RCSI scientists develop drug that stops killer sepsis

(L-R) Professor Steve Kerrigan and Dr Sinéad Hurley from the School of Pharmacy, Their pre-clinical trial has shown that the drug, called InnovoSep, has potential to stop all sepsis-causing bacteria from triggering organ damage in the early stages of the condition. (Credit: Maxwell Photography)

The almost 3,000 deaths from sepsis in Ireland could be prevented through the use of a new drug that stops the bacteria responsible in its tracks.

That’s according to scientists based at the Royal College of Surgeons in Ireland who have announced that a drug called InnovoSep, which was first developed to treat cancer, has demonstrated it can treat sepsis in preclinical trials.

Sepsis is caused when common bacteria  such as S. aureus or E. coli that live on the skin, eyes, or inside or nose, eyes or ears enter the blood where blood vessels have been damaged or exposed due to a cut, injury or infection.

Once in the blood, bacteria are, within seconds, transported around the body via the bloodstream, reaching  the vital organs, such as heart, liver and lungs, where, left untreated, they will cause organ failure and death.

“When the bacteria enter the blood it causes damage, and once we start to get damaged blood vessels we get blood vessels that are leaky,” explained Steve Kerrigan, Associate Professor of Pharmacology at RCSI.

“The way this drug works is, it stops the blood vessels getting damaged. This could be used to prevent somebody who’d be at high risk of developing sepsis, or prevent people who already have sepsis from getting worse,” Prof Kerrigan said.

It takes just 12 to 24 hours from the time bacteria enter the bloodstream for someone to die from sepsis-induced organ failure due to sepsis. The treatment is to use antibiotics, and survival depends on how fast the drugs are given.

The symptoms of sepsis are like the flu, with high temperature, rapid heart rate, low blood pressure, but the difference is that the symptoms advance in hours rather than over a number of days. In cases of suspected sepsis people are advised to immediately attend hospital A&E rather than visit the GP.

The rate of of sepsis is increasing at rate of about 10 percent per year, worldwide, a trend also being seen in Ireland. There are about 15,000 sepsis cases per annum here with some 3,000 deaths across all age groups.

Scientists do not yet understand why the number of sepsis cases are growing so rapidly around the world, but they suspect that antibiotic resistance, where bacteria find ways to survive antibiotic attack, is at the root of the issue.

The team at RCSI, led by Prof Steve Kerrigan, set out to find a drug that could prove effective against sepsis. They decided to investigate drugs that had been developed for other diseases but had failed to progress fully through clinical trials. This led them to InnovoSep, a drug developed to treat cancer.

The performance of the drug in preclinical trials were exciting,  and better than any other drugs that have been tested to treat sepsis, said Prof Kerrigan.

“It stops sepsis before it gets going,” explained Prof Kerrigan. “In a lot of the previous drugs, whey they have failed is because the horse has already bolted.”

It can take decades and hundreds of millions of euro to take a drug from the discovery stage and get it to market. But, because Innovosep has been trialled as a cancer drug, it could be available in five years, at a fraction of the cost.

The preclinical trials of InnovoSep were supported by the Enterprise Ireland Commercialisation Fund. The intention now, said Prof Kerrigan, is to conduct human trials of the drug in Ireland, and funding is being sought to do this.

Burning questions remain about Dublin’s ‘Waste-To-Energy’ incinerator

 

Dublin Waste to Energy [Pic Credit Blathnaid Mc Polin]

The Covanta Dublin Waste to Energy plant is now operating at full capacity, but questions remain around the safety and potential public health impact of the plant.

I visited the plant on 15th March 2018 to put these questions to its General Manager, John Daly, and to take a close up look at the technology that is required to incinerate 600,000 tonnes of black bin waste.

Listen below to the piece broadcast on Drivetime on 26th March 2018.

 

 

TCD scientists devise tool to predict impact of warming on parasitic disease.

Lyme Disease

TCD scientists have devised a method to predict the impact of global warming on parasitic diseases such as Lyme disease, which is caused by a tick. [Source: http://www.Macleans.ca]

The prediction of which infectious diseases will worsen and which will diminish with rising temperatures is now possible thanks to scientists at TCD.

The method can, the scientists say, identify which infectious diseases will have worsened or diminished effects with rising temperatures.

“Rising temperatures due to global warming can alter the proliferation and severity of infectious diseases, and this has broad implications for conservation and food security,” said Professor Pepin Luijckx, who led the study with William C Campbell, lecturer in parasite biology at TCD and graduate student Devin Kirk.

“It is therefore really important that we understand and identify the diseases that will become more harmful with rising temperatures, with a view to mitigating their impacts,” Prof Luijckx added.

Scientists have found it difficult to pinpoint the the precise  impact  rising temperature will have on the host and pathogen, and on disease, because temperature can affect these in different ways.

For example, while host immune function and pathogen infectivity may be higher as temperatures rise, pathogen longevity may be lower.   Additionally, to predict the severity of disease, scientists need data that doesn’t always exist on the temperature sensitivity of all the processes involved, especially for newly emergent diseases.

Solution 

The solution, the TCD scientists say, is that the so-called metabolic theory of ecology can be used to predict how various biological processes respond to temperature.    This theory is based on the idea that each process is controlled by enzymes, and that the activity and temperature dependence of these enzymes can be described using simple equations.

Even with limited data, the theory thus allows for the prediction of the temperature dependence of host and pathogen processes.

In their study, the scientists used the water flea and its pathogen and measured how processes such as host mortality, aging, parasite growth and damage done to the host changed over a wide temperature range. They used these measurements to determine the thermal dependencies of each of these processes using metabolic theory.

The results showed that the different processes had unique relationships with temperature. For example, while damage inflicted to the host per pathogen appeared to be independent of temperature, both host mortality and pathogen growth rate were strongly dependent — but in opposite ways.

“What is exciting is that these results demonstrate that linking and integrating metabolic theory within a mathematical model of host-pathogen interactions is effective in describing how and why disease interactions change with global warming,” Prof Luijckx said.

“Due to its simplicity and generality, the method we have developed could be widely applied to understand the likely impact of global warming on a variety of diseases, including diseases affecting aquaculture, such as salmonid diseases like Pancreas disease, pathogens of bee pollinators, such as Nosema, and growth of vector-borne and tick-borne diseases in their invertebrate hosts, such as malaria and Lyme disease,” the Prof concluded.

Immune system found to work better at certain times of day

The immune system has been found to work to a 24-hour hour circadian cycle, like the rest of our body [Source: greatist.com]

The immune system works better at certain times of day than others, according to new research, which could help point the way towards the development of new drugs for autoimmune disease such as multiple sclerosis (MS).

In a study published in Nature Communications, Professor Kingston Mills and Dr Caroline Sutton of TCD and Dr Annie Curtis of RCSI (Royal College of Surgeons Ireland), show that immune responses and regulation of autoimmunity are affected by the time of the day when the immune response is activated.

“In the year that the Nobel Prize in Medicine was awarded for discoveries on the molecular mechanisms controlling the circadian rhythm, our exciting findings suggest that our immune system is programmed to respond better to infection and insults encountered at different times in the 24-hour clock,” said Prof Mills.

“This has significant implications for the treatment of immune-mediated diseases and suggests there may be important differences in time of day response to drugs used to treat autoimmune diseases such as multiple sclerosis,” Prof Mills said. 

Using mice as a model organism, the researchers showed that a master circadian gene, BMAL1, is responsible for sensing and acting on time-of-the-day cues to suppress inflammation. Loss of BMAL1, or induction of autoimmunity at midday instead of midnight, causes more severe experimental autoimmune encephalomyelitis (an analogue of multiple sclerosis) in mice.

Circadian rhythms or 24-hour rhythms are generated by the body clock, allowing us to anticipate and respond to the 24-hour cycle of our planet.

Maintaining a good body clock is generally believed to lead to good health for humans, and disrupting the circadian rhythm (for example, as happens in some people working night shifts) has been associated with immune diseases such as multiple sclerosis; however, the underlying molecular links have been unclear.

“Our study also shows how disruption of our body clocks, which is quite common now given our 24/7 lifestyle and erratic eating and sleeping patterns, may have an impact on autoimmune conditions,” said Dr Curtis.

“We are really beginning to uncover exactly how important our body clocks are for health and wellbeing,” Dr Curtis added. 

Genetic map of Ireland charts impact of invasions and plantations

Researchers have found relatively high levels of West Norwegian-like (probably Viking) ancestry within Ireland [Source: irishhistorypodcast.ie]

The Irish DNA Atlas which has just been published in the journal Scientific Reports provides the first fine-scale genetic map of the island of Ireland.

The DNA Atlas, which was produced by researchers at the Royal College of Surgeons and the Genealogical Society of Ireland charts the genetic impact of major historical events such as the Norse Viking invasion and the Ulster Plantations as well as revealing genetic similarity in 10 distinct clusters.

The Atlas was developed by population geneticists and genealogists who came together to collect DNA samples from 196 Irish individuals with four generations of ancestry linked to specific areas across Ireland.

The analyses of the DNA, and comparison with thousands of further samples from Britain and Europe, are revealing seven clusters of Gaelic-Irish ancestry, and three of shared British-Irish ancestry.

Scientists expect that this genetic information will improve the diagnoses of diseases where genes play a strong role, particularly for people and populations with Irish roots.

Vision 

The researchers involved in the study believe the work will help deliver on the vision of the new FutureNeuro Science Foundation Ireland Research Centre, which is seeking to improve the diagnosis of rare neurological disorders and to personalise treatments of those.

“Having a genetic map of the Irish population will be invaluable in future studies of the genetic component of some common diseases in the Irish population, especially those diseases which show a difference in prevalence rates across the island of Ireland,” said Dr Sean Ennis, UCD ACoRD and Genomics Medicine Ireland.

Some of the information the Atlas has so far revealed include the findings that there are relatively high levels of people of Northwest French and West Norwegian origin in Ireland; that there is evidence of continual, low level migration between the north of Ireland and the south and west of Scotland; and that there are three genetic clusters with shared Irish-British ancestry which are mostly found in the north of Ireland and probably stem from the Ulster plantations.

TCD group to investigate health effects in Ireland from diesel emissions

A TCD team is to investigate the health impact of diesel emissions in Ireland (Pic: TCD)

Nitrogen dioxide, or NO2 is an air pollutant generated, for the most part, by diesel engines and can irritate airways and lead to respiratory disease, especially asthma.

In the past, Irish governments have encouraged the purchase of diesel cars through tax incentives in order to help meet the country’s obligation to control carbon dioxide, or CO2, which is the most significant greenhouse gas.

However, it has become clear that nitrogen dioxide, which is released by diesel engines, is a serious hazard to public health so this policy may change.

For many years the US had strict controls on nitrogen emissions from vehicles, and the EU is now looking to follow with its own more stringent nitrogen regime.

This research will involve a team of engineers, hospital consultants and environmental scientists based at TCD, and is funded by the Environmental Protection Agency‘s Research Programme 2014 to 2020.

The researchers will investigate the associations between NO2 and health impacts as it pertain to Ireland, with particular emphasis on vulnerable groups including children, the elderly and the socio-economically disadvantaged.

The team will identify a set of characteristics for the locations in Ireland that are at most risk of experiencing high levels of NO2.

“Traffic in urban areas contributes significantly to air pollution and the impact on individuals living and working in those areas is difficult to quantify,” said Margaret O’Mahony, Professor of Civil Engineering, and the project lead.

“The EPA funding will enable the team to investigate the associations between NO2 and its impact on health and wellbeing, which is an important step forward for environmental and health research in Ireland,” Prof O’Mahony added. 

The team will also examine the HSE drug prescription database to establish much-needed baseline data linking NO2 levels with the prescription of drugs used to treat asthma and chronic obstructive airways disease.

Other databases, such as the Growing up in Ireland (GUI) and the Irish Longitudinal Study on Ageing (TILDA), subject to their availability, will be explored to investigate if relationships between prevalence of respiratory symptoms in vulnerable groups and NO2 levels exist.

Finally, the team will identify a set of effective and efficient solutions to mitigate the impact of the transport sector on NO2 levels in Ireland.

My weekly science news round up on East Coast FM: weight loss; mindfulness; ancient Egypt; super volcano; Chinese space station

The latest science news from around the world 

Broadcast on The Morning Show on East Coast FM (20/10/2017)

A group of scientists say there is no evidence for many of the benefits claimed for mindfulness (Source: http://www.positivepsychologyprogram.com)

 

Every two lbs overweight knocks nine weeks off your life

Source: Telegraph, UK

  • Study of 600,000 people study link between longevity and lifestyle
  • Smoke pack of cigs per day, die seven years earlier on average
  • Edinburgh University researchers did this as a so-called big data project, which means analysing and cross referencing vast amounts of data.
  • If you are two stone overweight, then it will take, on average, six months off your life.
  • Data came from Europe, North America and Australia, via the UK Biobank.
  • But… also found that life is extended by one year for every year a person stays in education after school, on average. That’s a massive effect.
  • Life expectancy continuing to increase, and in the UK it stands now at 79.5 years for a man, on average, and 83.1 for a woman.
  • But, Public Health England found this year that the average ‘healthy’ average life expectancy – the number of years a person can live largely free of illness – is less than the age people get the state pension

Little proof mindfulness meditation works, say scientists

Source: Scientific American

  • Scientists in the US now asking where is the proof that mindfulness works? Question asked by a group of 15 prominent psychologists and cognitive scientists in the journal Perspectives on Psychological Science.
  • Lots of studies have been done on mindfulness and it has been reported to relieve stress, pain and even slow ageing.
  • But, these researchers are critical of these studies because they say they are poorly designed, they have inconsistent definitions are what mindfulness actually is, and often do not use a control group to rule out the placebo effect.
  • Only some 9 per cent of studies on mindfulness has been tested in clinical trials, one report said, and meta analysis of mindfulness research not impressive.
  • In 2014, a review of 47 meditation trials, involving over 3,500 people found that no evidence mindfulness enhanced enhanced attention, curtailed substance abuse, helped sleep or controlled weight.
  • Mindfulness meditation and training is now a huge industry, so there are vested interests promoting its effectiveness, the scientists state.
  • Less than 25 per cent of trials on mindfulness monitor potential negative effects and that is causing worry among scientists too.
  • The 2014 review did find some benefits, modest benefits, for anxiety, depression and pain from the use of mindfulness.
  • A reputable trial this year found that mindfulness attention training reduced self perceived stress, but not the stress hormone cortisol. What does it mean?
  • Another trial found that mindfulness increased the thickness of the prefrontal cortex around of the brain, which is associated with complex behaviour, decision making and shaping the personality.

Ancient Egypt brought down by volcanoes and climate change

Source: Independent UK

  • Volcanic eruptions caused riots and rebellions against Ptolemaic rule and Cleopatra was one of those leaders.
  • Ancient Egypt relied on monsoon weather to provide water irrigate the nile delta region, as does 70 per cent of the globe still today
  • Researchers at TCD and Yale looked at the historical records and used climate modelling methods (working backwards) to do this study.
  • Summer floods helped crops to grow, fed population and were the fundamental basis for the wealth of ancient Egypt at this time 350BC to 30 BC or so.

Yellowstone Super Volcano could erupt inside decades causing global volcanic winter

Source: Independent UK

  • The last time it erupted was 630,000 years ago and created the Yellowstone caldera, which is 40 miles wide.
  • The volcano is so big that if it erupted, it could choke the Earth’s entire atmosphere with ash, blocking out a lot of sunlight, causing temperatures to dip, and this would continue for years.
  • That last massive eruption, scientists at Arizona State have found, occurred following two influxes of fresh magma into the magma chamber.
  • The temperatures increased around the volcano as this happened over decades, not centuries, as previously thought.
  • This shows that the the yellowstone volcano could become dangerous inside decades, at any point, when temperatures start to rise.
  • Large parts of the USA would be covered in dangerous ash if it erupted, the Earth would dramatically cool, sunlight would struggle to get through and the impact would last more than a decade. Life would get very tough, esp in US.

Chinese space station will crash to Earth in months

Source: Guardian UK

  • The 8.5 tonne orbiting laboratory (two large male bull elephants) is now out of control, and in a death spiral, and the ISS will follow perhaps as earth as 2020.
  • The Tiangong-1, or heavenly palace, lab was launched in 2011 as part of China’s push to become a space superpower.
  • Visited by taikonauts including China’s first female taikonaut Liu Yang in 2012.
  • Much of the craft will burn up in the atmosphere, but scientists in the west estimate that pieces as large as 100kg (16 stone man) will crash to Earth anytime between now and April 2018.
  • Impossible to predict when and where the pieces will fall scientists say.
  • No-one has been hurt by space debris falling to Earth, but in 1979 NASA’s 77-tonne Skylab space station crashed to the ground with some large pieces landing outside Perth.

 

Plant proteins key to fighting hunger and global warming – TCD research

Legumes are high in protein density and have a relatively low environmental production cost (Source: Monash University)

The consumption of plant protein found in peas, beans and lentils can stave off global hunger and reduce the environmental impact of food production.

That’s according to a TCD study which shows that plant protein from legumes has the high nutrient density and the lowest environmental production costs.

The study led by Assistant Professor in Botany Mike Williams and conducted by students Shauna Maguire and Conor O’Brien was part of Project TRUE which is an initiative of the Wildlife Conservation Society.

The TCD researchers scored dietary protein sources in terms of both the environmental cost of production (which incorporates greenhouse gas emissions, groundwater pollution and land requirement), and their nutrient content.

“Plant protein sources, in this case legumes such as peas, beans and lentils, show the highest nutrient density and the lowest environmental costs associated with production,” said Professor Williams.

“For example, peas have a nutrient density to environmental footprint ratio approximately five times higher than equivalent amounts of lamb, pork, beef or chicken,” Prof Williams said.

“In other words, you receive more beneficial nutrients per 100 kcals of legumes than similar amounts of meat, and at far less an environmental cost,” Prof Williams added.

The researchers believe that providing quantitative estimates for sustainable food and agriculture can help consumers make more informed choices about how they will source the main protein component in their diet.

 

 

 

 

 

 

The consumption of plant protein found in peas, beans and lentils can stave off global hunger and reduce the environmental impact of food production.

That’s according to a TCD study which shows that plant protein from legumes has the high nutrient density and the lowest environmental production costs.

The study led by Assistant Professor in Botany Mike Williams and conducted by students Shauna Maguire and Conor O’Brien was part of Project TRUE which is an initiative of the Wildlife Conservation Society.

The TCD researchers scored dietary protein sources in terms of both the environmental cost of production (which incorporates greenhouse gas emissions, groundwater pollution and land requirement), and their nutrient content.

“Plant protein sources, in this case legumes such as peas, beans and lentils, show the highest nutrient density and the lowest environmental costs associated with production,” said Professor Williams.

“For example, peas have a nutrient density to environmental footprint ratio approximately five times higher than equivalent amounts of lamb, pork, beef or chicken,” Prof Williams said.

“In other words, you receive more beneficial nutrients per 100 kcals of legumes than similar amounts of meat, and at far less an environmental cost,” Prof Williams added.

The researchers believe that providing quantitative estimates for sustainable food and agriculture can help consumers make more informed choices about how they will source the main protein component in their diet.

 

 

 

 

 

 

Schizophrenia due to faulty brain wiring, according to NUIG co-led research

Changes in white matter right across the brain have been conclusively linked to schizophrenia in an international study co-led by NUIG (Pic: NUIG)

The hallucinations, delusions and cognitive difficulties experienced by people with schizophrenia are due to widespread damage to the brain’s wiring.

That’s according to research carried about by scientists across the world as part of the ENIGMA consortium and co-lead by NUI Galway.

“It’s almost 40 years since we had the first clues that schizophrenia was associated with changes in the brain structure,” said Professor Gary Donohue, NUIG, a senior author on the study published in Molecular Psychiatry.

“What the ENIGMA consortium has achieved here is to provide definitive proof that these changes are not specific to any one area of the brain, but rather reflect subtle, yet widespread changes throughout the brain.”

“In terms of the idea that schizophrenia might be caused by a mis-wiring of the brain, this study provides unequivocal evidence that this is the case,” said Professor Donohue. “The next step will be to identify the individual genetics variants that lead to the mis-wiring,” Prof Donohue added.

Schizophrenia has been the focus of neuroimaging studies for decades, yet its neurobiology remained only partially understood. The World Health Organisation has described the disease as a leading cause of disability, and more disabling than paraplegia or blindness in 18 to 35 year olds.

Prof Gary Donohoe, Psychology, NUIG, was a senior author on the research (Pic: Aengus McMahon)

The ENIGMA consortium brought together researchers from all over the world to conduct the first large-scale, co-ordinated study of white matter differences in people with schizophrenia.

The researchers examined samples from 4,322 individuals, and that large number allowed for greater power to identify changes across the entire brain than has been possible with previous studies.

The consortium team used a technology called diffusion tensor imaging to show that, in people with schizophrenia, the white matter fibres which connect different brain regions are frayed making communication between different regions ‘sub optimal’. Changes were seen right across the brain.

This is the first conclusive evidence to support the ‘dysconnectivity hypothesis’ which held that schizophrenia may involve abnormal or inefficient communication between brain regions due to disturbances in the pattern of white matter.

 

Alcohol drug found to be effective against lung cancer

Dr Martin Barr, School of Medicine, TCD, whose team has found that the anti-alcohol abuse drug, Antabuse, is effective against lung cancer

The FDA-approved alcohol aversion drug, disulfiram (Antabuse), has been found to be very effective in combating chemotherapy resistance in lung cancer.

Scientists based at TCD and St James’s Hospital, Dublin, have reported the finding for the most common type of lung cancer – non-small cell lung cancer (NSCLC) – in the journal Oncotarget.

“Disulfiram is an already approved drug will well tolerated side effects which can be taken orally,” said Dr Martin Barr, Adjust Assistant Professor and a lead investigator in the Thoracic Oncology Research Group, based at TCD and St James’s. 

“Its potential use may give chemotherapeutic drugs such as cisplatin, a new lease of life in the treatment of resistant drug tumours,” Dr Barr added.

Antabuse has been used to treat alcohol addiction for over 60 years and works by restricting the activity of aldehyde dehydrogenase (ALDH) the main enzyme involved in removing alcohol from the body.

It works by preventing the body from metabolising alcohol, and so the person consuming alcohol will start to feel sick.

Antabuse has now been also found – also by inhibiting ALDH – to decrease tumour cell growth and increase the body’s killing action against lung cancer stem cells. The killing of cancer stem cells is important, because this can prevent the cancer from recurring.

The scientists at TCD and St James’s, working with the Cancer Stem Cell Group at the Coombe Hospital, Dublin, found that lung cancer cells that have high levels of ALDH activity – which is a marker for the presence of cancer stem cells, – become resistant to chemotherapy.

This resistance means that cancer cells can survive chemotherapy and may explain why a large number of lung cancer patients receiving certain types of chemotherapy suffer a relapse in their cancer afterwards.

The development of new drugs is an expensive, time consuming business, and cancer scientists have begun to assess drugs already approved to treat non cancer illness such as Antabuse, for their effectiveness against cancer.

Lung cancer is the leading cause of cancer-related deaths worldwide and accounts for more deaths than breast, colon and prostate cancer combined. In Ireland there are more than 2,300 new cases of lung cancer per year and over 1,800 deaths.