Search results for "drug evaluation"
showing 10 items of 188 documents
Structure-based engineering of strictosidine synthase: auxiliary for alkaloid libraries.
2007
SummaryThe highly substrate-specific strictosidine synthase (EC 4.3.3.2) catalyzes the biological Pictet-Spengler condensation between tryptamine and secologanin, leading to the synthesis of about 2000 monoterpenoid indole alkaloids in higher plants. The crystal structure of Rauvolfia serpentina strictosidine synthase (STR1) in complex with strictosidine has been elucidated here, allowing the rational site-directed mutation of the active center of STR1 and resulting in modulation of its substrate acceptance. Here, we report on the rational redesign of STR1 by generation of a Val208Ala mutant, further describing the influence on substrate acceptance and the enzyme-catalyzed synthesis of 10-m…
ACELLULAR PERTUSSIS VACCINE COMPOSED OF GENETICALLY INACTIVATED PERTUSSIS TOXIN: SAFETY AND IMMUNOGENICITY IN 12- TO 24- AND 2-TO 4-MONTH-OLD CHILDREN
1992
To determine whether a nontoxic derivative of pertussis toxin obtained by recombinant DNA technology, PT-9K/129G, is a good candidate for a new pertussis vaccine, we examined the safety and the immunogenicity in children of a vaccine containing 15 micrograms of PT-9K/129G protein and 0.5 mg of aluminum hydroxide per dose. Fifty-three children 12 to 24 months of age and 21 infants aged 2 to 4 months were injected with two and three doses, respectively. The vaccine did not induce significant local or systemic reactions and elicited an increase of antibody titer in more than 98% of the children. The geometric mean of the toxin-neutralizing titers increased after each dose and was 85 units in c…
Application of Imprinted Synthetic Polymers in Binding Assay Development
2000
The first part of the review describes a method for the synthesis of molecularly imprinted polymers for use in binding assays. The method considers the many factors involved that affect the recognition properties of the materials and describes an approach to screening and optimization of these factors. The second part describes the development of binding assays using such polymers. This includes the use of different labels, the effect of solvent and buffer, the scale of the assay (amount of solid polymer), and how these influence the quality of the assay in terms of sensitivity, selectivity, and speed of analysis.
Luminometric sub-nanoliter droplet-to-droplet array (LUMDA) and its application to drug screening by phase I metabolism enzymes.
2012
Here we show the fabrication of the Luminometric Sub-nanoliter Droplet-to-droplet Array (LUMDA chip) by inkjet printing. The chip is easy to be implemented and allows for a multiplexed multi-step biochemical assay in sub-nanoliter liquid spots. This concept is here applied to the integral membrane enzyme CYP3A4, i.e. the most relevant enzymatic target for phase I drug metabolism, and to some structurally-related inhibitors.
Topical anti-inflammatory potential of quercetin in lipid-based nanosystems: In vivo and in vitro evaluation
2013
Purpose: To develop quercetin-loaded phospholipid vesicles, namely liposomes and PEVs (Penetration Enhancer-containing Vesicles), and to investigate their efficacy on TPA-induced skin inflammation. Methods: Vesicles were made from a mixture of phospholipids, quercetin and polyethylene glycol 400 (PEG), specifically added to increase drug solubility and penetration through the skin. Vesicle morphology and self-assembly were probed by Cryo-Transmission Electron Microscopy and Small/Wide Angle X-ray Scattering, as well as the main physico-chemical features by Light Scattering. The anti-inflammatory efficacy of quercetin nanovesicles was assessed in vivo on TPA-treated mice dorsal skin by the d…
Impact of
2018
Drosophila melanogaster has been for over a century the model of choice of several neurobiologists to decipher the formation and development of the nervous system as well as to mirror the pathophysiological conditions of many human neurodegenerative diseases. The rare disease Friedreich’s ataxia (FRDA) is not an exception. Since the isolation of the responsible gene more than two decades ago, the analysis of the fly orthologue has proven to be an excellent avenue to understand the development and progression of the disease, to unravel pivotal mechanisms underpinning the pathology and to identify genes and molecules that might well be either disease biomarkers or promising targets for therap…
One pot light assisted green synthesis, storage and antimicrobial activity of dextran stabilized silver nanoparticles.
2014
Background Green synthesis of nanomaterials finds the edge over chemical methods due to its environmental compatibility. Herein, we report green synthesis of silver nanoparticles (Ag NPs) mediated with dextran. Dextran was used as a stabilizer and capping agent to synthesize Ag NPs using silver nitrate (AgNO3) under diffused sunlight conditions. Results UV–vis spectra of as synthesized Ag nanoparticles showed characteristic surface plasmon band in the range from ~405-452 nm. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) studies showed spherical Ag NPs in the size regime of ~50-70 nm. Face centered cubic lattice of Ag NPs was confirmed by powder X-ray diffraction (PXRD…
Level of response and safety of pharmacological monotherapy in the treatment of acute bipolar I disorder phases: a systematic review and meta-analysi…
2010
In recent years, combinations of pharmacological treatments have become common for the treatment of bipolar disorder type I (BP I); however, this practice is usually not evidence-based and rarely considers monotherapy drug regimen (MDR) as an option in the treatment of acute phases of BP I. Therefore, we evaluated comparative data of commonly prescribed MDRs for both manic and depressive phases of BP I. Medline, PsycINFO, EMBASE, the Cochrane Library, the ClinicalStudyResults.org and other data sources were searched from 1949 to March 2009 for placebo and active controlled randomized clinical trials (RCTs). Risk ratios (RRs) for response, remission, and discontinuation rates due to adverse …
Effects of Mn2+ on the responses induced by different spasmogens in the oestrogen-primed rat uterus
1997
Abstract We investigated the effect of Mn 2+ on the mechanical responses evoked by high K + (60 mM) or low Na + (25 mM) solutions, oxytocin and neurokinin A in the oestrogen-primed rat uterus. In a Ca 2+ -free, Mn 2+ (0.54 mM)-containing solution, high K + or low Na + solutions produced contractions of smaller amplitude than those observed in a normal Ca 2+ (0.54 mM) solution, which were abolished by nifedipine (1 μM). Oxytocin (1 μM) and neurokinin A (1 μM, in the presence of phosphoramidon 1 μM) evoked nifedipine-insensitive contractile responses similar to (oxytocin) or smaller (neurokinin A) in amplitude than those observed in Ca 2+ (0.54 mM)-containing solution. In strips loaded with C…
The influence of ossein-hydroxyapatite compound ('Ossopan') on the healing of a bone defect.
1986
A study was undertaken in 60 adult rabbits in order to determine the effects of ossein-hydroxyapatite compound on bone healing. Standardized bony defects were produced in the distal femoral epiphyses, after which animals were randomized into four equal groups. An untreated group served as a control. One group received ossein-hydroxyapatite compound, 830 mg per day, a second group received bone mineral (ossein-hydroxyapatite compound reduced to ash, to remove organic constituents), 510 mg per day, and a third group received calcium carbonate, 650 mg per day. A series of fluorescent vital markers was administered to the animals from the 7th to the 32nd day after production of the defect. A th…