Uptake of the food-derived heterocyclic amine carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and its N-hydroxy metabolite into rat pancreatic acini and hepatocytes in vitro

Sinc DNA adducts of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) are formed at relatively high levels in the rat pancreas but not liver, we examined the uptake of PhIP and its N-hydroxy metabolite (N-OH-PhIP) into pancreatic acini and hepatocytes to determine if differential tissue uptake was a factor modulating the formation of PhIP-DNA adducts. In addition, since the precursors of PhIP formation are two amino acids and since various amino acid transporters have been identified in the pancreas, the possible involvement of these transporters in the uptake of PhIP and N-OH-PhIP was investigated. The uptake both heterocyclic compounds into both tissue preparations was rapid, with maximal uptake occurring with 1-2 min. However, PhIP uptake into pancreatic acini was significantly (2-way ANOVA, P < 0.05) greater than uptake of N-OH-PhIP into pancreatic acini and the uptake of both PhIP and N-OH-PhIP into hepatocytes. Although uptake was rapid, efflux of both compounds from both tissue preparations was also rapid. However, the efflux rate constant (1.86 +/- 0.6/min, mean +/- SEM) for PhIP) was significantly lower (Student's t-test, P < 0.05) than that for N-OH-PhIP (4.14 +/- 0.04/min) from pancreatic acini. This, combined with the increased uptake of PhIP into pancreatic acini , suggests that there is substantial but reversible binding of PhIP in the pancreas. The uptake of both PhIP and N-OH-PhIP into pancreatic acini and hepatocytes was not affected by the presence of various amino acids in the incubation buffer, indicating that amino acid transporters are not involved in uptake of these compounds. Furthermore, uptake of both compounds did not appear to be dependent on metabolic energy supply. The above data, together with the high octanol:buffer partition coefficients (logP = 1.322 and 1.301 for PhiP and N-OH-PhIP respectively) suggest that both uptake and efflux of PhIP and N-OH-PhIP are consistent with a process of passive diffusion. The tissue binding characteristics for PhIP in the pancreas may create conditions whereby pancreatic cytochrome P450 1A1 can catalyse the formation of N-OH-PhIP. While N-OH-PhIP is not the ultimate reactive DNA binding species, it has been shown to directly bind to and form DNA adducts. Therefore, it is possible that the apparent selective accumulation of PhIP may contribute to the high level of PhIP-DNA adducts formed in the rat pancreas.     

Cystosarcoma phyllodes of the prostate: MRI findings

Cystosarcoma phyllodes of the prostate is a rare, relatively benign sarcoma of the prostate. We describe the magnetic resonance imaging findings in an unusual case of cystosarcoma phyllodes which resulted in extensive local recurrence and sarcomatous degeneration. Although uncommon, radiologists should be aware of the existence of cystosarcoma phyllodes of the prostate.     

Forward telescoping: the question matters

This study examines the effect of pulse repetition rate (PRR), pulse intensity, and bicuculline on the minimum threshold (MT) and latency of inferior collicular neurons of the big brown bat, Eptesicus fuscus, under free-field stimulation conditions. It tests the hypothesis that changes in MT and latency of collicular neurons are co-dependent on PRR. The number of impulses in inferior collicular neurons (n = 245) increased either monotonically (25%) or non-monotonically (75%) with pulse intensity. Latencies either decreased to a plateau (72%), fluctuated unpredictably within 3 ms (21%) or changed very little (7%) with increasing pulse intensity. Latencies and MTs of most collicular neurons increased by 1.5-24 ms (mean +/- SD = 4.8 +/- 3.3 ms) and 4-75 dB (mean +/- SD = 22.1 +/- 16.2 dB) with increasing PRR. In most neurons (94%), the latency increase was completely (42%) or partially (52%) eliminated when pulse intensity was compensated for the MT increase with PRR. Complete elimination of latency was achieved by bicuculline application. In a few neurons (6%), the latency increase with PRR was not affected by compensated pulse intensity or bicuculline application.     

Input and central processing expressed in ERP and heart rate changes to rare target and rare nontarget stimuli

Whether late positive components of event-related potentials (ERPs) parallel changes in heart rate (HR) indicative of attention/orienting to rare stimuli has been debated. In the present study, a three-stimulus design was used, with rare target, rare nontarget, and frequent standard stimuli delivered under identical conditions except that instructions to subjects described the targets to which subjects should respond but did not describe the nontargets. In Experiment 1, stimuli varied among modalities; in Experiment 2, auditory stimuli were employed. Both ERPs and HR were consistent with automatic processing preceding two stages of controlled processing. Rare stimuli evoked larger parietal P300 and initial HR deceleration than standards. Presumably because of load-reducing effects of long interstimulus intervals, targets and nontargets were not distinguished before a late slow wave and a late phase of HR acceleration. Neither rare stimulus elicited a recognizable frontal P3a.     

Dose-titration to confirm the level of fenbendazole for control of Raillietina cesticillus in broiler chickens

A total of 452 broiler chickens, naturally infected with Raillietina cesticillus, were allotted into six treatment groups. One group was fed unmedicated broiler ration (Group 1), and the other five groups were fed broiler ration containing fenbendazole at 180 ppm for 3 days (38.5 mg/kg body weight [BW]), 240 ppm for 3 days (50.9 mg/kg BW), 120 ppm for 6 days (52.2 mg/kg BW), 180 ppm for 6 days (79.9 mg/kg BW), or 240 ppm for 6 days (104.3 mg/kg BW). Fenbendazole was 100.0% efficacious against R. cesticillus when administered in the diet at 240 ppm for 6 days; 99.9% at 240 ppm for 3 days and at 180 ppm for 6 days; 99.5% at 120 ppm for 6 days; and 96.9% at 180 ppm for 3 days. Fenbendazole treatment had no adverse effect on weight gain or feed intake.     

Sex pheromone of cranberry fruitworm,Acrobasis vaccinii riley (Lepidoptera: Pyralidae)

The following compounds and (approximate ratios) were identified in sex pheromone gland extracts of femaleAcrobasis vaccinii Riley by comparison of gas chromatography-mass spectrometric traces with those of synthetic standards: (E,Z)-, (Z,E)-, (Z,Z), and (E,E)-8, 10-pentadecadien-l-ol acetates (100:1:2:12), a dodecen-l-ol acetate (8), (Z)-8-, (Z)-9-, and (E)-9-pentadecen-l-ol acetates (3:23:4), two heptadecen-l-ol acetates (4:4), tetradecyl, pentadecyl, hexadecyl, and heptadecyl acetates (3:15:10:8), dodecan-l-ol (6), tetradecan-l-ol (5), and hexadecan-l-ol (23). The amount of (E,Z)-8, 10-pentadecadien-l-ol acetate (E8,Z10–15:Ac) in the extract was about 0.5 ng/female. Electroantennographic analysis of gas chromatographic fractions of female sex pheromone gland extract showed that the fraction containingE8,Z10–15:Ac elicited the greatest response. Alone,E8,Z10–15:Ac failed to elicit upwind flight of males in flight-tunnel tests, and traps baited with it did not catch males in field experiments. WhenE8,Z10–15:Ac was combined with (E)-9-pentadecen-l-ol acetate (100:4), male upwind flight response in flight-tunnel tests was equivalent to those obtained with extract of female sex pheromone glands (synthetic, 62%; natural, 51%), but the percent of males flying upwind that contacted the source was lower (synthetic, 47%; natural, 88%). The lower percent of source contact elicited by the synthetic pheromone could be a result of the difference in isomer ratios of 8,10–15:Ac in the natural and synthetic pheromone or could indicate that the synthetic pheromone is incomplete. Traps baited with the 100:4 combination caught large numbers of males in field experiments.     

Structure-Activity Relationship and Crystallographic Studies on 4-Hydroxypyrimidine HIF Prolyl Hydroxylase Domain Inhibitors

The 2-oxoglutarate-dependent hypoxia inducible factor prolyl hydroxylases (PHDs) are targets for treatment of a variety of diseases including anaemia. One PHD inhibitor is approved for use for the treatment of renal anaemia and others are in late stage clinical trials. The number of reported templates for PHD inhibition is limited. We report structure–activity relationship and crystallographic studies on a promising class of 4-hydroxypyrimidine-containing PHD inhibitors.     

Small-angle neutron scattering characterization of the structure of nanoporous carbons for energy-related applications

We used small-angle neutron scattering (SANS) and neutron contrast variation to study the structure of four nanoporous carbons prepared by thermo-chemical etching of titanium carbide TiC in chlorine at 300, 400, 600, and 800 °C with pore diameters ranging between ∼4 and ∼11 Å. SANS patterns were obtained from dry samples and samples saturated with deuterium oxide (D₂O) in order to delineate origin of the power law scattering in the low Q domain as well as to evaluate pore accessibility for D₂O molecules. SANS cross section of all samples was fitted to Debye-Anderson-Brumberger (DAB), DAB-Kirste-Porod models as well as to the Guinier and modified Guinier formulae for cylindrical objects, which allowed for evaluating the radii of gyration as well as the radii and lengths of the pores under cylindrical shape approximation. SANS data from D₂O-saturated samples indicate that strong upturn in the low Q limit usually observed in the scattering patterns from microporous carbon powders is due to the scattering from outer surface of the powder particles. Micropores are only partially filled with D₂O molecules due to geometrical constraints and or partial hydrophobicity of the carbon matrix. Structural parameters of the dry carbons obtained using SANS are compared with the results of the gas sorption measurements and the values agree for carbide-derived carbons (CDCs) obtained at high chlorination temperatures (>600 °C). For lower chlorination temperatures, pore radii obtained from gas sorption overestimate the actual pore size as calculated from SANS for two reasons: inaccessible small pores are present and the model-dependent fitting based on density functional theory models assumes non-spherical pores, whereas SANS clearly indicates that the pore shape in microporous CDC obtained at low chlorination temperatures is nearly spherical.