Cross-linked guar gum microspheres: A viable approach for improved delivery of anticancer drugs for the treatment of colorectal cancer

In the present work, guar gum microspheres containing methotrexate (MTX) were prepared and characterized for local release of drug in the colon, which is a prerequisite for the effective treatment of colorectal cancer. Guar gum microspheres were prepared by the emulsification method using glutaraldehyde as a cross-linking agent. Surface morphological characteristics were investigated using scanning electron microscopy. Particle size, shape, and surface morphology were significantly affected by guar gum concentration, glutaral dehyde concentration, emulsifier concentration (Span 80), stirring rate, stirring time, and operating temperature. MTX-loaded microspheres demonstrated high entrapment efficiency (75.7%). The in vitro drug release was investigated using a US Pharmacopeia paddle type (type II) dissolution rate test apparatus in different media (phosphate-buffered saline [PBS], gastrointestinal fluid of different pH, and rat cecal content release medium), which was found to be affected by a change to the guar gum concentration and glutaraldehyde concentration. The drug release in PBS (pH 7.4) and simulated gastric fluids followed a similar pattern and had a similar release rate, while a significant increase in percent cumulative drug release (91.0%) was observed in the medium containing rat cecal content. In in vivo studies, guar gum microspheres delivered most of their drug load (79.0%) to the colon, whereas plain drug suspensions could deliver only 23% of their total dose to the target site. Guar gum microspheres showed adequate potential in achieving local release of drug in in vitro release studies, and this finding was further endorsed with in vivo studies. Published: September 8, 2006     

Flux of certain radionuclides in the blood-clam Anadara granosa Linneaus under environmental conditions

The flux of fission product nuclides, caesium-137. cerium-144. and ruthenium-106, in the Bombay harbour ecosystem has been measured over a period of six years (1970–1976). during which the input of controlled low level radioactive waste was gradually reduced by more than 20 times. Of the various pelagic and benthic species studied, the arcid clam Anadara granosa Linn, showed a specific affinity for all three radionuclides; sequence of the degree of bio-accumulation was Ce ? Ru > Cs. Furthermore, the concentration of these nuclides in the tissues varied with the levels in the sedimentary material, which in turn was related to the inputs, maintaining some kind of equilibrium. On reaching maximum accumulation the levels of all three nuclides in the clam population decreased exponentially with time although the radioactivity was still available especially in the sediment. This decrease of radioactivity is defined as an ‘ecological loss rate’. The ecological half-time for cerium-144 and ruthenium-106 was about 3.6 times longer, and that of caesium-137 significantly shorter, than their respective physical half-lives. The ecological half-times of all three radionuclides were predominantly influenced by the environment rather than by the biological half-lives. This indicates that the biological half-lives of these nuclides were much shorter than their respective ecological half-lives. The biological half-time of caesium-137 was biphasic; the short-lived component had a half-time of about three days and the long-lived component had one of about 15 days.The bio-accumulation of an activation product nuclide cobalt-60 in A. granosa increased with the time of exposure and reached a level significantly higher than that of caesium-137, but was independent of the ambient concentrations and temperature. Thus the species was found to maintain the tissue concentration of fission product nuclides, cerium-144, ruthenium-106, and caesium-137 through adjusting physiological flux rates, in equilibrium with the changing levels of radionuclides in the environmental matrices, but not of the activation product nuclide cobalt-60.     

Thermodynamic constraints on the assembly and diversity of microbial ecosystems are different near to and far from equilibrium

Non-equilibrium thermodynamics has long been an area of substantial interest to ecologists because most fundamental biological processes, such as protein synthesis and respiration, are inherently energy-consuming. However, most of this interest has focused on developing coarse ecosystem-level maximisation principles, providing little insight into underlying mechanisms that lead to such emergent constraints. Microbial communities are a natural system to decipher this mechanistic basis because their interactions in the form of substrate consumption, metabolite production, and cross-feeding can be described explicitly in thermodynamic terms. Previous work has considered how thermodynamic constraints impact competition between pairs of species, but restrained from analysing how this manifests in complex dynamical systems. To address this gap, we develop a thermodynamic microbial community model with fully reversible reaction kinetics, which allows direct consideration of free-energy dissipation. This also allows species to interact via products rather than just substrates, increasing the dynamical complexity, and allowing a more nuanced classification of interaction types to emerge. Using this model, we find that community diversity increases with substrate lability, because greater free-energy availability allows for faster generation of niches. Thus, more niches are generated in the time frame of community establishment, leading to higher final species diversity. We also find that allowing species to make use of near-to-equilibrium reactions increases diversity in a low free-energy regime. In such a regime, two new thermodynamic interaction types that we identify here reach comparable strengths to the conventional (competition and facilitation) types, emphasising the key role that thermodynamics plays in community dynamics. Our results suggest that accounting for realistic thermodynamic constraints is vital for understanding the dynamics of real-world microbial communities.     

Larvicidal activity of Acacia nilotica extracts and isolation of D-pinitol--a bioactive carbohydrate

A low-molecular-weight, sugar-like compound other than glucose, fructose, sucrose, or myo-inositol showing lipophilic nature was isolated from the EtOH extract of Acacia nilotica. The structure of the compound was determined by spectral methods. This alicyclic polyalcohol was found to be D-pinitol (= 3-O-methyl-D-chiro-inositol; 1). The configuration of the compound was confirmed by single-crystal X-ray analysis. The compound 1 is known from Soybean, Australian mangroves, Fagonia indica, Arachis hypogaea, etc., but we have isolated this compound for the first time from the aerial parts of A. nilotica. Very few references have been cited for compound 1 for its entomological activity, and there are no reports on mosquitoes. Therefore, the crude extracts of A. nilotica were tested for its biological activity against mosquito larvae. Acetone extract at 500-ppm concentration showed chronic toxicity against Aedes aegypti and Culex quinquefasciatus IVth instar mosquito larvae. Such a biological activity has been observed for the first time for this plant. This study could be a stepping stone to a solution for destroying larval species as well as consumption of such a widely grown, problem weed, A. nilotica. This larvicidal agent, since it is derived from plant, is eco-friendly, cost effective, non-hazardous to non-target organisms and would be safe unlike commercially available insecticides.     

Selective deprotection of terminal isopropylidene acetals and trityl ethers using HClO4 supported on silica gel

Terminal isopropylidene acetals are selectively cleaved to the corresponding 1,2-diols in good to excellent yields in 6-24 h at room temperature by using the 'HClO4.SiO2' reagent system. Likewise, trityl ethers are readily cleaved to the corresponding alcohols in good to excellent yields within 2-3 h at room temperature. Work-up involves merely filtration of the reagent followed by purification of the crude product.     

Molecular mechanisms of autoimmunity triggered by microbial infection

Autoimmunity can be triggered by microbial infection. In this context, the discovery of Toll-like receptors (TLRs) provides new insights and research perspectives. TLRs induce innate and adaptive antimicrobial immune responses upon exposure to common pathogen-associated molecules, including lipopeptides, lipopolysaccharides, and nucleic acids. They also have the potential, however, to trigger autoimmune disease, as has been revealed by an increasing number of experimental reports. This review summarizes important facts about TLR biology, available data on their role in autoimmunity, and potential consequences for the management of patients with autoimmune disease.     

A blood stage fraction of Plasmodium berghei induces protective and long lasting immune response in BALB/c mice

Incorporation of the parasite's subcellular fractions in subunit vaccines can be a possible approach for formulation of vaccine against malaria. In this study, the immunogenicity and protective efficacy of 10,000 g fraction of blood stage Plasmodium berghei was evaluated in mouse model. This fraction induced higher levels of anti-parasite antibodies and provided complete and long lasting protection as compared to whole parasite antigens. Antiserum raised against it was immunoadsorbed on CNBr activated sepharose-4B to elute antigens from this fraction. Eluted antigens were characterized electrophoretically, and after lyophilization these were designated as ML-I (having 55, 64, 66, and 74 kDa proteins), ML-II (having 51, 64, 66, and 72 kDa proteins) and ML-III (having only 47 kDa protein) sub-fractions. Mice were immunized with these sub-fractions and immune responses induced by various immunization regimens were evaluated and compared with that of 10,000 g fraction. These sub-fractions imparted partial protection except ML-III, which was non-protective. 10,000 g fraction as a whole provided complete protection and generated significantly higher level of IL-2 and IFN-γ in immune mice. ML-I produced significant amount of IL-1 and IL-4 as compared to ML-II. Enhanced level of malaria-specific IgG1 was produced by ML-II, but IgG2a was significantly higher in ML-I immunized mice. Conclusively, this study identifies 10,000 g fraction as a promising blood stage vaccine candidate and suggests that a vaccine based upon multiple antigens may be more efficacious as compared to single antigen based formulations.