Reversing lipid woes in cystic fibrosis
Patients with cystic fibrosis (CF) – the most commonly inherited genetic disorder among Caucasians – have abnormalities in blood and tissue polyunsaturated fatty acid (PUFA) levels. In mouse models of CF, supplementation with the fatty acid DHA can reverse the PUFA abnormalities and CF-related pathologies.
Adam Seegmiller, M.D., Ph.D., and colleagues previously found in a cell culture model of CF that PUFA abnormalities correlated with increased expression and activity of certain fatty acid metabolic enzymes called desaturases. They have now demonstrated that addition of DHA or the fatty acid EPA to the cells reduces the expression and activity of these desaturases and reverses the PUFA abnormalities. They also uncovered other metabolic abnormalities in the CF cells, including increased fatty acid uptake and increased conversion of DHA to EPA.
The results, reported in the February Journal of Lipid Research, indicate that the fatty acid abnormalities of CF are related to alterations of PUFA metabolism – and that they may be reversed by supplementation with DHA and EPA.
This research was funded in part by the Edward and Nancy Fody Endowed Chair in Pathology and by the Vanderbilt Physician Scientist Training Program.
— Leigh MacMillan
‘Detangler’ binds, bends and cuts DNA
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Neil Osheroff, Ph.D., and colleagues utilized single-molecule fluorescence methods to study the individual steps of the topoisomerase II-mediated DNA cleavage reaction. They report in the Feb. 21 Proceedings of the National Academy of Sciences that the reaction proceeds through three ordered steps: nonspecific DNA binding, sequence-specific DNA bending, and DNA cleavage. They found that magnesium ions have roles in the DNA bending, and that cleavage of one DNA strand stabilizes bending and cleavage of the other strand.
The findings highlight the tight control of DNA cleavage to protect the genome and may provide leads for developing better chemotherapeutic agents.
This research was supported by Creative Research Initiatives, the National Research Foundation of Korea and the National Institute of General Medical Sciences.
— Leigh MacMillan
Combo combats dizziness
Orthostatic hypotension – a drop in blood pressure upon standing, causing dizziness and near-fainting – is one of the most disabling symptoms of autonomic failure, a disorder of the autonomic nervous system, which controls functions like heart rate, digestion and respiration.
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Italo Biaggioni, M.D., and colleagues have previously shown that atomoxetine, an ADHD medication in children, raised blood pressure 50 mmHg on average in patients with autonomic impairment of the central nervous system. But the drug may not work as well in patients with autonomic dysfunction in the peripheral nervous system.
They now report that the combination of yohimbine and atomoxetine – drugs that enhance the activity of the sympathetic nervous system in different ways – significantly increased blood pressure and improved orthostatic tolerance in 17 patients with peripheral autonomic failure; neither drug alone was effective. The results, in the March issue of Hypertension, suggest that this one-two punch therapy may be useful for patients who do not respond to these drugs individually.
The research was supported by grants from the National Institute of Neurological Disorders and Stroke, the National Heart, Lung and Blood Institute, the National Center for Research Resources, and the National Center for Advancing Translational Sciences of the National Institutes of Health, and the Paden Dysautomia Center.
— Melissa Marino
Urine biomarker for colon cancer?
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To assess the utility of PGE-M as a biomarker of colon cancer risk, Martha Shrubsole, Ph.D., and colleagues compared levels of PGE-M in the urine of patients with colorectal adenomas (precancerous lesions) versus controls.
In the February issue of Cancer Prevention Research, the investigators report that high levels of PGE-M in the urine was associated with increased risk of advanced or multiple adenomas, particularly among women. However, levels of PGE-M were not increased in patients with a less aggressive type of adenoma (single small tubular adenomas), suggesting that measuring urinary PGE-M may offer a way to distinguish which colon adenomas are more clinically significant.
The research was supported by grants from the National Cancer Institute.
— Melissa Marino
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.
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