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1.
Poor aqueous solubility is one of the recurrent drawbacks of many compounds in medicinal chemistry. To overcome this limitation, the dilution of drug candidates from stock solutions of an organic solvent is common practice. However, the precise characterisation of these compounds in aqueous solutions is often neglected, leading to some uncertainties regarding the nature of the actual active species. In this communication, we demonstrate that two ruthenium complexes previously reported by our group for their chemotherapeutic potential against cancer, namely [Ru(DIP)2(sq)](PF6) and [Ru(DIP)2(3-methoxysq)](PF6), where DIP is 4,7-diphenyl-1,10-phenanthroline, sq=semiquinonate and 3-methoxysq=3-methoxysemiquinonate, form colloids in water-DMSO (1 % v/v) mixtures that are invisible to the naked eyes. [Ru(DIP)2(3-methoxysq)](PF6) was found to form a highly stable and monodispersed colloid with nanoaggregates of ∼25 nm. In contrast, [Ru(DIP)2(sq)](PF6) was found to form large reticulates of mostly spherical aggregates which size was found to increase over time. The difference in size and shape distribution of drug candidates is of tremendous significance as the study of their biological activity might be severely affected. Overall, we strongly believe that these observations should be taken into account by the scientific community working on the development of metal-based drugs with poor water solubility. 相似文献
2.
Solenn Percelay Jean-Marie Billard Thomas Freret Annie Andrieux Michel Boulouard Valentine Bouet 《International journal of molecular sciences》2021,22(5)
For a better translation from treatment designs of schizophrenia to clinical efficiency, there is a crucial need to refine preclinical animal models. In order to consider the multifactorial nature of the disorder, a new mouse model associating three factors (genetic susceptibility—partial deletion of the MAP6 gene, early-life stress—maternal separation, and pharmacological treatment—chronic Δ-9-tetrahydrocannabinol during adolescence) has recently been described. While this model depicts a schizophrenia-like phenotype, the neurobiological correlates remain unknown. Synaptic transmission and functional plasticity of the CA1 hippocampal region of male and female 3-hit mice were therefore investigated using electrophysiological recordings on the hippocampus slice. While basal excitatory transmission remained unaffected, NMDA receptor (NMDAr)-mediated long-term potentiation (LTP) triggered by theta-burst (TBS) but not by high-frequency (HFS) stimulation was impaired in 3-hit mice. Isolated NMDAr activation was not affected or even increased in female 3-hit mice, revealing a sexual dimorphism. Considering that the regulation of LTP is more prone to inhibitory tone if triggered by TBS than by HFS, the weaker potentiation in 3-hit mice suggests a deficiency of intrinsic GABA regulatory mechanisms. Indeed, NMDAr activation was increased by GABAA receptor blockade in wild-type but not in 3-hit mice. This electrophysiological study highlights dysregulations of functional properties and plasticity in hippocampal networks of 3-hit mice, one of the mechanisms suspected to contribute to the pathophysiology of schizophrenia. It also shows differences between males and females, supporting the sexual dimorphism observed in the disorder. Combined with the previously reported study, the present data reinforce the face validity of the 3-hit model that will help to consider new therapeutic strategies for psychosis. 相似文献
3.
S. Abiraman H. K. Varma T. V. Kumari P. R. Umashankar Annie John 《Bulletin of Materials Science》2002,25(5):419-429
This study investigates quantitatively and qualitatively the sol-gel derived bioactive glass-ceramic system (BGS)—apatite-wollastonite
(AW) type granules in the size range of 0.5–1 mm, as an effective graft material for bone augmentation and restoration. Scanning
electron micrographs (SEM) of the sintered granules revealed the rough material surface with micropores in the range 10–30
μm. X-ray diffraction (XRD) pattern of the granules revealed the presence of crystalline phases of the hydroxyapatite and
wollastonite, and the functional groups of the silicate and phosphates were identified by Fourier transform infrared spectroscopy
(FT-IR). Thein vitro cell culture studies with L929 mouse fibroblast cell line showed very few cells adhered on the BGS disc after 24 h. This
could be due to the highly reactive surface of the disc concomitant with the crystallization but not due to the cytotoxicity
of the material, since the cellular viability (MTT assay) with the material was 80‰ Cytotoxicity and cytocompatibility studies
proved that the material was non-toxic and biocompatible. After 12 weeks of implantation of the BGS granules in the tibia
bone of New Zealand white rabbits, the granules were found to be well osteointegrated, as observed in the radiographs. Angiogram
with barium sulphate and Indian ink after 12 weeks showed the presence of microcapillaries in the vicinity of the implant
site implicating high vascularity. Gross observation of the implant site did not show any inflammation or necrosis. SEM of
the implanted site after 24 weeks revealed good osteointegration of the material with the newly formed bone and host bone.
New bone was also observed within the material, which was degrading. Histological evaluation of the bone healing with the
BGS granules in the tibial defect at all time intervals was without inflammation or fibrous tissue encapsulation. After 2
weeks the new bone was observed as a trabeculae network around the granules, and by 6 weeks the defect was completely closed
with immature woven bone. By 12 weeks mature woven bone was observed, and new immature woven bone was seen within the cracks
of the granules. After 24 weeks the defect was completely healed with lamellar bone and the size of the granules decreased.
Histomorphometrically the area percentage of new bone formed was 67.77% after 12 weeks and 63.37% after 24 weeks. Less bone
formation after 24 weeks was due to an increased implant surface area contributed by the material degradation and active bone
remodeling. The osteostimulative and osteoconductive potential of the BGS granules was established by tetracycline labelling
of the mineralizing areas by 2 and 6 weeks. This sol-gel derived BGS granules proved to be bioactive and resorbable which
in turn encouraged active bone formation. 相似文献
4.
Much of the research on early imitations is restricted to the problem of their existence, without trying to describe them. The aim of this research is to analyze the principal characteristics of neonatal imitations in order to differentiate them from the later imitations. The behaviours of 16 neonates were filmed. A facial and a manual model were used. A detailed analysis of newborn behaviour revealed several features of early imitations: They were selective, quite exact, integrated, and occurred with short-time latencies. These results are interpreted within a cognitive framework. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
5.
Dai J Park G Perry JL Il'ichev YV Bow DA Pritchard JB Faucet V Pfohl-Leszkowicz A Manderville RA Simon JD 《Accounts of chemical research》2004,37(11):874-881
Ochratoxins are a class of naturally occurring compounds produced by several fungi. The most toxic is ochratoxin A (OTA), and occurrence of some human nephropathies and tumors correlate with enhanced OTA exposure. In this Account, the following areas are examined: molecular details of the binding of OTA to human serum albumin (HSA), the influences of binding to HSA on the trans-port of OTA across epithelial cell membranes by organic anion transport proteins, the oxidative activation of OTA, and the formation of OTA adducts with biological molecules. These studies are beginning to provide a detailed chemical model for the trans-port, accumulation, and genotoxic and carcinogenic effects of OTA. 相似文献
6.
Christilin D. M. Annie Brighty Mary Dr M. Safish 《Multimedia Tools and Applications》2021,80(13):19441-19457
Multimedia Tools and Applications - While denoising 3D MRI, structural preservation is a very critical process in the medical region. However, Rician noise in MRI has affected the image quality... 相似文献
7.
To reconstruct a black box multivariate sparse polynomial from its floating point evaluations, the existing algorithms need to know upper bounds for both the number of terms in the polynomial and the partial degree in each of the variables. Here we present a new technique, based on Rutishauser’s qd-algorithm, in which we overcome both drawbacks. 相似文献
8.
Rajendran Mala Antony Annie Aglin Arul Selvaraj Ruby Celsia Sivalingam Geerthika Narbahvi Kiruthika Chinnathambi VazagaPriya Kumarapillai Srinivasa Kumar 《IET nanobiotechnology / IET》2017,11(5):612
Foley catheters are inevitable in health care unit. Pathogens colonise and form biofilm on catheter causing catheter‐associated urinary tract infection. Therefore, the authors aimed to functionalise catheter to resist biofilm formation. The authors impregnated urinary catheters with a synergistic combination of antibiotics and silver nanoparticles (SNPs) to evaluate antibiofilm efficacy in vitro and in vivo. SNPs were synthesised using Spirulina platensis. Synergy between the SNPs and antibiotics was determined by the checker‐board method. In vivo efficacy of the functionalised catheters was assessed in mice. Liver and kidney function tests of mice were performed. The in vitro anti‐adherence activity of the functionalised catheters was evaluated after 2 years. Nanoparticle sizes were 42–75 nm. Synergistic activity was observed among SNPs (2 µg/ml), amikacin (6.25 µg/ml), and nitrofurantoin (31.25 µg/ml). In mice, catheters functionalised with combinations of antibiotics and SNPs exhibited no colonisation until Day 14. Blood, liver, and kidney tests were normal. After 2 years, catheters functionalised with antibiotics exhibited 25% inhibition of bacterial adhesion, and catheters functionalised with the nanoparticle‐antibiotic combination exhibited 90% inhibition. Impregnation of urinary catheters with a synergistic combination of antibiotics and SNPs is an efficient and promising method for preventing biofilm formation.Inspec keywords: catheters, drugs, silver, nanoparticles, nanomedicine, liver, kidney, blood, microorganisms, adhesion, biomechanics, cellular biophysicsOther keywords: Foley catheters, synergistic nanoparticle‐antibiotics combination, silver nanoparticles, biofilm formation resitance, health care unit, pathogens, urinary tract infection, SNP, Spirulina platensis, checker‐board method, liver function, kidney function, vitro antiadherence activity, amikacin, nitrofurantoin, blood, bacterial adhesion, size 42 nm to 75 nm, Ag 相似文献
9.
Drawing upon the Entertainment–Education paradigm, this study evaluated the effectiveness of a computer-aided interactive test designed for stress management education targeting college students. The presence (vs. absence) of a virtual agent incorporated into the interactive test was proposed as the key factor that induces enjoyment and educational outcomes. The interactive test consisted of scenarios describing stressful situations that could occur in college students’ everyday lives. Furthermore, college students could relate the concerns raised by these hypothetical situations to the ways they manage their stress and mental health. After the student’s choice behavior in each scenario, a virtual agent conveyed health-related educational messages via a text-modal dialogue box. Participants who took the interactive test in which there was a virtual agent perceived the test as more educational and entertaining than those who took the test without a virtual agent. Results of a path analysis also revealed a significant mediating role of enjoyment on educational outcomes (i.e., students’ enjoyment of the interactive test mediated the effects of the presence of a virtual agent on their perceived educational value of health information), thus confirming the Entertainment–Education link. In addition, engaging in the interactive test resulted in stress management self-efficacy improvement. Theoretical and practical implications are discussed. 相似文献
10.