Decreasing myocardial estrogen receptors and antioxidant activity may be responsible for increasing ischemia- and reperfusion-induced ventricular arrhythmia in older female rats.

AIMS: This study aimed to investigate the relationship between ischemia- and reperfusion-induced arrhythmia and blood serum estrogen levels, myocardial estrogen receptor levels, antioxidant enzyme activities, and the effects of the estrogen receptor blocker, fulvestrant (ICI 182 780). MAIN METHODS: A total of 102 female Sprague-Dawley rats of different ages (2-3, 6-7, 14-15, and 20-21 months) were used in this study. Myocardial ischemia was produced by ligation of the descending branch of the left anterior descending coronary artery, and reperfusion was produced by releasing this artery. An electrocardiogram (ECG) and blood pressure were recorded for 6 min of ischemia and 6 min of reperfusion. The levels of superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT), estrogen receptor α (ERα), and estrogen receptor ß (ERß) in myocardial tissue and 17 beta-estradiol (E2) in blood serum were measured via enzyme-linked immunosorbent assay (ELISA). The results were compared using a Mann-Whitney U test, one-way analysis of variance (ANOVA), and a student's t-test. KEY FINDINGS: It is not the changes in serum estrogen levels but the decreasing myocardial estrogen receptors and antioxidant activities that could be responsible for the occurrence of more severe arrhythmia in response to reperfusion in older female rats. SIGNIFICANCE: The death rate due to a heart attack in younger men is higher than in women. However, it equalizes after the menopausal stage in women. In this study, the reason for the increasing sudden post-menopausal death rate in women was investigated experimentally.

Investigation of transmission computed tomography (CT) image quality and x-ray dose achievable from an experimental dual-mode benchtop x-ray fluorescence CT and transmission CT system.

OBJECTIVE: To investigate the image quality and x-ray dose associated with a transmission computed tomography (CT) component implemented within the same platform of an experimental benchtop x-ray fluorescence CT (XFCT) system for multimodal preclinical imaging applications. METHODS: Cone-beam CT scans were performed using an experimental benchtop CT + XFCT system and a cylindrically-shaped 3D-printed polymethyl methacrylate phantom (3 cm in diameter, 7 cm in height) loaded with various concentrations (0.05-1 wt. %) of gold nanoparticles (GNPs). Two commercial CT quality assurance phantoms containing 3D line-pair (LP) targets and contrast targets were also scanned. The x-ray beams of 40 and 62 kVp, both filtered by 0.08 mm Cu and 0.4 mm Al, were used with 17 ms of exposure time per projection at three current settings (2.5, 5, and 10 mA). The ordered-subset simultaneous algebraic reconstruction and total variation-minimization methods were used to reconstruct images. Sparse projection and short scan were considered to reduce the x-ray dose. The contrast-to-noise ratio (CNR) and modulation transfer function (MTF) were calculated. RESULTS: The lowest detectable concentration of GNPs (CNR > 5) and the highest spatial resolution (per MTF50%) were 0.10 wt. % and 9.5 LP/CM, respectively, based on the images reconstructed from 360 projections of the 40 kVp beam (or x-ray dose of 3.44 cGy). The background noise for the image resulting in the lowest GNP detection limit was 25 Hounsfield units. CONCLUSION: The transmission CT component within the current experimental benchtop CT + XFCT system produced images deemed acceptable for multimodal (CT + XFCT) imaging purposes, with less than 4 cGy of x-ray dose.

The protection of resveratrol and its combination with glibenclamide, but not berberine on the diabetic hearts against reperfusion-induced arrhythmias: the role of myocardial KATP channel.

CONTEXT: Cardiovascular dysfunctions such as life-threatening arrhythmias are one of the main reasons of mortality and morbidity in diabetic patients Objective: We aimed to investigate the long-term effects of resveratrol, berberine and glibenclamide combinations on the ischemia/reperfusion (I/R) induced arrhythmias in streptozotocin (STZ)-induced diabetic rats and to investigate the role of myocardial KATP channel in the possible anti-arrhythmic actions of the treatments. METHODS: Two days after induction of diabetes, diabetic rats were treated with resveratrol [5 mg/kg, intraperitoneally (i.p.)], berberine (10 mg/kg, i.p) and glibenclamide (5 mg/kg, i.p) for 6 weeks. On the 43th day, experimental animals were subjected to 6-min ischemia and 6-min reperfusion in vivo. RESULTS: The protein expression of Kir6.2 subunits was downregulated in the diabetic hearts. However, all drug treatments restored the protein expression of Kir6.2 subunits. Resveratrol alone and its combination with glibenclamide decreased the arrhythmia score, the arrhythmic period and the incidence of other types of arrhythmias during the reperfusion period. CONCLUSIONS: The combination of resveratrol with glibenclamide may alleviate reperfusion-induced arrhythmias via an underlying mechanism not be only associated with the restoration of the protein expression of Kir6.2 subunits but also associated with the other subunits or ion channels underlying cardiac action potential.

Development of an attenuation correction method for direct x-ray fluorescence (XRF) imaging utilizing gold L-shell XRF photons.

PURPOSE: This work proposes a semiempirical correction method for attenuation of x-ray fluorescence (XRF) photons and/or an excitation beam during direct XRF imaging (i.e., mapping) of gold nanoparticle (GNP) distribution utilizing gold L-shell XRF photons. METHODS: The current method was first devised by finding the two following relationships: (a) ratio of gold XRF peak intensity (Lα at ~9.7 keV and Lß at ~11.4 keV) vs pathlength of XRF photons; (b) XRF photon counts produced (Nxrf ) vs scattered photon counts produced (Nscat ). Monte Carlo simulations were performed using the Geant4 tool kit to characterize the aforementioned relationships for different tissue-like media. The applicability of the method was tested experimentally by acquiring 2D L-shell XRF images of custom-made phantoms using an experimental benchtop x-ray fluorescence computed tomography setup. RESULTS: The results show that the ratio of gold L-shell XRF peak intensities allowed an estimation of the pathlength of XRF photons, thus can be utilized to correct for attenuation of XRF photons after emission. The results also demonstrate that Nscat , through a proportionality N xrf ∝ N scat T where the exponent T depends on the energy of scattered photons, could be used to correct for attenuation of an excitation beam prior to producing XRF photons. The corrected XRF signal was found independent of the densities of tissue-like media present along the passage of an excitation beam or emitted XRF photons. CONCLUSIONS: The current results suggest that the developed attenuation correction method plays an essential role for the detection of GNPs on the order of parts-per-million, and also for the determination of GNP concentration/location within the imaging object made of tissue-like media, without any prior knowledge of the imaging object shape, under the conditions deemed relevant to biomedical applications of gold L-shell XRF-based imaging.

A Monte Carlo Model of a Benchtop X-Ray Fluorescence Computed Tomography System and Its Application to Validate a Deconvolution-Based X-Ray Fluorescence Signal Extraction Method.

In this study, we developed and validated a Geant4-based Monte Carlo (MC) model of an experimental benchtop X-ray fluorescence (XRF) computed tomography (XFCT) system for quantitative imaging of metallic nanoparticles such as gold nanoparticles (GNPs) injected into small animals for preclinical testing of various NP-based diagnostic and therapeutic approaches. Detailed hardware components of the current benchtop XFCT system, including the X-ray source, excitation beam collimation and filtration, custom imaging phantoms with GNP solutions, and single/ring/linear array detectors with custom collimation, were incorporated into the MC model. In conjunction with a known CdTe detector response function, a deconvolution-based XRF signal extraction method was also developed in this study, which enabled complete separation of gold K-shell XRF peaks even when they almost overlapped and facilitated extraction of XRF signals from a broadband Compton scattered photon background. The extracted signal-to-background ratios were comparable with those expected using an ideal detector with high enough energy resolution (e.g., 0.1 keV full-width at half-maximum). Once convoluted with the CdTe detector response function, the MC-calculated spectra for excitation beams or emitted photons and XFCT image spatial resolutions agreed well with those measured experimentally. Thus, the current MC model can be used to optimize the beam/imaging parameters (e.g., beam geometry, excitation X-ray beam energy, and X-ray filter material) as well as the design of critical hardware components (e.g., detector collimators) within the current benchtop XFCT system. Also, the current XRF signal extraction method can relax the usual stringent requirement of detector energy resolution while not degrading the sensitivity of benchtop XFCT.

Radiosensitization of Prostate Cancers In Vitro and In Vivo to Erbium-filtered Orthovoltage X-rays Using Actively Targeted Gold Nanoparticles.

Theoretical investigations suggest that gold nanoparticle (GNP)-mediated radiation dose enhancement and radiosensitization can be maximized when photons interact with gold, predominantly via photoelectric absorption. This makes ytterbium (Yb)-169, which emits photons with an average energy of 93 keV (just above the K-edge of gold), an ideal radioisotope for such purposes. This investigation tests the feasibility of tumor-specific prostate brachytherapy achievable with Yb-169 and actively targeted GNPs, using an external beam surrogate of Yb-169 created from an exotic filter material - erbium (Er) and a standard copper-filtered 250 kVp beam. The current in vitro study shows that treatment of prostate cancer cells with goserelin-conjugated gold nanorods (gGNRs) promotes gonadotropin releasing hormone receptor-mediated internalization and enhances radiosensitivity to both Er-filtered and standard 250 kVp beams, 14 and 10%, respectively. While the degree of GNP-mediated radiosensitization as seen from the in vitro study may be considered moderate, the current in vivo study shows that gGNR treatment plus Er-filtered x-ray irradiation is considerably more effective than radiation treatment alone (p < 0.0005), resulting in a striking reduction in tumor volume (50% smaller) 2 months following treatment. Overall, the current results provide strong evidence for the feasibility of tumor-specific prostate brachytherapy with Yb-169 and gGNRs.

X-ray characterization of mesophases of human telomeric G-quadruplexes and other DNA analogues.

Observed in the folds of guanine-rich oligonucleotides, non-canonical G-quadruplex structures are based on G-quartets formed by hydrogen bonding and cation-coordination of guanosines. In dilute 5'-guanosine monophosphate (GMP) solutions, G-quartets form by the self-assembly of four GMP nucleotides. We use x-ray diffraction to characterize the columnar liquid-crystalline mesophases in concentrated solutions of various model G-quadruplexes. We then probe the transitions between mesophases by varying the PEG solution osmotic pressure, thus mimicking in vivo molecular crowding conditions. Using the GMP-quadruplex, built by the stacking of G-quartets with no covalent linking between them, as the baseline, we report the liquid-crystalline phase behaviors of two other related G-quadruplexes: (i) the intramolecular parallel-stranded G-quadruplex formed by the 22-mer four-repeat human telomeric sequence AG3(TTAG3)3 and (ii) the intermolecular parallel-stranded G-quadruplex formed by the TG4T oligonucleotides. Finally, we compare the mesophases of the G-quadruplexes, under PEG-induced crowding conditions, with the corresponding mesophases of the canonical duplex and triplex DNA analogues.

DNA Equation of State: In Vitro vs In Viro.

We formulate a continuum approach to the equation of state (density dependence of osmotic pressure) of bulk DNA and encapsidated DNA, as well as review the phase diagram of DNA in the regime of densities relevant for DNA packing in bacteriophages. We derive the first integral of the equilibrium equations that connects the behavior of DNA in the bulk and in nanoscale enclosures, and we delineate the changes wrought upon the mesophase equilibria of encapsidated DNA. We show how multiphase equilibria and complicated spatial distribution of DNA density and orientation can emerge due to the curvature contribution to the DNA osmotic pressure within the capsid.

Investigation of X-ray permeability of surgical gloves coated with different contrast agents.

OBJECTIVE: We aimed to investigate the effectiveness and radiation protection capability of latex gloves coated with various contrast agents as an alternative to lead gloves. METHODS: The following six groups were created to evaluate the permeability of X-ray in this experimental study: lead gloves, two different non-ionic contrast media (iopromide 370/100 mg I/mL and iomeprol 400/100 mg I/mL), 10% povidone-iodine (PV-I), 240/240 g/mL barium sulphate and a mixture of equal amounts of all contrast agents. A radiation dose detector was placed in coated latex gloves for each one. The absorption values of radiation from latex gloves coated with various contrast agents were measured and compared with the absorption of radiation from lead gloves. This study was designed as an 'experimental study'. RESULTS: The mean absorption value of X-ray from lead gloves was 3.0±0.08 µG/s. The mean absorption values of X-ray from latex gloves coated with various contrast agents were 3.7±0.09 µG/s (iopromide 370/100 mg I/mL), 3.6±0.09 µG/s (iomeprol 400/100 mg I/mL), 3.7±0.04 µG/s (PV-I), 3.1±0.07 µG/s (barium sulphate) and 3.8±0.05 µG/s (mixture of all contrast agents). Latex gloves coated with barium sulphate provided the best radiation absorption compared with latex gloves coated with other radiodense contrast agents. CONCLUSION: Latex gloves coated with barium sulphate may provide protection equivalent to lead gloves.

The effects of ATP-dependent potassium channel opener; pinacidil, and blocker; glibenclamide, on the ischemia induced arrhythmia in partial and complete ligation of coronary artery in rats.

OBJECTIVES: Electrical inhomogeneity between ischemic and non ischemic myocardium is the basis of arrhythmia which occurs following coronary artery occlusion. The leakage of potassium from the ischemic region to the non ischemic region is very effective in the generation of these arrhythmias. The aim of this study is to research the effect of ATP-dependent potassium (KATP) channel blocker (glibenclamide) and opener (pinacidil) on ischemia induced arrhythmia in the presence of small and large infarct sizes. MATERIALS AND METHODS: In this study Sprague-Dawley male rats of 8-9 months of age were used. Ischemia was produced by the partial ligation of left coronary artery ramus descending (PL) for smaller infarct and complete ligation of this artery (CL) for larger infarct for 30 min. The arrhythmia score which was calculated from the duration and type of arrhythmia was significantly higher in animals which had a larger infarct area than the animals which had a smaller infarct. RESULTS: Glibenclamide increased the rate of arrhythmia in animals having smaller infarct but not in animals having larger infarct. Pinacidil did not affect the occurrence of arrhythmia in either group. There was a significant difference in the infarct size and risk of infarct zone between animals which had small and large infarct sizes. The effect of glibenclamide and pinacidil on the arrhythmias differed depend on decrease of infarct size. CONCLUSION: Glibenclamide is not effective to decrease ischemia induced arrhythmia in the presence of small and pinacidil in large ischemic zone.

Continuity of states between the cholesteric → line hexatic transition and the condensation transition in DNA solutions.

A new method of finely temperature-tuning osmotic pressure allows one to identify the cholesteric → line hexatic transition of oriented or unoriented long-fragment DNA bundles in monovalent salt solutions as first order, with a small but finite volume discontinuity. This transition is similar to the osmotic pressure-induced expanded → condensed DNA transition in polyvalent salt solutions at small enough polyvalent salt concentrations. Therefore there exists a continuity of states between the two. This finding, together with the corresponding empirical equation of state, effectively relates the phase diagram of DNA solutions for monovalent salts to that for polyvalent salts and sheds some light on the complicated interactions between DNA molecules at high densities.

Effect of ATP-dependent channel modulators on ischemia-induced arrhythmia change depending on age and gender.

The number of ATP-dependent potassium channels in myocardial cells has been previously shown to change depending on gender and age. Different effects of the ATP-dependent potassium channel blocker, glybenclamide and ATP-dependent potassium channel opener, pinacidil on ischemia or reperfusion-induced arrhythmia observed in various research might depend on different ages and genders of the animals used. The aim of this study is to research the effect of ATP-dependent potassium channel modulators on ischemia-induced arrhythmia in animals of different ages and genders. Sprague-Dawley rats of different ages and genders were used in this study. Ischemia was produced by the ligation of the left coronary artery for 30 min. Electrocardiogram (ECG), blood pressure, infarct area and blood glucose were determined during the 30 min of ischemia. An arrhythmia score from an ECG recorded during 30 min of ischemia was determined by examining the duration and type of arrhythmia. Different effects of glybenclamide and pinacidil on the arrhythmias were observed in male and female young and middle-age rats. Pinacidil decreased the infarct zone in younger female rats, but differences in the type and length of ischemia-induced arrhythmias between females and males disappeared in older age. The results of this study showed that the effect of ATP-dependent potassium channel modulators on ischemia-induced arrhythmia changed due to the age and gender of rats.

Omental torsion with left-sided inguinal hernia: a rare preoperative diagnosis.

Omental torsion is a rare disease. It can be difficult to identify if it is not clinically considered in the preoperative period, and this pathology may lead to an acute abdomen. We present the characteristic computed tomography findings and clinical particulars in a 34-year-old male patient with longstanding left inguinal hernia associated with an extraordinary diagnosis.

Carotid CT-angiography: low versus standard volume contrast media and low kV protocol for 128-slice MDCT.

Availability and utilization of computed tomography angiography has been increasing recently. We aimed to assess the effectiveness of low amount of contrast media and low kV value in order to reduce possible side effects of contrast media and to provide optimization of kV value in the evaluation of the carotid artery with multi-detector computed tomography angiography. Forty one patients were randomized into two groups. Contrast media was administered at a dose of 1 ml/kg in group A patients and of 0.5 ml/kg in group B patients. kV value of 120 in group A and 100 in group B were chosen. Bolus tracking technique was used. Attenuation values of certain arterial segments were measured, and values over 200 HU were considered as significant. North American Symptomatic Carotid Endartherectomy Trial criteria were utilized in the evaluation of stenosis. Image quality in arterial segments of all cases was found to be sufficient for diagnosis. Arterial attenuation values were found to be higher in group B than group A. When compared separately in all arterial segments, there was no statistically significant difference between the groups. For stenosis, 615 arterial segments were evaluated. Moderate stenosis in eight segments and severe stenosis in three segments were identified in group A. Occlusion in three segments, severe stenosis in three segments, and moderate stenosis in 25 segments were detected in group B. Better image quality can be obtained, and the amount of contrast media can be reduced using low kV technique in carotid artery multi-detector computed tomography angiography examination.