Reflux drying of aerosols.

The goal of our efforts has been to generate high aerosolized drug concentrations, so that the entire inhaled dose may be delivered to the animal in a relatively short time interval, typically one minute or less. In this report, we have examined the use of a reflux condenser coupled with an external heat source as a means to dry aerosol particles. The specific interest was to examine the parameters influencing the drying process and identify practical experimental conditions that would allow drying of aerosol particles. Aqueous solutions of cesium chloride were atomized with an ultrasonic driver, and the resulting cloud was subsequently passed through an externally heated column with an inner condenser cooled with flowing water. Increasing the airflow rate increased the output of total mass(water + CsCl) but decreased the particle transit efficiency. At a constant airflow rate, decreasing the wall-to-condenser temperature ratio led to a progressive increase in particle loss, but a maximum was observed in the water removal efficiency. While thermal diffusion and the thermophoretic effect may have an impact on the drying process, non-steady state conditions, convective currents, inertial impaction, turbulence, and changes in the condenser boundary layer are likely to have a role in particle drying. In spite of the numerous complexities, practical operating conditions were identified for efficient particle drying with high dry mass transit efficiency.

Gender difference in vascular and platelet reactivity to thromboxane A(2)-mimetic U46619 and to endothelial dependent vasodilation in Zucker fatty (hypertensive, hyperinsulinemic) diabetic rats.

We examined the hypothesis that gender differences exist in platelet and vascular reactivity in type-2 diabetes mellitus, using Zucker fatty diabetic rats of both sexes and their lean littermates. Type-2 diabetes is characterized by excessive platelet production of TXA(2), which is thrombogenic. Testosterone up-regulates platelet TXA(2) receptors and the aggregation response to thromboxane mimetics. Conversely, estrogen increases vascular nitric oxide (NO) production and inhibits platelet aggregation. Hemodynamic studies were undertaken with the determination of dose-response curve for MAP and renal cortical blood flow (RCF) in response to U46619, angiotensin-II, phenylephrine and endothelin-1, as well as the systemic hemodynamic response to acetylcholine and L-NG nitro-arginine methylester (L-NAME). Platelet aggregation response was evaluated using whole blood impedance aggregometry. There were significant gender differences in the systemic blood pressure and RCF response to TXA(2)-mimetic U46619 and angiotensin-II (P<0.02, ANOVA) but not to phenylephrine or endothelin-1. Male rats exhibited a paradoxical hypotensive response to U46619 (-18+/-11 mmHg) compared with a peak pressor response of +6+/-1 mmHg in female rats (P<0.01, ANOVA). The male rats exhibited an attenuated systemic vasodilator response (P<0.001, ANOVA) to acetylcholine (fall in MAP in male diabetic rats being -24+/-8 mmHg, compared with a fall of -50+/-8 mmHg in females), but a greater rise in the renal cortical resistance in response to NO inhibition by L-NAME (P<0.03) compared with the female rats. Both the slope (46+/-2) and the peak magnitude of the U46619-induced whole blood platelet aggregation (13+/-1) ohms were significantly higher (P<0.01, ANOVA) in male (n=10) compared with female diabetic rats (n=8) (29+/-0.8 slope, 10.0+/-0.8 ohms, respectively). Thus, the male diabetic Zucker rats exhibited an impaired response to vasoconstrictors (U46619 and angiotensin-II) and to endothelial (NO)-mediated vasodilation. The male gender may therefore be associated with the greater prothrombotic activity and a worse impairment of endothelial reactivity in the type-2 diabetic state.