Встановлення умовно терапевтичної дози сухого екстракту з листя салату посівного на моделі тетрахлорометанового ураження печінки щурів

Topicality. The search for natural remedies that would exhibit antiseptic, anti-inflammatory, detoxification, antioxidant, choleretic, hepatoprotective actions and positively influenced the entire body in order to create new medicines based on them is one of the pressing issues of modern pharmacology and pharmacy. Plants used for food can serve as a basis for new medicines.Aim. To establish a conditionally therapeutic dose of the extract from lettuce leaves in the experiment with simulated tetrachloromethane hepatitis in rats.Materials and methods. The experiments were carried out on white outbred male rats, who were simulated toxic liver damage with carbon tetrachloride (twice (every other day) at a dose of 1.0 ml/kg body weight). Euthanasia was performed using sodium thiopental on the fourth day after the introduction of carbon tetrachloride in compliance with all rules for working with vertebrate animals. For the study, extract doses of 50 mg, 100 mg, 150 mg and 200 mg per kilogram of body weight of the animal were used. The activity of lipid peroxidation was assessed by the content of TBAactive products, the activity of membrane-destructive processes - by the activity of aminotransferases (AsAT and AlAT), the state of the antioxidant system by the content of CP and catalase activity.Results and discussion. It was noted that the lesion of rats with carbon tetrachloride causes a significant (p ≤ 0.05)increase in serum levels of TBA-active products (2.1 times), ceruloplasmin (5.6 times) and aminotransferase activities. At the same time, a decrease in catalase activity is observed (by 5.8 times). The activity of AsAT and AlAT in the serum during this period increases almost equally – by 4 times. Significant changes in the studied parameters observed after application of a dose of 100 mg / kg of body weight of animals.Conclusions. A conditionally therapeutic dose of the extract is considered to be a dose of 100 mg/kg of bodyweight, which has a positive effect on the indices of lipid peroxidation, antioxidant system and cytolysis under conditions of modeled toxic hepatitis.Актуальность. Поиск природных средств, которые бы проявляли антисептическое, противовоспалительное, детоксикационное, антиоксидантное, желчегонное, гепатопротекторное действие и положительно влиялина весь организм с целью создания на их основе новых лекарственных средств – одно из актуальных направлений современной фармакологии и фармации. Растения, используемые в пищу, могут служить основой для новых медикаментов.Цель исследования – установить условно терапевтическую дозу экстракта из листьев салата посевного в эксперименте с моделируемым тетрахлорометановым гепатитом у крыс.Материалы и методы. Опыты проводили на белых беспородных крысах-самцах, которым моделировали токсическое поражение печени тетрахлорометаном (двукратно (через день) в дозе 1,0 мл/кг массы тела).Эвтаназию проводили с использованием тиопентала натрия на четвёртые сутки после введения тетрахлорометана с соблюдением всех правил работы с позвоночными животными. Для исследования использовали дозы экстракта 50 мг, 100 мг, 150 мг и 200 мг на килограмм массы тела животного. Активность процессов липопероксидации оценивали по содержанию ТБК-активных продуктов, активность мембранодеструктивных процессов – по активности аминотрансфераз (АсАТ и АлАТ), состояние антиоксидантной системы – по содержанию ЦП и ак-тивности каталазы.Результаты и их обсуждение. Отмечено, что поражение крыс тетрахлорметаном вызывает достоверное (р ≤ 0,05) повышение в сыворотке крови содержания ТБК-активных продуктов (в 2,1 раза), церулоплазмина (в 5,6 раза) и активности аминотрансфераз. Одновременно наблюдается снижение каталазной активности (в 5,8 раза). Активность АсАТ и АлАТ в сыворотке крови в этот период увеличивается практически одинаково – в 4 раза. Достоверные изменения исследуемых показателей отмеченны после применения дозы 100 мг/кг массы тела животных.Выводы. Условно терапевтической дозой экстракта можно считать дозу 100 мг/кг массы тела, которая проявила положительное влияние на показатели липопероксидации, антиоксидантной системы и цитолиза в условиях смоделированного токсического гепатита.Актуальність. Пошук природних засобів, які б чинили антисептичну, протизапальну, детоксикаційну, антиоксиданту, жовчогінну, гепатопротекторну дію та позитивно впливали на весь організм з метою створення на їх основі нових лікарських засобів – одне з актуальних завдань сучасної фармакології та фармації. Рослини, які використовуються в їжу, можуть служити основою для нових медикаментів.Мета дослідження – встановити умовно терапевтичну дозу екстракту з листя салату посівного в експерименті з модельованим тетрахлорометановим гепатитом у щурів.Матеріали та методи. Досліди проводили на білих безпородних щурах-самцях, яким моделювали токсичне ураження печінки тетрахлорометаном (дворазово (через день) в дозі 1,0 мл/кг маси тіла). Евтаназію проводили з використанням тіопенталу натрію на 4-у добу після введення тетрахлорометану з дотриманням усіх правил роботи з хребетними тваринами. Для дослідження використані дози екстракту 50 мг, 100 мг, 150 мг та 200 мг на кілограм маси тіла тварини. Активність процесів ліпопероксидації оцінювали за вмістом ТБК-активних продуктів, активність мембранодеструктивних процесів – за активністю амінотрансфераз (АсАТ та АлАТ), стан антиоксидантної системи оцінювали за вмістом ЦП та активністю каталази.Результати та їх обговорення. Відмічено, що ураження щурів тетрахлорометаном викликає вірогідне (р ≤ 0,05) підвищення у сироватці крові вмісту ТБК-активних продуктів (у 2,1 рази), церулоплазміну (у 5,6 рази)та активність амінотрансфераз. Одночасно спостерігається зниження каталазної активності (у 5,8 рази). Активність АсАТ та АлАТ у сироватці крові в цей період збільшується практично однаково – у 4 рази. Вірогідні зміни досліджуваних показників відмічені після застосування дози 100 мг/кг маси тіла тварин.Висновки. Умовно терапевтичною дозою екстракту можна вважати дозу 100 мг/кг маси тіла, яка проявилапозитивний вплив на показники ліпопероксидації, антиоксидантної системи та цитолізу в умовах змодельованого токсичного гепатиту

The impact of COVID-19 on kidney transplant recipients in pre-vaccination and delta strain era: a systematic review and meta-analysis

Herein, we performed a meta-analysis of published clinical outcomes of corona virus disease 2019 (COVID-19) in hospitalized kidney transplant recipients. A systematic database search was conducted between December 1, 2019 and April 20, 2020. We analyzed 48 studies comprising 3137 kidney transplant recipients with COVID-19. Fever (77%), cough (65%), dyspnea (48%), and gastrointestinal symptoms (28%) were predominant on hospital admission. The most common comorbidities were hypertension (83%), diabetes mellitus (34%), and cardiac disease (23%). The pooled prevalence of acute respiratory distress syndrome and acute kidney injury were 58% and 48%, respectively. Invasive ventilation and dialysis were required in 24% and 22% patients, respectively. In-hospital mortality rate was as high as 21%, and increased to over 50% for patients in intensive care unit (ICU) or requiring invasive ventilation. Risk of mortality in patients with acute respiratory distress syndrome (ARDS), on mechanical ventilation, and ICU admission was increased: OR = 19.59, OR = 3.80, and OR = 13.39, respectively. Mortality risk in the elderly was OR = 3.90; however, no such association was observed in terms of time since transplantation and gender. Fever, cough, dyspnea, and gastrointestinal symptoms were common on admission for COVID-19 in kidney transplant patients. Mortality was as high as 20% and increased to over 50% in patients in ICU and required invasive ventilation

Arguments against the requirement of a biological license application for human pancreatic islets: The position statement of the islets for us collaborative presented during the fda advisory committee meeting

The Food and Drug Administration (FDA) has been regulating human islets for allo-transplantation as a biologic drug in the US. Consequently, the requirement of a biological license application (BLA) approval before clinical use of islet transplantation as a standard of care procedure has stalled the development of the field for the last 20 years. Herein, we provide our commentary to the multiple FDA’s position papers and guidance for industry arguing that BLA requirement has been inappropriately applied to allogeneic islets, which was delivered to the FDA Cellular, Tissue and Gene Therapies Advisory Committee on 15 April 2021. We provided evidence that BLA requirement and drug related regulations are inadequate in reassuring islet product quality and potency as well as patient safety and clinical outcomes. As leaders in the field of transplantation and endocrinology under the “Islets for US Collaborative” designation, we examined the current regulatory status of islet transplantation in the US and identified several anticipated negative consequences of the BLA approval. In our commentary we also offer an alternative pathway for islet transplantation under the regulatory framework for organ transplantation, which would address deficiencies of in current system

An immune dysfunction score for stratification of patients with acute infection based on whole-blood gene expression

Dysregulated host responses to infection can lead to organ dysfunction and sepsis, causing millions of global deaths each year. To alleviate this burden, improved prognostication and biomarkers of response are urgently needed. We investigated the use of whole-blood transcriptomics for stratification of patients with severe infection by integrating data from 3149 samples from patients with sepsis due to community-acquired pneumonia or fecal peritonitis admitted to intensive care and healthy individuals into a gene expression reference map. We used this map to derive a quantitative sepsis response signature (SRSq) score reflective of immune dysfunction and predictive of clinical outcomes, which can be estimated using a 7- or 12-gene signature. Last, we built a machine learning framework, SepstratifieR, to deploy SRSq in adult and pediatric bacterial and viral sepsis, H1N1 influenza, and COVID-19, demonstrating clinically relevant stratification across diseases and revealing some of the physiological alterations linking immune dysregulation to mortality. Our method enables early identification of individuals with dysfunctional immune profiles, bringing us closer to precision medicine in infection.peer-reviewe

Calorimetric Study of Block-Copolymers of Poly(n-butyl acrylate) and Gradient Poly(n-butyl acrylate-co-methyl methacrylate)

The nanophase separation in diblock and triblock copolymers consisting of immiscible poly(n-butyl acrylate) (block A) and gradient copolymers of methyl methacrylate (MMA) and n-butyl acrylate (n BA) (block M/A) were investigated by means of their heat capacity, Cp, as a function of the composition of the blocks M/A and temperature. In all copolymers studied, both blocks are represented by their Cp and glass transition temperature, Tg, as well as the broadening of the transition-temperature range. The low-temperature transition of the blocks A is always close to that of the pure poly(n-butyl acrylate) and is independent of the analyzed compositions of the block copolymer, but broadened asymmetrically relative to the homopolymer due to the small phase size. The higher transition is related to the glass transition of the copolymer block of composition M/A. Besides the asymmetric broadening of the transition due to the phase separation, it decreases in Tg and broadens, in addition, symmetrically with increasing acrylate content. The concentration gradient is not able to introduce a further phase separation with a third glass transition inside the M/A block

A comparison of ATM and IP QoS network capabilities for handling LAN traffic with QoS differentiation

Now, a network operator must choose between two packet switched technologies for providing QoS in WAN networks, which are ATM and IP QoS [3, 4, 9]. As ATM has reached the maturity with capabilities for offering a number of different network services (i.e. CBR, VBR, ABR, UBR, GFR), the IP QoS with network services like expedited forwarding, assured forwarding, etc. is still at developing phase but never-theless is commonly regarded as capable to guarantee in near future similar QoS level as ATM. This paper tries to compare the efficiency of the mentioned technologies (in case of IP QoS network the AQUILA network concept [1, 2] is investigated) for handling traffic generated by LANs with QoS differentiation. This is extremely required since the applications running in LAN differ in QoS requirements and emitted traffic profiles (streaming, elastic). Therefore, a classification process of outgoing LAN traffic into predefined sub-streams should be performed at the entry point to WAN network (edge ATM switch or IP router). Furthermore, particular sub-streams are submitted to adequate WAN network service, available in ATM or IP QoS. The paper presents the experimental results, measured in the test bed, corresponding to QoS level and QoS differentiation provided by ATM and IP QoS core.For this purpose, a set of representative applications currently available to a LAN user was selected demanding from the core different QoS level. They correspond to streaming applications like VoIP with QoS objectives represented mainly by packet delay characteristics and elastic applications controlled by TCP protocol with minimum guaranteed through-put/goodput as target