This review deals with the characteristics of various inflammatory mediators identified in the middle ear during otitis media and in cholesteatoma. The role of each inflammatory mediator in the pathogenesis of otitis media and cholesteatoma has been discussed. Further, the relation of each inflammatory mediator to the pathophysiology of the middle and inner ear along with its mechanisms of pathological change has been described. The mechanisms of hearing loss including sensorineural hearing loss (SNHL) as a sequela of otitis media are also discussed. The passage of inflammatory mediators through the round window membrane into the scala tympani is indicated. In an experimental animal model, an application of cytokines and lipopolysaccharide (LPS), a bacterial toxin, on the round window membrane induced sensorineural hearing loss as identified through auditory brainstem response threshold shifts. An increase in permeability of the blood-labyrinth barrier (BLB) was observed following application of these inflammatory mediators and LPS. The leakage of the blood components into the lateral wall of the cochlea through an increase in BLB permeability appears to be related to the sensorineural hearing loss by hindering K+ recycling through the lateral wall disrupting the ion homeostasis of the endolymph. Further studies on the roles of various inflammatory mediators and bacterial toxins in inducing the sensorineumral hearing loss in otitis media should be pursued.

Apoptosis is an important process, both for normal development of the inner ear and for removal of oxidative-stress damaged sensory cells from the cochlea. Oxidative-stressors of auditory sensory cells include: loss of trophic factor support, ischemia-reperfusion, and ototoxins. Loss of trophic factor support and cisplatin ototoxicity, both initiate the intracellular production of reactive oxygen species and free radicals. The interaction of reactive oxygen species and free radicals with membrane phospholipids of auditory sensory cells creates aldehydic lipid peroxidation products. One of these aldehydes, 4-hydroxynonenal, functions as a mediator of apoptosis for both auditory neurons and hair cells. We present several approaches for the prevention of auditory sensory loss from reactive oxygen species-induced apoptosis: 1) preventing the formation of reactive oxygen species; (2) neutralizing the toxic products of membrane lipid peroxidation; and 3) blocking the damaged sensory cells' apoptotic pathway.

There is growing need for accurate information regarding the bioavailability of carotenoids, both with respect to carotenoidsper se and to the vitamin A value of provitamin A carotenoids in foods or supplement preparations. Little quantitative information is currently available, owing primarily to the lack of adequate methods to assess carotenoid bioavailability. Methods applied to xenobiotic drugs are in most cases not useful for carotenoids, many of which circulate in appreciable quantities in human plasma. Reported ranges of carotenoid bioavailability (% dose absorbed) range from 1-99, and variability is generally high both within and between treatments. With the current methods, relative bioavailability is more readily assessed than absolute bioavailability. The most commonly applied methods include measuring the increase in plasma carotenoid concentration following chronic intervention, and use of postprandial chylomicron (PPC) carotenoid or retinyl ester response following a single dose of carotenoid. The advantages and limitations of these approaches, together with examples of each, are discussed. A new PPC approach utilizing extrinsic-stable-isotope-labelled vitamin A (2H4-labelled retinyl acetate) is under development in our laboratory, and examples of its application are presented. The currently available data suggest that oil solutions of carotenoids are more bioavailable than those from food matrices, and heating can improve the bioavailability of carotenoids from some food products. Increased availability of labelled carotenoids and retinoids should aid the development of reliable methods of carotenoid bioavailability assessment. Such data are needed for dietary recommendations, supplement formulation, and design of intervention strategies involving carotenoids. Bioavailability : Carotenoids: Vitamin A: Postprandial chylomicron techniqueCarotenoids are lipid-soluble plant pigments common in photosynthetic plants, animal tissues, and in the bloodstream and tissues of human subjects consuming plant and animal products. These pigments are of physiological interest in human nutrition, since some are vitamin A precursors and many exhibit radical or singlet oxygen trapping activity (Miller et al. 1996), and as such have potential antioxidant effects in vivo. Consequently, it is of value to determine the bioavailability of carotenoids from both foods and supplement forms in human subjects, and identify and quantify those factors which significantly affect carotenoid uptake and tissue disposition. Reliable data are needed to formulate effective policies for combating vitamin A deficiency and prevention of chronic degenerative diseases. At the present time there is considerable debate over such issues as the actual vitamin A value offoods containing provitamin A carotenoids, and the relative importance of the large number of factors which may potentially influence carotenoid bioavailability. It is currently not possible to assign with confidence specific values to the absorption efficiency of a specific caro...

No abstract