Search results for "Wistar"
showing 10 items of 1094 documents
Spontaneous Epileptic Manifestations in a DCX Knockdown Model of Human Double Cortex
2010
Previous reports indicate that in utero knockdown of doublecortin (DCX) results in the genesis of a subcortical heterotopia reminiscent of the doublecortex observed in female patients with DCX mutations. It has also been shown that these rats display an increased susceptibility to convulsant agents and increased cortical neurons excitability; but it is presently unknown whether they display spontaneous seizures. Furthermore, the link between the size of heterotopia and the clinical manifestation remained to be elucidated. Using video--electrocorticogram recordings, we now report that DCX knockdown induces frequent spontaneous seizures commonly associated with myoclonic jerks in adult rats. …
Chronic fluoxetine treatment in middle-aged rats induces changes in the expression of plasticity-related molecules and in neurogenesis
2012
Abstract Background Antidepressants promote neuronal structural plasticity in young-adult rodents, but little is known of their effects on older animals. The polysialylated form of the neural cell adhesion molecule (PSA-NCAM) may mediate these structural changes through its anti-adhesive properties. PSA-NCAM is expressed in immature neurons and in a subpopulation of mature interneurons and its expression is modulated by antidepressants in the telencephalon of young-adult rodents. Results We have analyzed the effects of 14 days of fluoxetine treatment on the density of puncta expressing PSA-NCAM and different presynaptic markers in the medial prefrontal cortex, hippocampus and amygdala of mi…
Peroxisome proliferator-activated receptor γ ligands regulate neural stem cell proliferation and differentiation in vitro and in vivo.
2011
Peroxisome proliferator-activated receptor gamma (PPARγ) belongs to a family of ligand-activated nuclear receptors and its ligands are known to control many physiological and pathological situations. Its role in the central nervous system has been under intense analysis during the last years. Here we show a novel function for PPARγ in controlling stem cell expansion in the adult mammalian brain. Adult rats treated with pioglitazone, a specific ligand of PPARγ, had elevated numbers of proliferating progenitor cells in the subventricular zone and the rostral migratory stream. Electron microscopy analysis also showed important changes in the subventricular zone ultrastructure of pioglitazone-t…
Chronic cocaine exposure impairs progenitor proliferation but spares survival and maturation of neural precursors in adult rat dentate gyrus
2006
Recent observations indicate that drugs of abuse, including alcohol and opiates, impair adult neurogenesis in the hippocampus. We have studied in rats the impact of cocaine treatment (20 mg/kg, daily, i.p.) on cell proliferation, survival and maturation following short-term (8-day) and long-term (24-day) exposure. Using 5'-bromo-2-deoxyuridine (BrdU) and Ki-67 as mitotic markers at the end of the drug treatments, we found that both short- and long-term cocaine exposures significantly reduced cell proliferation in the dentate gyrus (DG) of the hippocampus. By labelling mitotic cells with BrdU pulses before or during the early stages of the drug treatment, we determined that long-term cocaine…
Drug gastrointestinal absorption in rat: Strain and gender differences.
2015
Predictive animal models of intestinal drug absorption are essential tools in drug development to identify compounds with promising biopharmaceutical properties. In situ perfusion absorption studies are routinely used in the preclinical setting to screen drug candidates. The objective of this work is to explore the differences in magnitude and variability on intestinal absorption associated with rat strain and gender. Metoprolol and Verapamil absorption rate coefficients were determined using the in situ closed loop perfusion model in four strains of rats and in both genders. Strains used were Sprague-Dawley, Wistar-Han, Wistar-Unilever, Long-Evans and CD∗IGS. In the case of Metoprolol only…
New antitrichomonal drug-like chemicals selected by bond (edge)-based TOMOCOMD-CARDD descriptors.
2008
Bond-based quadratic indices, new TOMOCOMD-CARDD molecular descriptors, and linear discriminant analysis (LDA) were used to discover novel lead trichomonacidals. The obtained LDA-based quantitative structure-activity relationships (QSAR) models, using nonstochastic and stochastic indices, were able to classify correctly 87.91% (87.50%) and 89.01% (84.38%) of the chemicals in training (test) sets, respectively. They showed large Matthews correlation coefficients of 0.75 (0.71) and 0.78 (0.65) for the training (test) sets, correspondingly. Later, both models were applied to the virtual screening of 21 chemicals to find new lead antitrichomonal agents. Predictions agreed with experimental resu…
Cationic Supramolecular Vesicular Aggregates for Pulmonary Tissue Selective Delivery in Anticancer Therapy
2016
The biopharmaceutical properties of supramolecular vesicular aggregates (SVAs) were characterized with regard to their physicochemical features and compared with cationic liposomes (CLs). Neutral and cationic SVAs were synthesized using two different copolymers of poly(aspartyl hydrazide) by thin-layer evaporation and extrusion techniques. Both copolymers were self-assembled in pre-formulated liposomes and formed neutral and cationic SVAs. Gemcitabine hydrochloride (GEM) was used as an anticancer drug and loaded by a pH gradient remote loading procedure, which significantly increased drug loading inside the SVAs. The resulting average size of the SVAs was 100 nm. The anticancer activity of …
In vitro and in vivo characterization of a new organic nitrate hybrid drug covalently bound to pioglitazone.
2014
<b><i>Background/Aims:</i></b> Organic nitrates represent a group of nitrovasodilators that are clinically used for the treatment of ischemic heart disease. The new compound CLC-3000 is an aminoethyl nitrate (AEN) derivative of pioglitazone, a thiazolidinedione antidiabetic agent combining the peroxisome proliferator-activated receptor &#947; agonist activity of pioglitazone with the NO-donating activity of the nitrate moiety. <b><i>Methods:</i></b> In vitro and in vivo characterization was performed by isometric tension recording, platelet function, bleeding time and detection of oxidative stress. <b><i>Results:</i></…
In-situ forming gel-like depot of a polyaspartamide-polylactide copolymer for once a week administration of Sulpiride
2015
Abstract Objectives An in-situ forming gel-like depot, prepared by using an appropriate polyaspartamide-polylactide graft copolymer, has been employed to release in a sustained way sulpiride. Methods α,β-poly(N-2-hydroxyethyl)-D,L-aspartamide-g-polylactic acid (PHEA-g-PLA) has been used as a polymer component. Its physicochemical properties make possible to dissolve it in N-methyl-2-pyrrolidone, with the obtainment of a solution able to form a gel-like depot once injected into a physiological medium. Cell compatibility of PHEA-g-PLA depot has been investigated, using murine dermal fibroblasts as cell model. 3-(4,5-Dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazo…
Effect of thickener on disintegration, dissolution and permeability of common drug products for elderly patients
2019
Dysphagia is a very common problem suffered by elderly patients. The use of thickeners during administration in these patients helps to prevent difficulties with swallowing larger solid dosage forms. However, there are several indications when the thickeners may influence disintegration and dissolution processes of solid dosage forms, potentially affecting therapeutic efficacy. In this paper the effects of a commonly used thickener on tablet disintegration, dissolution and subsequent absorption of 6 formulated drugs frequently used in elderly patients (Aspirin, Atenolol, Acenocumarol, Candesartan, Ramipril and Valsartan) in two different administration conditions (intact tablet and crushed …