Induction of phase II enzymes is an important mechanism of chemo-prevention. In our search for novel cancer chemopreventive agents, 4*-bromoflavone (4*BF) was found to significantly induce quinone reductase (QR) activity in cultured murine hepatoma 1c1c7 cells (concentration to double activity: 10

Ciguatoxins (CTX) are polyether neurotoxins that target voltage-gated sodium channels and are responsible for ciguatera, the most common fish-borne food poisoning in humans. This study characterizes the global transcriptional response of mouse liver to a symptomatic dose (0.26 ng/g) of the highly potent Pacific ciguatoxin-1 (P-CTX-1). At 1 h post-exposure 2.4 % of features on a 44K whole genome array were differentially expressed (p £ 0.0001), increasing to 5.2 % at 4 h and decreasing to 1.4 % by 24 h post-CTX exposure. Data were filtered (|fold change | ‡ 1.5 and p £ 0.0001 in at least one time point) and a trend set of 1550 genes were used for further analysis. Early gene expression was likely influenced prominently by an acute 4C decline in core body temperature by 1 h, which resolved by 8 h following exposure. An initial downregulation of 32 different solute carriers, many involved in sodium transport, was observed. Differential gene

Abstract. Chalcone derivatives were evaluated for their antifilarial activity on Setaria cervi using glutathione-S-transferase (GST) as a drug target. The compounds 1-(4-benzotriazol-1-yl-phenyl)-3-(4-methoxyphenyl)prop-2-en-1-one (5), and 3-(4-methoxyphenyl)-1-(4-pyrrolidin-1-yl-phenyl) prop-2-en-1-one (7) showed a significant suppression ( P < 0.01) in GST activity of adult female parasite extract at 3 µM concentration in vitro. However, GST activity was detected along with depletion in GSH level. Except Compounds 1 and 2, all exhibited a significant effect on the motility and viability of adult parasites. Compounds 3-(4-chlorophenyl)-1-(4-piperidin-1-yl-phenyl)prop-2-en-1-one (3), 1-(4-ben-zotriazol-1-yl-phenyl)-3-(4-methoxyphenyl)prop-2-en-1-one (5), and 3-(4-methoxyphenyl)-1-(4-pyrrolidin-1-yl-phenyl) prop-2-en-1-one (7) exhibited major irreversible effects on viability and resulted in parasite death and also inhibited the GST activity by 84–100 % in vitro. We report for the first time the antifilarial activity of chalcones on GST of adult para-sites. This study also strengthens our previous findings where GST is reported as a potential drug target for antifilarials. The main problem regarding the chemotherapy of filaria-sis is that no safe and effective drug is available yet to com-bat adult human filarial worms. One of the main reasons is that filarial parasites exhibit a very strong antioxidant system, which protects them from the reactive oxygen species (ROS)

Glycine conjugation, a phase II detoxification process, is catalyzed

of banks of genes that mediate advance of the cell through a critical phase of its growth cycle. Loss of pRB function deprives the clock and thus the cell of an important mecha-nism for braking cell proliferation through modulation of gene expression. pRB and the G1 Restriction Point pRB exerts most

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. To identify the mechanisms responsible for efficient antigen capture, we studied the endocytic capacity of DCs using fluorescein isothiocyanate--dextran, horseradish peroxidase, and lucifer yellow. We found that DCs use two distinct mechanisms for antigen capture. The first is a high level of fluid phase

First published as an Advance Article on the web 3rd January 2001 The electrochemical generation and characterisation of a variety of o-quinodimethanes (o-QDMs) are described together with the outcome of preparative experiments in which they are key intermediates. The quinodimethanes are conveniently formed, in DMF, by both direct and redox-catalysed electroreduction of 1,2-bis(halomethyl)arenes. Their predominant reaction is polymerisation to poly(o-xylylene) (o-PX) polymers. In the presence of dienophiles the electrogenerated o-QDMs may undergo efficient cycloaddition reaction and distinctions between the possible mechanisms have been attempted on the basis of voltammetric, preparative and stereochemical experiments. Contrary to the precedent of the corresponding methyl ester, diphenyl maleate radical-anion isomerises only slowly to the fumarate radical-anion, yet co-electrolysis of 2,3-bis(bromomethyl)-1,4-dimethoxybenzene and diphenyl maleate or diphenyl fumarate gives exclusively the corresponding trans-adduct. Co-electrolysis of dimethyl maleate with either 1,2-bis(bromomethyl)benzene (more easily reduced) or 2,3-bis(bromomethyl)-1,4-dimethoxybenzene (less easily reduced) gave only o-PX polymer. The results are rationalised in terms of a double nucleophilic substitution mechanism where electron transfer between dienophile radical-anion and dihalide is relatively slow. Where electron transfer from maleate or fumarate radical-anions is likely to be fast o-quinodimethanes are formed by redox-catalysis and they polymerise rather than undergo Diels–Alder reaction. Dimerisation of the dienophile radical-anions, with k2 = 104 to 105 M1 s1, does not apparently compete with nucleophilic substitution or, where relevant, electron transfer.

re an n TT genetic factors involved in complex pathologies such as asthma is arduous, not only because of human genetic trapolated from one ethnic group to another [3]. Phase II detoxification enzymes, particularly classes of

action costs, leading to more efficient, "friction-free" markets. Table 1. Functions of a market Internet Economics Matching buyers and sellers . Determination of product offerings - Product features offered by sellers - Aggregation of different products . Search (of buyers for sellers and of sellers for buyers) - Price and product information - Matching seller offerings with buyer preferences . Price discovery - Process and outcome in determination of prices Facilitation of transactions . Logistics - Delivery of information, good, or service to buyer . Settlement - Transfer of payment to seller . Trust - Credit system, reputations, rating agencies like Consumer Reports and Better Business Bureaus Institutional infrastucture . Legal - Commercial code, contract law, dispute resolution, intellectual property protection . Regulatory - Rules and regulations, monitoring, enforcement produ