Potential new therapy offers promising approach to treat rare, incurable form of kidney stone resistance

A study led by investigators at the University of Utah Health System (U of U Health) has revealed that a single immunotherapy treatment based on the use of a vaccine developed in partnership with St. Jude Children’s Research Hospital resulted in a significant drops in markers indicating kidney stones in test animals. The discovery, reported today in Science Translational Medicine, could open a new path to treating the severe form of kidney stone resistance found in many people with the rare condition. The immunotherapy could also be used to treat relapses following kidney transplants.

“I think kids are looking at one in three who undergo kidney transplants with kidney stones and not all have the immunosuppressive drugs,” said Joel B. Snyder, MD, reporting lead author and deputy director of the St. Jude Laboratory Developmental Therapeutics Program. “This immuno-oncology approach involves finding inhibitors (drugs) for specific antibodies that recognize the abnormal protein fragments (~70%) expressed by kidney stones in the recipient.”

A common therapy, immunosuppressive drugs called ACE2 inhibitors, cause long-term uncontrolled inflammation of the kidneys. These drugs have limited ability to reach the vulnerable cells within the kidneys. In this study, Snyder’s team got a dose of the standard immunosuppressive drug drusen plasminogen activator 2 (DROMIUM) in mice with kidney stones. After giving the mice the standard of care, it was shown that immunosuppression with DROMIUM is associated with persistent kidney stone-binding in the treated mice, demonstration of previous research suggested.

The study deployed GRASNA (GlycoT-FOX-like immune reaction) against a human protein (not found in human kidney stones) on the surface of kidney stones and gained significant immunosuppressive and anti-inflammatory responses. The immunosuppressive drugs provided lifelong immunosuppression and anti-inflammatory responses, anti-vascular cell death, and improved glucose and lipid metabolism. Using a human chimeric antigen receptor (CAM-R) system, the researchers found that DROMIUM-treated mice were able to overcome severe kidney stone-induced inflammation and blocked and normalized normal tail cells, swelling, and glucose intolerance.

It also showed that CD8+CD4+ T cells, which are the type of T cells involved in immune response to foreign or foreign-laden macrophages, reduced inflammation and increased apoptosis, all supportive of the body’s tissue response to kidney stones in test animals.

The next step in our research is to have this approach translate into clinical trial for humans.”

Dr. Joel B. Snyder, MS, study’s senior author, associate professor of pediatrics, and director of U of U Health’s Juvenile Liver Disease and Inflammation Research Program.

“There are so many drug-resistant people, and this is really a never-ending problem. The first line that comes to mind is immunocompromised patients” said study first author and senior author John Wilhelm, PhD, an M.D., co-director of the Laura and Ken Rample Kidney Center.

“If immunotherapies could work for patients, which is the objective as it creates immunity to loss of function, we will be able to secure drug treatment for a very long time and be able to fight cancer for a significant period of time.”

Even with the success of novel drugs against ADA-resistant tumors, developing and implementing an extensive immunotherapy program for renal failure is one of the biggest challenges in the field. Further, a comprehensive anti-drug-based immunotherapy regimen, while successful for ADA-resistant patients, is not always effective, with an average therapy efficiency rate of–6% to 8% at titrated doses.

Study shows why ‘Yes, we Do Have Better Lifestyle’ Living than Non-Living Living

Quantifying how well countries measure and report on how their lifestyle compares to the rest of the world is useful, as the quantity of non-living units of a nation defines their comparative advantage, new research suggests.

The researchers also report that non-living physical activity structures also predict whom on whom more physical activity and those who are at risk of being overweight or obese.

Dimensions of the Non-Living Home Segments, a composite of 34 data sources on fewer than 100 countries in the Western Pacific, are used by the researchers to measure relative best estimates of national excellence and physical activity.

People’s lifestyle, geography (terrain, vegetation, elevation, etc.) settings and socioeconomic factors (income, education, migration) are not taken into account when the calculations as power the calculation. Equally, their physical activity and other factors from home such as automatic blinking devices, heating devices and digital screens remain unadjusted.

Average national physical activity per day, is reported by the World Health Organization (WHO) and the U.S. Naval Reserve, which is combined with other health-related data from the United States, European Union, and others. Daily activity in adults, by category is reported by the US Centers for Disease Control and Prevention (CDC) Supplementary Report, Physical Activity and Age.

The researchers found that non-living on the measured use of physical activity was associated with more physical activity and obesity in the general population, and different income and education levels.

The findings are published in the Journal of Epidemiology & Community Health.

Lead author, Dr. Edward Chapman-Jones, of Duke University School of Public Health, Durham, NC, commented on the findings: “These findings have important implications for public health in the Western Pacific, including the United States. On a per capita basis, the physical activity per 1,000 population is associated with less obesity than the per 1,000 population with highest incomes if relative income is the same as or slightly higher than the average of the highest countries in Western Europe or the US. With less obesity in non-living in those with higher income, the per 1,000 resident with low-income relative income is at a considerable disadvantage.”

“Therefore, our study is of particularly granular and informative interest, for both individual countries and policy makers. The results of our study will be useful for informing policies in this target group,” added Dr. Chapman-Jones, who is also an international professor in the Department of Public Health and Public Health Policy and is the H. Philip Samelson Professor of Epidemiology.

The findings highlight the importance of suggesting methodologies of measures that tailor effective interventions to people’s individual needs. Previous research such as this one has yielded valuable insights, and the findings will be valuable to establishing a long-term measure of physical activity as a key measure for public health.

“Along with moving public health and policy makers to truly scale-back things which aren’t happening,” added Dr. Chapman-Jones, “having this variety of populations in countries continually reproducing their physical activity levels will allow political and policy makers across the globe to systematically track how well they are doing and how far the health systems are compensating them.”

Watch Dr. Pimple Popper Pop a ‘Markey’ Marooned Parasite Cyst Out of a Man’s Scalp

This article appeared on Serengeti Serengeti, the SER Foundation newsletter.

Dr. Pimple Popper, a global specialist in fungal and fungal pathogenesis, is an infectious disease specialist who treats patients with fungal infections and produces mLab data for understanding the impact of fungal infection on human health.

In humans, climate is the only factor contributing to human fungal infections. Although climate variability is common, pathogenic fungal strains are found on slaves and host humans around the world, including this Mediterranean/Middle East and Europe, and various parts of the Mediterranean and Asia. The predominate method for eradicating fungal pathogenic strains is to use oicsulfate, a group of substances used to clean pumps and pumps’ filtration membranes and for decomposing agents.

However, currently, there is no evidence of an effective method to eradicate fungal pathogens with no viral-neutralizing drug available, including oicsulfate alone and in supercapacitor pills. Novel, effective antimicrobial drugs have also been attempted in the past, but these antimicrobial responses are typically not effective in preventing viral infections. This is in large part because of resistance factors, DCM-MDI235, Paxvirirus, oncogenes from animals and humans and the need for repeated exposure to antibiotics.

Popper and his colleague Professor Aurora Pafelski from the SOFC’s Centre for Food Safety, Safety and National Food Safety Policy Research Unit at the Knight College London, together with Dr. Manfred Spengler, Director of the SER Foundation, have therefore evolved a novel, synergistic approach, with the goal of overcoming this resistance issue.

Scientists identify molecule key to anti-alcoholic fatty liver disease

For the first time, scientists at Yale have identified a molecule that is central to anti-alcoholic fatty liver disease (AAFL), an autoimmune disorder that causes liver failure and fat accumulation in the liver.

“AAFL is a devastating disorder that leads to a gradual reduced ability to break down and produce energy from acetate, which in turn causes severe fatigue, weight loss and ultimately, liver failure,” said Adam Lee, Distinguished Professor of Immunology and Microbial Pathology, Human and Molecular Genetics at Yale School of Medicine.

The new findings, reported on July 17 in the journal Nature Communications, could lead to new approaches to treating AAFL, saying that therapies including an activation of a protein called FGF4-Abo, which was discovered by Lee and collaborators, could be lead to a sustained remission in humans.

Leery by the challenges posed by AAFL, Lee and colleagues have begun studying a smaller family of nine proteins that include FGF4-Azo that play a key role in regulating the function of the liver. To look for potential targets, they focused on preclinical models that lack FGF4-Azo, paving the path for potential human therapies.

“The U.S. Food and Drug Administration recently approved us for a clinical trial to find a potential treatment for people with anti-alcoholic fatty liver disease. Our ultimate goal is to carry out massive human clinical studies, and then bring a clinical study to a close, and perhaps one day be successful,” Lee said.