Simulation of radionuclide atmospheric dispersion and dose assessment for inhabitants of Tehran province after a hypothetical accident of the Tehran Research Reactor.

Radiological dose assessment is one of the main categories of safety assessment for nuclear reactors and facilities. The radiation risks to the public and to the environment that may arise from these facilities have to be assessed and, if necessary, controlled. The main objective of this paper is the assessment of radiation doses to residents of Tehran province after a hypothetical accident of the Tehran Research Reactor (TRR) including the determination of any protective actions that might be needed for the benefit of people's health. The concentration of radionuclides in air and deposited on the ground surface as a result of a hypothetical radionuclide release from the TRR, following a hypothetical accident scenario, have been calculated by the HYSPLIT computer code. Simulations were performed using selected source terms taken from the TRR Final Safety Analysis Report (FSAR). Meteorological data of the Air Resources Laboratory of the National Oceanic and Atmospheric Administration (NOAA) have been used in these calculations. The simulation results indicate that maximum annual total effective dose equivalent values for the residents of the Tehran province are less than the protective action dose limits. Thus, it is concluded that during this hypothetical accident in the TRR, required safety due to public radiation is achieved and the residents of Tehran province are safe under a TRR accident condition.

The value of 18F-FDG PET in pediatric patients with post-transplant lymphoproliferative disorder at initial diagnosis.

PTLD is a serious complication of both solid organ and BMT. This study assessed whether (18) F-FDG PET, when added to CT scan, had additional value in the initial evaluation of PTLD in pediatric patients and whether PET/CT at baseline can reliably guide biopsy. This retrospective study evaluated 34 consecutive pediatric patients (14 female), aged 3.5-17.0 yr (mean age: 9.9 yr, s.d.: 4.9 yr), who had undergone (18) F-FDG PET/CT from May 2007 to December 2014 at initial diagnosis of PTLD following heart (n = 13), lung (n = 8), kidney (n = 4), liver (n = 3), liver and bowel (n = 3), and bone marrow (n = 3) transplantation. PTLD was diagnosed histopathologically in 33 patients and was based on clinical findings, elevated EBV, and imaging and follow-up results in one patient. On lesion-based analysis, (18) F-FDG PET showed more lesions than conventional CT scan (168 vs. 134), but CT revealed 22 lesions negative on PET. On per patient analysis, PET detected more lesions in 13 patients, CT identified more abnormalities in seven, and both showed the same number of lesions in 14. Adding (18) F-FDG PET to CT scans upstaged the disease in seven patients (20.5%). A combination of (18) F-FDG PET and CT was also useful in guiding biopsy, being positive in 36 of 39 samples (92.3%). These findings indicated that (18) F-FDG PET and CT are complementary at initial staging of pediatric PTLD and that (18) F-FDG PET/CT scanning can guide biopsies.

Ionic-liquid based dispersive liquid-liquid microextraction followed by high performance liquid chromatographic determination of anti-hypertensives in rat serum.

A novel, simple and eco-friendly ionic liquid based dispersive liquid-liquid microextraction followed by HPLC determination of anti-hypertensive drugs viz., eprosartan, valasartan, irbesartan, losartan and telmisartan in rat serum has been developed and validated. Experimental parameters influencing the extraction efficiency, nature and volume of the ionic liquid, dispenser solvent, extraction time and effect of salt were optimized. Under the optimum conditions, the extraction recoveries were between 92.85 and 98.50%. The relative standard deviations of intra-and inter-day accuracy varied between 1.9 and 9.1% (n=3). The linearity of the proposed method was 0.1-20µg/mL with coefficients of determination varying between 0.9979 and 0.9992.

Liquid chromatography tandem mass spectrometric studies of indinavir sulphate and its forced degradation products.

Indinavir sulphate was subjected to forced degradation under hydrolysis (acidic, basic and neutral), oxidation, photolysis and thermal stress as prescribed by ICH guidelines. It was degraded under acidic, basic, neutral and oxidative stress conditions, while it was stable under other conditions. After degradation total eight degradation products were formed. The degradation products were identified and their separation was accomplished on Waters XTerra(®) C(18) column (250 mm × 4.6mm i.d., 5 µm) using 20mM ammonium actate:acetonitrile as (50:50, v/v) mobile phase in an isocratic elution mode by LC. The method was extended to LC-MS/MS for characterization of the degradation products and the fragmentation pathways were proposed. The proposed structures of degradation products were also confirmed by HRMS studies. No previous reports were found in the literature regarding the characterization of degradation products of indinavir sulphate.

Liquid chromatography-mass spectrometric determination of losartan and its active metabolite on dried blood spots.

A simple and rapid quantitative bioanalytical liquid chromatography-tandem mass spectrometric (LC-MS/MS) method for simultaneous determination of losartan and its active metabolite, losartan carboxylic acid on rat dried blood spots was developed and validated as per regulatory guidelines. Losartan and its metabolite were extracted from dried blood spots using 50% aqueous methanol and separated on Waters XTerra(®) RP18 (250 mm × 4.6 mm, 5 µm) column using mobile phase composed of 40% acetonitrile and 60% aqueous ammonium acetate (10mM). The eluents were monitored using ESI tandem mass spectrometric detection with negative polarity in MRM mode using ion transitions m/z 421.2→179.0, m/z 435.3→157.0 and m/z 427.3→193.0 for losartan, losartan carboxylic acid and Irbesartan (internal standard), respectively. The method was validated over the linear range of 1-200 ng/mL and 5-1000 ng/mL with lower limits of quantification of 1.0 ng/mL and 5.0 ng/mL for losartan and losartan carboxylic acid, respectively. Inter and intra-day precision and accuracy (Bias) were below 5.96% and between -2.8 and 1.5%, respectively. The mean recoveries of the analytes from dried blood spots were between 89% and 97%. No significant carry over and matrix effects were observed. The stability of stock solution, whole blood, dried blood spot and processed samples were tested under different conditions and the results were found to be well within the acceptable limits. Additional validation parameters such as influence of hematocrit and spot volume were also evaluated and found to be well within the acceptable limits.

Tunneling transport in topological insulator normal metal/insulator/d-wave superconductor junctions.

We investigate the tunneling conductance in a normal metal/insulator/d-wave superconductor (NM/I/d-wave SC) junction with a barrier of thickness d and with an arbitrary gate voltage V(0) applied across the barrier region, formed on the surface of a topological insulator, using the Dirac-Bogoliubov-de Gennes equation and Blonder-Tinkham-Klapwijk (BTK) formalism. We find that the tunneling conductance as a function of both d and V(0) displays an oscillatory behavior whose amplitude decreases with increase of V(0). We also find that when the Andreev resonant condition is met, the tunneling conductance approaches a maximum value of 2G(0), independent of the gate voltage V(0).

LC-ESI-MS/MS determination of paclitaxel on dried blood spots.

A simple and rapid high-performance liquid chromatography-tandem mass spectrometric assay for determination of paclitaxel on rat dried blood spots was developed and validated. The extracted sample was chromatographed without further treatment using a reverse-phase Oyster ODS3, 4.6 × 50 mm, 3 µm column with mass spectrometry detection. The mobile phase comprised of acetonitrile-water, 60:40 v/v, with a flow rate of 0.4 mL/min was used. The calibration was linear over the range 0.2-20 ng/mL. The limits of detection and quantification were 0.08 and 0.2 ng/mL, respectively. The intra- and inter-day precision (CV%) and accuracy (relative error %) were less than 10 and 12%, respectively.

Rapid determination of rifaximin on dried blood spots by LC-ESI-MS.

The use of blood spot collection cards is a simple way to obtain specimens for therapeutic drug monitoring, assessing adherence to medications and preventing toxicity in a clinical setting. A high-throughput liquid chromatography-electrospray ionization mass spectrometric (LC-ESI-MS) method for determination of rifaximin on dried blood spots (DBS) was developed and validated. It involves solvent extraction of a punch of DBS followed by reversed-phase LC on a monolithic column consisting of a silica rod with bimodal pore structure and detection by ESI-MS. Rifampicin was used as an internal standard (IS). The run time was within 5.0 min with a very low back-pressure at a flow rate of 0.5 mL/min. The assay was linear from 0.1 to 10 ng/mL. The mean recovery was 98.42%. The developed method is very simple, rapid and useful for clinical applications.

Separation and characterization of forced degradation products of abacavir sulphate by LC-MS/MS.

Abacavir sulphate was subjected to forced degradation under the conditions of hydrolysis (acid, alkali and neutral), oxidation, photolysis and thermal stress as prescribed by ICH. Eight degradation products were formed and their separation was accomplished on Waters XTerra C18 (250 mm x 4.6 mm, 5 µm) column using 20 mM ammonium acetate:acetonitrile as a mobile phase in gradient elution mode by LC. The degradation products were characterized by LC-MS/MS and its fragmentation pathways were proposed. No previous reports were found in the literature regarding the degradation behavior of abacavir sulphate.

LC-MS/MS studies of ritonavir and its forced degradation products.

Forced degradation of ritonavir (RTV), under the conditions of hydrolysis (acidic, basic and neutral), oxidation, photolysis and thermal stress as prescribed by ICH was studied using LC-MS/MS. Eight degradation products were formed and their separation was accomplished on Waters XTerra C(18) column (250 mm x 4.6 mm i.d., 5 microm) using water:methanol:acetonitrile as (40:20:40, v/v/v) mobile phase in an isocratic elution mode by LC. The method was extended to LC-MS/MS for characterization of the degradation products and the pathways of decomposition were proposed. No previous reports were found in the literature regarding the characterization of degradation products of ritonavir.

On-line 2D-LC-ESI/MS/MS determination of rifaximin in rat serum.

A highly sensitive and selective on-line two-dimensional reversed-phase liquid chromatography/electrospray ionization-tandem mass spectrometry (2D-LC-ESI/MS/MS) method was developed and validated to determine rifaximin in rat serum by direct injection. The 2D-LC-ESI/MS/MS system consisted of a restricted access media column for trapping proteins as the first dimension and a Waters C(18 )column as second dimension using 0.1% aqueous acetic acid:acetonitrile as mobile phase in a gradient elution mode. Rifampacin was used as an internal standard. The linear dynamic range was 0.5-10 ng/mL (r(2) > 0.998). Acceptable precision and accuracy were obtained over the calibration range. The assay was successfully used in analysis of rat serum to support pharmacokinetic studies.

Rate of reaction with nitric oxide determines the hypertensive effect of cell-free hemoglobin.

Administration of extracellular hemoglobin-based oxygen carriers often induces mild increases in blood pressure. In order to test whether nitric oxide (NO) scavenging is responsible for the hypertensive effect, we constructed and tested a set of recombinant hemoglobins that vary in rates of reaction with NO. The results suggest that the rapid reactions of oxy- and deoxyhemoglobin with nitric oxide are the fundamental cause of the hypertension. The magnitude of the blood-pressure effect correlates directly with the in vitro rate of NO oxidation. Hemoglobins with decreased NO-scavenging activity may be more suitable for certain therapeutic applications than those that cause depletion of nitric oxide.

Quaternary structure regulates hemin dissociation from human hemoglobin.

Rate constants for hemin dissociation from the alpha and beta subunits of native and recombinant human hemoglobins were measured as a function of protein concentration at pH 7.0, 37 degrees C, using H64Y/V68F apomyoglobin as a hemin acceptor reagent. Hemin dissociation rates were also measured for native isolated alpha and beta chains and for recombinant hemoglobin tetramers stabilized by alpha subunit fusion. The rate constant for hemin dissociation from beta subunits in native hemoglobin increases from 1.5 h-1 in tetramers at high protein concentration to 15 h-1 in dimers at low concentrations. The rate of hemin dissociation from alpha subunits in native hemoglobin is significantly smaller (0.3-0.6 h-1) and shows little dependence on protein concentration. Recombinant hemoglobins containing a fused di-alpha subunit remain tetrameric under all concentrations and show rates of hemin loss similar to those observed for wild-type and native hemoglobin at high protein concentration. Rates of hemin dissociation from monomeric alpha and beta chains are much greater, 12 and 40 h-1, respectively, at pH 7, 37 degrees C. Aggregation of monomers to form alpha1beta1 dimers greatly stabilizes bound hemin in alpha chains, decreasing its rate of hemin loss approximately 20-fold. In contrast, dimer formation has little stabilizing effect on hemin binding to beta subunits. A significant reduction in the rate of hemin loss from beta subunits does occur after formation of the alpha1beta2 interface in tetrameric hemoglobin. These results suggest that native human hemoglobin may have evolved to lose heme rapidly after red cell lysis, allowing the prosthetic group to be removed by serum albumin and apohemopexin.