Evaluation of SAR for Amphotericin B Derivatives by Artificial Neural Network

Purpose: This study was designed to investigate the role of several descriptive structure-activity features in the antifungal drug, amphotericin B and analyze them by artificial neural networks. Method: Artificial neural networks (ANN) based on the back-propagation algorithm were applied to a structure-activity relationship (SAR) study for 17 amphotericin B derivatives with antifungal and membrane directed activity. A series of modified ANN architectures was made and the best result provided the ANN model for prediction of antifungal activity using the structural and biologic property descriptors. Results: The best architecture, in terms of cycles of calculation was 12-15-2. Among the most important factors were biological descriptors that correlated best with the model produced by ANN. Among the chemical and structural descriptors, positive charge on Y substitution was found to be the most important, followed by lack of availability of free carboxyl and parachor. Conclusion: This model is found to be useful to elucidate the structural requirements for the antifungal activity and can be applied in the design and activity prediction of the new amphotericin B derivatives. Keywords: Amphotericin B, SAR, Artificial Neural Network. > Tropical Journal of Pharmaceutical Research Vol. 4 (2) 2005: pp. 517-52

Membrane distillation for treating hydraulic fracturing produced waters

The reuse of wastewater for beneficial uses has become increasingly important in recent years. There is an urgent need to develop innovative and more effective technologies for treatment of wastewaters. Many of these wastewaters such as hydraulic fracturing produced waters, contain very high total dissolved solids (TDS). Treatment of hydraulic fracturing produced waters can be very challenging as not only can they exhibit very high TDS, in excess of 200,000 ppm, they also contain surfactants and small organic compounds. Pressure driven membrane processes such as reverse osmosis are impractical for treating very high salinity wastewaters due to the high osmotic back pressure that must be overcome. Membrane distillation has been proposed as a new unit operation for treatment of very high TDS wastewaters. Vapor pressure is the driving force for water recovery in membrane distillation. An advantages of membrane distillation is the fact that low grade waste heat may be used. Here we have screened a number of commercially available microporous hydrophobic membranes. We have characterized membrane surface as well as bulk properties. Using bulk membrane properties, we calculate a structural parameter that indicates membranes that display high permeate flux. Next these membranes were challenged with feed streams containing 100,000 ppm (1.7 M) NaCl. The feeds stream was concentrated until breakthrough of the feed liquid into the permeate. Breakthrough occurred when the permeate flux rose rapidly while the conductivity of the permeate increased above 50 mS cm-1. Finally, these membranes were tested with real produced waters. Membranes that enabled the greatest concentration of TDS were selected for testing. While membrane distillation could be used to concentrate the feed to the solubility limit of the dissolved species present, leakage of feed water through the membrane pores into the distillate often occurs well before this level of water recovery. Leakage occurs due the presence of oil and suspended solids in the feed which can adsorb on the membrane surface. Thus pretreatment of the feed is essential. Here we have investigated the use of electrocoagulation as a pretreatment step for membrane distillation. Suspended solids and oil can be effectively coagulated followed by sedimentation prior to membrane distillation. A laboratory scale electrocoagulation system containing aluminum electrodes was designed, optimized and employed successfully to pretreat the feed. Please click Additional Files below to see the full abstract

Antimicrobial peptides of the vaginal innate immunity and their role in the fight against sexually transmitted diseases

Some antimicrobial peptides (AMPs) are produced in the vaginal innate immune system and play an important role in protecting this organ against pathogenic agents. Moreover, sexually transmitted diseases have become a major problem in human societies and are rapidly spreading. The emergence of antibiotic-resistant microbes (superbugs) can pose a major threat to human societies and cause rapid spread of these diseases. Finding new antimicrobial compounds to fight superbugs is therefore essential. It has been shown that AMPs have good potential to become new antibiotics. The most important AMPs in the vaginal innate immune system are defensins, secretory leucocyte protease inhibitors, calprotectin, lysozyme, lactoferrin and elafin, which play an important role in host defence against sexually transmitted infections, modulation of immune responses and anticancer activities. Some AMPs, such as LL-37, magainin 2 and nisin, show both spermicidal and antimicrobial effects in the vagina. In this summary, we will discuss vaginal AMPs and continue to address some of the challenges of using peptides to control pathogens that are effective in sexually transmitted diseases. © 2019 The Author(s

Effect of non-nutritional factors on nisin production

When attempting to improve production of nisin, understanding the effect of non-nutritional factors is essential owing to a lack of adequate information about these factors among various investigations. Inorder to assess some of non-nutritional factors and how they influence the nisin production in batch cultivation, a laboratory scale study was performed. Lactococcus lactis subsp. lactis ATCC 11454 produced nisin and Micrococcus luteus ATCC 10240 was used in bioassay measurement as the nisinsensitive strain. The age and size of inoculum, initial pH value of the medium and flask volume/medium volume (F/M) ratio, temperature as well as agitation were studied by changing one factor at a time whilekeeping others constant in de Man, Rogosa and Sharpe (MRS) medium. Our results implied that pH value was positively related to increase nisin production. Two other important factors for a maximum nisin production were found to be agitation and flask volume/medium volume (F/M) ratio. Inoculum size more than 2.5% (v/v) had no effect on nisin production. The most suitable condition for inoculum age was 32-hour-old culture (at the end of log phase) and 27°C temperature provided maximum nisinproduction

Improved Refolding Efficacy of Recombinant Human Interferon α-2b via pH Modulation

Purpose: To increase the refolding yield of Recombinant Human Interferon α-2b in order to achieve a highly potent product.Methods: Interferon α-2b inclusion body was dissolved in tris-HCl buffer containing 6 M guanidine-HCl and CuSO4. Different refolding buffers were employed for refolding the target protein. The refolded proteins were then purified by affinity and gel filtration chromatography. The purified proteins were subjected to circular dichroism (CD) spectropolarimetry and assayed for biological activity in vitro.Results: Increment of pH to 8.5 improved refolding efficacies from 42.28 % to 71.22 %. However, the relative potency significantly increased up to pH 8.0 (from 19353546 to 28633902, p < 0.05) and then decreased to 21081305.00 at pH 8.5. The CD spectra demonstrated that by increasing pH to 8.5, the secondary structure of the protein was altered, probably due to increase in alpha-helix from 23.7 % at pH 7.0 to 28.1 %.Conclusion: Employing a low-cost and simple method, such as alteration of refolding buffer pH, results in higher refolding yield in downstream processing of rhIFN α-2b.Keywords: Recombinant human interferon α-2b, Refolding, Circular dichroism, Spectropolarimetry,Recombinant protein, pH effec

tert-Butyl 6-benzoyl-5-hydr­oxy-2-oxo-2H-chromene-4-carboxyl­ate

In the title compound, C21H18O6, a previously unknown coumarin derivative, the benzoyl substitutent makes a dihedral angle of 53.80 (16)° with the plane of the coumarin rings. An intramolecular O—H⋯O hydrogen bond is observed

Buthionine sulfoximine inhibits cytopathic effects and apoptosis induced by infection with AIK-HDC strain of measles virus

Background: Measles virus (MV) is a highly contagious agent which causes a major health problem in developing countries. We studied the effect of buthionine sulfoximine (BSO) on the replication of an AIK-HDC strain of MV and its induced apoptosis in Vero cell lines. Methods: In this study, toxicity of BSO on Vero cells was investigated first, resulted in determination of sub-lethal or non-toxic concentration zone of BSO for cells. Next, anti-viral effect of BSO at various time limits was evaluated and virus titer was determined at each stage either as 50 tissue culture infective dose (TCID) 50 or by plaque assay method. Using specific anti-measles IgG, anti-viral effect of BSO on MV replication cycle was evaluated through indirect immunofluorescence assay, meanwhile presence of viral RNA was investigated by RT-PCR and gel electrophoresis. Results: According to the experiments, BSO, at concentration of 50 μM, markedly inhibited the cytopathic effect (CPE) induced by MV. BSO also significantly inhibited apoptosis induced by MV. BSO either influences replication of MV genome, or may inhibit virion formation. Conclusion: These results suggest that the inhibition of CPE and apoptosis by BSO induced by MV may be associated with the effect of BSO on viral RNA genome. Therefore, it is suggested that MV infections can induce apoptosis through the activation of a common pathway that can be inhibited by BSO

Numerical study of a multiple-segment metal foam-PCM latent heat storage unit: Effect of porosity, pore density and location of heat source

This study numerically investigates the performance of the melting process for a PCM based heat storage system under the effect of different variables in a vertical container with a copper metal foam. Different cases were studied and compared including the effects of variable porosities and pore densities, non-equilibrium porous medium model, a multiple-segment metal foam case and different heater locations in the system on the liquid fraction and temperature as presented by contour plots and diagrams. The results show high performance for the copper foam-PCM unit compared with on its own PCM, for reducing the melting time by almost 85%. By changing the location of constant temperature heater from the bottom to the side and top surface, the melting time decreases by 70.5% and 4.7%, respectively. By using a multiple-segment porous system, the melting time reduces by 3.5% compared with the case of uniform porosity. Furthermore, the more accurate non-equilibrium numerical model shows a 7.4% difference in the melting time compared with the equilibrium model. This study optimises the design to improve practical application performance and to reduce waste energy

Numerical modelling of phase change material melting process embedded in porous media: Effect of heat storage size

The aim of this paper is to study the influence of enclosure size in latent heat thermal energy storage systems embedded in a porous medium for domestic usage of latent heat thermal energy storage heat exchangers. A 2-D rectangular enclosure is considered as the computational domain to study the heat transfer improvement for a phase change material embedded in a copper foam considering a constant heat flux from the bottom surface. Different dimensions of the composite system are examined compared with a system without a porous medium. The thermal non-equilibrium model with enthalpy-porosity method is employed for the effects of porous medium and phase change in the governing equations, respectively. The phase change material liquid fraction, temperature, velocity, stream lines and the rate of heat transfer are studied. The presence of a porous medium increases the heat transfer significantly, but the improvement in melting performance is strongly related to the system's dimensions. For the dimensions of 200 × 100 mm (W × H), the melting time of porous-phase change material with the porosity of 95% is reduced by 17% compared with phase change material-only system. For the same storage volume and total amount of thermal energy added, the melting time is lower for the system with a lower height, especially for the phase change material-only system due to a higher area of the input heat. The non-dimensional analysis results in curve-fitting correlations between the liquid fraction and Fo.Ste.Ra−0.02 for rectangular latent heat thermal energy storage systems for both phase change material-only and composite-phase change material systems within the parameter range of 1.16 less than less than Lf less than 1 and 0 less than Fo.Ste.Ra−0.02 less than 0.57. Over a range of system's volume, heat flux and surface area of the input heat flux, the benefit of composite phase change material is variable and, in some cases, is negligible compared with the phase change material-only system