Bioavailability comparison between a compound comprising hesperetin-7-glucoside with ß-cyclodextrin and a mixture of hesperidin and dextrin in healthy adult human males.

The pharmacokinetics of compounds comprising hesperetin-7-glucoside with ß-cyclodextrin and physically mixed hesperidin/dextrin was compared in 8 healthy adult male subjects in a nonrandomized, double-blind, cross-over, controlled study. For 0-24 h, the area under the curve of the total plasma hesperetin concentration after hesperetin-7-glucoside with ß-cyclodextrin consumption was >100-fold higher than that after hesperidin/dextrin consumption.

The threshold of the intermittent hypoxic exposure period to elicit polycythemia in rats.

It is not yet clear whether there is an intermittent hypoxia (IHx) threshold to elicit polycythemia and blood pressure elevation, and whether blood hemoglobin concentration ([Hb]) increases with an increase in the hypoxic exposure period. We have previously shown that repetitive exposure to 10% O2 for 60 min/day for up to 5 weeks does not produce polycythemia. In the present study, we evaluated the effect of IHx of 10% O2, 120 min/day for 1, 2, 3 and 4 weeks on [Hb], arterial blood pressure, heart rate and arterial blood gases in the rat. IHx of 10% O2, 120 min/day induced polycythemia at 1 week and produced a time-dependent increase in [Hb] from 0 week to 4 weeks. Arterial blood pressure significantly increased during IHx exposure for 4 weeks probably due to a combination of an increased sympathetic activity as well as increased blood viscosity. The IHx threshold for polycythemia might exist between 60 min/day and 120 min/day in this level of hypoxia.

Exposure to hypoxia results in uneven pulmonary blood flow distribution prior to pulmonary edema.

The effects of hypoxia on pulmonary arterial pressure (PAP) and on development of pulmonary edema, ascertained by changes in lung water and pulmonary vascular permeability were studied in rats using bronchoalveolar lavage (BAL). Rats were exposed to hypobaric hypoxia (P(B) = 290 Torr) for 24 h followed by 4 h of normobaric hypoxia (F(IO)2 0.07) (Hx). Controls were rats maintained in a normoxia (Nx). Mean PAP was 28.3 +/- 0.8 mmHg in Hx, and 18.8 +/- 1.7 mmHg in Nx (mean +/- SD). The wet-to-dry lung weight ratio was significantly higher in Hx. The ratio of fluorescence activity between BAL fluid and plasma 4 h after i.v. injection of FITC-albumin was higher in Hx, suggesting an increased pulmonary microvascular permeability in Hx. In a separate study, pulmonary blood flow distribution, measured after 10 min of hypoxia (F(IO)2 0.07) using non-radioactive microspheres, was significantly more heterogeneous than Nx, suggesting a non-homogeneous hypoxic pulmonary vasoconstriction. The combined data of both studies suggest that hypoxia induces heterogeneous pulmonary blood flow distribution which is followed by increased vascular permeability and the development of pulmonary edema.