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In a 79 week bioassay the pesticide synergist piperonyl butoxide (PBO) was shown to significantly increase the incidence of hepatocellular adenoma (but not hepatocellular carcinoma) in male CD-1 mice at dietary levels of 100 and 300 mg/kg/day PBO and in female mice at a dietary level of 300 mg/kg/day. As PBO is not a genotoxic agent, a series of investigative studies were undertaken to elucidate the mode of action (MOA) for PBO-induced mouse liver tumour formation. Male CD-1 mice were fed diets to provide intakes of 0 (control), 30, 100 and 300 mg/kg/day PBO and for purposes of comparison 500 ppm sodium phenobarbital (NaPB), a known constitutive androstane receptor (CAR) activator, for 7 and 14 days. Treatment with 100 and 300 mg/kg/day PBO and 500 ppm NaPB increased relative liver weight which was associated with hepatocyte hypertrophy, with hepatocyte replicative DNA synthesis (RDS) being increased after 7 days treatment. The treatment of CD-1 mice with 30-300 mg/kg/day PBO for 14 days resulted in significaof male CD-1 mouse hepatocytes for 4 days with 5-50 μM PBO, 10-1000 μM NaPB and 25 ng/mL epidermal growth factor (EGF) resulted in significant increases in hepatocyte RDS. While treatment of hepatocytes from one male and one female human donor with 5-500 μM PBO and 10-1000 μM NaPB for 4 days had no effect on hepatocyte RDS, treatment with EGF resulted in significant increases in RDS in both human hepatocyte preparations. In summary, PBO is predominantly a hepatic CAR activator at carcinogenic dose levels in CD-1 mice, with activation of hepatic CAR resulting in a suppression of the effect of PBO on hepatic PPARα. A robust MOA for PBO-induced mouse liver tumour formation has been established, this MOA being similar to that previously identified for NaPB and some other rodent liver CAR activators. Based on the lack of effect of PBO on RDS in human hepatocytes, it is considered that the MOA for PBO-induced mouse liver tumour formation is qualitatively not plausible for humans. The antifungal properties of Illicium verum essential oil (IV-EO) against a toxigenic strain of Aspergillus flavus (A. flavus) were analyzed in order to determine its use in the preservation of lotus seeds. GC/MS analysis of IV-EO revealed that its main components are trans-anethole (91.32%), D-Limonene (2.0%) and estragole (2.0%). The antifungal activity of IV-EO against A. flavus infection was analyzed in vitro upon A. flavus with the minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) determined to be 2.0 and 4.0 μL/mL, respectively. IV-EO exhibited strong inhibitory effects on the mycelial growth and spore production of A. flavus, and caused a significant reduction in dry mycelium weight and aflatoxin B1 and B2 (AFB1 and AFB2) biosynthesis. Complete inhibition was observed at an IV-EO concentration of 3.6 μL/mL. Analysis in an in vivo (food system) demonstrated that IV-EO inhibited AFB1 and AFB2 accumulation in lotus seeds to varying degrees depending on its concentration, and completely inhibited aflatoxin production at concentrations above 6.0 μL/g. Morphological studies carried out using SEM revealed that ultra-structural changes in the hyphae and conidiophore structures following IV-EO treatment. Therefore, IV-EO has demonstrated its practical efficacy as a new biological fumigant in the preservation of lotus seeds. RAD51 inhibitor A comprehensive toxicokinetic analysis of citrinin (CIT) revealed interspecies differences for all toxicokinetic parameters and in absolute oral bioavailability. Oral bioavailability for CIT was complete for broilers (113-131%), while ranging from 37 to 44% in pigs. CIT was more rapidly absorbed in pigs (Tmax = 0.92 h) compared to broiler chickens (Tmax = 7.33 h). The elimination of CIT was slower in pigs (T1/2el = 26.81 h after intravenous (IV) administration) compared to chickens (T1/2el = 1.97 h after IV administration), due to the striking difference in clearance (Cliv=9.87 mL/h/kg for pigs versus Cliv = 863.09 mL/h/kg for broilers). Also, the volume of distribution differed significantly between pigs (Vd = 0.30 L/kg after IV administration) and chickens (Vd = 2.46 L/kg after IV administration). However, plasma protein binding did not differ statistically significant (91-98%). It is imperative to further investigate biotransformation and elimination pathways in different species, including humans. Carbohydrates are considered as promising targets for vaccine development against infectious diseases where cell surface glycan's on many infectious agents are attributed to playing an important role in pathogenesis. Understanding the relationship between carbohydrates and immune components at a molecular level is crucial for the development of well-defined vaccines. Recently, carbohydrate immunology research has been accelerated by the development of new technologies that contribute to the design of optimum antigens, synthesis of antigens and the studies of antigen-antibody interactions, and as a result, several promising carbohydrate-based vaccine candidates have been prepared in recent years. This article briefly presents the mechanistic pathways of polysaccharide, glycoconjugate, glycolipid and zwitterionic vaccines and the interplay between carbohydrate antigen and immune response. V.Reduced responsiveness to emotional stimuli ('emotional dampening') has been observed in normotensives with elevated blood pressure (BP) and hypertensives but it is not known whether this is due to aberrant responding to emotional information at the involuntary level and whether it is also associated with minimal elevations in BP in the normal range. In this study, we examined emotional dampening using the affect-modulated startle paradigm given its proven sensitivity to motivational states of approach and withdrawal, typically independent of conscious intentional control. Acoustically elicited startle eye-blink modulation was measured using electromyography of the orbicularis oculi muscle beneath the left eye in 59 healthy individuals while they viewed pleasant, unpleasant and neutral standardized pictures. The expected startle attenuation to pleasant pictures, and startle potentiation to unpleasant pictures, relative to neutral pictures, was found in people in the comparison (N = 29) but not elevated BP (N = 30) group.

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