January 11, 2008

Aliquots — Research highlights from VUMC laboratories

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We welcome suggestions for research to highlight in Aliquots. The items should be primary research articles (no reviews, editorials or commentaries) published within the last two months in a peer-reviewed journal. Please send the article citation (PDF if available) and any other feedback about the column to: aliquots@vanderbilt.edu.

Compounds combat parasite infection

Single-celled parasites called trypanosomes, responsible for tropical diseases like sleeping sickness and Chagas disease, afflict millions in Africa and Central and South America. The few available treatments can be highly toxic, difficult to administer and have limited efficacy in the chronic stages of disease.

In the November issue of Chemistry & Biology, Galina Lepesheva, Ph.D., and colleagues report that inhibiting an enzyme (CYP51) involved in the synthesis of sterols — lipid molecules essential for cell membrane function and integrity — may offer a new strategy for treating these infections.

The researchers identified compounds that inhibit trypanosomal CYP51 and found that their ability to inhibit the enzyme correlated with their ability to inhibit growth of trypanosomal cells in culture. The results suggest that sterol synthesis is required for parasite growth and development and may represent a promising target for anti-parasitic drugs.

— Melissa Marino

Bad vibrations

As any professional singer can attest, the vocal cords are subject to potentially damaging vibration daily. The tissues have developed mechanisms to withstand such repeated mechanical stress, possibly involving enzymes like matrix metalloproteinases (MMPs) that help maintain the balance between degradation and synthesis of extracellular matrix.

Using a rabbit model, Bernard Rousseau, Ph.D., and colleagues investigated the effects of prolonged phonation — vibration of the vocal cords to generate sound — on expression of factors involved in ECM homeostasis. They found that three hours of experimentally induced phonation (within the range of human voice production) caused a significant increase in MMP-1 expression consistent with the amount of MMP elevation seen during wound healing or in response to tissue injury.

The results, reported in the January issue of Otolarygology – Head and Neck Surgery, provide insight into how such processes contribute to maintaining the integrity of the vocal cords and suggest possible targets for the treatment and prevention of voice disorders.

— Melissa Marino

Drug lessens obesity-related risks

As waistlines around the world increase, so do a host of other risk factors — altered blood lipids, high blood pressure, impaired glucose metabolism — that predispose patients to cardiovascular disease and diabetes. Glucocorticoids (steroid hormones such as cortisol) are thought to play a role in the pathology of this “metabolic syndrome.” The enzyme 11beta-HSD1, which regenerates glucocorticoids in key metabolic tissues, has emerged as a promising drug target for patients with metabolic syndrome.

Alli Nuotio-Antar, Ph.D., David Hachey, Ph.D., and Alyssa Hasty, Ph.D., evaluated the effects of the drug carbenoxolone (an inhibitor of 11beta-HSD1) in mouse models of obesity and elevated blood lipids. In the December American Journal of Physiology – Endocrinology and Metabolism, they report that carbenoxolone improved body composition, basal metabolic rate, insulin resistance, lipoprotein metabolism and atherosclerosis in severely obese and insulin-resistant mice. The findings support the notion that targeting 11beta-HSD1 may be a valuable therapy for patients with metabolic syndrome risk factors.

— Leigh MacMillan

Priming kids’ marrow for transplant

Bone marrow transplants using higher cell “doses” offer more rapid engraftment, less risk of graft-versus-host disease (GVHD), and improved survival. Peripheral blood stem cells (mobilized by granulocyte colony-stimulating growth factor, G-CSF) offer a high cell dose, but may increase the risk of GVHD in children. One way to potentially increase transplant cell dose without increasing the risk of GVHD is to use marrow from donors pre-treated with G-CSF.

Haydar Frangoul, M.D., and colleagues in the Pediatric Blood and Marrow Transplant Consortium, evaluated G-CSF-primed bone marrow transplants in pediatric patients. They report in the journal Blood that G-CSF is safe to use in pediatric donors, increases the yield of marrow cells and does not increase the risk of acute or chronic GVHD.

The investigators conclude that G-CSF-primed bone marrow is a safe and feasible source of stem cells from related pediatric donors and have launched a phase 3 randomized trial to compare primed and non-primed marrow.

— Leigh MacMillan

Past Aliquots

June 22, 2012
June 8, 2012
May 11, 2012
April 27, 2012
April 13, 2012
March 30, 2012
March 16, 2012