We tested the hypothesis that quercetin, a potent Fe(2+)-chelating flavonoid, would decrease secondary damage following spinal cord trauma. MRI studies using the relaxation of the T1 proton signal caused by Fe(2+) ions and the dose-dependent reversal of this effect by addition of quercetin in aqueous solution were used to guide us to the dosage of quercetin to be used in animal experimentations. Forty-four male Wistar rats were used in two experimental series to test the hypothesis that administration of quercetin improves recovery of motor function after acute traumatic spinal cord injury. Animals were subjected to laminectomy and subjected to an extradural 40-g force clip compression for 5 sec at T7. Quercetin or saline was administered intraperitoneally 1 h after injury and then every 12 hr thereafter. Recovery of motor function was assessed using BBB scores at weekly intervals for 4 weeks. A dose of 2.5 micromoles quercetin/kg body weight did not result in significantly better functional outcome, whereas doses ranging from 5 to 100 micromoles quercetin/kg body weight resulted in a significantly better functional outcome with half or more of the animals walking, although with deficit; in contrast, no animals walked in the group of saline-treated animals. No significant differences in behavioral outcome were seen amongst the doses ranging from 5 to 100 micromol/kg, nor was there a difference if animals were treated for 4 or 10 days. Therapeutic outcome was coincident with more efficient iron clearance, suggesting that one possible mechanism whereby quercetin decreases secondary damage is through iron chelation.
AND EDWRRI) C. K E N U A L L Divssion or Rioclkcmislr~j, Tlie M a yo Fowndatron, Rockester, lI!fi?rneso ta FOUR FIGURES Rlorphologic changes in certain of the ductless glands have h e n induced by administration of largc amounts of thc hormone secreted by thc gland. It was shown by Moorc aiid Price ('Xi?) that injection of rats with large amounts of cither tlie follicular hormone 01-the testicular hormone induced atmphy of thc gonads of either sex. Loeb, Eassett and Friedman ( '30) observed regressive changes in the thyroid gland followiiig administration of excessive amounts of thyroid subs tance .'Phis report covers tlie results of experiments whcrcin we liavc studied tlie cffect of administration of largc amounts of tlie hormoiic of the adrenal cortex and, also, of two crystalline compounds separated from the adrenal gland, which possess cortin-like activity, on tlie size and morphology of the adrenal glarids in wliitc rats.
METI-IODAMale rats of the Wistar strain which wciglicd 180 to 182 gm. were used. They were kept in separate cages and maintained on an adequate commercial diet which contains 0.24$> of sodium and l.0./; of potassium. Cortin was administered in 363
Understanding the physiological processes underlying the ability of Mycobacterium abscessus to become a chronic pathogen of the cystic fibrosis (CF) lung is important to the development of prophylactic and therapeutic strategies to better control and treat pulmonary infections caused by these bacteria. Gene expression profiling of a diversity of M. abscessus complex isolates points to amino acids being significant sources of carbon and energy for M. abscessus in both CF sputum and synthetic CF medium and to the bacterium undergoing an important metabolic reprogramming in order to adapt to this particular nutritional environment. Cell envelope analyses conducted on the same representative isolates further revealed unexpected structural alterations in major cell surface glycolipids known as the glycopeptidolipids (GPLs). Besides showing an increase in triglycosylated forms of these lipids, CF sputum-and synthetic CF medium-grown isolates presented as yet unknown forms of GPLs representing as much as 10% to 20% of the total GPL content of the cells, in which the classical amino alcohol located at the carboxy terminal of the peptide, alaninol, is replaced with the branched-chain amino alcohol leucinol. Importantly, both these lipid changes were exacerbated by the presence of mucin in the culture medium. Collectively, our results reveal potential new drug targets against M. abscessus in the CF airway and point to mucin as an important host signal modulating the cell surface composition of this pathogen.
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