Tag: Medicines

Three Brothers Are Making Research a Family Affair

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From left to right: Caleb, Paul, and Adam Worsley sitting on stools in a chemistry lab.
Caleb, Paul, and Adam Worsley. Credit: Pittsburg State University.

“You’re doing something really important with people who are important to you,” Paul Worsley remarks when asked about having his younger brothers Caleb and Adam as lab mates. The trio are undergraduate students working in the lab of Santimukul Santra, Ph.D., at Pittsburg State University in Pittsburg, Kansas.

Paul seated at his chemistry fume hood. Credit: Pittsburg State University.

All three brothers are part of the Kansas IDeA Networks of Biomedical Research Excellence (K-INBRE). Paul is currently a junior majoring in biology and history. He plans to go to medical school when he graduates, but his time in the lab has given him a love for research—and has even led him to toy with the idea of going to graduate school instead. His twin brothers Caleb and Adam are only freshmen, but they both think they want to pursue scientific research when they graduate.

When Paul was a sophomore, he applied for a K-INBRE research spot in Dr. Santra’s lab and was immediately accepted. He quickly realized that organic chemistry in the lab was much different—and more exciting—than anything he’d seen in the classroom. “I like organic synthesis because it really tests your knowledge,” he says. “Answering exam questions is way different than actually doing it in a lab.” Despite the challenges that came with research, Paul was clearly doing great work because one day Dr. Santra joked, “Hey, you got any brothers?” Paul responded, “Actually, yes.”

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In Other Words: Some Antagonists Are Heroes

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Many of us learned in English class that an antagonist is a person or thing that a hero fights. But in biomedical science, an antagonist is a molecule that binds to a cellular receptor to prevent a response, such as a muscle contraction or hormone release. Antagonists can be important medical treatments, like the antagonist naloxone—also known as Narcan —that can reverse an opioid overdose.

Below the title “Antagonist: In Other Words,” two images are separated by a jagged line. On the left is a dark figure with a hat, and on the right is an antagonist bound to a ribbon model depiction of a receptor. Under the images, text reads: “Did you know? In biomedical science, an antagonist is a molecule that binds to a cellular receptor to prevent a response, such as a muscle contraction or hormone release.” 
Credit: NIGMS; Yekaterina Kadyshevskaya, The Scripps Research Institute.
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Discovering Better Ways to Build Medicinal Molecules

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Dr. Baran standing in front of a chemistry fume hood with molecular structures drawn on it.
Dr. Phil Baran. Credit: Scripps Research.

“I love the mystery of chemistry. It explores the great unknown of the universe,” says Phil Baran, Ph.D., a professor of chemistry at Scripps Research, La Jolla, California. His passion for the subject catalyzed a successful career in organic synthesis—building molecules that are the foundation of living things and can be developed as medicines.

Setting His Sights on Science

School didn’t interest Dr. Baran until he found chemistry in 10th grade. “From there, the mission was clear: do whatever was required to do chemistry for the rest of my life,” he says. At the time, that meant achieving certain grades, so he focused on improving his academic performance. He also took courses at a community college and graduated with his high school diploma and associate degree simultaneously.

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COVID-19 Vaccine and Therapeutic Trials ACTIV-ate in West Virginia

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Hands in medical gloves drawing liquid from a vial into a syringe with a model of SARS-CoV-2 in the background. ACTIV clinical trials will evaluate the safety and efficacy of COVID-19 treatments and vaccines. Credit: iStock.

Since the virus that causes COVID-19, known as SARS-CoV-2, was first reported in late 2019, scientists have launched hundreds of studies on strategies for diagnosis, prevention, and treatment. To prioritize the most promising vaccine and therapeutics candidates, streamline clinical trials, and coordinate regulatory processes, the National Institutes of Health (NIH) and the Foundation for the NIH have established the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) partnership. ACTIV brings together eight government entities, 20 biopharmaceutical companies, and four nonprofit organizations.

The public-private partnership provides infrastructure, subject matter expertise, and funding to efficiently bring the most promising therapeutics and vaccines into clinical trials. Five ACTIV therapeutic trials are underway. NIGMS-supported Institutional Development Award Program Infrastructure for Clinical and Translational Research (IDeA-CTR) networks reach historically underserved areas and populations, which are important participants in such trials.

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Career Conversations: Q&A with Organic Chemist Osvaldo Gutierrez

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Osvaldo Gutierrez, Ph.D., was born in Rancho Los Prietos, a small town in central Mexico where his grandmother served as a midwife. Seeing how his grandmother helped people through her work inspired Dr. Gutierrez to pursue a career where he, too, could help people. His family emigrated to the United States when he was young. Despite challenges he faced in a new country, he graduated from high school, attended community college, and was accepted to the University of California, Los Angeles. He originally planned to become a medical doctor, but an undergraduate research experience sparked an interest in chemistry, and he ultimately earned a Ph.D. in the field.

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Pathways: The Superbug Issue

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Cover of Pathways student magazine showing blueish-green virus particles and text that reads, Stop the Spread of Superbugs (Yes, you can help!). Cover of Pathways student magazine.

NIGMS and Scholastic bring you our latest issue of Pathways, which focuses on superbugs—infectious microbes that can’t be fought off with medicines. Viruses that can’t be prevented with vaccines, such as the common cold, and antibiotic-resistant bacteria both fall into this category.

Pathways, designed for students in grades 6 through 12, is a collection of free resources that teaches students about basic science and its importance to health, as well as exciting research careers.

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Exploring Nature’s Treasure Trove of Helpful Compounds

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An oblong shell with white-and-brown markings. A cone snail shell. Credit: Kerry Matz, University of Utah.

Over the years, scientists have discovered many compounds in nature that have led to the development of medications. For instance, the molecular structure for aspirin came from willow tree bark, and penicillin was found in a type of mold. And uses of natural products aren’t limited to medicine cabinet staples and antibiotics. A cancer drug was originally found in the bark of the Pacific yew tree, and a medication for chronic pain relief was first isolated from cone snail venom. Today, NIGMS supports scientists in the earliest stages of investigating natural products made by plants, fungi, bacteria, and animals. The results could inform future research and bring advances to the field of medicine.

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RNA Polymerase: A Target for New Antibiotic Drugs?

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DNA, with its double-helix shape, is the stuff of genes. But genes themselves are only “recipes” for protein molecules, which are molecules that do the real heavy lifting (or do much of the work) inside cells.

RNAP illustrated as a crab claw, clamping on a DNA double helix. Artist interpretation of RNAP grasping and unwinding a DNA double helix. Credit: Wei Lin and Richard H. Ebright.

Here’s how it works. A molecular machine called RNA polymerase (RNAP) travels along DNA to find a place where a gene begins. RNAP uses a crab-claw-like structure to grasp and unwind the DNA double helix at that spot. RNAP then copies (“transcribes”) the gene into messenger RNA (mRNA), a molecule similar to DNA.

The mRNA molecule travels to one of the cell’s many protein-making factories (ribosomes), which use the mRNA message as instructions for making a specific protein.

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Americans Fighting the Opioid Crisis in Their Own Backyards

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Heat maps of the U.S. for 2003 through 2014, showing overdose deaths per 100,000. The heat maps illustrate significant increase of deaths over the years, with deaths concentrated in western U.S. and parts of eastern U.S.

Credit: New York Times article, Jan. 19, 2016.

The United States is in the midst of an opioid overdose epidemic. The rates of opioid addiction, babies born addicted to opioids, and overdoses have skyrocketed in the past decade. No population has been hit harder than rural communities. Many of these communities are in states with historically low levels of funding from the National Institutes of Health (NIH). NIGMS’ Institutional Development Award (IDeA) program builds research capacities in these states by supporting basic, clinical, and translational research, as well as faculty development and infrastructure improvements. IDeA-funded programs in many states have begun prioritizing research focused on reducing the burden of opioid addiction. Below is a snapshot of three of these programs, and how they are working to help their communities:

Vermont Center on Behavior and HealthLink to external web site

Because there are generally fewer treatment resources in rural areas compared to larger cities, it can take longer for people addicted to opioids in rural settings to get the care they need. The Vermont Center on Behavior and Health works to address this need and its major implications.

“One very disconcerting trend we’re seeing with this recent crisis is that opioid-addicted individuals are being placed on wait lists lasting months to a year without any kind of treatment,” says Vermont Center on Behavior and Health director Stephen Higgins. “And it’s very unlikely that anyone who is opioid addicted is just going to abstain while they are on a wait list.”

In urban areas, buprenorphine—an approved medication for opioid addiction that can prevent or reduce withdrawal symptoms—is generally dispensed by trained physicians at treatment clinics. Unfortunately, many rural communities don’t have enough physicians and clinics to serve patients in need. While waiting for treatment, patients are at risk of premature death, overdose, and contracting diseases such as HIV.

Stacey Sigmon, a faculty member in the Vermont Center on Behavior Health, has developed a method to help tackle this problem: a modified version of a tamper-proof device that delivers daily doses of buprenorphine. The advantage of using the modified device is that it makes each day’s dose available during a preprogrammed 3-hour window within the patient’s home, eliminating the need to visit a clinic.

During a study, participants in the treatment group received interim buprenorphine from the device. They also received daily calls to assess drug use, craving, and withdrawal. Participants in the control group didn’t receive buprenorphine. They remained on the waiting list of their local clinic and didn’t receive phone calls. The results, published in the New England Journal of Medicine (NEJM), indicate that the device works. Participants who received the interim buprenorphine treatment submitted a higher percentage of drug test specimens that were negative for opioids than those in the control group at 4 weeks (88 percent vs. 0 percent), 8 weeks (84 percent vs. 0 percent), and 12 weeks (68 percent vs. 0 percent). Sigmon and colleagues are currently testing the device with a much larger group of participants.

“This tool is now available to other rural states that are also being devastated by this crisis and are not so far along in beefing up treatment capacity,” says Higgins.

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Taking the Guesswork Out of Pain Management

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How do you measure pain? A patient’s furrowed brow, a child’s cries or tears—all are signs of pain. But what if the patient suffers from severe dementia and can’t describe what she is feeling or is a young child who can’t yet talk? Caregivers can help read the signs of pain, but their interpretations may differ greatly from patient to patient, because people have different ways of showing discomfort. And when the patient is unconscious, such as during surgery or while in intensive care, the caregiving team has even fewer ways to measure pain.

Assessing pain is an inexact science. It includes both subjective and objective measures. A patient might be asked during a subjective assessment (performed, perhaps, with a caregiver showing a pain-rating scale such as the one in the figure), “How much pain are you feeling today?” That feedback is coupled with biological markers such as an increased heart rate, dilated pupils, sweating, and inflammation as well as blood tests to monitor high levels of the stress hormone cortisol. Combined, these measurements can give doctors a fairly clear picture of how much pain a patient feels.

Pain scale--0 for no hurt to 10 for hurts worst. Patients can point to one of the faces on this subjective pain scale to show caregivers the level of pain they are experiencing. Credit: Wong-Baker Faces Foundation.

But imagine if members of the surgical or caregiving team could actually “see” how the patient is feeling? Such insight would let them select better drugs to use during and after surgery, tailoring care to each patient. That tool could be put into service in the operating room and by the bedside in intensive care, giving nonstop reports of pain as the patient experiences it.

An objective measure of pain also has uses beyond the operating room and intensive care unit. Given the high risk for opioid misuse, such a measure could take the guesswork out of pain management and give doctors a more accurate indication of pain levels to prevent over-prescribing opioid pain relievers.

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