-drug resistant TB strains.’

He said the research could be key to shortening the course of therapy because it can clear out the dormant, hard-to-kill bacteria. This could lead to improving patient outcomes and slowing the evolution of drug-resistant TB.

After screening 540,000 different compounds, Abramovitch also found five other possible chemical inhibitors that target the Mtb oxygen sensor in various ways and could be effective in treatment as well.

‘Two billion people worldwide are infected with Mtb,’ Abramovitch said. ‘TB is a global problem that requires new tools to slow its spread and overcome drug resistance. This new method of targeting dormant bacteria is exciting because it shows us a new way to kill it. ‘

Michigan State University msutoday.msu.edu/news/2016/ancient-chinese-malaria-remedy-fights-tb/

Neurosurgeons want the quickest, most accurate information to help them make decisions during brain tumour surgery. A new method could accelerate that process.

Neurosurgeons and pathologists at Michigan Medicine are the first to execute stimulated Raman histology (SRH), a method that improves speed and diagnostic efficiency, in an operating room.

The researchers imaged tissue from 101 neurosurgical patients using conventional methods and the new method. Both techniques produced accurate results, they found, but the new method was much faster.

SRH, if applied widely, could change the pace and structure of an operation.

‘By achieving excellent image quality in fresh tissues, we’re able to make a diagnosis during surgery,’ says first author Daniel A. Orringer, M.D., assistant professor of neurosurgery at the University of Michigan Medical School. ‘This eliminates the lengthy process of sending tissues out of the OR for processing and interpretation.’

Today’s workflow for determining a diagnosis during an operation requires the surgeon wait 30 to 40 minutes while tissue is sent to a pathology lab for processing, sectioning, staining, mounting and interpretation. The entire team in the operating room may be idle while waiting for pathology results, Orringer says.

‘Our technique may disrupt the intraoperative diagnosis process in a great way, reducing it from a 30-minute process to about three minutes,’ Orringer says. ‘Initially, we developed this technology as a means of helping surgeons detect microscopic tumour, but we found the technology was capable of much more than guiding surgery.’

Stimulated Raman scattering microscopy, the technology behind SRH, was developed in 2008, but the hazardous lasers involved made it unsuitable for use in an operating room. A clinical version has now been developed and tested in the operating room for more than a year at U-M, with the fibre-laser-based microscope mounted onto a clinical cart that plugs into the wall.

To interpret the samples, researchers developed SRH, which creates images similar to those currently in use.

SRH uses virtual colouring to highlight the cellular and architectural features of brain tumours, with a result resembling traditional staining. The pathologist is then able to differentiate the tumour tissue from normal brain as usual.

‘It’s very similar to what we currently do in our intraoperative diagnosis, with the exception that the tissue is fresh, has not been processed or stained,’ says senior author Sandra Camelo-Piragua, M.D., assistant professor of pathology at U-M.

In the Nature Biomedical Engineering study, neuropathologists were given 30 specimen samples processed by SRH or traditional methods. They were told the same information about each patient’s medical history and the location of the tumour and asked to make a diagnosis.

Those pathologists, the U-M researchers found, were equally likely to make a correct diagnosis, whether they used SRH or conventional slides.

‘SRH imaging will ensure that appropriate and good-quality tissue is collected to reach our ultimate goal: accurate diagnosis,’ Camelo-Piragua says.

University of Michigan labblog.uofmhealth.org/health-tech/new-technique-slashes-diagnosis-time-during-brain-surgery

Researchers at the University of Huddersfield have developed a new lab technique that may aid the development and success rate of an important anti-cancer treatment. Used particularly in cases of liver cancer, polymer beads are injected into arteries that feed a tumour, where they block the blood flow, cutting off the supply of oxygen and nutrients. The beads then also release an anticancer drug directly into the tumour, reducing the systemic side effects.

What developers need is a safe way of predicting what would happen in a patient’s body if the beads and the drug they contain are modified. Now the new research has provided them with a method.

‘There was no lab mimic that was able to adequately predict how the drug was released from these drug-eluting beads once they were in the body,’ said one of the co-authors, University of Huddersfield pharmaceutical science lecturer and researcher Dr Laura Waters. ‘The article describes a way of doing it in the lab. We compared our results with in vivo data and proved that the method worked.’

Dr Waters is supervising the PhD researcher Tanya Swaine, a graduate of the University of Huddersfield whose doctoral project is sponsored by the company BTG, which manufactures the embolization beads that are used in the therapy.

Tanya and co-researchers were able to carry out lab experiments in which a buffer was pumped at different rates through the beads. They also modified the quantities of drug contained in the beads. By comparing their laboratory observations with in vivo data, the research team was able to establish the validity of their simulation technique.

It will be of practical value to any medical researcher working on a bead-based system, said Dr Waters, enabling them to make accurate predictions without running any risks to patients.

Professor Andy Lewis, Director of R&D at BTG and industrial supervisor in the collaboration commented: ‘We are continually innovating our drug-eluting bead technologies to introduce new features, such as X-ray visibility or biodegradability. It’s important from a product development perspective that if we wanted to put other drugs into the beads, or change anything about their chemistry, we could use this system to predict product behaviour before it is given to people.’

University of Huddersfield www.eurekalert.org/pub_releases/2016-10/uoh-nrp102816.php

Continuous heart monitoring for up to 14 days revealed a higher risk of ischemic stroke among patients who experienced a higher burden of atrial fibrillation, according to Kaiser Permanente research. Patients with a specific irregular heartbeat, called atrial fibrillation (AFib), who were not taking medication to prevent blood clots (anticoagulants), were monitored using a special electrocardiogram (ECG) patch that continuously records the heart’s electrical activity for two weeks and is then analysed for the occurrence and burden of different arrhythmias.
Atrial fibrillation is a major risk factor for stroke and is the most common cardiac irregularity seen by physicians. It currently affects up to an estimated 6 million people in the United States.
Researchers monitored 771 adults with paroxysmal (intermittent) atrial fibrillation treated in Kaiser Permanente’s Northern and Southern California regions over a 3-year period. They found that for each doubling of the amount of time that a patient’s heart was in atrial fibrillation during the monitoring period, there was a 33 percent increased risk of subsequent stroke, independent of other known risk factors.
The burden of atrial fibrillation was defined as the percentage of time spent in this irregular heart rhythm during the monitoring period, which averaged 13.8 days. The findings were derived by linking detailed clinical outcome data from Kaiser Permanente’s electronic medical records with the patch manufacturer’s database of analysed heartbeat data.
‘The availability of data collected from continuous, non-invasive ECG monitoring strategies allows for more comprehensive identification of atrial fibrillation burden, which in turn can help at-risk patients and their providers better evaluate treatment options for reducing the risk of stroke,’ said Alan Go, MD, chief of cardiovascular and metabolic conditions research.

Kaiser Permanente Northern California Division of Research. http://tinyurl.com/h8gbk8b

Case Western Reserve University researchers have developed a portable sensor that can assess the clotting ability of a person’s blood 95 times faster than current methods-using only a single drop of blood.
Even better, the device provides more information about the blood than existing approaches.
Rapid and accurate assessments are essential to ensuring that patients prone to blood clots-as well as those who have difficulty clotting-receive care appropriate to their conditions.
Recently, XaTek, a new Cleveland-based company, licensed the technology for the device-called ClotChip-with a goal of bringing it to market within the next three years. Case Western Reserve’s Technology Transfer Office negotiated the agreement between the university and the company.
‘ClotChip is designed to minimize the time and effort for blood-sample preparation. [It can] be used at the doctor’s office or other points of care for patients on anticoagulation therapy, antiplatelet therapy or who have suffered a traumatic injury causing bleeding,’ said Pedram Mohseni, professor of electrical engineering and computer science at Case Western Reserve, who led the development of ClotChip with Michael Suster, senior research associate in the EECS department.
Existing measures typically require patients to visits laboratories where expert technicians administer tests, an approach that typically is time-consuming and expensive. While a few methods exist to allow on-site testing, to date they have not proved nearly as precise as laboratory-based versions.
In preliminary tests, however, Case Western Reserve’s technology provided results in 15 minutes, as compared to conventional measures that can take a day or longer to yield results. ClotChip also provided more information about the coagulation process, including the effects of a new class of drugs called target-specific oral anticoagulants, or TSOACs.
TSOAC drugs block clots from forming in a different way than warfarin which had dominated the market for decades. Warfarin, however, can interact negatively with several medications and foods and also requires frequent blood tests to monitor the drug’s effects.
To monitor clotting, ClotChip uses an electrical technique called miniaturized dielectric spectroscopy, an approach that Mohseni, Suster and their team began developing six years ago. In essence, the technique applies an external electric field to the drop of blood, then quantitatively measures how the blood affects that field. The measurements reflect the ability of the blood to clot.
Because the device works so quickly, emergency responders could use it on site to determine whether a patient in trauma is on one of the blood thinner medications. Such critical information also could be invaluable to medics in wartime.

Case Western Reserve University http://tinyurl.com/zlo6h5s