Quantitative Microscopy of Hepatic Changes Induced by Phenethyl Isothiocyanate in Fischer-344 Rats Fed Either a Cereal-Based Diet or a Purified Diet

Hepatic changes induced by phenethyl isothiocyanate (PEITC) in the liver of rats were determined by quantitative microscopy. Groups of male Fischer-344 rats were fed either a standard, cereal-based diet (Wayne rodent meal) or a purified diet (AIN-76A) containing PEITC at concentrations of 0.75 and 6.0 mmol/kg for 13 wk. Severe hepatic lipidosis was observed in control rats fed the purified diet. Addition of PEITC to the purified diet significantly reduced lipid content in hepatocytes. In contrast, lipid content in the liver of the rats fed the cereal-based diet containing PEITC was greater than in control rats maintained on the same diet. In addition, dose-related reductions in hepatocyte, lipid droplet, peroxisome, and mitochondrial volumes were observed in PEITC-treated rats fed the cereal-based diet. These results indicate that PEITC exerts differential effects on the liver of rats fed either the cereal-based or purified diet.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68493/2/10.1177_019262339502300602.pd

QTL analysis for resistance to foliar damage caused by Thrips tabaci and Frankliniella schultzei (Thysanoptera: Thripidae) feeding in cowpea [Vigna unguiculata (L.) Walp.]

Three quantitative trait loci (QTL) for resistance to Thrips tabaci and Frankliniella schultzei were identified using a cowpea recombinant inbred population of 127 F2:8 lines. An amplified fragment length polymorphism (AFLP) genetic linkage map and foliar feeding damage ratings were used to identify genomic regions contributing toward resistance to thrips damage. Based on Pearson correlation analysis, damage ratings were highly correlated (r ≥ 0.7463) across seven field experiments conducted in 2006, 2007, and 2008. Using the Kruskall–Wallis and Multiple-QTL model mapping packages of MapQTL 4.0 software, three QTL, Thr-1, Thr-2, and Thr-3, were identified on linkage groups 5 and 7 accounting for between 9.1 and 32.1% of the phenotypic variance. AFLP markers ACC-CAT7, ACG-CTC5, and AGG-CAT1 co-located with QTL peaks for Thr-1, Thr-2, and Thr-3, respectively. Results of this study will provide a resource for molecular marker development and the genetic characterization of foliar thrips resistance in cowpea

Static cut-points of hypertension and increased arterial stiffness in children and adolescents: The International Childhood Vascular Function Evaluation Consortium

Pediatric elevated blood pressure (BP) and hypertension are usually defined using traditional BP tables at the 90th and 95th percentiles, respectively, based on sex, age, and height, which are cumbersome to use in clinical practice. The authors aimed to assess the performance of the static cut-points (120/80 mm Hg and 130/80 mm Hg for defining elevated BP and hypertension for adolescents, respectively; and 110/70 mm Hg and 120/80 mm Hg for children, respectively) in predicting increased arterial stiffness. Using data from five population-based cross-sectional studies conducted in Brazil, China, Korea, and New Zealand, a total of 2546 children and adolescents aged 6-17 years were included. Increased arterial stiffness was defined as pulse wave velocity >= sex-specific, age-specific, and study population-specific 90th percentile. Compared to youth with normal BP, those with hypertension defined using the 2017 American Academy of Pediatrics guideline (hereafter referred to as "percentile-based cut-points") and the static cut-points were at similar risk of increased arterial stiffness, with odds ratios and 95% confidence intervals of 2.35 (1.74-3.17) and 3.07 (2.20-4.28), respectively. Area under the receiver operating characteristic curve and net reclassification improvement methods confirmed the similar performance of static cut-points and percentile-based cut-points (P for difference > .05). In conclusion, the static cut-points performed similarly well when compared with the percentile-based cut-points in predicting childhood increased arterial stiffness. Use of static cut-points to define hypertension in childhood might simplify identification of children with abnormal BP in clinical practice

A simulation study comparing supertree and combined analysis methods using SMIDGen

<p>Abstract</p> <p>Background</p> <p>Supertree methods comprise one approach to reconstructing large molecular phylogenies given multi-marker datasets: trees are estimated on each marker and then combined into a tree (the "supertree") on the entire set of taxa. Supertrees can be constructed using various algorithmic techniques, with the most common being matrix representation with parsimony (MRP). When the data allow, the competing approach is a combined analysis (also known as a "supermatrix" or "total evidence" approach) whereby the different sequence data matrices for each of the different subsets of taxa are concatenated into a single supermatrix, and a tree is estimated on that supermatrix.</p> <p>Results</p> <p>In this paper, we describe an extensive simulation study we performed comparing two supertree methods, MRP and weighted MRP, to combined analysis methods on large model trees. A key contribution of this study is our novel simulation methodology (Super-Method Input Data Generator, or <it>SMIDGen</it>) that better reflects biological processes and the practices of systematists than earlier simulations. We show that combined analysis based upon maximum likelihood outperforms MRP and weighted MRP, giving especially big improvements when the largest subtree does not contain most of the taxa.</p> <p>Conclusions</p> <p>This study demonstrates that MRP and weighted MRP produce distinctly less accurate trees than combined analyses for a given base method (maximum parsimony or maximum likelihood). Since there are situations in which combined analyses are not feasible, there is a clear need for better supertree methods. The source tree and combined datasets used in this study can be used to test other supertree and combined analysis methods.</p

Hydrokinetic Turbine Effects on Fish Swimming Behaviour

Hydrokinetic turbines, targeting the kinetic energy of fast-flowing currents, are under development with some turbines already deployed at ocean sites around the world. It remains virtually unknown as to how these technologies affect fish, and rotor collisions have been postulated as a major concern. In this study the effects of a vertical axis hydrokinetic rotor with rotational speeds up to 70 rpm were tested on the swimming patterns of naturally occurring fish in a subtropical tidal channel. Fish movements were recorded with and without the rotor in place. Results showed that no fish collided with the rotor and only a few specimens passed through rotor blades. Overall, fish reduced their movements through the area when the rotor was present. This deterrent effect on fish increased with current speed. Fish that passed the rotor avoided the near-field, about 0.3 m from the rotor for benthic reef fish. Large predatory fish were particularly cautious of the rotor and never moved closer than 1.7 m in current speeds above 0.6 ms-1. The effects of the rotor differed among taxa and feeding guilds and it is suggested that fish boldness and body shape influenced responses. In conclusion, the tested hydrokinetic turbine rotor proved non-hazardous to fish during the investigated conditions. However, the results indicate that arrays comprising multiple turbines may restrict fish movements, particularly for large species, with possible effects on habitat connectivity if migration routes are exploited. Arrays of the investigated turbine type and comparable systems should therefore be designed with gaps of several metres width to allow large fish to pass through. In combination with further research the insights from this study can be used for guiding the design of hydrokinetic turbine arrays where needed, so preventing ecological impacts

Orally available Mn porphyrins with superoxide dismutase and catalase activities

Superoxide dismutase/catalase mimetics, such as salen Mn complexes and certain metalloporphyrins, catalytically neutralize reactive oxygen and nitrogen species, which have been implicated in the pathogenesis of many serious diseases. Both classes of mimetic are protective in animal models of oxidative stress. However, only AEOL11207 and EUK-418, two uncharged Mn porphyrins, have been shown to be orally bioavailable. In this study, EUK-418 and several new analogs (the EUK-400 series) were synthesized and shown to exhibit superoxide dismutase, catalase, and peroxidase activities in vitro. Some also protected PC12 cells against staurosporine-induced cell death. All EUK-400 compounds were stable in simulated gastric fluid, and most were substantially more lipophilic than the salen Mn complexes EUK-189 and EUK-207, which lack oral activity. Pharmacokinetics studies demonstrate the presence of all EUK-400 series compounds in the plasma of rats after oral administration. These EUK-400 series compounds are potential oral therapeutic agents for cellular damage caused by oxidative stress

Etiological study of esophageal squamous cell carcinoma in an endemic region: a population-based case control study in Huaian, China

BACKGROUND: Continuous exposure to various environmental carcinogens and genetic polymorphisms of xenobiotic-metabolizing enzymes (XME) are associated with many types of human cancers, including esophageal squamous cell carcinoma (ESCC). Huaian, China, is one of the endemic regions of ESCC, but fewer studies have been done in characterizing the risk factors of ESCC in this area. The aims of this study is to evaluate the etiological roles of demographic parameters, environmental and food-borne carcinogens exposure, and XME polymorphisms in formation of ESCC, and to investigate possible gene-gene and gene-environment interactions associated with ESCC in Huaian, China. METHODS: A population based case-control study was conducted in 107 ESCC newly diagnosed cases and 107 residency- age-, and sex-matched controls in 5 townships of Huaian. In addition to regular epidemiological and food frequency questionnaire analyses, genetic polymorphisms of phase I enzymes CYP1A1, CYP1B1, CYP2A6, and CYP2E1, and phase II enzymes GSTM1, GSTT1, GSTP1, and microsomal epoxide hydrolase (EPHX) were assessed from genomic DNA using PCR based techniques. RESULTS: Consuming acrid food, fatty meat, moldy food, salted and pickled vegetables, eating fast, introverted personality, passive smoking, a family history of cancer, esophageal lesion, and infection with Helicobacter pylori were significant risk factors for ESCC (P < 0.05). Regular clean up of food storage utensils, green tea consumption, and alcohol abstinence were protective factors for ESCC (P < 0.01). The frequency of the GSTT1 null genotype was higher in cases (59.4%) compared to controls (47.2%) with an odds ratio (OR) of 1.68 and 95% confidence interval (CI) from 0.96 to 2.97 (P = 0.07), especially in males (OR = 2.78; 95% CI = 1.22–6.25; P = 0.01). No associations were found between polymorphisms of CYP1A1, CYP1B1, CYP2A6, CYP2E1, GSTM1, GSTP1, and EPHX and ESCC (P > 0.05). CONCLUSION: Our results demonstrated that dietary and environmental exposures, some demographic parameters and genetic polymorphism of GSTT1 may play important roles in the development of ESCC in Huaian area, China

Hydroxybenzothiazoles as New Nonsteroidal Inhibitors of 17β-Hydroxysteroid Dehydrogenase Type 1 (17β-HSD1)

17β-estradiol (E2), the most potent estrogen in humans, known to be involved in the development and progession of estrogen-dependent diseases (EDD) like breast cancer and endometriosis. 17β-HSD1, which catalyses the reduction of the weak estrogen estrone (E1) to E2, is often overexpressed in breast cancer and endometriotic tissues. An inhibition of 17β-HSD1 could selectively reduce the local E2-level thus allowing for a novel, targeted approach in the treatment of EDD. Continuing our search for new nonsteroidal 17β-HSD1 inhibitors, a novel pharmacophore model was derived from crystallographic data and used for the virtual screening of a small library of compounds. Subsequent experimental verification of the virtual hits led to the identification of the moderately active compound 5. Rigidification and further structure modifications resulted in the discovery of a novel class of 17β-HSD1 inhibitors bearing a benzothiazole-scaffold linked to a phenyl ring via keto- or amide-bridge. Their putative binding modes were investigated by correlating their biological data with features of the pharmacophore model. The most active keto-derivative 6 shows IC50-values in the nanomolar range for the transformation of E1 to E2 by 17β-HSD1, reasonable selectivity against 17β-HSD2 but pronounced affinity to the estrogen receptors (ERs). On the other hand, the best amide-derivative 21 shows only medium 17β-HSD1 inhibitory activity at the target enzyme as well as fair selectivity against 17β-HSD2 and ERs. The compounds 6 and 21 can be regarded as first benzothiazole-type 17β-HSD1 inhibitors for the development of potential therapeutics

Growth-inhibitory effects of the chemopreventive agent indole-3-carbinol are increased in combination with the polyamine putrescine in the SW480 colon tumour cell line

BACKGROUND: Many tumours undergo disregulation of polyamine homeostasis and upregulation of ornithine decarboxylase (ODC) activity, which can promote carcinogenesis. In animal models of colon carcinogenesis, inhibition of ODC activity by difluoromethylornithine (DFMO) has been shown to reduce the number and size of colon adenomas and carcinomas. Indole-3-carbinol (I3C) has shown promising chemopreventive activity against a range of human tumour cell types, but little is known about the effect of this agent on colon cell lines. Here, we investigated whether inhibition of ODC by I3C could contribute to a chemopreventive effect in colon cell lines. METHODS: Cell cycle progression and induction of apoptosis were assessed by flow cytometry. Ornithine decarboxylase activity was determined by liberation of CO(2 )from (14)C-labelled substrate, and polyamine levels were measured by HPLC. RESULTS: I3C inhibited proliferation of the human colon tumour cell lines HT29 and SW480, and of the normal tissue-derived HCEC line, and at higher concentrations induced apoptosis in SW480 cells. The agent also caused a decrease in ODC activity in a dose-dependent manner. While administration of exogenous putrescine reversed the growth-inhibitory effect of DFMO, it did not reverse the growth-inhibition following an I3C treatment, and in the case of the SW480 cell line, the effect was actually enhanced. In this cell line, combination treatment caused a slight increase in the proportion of cells in the G(2)/M phase of the cell cycle, and increased the proportion of cells undergoing necrosis, but did not predispose cells to apoptosis. Indole-3-carbinol also caused an increase in intracellular spermine levels, which was not modulated by putrescine co-administration. CONCLUSION: While indole-3-carbinol decreased ornithine decarboxylase activity in the colon cell lines, it appears unlikely that this constitutes a major mechanism by which the agent exerts its antiproliferative effect, although accumulation of spermine may cause cytotoxicity and contribute to cell death. The precise mechanism by which putrescine enhances the growth inhibitory effect of the agent remains to be elucidated, but does result in cells undergoing necrosis, possibly following accumulation in the G(2)/M phase of the cell cycle