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Archive - Mar 31, 2017

Removal of Inhibitory Antibodies As New Treatment for Bronchiectasis with Antibiotic-Resistant Pseudomonas auruginosa

A study, published in the April 2017 issue of the American Journal of Respiratory and Critical Care Medicine, describes a new treatment pathway for antibiotic-resistant bacteria and infectious diseases with benefits for patients and health care providers. Researchers from the University of Birmingham and Newcastle University in the UK found that the unusual approach of removing antibodies from the blood stream reduced the effects of chronic infections, the requirement for days spent in hospital, and the use of antibiotics. In this study, the team identified two patients with bronchiectasis who suffered with chronic Pseudomonas aeruginosa infections that were resistant to many antibiotics: a 64-year-old male, diagnosed with bronchiectasis at age 15, and a 69-year-old female who had bronchiectasis from childhood. Bronchiectasis is a disease that leads to permanent enlargement of the airways in the lung and affects over 300,000 patients in the UK. Symptoms are debilitating for patients, and typically include a chronic cough, shortness of breath, coughing up blood, and chest pain. Bronchiectasis often affects patients beyond the age at which lung transplantation is possible. Chronic Pseudomonas aeruginosa lung infections commonly occur in patients suffering from bronchiectasis. Pseudomonas aeruginosa is a common bacterium that can cause disease and is known as a multidrug resistant pathogen, recognized for its advanced antibiotic resistance mechanisms and association with serious illnesses. The patients volunteered to be part of an explorative treatment that built on previous findings from the research group that were reported in 2014 (

Experimental Small Molecule Shows Potential for Preventing Methamphetamine Relapse

FNew research from The Scripps Research Institute (TSRI) suggests that the reason methamphetamine (meth) users find it so hard to quit—88 percent of them relapse, even after rehab—is that meth takes advantage of the brain’s natural learning process. The TSRI study in rodent models shows that ceasing meth use prompts new neurons to form in a brain region tied to learning and memory, suggesting that the brain is strengthening memories tied to drug-seeking behavior. “New neuronal growth is normally thought of as a good thing, but we captured these new neurons assisting with ‘bad’ behaviors,” said Chitra Mandyam (photo), Ph.D., who led the research as an Associate Professor at TSRI before starting a new position at the Veterans Medical Research Foundation and the University of California, San Diego. The scientists discovered that they could block relapse by giving animals a synthetic small molecule to stop new neurons from forming. This molecule, called isoxazole-9 (Isx-9), also appeared to reverse abnormal neuronal growth that developed during meth use. The new research was published online on March 28, 2017 in Molecular Psychiatry. The article is titled “A Synthetic Small-Molecule Isoxazole-9 Protects Against Methamphetamine Relapse.” Neurons are born all the time in a process called neurogenesis. In a 2010 study, Dr. Mandyam and her colleagues at TSRI showed that increased neurogenesis is tied to a higher risk of drug relapse, but they weren’t sure of the new neurons’ role in the process. The researchers were especially curious about a “burst” of neurogenesis that occurs during abstinence from meth. The new study may explain why the brain is so eager to make neurons during abstinence: meth hijacks the natural neurogenesis process.

Circulating Adipose-Derived Exosomal miRNAs Can Regulate Gene Expression in Distant Tissues; Constitutes Newly Described Mechanism of Cell-Cell Crosstalk

Researchers from the Harvard Medical School, the Joslin Diabetes Center, and collaborating institutions have shown that adipose tissue is an important source of circulating exosomal miRNA in both mice and humans, and that different adipose depots contribute different exosomal miRNAs to the circulation. In an article published in the February 23, 2017 issue of Nature, the research team stated that its data shows that these adipose-derived circulating miRNAs can have far-reaching systemic effects, including on the regulation of mRNA expression and translation. The scientists note that adipose tissue transplantation, especially brown adipose tissue (BAT) transplantation, improves glucose tolerance and lowers levels of circulating insulin and FGF21, as well as of hepatic Fgf21 mRNA in recipient mice. Because the adipose-derived miRNAs are produced by different adipose depots, the levels of these miRNAs could also change in diseases with altered fat mass, such as lipodystrophy and obesity, or with altered adipose distribution and function, such as diabetes and aging. The researchers conclude that adipose derived exosomal miRNAs constitute a previously undescribed class of adipokines that can act as regulators of metabolism in distant tissues, providing a new mechanism of cell-cell crosstalk. The Nature article is titled “Adipose-Derived Circulating miRNAs Regulate Gene Expression in Other Tissues.” In addition to the Harvard Medical School and the Joslin Diabetes Center, the collaborating researchers came from Boston University, University Hospital in Zurich, Switzerland, Massachusetts General Hospital, and NIH.

[Nature abstract]

Three Additional Gene Loci Associated with Corneal Disease FECD

Corneal diseases are among the most common causes of visual impairment and blindness, with Fuchs endothelial corneal dystrophy (FECD), a gradual swelling and clouding of the cornea, being the most common reason for eventual corneal transplants. In work reported online on March 30,2017 in Nature Communications, researchers at the University of California San Diego School of Medicine, with colleagues at Case Western University, Duke University, the National Institutes of Health and elsewhere, have identified three novel genomic loci linked to FECD, which often clusters in families and is roughly 39 percent heritable. The open-acccess article is titled “Genome-Wide Association Study Identifies Three Novel Loci in Fuchs Endothelial Corneal Dystrophy.” “Previously, there was one known FECD locus. We've expanded that number to four," said the study's first author Natalie A. Afshari, M.D., Professor of Ophthalmology, Stuart Brown M.D. Chair in Ophthalmology in Memory of Donald Shiley, and Chief of Cornea and Refractive Surgery at the Shiley Eye Institute at UC San Diego Health. "These findings provide a deeper understanding of the pathology of FECD, which in turn will help us develop better therapies for treating or preventing this disabling disease." FECD affects the innermost layer of cells in the cornea (the transparent front cover of the eye), called the endothelium. The endothelium is responsible for maintaining the proper amount of fluid in the cornea, keeping it clear. FECD is a progressive disorder in which the endothelium slowly degrades, with lost clarity, pain, and severely impaired vision. It affects 4 percent of the U.S. population above age 40 and worsens with age. Women are two to four times more frequently affected than men.