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81.
Elien Peeters Geert Hooyberghs Stijn Robijns Kai Waldrant Ami De Weerdt Nicolas Delattin Veerle Liebens Soňa Kucharíková Hélène Tournu Natalie Verstraeten Barbara Dovgan Lenart Girandon Mirjam Fr?hlich Katrijn De Brucker Patrick Van Dijck Jan Michiels Bruno P. A. Cammue Karin Thevissen Jozef Vanderleyden Erik Van der Eycken Hans P. Steenackers 《Antimicrobial agents and chemotherapy》2016,60(11):6483-6497
We previously synthesized several series of compounds, based on the 5-aryl-2-aminoimidazole scaffold, that showed activity preventing the formation of Salmonella enterica serovar Typhimurium and Pseudomonas aeruginosa biofilms. Here, we further studied the activity spectrum of a number of the most active N1- and 2N-substituted 5-aryl-2-aminoimidazoles against a broad panel of biofilms formed by monospecies and mixed species of bacteria and fungi. An N1-substituted compound showed very strong activity against the biofilms formed by Gram-negative and Gram-positive bacteria and the fungus Candida albicans but was previously shown to be toxic against various eukaryotic cell lines. In contrast, 2N-substituted compounds were nontoxic and active against biofilms formed by Gram-negative bacteria and C. albicans but had reduced activity against biofilms formed by Gram-positive bacteria. In an attempt to develop nontoxic compounds with potent activity against biofilms formed by Gram-positive bacteria for application in antibiofilm coatings for medical implants, we synthesized novel compounds with substituents at both the N1 and 2N positions and tested these compounds for antibiofilm activity and toxicity. Interestingly, most of these N1-,2N-disubstituted 5-aryl-2-aminoimidazoles showed very strong activity against biofilms formed by Gram-positive bacteria and C. albicans in various setups with biofilms formed by monospecies and mixed species but lost activity against biofilms formed by Gram-negative bacteria. In light of application of these compounds as anti-infective coatings on orthopedic implants, toxicity against two bone cell lines and the functionality of these cells were tested. The N1-,2N-disubstituted 5-aryl-2-aminoimidazoles in general did not affect the viability of bone cells and even induced calcium deposition. This indicates that modulating the substitution pattern on positions N1 and 2N of the 5-aryl-2-aminoimidazole scaffold allows fine-tuning of both the antibiofilm activity spectrum and toxicity. 相似文献
82.
Deshane J Chen S Caballero S Grochot-Przeczek A Was H Li Calzi S Lach R Hock TD Chen B Hill-Kapturczak N Siegal GP Dulak J Jozkowicz A Grant MB Agarwal A 《The Journal of experimental medicine》2007,204(3):605-618
Stromal cell-derived factor 1 (SDF-1) plays a major role in the migration, recruitment, and retention of endothelial progenitor cells to sites of ischemic injury and contributes to neovascularization. We provide direct evidence demonstrating an important role for heme oxygenase 1 (HO-1) in mediating the proangiogenic effects of SDF-1. Nanomolar concentrations of SDF-1 induced HO-1 in endothelial cells through a protein kinase C zeta-dependent and vascular endothelial growth factor-independent mechanism. SDF-1-induced endothelial tube formation and migration was impaired in HO-1-deficient cells. Aortic rings from HO-1(-/-) mice were unable to form capillary sprouts in response to SDF-1, a defect reversed by CO, a byproduct of the HO-1 reaction. Phosphorylation of vasodilator-stimulated phosphoprotein was impaired in HO-1(-/-) cells, an event that was restored by CO. The functional significance of HO-1 in the proangiogenic effects of SDF-1 was confirmed in Matrigel plug, wound healing, and retinal ischemia models in vivo. The absence of HO-1 was associated with impaired wound healing. Intravitreal adoptive transfer of HO-1-deficient endothelial precursors showed defective homing and reendothelialization of the retinal vasculature compared with HO-1 wild-type cells following ischemia. These findings demonstrate a mechanistic role for HO-1 in SDF-1-mediated angiogenesis and provide new avenues for therapeutic approaches in vascular repair. 相似文献
83.
Role of tension receptors in dyspeptic patients with hypersensitivity to gastric distention 总被引:6,自引:0,他引:6
BACKGROUND & AIMS: Studies in health have shown that tension-sensitive mechanoreceptors mediate sensitivity to gastric distention. A role for these mechanoreceptors in perception or symptoms in hypersensitive functional dyspepsia (FD) has not been established. Tension-sensitive mechanoreceptors are activated during phasic contractions and inactivated during gastric relaxation. The aim of the present study was to investigate whether hypersensitive FD patients perceive spontaneous changes in fundic wall tension and whether fundus-relaxing drugs decrease sensitivity to gastric distention and meal-related symptoms. METHODS: Fifty patients were selected after a barostat study established gastric hypersensitivity. In 12 patients, an intragastric balloon was inflated with a fixed volume just below perception thresholds and patients were asked to indicate changes in perception on a keypad, and the relationship between perception and contractions was analyzed. In 20 patients, we studied the influence of the fundus-relaxing drug sumatriptan on sensitivity to gastric distention. In, respectively, 10 and 8 patients, we studied the influence of the fundus-relaxing drugs sumatriptan and clonidine on meal-related symptoms. RESULTS: The majority of patients had a statistically significant association between perception and phasic isovolumetric contractions. Pretreatment with sumatriptan increased both pressures and volumes needed to induce first perception and discomfort. Pretreatment with sumatriptan and clonidine both significantly decreased meal-induced symptoms. CONCLUSIONS: Patients with hypersensitivity to gastric distention perceive isovolumetric phasic contractions of the proximal stomach. Fundus-relaxing drugs decrease sensitivity to gastric distention and decrease meal-induced symptoms in these patients. The findings are compatible with involvement of tension mechanoreceptors in symptom generation in hypersensitive FD. 相似文献
84.
85.
Calcifying epithelial odontogenic tumour (Pindborg tumour) is a rare benign neoplasm with a poorly understood histogenesis. This report describes a single case of a maxillary calcifying epithelial odontogenic tumour including immunohistochemical analysis. The vast majority of tumour cells were positive for CK5/6 and p63. Furthermore, basal cells also displayed moderate reaction for vimentin and strong membranous positivity for podoplanin. Interestingly, the tumour invaded the dental pulp of the partially disintegrated tooth root. While the tumour showed focal connection with the superficial gingival epithelium and revealed intercellular bridges, the findings of this case study seem to support the suggestion of an epithelial origin of a calcifying epithelial odontogenic tumour derived from the dental lamina. 相似文献
86.
87.
Verraedt E Braem A Chaudhari A Thevissen K Adams E Van Mellaert L Cammue BP Duyck J Anné J Vleugels J Martens JA 《International journal of pharmaceutics》2011,419(1-2):28-32
Amorphous microporous silica (AMS) serving as a reservoir for controlled release of a bioactive agent was applied in the open porosity of a titanium coating on a Ti-6Al-4V metal substrate. The pores of the AMS emptied by calcination were loaded with chlorhexidine diacetate (CHX) via incipient wetness impregnation with CHX solution, followed by solvent evaporation. Using this CHX loaded AMS system on titanium substrate sustained release of CHX into physiological medium was obtained over a 10 day-period. CHX released from the AMS coating was demonstrated to be effective in killing planktonic cultures of the human pathogens Candida albicans and Staphylococcus epidermidis. This surface modification of titanium bodies with AMS controlled release functionality for a bioactive compound potentially can be applied on dental and orthopaedic implants to abate implant-associated microbial infection. 相似文献
88.
89.
Levecke B Rinaldi L Charlier J Maurelli MP Morgoglione ME Vercruysse J Cringoli G 《Parasitology research》2011,109(3):953-957
The faecal egg count reduction test (FECR) is the recommended technique to monitor anthelmintic drug efficacy in livestock.
However, results are often inconclusive due to the low analytic sensitivity of the diagnostic technique or the conflict in
results from FECR formulae. A novel experimental set-up was, therefore, used to compare the impact of analytic sensitivity
and formulae on FECR results. Four McMaster techniques (analytic sensitivities 50, 33.3, 15 and 10) and a FLOTAC technique
(analytic sensitivity ~ 1) were used on faecal samples of 30 calves with a FEC of less than 200 eggs per gram. True drug efficacies
of 70%, 80% and 90% were experimentally mimicked by comparing FEC before and after dilution (3:10, 2:10 and 1:10, respectively).
The FECR was summarized using group (FECR(1)) and individual (FECR(2)) based formulae. There was a significant increase in
precision of FECR when the analytic sensitivity increased (p < 0.0001). The precision also depended on the formula used, FECR(1) (p < 0.05) resulting in more precise FECR compared to FECR(2). The accuracy of the FECR differed marginally between the two
formulae (p = 0.06), FECR(1) being more accurate. In conclusion, the present study describes a novel methodology to compare techniques
for the precision and the accuracy of their FECR results. The results underscored that techniques with high analytic sensitivity
will improve the interpretation of FECR in animal populations where baseline FEC are low. They also point out that the precision
of individual-based formulae is affected by the analytic sensitivity. 相似文献
90.