Effective diagnosis and treatment of tuberculosis (TB) is notoriously difficult and the incidence of drug-resistant strains is increasing. However, using T-cell based diagnostic test systems,  Lophius Biosciences has achieved its first successfully concluded clinical Proof of Principle study with respect to detection of active TB using its novel T-Track TB test, which is based on the company’s proprietary Reverse T Cell Technology (RT Technology). The clinical Proof of Principle was concluded in India with a cohort of 44 patients. Results demonstrated that the new TB test was able to detect active TB in in 10 of 12 non-treated patients. Besides its high sensitivity and specificity the test also demonstrated a remarkably short turnaround time of 2 days, which compares favourably to currently used detection methods. These results suggest that the T-Track TB test could represent an innovative and fast detection approach for this area of strong medical need.

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Oxidative stress is believed to cause a number of diseases. Up to now, it has been common practice to measure oxidative stress levels by determining the oxidation state of a small molecule called glutathione in cell extracts. Scientists from the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) have been the first to discover that cells under stress deposit their oxidised glutathione in a cellular waste repository. This protects cells from oxidative stress – and questions the validity of the conventional measuring method.
Cancer, Alzheimer’s, arteriosclerosis– the list of diseases which have been linked to oxidative stress is long and even includes the very process of ageing. Oxidative stress is caused by so-called reactive oxygen compounds, which include the notorious ‘free radicals’. If a cell is exposed to more reactive oxygen compounds than it can instantly degrade, it is under oxidative stress. As a result, important components such as proteins, DNA and lipids are oxidised and thus get damaged.
To determine whether a cell is under oxidative stress, scientists often analyse the oxidation state of glutathione. Glutathione is a small molecule which gets oxidised to protect the cell from reactive oxygen compounds. In theory, the amount of oxidised glutathione should therefore indicate whether a cell is healthy or under oxidative stress. However, researchers in the team of Associate Professor (PD) Dr. Tobias Dick have demonstrated that this hypothesis, which is the basis of a large number of scientific studies, is deceptive.
‘Up to now, it was necessary to destroy the cells in order to measure the amount of oxidised glutathione,’ Tobias Dick explains. ‘However, this means that any spatial resolution is lost.’ Therefore, virtually nothing was known about where exactly oxidised glutathione is found in the cells. Scientists have presumed that it remains in the cytoplasm, where it is formed.
To find out more about the whereabouts of glutathione in the cell, Tobias Dick and co-workers developed biosensors which indicate the oxidation state of glutathione in intact cells by releasing light signals. In yeast cells, the researchers were able, for the first time, to follow the path of oxidised glutathione through the living cell in real time. They were surprised to find that, rather than remaining in the cytoplasm, it promptly gets locked up in a safe depot, the vacuole.
The cytoplasm, where all important cellular metabolic processes happen, is thus reliably protected from oxidative damage. Cells that would have been considered to be under oxidative stress using the conventional method appeared entirely healthy in their cytoplasm. Tobias Dick and his team could subsequently show that this is not only true for yeast cells but also for various mammalian cells and also for cancer cells.
These results mean that – contrary to previously held beliefs – the level of oxidative glutathione does not indicate whether or not a cell is under oxidative stress. ‘Therefore, it is important to re-evaluate prior studies that have established a link between oxidative stress and various diseases based on the conventional method.’ The German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ)

Johns Hopkins researchers have created a synthetic protein that, when activated by ultraviolet light, can guide doctors to places within the body where cancer, arthritis and other serious medical disorders can be detected.
The technique could lead to a new type of diagnostic imaging technology and may someday serve as a way to move medications to parts of the body where signs of disease have been found. In a study the researchers reported success in using the synthetic protein in mouse models to locate prostate and pancreatic cancers, as well as to detect abnormal bone growth activity associated with Marfan syndrome.
The synthetic protein developed by the Johns Hopkins team does not zero in directly on the diseased cells. Instead, it binds to nearby collagen that has been degraded by various health disorders. Collagen, the body’s most abundant protein, provides structure and creates a sturdy framework upon which cells build nerves, bone and skin. Some buildup and degradation of collagen is normal, but disease cells such as cancer can send out enzymes that break down collagen at an accelerated pace. It is this excessive damage, caused by disease, that the new synthetic protein can detect, the researchers said.
‘These disease cells are like burglars who break into a house and do lots of damage but who are not there when the police arrive,’ said S. Michael Yu, a faculty member in the Whiting School of Engineering’s Department of Materials Science and Engineering. ‘Instead of looking for the burglars, our synthetic protein is reacting to evidence left at the scene of the crime,’ said Yu, who was principal investigator in the study.
A key collaborator was Martin Pomper, a School of Medicine professor of radiology and co-principal investigator of the Johns Hopkins Center of Cancer Nanotechnology Excellence. Pomper and Yu met as fellow affiliates of the Johns Hopkins Institute for NanoBioTechnology. ‘A major unmet medical need is for a better non-invasive characterisation of disrupted collagen, which occurs in a wide variety of disorders,’ Pomper said. ‘Michael has found what could be a very elegant and practical solution, which we are converting into a suite of imaging and potential agents for diagnosis and treatment.’
The synthetic proteins used in the study are called collagen mimetic peptides or CMPs. These tiny bits of protein are attracted to and physically bind to degraded strands of collagen, particularly those damaged by disease. Fluorescent tags are placed on each CMP so that it will show up when doctors scan tissue with fluorescent imaging equipment. The glowing areas indicate the location of damaged collagen that is likely to be associated with disease.
In developing the technique, the researchers faced a challenge because CMPs tend to bind with one another and form their own structures, similar to DNA, in a way that would cause them to ignore the disease-linked collagen targeted by the researchers.
To remedy this, the study’s lead author, Yang Li, synthesized CMPs that possess a chemical ‘cage’ to keep the proteins from binding with one another. Just prior to entering the bloodstream to search for damaged collagen, a powerful ultraviolet light is used to ‘unlock’ the cage and allow the CMPs to initiate their disease-tracking mission. Li is a doctoral student from the Department of Chemistry in the Krieger School of Arts and Sciences at Johns Hopkins. Yu, who holds a joint appointment in that department, is his doctoral adviser.
Yu’s team tested Li’s fluorescently tagged and caged peptides by injecting them into lab mice that possessed both prostate and pancreatic human cancer cells. Through a series of fluorescent images taken over four days, researchers tracked single strands of the synthetic protein spreading throughout the tumour sites via blood vessels and binding to collagen that had been damaged by cancer.
Similar in vivo tests showed that the CMP can target bones and cartilage that contain large amounts of degraded collagen. Therefore, the new protein could be used for diagnosis and treatment related to bone and cartilage damage. John Hhopkins University

The risk of death resulting from heart attack is higher in people with schizophrenia than in the general public, according to scientists at the Centre for Addiction and Mental Health (CAMH) and the Institute for Clinical Evaluative Sciences (ICES).
On average, people with schizophrenia have a life-span 20 years shorter than the general population. This is partly due to factors such as smoking, increased rates of diabetes, and metabolic problems brought on by the use of some anti-psychotic medications. These factors often worsen once a cardiac condition arises because people with schizophrenia are less likely to make the necessary lifestyle changes, such as diet and exercise, to offset the problem.
This study examined mortality and access to cardiac care after heart attacks (acute myocardial infarction) in those with schizophrenia.
Dr. Paul Kurdyak, Chief, Division of General and Health Systems Psychiatry at CAMH, analysed four years of Ontario-wide patient data and tracked all incidents of heart attack among people with schizophrenia, and compared results to people without schizophrenia.
‘When we looked at the data, we found that people with schizophrenia were 56 per cent more likely to die after discharge from hospital following a heart attack than those who did not have schizophrenia,’ says Dr. Kurdyak, also an Adjunct Scientist at ICES. ‘We also found that patients with schizophrenia, despite the increase in mortality risk after a heart attack, were half as likely to receive life-saving cardiac procedures and care from cardiologists than those without schizophrenia.’
Specifically, the study found that people with schizophrenia were 50 per cent less likely to receive cardiac procedures or to see a cardiologist within 30 days of discharge from hospital.
‘The numbers tell us that people with schizophrenia– the ones who are at most risk to develop and subsequently die from heart attacks — are not receiving adequate care,’ says Dr. Kurdyak. ‘The possible solutions are two-fold: prevention is one. We need to support patients whom we know are at risk of developing medication-related metabolic issues by working with them to provide strategies to offset weight gain, such as healthy eating and physical activity. The other part is aftercare – the mental health care team, primary care providers, and the cardiac specialists need to work together to ensure that patients are seen again after a first incident of heart attack.’ EurekAlert