Day: July 19, 2021

Categories : Cardiovascular Disease New Compounds and TreatmentsTags :

A Treatment for Heart Attack from Spider Venom

On By ModernMedia
Photo by Adrián Valverde on Unsplash
Photo by Adrián Valverde on Unsplash

A protein found in the venom of one of the world’s deadliest spiders has been shown to preserve heart cells, and could be developed into a potentially life-saving treatment for heart attack victims.

A drug candidate developed from a molecule found in the venom of the Fraser Island (K’gari) funnel web spider can prevent damage caused by a heart attack and extend the life of donor hearts used for organ transplants. This would not be the first investigation into a clinical application for spider venom, however. Tarantula spider venom has also been investigated as a potent anaesthetic.

The discovery was made by a team led by Dr Nathan Palpant and Professor Glenn King from The University of Queensland (UQ) and Professor Peter Macdonald from the Victor Chang Cardiac Research Institute.

Dr Palpant, from UQ’s Institute for Molecular Bioscience (IMB), said the drug candidate worked by stopping a ‘death signal’ sent from the heart in the wake of an attack.

“After a heart attack, blood flow to the heart is reduced, resulting in a lack of oxygen to heart muscle,” Dr Palpant said. “The lack of oxygen causes the cell environment to become acidic, which combine to send a message for heart cells to die.

“Despite decades of research, no one has been able to develop a drug that stops this death signal in heart cells, which is one of the reasons why heart disease continues to be the leading cause of death in the world.”

Using beating human heart cells exposed to heart attack stresses, Dr Palpant tested the drug candidate, a protein called Hi1a, to see if the drug improved the cells’ survival.

“The Hi1a protein from spider venom blocks acid-sensing ion channels in the heart, so the death message is blocked, cell death is reduced, and we see improved heart cell survival.”

At present, there are no drugs in clinical use that prevent the damage caused by heart attacks.

Professor Macdonald of Victor Chang Cardiac Research Institute said that this incredible result had been decades in the making.

“This will not only help the hundreds of thousands of people who have a heart attack every year around the world, it could also increase the number and quality of donor hearts, which will give hope to those waiting on the transplant list,” said Professor MacDonald, who is also a senior cardiologist at St Vincent’s Hospital in Sydney.

“The survival of heart cells is vital in heart transplants — treating hearts with Hi1a and reducing cell death will increase how far the heart can be transported and improve the likelihood of a successful transplant,” added Prof MacDonald. “Usually, if the donor heart has stopped beating for more than 30 minutes before retrieval, the heart can’t be used — even if we can buy an extra 10 minutes, that could make the difference between someone having a heart and someone missing out. For people who are literally on death’s door, this could be life-changing.”

The discovery builds on earlier work by Professor King, who identified a small protein in the venom of the Fraser Island (K’gari) funnel-web spider that was shown to markedly improve recovery from stroke.

“We discovered this small protein, Hi1a, amazingly reduces damage to the brain even when it is given up to eight hours after stroke onset,” Professor King said.

“It made sense to also test Hi1a on heart cells, because like the brain, the heart is one of the most sensitive organs in the body to the loss of blood flow and lack of oxygen.

“For heart attack victims, our vision for the future is that Hi1a could be administered by first responders in the ambulance, which would really change the health outcomes of heart disease.”

“This is particularly important in rural and remote parts of Australia where patients and treating hospitals can be long distances apart — and when every second counts.”

Also, this could help for the transfer of donor hearts for cardiac transplantation — allowing these donor hearts to be transported over longer distances and therefore increasing the network of available donors and recipients.

The protein has been tested in human heart cells, and the team are aiming for human clinical trials for both stroke and heart disease within 2-3 years.

Source: ScienceDaily

Journal information: Meredith A. Redd, et al. Therapeutic Inhibition of Acid Sensing Ion Channel 1a Recovers Heart Function After Ischemia-Reperfusion Injury. Circulation, 2021; DOI: 10.1161/CIRCULATIONAHA.121.054360

Categories : Antibiotics Diseases, Syndromes and ConditionsTags :

Untreated Sewage is a Driver of Antibiotic Resistance

On By ModernMedia
Photo by Jordan Opel on Unsplash
Photo by Jordan Opel on Unsplash

Contamination of urban lakes, rivers and surface water by human waste is creating pools of ‘superbugs’ in Low- and Middle-Income Countries (LMIC), according to new research. However, improving access to clean water, sanitation and sewerage infrastructure could help to improve public health.

For the study, researchers studied bodies of water in urban and rural sites in three areas of Bangladesh: Mymensingh, Shariatpur and Dhaka. In comparison to rural settings, they detected more antibiotic resistant faecal coliforms in urban surface water , consistent with reports of such bacteria in rivers across Asia. Their findings were published in mSystems.

Lead author Willem van Schaik, Professor of Microbiology and Infection at the University of Birmingham, commented: “The rivers and lakes of Dhaka are surrounded by highly-populated slums in which human waste is directly released into the water. The presence of human gut bacteria links to high levels of antibiotic resistance genes, suggesting that such contamination is driving the presence of these ‘superbugs’ in surface water.

“Interventions aimed at improving access to clean water, sanitation and sewerage infrastructure may thus be important to reduce the risk of antimicrobial resistance spreading in Bangladesh and other LMICs. While levels of antibiotic resistance genes are considerably lower in rural than in urban settings, we found that antibiotics are commonly used in fish farming and further policies need to be developed to reduce their use.”

Infections from antibiotic-resistant bacteria are on the rise globally, but the clinical issues posed by these bacteria are particularly alarming in LMICs, with significant morbidity and mortality. As in other LMICs, multidrug-resistant E. coli has a relatively high prevalence in healthy humans in Bangladesh.

With a population of around 16 million people, Dhaka’s population density ranks among the highest of any megacity, but less than 20% of its households have a sewerage connection.

Urban surface waters in Bangladesh are particularly rich in antibiotic resistance genes, the researchers discovered, with a higher number of them associated with plasmids — vehicles of genetic exchange among bacteria — indicating that they are more likely to spread through the population.

Antibiotic-resistant bacteria that colonise the human gut can be passed into rivers, lakes and coastal areas through the release of untreated wastewater, the overflow of pit latrines during monsoon season or by practices such as open defecation.

Such contaminated environments are often used for bathing, for the washing of clothes and food utensils, thereby risking human gut colonisation by antibiotic-resistant bacteria.

The researchers from the University of Birmingham and the International Centre for Diarrhoeal Disease Research, Bangladesh called for further research to quantify the drivers of antibiotic resistance in surface waters in Bangladesh.

Source: University of Birmingham

Journal information: McInnes, R.S., et al. (2021) Metagenome-Wide Analysis of Rural and Urban Surface Waters and Sediments in Bangladesh Identifies Human Waste as a Driver of Antibiotic Resistance. mSystems. doi.org/10.1128/mSystems.00137-21.

Categories : Uncategorized

No Azithromycin Benefit in Mild COVID

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Photo by Tamanna Rumee on Unsplash
Photo by Tamanna Rumee on Unsplash

A small study has found that the antibiotic azithromycin had no effect in prevention of COVID symptoms among non-hospitalised patients, and could increase hospitalisation risk, even though the antibiotic is widely used for the disease.

“These findings do not support the routine use of azithromycin for outpatient SARS-CoV-2 infection,” said lead author Catherine E Oldenburg, ScD, MPH, an assistant professor with the UCSF Proctor Foundation. 

Azithromycin, a broad-spectrum antibiotic of the macrolide class, is widely prescribed as a treatment for COVID-19 in the United States and the rest of the world. “The hypothesis is that it has anti-inflammatory properties that may help prevent progression if treated early in the disease,” said Oldenburg. “We did not find this to be the case.”

The study was published in the Journal of the American Medical Association.

The study recruited 263 non-hospitalised participants who had tested positive for SARS-CoV-2 seven days or sooner before entering the study. Of these, 171 participants were randomised to receive\ a single, 1.2 gram oral dose of azithromycin and 92 received an identical placebo.
At day 14, 50 percent of the participants remained symptom-free in both groups. By day 21, five of the participants who received azithromycin had been hospitalised with severe COVID symptoms and none of the placebo group had been hospitalised.

From these findings, the researchers concluded that treatment with a single dose of azithromycin compared to placebo did not result in greater likelihood of being symptom-free.

“Most of the trials done so far with azithromycin have focused on hospitalised patients with pretty severe disease,” said Oldenburg. “Our paper is one of the first placebo-controlled studies showing no role for azithromycin in outpatients.”

The PRINCIPLE study being conducted in the UK investigating common medications for community treatment of moderate COVID also found no benefit to using azithromycin.

Source: University of California, San Francisco

Journal information: Catherine E. Oldenburg et al, Effect of Oral Azithromycin vs Placebo on COVID-19 Symptoms in Outpatients With SARS-CoV-2 Infection, JAMA (2021). DOI: 10.1001/jama.2021.11517

Categories : Medical Research & TechnologyTags :

Artificial Sweetener Delivers a Protective Carbon Monoxide Dose

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Photo by Sharon McCutcheon on Unsplash
Photo by Sharon McCutcheon on Unsplash

An oral prodrug has been developed which uses artificial sweeteners to deliver a protective carbon monoxide dose which protects against acute kidney injury.

Although carbon monoxide (CO) gas is toxic in large doses, with some 50 000 people suffering CO poisoning each year in the US, scientists have discovered it can reduce inflammation and protect cells against injury. The  protective effects of CO against injury in the kidneys, lungs, gastrointestinal tract and liver, among other organs has been shown in previous research. For the past five years, Wang and his collaborators have worked to design a safe way to deliver CO to human patients via prodrugs, which are inactive compounds that must undergo a chemical process in the body to release the active pharmacological agent. Their paper was published in Chemical Science.

Using two common artificial sweeteners, saccharine and acesulfame, as ‘carrier’ molecules for a prodrug, Prof Wang’s team were able to create an oral administration route for CO. They designed the molecules to release CO as they decomposed from water exposure. These are the first examples of orally active, organic CO prodrugs using a benign carrier that is approved by the Food & Drug Administration with a demonstrated safety profile.

“It’s difficult to deliver a gas, much less a poisonous gas, as a therapeutic to patients, and this work represents a pivotal step forward in developing alternative delivery forms,” said Prof Wang, a Georgia Research Alliance Eminent Scholar. “We wanted to work with a carrier that has a very well characterized safety profile, which confers a higher degree of certainty that it will be safe to use in a pill for human consumption.”

The scientists tested one of the prodrugs, CO-306, for pharmacological efficacy against acute kidney damage. CO-306, which uses saccharine as a carrier molecule, was administered to mice and it was found that it reduced biomarkers for kidney injury, indicating it could be developed working therapy. The type of kidney injury modelled mimicked those in humans that occur with extensive muscle damage, sickle cell disease, a common type of malaria, cardiopulmonary bypass surgery and severe sepsis.

Further animal model studies and safety assessments on CO-306 are planned by Wang and colleagues before they progress to human clinical studies. They also plan to test CO-306 for efficacy against other types of organ injuries.

Additionally, CO-based therapies hold promise as a method of reducing the likelihood of organ damage during transplantation and improving outcomes for transplant patients, according to Prof Wang.

“Science shows that exposing organs to CO gas can help preserve organs and prevent them from deteriorating during the process of transplantation,” he said. “Now we need to demonstrate that these prodrugs can have a similar effect.”

Source: Georgia State University

Journal information: De La Cruz, L. K., et al. (2021) Adapting decarbonylation chemistry for the development of prodrugs capable of in vivo delivery of carbon monoxide utilizing sweeteners as carrier molecules. Chemical Science. doi.org/10.1039/D1SC02711E.

Categories : Skeletal SystemTags :

New Insights into What Stimulates Bone Growth

On By ModernMedia
Photo by Nino Liverani on Unsplash
Photo by Nino Liverani on Unsplash

Researchers have discovered some new insights into how bone mass is maintained and how physical load stimulates bone growth.

Researchers from the National Cerebral and Cardiovascular Center Research Institute in Japan have revealed that the expression of the peptide osteocrin (OSTN) is influenced by load – decreasing when load is reduced, and increasing when it is added. Their study was published in Cell Reports.

Bones and skeletal muscles are strengthened by loads produced in exercise, preventing bone and muscle atrophy, and maintaining bone and muscle strength is important for maintaining physical activity. The growth of long bones, such as the femur and tibia, is a very complex process controlled by genetic and environmental factors, such as exercise and gravity.

Understanding bone loss would help retain bone density and strength in people who are unable to exercise due to immobility, the elderly, as well as astronauts in spaceflight.

Study lead author Haruko Watanabe-Takano said, “Not much is known about how mechanical force initiates biochemical signals to control bone growth. We investigated how load is related to the metabolic balance adjustment of bone maintenance.”

Bone mass and strength is maintained by the balanced activities of two types of cells – the bone-genearting osteoblasts, and the bone-dissolving osteoclasts – and is thought to be made in response to load demand. Specifically, the team investigated the expression of OSTN, a peptide produced by osteoblasts, in mice. OSTN is critical to the regulation of bone growth, as well as physical endurance.

The researchers found that OSTN was very strongly expressed in bones such as the tibia, radius, and ulna, and in regions experiencing load. They determined that OSTN was secreted by the periosteal osteoblasts in these bones. The periosteum is a fibrous membrane that covers nearly every bone in the body, except for the joints of the long bones. This tissue has a major role in bone growth and bone repair and has an impact on the blood supply of bone as well as skeletal muscle. Despite its importance, it has received little attention in the literature and in some ways is not well understood.

“We also found that OSTN expression decreased when load was reduced, and was increased by load stimulation,” says Watanabe-Takano. “Moreover, when we genetically engineered mice lacking OSTN, we found that they had reduced bone mass compared with normal mice and lacked load-induced recovery of bone mass after prolonged load reduction. Thus, we concluded that OSTN makes bone in response to stimulation by load, promoting bone formation.”

The team found that to create this effect, OSTN increases levels of another peptide, called C natriuretic peptide, which in turn drives bone-forming osteoblasts to multiply, mature, and become functional.

The findings have implications for treatments for bed-ridden patients and others at risk of bone loss, such as the elderly. Further studies will explore issues such as how periosteal cells detect load stimulation.

Source: News-Medical.Net

Journal information: Watanabe-Takano, H., et al. (2021) Mechanical load regulates bone growth via periosteal Osteocrin. Cell Reports. doi.org/10.1016/j.celrep.2021.109380.

Categories : COVID General InterestTags :

First Olympic COVID Cases Among SA Soccer Team

On By ModernMedia
Photo by Bryan Turner on Unsplash
Photo by Bryan Turner on Unsplash

Three members of the South African soccer team staying in the Olympic Village have tested positive for COVID just days before the Olympic opening ceremonies. They are also the first Olympic athletes who tested positive in the tightly-monitored athletes’ enclave along a Tokyo waterfront.

The South African team said in a July 17 statement that defender Thabiso Monyane, midfielder Kamohelo Mahlatsi, and Mario Masha, a video analyst on the coaching staff, had tested positive on the weekend. All South African players had tested negative when they departed for Tokyo on July 13. The entire South African football team is now under quarantine, raising doubts whether they’ll be cleared for their July 22 match against Japan.

Since the announcement, South African rugby Sevens coach Neil Powell as well as an unnamed member of the female US gymnastics team have also tested positive. Outside the athlete’s complex, positive results have been reported for South Korean IOC official Ryu Seung, an unnamed member of the Nigerian delegation, and an unnamed athlete.

Despite the country’s best efforts to contain the virus, COVID remains a big concern in Tokyo at the world’s largest sporting event, expected to draw about 11 000 athletes from 200 nations. The Tokyo Olympic Committee has introduced measures such as banning spectators at games, daily COVID screening for athletes, and limiting stays at the Olympic Village to seven days.

With Japan still under a state of emergency and the COVID delta variant spreading rapidly, many continue to appeal to the International Olympic Committee to cancel the games. But some experts said that at this point a cancellation would cost Japan $16.4 billion. It would also run the risk of being sued by the IOC for breach of contract.

Addressing the outbreaks in an effort to rally local support for the events, IOC president Thomas Bach said, “We are well aware of the skepticism a number of people have here in Japan,” he said. “My appeal to the Japanese people is to welcome the athletes for their competitions.”

Source: Quartz