Search results for "drug evaluation"
showing 10 items of 188 documents
Rotarod impairment: catalepsy-like screening test for antipsychotic side effects.
2009
Extrapyramidal motoric symptoms are casual side effects under antipsychotic medication. New generation antipsychotics are expected to have a reduced risk due to different receptor affinities. Here, haloperidol and the new generation antipsychotics, risperidone, amisulpride, and aripiprazole, were examined with both catalepsy test and rotarod performance test to screen for their usability in mice. Mice treated with haloperidol, risperidone, and aripiprazole showed dose and time-dependent impairment. Amisulpride-treated mice showed no signs of catalepsy. Catalepsy test and rotarod performance test were useful methods to detect side effects of both generation antipsychotics. Catalepsy test pro…
Effects of clozapine metabolites and chronic clozapine treatment on rat brain GABAA receptors
1996
Abstract Similarly to clozapine, a clozapine metabolite, N -desmethylclozapine, but not clozapine N -oxide, antagonized brain γ-aminobutyric acid type A (GABA A ) receptors at high micromolar concentrations. However, daily subcutaneous injections of clozapine (10 and 25 mg/kg) and haloperidol (0.5 mg/kg) for 14 days failed to alter the modulation by GABA of rat cerebrocortical and cerebellar benzodiazepine ([ 3 H]flunitrazepam) or convulsant ( t -[ 35 S]bicyclophosphorothionate) binding sites of the GABA A receptor. The results thus suggest that the GABA A receptor antagonism exerted by chronic in vivo clozapine treatment is weak as compared to this treatment's actions on certain monoamine …
Enhanced serum levels of soluble HLA class I molecules are induced by treatment with recombinant interferon-gamma (IFN-γ)
1991
SUMMARY In order to investigate serum levels of soluble HLA class I antigens after single injection of various doses of recombinant IFN-γ (rIFN-γ) and to correlate the changes observed to beta-2-microglobulin serum levels, we studied five patients with metastasizing renal cell carcinoma. Each patient received three treatment cycles of 10, 100 and 500 μg rIFN-γ three times at weekly intervals. The treatment cycles were separated by a therapy-free interval of 2 weeks. The order of dose levels was randomly assigned to each patient. Serum levels of soluble HLA class I proteins were measured by an ELISA in samples drawn immediately before and 4, 24, 48, 72 and 168 h after each administration of …
The efficacy of BCG TICE and BCG Connaught in a cohort of 2,099 patients with T1G3 non–muscle-invasive bladder cancer
2016
BACKGROUND Potential differences in efficacy of different bacillus Calmette-Guerin (BCG) strains are of importance for daily practice, especially in the era of BCG shortage. OBJECTIVE To retrospectively compare the outcome with BCG Connaught and BCG TICE in a large study cohort of pT1 high-grade non-muscle-invasive bladder cancer patients. DESIGN, SETTING, AND PARTICIPANTS Individual patient data were collected for 2,451 patients with primary T1G3 tumors from 23 centers who were treated with BCG for the first time between 1990 and 2011. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Using Cox multivariable regression and adjusting for the most important prognostic factors in this nonrandomiz…
Drug release from alpha,beta-poly(N-2-hydroxyethyl)-DL-aspartamide-based microparticles.
2004
Abstract Spherical pH-sensitive microparticles have been prepared by reverse phase suspension polymerization technique. Starting polymer has been α , β -poly( N -2-hydroxyethyl)- dl -aspartamide (PHEA) partially derivatized with glycidylmethacrylate (GMA). PHEA-GMA copolymer (PHG) has been crosslinked in the presence of acrylic acid (AA) or methacrylic acid (MA) at various concentration. The obtained microparticles have been characterized by FT-IR spectrophotometry, particle size distribution analysis and scanning electron microscopy. In order to have information about water affinity of the prepared samples, swelling measurements have been carried out in aqueous media which simulate some bi…
Evaluation of the cytotoxic effect of 7keto-stigmasterol and 7keto-cholesterol in human intestinal (Caco-2) cells
2012
The biological implications of cholesterol oxidation products have been investigated, though research on plant sterol oxidation products is scarce and in some cases contradictory. The cytotoxicity of 7keto(k)-stigmasterol versus 7keto(k)-cholesterol at different concentrations (0-120 μM) and incubation times (4-24h), in intestinal epithelial cells (Caco-2 cells) was evaluated. The 3-[4,5-dimethylthiazol-2-yl]-2,3-diphenyl tetrazolium bromide and neutral red uptake tests, mitochondrial membrane potential (ΔΨm), and relative DNA and RNA contents in the cell cycle phases were determined. Possible interaction effects between 7k-derivatives or non-oxidized stigmasterol were monitored. Endo/lysos…
Computational Identification of Chemical Compounds with Potential Activity against Leishmania amazonensis using Nonlinear Machine Learning Techniques.
2019
Leishmaniasis is a poverty-related disease endemic in 98 countries worldwide, with morbidity and mortality increasing daily. All currently used first-line and second-line drugs for the treatment of leishmaniasis exhibit several drawbacks including toxicity, high costs and route of administration. Consequently, the development of new treatments for leishmaniasis is a priority in the field of neglected tropical diseases. The aim of this work is to develop computational models those allow the identification of new chemical compounds with potential anti-leishmanial activity. A data set of 116 organic chemicals, assayed against promastigotes of Leishmania amazonensis, is used to develop the the…
Inhibitors of inducible NO synthase expression: total synthesis of (S)-curvularin and its ring homologues.
2008
(S)-Curvularin and its 13-, 14-, and 16-membered lactone homologues were synthesized through a uniform strategy in which a Kochi oxidative decarboxylation and ring-closing metathesis reactions constitute the key processes. In the evaluation of the anti-inflammatory effects of the synthesized compounds in assays using cells stably transfected with a human iNOS promoter-luciferase reporter gene construct, the 14- and 16-membered homologues showed a slightly higher inhibitory effect towards iNOS promoter activity than curvularin itself. However, the larger ring homologues also exhibited higher cytotoxicity, manifest in downregulated eNOS promoter activity. In contrast, the di-O-acetyl and 4-ch…
Molecular topology as novel strategy for discovery of drugs with aβ lowering and anti-aggregation dual activities for Alzheimer's disease.
2014
Background and Purpose: In this study, we demonstrate the use of Molecular topology (MT) in an Alzheimer's disease (AD) drug discovery program. MT uses and expands upon the principles governing the molecular connectivity theory of numerically characterizing molecular structures, in the present case, active anti-AD drugs/agents, using topological descriptors to build models. Topological characterization has been shown to embody sufficient molecular information to provide strong correlation to therapeutic efficacy. Experimental Approach: We used MT to include multiple bioactive properties that allows for the identification of multifunctional single agent compounds, in this case, the dual func…
Targeting the Class A Carbapenemase GES-5 via Virtual Screening
2020
The worldwide spread of &beta