E-cigarette vapour disables lung's protective cells

Agencies
August 14, 2018

London, Aug 14: E-cigarette vapour disables key immune cells in the lung that keep the air spaces clear of potentially harmful particles, say scientists who warn that vaping may be more harmful than traditional smoking.

The vapour impairs the activity of alveolar macrophages, which engulf and remove dust particles, bacteria, and allergens that have evaded the other mechanical defences of the respiratory tract.

The findings, published online in the journal Thorax, suggest that while further research is needed to better understand the long term health impact of vaping, e-cigarettes may be more harmful than we think, as some of the effects were similar to those seen in regular smokers and people with chronic lung disease.

Vaping is increasing in popularity, but most of the current body of research has focused on the chemical composition of e-cigarette liquid before it is vaped.

Researchers from the University of Birmingham and Swansea University in the UK devised a mechanical procedure to mimic vaping and produce condensate from the vapour.

They extracted alveolar macrophages from lung tissue samples provided by eight non-smokers who had never had asthma or chronic obstructive pulmonary disease (COPD).

A third of the cells were exposed to plain e-cigarette fluid, a third to different strengths of the artificially vaped condensate with and without nicotine, and a third to nothing for 24 hours.

The results showed that the condensate was significantly more harmful to the cells than e-cigarette fluid and that these effects worsened as the 'dose' increased.

After 24 hours of exposure, the total number of viable cells exposed to the vaped condensate was significantly reduced compared to the untreated cells, and condensate containing nicotine exaggerated this effect.

Exposure to the condensate increased cell death and boosted production of oxygen free radicals by a factor of 50, and it significantly increased the production of inflammatory chemicals - more so when the condensate contained nicotine.

What is more, the ability of cells exposed to vaped condensate to engulf bacteria was significantly impaired, although treatment with an antioxidant restored this function and helped lessen some of the other harmful effects.

The researchers conclude that the vaping process itself can damage vital immune system cells, at least under laboratory conditions.

"Importantly, exposure of macrophages to [e-cigarette vapour condensate] induced many of the same cellular and functional changes in [alveolar macrophage] function seen in cigarette smokers and patients with COPD," they said. 

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Agencies
June 29,2020

Washington DC, Jun 29: Young children with narrow retinal artery diameters were more likely to develop higher blood pressure, and children with higher blood pressure levels were more likely to develop retinal microvascular impairment during early childhood, according to a new study.

The first study to show this connection in children was published today in Hypertension, an American Heart Association journal.

High blood pressure, the main risk factor for the development of cardiovascular disease (CVD), can manifest as early as childhood, and the prevalence of high blood pressure among children continues to rise. In previous studies, analysis of blood vessels in the retina has shown promise as a predictor of CVD risk among adults. In the study titled, "Retinal Vessel Diameters and Blood Pressure Progression in Children," researchers sought to predict the development of high blood pressure in children over four years based on retinal blood vessel measurements.

"Hypertension continues as the main risk factor for the development of cardiovascular diseases and mortality," says Henner Hanssen, M.D., the study's lead author and a professor in the department of sport, exercise and health at the University of Basel in Switzerland. 

"Primary prevention strategies are needed to focus on screening retinal microvascular health and blood pressure in young children in order to identify those at increased risk of developing hypertension. The earlier we can provide treatment and implement lifestyle changes to reduce hypertension, the greater the benefit for these children."

Researchers screened 262 children ages six to eight from 26 schools in Basel, Switzerland, in 2014, for baseline blood pressure and retinal arterial measurements. Both measures were taken again in 2018. Blood pressure measurements at both baseline and follow-up were performed in a sitting position after a minimum of five minutes of rest and were categorized based on the American Academy of Pediatrics' blood pressure guidelines. These guidelines utilize the same measurements as the American Heart Association/American College of Cardiology 2017 Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults.

Results from the analysis indicate: children with narrower retinal vessel diameters at baseline developed higher systolic blood pressure at follow-up; retinal vessel diameters could explain 29 -31 per cent of the changes in systolic blood pressure progression between 2014 and 2018; children with higher blood pressure levels at baseline developed significantly narrower arteriolar diameters at follow-up, depending on weight and cardiorespiratory fitness; and initial blood pressure measures explained 66-69 per cent of the change in retinal arteriolar diameter from baseline to follow-up.

"Early childhood assessments of retinal microvascular health and blood pressure monitoring can improve cardiovascular risk classification. Timely primary prevention strategies for children at risk of developing hypertension could potentially counteract its growing burden among both children and adults," said Hanssen.

Researchers noted limitations of their study include that they could not confirm blood pressure measurements over a single 24-hour period, so they would not account for "white coat" hypertension, a condition where patients have high blood pressure readings when measured in a medical setting.

Developmental stage including puberty status of each child was not accounted for in the study, as well as genetic factors or birth weight - variables that could impact blood pressure development and microvascular health.

In addition, reference values for appropriate retinal vessel diameters in children do not currently exist, so future studies are needed to determine age-related normal values during childhood.

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Agencies
July 2,2020

The American pharmaceutical giant Pfizer Inc. and the European biotechnology company BioNTech SE have conducted an experimental trial of a COVID-19 vaccine candidate and found it to be safe, well-tolerated, and capable of generating antibodies in the patients.

The study, which is yet to be peer-reviewed, describes the preliminary clinical data for the candidate vaccine -- nucleoside-modified messenger RNA (modRNA), BNT162b1.

It said the amount of antibodies produced in participants after they received two shots of the vaccine candidate was greater than that reported in patients receiving convalescent plasma from recovered COVID-19 patients.

"I was glad to see Pfizer put up their phase 1 trial data today. Virus neutralizing antibody titers achieved after two doses are greater than convalescent antibody titers," tweeted Peter Hotez, a vaccine scientist from Baylor College of Medicine in the US, who was unrelated to the study.

Researchers, including those from New York University in the US, who were involved in the study, said the candidate vaccine enables human cells to produce an optimised version of the receptor binding domain (RBD) antigen -- a part of the spike (S) protein of SARS-CoV-2 which it uses to gain entry into human cells.

"Robust immunogenicity was observed after vaccination with BNT162b1," the scientists noted in the study.

They said the program is evaluating at least four experimental vaccines, each of which represents a unique combination of mRNA format and target component of the novel coronavirus, SARS-CoV-2.

Based on the study's findings, they said BNT162b1 could be administered in a quantity that was well tolerated, potentially generating a dose dependent production of immune system molecules in the patients.

The research noted that patients treated with the vaccine candidate produced nearly 1.8 to 2.8 fold greater levels of RBD-binding antibodies that could neutralise SARS-CoV-2.

"We are encouraged by the clinical data of BNT162b1, one of four mRNA constructs we are evaluating clinically, and for which we have positive, preliminary, topline findings," said Kathrin U. Jansen, study co-author and Senior Vice President and Head of Vaccine Research & Development, Pfizer.

"We look forward to publishing our clinical data in a peer-reviewed journal as quickly as possible," Jansen said.

According to Ugur Sahin, CEO and Co-founder of BioNTech, and another co-author of the study, the preliminary data are encouraging as they provide an initial signal that BNT162b1 is able to produce neutralising antibody responses in humans.

He said the immune response observed in the patients treated with the experimental vaccine are at, or above, the levels observed from convalescent sera, adding that it does so at "relatively low dose levels."

"We look forward to providing further data updates on BNT162b1," Sahin said.

According to a statement from Pfizer, the initial part of the study included 45 healthy adults 18 to 55 years of age.

It said the priliminary data for BNT162b1 was evaluated in 24 subjects who received two injections of 10 microgrammes ( g) and 30 g -- 12 subjects who received a single injection of 100 g, and 9 subjects who received two doses of a dummy vaccine.

The study noted that participants received two doses, 21 days apart, of placebo, 10 g or 30 g of BNT162b1, or received a single dose of 100 g of the vaccine candidate.

According to the scientists, the highest neutralising concentrations of antibodies were observed seven days after the second dose of 10 g, or 30 g on day 28 after vaccination.

They said the neutralising concentrations were 1.8- and 2.8-times that observed in a panel of 38 blood samples from people who had contracted the virus.

In all 24 subjects who received two vaccinations at 10 g and 30 g dose levels, elevation of RBD-binding antibody concentrations was observed after the second injection, the study noted.

It said these concentrations are 8- and 46.3-times the concentration seen in a panel of 38 blood samples from those infected with the novel coronavirus.

At the 10 g or 30 g dose levels, the scientists said adverse reactions, including low grade fever, were more common after the second dose than the first dose.

According to Pfizer, local reactions and systemic events after injection with 10 g and 30 g of BNT162b1 were "dose-dependent, generally mild to moderate, and transient."

It said the most commonly reported local reaction was injection site pain, which was mild to moderate, except in one of 12 subjects who received a 100 g dose, which was severe.

The study noted that there was no serious adverse events reported by the patients.

Citing the limitations of the research, the scientists said the immunity generated in the participants in the form of the T cells and B cells of their immune system, and the level of immunity needed to protect one from COVID-19 are unknown.

With these preliminary data, along with additional data being generated, Pfizer noted in the statement that the two companies will determine a dose level, and select among multiple vaccine candidates to seek to progress to a large, global safety and efficacy trial, which may involve up to 30,000 healthy participants if regulatory approval to proceed is received.

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News Network
January 31,2020

Jan 31: Cervical cancer could be eliminated worldwide as a public health issue within the next 100 years, according to two studies which may lead to better strategies for screening and vaccination against the malignant disease.

According to the studies, published in the journal The Lancet, more than 74 million cervical cancer cases, and 60 million deaths could be averted, and the disease eliminated in the 78 countries which have the highest disease burden.

The researchers, including those from Laval University in Canada, said cervical cancer is the second most frequent cancer among women in low-income and lower-middle-income countries (LMICs) with 2,90,000 (51 per cent) of the 5,70,000 new cases worldwide reported in women living in LMICs.

In the current studies, the scientists used the WHO draft strategy of cervical cancer elimination which defines plans for vaccination against the disease's causative agent, the human papillomavirus (HPV).

These plans, they explained, call for 90 per cent of girls to be vaccinated against HPV by 2030, and for 70 per cent of women to be screened for cervical cancer once or twice in their lifetime.

About 90 per cent of women with precancerous lesions, or cervical cancer are also advised to receive appropriate treatment, according to the WHO draft strategy, the scientists said.

In the second study, the research team analysed the impact of three elements of the WHO strategy on deaths from cervical cancer -- modelling the impact of scaling up cancer treatment, as well as vaccination and screening

"Our findings emphasise the importance of acting immediately to combat cervical cancer on all three fronts," said Karen Canfell from the University of Sydney in Australia, who co-led both the studies.

"In just 10 years, it's possible to reduce deaths from the disease by a third and, over the next century, more than 60 million women's lives could be saved. This would represent an enormous gain in terms of both quality of life, and lives saved," Canfell said.

By adding the two screening tests, and with the treatment of precancerous cervical lesions, cases of the cancer may drop by 97 per cent, and 72 million cervical cancer cases could be averted over the next century, the researchers said.

Scaling-up of appropriate cancer treatment could avert 62 million cervical cancer deaths, the study noted.

"For the first time, we've estimated how many cases of cervical cancer could be averted if WHO's strategy is rolled out and when elimination might occur," said Marc Brisson, study co-author from Laval University.

"Our results suggest that to eliminate cervical cancer it will be necessary to achieve both high vaccination coverage, and a high uptake of screening and treatment, especially in countries with the highest burden of the disease," Brisson added.

Based on the results of the studies, WHO's cervical cancer elimination strategy has been updated which will be presented for adoption at the World Health Assembly in May 2020, the scientists noted.

"If the strategy is adopted and applied by member states, cervical cancer could be eliminated in high income countries by 2040, and across the globe within the next century, which would be a phenomenal victory for women's health," Brisson said.

"However, this can only be achieved with considerable international financial and political commitment, in order to scale-up prevention and treatment," he added.

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