МЕТОДИЧЕСКИЕ АСПЕКТЫ ПРОВЕДЕНИЯ ФОТОДИНАМИЧЕСКОЙ ТЕРАПИИ СОЛИДНОЙ КАРЦИНОМЫ ЭРЛИХА У МЫШЕЙ ЛИНИИ BALB/C С РАЗЛИЧНОЙ ЛОКАЛИЗАЦИЕЙ ОПУХОЛИ

Background. Photodynamic Therapy is one of the treatment methods used in modern oncology. Evaluation of the efficacy in vivo of photosensitizers on tumor models is generally accepted, but the photodynamic  therapy technique in mice is not without drawbacks.The purpose of the study was evaluation of the efficacy of photodynamic therapy in mice with Ehrlich tumor model after subcutaneous and intracutaneous injection of tumor cells.Material and Methods. The study was conducted on BAL B/C mice of both sexes. Fotoditazin® and Radachlorin® were used as photosensitizers. For photoactivation, the Alod laser apparatus with a wavelength of 662 nm was used.Results. A comparison of photodynamic therapy with subcutaneous and intracutaneous localization of Ehrlich tumor was performed. It was shown that depending on the location and depth of inoculation of Ehrlich tumor, the pharmacokinetics (both the fluorescence intensity over time and the contrast ratio of the tumor/surrounding tissue) and pharmacodynamics (tumor growth inhibition, survival) of photosensitizers are significantly different. Higher contrast of the tumor/surrounding tissue is observed with intracutaneous localization of the tumor.Conclusion. A model with intracutaneous localization of Ehrlich tumor can be recommended for a primary assessment of efficacy; it allows the use of fewer animals in the experiment. When planning experiments to study photosensitizers and evaluating their results, the advantages and disadvantages of different methods for modeling tumors in mice should be taken into account.Введение. Фотодинамическая терапия – один из методов лечения, применяемых в  современной онкологии. Оценка эффективности фотосенсибилизаторов in vivo на  моделях опухолей является общепринятой, однако методика проведения  фотодинамической терапии у мышей не лишена недостатков. Цель исследования – оценить эффективность фотодинамической терапии у мышей на модели опухоли Эрлиха при подкожной и внутрикожной инъекции опухолевых клеток. Материал и методы. Исследование проведено на мышах BalB/c обоего пола. В качестве фотосенсибилизаторов использовали препараты Фотодитазин и Радахлорин.  Для фотоактивации применяли лазерный аппарат Алод с длиной волны 662 нм. Результаты. Проведено сравнение фотодинамической терапии при подкожной и внутрикожной локализации опухоли Эрлиха. Показано, что в зависимости от  локализации и глубины инъекции опухоли Эрлиха в значительной степени различаются фармакокинетика (как интенсивность флуоресценции во времени, так и контрастность по отношению опухоль/окружающие ткани) и фармакодинамика (торможение роста  опухоли, выживаемость животных) фотосенсибилизаторов. Большая контрастность опухоль/окружающие ткани наблюдается при внутрикожной локализации опухоли. Заключение. Модель с внутрикожной локализацией опухоли Эрлиха может быть рекомендована для первичной оценки эффективности и позволяет использовать меньшее число животных в эксперименте. При планировании экспериментов по изучению фотосенсибилизаторов и оценке их результатов должны учитываться преимущества и недостатки разных способов моделирования опухоли у мышей. 

Эффективность и безопасность препарата нарлапревир при хроническом гепатите С в реальной клинической практике

Objective: to analyze the efficacy and safety of using direct antiviral action drug narlaprevir/ritonavir in combination with the prolonged alpha-interferon and ribavirin drugs in the conditions of day-time hospitals of St. Petersburg and. Novgorod.Materials and methods: The study included. 35 patients with CHC of the 1st genotype. For treating these patients, a three-component regimen was used, which included the use of narlaprevir/ritonavir in combination, with peg-interferon and ribavirin.Results: among all patients included, in the study, a sustained, virological response was noted, in 85,7%. Early virological response was observed, in 91,3% cases. The recurrence rate was observed, in 10% patients. In 3 patients, therapy was interrupted, for the following reasons: due to inefficiency, the development of serious adverse events, and on its own initiative.Conclusion: the data obtained, demonstrate high, virological and. clinical efficacy and. safety of narlaprevir in combination with peg-interferon and ribavirin, in the treatment of chronic viral hepatitis C.Цель: проанализировать эффективность и безопасность применения препарата прямого противовирусного действия нарлапревира в сочетании c ритонавиром и препаратами пролонгированного альфа-интерферона и рибавирина в условиях дневных стационаров Санкт-Петербурга и Великого Новгорода.Материалы, и методы: в исследование были включены. 35 пациентов с хроническим, гепатитом. С (ХГС) 1 генотипа. Для терапии данных больных применялась схема лечения, включавшая нарлапревир в сочетании с ритонавиром., пег-интерфероном и рибавирином.Результаты: устойчивый вирусологический ответ, через 24 недели после окончания терапии (УВО 24) был отмечен у 85,7% пациентов, при этом, вирусологический ответ, на момент окончания терапии составил 91,4%. У 3 пациентов терапия была прервана по следующим, причинам: в связи с неэффективностью, развитием, нежелательных явлений. У 2 пациентов развился рецидив.Заключение: полученные данные демонстрируют высокую эффективность и безопасность препарата нарлапревир при терапии ХГС в комбинации с ритонавиром, пегилированным интерфероном и рибавирином. в условиях рутинной клинической практики

METHODOLOGICAL ASPECTS OF PHOTODYNAMIC THERAPY OF EHRLICH SOLID CARCINOMA IN BALB/C MOUSE STRAIN WITH VARIOUS TUMOR LOCALIZATION

Background. Photodynamic Therapy is one of the treatment methods used in modern oncology. Evaluation of the efficacy in vivo of photosensitizers on tumor models is generally accepted, but the photodynamic  therapy technique in mice is not without drawbacks.The purpose of the study was evaluation of the efficacy of photodynamic therapy in mice with Ehrlich tumor model after subcutaneous and intracutaneous injection of tumor cells.Material and Methods. The study was conducted on BAL B/C mice of both sexes. Fotoditazin® and Radachlorin® were used as photosensitizers. For photoactivation, the Alod laser apparatus with a wavelength of 662 nm was used.Results. A comparison of photodynamic therapy with subcutaneous and intracutaneous localization of Ehrlich tumor was performed. It was shown that depending on the location and depth of inoculation of Ehrlich tumor, the pharmacokinetics (both the fluorescence intensity over time and the contrast ratio of the tumor/surrounding tissue) and pharmacodynamics (tumor growth inhibition, survival) of photosensitizers are significantly different. Higher contrast of the tumor/surrounding tissue is observed with intracutaneous localization of the tumor.Conclusion. A model with intracutaneous localization of Ehrlich tumor can be recommended for a primary assessment of efficacy; it allows the use of fewer animals in the experiment. When planning experiments to study photosensitizers and evaluating their results, the advantages and disadvantages of different methods for modeling tumors in mice should be taken into account

Effectiveness and safety of narlaprevir in real clinical practice of chronic hepatitis C

Objective: to analyze the efficacy and safety of using direct antiviral action drug narlaprevir/ritonavir in combination with the prolonged alpha-interferon and ribavirin drugs in the conditions of day-time hospitals of St. Petersburg and. Novgorod.Materials and methods: The study included. 35 patients with CHC of the 1st genotype. For treating these patients, a three-component regimen was used, which included the use of narlaprevir/ritonavir in combination, with peg-interferon and ribavirin.Results: among all patients included, in the study, a sustained, virological response was noted, in 85,7%. Early virological response was observed, in 91,3% cases. The recurrence rate was observed, in 10% patients. In 3 patients, therapy was interrupted, for the following reasons: due to inefficiency, the development of serious adverse events, and on its own initiative.Conclusion: the data obtained, demonstrate high, virological and. clinical efficacy and. safety of narlaprevir in combination with peg-interferon and ribavirin, in the treatment of chronic viral hepatitis C

Facile MoS<inf>2</inf> growth on reduced graphene-oxide via liquid phase method

Single and few-layers MoS2 were uniformly grown on the surface of chemically reduced graphene oxide (r-GO), via a facile liquid phase approach. The method is based on a simple functionalization of r-GO with oleyl amine which seems to affect significantly the MoS2 way of growth. Scanning-transmission-electron microscopy (STEM) analysis revealed the presence of single-layer MoS2 on the surface of a few-layers r-GO. This result was also confirmed by atomic-force microscopy (AFM) images. X-ray photoemission spectroscopy (XPS) and Raman spectroscopy were used for in-depth structural characterization. Furthermore, we have successfully applied the method to synthesize MoS2 nanocomposites with multi wall carbon nanotubes (CN) and carbon nanofibers (CNF). The results demonstrate clearly the selective MoS2 growth on both carbon-based supports

AI-Human Hybrid Workflow Enhances Teleophthalmology for the Detection of Diabetic Retinopathy

Objective: Detection of diabetic retinopathy (DR) outside of specialized eye care settings is an important means of access to vision-preserving health maintenance. Remote interpretation of fundus photographs acquired in a primary care or other nonophthalmic setting in a store-and-forward manner is a predominant paradigm of teleophthalmology screening programs. Artificial intelligence (AI)-based image interpretation offers an alternative means of DR detection. IDx-DR (Digital Diagnostics Inc) is a Food and Drug Administration-authorized autonomous testing device for DR. We evaluated the diagnostic performance of IDx-DR compared with human-based teleophthalmology over 2 and a half years. Additionally, we evaluated an AI-human hybrid workflow that combines AI-system evaluation with human expert-based assessment for referable cases. Design: Prospective cohort study and retrospective analysis. Participants: Diabetic patients ≥ 18 years old without a prior DR diagnosis or DR examination in the past year presenting for routine DR screening in a primary care clinic. Methods: Macula-centered and optic nerve-centered fundus photographs were evaluated by an AI algorithm followed by consensus-based overreading by retina specialists at the Stanford Ophthalmic Reading Center. Detection of more-than-mild diabetic retinopathy (MTMDR) was compared with in-person examination by a retina specialist. Main Outcome Measures: Sensitivity, specificity, accuracy, positive predictive value, and gradability achieved by the AI algorithm and retina specialists. Results: The AI algorithm had higher sensitivity (95.5% sensitivity; 95% confidence interval [CI], 86.7%–100%) but lower specificity (60.3% specificity; 95% CI, 47.7%–72.9%) for detection of MTMDR compared with remote image interpretation by retina specialists (69.5% sensitivity; 95% CI, 50.7%–88.3%; 96.9% specificity; 95% CI, 93.5%–100%). Gradability of encounters was also lower for the AI algorithm (62.5%) compared with retina specialists (93.1%). A 2-step AI-human hybrid workflow in which the AI algorithm initially rendered an assessment followed by overread by a retina specialist of MTMDR-positive encounters resulted in a sensitivity of 95.5% (95% CI, 86.7%–100%) and a specificity of 98.2% (95% CI, 94.6%–100%). Similarly, a 2-step overread by retina specialists of AI-ungradable encounters improved gradability from 63.5% to 95.6% of encounters. Conclusions: Implementation of an AI-human hybrid teleophthalmology workflow may both decrease reliance on human specialist effort and improve diagnostic accuracy. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references