Tag: 23/8/22

Reducing the Rebleeding Risk from Obscure Gastrointestinal Bleeding

Anatomy of the gut
Source: Pixabay CC0

In a study published in Gastrointestinal Endoscopy, clinical investigators found that the five-year risk of rebleeding in obscure gastrointestinal bleeding was found to be as high as 41.7%, but capsule endoscopy examinations and subsequent interventions substantially reduced the risk. Factors such as anticoagulant use were also found to be independent predictors of rebleeding risk.

Obscure gastrointestinal bleeding (OGIB) is defined as gastrointestinal bleeding from a source that cannot be identified on upper or lower gastrointestinal endoscopy. OGIB is considered an important indication for capsule endoscopy (CE). CE is particularly useful for the detection of vascular and small ulcerative lesions, conditions frequently associated with OGIB.

Previous studies have shown that patients with severe comorbidities have a higher rate of positive CE findings (observations of mucosal breaks, vascular lesions, tumours, or blood retention) for OGIB. Additionally, for OGIB in which the initial CE fails to identify bleeding lesions, repeated CE can detect lesions at a higher rate. However, there have been no reports with a sufficiently large number of cases on the long-term outcomes of OGIB detected by CE and the risk of rebleeding.

To fill this knowledge gap, investigators followed up on 389 patients who underwent CE as their initial small intestinal examination for OGIB and evaluated the risk of rebleeding over the long term. In addition, the team evaluated the risk of rebleeding in OGIB, in which no source of rebleeding was found in any part of the gastrointestinal tract, including the small intestine.

The overall cumulative rebleeding rate during the five years after CE was 41.7%. In patients with positive CE findings, the cumulative rebleeding rate was 48.0%. The cumulative rebleeding rate in patients who had therapeutic intervention resulting from positive CE findings was 31.8%.

Furthermore, overt OGIB, anticoagulants, positive balloon-assisted enteroscopy after CE, and iron supplements without therapeutic intervention were found to be independent predictors of rebleeding. Among the components of an index assessing the severity of complications, liver cirrhosis was an independent predictor associated with rebleeding in patients with OGIB.

“If capsule endoscopy can be used to properly diagnose and lead to therapeutic intervention, the risk of rebleeding can be reduced,” concluded study leader Dr Otani. “Even if the endoscopy does not detect any lesions, adequate follow-up is necessary. Here at Osaka Metropolitan University, we have been utilising this tool clinically since its early days and have accumulated some of the world’s leading clinical data. This study revealed a high rebleeding rate in OGIB patients and clarified the effects of rebleeding predictors and therapeutic intervention. We have high expectations that this will lead to better medical care in the future.”

Source: Osaka Metropolitan University

Hydrogen Peroxide Clue to Repairing Nerve Damage

A healthy neuron.
A healthy neuron. Credit: NIH

Zebrafish and human DNA are over 70% similar, and the fish is widely used for biomedical research, particularly in its capacity for appendage and nerve damage regeneration. Now, the researcher who discovered the role of hydrogen peroxide in these restorative processes delves deeper in a recent study published in the Proceedings of the National Academy of Science (PNAS).

In 2011, Dr Sandra Rieger made the groundbreaking discovery that hydrogen peroxide is produced in the epidermis and is responsible for promoting nerve regeneration following injury.

Dr Rieger stated, “It was a great discovery, but at the time we did not know the exact molecular mechanisms that drove nerve regeneration after injury.”

In her latest study, Rieger and her colleagues investigated how hydrogen peroxide stimulates nerve regeneration. They studied this process using time-lapse imaging with fluorescent labelling of proteins in zebrafish and mutant analysis.

“Time-lapse imaging provides a detailed view of the biological processes and relationships between nerves and skin, as well as how these interactions lead to regeneration,” explained Dr Rieger. “The findings we sought will answer the question of how the skin affects regeneration, as the skin is so important in producing factors that are essential to the regeneration process.”

Hydrogen peroxide was found to react to Epidermal Growth Factor Receptor (EGFR) in the skin, which is essential for skin remodelling and aids nerve regrowth into the wound. “This is vital for the restoration of the skin,” said Dr Rieger.

“However, we discovered that if hydrogen peroxide is not present in neurons, nerve endings also cannot regenerate,” Dr Rieger continued. “It appears that both neurons and skin require hydrogen peroxide to coordinate the regeneration of their nerve endings.”

It is hoped that these findings will pave the way for future studies that lead to improved therapies for restoring skin and nervous system functions.

Source: University of Miami

COVID Risks a ‘Lost Generation’ for Psychiatry Research

Photo by Alex Green on Pexels

The field of psychiatry research risks a “lost generation” due to the difficulties of COVID, warn the authors of an editorial published in The Lancet. The burden of the pandemic has strained the critical aspect of the mentor-mentee relationship and the difficult period between the end of training and beginning research as an independent professional.

The authors, Erika E Forbes and David J Kupfer, are directors of the US-based Career Development Institute for Psychiatry, which provides teaching and mentoring programme for those embarking on a career into academic psychiatry, note that the pandemic has had a significant impact on this stage of development. The same challenges noted by the authors no doubt apply to the field of clinical psychology as well, which is also dependent on mentoring.

Both mentors and mentees are exhausted from health-related uncertainty, from Zoom meetings, and struggling to effectively collaborate, they wrote.

They note that starting a career as a scientist is a challenge even in the most stable times, but is now particularly gruelling, something they have recently borne witness to.

“At our April 2022 annual workshop, our fellows were dispirited, telling us that they feel neglected, undermined, and in some cases emotionally abused by the mentors at their home institutions. Many cannot envision a way forward.”

Though the authors are optimistic about adapting to COVID, with the limited of virtual settings and the new acknowledgement of how daily struggles impact work, they cannot deny that cannot deny that “psychiatry research is in a mentoring crisis.”

Mentoring is different in the COVID era, they stress. “If we accept that research will not go back to the pre-pandemic ways, adapt our behaviour to current realities, and enhance our commitment to supporting and guiding others, early-career scientists will again be able to thrive,” the authors conclude.

Non-nutritive Sweeteners Impact Human Glycaemic Responses

Photo by Amit Lahav on Unsplash

Since the late 1800s, non-nutritive sweeteners have been used to provide sweetness without sugar. Long been believed to have no effect on the human body, researchers reporting in the journal Cell now challenge this notion by finding that these sugar substitutes are not inert, and, in fact, some can alter human consumers’ microbiomes and thereby their glycaemic responses – albeit in a highly individualised fashion.

Previous research has already found found that non-nutritive sweeteners affected the microbiomes of mice in ways that could impact their glycaemic responses, something which the same researchers now investigated in humans.

To address this important question, the research team carefully screened over 1300 individuals for those who strictly avoid non-nutritive sweeteners in their day-to-day lives, and identified a cohort of 120 individuals. These participants were broken into six groups: two controls and four who ingested well below the FDA daily allowances of either aspartame, saccharin, stevia, or sucralose.

“In subjects consuming the non-nutritive sweeteners, we could identify very distinct changes in the composition and function of gut microbes, and the molecules they secret into peripheral blood. This seemed to suggest that gut microbes in the human body are rather responsive to each of these sweeteners,” said senior author Eran Elinav, an immunologist and microbiome researcher. “When we looked at consumers of non-nutritive sweeteners as groups, we found that two of the non-nutritive sweeteners, saccharin and sucralose, significantly impacted glucose tolerance in healthy adults. Interestingly, changes in the microbes were highly correlated with the alterations noted in people’s glycaemic responses.”

To prove the microbiomes were responsible, the researchers transferred microbial samples from the study subjects to mice that have been raised in completely sterile conditions, with no microbiome of their own.

“The results were quite striking,” explained Elinav. “In all of the non-nutritive sweetener groups, but in none of the controls, when we transferred into these sterile mice the microbiome of the top responder individuals collected at a time point in which they were consuming the respective non-nutritive sweeteners, the recipient mice developed glycaemic alterations that very significantly mirrored those of the donor individuals. In contrast, the bottom responders’ microbiomes were mostly unable to elicit such glycaemic responses,” he added. “These results suggest that the microbiome changes in response to human consumption of non-nutritive sweetener may, at times, induce glycaemic changes in consumers in a highly personalised manner.”

Elinav says that he expects the effects of the sweeteners will vary across individuals because of how unique our microbiomes are. “We need to raise awareness of the fact that non-nutritive sweeteners are not inert to the human body as we originally believed. With that said, the clinical health implications of the changes they may elicit in humans remain unknown and merit future long-term studies.”

“In the meantime, we need to continue searching for solutions to our sweet tooth craving, while avoiding sugar, which is clearly most harmful to our metabolic health,” says Elinav. “In my personal view, drinking only water seems to be the best solution.”

Source: Science Daily

Traditional Japanese Herbal Medicine Found to Alleviate Colitis

Gut microbiome. Credit: Darryl Leja, NIH

A Japanese study published in Frontiers in Immunology shows that a traditional herbal mix called daikenchuto reduced the severity of colitis in lab mice by preventing the loss of important gut bacteria and by raisin levels of anti-inflammatory immune cells in the colon.

Colitis is a chronic inflammation of the colon, characterised by an imbalance in gut bacteria and an abnormal immune response. Its prevalence has doubled over the last 20 years and although there are many treatments, they are only partially effective. This has led some researchers to take a closer look at traditional Asian herbal medicines.

Daikenchuto (DKT) is a formula containing specific amounts of ginger, pepper, ginseng, and maltose, and is one of 148 herbal medicines called Kampo, which have been developed in Japan and are often prescribed by doctors to treat a variety of illnesses. Numerous studies conducted in Japan and the United States have provided clinical evidence of DKT’s effect on colonic transit and postoperative ileus.

DKT was shown by previous research to have possible use in colitis treatment, but molecular level evidence has been lacking. Researchers at the RIKEN Center for Integrative Medical Sciences (IMS) in Japan conducted a detailed examination of its effects on a mouse model of colitis.

Colitis was induced in mice using dextran sodium sulfate, which is toxic to the cells that line the colon. When these mice were given DKT, their body weights remained normal, and they had lower clinical scores for colitis. Additional analysis revealed much less damage to the cells lining the colon. Having thus shown that DKT does indeed help protect against colitis, the researchers proceeded to analyze the gut microbiome of the mice and expression levels of anti-inflammatory immune cells.

Colitis is associated with an imbalance in gut microbiota, and analysis showed that a family of lactic acid bacteria were depleted in the colitic mice of this study. Also depleted was one of their metabolites, a short-chain fatty acid called propionate. Treating the model mice with DKT restored much of these missing bacteria – particularly Lactobacillus – and levels of propionate were normal.

Colitis is also associated with an abnormal immune response that causes the characteristic intestinal inflammation. When the team looked at innate intestinal immune cells, they found that levels ILC3 cells were lower in the untreated colitic mice than in the DKT-treated colonic mice, and that mice engineered to lack ILC3 suffered more and could not benefit from DKT treatment. This means that ILC3s are critical for protecting against colitis and that DKT works by interacting with them. Lastly, qPCR analysis indicated that these important immune cells had receptors for propionate, called GPR43, on their surface.

Daikenchuto is commonly prescribed to prevent and treat gastrointestinal diseases, as well as for reducing intestinal obstruction after colorectal cancer surgery,” said Naoko Satoh-Takayama. “Here we have shown that it can also alleviate intestinal diseases like colitis by rebalancing Lactobacillus levels in the gut microbiome. This likely helps reduce inflammatory immune responses by promoting the activity of type 3 innate lymphoid cells.”

Source: RIKEN