STRUCTURAL TRANSFORMATIONS IN AXILLARY AND MESENTERIC LYMPH NODES IN CHEMOTHERAPY AND SURGICAL TREATMENT OF EXPERIMENTAL MAMMARY TUMOR

Was conducted histological study axillary and mesenteric lymph nodes in breast cancer induced by intramammary administration of N-methyl-N-nitrosourea, chemotherapy according to the CMF scheme (cyclophosphamide, methotrexate, 5-fluorouracil), operative removal of breast tumors (6.5 months from the beginning of the experiment). The results of the study. At chemotherapy of breast cancer, compared with the group with breast cancer without treatment, there was a decrease in the number of tumor cells in the axillary lymph nodes in comparison with mesenteric lymph nodes. The decrease in the area of the paracortical zone and the area of secondary lymphoid nodes remain in the axillary lymph nodes, in comparison with breast cancer without treatment. The reduction of the paracortical zone square remains in mesenteric lymph nodes. The area of lymphoid nodules with germinative centers decreases. The number of postcapillary venules with high endothelium and the number of macrophages in structural zones grow down. In the axillary lymph nodes after surgical treatment of breast cancer and chemotherapy in comparison with the treatment of breast cancer only with cytostatics, there is decrease in the area of the paracortical zone (with an increase in the number of small lymphocytes) and medullare cords. The area of lymphoid nodules with germinative and without germinative centers increases. In mesenteric lymph nodes, drainage function is reduced, increased the area of the paracortical zone, reduced the areas of lymphoid nodules with germinative centers and medullare cords (increased proliferative activity of cells), macrophage reaction in the cortical substance was revealed. Conclusion. The severity of structural transformations in cytoarchitectonics of the axillary and mesenteric lymph nodes depends on the treatment method

Стеноз трахеи и релаксация диафрагмы постковидной этиологии

Pandemic of the new coronavirus infection has presented the medical community with challenges that call for immediate action. An increase in the number of severe cases of COVID-19 requiring mechanical ventilation inevitably leads not only to an increase in the complication rates, but also to combined complications. A clinical case of a combined tracheal stenosis and diaphragm after severe COVID-19 is presented here. The aim of this publication was to improve treatment outcomes of patients with multiorgan complications of post-COVID origin. Conclusion. Combined complications of a severe coronavirus infection worsen the rehabilitation prognosis, and require surgical treatment.При пандемии новой коронавирусной инфекции (НКИ) перед медицинским сообществом ставятся задачи, для решения которых требуются безотлагательные меры. Наблюдается рост числа тяжелых случаев COVID-19 (COronaVIrus Disease 2019), вызванных коронавирусом SARS-CoV-2 (Severe Acute Respiratory Syndrome-related CoronaVirus 2), при которых требуется искусственная вентиляция легких; при этом неминуемо не только увеличивается число осложнений, но и отмечается сочетание нескольких осложнений у одного пациента. Представлено клиническое наблюдение сочетания стеноза трахеи и релаксации диафрагмы постковидной этиологии у пациентки, перенесшей COVID-19 тяжелого течения. Целью работы явилось улучшение результатов лечения у пациентов с мультиорганными осложнениями постковидной этиологии. Заключение. При сочетании осложнений у пациентов после НКИ тяжелого течения ухудшается прогноз реабилитации, при лечении таких пациентов следует применять активную хирургическую тактику

Обеспечение искусственной однолегочной вентиляции при посттрахеостомическом стенозе трахеи для торакоскопической пластики правого купола диафрагмы

The article is devoted to the consideration of a clinical case of providing artifcial one-lung ventilation for performing thoracoscopic plastic of the right dome of the diaphragm in a patient with grade 3 posttracheostomy cicatricial tracheal stenosis. The patient is presented after a new coronavirus infection COVID-19 from 2020, prolonged mechanical ventilation through a tracheostomy tube (74 days), the development of medium thoracic cicatricial tracheal stenosis of grade 3 (the lumen of the narrowest part of the trachea is 4 mm) after decannulation and the development of relaxation of the right dome of the diaphragm (according to CT data, the dome is located at the level of the IV intercostal space). The frst stage under conditions of combined general anesthesia and high-frequency ventilation of the lungs was performed to restore the lumen of the trachea by bougienage of the stenosis area with tubes of a rigid endoscope under the control of a fberoptic bronchoscope with further nasotracheal intubation with a thermoplastic single-lumen endotracheal tube with a diameter of 8.0 with a cuff. At the second stage, during thoracoscopic plastic of the right dome of the diaphragm, to provide artifcial one-lung ventilation, a bronchial blocker was used, introduced through the same endotracheal tube into the right main bronchus under the control of a fberoptic bronchoscope.Рассмотрен клинический случай обеспечения искусственной однолегочной вентиляции для выполнения торакоскопической пластики правого купола диафрагмы у пациентки с посттрахеостомическим рубцовым стенозом 3-й степени. Представлена пациентка после перенесенной новой коронавирусной инфекции COVID-19 от 2020 г., длительной искусственной вентиляции легких через трахеостомическую трубку (74 дня), с развитием среднегрудного рубцового стеноза трахеи 3-й степени (просвет наиболее узкой части трахеи – 4 мм) после деканюляции и развитием релаксации правого купола диафрагмы (по данным компьютерной томографии, купол расположен на уровне IV межреберья). Первым этапом в условиях комбинированной общей анестезии и высокочастотной вентиляции легких выполнено восстановление просвета трахеи путем бужирования области стеноза тубусами жесткого эндоскопа под контролем фибробронхоскопа с дальнейшей назотрахеальной интубацией термопластической однопросветной интубационной трубкой диаметром 8,0 мм с манжетой. Вторым этапом во время торакоскопической пластики правого купола диафрагмы для обеспечения искусственной однолегочной вентиляции использовали бронхиальный блокатор, введенный через ту же интубационную трубку в правый главный бронх под контролем фибробронхоскопа

CORRELATION BETWEEN CYTOKINE CONTENT IN LYMPH OF THORACIC LYMPH DUCT AND MESENTERIC LYMPH NODE STRUCTURAL TRANSFORMATIONS IN EXPERIMENTAL MAMMARY TUMOR AND CHEMOTHERAPY

The aim of the study was to fulfill correlation analysis of morphometry of the mesenteric lymph nodes and the concentration of cytokines in the lymph of the thoracic duct in breast cancer induced by intramammary administration of N-methyl-N-nitrosourea, chemotherapy according to the CMF scheme (cyclophosphamide, methotrexate, 5-fluorouracil). The results of the study. At breast cancer revealed positive correlation: in the germinative centers and medullary cords of cytokine IL-5 with mitotically dividing cells, chemokines MIP-1α with average lymphocytes, in the germinative centers of immunoblasts with cytokine GRO/KC, in the paracortical zone chemokine MCP-1 with macrophages, reticular cells with IL-6 and M-CSF, in the medullary sinuses chemokine GRO/KC with small lymphocytes and mature plasma cells (number which decreases). All this may indicate the activity of the local immune response in the lymph nodes aimed on the antitumor protection. After chemotherapy of breast cancer, compared with breast cancer without treatment, revealed positive relationship, which may indicate increased immunomodulatory and antitumor actions of cytokines: correlation of interferon IFNγ with small lymphocytes (number which increased) and macrophages in the germinative centers and mitotically dividing cells in the medullary cords, correlation in the germinative centers of immunoblasts with MIP-1α and increased of number small lymphocytes in T-dependent zone lymph nodes, correlation in medullary cords of interleukin IL-17 with mature plasma cells (number which increased) , correlation of interleukin IL-18 with mature plasma cells in medullary sinuses. Conclusion. Study of the correlation of the concentration of cytokines in the lymph of the thoracic duct with structural changes in the mesenteric lymph nodes revealed dependencies aimed at increasing the immunomodulating and antitumor effects of cytokines

ФАКТОРЫ РИСКА СИМУЛЬТАННЫХ ОПЕРАЦИЙ ПРИ СОЧЕТАНИИ РАКА ЛЕГКОГО И СЕРДЕЧНО-СОСУДИСТОЙ ПАТОЛОГИИ

Currently, there is a global trend of growing frequency of concurrent lung malignant tumors and cardiac vascular pathology, in particular, ischemic heard disease. The literature review demonstrates, that development of surgery, anesthesiology and intensive care allows expanding limits for treatment of such patients through simultaneous surgery when lungs and heart are operated at the same time.The article analyzes the personal experience of the authors and international publications, it contemplates on safe performance of simultaneous and multi-organ surgeries, involving respiratory and blood circulation systems, different approaches to surgery, its specific features, benefits, and limitations. Specialists from Russian Surgery Research Center named after B.V. Petrovsky find it preferable to perform simultaneous staged surgery of the lungs, mediastinum and cardiac vascular system. There is a certain sequence of stages. It demonstrates that the first stage may include isolation of abnormal masses of the lung (mediastinum) and lung hilus, if necessary. After that cardiac surgery is performed, and as a final stage, the whole abnormal focus is isolated and resected.В настоящее время во всем мире отмечается тенденция к увеличению частоты встречаемости сочетания злокачественных новообразований легких с сердечно-сосудистой патологией, в частности ишемической болезнью сердца. Анализ литературы показывает, что развитие хирургии, анестезиологии и реаниматологии позволяет расширить границы лечения таких больных путем проведения симультанных операций, когда вмешательство на сердце и легких происходит одновременно.В статье представлен анализ собственного опыта, а также зарубежных авторов, рассмотрены проблемы безопасного проведения сочетанных и мультиорганных операций на органах системы дыхания и кровообращения и варианты подходов к хирургическому лечению, их особенности, преимущества и недостатки. Специалисты РНЦХ считают предпочтительным одномоментное этапное проведение хирургического вмешательства на легком и структурах средостения и сердечно-сосудистой системы. Предусмотрена последовательность этапов. Показано, что первым этапом может выполняться выделение патологических образований легкого (средостения) и корня легкого при необходимости. Затем проводится кардиохирургический этап и в заключение ‒ выделение и удаление всего патологического очага в комплексе

The effects of material formulation and manufacturing process on mechanical and thermal properties of epoxy/clay nanocomposites

A holistic study was conducted to investigate the combined effect of three different pre-mixing processes, namely mechanical mixing, ultrasonication and centrifugation, on mechanical and thermal properties of epoxy/clay nanocomposites reinforced with different platelet-like montmorillonite (MMT) clays (Cloisite Na+, Cloisite 10A, Cloisite 15 or Cloisite 93A) at clay contents of 3–10 wt%. Furthermore, the effect of combined pre-mixing processes and material formulation on clay dispersion and corresponding material properties of resulting composites was investigated using X-ray diffraction (XRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM), flexural and Charpy impact tests, Rockwell hardness tests and differential scanning calorimetry (DSC). A high level of clay agglomeration and partially intercalated/exfoliated clay structures were observed regardless of clay type and content. Epoxy/clay nanocomposites demonstrate an overall noticeable improvement of up to 10 % in the glass transition temperature (Tg) compared to that of neat epoxy, which is interpreted by the inclusion of MMT clays acting as rigid fillers to restrict the chain mobility of epoxy matrices. The impact strength of epoxy/clay nanocomposites was also found to increase by up to 24 % with the addition of 3 wt% Cloisite Na+ clays. However, their flexural strength and hardness diminished when compared to those of neat epoxy, arising from several effects including clay agglomeration, widely distributed microvoids and microcracks as well as weak interfacial bonding between clay particles and epoxy matrices, as confirmed from TEM and SEM results. Overall, it is suggested that an improved technique should be used for the combination of pre-mixing processes in order to achieve the optimal manufacturing condition of uniform clay dispersion and minimal void contents

Анестезиологическое обеспечение торакоскопических операций на легких и органах средостения

The objective of the review: analysis of innovations in the conceptual justification and methodological support of anesthetic protection of thoracic surgical interventions.Results: optimization of methods of anesthetic protection should be aimed at solving both surgical requirements such as creating conditions for surgical comfort and at the same time, ensuring the maximum achievable level of protection efficiency and patient safety. When solving the problems of patient protection in thoracic surgery in general and thoracoscopic surgery in particular, the special attention is paid to ensuring effective gas exchange and optimal anesthesia methods corresponding to them within the framework of the multi-component concept. It is important to consider that weaning from mechanical ventilation and the careful collapse of the operated lung are absolute indications for thoracoscopic surgery. This approach is used due to the need to provide space in the pleural cavity for instrumental manipulations during surgery.Цель обзора: анализ инноваций в концептуальное обоснование и методическое обеспечение анестезиологической защиты торакальных хирургических вмешательств.Результаты: оптимизация методов анестезиологической защиты должна быть направлена на решение как хирургических требований, таких как создание условий хирургического комфорта, так и одновременное обеспечение максимально достижимого уровня эффективности защиты и безопасности пациентов. Основное внимание при решении проблем защиты пациента в торакальной хирургии вообще и в торакоскопической в частности принадлежит возможностям обеспечения эффективного газообмена и оптимально соответствующих им методов анестезии в рамках концепции многокомпонентности. Важно учитывать, что выключение из вентиляции и тщательное коллабирование оперируемого легкого имеют абсолютные показания для торакоскопической хирургии. Такой подход продиктован потребностью в обеспечении пространства в плевральной полости для инструментального выполнения хирургических действий

The HSP90 Inhibitor NVP-AUY922 Radiosensitizes by Abrogation of Homologous Recombination Resulting in Mitotic Entry with Unresolved DNA Damage

Heat shock protein 90 (HSP90) is a molecular chaperone responsible for the conformational maintenance of a number of client proteins that play key roles in cell cycle arrest, DNA damage repair and apoptosis following radiation. HSP90 inhibitors exhibit antitumor activity by modulating the stabilisation and activation of HSP90 client proteins. We sought to evaluate NVP-AUY922, the most potent HSP90 inhibitor yet reported, in preclinical radiosensitization studies.NVP-AUY922 potently radiosensitized cells in vitro at low nanomolar concentrations with a concurrent depletion of radioresistance-linked client proteins. Radiosensitization by NVP-AUY922 was verified for the first time in vivo in a human head and neck squamous cell carcinoma xenograft model in athymic mice, as measured by delayed tumor growth and increased surrogate end-point survival (p = <0.0001). NVP-AUY922 was shown to ubiquitously inhibit resolution of dsDNA damage repair correlating to delayed Rad51 foci formation in all cell lines tested. Additionally, NVP-AUY922 induced a stalled mitotic phenotype, in a cell line-dependent manner, in HeLa and HN5 cell lines irrespective of radiation exposure. Cell cycle analysis indicated that NVP-AUY922 induced aberrant mitotic entry in all cell lines tested in the presence of radiation-induced DNA damage due to ubiquitous CHK1 depletion, but resultant downstream cell cycle effects were cell line dependent.These results identify NVP-AUY922 as the most potent HSP90-mediated radiosensitizer yet reported in vitro, and for the first time validate it in a clinically relevant in vivo model. Mechanistic analysis at clinically achievable concentrations demonstrated that radiosensitization is mediated by the combinatorial inhibition of cell growth and survival pathways, ubiquitous delay in Rad51-mediated homologous recombination and CHK1-mediated G(2)/M arrest, but that the contribution of cell cycle perturbation to radiosensitization may be cell line specific

Transient Ureteral Obstruction Prevents against Kidney Ischemia/Reperfusion Injury via Hypoxia-Inducible Factor (HIF)-2α Activation

Although the protective effect of transient ureteral obstruction (UO) prior to ischemia on subsequent renal ischemia/reperfusion (I/R) injury has been documented, the underlying molecular mechanism remains to be understood. We showed in the current study that 24 h of UO led to renal tubular hypoxia in the ipsilateral kidney in mice, with the accumulation of hypoxia-inducible factor (HIF)-2α, which lasted for a week after the release of UO. To address the functions of HIF-2α in UO-mediated protection of renal IRI, we utilized the Mx-Cre/loxP recombination system to knock out target genes. Inactivation of HIF-2α, but not HIF-1α blunted the renal protective effects of UO, as demonstrated by much higher serum creatinine level and severer histological damage. UO failed to prevent postischemic neutrophil infiltration and apoptosis induction in HIF-2α knockout mice, which also diminished the postobstructive up-regulation of the protective molecule, heat shock protein (HSP)-27. The renal protective effects of UO were associated with the improvement of the postischemic recovery of intra-renal microvascular blood flow, which was also dependent on the activation of HIF-2α. Our results demonstrated that UO protected the kidney via activation of HIF-2α, which reduced tubular damages via preservation of adequate renal microvascular perfusion after ischemia. Thus, preconditional HIF-2α activation might serve as a novel therapeutic strategy for the treatment of ischemic acute renal failure