Negative affect as a predisposing factor for cortisol release after an acute stress--the impact of unpleasant priming.

Glucocorticoids have a key role in stress responses. There are, however, substantial differences in cortisol reactivity among individuals. We investigated if affective trait and mood induction influence the reactivity to psychological stress in a group of 63 young adults, male (n=27) and female (n=36), aged ca. 21 years. On the experimental day the participants viewed either a block of pleasant or unpleasant pictures for 5 min to induce positive or negative mood, respectively. Then, they had 5 min to prepare a speech to be delivered in front of a video-camera. Saliva samples were collected to measure cortisol, and questionnaire-based affective scales were used to estimate emotional states and traits. Compared to basal levels, a cortisol response to the acute speech stressor was only seen for those who had first viewed unpleasant pictures and scored above the average on the negative affect scale. There were no sex differences. In conclusion, high negative affect associated with exposure to an unpleasant context increased sensitivity to an acute stressor, and was critical to stimulation of cortisol release by the speech stressor.

Development of an efficient single-step freeze-drying cycle for protein formulations.

PURPOSE: An efficient freeze-drying cycle for recombinant human interleukin-1 receptor antagonist (rhIL-1ra) formulations, which contained glycine and sucrose as excipients, was developed. METHODS: Development was based on characterizing the frozen formulations by thermal analysis and by examining the effect of various lyophilization process parameters on the sublimation rate of ice. RESULTS: Thermal analysis showed that the metastable glass of glycine in frozen formulation could be devitrified by slowly warming the frozen product to -15 degrees C. During drying, the sublimation rate of ice was increased as a linear function of the difference between the vapor pressure of ice at the product temperature (PO) and the chamber pressure (PC). Therefore, the product temperature (Tp) was maintained as high as possible at temperatures below Tg' of the formulation, in order to maximize the PO without allowing the collapse of cake. Although various combinations of shelf temperatures and chamber pressures could be used to obtain the same Tp, the combination of higher shelf temperature and lower chamber pressure was used to maximize sublimation rate. CONCLUSIONS: A single-step drying cycle was developed to take advantage of these observations. The shelf temperature was set for the secondary drying and the product temperature during primary drying was maintained below Tg' by adjusting the chamber pressure. As the sublimation completed, the product temperature increased naturally to the shelf temperature for the secondary drying. This process resulted in successful drying of 1 ml of rhIL-1ra formulation to 0.4% moisture content within 6 hours.