Developmental regulation of prostaglandin E2 synthase in porcine ductus arteriosus

The synthesis of PGE(2), the major vasodilator prostanoid of the ductus arteriosus (DA), is catalyzed by PGE(2) synthases (PGES). The factors implicated in increased PGE(2) synthesis in the perinatal DA are not known. We studied the developmental changes of PGES along with that of cyclooxygenase (COX)-2 and cytosolic phospholipase A(2) (cPLA(2)) in the DA of fetal (75-90% gestation) and immediately postnatal newborn (NB) piglets. Levels of microsomal PGES (mPGES), COX-2, and PGE(2) in the DA of NB were approximately 7-fold higher than in fetus; activities of cytosolic PGES (cPGES) and cPLA(2) in DA of the fetus and NB did not differ. Because platelet-activating factor (PAF) could regulate COX-2 expression, the former was measured and found to be more abundant in the DA of the NB than of fetus. PAF elicited an increase in mPGES, COX-2, and PGE(2) in fetal DA to levels approaching those of the NB; cPGES, cPLA(2), and COX-1 were unaffected. In perinatal NB DA, PAF receptor antagonists BN-52021 and THG-315 reduced mPGES, COX-2, and PGE(2) levels and were associated with increased DA tone. It is concluded that PAF contributes in regulating DA tone by governing mPGES, COX-2, and ensuing PGE(2) levels in the perinate.     

Dietary effects of harmine,a β-carboline alkaloid,on development,energy reserves and α-amylase activity of Plodia interpunctella Hübner (Lepidoptera: Pyralidae)

The physiological and developmental effects of harmine, a β-carboline alkaloid, on the insect pest Plodia interpunctella have been analyzed. When added at the larval diet, harmine induced a strong reduction of larvae weight, cannibalism between larvae, in addition to significant mortality. On the other hand, it caused a remarkable development disruption, manifested by both delay and reduction of pupation and adult emergence. Using spectrophotometric assays, we have shown that harmine ingestion provoked a severe reduction in protein, glycogen and lipid contents. Beside, when larvae fed harmine, the activity of the digestive enzyme α-amylase was strongly reduced. In conclusion, our experiments clearly show the susceptibility of P. interpunctella to harmine ingestion revealing the potent bioinsecticidal effect of harmine.     

Insecticidal effects of extracts of seven plant species on larval development, alpha-amylase activity and offspring production of Tribolium castaneum (Herbst) (Insecta: Coleoptera: Tenebrionidae)

Bioinsecticidal effects of methanol extracts from seven plant species on Tribolium castaneum were investigated. Centaurium erythraea, Peganum harmala, Ajuga iva, Aristolochia baetica, Pteridium aquilinum and Raphanus raphanistrum extracts inhibit growth of larvae. C. erythraea was the most toxic with 63% mortality 10 days after treatment, followed by P. harmala with 58%. C. erythraea and P. aquilinum reduce the emergence rate respectively of 66% and 19%. The duration of larval period was shortened by Launaea arborescens, P. aquilinum and A. iva extracts, whereas R. raphanistrum and P. harmala extracts extend the larval period when compared to the control. Extracts of C. erythraea, P. harmala, A. iva and A. baetica inhibited F1 progeny production. Larvae possess three alpha-amylase isoforms as determined by SDS-PAGE. Larvae fed on treated diet had lower alpha-amylase activity than larvae feed on untreated diet. C. erythraea and P. harmala are the most potent extracts. These plant extracts could be useful to reduce seed damage caused by this pest species.     

Validation of Monte Carlo multithreading TOpas 3.6 software in order to simulate the 6 MV Elekta Synergy MLCi2 platform linac

BackgroundMonte Carlo simulation is generally appreciated as an extraordinary technique to investigate particle physics processes and interactions in nuclear medicine and Radiation Therapy. The present task validates a new methodology of Monte Carlo simulation based on the Multithreading technique to reduce CPU time to simulate a 6 MV photon beam provided by the Elekta Synergy MLCi2 platform medical linear accelerator treatment head utilizing TOpas version 3.6 Monte Carlo software and the Slurm Marwan cluster.Materials and methodsThe simulation includes the linear accelerator (LINAC) major components. Calculations are performed for the photon beam with several treatment field sizes varying from 3 × 3 to 10 × 10 cm² at a 100 cm of distance from the source to the surface of the IBA dosimetry water box. The simulation was wholly approved by comparison with experimental distributions. To evaluate simulation accuracy, gamma index formalism for (2%/2mm) and (3%/2mm) criteria, Distance To Agreement DTA, and the estimator standard error ɛ and ɛ_max are used.ResultsGood agreement between simulations and measurements was observed for depth doses and lateral dose profiles, respectively. The gamma index comparisons also highlighted this agreement; more than 97% of the points for all simulations satisfy the quality assurance criteria of (2%/2mm). Regarding calculation performance, the event processing speed is faster using Gate-[mp] compared to TOpas-[mt] mode when running the identical simulation code for both.ConclusionsConsequently, according to the achieved results, the proposed methodology shows the first validation of TOpas in radiotherapy linacs simulations and a reduction in calculation time, capping simulation accuracy as much as possible. For this reason, this software is recommended to be serviceable for Treatment Planning Systems (TPS) purposes.     

Monte Carlo evaluation of particle interactions within the patient-dependent part of Elekta 6 MV photon beam applying IAEA phase space data

BackgroundThis work aims to provide a simulated method to be used by designers of medical accelerators and in clinical centers to manage and minimize particles’ interaction in the patient-dependent part of a 6 MV X-Ray Beam generated by the Elekta linear accelerator system, based on the latest GATE software version 9.0 Monte Carlo simulation, IAEA phase space data, and the last version of “Slurm” computing cluster.Materials and methodsThe experimental results are obtained using the Elekta 6 MV accelerator. The simulation MC developed includes the majority of the patient-dependent segments, such as Multi-Leaf Collimator (MLC), Tongue and Groove T&G, Rounded leaf Part, including the Jaws (XY). This model is used, with a simulated Iba Blue Phantom 2 homogeneous water phantom with dimensions 480 × 480 × 410 mm³, positioned at a Source-to-Surface-Distance (SSD) of 100 cm, all of the interactions of the mega voltage 6 MV radiations in water are simulated. The IAEA phase space (PS) provided by the International Atomic Energy Agency database and cluster computing (Slurm HPC-MARWAN, CNRST, Morocco) are employed to reduce our simulation time.ResultsThe results confirm that there are many interactions in all areas and the patient-dependent part’s internal structures. Thus, electrons and positrons participation appear in the generated field previously designed to be an X-ray beam. Besides, to validate our implementation geometry, the PDD’s and transverse profiles, at a depth ranging from 1.5 to 20 cm, for a field size of 10 × 10 cm², the beam quality such as D_10%, d_max (cm), d₈₀ (cm), TPR_(20/10), the two relative differences in dose were derived on σ_i and σ_i,max are calculated, respectively. Additionally, gamma index formalism for 2%/2 mm criteria is used. Once and for all, we typically take a good agreement between simulation MC GATE 9.0 and the experiment data with an error less than 2%/2 mm.ConclusionsIn the field of X-ray photons, a significant contribution of electrons and positrons has been found. This contribution could be enough to be essential or affect the delivered dose. A good agreement of 98% between this new approach of simulation MC GATE 9.0 software based on IAEA phase space and experimental dose distributions is observed regarding the validation tests used in this task.     

Dosimetric study of Hounsfield number correction effect in areas influenced by contrast product in lungs case

BackgroundThe aim of the study was dosimetric effect quantification of exclusive computed tomography (CT) use with an intravenous (IV) contrast agent (CA ), on dose distribution of 3D-CRT treatment plans for lung cancer. Furthermore, dosimetric advantage investigation of manually contrast-enhanced region overriding, especially the heart.Materials and methodsTen patients with lung cancer were considered. For each patient two planning CT sets were initially taken with and without CA. Treatment planning were optimized based on CT scans without CA. All plans were copied and recomputed on scans with CA. In addition, scans with IV contrast were copied and density correction was performed for heart contrast enhanced. Same plans were copied and replaced to undo dose calculation errors that may be caused by CA. Eventually, dosimetric evaluations based on dose volume histograms (DVHs) of planning target volumes (PTV) and organs at-risk were studied and analyzed using the Wilcoxon’s signed rank test.ResultsThere is no statistically significant difference in dose calculation for the PTV maximum, mean, minimum doses, spinal cord maximum doses and lung volumes that received 20 and 30 Gy, between planes calculated with and without contrast scans (p > 0.05) and also for contrast scan, with manual regions overriding.ConclusionsDose difference caused by the contrast agent is negligible and not significant. Therefore, there is no justification to perform two scans, and using an IV contrast enhanced scan for dose calculation is sufficient.     

Prostanoid receptors: ontogeny and implications in vascular physiology

Prostanoids exert significant effects on circulatory beds. They play a role in the response of the vasculature to adjustments in perfusion pressure and oxygen and carbon dioxide tension, and they mediate the actions of numerous factors. The role of prostanoids in governing circulation of the perinate is suggested to surpass that in the adult. Prostanoids are abundantly generated in the perinate. They have been implicated in autoregulation of blood flow as studied in brain and eyes. Prostaglandins are also dominant regulators of ductus arteriosus tone. The effects of these autacoids are mediated through specific G protein-coupled receptors. In addition to the pharmacological characterization of the prostanoid receptors, important advances in understanding the biology of these receptors have been made in the last decade. Their cloning and the development of animals with disrupted genes of these receptors have been very informative. The involvement of prostanoid receptors in the developing subject, especially on brain and ocular vasculature and on ductus arteriosus, has also begun to be investigated; the expression of these receptors changes with development. Some but not all of the ontogenic changes in these receptors are attributed to homologous regulation. Interestingly, in the process of elucidating their effects, functional perinuclear prostaglandin E2 receptors have been uncovered. This article reviews prostanoid receptors and addresses implications on the developing subject with attention to vascular physiology.     

Characterization of PGE2 receptors in fetal and newborn lamb ductus arteriosus

Although the role of PGE2 in maintaining ductus arteriosus (DA) patency is well established, the specific PGE2 receptor subtype(s) (EP) involved have not been clearly identified. We used late gestation fetal and neonatal lambs to study developmental regulation of EP receptors. In the fetal DA, radioligand binding and RT-PCR assays virtually failed to detect EP1 but detected EP2, EP3D, and EP4 receptors in equivalent proportions. In the newborn lamb, DA total density was one-third of that found in the fetus and only EP2 was detected. Stimulation of EP2 and EP4 increased cAMP formation and was associated with DA relaxation. Though stimulation of EP3 inhibited cAMP formation, it surprisingly relaxed the fetal DA both in vitro and in vivo. This EP3-induced relaxation was specifically diminished by the ATP-sensitive K(+) (K(ATP)) channel blocker glibenclamide. In conclusion, PGE2 dilates the late gestation fetal DA through pathways that involve either cAMP (EP2 and EP4) or K(ATP) channels (EP3). The loss of EP3 and EP4 receptors in the newborn DA is consistent with its decreased responsiveness to PGE2.     

Nuclear-to-cytoplasmic Relocalization of the Proliferating Cell Nuclear Antigen (PCNA) during Differentiation Involves a Chromosome Region Maintenance 1 (CRM1)-dependent Export and Is a Prerequisite for PCNA Antiapoptotic Activity in Mature Neutrophils

Neutrophils are deprived of proliferative capacity and have a tightly controlled lifespan to avoid their persistence at the site of injury. We have recently described that the proliferating cell nuclear antigen (PCNA), a nuclear factor involved in DNA replication and repair of proliferating cells, is a key regulator of neutrophil survival. In neutrophils, PCNA was localized exclusively in the cytoplasm due to its nuclear-to-cytoplasmic relocalization during granulocytic differentiation. We showed here that leptomycin B, an inhibitor of the chromosome region maintenance 1 (CRM1) exportin, inhibited PCNA relocalization during granulocytic differentiation of HL-60 and NB4 promyelocytic cell lines and of human CD34⁺ primary cells. Using enhanced green fluorescent protein fusion constructs, we have demonstrated that PCNA relocalization involved a nuclear export signal (NES) located from Ile-11 to Ile-23 in the PCNA sequence. However, this NES, located at the inner face of the PCNA trimer, was not functional in wild-type PCNA, but instead, was fully active and leptomycin B-sensitive in the monomeric PCNAY114A mutant. To test whether a defect in PCNA cytoplasmic relocalization would affect its antiapoptotic activity in mature neutrophils, a chimeric PCNA fused with the SV40 nuclear localization sequence (NLS) was generated to preclude its cytoplasmic localization. As expected, neutrophil-differentiated PLB985 cells expressing ectopic SV40NLS-PCNA had an increased nuclear PCNA as compared with cells expressing wild-type PCNA. Accordingly, the nuclear PCNA mutant did not show any antiapoptotic activity as compared with wild-type PCNA. Nuclear-to-cytoplasmic relocalization that occurred during myeloid differentiation is essential for PCNA antiapoptotic activity in mature neutrophils and is dependent on the newly identified monomerization-dependent PCNA NES.     

Tailing of survivor curves of clostridial spores heated in edible oils

Tailing of survivor curves was observed for Clostridium sporogenes PA 3679 and Cl. botulinum 62A spores heated whilst suspended in edible oils, but not for the same spores suspended in buffer (pH 7˙2) or mineral oil or for Bacillus cereus F4165/75 spores suspended in buffer or oils. The tailing cannot be ascribed to a genetic or developmental heterogeneity in the resistance of the spore population or to a heterogeneity of the treatment severity during heating. Heat adaptation due to the release of protective factor(s), to the selection for resistant spores or to the diffusion of oil constituents inside the spore protoplast to protect key molecules from heat denaturation was also ruled out. The tailing can be ascribed to spore clumping during the course of heating or to a heterogeneity in heat resistance of germination system(s) within spores, concurrently with the activation of a dormant germination system. It is probably caused by some oleic acid containing triglycerides.