Abnormalities of diastolic filling of the left ventricle associated with aging are less pronounced in exercise-trained individuals.

To determine whether exercise training has an effect on left ventricular diastolic dysfunction associated with the normal aging process, we studied a group of 20 normal healthy adult distance runners (mean miles currently run per week was 45 for an average of 15 years) and 20 normal healthy sedentary individuals (who currently walk less than 1 mile per day and are not involved in a regular exercise program) matched for age and systolic and diastolic blood pressure with the runners. Doppler echocardiographic indices of left ventricular diastolic filling were significantly different between the two groups. The exercise group when compared with the sedentary group had significantly decreased late diastolic peak filling velocity (0.51 +/- 0.11 m/sec versus 0.66 +/- 0.20 m/sec; p = 0.003), late diastolic velocity-time integral (5.2 +/- 1.5 cm versus 6.6 +/- 2.2 cm; p = 0.02), increased early-to-late peak filling velocity ratio (1.29 +/- 0.38 versus 0.96 +/- 0.24; p = 0.001), and early-to-late velocity-time integral ratio (2.08 +/- 0.51 versus 1.42 +/- 0.47; p less than 0.001). We conclude that the left ventricular diastolic dysfunction associated with "normal" aging is less pronounced in those persons who are exercise-trained.

Precorneal factors influencing the ocular distribution of topically applied liposomal inulin.

The primary objective of this study was to investigate the effect of several precorneal factors on the retention of liposomes in tears and their interaction with the corneal and conjunctival surfaces. It was found that adsorption of liposomes onto these surfaces was requisite to the ocular absorption of inulin. Over a range of 10 to 50 microliter, the availability of binding sites at the corneal and conjunctival surfaces rather than the size of the instilled volume controlled the extent of liposomal adsorption and ultimately availability of inulin to the intraocular tissues. The inulin liposomes were in facile association with the adsorptive surfaces, as evidenced by their low resistance to removal by rinsing the eye with saline and by the lack of sustained inulin concentrations in any of the ocular tissues studied. This property of liposomes, coupled with the slow rate (1% per hour) at which they released inulin, was responsible for the absence of inulin in the aqueous humor as late as 240 minutes post-dosing. It was concluded that, for liposomes to be effective in ocular drug delivery, they must show affinity for and be bound to the corneal surface and, in addition, must release their contents at optimal rates.

Subcellular distribution of esterases in the bovine eye.

The distribution of esterases within a cell can influence the rate and extent at which drugs containing ester linkages would be hydrolyzed. The objective of this study was to evaluate the subcellular distribution of esterases in the bovine eye. Ocular tissue homogenates were subjected to differential centrifugation to yield mitochondrial, microsomal and cytoplasmic fractions. Each fraction was then incubated with 1- or 2-naphthyl esters and its esterase activity determined. No esterase activity was detected in the mitochondrial fraction. For the corneal epithelium and iris-ciliary body about 80% of the esterase activity in the tissue homogenates, on a per milligram protein basis, was associated with the microsomes, the remainder was associated with the cytoplasm. Of the tissues studied, the iris-ciliary body had the highest esterase activity, 15 and 7 times that in the corneal epithelium and corneal stroma, respectively. The corneal endothelium was devoid of esterase activity. In comparison with the rabbit eye, the specific esterase activity in the bovine eye was lower. Surprisingly, unlike the rabbit, the corneal epithelium of the bovine eye was enzymatically less active than the stroma. Based on these preliminary data, it was concluded that the esterase activity varies with the tissue and that within a cell the esterases were distributed between the cytoplasm and the microsomes according to a ratio specific for a tissue.