Multicomponent coating in purulent wound healing: A randomised controlled experimental study

Background. Purulent wound healing is a pressing surgical challenge relevant in 30−35% of patient cases. To the more, wound infectious agents elaborate resistance to available drugs warranting the development of new drug combinations exserting a multidirectional effect on the wound process.Objective. Using a purulent wound model to experimentally evaluate the efficiency of a new multicomponent wound coating comprised of polyethylene oxide and carboxymethylcellulose sodium-immobilised dioxidine, methyluracil, metronidazole and lidocaine hydrochloride in comparison with a legal approved wound coating drug preparation of beeswax and propolis-based dioxidine ointment.Methods. The antimicrobial activity range (disk-diffusion method) and local anaesthetic effect (Rainier’s method) of the developed wound coating have been assessed. The healing process was studied in a purulent wound model with 72 Wistar rats divided between two equal groups. The following methods were applied: visual wound inspection (wound cleansing time, absence of wound-surrounding tissue oedema, granulation and epithelisation), planimetric parameter estimation (wound area, healing rate, wound area reduction ratio), wound contamination and pH measurement, wound section cell morphometry (granulocyte, macrophage, lymphocyte and fibroblast counts, cell index estimation). Daily dressings were applied for 15 days.Results. The developed wound coating exhibited high efficiency against Gram-positive and Gram-negative bacteria in the zone of inhibition tests. Its local anaesthetic effect was significantly superior to the approved drug by the duration of action. The wound area reduction was 94.2 (93.7; 94.8)% in the experimental group and 86 (84.2; 88.8)% in the control (differences statistically significant) already on day 10. A maximal healing rate in both groups was registered in phase 1 of the wound process being 1.4 times higher in experiment compared to the control. The wound contamination was significantly lower in experiment vs. control on day 8 (p = 0.0075). Wound pH negatively correlated with the fibroblast count and positively — with the contamination level.Conclusion. The study demonstrates high efficiency of the developed wound coating against infectious agents and its positive healing impact via reducing phase 1 and stimulating proliferation in phase 2 of the wound process

High frequency magnetic oscillations of the organic metal θ\theta-(ET)4_4ZnBr4_4(C6_6H4_4Cl2_2) in pulsed magnetic field of up to 81 T

De Haas-van Alphen oscillations of the organic metal $\theta$-(ET)$_4$ZnBr$_4$(C$_6$H$_4$Cl$_2$) are studied in pulsed magnetic fields up to 81 T. The long decay time of the pulse allows determining reliable field-dependent amplitudes of Fourier components with frequencies up to several kiloteslas. The Fourier spectrum is in agreement with the model of a linear chain of coupled orbits. In this model, all the observed frequencies are linear combinations of the frequency linked to the basic orbit $\alpha$ and to the magnetic-breakdown orbit $\beta$.Comment: 6 pages, 4 figure

Quantum oscillations in the linear chain of coupled orbits: the organic metal with two cation layers theta-(ET)(4)CoBr(4)(C(6)H(4)Cl(2))

Analytical formulae for de Haas-van Alphen (dHvA) oscillations in linear chain of coupled two-dimensional (2D) orbits (Pippard's model) are derived systematically taking into account the chemical potential oscillations in magnetic field. Although corrective terms are observed, basic (alpha) and magnetic breakdown-induced (beta and 2beta - alpha) orbits can be accounted for by the Lifshits-Kosevich (LK) and Falicov-Stachowiak semiclassical models in the explored field and temperature ranges. In contrast, the 'forbidden orbit' beta - alpha amplitude is described by a non-LK equation involving a product of two classical orbit amplitudes. Furthermore, strongly non-monotonic field and temperature dependence may be observed for the second harmonics of basic frequencies such as 2alpha and the magnetic breakdown orbit beta + alpha, depending on the value of the spin damping factors. These features are in agreement with the dHvA oscillation spectra of the strongly 2D organic metal theta- theta-(ET)(4)CoBr(4)(C(6)H(4)Cl(2)).Comment: to be published in Europhysics Letters (2012

Многокомпонентное раневое покрытие в лечении экспериментальной гнойной раны

Objectives. To substantiate the effectiveness of the wound coating developed by us, which combines broad-spectrum antimicrobial effect, sorption activity, analgesic effect and prolonged action on a purulent wound.Materials and methods. The material for the study was wound coating in the form of a film developed at Kursk State Medical University (Russian patent number 2605343). Experimental animals (Wistar rats) were divided into 2 groups (comparative and experimental) of 36 animals in each. In all the experimental animals a purulent wound was modeled according to the method proposed by P.I. Tolstikh. Local anesthetic activity was determined on rabbits of the Chinchilla breed (20 individuals in each group). In the course of the study, the following methods were used: microbiological method (identification of the areas of growth retardation and wound contamination), visual assessment of the wounds, planimetric method, pH evaluation of the wounds, and Renier’s technique (for determination of the anesthetic activity). The data were processed statistically, and the statistical significance of the differences was determined using the nonparametric Mann – Whitney test. The differences were considered statistically significant at p ≤ 0.05.Results. Before the experiment on animals, high efficacy of the developed film was proven for the most common test strains of microorganisms capable of causing wound infection, using the microbiological method of investigation. Using the Renier’s method, the ability of the film to provide a local anesthetic effect was demonstrated, which was significantly higher than that of the 2% lidocaine ointment. Following visual evaluation of the wound, it was found that purification and regeneration of the wounds occurred earlier in the animals from the experimental group. The speed of wound healing in the experimental group was 1.3 times higher at 1–3 days, whereas at 5–8 days the situation was reversed in favor of the comparison group. In addition, at day 8 wound contamination in the experimental group was 1.2 times lower than in the comparison group. According to the results of the pH evaluation, significant differences between the groups were noted at days 5, 8, 15. Approximation of pH values to those of intact skin also proved the effectiveness of using the developed film.Conclusion. The results of the conducted studies confirmed broad-spectrum antimicrobial activity of the developed film, its local anesthetic activity and efficacy in treatment of experimental purulent wounds, which allows to recommend it for further preclinical trials. Цель. Обосновать эффективность применения разработанного нами раневого покрытия, которое сочетает в себе противомикробный эффект широкого спектра, сорбционную активность, обезболивающее влияние, пролонгированное действие, на модели гнойной раны в эксперименте.Материалы и методы. Материалом для исследования послужило раневое покрытие в виде пленки, разработанное на базе Курского государственного медицинского университета (патент на изобретение РФ № 2605343). Экспериментальные животные (крысы породы Вистар) были распределены на две группы (сравнения и опытная) по 36 животных в каждой. Всем подопытным животным моделировалась гнойная рана по методике П.И. Толстых. Местно-анестезирующую активность определяли на кроликах породы шиншилла (по 20 особей в каждой группе). В ходе исследования применялись следующие методы: микробиологический (определение зон задержки роста и обсемененности ран), визуальная оценка состояния ран, планиметрический, рН-метрия ран, метод Ренье (для определения анестезирующей активности). Данные обработаны статистически, достоверность отличий определяли по непараметрическому критерию Манна – Уитни. Различия между группами считались статистически значимыми при р ≤ 0,05.Результаты. До начала эксперимента на животных на основании микробиологического метода исследования была показана высокая эффективность разработанной пленки в отношении наиболее распространенных тест-штаммов микроорганизмов, способных вызывать раневую инфекцию. Также на основании метода Ренье показана ее способность оказывать местно-анестезирующее действие, достоверно превосходящее по эффективности 2%-ю лидокаиновую мазь. На основании визуальной оценки раны выявлено, что очищение и регенерация ран наступали раньше у животных в опытной группе. Скорость заживления ран в опытной группе была в 1,3 раза выше на сроке 1–3-и сут, а на 5–8-е сут ситуация была обратной в пользу группы сравнения. Кроме того, обсемененность ран в опытной группе была в 1,2 раза ниже на 8-е сут, нежели в группе сравнения. По результатам рНметрии достоверные различия между группами были отмечены на 5-, 8-, 15-е сут. Приближение значений рН к значениям неповрежденной кожи также доказывала эффективность применения разработанной пленки.Заключение. Результаты проведенных исследований подтвердили широкий спектр противомикробного действия разработанной пленки, ее местно-анестезирующую активность, эффективность при лечении экспериментальных гнойных ран, что позволяет рекомендовать ее для дальнейших доклинических испытаний.

Применение многокомпонентной пленки в лечении ран в эксперименте

Objectives. To optimize treatment of purulent wounds with the help of a wound coating with a multidirectional action that combines broad-spectrum antimicrobial effect, stimulation of regeneration, sorption activity and local anesthetic action. Materials and methods. The material for the study was a wound covering in the form of a film developed by the authors at Kursk State Medical University (Russian patent No. 2601897). Theexperiment was performed on laboratory animals (Wistar rats), which were divided into 2 groups (comparison and experimental), each group containing 36 animals. Purulent wound was modeled in the animals according to the method of P.I. Tolstykh. To evaluate the effectiveness of the treatment, the following methods were used: microbiological method (determination of areas of growth retardation and bacterial contamination in the wounds), Renier’s method (determination of local anesthetic activity), visual assessment of wounds, planimetric method (measurement of the wound area, percentage of area reduction and healing speed) and measurement of pH in the wounds. The statistical significance of the differences was determined with the nonparametric Mann–Whitney test. The differences were considered statistically significant at p ˂ 0.05. Results. Initially, high efficiency of the film was detected in vitro for the most common strains of test organisms, which werewound infection pathogens. The Renier index was 1.2 times higher in the film with chlorhexidine than in 2% lidocaine ointment, and the duration of general anesthesia was 25% longer. Following visual assessment of the wounds we revealed that purification and regeneration of the wounds first occurred in the animals in the experimental group; however, no statistical significance was detected. The maximal differences in the healing speed (1.6 times) were observed at 3–5 days, and the contamination of the wounds was 1.3 times lower in the experimental group than in the comparison group. According to the results of pH assessment, significant differences between the groups were noted only on day 15. Approximation of pH values to intact skin values also proved the effectiveness of treatment. Conclusion. The developed contact wound covering has high antimicrobial activity against a broad spectrum of wound infection pathogens, creates a fairly good local anesthetic effect, significantly speeds up the healing process and reduces bacterial contamination of the wound area. Thus, the developed wound covering can be recommended for further studies in the clinical setting for treatment of inflammatory processes in soft tissues.Цель. Оптимизировать лечение гнойных ран с помощью разработанного раневого покрытия с разнонаправленным действием, которое сочетает в себе противомикробный эффект широкого спектра, стимуляцию регенерации, сорбционную активность, местное анестезирующее действие. Материалы и методы. Материалом для исследования явилось разработанное нами на базе Курского государственного медицинского университета раневое покрытие в виде пленки (патент на изобретение РФ № 2601897). Эксперимент выполнен на лабораторных животных (самцы крыс породы Вистар), которые были разделены на две группы (сравнения и опытная) по 36 животных в каждой. Животным моделировалась гнойная рана по методике П.И. Толстых. Для оценки эффективности лечения применялись следующие методы: микробиологический (определение зон задержки роста и обсемененности ран), Ренье (для определения местной анестезирующей активности), планиметрический (измеряли площадь ран, долю (%) уменьшения площади и скорость заживления). Проводили визуальную оценку состояния ран и их рН-метрию. Статистическую значимость различий определяли по непараметрическому критерию Манна – Уитни. Различия считались достоверными при р ˂ 0,05. Результаты. Изначально в эксперименте in vitro была выявлена высокая эффективность разработанной пленки в отношении наиболее распространенных тест-штаммов микроорганизмов – возбудителей раневой инфекции. Индекс Ренье был в 1,2 раза выше у разработанной пленки с хлоргексидином, чем у 2%-й лидокаиновой мази, а длительность общей анестезии – на 25% дольше. На основании визуальной оценки раны показано, что очищение и регенерация ран наступали раньше у животных в опытной группе, однако статистическая достоверность различий не выявлена. Максимальные различия по скорости заживления в 1,6 раза и отмечены на сроке 3–5-е сут, а обсемененность ран была в 1,3 раза ниже в опытной группе, чем в группе сравнения. По результатам рН-метрии достоверные различия между группами выявлены лишь на 15-е сут. Приближение значений рН к значениям неповрежденной кожи также доказывала эффективность лечения. Заключение. Разработанное нами раневое покрытие обладает высокой противомикробной активностью в отношении широкого спектра возбудителей раневой инфекции, создает достаточно хороший местно-анестезирующий эффект, статистически значимо ускоряет процесс сокращения площади и обсемененности ран. Таким образом, разработанное нами раневое покрытие можно рекомендовать для дальнейших исследований в клинике для лечения гнойно-воспалительных процессов мягких тканей.

Роль нутриентов и пробиотических препаратов в терапии депрессии

Currently, a growing amount of data is emerging on the role of various environmental factors (nutrients, gut microbiota, etc.) on formation of depression. The impact on these factors can be effective not only in treatment of major depressive disorder, but also in its early prevention. Therefore, a more detailed study of environmental factors in depression can lead both to a better understanding of the etiology and pathogenesis of the disorder and to optimization of approaches to its treatment. The aim of the review was to assess the potential role of a number of environmental factors associated with nutritional aspects and characteristics of individual microflora, as well as to review the prospects of a strategy for affecting these factors in treatment and prevention of depression. В настоящее время появляется все больше сведений о роли различных экологических факторов (особенностей питания, бактериальной флоры человека и проч.) в формировании депрессии. Воздействие на указанные факторы может быть эффективно не только в лечении депрессивного расстройства, но и его ранней профилактике. Таким образом, более подробное изучение роли экологических факторов в формировании депрессии может способствовать как лучшему пониманию этиопатогенеза данного заболевания, так и оптимизации подходов по борьбе с ним.Цель обзора: оценить потенциальную роль в формировании депрессии ряда экологических факторов, связанных с нутритивными аспектами и особенностями микрофлоры индивида, а также перспективность стратегии воздействия на данные факторы в лечении и профилактике депрессивного расстройства.

Global Retinoblastoma Presentation and Analysis by National Income Level

Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low- A nd middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI, 4.30-7.68]). Conclusions and Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs

Travel burden and clinical presentation of retinoblastoma: analysis of 1024 patients from 43 African countries and 518 patients from 40 European countries

BACKGROUND: The travel distance from home to a treatment centre, which may impact the stage at diagnosis, has not been investigated for retinoblastoma, the most common childhood eye cancer. We aimed to investigate the travel burden and its impact on clinical presentation in a large sample of patients with retinoblastoma from Africa and Europe. METHODS: A cross-sectional analysis including 518 treatment-naïve patients with retinoblastoma residing in 40 European countries and 1024 treatment-naïve patients with retinoblastoma residing in 43 African countries. RESULTS: Capture rate was 42.2% of expected patients from Africa and 108.8% from Europe. African patients were older (95% CI -12.4 to -5.4, p<0.001), had fewer cases of familial retinoblastoma (95% CI 2.0 to 5.3, p<0.001) and presented with more advanced disease (95% CI 6.0 to 9.8, p<0.001); 43.4% and 15.4% of Africans had extraocular retinoblastoma and distant metastasis at the time of diagnosis, respectively, compared to 2.9% and 1.0% of the Europeans. To reach a retinoblastoma centre, European patients travelled 421.8 km compared to Africans who travelled 185.7 km (p<0.001). On regression analysis, lower-national income level, African residence and older age (p<0.001), but not travel distance (p=0.19), were risk factors for advanced disease. CONCLUSIONS: Fewer than half the expected number of patients with retinoblastoma presented to African referral centres in 2017, suggesting poor awareness or other barriers to access. Despite the relatively shorter distance travelled by African patients, they presented with later-stage disease. Health education about retinoblastoma is needed for carers and health workers in Africa in order to increase capture rate and promote early referral