A pilot study of an anti-endotoxin Ig-enriched bovine colostrum to prevent experimental sepsis

Despite the dramatic increase in antimicrobial resistance, there is a dearth of antibiotics in development and few pharmaceutical companies working in the field. Further, any new antibiotics are likely to have a short shelf life. Ab-based interventions offer alternatives that are not likely to be circumvented by the widely prevalent antibiotic resistance genes. Bovine colostrum (BC)—the first milk after parturition, rich in nutrients and immune components—promotes gut integrity and modulates the gut microbiome. We developed a hyperimmune BC (HBC) enriched in Abs to a highly conserved LOS core region of Gram-negative bacteria by immunizing pregnant cows with a vaccine comprised of detoxified LOS from Escherichia coli O111 Rc (J5) mutant non-covalently complexed to group B meningococcal outer membrane protein (J5dLOS/OMP). This vaccine generated robust levels of anti-J5 LOS Ab in the colostrum. When given orally to neutropenic rats challenged orally with Pseudomonas aeruginosa, administration of HBC improved survival compared to non-immune rats, while both BC preparations improved survival compared to PBS controls. Elevated circulating endotoxin levels correlated with mortality. HBC and to a lesser extent non-immune BC reduced bacterial burden from the liver, lung, and spleen. We conclude that HBC and to a lesser extent BC may be effective supplements that improve outcome from lethal gut-derived disseminated infection and may reduce transmission of Gram-negative bacilli from the gastrointestinal tract.     

Involvement of peripheral noradrenaline and 5-hydroxytryptamine in carrageenin-induced pedal oedema in rats

Role of peripheral and central noradrenaline and 5-hydroxytryptamine in the carrageenin-induced pedal oedema in rats was studied using agents which influence catecholamine synthesis and receptor activity of noradrenaline and 5-hydroxytryptamine. Reserpine, guanethidine, α-methyl-p-tyrosine, diethyldithiocarbamate, 6-hydroxydopamine, phenoxybenzamine, phentolamine, chlorpromazine and yohimbine markedly inhibited carrageenin-induced pedal oedema. However, 6-hydroxydopamine given intracerebroventricularly, 5,6-dihydroxytryptamine,p-chlorophenylalanine, lower dose of yohimbine, pro pranolol, haloperidol, cyproheptadine and mepyramine did not alter the carrageenin-induced oedema, whereas, cyproheptadine and mepyramine given simultaneously, markedly inhibited carrageenin-induced oedema. Our studies indicate that the process of oedema formation in rats by carrageenin involves both the peripheral noradrenaline and 5-hydroxytryptamine Communication No. 58 from IDPL Research Centre, Hyderabad.     

Celogentin mimetics as inhibitors of tubulin polymerization

Bicyclic analogues of celogentin C have been synthesized in which the side chain–side chain cross‐links are replaced by thioether bonds. Several of the simplified bicyclic peptides displayed potent inhibition of tubulin polymerization.     

Ebolavirus VP35 Coats the Backbone of Double-Stranded RNA for Interferon Antagonism

Recognition of viral double-stranded RNA (dsRNA) activates interferon production and immune signaling in host cells. Crystal structures of ebolavirus VP35 show that it caps dsRNA ends to prevent sensing by pattern recognition receptors such as RIG-I. In contrast, structures of marburgvirus VP35 show that it primarily coats the dsRNA backbone. Here, we demonstrate that ebolavirus VP35 also coats the dsRNA backbone in solution, although binding to the dsRNA ends probably constitutes the initial binding event.     

Optimization and characterization of sertaconazole nitrate flexisomes embedded in hydrogel for improved antifungal activity

The aim of the present research work was to develop, characterize and optimize sertaconazole nitrate (STZN) embedded flexisomes (STZN-FS) to improve the cutaneous anti-fungal activity of STZN. Flexisomes are self-aggregating, flexible, deformable lipidic vesicles possessing an aqueous core. A 3² factorial design was implemented to optimize the effects of the critical material attributes of concentration of phospholipid (X₁) and edge activator (X₂) on the critical quality attributes of particle size (Y₁), entrapment efficiency (Y₂), and deformability index (Y₃). Statistical analysis was performed to be identify the best fit model and determine its significance. The sizes of the optimized STZN-FS were found to be 246.2?±?2.49?nm with entrapment efficiencies of 86.16?±?0.56% and deformability indices of 30.46?±?0.41. Zeta potential analysis showed negatively charged surface with a zeta potential value of ?30.9?mV. TEM analysis showed spherical shapes, confirming the vesicular characteristics. The optimized STZN-FS were further formulated into hydrogels. The % drug diffusion of STZN-FS hydrogels was found to be 13.24% and drug deposition in the skin layers was found to be 83.54%, showing that a high concentration of the drug was available at the site of action. The zone of inhibition STZN-FS hydrogel (30?mm) was higher than the marketed formulation (22?mm) and the plain STZN hydrogel (14?mm) against Candida albicans. From the above studies, it was concluded that STZN loaded STZN-FS shows high flexibility and enhanced antifungal activity. STZN-FS are thus found to be potential carriers for drug deposition in skin layers without disturbing their integrity.     

Towards a Sustainable Paper Cycle: A Summary

The production of paper is a key economic activity accounting in value terms for about 2.5% of the world's industrial production and 2% of world trade. Paper products make a vital contribution to education, communications, packaging, and health care. In recent years the paper cycle has become the focus of environmental concerns about the impacts of forestry pollution from manufacturing, and waste. To address these concerns, the World Business Council for Sustainable Development commissioned the International Institute for Environment and Development (IIED) to examine the sustainability of the paper cycle. The first phase ofthe study involved a review of literature related to the paper cycle to identify the main debates and gaps in knowledge. This was followed by a journal of Industrial Ecology wide-ranging program of research and consultation on various aspects of the paper cycle. This article summarizes the key findings of the study for different stages of the cycle covering issues such as the impacts of forestry, the outlook for fiber supply, the role of nonwood fiber; the environmental and social impacts of pulp and paper manufacturing, the choice of options for wastepaper and the contribution of the paper cycle to greenhouse gas emissions. The study makes a number of recommendations for the pulp and paper industry, governments, international agencies, consumers, and nongovernmental organizations     

Color Space Geometry Uncovered with Magnetoencephalography

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