High absolute bioavailability of methylene blue given as an aqueous oral formulation

Purpose  Methylene blue (MB) has recently been reevaluated for malaria treatment. With the aim of excluding treatment failures due to low bioavailability, we have investigated the absolute bioavailability of MB given as an aqueous oral formulation and its interaction with chloroquine (CQ). Methods  A phase I study in 16 healthy individuals was performed as a monocenter prospective open randomized intra-individual cross-over comparison of MB single doses [50 mg intravenous (i.v.), 500 mg orally, separated by a 1-week wash-out]. After a second week, the group was split for a randomized parallel group comparison of CQ 750 mg administered orally alone or combined with 500 mg MB orally. Results  Mean MB plasma area under the substrate concentration–time curve () was 7,639 ± 3,384 ng/mL*h and 51,171 ± 17,147 ng/mL*h after i.v. and oral administration, respectively (dosage 1:10), and 76,897 ± 46,037 ng/mL*h after MB combined with CQ. The absolute bioavailability was 72.3 ± 23.9%. Co-administration with CQ significantly increased MB plasma concentrations (p ≤ 0.016); CQ kinetics remained unaffected. Conclusion  The absolute bioavailability of MB is high. Co-administration of MB and CQ increases plasma, but not whole blood MB concentrations.     

An alternative application for reuse of leaching residues: Determination of adsorption behaviour for methylene blue and process optimization

In this study, the potential efficiency in adsorption process, as a functional use route, of laterite ore residues (LR) produced from atmospheric acid leaching was evaluated for methylene blue (MB) removal representing cationic organic pollutants discharged in large amounts from industry into aquatic environment. Adsorption process was optimized by using Box-Behnken design based on Response Surface Methodology (RSM) to determine correlation between responses as, adsorption efficiency (%) and adsorption capacity (mg/g), and 3 independent variables with 3 levels (pH, initial MB concentration and LR amount). 98.29 ± 0.63% of adsorption efficiency and 3.072 ± 0.280 mg/g of adsorption capacity were achieved in determined optimum conditions; pH = 5.2, C₀ = 50 mg/L MB and m = 0.40 g. The good agreement between predicted and experimental values observed by comparison of values showed accuracy of model at 95% confidence level. Furthermore, it was determined that nature of adsorption equilibrium complied Freundlich isotherm model and adsorption mechanism was well defined with pseudo-second-order kinetics model. Thus, process exhibited a heterogeneous multilayer adsorption behavior and mainly controlled by chemical reactions. Furthermore, the adsorption mechanism was determined by characterization of residues, before and after adsorption by scanning electron microscopy with energy dispersive of X-ray (SEM?EDAX), Fourier-transform infrared (FTIR) spectroscopy, and X-ray diffraction (XRD).     

Spectrophotometric determination of methylene blue in biological fluids after ion-pair extraction and evidence of its adsorption on plastic polymers

Methylene blue has gained a renewed interest in medicine. It is now used in combination with visible light as a photoinactivating agent of membrane viruses such as HIV and HBV in single-donor fresh frozen plasma. MB has also been proposed for the prophylaxis and reversal of ifosfamide induced encephalopathy and in septic shock. In spite of its wide use, its pharmacokinetics in humans are little known and an improved methodology for its quantitation in biological fluids was therefore required. We report an improved spectrophotometric determination of methylene blue in whole blood, plasma and urine. Liquid-liquid ion-pair extraction of MB from the biological matrix is achieved by addition of 500 μl (to 1.2 ml whole-blood aliquot) or 125 μl (to 1 ml plasma or 250 μl urine) of 5% sodium hexanesulfonate solution and subsequent extraction with 2.0 ml 1,2-dichloroethane. After centrifugation, the organic layer is assayed at 657 nm. In urine samples, the reduced form leucomethylene blue is also assayed after oxidation to methylene blue (addition of 38 μl HCl 0.5M to 250 μl urine sample and heating on a water bath at 70°C for 1 min) prior to the ion-pairing extraction. Methylene blue can be accurately determined in spiked whole blood and plasma over the working range 0.1–9.1 μg/ml. At higher concentrations, likely to occur in urine (up to 55 μg/ml), the measurements deviate more than 10% from the nominal values. Analysis of spiked samples shows that methylene blue is adsorbed to some extent to polypropylene and polystyrene plastic tubes. This phenomenon is influenced by the biological matrix and is more marked with low volumes of concentrated (>3 μg/ml) samples. At low concentrations, the adsorption is likely to occur but is more difficult to quantitate due to assay variability. This phenomenon should be kept in mind since it could potentially affect the biological activity of methylene blue.     

H2SO4-modified Aloe vera leaf shells for the removal of P-chlorophenol and methylene blue from aqueous environment

Abstract

In this study, the surface properties of activated carbon from Aloe vera leaf shells were modified by sulfuric acid Aloe vera-acid activated carbon (AV-AAC) and then used as a novel adsorbent to remove para-chlorophenol (p-CP) and methylene blue (MB) from aqueous solutions. The adsorbent was characterized by scanning electron microscopy (SEM), energy-dispersive X-ray (EDX) analysis and Fourier transform infrared spectra (FTIR). The maximum monolayer adsorption capacities were found to be 137 and 192.3?mg/g for p-CP and MB, respectively. Due to low-cost and high adsorption capacity, AV-AAC can be considered as an effective adsorbent for wastewater treatment containing p-CP or MB.     

亚甲蓝对感染性休克犬血液动力学和氧合功能的影响

目的　观察鸟苷酸环化酶抑制药亚甲蓝 (MB)对感染性休克犬血液动力学和氧合功能的影响。方法　采用内毒素静脉注入诱导的 1 1只感染性休克犬模型 ,输注 0 9%的氯化钠后 ,MB2mg/kg1 5分钟内静脉注入。经右颈内静脉放置的肺动脉导管测定基础、休克 1小时、输注生理盐水后和MB注入后 30、60、1 2 0、1 80分钟血液动力学 ,分析动脉、混合静脉血气和动脉血乳酸 ,计算氧合。结果　MB注入明显增加感染性休克犬平均动脉压 (MAP)、体血管阻力 (SVR)和左心室作功(LVSW) ,不影响肺动脉压 (PAP)、肺动脉嵌顿压 (PAOP)、心输出量 (CO)、氧输送 (DO2 )和氧摄取(VO2 ) (P >0 0 5)。MAP、SVR和LVSW的增高以 30分钟最为明显 ,分别从 (96 4± 1 6 6)mmHg、(4332 5± 75 8)dyne .sec .cm- 5、(1 4 0± 1 8) g .m升高到 (1 2 9 9± 1 8 3)mmHg、(52 67 1± 94 6)dyne.sec .cm- 5、(1 7 1± 2 6)g .m(P <0 0 1 ) ,1 80分钟基本回复。内毒素注入增加动脉血乳酸 (P <0 0 5) ;MB注入降低乳酸 ,1 2 0分钟最明显 ,从 (4 3± 1 3)mmol/L下降到 (3 4± 1 2 )mmol/L(P <0 0 5)。结论　MB注入改善感染性休克血液动力学 ,降低血乳酸 ,不影响氧合     

亚甲蓝类似物的合成及其与牛血清白蛋白相互作用的研究

目的 合成3种亚甲蓝类似物3,7-二(二正丙胺基)-吩噻嗪-5-鎓碘化物、3,7-二(二正丁胺基)-吩噻嗪-5-鎓碘化物和3,7-二(二正戊胺基)-吩噻嗪-5-鎓碘化物,并研究模拟生理条件下这3种亚甲蓝类似物与牛血清白蛋白的相互作用.方法 通过1H-NMR及MS对这3种亚甲蓝类似物进行结构表征,应用荧光光谱法研究了模拟生理条件下这3种亚甲蓝类似物与牛血清白蛋白的相互作用.结果 3种亚甲蓝类似物和BSA相互作用形成了蛋白质-药物复合物并猝灭其固有荧光,亚甲蓝类似物与BSA相互作用过程的ΔG0<0,亚甲蓝类似物与BSA荧光残基间的距离r均小于7 nm.结论 亚甲蓝类似物和BSA相互作用的猝灭机制为静态猝灭,二者之间的反应是自发进行的.非辐射能量转移理论表明BSA与亚甲蓝类似物之间存在非辐射能量转移.同步荧光光谱和三维荧光光谱的研究结果表明,亚甲蓝类似物与BSA的相互作用导致BSA构象发生变化.     

In vivo lymphatic targeting of methylene blue with microemulsion and multiple microemulsion

Three formulations including methylene blue solution (MB-S), MB water-in-oil microemulsion (MB-ME), and MB multiple microemulsion (MB-MME) were prepared with the aim to evaluate whether the three formulations can carry MB target to regional lymph nodes and show lymphatic tropism after subcutaneous administration. The pseudo-ternary phase diagrams were also studied. The morphology of MB-ME and MB-MME was examined by transmission electron microscopy to characterize the microstructure. The particle size and viscosity were also measured. MB concentrations in plasma, lymph nodes, and limb soles were quantitatively analyzed using HPLC. Results show that MME can target MB to regional lymph nodes, and can be employed as a potential lymph tracer in sentinel lymph node biopsy.     

Preparation and characterization of biochar derived from the fruit seed of Cedrela odorata L and evaluation of its adsorption capacity with methylene blue

Biochar has proven to be an effective tool in several aspects of environmental management; as well as many other applications. Herein we report biochar derived from the capsule-like interior of the seeds of Cedrela odorata L, prepared via pyrolysis at 400 °C. The biochar was characterized using: Elemental analysis, Fourier-transform infrared spectroscopy (FT-IR), Scanning electron microscopy (SEM), X-ray diffraction (XRD), Thermal gravimetric analysis (TGA) and Raman Spectroscopy. Results demonstrate that a biochar of high thermal stability and porosity was obtained, with surface functional groups that enhance the adsorption process. Equilibrium adsorption data were consistent with the Langmuir isotherm model, indicating surface homogeneity, with maximum adsorption capacity of 158.8 mg/g. These results demonstrate that the biochar is an efficient adsorbent for the removal of MB dye from aqueous solution; and suggests its utility for further exploration in removing heavy metals from water as well as its use as a solid support in catalysis.     

Adsorption of quinolone,tetracycline, and penicillin antibiotics from aqueous solution using activated carbons: Review

Antibiotics, an important type of pharmaceutical pollutant, have attracted many researchers to the study of their removal from aqueous solutions. Activated carbon (AC) has been widely used as highly effective adsorbent for antibiotics because of its large specific surface area, high porosity, and favorable pore size distribution. In this article, the adsorption performance of AC towards three major types of antibiotics such as tetracyclines, quinolones, and penicillins were reviewed. According to collected data, maximum adsorption capacities of 1340.8, 638.6, and 570.4 mg/g were reported for tetracyclines, quinolones, and penicillins, respectively. The values of 1/n for Freundlich isotherm were less than unity, suggesting that the adsorption was nonlinear and favorable. Adsorption kinetics followed closely the pseudo-second-order model and analysis using the Weber-Morris model revealed that the intra-particle diffusion was not the only rate controlling step. AC adsorption demonstrated superior performance for all selected drugs, thus being efficient technology for treatment of these pollutants.     

Investigation of in vivo toxicity of hydroxylamine sulfate and the efficiency of intoxication treatment by α-tocopherol acetate and methylene blue

ObjectivesInvestigation of hydroxylamine sulfate toxicity mechanism in vivo and estimation of α-tocopherol acetate and methylene blue efficiency in poisoning treatments.MethodsIn vivo experiments were conducted on 102 Wistar Han rats. The experiments investigated the hematotoxic and oxidative stress effects of hydroxylamine sulfate in acute and subacute toxicity treatment of animals. Electron Spin Resonance was used for quantitative determination of blood and liver tissue parameters alterations after intoxication. The osmotic fragility of erythrocytes, lipid peroxidation intensity and level of SH-groups in liver of rats were determined by established biochemical assays.ResultsHydroxylamine sulfate cause an acute hematotoxicity and oxidative stress in vivo as demonstrated by the appearance of free oxidized iron in blood, reduced glutathione content and increased lipid peroxidation in liver. The experimental studies showed the formation of Hb–NO, MetHb in erythrocytes and as well of stable complex of reduced iron (Fe²⁺) with hydroxylamine sulfate. Methylene blue treatment does not reduce the Hb–NO or MetHb levels in intoxicated animals while administration of α-tocopherol acetate reduces substantially lipid peroxidation.ConclusionsOxidative stress is a key mechanism of acute hematotoxicity caused by hydroxylamine sulfate. Methylene blue is not suitable antidote in case of hydroxylamine intoxication.     

亚甲蓝和泛影葡胺定位法切除乳腺微小病变

目的探讨B超下亚甲蓝和泛影葡胺定位法在乳腺微小病灶（直径≤1．0cm）切除和诊断中的作用。方法对136例患者212个乳腺病灶在B超下进行亚甲蓝和泛影葡胺染色定位并手术切除。结果136例患者212病灶全部成功切除,其中7例为早期浸润型导管癌,1例为导管内癌。结论亚甲蓝和泛影葡胺技术可有效提高对乳腺微小病灶切除的准确性以及早期乳腺癌的诊断率,安全性好。     

Adsorption of hexavalent chromium in aqueous solution on activated carbon prepared from apple peels

In the present study, activated carbon prepared from apple peels (ACAP) was used to remove chromium (VI) from aqueous solution. The characterization of this ACAP has been performed using different analytical techniques such as FTIR and SEM. The adsorption parameters studied were: pH [2- 7], adsorbent dose [0.025–0.15 g/50 mL], initial Cr(VI) concentration [10–50 mg/L] and temperature [10–40 °C]. Maximum Cr(VI) adsorption of 36.01 mg/g was achieved using Cr(VI) concentration of 50 mg/L, pH of 2, adsorbent dose of 0.05 g/50 mL, contact time of 4 h and temperature of 28 °C. This ACAP gave a Cr(VI) adsorption capacity better than a commercial activated carbon. The experimental data fitted well to Freundlich isotherm (R² = 0.99) and kinetics followed the pseudo-second order model. Thermodynamic parameters, ΔG < 0, ΔH° = 1.99 (Kcal/mol) and ΔS° = 0.0079 (Kcal/K mol) indicate that the adsorption process is spontaneous and endothermic.     

Synthesis and characterization of MOF-5 incorporated waste-derived siliceous materials for the removal of malachite green dye from aqueous solution

The synthesis of MOF-5 and its modification have been investigated towards malachite green (MG) dye removal. The modified MOF-5 adsorbents have been prepared using waste-derived siliceous materials, i.e., rice husk ash (RHA) and/or coal fly ash (CFA) at different ratio. The MOF-5/RHA&CFA/2:1 has been chosen as the best adsorbent for MG dye removal from the aqueous solutions. The adsorption characteristics of the modified MOF-5 for MG dye removal was studied varying various parameters. The MG adsorption efficiency increases with increasing the shaking rate and contact time, but remained constant after 300 rpm and 4 h, respectively. The maximum adsorption capacity of 39.47 mg/g was obtained at adsorbent amount of 0.3 g, initial dye concentration of 150 mg/L, temperature of 30 °C, shaking rate of 200 rpm, contact time of 2 h, and original solution pH. The optimum temperature, pH, and amount of adsorbent for effective MG dye adsorption were 40 °C, 11.5, and 0.2 g, respectively. XRD analysis indicated the presence of crystalline materials has become reduced when RHA and CFA were being incorporated in MOF-5. FTIR analysis showed significant functional groups in the spectrum for both prepared and spent adsorbents. The SEM micrograph results revealed the rough surface morphology with many pores on the MOF-5/RHA&CFA/2:1 before MG adsorption and became smooth and less porous after MG adsorption. While BET analysis indicated that the surface area does not affect the MG dye adsorption efficiency. This study showed that modified MOF-5 adsorbents were successfully used for the removal of MG dye.     

Computation of adsorption parameters for the removal of dye from wastewater by microwave assisted sawdust: Theoretical and experimental analysis

In this research, the microwave assistance has been employed for the preparation of novel material from agro/natural bio-waste i.e. sawdust, for the effective removal of methylene blue (MB) dye from aqueous solution. The characterization of the newly prepared microwave assisted sawdust (MASD) material was performed by using FTIR, SEM and XRD analyses. In order to obtain the maximum removal of MB dye from wastewater, the adsorption experimental parameters such as initial dye concentration, contact time, solution pH and adsorbent dosage were optimized by trial and error approach. The obtained experimental results were applied to the different theoretical models to predict the system behaviour. The optimum conditions for the maximum removal MB dye from aqueous solution for an initial MB dye concentration of 25 mg/L was calculated as: adsorbent dose of 3 g/L, contact time of 90 min, solution pH of 7.0 and at the temperature of 30 °C. Freundlich and pseudo-second order models was best obeyed with the studied experimental data. Langmuir maximum monolayer adsorption capacity of MASD for MB dye removal was calculated as 58.14 mg of MB dye/g of MASD. Adsorption diffusion model stated that the present adsorption system was controlled by intraparticle diffusion model. The obtained results proposed that, novel MASD was considered to be an effective and low-cost adsorbent material for the removal of dye from wastewater.     

异舒泛蓝淋巴显像在16例头颈部鳞癌中的应用

目的 明确在头颈部鳞癌中，异舒泛蓝琳巴显像及前哨淋巴结活检术是否能准确显示肿瘤原发的淋巴引流。方法 在术中应周肿瘤原发灶周围注射异舒泛蓝的方法对16例头颈部鳞状细胞癌患者进行研究。结果 所有患者均未发现蓝染淋巴结。结论 异舒泛蓝术中淋巴显像这一技术在头颈部鳞癌的应用仍须进一步研究。     

Adsorptive removal of basic blue 41 using pistachio shell adsorbent - Performance in batch and column system

In present study, pistachio shell was used as an adsorbent to remove Basic blue 41 dye (BB 41) from textile wastewater effluents with a batch and a continuous system. The structure and characteristics of the pistachio shell were determined by pH_pzc, FTIR spectroscopy, BET surface area and SEM-EDX analysis. A batch system was used to investigate the effects of dye concentration, pH, quantity and particle size of adsorbent, reaction duration, temperature and ion strength on dye removal performance were investigated. The error analysis methods were employed to get adsorption kinetics and the best-fitting isotherm models for adsorption of BB 41 dye. The results of modeling studies proved that Langmuir isotherms and pseudo-second-order kinetics the best represented adsorption kinetics and isotherm data. Present findings revealed that BB 41 removal was a feasible, spontaneous and endothermic process. Decreasing removal (%) rates were with increasing NaCl and SDS concentrations. After three cycles, regeneration efficiency was calculated as 65.39%. Continuous mode of operation was used for optimization of process parameters such as initial pollutant concentration, effluent flow rate and bed height. In continuous system, maximum adsorption capacity was identified as 41.77 mg/g. The Adams-Bohart, Thomas and Yoon-Nelson models were used to find of the best fitting model for experimental data of continuous mode of operation. Pistachio shell had yielded quite high adsorption of dye, thus it was also conduced that pistachio shell could effectively and reliably be utilized in treatment of wastewater effluents of textile industry containing Basic blue 41 textile dye.     

Adsorptive removal of Safranin-O dye from aqueous medium using coconut coir and its acid-treated forms: Adsorption study,scale-up design,MPR and GA-ANN modeling

Coconut coir (Cocos nucifera L.), particle size 300–850 μm, has been identified as an adsorbent for safranin-O dye removal from aqueous solution. Bioadsorption efficiency is improved by modifying untreated coconut coir (UCC) with 1 N phosphoric acid (PCC) and 1 N sulphuric acid (SCC). The acid treatment enhances the surface area of adsorbents and accelerates more dye uptake. The adsorption process is optimized by varying the physicochemical conditions like initial pH, adsorbent amount, contact time, initial dye concentration, and temperatures. The adsorption process's optimum pH is 4, 6, and 6, respectively, using UCC, PCC, and SCC adsorbents.In contrast, more than 98% of dye removal has been observed at the lower concentration of dyes up to 200 mg/L at 303 K. Maximum dye removal is possible at 75 mg/L of dye concentration. UCC, PCC, and SCC adsorbents’ adsorption capacity is 80.32 mg/g, 96.81 mg/g, and 89.53 mg/g, respectively, at 303 K temperature. Langmuir and Tempkin model and the pseudo-second-order model are the best-fitted models for isotherm and kinetic study. Thermodynamic parameters indicate the adsorption process is viable, spontaneous, exothermic. 75% glacial acetic acid is the most potent solvent for safranin-O dye extraction from dye loaded biomass. The functional groups and different interactions are identified to establish the adsorption mechanism. The PCC adsorbent has been used for scale-up design. The multiple polynomial regression (MPR) successfully predicts the dye removal efficiency for individual adsorbents. The modeling of the Genetic Algorithm has also been done successfully.     

Investigation of drug self-association in aqueous solution using calorimetry, conductivity, and osmometry

Based on heat of dilution, osmotic coefficient and conductivity data, it is evident that the compound of interest in this study undergoes self-association in aqueous solution. The average aggregation number for the association product is small, not greater than 4. The likely association products are cation-cation dimer, cation-cation-anion or all cation trimer, and/or cation-cation-cation-anion tetramer. The observed self-association in aqueous solution is purely enthalpy driven, being entropy disfavored, indicating that the driving force for the self-association is likely to be either hydrogen bonding or π-π interaction or both, but not hydrophobic interaction or pure electrostatic interaction.     

Green synthesis of silver nanoparticles using aqueous extracts of three Sideritis species from Turkey and evaluations bioactivity potentials

The members of the genus Sideritis have a wide variety of phytochemicals and thus the genus are gaining interest to fabricate nanoparticles (via green synthesis) as sources reducing or stabilizer agents. In the present study, silver nanoparticles (AgNPs) were synthesized by an easy and eco-friendly method using aqueous extracts of three Sideritis species (Sideritis argyrea (SA), S. brevidens (SB), and S. lycia (SL)). These AgNPs were investigated in terms of cholinesterase (AChE: acetylcholinesterase and BChE: butyrylcholinesterase) and tyrosinase activities. The presence of (111), (200), (220) and (311) planes in Bragg's reflections verified the fcc (face-cantered-cubic) crystalline AgNPs. Sideritis species-directed AgNPs were characterized by surface plasmon resonance at 428–440 nm. Transmission electron microscopy (TEM) characterizations were showed the spherical and monodispersed of the AgNPs with an average particle size of 22–26 nm. Fourier transform infrared (FTIR) spectra were revealed functional groups responsible for the reduction of silver ions. Also, for the AgNPs were confirmed by the characterizations of Zeta Potential and Dynamic Light Scattering (DLS). Chlorogenic acid (CGA) was found as major component for all three species. We demonstrated that Sideritis-directed AgNPs showed excellent inhibitory activity against BChE, while Sideritis extracts have no effective inhibitory activity against AChE. Among AgNPs, SA AgNPs exhibited the greatest tyrosinase inhibitory activity with the value of 33.02 mg kojic acid equivalents (KAE)/g, following CGA AgNPs (18.31 mg KAE/g) and SB AgNPs (5.46 mg KAE/g). Regarding the extracts, they had similar tyrosinase inhibition activity (33.61–36.34 mg KAE/g). Our findings suggest that the green synthesis by using Sideritis extracts could be open a new horizon in the biotechnological applications such as bioactivity and drug delivery.