Asthma Medications Can Safeguard Against Life-Threatening Allergic Reactions

Stephanie Eisenbarth and Adam Williams prepare peanuts for allergy research in their lab

Northwestern University

Research indicates that common asthma treatments may offer protection against anaphylaxis, a severe allergic reaction. The drug Zileuton, traditionally used for asthma, is now being considered for individuals facing serious food allergies.

Despite the prevalence of food allergies, it can be challenging to foresee the risk of anaphylaxis for an individual. Scientists are investigating why some individuals with positive food allergen tests do not show symptoms, while others have severe, potentially deadly reactions.

“Our aim is to discover methods to help individuals with symptomatic food allergies manage their reactions to allergens,” states Stephanie Eisenbarth from Northwestern University, Illinois.

Eisenbarth and her research team anticipated that mice exposed to peanuts would experience anaphylaxis. They administered a single oral dose of Zileuton to a group of 5-10 mice sensitized to peanut allergens approximately one hour prior to feeding them peanut extract. The control group did not receive any medication. Observations revealed that almost all Zileuton-treated mice showed no symptoms of anaphylaxis, whereas the control group exhibited clear signs of it.

Most dietary proteins are usually broken down, but some can be actively absorbed through the intestines and enter the bloodstream directly. In individuals with severe allergies, these proteins can trigger immune responses, leading to anaphylaxis.

During allergic reactions, the body releases chemicals known as leukotrienes. The researchers found that leukotrienes play a role in the number of intact proteins that penetrate the intestine. They also identified a gene called DPEP1 that is crucial in regulating leukotriene levels.

One significant action of Zileuton is inhibiting the enzyme five lipoxygenase, essential for leukotriene production. Administering this drug to mice lowered leukotriene levels, while DPEP1 also suppressed remaining leukotrienes, preventing allergen absorption and halting anaphylaxis in susceptible mice. A single dose of Zileuton cut the anaphylaxis rate by 95%.

“We can differentiate between mice that respond to food allergens and those that do not. We are now evaluating whether the same asthma medications can limit allergen absorption in the intestines of people with food allergies.”

Jorge Emiliano Gomez Medellin from the University of Chicago suggests that these straightforward tablets might significantly alleviate the consequences of accidental allergen exposure. He added that while Zileuton could potentially inhibit the absorption of food allergens, it won’t alter an individual’s underlying sensitivity over time.

“Nonetheless, Zileuton could be a valuable tool in combating food allergies,” he concludes.

Source: www.newscientist.com

Life-Threatening Symptoms of Benzodiazepine Withdrawal

Tasha Hedges used Xanax for two decades to manage her anxiety and panic attacks, following her psychiatrist’s recommendations. However, in 2022, her doctor passed away unexpectedly.

Although the general practitioner continued the prescription, he retired shortly thereafter. The next physician moved to Canada, leaving Hedges to eventually find another psychiatrist.

“The first thing he did was yell at me for being on Xanax for too long,” she recounted from W.Va.

Typically, discontinuing the medication requires a gradual reduction of dosage over several months or years, referred to as tapering. However, Hedges stopped abruptly, facing severe withdrawal symptoms such as hot flashes, cold sweats, restlessness, shaking, and teeth grinding.

“It was a nightmare,” she described. Two years after ceasing the medication, she still grapples with repercussions. “My brain wasn’t the same.”

Online support groups and platforms like Benzobuddies indicate that individuals like Hedges are physically dependent on benzodiazepines. Many encounter serious and potentially dangerous withdrawal symptoms when their medication is abruptly ceased or tapered too quickly, leading to extended periods without treatment. Some healthcare providers hesitate to prescribe these medications due to associated risks and stigma.

“They’re often seen as highly addictive,” noted Ronald M. Winchell, a clinical psychiatry professor at Columbia University, who posed several questions to consider: “Would I initiate this treatment? Is it appropriate? Is it safe? Could my patients misuse it? What do my peers think?”

Prescriptions for benzodiazepines such as Xanax, Ativan, and Klonopin have declined since 2016 due to provider concerns. Nonetheless, these medications remain quick and effective solutions, often being among the most prescribed in the country for anxiety and sleep disorders. In 2019, around 92 million benzodiazepine prescriptions were issued in the U.S., according to the Food and Drug Administration.

Current guidelines advise prescribers to use the lowest effective dose for the shortest duration, typically less than four weeks. However, many patients remain on these medications for longer periods. An FDA review in 2018 indicated that approximately half of patients had used the drugs for over two months. Dr. Edward K. Silverman, a professor emeritus of psychiatry at Tufts University School of Medicine, highlighted that some patients stay on these medications without regular consultations.

Patients can develop physical dependence within weeks of stable benzodiazepine use. Stopping the medication, even after a brief period, necessitates a carefully managed process. Unfortunately, many healthcare providers lack adequate training in tapering prescriptions. To clarify the process, an expert from the American Society of Addiction Medicine released new guidelines in March for dosage reduction developed with FDA funding.

“It’s absolutely reckless to force people into rapid tapering,” Dr. Silverman stated.

Jodie Jerlow, 60, began using Klonopin for insomnia 25 years ago while in Dallas. After her psychiatrist retired for health reasons, she found another doctor who recommended two additional benzodiazepines, Xanax and Ativan, while working towards withdrawing from Klonopin.

After about six months on all three medications, Jerlow grew frustrated and decided to take matters into her own hands. She successfully tapered off Klonopin and Xanax.

She is still working to discontinue Ativan with assistance from her general practitioner and a coach at the nonprofit Benzodiazepine Information Coalition.

Initially, Jerlow noted she tapered too quickly, experiencing headaches, nausea, and agoraphobia. However, one of the most distressing withdrawal symptoms was suicidal ideation.

“It felt like background noise. ‘It’s going to be easy,’” she recalled.

These were feelings she had never encountered before reducing her medication.

In 2023, advocates for those harmed by benzodiazepines reported various long-term symptoms that may arise during use, tapering, or discontinuation, including benzodiazepine-induced neurological dysfunction or binding.

While not everyone experiences binding, experts agree that with a well-planned tapering strategy, side effects can be lessened.

Dr. Carl Zalzman, a psychiatry professor at Harvard Medical School and former president of the American Psychiatry Association’s Benzodiazepine Task Force, commented on the issue.

Despite their existence since the 1960s, many healthcare providers are still at a loss regarding how to help patients discontinue these medications effectively. There is no one-size-fits-all tapering strategy. Some patients experience withdrawal symptoms, and others require continued access to medications while tapering slow.

Dr. Silverman recalled a patient who had to meticulously slice pills with a razor blade to gradually decrease dosage and mitigate severe side effects.

The new guidelines from ASAM, which address the limited studies available on effective tapering, mainly rely on clinical experience. They advise clinicians to review the risks and benefits of benzodiazepine prescriptions at least every three months, recommending a dosage reduction of 5-10% every 2-4 weeks. The guidelines stress that long-term users may need to taper for over a year and should be monitored post-discontinuation.

“Most of us were never informed of the potential for dependency and long-term complications,” said De Foster, an advocate for those suffering from benzodiazepine complications, who contributed to the new guidelines. He emphasized, “A slow taper can be challenging, but a sudden withdrawal is perilous.”

ASAM’s guidance came too late for Ratasha Marberry, 49, a New York resident who became physically dependent on Klonopin. In 2022, she entered an addiction detox center, desperate to stop the medication she had been prescribed for insomnia. The facility’s provider took her off the medication in just five days.

She shared that it felt like collapsing as she faced nights filled with turmoil akin to “a lion in the room that you can’t see but are fighting against.” She later visited another facility in Florida where she was prescribed antidepressants. Within weeks, she began to feel a significant improvement.

Now she states, “I’m sleeping like a strange baby.”

She reflects, “Should I have been prescribed this drug for an extended period rather than a benzodiazepine?”

“When I think back to my experiences, I cry,” she confessed. “It wasn’t physical pain, but rather emotional suffering. I’m thankful to be alive.”

If you are in crisis or contemplating suicide, reach out to 988 for the National Suicide Prevention Lifeline; visit Speaking of Suicide for additional resources.

Source: www.nytimes.com

Hurricane Milton Threatens Florida with Life-Threatening Storm Surge

A storm surge is when hurricane force winds push shallow water towards the coast, causing an abnormal rise in water levels during a storm. Factors such as wind, the angle of approach of the storm, ocean floor shape, and storm’s low pressure all play a role in the intensity of the surge.

Storm surge is a deadly threat from hurricanes as it can quickly flood coastal areas and penetrate far inland.

West Florida’s shallow coastline along the Gulf of Mexico is particularly vulnerable to storm surges due to its gentle slopes and the continental shelf being close to the surface, making it easier for water to rise.

Climate change-induced rising sea levels further increase the risk of flooding in the region, and the impending Hurricane Milton has the potential to cause significant damage.

While the exact landing location of Milton is uncertain, small changes in its path can have a significant impact in areas like Tampa Bay. The National Hurricane Center is closely monitoring the storm’s movements and advising residents to be prepared for potential evacuation orders.

Historically, Tampa Bay is at high risk of storm surges due to its underwater topography acting as a funnel for floodwaters. The city’s urban development has also increased the vulnerability of its population and coastal structures to storm-related threats.

As Milton approaches Florida, its size may increase while its winds could weaken, affecting the height of storm surges. Local officials are urging residents to follow evacuation orders to ensure their safety.

Storm surge is a serious concern, particularly with major hurricanes classified as Category 3 or higher. Even lower-ranking storms can produce devastating storm surges, as seen with hurricanes like Katrina and Ike in the past.

Source: www.nbcnews.com

Researchers discover new method for treating life-threatening liver condition

New research reveals the role of omega-3 fatty acids in the fight against non-alcoholic steatohepatitis (NASH)

Using innovative analytical techniques, researchers determined that omega-3 targets betacellulin, a protein that contributes to liver fibrosis. This discovery opens new avenues for NASH drug research and highlights the importance of omega-3s in the diet for liver health.

A recent study conducted by Oregon State University revealed new insights into how certain polyunsaturated fatty acids, particularly omega-3s, fight serious liver conditions. This discovery paves the way for research into new drugs for nonalcoholic steatohepatitis (NASH), for which there is currently no FDA-approved treatment.

Scientists including Natalia Shulzhenko, Andrei Morgan, and Donald Jump at Oregon State University used a technique known as multiomic network analysis to find that omega-3 supplements can be used to treat nonalcoholic steatohepatitis. This mechanism involves betacellulin, a protein growth factor that contributes to liver fibrosis and other serious liver conditions.

The results of this research have recently been published in EMBO molecular medicine. NASH is associated with a disease known as metabolic syndrome, and it is crucial to understand the role of omega-3s in the fight against NASH.

In this study, scientists used both a mouse model and human liver transcriptome data to determine that omega-3 PUFAs reduce, or downregulate, betacellulin in both mice and humans with NASH. This discovery not only significantly advances our understanding of how NASH begins and progresses, but also opens new doors for pharmaceutical research. Researchers say the discovery of betacellulin as a new drug target may help explore precision medicine approaches to NASH treatment and liver cancer prevention by using specific omega-3 PUFAs.

In addition to dietary supplements, omega-3 PUFAs can be found in cold-water fatty fish such as salmon and mackerel, as well as in some nuts, seeds, and vegetable oils. Omega-3 PUFAs are essential fatty acids that are not produced by the body but must be obtained from the diet.

Reference:

Jyothi Padiadpu, Manuel Garcia-Jaramillo, Nolan K Newman, Written by Jacob W Pederson, Richard Rodrigues, Zhipeng Lee, Sekhavir Singh, Philippe Monnier, Giorgio Trinchieri, Kevin Brown, Amiran K. Zutsev, Natalia Shulzhenko, Donald B. Jump, Andrei Morgan, 2023 October 20th, EMBO molecular medicine. DOI: 10.15252/emm.202318367

Jyoti Padyap, a postdoctoral fellow in the OSU College of Pharmacy, is the study’s lead author. Other Oregon State researchers who contributed to the paper were Nolan Newman, Richard Rodriguez, Sehajivir Singh, Manuel Garcia-Jaramillo, Jacob Pederson, Jipeng Li, Philip Monnier, and Kevin Brown.

This research was supported by a grant from the National Institute of Diabetes and Digestive and Kidney Diseases, part of the National Institutes of Health.

Source: scitechdaily.com