Noise-induced transient microlesions in the cell membranes of auditory hair cells.

Several types of nonauditory cells recover from transitory mechanically induced microlesions in their cell membranes. We report evidence that hair cells in the auditory papilla of the alligator lizard suffered similar membrane wounding when exposed to noise loud enough to induce a temporary threshold shift. Lucifer yellow, a molecular marker that does not normally penetrate through the cell membrane into the cytoplasm, was introduced into the extracellular fluid bathing the basolateral membrane of the hair cells. We assessed the effect of loud noise on the function of the ear by measuring compound action potentials of the auditory nerve before exposure to the noise, immediately after cessation of the noise, and after recovering overnight. Hair cells that were exposed to the noise took up much more Lucifer yellow than hair cells that were not exposed. We propose that the Lucifer yellow entered the hair cells via noise-induced lesions in their cell membranes, and that the cells were able to survive and recover functionally.

Afferent synaptic changes in auditory hair cells during noise-induced temporary threshold shift.

This study presents evidence in support of the hypothesis that one of the sites of failure during noise-induced temporary threshold shift (TTS) is the afferent synapse between auditory hair cells and auditory nerve fibers. Our results show clear evidence indicating changes in the quantity of afferent synapses and the morphology of presynaptic structures in the alligator lizard auditory hair cells during TTS. In TTS hair cells there are statistically significant decreases in: 1) the number of afferent synapses, 2) the number of synaptic vesicles at the afferent synapses, 3) the size of synaptic bodies, and 4) the packing density of synaptic vesicles around the synaptic body. These results suggest that the presynaptic components of the afferent synapse reflect the functional state of the synapse, and that the reduction of these synapses, both in number and component size, contributes to TTS.

Dietary fish oil augments nitric oxide production or release in patients with type 2 (non-insulin-dependent) diabetes mellitus.

Decreased release of nitric oxide from damaged endothelium is responsible for the impaired endothelium-dependent vasodilator responses found in animal models of vascular disease. Dietary supplementation with fish oils has been shown to augment endothelium-dependent relaxations, principally by improving the release of nitric oxide from injured endothelium. Using forearm venous occlusion plethysmography we studied vascular responses to 60, 120, 180 and 240 nmol/min of acetylcholine (an endothelium-dependent vasodilator) and 3, 6 and 9 nmol/min of glyceryl trinitrate (an endothelium-independent vasodilator) infused into the brachial artery in 23 patients with Type 2 (non-insulin-dependent) diabetes mellitus. NG monomethyl-L-arginine was employed to inhibit stimulated and basal release of nitric oxide from the endothelium. On completion of the baseline studies patients randomly received either fish oil or matching olive oil capsules in a double-blind crossover fashion for 6 weeks followed by a 6-week washout period and a final 6-week treatment phase. Studies, identical to the initial baseline studies, were performed at the end of the active treatment periods at 6 and 18 weeks. Fish oil supplementation significantly improved forearm blood flow responses to each dose of acetylcholine when compared to the vasodilator responses recorded at baseline and after olive oil administration (p < 0.01). Neither fish oil nor olive oil supplementation produced any significant changes in forearm blood flow to the incremental infusions of glyceryl trinitrate when compared with responses recorded during the baseline studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Impaired endothelium-dependent and independent vasodilation in patients with type 2 (non-insulin-dependent) diabetes mellitus.

The endothelium plays a pivotal role in modulating the reactivity of vascular smooth muscle through the formation of several vasoactive substances. We examined the effects of endothelium-dependent and independent vasodilators on forearm blood flow in 29 patients with Type 2 (non-insulin-dependent) diabetes mellitus and in 21 control subjects, using venous occlusion plethysmography. Via a brachial artery cannula, increasing amounts of acetylcholine and glyceryl trinitrate were infused in doses of 60, 120, 180 and 240 mmol per min and 3, 6 and 9 nmol per min respectively. NG monomethyl-L-arginine, a stereospecific inhibitor of endothelium derived relaxing factor, was infused to inhibit basal and stimulated release of this dilator substance. Reactive hyperaemic forearm blood flow did not differ between groups. Forearm blood flow responses to each dose of acetylcholine were significantly greater in control than diabetic subjects (p less than 0.01 for all doses). NG monomethyl-L-arginine attenuated forearm blood flow from maximal stimulated values when responses were compared with the natural decline to acetylcholine in forearm flow in both control and diabetic subjects (p less than 0.05 for both groups), but had no effect on basal blood flow responses. Forearm blood flow responses to each dose of glyceryl trinitrate were significantly greater in control than diabetic subjects (p less than 0.05 for all). These data provide evidence for endothelial and smooth muscle dysfunction in diabetes which may have important therapeutic implications.