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Background: The vascular endothelium is the interface between the blood and vascular smooth muscle in arteries. It is easily damaged by oxidative stress. Recent studies show that Asians are more susceptible than Caucasians to impairment of endothelial function. This study examined endothelial function in US-born Caucasians, Asians from Korea, and US-born Asians (almost all Korean decent) and examined the effect of coenzyme Q10 (CoQ10) on endothelial function., Material and Methods: Twenty Caucasians and 30 Asians participated (<35 years old, males and females). Endothelial function was assessed by the skin blood flow response to local heat using a thermode for 6 minutes at 44°C and by vascular occlusion for 4 minutes followed by release and measurement of skin blood flow for 2 minutes. In the US-born subjects, the experiments were repeated after 2-week administration of CoQ10 or a placebo., Results: When applying 6 minutes of local heat at 44°C, the skin blood flows were significantly higher in Caucasians than both Asian groups Asians. Likewise after vascular occlusion, the blood flow response was greater in Caucasians compared to Asians. Asians born in Asia had the lowest response of the 3 groups of subjects. Administering CoQ10 for 2 weeks eliminated much of the difference between the groups, whereas there was no difference with a placebo., Conclusions: These findings suggest that Asians either born in Asia or the US may have lower endothelial function than Caucasians. This may be explained, in part, by genetic variations causing increased oxidative stress from westernized diets in Asians. Co enzyme Q10 administration narrows the difference between the groups.

Background: The measurement of the pharmacodynamic response allows the noninvasive quantification of cutaneous drug penetration., Aims: The objective of this study was to investigate whether the experimental methods described in the US Food and Drug Administration Guidance for Industry "Topical Dermatologic Corticosteroids: In vivo Bioequivalence" may be transferred to other response parameters such as skin redness and surface temperature., Methods: Drug penetration experiments with methyl nicotinate in two different lipophilic vehicles were performed according to the FDA guidance for corticosteroid bioequivalence testing measuring the cutaneous erythema and skin temperature response., Results: The guidance methodology was transferred to the response parameters redness and temperature. Bioequivalence testing was feasible with these response parameters., Conclusions: An open one-compartment model could only be confirmed for skin redness data by a compartmental analysis of response vs. time profiles. The obtained temperature data can neither be described by an open one-compartment nor by a two-compartment model. A correlation between skin color and skin surface temperature could not be found.

Comparisons of physiological responses to 0, 0.5, 1, and 2 mg atropine (IM) were made in seven males (X +/- SD: age, 24 +/- 3 years; ht, 174 +/- 12 cm; wt, 76 +/- 3 kg) while they exercised (approximately 390 W) in a hot-dry (40 degrees C, 20% rh) environment. Responses to 4 mg, as well as repeatability of responses to 2 mg, were studied in two and six of these subjects, respectively. On 8 test days an intramuscular injection of atropine or saline control was administered 20 min before subjects walked on a treadmill for two 50-min bouts. Heart rate (HR) during exercise did not change in the control trial but by min 50 increased during all atropine trials (P less than 0.01). Rectal temperature (Tre) increased (P less than 0.01) in all trials by min 50 and continued increasing (P less than 0.01) in the 2-mg trial during the second exercise bout. For the two subjects tested with all dosages (0.5 - 4 mg atropine), the change in HR and Tre between the atropine and control trials at 50 min of exercise was regressed against the various atropine dosages. The relationship (r = 0.92) for HR was curvilinear while the relationship (r = 0.99) for Tre was linear. Mean weighted skin temperature (Tsk) was relatively constant during exercise and was warmer (P less than 0.05) with increasing atropine dosage. In a repeat 2 mg trial, HR was 6 bt . min-1 lower (P less than 0.05) on the second exposure but Tre was the same (P greater than 0.05) on both days. For subjects walking in the heat, three new observations were: 1) 0.5 mg of atropine resulted in increased HR and Tsk compared to control values; 2) HR was elevated but the magnitude of change decreased with increasing dosage, while the elevation in Tre was consistent with increasing dosage; and 3) rectal temperatures (in trials with and without atropine) were unaffected by previous days of atropine administration.