Breaking News
April 20, 2019 - Texas A&M AgriLife becomes the newest member of NutriRECS international consortium
April 20, 2019 - In most states, insurance won’t cover addiction treatments
April 20, 2019 - Computer-based memory games may be beneficial for individuals with fragile X syndrome
April 20, 2019 - Timing of food intake influences molecular clock in the liver of mice
April 20, 2019 - Precise decoding of breast cancer cells paves way for new treatment option
April 20, 2019 - Scientists use 3D imaging to help model complex processes performed by placenta
April 20, 2019 - MediciNova Announces Plans to Move Forward with a Phase 3 Trial of MN-166 (ibudilast) in ALS
April 20, 2019 - Genetic variants that protect against obesity could aid new weight loss medicines
April 20, 2019 - New technology developed for microscopic imaging in living organisms
April 20, 2019 - when quitting cigarettes, consider using more nicotine, not less
April 20, 2019 - Key proteins can block Listeria without triggering the death of host cells
April 20, 2019 - Researchers create a working model of cerebral tract to study brain function
April 20, 2019 - New study shows that microbes can help break toxic chemical in dust
April 20, 2019 - Scientists use NIR light and injected DNA nanodevice to guide stem cells to injury
April 20, 2019 - Microbial Features ID’d for Pediatric Irritable Bowel Syndrome
April 20, 2019 - Study reveals patterns of drug intoxication deaths, organ donors across the US
April 20, 2019 - Scientists deploy CRISPR gene-editing tool to engineer multiple edits
April 20, 2019 - AHA News: Here’s How Middle-Aged People — Especially Women — Can Avoid a Heart Attack
April 20, 2019 - Charcot foot: MedlinePlus Medical Encyclopedia
April 20, 2019 - France to ban popular breast implants over cancer risk: media
April 20, 2019 - Researchers explore whether time of day can affect the body’s response to physical exertion
April 20, 2019 - CPAP brings longer life for obese people with sleep apnea: Study
April 20, 2019 - New discovery transforms conventional microfluidics into open-space microfluidics
April 20, 2019 - An accurate estimation of the overall cost of bacterial resistance in French hospitals during 2015 and 2016
April 20, 2019 - ‘PRO-cision Medicine’ approach helps personalize care for patients with cancer
April 19, 2019 - TG Therapeutics Receives Orphan Drug Designation for Umbralisib from the U.S. Food and Drug Administration for the Treatment of Marginal Zone Lymphoma
April 19, 2019 - Screen time—even before bed—has little impact on teen well-being: study
April 19, 2019 - Cytosurge’s first FluidFM User Conference
April 19, 2019 - New study finds that previously described differences among endoscopists are not true
April 19, 2019 - Study compares effectiveness and cost of gene therapy and HSCT in major beta-thalassemia
April 19, 2019 - Scientific breakthrough provides new hope for people living with multiple sclerosis
April 19, 2019 - New Virtual Reality Therapy game could offer relief for patients with chronic pain, mobility issues
April 19, 2019 - Emergency medicine doctors find better way to treat severe epileptic seizures in children
April 19, 2019 - MedlinePlus: Cholesterol Good and Bad
April 19, 2019 - For busy medical students, two-hour meditation study may be as beneficial as longer course
April 19, 2019 - Music therapy helps young patients feel better
April 19, 2019 - Molecular target UNC45A is essential for cancer cell proliferation and tumor growth
April 19, 2019 - Crackling and wheezing could be the sounds of a progressing lung disease
April 19, 2019 - Key research takeaways from ECCMID 2019
April 19, 2019 - AI Can Identify Model of Cardiac Rhythm Device From Chest X-Ray
April 19, 2019 - New way to combat childhood anxiety: treat the parents
April 19, 2019 - Women getting C-sections best judge of own pain medication needs | News Center
April 19, 2019 - Light-intensity physical activity associated with healthy brain aging
April 19, 2019 - Immune responses that prevent fungal infections may eliminate Trichinella spiralis
April 19, 2019 - Exercising in the morning, rather than at night, may yield better results, shows study
April 19, 2019 - Why eating ‘right’ could cause you to stray from your diet
April 19, 2019 - Health Tip: Antidepressant Precautions – Drugs.com MedNews
April 19, 2019 - Bigger portions lead to preschoolers eating more over time
April 19, 2019 - Specific strains of Staphylococcus aureus linked to wounds that do not heal
April 19, 2019 - Morning exercise may burn more calories
April 19, 2019 - Revolutionary discovery paves new way for treatment of necrotizing enterocolitis
April 19, 2019 - Drug that treats high blood pressure shows promise against neurodegenerative diseases
April 19, 2019 - More care is needed for patients after kidney transplantations, reports research
April 19, 2019 - Virtual reality offers benefits for Parkinson’s disease patients
April 19, 2019 - Liver Illness Strikes Latino Children Like A ‘Silent Tsunami’
April 19, 2019 - Disruptive behaviors in autistic children linked to reduced brain connectivity
April 19, 2019 - New insights into how vitamin D affects immune system
April 19, 2019 - Research sheds light on how hepatitis B virus establishes chronic infection
April 19, 2019 - New scoring system based on genetic markers predicts obesity risk at birth
April 19, 2019 - Pfizer Announces Presentation of Data from a Phase 2 Study of its 20-Valent Pneumococcal Conjugate Vaccine Candidate Being Investigated for the Prevention of Invasive Disease and Pneumonia in Adults Aged 18 Years and Older
April 19, 2019 - Exercise can improve non-motor symptoms of Parkinson’s disease
April 19, 2019 - Phasefocus to launch new cell imaging system
April 19, 2019 - KZFPs play a key role in the regulation of human genome
April 19, 2019 - DWK Life Sciences offers Workflow Solutions to improve productivity
April 19, 2019 - Bedfont wins 2nd accolade at the South East FSB Awards 2019
April 19, 2019 - Extracts of ginkgo seeds show antibacterial activity on pathogens that cause skin infections
April 19, 2019 - Groundbreaking experiment in pigs challenges the notion about brain damage
April 19, 2019 - Improving the quality of digital pathology imaging
April 19, 2019 - Scientists get closer to injecting artificial lymph nodes into people to fight disease
April 19, 2019 - Exercises and swimming goggles may reduce adverse effects on eye during long spaceflights
April 19, 2019 - Review suggests a reciprocal relationship between obesity and self-control
April 19, 2019 - Synthetic biologists add analog-to-digital signal processing to genetic circuitry of living cells
April 19, 2019 - Study identifies how enterococci bacteria cause antibiotic-resistant bloodstream infections
April 19, 2019 - Triple negative breast cancer develop resistance to chemotherapy by turning on molecular pathway
April 19, 2019 - Researchers identify key clues to brain and pancreas development
April 19, 2019 - Metformin May Cut Risk for Prematurity, Miscarriage in PCOS
April 19, 2019 - Obese mouse mothers trigger heart problems in offspring
April 19, 2019 - Research sheds light on how leukemia cells become resistant to drugs
April 19, 2019 - Health Tip: Stopping Nosebleeds – Drugs.com MedNews
April 19, 2019 - Pediatric endocrinologist gives iconic ‘Mona Lisa’ a second medical opinion
Synthetic peptide appears to disrupt inflammation and protect kidneys from nephritis

Synthetic peptide appears to disrupt inflammation and protect kidneys from nephritis

image_pdfDownload PDFimage_print

A synthetic peptide appears to directly disrupt the destructive inflammation that occurs in nephritis, enabling the kidneys to better recover and maintain their important functions, investigators report.

Whether they gave the peptide body-wide or delivered it directly to the kidneys, it reduced the movement of immune cells into the kidneys, resolved inflammation and damage and improved kidney function, without increasing blood pressure, they report in the journal Kidney International.

Things like a serious infection or injury, and diseases like uncontrolled hypertension and diabetes, can cause acute or chronic nephritis, which affects both kidneys and the million filtering units in each. Particularly when it’s chronic, patients often wind up in kidney failure and on dialysis, which has basic scientists and physicians alike looking for better interventions.

So the investigators gave the peptide the same way it might one day be given to patients, within a few days of signs of kidney inflammation. They found it enabled an animal model of moderate nephritis to avoid hallmark problems like excessive inflammation and protein in the urine, a sign of kidney dysfunction, says Dr. Rudolf Lucas, vascular biologist in the Vascular Biology Center at the Medical College of Georgia at Augusta University.

Levels of urea in the blood, a waste product from the body’s use of protein that should be eliminated by the kidneys, also dropped as did weight gain, largely from retaining urine, which also can occur with kidney disease.

In a model mimicking severe nephritis, which is essentially 100 percent lethal to the kidneys in humans and deadly to the mouse model, with treatment there was instead an 80 percent survival of the mice. “I think that is pretty promising,” says Lucas, the study’s corresponding author.

At later stages of the disease, low doses of the peptide also reduced the level of T cells, drivers of the immune response and inflammation, moving into the area. In fact, levels were essentially normal.

“The peptide appears to actually improve the general condition of the kidney over time,” Lucas says. In fact, he now wants to study whether the peptide can aid recovery from chronic kidney disease, which many patients experience if their kidneys are not completely destroyed by nephritis.

They say the peptide, which has already been tested in Europe in patients with acute lung injury, like pneumonia or trauma, and is being pursued in lung transplant patients as well, holds promise for a targeted therapy for acute nephritis.

“We showed that it reversed inflammation in the kidney during the course of nephritis,” says Dr. Michael Madaio, nephrologist, chair emeritus of the MCG Department of Medicine and the study’s co-corresponding author. “We showed that it was effective and that it was a local effect within the kidney itself.”

Current therapies, like corticoid steroids, generally suppress the immune response, leaving patients at risk for infection and even cancer.

“We’ve been looking for a great way to treat this,” says Madaio, whose lab developed the antibody that delivered the peptide right to the kidneys. “In theory, this could take the place of the anti-inflammatory effect of steroids,” says Madaio. “That would be great.”

The TIP peptide Lucas developed is a synthetic version of the tip of tumor necrosis factor, or TNF, which, as its name implies, is known to target cancer. But TNF is also a primary instigator of destructive inflammation in nephritis.

In a mouse model of nephritis, they watched immune cells arrive in response to an attack on the kidney – in this case a toxin – which in turn generated a lot of TNF. TNF then activated two main inflammation-promoting pathways in the endothelial cells that line the million kidney filtering units, called glomeruli, in each kidney as well as the podocytes, cells that wrap around the tiny capillaries of the filtering units. The most important of the inflammation-promoting pathways activated by TNF in this case are p38 MAP kinase along with NF-kB.

To worsen the scenario, TNF also decreased production of things like nitric oxide, a powerful blood vessel dilator that could help the kidneys recover, as well as prostaglandin E2, which can suppress the immune response and inflammation.

“This is how high levels of TNF are bad for us, and the consequence of this is now you get an increased protein in your urine and you will get increased renal inflammation and that is not what you want,” Lucas says.

They would find the TIP peptide directly counteracts those negative changes.

“If we give the TIP peptide, we restore basal levels,” Lucas says of prostaglandin E2, which in turn, induces nitric oxide. “So we restore two factors which are known to be protective in nephrotoxic nephritis,” he says.

While the more obvious route would be directly suppressing TNF, that might not be a good idea because of its important roles in fighting infections and other invaders, which is already a concern for current treatments, they say.

“We think a better approach might be factors that interfere with the deleterious TNF signaling, which induces the profound inflammation in the kidneys, without interfering with TNF’s defense role against bacteria,” Lucas says.

He’d found in the lungs, the peptide directly activates ENaC-alpha, a subunit of natural body channels which mediate sodium uptake and play a role in fluid movement, Lucas explains, noting fluid’s natural propensity to follow sodium, or salt.

While the peptide’s activation of ENC-alpha in the lungs is a good thing in pneumonia where fluid literally interferes with breathing, the investigators were concerned that activating ENaC-alpha in the kidneys might disturb normal sodium retention, which is important to the kidney’s role in blood pressure regulation.

They found instead that the TIP peptide delivered directly to the kidneys not only reduced inflammation but actually decreased blood pressure, even in the face of a high-salt diet, and without interfering with the infection-fighting role of TNF.

Inflammation of the kidneys filtering units, called glomerulonephritis, is responsible for about 10-20 percent of the extensive kidney damage patients experience, although the affected pathway is common to many forms of progressive kidney damage.

“Your kidneys simply don’t function quite as well as any more,” Lucas says. “Your glomerular filtration goes down the drain, your body weight increases because you retain more urine. TNF is a crucial mediator of this pathology.”

TNF and another pro-inflammatory substance called interleukin 1, produce products like reactive oxygen species that damage both the filters and the elastic cells that wrap around their exterior.

Lucas recently received a $2.5 million grant from the National Institutes of Health to further pursue evidence that activating ENaC-alpha with his peptide can help eliminate deadly fluid buildup in the lungs that can occur in pneumonia. “This is a very different approach from the work in the lungs,” Lucas says of the new work in the kidneys.

“In the kidneys, the peptide directly interferes with a major cause of the problem which is p38,” Lucas says, noting that p38 is known to play an important role in cells that line blood vessels and the heart, and like those lining the glomeruli.

Madaio was corresponding author of a study this summer also in Kidney International that showed that using the same antibody, this time to deliver the anti-inflammatory protein kinase C-alpha inhibitor directly to the kidney, enabled the organ’s recovery in a similar model of nephritis. They also found that the kidney cell powerhouses, called mitochondria, are particularly impacted by acute and chronic inflammation and that the protein they delivered restored mitochondrial function.

There are about a million filtering units, called nephrons, in each kidney that remove waste, acid and excess fluid from the blood, which get excreted into the urine. Nephrons also put good stuff, like nutrients, back into the bloodstream. The glomerulus, a cluster of blood vessels inside the nephrons, function as the actual filter.

Source:

http://www.augusta.edu/mcg/

Tagged with:

About author

Related Articles