Tag: 23/8/21

Human Breast Milk Could Yield Antibiotic Secrets

Researchers believe that antibacterial properties of sugars in human breast milk could be harnessed for new antimicrobial therapies.

Group B Streptococcus (GBS) bacteria are a common cause of blood infections, meningitis and stillbirth in newborns, and are becoming resistant to antibiotics. Researchers have now discovered that human milk oligosaccharides (HMOs), short strings of sugar molecules abundant in breast milk, can help prevent GBS infections in human cells and tissues and in mice. This might yield new antibiotic treatments, the researchers believe. 

“Our lab has previously shown that mixtures of HMOs isolated from the milk of several different donor mothers have antimicrobial and antibiofilm activity against GBS,” says Rebecca Moore, who is presenting the work at a meeting of the American Chemical Society (ACS). “We wanted to jump from these in vitro studies to see whether HMOs could prevent infections in cells and tissues from a pregnant woman, and in pregnant mice.” Moore is a graduate student in the labs of Steven Townsend, PhD, at Vanderbilt University and Jennifer Gaddy, PhD, at Vanderbilt University Medical Center.

According to the US Centers for Disease Control and Prevention, about 2000 babies in the U.S. get GBS each year, with 4-6% of them dying from it. The bacteria are often transferred from mother to baby during labour and delivery. An expectant mother who tests positive for GBS is usually given intravenous antibiotics during labor to help prevent early-onset infections, which occur during the first week of life. Notably, late-onset infections (which happen from one week to three months after birth) are more common in formula-fed than breastfed infants, suggesting breast milk has factors which could help protect against GBS. If so, the sugars could be a replacement for current antibiotics which are steadily becoming less effective.

The researchers studied the effects of combined HMOs from several mothers on GBS infection of placental macrophages and of the gestational membrane. “We found that HMOs were able to completely inhibit bacterial growth in both the macrophages and the membranes, so we very quickly turned to looking at a mouse model,” Moore says. They examined whether HMOs could prevent a GBS infection from spreading through the reproductive tract of pregnant mice. “In five different parts of the reproductive tract, we saw significantly decreased GBS infection with HMO treatment,” Moore notes.

To determine which HMOs and other oligosaccharides have these antimicrobial effects and why, the researchers made an artificial two-species microbiome with GBS and the beneficial Streptococcus salivarius species growing in a tissue culture plate, separated by a semi-permeable membrane. Then, the researchers added oligosaccharides that are commonly added to infant formula, called galacto-oligosaccharides (GOS), which are derived from plants. In the absence of the sugar, GBS suppressed the growth of the “good” bacteria, but GOS helped this beneficial species grow. “We concluded that GBS is producing lactic acid that inhibits growth, and then when we add the oligosaccharide, the beneficial species can use it as a food source to overcome this suppression,” Moore explained.
The first HMOs tested did not have this effect, but Townsend says it’s likely that one or more of the over 200 unique sugars in human milk will show activity in the artificial microbiome assay. There are likely two reasons why HMOs can treat and prevent GBS infection: they prevent pathogens from sticking to tissue surfaces and forming a biofilm, and they could also act as a prebiotic by promoting good bacteria growth.

“HMOs have been around as long as humans have, and bacteria have not figured them out. Presumably, that’s because there are so many in milk, and they’re constantly changing during a baby’s development,” Townsend said. “But if we could learn more about how they work, it’s possible that we could treat different types of infections with mixtures of HMOs, and maybe one day this could be a substitute for antibiotics in adults, as well as babies.”

Source: American Chemical Society

Stress Signal From Fat Cells Induces Protective Effect in Heart

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A stress signal sent from fat cells to the heart could be protective against obesity-induced cardiac damage, according to new research. 

This might help explain the ‘obesity paradox’, where obese individuals have better short- and medium-term cardiovascular disease prognoses compared with those who are normal weight, but have worse long-term outcomes.

“The mechanism we have identified here could be one of many that protects the heart in obesity,” said study leader Philipp E. Scherer, PhD, Professor of Internal Medicine and Cell Biology at UTSW who has long studied fat metabolism.

Study co-leader Clair Crewe, PhD, Assistant Instructor of Internal Medicine at UTSW, explained that the metabolic stress of obesity gradually makes fat tissue dysfunctional, causing shrinkage and death of its mitochondria. This unhealthy fat loses the ability to store lipids generated by excess calories in food, causing lipotoxicity and poisoning other organs. However some organs, including the heart, preemptively defend against lipotoxicity. How the heart actually senses fat’s dysfunctional state has been unknown so far.

The researchers used a genetic technique to speed the loss of mitochondrial mass and function in mice. The mice were fed a high-fat diet and became obese, and their fat cells began sending out extracellular vesicles filled with small pieces of dying mitochondria. Some of these mitochondrial snippets travelled through the bloodstream to the heart and triggered oxidative stress.

Cardiaccells produce a flood of protective antioxidant molecules to counteract this stress, and this protective backlash was so strong that when the scientists injected mice with extracellular vesicles filled with mitochondrial snippets and then induced a heart attack, the animals had significantly less damage to their hearts compared with mice that didn’t receive an injection.

Fat tissue from obese human patients showed that these cells also release mitochondria-filled extracellular vesicles.

The heart and other organs in obese individuals are eventually overwhelmed by lipotoxic effects, resulting in a number of obesity’s comorbidities. If the protective mechanism identified in this study could be artificially generated, it could result in new ways of treating obesity’s negative consequences. This might even be adapted to treat normal weight individuals.

“By better understanding the distress signal from fat,” Dr Crewe said, “we may be able to harness the mechanism to improve heart health in obese and non-obese individuals alike.”

The team’s findings were published in Cell Metabolism.

Source: UT Southwestern Medical Center

Eight Factors Predict Gastrointestinal Bleeding Risk after Heart Attack

Using machine learning, researchers at Karolinska Institutet have identified eight primary factors that increase the risk of a common bleeding complication after heart attack.

Some of these factors had been known already, however, the researchers have found additional predictors, such as smoking, blood pressure and blood glucose. The study was published in the European Heart Journal – Cardiovascular Pharmacotherapy.

“If we can identify patients at high risk of upper gastrointestinal bleeding following heart attack, doctors will be able to take prophylactic measures to mitigate this risk,” said the study’s corresponding author Moa Simonsson, deputy consultant at Karolinska University Hospital and doctoral student. “There are, for instance, drugs that combat bleeding complications, gut bacteria tests that can be used on risk groups and other possibilities for personalised treatment for heart attack patients at high risk of bleeding complications.”

Upper gastrointestinal (GI) tract bleeding is one of the most common bleeding complications following acute myocardial infarction. The condition requires a lot of resources to treat, causes considerable suffering and increases mortality risk. Bleeding complications also limit antithrombotic use, which in turn can worsen the cardiovascular prognosis.

Over the past 20 years, a close focus on bleeding has resulted in several strategies for reducing the risk of upper gastrointestinal tract bleeding. However, few studies on this complication include a diverse population of heart attack patients.

For the current study, the researchers sourced data from the national SWEDEHEART registry on almost 150 000 patients with acute myocardial infarction between 2007 and 2016. Approximately 1.5 percent of these patients suffered GI bleeding within a year of their heart attack, and they also had an increased risk of death and stroke.
Several known factors that increase the risk of upper GI tract bleeding were confirmed by the analysis, including low levels of haemoglobin, previous upper GI tract bleeding, age and intensive antithrombotic treatment.

Using an algorithm, the researchers also identified additional risk factors, including smoking, blood pressure, blood glucose and previous treatment for stomach disorders, such as ulcers and acid reflux.

“If you combine traditional statistical models with machine learning methods, you can create unique opportunities to find key risk factors for previously unknown cardiovascular events,” explained co-author Philip Sarajlic, doctoral student at Karolinska Institutet. “This makes it possible for us to make effective use of valuable data from the medical quality registry by taking account of complex relationships between risk factors and outcomes in order to further optimise the current recommendations for patient care.”

The researchers will soon begin a major clinical study to explore the significance of diagnosis and treatment of a common infection in the upper GI tract.

“A pilot study last year showed a two-fold increase in the presence of Helicobacter Pylori in heart attack patients,” said last author Robin Hofmann, researcher and consultant at Karolinska Institutet. “We will now proceed with a large randomized study to ascertain whether a systematic screening of heart attack patients for Hp infection and, where relevant, its treatment, can reduce bleeding complications and improve prognosis after heart attack.”

Source: Karolinska Institute

Anticoagulation Improves Survival Odds of Moderately Ill COVID Patients

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If treated with therapeutic-dose anticoagulation, moderately ill patients hospitalised with COVID have better odds of survival, according to an international study published in The New England Journal of Medicine.

COVID patients frequently develop a pro-coagulative state caused by virus-induced endothelial dysfunction, cytokine storm and complement cascade hyperactivation. Thrombotic risk appears directly related to disease severity and worsens patients’ prognosis.

Moderately ill COVID patients treated with therapeutic-dose anticoagulation with unfractionated or low molecular-weight heparin were 27% less likely to need cardiovascular respiratory organ support such as intubation, said Ambarish Pandey, MD, Assistant Professor of Internal Medicine at UT Southwestern, who served as site investigator and . Moderately ill patients had a 4% increased chance of survival until discharge without requiring organ support with anticoagulants, according to the study involving 2200 patients.

“The 4% increase in survival to discharge without needing organ support represents a very meaningful clinical improvement in these patients,” said Dr Pandey, a Texas Health Resources Clinical Scholar specialising in preventive cardiology and heart failure with preserved ejection fraction. “If we treat 1,000 patients who are hospitalized with COVID with moderate illness, an additional 40 patients would have meaningful improvement in clinical status.”

Moderately ill patients were defined as those who did not need intensive care unit-level support. The participating platforms for the study, included Antithrombotic Therapy to Ameliorate Complications of COVID-19 (ATTACC); A Multicenter, Adaptive, Randomized Controlled Platform Trial of the Safety and Efficacy of Antithrombotic Strategies in Hospitalized Adults with COVID-19 (ACTIV-4a); and Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP). 

A parallel study reported in The New England Journal of Medicine found however that therapeutic-dose anticoagulation did not help severely ill patients.

Source: UT Southwestern Medical Center

After Anti-vaxx Protest, Western Cape Government Speaks Out

Photo by Marisol Benitez on Unsplash

After a group of anti-vaxxer demonstrators gathered outside Groote Schuur Hospital (GSH), Western Cape Health authorities have slammed anti-vaxxers for inflaming vaccine hesitancy. Even so, there was a record vaccination turnout on Friday when inoculations were offered to over 18s.

“I just don’t understand why people don’t believe us when we say that the vaccines are safe,” Western Cape Health Department’s Dr Saadiq Kariem said, warning of the damage that misinformation can do.

“There’s no 3G in the vaccine. There’s certainly no conspiracy theory. All we’re trying to do is help by making sure that the population is as protected as possible against coronavirus,” Dr Kariem said, adding that it was even more dangerous when medical professionals were against the shots.

“It just baffles my mind how other medical professionals can, in fact, be anti-vaccination because people will believe professionals, you know, and take their word as they’ve studied this field,” he added. Some of the protesters were carrying signs in support of controversial anti-vaxxer doctors.

IOL reports that one man who was employed by the hospital and chose not to be named, stood alone in the street and faced down the protesters with a sign saying “Covidiots”. He said the pandemic had been happening for 18 months, and that the ignorance of the crowd was disgraceful.

Just before the protests got underway, the University of Cape Town had released a statement in support of GSH. “The Faculty stands in solidarity with the staff (including cleaners, security, admin staff, drivers etc) of GSH. We stand in support of their work and the herculean efforts they have taken across the era of this pandemic under extremely challenging circumstances and often at personal risk. We salute the work of our partners in delivering the best possible care in responding to the world’s greatest human tragedy.”

Source: Eyewitness News