Influence of polychemotherapy on the morphology of metastases and kidney of resistant RLS-bearing mice

Aim: Polychemotherapy (PCT), widely used for the antitumor treatment has a pronounced toxic effect on the organism, and its cytostatic effect sometimes is canceled by multidrug resistance of a neoplasia. Comprehension of the nature and development of pathological changes caused by the PCT during the treatment of cancer is very important to improve the efficiency of the therapy and to clarify the mechanisms of tumor-host interactions. This study was aimed to examine PCT impact on kidney cells and tissues in mice with transplanted resistant lymphosacroma (RLS) and to analyze morphology of metastases of the tumor in kidney during PCT. Materials and Methods: Male mice CBA/LacSto (55 animals) were intramuscularly implanted in the right hind paw by 105 cells/ml of tumor RLS (a diffuse large B-cell lymphosarcoma) with multi-drug resistance (MDR) phenotype. Mice received combination of cyclophosphamide (50 mg/kg), oncovin (0.1 mg/kg), hydroxydaunorubicin (4 mg/kg), and prednisone (5 mg/kg) accordingly to CHOP scheme each 7 days after inoculation of the tumor. The kidneys were sampled on days 1, 3 and 7 after each series of injection of PCT preparations and processed for light and electron microscopy, immunohistochemical analysis of Ki-67 and Apaf-1 proteins also was performed. Results: Tumor RLS produced metastases comprised of small cells in the kidneys of mice after 8 days post inoculation. Application of PCT resulted in destruction of small-cell metastases and development of many large-cell metastases in kidney. Application of PCT induced the development of prominent damage of nephron cells, primarily in S3 segments of proximal tubules. Even one series of PCT caused reduction of basal plasma folds in these cells and alteration of mitochondria. Damage of proximal tubules and involvement of distal tubules, renal bodies and interstitial tissue in the pathologic process, increased during the experiment. This work presents the description of morphological changes in kidney as well as of the tumor metastases under PCT influence. Conclusion: The obtained data should be considered while designing of remedies for recovery of internal organs functions after antitumor PCT

New group of transmembrane proteins associated with desiccation tolerance in the anhydrobiotic midge Polypedilum vanderplanki

© 2020, The Author(s). Larvae of the sleeping chironomid Polypedilum vanderplanki are known for their extraordinary ability to survive complete desiccation in an ametabolic state called “anhydrobiosis”. The unique feature of P. vanderplanki genome is the presence of expanded gene clusters associated with anhydrobiosis. While several such clusters represent orthologues of known genes, there is a distinct set of genes unique for P. vanderplanki. These include Lea-Island-Located (LIL) genes with no known orthologues except two of LEA genes of P. vanderplanki, PvLea1 and PvLea3. However, PvLIL proteins lack typical features of LEA such as the state of intrinsic disorder, hydrophilicity and characteristic LEA_4 motif. They possess four to five transmembrane domains each and we confirmed membrane targeting for three PvLILs. Conserved amino acids in PvLIL are located in transmembrane domains or nearby. PvLEA1 and PvLEA3 proteins are chimeras combining LEA-like parts and transmembrane domains, shared with PvLIL proteins. We have found that PvLil genes are highly upregulated during anhydrobiosis induction both in larvae of P. vanderplanki and P. vanderplanki-derived cultured cell line, Pv11. Thus, PvLil are a new intriguing group of genes that are likely to be associated with anhydrobiosis due to their common origin with some LEA genes and their induction during anhydrobiosis

Neutralizing activity of sera from sputnik v-vaccinated people against variants of concern (VOC: B.1.1.7, B.1.351, P.1, B.1.617.2, B.1.617.3) and Moscow endemic SARS-CoV-2 variants

Since the beginning of the 2021 year, all the main six vaccines against COVID-19 have been used in mass vaccination companies around the world. Virus neutralization and epidemiological efficacy drop obtained for several vaccines against the B.1.1.7, B.1.351 P.1, and B.1.617 genotypes are of concern. There is a growing number of reports on mutations in receptor-binding domain (RBD) increasing the transmissibility of the virus and escaping the neutralizing effect of antibodies. The Sputnik V vaccine is currently approved for use in more than 66 countries but its activity against variants of concern (VOC) is not extensively studied yet. Virus-neutralizing activity (VNA) of sera obtained from people vaccinated with Sputnik V in relation to internationally relevant genetic lineages B.1.1.7, B.1.351, P.1, B.1.617.2, B.1.617.3 and Moscow endemic variants B.1.1.141 (T385I) and B.1.1.317 (S477N, A522S) with mutations in the RBD domain has been assessed. The data obtained indicate no significant differences in VNA against B.1.1.7, B.1.617.3 and local genetic lineages B.1.1.141 (T385I), B.1.1.317 (S477N, A522S) with RBD mutations. For the B.1.351, P.1, and B.1.617.2 statistically significant 3.1-, 2.8-, and 2.5-fold, respectively, VNA reduction was observed. Notably, this decrease is lower than that reported in publications for other vaccines. However, a direct comparative study is necessary for a conclusion. Thus, sera from “Sputnik V”-vaccinated retain neutralizing activity against VOC B.1.1.7, B.1.351, P.1, B.1.617.2, B.1.617.3 as well as local genetic lineages B.1.1.141 and B.1.1.317 circulating in Moscow. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

РЕКОМЕНДАЦИИ ПО ВЕДЕНИЮ ПЕРВИЧНЫХ ПАЦИЕНТОВ С СИМПТОМАМИ ДИСПЕПСИИ

Aim: To develop evidence-based recommendations for primary care physicians and general practitioners (GP) on choosing the proper management tactics and making valuable & quick diagnostic decisions at outpatient phase for patients with symptoms of dyspepsia, and also reveal possible oncology on time. Summary of recommendations: Approximately 40% of the patients in Russia presenting to primary care with symptoms of dyspepsia. A doctor has to focus on the warning signs, which may require an urgent additional examination & the consultation with a surgeon/onco-surgeon or other specialists if required. With regard to a risk of cancer, a doctor should be more cautious in patients over 45 years of age. Early diagnosis of oncology depends mainly on cautiousness of GP, primary care physicians and their knowledge, future tactics with regard to the patients. From the mandatory diagnostic tests during the first visit, esophagogastroduodenoscopy and H. pylori diagnostics helps to exclude any organic esophagus and stomach pathology, possible oncology. While waiting for endoscopy results, a physician should use the preliminary diagnoses “Uninvestigated Dyspepsia” (ICD-10 К 31.9) (disease of stomach and duodenum, unspecified). After exclusion of all warning signs, therapy of dyspepsia should be in accordance to the order of the Ministry of Health No 248 which gives an option to use proton pump inhibitors (omeprazole or rabeprazole 20 mg daily) in combination with prokinetic (domperidone 30 mg daily). Fixed drug combination of omeprazole 20 mg and modified-release domperidone 30 mg/daily (Omez® DSR) is medically reasonable. Conclusion: The introduction of this recommendation into clinical practice will help clinicians to prevent diagnostic mistakes, unreasonable use of expensive diagnostic examinations and inappropriate treatment leads to improvement in the overall prognosis and quality of life for the patients.Цель. Представить рекомендации диагностики и лечения пациентов с симптомами диспепсии на этапе амбулаторно-поликлинической помощи, обобщающие зарубежный и отечественный опыт ведения данной категории больных. Основная цель рекомендаций - помочь терапевту и врачу общей практики (ВОП) на амбулаторном этапе принять правильное решение о тактике ведения больного, и в максимально короткий срок поставить правильный диагноз, а также вовремя выявить у пациента наличие онкологической патологии. Основные положения. Около 40% обращений пациентов на амбулаторно-поликлиническом приеме в России связано с симптомами диспепсии. Врач, в первую очередь, должен исключить наличие «тревожных признаков», которые требуют незамедлительного дополнительного обследования пациента, привлечения хирурга и/или других специалистов и госпитализации больного. Доктор должен иметь онкологическую настороженность, особенно, при обращении пациентов в возрасте 45 лет и старше, так как ранняя диагностика злокачественных новообразований (ЗНО) зависит главным образом от онкологической настороженности терапевтов, врачей общей практики и их знаний, дальнейшей тактики в отношении больного. Эзофагогастродуоденоскопия и тесты на H. pylori являются обязательными методами исследования на этапе диагностического поиска и позволяют исключить органические заболевания пищевода и желудка, наличие онкологии. До получения результатов эндоскопического исследования следует выставлять предварительный диагноз «Диспепсия Неуточненная» и шифровать под рубрикой МКБ-10 К 31.9 (болезнь желудка и двенадцатиперстной кишки неуточненная). После исключения «тревожных признаков» терапия диспепсии проводится согласно Приказу МЗ РФ № 248 и включает назначение ингибиторов протонной помпы (омепразол или рабепразол 20 мг/сут) в комбинации с прокинетиком (домперидон 30 мг/сут). Оправдано применение фиксированной комбинации омепразола 20 мг с домперидоном модифицированного высвобождения 30 мг/сут (Омез® ДСР). Заключение. Внедрение рекомендаций в клиническую практику поможет врачу избежать ошибок при постановке диагноза, применения необоснованных и нередко дорогостоящих методов обследования, нерационального лечения, что позволит улучшить прогноз и качество жизни пациентов

РЕКОМЕНДАЦИИ ПО ВЕДЕНИЮ ПЕРВИЧНЫХ ПАЦИЕНТОВ С СИМПТОМАМИ ДИСПЕПСИИ

Aim: To develop evidence-based recommendations for primary care physicians and general practitioners (GP) on choosing the proper management tactics and making valuable & quick diagnostic decisions at outpatient phase for patients with symptoms of dyspepsia, and also reveal possible oncology on time. Summary of recommendations: Approximately 40% of the patients in Russia presenting to primary care with symptoms of dyspepsia. A doctor has to focus on the warning signs, which may require an urgent additional examination & the consultation with a surgeon/onco-surgeon or other specialists if required. With regard to a risk of cancer, a doctor should be more cautious in patients over 45 years of age. Early diagnosis of oncology depends mainly on cautiousness of GP, primary care physicians and their knowledge, future tactics with regard to the patients. From the mandatory diagnostic tests during the first visit, esophagogastroduodenoscopy and H. pylori diagnostics helps to exclude any organic esophagus and stomach pathology, possible oncology. While waiting for endoscopy results, a physician should use the preliminary diagnoses “Uninvestigated Dyspepsia” (ICD-10 К 31.9) (disease of stomach and duodenum, unspecified). After exclusion of all warning signs, therapy of dyspepsia should be in accordance to the order of the Ministry of Health No 248 which gives an option to use proton pump inhibitors (omeprazole or rabeprazole 20 mg daily) in combination with prokinetic (domperidone 30 mg daily). Fixed drug combination of omeprazole 20 mg and modified-release domperidone 30 mg/daily (Omez® DSR) is medically reasonable. Conclusion: The introduction of this recommendation into clinical practice will help clinicians to prevent diagnostic mistakes, unreasonable use of expensive diagnostic examinations and inappropriate treatment leads to improvement in the overall prognosis and quality of life for the patients.Цель. Представить рекомендации диагностики и лечения пациентов с симптомами диспепсии на этапе амбулаторно-поликлинической помощи, обобщающие зарубежный и отечественный опыт ведения данной категории больных. Основная цель рекомендаций - помочь терапевту и врачу общей практики (ВОП) на амбулаторном этапе принять правильное решение о тактике ведения больного, и в максимально короткий срок поставить правильный диагноз, а также вовремя выявить у пациента наличие онкологической патологии. Основные положения. Около 40% обращений пациентов на амбулаторно-поликлиническом приеме в России связано с симптомами диспепсии. Врач, в первую очередь, должен исключить наличие «тревожных признаков», которые требуют незамедлительного дополнительного обследования пациента, привлечения хирурга и/или других специалистов и госпитализации больного. Доктор должен иметь онкологическую настороженность, особенно, при обращении пациентов в возрасте 45 лет и старше, так как ранняя диагностика злокачественных новообразований (ЗНО) зависит главным образом от онкологической настороженности терапевтов, врачей общей практики и их знаний, дальнейшей тактики в отношении больного. Эзофагогастродуоденоскопия и тесты на H. pylori являются обязательными методами исследования на этапе диагностического поиска и позволяют исключить органические заболевания пищевода и желудка, наличие онкологии. До получения результатов эндоскопического исследования следует выставлять предварительный диагноз «Диспепсия Неуточненная» и шифровать под рубрикой МКБ-10 К 31.9 (болезнь желудка и двенадцатиперстной кишки неуточненная). После исключения «тревожных признаков» терапия диспепсии проводится согласно Приказу МЗ РФ № 248 и включает назначение ингибиторов протонной помпы (омепразол или рабепразол 20 мг/сут) в комбинации с прокинетиком (домперидон 30 мг/сут). Оправдано применение фиксированной комбинации омепразола 20 мг с домперидоном модифицированного высвобождения 30 мг/сут (Омез® ДСР). Заключение. Внедрение рекомендаций в клиническую практику поможет врачу избежать ошибок при постановке диагноза, применения необоснованных и нередко дорогостоящих методов обследования, нерационального лечения, что позволит улучшить прогноз и качество жизни пациентов