Protonation of the polyhedral anion [closo-B(10)H(10)](2-) under superacidic conditions apparently generates an electrophilic intermediate, [B(10)H(13)](+), that forms 6-R-nido-B(10)H(13) (R = aryl, alkyl, triflate) derivatives by electrophilic aromatic substitution, C-H bond activation, or ion-pair collapse, respectively. The proposed mechanism of formation of the 6-R-nido-B(10)H(13) derivatives via the boranocation [B(10)H(13)](+) is discussed. The synthesis of carboranes, starting from 6-R-nido-B(10)H(13) decaboranes, and single-crystal X-ray diffraction analyses of several 6-R-nido-B(10)H(13) decaboranes and carboranes are described.
Effective utilization of [closo-B12H12](2-) derivatives in targeted drug delivery applications depends upon an efficient strategy to differentiate at least one of the 12 vertices on the B12(2-) core. Precursor molecules must also be able to withstand the initial harsh hydrogen peroxide treatment necessary for hydroxylation of the B-H vertices. We report here a method for preparation of the ammonio derivative [closo-B12(OH)11NH3](-) and also demonstrate its utility in construction of a targeted drug delivery scaffold. Treatment of the precursor [closo-B12H11NH3](-) with hydrogen peroxide gives the corresponding nitro derivative [closo-B12(OH)11NO2](2-) in good yield. The nitro group is easily reduced with hydrogen over a Raney nickel catalyst to produce [closo-B12(OH)11NH3](-). The 11 hydroxyl groups can then be readily converted to carbonates or carbamates. As a proof-of-principle of its utility as a drug delivery system, we used the resulting vertex-differentiated ammonio derivative to construct a platinated pro-drug possessing 11 copies of a carboplatin analogue conjugated to the B12(2-) core via carbamate linkage and a fluorescein molecule attached at the remaining vertex by an amide linkage. In vitro cytotoxicity assays demonstrated that activity of an untagged analog was similar to carboplatin against platinum-sensitive A459 cells and higher than carboplatin against platinum-resistant SK-OV-3 cells. Further fluorescence microscopy revealed that the fluorescein-tagged pro-drug localizes to the nuclei of A459 cells.
Per-B-hydroxylation of a polyhedral borane anion has been demonstrated by the catalytic hydroxylation of icosahedral [closo-B(12)H(12)](2-) using soft electrophiles such as platinum group metal catalysts or iodine cation. A new route to [closo-B(12)(OH)(12)](2-) from [closo-B(12)H(12)](2-) without the use of H(2)O(2) oxidant provides an alternative hydroxylation process.
The paper reviews literature on the current aspects of the diagnosis and expert appraisal of focal osteoplastic masses in the lung upon dust exposure to dust factors. It considers different aspects of the pathogenesis of osteoplastic changes in the tissue structural elements of pulmonary histione. Current views on the prevalence, etiology, and pathogenesis, as well as morphological changes in the development of this abnormality, its association with the dust damaging effects of human activities are reflected.
Государственное бюджетное образовательное учреждение дополнительного профессионального образования «Новокузнецкий государственный институт усовершенствование врачей» Минздрава РФ, научно-исследовательская лаборатория патологической анатомии, Новокузнецк, Россия Проведено гистоморфометрическое исследование сосудов малого круга кровообращения в ткани легких 17 шахтеров, про-работавших в условиях запыленности в среднем 14,1±0,5 года, считавшихся здоровыми по результатам динамического наблю-дения и погибших при техногенной катастрофе. Результаты исследования показали, что в сосудах легких шахтеров происходит увеличение толщины эндотелиального слоя, гипертрофия гладкомышечных структур и развитие периваскулярного склероза. Из-менения структур стенки сосуда приводят к его утолщению и уменьшению относительного просвета сосуда, что создает условия для развития легочной гипертонии. гипертрофия гладкомышечного компонента медии рассматривается как одно из проявлений системного кониотического процесса, разыгрывающегося в стенке легочных сосудов и, как следствие, обусловливающего даль-нейшее повышение артериального давления вторичного характера. Полученные результаты диктуют необходимость разработки методов раннего мониторинга сердечно-сосудистой системы у работников угольной промышленности для выявления латентной и начальной стадий легочной гипертонии.Ключевые слова: сосуды малого круга кровообращения, артериальная гипертензия, периваскулярный фиброз, эндотелиоз, гипертрофия мышечного слоя. We carried out gistomorphometrical researches of vessels of the small circle of blood circulation in the pulmonary tissue of 17 miners which had worked under dust conditions on the average 14,1±0,5 years. they were considered as healthy according to the results of dynamic observation and they perished due to technogenic catastrophe. the results showed that the thickening of the endothelial layer, the hypertrophy of smooth muscle structures and the development of perivascular sclerosis are happened in the vessels of the lungs of miners. Changes of the structure of the vessel wall lead to its thickening and reduction the lumen of the vessel, that creates conditions for the development of pulmonary hypertension. the hypertrophy of smooth muscle structures is considered as one of the manifestations of systemic coniotic processes which occur in the wall of the pulmonary vessels and consequently causes a further increase in blood pressure that has secondary character. the obtained results dictate the need to develop methods of early monitoring of the cardiovascular system in coal workers to detect latent and the initial stages of pulmonary hypertension. PATHOGENETIC ASPECTS OF DEVELOPMENTKey words: vessels of pulmonary circulation, arterial hypertension, perivascular fibrosis, endotheliosis, hypertrophy of the muscle layer Представления о развитии вторичной легочной гипертонии при заболеваниях легких, включая и пневмокониозы, дискутабельны в части опреде-ления сроков ее появления, патогенетических ме-ханизмов и компенсации тканевых структурных ...
Introduction. The combined impact of unfavorable factors of the production environment in miners leads to the development of associated pathology of the bronchopulmonary and cardiovascular systems, the predisposition to which depends on the individual susceptibility of the body. In this regard, it is important to comprehensively study the pathogenetic mechanisms underlying the formation and course of occupational and work-related diseases for a personalized approach to the diagnosis, prevention and therapy of this pathology. The purpose of this study was to study the mechanisms of damage to the cardiovascular system in miners with dust lung pathology on the basis of morphological and genetic studies. Materials and methods. For genetic studies, venous blood drawing was conducted in 190 Kuzbass miners. The main group included 126 miners of the main professions with the previously proven diagnosis "dust lung pathology", the comparison group consisted of 64 workers without a proven diagnosis working in similar sanitary and hygienic conditions. Morphometric studies were carried out using autopsy material obtained during 80 forensic medical examinations of miners in the Kemerovo region. All the miners were divided into 4 groups depending on their underground work experience. The control group was formed from 20 cases of forensic medical examinations of men who died in road accidents and did not have organ pathology according to the results of autopsies. Results. The study of the autopsy material revealed the presence of morphostructural changes in the vascular walls of the miners’ hearts in the form of hypertrophy of the smooth muscle cells of the medial layers, thickening of the endothelial lining, and the development of fibroplastic changes in the perivascular zones. These changes began to form from the first years of work in the underground conditions and progressed with increasing work experience contributing to the "recalibration" of the heart vessels with the formation of the lumen "obstruction". One of the mechanisms of endothelial damage in miners was a change in the expression of the EDN1 gene, which regulates the synthesis of endothelin-1. The risk and resistance genotypes of the development of dust lung pathology for the rs5370 polymorphism of the EDN1 gene were identified. Morphostructural rearrangement of the endothelium in the combination with its pathological activation contributed to the occurrence of endothelial dysfunction in miners. Conclusions. The conducted studies of the parameters of the vascular endothelium indicate its key role in the pathogenesis of bronchopulmonary and cardiovascular pathology in miners of the main professions. Getting into the body of workers, particles of coal-rock dust lead to morphostructural rearrangement of the cells of the endothelial layer and its pathological activation. The contribution of molecular and genetic mechanisms to the development of occupational lung pathology and associated diseases of the circulatory system in miners is revealed. Ethics. The studies were carried out in compliance with the ethical standards of the Bioethical Committee of the Research Institute for Complex Problems of Hygiene and Occupational Diseases, elaborated on the basis of the Helsinki Declaration of the World Medical Association "Ethical Principles for Conducting Human Scientific Medical Research" as amended in 2013 and the "Rules of Clinical Practice in the Russian Federation" approved by the Order of the Ministry of Health of the Russian Federation No. 266 dated 19.06.2003. All workers were informed about their participation in the molecular-genetic study and gave written consent to carry it out. The research of the dead miners was based on the secondary examination of blocks and ready-made histological micro-preparations of the material of the Bureau for Forensic Medical Expert Examination of the cities of Novokuznetsk, Osinniki, and Prokopyevsk. The study of pathomorphological material was carried out in accordance with the Federal Law of 21.11.2011, No. 323-FZ "On the Fundamentals of Health Protection of Citizens in the Russian Federation", in particular, with Article 67 "Carrying out pathological and anatomical autopsies", Federal Law of 12.01.1996, No. 8-FZ "On burial and funeral business" (Article 5, paragraphs 1, 2), as well as on the basis of the Order of the Ministry of Health of April 29, 1994, No. 82 "On the procedure for conducting pathological and anatomical autopsy" (Annex to the Order of the Ministry of Health and Medical Industry of 29.04.1994 No. 82), the Order of the Ministry of Health of Russia of 24.03.2016. No. 179n "On the rules for conducting pathological and anatomical examinations".
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