Naturally occurring molecule may help prevent and treat atherosclerosis

Resolvin E1, a molecule produced naturally in the body from an omega -3 fish oil, topically applied on gum tissues not only prevents and treats gum disease as previously shown (Hasturk et al 2006 and 2007), but also decreases the likelihood for advanced arterial atherosclerotic plaques to rupture and form a dangerous thrombus or blood clot.

The findings, which appear in the journal Current Atherosclerosis Reports, could lead to effective preventive and therapeutic treatments in people with heart disease and/or gum disease without unwanted side effects.

Inflammation is a key pathology of atherosclerosis and may be a major driving force for heart attacks and stroke. There is increasing evidence from numerous research groups that chronic inflammatory diseases including, diabetes, heart disease, rheumatoid arthritis, colitis, pulmonary and kidney diseases, cancer and Alzheimer’s disease can benefit by the use of the pro-resolving lipid mediators, resolvins and lipoxins.

To test the effectiveness of lipid mediators on advanced atherosclerosis, researchers from BUSM and The Forsyth Institute used two groups of an experimental model that possessed highly inflamed advanced atherosclerosis. The first group was treated with a solution applied on gum tissues that contained Resolvin E1 while the second group was treated with salt water as a control. The group treated with the inflammation- lowering lipid mediator (Resolvin E1) had minimal atherosclerosis and reduced plaque rupture in their aortic artery, while atherosclerosis advanced to more severe form of the disease in the control group.

“Current therapies for advanced atherosclerosis are inadequate and often carry high risks, and the Resolvin E1 therapy could provide a very effective and safe therapy that can be taken daily, which would also serve as a preventive approach for plaque inflammation and acute clinical events of heart attack and stroke,” explained corresponding author James A. Hamilton, PhD, professor of physiology and biophysics and research professor of medicine at BUSM.

The researchers believe these findings support a paradigm shift in the treatment of both localized and systematic inflammatory conditions that are increasingly prevalent in type 2 diabetes and obesity and may be applicable to other chronic inflammatory diseases.

Kevlar-based artificial cartilage mimics properties of the real thing

The unparalleled liquid strength of cartilage, which is about 80% water, withstands some of the toughest forces on our bodies.

Synthetic materials couldn’t match it – until ‘Kevlartilage’ was developed by researchers at the University of Michigan and Jiangnan University.

“We know that we consist mostly of water – all life does – and yet our bodies have a lot of structural stability,” said Nicholas Kotov, the Joseph B. and Florence V. Cejka Professor of Engineering at U-M, who led the study. “Understanding cartilage is understanding how life forms can combine properties that are sometimes unthinkable together.”

While other varieties of synthetic cartilage are already undergoing clinical trials, these materials fall into two camps that choose between cartilage attributes, unable to achieve that unlikely combination of strength and water content.

The other synthetic materials that mimic the physical properties of cartilage don’t contain enough water to transport the nutrients that cells need to thrive, Kotov said.

Meanwhile, hydrogels – which incorporate water into a network of long, flexible molecules – can be designed with enough water to support the growth of the chondrocytes cells that build up natural cartilage. Yet those hydrogels aren’t especially strong. They tear under strains a fraction of what cartilage can handle.

The new Kevlar-based hydrogel recreates the magic of cartilage by combining a network of tough nanofibers from Kevlar – the “aramid” fibres best known for making bulletproof vests – with a material commonly used in hydrogel cartilage replacements, called polyvinyl alcohol, or PVA.

In natural cartilage, the network of proteins and other biomolecules gets its strength by resisting the flow of water among its chambers. The pressure from the water reconfigures the network, enabling it to deform without breaking. Water is released in the process, and the network recovers by absorbing water later.

This mechanism enables high impact joints, such as knees, to stand up to punishing forces. Running repeatedly pounds the cartilage between the bones, forcing water out and making the cartilage more pliable as a result. Then, when the runner rests, the cartilage absorbs water so that it provides strong resistance to compression again. The synthetic cartilage boasts the same mechanism, releasing water under stress and later recovering by absorbing water like a sponge. The aramid nanofibers build the framework of the material, while the PVA traps water inside the network when the material is exposed to stretching or compression. Even versions of the material that were 92% water were comparable in strength to cartilage, with the 70%version achieving the resilience of rubber.

As the aramid nanofibers and PVA don’t harm adjacent cells, Kotov anticipates that this synthetic cartilage may be a suitable implant for some situations, such as the deeper parts of the knee. He also wonders whether chondrocytes might be able to take up residence inside the synthetic network to produce a hybrid cartilage.

But his potential applications are not limited to cartilage. He suspects that similar networks, with different proportions of aramid nanofibers, PVA and water, may be able to stand in for other soft tissues.

Gene marker could identify sickle cell patients with highest risk of complications

Researchers have found a genotype that could help identify sickle cell disease (SCD) patients at greatest risk of common, yet severe, complications of SCD. The findings were presented at the American Physiological Society’s Physiological and Pathophysiological Consequences of Sickle Cell Disease conference in Washington, D.C.m in November. The chronic breakdown of red blood cells (haemolysis) is a hallmark of SCD that increases during times of illness. Haemolysis leads to the release of haemoglobin – and a protein that binds with it called haptoglobin – that increase a patient’s chances of developing acute chest syndrome (ACS).

“ACS is defined broadly as increased respiratory effort, fever and a new radiodensity on chest X-ray. ACS is a significant cause of hospitalizations and death in children and adults with SCD,” said the study’s lead author, Shaina Willen, MD, of Vanderbilt University Medical Center in Tennessee. ACS is a common complication among SCD patients, affecting roughly 50% at least once in their lifetime.

HP1-1, HP1-2 and HP2-2 are the three genetic markers (genotypes) associated with haptoglobin. These genotypes predict how effective an individual’s haptoglobin is at binding to and clearing away excess haemoglobin. The haptoglobin in people with the HP2-2 genotype is not as effective in haemoglobin-binding, and HP2- 2 has been linked to increased cellular (oxidative) damage.The research team hypothesized that patients with the HP2- 2 genotype would be more susceptible to SCD-related complications including ACS, pain, stroke, retinal problems in the eyes, kidney disease and high blood pressure in the arteries of the lungs than patients with HP1-1 and HP1-2 genotypes.

The researchers tested 58 adults with SCD and found that 90% of those with the HP2-2 genotype had two or more SCD-related complications compared with 46.7% and 56.3% of those with the HP1-1 and HP1-2 genotypes, respectively.

“Our study has identified an increased risk for the development of sickle cell disease-related complications among adult participants with the HP2-2 genotype,” Willen explained. “We have also found that children with the HP2-2 genotype are at increased risk for the development of pain episodes which is the most common cause of hospitalization in children and adults with SCD.

“This finding may identify both adults and children at risk for developing diseaserelated complications. The impact of the HP2-2 genotype on the ability of haptoglobin to scavenge products of haemolysis may provide therapeutic targets to investigate related to the oxidative effect of cellfree haemoglobin and the pathophysiology of complications in SCD.”


Brain astrocytes linked to Alzheimer’s disease

Astrocytes, the supporting cells of the brain, could play a significant role in the pathogenesis of Alzheimer’s disease (AD), according to a new study from the University of Eastern Finland. This is the first time researchers discovered a direct association between astrocytes and AD. Published in Stem Cell Reports, the study investigated the brain cell function of familial AD patients by using stem cell technologies.

Alzheimer’s disease is the most common dementia type, with no treatment to slow down the progression of the disease currently available. The mechanisms of AD are poorly understood, and drug therapy has focused on restoring the normal function of neurons and microglia, i.e. cells mediating brain inflammation. The new study shows that astrocytes, also known as the housekeeping cells of the brain, promote the decline of neuron function in AD. The findings suggest that at least some familial forms of AD are strongly associated with irregular astrocyte function, which promotes brain inflammation and weakens neurons’ energy production and signalling.

Astrocytes are important brain cells, as they support neurons in many different ways. Astrocytes are responsible, for example, for the energy production of the brain, ion and pH balance, and they regulate synapse formation, the connections between neurons. Recent evidence suggests that human astrocytes are very different from their rodent counterparts and thus, it would be essential to use human cells to study human diseases. However, the availability of human astrocytes for research has been very limited.

The study used the induced pluripotent stem cell technology, which enables the generation of pluripotent stem cells from human skin fibroblasts. These induced stem cells can then be further differentiated to brain cells, e.g. neurons and astrocytes, with the same genetic background as the donor had.

The study compared astrocytes from familial AD patients carrying a mutation in the presenilin 1 gene to astrocytes from healthy donors, and the effects of these cells on healthy neurons were also analysed.

The researchers found that astrocytes in patients with Alzheimer’s disease produced significantly more beta-amyloid than astrocytes in persons without AD. Beta-amyloid is a toxic protein that is known to accumulate in the brains of AD patients. In addition, AD astrocytes secreted more cytokines, which are thought to mediate inflammation. AD astrocytes also showed alterations in their energy metabolism which likely led to increased production of reactive oxygen species and reduced production of lactate, an important energy substrate for neurons. Finally, when astrocytes were co-cultured with healthy neurons, AD astrocytes caused significant changes on the signalling activity of neurons when compared to healthy astrocytes.

This study was the first to show that astrocytes in patients with Alzheimer’s disease manifest many pathological changes typical of AD. Astrocytes could thus play a key role in the early stages of the disease and changes in the function of these cells could lead to neurodegeneration.

“The induced pluripotent stem cells we used in this study proved to be extremely useful in disease modelling, and they could offer an excellent platform for drug discovery and testing new therapeutic targets for Alzheimer’s disease in the future,” says Early Stage Researcher Minna Oksanen, the lead author of the study.

• doi: 10.1016/j.stemcr.2017.10.016

Worldwide, nearly 6% of cancers are attributable to diabetes and high BMI

Diabetes and high BMI (a BMI over 25 kg/ m2) were the cause of 5.6% of new cancer cases worldwide in 2012 – equivalent to 792600 cases, according to the first study to quantify the proportion of cancers attributable to diabetes and high BMI published in The Lancet Diabetes & Endocrinology journal.

When considered individually, 544,300 cases of cancer were attributable to high BMI (equivalent to 3.9% of all cancers), and 280,100 were attributable to diabetes (2%).

Estimates suggest that 422 million adults have diabetes and 2.01 billion adults are overweight or obese, globally. Both high BMI and diabetes are risk factors for various types of cancer, potentially due to biological changes caused by diabetes and high BMI – such as high insulin, high sugar levels, chronic inflammation, and dysregulated sex hormones such as oestrogen – having adverse effects on the body.

With these two risk factors becoming increasingly widespread, the proportion of attributable cancers is set to grow further.

“As the prevalence of these cancer risk factors increases, clinical and public health efforts should focus on identifying preventive and screening measures for populations and for individual patients. It is important that effective food policies are implemented to tackle the rising prevalence of diabetes, high BMI and the diseases related to these risk factors,” says lead author Dr Jonathan Pearson-Stuttard, Imperial College London, UK.

The study assessed the increase in new cases of 18 cancers based on the prevalence of diabetes and high BMI in 175 countries between 1980 and 2002.

To conduct the study, the authors gathered data on the incidence of 12 types of cancer from 175 countries in 2012. They combined this with data on high BMI and on diabetes. They matched the data sets by age group and sex to take account of age differences using diabetes and BMI data from 2002 to calculate cancer incidence in 2012 attributable to these risks.

Most of the cancer cases attributable to diabetes and high BMI occurred in high-income western countries (38.2%, 303,000/792,600 cases), and the second largest proportion occurring in east and southeast Asian countries (24.1%, 190,900/792,600 cases).

Although cancers are still less common in some low and middle-income countries than in high-income nations, the population of these countries experienced particularly large impacts from diabetes and high BMI. For example, between 9% and 14% of all cancer cases in Mongolia, Egypt, Kuwait, and Vanuatu were due to high BMI and diabetes. Meanwhile Tanzania, Mozambique, and Madagascar had the lowest proportion of cases attributable to high BMI and diabetes. This reflects geographical differences in the prevalence of diabetes and obesity as well as incidence of cancers affected by them.

Globally, liver cancer and endometrial cancer contributed the highest number of cancer cases caused by diabetes and high BMI (24.5%, 187,600/766,000 cases, and 38.4% 121,700/317,000 cases, respectively). However, the number of cases of different cancers varied globally, and in highincome Asia Pacific and east and southeast Asian countries liver cancer caused 30.7% and 53.8% of cases respectively, while in high-income western countries, central and eastern Europe, and sub-Saharan Africa breast and endometrial cancers contributed 40.9% of cancer cases.

Globally, the growing number of people with diabetes between 1980 and 2002 led to 77,000 new cases of attributable cancers in 2012 (26.1% increase). Similar increases in the number of people with high BMI led to 174,040 new cases of weight-related cancers (a 31.9% increase) over the same time.

Low- and middle-income countries across Asia and sub-Saharan Africa saw the largest increases in cancers due to diabetes and overweight and obesity, as the levels of diabetes and high BMI in these regions increased substantially between 1980 and 2002. For example, the number of diabetes-related cancers grew by 88% in 2012 for men in south Asia, increasing from 3500 cases in 1990 to 6600 cases in 2012. Similarly, cancer cases attributable to high BMI in women in sub-Saharan Africa increased by 80% - from 5400 cases in 1990 to 9700 cases in 2012.

The proportion of cancers related to diabetes and high BMI is expected to increase even further globally as the prevalence of the two risk factors increases. Using projected prevalence of diabetes and high BMI for 2025 compared with prevalence in 2002, the researchers estimate that the proportion of related cancers will grow by more than 30% in women and 20% in men on average.

Dr Pearson-Stuttard adds: “Increases in diabetes and high BMI worldwide could lead to a substantial increase in the proportion of cancers attributable to these risk factors, if nothing is done to reduce them. These projections are particularly alarming when considering the high and increasing cost of cancer and metabolic diseases, and highlight the need to improve control measures, and increase awareness of the link between cancer, diabetes, and high BMI.”

The authors note that the 10 year lag between risk factor exposure and cancer development is a simple estimate of how long it takes for cancer to develop so may not include full exposure to the risk. There is growing evidence suggesting that diabetes is also related to myeloma, bladder, kidney, and oesophageal cancer, meaning the study may underestimate the burden of cancers due to diabetes.

• doi: 10.1016/S2213-8587(17)30366-2

Immediate treatment with clot-stabilising drug could save thousands of lives

Time is of the essence when it comes to administering the clot-stabilising drug tranexamic acid to people with serious injury or women with severe bleeding after childbirth, according to a meta-analysis of over 40,000 patients, published in The Lancet. The study found that the likelihood of death due to blood loss was reduced by over 70% if the low-cost, readilyavailable drug was given immediately after injury or birth. But the chances of survival fell by 10% for each 15-minute delay, with no benefit seen after 3 hours.

“Responding quickly can be the difference between life and death, and that means patients must be treated urgently at the scene of injury or as soon as the diagnosis of haemorrhage is made. We have to make sure tranexamic acid is available before patients reach hospital and whenever a woman gives birth,” says Professor Ian Roberts from the London School of Hygiene & Tropical Medicine, UK, who initiated the study.

Every year, more than 2 million people worldwide die from traumatic extracranial bleeding, often as a result of road traffic injuries and violence. Furthermore, postpartum haemorrhage is the leading cause of maternal death worldwide, killing around 100,000 women a year.

Antifibrinolytic drugs such as tranexamic acid, aminocaproic acid, and aprotinin work by stopping blood clots from breaking down and reducing bleeding. They have been used for many years to reduce heavy menstrual bleeding and are often given during surgery to reduce the need for blood transfusions.

This new study builds on previous research from the WOMAN and CRASH-2 trials which showed that tranexamic acid cut deaths due to post-partum haemorrhage and bleeding after serious injury by about a third if given within 3 hours of bleeding onset. In this new analysis, Roberts and colleagues did a meta-analysis of individual patient data from these two trials, involving 40,138 men and women and found that almost two-thirds of bleeding deaths occurred within 12 hours of onset (884 of 1,408 bleeding deaths). Deaths due to post-partum haemorrhage peaked 2-3 hours after childbirth.

Overall, survival from severe bleeding was increased by a fifth with the use of tranexamic acid compared to placebo, irrespective of the site of bleeding (1.5% of women given tranexamic acid died of bleeding [155/10034] vs 1.9% of women given placebo plus standard care [190/9977], and 4.9% trauma patients given tranexamic acid died of bleeding [489/10060] vs 5.7% given placebo and standard care [574/10067]). This figure rose to 70% if the drug was administered immediately. For every 15-minute delay in treatment, survival benefit was cut by about 10%, even after taking into account age and systolic blood pressure, which are strong risk factors for death due to bleeding. No benefit was seen if treatment was delayed beyond 3 hours.

The researchers also found no evidence of complications or increased risk of clotting (i.e., heart attack, stroke, pulmonary embolism, and deep vein thrombosis) compared to placebo, and fewer cases of heart attacks were noted with tranexamic acid.

The authors explain that because treatment delay may be underestimated in trauma (many injuries are unwitnessed), and overestimated in post-partum haemorrhage (birth is taken as the time of bleeding onset), they did sensitivity analyses to test a range of plausible errors. Their results support the conclusion that prompt treatment is essential.

Professor Roberts explains: “Tranexamic acid is safe, cheap, easily administered, and does not need to be refrigerated. Most haemorrhage deaths occur within hours of bleeding onset. Prompt treatment has the potential to save thousands of additional lives worldwide every year.”

“Given the importance of early treatment, time from bleeding onset to early treatment should be audited and communicated to healthcare professionals. Establishing national or regional quality improvement initiatives, with best practice benchmarking of time to treatment, might improve survival. More research is needed to improve our understanding of the mechanism of action of this life-saving treatment.” a

New imaging technique enables view of sub-cellular structures of living cells

To undergo high-resolution imaging, cells often must be sliced and diced, dehydrated, painted with toxic stains, or embedded in resin. For cells, the result is certain death.

But if researchers can only view the inner workings of dead cells, they’re only seeing part of the story. They cannot monitor living cells’ dynamic real-time processes, such as metabolic reactions or responses to diseases or treatments.

“Sub-cellular components and structures have a profound influence on the behaviour of the complex cellular machinery and systems biology,” said Northwestern University’s Materials Science and Engineering Department’s Gajendra Shekhawat. “However, unravelling the structures and components inside the cell is very challenging because they are so fragile.”

Now Shekhawat and Vinayak P. Dravid, the Abraham Harris Professor of Materials Science and Engineering, have developed a novel non-invasive imaging system that makes it possible to view the sub-cellular architecture of live cells at nanometrescale resolution.

Called Ultrasound Bioprobe, the technique combines ultrasound waves with atomic force microscopy, interacting withlive cells to determine the changes in their mechanical behaviour.

Supported by the US National Science Foundation (NSF) and the National Heart, Lung, and Blood Institute, the research was recently published in Science Advances. Shekhawat and Dravid served as the paper’s co-corresponding authors. Shekhawat, a research associate professor in materials science and engineering, was also the first author of the paper. The research was completed in the Northwestern University Atomic and Nanoscale Characterization Experimental (NUANCE) Center.

Despite recent advances in imaging, there is currently no single method that provides high-resolution and high-sensitivity images of living sub-cellular structures. Fluorescent and confocal microscopy, which are traditional methods for monitoring the biological interactions inside cells, suffer from poor spatial resolution and require invasive dyes or labels to enhance contrast and highlight structures within biological tissues. Light and acoustic wave imaging are unable to view structures smaller than a few hundred nanometres. Scanning probe microscopy can provide very high spatial resolution but can only identify surface structures rather than peer inside a cell. And while electron microscopy can view fine details at the sub-cellular level, it’s a destructive technique that cannot be used for living biological tissues.

“Many roadblocks have existed,” said Dravid, who directs the NUANCE Center and the SHyNE Resource. “Characterization of the complex dynamics of biological processes, especially signal pathways at nanoscale resolution, has remained a challenge.”

Shekhawat and Dravid’s Ultrasound Bioprobe, however, bypasses these issues. Its ultrasound waves non-invasively image deeply buried intracellular features. And its atomic force microscopy probe provides high sensitivity and mechanical contrast of the scattered ultrasound waves. The result? Non-destructive, remarkably high-contrast, nanoscale images of structures and components deep inside living tissues and cells.

“Using this non-invasive approach, we can monitor real-time imaging of the nanomechanical changes in complex biological systems,” Shekhawat said. “This could provide clues for early diagnostics and potential pathways for developing therapeutic strategies.”

Next, the team plans to expand its technique to diverse biomedical applications, such as the nanomechanics of soft tissues such as skin, enamels, and bones to probe their three-dimensional architecture down to nanoscale spatial resolution.


Pre-hospital treatment can help seriously injured patients

Researchers may have paved the way for the development of potentially new lifesaving treatments to be administered to seriously injured patients in the critical first hour of injury.

By testing the blood samples of 91 patients taken at the scene of major accidents, the researchers were able for the first time to establish how quickly the lining of blood vessels are damaged, which can lead to a rapid deterioration and even organ failure.

The research, published in Shock, is part of the ongoing ‘Golden Hour’ study led by scientists from the University of Birmingham’s Institute of Inflammation and Ageing, the NIHR Surgical Reconstruction and Microbiology Research Centre (SRMRC) and the Royal Centre for Defence Medicine at Queen Elizabeth Hospital, Birmingham.

A major £10 million study, Golden Hour aims at improving outcomes for patients by developing the understanding of what happens to the immune system within the first 60 minutes from the moment of traumatic injury – a crucial time in which prompt medical treatment is key to survival.

Major David Naumann, a research fellow at the Royal Centre for Defence Medicine and the University of Birmingham, said: “When someone is very seriously injured, for example in a car crash, the body sometimes behaves as if there is a massive infection that it needs to fight, even when none is present. When this happens, the immune system can cause the patient to deteriorate rapidly and could even cause their organs to fail.”

Dr Jon Hazeldine, of the University of Birmingham, said: “One of the things that may be to blame for this process is endotheliopathy which occurs when the lining of blood vessels is damaged. Prior to our study, it was not known when this process happens after injury, or whether having endotheliopathy within an hour of injury might lead to organ failure later on in hospital.”

Professor Janet Lord, of the University of Birmingham, said: “We found that the damage to the lining of the blood vessels happens within minutes of injury, even before an ambulance has arrived, which has never been shown before. We also found that if the lining of the blood vessels improves in the following few hours that patients have lower rates of organ failure.”

Professor Tony Belli, also of the University of Birmingham, added: “Our research has identified a potential target for treatment, to heal the damaged blood vessels, which could be administered by ambulance and helicopter crews on arrival at the scene of injury and improve outcomes for injured patients. As part of our ongoing Golden Hour study we have several ongoing studies examining the causes of endotheliopathy and which treatments may best be used to treat it.”

Key to the research was an around-theclock blood sampling and analysis operation working in collaboration with ambulance and air ambulance services, which has seen paramedics being specially trained to take blood samples from patients at the scene of major traumas.

The observational study used the blood samples taken from 91 seriously injured patients at the scene of a major trauma. Of the 91 patients, who had an average age of 38, 78 were male and 13 were female. Nineteen non-injured individuals were also used as a healthy control. Biomarkers were used to detect endiotheliopathy within the blood. Endiotheliopathy was found to occur five to eight minutes after injury.

• doi: 10.1097/SHK.0000000000000999

Better understanding of nasal sinus pathways could lead to new instructions for nasal sprays

Sinus infections, inflammation and nasal congestion constantly plague peoplearound the world, often leading to unpleasant symptoms and even missed days of work. Traditional nasal spray anti-inflammatory medications attempt to treat the symptoms noninvasively, but are not very efficient in transmitting the active drug ingredients directly into the sinus cavities.

Paranasal sinuses are essentially hollow cavities in the skull surrounding your nasal cavity. While the role of the sinuses is debated, it is believed they function to decrease the weight of the anterior skull, increase voice resonance and buffer against facial trauma. Their location and structure provide the ideal environment for bacterial growth, infection or viral deposition, often leading to diseases like chronic rhinosinusitis (CRS). The typical treatments for these conditions consist of topical medications (nasal sprays) and oral antibiotics.

Researchers Saikat Basu, Zainab Farzal and Julia S. Kimbell of the University of North Carolina’s School of Medicine presented their research on the anatomybased flow physics in nasal cavities which generate “magical” streamlines for sinus drug delivery at the 70th annual meeting of the American Physical Society’s Division of Fluid Dynamics, in November 2017, in Colorado.

“We found that current package instructions for such sprays are not optimal for maximal drug transport to the sinuses, which is a function of various factors like head orientation of the patient, breathing rates and the spray bottle orientation during drug spray,” Basu said.

For the medication to have the greatest effects, the active ingredients must deposit inside or in close proximity of the affected sinus cavities. To ensure accurate anatomical representation in the numerical simulations of the sprayed drug transport process, they used computed tomography (CT) scans from CRS patients and imaging software to develop anatomically realistic digital 3-D models.

Understanding the physics of sinus airflow pathways enables the identification of optimal release points for the nasal sprays. Advances in anatomical modelling make it possible to determine the effect of specific drug routes.

“Ambient respiratory flow physics exert a considerable influence on the transport of sprayed particles in our nasal cavities,” Basu said. “With the advances in computational capacities, it is now possible to develop digital 3-D models of complex physiological systems and track transport processes therein through computational fluid mechanics.”

The preliminary results of this study are relevant to both the consumer and the manufacturer of nasal sprays. The researchers found that when the spray nozzle was inserted deeper into the nose (10mm) that it performed better and that while the current instructions for the spray bottle recommend holding it at 22.5 degrees, drug transport was better at an angle of 35-45 degrees. Drug providers will be able to recommend more effective instructions and application techniques to ensure that the spray reaches its target. Findings might also suggest improvements in the design of the spray console that would amplify the medication deposits inside the sinus cavities.

Vaccine for cutaneous leishmaniasis looks promising

A research team at The University of Texas at El Paso is one step closer to developing an effective human vaccine for cutaneous leishmaniasis.

UTEP biological sciences doctoral student Eva Iniguez; her mentors Rosa Maldonado, Ph.D., and Igor Almeida, Ph.D.; and their teams and collaborators in Liverpool (Alvaro Acosta-Serrano, Ph.D.) and Saudi Arabia (Waleed Al-Salem, Ph.D.), recently published their research findings in PLOS Neglected Tropical Diseases, the first journal solely devoted to the world’s most neglected tropical diseases.

Leishmaniasis is caused by the protozoan leishmania parasites, which are transmitted by the bite of infected female phlebotomine sandflies – flies that are three times smaller than a mosquito. According to the World Health Organization, there are an estimated 700,000 to 1 million new cases annually, and they cause 20,000-30,000 deaths each year. The disease affects some of the poorest people in more than 90 countries in the tropics, subtropics.

“I think we are in a very good position with this vaccine candidate,” Maldonado said. “It is very promising.”

During the team’s more than four years of research at UTEP’s Border Biomedical Research Center, they discovered a vaccine formulation that resulted in a 96% decrease in the lesions caused by the illness and showed an 86% protection rate from the disease in mice. The team counted on the expertise of UTEP chemist Katja Michael, Ph.D., to synthesize molecules used in the study.

“It was really hard to get to this point,” Iniguez said. “There was a lot of standardization, but I am very happy. It is significant protection that we observed and we have all the immunology to understand how the vaccine is working in the system.”

Maldonado and Almeida have each studied Chagas disease for more than 25 years and recently received a patent for the first synthetic Chagas vaccine. That work helped them initiate this research with leishmaniasis, as molecules are different in the diseases but there are similar carbohydrates between the parasites.

The team has submitted a patent application for their cutaneous leishmaniasis vaccine. Currently, there is no vaccine for the disease in humans. Treatment used now is very toxic, painful and lengthy – requiring patients to be hospitalized for almost three weeks for intravenous treatment. A vaccine does exist to treat cutaneous leishmaniasis in canines. It is approved for use in the United Kingdom.

• doi: 10.1371/journal.pntd.0006039



Date of upload: 19th Jan 2018

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