Sympathetic Nerve Innervation and Metabolism in Ischemic Myocardium in Response To Remote Ischemic Conditioning

Background Multiple potential interventions have been tested to protect the heart against myocardial ischemia/reperfusion (MIR) injury. Remote ischemic conditioning (RIC), an endogenous cardioprotective approach, could markedly improve cardiac function post-myocardial ischemia injury. In this study, we aimed to assess the effects of RIC on cardiac sympathetic nerve innervation and metabolism in the association with Chondroitin sulfate proteoglycans (GSPG). Methods Transient myocardial ischemia (30 min) is induced by ligature of the left anterior descending coronary artery ligation (LAD) in male Sprague Dawley rats (250-350 g), in vivo cardiac [11C]mHED and 2-[18F]FDG PET scans were performed at 14 days after ischemia. Remote ischemic preconditioning (RIPerc) was induced by three cycles of five-minute-long unilateral hind limb ischemia and intermittent five minutes of reperfusion during LAD occlusion period. The quantitative parameters were quantified in parametric polar maps. This standardized format facilitates the regional radioactive quantification of parameters in deficit regions to remote areas. The ex vivo radionuclide distribution was additionally identified using autoradiography. Myocardial neuron density and GSPG expression were assessed by immunohistochemistry. Results There was no significant difference in the metabolism-defected to the remote activity ratio (44.6±4.8% vs. 45.4±4.4%) between control rats (MIR) and treated (MIR+RIPerc) rats (P>0.05). Additionally, the mean nervous activity of denervated myocardium activity was significantly elevated in rats with RIPerc coupled with reduced denervated myocardium size compared to the rats MIR group (35.9±7.1% vs. 28.9±2.3% of the left ventricular (LV) remote area (P<0.05). These findings were associated with preserved LV systolic function and a significant reduction in GSPG expression in the myocardium. Conclusion RIPerc presented the effect on cardiac sympathetic nerve innervation following ischemia, but there is no significant effect on myocardial metabolism. A long-term outcome study is warranted.

Distribution of some natural and anthropogenic radionuclides in the sediments and seawater along the coastal areas of North Sulawesi

Studies on the radionuclide distribution of some naturally occurring radioactive materials (NORM) and anthropogenic radionuclides in the sediments of the coastal areas of North Sulawesi were conducted to provide baseline data for the effective monitoring of radioactive fallout in these areas. Sediment samples were collected by a van Veen grab samples about 100 – 300 m from the shoreline, and 60 L of seawater was pre-concentration to precipitated 137Cs. Activity concentration of the three main natural radionuclides (222Ra, 232Th, and 40K) and 137Cs were determined using a high-resolution HPGe gamma-spectroscopy system and presenting background about the radiological levels and assessing the associated hazards. The activity of 226Ra ranged from 2.1 to 9.5 Bq kg−1 with an average value of 5.9 Bq kg−1. The activity of 232Th varies from 2.4 to 10.4 Bq kg−1 with an average value of 5.2 Bq kg−1. The 40K ranges between 169.1 to 492.7 Bq kg−1 with an average value of 238.8 Bq kg−1. The average activity concentration of 40K (238.8 Bq kg−1) in the sediment samples was lower than the worldwide average concentration (420 Bq kg−1). The current level of activity 137Cs varied from 0.05 to 0.40 Bq kg−1 in sediment samples and 0.98 to 1.33 Bq m−3 in seawater samples. 134Cs in all samples were not detected or below the detection limit. This fact indicated that radioactive cesium in Celebes Sea areas of North Sulawesi still originated from global fallout and insignificant influenced by the FDNPP accident. All radionuclide radiation values in the recent study are lower than the world average. Therefore, the potential danger of radiation generated from the surrounding environment has not yet caused a radiological health impact for the people living on the coast of North Sulawesi. Natural and artificial radionuclide activity data in this study will be used as the basis for sedimentary activity along the coast of North Sulawesi.

A Conjugation Strategy to Modulate Antigen Binding and FcRn Interaction Leads to Improved Tumor Targeting and Radioimmunotherapy Efficacy with an Antibody Targeting Prostate-Specific Antigen

Background: The humanized monoclonal antibody (mAb) hu5A10 specifically targets and internalizes prostate cancer cells by binding to prostate specific antigen (PSA). Preclinical evaluations have shown that hu5A10 is an excellent vehicle for prostate cancer (PCa) radiotheranostics. We studied the impact of different chelates and conjugation ratios on hu5A10′s target affinity, neonatal fc-receptor interaction on in vivo targeting efficacy, and possible enhanced therapeutic efficacy. Methods: In our experiment, humanized 5A10 (hu5A10) was conjugated with DOTA or DTPA at a molar ratio of 3:1, 6:1, and 12:1. Surface plasmon resonance (SPR) was used to study antigen and FcRn binding to the antibody conjugates. [111In]hu5A10 radio-immunoconjugates were administered intravenously into BALB/c mice carrying subcutaneous LNCaP xenografts. Serial Single-photon emission computed tomography (SPECT) images were obtained during the first week. Tumors were harvested and radionuclide distribution was analyzed by autoradiography along with microanatomy and immunohistochemistry. Results: As seen by SPR, the binding to PSA was clearly affected by the chelate-to-antibody ratio. Similarly, FcRn (neonatal fc-receptor) interacted less with antibodies conjugated at high ratios of chelator, which was more pronounced for DOTA conjugates. The autoradiography data indicated a higher distribution of radioactivity to the rim of the tumor for lower ratios and a more homogenous distribution at higher ratios. Mice injected with ratio 3:1 111In-DOTA-hu5A10 showed no significant difference in tumor volume when compared to mice given vehicle over a time period of 3 weeks. Mice given a similar injection of ratio 6:1 111In-DOTA-hu5A10 or 6:1 111In-DTPA-hu5A10 or 12:1 111In-DTPA-hu5A10 showed significant tumor growth retardation. Conclusions: The present study demonstrated that the radiolabeling strategy could positively modify the hu5A10′s capacity to bind PSA and complex with the FcRn-receptor, which resulted in more homogenous activity distribution in tumors and enhanced therapy efficacy.

Migration of 238U and 226Ra Radionuclides in Technogenic Permafrost Taiga Landscapes of Southern Yakutia, Russia

This article describes the features and migration patterns of natural long-lived heavy radionuclides 238U and 226Ra in the major components of the environment including rocks, river waters, soils, and vegetation of permafrost taiga landscapes of Southern Yakutia, which helped us to understand the scale and levels of their radioactive contamination. Different methods have been used in this study to determine the content of 238U and 226Ra in various samples, including gamma-ray spectrometry, X-ray spectroscopy, laser excited luminescence, and emanation method. It was determined that the main source of radioactive pollution of soil and vegetation cover, as well as surface waters in these technogenic landscapes, are the dumps of radioactive rock that were formed here as the result of geological exploration carried out in this area during the last third of the 20th century. The rocks studied were initially characterized by a coarse, mainly stony gravelly composition and contrasting radiation parameters, where the gamma radiation exposure rate varied between 1.71 and 16.7 µSv/h, and the contents of 238U and 226Ra were within the range 126–1620 mg/kg and 428–5508 × 10−7 mg/kg, respectively, and the 226Ra: 238U ratio was 1.0. This ratio shifted later on from the equilibrium state towards the excess of either 238U or 226Ra, due to the processes of air, water, and biogenic migration. Two types of 238U and 226Ra radionuclides migration were observed in studied soils, namely aerotechnogenic and hydrotechnogenic, each of which results in a different intraprofile radionuclide distribution and different levels of radioactive contamination. In this study, we also identified plants capable of selective accumulation of certain radionuclides, including Siberian mountain ash (Sorbus sibiricus), which selectively absorbs 226Ra, and terrestrial green and aquatic mosses, which accumulate significant amounts of 238U.

Sensitivity Analysis for Release and Transport Behavior of Radionuclide of the 1F Unit-1 Accident Using SAMPSON

To support the 1F decommissioning project, the Institute of Applied Energy has been analyzing the course of the accident using the SAMPSON code with an aim to grasp radionuclide distribution in 1F NPP. The present study has mainly focused on molybdenum release from a fuel pellet and chemical forms of iodine during the early phase of the accident because a release rate of semi-volatile FPs has various uncertainties. The present simulation set the detrimental factor of molybdenum used in FP release model as a sensitive parameter. The simulation results indicate that more molybdenum release causes more generation of hydrogen iodide and more deposition of iodine inside Reactor Pressure Vessel (RPV) because the adsorption velocity of hydrogen iodide is comparatively higher than deposition velocities of another FPs.