Tag Archives: pneumonia
Cannabidiol (CBD), the main nonpsychoactive ingredient of the cannabis plant, can kill Gram-positive bacteria and, more impressively, Gram-negative bacteria, which excel at antibiotic resistance because they enjoy an extra layer of protection, an outer cell membrane. The ability of CBD to slay Gram-negative bacteria is a new finding, one reported by a team of scientists in Australia. According to the scientists, CBD analogs could constitute the first new class of antibiotics against Gram-negative bacteria that has been developed since the 1960s.
The new finding appeared in the journal Communications Biology, in an article titled, “The antimicrobial potential of cannabidiol.” According to this article, CBD not only killed Gram-positive bacteria such as highly resistant Staphylococcus aureus, Streptococcus pneumoniae, and Clostridioides difficile, it also showed potency against the Gram-negative bacteria Neisseria gonorrhoeae, Neisseria meningitides, Moraxella catarrhalis, and Legionella pneumophila. These Gram-negative bacteria are responsible for sexually transmitted gonorrhea, life-threatening meningitis, airway infections (such as bronchitis and pneumonia), and Legionnaires’ disease, respectively.
“Our results demonstrate that cannabidiol has excellent activity against biofilms, little propensity to induce resistance, and topical in vivo efficacy,” the authors of the article wrote. “Multiple mode-of-action studies point to membrane disruption as cannabidiol’s primary mechanism.”
The authors included scientists from the University of Queensland in Australia and Botanix Pharmaceuticals. At the University of Queensland’s Centre for Superbug Solutions, scientists led by associate professor Mark Blaskovich, PhD, mimicked a two-week patient treatment in laboratory models to see how fast the bacteria mutated to try to outwit CBD’s killing power.
“Cannabidiol showed a low tendency to cause resistance in bacteria even when we sped up potential development by increasing concentrations of the antibiotic during ‘treatment,’” said Blaskovich, the corresponding author of the article in Communications Biology. “We think that cannabidiol kills bacteria by bursting their outer cell membranes, but we don’t know yet exactly how it does that, and we need to do further research.”
Tiny artificial lungs grown in a lab from adult stem cells have allowed scientists to watch how coronavirus infects the lungs in a new ‘major breakthrough‘. Researchers from Duke University and Cambridge University produced artificial lungs in two independent and separate studies to examine the spread of Covid-19. The ‘living lung‘ models minimic the tiny air sacs that take up the oxygen we breathe, known to be where most serious lung damage from the deadly virus takes place. Having access to the models to test the spread of SAS-CoV-2, the virus responsible for Covid-19, will allow researchers to test potential drugs and gain a better understanding of why some people suffer from the disease worse than others.
In both studies the 3D min-lung models were grown from stem cells that repair the deepest portions of the lungs when SARS-CoV-2 attacks – known as alveolar cells. To date, there have been more than 40 million cases of COVID-19 and almost 1.13 million deaths worldwide. The main target tissues of SARS-CoV-2, especially in patients that develop pneumonia, appear to be alveoli, according to the Cambridge team. They extracted the alveoli cells from donated tissue and reprogrammed them back to their earlier ‘stem cell‘ stage and forced them to grow into self-organising alveolar-like 3D structures that mimic the behaviour of key lung tissue. Dr Joo-Hyeon Lee, co-senior author of the Cambridge paper, said we still know surprisingly little about how SARS-CoV-2 infects the lungs and causes disease.
Representative image of three – dimensional human lung alveolar organoid produced by the Cambridge and Korean researchers to better understand SARS-CoV-2
‘Our approach has allowed us to grow 3D models of key lung tissue – in a sense, “mini-lungs” – in the lab and study what happens when they become infected.’
Duke researchers took a similar approach. The team, led by Duke cell biologist Purushothama Rao Tata, say their model will allow for hundreds of experiments to be run simultaneously to screen for new drug candidates. ‘This is a versatile model system that allows us to study not only SARS-CoV-2, but any respiratory virus that targets these cells, including influenza,‘ Tata said.
Both teams infected models with a strain of SARS-CoV-2 to better understand who the virus spreads and what happens in the lung cells in response to the disease. The Cambridge team worked with researchers from South Korea to take a sample of the virus from a patient who was infected in January after travelling to Wuhan. Using a combination of fluorescence imaging and single cell genetic analysis, they were able to study how the cells responded to the virus.
When the 3D models were exposed to SARS-CoV-2, the virus began to replicate rapidly, reaching full cellular infection just six hours after infection. Replication enables the virus to spread throughout the body, infecting other cells and tissue, explained the Cambridge research team. Around the same time, the cells began to produce interferons – proteins that act as warning signals to neighbouring cells, telling them to activate their defences. After 48 hours, the interferons triggered the innate immune response – its first line of defence – and the cells started fighting back against infection. Sixty hours after infection, a subset of alveolar cells began to disintegrate, leading to cell death and damage to the lung tissue.
French researchers are planning to test nicotine patches on coronavirus patients and frontline health workers after a study suggested smokers may be much less at risk of contracting the virus.
The study at a major Paris hospital suggests a substance in tobacco – possibly nicotine – may be stopping patients who smoke from catching Covid-19. Clinical trials of nicotine patches are awaiting the approval of the country’s health authorities.
However, the researchers insisted they were not encouraging the population to take up smoking, which carries other potentially fatal health risks and kills 50% of those who take it up. While nicotine may protect those from the virus, smokers who have caught it often develop more serious symptoms because of the toxic effect of tobacco smoke on the lungs, they say.
The team at Pitié-Salpêtrière hospital questioned 480 patients who tested positive for the virus, 350 of whom were hospitalised while the rest with less serious symptoms were allowed home. It found that of those admitted to hospital, whose median age was 65, only 4.4% were regular smokers. Among those released home, with a median age of 44, 5.3% smoked. Taking into account the age and sex of the patients, the researchers discovered the number of smokers was much lower than that in the general population estimated by the French health authority Santé Publique France at about 40% for those aged 44-53 and between 8.8% and 11.3% for those aged 65-75.
The renowned French neurobiologist Jean-Pierre Changeux, who reviewed the study, suggested the nicotine might stop the virus from reaching cells in the body preventing its spread. Nicotine may also lessen the overreaction of the body’s immune system that has been found in the most severe cases of Covid-19 infection.
The findings are to be verified in a clinical study in which frontline health workers, hospital patients with the Covid-19 virus and those in intensive care will be given nicotine patches. The results confirm a Chinese study published at the end of March in the New England Journal of Medicine that suggested only 12.6% of 1,000 people infected with the virus were smokers while the number of smokers in China is around 28%. In France, figures from Paris hospitals showed that of 11,000 patients admitted to hospital with Covid-19, 8.5% were smokers. The total number of smokers in France is estimated at around 25.4%.
“Our cross-sectional study strongly suggests that those who smoke every day are much less likely to develop a symptomatic or severe infection with Sars-CoV-2 compared with the general population,” the Pitié-Salpêtrière report authors wrote. “The effect is significant. It divides the risk by five for ambulatory patients and by four for those admitted to hospital. We rarely see this in medicine,” it added.
US Food and Drug Administration (FDA) officials announced today they have approved plans for nationwide trials of two treatments for Covid-19, the global pandemic disease caused by the new coronavirus—and for their simultaneous use in perhaps hundreds of hospitals.
The therapeutic agents—convalescent plasma and hyperimmune globulin—are both derived from the blood of people who have recovered from the disease, decoctions of the antibodies that the human immune system makes to fight off germs.
“This is an important area of research—the use of products made from a recovered patient’s blood to potentially treat Covid-19,” said FDA commissioner Stephen Hahn in a release announcing the trials. “The FDA had played a key role in organizing a partnership between industry, academic institutions, and government agencies to facilitate expanded access to convalescent plasma. This is certainly a great example of how we can all come together to take swift action to help the American people during a crisis.”
Physicians are already using a somewhat haphazard collection of antiviral and other drugs for people critically ill with Covid-19, because they don’t have any other options. Nothing—no drug, no vaccine—is approved for use specifically against Covid-19 in the United States, so any new possibility is a hopeful one. Convalescent plasma and hyperimmune globulin join the rarified group of therapeutics that scientists are testing, including a trial of the Ebola drug remdesivir and the much-hyped antimalarial/immune suppressants chloroquine and hydroxychloroquine.
Using blood products from people who’ve already beaten a disease is a century-old approach, predating vaccines and antibiotics. Inspired by its use against polio, two physicians at a Naval hospital in Massachusetts tried it on people who had pneumonia as a result of influenza in 1918, with enough success to warrant more tests. The quality of actual studies of efficacy has varied over the decades, but health care workers used convalescent plasma against SARS, MERS, and Ebola. And a couple of studies—small and preliminary—have shown convalescent plasma having some promise against SARS-CoV-2 as well.
At Houston Methodist Hospital, James Musser, the chair of Pathology and Genome Medicine, is a friend of Arturo Casadevall, the Johns Hopkins University immunologist who proposed using convalescent serum early in the pandemic. Musser pushed to get his hospital involved, putting out a call for donors—people who had confirmed positive tests for the virus and had gone at least 14 days without symptoms. His hospital is already doing compassionate-use transfusions. “So far, as of yesterday, we’ve transfused four patients,” Musser said on Thursday. He expected a fifth to receive plasma today. And how’d it work? “The truth is, it’s far too early,” Musser says. “We, nationally, need to do controlled trials and understand, first and foremost, is this a safe therapeutic? There’s lots of reasons to think it will be, but you never know.”
Zhongnan Hospital of Wuhan University in Wuhan, China, is at the heart of the outbreak of Covid-19, the disease caused by the new coronavirus SARS-CoV-2 that has shut down cities in China, South Korea, Iran, and Italy. That’s forced the hospital to become a testbed for how quickly a modern medical center can adapt to a new infectious disease epidemic.
One experiment is underway in Zhongnan’s radiology department, where staff are using artificial intelligence software to detect visual signs of the pneumonia associated with Covid-19 on lung CT scan images. Haibo Xu, professor and chair of radiology at Zhongnan Hospital, says the software helps overworked staff screen patients and prioritize those most likely to have Covid-19 for further examination and testing.
Detecting pneumonia on a scan doesn’t alone confirm a person has the disease, but Xu says doing so helps staff diagnose, isolate, and treat patients more quickly. The software “can identify typical signs or partial signs of Covid-19 pneumonia,” he wrotel. Doctors can then follow up with other examinations and lab tests to confirm a diagnosis of the disease. Xu says his department was quickly overwhelmed as the virus spread through Wuhan in January.
The software in use at Zhongnan was created by Beijing startup Infervision, which says its Covid-19 tool has been deployed at 34 hospitals in China and used to review more than 32,000 cases. The startup, founded in 2015 with funding from investors including early Google backer Sequoia Capital, is an example of how China has embraced applying artificial intelligence to medicine.
China’s government has urged development of AI tools for healthcare as part of sweeping national investments in artificial intelligence. China’s relatively lax rules on privacy allow companies such as Infervision to gather medical data to train machine learning algorithms in tasks like reading scans more easily than US or European rivals.
Infervision created its main product, software that flags possible lung problems on CT scans, using hundreds of thousands of lung images collected from major Chinese hospitals. The software is in use at hospitals in China, and being evaluated by clinics in Europe, and the US, primarily to detect potentially cancerous lung nodules. Infervision began work on its Covid-19 detector early in the outbreak after noticing a sudden shift in how existing customers were using its lung-scan-reading software. In mid-January, not long after the US Centers for Disease Control advised against travel to Wuhan due to the new disease, hospitals in Hubei Province began employing a previously little-used feature of Infervision’s software that looks for evidence of pneumonia, says CEO Kuan Chen. “We realized it was coming from the outbreak,” he says.
A new compound which visualises and kills antibiotic-resistant superbugs has been discovered by scientists at the University of Sheffield and Rutherford Appleton Laboratory (RAL). The team, led by Professor Jim Thomas, from the University of Sheffield’s Department of Chemistry, is testing new compounds developed by his PhD student Kirsty Smitten on antibiotic resistant gram-negative bacteria, including pathogenic E. coli.
Gram-negative bacteria strains can cause infections including pneumonia, urinary tract infections and bloodstream infections. They are difficult to treat as the cell wall of the bacteria prevents drugs from getting into the microbe. Antimicrobial resistance is already responsible for 25,000 deaths in the EU each year, and unless this rapidly emerging threat is addressed, it’s estimated by 2050 more than 10 million people could die every year due to antibiotic resistant infections. Doctors have not had a new treatment for gram-negative bacteria in the last 50 years, and no potential drugs have entered clinical trials since 2010.
The new drug compound has a range of exciting opportunities. As Professor Jim Thomas explains: “As the compound is luminescent it glows when exposed to light. This means the uptake and effect on bacteria can be followed by the advanced microscope techniques available at RAL.
Gram negative bacteria. Credit: University of Sheffield
“As the compound is luminescent it glows when exposed to light. This means the uptake and effect on bacteria can be followed by the advanced microscope techniques available at RAL“, explains Professor Jim Thomas. “This breakthrough could lead to vital new treatments to life-threatening superbugs and the growing risk posed by antimicrobial resistance.”
The studies at Sheffield and RAL have shown the compound seems to have several modes of action, making it more difficult for resistance to emerge in the bacteria. The next step of the research will be to test it against other multi-resistant bacteria.
The difficulty in spotting minute amounts of disease circulating in the bloodstream has proven a stumbling block in the detection and treatment of cancers that advance stealthily with few symptoms. With a novel electrochemical biosensing device that identifies the tiniest signals these biomarkers emit, a pair of NJIT inventors are hoping to bridge this gap. Their work in disease detection is an illustration of the power of electrical sensing – and the growing role of engineers – in medical research.
“Ideally, there would be a simple, inexpensive test – performed at a regular patient visit in the absence of specific symptoms – to screen for some of the more silent, deadly cancers,” says Bharath Babu Nunna, a recent Ph.D. graduate who worked with Eon Soo Lee, an assistant professor of mechanical engineering, to develop a nanotechnology-enhanced biochip to detect cancers, malaria and viral diseases such as pneumonia early in their progression with a pin prick blood test.
Their device includes a microfluidic channel through which a tiny amount of drawn blood flows past a sensing platform coated with biological agents that bind with targeted biomarkers of disease in body fluids such as blood, tears and urine – thereby triggering an electrical nanocircuit that signals their presence. In research recently published in Nano Covergence, Nunna and his co-authors demonstrated the use of gold nanoparticles to enhance the sensor signal response of their device in cancer detection, among other findings.
One of the device’s core innovations is the ability to separate blood plasma from whole blood in its microfluidic channels. Blood plasma carries the disease biomarkers and it is therefore necessary to separate it to enhance the “signal to noise ratio” in order to achieve a highly accurate test. The standalone device analyzes a blood sample within two minutes with no need for external equipment.
“Our approach detects targeted disease biomolecules at the femto scale concentration, which is smaller than nano and even pico scale, and is akin to searching for a planet in a galaxy cluster. Current sensing technology is limited to concentrations a thousand times larger. Using a nanoscale platform allows us to identify these lower levels of disease,” Nunna says, adding, “And by separating the plasma from the blood, we are able to concentrate the disease biomarkers.”