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Vitellogenin (VTG) synthesis has been described as an ideal system to study the hormonal regulation of gene expression. In Xenopus the molecular aspects of this control have been analyzed; however, in other non-mammalian species such as reptiles, very few studies approaching this level have been undertaken. We report on the induction by estradiol-17 beta of VTG-like proteins in liver explants from adult males and immature male and female lizards (A. pulchellus). A concentration of 10(-7) M was optimum for adult males while a higher concentration (10(-6) M) is required for the immature animals. No differences were observed in the hormonal induction in male and female immature animals, suggesting that there are no sexual distinctions in the liver at this stage. The effect of the hormone in male liver appears to be primarily on mRNA synthesis, since increases in 3H-uridine incorporation in total RNA were prevented by addition of 1 microgram/ml of the RNA polymerase II inhibitor alpha-Amanitin; however, rRNA synthesis was also increased as observed by agarose gel analysis. A 48 hr lag period was required for the detection of the intracellular as well as the secreted VTG-like protein. Electrophoretical analysis of the secretory products revealed the induction of a group of phosphoproteins immunologically related to yolk lipovitellin whose molecular weights range from 116,000 to 200,000.

Purpose A near-infrared (NIR) spectroscopic method was developed for real time analysis of the active pharmaceutical ingredient (API) in blends from a continuous manufacturing process. The sampling and analytical errors of these determinations were estimated through variographic analysis. Methods Thirty-three calibration blends were prepared in laboratory scale equipment with a concentration range spanning from 70 to 130% of API target concentration. The NIR calibration model was validated using three independent validation sets (prepared in laboratory and pilot plant facilities and in the CM equipment). Real-time NIR spectra were obtained with an interface where three NIR spectrometers monitored the CM process. A variographic study was performed with the NIR predictions of drug concentration in blends. Results A total of 1800 NIR spectra were obtained throughout a CM run that lasted 2.5 h. Two NIR spectrometers (M1 and M2) monitored the CM run while located in positions b-1 and b-3 of the sensing interface. These two positions yielded very similar results. The average NIR predictions for blends were 101.67% LC for the first run using spectrometer M1 and 103.60% LC with M2. The second run provided an average NIR prediction of 101.19% LC with M1 and 103.16% LC with M2. The average drug concentration in tablets was 100.63% LC for the first run and 100.42% LC for the second run. Variograms showed a low sill and a flat, stable variogram demonstrating good mixing of the blend. Conclusion The CM process provided tablets with excellent content uniformity. The sampling and analytical errors and the true process variation were easily discerned through variographic analysis.

The term "Advanced Pharmaceutical Manufacturing" (APM) has become an ubiquitous buzzword with deep potential policy implications. There is a real danger that APM will be seen as a general panacea for solving economic woes and drug shortages, devoiding it from specific meaning, and depriving the technical community of focus much needed for its development and implementation. This paper first discusses several semantic definitions of APM that have been proposed in the field. A functional definition of APM is then presented as: A system that is designed using predictive models, where automation minimizes human intervention while enabling closed loop process control and real time quality assurance, where performance has been optimized to maximize desired process goals, where flexible amounts of product with equivalent attributes can be manufactured, and where equivalent processes can be implemented at multiple locations to manufacture products with equivalent critical quality attributes. The proposed definition is presented to motivate discussion and elicit contributions from other stakeholders, and to contribute to the development of a consensus framework for design, development, implementation, and evaluation of APM.