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Your body naturally produces opioids without causing addiction or overdose – studying how this process works could help reduce the side effects of opioid drugs

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Your body naturally produces opioids without causing addiction or overdose – studying how this process works could help reduce the side effects of opioid drugs

Opioid neurotransmitters are located in many of the body, the brain, spine and gut.
ALIOUI Mohammed Elamine/iStock via Getty Images Plus

John Michael Streicher, University of Arizona

Opioid such as morphine and fentanyl are like the two- Roman god Janus: The kindly face delivers pain relief to millions of sufferers, while the grim face drives an opioid abuse and overdose crisis that claimed nearly 70,000 lives in the U.S. in 2020 alone.

Scientists like me who study pain and opioids have been seeking a way to separate these two seemingly inseparable faces of opioids. Researchers are trying to design drugs that deliver effective pain relief without the risk of side effects, including addiction and overdose.

One possible path to achieving that goal lies in understanding the molecular pathways opioids use to carry out their effects in your body.

How do opioids work?

The opioid system in your body is a set of neurotransmitters your brain naturally produces that enable communication between neurons and activate protein receptors. These neurotransmitters include small proteinlike molecules like enkephalins and endorphins. These molecules regulate a tremendous number of functions in your body, including pain, pleasure, memory, the movements of your digestive system and more.

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Opioid neurotransmitters activate receptors that are located in a lot of places in your body, including pain centers in your spinal cord and brain, reward and pleasure centers in your brain, and throughout the neurons in your gut. Normally, opioid neurotransmitters are released in only small quantities in these exact locations, so your body can use this system in a balanced way to regulate itself.

The opioids your body produces and opioid drugs bind to the same receptors.

The problem comes when you take an opioid drug like morphine or fentanyl, especially at high doses for a long time. These drugs travel through the bloodstream and can activate every opioid receptor in your body. You'll get pain relief through the pain centers in your spinal cord and brain. But you'll also get a euphoric high when those drugs hit your brain's reward and pleasure centers, and that could lead to addiction with repeated use. When the drug hits your gut, you may develop constipation, along with other common opioid side effects.

Targeting opioid signal transduction

How can scientists design opioid drugs that won't cause side effects?

One approach my research team and I take is to understand how cells respond when they the message from an opioid neurotransmitter. Neuroscientists call this opioid receptor signal transduction. Just as neurotransmitters are a communication network within your brain, each neuron also has a communication network that connects receptors to proteins within the neuron. When these connections are made, they trigger specific effects like pain relief. So, after a natural opioid neurotransmitter or a synthetic opioid drug activates an opioid receptor, it activates proteins within the cell that carry out the effects of the neurotransmitter or the drug.

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Cells communicate with one another in multiple ways.

Opioid signal transduction is complex, and scientists are just starting to figure out how it works. However, one thing is clear: Not every protein involved in this process does the same thing. Some are more important for pain relief, while some are more important for side effects like respiratory depression, or the decrease in breathing rate that makes overdoses fatal.

So what if we target the “good” signals like pain relief, and avoid the “bad” signals that to addiction and ? Researchers are tackling this idea in different ways. In fact, in 2020 the U.S. Food and Drug Administration approved the first opioid drug based on this idea, oliceridine, as a painkiller with fewer respiratory side effects.

However, relying on just one drug has downsides. That drug might not work well for all people or for all types of pain. It could also have other side effects that show up only later on. Plenty of options are needed to treat all in need.

drawing depicting a tangle of red, blue and yellow curly and straight lines
This figure shows the structure of Hsp90.
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My research team is targeting a protein called Heat shock protein 90, or Hsp90, which has many functions inside each cell. Hsp90 has been a hot target in the cancer field for years, with researchers developing Hsp90 inhibitors as a treatment for many cancer types.

We've found that Hsp90 is also really important in regulating opioid signal transduction. Blocking Hsp90 in the brain blocked opioid pain relief. However, blocking Hsp90 in the spinal cord increased opioid pain relief. Our recently published work uncovered more details on exactly how inhibiting Hsp90 leads to increased pain relief in the spinal cord.

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Our work shows that manipulating opioid signaling through Hsp90 offers a path forward to improve opioid drugs. Taking an Hsp90 inhibitor that targets the spinal cord along with an opioid drug could improve the pain relief the opioid provides while decreasing its side effects. With improved pain relief, you can take less opioid and reduce your risk of addiction. We are currently developing a new generation of Hsp90 inhibitors that could realize this goal.

There may be many paths to developing an improved opioid drug without the burdensome side effects of current drugs like morphine and fentanyl. Separating the kindly and grim faces of the opioid Janus could help provide pain relief we need without addiction and overdose.The Conversation

John Michael Streicher, Associate Professor of Pharmacology, University of Arizona

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Did you miss our previous article…
https://www.biloxinewsevents.com/?p=245667

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Transporting hazardous materials across the country isn’t easy − that’s why there’s a host of regulations in place

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theconversation.com – Michael F. Gorman, Professor of Business Analytics and Operations Management, of Dayton – 2024-04-22 07:39:34
Hazardous materials regulations make sure that the vehicles carrying them have the right labels.
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Michael F. Gorman, University of Dayton

Ever wonder what those colorful signs with symbols and numbers on the backs of trucks mean? They're just one visible part of a web of regulations that aim to keep workers and the safe while shipping hazardous waste.

Transporting hazardous materials such as dangerous gases, poisons, harmful chemicals, corrosives and radioactive material across the country is risky. But because approximately 3 billion pounds of hazardous material needs to go from place to place in the U.S. each year, it's unavoidable.

With all the material that needs to cross the country, hazardous material spills from both truck and rail transportation are relatively unavoidable. But good regulations can keep these incidents to a minimum.

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As an operations and logistics expert, I've studied hazardous materials transportation for years. agencies from the municipal to federal levels have rules governing the handling and transportation of these materials, though they can be a little complicated.

A hazardous material is anything that can cause a health or safety risk to people or the environment. Regulators put hazardous materials into nine categories and rate them based on the level of danger they pose during transport and handling.

These ratings anyone associated with the shipment take precautions and figure out the right packaging and transportation methods for each type of hazardous material.

Who regulates hazardous material?

A number of agencies across the country closely scrutinize the entire hazardous materials supply chain from start to finish. The Occupational Safety and Health Administration regulates the proper handling of hazardous materials where they're either manufactured or used. OSHA puts limits on how much hazardous material one person can be exposed to and for how long.

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If the material spills, or if there's any left over when they're done being used, the U.S. Environmental Protection Agency, handles its disposal. Both EPA and OSHA regulations into play during spills.

In between, the U.S. Department of Transportation regulates all of the movement of hazardous materials through four of its administrations.

The Pipeline and Hazardous Materials Safety Administration regulates the transportation of hazardous materials by truck, rail, pipeline and ship. The Federal Railroad Administration plays a role in regulating rail shipments, just as the Federal Highway Administration oversees movement over the road. In the , the Federal Aviation Administration regulates hazardous materials.

Key regulations

Two essential regulations govern the handling and transportation of hazardous materials. In 1975, the EPA published the Hazardous Material Transportation Act, which protects people and property from hazardous material transportation risks.

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This act gave the secretary of transportation more regulatory and enforcement authority than before. It gave the secretary power to designate materials as hazardous, add packaging requirements and come up with operating rules.

The Pipeline and Hazardous Materials Safety Administration oversees hazardous materials regulations that apply to everything from packaging and labeling to loading and unloading procedures. They also include requirements for workers who have to handle hazardous materials and plans to make sure these materials stay secure.

Along with the Federal Highway Administration, the Pipeline and Hazardous Materials Safety Administration and the Federal Motor Carrier Safety Administration regulate hazardous material movement by road.

A white label reading
Hazardous material regulations require proper labeling of trucks carrying materials.
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Trucking companies transporting hazardous materials need to use specific vehicles and qualified drivers to comply with Federal Motor Carrier Safety Administration regulations. Drivers transporting hazardous materials must have specialized training and a hazardous materials endorsement on their commercial driver's license.

The Pipeline and Hazardous Materials Safety Administration's and the Federal Railroad Administration's regulations for rail shipments require that rail cars fit physical and structural specifications. These specifications include thick tanks and pressure release devices. Rail cars also have to undergo inspections and maintenance, per these rules.

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The crew in charge of a hazardous materials train needs specialized training. And rail carriers need to have emergency response plans in case of a hazardous material spill.

Both truck and rail companies must follow regulations that require the proper classification, packaging and labeling of hazardous materials. The symbols on these labels let handlers and emergency responders know the potential risks the materials pose.

The Pipeline and Hazardous Materials Safety Administration's security regulations prevent or sabotage of hazardous materials. They make sure that only authorized people can access the shipments. These regulations may require background checks for workers, secure storage facilities, and that track and monitor hazardous material.

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Hazardous material shipments and incidents both have increased in the past 10 years. Anyone involved in the supply chain needs to understand hazardous material regulations.

Sticking to these rules helps get these materials from place to place safely. It also keeps safe those who handle them and minimizes the risk of accidents, injuries and environmental harm.The Conversation

Michael F. Gorman, Professor of Business Analytics and Operations Management, University of Dayton

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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Chemical pollutants can change your skin bacteria and increase your eczema risk − new research explores how

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theconversation.com – Ian Myles, Chief, Epithelial Unit, National Institute of Allergy and Infectious Diseases – 2024-04-22 07:39:19
Certain chemicals in synthetic fabrics such as spandex, nylon and polyester can alter the skin microbiome.
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Ian Myles, National Institute of Allergy and Infectious Diseases

“We haven't had a full night's sleep since our son was born eight years ago,” said Mrs. B, pointing to her son's dry, red and itchy skin.

Her son has had eczema his entire . Also known as atopic dermatitis, this chronic skin disease affects about 1 in 5 children in the industrialized world. Some studies have found rates of eczema in developing nations to be over thirtyfold lower with industrialized nations.

However, rates of eczema didn't spike with the Industrial Revolution, which began around 1760. Instead, eczema in countries such as the U.S., Finland and other countries started rapidly rising around 1970.

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What caused eczema rates to spike?

I am an allergist and immunologist working with a team of researchers to study trends in U.S. eczema rates. Scientists know that factors such as diets rich in processed foods as well as exposure to specific detergents and chemicals increase the risk of developing eczema. Living near factories, major roadways or wildfires increase the risk of developing eczema. Environmental exposures may also from inside the house through paint, plastics, cigarette smoke or synthetic fabrics such as spandex, nylon and polyester.

While researchers have paid a lot of attention to genetics, the best predictor of whether a child will develop eczema isn't in their genes but the environment they lived in for their first few years of life.

There's something in the air

To figure out what environmental changes may have caused a spike in eczema in the U.S., we began by looking for potential eczema hot spots – places with eczema rates that were much higher than the national average. Then we looked at databases from the U.S. Environmental Protection Agency to see which chemicals were most common in those areas.

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For eczema, along with the allergic diseases that routinely develop with it – peanut allergy and asthma – two chemical classes leaped off the page: diisocyanates and xylene.

Diisocyanates were first manufactured in the U.S. around 1970 for the production of spandex, nonlatex foam, paint and polyurethane. The manufacture of xylene also increased around that time, alongside an increase in the production of polyester and other materials.

Row of people wearing masks sewing clothes in a textile factory
Chemicals involved in clothing production can be hazardous to health.
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The chemically active portion of the diisocyanates and xylene molecules are also found in cigarette smoke and wildfires. After 1975, when all new cars became outfitted with a new technology that converted exhaust gas to less toxic chemicals, isocyanate and xylene both became components of automobile exhaust.

Research has found that exposing mice to isocyanates and xylene can directly cause eczema, itch and inflammation by increasing the activity of receptors involved in itch, pain and temperature sensation. These receptors are also more active in mice placed on unhealthy diets. How directly exposing mice to these toxins compares to the typical levels of exposure in people is still unclear.

How and why might these chemicals be linked to rising rates of eczema?

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Skin microbiome and pollution

Every person is coated with millions of microorganisms that on the skin, collectively referred to as the skin microbiome. While researchers don't know everything about how friendly bacteria the skin, we do know that people need these organisms to produce certain types of lipids, or oils, that keep the skin sealed from the and stave off infection.

You've probably seen moisturizers and other skin products containing ceramides, a group of lipids that play an important role in protecting the skin. The amount of ceramides and related compounds on a child's skin during their first few weeks of life is a consistent and significant predictor of whether they will go on to develop eczema. The less ceramides they have on their skin, the more likely they'll develop eczema.

Person applying ointment to baby's face
The skin microbiome produces lipids commonly found in moisturizers.
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To see which toxins could prevent production of the beneficial lipids that prevent eczema, my team and I used skin bacteria as canaries in the coal mine. In the lab, we exposed bacteria that directly make ceramides (such as Roseomonas mucosa), bacteria that help the body make its own ceramides (such as Staphylococcus epidermidis) and bacteria that make other beneficial lipids (such as Staphylococcus cohnii) to isocyanates and xylene. We made sure to expose the bacteria to levels of these chemicals that are similar to what people might be exposed to in the real world, such as the standard levels released from a factory or the fumes of polyurethane glue from a hardware store.

We found that exposing these bacteria to isocyanates or xylene led them to stop making ceramides and instead make amino acids such as lysine. Lysine helps protect the bacteria from the harms of the toxins but doesn't provide the health benefits of ceramides.

We then evaluated how bed sheets manufactured using isocyanates or xylene affect the skin's bacteria. We found that harmful bacteria such as Staphylococcus aureus proliferated on nylon, spandex and polyester but could not survive on cotton or bamboo. Bacteria that help keep skin healthy could live on any fabric, but, just as with air pollution, the amount of beneficial lipids they made dropped to less than half the levels made when grown on fabrics like cotton.

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Addressing pollution's effects on skin

What can be done about the connection between pollution and eczema?

Detectors capable of sensing low levels of isocyanate or xylene could help track pollutants and predict eczema flare-ups across a community. Better detectors can also help researchers identify air filtration that can scrub these chemicals from the environment. Within the U.S., people can use the EPA Toxics Tracker to look up which pollutants are most common near their home.

In the meantime, improving your microbial balance may require avoiding products that limit the growth of healthy skin bacteria. This may include certain skin care products, detergents and cleansers. Particularly for kids under 4, avoiding cigarette smoke, synthetic fabrics, nonlatex foams, polyurethanes and some paints may be advised.

Replacing bacteria that has been overly exposed to these chemicals may also help. For example, my research has shown that applying Roseomonas mucosa, a ceramide-producing bacterium that lives on healthy skin, can to a monthslong reduction in typical eczema symptoms compared with placebo. Researchers are also studying other potential probiotic treatments for eczema.

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Evaluating the environmental causes of diseases that have become increasingly common in an increasingly industrialized world can help protect from chemical triggers of conditions such as eczema. I believe that it may one day allow us to get back to a time when these diseases were uncommon.The Conversation

Ian Myles, Chief, Epithelial Therapeutics Unit, National Institute of Allergy and Infectious Diseases

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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Poor media literacy in the social media age

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theconversation.com – Nir Eisikovits, Professor of Philosophy and Director, Applied Ethics Center, UMass Boston – 2024-04-19 10:01:58

Tiktok is not the only social app to pose the threats it's been accused of.

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Nir Eisikovits, UMass Boston

The U.S. moved closer to banning the social media app TikTok after the House of Representatives attached the measure to an emergency spending bill on Apr. 17, 2024. The move could improve the bill's chances in the Senate, and has indicated that he will sign the bill if it reaches his desk.

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The bill would force ByteDance, the Chinese company that owns TikTok, to either sell its American holdings to a U.S. company or face a ban in the country. The company has said it will fight any effort to force a sale.

The proposed legislation was motivated by a set of national security concerns. For one, ByteDance can be required to assist the Chinese Communist Party in gathering intelligence, according to the Chinese National Intelligence Law. In other words, the data TikTok collects can, in theory, be used by the Chinese government.

Furthermore, TikTok's popularity in the United States, and the fact that many young people get their from the platform – one-third of Americans under the age of 30 – turns it into a potent instrument for Chinese political influence.

Indeed, the U.S. Office of the Director of National Intelligence recently claimed that TikTok accounts run by a Chinese propaganda arm of the government targeted candidates from both political parties during the U.S. midterm election cycle in 2022, and the Chinese Communist Party might attempt to influence the U.S. elections in 2024 in order to sideline critics of China and magnify U.S. social divisions.

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To these worries, proponents of the legislation have appended two more arguments: It's only right to curtail TikTok because China bans most U.S.-based social media networks from operating there, and there would be nothing new in such a ban, since the U.S. already restricts the foreign ownership of important media networks.

Some of these arguments are stronger than others.

China doesn't need TikTok to collect data about Americans. The Chinese government can buy all the data it wants from data brokers because the U.S. has no federal data privacy laws to speak of. The fact that China, a country that Americans criticize for its authoritarian practices, bans social media platforms is hardly a reason for the U.S. to do the same.

The debate about banning TikTok tends to miss the larger picture of social media literacy.

I believe the cumulative force of these claims is substantial and the legislation, on balance, is plausible. But banning the app is also a red herring.

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In the past few years, my colleagues and I at UMass Boston's Applied Ethics Center have been studying the impact of AI systems on how people understand themselves. Here's why I think the recent move against TikTok misses the larger point: Americans' sources of information have declined in quality and the problem goes beyond any one social media platform.

The deeper problem

Perhaps the most compelling argument for banning TikTok is that the app's ubiquity and the fact that so many young Americans get their news from it turns it into an effective tool for political influence. But the proposed solution of switching to American ownership of the app ignores an even more fundamental threat.

The deeper problem is not that the Chinese government can easily manipulate content on the app. It is, rather, that people think it is OK to get their news from social media in the first place. In other words, the real national security vulnerability is that people have acquiesced to informing themselves through social media.

Social media is not made to inform people. It is designed to capture consumer attention for the sake of advertisers. With slight variations, that's the business model of all platforms. That's why a lot of the content people encounter on social media is violent, divisive and disturbing. Controversial posts that generate strong feelings literally capture users' notice, hold their gaze for longer, and advertisers with improved opportunities to monetize engagement.

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There's an important difference between actively consuming serious, well-vetted information and being manipulated to spend as much time as possible on a platform. The former is the lifeblood of democratic citizenship because being a citizen who participates in political -making requires having reliable information on the issues of the day. The latter amounts to letting your attention get hijacked for someone else's financial gain.

If TikTok is banned, many of its users are likely to migrate to Instagram and YouTube. This would benefit Meta and Google, their parent companies, but it wouldn't benefit national security. People would still be exposed to as much junk news as before, and experience shows that these social media platforms could be vulnerable to manipulation as well. After all, the Russians primarily used Facebook and Twitter to meddle in the 2016 election.

Media literacy is especially critical in the age of social media.

Media and technology literacy

That Americans have settled on getting their information from outlets that are uninterested in informing them undermines the very requirement of serious political participation, namely educated decision-making. This problem is not going to be solved by restricting access to foreign apps.

Research suggests that it will only be alleviated by inculcating media and technology literacy habits from an early age. This involves teaching young people how social media companies make money, how algorithms shape what they see on their phones, and how different types of content affect them psychologically.

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My colleagues and I have just launched a pilot program to boost digital media literacy with the Boston Mayor's Youth Council. We are talking to Boston's youth leaders about how the technologies they use everyday undermine their privacy, about the role of algorithms in shaping everything from their in music to their political sympathies, and about how generative AI is going to influence their ability to think and write clearly and even who they count as friends.

We are planning to present them with evidence about the adverse effects of excessive social media use on their mental . We are going to talk to them about taking time away from their phones and developing a healthy skepticism towards what they see on social media.

Protecting people's capacity for critical thinking is a that calls for bipartisan attention. Some of these measures to boost media and technology literacy might not be popular among tech users and tech companies. But I believe they are necessary for raising thoughtful citizens rather than passive social media consumers who have surrendered their attention to commercial and political actors who do not have their interests at heart.The Conversation

Nir Eisikovits, Professor of Philosophy and Director, Applied Ethics Center, UMass Boston

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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