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Archive - Feb 6, 2019

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Pathway for Bacterial Synthesis of Streptozotocin Revealed; Antibiotic Also Treatment for Pancreatic Cancer; Molecule’s Reactive “Warhead” Is Nitrosamine; Nitrosamine Reaction “Has Very Limited, If Any, Precedent in Biological or Synthetic Chemistry"

For decades, scientists and doctors have known that bacteria in soil were capable of manufacturing streptozotocin, an antibiotic compound that is also an important treatment for certain types of pancreatic cancer. What was less clear, however, was exactly how bacteria managed to do it. Led by Dr. Emily Balskus, Professor of Chemistry and Chemical Biology at Harvard University, a team of researchers has untangled that process, showing for the first time that the compound is produced through an enzymatic pathway and revealing the novel chemistry that drives the process. The study is described in an article published online on February 6, 2019 in Nature. The article is titled “An N-Nitrosating Metalloenzyme Constructs the Pharmacophore of Streptozotocin.” What makes the molecule such an effective anti-cancer agent, is a chemical structure known as a nitrosamine - what Dr. Balskus called the molecule's reactive "warhead." Known to be highly reactive, nitrosamines have been shown to be toxic in a host of other compounds, and are most commonly known outside of cancer treatment as a carcinogens found in everything from tobacco to cured meats. "This chemical motif has a great deal of biological relevance, and has been investigated thoroughly," Dr. Balskus said. "Until our work, the view of how this chemical motif was generated in biological systems involved non-enzymatic chemistry - it was just something that occurred under the right conditions." Dr. Balskus and colleagues, however, suspected the story may be more complex, and set out to explore whether bacteria evolved a natural pathway to produce nitrosamine compounds. "That's what we found in this paper," she explained.

Magnets Offer Alternative for Patients with Major Depression, UT Southwestern Results Demonstrate

Janice Blake was depressed and psychotic. She saw imaginary people in her food and wouldn’t eat. She believed an imposter was posing as her brother. She was on the brink of committing suicide, a hopeless woman spiraling into the depths of her mental illness after the medications that had helped her cope for 26 years could no longer keep her sane. Mrs. Blake’s family then offered her a choice in hopes of saving her life: get placed in a long-term mental health facility or undergo electroconvulsive therapy (ECT) at UT Southwestern’s Peter O’Donnell Jr. Brain Institute. “I was afraid to try ECT,” said Mrs. Blake, 65, whose perception of the treatment involved patients being painfully shocked with electricity. Yet Mrs. Blake reluctantly agreed, and quickly discovered ECT was nothing like the disturbing Hollywood depictions she had seen. After only a few treatments, her paranoia and depression dissipated, restoring the rational, smiling person her family feared would never return. “It did save my life,” Mrs. Blake said. “It just brought me back to who I was a long time ago. Fun-loving, happy, and outgoing.” Although the therapy can improve severe depression, ECT has been associated with temporary memory loss – a side effect that has contributed to its stigma and pushed UT Southwestern to test a new form of brain stimulation that may entice other patients to seek help.The National Institute of Mental Health (NIMH) is funding a five-year clinical trial that expands on preliminary research indicating that an alternative brain stimulation method involving magnetic fields can ease depression without cognitive side effects. If proven effective, magnetic seizure therapy (MST) could usher in a new era of depression treatment that turns these therapies from a desperate last resort to an accepted, frontline option for severely depressed patients.