Selenium salts and chromosome damage

Sodium selenite and sodium selenate, fed by gavaging to age-matched male Swiss albino mice and observed after 24 h following a colchicine-fixative-air drying-Giemsa schedule, were found to induce chromosome breaks and spindle disturbances in bone marrow cells. The four concentrations used were fractions of LD₅₀ and the effects were directly proportionate to the concentration of the chemical. Sodium selenite induced a slightly higher frequency of chromosomal aberrations than sodium selenate.     

Evaluation of Postharvest-Processed Oysters by Using PCR-Based Most-Probable-Number Enumeration of Vibrio vulnificus Bacteria

Postharvest processing (PHP) is used to reduce levels of Vibrio vulnificus in oysters, but process validation is labor-intensive and expensive. Therefore, quantitative PCR was evaluated as a rapid confirmation method for most-probable-number enumeration (QPCR-MPN) of V. vulnificus bacteria in PHP oysters. QPCR-MPN showed excellent correlation (R² = 0.97) with standard MPN and increased assay sensitivity and efficiency.     

Comparison of clastogenic effects of inorganic selenium salts in mice in vivo as related to concentrations and duration of exposure

Inorganic selenium compounds in the diet have been known to protect against cancer in laboratory animals, but were harmful in high concentrations. In the present work, the relative effects of two salts, sodium selenite and sodium selenate, administered to mice in vivo, in different concentrations and durations of exposure, were compared. Aqueous solutions of each salt (7, 14, 21 and 28 mg Kg^–1 bw) were fed by gavaging to mice matched in age and sex. The animals were sacrificed at intervals of 6, 12, 18 and 24 h and chromosome preparations were made following the usual schedule of colchicine-hypotonic-fixative-airdrying-Giemsa staining. The endpoints screened were chromosomal aberrations (CA) and damaged cells (DC). Both salts affected chromosome structure and spindle formation, sodium selenite being more cytotoxic than sodium selenate. The frequencies of aberrations induced were directly proportional to the concentrations used and duration of exposure.     

In Vitro Selection Against Ascochyta Blight of Chickpea (Cicer arietinum L)

Callus cultures established on MS medium containing 2.0 mg l^-1 2, 4-D were inoculated on the regeneration medium supplemented with different concentrations (0.5, 1.0, 1.5, 2.0, 2.5 and 3%, v/v) of culture filtrate (CF) of Ascochyta rabiei infesting chickpea. Out of 486 callus pieces and 270 regenerants obtained from immature embryo derived callus screened, 50 callus lines and 74 regenerants were found resistant. Further, these resistant callus lines and regenerants were subjected to stability test by growing them on a medium containing 3% CF. Seventeen callus lines and 28 regenerants of the selected lines showed normal growth on the selection medium. The regenerated plants were tested in pots under artificial epiphytotic conditions where they showed normal growth behaviour and high degree of resistance.     

Reevaluation of the effect of dietary restriction on different recombinant inbred lines of male and female mice

Dietary restriction (DR) was reported to either have no effect or reduce the lifespan of the majority of the 41‐recombinant inbred (RI) lines studied by Liao et al. (Aging Cell, 2010, 9, 92). In an appropriately power longevity study (n > 30 mice/group), we measured the lifespan of the four RI lines (115‐RI, 97‐RI, 98‐RI, and 107‐RI) that were reported to have the greatest decrease in lifespan when fed 40% DR. DR increased the median lifespan of female RI‐115, 97‐RI, and 107‐RI mice and male 115‐RI mice. DR had little effect (<4%) on the median lifespan of female and male 98‐RI mice and male 97‐RI mice and reduced the lifespan of male 107‐RI mice over 20%. While our study was unable to replicate the effect of DR on the lifespan of the RI mice (except male 107‐RI mice) reported by Liao et al. (Aging Cell, 2010, 9, 92), we found that the genotype of a mouse had a major impact on the effect of DR on lifespan, with the effect of DR ranging from a 50% increase to a 22% decrease in median lifespan. No correlation was observed between the changes in either body composition or glucose tolerance induced by DR and the changes observed in lifespan of the four RI lines of male and female mice. These four RI lines of mice give the research community a unique resource where investigators for the first time can study the anti‐aging mechanism of DR by comparing mice in which DR increases lifespan to mice where DR has either no effect or reduces lifespan.     

Therapeutic efficacy of rifaximin loaded tamarind gum polysaccharide nanoparticles in TNBS induced IBD model Wistar rats

BackgroundRifaximin is a non-systemic antibiotic used in the treatment of inflammatory bowel disease (IBD). Antibiotics are demonstrating a significant role in the treatment of IBD by altering the dysbiotic colonic microbiota and decreases the immunogenic and inflammatory response in the patient population. Mucoadhesive colon targeted nanoparticles provide the site-specific delivery and extended stay in the colon. Since the bacteria occupy the lumen, spread over the surface of epithelial cells, and adhere to the mucosa, delivering the rifaximin as a nanoparticles with the mucoadhesive polymer enhances the therapeutic efficacy in IBD. The objective was to fabricate and characterize the rifaximin loaded tamarind gum nanoparticles and study the therapeutic efficacy in the TNBS-induced IBD model ratsMaterials and methodsThe experimentation includes fabrication and characterization of drug excipient compatibility by FTIR. The fabricated nanoparticles were characterized for the hydrodynamic size and zeta potential by photon correlation spectroscopy and also analyzed by TEM. Selected best formulation was subjected to the therapeutic efficacy study in TNBS-induced IBD rats, and the macroscopic, microscopic and biochemical parameters were reported.ResultsThe study demonstrated that the formulation TGN1 is best formulation in terms of nanoparticle characterization and hydrodynamic size which showed the hydrodynamic size of 171.4 nm and the zeta potential of −26.44 mV and other parameters such as TEM and drug release studies were also reported.ConclusionsThe therapeutic efficacy study revealed that TGN1 is efficiently reduced the IBD inflammatory conditions as compared to the TNBS control group and reference drug mesalamine group.     

Production of sapogenins (stigmasterol and hecogenin) from genetically transformed hairy root cultures of <Emphasis Type="Italic">Chlorophytum borivilianum</Emphasis> (Safed musli)

Chlorophytum borivilianum belonging to the family Liliaceae, is distributed in the pantropical regions of India and South Africa. The sapogenins (stigmasterol and hecogenin) of C. borivilianum are well known for their appetizing and aphrodisiac properties. The present study involves enhancing the sapogenin content in C. borivilianum by genetic transformations with Agrobacterium rhizogenes strains (MTCC 2364 and 532, PRT Gus). A maximum transformation frequency of 98% was obtained with Agrobacterium rhizogenes MTCC 2364 strain with rhizome explants after a co-cultivation period of 48 h. Two potential rhizoclones (2364a and 2364b) were selected for the production of stigmasterol and hecogenin. The maximum production of stigmasterol (83.952?±?0.01 mg/g) was seen in 2364b rhizoclone, whereas, the highest accumulation of hecogenin (81.52?±?0.02 mg/g) was observed in 2364a rhizoclone. The C. borivilianum hairy root cultures obtained in this study provide a continuous and sustainable production of stigmasterol and hecogenin on a commercial scale.     

Identification and characterization of a spontaneously aggregating amyloid-forming variant of human PrP((90-231)) through phage-display screening of variants randomized between residues 101 and 112

The N-terminal 'unstructured' region of the human prion protein [PrP((90-231))] is believed to play a role in its aggregation because mutations in this region are associated with seeding-independent deposition disorders like Gerstmann-Straussler-Scheinker disease (GSS). One way of examining the effects of such mutations is to search combinatorially derived libraries for sequence variants showing a propensity to aggregate and/or the ability to interact with prion molecules folded into a beta-sheet-based conformation (i.e., beta-PrP or PrP(Sc)). We created a library of 1.8x10(7) variants randomized between positions 101 and 112, displayed it on filamentous bacteriophage, and 'spiked' it with a approximately 25% population of phages-bearing wild-type prion (wt-PrP). Screening was performed through four rounds of biopanning and amplification against immobilized beta-PrP, and yielded three beta-PrP-binding populations: wt-PrP (26% representation) and two non-wt-PrP variants ( approximately 10% and approximately 64% representation, respectively). The remarkable enrichment of one non-wt-PrP variant (MutPrP) incorporating residues KPSKPKTNMKHM in place of KGVLTWFSPLWQ, despite its initial representation at a 5 million-fold lower level than wt-PrP, caused us to produce it and discover: (i) that it readily aggregates into thioflavin-T-binding amyloids between pH 6.0 and 9.0, (ii) that it adopts a soluble beta-sheet based monomeric structure at pH 10.0, (iii) that it is less thermally stable and more compact than wt-PrP, and (iv) that it displays significantly greater resistance to proteolysis than wt-PrP. Our results suggest that sequence variations in the 101-112 region can indeed predispose the prion for aggregation.     

Identification and SAR around N-{2-[4-(2,3-dihydro-benzo[1,4]dioxin-2-ylmethyl)-[1,4]diazepan-1-yl]-ethyl}-2-phenoxy-nicotinamide, a selective alpha2C adrenergic receptor antagonist

The discovery of the CNS-penetrant and selective alpha(2C) adrenergic receptor antagonist N-{2-[4-(2,3-dihydro-benzo[1,4]dioxin-2-ylmethyl)-[1,4]diazepan-1-yl]-ethyl}-2-phenoxy-nicotinamide, 13 is described. Structure-activity studies demonstrate the structural requirements for binding affinity, functional activity, and selectivity over other alpha(2)-AR subtypes.