Morbidity dynamics in proton–photon or photon radiation therapy for locally advanced prostate cancer

Aim

This study evaluated the frequency and long-term dynamics of early and late post irradiation damage after proton–photon or photon therapy for locally advanced prostate cancer.

Evaluation of PENFAST – A fast Monte Carlo code for dose calculations in photon and electron radiotherapy treatment planning

The aim of the present study is to demonstrate the potential of accelerated dose calculations, using the fast Monte Carlo (MC) code referred to as PENFAST, rather than the conventional MC code PENELOPE, without losing accuracy in the computed dose. For this purpose, experimental measurements of dose distributions in homogeneous and inhomogeneous phantoms were compared with simulated results using both PENELOPE and PENFAST. The simulations and experiments were performed using a Saturne 43 linac operated at 12 MV (photons), and at 18 MeV (electrons). Pre-calculated phase space files (PSFs) were used as input data to both the PENELOPE and PENFAST dose simulations. Since depth–dose and dose profile comparisons between simulations and measurements in water were found to be in good agreement (within ±1% to 1 mm), the PSF calculation is considered to have been validated. In addition, measured dose distributions were compared to simulated results in a set of clinically relevant, inhomogeneous phantoms, consisting of lung and bone heterogeneities in a water tank. In general, the PENFAST results agree to within a 1% to 1 mm difference with those produced by PENELOPE, and to within a 2% to 2 mm difference with measured values. Our study thus provides a pre-clinical validation of the PENFAST code. It also demonstrates that PENFAST provides accurate results for both photon and electron beams, equivalent to those obtained with PENELOPE. CPU time comparisons between both MC codes show that PENFAST is generally about 9–21 times faster than PENELOPE.     

GafChromic® EBT3 films for patient specific IMRT QA using a multichannel approach

PurposeTo evaluate EBT3 for pre-treatment patient specific quality assurance (QA). The method we propose combines the experience gained in our center with the guidelines of the protocol proposed by Lewis et al. in 2012. To compare the multichannel approach with the single channel dosimetry.MethodsGafchromic® EBT3 films were irradiated both at linac and TomoTherapy and calibration curves were obtained. A series of irradiations with simple fields (uniform dose distributions on regular shaped targets) was performed. In a second stage, films were exposed to full clinical plans at linac (step and shoot IMRT and VMAT). At TomoTherapy dose maps were obtained for a clinical plan in three different coronal planes. Films were digitized using an Epson 10000XL scanner and FilmQA™ Pro software was employed for the analysis.ResultsThe measured calibration curves suggest that, at least for the two beams taken into account (6 MV linac and TomoTherapy), a single calibration can be successfully adopted for each film lot. The application of the multichannel optimization method strongly improves the results in terms of gamma passing rates of the comparison between measured and calculated maps.ConclusionsUp to now EBT films, although attractive, were not preferred for routine patient specific QA due to their complex and time consuming processing and to the challenging work of characterization. The application of the mentioned protocol, together with some additional precautions, and the adoption of the multichannel optimization dosimetry, make this detector a handy and reliable tool for patient specific QA.     

Concerted involvement of cooperative proton–electron linkage and water production in the proton pump of cytochrome c oxidase

In cytochrome c oxidase, oxido-reductions of heme a/Cu_A and heme a₃/Cu_B are cooperatively linked to proton transfer at acid/base groups in the enzyme. H⁺/e⁻ cooperative linkage at Fe_a3/Cu_B is envisaged to be involved in proton pump mechanisms confined to the binuclear center. Models have also been proposed which involve a role in proton pumping of cooperative H⁺/e⁻ linkage at heme a (and Cu_A). Observations will be presented on: (i) proton consumption in the reduction of molecular oxygen to H₂O in soluble bovine heart cytochrome c oxidase; (ii) proton release/uptake associated with anaerobic oxidation/reduction of heme a/Cu_A and heme a₃/Cu_B in the soluble oxidase; (iii) H⁺ release in the external phase (i.e. H⁺ pumping) associated with the oxidative (R → O transition), reductive (O → R transition) and a full catalytic cycle (R → O → R transition) of membrane-reconstituted cytochrome c oxidase. A model is presented in which cooperative H⁺/e⁻ linkage at heme a/Cu_A and heme a₃/Cu_B with acid/base clusters, C₁ and C₂ respectively, and protonmotive steps of the reduction of O₂ to water are involved in proton pumping.     

Evaluation of two visual birdscarers,the Peaceful Pyramid® and an eye‐spot balloon,in two vineyards

Abstract

The effectiveness of a visual birdscarer, the Peaceful Pyramid®, relative to a much‐cheaper eye‐spot balloon was investigated experimentally in two vineyards in Canterbury, New Zealand. Monitoring of bird damage to natural bunches of Riesling grapes within vineyard blocks showed that the rate of starling (Sturnus vulgaris) damage to the crop was reduced significantly by the balloon relative to pyramid and control plots. Nevertheless, after 24 days of monitoring, birds in the balloon plot had damaged 75% of the grapes, respectively (cf. 84% in the pyramid plot). In a second trial, clusters of table grapes were attached to vineyard wire at a Lincoln vineyard. The balloon and pyramid both reduced bird damage to clusters within 15 m of the device, but had no measurable effect on clusters further away. We conclude that neither device would provide growers with any economically significant reduction in grape damage. This study highlights the importance of undertaking quantitative assessments of the numerous bird‐scaring technologies presently available to growers.     

Interaction of electron leak and proton leak in respiratory chain of mitochondria——Proton leak induced by superoxide from an electron leak pathway of univalent reduction of oxygen

By incubating the isolated rat myocardial mitochondria with xanthine-xanthine oxidase, anexogenous superoxide (O2) generating system, and by ischemia-reperfusion procedure of isolated rat heart as an endogenous O2 generating system, it was found that both sources of O2 showed the same injurious effects on mitochondrial function resulting in (i) increasing proton leak rate, lowering proton pumping activity and Ht/2e ratio of respiratory chain, and (ii) decreasing transmembrane potential of energized mitochondria] inner membrane by succinate oxidation. The injurious effects of O2 on these mitochondrial bioenergitical parameters mentioned above exhibited a dosage- or reaction time-dependent mode. (X has no effects on the electron transfer activity and transmembrane potential of nonenergized mitochondria. Being a superoxide scavenger, 3, 4-dihydroxylphenyl lactate showed obvious protection effects against damage of both exogenous superoxide sources from xanthine-xanthine oxidase system and endogenous Or sou     

Advanced assessment of the physicochemical characteristics of Remicade® and Inflectra® by sensitive LC/MS techniques

In this study, we demonstrate the utility of ultra-performance liquid chromatography coupled to mass spectrometry (MS) and ion-mobility spectrometry (IMS) to characterize and compare reference and biosimilar monoclonal antibodies (mAbs) at an advanced level. Specifically, we focus on infliximab and compared the glycan profiles, higher order structures, and their host cell proteins (HCPs) of the reference and biosimilar products, which have the brand names Remicade® and Inflectra®, respectively. Overall, the biosimilar attributes mirrored those of the reference product to a very high degree. The glycan profiling analysis demonstrated a high degree of similarity, especially among the higher abundance glycans. Some differences were observed for the lower abundance glycans. Glycans terminated with N-glycolylneuraminic acid were generally observed to be at higher normalized abundance levels on the biosimilar mAb, while those possessing α-linked galactose pairs were more often expressed at higher levels on the reference molecule. Hydrogen deuterium exchange (HDX) analyses further confirmed the higher-order similarity of the 2 molecules. These results demonstrated only very slight differences between the 2 products, which, interestingly, seemed to be in the area where the N-linked glycans reside. The HCP analysis by a 2D-UPLC IMS-MS approach revealed that the same 2 HCPs were present in both mAb samples. Our ability to perform these types of analyses and acquire insightful data for biosimilarity assessment is based upon our highly sensitive UPLC MS and IMS methods.     

Evaluation of pharmacodynamic activities of EPs® 7630, a special extract from roots of Pelargonium sidoides,in animals models of cough,secretolytic activity and acute bronchitis

BackgroundEPs^® 7630 is a proprietary aqueous-ethanolic extract from roots of Pelargonium sidoides DC and has been demonstrated to dispose among others of antibacterial, antiviral, immunomodulatory, antioxidant, and tissue-protective activity. It is an approved medicinal product in more than 50 countries for the treatment of airway infections such as acute bronchitis, common cold, and sinusitis.PurposeWhile the pharmacological effects of EPs^® 7630 have extensively been evaluated in diverse in vitro test systems, the number of publications reporting results from in vivo models is limited.Study designIn the present study antitussive, secretolytic, and anti-inflammatory effects of EPs^® 7630 were assessed in animal experiments following oral administration at human equivalent doses.MethodsAntitussive effects were evaluated using ammonia- and citric acid-induced models of cough in mice (20, 40, 120 mg/kg) and guinea pigs (10, 20, 45 mg/kg), respectively. For the determination of secretolytic activity tracheobronchial secretion of intraperitoneally injected phenol red was determined in mice, while antiinflammatory action was assessed in an acute bacterial bronchitis model in rats.ResultsA significant and dose-dependent reduction of cough frequency was observed in both cough models, which was accompanied by a prolongation of cough latency time. Similarly, the extract exerted a marked secretolytic activity in mice. Induction of acute bacterial bronchitis caused characteristic histopathological changes in lung tissue adjacent to trachea and bronchi. The degree of these lesions was significantly reduced in rats treated with EPs^® 7630 at doses of 30 and 60 mg/kg. This protective effect at least partially seems to be mediated by an up-regulation of superoxide dismutase and a subsequent protective effect against oxidative stress as indicated by a reduced serum level of malondialdehyde.ConclusionThe present data further support the therapeutic use of EPs^® 7630 in respiratory tract infections and provide a basis for detailed studies on its bioactive constituents as well as their in vivo mode of action.     

Evaluation and validation of Biolog OmniLog® system for antibacterial activity assays

Minimal inhibitory concentration of antimicrobials, determined by the broth microdilution method, requires visual assessment or absorbance measurement using a spectrophotometer. Both procedures are usually performed manually, requiring the presence of an operator to assess the plates at specific time point. To increase the throughput of antimicrobial susceptibility testing, and concurrently convert into an automatic assay, the Biolog OmniLog^® system was validated for a new, label-free application using standard 96-well microplates. OmniLog was evaluated for its signal strength to ensure that the signal intensity, detected and measured by the system's camera, was satisfactory. Variability due to the plate location inside the OmniLog incubator, as well as variation between wells, was investigated. Then the system was validated by determining the minimal inhibitory concentration of ciprofloxacin, piperacillin and linezolid against a selected Gram-negative and Gram-positive strains. No significant difference was observed in relation to position of the plates within the system. Plate edge effects were noticeable, thus the edge wells were not included in further experiments. Minimal inhibitory concentration results were comparable to those obtained by conventional protocol as well as to values defined by the Clinical Laboratory Standards Institute or published in the literature.     

Characterization of passive dosimeters in proton pencil beam scanning – A EURADOS intercomparison for mailed dosimetry audits in proton therapy centres

The lack of mailed dosimetry audits of proton therapy centres in Europe has encouraged researchers of EURADOS Working Group 9 (WG9) to compare response of several existing passive detector systems in therapeutic pencil beam scanning.Alanine Electron Paramagnetic Resonance dosimetry systems from 3 different institutes (ISS, Italy; UH, Belgium and IFJ PAN, Poland), ^natLiF:Mg, Ti (MTS-N) and ^natLiF:Mg, Cu, P (MCP-N) thermoluminescent dosimeters (TLDs), GD-352M radiophotoluminescent glass dosimeters (RPLGDs) and Al₂O₃:C optically stimulated dosimeters (OSLDs) were evaluate. Dosimeter repeatability, batch reproducibility and response in therapeutic Pencil Beam Scanning were verified for implementation as mail auditing system.Alanine detectors demonstrated the lowest linear energy transfer (LET) dependence with an agreement between measured and treatment planning system (TPS) dose below 1%. The OSLDs measured on average a 6.3% lower dose compared to TPS calculation, with no significant difference between varying modulations and ranges. Both GD-352M and MCP-N measured a lower dose than the TPS and luminescent response was dependent on the LET of the therapeutic proton beam. Thermoluminescent response of MTS-N was also found to be dependent on the LET and a higher dose than TPS was measured with the most pronounced increase of 11%.As alanine detectors are characterized by the lowest energy dependence for different parameters of therapeutic pencil beam scanning they are suitable candidates for mail auditing in proton therapy. The response of luminescence detector systems have shown promises even though more careful calibration and corrections are needed for its implementation as part of a mailed dosimetry audit system.     

Simultaneous production of mixed electron–photon beam in a medical LINAC: A feasibility study

PurposeThe electron or photon beams might be used for treatment of tumors. Each beam has its own advantage and disadvantages. Combo beam can increase the advantages. No investigation has been performed for producing simultaneous mixed electron and photon beam. In current study a device has been added to the Medical Linac to produce a mixed photon–electron beam.MethodsFirstly a Varian 2300CD head was simulated by MCNP Monte Carlo Code. Two sets of perforated lead sheets with 1 and 2 mm thickness and 0.2, 0.3, and 0.5 cm punches then placed at the top of the applicator holder tray. This layer produces bremsstrahlung x-ray upon impinging fraction electrons on it. The remaining fraction of electrons passes through the holes. The simulation was performed for 10 × 10, 6 × 6, and 4 × 4 cm² field size.ResultsFor 10 × 10 cm² field size, among the punched targets, the largest penumbra difference between the depth of 1 and 7 cm was 72%. This difference for photon and electron beams were 31% and 325% respectively. A maximum of 39% photon percentage was produced by 2 mm target with 0.2 cm holes diameter layer. The minimum surface dose value was 4% lesser than pure electron beam. For small fields, unlike the pure electron beam, the PDD, penumbra, and flatness variations were negligible.ConclusionsThe advantages of mixing the electron and photon beam is reduction of pure electron's penumbra dependency with the depth, especially for small fields, also decreasing of dramatic changes of PDD curve with irradiation field size.     

M?ssbauer spectroscopy, electron microscopy and electron diffraction studies of the iron cores in various human and animal haemosiderins

M?ssbauer spectroscopy has indicated significant differences in the iron-containing cores of various haemosiderins. In the present study, haemosiderin was isolated from a number of animal species including man. In addition, haemosiderin was isolated from patients with primary idiopathic haemochromatosis or with secondary (transfusional) iron-overload. The iron cores of the animal and normal human haemosiderin appear to be very similar by M?ssbauer spectroscopy, and the electron diffraction data indicate a ferrihydrite structure similar to that of ferritin cores. The haemosiderin isolated from secondary iron-overload shows anomalous behaviour in its temperature-dependent M?ssbauer spectra. This can be understood in terms of the microcrystalline goethite structure of the cores as indicated by electron diffraction. The haemosiderin cores obtained in the case of primary haemochromatosis have an amorphous Fe(III) oxide structure and show M?ssbauer spectra characteristic of a magnetically disordered material, which only orders at very low temperatures.     

Amplitude−temporal characteristics of a supershort avalanche electron beam generated during subnanosecond breakdown in air and nitrogen

The amplitude?temporal characteristics of a supershort avalanche electron beam (SAEB) with an amplitude of up to 100 A, as well as of the breakdown voltage and discharge current, are studied experimentally with a picosecond time resolution. The waveforms of discharge and SAEB currents are synchronized with those of the voltage pulses. It is shown that the amplitude?temporal characteristics of the SAEB depend on the gap length and the designs of the gas diode and cathode. The mechanism for the generation of runaway electron beams in atmospheric-pressure gases is analyzed on the basis of the obtained experimental data.     

Evaluation of two commercial methods for the susceptibility testing of Candida species: Vitek 2® and Sensititre YeastOne®

Background

An increased incidence of fungal infections caused by Candida species, especially Candida glabrata and Candida krusei, which are less susceptible to azoles, has been observed. Standardized susceptibility testing is essential for clinical management and for monitoring the epidemiology of resistance.

Anti-staphylococcal effect of enterocin in Sunar® and yogurt

Enterocin was used to control the growth of Staphylococcus aureus strains SA1 and Oxford 209P in Sunar (milk nourishment for suckling babies) and during the yogurt-making process. Reduction by three orders of magnitude was noted in the growth of SA1 strain in Sunar milk nourishment between the enterocin-containing (ES) and the control samples (CS) at 1-d cultivation. An inhibitory effect of enterocin was observed when surviving of SA1 cells were checked 6 h after the start of cultivation (2 h after enterocin application; enterocin was applied after 4 h). Decrease in the count of Oxford 209P strain in yogurt was detected in ES after 1 d of storage in comparison with CS (10(3) and 10(0) CFU mL-1 g-1). Thus a decrease by three orders of magnitude was found between ES and CS at the time mentioned. On the other hand, no bacteriocin activity was detected in ES after 1 d. Activity was detected only immediately after enterocin addition to ES (400 AU/mL) as well as after 1 and 3 1/2 h (200 AU/mL). Although the slight regrowth of the indicator was obtained up to 1 week of yogurt storage, the difference between ES and CS persisted. The lowest pH of the final yogurt product was noted in the reference yogurt sample but differences among the pH values of yogurt samples were not significant.