Day: January 12, 2021

New Study Reveals T-Cell Role in Periodontitis and Bone Loss

There are mechanisms involved in diseases of bone loss, such as periodontitis that are still not well understood, but an unexpected behaviour of a type of T-cell may shed new light on the matter.

Looking at periodontal disease in mice, scientists found that regulatory T (Treg) cells start behaving unexpectedly. They lose their ability to regulate bone loss and begin to promote inflammation instead.

“That is important because, in many therapies analyzed in in-vivo models, researchers usually check if the number of regulatory T cells has increased. But they should check if these cells are indeed functioning,” said lead author Dr Carla Alvarez, a postdoctoral researcher at the Forsyth Institute.

In periodontal disease, bone loss occurs because the immune system responds disproportionately, destroying tissue through inflammation. The Treg cells normally suppress the immune system but lose the ability to do so during periodontal disease.

Understanding this falls into the field of osteoimmunology, which is about understanding the interaction of bone metabolism and the immune system. “This is an interesting mechanism highlighting how the bone loss is taking place in periodontal disease,” said Dr Alpdogan Kantarci, at Forsyth and co-author of the paper.

A potential treatment for periodontal disease would involve reactivating the Treg cell’s immunosuppression function, but this is a complex, nonlinear task complicated by the fact that periodontal disease is initiated by oral microbes.

“The relationship between immune response and bone is not so straightforward,” said Alvarez. “There are multiple components. You have to imagine a complex network of signaling and cells that participate.”
The researchers’ next step is to examine the process in humans.

Source:Medical Xpress

Journal information: Alvarez, C., Suliman, S., Almarhoumi, R. et al. Regulatory T cell phenotype and anti-osteoclastogenic function in experimental periodontitis. Sci Rep 10, 19018 (2020). doi.org/10.1038/s41598-020-76038-w

Ebola Vaccine Stockpile Being Created

The International Coordinating Group (ICG) announced on Monday that it was creating a stockpile of the Ebola vaccine in Switzerland, to help contain future outbreaks. Between 2014 and 2016, the haemorrhagic fever claimed 11 300 lives, with a fatality rate of 90%.

The single dose Ebola vaccine was trialled with 350 000 in Guinea and in the 2018-2020 DRC outbreak under “compassionate use”. The vaccine was jointly developed by the World Health Organization (WHO), UNICEF, the International Federation of Red Cross and Red Crescent Societies (IFRC) and Médecins Sans Frontières (MSF), with Gavi, the Vaccine Alliance, providing financial support.Countries requesting a vaccine will be able to receive a response in 48 hours, with a goal for a seven day delivery time.Unlike COVID, Ebola is a rare and unpredictable disease, and thus there is the need to create a reserve for the vaccine as opposed there being a “natural market” for it.

“We are proud to be part of this unprecedented effort to help bring potential Ebola outbreaks quickly under control,” said Henrietta Fore, UNICEF executive director, in a press release, saying that when it comes to dealing with disease outbreaks, “preparedness is key.”

She said the vaccine stash is a “remarkable achievement” that will allow vaccines to be delivered to those who need them in a timely manner. 
Assembling the required 500 000 doses for the stockpile will take some to three years, with 6890 doses currently available for outbreak response. The WHO, UNICEF, Gavi, and vaccine manufacturers are in the meantime are ready to escalate production if needed.

Source: Voice of America News

Link Found Between Telomeres and COVID Lung Damage

Researchers developing a therapy to regenerate lung tissue damaged by severe COVID have postulated that shortened telomeres are associated with the damage.

Telomeres are structures at the ends of chromosomes that maintain their integrity, and a small portion of them are lost with each cell division, such as when regenerating damaged tissue. As the telomere sections shorten, they eventually become unable to divide and are senescent. The team was already working on a way to regenerate lung tissue in pulmonary fibrosis, and adapted their research to the COVID pandemic. In pulmonary fibrosis, lung tissue becomes scarred and rigid, resulting in reduced lung capacity. In previous research, they had shown that telomere damage to the alveolar type II pneumocytes – which happen to be the same cells targeted by SARS-CoV-2.

Maria A Blasco, a researcher at CNIO said, “When I read that type II alveolar pneumocytes were involved in COVID-19, I immediately thought that telomeres might be involved.” The researchers believe short telomeres hinder tissue regeneration after severe COVID.

Blasco explained, “we know that the virus infects alveolar type II pneumocytes and that these cells are involved in lung regeneration; we also know that if they have telomeric damage they cannot regenerate, which induces fibrosis. This is what is seen in patients with lung lesions after COVID-19: we think they develop pulmonary fibrosis because they have shorter telomeres, which limits the regenerative capacity of their lungs.”

To support this, the team analysed the telomeres of 89 COVID patients. Although it might be expected that older patients had shorter telomeres, the researchers found that all of those with severe COVID had shorter telomeres – regardless of age.

The researchers wrote: “These findings demonstrate that molecular hallmarks of aging, such as the presence of short telomeres, can influence the severity of COVID-19 pathologies.”The involvement of shorter telomeres opens up the possibility of using telomerase to lengthen them again, as a potential treatment.The team will now move to an experimental mouse model, infecting mice with short telomeres and no telomerase with COVID, giving telomerase to some to see if the lung tissue can regenerate after severe COVID.

Source:News-Medical.Net

Journal information: Sanchez-Vazquez R, Guío-Carrión A, Zapatero-Gaviria A, Martínez P, Blasco M. Shorter telomere lengths in patients with severe COVID-19 disease. Aging (Albany NY). 2021. doi:10.18632/aging.202463

A Growing Need to Expand Aneurysm Warnings for Fluoroquinolones

New research suggests that the fluoroquinolone class of antibiotics may increase the risk of aortic aneurysm (AA).

In 2018 the US Food and Drug Administration added warnings for people at risk of aortic disease, based on data from its reporting system plus four epidemiological studies in other countries. According to a study by a team led by Melina Kibbe, MD at the University of North Carolina at Chapel Hill, cases of AA formation or dissection were 7.5 per 10 000 prescription fills for fluoroquinolones at 90 days compared with 4.6 per 10 000 fills for comparison antibiotics.

Fluoroquinolones include ciprofloxacin, gemifloxacin, levofloxacin, moxifloxacin, norfloxacin, and ofloxacin. The FDA had already warned that fluoroquinolones could cause tendon damage and rupture, peripheral nerve damage, mental health disturbance, hypoglycaemic coma and that they are associated with Clostridium difficile infection.

Using a database of health insurance claims for almost 28 million individuals aged 18 to 64,  the researchers searched for associations between fluoroquinolone prescriptions and aneurysms, compared to other antibiotic types.

Fluoroquinolones were associated with excess abdominal AAs (HR 1.31, 95% CI 1.25-1.37) and iliac artery aneurysms (HR 1.60, 95% CI 1.33-1.91), though associations with aortic dissection  or thoracic aortic aneurysm did not reach significance.

“As such, regional differences in the etiology, incidence, and clinical management of aortic disease in the thoracic vs abdominal aorta should be carefully considered,” wrote the researchers.

Adults over 35 also had a greater risk of AA with fluoroquinolones compared to younger cohorts. Limitations of the study included not controlling for the possibility of pre-existing aneurysms, or for the presence of risk factors such as smoking.

However, the researchers believe the results are significant enough to warrant attention. “Almost regardless, this large cohort study of a U.S. population suggests it is time once again to rethink the use of this class of antibiotics for patients with or without aortic disease,” they wrote.

Source: MedPage Today

Journal information: Newton E, Akerman A, Strassle P, Kibbe M. Association of Fluoroquinolone Use With Short-term Risk of Development of Aortic Aneurysm. JAMA Surg. 2021. doi:10.1001/jamasurg.2020.6165

Gauteng Doctors’ Struggle in COVID “Fever Tents”

Angry doctors have opened up concerning recent images of severely ill patients at Steve Biko Academic Hospital (SBAH) being treated in tents amid pouring rain. These images came as David Makhura and MEC for Health Dr Nomathemba Mokgethi visited the hospital on Monday.

Speaking on condition of anonymity, two doctors at SBAH spoke to Daily Maverick about the reality of the situation. The doctors described a desperate situation of overwhelmed facilities, with patients possibly dying as much from the cold and rain as from untreated COVID – or indeed, a condition that presents similarly to COVID.

The image presented to the public by the government is “smoke and mirrors”, said Dr Felicia (not her real name). “This is a show. They [health officials] are lying to you people. They are lying. They are covering it up,” she said.”Fever tents” have been set up outside the Emergency Department, where patients remain while they are being screened for COVID. If they test negative, they are admitted to SBAH If they test positive, they are sent to Tshwane District Hospital.”

According to Dr Felicia, conditions in the tents are abysmal. “There is no nursing, there is no oxygen or beds in these tents. There is no oxygen in the tanks, we actually just do 10 minutes of CPR and many times we don’t have PPE to do it in.”

As infections continue to rise in South Africa, approaching 250 000 active cases, hospitals are buckling under the pressure, and doctors are expecting the worst to come.

Dr Monica (not her real name) spoke of her feelings of the situation. “I don’t feel like I am being protected by our hospital right now. I am running around like a chicken without a head. I feel very hopeless. I feel like I should not care anymore. Caring is actually just hurting me and the patients because instead of me doing what I said I was going to do when I left medicine, I am treating these people like numbers. Someone dies and you have to shrug your shoulders and move on to the next. There is not even a minute to mourn a person or to figure out what went wrong. I feel completely hopeless,” she said.

Dr Monica said people need to stop politicising the pandemic, and get the hospitals the resources they need. She also implored the reporters to convey their message. “Tell the people out there, this is serious. They must wear masks, they must social distance,” she said, breaking off and running to attend to a patient.

Source: Daily Maverick