Synergistic and antagonistic interactions of binary mixtures of polycyclic aromatic hydrocarbons in the upregulation of CYP1 activity and mRNA levels in precision-cut rat liver slices

The current studies investigate whether synergistic or antagonistic interactions in the upregulation of CYP1 activity occur in binary mixtures of polycyclic aromatic hydrocarbons (PAHs) involving benzo[a]pyrene and five other structurally diverse PAHs of varying carcinogenic activity. Precision-cut rat liver slices were incubated with benzo[a]pyrene alone or in combination with a range of concentrations of a second PAH, and ethoxyresorufin O-deethylase, CYP1A1 and CYP1B1 mRNA levels determined. Concurrent incubation of benzo[a]pyrene with either dibenzo[a,h]anthracene or fluoranthene in liver slices led to a synergistic interaction, at least at low concentrations, in that ethoxyresorufin O-deethylase activity was statistically higher than the added effects when the slices were incubated with the individual compounds. In contrast, benzo[b]fluoranthene and, at high doses only, dibenzo[a,l]pyrene gave rise to antagonism, whereas 1-methylphenanthrene had no effect at all concentrations studied. When CYP1A1 mRNA levels were monitored, benzo[b]fluoranthene gave rise to an antagonistic response when incubated with benzo[a]pyrene, whereas all other compounds displayed synergism, with 1-methylphenathrene being the least effective. A similar picture emerged when CYP1B1 mRNA levels were determined, though the effects were less pronounced. In conclusion, it has been demonstrated that the benzo[a]pyrene-mediated upregulation of CYP1, at the mRNA and activity levels, is synergistically and antagonistically modulated by other PAHs

Cytochromes P450 and species differences in xenobiotic metabolism and activation of carcinogen.

The importance of cytochrome P450 isoforms to species differences in the metabolism of foreign compounds and activation of procarcinogens has been identified. The possible range of P450 isozymes in significant variations in toxicity exhibited by experimental rodent species may have a relevance to chemical risk assessment, especially as human P450s are likely to show changes in the way they metabolize xenobiotics. Consequently, in the safety evaluation of chemicals, we should be cautious in extrapolating results from experimental animal models to humans. This paper focuses on examples in which species differences in P450s lead to significant alterations in carcinogenic response, and includes a discussion of the current procedures for toxicity screening, with an emphasis on short-term tests

Cyprus' image—a sun and sea destination—as a detrimental factor to seasonal fluctuations. Exploration into motivational factors for holidaying in Cyprus

Cyprus is established as a summer destination. To aid the destination in developing its winter season as well, this research uses a qualitative inductive approach to explore the tourists’ current image of the island and their motivations of visiting it. The research indicates that the current image, which essentially portrays Cyprus as a sun-and-sea destination is thought to dissuade tourists from perceiving the island as a year-round destination. Nonetheless, increasing the pull factors of the destination through the development of unique special interest products can help in extending the tourism season as well as broaden its narrow image

Mutagenicity testing of 9-N-substituted adenines and their N-oxidation products.

Adenine together with certain 9-N-substituted derivatives such as 9-methyl, 9-benzyl, 9-benzhydryl, and 9-trityl were tested against Salmonella typhimurium strains TA97, TA98, and TA100 in the absence and presence of rat hepatic S9 prepared from Aroclor 1254 pretreated rats. All compounds were positive toward TA98 in the presence of the metabolic activating system, whereas they all lacked mutagenic activity in the absence of S9, and toward TA97 and TA100 with or without S9 when tested at 100 ng/plate. A similar pattern was observed for the corresponding 1-N-oxides. 6-Hydroxylaminopurine was not mutagenic toward TA100 at 100 ng/plate, whereas it was toxic toward TA97 and TA98 at this level. When tested at 1 ng/plate, hydroxylaminopurine was still toxic to TA98 but produced twice the spontaneous reversion rate to TA97 without metabolic activation. Surprisingly, 9-methyl-6-hydroxylaminopurine was only active toward TA98 in the presence of S9, whereas 9-benzyl-6-hydroxylaminopurine was highly active toward TA97 and TA100 in the absence of S9 and even more active in the presence of S9. This compound was inactive toward TA98 in the absence of S9. The results generally support the concept that nuclear N-oxidation of aminoazaheterocycles is a detoxication process, whereas N-hydroxylation of the exo amino group is a toxication reaction

A Bayesian test for the appropriateness of a model in the biomagnetic inverse problem

This paper extends the work of Clarke [1] on the Bayesian foundations of the biomagnetic inverse problem. It derives expressions for the expectation and variance of the a posteriori source current probability distribution given a prior source current probability distribution, a source space weight function and a data set. The calculation of the variance enables the construction of a Bayesian test for the appropriateness of any source model that is chosen as the a priori infomation. The test is illustrated using both simulated (multi-dipole) data and the results of a study of early latency processing of images of human faces. [1] C.J.S. Clarke. Error estimates in the biomagnetic inverse problem. Inverse Problems, 10:77--86, 1994.Comment: 13 pages, 16 figures. Submitted to Inverse Problem

Evaluation of fast spin echo MRI sequence for an MRI guided high intensity focused ultrasound system for in vivo rabbit liver ablation

The effectiveness of magnetic resonance imaging (MRI) to monitor thermal lesions created by High Intensity Focused Ultrasound (HIFU) in rabbit liver in vivo is investigated. The MRI sequences of T1-weighted, and T2-weighted fast spin echo (FSE) were evaluated. The main goal in this paper was to find the range of repetition time (TR) and range of echo time (TE) which maximizes the contrast to noise ratio (CNR). An ultrasonic transducer operating at 2 MHz was used, which is navigated using a positioning device. With T1W FSE the range of TR under which CNR is maximized ranges from 400 to 900 ms. The maximum contrast measured is approximately 25. With T2W FSE the range of TE that establishes maximum contrast is between 40 ms and 80 ms, with CNR of approximately 14. T1W FSE is much better than T2W FSE in detecting thermal lesions in liver. Both T1W and T2 W FSE were proven successful to image thermal lesions created by HIFU in rabbit liver in vivo

Diffuse precordial ST-segment elevation in inferior-right myocardial infarction

A right ventricular (RV) myocardial infarction (MI) may yield precordial ST-segment elevation (STE). Accordingly, combined inferior and precordial STE may be produced during an inferior-RV MI. Such an electrocardiographic picture may be mistakenly regarded as showing wrapped left anterior descending artery (LADA) occlusion or double vessel occlusion. We present a patient with inferior-RV MI and STE in the inferior, all precordial and right chest leads, in whom the diffuse precordial STE was probably mistakenly regarded as showing anterior MI. However, the STE resolution in V1-V2 and late R’ wave in V1, which were combined with a recanalized RV branch, favored the RV origin of this STE. Furthermore, the LADA was patent when V3-V6 showed severe ischemia, while its lesion was angiographically stable. Thus its simultaneous occlusion was unlikely. The late R’ wave in V1 indicates RV transmural conduction delay;as highlighted herein, it is diagnostic of a RV myocardial infarction. (Cardiol J 2010; 17, 6: 628-631

MRI monitoring of lesions created at temperature below the boiling point and of lesions created above the boiling point using high intensity focused ultrasound

Magnetic Resonance Imaging (MRI) was utilized to monitor lesions created at temperature below the boiling point and lesions created at temperature above the boiling point using High Intensity Focused Ultrasound (HIFU) in freshly excised kidney, liver and brain and in vivo rabbit kidney and brain. T2-weighted fast spin echo (FSE) was proven as an excellent MRI sequence that can detect lesions with temperature above the boiling point in kidney. This advantage is attributed to the significant difference in signal intensity between the cavity and the thermal lesion. In liver the MRI sequence of Proton Density is recommended to detect lesions above boiling. In brain T1-W FSE was the optimum pulse sequence to detect lesions of either type. In order to monitor the temperature elevation during a HIFU exposure, T1-weighted fast spoiled gradient (FSPGR) was used. The shape of the focal temperature distribution was uniform with the absence of boiling, whereas with an exposure affected by boiling, the temperature distribution could be of irregular shape, demonstrating the drastic effects taking place during boiling. In order to confirm that boiling occurred, the temperature was estimated using the widely used method of Proton Resonance Frequency (PRF) shift