Forced stress test

Fig. 1. Forced stress test. Results of automatic optimization of the separation of an active pharmaceutical ingredient (API) impurities and degradation products are present at concentration levels of 0.01-0.7% relative to the API. Software ChromSword 3.1, ChemStation 10.2. Agilent 1100 HPLC system. Column Inertsil ODS-3, 5 pm, 15 cm x 4.6 mm.

Behavioral alterations induced by stressful experiences frequently include increased anxiety-related behavior. Accordingly, anxiety has been hypothesized to play a role in stress-coping behavior (Ferre et al. 1994). The most regularly used tests for stress-coping behavior is the so-called forced swim test, which has been developed by Porsolt et al. (1977) as a behavioral paradigm to identify compounds with antidepressant efficacy in humans Mice or rats are forced to... 

West PA (1990) Neimobehavioral studies of forced swimming. The role of learning and memory in the forced swim test ProgNeimopsychopharmacol Biol Psychiatry 14 863-875 WUlner P (1997) Validity, reliability and utility of the chronic mild stress model of depression a 10-year review and evaluation. Psychopharmacology (Berl) 134 319-329 WUlner P, Muscat R, Papp M (1992) Chronic mUd stress-induced anhedonia a realistic animal model of depression. Neimosci Biobehav Rev 16 525-534 WUson JH (2000) A conspecific attenuates prolactin responses to open-field exposure in rats. Horm Behav 38 39-43... 

In humans, the antidepressant activity of NMDA receptor antagonists has not been evaluated extensively (Skohiick 1999). In animal models of depression, NMDA receptor antagonists have been reported to exert positive effects in most studies (Trullas 1997). This concerns mainly the forced swim test (Maj 1992 Moryl et al. 1993 PrzegaUnski et al. 1997) and stress-induced anhe-donia (Papp and Moryl 1994). Amantadine but not memantine was effective against reserpine-induced hypothermia (Moryl et al. 1993). In the forced swim test, both amino-adamantanes produced specific antidepressive-like activity (Moryl et al. 1993). 

Stogner KA, Holmes PV (2000) Neuropeptide-Y exerts antidepressant-like effects in the forced swim test in rats. Eur J Pharmacol 387 R9-R10 Stout SC, Owens MJ, Nemeroff CB (2002) Regulation of corticotropin-releasing factor neuronal systems and hypothalamic-pituitary-adrenal axis activity by stress and chronic antidepressant treatment. J Pharmacol Exp Ther 300 1085-1092 StrOhle A, Jahn H, Montkowski A, Liebsch G, Boll E, Landgraf R, Holsboer F, Wiedemann K (1997) Central and peripheral administration of atriopeptin is anxiolytic in rats. Neuroendocrinology 65 210-215... 

ASTM D575105 does not primarily recommend the generation of a stress/strain curve but details two methods - force at given deflection and deflection at given force. The test piece is a cylinder 28.6 0.1 mm diameter and 12.5 0.5 mm thick from which all moulded surface layers have been removed. The removal of moulded surfaces is presumably to eliminate skin effects, although such effects, if significant, would be present in a moulded product and one would expect to test in the same condition. 

Stress testing is conducted to provide data on forced decomposition products and decomposition mechanisms for the drug substance. 

Recent publications on the topic of stress testing/forced degradation studies reveal that there is still a tremendous variability in the conditions... 

As described in the PhRMA Available Guidance and Best Practices article on forced degradation studies (12), stress testing should include condi-... 

Table 1 General Protocol for Forced Degradation Studies (Stress Testing) of Drug Substance and Drug Products...

Once a story is developed, it is crucial to stress test it. This can be achieved by looking at it from the viewpoint of the different audiences, such as customers, investors, or employees how would this particular audience respond to the telling of the current story What does it take to turn skeptics into believers and passive onlookers into active participants The next test would be to develop a full story variant for each audience. The variants for employees may be extended further in a story cascade . What form does the story take for key groups, such as business units, functional units, and front-line teams Is this a good story for the R D personnel, one that will increase the company s momentum in innovation Will the sales force be sufficiently excited and motivated by the story to reach the required sales volumes Of course, it is not really possible to define precisely what the story will mean to an audience, group, or particular individual. In the end, everyone connected with the corporation will tell their own version, but ideally in close alignment with the general theme. 

This interpretation of immobility in the forced swim test has been challenged numerous times since its creation. It was proposed that these behaviors are not emotional responses to stressful situations, but a learned response that occurs during extended or between successive swim exposures. The learned response might be considered an adaptive strategy used to conserve energy required for swimming and survival [for review see 4], Based on these interpretations, it was suggested that antidepressants may decrease immobility by... 

FTMA is a forced vibration test method based on direct measurement of stress and strain spectra. As with all forced vibration methods, FTMA is subject to spurious wave effects at high frequencies. The lower frequency limit is determined by transducers, signal conditioners, etc. The lower limit in this research was 35 Hz as determined by the inherent properties of the piezoelectric transducers. With different transducers (for example load cell for the force and LVDT for displacement measurements) and signal conditioners, FTMA should measure material properties down to much lower frequencies. 

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