Search results for " Inhibition"
showing 10 items of 435 documents
Enzyme Inhibition Microassays on Blu-Ray Disks for Drug Discovery
2019
[EN] An enzyme inhibition-based assay for drug discovery developed by microarraing on Blu-ray disks is presented. As a proof-of-concept, the system screens a selected molecule library of potential chemical inhibitors against the glycoenzyme peroxidase, identifying the promising lead compounds with high selectivity using standard Blu-ray disks and drives. In order to face the first drug discovery stages, we establish the bases for a high-throughput screening assay and a methodology based on hypersurfaces suitable to manage a high number of data as well.
Possible Contribution of T-pattern Detection and Analysis to the Study of the Behavioral Correlates of Afferent Inhibition.
2020
A pivotal tenet in modern behavioral sciences is that the study of behavior, in its most intimate structure, necessarily deals with time and, for this reason, behavioral dynamics are not intuitively perceivable and/or detectable (Eibl-Eibesfeldt, 1970). In reality, the possibility to describe a given behavior in terms of its structural/temporal features makes available new and detailed information otherwise unavailable. The aim of the present paper is to discuss the possible application of T-pattern detection and analysis, i.e., a multivariate approach specifically developed to describe the temporal structure of behavior, to the study of an important and still scantly investigated issue, na…
Mutant HRAS as novel target for MEK and mTOR inhibitors.
2015
HRAS is a frequently mutated oncogene in cancer. However, mutant HRAS as drug target has not been investigated so far. Here, we show that mutant HRAS hyperactivates the RAS and the mTOR pathway in various cancer cell lines including lung, bladder and esophageal cancer. HRAS mutation sensitized toward growth inhibition by the MEK inhibitors AZD6244, MEK162 and PD0325901. Further, we found that MEK inhibitors induce apoptosis in mutant HRAS cell lines but not in cell lines lacking RAS mutations. In addition, knockdown of HRAS by siRNA blocked cell growth in mutant HRAS cell lines. Inhibition of the PI3K pathway alone or in combination with MEK inhibitors did not alter signaling nor had an imp…
Plasma membrane glycoproteins covalently bound to silica beads as a model for molecular studies of cell-cell interactions in culture.
1987
Abstract In previous studies, we have shown that plasma membrane glycoproteins are of major importance in the density-dependent regulation of growth of normal diploid fibroblasts. Due to the hydrophobic portions of these molecules, functional studies in cell culture are often diffucult to perform and to interpret. Specially, the addition of these molecules in soluble form to cell culture, after depletion of detergents needed for their solubilization, leads to aggregation and internalization. Therefore, we developed a method for the covalent immobilization of the solubilized plasma membrane proteins to derivatized silica beads for further investigations on the molecular nature of the active …
Immunology of dermatophytosis
1983
By causing experimental lesions of dermatophytosis in rabbits inoculated and reinoculated with T. mentagrophytes var. granulosum and T. rubrum a study was carried out of the state of cellular immunity response, during infection, and also of the antigens responsible for the sensitization. Cellular immunity response was detected using the leucocyte migration test (L.M.T.) in the presence of antigenic compounds of the 'Keratinase' of Eleuterio et al.
Expression of inhibitory glycine receptors in postnatal rat cerebral cortex.
1993
The developmental expression of inhibitory glycine receptors was analyzed in postnatal rat cerebral cortex using the specific monoclonal antibody, MAb 4a. This antibody defines an epitope common to all known glycine receptor alpha-subunits. At birth, high levels of immunoreactivity were found, which transiently increased during the second postnatal week, but subsequently declined to low adult levels. Biochemical analysis of the MAb 4a antigen from parietal areas indicates that cortical glycine receptors correspond to the neonatal receptor isoform previously identified in spinal cord of newborn animals. Immunocytochemistry showed that, within 2 weeks after birth, MAb 4a-reactive glycine rece…
Human Prostate Cancer: A Direct Role for Oestrogens
2007
We have studied the response to oestrogen and expression of oestrogen receptors in responsive LNCaP and androgen non-responsive PC3 human prostate cancer cell lines. Growth of LNCaP cells is significantly stimulated by physiological concentrations of oestradiol; this growth increase appears to be comparable to that induced by either testosterone or dihydrotestosterone. In contrast, oestradiol significantly inhibits the proliferation of PC3 cells. We also present novel evidence for functional oestrogen binding in LNCaP cells. This evidence was first obtained by means of radioligand binding assays and was further corroborated using: (a) immunocytochemical analysis of oestrogen and progesteron…
Retinoid X receptor agonists impair arterial mononuclear cell recruitment through peroxisome proliferator-activated receptor-γ activation.
2012
Abstract Mononuclear cell migration into the vascular subendothelium constitutes an early event of the atherogenic process. Because the effect of retinoid X receptor (RXR)α on arterial mononuclear leukocyte recruitment is poorly understood, this study investigated whether RXR agonists can affect this response and the underlying mechanisms involved. Decreased RXRα expression was detected after 4 h stimulation of human umbilical arterial endothelial cells with TNF-α. Interestingly, under physiological flow conditions, TNF-α–induced endothelial adhesion of human mononuclear cells was concentration-dependently inhibited by preincubation of the human umbilical arterial endothelial cells with RXR…
In vivo antihypertensive mechanism of lactoferrin-derived peptides: Reversion of angiotensin I- and angiotensin II-induced hypertension in Wistar rats
2015
Novel peptides with antihypertensive effects in SHR rats have previously been identified in lactoferrin (LF) hydrolysates. To investigate their in vivo antihypertensive mechanism, we have assessed the blood pressure lowering effects of two of these LF-derived peptides (RPYL and DPYKLRP) in Wistar rats subjected to either angiotensin I- or angiotensin II-induced hypertension. Blood pressure was measured by the tail-cuff method, hypertension was induced by subcutaneous infusion of angiotensins, and then captopril, valsartan or LF-derived peptides orally administered. Angiotensin I- and angiotensin II-induced hypertension were reversed by captopril and valsartan, respectively. RPYL and DPYKLRP…
Study and modulation of human cortical excitability with transcranial magnetic stimulation.
1998
Transcranial magnetic stimulation (TMS) can be applied in different paradigms to obtain a measure of various aspects of cortical excitability. These different TMS paradigms provide information about different neurotransmitter systems, enhance our understanding about the pathophysiology of neuropsychiatric conditions, and in the future may be helpful as a guide for pharmacological interventions. In addition, repetitive TMS (rTMS) modulates cortical excitability beyond the duration of the rTMS trains themselves. Depending on rTMS parameters, a lasting inhibition or facilitation of cortical excitability can be induced. These effects can be demonstrated neurophysiologically or by combining rTMS…