Synthesis and biological evaluation of potential modulators of malarial glutathione-S-transferase(s)

Glutathione-S-transferase(s) (E.C.2.5.1.18, GSTs) have been investigated in parasitic protozoans with respect to their biochemistry and they have been identified as potential vaccine candidates in protozoan parasites and as a target in the synthesis of new antiparasitic agents. In a search towards the identification of novel biochemical targets for antimalarial drug design, the area of Plasmodium glutathione metabolism provides a number of promising chemotherapeutic targets. GST activity was determined in various subcellular fractions of malarial parasites Plasmodium yoelii and was found to be localized mainly in the cytosolic fraction (specific activity, c. 0.058 +/- 0.016 micromol/min/mg protein). Hemin, a known inhibitor of mammalian GST(s), maximally inhibited this enzyme from P. yoelii to nearly 86%. In a search towards synthetic modulators of malarial GST(s), 575 compounds belonging to various chemical classes were screened for their effect on crude GST from P. yoelii and 92 compounds belonging to various chemical classes were studied on recombinant GST from P. falciparum. Among all the compounds screened, 83 compounds inhibited/stimulated the enzyme from P. yoelii/P. falciparum to the extent of 40% or more.     

Bioaccumulation and biosorption of Co2+ by Neurospora crassa

Summary Mycelial biomass of wild type and a Co²⁺-resistant N.crassa (cor) was used to remove Co²⁺ from aqueous media. Mycelia obtained from growth in nitrate N-medium (NaNO₃) was more effective than ammonium N-medium (NH₄NO₃), in removing Co²⁺. Co²⁺-resistant N.crassa cor was more efficient than wild type in removing Co²⁺ from medium containing higher concentrations (500 mg/L). Metal removal was linear up to 12 h at which 35–60% Co²⁺ is depleted from medium, reaching near saturation by 24 h (90% removal). Co²⁺ removal was as efficient even from pure solutions and sodium azide inhibited the process up to 60%. Cell walls prepared from nitrate N-medium grown mycelia bound 3–5 fold more Co²⁺ when compared to ammonium N-medium. The importance of bioaccumulation and biosorption in bioremediating toxic metal ions from effluents is discussed.     

Filtering Decanting Water in Fly-Ash Lagoons Using Geotextiles — An Experimental Study

Disposal of fly-ash at thermal power stations is carried out in the form of ash slurry by mixing the ash with water. The ash slurry is stored in an ash pond. The water in the slurry is gradually drained out, through decanting wells, earthen embankments, and over spillways, leaving the ash to be deposited in the pond. It is observed that the design of decanting wells presently used allows a considerable amount of fly-ash to flow out with the water, leading to the contamination of soil and water courses. Further, it is observed that the failure of earthen embankments of ash ponds, which results in major damage to the environment, is mainly due to ineffective functioning of filters. This article presents the details of an experimental investigation carried out to study the role of geotextiles in improving the performance of decanting wells and different drainage systems in earthen embankments. Two series of experiments were carried out. In the first series a model-decanting well was tested with two different Geotextiles linings. In the second series, a number of model earthen embankments were tested with and without geotextiles. The economics of providing geotextiles in earthen embankments was studied. The results indicated that the use of Geotextiles improve the performance of decanting wells by reducing the amount of ash flowing into the decanting well and drainage system. Further, the use of Geotextiles has shown an improvement in the performance of earthen embankment used for ash ponds. The use of Geotextiles in earthen embankment is shown to be economical compared to the conventional drainage system.     

A multiplex PCR technique to characterize human bone marrow derived mesenchymal stem cells

Human mesenchymal stem cells (MSCs), with capacity to differentiate into adipocytes, osteoblasts and chondrocytes, offer potential for the development of novel treatments. A critical question in MSCs biology is whether this cell population possesses a relatively uniform differentiation capability or is comprised of distinct subsets of progenitors committed to differentiate in particular pathways. To quantify the changes during growth of MSCs, we analyzed the mesenchymal phenotype and differentiation ability using a multi-marker PCR with six primer sets specific for CD73, CD90, CD105, CD166, CD45 and β-actin allowing a gel-based differential detection of the PCR products. To determine degree of variability of MSCs populations in terms of proliferation, cell proliferation assays were performed on expanded MSCs up to the sixth passage. At each passage, the osteogenic and adipogenic differentiation potentials of MSCs were verified by culture in inductive media. RT-PCR and cytochemical analysis revealed that, despite the loss of multipotentiality during expansion, certain markers remain expressed, indicating that these markers are unlikely to be reflective of the MSC’s true ‘stem cell’ nature. Our results suggest that decrease in the expression of MSCs specific markers correlates with down-regulation of proliferation ability and differentiation efficiency of MSCs.     

Interaction of Pb and Cd with gum kondagogu (Cochlospermum gossypium): A natural carbohydrate polymer with biosorbent properties

Gum kondagogu (Cochlospermum gossypium), an exudates tree gum from India was explored for its potential to decontaminate toxic metals (Pb²⁺ and Cd²⁺). Optimum biosorption of metals were determined by investigating the contact time, pH, initial concentration of metal ions and biosorbent dose at 25 ± 2 °C. The maximum metal biosorption capacity for gum kondagogu was observed for Pb²⁺ (48.52 mg g⁻¹) and Cd²⁺ (47.48 mg g⁻¹) as calculated by Langmuir isotherm model. Kinetic studies showed that the biosorption rates could be described by pseudo-second-order expression. The metal interactions with biopolymer were assessed by FT-IR, SEM–EDXA and XPS analysis. Results based on these techniques suggest that mechanism of metal binding by the biopolymer involves micro-precipitation, ion-exchange and metal complexation.     

Improved somatic embryogenesis of grapevine (<Emphasis Type="Italic">Vitis vinifera</Emphasis>) with focus on induction parameters and efficient plant regeneration

A study of four parameters (induction medium, floral explant, developmental stage and year) was carried out to determine the best combination for the embryogenesis induction of eight grapevine (Vitis vinifera L.) cultivars. Anthers and ovaries were extracted from flower buds at three developmental phases and incubated in two induction media over two consecutive years. As average, the percentage of embryogenesis on Nitsch and Nitsch-derived medium (9.1%) was higher than in Murashige and Skoog-derived medium (5.9%) and embryogenesis from ovaries (10.1%) was 2-fold higher than from anthers (4.9%). Earlier flower developmental stages (II–III) favored embryogenic induction from anthers, while later stages (III–V) did it from ovaries. Induction of embryogenic cultures was genotype dependent. Two years after the establishment of the embryogenic lines, an average of 48.0% of the pro-embryogenic masses were viable and suitable to initiate cell suspensions. Embryogenic cultures of four genotypes showed a high percentage of conversion from embryos to plants: Albariño (61.8%), Garnacha (48.8%), Tempanillo (71.0%) and Sultanina (69.0%). Moreover, cell suspensions were competent for transient transformation based on β-glucuronidase assay, as up to 6,387 blue spots per Petri plate after Biolistic bombardment were obtained. Here, we present the advantage of ovaries over anthers for the embryogenesis induction of several grapevine cultivars. This is the first report of embryogenesis from the cultivars Albariño, Verdejo and Muscat Hamburg as well as transient transformation of Albariño and Tempranillo.     

Oral Bioavailability Enhancement of Exemestane from Self-Microemulsifying Drug Delivery System (SMEDDS)

Limited aqueous solubility of exemestane leads to high variability in absorption after oral administration. To improve the solubility and bioavailability of exemestane, the self-microemulsifying drug delivery system (SMEDDS) was developed. SMEDDS comprises of isotropic mixture of natural or synthetic oil, surfactant, and cosurfactant, which, upon dilution with aqueous media, spontaneously form fine o/w microemulsion with less than 100 nm in droplet size. Solubility of exemestane were determined in various vehicles. Ternary phase diagrams were plotted to identify the efficient self-emulsification region. Dilution studies, droplet size, and zeta potential of the formulations were investigated. The release of exemestane from SMEDDS capsules was studied using USP dissolution apparatus in different dissolution media and compared the release of exemestane from a conventional tablet. Oral pharmacokinetic study was performed in female Wistar rats (n = 8) at the dose of 30 mg kg⁻¹. The absorption of exemestane from SMEDDS form resulted in about 2.9-fold increase in bioavailability compared with the suspension. Our studies illustrated the potential use of SMEDDS for the delivery of hydrophobic compounds, such as exemestane by the oral route.Key words: bioavailability enhancement, exemestane, microemulsion, SMEDDS