Advantages and disadvantages of insurance medicine

Insurance medicine is an ideal guarantee mechanism for obtaining high-quality medical care. But it has its drawbacks. Insurance medicine has a big difference between budget financing medicine, namely in the principles of financing. During insurance medicine, the number of places in hospitals is reduced to optimal indicators, but each patient is provided with a high level of treatment. And in terms of budget funding, the state seeks to increase the number of hospitals. After analyzing current events, we can conclude that it is state support that is most effective for overcoming pandemics

Аминокислотные производные природных хлоринов как платформа для создания таргетных фотосенсибилизаторов в онкологии

Objectives. This study aims to obtain the amino acid derivatives of chlorophyll a and bacteriochlorophyll a for the targeted delivery of pigments to tumor foci. This will increase biocompatibility and, as a result, reduce toxic side effects. In addition to photodynamic efficiency, an additional cytotoxic effect is expected for the obtained conjugates of photosensitizers (PSs) with amino acids. This is owing to the participation of the latter in intracellular biochemical processes, including interaction with the components of the glutathione antioxidant system, leading to the vulnerability of tumor cells to oxidative stress.Methods. In this work, we have implemented the optimization of the structure of a highly efficient infrared PS based on O-propyloxim-N-propoxybacteriopurpurinimide (DPBP), absorbing at 800 nm and showing photodynamic efficacy for the treatment of deep-seated and pigmented tumors, by introducing L-lysine, L-arginine, methionine sulfoximine (MSO), and buthionine sulfoximine (BSO) methyl esters. The structure of the obtained compounds was proved by mass spectrometry and nuclear magnetic resonance spectroscopy, and the photoinduced cytotoxicity was studied in vitro on the HeLa cell line.Results. Conjugates of DPBP with amino acids and their derivatives, such as lysine, arginine, MSO, and BSO have been prepared. The chelating ability of DPBP conjugate with lysine was shown, and its Sn(IV) complex was obtained.Conclusions. Biological testing of DPBP with MSO and BSO showed a 5–6-fold increase in photoinduced cytotoxicity compared to the parent DPBP PS. Additionally, a high internalization of pigments by tumor cells was found, and the dark cytotoxicity (in the absence of irradiation) of DPBP-MSO and DPBP-BSO increased fourfold compared to the initial DPBP compound. This can be explained by the participation of methionine derivatives in the biochemical processes of the tumor cell.Цели. Целью настоящей работы является получение аминокислотных производных хлорофилла а и бактериохлорофилла а для направленной доставки пигментов в опухолевые очаги, увеличения биосовместимости и, как следствие, уменьшения побочного токсического действия. Кроме фотодинамической эффективности для полученных конъюгатов фотосенсибилизаторов с аминокислотами ожидается дополнительный цитотоксический эффект, вызванный участием последних во внутриклеточных биохимических процессах, включая взаимодействие с компонентами глутатионовой антиоксидантной системы, приводящее к уязвимости опухолевых клеток к окислительному стрессу.Методы. В настоящей работе реализована оптимизация структуры высокоэффективного ИК-фотосенсибилизатора на основе О-пропилоксим-N-пропоксибактериопурпуринимида (DPBP), поглощающего при 800 нм и показавшего фотодинамическую эффективность для лечения глубокозалегающих и пигментированных опухолей, путем введения на периферию макроцикла метиловых эфиров L-лизина, L-аргинина, метионинсульфоксимина (MSO) и бутионинсульфоксимина (BSO). Структура полученных соединений доказана методами масс-спектрометрии и ЯМР-спектроскопии, а фотоиндуцированная цитотоксичность исследована in vitro на линии клеток HeLa.Результаты. Были получены конъюгаты О-пропилоксим-N-пропоксибактериопурпуринимида с аминокислотами и их производными, такими как, лизин, аргинин, метионинсульфоксимин и бутионинсульфоксимин. Показана хелатирующая способность конъюгата DPBP с лизином и получен его Sn(IV)-комплекс.Выводы. Биологические испытания DPBP с метионинсульфоксимином и бутионинсульфоксимином показали 5–6 кратное увеличение фотоиндуцированной цитотоксичности по сравнению с исходным фотосенсибилизатором DPBP. При этом обнаружена высокая интернализация пигментов опухолевыми клетками, а темновая цитотоксичность (при отсутствии облучения) DPBP-MSO и DPBP-BSO увеличилась в 4 раза по сравнению с исходным соединением DPBP, что может быть объяснено участием производных метионина в биохимических процессах опухолевой клетки

Diquat Derivatives: Highly Active, Two-Dimensional Nonlinear Optical Chromophores with Potential Redox Switchability

In this article, we present a detailed study of structure−activity relationships in diquaternized 2,2′-bipyridyl (diquat) derivatives. Sixteen new chromophores have been synthesized, with variations in the amino electron donor substituents, π-conjugated bridge, and alkyl diquaternizing unit. Our aim is to combine very large, two-dimensional (2D) quadratic nonlinear optical (NLO) responses with reversible redox chemistry. The chromophores have been characterized as their PF_6^− salts by using various techniques including electronic absorption spectroscopy and cyclic voltammetry. Their visible absorption spectra are dominated by intense π → π^* intramolecular charge-transfer (ICT) bands, and all show two reversible diquat-based reductions. First hyperpolarizabilities β have been measured by using hyper-Rayleigh scattering with an 800 nm laser, and Stark spectroscopy of the ICT bands affords estimated static first hyperpolarizabilities β_0. The directly and indirectly derived β values are large and increase with the extent of π-conjugation and electron donor strength. Extending the quaternizing alkyl linkage always increases the ICT energy and decreases the E_(1/2) values for diquat reduction, but a compensating increase in the ICT intensity prevents significant decreases in Stark-based β_0 responses. Nine single-crystal X-ray structures have also been obtained. Time-dependent density functional theory clarifies the molecular electronic/optical properties, and finite field calculations agree with polarized HRS data in that the NLO responses of the disubstituted species are dominated by ‘off-diagonal’ β_(zyy) components. The most significant findings of these studies are: (i) β_0 values as much as 6 times that of the chromophore in the technologically important material (E)-4′-(dimethylamino)-N-methyl-4-stilbazolium tosylate; (ii) reversible electrochemistry that offers potential for redox-switching of optical properties over multiple states; (iii) strongly 2D NLO responses that may be exploited for novel practical applications; (iv) a new polar material, suitable for bulk NLO behavior

Evolution of Linear Absorption and Nonlinear Optical Properties in V-Shaped Ruthenium(II)-Based Chromophores

In this article, we describe a series of complexes with electron-rich cis-{Ru^(II)(NH_3)_4}^(2+) centers coordinated to two pyridyl ligands bearing N-methyl/arylpyridinium electron-acceptor groups. These V-shaped dipolar species are new, extended members of a class of chromophores first reported by us (Coe, B. J. et al. J. Am. Chem. Soc. 2005, 127, 4845−4859). They have been isolated as their PF_6− salts and characterized by using various techniques including ^1H NMR and electronic absorption spectroscopies and cyclic voltammetry. Reversible Ru^(III/II) waves show that the new complexes are potentially redox-switchable chromophores. Single crystal X-ray structures have been obtained for four complex salts; three of these crystallize noncentrosymmetrically, but with the individual molecular dipoles aligned largely antiparallel. Very large molecular first hyperpolarizabilities β have been determined by using hyper-Rayleigh scattering (HRS) with an 800 nm laser and also via Stark (electroabsorption) spectroscopic studies on the intense, visible d → π^* metal-to-ligand charge-transfer (MLCT) and π → π^* intraligand charge-transfer (ILCT) bands. The latter measurements afford total nonresonant β_0 responses as high as ca. 600 × 10^(−30) esu. These pseudo-C_(2v) chromophores show two substantial components of the β tensor, β_(zzz) and β_(zyy), although the relative significance of these varies with the physical method applied. According to HRS, β_(zzz) dominates in all cases, whereas the Stark analyses indicate that β_(zyy) is dominant in the shorter chromophores, but β_(zzz) and β_(zyy) are similar for the extended species. In contrast, finite field calculations predict that β_(zyy) is always the major component. Time-dependent density functional theory calculations predict increasing ILCT character for the nominally MLCT transitions and accompanying blue-shifts of the visible absorptions, as the ligand π-systems are extended. Such unusual behavior has also been observed with related 1D complexes (Coe, B. J. et al. J. Am. Chem. Soc. 2004, 126, 3880−3891)

Солюбилизация гидрофобного фотосенсибилизатора бактериохлоринового ряда в мицеллах поверхностно-активных веществ

The aim of the paper was to obtain a stable micellar emulsion of potent photosensitizer (PS) – O-propyloxime-N-propoxybacteriopurpurinimide methyl ester absorbing light in long-wave region of the spectrum (λmax = 800±2 нм). Solubilizates of the dye based on different surfactants (Kolliphor ELP, Poloxamer 407, Emuxol 268) were obtained. Taking into account the physical and chemical parameters, the most potent micellar emulsion for injection was selected and characterized. The emulsion based on Kolliphor ELP remains stable for 4 months, with no changes in the fluorescence spectrum and absorption, as well as the particle diameter.Целью настоящей работы являлось получение стабильной мицеллярной эмульсии перспективного фотосенсибилизатора (ФС) – метилового эфира О-пропилоксим-N-пропоксибактериопурпуринимида, поглощающего в длинноволновой области спектра (λmax = 800±2 нм). В процессе работы были получены солюбилизаты красителя на основе поверхностно-активных веществ (ПАВ): Kolliphor ELP, Poloxamer 407, Эмуксол 268. По физико-химическим параметрам отобрана и охарактеризована наиболее перспективная мицеллярная эмульсия ФС для парентерального введения. Выбранная эмульсия на основе Kolliphor ELP остается стабильной в течение 4 мес, в течение которых остаются неизменными спектр флуоресценции и поглощения и диаметр мицелл

МОРФОФУНКЦИОНАЛЬНЫЕ ХАРАКТЕРИСТИКИ САРКОМЫ М-1 КРЫС ПОСЛЕ ФОТОДИНАМИЧЕСКОЙ ТЕРАПИИ С ПРОИЗВОДНЫМ БАКТЕРИОХЛОРОФИЛЛА А

The study of the functional morphology of rat sarcoma M-1 after photodynamic therapy using bacteriopurpurinimide disulfide derivative (disulfide-BPI) as a photosensitizer is described. The research methods included immunohistochemistry for PCNA and CD31, evaluation of mitotic activity and apoptosis of tumor cells, as well as computer analysis of microscopic images. Photoinduced antitumor effect was shown to be due to the destruction of sarcoma M-1 vascular bed, the rapid inhibition of proliferative activity and devitalization of tumor cells by apoptosis and necrosis. It is reasonable to suppose that in the early stages after photodynamic therapy destruction of the microvasculature and photocytostatic shock of tumor cells with subsequent development of necrosis are caused by direct influence of the light flux on sensitized cellular elements in parenchyma and stroma of tumors. The efficiency of photodynamic therapy with the novel photosensitizer is determined by the sequence of destructive and inflammatory changes in tumor parenchyma and surrounding tissues, as well as repopulation potential of tumor cells survived after treatment.В работе описаны результаты изучения функциональной морфологии саркомы М-1 крыс после фотодинамической терапии с применением в качестве фотосенсибилизатора дисульфидного производного бактериопурпуринимида (дисульфид-БПИ). Методы исследования включали иммуноокрашивание на PCNA и CD31, определение митотической активности и апоптотической гибели опухолевых клеток, а также компьютерный анализ микроскопических изображений. Показано, что фотоиндуцированное противоопухолевое действие обусловлено разрушением сосудистого русла саркомы М-1, быстрым ингибированием пролиферативной активности и девитализацией опухолевых клеток путем апоптоза и некроза. Есть основания полагать, что в ранние сроки после фотодинамической терапии деструкция микроциркуляторного русла и фотоцитостатический шок опухолевых клеток с последующим развитием некроза обусловлены прямым воздействием светового потока на сенсибилизированные клеточные элементы паренхимы и стромы опухолей. Эффективность фотодинамической терапии с новым фотосенсибилизатором определяется последовательностью деструктивных и воспалительных изменений в паренхиме опухолей и окружающих тканях, а также репопуляционным потенциалом выживших после лечения опухолевых клеток