Effects of ethanol and other alkanols on passive proton influx in the yeast Saccharomyces cerevisiae

Ethanol, isopropanol, propanol and butanol enhanced the passive influx of protons into deenergized cells of Saccharomyces cerevisiae. The influx followed first-order kinetics with a rate constant that increased exponentially with the alkanol concentration. The exponential enhancement constants increased with the lipid solubility of the alkanols, which indicated hydrophobic membrane regions as the target sites. While the enhancement constants were independent of pH over the range tested (3.3–5.0), the rate constants decreased linearly with increasing extracellular proton concentration, indicating the presence of an additional surface barrier against proton penetration, the effectiveness of which increased with protonation. The alkanols affected the acidification curves of energized yeast suspensions in such a way that the final pH values were linear functions of the alkanol concentrations. These results were consistent with a balance between active and passive proton movements at the final pH, the exponential enhancement constants calculated from the slopes being nearly identical with those obtained with deenergized cells. It was concluded that passive proton influx contributes to the kinetics of acidification in S. cerevisiae and that uncoupling contributes to the overall kinetics of alkanol-inhibited secondary active transport across the yeast plasma membrane.     

Conversion factors for effective dose and organ doses with the air kerma area product in patients undergoing percutaneous transhepatic biliary drainage and trans arterial chemoembolization

Conversion factors used to estimate effective (E) and organ doses (H_T) from air Kerma area product (KAP) are required to estimate population doses in percutaneous transhepatic biliary drainage (PTBD) and trans arterial chemoembolization (TACE) interventional procedures.In this study, E and H_T for ten critical organs/tissues, were derived in 64 PTBD and 48 TACE procedures and in 14,540 irradiation events from dosimetric, technical and geometrical information included in the radiation dose structured report using the PCXMC Monte Carlo model, and the ICRP 103 organ weighting factors. Conversion factors of: 0.13; 0.19; 0.26 and 0.32 mSv Gy⁻¹ cm⁻² were established for irradiation events characterized by a Cu filtration of 0.0; 0.1; 0.4 and 0.9 mm, respectively. While a single coefficient of conversion is not able to provide estimates of E with enough accuracy, a high agreement is obtained between E estimated through Monte Carlo methods and E estimated through E/KAP conversion factors accounting separately for the different modes of fluoroscopy and the fluorography component of the procedures.An algorithm for the estimation of effective and organ doses from KAP has been established in biliary procedures which considers the Cu filtration in the X-ray irradiation events. A similar algorithm could be easily extended to other interventional procedures and incorporated in radiation dose monitoring systems to provide dosimetric estimates automatically with enough accuracy to assess population doses.     

On the eptihermal neutron energy limit for Accelerator-Based Boron Neutron Capture Therapy (AB-BNCT): Study and impact of new energy limits

Background and purpose: Accelerator-Based Boron Neutron Capture Therapy is a radiotherapy based on compact accelerator neutron sources requiring an epithermal neutron field for tumour irradiations. Neutrons of 10 keV are considered as the maximum optimised energy to treat deep-seated tumours. We investigated, by means of Monte Carlo simulations, the epithermal range from 10 eV to 10 keV in order to optimise the maximum epithermal neutron energy as a function of the tumour depth.Methods: A Snyder head phantom was simulated and mono-energetic neutrons with 4 different incident energies were used: 10 eV, 100 eV, 1 keV and 10 keV. ¹⁰B capture rates and absorbed dose composition on every tissue were calculated to describe and compare the effects of lowering the maximum epithermal energy. The Therapeutic Gain (TG) was estimated considering the whole brain volume.Results: For tumours seated at 4 cm depth, 10 eV, 100 eV and 1 keV neutrons provided respectively 54%, 36% and 18% increase on the TG compared to 10 keV neutrons. Neutrons with energies between 10 eV and 1 keV provided higher TG than 10 keV neutrons for tumours seated up to 6.4 cm depth inside the head. The size of the tumour does not change these results.Conclusions: Using lower epithermal energy neutrons for AB-BNCT tumour irradiation could improve treatment efficacy, delivering more therapeutic dose while reducing the dose in healthy tissues. This could lead to new Beam Shape Assembly designs in order to optimise the BNCT irradiation.     

Amarcord: I Remember

I have tried to offer a historical account of a success story, as I saw it develop from the early times when it interested only a few aficionados to the present times when it has pervaded most of cell biochemistry and physiology. It is of course the story of calcium signaling. It became my topic of work when I was a young postdoctoral fellow at The Johns Hopkins University. I entered it through a side door, that of mitochondria, which had been my area of work during my earlier days in Italy. The 1960s and 1970s were glorious times for mitochondrial calcium signaling, but the golden period was not going to last. As I have discussed below, mitochondrial calcium gradually lost appeal, entering a long period of oblivion. Its fading happened as the general area of calcium signaling was instead experiencing a phase of explosive growth, with landmark discoveries at the molecular and cellular levels. These discoveries established that calcium signaling was one of the most important areas of cell biology. However, mitochondria as calcium partners were not dead; they were only dormant. In the 1990s, they were rescued from their state of neglect to the central position of the regulation of cellular calcium signaling, which they had once rightly occupied. Meanwhile, it had also become clear that calcium is an ambivalent messenger. Hardly anything important occurs in cells without the participation of the calcium message, but calcium must be controlled with absolute precision. This is an imperative necessity, which becomes unfortunately impaired in a number of disease conditions that transform calcium into a messenger of death.     

Solution structure of agelenin, an insecticidal peptide isolated from the spider Agelena opulenta, and its structural similarities to insect-specific calcium channel inhibitors

Agelenin, isolated from the Agelenidae spider Agelena opulenta, is a peptide composed of 35 amino acids. We determined the three-dimensional structure of agelenin using two-dimensional NMR spectroscopy. The structure is composed of a short antiparallel beta-sheet and four beta-turns, which are stabilized by three disulfide bonds. Agelenin has characteristic residues, Phe9, Ser28 and Arg33, which are arranged similarly to the pharmacophore of the insect channel inhibitor, omega-atracotoxin-Hv1a. These observations suggest that agelenin and omega-atracotoxin-Hv1a bind to insect calcium channels in a similar manner. We also suggest that another mode of action may operate in the channel inhibition by omega-agatoxin-IVA and omega-atracotoxin-Hv2a.     

Proton irradiation induced reactive oxygen species promote morphological and functional changes in HepG2 cells

The increased use of proton therapy has led to the need of better understanding the cellular mechanisms involved. The aim of this study was to investigate the effects induced by the accelerated proton beam in hepatocarcinoma cells. An existing facility in IFIN-HH, a 3 MV Tandetron? accelerator, was used to irradiate HepG2 human hepatocarcinoma cells with doses between 0 and 3 Gy. Colony formation was used to assess the influence of radiation on cell long-term replication. Also, the changes induced at the mitochondrial level were shown by increased ROS and ATP levels as well as a decrease in the mitochondrial membrane potential. An increased dose has induced DNA damages and G₂/M cell cycle arrest which leads to caspase 3/7 mediated apoptosis and senescence induction. Finally, the morphological and ultrastructural changes were observed at the membrane level and the nucleus of the irradiated cells. Thus, proton irradiation induces both morphological and functional changes in HepG2 cells.     

The International Atomic Energy Agency action plan on radiation protection of patients and staff in interventional procedures: Achieving change in practice

IntroductionThe International Atomic Energy Agency (IAEA) organized the 3rd international conference on radiation protection (RP) of patients in December 2017. This paper presents the conclusions on the interventional procedures (IP) session.Material and methodsThe IAEA conference was conducted as a series of plenary sessions followed by various thematic sessions. “Radiation protection of patients and staff in interventional procedures” session keynote speakers presented information on: 1) Risk management of skin injuries, 2) Occupational radiation risks and 3) RP for paediatric patients. Then, a summary of the session-related papers was presented by a rapporteur, followed by an open question-and-answer discussion.ResultsSixty-seven percent (67%) of papers came from Europe. Forty-four percent (44%) were patient studies, 44% were occupational and 12% were combined studies. Occupational studies were mostly on eye lens dosimetry. The rest were on scattered radiation measurements and dose tracking. The majority of patient studies related to patient exposure with only one study on paediatric patients. Automatic patient dose reporting is considered as a first step for dose optimization. Despite efforts, paediatric IP radiation dose data are still scarce. The keynote speakers outlined recent achievements but also challenges in the field. Forecasting technology, task-specific targeted education from educators familiar with the clinical situation, more accurate estimation of lens doses and improved identification of high-risk professional groups are some of the areas they focused on.ConclusionsManufacturers play an important role in making patients safer. Low dose technologies are still expensive and manufacturers should make these affordable in less resourced countries. Automatic patient dose reporting and real-time skin dose map are important for dose optimization. Clinical audit and better QA processes together with more studies on the impact of lens opacities in clinical practice and on paediatric patients are needed.     

Is volumetric modulated arc therapy with constant dose rate a valid option in radiation therapy for head and neck cancer patients?

Background

Intensity-modulated radiotherapy (IMRT) improves dose distribution in head and neck (HN) radiation therapy. Volumetric-modulated arc therapy (VMAT), a new form of IMRT, delivers radiation in single or multiple arcs, varying dose rates (VDR-VMAT) and gantry speeds, has gained considerable attention. Constant dose rate VMAT (CDR-VMAT) associated with a fixed gantry speed does not require a dedicated linear accelerator like VDR-VMAT. The present study explored the feasibility, efficiency and delivery accuracy of CDR-VMAT, by comparing it with IMRT and VDR-VMAT in treatment planning for HN cancer.

High-precision quality assurance of robotic couches with six degrees of freedom

A robotic couch capable of six degrees of freedom (6-DoF) of motion was introduced for state-of-the-art radiation therapy. Patient treatment requires precise quality assurance (QA) of 6-DoF. Unfortunately, conventional methods do not provide the requisite accuracy and precision. Therefore, we developed a high-precision automated QA system using a visual tracking system (VTS). The VTS comprises four motion-sensing cameras, a cube with infrared reflective markers. To acquire data in treatment room coordinates, a transformation matrix from VTS coordinates to treatment room coordinates was determined.The mean error and standard deviation of linear and rotational motions, as well as couch sagging were analyzed from continuously acquired images in the moving couch. The accuracy of VTS was 0.024 mm deviation for the sinusoidal motion, and the accuracy of the transformation matrix was 0.02 mm. In a cross-comparison, the difference between Laser Tracker (FARO) measurements was 0.14 ± 0.12 mm for translation and 0.032 ± 0.026° on average for yaw rotation. The new system provides QA of yaw, pitch and roll motion as well as sagging of the couch and sub-millimeter/degree accuracy together with precision.     

Gamma and X-ray irradiation as a phytosanitary treatment against various stages of Planococcus lilacinus (Hemiptera: Pseudococcidae)

The cacao mealybug, Planococcus lilacinus Cock, is an important quarantine pest. Infested commodity should be subject to appropriate phytosanitary treatment, while irradiation is recommended for the cacao mealybug. Radio-tolerance comparison tests were conducted on the crawler, nymphs, and adult females of P. lilacinus at the X-ray radiation doses of 40, 80, and 120 Gy, respectively. The results showed that irradiation had a strong effect on preventing of development and reproduction; the adult female stage was identified as the most tolerant. During the following dose–response tests, among young and late females X-ray-irradiation (20–100 Gy), the late females were most tolerant when preventing F₁ generation 2nd instars emergence was used as the evaluation criterion. Minimum absorbed dose and its 95 % fiducial limits to provide probit 9 efficacy at 95 % confidence level (100 % mortality/inhibition in an estimated population of 93,616 individuals) were 131.5 Gy (122.5, 142.6 Gy) and 144.4 Gy (132.7, 159.4 Gy), estimating from the probit analysis on dose-mortality data of 1–30 and 1–10-day-old neonates laid by late females, respectively. In the large-scale confirmatory tests, a total of estimating 97,384 late females of P. lilacinus rearing on the pumpkins fruits were irradiated with gamma-ray at the target dose of 135 or 145 Gy (measured doses 126.1–163.0 Gy), which resulted in no F₁ generation 2nd nymphs developing during a 6-week post-treatment period. The treatment efficacy calculated is 99.9969 % at the 95 % confidence level. Therefore, a minimum absorbed dose of 163.0 Gy is recommended for phytosanitary treatment of P. lilacinus in infested commodity.