Intravenous Reelin rescues despair-like behavior, Reelin cells in the dentate sub-granular zone, and spleen atrophy in the cyclic corticosterone model of recurring depressive episodes.

Novel antidepressants are predominantly evaluated preclinically in rodent models of chronic stress in which animals experience a single prolonged exposure to chronic stress prior to treatment. Rodent models of a single episode of chronic stress translate poorly to human depressive disorders, which are commonly marked by recurring depressive episodes. Intravenous administration of Reelin has previously been shown to resolve immobility in the forced swim test of rats exposed to a single prolonged exposure to chronic stress. To determine whether Reelin has antidepressant-like properties in a model of recurring depressive episodes, Long-Evans rats (N = 57) were exposed to multiple cycles of chronic stress and stress-free periods before the administration of a single injection of Reelin during the final cycle of chronic stress. The animals then performed in the forced swim test and open field test before the post-mortem evaluation of Reelin cell counts in the sub-granular zone of the dentate gyrus to determine the impact of treatment on hippocampal Reelin levels and spleen white pulp to evaluate the role of Reelin treatment in peripheral inflammation. The results show a single Reelin injection reversed elevated levels of immobility in the forced swim test in both male and female subjects exposed to the cyclic chronic stress model of recurring depressive episodes. Treatment with Reelin also restored Reelin-positive cell counts in the dentate gyrus sub-granular zone and reversed atrophy of spleen white pulp. The results shown here indicate that treatment with Reelin could effectively resolve alterations in forced swim test behavior caused by the cyclic corticosterone model of recurring depressive episodes and that Reelin homeostasis is important for regulating stress-related inflammation. Future preclinical antidepressant research should incorporate models of multiple depressive episodes to improve the translation of preclinical rodent research to human depressive disorders.

Estudio acelerado de estabilidad de didanosina:estudios preliminares / Accelerated stability study of didanosine: preliminary study

En este trabajo se ha llevado a cabo un estudio acelerado de estabilidad del fármaco didanosina (ddI), un análogo de nucleósido empleado en el tratamiento del síndrome de inmunodeficiencia adquirida (SIDA). Didanosina fue sometida a diferentes condiciones de temperatura y humedad durante 3 meses. Las muestras se analizaron por cromatografía líquida de alta resolución (HPLC); la linealidad, exactitud y precisión del método fueron adecuadas. De las condiciones estudiadas, los niveles superiores de temperatura y humedad fueron los que influyeron con mayor significación sobre la estabilidad del fármaco. (AU)

Eudragit RS-PM and Ethocel 100 Premium: influence over the behavior of didanosine inert matrix system.

Inert matrices of didanosine (ddI) were elaborated as controlled release dosage forms, using two different types of polymers: Eudragit RS-PM, an anionic acrylic acid copolymer, and Ethocel 100 Premium, an ethylcellulose. A preformulation study of the drug was designed to address the following points: (a) the development of two alternative methods (high performance liquid chromatography (HPLC) and UV spectrophotometry) for the analysis and quantifying of ddI; (b) the determination of the aqueous solubility of ddI; and (c) the characterization of ddI from the following points of view: morphological (scanning electronic microscopy (SEM)) and thermal (differential scanning calorimetry (DSC)). Furthermore, some of these techniques were used for the characterization of those components which will be included in the oral controlled release system to be developed. The in vitro release of ddI matrices was studied at pH 7.4, because of the instability of ddI at pH values lower than 3 units. A significant reduction in the release rate of drug from both ddI controlled release systems was found. Furthermore, Ethocel 100 Premium showed a minor efficiency in the dissolution process, with a reduction of more than double in the final dissolution efficiency (DE) value. This parameter and the fit factors (f1 and f2) have been compared for the characterization of dissolution profiles.

Alginate/chitosan particulate systems for sodium diclofenac release.

Alginate/chitosan particles were prepared by ionic gelation (Ca2+ and Al3+) for the sodium diclofenac release. The systems were characterized by electron microscopy and differential scanning calorimetry. The ability to release the active substance was examined as a function of some technological parameters and pH of dissolution medium. The release of sodium diclofenac is prevented at acidic pH, while is complete in a few minutes when pH is raised up to 6.4 and 7.2. The alginate/chitosan ratio and the nature of the gelifying cation allow a control of the release rate of the drug. The release mechanism was briefly discussed.

Effectiveness of repeated administration of a new oral naltrexone controlled-release system on morphine analgesia.

Naltrexone hydrochloride, an opioid antagonist used as an adjunct to the maintenance of the opioid-free state for detoxified individuals, was introduced into the polymeric structure of Eudragit L30D, an anionic copolymer based on polymethacrylic acid and ethylacrylate. From the results of a preclinical study, this complexation technique can be considered as a useful tool in the design of oral controlled-release systems (naltrexone-Eudragit L) capable of inducing long-lasting effects in-vivo. The biopharmaceutical characterization of the naltrexone-Eudragit L complex in comparison with naltrexone hydrochloride using the mouse hot-plate model has been previously carried out. The results showed a longer effect, an enhancement of 23.47% of the area under the curve of the inhibition of analgesic activity vs time, and a delay of 51.80% in the t1/2 value induced by the complex, compared with those induced by conventional naltrexone. In this study, a regimen of chronic administration of naltrexone-Eudragit L was established. Thus, in an 8-day treatment (4 doses in alternate days) this oral controlled-release system effectively antagonized the analgesic effect of morphine for 8 h, whereas naltrexone hydrochloride has to be administered over 16 days (8 doses in alternate days) to induce the same effect. In the 16-day schedule the complex-induced antagonism lasted over 14 h after administration.