Эффективность фотодинамической терапии базальноклеточного рака кожи с местным введением радахлорина

The results of evaluation of the efficiency of photodynamic therapy with photosensitizer radachlorine for basal cell carcinoma are represented. The study included patients with primary and recurrent cancer, solitary and multiple foci of different histological subtypes. All tumors corresponded stages T1-2N0M0. The radachlorine solution was injected into pathological focus at dose of 1.75-3.50 mg/ cm2 of tumor 15 min before the onset of irradiation (wavelength of 662 nm, light dose of 300 J/cm2). The evaluation of efficiency by means of short-term and long-term outcomes was performed on the basis of clinical and cytological data. According to shortterm outcomes evaluation, the total tumor regression was in 43 (95,5%) patients for 47 (95,9%) tumors. The partial regression was achieved in 2 (4,5%) patients, who subsequently had one repeated course of photodynamic therapy with short-term outcome as total tumor regression. All patients with multiple, superficial and nodal forms of basal cell carcinoma had total tumor regression in 100% of cases, with ulcerated form – in 94,4%, with morphea-like form – in 83,3%. During follow-up in subjects, 44 (97,7%) patients had 5-year recurrence-free period. The relapse of tumor was detected in 1 (2,3%) patient after PDT for primary cancer of nasal ala stage Т2N0M0 of solid and adenoid histological subtype. Thus, photodynamic therapy with intralesional injection of radachlorine showed high efficiency for treating all existent clinical forms and histological subtypes of basal cell carcinoma. В работе представлены результаты оценки эффективности фотодинамической терапии базальноклеточного рака кожи с фотосенсибилизатором радахлорин. В исследование были включены пациенты с первичным и рецидивным раком, с солитарными или множественными очагами различного гистологического подтипа. Все опухоли были в стадии Т1-2N0M0. Раствор радахлорина вводили инъекционно внутрь патологического очага в дозе 1,75–3,50 мг/см2 опухоли за 15 мин до начала облучения (длина волны облучения 662 нм, световая доза 300 Дж/см2). Оценку эффективности непосредственных и отдаленных результатов осуществляли на основании клинических и цитологических данных. При оценке непосредственных результатов лечения полная регрессия установлена у 43 (95,5%) больных в отношении 47 (95,9%) опухолей. Частичная регрессия получена у 2 (4,5%) больных, которым впослед- ствии было проведено по одному повторному курсу фотодинамической терапии, после чего непосредственный результат лечения был оценен, как полная регрессия. У всех больных с множественной, поверхностной и нодулярными формами базальноклеточного рака полная регрессия новообразований отмечена в 100% случаев, с язвенной формой – в 94,4%, склеродермоподобной формой – в 83,3%. При динамическом наблюдении за пациентами, участвовавшими в исследовании, у 44 (97,7%) больных зарегистрирован 5-летний безрецидивный период. Рецидив опухоли выявлен у 1 (2,3%) пациента после ФДТ первичного рака кожи крыла носа стадии Т2N0M0 солидно-аденоидного гистологического подтипа. Таким образом, фотодинамическая терапия с внутриочаговым применением радахлорина показала высокую эффективность в лечении всех существующих клинических форм и гистологических подтипов базальноклеточного рака кожи.

Внутриочаговое введение фотолона при фотодинамической терапии базальноклеточного рака кожи

The new method of photodynamic therapy for basal cell skin carcinoma with intralesional injection of photolon (at dose of 1.44-2.50 mg/cm3 of tumor volume 15 min before irradiation) was developed in the department of dermatology, venerology and dermatooncology in The State Budgetary Healthcare Institution of Moscow Area Moscows regional research clinical institute n.a. M.F. Vladimirskiy. The efficacy of the developed method was evaluated in clinical studies in 30 patients comparing with the group of 32 patients who had conventional PDT with typical intravenous injection of photolon (at dose of 2.0–2.5 mg/kg of body weight 3 h before irradiation). The characteristics of irradiation were the same both in the study and in the control groups: power density of 0.31-0.47 W/cm2, light dose of 300 J/cm2. Compared PDT regimens had similar efficiency. As a result of the performed treatment complete tumor regression was achieved in 93.3% patients with intralesional injection of photolon and in 90.6% patients with intravenous injection. The rate of patients with 2-year recurrence-free survival after intralesional injection of photolon accounted for 96.7%; after intravenous injection – 93.8%. However, the developed method demonstrated superior safety comparing with intravenous injection of photolon: such as there was no need for light regimen after intralesional injection of photolon, there were no cases of skin phototoxicity (12.5% for intravenous injection), no increasing of transaminases (37.5% for intravenous injection).В отделении дерматовенерологии и дерматоонкологии ГБУЗ МО «Московский областной научно-исследовательский клинический институт им. М.Ф. Владимирского» была разработана новая методика фотодинамической терапии базальноклеточного рака кожи с внутриочаговым введением препарата фотолон (в дозе 1,44–2,50 мг/см3 объема опухоли за 15 мин до облучения). Эффективность разработанной методики была оценена в клинических исследованиях на 30 пациентах в сравнении с группой из 32 больных, которым проводили ФДТ с традиционным внутривенным введением фотолона (в дозе 2,0–2,5 мг/кг веса пациента за 3 ч до облучения). Параметры облучения основной и контрольной групп совпадали: плотность мощности 0,31–0,47 Вт/см2, плотность энергии 300 Дж/см2. Сравниваемые режимы ФДТ показали близкую эффективность. В результате проведенного лечения полная регрессия опухолевого очага была достигнута у 93,3% больных при внутриочаговом введении фотолона и у 90,6% больных при внутривенном введении. Доля пациентов, достигших 2-летнего безрецидивного периода после внутриочагового введения фотолона, составила 96,7%; после внутривенного введения – 93,8%. В то же время разработанная методика показала преимущество по безопасности по сравнению с внутривенным введением фотолона: в том числе после внутриочагового введения фотолона не требовалось соблюдения светового режима, не было отмечено случаев кожной фототоксичности (12,5% при внутривенном введении), повышения трансаминаз (37,5% при внутривенном введении)

Effect of temperature, relative humidity and aphid developmental stage on the efficacy of the mycoinsecticide Mycotal® against Myzus persicae

The green peach aphid, Myzus persicae, is a major pest worldwide. An examination of the impact of temperature, relative humidity and developmental stages of M. persicae on the efficacy of the whitefly mycoinsecticide Mycotal®, based on Lecanicillium muscarium and the effects of infection on aphid fecundity was evaluated under controlled conditions. Although this fungus can be grown at a broad range of temperatures (15-30oC), the optimum temperature for control of M. persicae ranged between 20 and 30oC. L. muscarium had high efficacy as a microbial control against M. persicae between 55 and 90% relative humidity. Total mortality of aphids treated with different spore dosages of L. muscarium varied according to the developmental stage: adults, fourth and third instar nymphs of proved more susceptible than first instar nymphs. Although the fungus did not affect the rate of nymph production, the reproductive period of aphids significantly decreased with increasing the spore dosage. Thus, total fecundity of treated aphids was 22.6 ± 1.1 and 31.6 ± 2.4 offspring per adult at the medium (644 ± viable spore/mm2) and low (330 ± 40 viable spore/mm2) dosages, compared with 45.7 ± 4.3 offspring per untreated aphid. The results suggest that L. muscarium has the potential as a biological control agent of M. persicae. However, fungal infection appears to have no sub-lethal effects on the fitness of the host’s progeny

Прогнозирование степени перегрузки правых камер сердца у пациентов с острой массивной тромбоэмболией легочной артерии на основании результатов КТ-диагностики

The study group included 147 patients at the stage of preparation for emergency surgical treatment of acute massive PE in the period from March 2012 to December 2019 inclusive. As CT indicators of overload of the right chambers of the heart, the usual CT indicators that do not require the use of expert – class computed tomographs were taken – they were the superior vena cava, inferior vena cava, unpaired vein; reflux of the contrast drug into the inferior vena cava; reflux of the contrast drug into the hepatic veins. In the course of the study, a comparative analysis of the average pressure in the pulmonary artery with the above CT indicators was performed. The most stable statistical relationship with the indicators of mean pressure in the pulmonary artery was demonstrated by CT parameters – the diameter of the unpaired vein and the reflux of the contrast agent into the hepatic veins. Based on the results of the work, a method for calculating the actual values of the average pressure in the pulmonary artery based on the CT parameter of the diameter of the unpaired vein is proposed.В группу исследования вошло 147 пациентов на этапе подготовки к экстренному хирургическому лечению острой массивной тромбоэмболии легочной артерии (ТЭЛА) в период с марта 2012 г. по декабрь 2019 г. включительно. В качестве КТ-показателей перегрузки правых камер сердца взяты обычные КТ-показатели, не требующие использования компьютерных томографов экспертного класса, ими стали верхняя полая вена, нижняя полая вена, непарная вена; рефлюкс контрастного препарата в нижнюю полую вену; рефлюкс контрастного препарата в печеночные вены. В ходе исследования проведен сравнительный анализ среднего давления в легочной артерии с вышеуказанными КТ-показателями. Наиболее устойчивую статистическую взаимосвязь с показателями среднего давления в легочной артерии продемонстрировали КТ-параметры – диаметр непарной вены и рефлюкс контрастного препарата в печеночные вены. По результатам работы предложена методика расчета фактических значений среднего давления в легочной артерии на основании КТ-параметра “диаметр непарной вены”

Carbonization and Regeneration of Mo/ZSM-5 Catalysts for Methane Dehydroaromatization

The character of carbonaceous deposits formed during methane dehydroaromatization reaction in the presence of Mo/ZSM-5 catalysts was studied by differential thermal analysis. The dependence of the concentration and condensation degree (C/H ratio) of the carbonaceous deposits on the catalyst synthesis conditions (Mo content = 1-10%, Si/Al ratio in the initial H-ZSM-5 = 17-45) and reaction conditions (feed flow rate = 405-1620 h-1, methane concentration = 90-98%, reaction temperature = 720-780 °C) was investigated. The oxidative treatment conditions of carbonized Mo/ZSM-5 catalysts providing stable operation of the catalysts under multiple reaction-oxidative treatment cycles were selected

Cystatin C Deficiency Promotes Epidermal Dysplasia in K14-HPV16 Transgenic Mice

Cysteine protease cathepsins are important in extracellular matrix protein degradation, cell apoptosis, and angiogenesis. Mice lacking cathepsins are protected from tumor progression in several animal models, suggesting that the regulation of cathepsin activities controls the growth of various malignant tumors.We tested the role of cathepsins using a mouse model of multistage epithelial carcinogenesis, in which the human keratin-14 promoter/enhancer drove the expression of human papillomavirus type 16 (HPV16) early region E6/E7 transgenes. During the progression of premalignant dysplasia, we observed increased expression of cysteine protease cathepsin S, but concomitantly reduced expression of cathepsin endogenous inhibitor cystatin C in the skin tissue extract. Absence of cystatin C in these transgenic mice resulted in more progression of dysplasia to carcinoma in situ on the face, ear, chest, and tail. Chest and ear skin extract real time PCR and immunoblot analysis, mouse serum sample ELISA, tissue immunohistological analysis, and tissue extract-mediated in vitro elastinolysis and collagenolysis assays demonstrated that cystatin C deficiency significantly increased cathepsin expression and activity. In skin from both the chest and ear, we found that the absence of cystatin C reduced epithelial cell apoptosis but increased proliferation. From the same tissue preparations, we detected significantly higher levels of pro-angiogenic laminin 5-derived γ2 peptides and concurrently increased neovascularization in cystatin C-deficient mice, compared to those from wild-type control mice.Enhanced cathepsin expression and activity in cystatin C-deficient mice contributed to the progression of dysplasia by altering premalignant tissue epithelial proliferation, apoptosis, and neovascularization

Scientific, institutional and personal rivalries among Soviet geographers in the late Stalin era

Scientific, institutional and personal rivalries between three key centres of geographical research and scholarship (the Academy of Sciences Institute of Geography and the Faculties of Geography at Moscow and Leningrad State Universities) are surveyed for the period from 1945 to the early 1950s. It is argued that the debates and rivalries between members of the three institutions appear to have been motivated by a variety of scientific, ideological, institutional and personal factors, but that genuine scientific disagreements were at least as important as political and ideological factors in influencing the course of the debates and in determining their final outcome

Assessment of proteolytic degradation of the basement membrane: a fragment of type IV collagen as a biochemical marker for liver fibrosis

<p>Abstract</p> <p>Background</p> <p>Collagen deposition and an altered matrix metalloproteinase (MMP) expression profile are hallmarks of fibrosis. Type IV collagen is the most abundant structural basement membrane component of tissue, which increases 14-fold during fibrogenesis in the liver. Proteolytic degradation of collagens by proteases produces small fragments, so-called neoepitopes, which are released systemically. Technologies investigating MMP-generated fragments of collagens may provide more useful information than traditional serological assays that crudely measure total protein. In the present study, we developed an ELISA for the quantification of a neoepitope generated by MMP degradation of type IV collagen and evaluated the association of this neoepitope with liver fibrosis in two animal models.</p> <p>Methods</p> <p>Type IV collagen was degraded <it>in vitro </it>by a variety of proteases. Mass spectrometric analysis revealed more than 200 different degradation fragments. A specific peptide sequence, 1438'GTPSVDHGFL'1447 (CO4-MMP), in the α1 chain of type IV collagen generated by MMP-9 was selected for ELISA development. ELISA was used to determine serum levels of the CO4-MMP neoepitope in two rat models of liver fibrosis: inhalation of carbon tetrachloride (CCl₄) and bile duct ligation (BDL). The levels were correlated to histological findings using Sirius red staining.</p> <p>Results</p> <p>A technically robust assay was produced that is specific to the type IV degradation fragment, GTPSVDHGFL. CO4-MMP serum levels increased significantly in all BDL groups compared to baseline, with a maximum increase of 248% seen two weeks after BDL. There were no changes in CO4-MMP levels in sham-operated rats. In the CCl₄model, levels of CO4-MMP were significantly elevated at weeks 12, 16 and 20 compared to baseline levels, with a maximum increase of 88% after 20 weeks. CO4-MMP levels correlated to Sirius red staining results.</p> <p>Conclusion</p> <p>This ELISA is the first assay developed for assessment of proteolytic degraded type IV collagen, which, by enabling quantification of basement membrane degradation, could be relevant in investigating various fibrogenic pathologies. The CO4-MMP degradation fragment was highly associated with liver fibrosis in the two animal models studied.</p

Дифференциальная диагностика токсического эпидермального некролиза (синдрома Лайелла) в ОРИТ: клинические наблюдения

Toxic epidermal necrolysis (TEN) is a critical life-threating condition developing as the total detachment of epidermidis and characterized by severe pathological reactions of all body systems. The current article describes two cases of TEN with similar clinical and laboratory signs. In one case the diagnosis of TEN was subsequently refused.The objective: analysis of methods of clinical and differential diagnostics of conditions accompanied with massive epidermidis detachment in ICU patients.Results. The immunomorphological evaluation of skin specimen obtained from the patient with a torpid form of TEN showed linear IgG fixation in the intercellular space of stratum basale, stratum spinosum and stratum granulosum and C3 fixation in the intercellular space of stratum basale.Conclusion. The complex of anamnesis data and pathomorphological evaluation of skin are crucial for the diagnosis and treatment of patients with atypical TEN.Токсический эпидермальный некролиз (ТЭН) – критическое жизнеугрожающее состояние, развивающееся в виде тотального отслоения эпидермиса и характеризующееся тяжелыми реакциями со стороны всех систем организма. Приведено описание двух клинических случаев со сходной клинико-лабораторной симптоматикой, в одном из которых диагноз ТЭН впоследствии был опровергнут.Цель: анализ методов клинической и лабораторной дифференциальной диагностики состояний, сопровождающихся массивной отслойкой эпидермиса, у пациентов, пребывающих в ОРИТ.Результаты. При иммуноморфологическом исследовании биоптата кожи, полученного от пациентки с торпидным течением ТЭН, обнаружена четкая линейная фиксация IgG в межклеточной связывающей субстанции (МСС) базального, шиповатого и зернистого слоев эпидермиса, а также фиксация С3-компонента комплемента в МСС базального слоя эпидермиса.Заключение. Совокупность анамнестических сведений и результатов патоморфологического исследования методом прямой иммунофлюоресценции имеет критически важное значение для установления диагноза и выбора лечебной тактики у пациентов с атипичным течением ТЭН

Cathepsin K Null Mice Show Reduced Adiposity during the Rapid Accumulation of Fat Stores

Growing evidences indicate that proteases are implicated in adipogenesis and in the onset of obesity. We previously reported that the cysteine protease cathepsin K (ctsk) is overexpressed in the white adipose tissue (WAT) of obese individuals. We herein characterized the WAT and the metabolic phenotype of ctsk deficient animals (ctsk−/−). When the growth rate of ctsk−/− was compared to that of the wild type animals (WT), we could establish a time window (5–8 weeks of age) within which ctsk−/−display significantly lower body weight and WAT size as compared to WT. Such a difference was not observable in older mice. Upon treatment with high fat diet (HFD) for 12 weeks ctsk−/− gained significantly less weight than WT and showed reduced brown adipose tissue, liver mass and a lower percentage of body fat. Plasma triglycerides, cholesterol and leptin were significantly lower in HFD-fed-ctsk−/− as compared to HFD-fed WT animals. Adipocyte lipolysis rates were increased in both young and HFD-fed-ctsk−/−, as compared to WT. Carnitine palmitoyl transferase-1 activity, was higher in mitochondria isolated from the WAT of HFD treated ctsk−/− as compared to WT. Together, these data indicate that ctsk ablation in mice results in reduced body fat content under conditions requiring a rapid accumulation of fat stores. This observation could be partly explained by an increased release and/or utilization of FFA and by an augmented ratio of lipolysis/lipogenesis. These results also demonstrate that under a HFD, ctsk deficiency confers a partial resistance to the development of dyslipidemia