Autoantibodies against MDA-LDL in subjects with severe and minor atherosclerosis and healthy population controls

Autoantibodies against oxidized low-density lipoprotein (LDL) have been reported to be associated with atherosclerosis. However, data are not consistent. We compared the titres of autoantibodies to malondialdehyde-modified LDL in three groups, a case group with angiographically documented severe coronary stenosis (> 80% stenosis in at least 1 vessel, n = 47), a hospital control group with minor stenosis on the coronary angiography (< 50% stenosis in all three major vessels, n = 47) and a healthy population control group with no history of coronary heart disease (n = 49). Age ranged from 26 to 68 years. Subjects were frequency-matched for gender distribution and storage time of the blood samples. No relevant differences in autoantibody titre between case and control groups were found. The mean autoantibody titres (± S.D.) were 1.44 ± 1.82, 1.46 ± 1.40 and 1.62 ± 1.95 for cases, hospital controls and population controls, respectively. No correlations were found between autoantibody titre and age, number of cigarettes smoked and LDL or total cholesterol. Autoantibody titres were correlated wit

Functional Hair Cell Mechanotransducer Channels Are Required for Aminoglycoside Ototoxicity

Aminoglycosides (AG) are commonly prescribed antibiotics with potent bactericidal activities. One main side effect is permanent sensorineural hearing loss, induced by selective inner ear sensory hair cell death. Much work has focused on AG's initiating cell death processes, however, fewer studies exist defining mechanisms of AG uptake by hair cells. The current study investigated two proposed mechanisms of AG transport in mammalian hair cells: mechanotransducer (MET) channels and endocytosis. To study these two mechanisms, rat cochlear explants were cultured as whole organs in gentamicin-containing media. Two-photon imaging of Texas Red conjugated gentamicin (GTTR) uptake into live hair cells was rapid and selective. Hypocalcemia, which increases the open probability of MET channels, increased AG entry into hair cells. Three blockers of MET channels (curare, quinine, and amiloride) significantly reduced GTTR uptake, whereas the endocytosis inhibitor concanavalin A did not. Dynosore quenched the fluorescence of GTTR and could not be tested. Pharmacologic blockade of MET channels with curare or quinine, but not concanavalin A or dynosore, prevented hair cell loss when challenged with gentamicin for up to 96 hours. Taken together, data indicate that the patency of MET channels mediated AG entry into hair cells and its toxicity. Results suggest that limiting permeation of AGs through MET channel or preventing their entry into endolymph are potential therapeutic targets for preventing hair cell death and hearing loss

Clinical Considerations for Routine Auditory and Vestibular Monitoring in Patients with Cystic Fibrosis

Purpose Specific classes of antibiotics, such as aminoglycosides, have well-established adverse events producing permanent hearing loss, tinnitus, and balance and/or vestibular problems (i.e., ototoxicity). Although these antibiotics are frequently used to treat pseudomonas and other bacterial infections in patients with cystic fibrosis (CF), there are no formalized recommendations describing approaches to implementation of guideline adherent ototoxicity monitoring as part of CF clinical care. Method This consensus statement was developed by the International Ototoxicity Management Working Group (IOMG) Ad Hoc Committee on Aminoglycoside Antibiotics to address the clinical need for ototoxicity management in CF patients treated with known ototoxic medications. These clinical protocol considerations were created using consensus opinion from a community of international experts and available evidence specific to patients with CF, as well as published national and international guidelines on ototoxicity monitoring. Results The IOMG advocates four clinical recommendations for implementing routine and guideline adherent ototoxicity management in patients with CF. These are (a) including questions about hearing, tinnitus, and balance/vestibular problems as part of the routine CF case history for all patients; (b) utilizing timely point-of-care measures; (c) establishing a baseline and conducting posttreatment evaluations for each course of intravenous ototoxic drug treatment; and (d) repeating annual hearing and vestibular evaluations for all patients with a history of ototoxic antibiotic exposure. Conclusion Increased efforts for implementation of an ototoxicity management program in the CF care team model will improve identification of ototoxicity signs and symptoms, allow for timely therapeutic follow-up, and provide the clinician and patient an opportunity to make an informed decision about potential treatment modifications to minimize adverse events