Les alicaments et la drépanocytose : une mini-revue

Sickle cell disease is a genetic disease affecting particularly the black African population and its diaspora. In recent years, the phytotherapeutical approach seems to show progress with in vitro validation of antisickling activity of several plants used in traditional African medicine against sickle cell disease and isolation of some active molecules. The use of edible medicinal plants is an interesting approach since these plants can be integrated into the daily diet of patient suffering from this chronic disease. Among nearly 75 plants used in Congolese traditional medicine identified by our research team, 16 species belonging to 12 families of edible plants including: Cajanus cajan, Sorghum bicolor, Ipomea batata, Moringa morindoides, Adansania digitata, Ocimum basilicum, Vigna unguiculata. The antisickling activity of these plants used by traditional healers was confirmed in vitro using several tests including Emmel test, hemolysis test and antioxidant activity test. Fifteen of these plants have actually shown biological activity justifying their use in traditional medicine. This activity mainly observed in the polar extracts is mainly due to anthocyanins and organic acids and their derivatives. These plants can be used as nutraceuticals in the treatment of sickle cell disease and the tests done with Vigna unguculata are encouraging.     

Synthesis and characterization of PEG modified N-trimethylaminoethylmethacrylate chitosan nanoparticles

Chitosan-N-trimethylaminoethylmethacrylate chloride-PEG (CS-TM-PEG) copolymers were synthesized in order to improve the solubility of chitosan in physiological environment, and enhance the biocompatibility of quaternized chitosan. The result of ¹H NMR confirmed that PEG had been combined with amino groups of quaternized chitosan. The profile of hemolysis assay showed that Chitosan-N-trimethylaminoethylmethacrylate chloride (CS-TM) copolymer exhibited hemolytic activity from 10.31% to 13.58%, while CS-TM-PEG copolymer had hemolytic activity from 4.76% to 7.05% at copolymer concentrations from 250 to 2000 μg/ml. Through PEG modification, the hemolytic activity could be reduced to a half. CS-TM-PEG copolymer-insulin nanoparticles were prepared based on ionic gelation process of positively charged copolymers and negatively charged insulin. The nanoparticles were characterized in terms of particle size, TEM, association efficiency and in vitro release. These nanoparticles were 200-400 nm in size and insulin association efficiency of optimal formulations was found up to 90%. In vitro release showed that the nanoparticles provided an initial burst release followed by a sustained release with the sensitivity of ionic strength and pH values.     

Analysis of palytoxin-like in Ostreopsis cultures by liquid chromatography with precolumn derivatization and fluorescence detection

A rapid liquid-chromatography (LC) method is presented which uses fluorescence detection (FLD) for palytoxin analogues analysis in benthic dinoflagellates of the genus Ostreopsis. The amino-acidic reagent 6-aminoquinolyl-N-hydroxisuccinimidyl carbamate (AccQ) was used for fluorescence labelling followed by LC-FLD.The efficacy of the method is exemplified by comparison of the results of the quantification obtained by LC-FLD and the hemolytic assay performed for palytoxins for which a highly significant linear correlation was achieved (r² = 0.9118). The derivatized palytoxin analogues were determined in the range of 0.75-25 ng.The proposed method was successfully applied to the determination and quantification of palytoxin analogues in 14 samples from different strains of Ostreopsis from different locations (Western Mediterranean Sea, Canary Islands, Madeira Islands and Southern coasts of Brazil). To confirm the chemical structure of the toxins, samples were also analyzed by liquid chromatography coupled with mass spectrometry (LC-MS) with a system that has a poorer sensitivity when compared with LC-FLD detection and the hemolytic assay. The successful use of this method with dinoflagellates is a good indicator of suitability for other types of marine samples.     

Biocompatibility study for PVP wound dressing obtained in different conditions

Hydrogels composed of PVP, PEG and agar, produced by simultaneous crosslinking and package sterilization by ionizing radiation, are used mainly as wound dressing. In this study, membranes prepared in different conditions were tested for their properties including in vitro biocompatibility. The results showed that the mechanical properties were in an acceptable range of values and that the membranes can be considered as non toxic and non hemolytic to the cells.     

Synthesis and biological evaluation of echinocystic acid derivatives as HCV entry inhibitors

A series of echinocystic acid (EA) 28-COOH derivatives was synthesized, and their anti-HCV entry activity was evaluated by HCVpp and VSVpp entry assay. It was found that some of them showed moderate anti-HCV entry activity, especially compound 12, and these modifications also removed the undesired hemolytic effect.     

Development of a hollow fiber membrane module for using implantable artificial lung

This study examined the effects of multiple mechanical forces on gas exchange and hemolysis in intravascular lung assist devices (IVLAD). Specific attention was paid to on the effect of membrane vibration. This study adhered to the recommended practice for the assessment of hemolysis described by the American Society of Testing and Materials (ASTM). The results showed a higher oxygen (O₂) transfer rate and carbon dioxide (CO₂) removal rate in each excited frequency bandwidth than those without vibration. The maximum oxygen transfer and carbon dioxide removal rate occurred at frequency band of 7 Hz. The gas exchange improved maximum 52%. The plasma-free hemoglobin was 11.2 ± 0.57 and 14.4 ± 0.74 mg/100 ml by exciting a piezo-vibrator with a sinusoidal wave magnitude of DC10 V and DC50 V, respectively. The NIHO value was determined to be 59 ± 2.76 and 95 ± 4.32 mg/100 ml by exciting a piezo-vibrator with a sinusoidal wave magnitude of DC10 V and DC50 V, respectively. In conclusion, piezoelectric lead zirconate titanate (PZT) materials are exciting systems for improving the oxygen transfer efficiency and blood suitability of hollow fiber membrane in the development of new IVLAD.     

羧基化氧化石墨烯-谷氨酸复合物的抗凝血性能

将手性的L-谷氨酸(Glu)接枝到羧基化氧化石墨烯片层上, 制备了一种羧基化氧化的氧化石墨烯-谷氨酸复合物(GeneO-Glu), 提高了羧基化的氧化石墨烯的生物相容性. 利用红外光谱、 静态水接触角、 X射线衍射及热重分析等手段对所合成的GeneO-Glu复合物进行了表征, 并对其复合机理进行了探讨. 结果表明, Glu可在一定条件下通过化学反应键合在羧基化的氧化石墨烯片层上. 血浆复钙时间随着复合物浓度的增加而增加; 不同pH值条件下合成的复合物在不同浓度下的溶血率均小于5%, GeneO-Glu复合物在低浓度时即表现出优良的抗凝血性能.     

Crystallographic dependency of waste cow bone,hydroxyapatite, and β-tricalcium phosphate for biomedical application

In this research, waste cow bone was chosen as a sustainable source of biomaterials in pure hydroxyapatite form and synthesized hydroxyapatite (HAP) was prepared as a biphasic HAP (hydroxyapatite and β-tricalcium phosphate phase) and subsequently pure β-tricalcium phosphate (β-TCP). The samples were characterized by employing X-Ray diffraction (XRD), scanning electron microscopy (SEM), Fourier transform infrared (FT-IR) instrumentation, and in-depth crystallographic analysis was performed by calculating crystallite size, lattice parameters, HAp percentage, the volume fraction of β-TCP, β-TCP percentage, crystallinity index, degree of crystallinity, microstrain, and dislocation density. Excellent results was noticed for biocompatible properties such as cytotoxicity, hemolysis, and antimicrobial (E. coli, S. aureus, and A. niger). A relationship was established among the synthesized products and the crystallographic parameters.     

Kinetic study of all-or-none hemolysis induced by cationic amphiphilic polymethacrylates with antimicrobial activity

To gain an understanding of the toxicity of antimicrobial polymers to human cells, their hemolytic action was investigated using human red blood cells (RBCs). We examined the hemolysis induced by cationic amphiphilicmethacrylate random copolymers, which have amino ethyl sidechains as cationic units and either butyl or methyl methacrylate as hydrophobic units. The polymer with 30 mol% butyl sidechains (B30) displayed higher hemolytic toxicity than the polymer with 59 mol% methyl sidechains (M59). B30 also induced faster release of hemoglobin from RBCs than M59. A new theoretical model is proposed based on two consecutive steps to form active polymer species on the RBC membranes, which are associated to RBC lysis. This model takes the all-or-none release of hemoglobin by the rupture of RBCs into account, providing new insight into the polymer-induced hemolysis regarding how individual or collective cells respond to the polymers.     

The Hemolytic Properties of Chemically Modified Cyclodextrins

The hemolytic properties of naturalcyclodextrins, especially of the more commoncyclomaltoheptaose entity, severely hamper theirpotential use as carriers in pharmaceuticalapplications where parenteral administration isconcerned. A systematic investigation on the role ofchemical modifications with regard to the hemolyticcharacter was carried out involving C-6 branchedneutral, anionic, cationic and amphoteric derivatives.From these data, conclusions have been drawnabout the charge and the geometry of the modification: (i)Substitution at primary hydroxyl groups usuallydecreases the hemolytic character and the geometry ofthe substituent affects the hemolytic property; (ii)introduction of an amino group, resulting in apositive charge at physiological pH, decreases thehemolytic character; (iii) negative charges arecomparatively less effective in reducing the hemolyticcharacter; (iv) zwitterionic groups seem to enhancethe hemolytic character of the cyclodextrin molecule.