The Key Events Dose-Response Framework: A Foundation for Examining Variability in Elicitation Thresholds for Food Allergens

Food allergies are caused by immunological reactions in individuals sensitized to normal protein components of foods. For any given sensitized individual, the severity of a reaction is generally assumed to be proportional to the dose of allergenic protein. There is substantial clinical evidence that “threshold” doses exist for the elicitation of an allergic reaction; however, the threshold (i.e., lowest dose that elicits a reaction) varies substantially across the sensitized population. Current approaches to protecting sensitized individuals from exposure to food allergens are highly qualitative (i.e., they rely on food avoidance). The Key Events Dose-Response Framework is an analytical approach for refining understanding of the biological basis of the dose-response. Application of this approach to food allergy provides a foundation for a more rigorous quantitative understanding of variability in allergic response. This study reviews the allergic disease process and the current approaches to identifying thresholds for food allergens. The pathway of key biological events occurring between food intake and allergic response is considered, along with factors that may determine the nature and severity of response to food allergens. Data needs, as well as implications for identifying thresholds, and for characterizing variability in thresholds, are also discussed

ПЕРВЫЙ КЛИНИЧЕСКИЙ ОПЫТ ПРИМЕНЕНИЯ КОЛОНОК ДЛЯ ЛПС-АДСОРБЦИИ «ТОКСИПАК» В ЛЕЧЕНИИ ПАЦИЕНТОВ С СЕПСИСОМ

Endotoxicosis is one of the main factors of the pathogenesis of multiple organic dysfunctions in gram-negative sepsis, induced by the accumulation of lipopolysaccharides - wall components of gram-negative bacteria. In vitro removal of them (LPS-adsorption) promotes better treatment outcomes in sepsis patients. Development and introduction of the Russian tools for LPS-adsorption becomes more crucial. Objective: to evaluate the efficiency and safety of the column of Toxipak for endotoxin removal, manufactured by POCARD Ltd. Materials and methods: 7 adult sepsis patients who had LPS-adsorption were included into the study. The changes of the following parameters were monitored in the patients: temperature, pulse, arterial pressure, respiration rate, central venous pressure, oxygen saturation, hourly rate of diuresis, oxygenation index was calculated, hematologic and biochemical blood parameters were tested as well as coagulation system rates, endotoxin level, C-reactive protein (CRP), procalcitonin, and interleukins (IL) 1, 6, 8. Criteria of the system inflammatory response and SOFA score were used for the comprehensive evaluation of clinical status. The adverse events, duration of stay in the intensive care ward and 18- and 24-day mortality were followed up during manipulations. Results: the studied column provided no negative effect on the cellular and biochemical composition, main parameters of clotting system and acid-base balance of blood. Its use resulted in the reduction of endotoxin (LPS) (by 64%), CRP (by 14%), IL-1 (by 38%) in blood, increase of oxygenation index, and renal function improvement. LPS adsorption promoted the reduction of clinical and laboratory signs of system inflammatory response, and severity of organ dysfunction (from 6.0 to 3.0 as per SOFA score) in patients with sepsis and septic shock. Conclusion: Toxipak column is safe and efficient for removal of endotoxins from blood. Одним из основных факторов патогенеза множественной органной дисфункции при грамотрицательном сепсисе является эндотоксикоз, обусловленный накоплением липополисахаридов – компонентов стенки грамотрицательных бактерий. Их экстракорпоральное удаление (ЛПС-адсорбция) способствует улучшению результатов лечения пациентов с сепсисом. Разработка и внедрение в практику отечественных устройств для ЛПС-адсорбции является актуальной задачей. Цель: провести оценку эффективности и безопасности колонок «Токсипак» для удаления эндотоксинов производства ЗАО НПФ «ПОКАРД». Материал и методы: в исследование включено 7 взрослых пациентов с сепсисом, которым выполнено 10 ЛПС-адсорбций. У пациентов в динамике измеряли температуру тела, пульс, артериальное давление, частоту дыхания, центральное венозное давление, сатурацию кислорода, почасовой темп диуреза, рассчитывали индекс оксигенации, в крови определяли гематологические и биохимические показатели, показатели системы свертывания, уровень эндотоксина, С-реактивного белка (СРБ), прокальцитонина, интерлейкинов (ИЛ) 1, 6, 8. Для интегральной оценки клинического статуса использовали критерии системной воспалительной реакции и шкалу SOFA. Оценивали нежелательные явления в ходе проведения процедур, длительность пребывания в отделении реанимации и интенсивной терапии, 14- и 28-дневную летальность. Результаты: изученные колонки не оказывали отрицательного влияния на клеточный и биохимический состав крови, основные показатели системы свертывания и кислотно-основное состояние крови. В результате их использования в крови достоверно уменьшилась концентрация эндотоксинов (ЛПС) (на 64%), СРБ (на 14%) и ИЛ-1 (на 38%), повысился индекс оксигенации, улучшилась функция почек. ЛПС-адсорбция способствовала ослаблению клинических и лабораторных проявлений системной воспалительной реакции, снижению выраженности органной дисфункции (с 6,0 до 3,0 баллов по шкале SOFA) у пациентов с сепсисом и септическим шоком. Вывод: колонки «Токсипак» эффективно удаляют из крови эндотоксины и являются безопасными.

Сравнение эффектов селективной плазмофильтрации, плазмодиафильтрации с системами MARS и Prometheus при лечении печеночной недостаточности

The mortality of patients with hepatic failure remains high. Often the patient's life can be saved only with extracorporeal liver support (ELS). ELS systems – MARS® и Prometheus® have proved their efficacy but their widespread use is constrained by their very high cost. Introduction in clinical practice of new affordable ELS systems is a topical issue. The objective: to compare clinical and laboratory effects of selective plasma exchange (SPE), plasmadialfiltration (PDF) with use of the selective membrane plasma separators EvaclioTM and MARS® and Prometheus® (FPSA) systems in the treatment of liver failure. Subjects and methods: 15 extracorporeal procedures of each type were performed in 52 patients with acute liver failure (14) and acute-on-chronic liver failure (38): MARS, FPSA, PDF, SPE with use of Evaclio ЕС-2C, and ЕС-3C, ЕС-4C. The clinical and laboratory parameters (total, direct and indirect bilirubin, total protein, albumin, creatinine, urea, etc.), severity of the condition according to MELD score were determined before and after the session and the next morning. Changes, side effects and complications of procedures were assessed and compared. Results. Reduction of concentration of direct bilirubin was comparable with FPSA, PDF and SPE on Evaclio ЕС-3C20 и ЕС-4C20 (38-42%), indirect bilirubin – with PDF and SPE on Evaclio ЕС-3C20 и ЕС-4C20 (29-34%). Low-molecular metabolites (urea, creatinine) were better removed with FPSA (35-44%) and PDF (40-42%). The reduction of their concentration with SPE was insignificant. The reduction of albumin level was the highest with FPSA (10.2%) and SPE on Evaclio ЕС-4C20 (14.3%). All investigated ELS methods did not exert a significant influence on the basic parameters of blood coagulation and quantity of blood cells. No side effects and complications were observed. Conclusion: Selective plasma exchange and plasmadiafiltration are generally comparable in clinical and laboratory effects in the treatment of liver failure with MARS and Prometheus system provided significantly lower costs.Летальность пациентов c печеночной недостаточностью остается высокой. Часто спасение жизни пациента возможно только с использованием экстракорпоральной детоксикации (ЭКД). Системы экстракорпоральной поддержки печени MARS® и Prometheus® продемонстрировали свою эффективность, однако их широкому использованию препятствует очень высокая стоимость. Внедрение в клиническую практику новых, более доступных методов ЭКД является актуальной задачей. Цель: сравнение клинических и лабораторных эффектов процедур селективной плазмофильтрации (СПФ), плазмодиафильтрации (ПДФ) с использованием фракционаторов плазмы EvaclioTM, систем MARS® и Prometheus® (FPSA) при лечении печеночной недостаточности. Материалы и методы: 52 пациентам с острой (14) и декомпенсацией хронической печеночной недостаточности (38) выполнено по 15 экстракорпоральных процедур: MARS, FPSA, ПДФ, СПФ с использованием фракционаторов Evaclio ЕС-2C, ЕС-3C, ЕС-4C. До, сразу после и на следующее утро исследовались клинические и лабораторные (билирубин и фракции, общий белок, альбумин, мочевина, креатинин и др.) показатели, тяжесть состояния по шкале MELD. Оценивались и сравнивались их динамика, побочные эффекты и осложнения процедур. Результаты. Уменьшение концентрации прямого билирубина было сравнимо при FPSA, ПДФ и СПФ на Evaclio ЕС-3C20 и ЕС-4C20 (38‒42%), непрямого билирубина – при ПДФ и СПФ на Evaclio ЕС-3C20 и ЕС-4C20 (29‒34%). Низкомолекулярные метаболиты (мочевина и креатинин) лучше всего удалялись при FPSA (35‒44%) и ПДФ (40‒42%). Снижение их концентрации при СПФ было незначительным. Снижение уровня альбумина было наибольшим при FPSA (10,2%) и СПФ на Evaclio ЕС-4C20 (14,3%). Все исследованные методы ЭКД не оказывали существенного влияния на основные показатели системы свертывания и клеточный состав крови. Побочных реакций и осложнений не отмечено. Вывод. СПД и ПДФ по клиническим и лабораторным эффектам не уступают системам MARS® и Prometheus® при существенно меньшей стоимости

Cashew nut allergy: clinical relevance and allergen characterisation

Cashew plant (Anacardium occidentale L.) is the most relevant species of the Anacardium genus. It presents high economic value since it is widely used in human nutrition and in several industrial applications. Cashew nut is a well-appreciated food (belongs to the tree nut group), being widely consumed as snacks and in processed foods by the majority of world's population. However, cashew nut is also classified as a potent allergenic food known to be responsible for triggering severe and systemic immune reactions (e.g. anaphylaxis) in sensitised/allergic individuals that often demand epinephrine treatment and hospitalisation. So far, three groups of allergenic proteins have been identified and characterised in cashew nut: Ana o 1 and Ana o 2 (cupin superfamily) and Ana o 3 (prolamin superfamily), which are all classified as major allergens. The prevalence of cashew nut allergy seems to be rising in industrialised countries with the increasing consumption of this nut. There is still no cure for cashew nut allergy, as well as for other food allergies; thus, the allergic patients are advised to eliminate it from their diets. Accordingly, when carefully choosing processed foods that are commercially available, the allergic consumers have to rely on proper food labelling. In this sense, the control of labelling compliance is much needed, which has prompted the development of proficient analytical methods for allergen analysis. In the recent years, significant research advances in cashew nut allergy have been accomplished, which are highlighted and discussed in this review.This work was supported by FCT/MEC through national funds and co-financed by FEDER, under the Partnership Agreement PT2020 with grant no. UID/QUI/50006/2013–POCI/01/ 0145/FEDER/007265. Joana Costa is grateful to FCT post-doctoral grant (SFRH/BPD/102404/2014) financed by POPH-QREN (subsidised by FSE and MCTES).info:eu-repo/semantics/publishedVersio

Antegrade pampiniform plexus venography in recurrent varicocele: Case report and anatomy review

Varicoceles are often treated with percutaneous embolization, using fibered coils and sclerosing agents, with the latter targeted at occlusion of pre-existing collateral veins. While various methods of surgical and embolization treatment are available, varicoceles may still recur from venous collateralization. We present a case, where following demonstration of complete occlusion of the right and left gonadal veins, direct puncture of the pampiniform venous plexus under ultrasound guidance revealed recurrent varicoceles supplied by anastomoses from the ipsilateral saphenous and femoral veins to the pampiniform plexus. In doing so, we describe a technique of percutaneous pampiniform venography in a case where the pertinent anatomy was not easily demonstrated by other methods

FIRST CLINICAL EXPERIENCE OF USING COLUMN FOR LPS-ADSORPTION OF TOXIPAK IN TREATMENT OF SEPSIS PATIENTS

Endotoxicosis is one of the main factors of the pathogenesis of multiple organic dysfunctions in gram-negative sepsis, induced by the accumulation of lipopolysaccharides - wall components of gram-negative bacteria. In vitro removal of them (LPS-adsorption) promotes better treatment outcomes in sepsis patients. Development and introduction of the Russian tools for LPS-adsorption becomes more crucial. Objective: to evaluate the efficiency and safety of the column of Toxipak for endotoxin removal, manufactured by POCARD Ltd. Materials and methods: 7 adult sepsis patients who had LPS-adsorption were included into the study. The changes of the following parameters were monitored in the patients: temperature, pulse, arterial pressure, respiration rate, central venous pressure, oxygen saturation, hourly rate of diuresis, oxygenation index was calculated, hematologic and biochemical blood parameters were tested as well as coagulation system rates, endotoxin level, C-reactive protein (CRP), procalcitonin, and interleukins (IL) 1, 6, 8. Criteria of the system inflammatory response and SOFA score were used for the comprehensive evaluation of clinical status. The adverse events, duration of stay in the intensive care ward and 18- and 24-day mortality were followed up during manipulations. Results: the studied column provided no negative effect on the cellular and biochemical composition, main parameters of clotting system and acid-base balance of blood. Its use resulted in the reduction of endotoxin (LPS) (by 64%), CRP (by 14%), IL-1 (by 38%) in blood, increase of oxygenation index, and renal function improvement. LPS adsorption promoted the reduction of clinical and laboratory signs of system inflammatory response, and severity of organ dysfunction (from 6.0 to 3.0 as per SOFA score) in patients with sepsis and septic shock. Conclusion: Toxipak column is safe and efficient for removal of endotoxins from blood

AllerTool: A web server for predicting allergenicity and allergic cross-reactivity in proteins

10.1093/bioinformatics/btl621Bioinformatics234504-506BOIN

Comparison of selective plasma exchange and plasmadialfiltration with MARS and Prometheus systems in the treatment of liver failure

The mortality of patients with hepatic failure remains high. Often the patient's life can be saved only with extracorporeal liver support (ELS). ELS systems – MARS® и Prometheus® have proved their efficacy but their widespread use is constrained by their very high cost. Introduction in clinical practice of new affordable ELS systems is a topical issue. The objective: to compare clinical and laboratory effects of selective plasma exchange (SPE), plasmadialfiltration (PDF) with use of the selective membrane plasma separators EvaclioTM and MARS® and Prometheus® (FPSA) systems in the treatment of liver failure. Subjects and methods: 15 extracorporeal procedures of each type were performed in 52 patients with acute liver failure (14) and acute-on-chronic liver failure (38): MARS, FPSA, PDF, SPE with use of Evaclio ЕС-2C, and ЕС-3C, ЕС-4C. The clinical and laboratory parameters (total, direct and indirect bilirubin, total protein, albumin, creatinine, urea, etc.), severity of the condition according to MELD score were determined before and after the session and the next morning. Changes, side effects and complications of procedures were assessed and compared. Results. Reduction of concentration of direct bilirubin was comparable with FPSA, PDF and SPE on Evaclio ЕС-3C20 и ЕС-4C20 (38-42%), indirect bilirubin – with PDF and SPE on Evaclio ЕС-3C20 и ЕС-4C20 (29-34%). Low-molecular metabolites (urea, creatinine) were better removed with FPSA (35-44%) and PDF (40-42%). The reduction of their concentration with SPE was insignificant. The reduction of albumin level was the highest with FPSA (10.2%) and SPE on Evaclio ЕС-4C20 (14.3%). All investigated ELS methods did not exert a significant influence on the basic parameters of blood coagulation and quantity of blood cells. No side effects and complications were observed. Conclusion: Selective plasma exchange and plasmadiafiltration are generally comparable in clinical and laboratory effects in the treatment of liver failure with MARS and Prometheus system provided significantly lower costs