Search results for "techniques"

Margination of Fluorescent Polylactic Acid-Polyaspartamide based Nanoparticles in Microcapillaries In Vitro: the Effect of Hematocrit and Pressure.

2017

The last decade has seen the emergence of vascular-targeted drug delivery systems as a promising approach for the treatment of many diseases, such as cardiovascular diseases and cancer. In this field, one of the major challenges is carrier margination propensity (i.e., particle migration from blood flow to vessel walls); indeed, binding of these particles to targeted cells and tissues is only possible if there is direct carrier–wall interaction. Here, a microfluidic system mimicking the hydrodynamic conditions of human microcirculation in vitro is used to investigate the effect of red blood cells (RBCs) on a carrier margination in relation to RBC concentration (hematocrit) and pressure drop…

Mechanism of action of Rhodiola, salidroside, tyrosol and triandrin in isolated neuroglial cells: An interactive pathway analysis of the downstream e…

2014

Abstract Aim The aim of this study was to identify the targets (genes, interactive signaling pathways, and molecular networks) of Rhodiola rosea extract in isolated neuroglia cells and to predict the effects of Rhodiola extract on cellular functions and diseases. In addition, the potential mechanism of action of Rhodiola rosea extract was elucidated, and the “active principle” among the three isolated constituents (salidroside, triandrin, and tyrosol) was identified. Methods Gene expression profiling was performed using the T98G human neuroglia cell line after treatment with the Rhodiola rosea SHR-5 extract and several of its individual constituents (salidroside, triandrin and tyrosol). An …

Long-term expression of the human alpha1-antitrypsin gene in mice employing anionic and cationic liposome vector.

1997

The complete process of gene therapy involves three important steps: targeting, delivery, and gene expression. Since each step can be related to the pharmacological concept of affinity, bioavailability, and intrinsic capacity, this commentary examines, from this perspective, the efficiency of anionic and cationic liposomes as vectors for the in vivo gene transfer of the human alpha1-antitrypsin gene. Small liposomes represent the first generation of liposomes destined for the liver parenchymal cell. Although the final efficiency of gene transfer is low, we found that small liposomes are a kind of high-affinity hepatocyte-destined vector because the dose range for mediating the response is t…

Arachidonic acid relaxes human pulmonary arteries through K+ channels and nitric oxide pathways.

2004

We aimed to investigate the role of K(+) channels and nitric oxide (NO) on the relaxant effects of arachidonic acid in the human intralobar pulmonary arteries. Arachidonic acid produced a concentration-dependent relaxation (E(max)=93+/-3% of maximal relaxation induced by papaverine 0.1 mM;-log EC(30)=7.03+/-0.09) that was antagonized by the cyclooxygenase inhibitor indomethacin (1 microM), by the combination of cyclooxygenase blockade and cytochrome P450 (CYP) blockade with 17-octadecynoic acid (17-ODYA, 10 microM), by the combination of cyclooxygenase inhibition and NO synthase (NOS) inhibition with N(omega)-nitro-l-arginine (l-NOARG, 100 microM), by the simultaneous inhibition of CYP and …

The main determinant of furosemide inhibition on GABA(A) receptors is located close to the first transmembrane domain.

1998

Inhibitory GABA(A) receptors are regulated by numerous allosteric modulators, the most receptor-subtype specific of which is furosemide. It recognises receptors of the subunit composition alpha6beta2/3gamma2, restricted to cerebellar granule cells. To locate furosemide's site of action we constructed chimeras of the furosemide-sensitive alpha6 and the furosemide-insensitive alpha1 subunit, and expressed and studied them together with the beta3 and gamma2 subunits in Xenopus oocytes by the two-electrode voltage clamp technique. The inhibition of GABA-induced currents by furosemide mainly depended on a short domain proximal to the first transmembrane region of the alpha6 subunit.

The ionic dependence of calcium efflux from guinea pig auricles.

1968

Hepatocyte cell lines: their use, scope and limitations in drug metabolism studies.

2006

Gaining knowledge on the metabolism of a drug, the enzymes involved and its inhibition or induction potential is a necessary step in pharmaceutical development of new compounds. Primary human hepatocytes are considered a cellular model of reference, as they express the majority of drug-metabolising enzymes, respond to enzyme inducers and are capable of generating in vitro a metabolic profile similar to what is found in vivo. However, hepatocytes show phenotypic instability and have a restricted accessibility. Different alternatives have been explored in the past recent years to overcome the limitations of primary hepatocytes. These include immortalisation of adult or fetal human hepatic cel…

Variability of permeability estimation from different protocols of subculture and transport experiments in cell monolayers.

2014

Abstract Introduction In vitro models with high predictive ability have been revealed as strong tools for pharmaceutical industry. However, the variability in permeability estimations complicates the comparison and combination of data from different laboratories and it makes necessary the careful validation of the model and the continuous suitability demonstration. The adequate standardization of pre-experimental, experimental and post-experimental factors might help to reduce the inter- and intra-laboratory variability in permeability values. Methods The objective of this paper is the evaluation of the effect of passage number, experimental protocol, time after seeding and calculation meth…

Effects of (+)-tubocurarine on [3H]acetylcholine release from the rat phrenic nerve at different stimulation frequencies and train lengths

1987

The effect of (+)-tubocurarine (TC) on the release of [3H]acetylcholine from the rat phrenic nerve-hemidiaphragm preincubated with [3H]choline was investigated at different stimulation frequencies and train lengths. At 0.5 Hz (100 pulses) TC failed to modulate the evoked acetylcholine release. A slight (30%) inhibition was observed at 1 Hz (100 pulses). Release of acetylcholine evoked at 5, 25 and 50 Hz (100 pulses) or 100 Hz (200 pulses) was markedly reduced by TC. The degree of inhibition (60%) was similar between 5 Hz and 100 Hz. A concentration of 1 mumol/l TC was a maximal effective concentration at 5 Hz whilst at all higher stimulation frequencies a 10-fold higher concentration was ne…

Didactic video as an alternative to in vivo assays in practical lessons of pharmacology

2010

La Farmacología es una ciencia eminentemente práctica, en la que tiene gran relevancia la investigación "in vivo" con animales de experimentación. Los conocimientos impartidos en las clases teóricas, seminarios y tutorías, se completan con la enseñanza en las sesiones prácticas. Sin embargo, algunos aspectos importantes de esta enseñanza práctica, que incluyen la realización de ensayos “in vivo”, resulta problemático impartirlos correctamente con la normativa actual sobre la utilización de animales de laboratorio. Por ello, nos planteamos la realización de unos vídeos demostrativos de las técnicas experimentales utilizadas en algunas de las sesiones prácticas de las asignaturasde Farmacolog…