Month: November 2022

Multiple Sclerosis Therapy also Improves Gut Flora Composition

Gut microbiome. Credit: Darryl Leja, NIH

Dimethyl fumarate, a medication used to treat MS also has a beneficial effect on the composition of the intestinal flora, according to research published in Gut Microbes. Conversely, the gut flora also plays a role in which side effects occur during treatment with the medication.

Few previous studies have examined the effects of MS treatments on intestinal flora and on the role their composition plays with regard to efficacy and side effects. A team of researchers at the University of Basel and the University Hospital Basel has now examined these questions in a group of 20 MS patients being treated with dimethyl fumarate.

Dimethyl fumarate reduces the number of MS flare-ups by interfering with the metabolic processes of certain immune cells. However, the therapy is also associated with side effects, including hot flashes and gastrointestinal complaints, and in some cases lymphopenia, a lack of lymphocytes such as B cells and T cells in the blood. This can lead to severe complications.

More ‘good’ bacteria

In their study, the researchers led by Professor Anne-Katrin Pröbstel and Professor Adrian Egli, examined stool and blood samples from participants before and during the first twelve months of the treatment. Their focus was on the composition of the gut microbiome. Pröbstel and her team also measured the number of lymphocytes in the blood in order to identify patients who were experiencing lymphopenia as a side effect.

After only three months of treatment, the research team was already able to identify changes to the gut microbiome: “We were able to show that the gut bacteria of patients receiving the medication started to become more like the composition seen in healthy individuals,” Pröbstel explained. Treatment with dimethyl fumarate reduced the proportion of pro-inflammatory types of bacteria, which have been associated with MS, and supported the growth of “good” bacteria.

Furthermore, the researchers were able to draw a connection between the composition of the gut microbiome and the development of lymphopenia: The presence of Akkermansia muciniphila bacteria combined with the lack of Prevotella copri bacteria emerged as a risk factor for this side effect. The authors therefore suspect that P. copri may protect against lymphopenia.

Interaction between therapy and gut flora

“Our data suggest that immunomodulatory therapies affect not only immune cells, but also positively influence the gut microbiome,” Pröbstel explains. The connection between gut bacteria and clinical side effects of the treatment may eventually enable early identification of patients at risk of developing lymphopenia. Microbiologist Egli continues: “In the future, this relatively new field of microbiology may help us better understand the effects and side effects of many medications with regard to gut bacteria, and to personalise treatment accordingly.”

“What we have so far is only a pilot study with a relatively small number of participants,” she cautioned. Larger-scale studies are needed to confirm the results and explore the potential for supporting MS therapies via gut flora and for predicting side effects in advance.

Source: University of Basel

Aerobic Exercise Creates a Metabolic Shield against Metastatic Cancer

Old man jogging
Photo by Barbra Olsen on Pexels

A new study at Tel Aviv University found that aerobic exercise can reduce the risk of metastatic cancer by 72%. According to the researchers, intensity aerobic exercise increases the glucose consumption of internal organs, thereby reducing the availability of energy to the tumour.  The paper was published in Cancer Research.

Previous studies have demonstrated that physical exercise reduces the risk for some types of cancer by up to 35%. This is similar to the positive impact of exercise on other conditions, such as heart disease and diabetes.

In this study, Prof Levy and Dr Gepner added new insight, showing that high-intensity aerobic exercise, which derives its energy from sugar, can reduce the risk of metastatic cancer by as much as 72%. “If the general message to the public so far has been ‘be active, be healthy’,” they say, “now we can explain how aerobic activity can maximise the prevention of the most aggressive and metastatic types of cancer.”

The study combined lab models trained under a strict exercise regimen, with data from healthy human volunteers examined before and after running. The human data, obtained from an epidemiological study that monitored 3000 individuals for about 20 years, indicated 72% less metastatic cancer in participants who reported regular aerobic activity at high intensity, compared to those who did not engage in physical exercise.

The animal model exhibited a similar outcome, enabling the researchers to identify its underlying mechanism. They found that aerobic activity significantly reduced the development of metastatic tumours in the lab models’ lymph nodes, lungs, and liver. The researchers hypothesised that in both humans and model animals, this favourable outcome is related to the enhanced rate of glucose consumption induced by exercise.

‘Exercise changes the whole body’

“Our study is the first to investigate the impact of exercise on the internal organs in which metastases usually develop, like the lungs, liver, and lymph nodes,” explains Prof Levy.

“Examining the cells of these organs, we found a rise in the number of glucose receptors during high-intensity aerobic activity – increasing glucose intake and turning the organs into effective energy-consumption machines, very much like the muscles. We assume that this happens because the organs must compete for sugar resources with the muscles, known to burn large quantities of glucose during physical exercise. Consequently, if cancer develops, the fierce competition over glucose reduces the availability of energy that is critical to metastasis.”

“Moreover,” she offers, “when a person exercises regularly, this condition becomes permanent: the tissues of internal organs change and become similar to muscle tissue. We all know that sports and physical exercise are good for our health. Our study, examining the internal organs, discovered that exercise changes the whole body, so that the cancer cannot spread, and the primary tumour also shrinks in size.”  

“Our results indicate that unlike fat-burning exercise, which is relatively moderate, it is a high-intensity aerobic activity that helps in cancer prevention,” adds Dr Gepner. “If the optimal intensity range for burning fat is 65–70% of the maximum pulse rate, sugar burning requires 80–85% – even if only for brief intervals.”

“For example: a one-minute sprint followed by walking, then another sprint. In the past, such intervals were mostly typical of athletes’ training regimens, but today we also see them in other exercise routines, such as heart and lung rehabilitation. Our results suggest that healthy individuals should also include high-intensity components in their fitness programs. We believe that future studies will enable personalized medicine for preventing specific cancers, with physicians reviewing family histories to recommend the right kind of physical activity. It must be emphasized that physical exercise, with its unique metabolic and physiological effects, exhibits a higher level of cancer prevention than any medication or medical intervention to date.”  

Source: Tel Aviv University

Bacteria in Severe Oral Infections Linked to Other Diseases

Dentist checking teeth
Image by Caroline LM on Unsplash

To date, there has been little research into identifying the bacteria found in severe oral infections, despite long-suspected links to other diseases. Now, a study from Karolinska Institutet has characterised the microbial composition of these, with many known to be linked to other disease. The study is published in Microbiology Spectrum.

There is growing evidence linking oral health and common diseases, such as cancer, cardiovascular disease, diabetes and Alzheimer’s disease. However, there have been few longitudinal studies identifying which bacteria occur in infected oral- and maxillofacial regions.

Researchers at Karolinska Institutet have now analysed samples collected between 2010 and 2020 at the Karolinska University Hospital in Sweden from patients with severe oral infections and produced a list of the most common bacteria.

“We’re reporting here, for the first time, the microbial composition of bacterial infections from samples collected over a ten-year period in Stockholm County,” says Professor Margaret Sällberg Chen of the Department of Dental Medicine. “The results show that several bacterial infections with link to systemic diseases are constantly present and some have even increased over the past decade in Stockholm.”

A role in other diseases

The study shows that the most common bacterial phyla amongst the samples were Firmicutes, Bacteroidetes, Proteobacteria and Actinobacteria, while the most common genera were Streptococcus spp, Prevotella spp, and Staphylococcus spp.

“Our results provide new insight into the diversity and prevalence of harmful microbes in oral infections,” says Professor Sällberg Chen. “The finding isn’t only of importance to dental medicine, it also helps us understand the role of dental infection in patients with underlying diseases. If a certain bacterium infects and causes damage in the mouth, it’s very likely that it can be harmful to tissues elsewhere in the body as the infection spreads.”

The research group has previously shown that the occurrence of oral bacteria in the pancreas reflects the severity of pancreatic tumours.

Improve diagnostics and therapy

The study was conducted using 1014 samples from as many patients, of whom 469 were women and 545 men, and a mass-spectrometric method called MALDI-TOF that rapidly identifies individual living bacteria in a sample, but that is rarely used in dental care.

“Our study was a single centre epidemiology study and to ensure the validity of the results we need to make more and larger studies,” says adjunct Professor Volkan Özenci at the Department of Laboratory Medicine. “We now hope that dentists will collaborate with clinical microbiology laboratories more to gain a better understanding of the bacteria that cause dental infections, to improve diagnostics and therapeutic management of oral infections.”

The study is part of Khaled Al-Manei’s doctoral thesis, the next step of which is a similar epidemiological study of fungal infections in the mouth that aims to identify new fungi and microbes and understand what causes their possible malignancy. 

Source: Karolinska Institutet

Supporting Men Living with HIV Own their Health

According to World Population Review, South Africa has one of the highest HIV prevalence in the world; ranking 4th with 19.1% in 2020, coupled with the highest burden of people living with HIV (PLHIV) globally, at an estimated 8.45 million.

In an effort to address these issues, and particularly change the stigma associated with the disease, the United States President’s Emergency Plan for AIDS Relief (PEPFAR), the United States Agency for International Development (USAID) and the National Department of Health (NDoH) partnered with Project Last Mile and FCB Joburg to launch MINA. For Men. For Health, an initiative aimed at encouraging men to get tested for HIV and provide communal support to begin – and stay on – treatment for those who tested HIV positive.    

The campaign seeks to unpack the societal stigmas that result in men not wanting to get tested and then to adhere to taking Antiretroviral Treatment (ART). Beyond this, the campaign provided a safe space for men to express and share their experiences and fears and to address the various misconceptions about living with HIV. Leaning on insights garnered through community coaches and interactions with men living with HIV, a platform was created which gave men the tools and resources they need to take control of their lives and their HIV status. This was MINA. For Men. For Health.

The campaign’s concept emanated from the idea that men could dispel fears of prioritising their health, giving them exposure to a community of men just like them, which remains a great source of support. In the execution stage, this was coupled with brand ambassadors and social media assets that carried the campaign on social platforms, including collateral for presence and awareness in clinics across the country in severely affected communities. The in-clinic journey was an integral part of the campaign as it was vital to intercept and engage clients in real-time who may have been at the clinic for other reasons, to consider getting tested for HIV or begin/continue with their treatment.

MINA. For Men. For Health has demonstrated success in areas where individuals were exposed to brand messaging. Some key statistics include:

1. For every R17 of PEPFAR funding, R51 of earned media was generated.

2. On average, 48 000 more men tested for HIV per quarter in MINA. For Men. For Health activity facilities than non-activity facilities post-launch.

3. Nationally, first quarter post-launch saw a 7% increase in men’s linkage to care.

There has been a notable increase in the number of men who tested for HIV over the campaign period, with more than 107 290 men having tested since campaign’s inception in November 2020, with a subsequent increase in men commencing ART.

“The efforts and campaigns providing a positive narrative around HIV are now showing success across the board in combating the perceptions around the disease. In addition, the campaign is generating a positive framework to aid men living with HIV to express themselves, get the necessary care, and remain on treatment.” says Rodney Knotts, Senior Marketing Advisor at USAID.

“Currently, we are looking at ways to increase the presence of MINA. For Men. For Health, as mass media and social marketing have long been used as tools to increase education, decrease stigma, and promote behaviour change in the fight against HIV/AIDS in South Africa,” says Jonathan Wolberg, Creative Director at FCB Joburg.

Although South Africa has made significant strides over the last decade in combating HIV-AIDS, complacency will turn back the clock on gains made through consistent community engagement, screening and treatment.

MINA. For Men. For Health continues to play an essential role in addressing this public health challenge that still very much has a place in South African society. 

“MINA. For Men. For Health is all about changing and mainstreaming conversations around HIV.  With our above-the-line, digital and in clinic campaign, we not only hope to support and empower men living with HIV, but also their partners, families and communities.  Our goal is to impact social change and perceptions for all South Africans around this completely treatable chronic condition,” says Amanda Manchia, PLM Strategic Marketing Project Lead.

If you’d like to be part of the MINA. For Men. For Health movement, visit or  @MINAForMenForHealth on Facebook.

New Material Speeds up Diabetic Wound Healing

Photo by Diana Polekhina on Unsplash

University of Nottingham researchers have discovered a new class of polymer that can aid healing in hard-to-treat diabetic wounds by providing instructions to both immune and non-immune cells. This new material that can be applied to diabetic wounds to accelerated healing with just one application. The findings have been published in Advanced Materials.

Wound healing is a complex biological process that involves various cell types working together, with a cell type called fibroblasts playing a critical role in forming new tissue required for healing. Diabetes can disrupt these processes in cells making wound healing slow and difficult to treat. This can lead to infection and in extreme cases the need for amputation.

Experts from the School of Life Sciences and Pharmacy screened 315 different polymer surfaces, examining the different chemical make-up of each until they identified a polymer type that actively drives fibroblasts and immune cells to promote healing. A team from the School of Engineering made small particles that are decorated with this polymer on their surface. These particles could be directly applied to the wound area.

The long, repeating chain structure of polymers gives them unique properties that can be tailored for different uses. Using polymer microparticles the team showed how this new material, when delivered to a wound on an animal model, produces three times more fibroblast activity over a period of up to 96 hours and achieved more than 80% wound closure.

This new polymer could be applied as a coating to standard wound dressings to provide a fast and effective treatment.

Source: University of Nottingham

Proportions of Immune Cells can Predict ALS Progression

Source: Pixabay CC0

By measuring the proportions of certain immune cells in the cerebrospinal fluid when diagnosing amyotrophic lateral sclerosis (ALS), it is possible to predict the disease’s speed of progression, according to a study from Karolinska Institutet published in Nature Communications.

ALS is a rare, but fatal disease that affects the nerve cells and leads to paralysis of voluntary muscles and death. This new research offers a way to predict the course of the disease in ALS patients.

Between March 2016 and March 2020, researchers collected fresh blood and cerebrospinal fluid from 89 patients in Stockholm who had recently been diagnosed with ALS, and followed-up until October 2020.

The study shows that a high proportion of so-called effector T cells are associated with a low survival rate. At the same time, a high proportion of activated regulatory T cells indicate a protective role against the rapid disease progression. The findings provide new evidence for the involvement of T cells in the course of the disease and show that certain types of effector T cells accumulate in the cerebrospinal fluid of ALS patients.

“The study could contribute to the development of new treatments that target immune cells to slow down the course of the disease,” says study first author Solmaz Yazdani, a doctoral student at the Institute of Environmental Medicine at Karolinska Institutet.

The next step in her research is to study how T cells contribute to the course of the disease.

“We have plans to collect samples from these individuals to study changes in the immune cells over time. In addition, we want to study effector T cells in more detail to understand their role in ALS.”

Source: Karolinska Institutet

To Fight the Opioid Epidemic, Researchers Create a Vaccine that Blocks Fentanyl

Photo by Pharmacy Images on Unsplash

Researchers have developed a vaccine that blocks fentanyl’s to enter the brain, thus eliminating the dangerous synthetic opioid’s “high”. The breakthrough discovery, reported in the journal Pharmaceutics, could have major implications for the rampant problem of opioid addiction by becoming a relapse prevention agent for people trying to quit using opioids.

While Opioid Use Disorder (OUD) is treatable, studies estimate that 80% of those dependent on the drug suffer a relapse. Fentanyl is 50 times stronger than heroin and 100 times stronger than morphine. Consumption of about 2mg of fentanyl (the size of two grains of rice) is likely to be fatal depending on bodyweight. Current treatments for OUD are methadone, buprenorphine and naltrexone. Naloxone is given in opioid overdose situations and can temporarily reverse the effects of the opioids.

“We believe these findings could have a significant impact on a very serious problem plaguing society for years – opioid misuse. Our vaccine is able to generate anti-fentanyl antibodies that bind to the consumed fentanyl and prevent it from entering the brain, allowing it to be eliminated out of the body via the kidneys. Thus, the individual will not feel the euphoric effects and can ‘get back on the wagon’ to sobriety,” said lead author Colin Haile, a research associate professor of psychology at University of Houston.

No any adverse side effects from the vaccine were observed in trial animals. The team plans to start manufacturing clinical-grade vaccine in the coming months with clinical trials in humans planned soon.

Fentanyl is an especially dangerous threat because it is often added to street drugs like cocaine, methamphetamine and other opioids, such as oxycodone and hydrocodone/acetaminophen pills, and even to counterfeit benzodiazepines like Xanax. These counterfeit drugs laced with fentanyl add to the amount of fentanyl overdoses in individuals who do not ordinarily consume opioids.

“The anti-fentanyl antibodies were specific to fentanyl and a fentanyl derivative and did not cross-react with other opioids, such as morphine. That means a vaccinated person would still be able to be treated for pain relief with other opioids,” said Haile.

The vaccine tested contains an adjuvant derived from E. coli named dmLT. An adjuvant molecule boosts the immune system’s response to vaccines, a critical component for the effectiveness of anti-addiction vaccines.

Therese Kosten, professor of psychology and director of the Developmental, Cognitive & Behavioral Neuroscience program at UH, calls the new vaccine a potential “game changer.”

“Fentanyl use and overdose is a particular treatment challenge that is not adequately addressed with current medications because of its pharmacodynamics and managing acute overdose with the short-acting naloxone is not appropriately effective as multiple doses of naloxone are often needed to reverse fentanyl’s fatal effects,” said Kosten, senior author of the study.

Source: University of Houston

Apixaban Flops in HEAL-COVID Recovery Trial

Image from Pixabay

A major UK-wide trial has found that the the oral anticoagulant apixaban does not help patients recovering from moderate and severe COVID compared to standard care – despite this approach being offered to patients.

To date, more than a thousand NHS patients hospitalised with COVID have taken part in HEAL-COVID, a platform trial that is aiming to find treatments to reduce the number who die or are readmitted following their time in hospital.

The trial’s preliminary results have shown that prescribing the oral anticoagulant Apixaban does not affect subsequent mortality or rehospitalisation of COVID over the following year (apixaban 29.1%, versus standard care 30.8%).

As well as being ineffective, anticoagulant therapy has known serious side effects, and these were experienced by participants in the trial with a small number of the 402 participants receiving apixaban discontinuing due to bleeding events.

There was also no benefit from Apixaban in terms of the number of days alive and out of hospital at day 60 after randomisation (apixaban 59 days, versus standard care 59 days).

Following these results, the trial will continue to test atorvastatin, which acts on other mechanisms of disease that are thought to be important in COVID.

Chief Investigator for the trial Professor Charlotte Summers is an intensive care specialist at Addenbrooke’s Hospital and the University of Cambridge.  She said: “These first findings from HEAL-COVID show us that a blood thinning drug, commonly thought to be a useful intervention in the post-hospital phase is actually ineffective at stopping people dying or being readmitted to hospital.  This finding is important because it will prevent unnecessary harm occurring to people for no benefit.   It also means we must continue our search for therapies that improve longer term recovery for this devastating disease.”

HEAL-COVID enrols patients when they are discharged from hospital, following their first admission for COVID.  They are randomised to a treatment and their progress tracked.

Source: University of Liverpool

Chemo Drug Ifosfamide could Increase Disease Risk for Survivors’ Descendants

The common chemotherapy drug ifosfamide could leave a lasting toxic legacy for children and grandchildren of adolescent cancer survivors, suggests a study published online in iScience.

Researchers from Washington State University found that male rats given ifosfamide during adolescence had offspring and grand-offspring with increased incidence of disease. Other studies have shown that cancer treatments can increase patients’ chance of developing disease later in life, this is one of the first-known studies showing that susceptibility can be passed down to a third generation of unexposed offspring.

“The findings suggest that if a patient receives chemotherapy, and then later has children, that their grandchildren, and even great-grandchildren, may have an increased disease susceptibility due to their ancestors’ chemotherapy exposure,” said corresponding author Michael Skinner, a WSU biologist and corresponding author on the study.

Skinner emphasised that the findings should not dissuade cancer patients from undertaking chemotherapy since it can be a very effective treatment. Chemotherapy drugs kill cancerous cells and stop multiplication, but have many side effects, including on reproductive systems.

The researchers therefore recommend that cancer patients who plan to have children later take precautions, such as using cryopreservation to freeze sperm or ova before having chemotherapy.

In the study, researchers exposed a set of young male rats to ifosfamide over three days, mimicking a course of treatment an adolescent human cancer patient might receive. Those rats were later bred with unexposed female rats. The resulting offspring were bred again with another set of unexposed rats.

The first-generation offspring had some exposure to the chemotherapy drug since their fathers’ sperm was exposed, but researchers found greater incidence of disease in not only the first- but also the second-generation, who had no direct exposure to the drug. While there were some differences by generation and sex, the associated problems included greater incidence of kidney and testis diseases as well as delayed onset of puberty and abnormally low anxiety, indicating a lowered ability to assess risk.

The researchers also looked for epigenetic changes. Previous research has shown that exposure to toxicants, particularly during development, can create epigenetic changes that can be passed down through sperm and ova.

The results of the researchers’ analysis showed epigenetic changes in two generations linked to the chemotherapy exposure of the originally exposed rats. The fact that these changes could be seen in the grand-offspring, who had no direct exposure to the chemotherapy drug, indicates that the negative effects were passed down through epigenetic inheritance.

Skinner and colleagues at Seattle Children’s Research Institute are currently working on a human study with former adolescent cancer patients to learn more about the effects chemotherapy exposure has on fertility and disease susceptibility later in life.

A better knowledge of chemotherapy’s epigenetic shifts could also help inform patients of their likelihood of developing certain diseases, creating the possibility of earlier prevention and treatment strategies, Skinner said.

“We could potentially determine if a person’s exposure had these epigenetic shifts that could direct what diseases they’re going to develop, and what they’re going to potentially pass on to their grandchildren,” he said. “We could use epigenetics to help diagnose whether they’re going to have a susceptibility to disease.”

Source: Washington State University

Cannabis Medical Trials get Positive Media Coverage Despite Results

Cannabis plants
Photo by Crystalweed Cannabis on Unsplash

In many trials testing cannabis for pain relief, there is no significant difference between placebo and the active cannabinoid substance. Still, these studies receive significant media coverage regardless of the clinical outcome, according to a study published in JAMA Network Open.

“We see that cannabis studies are often described in positive terms in the media regardless of their results,” says the study’s first author Filip Gedin, postdoc researcher at Karolinska Institutet. “This is problematic and can influence expectations when it comes to the effects of cannabis therapy on pain. The greater the benefit a treatment is assumed to have, the more potential harms can be tolerated.”

The study is based on an analysis of published clinical studies in which cannabis has been compared with placebo for the treatment of clinical pain. The change in pain intensity before and after treatment were the study’s primary outcome measurement.

The analysis drew on 20 studies published up to September 2021 involving almost 1500 individuals.

No difference between cannabis and placebo

The results of the study show that pain is rated as being significantly less intense after treatment with placebo, with a moderate to large effect. The researchers also observed no difference in pain reduction between cannabis and placebo, which corroborates results from another recently published meta-analysis. 

“There is a distinct and clinically relevant placebo response in studies of cannabis for pain,” says Dr Gedin.

The researchers also examined a possible connection between the magnitude of the therapeutic effect shown by the cannabis studies and the coverage they receive in the media and in academic journals. Media presence was measured through Altmetric, which is a method of evaluating mentions in the media, in blogs and on social media. Academic impact was measured in terms of citations by other researchers.

The analysis of media presence included a total of 136 news items in traditional media and in blogs and was categorised as positive, negative or neutral, depending on how the results were presented concerning the effectiveness of cannabis as a treatment for pain.

Lots of media attention

The researchers found that the cannabis studies received much greater media attention than other published studies. The coverage was substantial regardless of the magnitude of the placebo response and regardless of the therapeutic effect of cannabis. They also observed no link between the proportion of positively described news about a study and the effect it reported. 

The researchers add the caveat that their study combined trials of varying designs and quality and therefore the results should be interpreted with caution.

This research was financed by Riksbankens Jubileumsfond (Karin Jensen). The researchers report no potential conflicts of interest.

Source: Karolinska Institute