Stomach-specific drug delivery of 5-fluorouracil using floating alginate beads

A multiple-unit-type oral floating dosage form (FDF) of 5-fluorouracil (5-FU) was developed to prolong gastric residence time, target stomach cancer, and increase drug bioavailability. The floating bead formulations were prepared by dispersing 5-FU together with calcium carbonate into a mixture of sodium alginate and hydroxypropyl methylcellulose solution and then dripping the dispersion into an acidified solution of calcium chloride. Calcium alginate beads were formed, as alginate undergoes ionotropic gelation by calcium ions and carbon dioxide develops from the reaction of carbonate salts with acid. The evolving gas permeated through the alginate matrix, leaving gas bubbles or pores, which provided the beads buoyancy. The prepared beads were evaluated for percent drug loading, drug entrapment efficiency, image, surface topography, buoyancy, and in vitro release. The formulations were optimized for different weight ratios of gas-forming agent and sodium alginate. The beads containing higher amounts of calcium carbonate demonstrated instantaneous, complete, and excellent floating ability over a period of 24 hours. The optimized formulation was subjected to in vivo antitumor studies to check the therapeutic efficacy of the floating dosage forms containing 5-FU against benzo(a)pyrene-induced stomach tumors in albino female mice (Balb/C strain). The multiple-bead FDF was found to reduce the tumor incidence in mice by 74%, while the conventional tablet dosage form reduced this incidence by only 25%. Results indicate that FDF performed significantly better than the simple tablet dosage form. Published: June 22, 2007     

Sodium chloride induced changes in leaf growth, and pigment and protein contents in two rice cultivars

Rice (Oryza sativa L.) seedlings were grown under NaCl stress. The leaf growth of resistant cv. Damodar was less affected than that of the susceptible cv. Jaya. The leaf protein content showed no distinct cultivar or age dependent differences under NaCl salinity. There was a significant increase in chlorophyll (Chl) and carotenoid (Car) contents of 25-d-oldseedlings of both cv. Jaya and cv. Damodar. However, Chl and Car content of 15-d-old seedlings of cv. Jaya decreased and that of cv. Damodar increased, under NaCl stress. This revised version was published online in July 2006 with corrections to the Cover Date.     

Morphogenesis in Isolated Microspore Cultures of <Emphasis Type="Italic">Brassica juncea</Emphasis>

Androgenesis is a phenomenon in which microspores are made to bypass the sexual pathway and follow the sporophytic mode of development to generate new plants without the intervention of fertilization under specialized in vitro conditions. Microspore culture provides an ideal system, with a large, relatively uniform population of haploid cells, for use in mutant selection, genetic transformation and in studies on the molecular mechanism of induction of androgenesis and embryogenesis. This paper involves a study on establishing a reproducible and efficient protocol for microspore embryogenesis in various varieties of Brassica juncea. The genotype had a pronounced effect on androgenic response in microspore cultures. The cultivar Rajat exhibited the most response, producing around 3500 embryos/100 buds. The microspores of B. juncea cv. PR-45 from ed plants maintained at a day/night temperature of 10 °C/5 °C form embryos with suspensors with varied morphology. The microspore embryos germinated to produce plants with frequencies. These plants exhibited 52% survival and 74% fertility.     

Guanidinium chloride- and urea-induced unfolding of FprA, a mycobacterium NADPH-ferredoxin reductase: stabilization of an apo-protein by GdmCl

The guanidinium chloride- and urea-induced unfolding of FprA, a mycobacterium NADPH-ferredoxin reductase, was examined in detail using multiple spectroscopic techniques, enzyme activity measurements and size exclusion chromatography. The equilibrium unfolding of FprA by urea is a cooperative process where no stabilization of any partially folded intermediate of protein is observed. In comparison, the unfolding of FprA by guanidinium chloride proceeds through intermediates that are stabilized by interaction of protein with guanidinium chloride. In the presence of low concentrations of guanidinium chloride the protein undergoes compaction of the native conformation; this is due to optimization of charge in the native protein caused by electrostatic shielding by the guanidinium cation of charges on the polar groups located on the protein side chains. At a guanidinium chloride concentration of about 0.8 m, stabilization of apo-protein was observed. The stabilization of apo-FprA by guanidinium chloride is probably the result of direct binding of the Gdm+ cation to protein. The results presented here suggest that the difference between the urea- and guanidinium chloride-induced unfolding of FprA could be due to electrostatic interactions stabilizating the native conformation of this protein.     

Elicitor-induced rosmarinic acid accumulation and secondary metabolism enzyme activities in Solenostemon scutellarioides

This study aimed to improve rosmarinic acid (RA) production in the whole plant culture of Solenostemon scutellarioides through elicitation. Amongst selected elicitors methyl jasmonate (MJ), salicylic acid (SA), and yeast extract (YE) caused significant elevation in RA accumulation. Elicitation with MJ (50 μM) and SA (50 μM) caused almost 1.7 and 1.4-fold increase in RA accumulation, respectively, within day 1. While YE (100 μg ml^?1) elicitation showed highest RA content (~1.5-fold) in day 3. Preceding the elicitor-induced RA accumulation, there was a notable alteration in the specific activities of RA biosynthetic enzymes viz. phenylalanine ammonia lyase, tyrosine aminotransferase, hydroxyl-phenylpyruvate reductase and rosmarinic acid synthase up on MJ (50 μM), SA (50 μM) and YE (100 mg ml^?1) elicitation. Based on differential responses of aforementioned enzymes, RA synthesis was further scaled up through combination of elicitors in pre-optimized doses. In synergy study, at a time exposure with MJ + SA + YE and MJ + SA followed by YE after 24 h has been found to produce significant elevation of RA (2.0 and 1.9-fold, respectively) within 24 h while later maintained a steady state increased level (~1.7 ± 0.2-fold) over control up to day 7.     

Inhibitors of EGFR Signaling Retard Cytotoxicity of Fenretinide in Rat Gliosarcoma Cells

Purpose Fenretinide, 4-(N-hydroxyphenyl) retinamide, (4-HPR) is a well tolerated analog of alltrans retinoic acid. The gangliosideGM3, is a non-specific inhibitor of EGF receptor autophosphorylation (EGFR-phos). Both compounds were found preferentially cytotoxic to malignant and proliferating cells when compared to non-proliferating normal brain cells. Some of the small molecule inhibitors of EGFR-phos are also known to inhibit growth of brain tumors at relatively non-toxic doses. The purpose of this investigation was to evaluate if 4-HPR and inhibitors of EGFR-phos could be used together in the treatment of brain tumors. Methods The 9L rat gliosarcoma cells were treated in vitro with 4-HPR either alone or in combination with the non-specific or specific inhibitors of EGFR-phos, GM3 or AG-1478, respectively. The relative viability of the control and treated cells was determined using 3-(4,5-imethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The experimental data were analyzed for statistical significance. Results In contrast to the expected additive/synergistic effect on cell growth inhibition, the sub-toxic and toxic concentrations of 4-HPR protected GM3 treated cells. The viable cells were 3.86 times higher following GM3 plus 4-HPR treatments compared to GM3 treatment alone. Additionally, a specific inhibitor of EGFR-phos signaling, AG-1478 caused a concentration dependent protection of cells from the toxicity of 4-HPR. Our results show counteracting cytotoxic responses of 4-HPR and EGFR-phos inhibitors when used together in 9L rat gliosarcoma cells.     

Comparative studies on carcass characteristics of marketable size farmed mrigal Cirrhinus mrigala, (Hamilton, 1822), and silver carp Hypophthalmichthys molitrix, (Val., 1844)

The carcass traits and commercial characteristics of farmed freshwater Cirrhinus mrigala and Hypophthalmichthys molitrix were investigated to calculate yield data useful for programming semi‐automated processing units. Specimens with average weights of 2500 and 3400 g were collected from both mrigal and silver carps, respectively. Samples were taken from grow‐out culture ponds of the Central Institute of Freshwater Aquaculture (CIFA), Odisha State, India. Carcass and offal yields as well as carcass cutability were assessed. Head yields were recorded as 14.9 and 27.5% for mrigal and silver carp, respectively. The gutted yield, headless yield and skinless dressed round percentages were determined as 89.4, 74.5 and 67.6% for mrigal and 92.8, 65.4 and 62.0% for silver carps, respectively. The meat: bone ratio in filleting averaged 4.8 for mrigal and 3.1 for silver carp. The middle cut of mrigal had both the highest total yield percentage and highest meat yield, whereas this was equally distributed between both the fore and middle cuts in silver carp. In both mrigal and silver carp the dry matter, ether extract and protein percentages were highest in the fore cut followed by middle and hind cut. In silver carp the percentage fat content was found to be significantly higher than in mrigal.