Medical Bulletin 09/ September/ 2024
Research Identifies Altered Serum Protein Linked to Periodontitis and Cardiovascular Disease
Individuals with periodontitis have altered concentrations of various proteins in their blood, according to a new study from Umeå University, Sweden. These findings published in the Journal of Dental Research pave the way for research into biomarkers for periodontitis and the underlying causes of the disease.
Researchers at Umeå University have now shown that individuals with periodontitis exhibit a unique inflammatory protein profile in their blood. The findings indicate, among other things, that severe periodontitis is associated with significantly reduced levels of a protein called EGF -epidermal growth factor, which is crucial for wound healing. The levels of a protein associated with cardiovascular disease, OLR-1 -oxidized low-density lipoprotein 1, are also significantly lower in individuals with severe periodontitis compared to healthy individuals.
“By identifying the blood biomarkers that may be crucial for the development of severe periodontitis, we can proceed to research drugs that specifically aims to slow down the disease progression,” says Pernilla Lundberg, periodontist and professor at the Department of Odontology at Umeå University, who led the study.
Periodontitis involves inflammation of the gums that leads to the breakdown of the supporting tissues around the teeth and can, in severe cases, result in tooth loss. Individuals with severe periodontitis are also more often affected by other serious diseases, such as cardiovascular disease and rheumatism, but the mechanisms behind these connections remain unclear.
Pernilla Lundberg adds that, “Thanks to the large number of participants in the study, the results are highly accurate, and we can use the material to continue finding more clues.”
Reference: Wänman M, Betnér S, Esberg A, et al. The PerioGene North Study Uncovers Serum Proteins Related to Periodontitis. Journal of Dental Research. 2024;0(0). doi:10.1177/00220345241263320
Study Finds Periodontal Pathogen Can Aggravate Rheumatoid Arthritis Symptoms
Research published in the International Journal of Oral Science has shown that periodontal disease with Aggregatibacter actinomycetemcomitans can exacerbate symptoms of rheumatoid arthritis (RA), but the molecular mechanisms behind this remain unclear.
In a recent study, researchers conducted several experiments in a mouse model of arthritis to shed light on this topic. Their findings reveal the crucial role of macrophages and the protein caspase-11 in this context, hinting at promising therapeutic targets for RA and other periodontal infection-related diseases.
Periodontal disease, which affects the gums and tissues that surround the teeth, is one of the most prevalent dental conditions worldwide. Most often caused by the formation and accumulation of bacterial biofilm around the teeth, periodontal disease can ultimately lead to tooth loss if left unattended.
Over the past few decades, clinical studies have revealed that the periodontal pathogen Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans) is closely related to the onset and worsening of rheumatoid arthritis (RA), a serious autoimmune disease that affects joints.
For the present study, the researchers conducted preliminary experiments to confirm whether A. actinomycetemcomitans infection influenced arthritis in mice.
To this end, they used the collagen antibody-induced arthritis mouse model, which is a well-established experimental model that mimics several aspects of RA in humans.
They found that infection with this specific bacterium led to increased limb swelling, cellular infiltration into the lining of the joints, and higher levels of the inflammatory cytokine interleukin-1β (IL-1β) within the limbs.
Notably, these symptoms of worsening RA could be suppressed by administering a chemical agent called clodronate that depletes macrophages -- a type of immune cell.
This demonstrated that macrophages were somehow involved in aggravating RA caused by A. actinomycetemcomitans infection.
Further investigation using macrophages derived from mouse bone marrow revealed that A. actinomycetemcomitans infection increased the production of IL-1β. In turn, this triggered the activation of a multiprotein complex known as the inflammasome, which plays a key role in initiating and modulating the body's inflammatory response to infections.
The researchers added yet one more piece to this puzzle using caspase-11-deficient mice.
In these animals, inflammasome activation due to A. actinomycetemcomitans was suppressed.
Most importantly, caspase-11-deficient mice exhibited less deterioration of arthritis symptoms, hinting at the important role that caspase-11 plays in this context.
"Our research findings provide new insights into the link between periodontal pathogenic bacteria and the exacerbation of arthritis through inflammasome activation, offering important information on the long-debated relationship between periodontal disease and systemic diseases," highlights Professor Toshihiko Suzuki, one of the lead authors of the study.
Reference: Tokuju Okano, Hiroshi Ashida, Noriko Komatsu, Masayuki Tsukasaki, Tamako Iida, Marie Iwasawa, Yuto Takahashi, Yasuo Takeuchi, Takanori Iwata, Miwa Sasai, Masahiro Yamamoto, Hiroshi Takayanagi, Toshihiko Suzuki. Caspase-11 mediated inflammasome activation in macrophages by systemic infection of A. actinomycetemcomitans exacerbates arthritis. International Journal of Oral Science, 2024; 16 (1) DOI: 10.1038/s41368-024-00315-x
Pregnancy Exposure to PAFS Linked to Long-Term Weight Gain and Heart Issues: Study Reveals
Women with higher levels of per- and polyfluoroalkyl substances (PFAS) during pregnancy may experience long-term weight gain and heart problems later in life, according to new research published in The Journal of Clinical Endocrinology & Metabolism.
PFAS are manmade chemicals found in food packaging, cookware, clothes, drinking water, personal care products and many other consumer goods. These endocrine-disrupting chemicals (EDCs) can interfere with hormones and cause health issues such as obesity, infertility and cancer.
“Our study supports the idea that pregnancy may be a sensitive period of PFAS exposure as it may be associated with long-term weight gain and subsequent adverse cardiometabolic health outcomes in women,” said the study’s first author Jordan Burdeau, Ph.D., of the Harvard T.H. Chan School of Public Health in Boston, Mass. “Our findings may improve understanding of the effects of PFAS on cardiometabolic health during pregnancy, which in turn may improve early prevention or detection of adverse cardiometabolic health outcomes in women.”
The researchers studied 547 pregnant women in their early 30s, comparing their PFAS levels during pregnancy with cardiometabolic health outcomes at age 50. They found women with higher levels of PFAS in their blood during early pregnancy weighed more and had more body fat at 50 years old than those with lower levels, potentially making them more susceptible to obesity and heart health problems later in life.
“It’s important to try to limit your PFAS exposure as it could reduce your risk of health issues later in life,” Burdeau said.
Reference: Jordan A Burdeau, Briana J K Stephenson, Jorge E Chavarro, Shruthi Mahalingaiah, Emma V Preston, Marie-France Hivert, Emily Oken, Antonia M Calafat, Sheryl L Rifas-Shiman, Ami R Zota, Tamarra James-Todd, Early Pregnancy Plasma Per- and Polyfluoroalkyl Substances (PFAS) and Maternal Midlife Adiposity, The Journal of Clinical Endocrinology & Metabolism, 2024;, dgae542, https://doi.org/10.1210/clinem/dgae542
Clinical Trial Finds Administering Potassium at 3.6 mEq/L as Effective as Standard 4.5 mEq/L Threshold Post Cardiac Surgery
A new study has shown that a lower threshold for potassium supplementation after cardiac surgery saves patient costs and does not create any further risks of atrial fibrillation or other dysrhythmias.
It’s common practice for patients to receive intravenous potassium supplementation after any form of heart surgery if their potassium levels drop below 4.5 mEq/L (Milliequivalents per litre). However, a new clinical trial whose results are published in JAMA NetworkTrusted Source, suggests that potassium supplementation only at levels below 3.6 mEq/L is non-inferior to standard practice as a way to lower the risk of atrial fibrillation (AFib) after surgery.
The risk of AFib increases with age, but it can sometimes occur among young people. People with AFib may have a much faster heart rate than usual, and the heart does not pump blood around the body efficiently. Blood may collect or pool in the heart, increasing the likelihood of clots.
it is the most frequent postoperative adverse event, and according to the authors of the new study, it can lead to expensive hospital bills, longer hospital stays, and a higher risk of death.
Researchers conducted a randomized clinical trial at 23 cardiac surgical centers utilizing 1,690 patients with no history of atrial dysrhythmias who were scheduled for isolated coronary artery bypass grafting surgery.
Of those, 843 were in the group with the “relaxed” standard for supplementation. The lowered threshold for potassium supplementation did not result in any further adverse developments or increased heart dysrhythmias, and the cost savings per patient in the “relaxed” group had a mean difference of $111.89.
Reference: O’Brien B, Campbell NG, Allen E, et al. Potassium Supplementation and Prevention of Atrial Fibrillation After Cardiac Surgery: The TIGHT K Randomized Clinical Trial. JAMA. Published online August 31, 2024. doi:10.1001/jama.2024.17888
Clinical Trial Reveals 100 times Vision Improvement In Patients with Inherited Retinal Disease
The vision of people with a rare inherited condition that causes them to lose much of their sight early in childhood was 100 times better after they received gene therapy to address the genetic mutation causing it. Some patients even experienced a 10,000-fold improvement in their vision after receiving the highest dose of the therapy, according to researchers from the Perelman School of Medicine at the University of Pennsylvania who co-led the clinical trial published in The Lancet.
“That 10,000-fold improvement is the same as a patient being able to see their surroundings on a moonlit night outdoors as opposed to requiring bright indoor lighting before treatment,” said the study’s lead author, Artur Cideciyan, PhD, a research professor of Ophthalmology and co-director of the Center for Hereditary Retinal Degenerations. “One patient reported for the first time being able to navigate at midnight outdoors only with the light of a bonfire.”
A total of 15 people participated in the Phase 1/2 trial, including three pediatric patients. Each patient had Leber congenital amaurosis as the result of mutations in the GUCY2D gene, which is essential to producing proteins critical for vision. This specific condition, which affects less than 100,000 people worldwide and is abbreviated as LCA1, causes significant amount of vision loss as early as infancy.
All subjects had severe vision loss with their best measure of vision being equal or worse than 20/80—meaning if a typically-sighted person could see an object clearly at 80 feet, these patients would have to move up to at least 20 feet to see it. Glasses provide limited benefit to these patients because they correct abnormalities in the optical focusing ability of the eye, and are unable to address medical causes of vision loss, such as genetic retinal diseases like LCA1.
The trial tested different dosage levels of the gene therapy, ATSN-101, which was adapted from the AAV5 microorganism and was surgically injected under the retina. For the first part of the study, cohorts of three adults each received one of the three different dosages: Low, mid, and high. Evaluations were held between each level of dosage to ensure that they were safe before upping the dosage for the next cohort. A second phase of the study involved only administering the high dosage levels to both an adult cohort of three and a pediatric cohort of three, again after safety reviews of the previous cohorts.
Improvements were noticed quickly, often within the first month, after the therapy was applied and lasted for at least 12 months. Observations of participating patients are also ongoing. Three of six high-dosage patients who were tested to navigate a mobility course in varying levels of light achieved the maximum-possible score. Other tests used eye charts or measured the dimmest flashes of light patients perceived in a dark environment.
Of the nine patients who received the maximum dosage, two had the 10,000-fold improvement in vision.
“Even though we previously predicted a large vision improvement potential in LCA1, we did not know how receptive patients’ photoreceptors would be to treatment after decades of blindness,” said Cideciyan. “It is very satisfying to see a successful multi-center trial that shows gene therapy can be dramatically efficacious.”
Reference: Yang, P., et al. (2024). Safety and efficacy of ATSN-101 in patients with Leber congenital amaurosis caused by biallelic mutations in GUCY2D: A phase 1/2, multicentre, open-label, unilateral dose escalation study. The Lancet, 404(10456), 962–970. https://doi.org/10.1016/S0140-6736(24)01447-8
Randomised Trial Finds Low-Impact Exercise and Yoga Effective for Managing Urinary Incontinence
Older women struggling with urinary incontinence can benefit from regular, low-impact exercise, with yoga as well as stretching and strengthening showing benefits in a new study published in Annals of Internal Medicine.
The research, led by scientists at Stanford Medicine and the University of California, San Francisco, is part of a larger effort to identify low-risk, low-cost ways to treat one of the most common health problems women face as they age.
After 12 weeks of a low-impact yoga program, study participants had about 65% fewer episodes of incontinence. Women in a control group doing stretching and strengthening exercises experienced a similar benefit over the same time period. The benefits are on par with the effects of medications used to address incontinence, the researchers said.
“Our study was testing the kind of yoga that just about anyone can do, with modifications for different physical abilities,” said the study’s senior author, Leslee Subak, MD, chair of obstetrics and gynecology at Stanford Medicine. “What I love about it is that it’s safe, inexpensive, doesn’t require a doctor and accessible wherever you live.” Because the trial was conducted partly during the COVID-19 pandemic, many participants received their yoga or exercise instruction via online meetings, exercising in their own homes, she noted.
Urinary incontinence, which affects more than half of middle-aged women and up to 80% of 80-year-olds, can lead to a variety of other problems, from social isolation to bone fractures caused by falls. But there is help.
“Part of the problem is that incontinence is stigmatized; we don’t talk about it,” said Subak, . “Or we hear folklore about this being normal when you get older. In fact, it’s very common but it’s not inevitable, and we have very effective ways of treating it.”
Reference: Huang, A. J., Chesney, M., Schembri, M., Raghunathan, H., Vittinghoff, E., Mendes, W. B., Pawlowsky, S., & Subak, L. L. (2024). Efficacy of a therapeutic pelvic yoga program versus a physical conditioning program on urinary incontinence in women: A randomized trial. Annals of Internal Medicine. https://doi.org/10.7326/M23-3
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