Search results for "Transporte"
showing 10 items of 743 documents
Induction of Human P-Glycoprotein in Caco-2 cells: Development of a Highly Sensitive Assay System for P-Glycoprotein-Mediated Drug Transport
2006
The aim of this work is to develop a highly sensitive assay system for P-gp-mediated transport by using two methods, induction of P-gp and short-term culture of Caco-2 cells. To induce P-gp in Caco-2 cells, cells were cultured in vinblastine-containing medium. The mRNA level of P-gp was approximately 7-fold higher in Caco-2 cells cultured with vinblastine (P-gp-induced Caco-2 cells) than in control cells. Western blot analysis showed a significant increase in P-gp expression. After cell differentiation, the mRNA level of P-gp was downregulated, however, P-gp-induced Caco-2 cells still possessed a 5.6-fold higher mRNA level of P-gp compared to control cells. Polarized transport of substrate …
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…
Pharmacogenomic and molecular docking studies on the cytotoxicity of the natural steroid wortmannin against multidrug-resistant tumor cells
2014
Wortmannin is a cytotoxic compound derived from the endophytic fungi Fusarium oxysporum, Penicillium wortmannii and Penicillium funiculosum that occurs in many plants, including medicinal herbs. The rationale to develop novel anticancer drugs is the frequent development of tumor resistance to the existing antineoplasic agents. Therefore, it is mandatory to analyze resistance mechanisms of novel drug candidates such as wortmannin as well to bring effective drugs into the clinic that have the potential to bypass or overcome resistance to established drugs and to substantially increase life span of cancer patients. In the present project, we found that P-glycoprotein-overexpressing tumor cells…
Multifactorial nature of hepatocellular carcinoma drug resistance: Could plant polyphenols be helpful?
2007
Primary hepatocellular carcinoma (HCC) is a quite frequent tumor which results in high mortality and most often exhibits a poor response to present drug therapies. Clearly, a thorough understanding of the biological bases of this malignancy might suggest new strategies for its treatment. Here we examine the evidences that both "pharmacological" mechanisms (e.g. drug transporter or detoxification enzyme over-expression) and alterations in other critical factors, including the IAPs (Inhibitory of Apoptosis Proteins), involved in enhancement of cell survival and proliferation may determine the therapeutic resistance of HCC; we also underline the possible role in the process of the activation o…
A high-quality homology model for the human dopamine transporter validated for drug design purposes.
2018
The human dopamine transporter (hDAT) plays many vital functions within the central nervous system and is thus targeted by many pharmaceutical agents. Dopamine-related therapies are in current development for individuals with dopamine-related disorders including depression, Parkinson's disease, and psychostimulant addictions such as cocaine abuse. Yet, most efforts to develop new dopamine therapies are within costly structure-activity relationship studies. Through structure-based drug design techniques, the binding site of hDAT can be utilized to develop novel selective and potent dopamine therapies at reduced costs. However, no structural models of hDAT specifically validated for rational …
Biowaiver Monographs for Immediate Release Solid Oral Dosage Forms: Metformin Hydrochloride.
2021
Abstract Data are examined regarding possible waiver of in vivo bioequivalence testing (i.e. biowaiver) for approval of metformin hydrochloride (metformin) immediate-release solid oral dosage forms. Data include metformin's Biopharmaceutics Classification System (BCS) properties, including potential excipient interactions. Metformin is a prototypical transporter-mediated drug and is highly soluble, but only 50% of an orally administered dose is absorbed from the gut. Therefore, metformin is a BCS Class III substance. A BCS-based approval approach for major changes to marketed products and new generics is admissible if test and reference dosage forms have the identical active pharmaceutical …
Relevance of Multidrug Resistance Proteins on the Clinical Efficacy of Cancer Therapy
2005
Variations in drug uptake and efflux, as well as changes in intracellular drug entrapment and distribution may represent important resistance mechanisms to cancer therapy. A variety of ATP binding cassette transporters (ABC) localised in multiple cell membranes is implied in those phenomena, representing a mechanism of protection of cells against xenobiotics. Many cancer cell lines over express some ABC transporters, especially p-glycoprotein, MRP1 and BCRP. This over expression is related to worse cancer treatment outcome and, in some cases, reduced overall survival of cancer patients. This paper reviews the location and physiological role of the three transporters mentioned and also descr…
Induction of Drug Transporters Alters Disposition of Risperidone - A Study in Mice
2010
Pharmacokinetic interactions, e.g. modulation of drug transporters like P-glycoprotein at the blood-brain barrier, can be a reason for treatment non-response. This study focuses on the influence of induction of drug transporters on the disposition of the antipsychotic drugs risperidone and 9-hydroxyrisperidone. Brain and serum concentrations of risperidone and its active metabolite 9-hydroxyrisperidone, which are known P-glycoprotein substrates, were measured after drug transporter induction with rifampicin, dexamethasone or 5-pregnene-3beta-ol-20-on-16alpha-carbonitrile using high performance liquid chromatography. Disposition of risperidone and 9-hydroxyrisperidone was dramatically decrea…
Relevancia clínica de la selectividad de los inhibidores del cotransportador sodio-glucosa tipo 2
2016
Selectivity is the property of a drug to preferentially bind to a biological structure. Most drugs can bind and stimulate or inhibit more than one system. Therefore, it is important that they are selective for the intended site and that the doses used do not have effects on other sites, which could provoke adverse reactions. Selectivity is assessed through in vitro experiments on organs or isolated cells. If the aim is to compare drugs, the experiment should be conducted in the same tissue and with the same design. Even so, the results cannot be directly extrapolated to clinical practice due to the influence of pharmacokinetic properties, which allow an adequate dose of the drug to reach th…
Intracellular retention of ABL kinase inhibitors determines commitment to apoptosis in CML cells
2012
PLoS one 7(7), e40853 (2012). doi:10.1371/journal.pone.0040853