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New Immune Pathway Involved in Resistance to Parasite Worms Found in Undercooked Pork

 

 

 

|| Monday: April 29: 2019: Lancaster University News || ά. Scientists from Lancaster University have discovered that immune responses, originally found to prevent fungal infections, are, also, important in eliminating Trichinella Spiralis, a round worm and the causative agent of Trichinosis. People acquire Trichinellosis by consuming raw or undercooked meat, infected with the Trichinella parasite, particularly, wild game meat or pork.

Consumption of contaminated meat contains ‘nurse cells’ of the parasite. Once in the stomach these ‘nurse cells’ hatch, releasing infective larvae, which, then, bury themselves within the lining of the small intestine. Previously, immune responses to expel the parasite have been shown to rely on white blood cells, called, T-helper two cells, specialised for eliminating gastro-intestinal parasites. However, scientists at Lancaster discovered that following this T-helper two response, a second T-helper 17 response, previously, shown to be specialised for eliminating fungal infections and certain bacterial infections occurred.

In collaboration with Professors Mark Travis and Richard Grencis from the University of Manchester, they were able to identify how these T-helper 17 cells arose and that they were key in maintaining the intestinal muscle contractions needed to flush out the worms.

The findings have been published in the journal PLOS Pathogens and show that mice, lacking the ability to activate a key signalling molecule, important in producing T-helper 17 cells have a reduced ability to expel the parasite. Interestingly, they saw a delayed transit time in the small intestine hinting at alterations in muscle contraction.

In isolating the small intestine they demonstrated that a key molecule, produced from T-helper 17 cells, termed IL-17, could increase intestinal contraction and restoring levels of this IL-17 in their mice rescued their ability to expel the parasite.

“We were quite surprised by what we found during this study. Normally, these immune responses are thought of as acting quite distinctly, depending on what type of infection you, may, have. It’s well established that the T-helper two response is beneficial during gastro-intestinal worm infections, so, traditionally, any other response would be thought of as hindering worm expulsion. So, it was quite surprising to see that this late acting T-helper 17 response was actually beneficial to the mouse’s ability to resolve an infection and get rid of the worm.’’ said Dr John Worthington from the Department of Biomedical and Life Science in the Faculty of Health and Medicine led the research.

“Our study provides novel insights into how the immune system interacts with muscle contraction during intestinal inflammation. Although, the occurrence of this infection is very rare in the developed world, we hope, it will help us to design new treatments for the many millions of people, who suffer from intestinal parasitic infections worldwide and, may, even, inform other intestinal diseases, involving altered muscle function.”::::ω.

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Antibody Therapy Training Phagocytes to Destroy Tumours Now Tested on Patients
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

|| February 25: 2019: University of Turku News || ά. Developed by researchers at the University of Turku, an immune-therapeutic antibody therapy re-educates macrophages to activate passivated cytotoxic T-cells to kill cancer. The antibody therapy prevented the growth of tumours in several mouse models. The development of the therapy has now progressed to patient testing in a phase I:II clinical trial. One reason behind many unsuccessful cancer treatments is the cancers’ ability to hijack the immune system to support its own growth.

This is assisted by the so-called tumour-associated macrophages, that can be educated by cancer cells to dampen anti-tumour immune responses. Macrophages are phagocytes, that form the first line of defence towards invading pathogens and they have a crucial role in maintaining tissue homeostasis. Macrophages have a large repertoire of functions in immune activation and resolving inflammation. In collaboration with Professor Sirpa Jalkanen, of Immunology, Dr Maija Hollmén’s research group investigated the possibility to utilise tumour-associated macrophages to increase the immunological detection and killing of cancer cells.

Professor Jalkanen has studied the function of Clever-1 for a long time. Previously, her group has observed that Clever-1 controls leukocyte trafficking between tissues. Published in the journal Clinical Cancer Research, the Study found that blocking Clever-1 function on macrophages activated the immune system and was highly effective in inhibiting cancer progression.

By inhibiting Clever-1 functions, tumour-associated macrophages, that, normally, impair adaptive immune cell activation, such as, cancer cell killing by cytotoxic T-cells, were managed to be re-educated so that they had increased ability to present antigen and secrete pro-inflammatory cytokines, leading to increased activation of killer T-cells.

‘’These results are highly promising and present a completely new way to activate anti-cancer immunity.’’ says Doctoral Candidate Miro Viitala, who is the main Author of the Paper.

‘’Macrophages are an ideal drug development target as they express several molecules, that can be activated or impaired to transfer the macrophages into cells, that destroy cancer. In itself, this would increase beneficial inflammation in the tumour micro-environment, which would improve the efficiency of immune checkpoint inhibitors in those patients, whose response is weak due to lack of tumour-specific T-cell activation.’’

The antibody therapy, targeting Clever-1 worked in the studied tumour mouse models as efficiently as the PD-1 antibody therapy, that is in clinical use. The PD-1 antibody maintains the functionality of the killer T-cells. It is notable that the Clever-1 antibody therapy, targeting macrophages, also, increased the activity of the killer T-cells efficiently.

In certain mouse models of cancer, a combination of anti-Clever-1 and anti-PD-1 therapies prevented tumour growth and formation of metastases more effectively than either treatment alone.

‘’Every cancer is different. Therefore, it is important to explore the types of cancer where Clever-1 antibody therapy most effectively works on and to find biomarkers, that can be used to identify beforehand the patients, that will benefit the most from this kind of therapy.’’ Viitala says.

The Paper: Immunotherapeutic Blockade of Macrophage Clever-1 Reactivates the CD8+ T Cell Response Against Immunosuppressive Tumors: Miro Viitala, Reetta Virtakoivu, Sina Tadayon, Jenna Rannikko, Sirpa Jalkanen, Maija Hollmén: Published in the journal Clinical Cancer Research:  February 12: 2019

More information: Maija Hollmén:::ω.

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New Clinical Trial for Osteo-Arthritis Drug Gets Funding

 

 

 

|| February 22: 2019: University of Liverpool News || ά. An innovative treatment for Osteo-arthritis, being trialled at the University of Liverpool, has been awarded a grant from Innovate UK, the leading government innovation agency. Osteoarthritis is the most common type of Arthritis in the UK, affecting more than eight million people and is the leading cause of joint pain and stiffness in older people. The University’s Clinical Trials Unit, in partnership with AKL Research and Development Ltd and the NHS, is leading a clinical trial to test a potential new drug treatment for Osteo-arthritis.

As part of their research and development programme, AKLRD identifies promising phytochemicals, found in natural products, which can be synthesised. Trials have identified two molecules, which act synergistically and have been brought together to create the ‘APPA’, a patented drug, which is an investigational medicine and not yet approved for use. In a variety of pre-clinical animal testing trials, APPA clearly demonstrated significant pain relief from Osteo-athritis, improved functionality and the slowing of cartilage destruction. These results led to the clinical trial being launched.

Innovate UK is part of UK Research and Innovation with a remit to drive the science and technology innovations, that will grow the UK economy. It has recognised APPA’s potential as a powerful treatment despite it only being at the Phase One trial stage, awarding AKLRD £675,000. This will contribute to the development of APPA in its Phase Two trial, which is expected to commence later this year, based on anticipated favourable results in the Phase One trial.

The trial, which is a partnership between the University of Liverpool, the pharmaceutical Industry and the NHS, is being led by Rheumatologist Professor Robert Moots from the University’s Institute of Ageing and Chronic Disease and is occurring in the Phase I unit at the Royal Liverpool University Hospital.

Professor Moots, said, “Millions of osteo-arthritis patients are suffering every day with severe pain because the current prescription drugs available are, often, not effective or can not be used long-term. “APPA has the potential to be an effective treatment for OA, that could not only tackle the pain it causes but, do so with excellent tolerability and, also, we hope, stop the disease from causing further joint damage. It’s incredibly exciting that Innovate UK has clearly recognised the potential of this new drug, which could transform the lives of OA patients.”

Mr David Miles, the Chief Executive Officer of AKLRD, said, “For APPA to be recognised as a disruptive innovation is incredibly exciting. The award from Innovate UK will allow us to secure the future development of what we believe could be an important medicine for OA patients, who currently have limited treatment options. We believe APPA not only tackles pain but will, also, put the brakes on the inflammatory cascade, that we know is responsible for the devastating consequences of OA.”

Mr Chris Sawyer, Innovation Lead, at Innovate UK, said, “This is an exciting area of research in a disease with high incidence and major debilitation in many sufferers. Supporting AKLRD to pursue the development of this important medicine is aligned perfectly with Innovate UK’s objective to support UK business growth in the health and life sciences sector.

AKLRD underwent a highly competitive process to be awarded the grant, with five independent expert assessors evaluating its submission. The assessors praised the ‘strong’ and ‘exciting proposal with large potential’ and described AKLRD’s work as an ‘exciting area of research in a disease with high incidence and major debilitation in many sufferers.”

Innovate UK is part of UK Research and Innovation with a remit to drive the science and technology innovations that will grow the UK economy. Since 2007 Innovate UK has committed more than £01.8 billion to innovation, helping 8,000 organisations with projects, estimated to add more than £16 billion to the UK economy and nearly 70,000 jobs. Innovate UK competitions provide grants between £25,000 and £10 million.

The forthcoming Phase II trial will be recruiting nationally in collaboration with Aintree University Hospital NHS Foundation Trust.:::ω.

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New Rapid Test for Sepsis Could Save Thousands of Lives

 

 

 

|| February 21: 2019: University of Strathclyde News || ά. Researchers at the University of Strathclyde have developed an innovative, low cost test for earlier diagnosis of Sepsis, which could save thousands of lives. The simple system for sensitive real-time measurement of the life threatening condition is much quicker than existing hospital tests, which can take up to 72 hours to process. Using a micro-electrode, a bio-sensor, this device is used to detect, if, one of the protein biomarkers of Sepsis, interleukin-6, is present in the bloodstream.

IL-6 is a molecule, secreted by the immune system and the levels of it in the blood increase in many of those, who have the condition. The results of the research project show that increased levels of the molecule can be detected by the test as quickly as two and a half minutes. The small size of the devices, micro-electrodes on a needle shaped substrates, makes them ideal for initial testing and, also, continuous monitoring for Sepsis, which is notoriously difficult to diagnose. Dr Damion Corrigan, from the department of Biomedical Engineering at Strathclyde, said, “The research shows that the tools we’ve developed could underpin a rapid test for Sepsis.

We’ve developed a needle shaped sensor with different electrodes and have shown we can detect one sepsis biomarker in almost real time, at the clinically relevant levels. When levels go up, as they do in Sepsis, we can detect that, too. Sepsis is quite complex and difficult to diagnose but IL-6 is one of the best markers.

Our research so far shows you can measure a single Sepsis marker but, there are, actually, eight sensors on the needle, each about the same diameter as a human hair and the idea is that in the future we can get multiple markers on the one microchip for a more comprehensive test.”

The device takes a pin prick of blood, which is, then, put on the chip for the result to be read. Its needle shape means it can, also, be implanted and used on patients in intensive care. The UK Sepsis Trust estimates that around 52,000 people in the UK die every year and six million globally from the condition, yet, with early diagnosis and the correct treatment, most people make a full recovery.

Sepsis develops, when the chemicals the immune system releases into the bloodstream to fight an infection instead cause inflammation throughout the entire body. Without quick treatment, it can lead to multiple organ failure and death. A delay of just one hour for giving the correct antibiotic can mean an increase in the likelihood of death.

It is, usually, diagnosed, based on simple measurements, such as, body temperature, heart rate and breathing rate, with patients, often, giving a blood test. There is a reliance on clinical judgement and hospital laboratory techniques to diagnose the condition, that can take up to 72 hours to provide a result. Researchers at the University of Leeds, Dr Chris Russell and Dr Paul Steenson, made the sensing element, using micro-fabrication, while the Strathclyde team did all the measurements and developed the test using the sensor.

Dr Corrigan said, “At the moment the 72-hour blood test is a very labour intensive process because the doctor orders the test on a computer with samples going to a central laboratory for processing and return of the result. The type of test we envisage could, for example, be at the bedside and involve doctors or nurses being able to monitor levels of Sepsis biomarkers for themselves. If, GP surgeries had access they could, also, do quick tests, which could, potentially, save lives. It could, also, be available in AandE departments so that anyone coming in with a question mark could be quickly ruled in or out.

With sepsis, the timing is key. For every hour that you delay the antibiotic treatment, the likelihood of death increases. I would hope the test could improve survival rates by ensuring people get treatment more quickly. It’s not just saving lives, a lot of people, who survive Sepsis, suffer life changing effects, including, limb loss, kidney failure and post-traumatic stress disorder. The test could stop a lot of suffering.”

The project’s Clinical Advisor and Co-author of the Paper, Consultant Anaesthetist Dr David Alcorn, who is based at Paisley’s Royal Alexandra Hospital, said that he believed the ‘extraordinary’ technology could have global implications. He said, “Dr Corrigan and his team have produced a tiny electrode capable of detecting Sepsis and, at the same time, diagnosing the type of infection and the recommended antibiotic, all in the space of minutes. “The implications for this are massive and the ability to give the right antibiotic at the right time to the right patient is extraordinary.

Finding the correct drug not only targets care for that patient but, will cut down on needless antibiotics and the reduced chance of antibiotic resistance. I can, definitely, see this having a clear use in hospitals, not only in this country but, all round the world.”

Dr Ron Daniels BEM, the CEO of the UK Sepsis Trust said that the earlier diagnosis and treatment across the UK would save at least 14,000 lives a year. He said, "Any kind of test, that enables us to identify Sepsis earlier, before symptoms, even, present themselves, could help save, even, more lives and bring us closer to our goal of ending preventable deaths from Sepsis.

Systems like this are so important as, with every hour before the right antibiotics is administered, risk of death increases. No test is perfect in the identification of Sepsis, so it’s crucial we continue to educate clinicians to think sepsis in order to prompt them to use such tests."

The project was funded by Tenovus Scotland and the Dowager Countess Eleanor Peel Trust. A Spokesman for the Trust said, “We are very encouraged by the success of the project and look forward to future developments arising from the work.” Professor Alan Foulis, the Chair of Tenovus Scotland Strathclyde, said, "Tenovus Scotland aims to support pilot scientific studies with real clinical potential, so this is an excellent example of the kind of research we like to fund.”

One family, who the test could have made a difference to was the Sutherlands. After Mr Sutherland developed a persistent sore throat in 2015 he visited his GP but, was sent home without treatment after it was ruled he was simply suffering from a virus. Just hours after a second visit that same week to an emergency doctor, father of two from Fishcross in Clackmannanshire, who has two young daughters Lacey, eight, and Isla, four, collapsed at home.

His wife Ms Melanie Sutherland called an ambulance and on arrival at hospital suffered two cardiac arrests. Mr Sutherland had Sepsis and as his body went into shock and his organs started to shut down, doctors warned his wife that he might not survive the night. After eight days in a coma, he woke up and went on to make an almost complete recovery. But the couple believe that had their GP had access to the simple test developed by Strathclyde researchers that Mr Sutherland might have been diagnosed long before his condition became life threatening.

Mr Sutherland said, “I started to feel unwell over the weekend with a sore throat. That Tuesday I went to the doctors, when it got worse but, they told me, it was a vital infection and sent me away. As the week went on, it got worse and by the Thursday it was really bad. My wife took me to the out of hours doctor that night and by this point I was really unwell and could barely move. But I was given an anti-sickness injection and, then, I was sent home.

No one mentioned Sepsis, although, looking back, I had all the symptoms. It’s hard to diagnose, so, if, this test had been around, it could have made all the difference to what happened with me.” Nursery Learning Assistant Ms Melanie Sutherland, 29, said, “I phoned an ambulance and when I told one of the paramedics that Ryan had had a sore throat, he mentioned Sepsis for the first time. I didn’t, even, know what it was. “Ryan was so unwell they had to stabilise him before they could move him. By the time I arrived at Forth Valley Royal Hospital twenty minutes behind the ambulance he was already in intensive care after suffering two cardiac arrests.

He had gone into Septic shock and his throat was so closed over they struggled to get the tube for him to breathe down it. His body was starting to shut down. It was terrifying. They told me he may not last the night.”

Mr Sutherland’s life hung in the balance but, after eight days he woke up. He had lost three stones in weight and was so weak he had to walk with a zimmer frame at first.

The Paper: Published: Science Direct

Caption: Image: University of Strathclyde:::ω.

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Diabetes: Human Cells Can Also Change Functions: New Research May Pave the Way for New Diabetes Treatment