Влияния ингибитора синтаз оксида азота Т1023 на развитие лучевого пневмофиброза у крыс

The purpose of the work was to study the ability of the NOS inhibitor T1023 to prevent late radiation injuries. Methods: the effects of T1023 (75 mg / kg, once i.p. 30 minutes before the irradiation) on the development of post-radiation pulmonitis and pneumofibrosis in rats with thoracic exposure to g-radiation at  a dose of 12.5 Gy were studied histopathologically and morphometrically. The results of the studies showed that there wasn’t a significant objective effect of T1023 on the development of early radiation-induced lung injuries  (9 weeks after irradiation). But it prevented late radiation induced lung injuaries (26 weeks after irradiation) – there were a significant lesser pathomorphological manifestations of post-radiation pulmonitis, proliferation of connective tissue and the development of fibrotic changes in the lung parenchyma. At this stage, the action of T1023 clearly contributed to the preservation of the normal histostructure of the lungs, reducing by 40% the content of compaction zones in the parenchyma. The ability of the NOS inhibitor T1023 to significantly limit the development of lungs late radiation reaction confirms the promise of further development  of this compound as a means for prevention radiation therapy complications.Целью работы являлось изучение способности ингибитора синтаз оксида азота Т1023 к профилактике поздних лучевых повреждений. Методы работы включали гистопатологические и морфометрические исследования влияния радиозащитного действия соединения Т1023 (75 мг/кг, однократно внутрибрюшинно за 30 мин до облучения) на развитие постлучевого пульмонита и пневмофиброза у крыс при торакальном воздействии γ-излучения в дозе 12,5 Гр. Результаты исследований показали, что радиозащитное действие соединения Т1023 не оказывало существенного объективного влияния на раннем этапе (9 недель) развития радиационно-индуцированных повреждений легких. Но на этапе полного развития лучевой реакции легких (26 недель) превентивное радиозащитное действие Т1023 сопровождалось объективно выраженным и статистически значимым ограничением патоморфологических проявлений постлучевого пульмонита, разрастания соединительной ткани и развития фиброзных изменений в паренхиме легких. На этом сроке действие Т1023 отчетливо способствовало сохранению нормальной гистоструктуры легких, снижая на 40% содержание в паренхиме зон уплотнения. Показанная в работе способность ингибитора синтаз оксида азота Т1023 существенно ограничивать развитие поздней лучевой реакции легких подтверждает перспективность дальнейшей разработки этого соединения в качестве средства профилактики осложнений лучевой терапии

RBE of "Prometeus" Facility Protons for Irradiation of Tumor Cells in Vitro with One and Three Fields

The study was aimed to the biological effectiveness of the proton scanning beam of the first Russian medical facility. The clonogenic assay of B-16 tumor cells was used as a test system. Cell irradiation was carried out in a suspension condition in a water phantom. Single and three-field exposures were studied. The dose interval was 2-8 Gy. The energy range from 47.5 to 92.0 MeV was used for the Bragg peak formation. The relative biological effectiveness of protons comparing to gamma-rays was 1.2 for single-field and 1.5 for three-field irradiation. The results obtained agree with literature data related to the used cell culture (B-16) and linear energy transfer range (3÷8 keV/µm)

1-Isobutanoil-2-isopropylisothiourea Phosphate, T1082: A Safe and Effective Prevention of Radiotherapy Complications in Oncology

The radioprotective effects of a new 1-isobutanoil-2-isopropylisothiourea derivative named T1082 are presented. Research methods included toxic characteristics, radioprotective activity (Till– McCulloch’s test and 30-day survival test) in γ-ray total-body-irradiated mice, and a clinical and histological study of the effect of T1082 on acute radiation skin reactions (RSR) in rats after a single or fractionated β-ray local irradiation. T1082 is more effective than its analogue, the NOS inhibitor T1023, at low concentrations and doses (1/12–1/8 LD10 ), both parenterally and intragastrically. In this case, its therapeutic index (LD50 /ED50 ) reaches 30, and the optimal radioprotective doses (ED84–98 —141–224 mg/kg) are an order less than the maximum tolerated doses—1/16–1/10 LD10 . These properties allowed T1082, at a low intragastrical dose (160 mg/kg; 1/14 LD10), to significantly limit the severity of acute RSR after single (40 Gy) and fractionated (78 Gy) β-ray irradiation. The results confirm T1082 as one of the safest emergency radioprotectors and indicate the prospects for its further development as a pharmacological agent for the prevention of RT complications. © 2022 by the authors. Licensee MDPI, Basel, Switzerland

Analysis of Metrological Provision Problems of a Test Stand for Testing Radio-Electronic Products for Resistance to Irradiation with High-Energy Heavy Ions

Abstract: The problems of the metrological certification of beams of high-energy heavy charged particles (HCPs) and protons that will be used in the study—as well as testing for radiation resistance—of promising products of semiconductor micro- and nanoelectronics, solid-state microwave electronics, and micromechanical systems are considered. One of the main requirements for such beams is ensuring the desired range of linear energy transfer (LET). Two methods for changing the LET are considered, one of which is based on using the ions of various types (16O, 22Ne, 40Ar, 56Fe, 84Kr, 136Xe, 209Bi), and the other is based on using ion of the same type (197Au), but with different energies. The advantages of using both methods are considered and the problems arising when using the second method are analyzed. © 2019, Pleiades Publishing, Ltd