Blood-stage antiplasmodial activity and oocyst formation-blockage of metallo copper-cinchonine complex

In the fight against malaria, the key is early treatment with antimalarial chemotherapy, such as artemisinin-based combination treatments (ACTs). However, Plasmodium has acquired multidrug resistance, including the emergence of P. falciparum strains with resistance to ACT. The development of novel antimalarial molecules, that are capable of interfering in the asexual and sexual blood stages, is important to slow down the transmission in endemic areas. In this work, we studied the ability of the mettalo copper-cinchonine complex to interfere in the sexual and asexual stages of Plasmodium. The tested compound in the in vitro assay was a cinchonine derivative, named CinCu (Bis[Cinchoninium Tetrachlorocuprate(II)]trihydrate). Its biological functions were assessed by antiplasmodial activity in vitro against chloroquine-resistant P. falciparum W2 strain. The mice model of P. berghei ANKA infection was used to analyze the antimalarial activity of CinCu and chloroquine and their acute toxicity. The oocyst formation-blocking assay was performed by experimental infection of Anopheles aquasalis with P. vivax infected blood, which was treated with different concentrations of CinCu, cinchonine, and primaquine. We found that CinCu was able to suppress as high as 81.58% of parasitemia in vitro, being considered a molecule with high antiplasmodial activity and low toxicity. The in vivo analysis showed that CinCu suppressed parasitemia at 34% up to 87.19%, being a partially active molecule against the blood-stage forms of P. berghei ANKA, without inducing severe clinical signs in the treated groups. The transmission-blocking assay revealed that both cinchonine and primaquine were able to reduce the infection intensity of P. vivax in A. aquasalis, leading to a decrease in the number of oocysts recovered from the mosquitoes’ midgut. Regarding the effect of CinCu, the copper-complex was not able to induce inhibition of P. vivax infection; however, it was able to induce an important reduction in the intensity of oocyst formation by about 2.4 times. It is plausible that the metallo-compound also be able to interfere with the differentiation of parasite stages and/or ookinete-secreted chitinase into the peritrophic matrix of mosquitoes, promoting a reduction in the number of oocysts formed. Taken together, the results suggest that this compound is promising as a prototype for the development of new antimalarial drugs. Furthermore, our study can draw a new pathway for repositioning already-known antimalarial drugs by editing their chemical structure to improve the antimalarial activity against the asexual and sexual stages of the parasite

Surface Study of Selected Biomaterials Using Vibrational Spectroscopy

Vibrational spectroscopy has been extensively used for in vitro and in vivo investigations of degradation mechanism and kinetics of different biomedical materials as well as it has been used to characterize the crystalline and amorphous domains in bio-mineralization process. Infrared and Raman spectroscopy methods are valuable tools in the biomaterials engineering allowing to study processes occurring during their preparation. In vitro tests, where the materials are immersed in simulated body fluids and/or artificial saliva, were used to evaluate the biocompatibility of biomaterials. This kind of tests are a wide range of repeatable and reproducible methods, which are regulated by international standards for commercial use and scientific development of new materials and products. The aim of this work was to examine phase composition of materials applied in dentistry. The bioactivity of such biomaterials was studied by immersing the samples in synthetic body fluid and artificial saliva. The changes were determined by the Fourier transform infrared and Raman microspectroscopy as well as scanning electron microscopy. It was found that results obtained by vibrational spectroscopy show the differences between the studied samples. Chemical reactions occurring during incubation of cements in artificial saliva as well as in synthetic body fluid result in formation of phosphates which deposit on the cement surface

Surface Study of Selected Biomaterials Using Vibrational Spectroscopy

Vibrational spectroscopy has been extensively used for in vitro and in vivo investigations of degradation mechanism and kinetics of different biomedical materials as well as it has been used to characterize the crystalline and amorphous domains in bio-mineralization process. Infrared and Raman spectroscopy methods are valuable tools in the biomaterials engineering allowing to study processes occurring during their preparation. In vitro tests, where the materials are immersed in simulated body fluids and/or artificial saliva, were used to evaluate the biocompatibility of biomaterials. This kind of tests are a wide range of repeatable and reproducible methods, which are regulated by international standards for commercial use and scientific development of new materials and products. The aim of this work was to examine phase composition of materials applied in dentistry. The bioactivity of such biomaterials was studied by immersing the samples in synthetic body fluid and artificial saliva. The changes were determined by the Fourier transform infrared and Raman microspectroscopy as well as scanning electron microscopy. It was found that results obtained by vibrational spectroscopy show the differences between the studied samples. Chemical reactions occurring during incubation of cements in artificial saliva as well as in synthetic body fluid result in formation of phosphates which deposit on the cement surface

Physiochemical and biological evaluation of thin CNTs layers

Carbon nanotubes are nanometric-sized materiale which possess a set of interesting features that favor their applications in various fields of materials engineering, including biomedical applications. However, their usage as implants or in nanomedicine raises many questions, regarding their potential cytotoxicity, relative to their length, diameter, structure and functional groups, present on their outer walls. The given study presents a physiochemical and biological in vitro (in accordance with EN-ISO 10993-5) evaluation of thin carbon nanotubes films, deposited on the surface of titanium, by means of the EPD process. Experiments were carried out on commercially available, pre-functionalized with OH groups, multi-walled carbon nanotubes. The obtained material is proven to be biocompatible, with no cytotoxic effect on the human fetal osteoblast cell line. During the study, selectivity of the EPD process was proven - performed experiments revealed that the process favors deposition of CNTs with chosen set of features from the stock solution. Presented results point out that the EPD process can be successfully applied as a method for fractioning the CNTs, aimed to fabricate non-toxic layers that might be considered for various biomedical applications

An attenuated total reflection (ATR) and Raman spectroscopic investigation into the effects of chloroquine on Plasmodium falciparum-infected red blood cells

Attenuated Total Reflection Fourier Transform Infrared (ATR-FTIR) and Raman spectroscopy were used to compare chloroquine (CQ)-treated and untreated cultured Plasmodium falciparum-infected human red blood cells (iRBCs). The studies were carried out in parallel from the same starting cultures using both spectroscopic techniques, in duplicate. ATR FTIR spectra showed modifications in the heme vibrational bands as well as increases in the CH2/CH3 stretching bands in the 3100–2800 cm−1 region of CQ-treated iRBCs consistent with an increase in lipid content. Other changes consisted of secondary structural variations including shifts in the amide I and II modes, along with changes in RNA and carbohydrate bands. Raman microspectroscopy of single red blood cells using 532 nm revealed subtle changes in the positions and intensity of ν37 of the core size region marker band and ν4 in the pyrrole ring-stretching region between untreated and CQ-treated iRBCs. Similar patterns in the corresponding relations were also observed in the non-fundamental (overtone region) between the control and treated cells. These differences were consistent with higher levels of oxygenated hemoglobin (oxyHb) in the treated cells as shown in a Principle Component Analysis (PCA) loadings plot. The results obtained demonstrate that vibrational spectroscopic techniques can provide insight into the effect of quinolines on iRBCs and thus may assist understanding the sensitivity and resistance of new and existing anti-malarial drugs

Réseaux anisotropes par réticulation de monomères diepoxy cristaux liquides orientés sous champ magnétique

PARIS-BIUSJ-Thèses (751052125) / SudocPARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF