Influence of oxidative stress on aryl hydrocarbon receptor signaling

The aryl hydrocarbon receptor (AHR), a multifunctional protein and a key regulator of drug metabolizing enzymes, belongs to the basic-helix-loop-helix (bHLH)/PAS (Per- Arnt-Sim) super-family of transcription factors. The AHR responds to exogenous and endogenous chemicals by induction or repression of a large number of genes involved in many physiological processes and normal development. The diverse spectrum of AHR activators from well-known planar hydrophobic halogenated aromatic hydrocarbons (HAHs) to chemical compounds whose structure and physicochemical properties are very different from classical AHR ligands suggests that the AHR has a tremendously promiscuous ligand binding pocket. Due to the absence of a 3D structure of the ligand binding domain, promiscuity of the AHR has remained elusive. However, increasing experimental evidence indicate that the non- typical AHR ligands might activate the AHR signaling pathway indirectly by inhibiting the metabolic turnover of an endogenous ligand of the AHR. Therefore, the objective of this thesis was to characterize the inhibition of degradation of 6-formylindolo[3,2- b]carbazole (FICZ), the suggested natural high affinity AHR ligand, as a mechanism that could explain the earlier described agonistic properties of structurally very diverse AHR activators. The obtained results show that FICZ is a potent AHR agonist in vitro and in vivo which can distribute to the body through systemic circulation and induce cytochrome P450 1A1 (CYP1A1) the prototypical AHR target in various organs. The studies presented in this thesis demonstrate that if the metabolic clearance of FICZ is compromised, femtomolar concentrations of FICZ are sufficient to activate AHR signaling. The AHR signaling pathway seems to be sensitive to oxidative stress but the redox regulation of AHR has not been well characterized. Studies on dioxin and other reactive oxygen species (ROS) producing agents have demonstrated that the AHR is a mediator of oxidative stress. Indeed, AHR works in close concert with the master regulator of antioxidant responses, nuclear factor (erythroid-derived 2)-like 2 (Nrf2). Multiple sources of ROS appear to be involved in modulating AHR signaling and probably via three major systems, microsomes, mitochondria and NADPH oxidase enzymes (NOXs). Furthermore, it has been observed that many environmental pollutants, including metals and other NOX-activators increase the levels of the diffusible molecule hydrogen peroxide (H2O2) and change the cellular redox status and thereby interfere with cell growth kinetics and the endogenous functions of the AHR. To increase the understanding of downstream adaptive responses to oxidative stress, including up-regulation of antioxidant genes and modulation of AHR signaling was another objective of this work. The findings demonstrate that superoxide anion (O2−.) or H2O2 produced by NOXs can negatively and positively modulate the AHR signaling pathway. The importance of cellular redox levels which can influence endogenously activated AHR signaling broadens our earlier knowledge and explains why many oxidants behave both as AHR antagonists and agonists. In summary, this thesis extends the mechanistic understanding of the promiscuity of AHR and provides important information with regard to the redox regulation of AHR endogenous signaling

Quantum non-Markovianity, quantum coherence and extractable work in a general quantum process

A key concept in quantum thermodynamics is extractable work, which specifies the maximum amount of work that can be extracted from a quantum system. Different quantities are used to measure extractable work, the most prevalent of which are ergotropy and the difference between the non-equilibrium and equilibrium quantum free energy. Using the former, we investigate the evolution of extractable work when an open quantum system goes through a general quantum process described by a completely-positive and trace-preserving dynamical map. We derive a fundamental equation of thermodynamics for such processes as a relation between the distinct sorts of energy change in such a way the first and second laws of thermodynamics are combined. We then identify the contributions made by the reversible and irreversible processes in this equation and demonstrate that they are respectively responsible for the heat flow and change in the extractable work during the process. Furthermore, we discuss the potential benefit of this assignment in favor of a clear explanation of the impact of quantum effects on the evolution of extractable work. Specifically, we establish this by directly connecting the extractable work with standard quantifiers of quantum non-Markovianity and quantum coherence during the process. We illustrate these results with two examples.Comment: 8 pages, 2 figure

Evaluation of gastrointestinal injury in blunt abdominal trauma "FAST is not reliable": the role of repeated ultrasonography

<p>Abstract</p> <p>Background</p> <p>To determine the diagnostic Accuracy of Focused Assessment Sonography for Trauma (FAST) and repeated FAST in the patients with blunt abdominal trauma.</p> <p>Methods</p> <p>In this retrospective study we collected the data of all patients from September 2007 to July 2011 with gastrointestinal injury. The intraoperative outcome was compared with FAST technique and the repeated or delayed sonography.</p> <p>Results</p> <p>A total number of 1550 patients with blunt abdominal trauma underwent FAST in a period of 4 years in our hospital. Eighty-eight (5.67%) patients were found to have gastrointestinal injury after exploratory laparotomy. Fifty-five (62.5%) patients had isolated gastrointestinal injury and 33 (37.5%) patients had concomitant injury to the other solid organs. In those with isolated gastrointestinal injury, the sensitivity of FAST was 38.5%. Repeated ultrsonography was performed in 34 patients with false negative initial FAST after 12-24 hours. The sensitivity of repeated ultrasonography in negative initial FAST patients in detection of gastrointestinal injury was 85.2% (95% CI, 68.1%, and 94.4%).</p> <p>Conclusion</p> <p>Repeated sonography after 12 to 24 hours in patients with negative initial FAST but sustain abdominal symptom can facilitated a diagnosis of GI tract injury and can be as effective method instead of Computed tomography in developing country.</p

Evaluation of retrobulbar blood flow in patients with age-related cataract; color Doppler ultrasonographic findings

Afshin Mohammadi1, Nilofar Khorasani2, Farzad Moloudi2, Mohammad Ghasemi-rad31Department of Radiology, Urmia University of Medical Sciences, Urmia, Iran; 2Student Research Committee, Urmia University of Medical Sciences, Urmia, Iran; 3Genius and Talented Student Organization, Student Research Committee, Urmia University of Medical Sciences, Urmia, IranObjectives: Cataracts are the most common cause of blindness worldwide, with cataract surgery being the most common ophthalmic procedure. To our best knowledge, this is the first case-control study with a large number of participants to evaluate ocular blood flow in patients with cataracts.Materials and methods: Color Doppler and duplex sonography of the orbital vessels was performed in 224 eyes of 112 patients with known bilateral age-related cataracts and in 76 eyes of 38 healthy age- and sex-matched volunteers.Results: The mean &amp;plusmn; (standard deviation [SD]) of peak systolic velocity (PSV) of the ophthalmic artery in patients with cataracts (34.59 &amp;plusmn; 22.49 cm/second) was significantly different to that in controls (52.11 &amp;plusmn; 14.01 cm/second) (P &amp;lt; 0.001). The mean &amp;plusmn; SD PSV of the central retinal artery in patients with cataracts (15.31 &amp;plusmn; 4.93 cm/second) was significantly different to that in controls (9.61 &amp;plusmn; 5.64 cm/second) (P &amp;lt; 0.001).Conclusion: The mean PSV and resistive index (RI) of the ophthalmic and central retinal arteries were lower in cataract patients when compared with normal subjects. This suggests that ocular hypoperfusion and changes in ocular hemodynamic may have a role in the formation of age-related cataracts.Keywords: retrobulbar blood flow, age-related, cataract, color Doppler ultrasonographi

Evaluation of mouse embryos produced in vitro after electromagnetic waves exposure; Morphometric study.

INTRODUCTION Today, the use of electromagnetic waves in medical diagnostic devices, such as magnetic resonance imaging (MRI), has increased, and many of its biological effects have been reported. The aim of the present study was to assess the biological effects of 1.5 Tesla (T) magnetic resonance imaging (MRI) on fertility and reproductive parameters. METHODS Eighty adult male and female NMRI mice (NMRI: Naval Medical Research Institute) of age 6-8 weeks were studied and randomly divided into two study and control groups. After confirmation of pregnancy, the mice in the study group were exposed to the MRI (1.5 T) machine's waves over the next three weeks, once a week for 36 minutes. One day and thirty-five days after the last radiation, the mice were killed in order to do the in vitro fertilization (IVF) by neck beads' displacement and the impact on the evolution of embryos, and its quality was studied. Data were analyzed using SPSS version 20 and the significance level of less than 0.05 was considered. RESULTS Embryo morphometry showed that the total diameter and the cytoplasm diameter of the study group embryos suffered significant reduction compared to the control group, 1 day after the last irradiation (p < 0.05), but the diameter of the perivitelline space of this group's embryos had a significant increase (p < 0.05). The qualitative results during 35 days after irradiation showed that morphologically parameters of the embryos in the study group had no significant differences from the control group. CONCLUSION Exposure to MRI irradiation can transiently disturb the development of mouse embryos and fertility, but these effects are reversible 35 days after the last irradiation

Feasibility study of wastewater reuse for irrigation in Isfahan, Iran

Abstract: Wastewater reuse is one of the main options that can be considered as a new source of water in regions where water is scarce. The main purpose of this study is to determine the feasibility of Isfahan’s north wastewater treatment plant effluent for agricultural irrigation. To evaluate suitability of treated wastewater for irrigation, important indicators like Sodium Adsorption Ratio (SAR), Soluble Sodium Percentage (SSP)and Potential Salinity were investigated. In this study the SAR value for effluent was 2.62 and according to approved criteria by Food and Agriculture Organization (FAO) it was excellent for irrigation,SSPwas 39.7% so it has good quality for irrigation usage and the potential salinity was 4.81 meq/L, thusaccording to approved criteria by FAO it is medium for soil permeability.Also the EC value of effluent was 1250 µS/cm (1.25 dS/m) and according to approved criteria by FAO it was permissible for irrigatio