色情视频

An infection transmitted by vampire bugs, a disease that attacks the heart, and glowing green microscopic parasites. These eerie elements are all part of a project led by 色情视频 associate professor which tests a new theory on why treatments fail to cure a range of diseases.

Getting sick can be scary and what鈥檚 even more frightening is when treatments don鈥檛 work. A key culprit behind treatment failure is antimicrobial resistance, a huge issue in health care today which occurs when microbes have built up an immunity to the drugs used to treat them.

McCall鈥檚 lab argues there may be another factor working alongside antimicrobial resistance to prevent drugs from killing pathogens: Drugs may not be getting to the right location in the first place. Researchers have explored this idea in cancer studies but this project represents one of the few, if only, focused on infectious diseases.

Through a collaboration between McCall鈥檚 lab at 色情视频, Zhibo Yang at the University of Oklahoma, James Papin at the University of Oklahoma Health Sciences Center and Carolyn Ibberson at the University of Tennessee in Knoxville, this NIH-funded project aims to determine how drug levels in cells could lead to treatment failure in essentially each category of infection. 

McCall鈥檚 lab will test the theory first in a parasitic infection model, before Papin and Ibberson鈥檚 labs test it in viral and bacterial infections, respectively. The Yang lab will perform single-mass spectrometry to quantify drug levels in these biological systems.

A Tricky-to-Treat Disease 

Second year chemistry-biochemistry doctoral student Luis Ernst pulls up racks of frozen T. cruzi parasite samples from an ultracold liquid nitrogen tank (Bryana Quintana/色情视频)

For their part of the project, McCall鈥檚 lab is using the parasite Trypanosoma cruzi, which causes Chagas disease and is primarily spread through the bloodsucking triatomine bug. Once T. cruzi has invaded cells, the disease progresses to attack the heart and gut.

Chagas disease affects an estimated , particularly impoverished populations with low access to health care in Latin America and the southern United States. While treatments are available, they can have severe side effects. Making matters worse is the fact that although the disease must be treated early to ensure optimal outcomes, people are often asymptomatic at the start which makes it difficult to diagnose and treat.

鈥淓ssentially 20% of people who take Chagas disease medication are not able to finish their treatment because the side effects are so intense,鈥� first-year chemistry doctoral student Ariel Pernela said. 鈥淎nd they have to take it for a long time, up to two months, so these medications are not ideal.鈥�

McCall鈥檚 lab hopes to use this disease as a way to better understand how drug levels in cells impact treatment efficacy. To do this, they will grow cell samples in the lab, infect them with T. cruzi parasites, then administer the treatments and examine how they affect each cell before sending the samples to Yang鈥檚 lab to measure drug levels in the cells.

鈥淭he parasites are fluorescent so we can locate them. When we start the treatment, you can see that the fluorescence goes down when the parasite dies and then we can see in which cells parasites persist because we have a fluorescent signal,鈥� said Luis Ernst, a second-year chemistry doctoral student. 鈥淭hen we can compare how much of the drug was in the cell in which parasites were killed and how much of the drug was in the cell in which parasites persist.鈥�

The researchers predict higher levels of drugs in cells with fewer parasites, indicating the medication entered these cells and worked as intended, whereas treated cells that still contain parasites will show lower drug levels, meaning not enough medication got inside the cell to be effective.

Upgrading Treatment

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McCall said if her team鈥檚 hypothesis is correct, it 鈥渃ould change how we do drug development.鈥� 

Testing drug levels in each cell could prove a key, time- and money-saving step in verifying drug efficacy prior to clinical trials, not to mention one which makes testing safer. This research could also elucidate a need to alter drug formulas, or adjust factors like dosage or length of treatment to make medications more effective.

Drug delivery issues also have the potential to increase antimicrobial resistance, McCall explains. If a cell contains low drug levels, pathogens are able to survive and learn how to defend against the drug. The opposite could also be true, as pathogens can pump drugs out of the cell and encourage cells they infect to do the same, which contributes to resistance. So, this study could provide further insight into ways to curb this widespread issue.

鈥淭reatment is at the center of health. Prevention is extremely important but you are going to get sick, hopefully very rarely, and when you do, you want treatments that are going to work,鈥� McCall said. 鈥淭his research is part of making those good treatments, understanding what we have now and always evolving to make better ones, so you don't have a situation where people can't be treated or they get something that doesn't work for them.鈥�