Thermal- and Oxidative Stress Causes Enhanced Release of NKG2D Ligand-Bearing Immunosuppressive Exosomes in Leukemia/Lymphoma T and B Cells

Immune evasion from NK surveillance related to inadequate NK-cell function has been suggested as an explanation of the high incidence of relapse and fatal outcome of many blood malignancies. In this report we have used Jurkat and Raji cell lines as a model for studies of the NKG2D receptor-ligand system in T-and B cell leukemia/lymphoma. Using real-time quantitative RT-PCR and immunoflow cytometry we show that Jurkat and Raji cells constitutively express mRNA and protein for the stress-inducible NKG2D ligands MICA/B and ULBP1 and 2, and up-regulate the expression in a cell-line specific and stress-specific manner. Furthermore, we revealed by electron microscopy, immunoflow cytometry and western blot that these ligands were expressed and secreted on exosomes, nanometer-sized microvesicles of endosomal origin. Acting as a decoy, the NKG2D ligand-bearing exosomes downregulate the in vitro NKG2D receptor-mediated cytotoxicity and thus impair NK-cell function. Interestingly, thermal and oxidative stress enhanced the exosome secretion generating more soluble NKG2D ligands that aggravated the impairment of the cytotoxic response. Taken together, our results might partly explain the clinically observed NK-cell dysfunction in patients suffering from leukemia/lymphoma. The adverse effect of thermal and oxidative stress, enhancing the release of immunosuppressive exosomes, should be considered when cytostatic and hyperthermal anti-cancer therapies are designed

Отдаленные последствия недоношенности: нарушения физического развития и пищевого поведения детей и подростков

Aim. To characterize the physical development (PD) and eating behavior (EB) of children and adolescents born prematurely.Materials and methods. The study involved 123 people born in the period 1997-2008, 58 children born prematurely, age (12 ± 1.3) years, gestation period (33.07 ± 1.9) weeks (main group). The control group consisted of 65 full-term peers, age (12.7 ± 2.2) years, gestational age (39.5 ± 0.8) weeks. Participants were evaluated by PD (height, weight, body mass index (BMI), waist circumference (WC), throat circumference (TC)) under the WHO AnthroPlus program, and EB using the Dutch DEBQ questionnaire.Results. Growth and Z-score growth of boys and girls of the main group is lower than that of their fullterm peers, p = 0.04; 0.004 (p < 0.0001 for Z-score growth). Z-score BMI in boys and girls of the main group is higher than in full-term, p = 0.04; 0.01. WC/TC the girls of the main group is higher than in fullterm peers, p < 0.0001. In premature boys, the restrictive type is 13.3%, emotional and external – 50%, the combination of emotional and external – 33.3%. In the control restrictive – 5,7%, emotional – 28,6%, external – 32,3%, the combination of emotional and external – 10,8%, the combination of all three types – 5,7%. In the group of premature girls restrictive –7.1% against 36.7% in the control, (p = 0.007), emotsiogenic – 10.7% against 36.6% of the control (p = 0.02), external – 10.3% against 60% of the control (p = 0.003). In the control group the combination of external and emotiogenic – 16.7% (in the primary group is 0, p = 0.02). Preterm boys emotiogenic and external and their combination more often than girls (p = 0.001; 0.02; 0.001).Conclusion. Children and adolescents born prematurely are below full-term peers and have a high z-score of BMI. Boys realize violations of external and emotional types, and their combination. Цель. Охарактеризовать физическое развития (ФР) и пищевое поведение (ПП) детей и подростков, родившихся недоношенными.Материалы и методы. В исследовании приняли участие 123 человека, родившихся в 1997–2008 гг., в том числе 58 недоношенных детей, возраст (12 ± 1,3) лет, срок гестации (33,07 ± 1,9) нед (основная группа). Группу контроля составили 65 доношенных сверстников, возраст (12,7 ± 2,2) лет, срок гестации (39,5 ± 0,8) нед. Участникам проведена оценка ФР (рост, вес, индекс массы тела (ИМТ), окружность талии (ОТ), окружность бедер (ОБ)) по программе WHO AnthroPlus и ПП с помощью голландского опросника DEBQ.Результаты. В исследовании показано, что рост и z-score роста мальчиков и девочек основной группы ниже, чем у их доношенных сверстников, р = 0,04; р = 0,004 соответственно (р < 0,0001 для z-score роста). Отмечено, что z-score ИМТ у мальчиков и девочек основной группы выше, чем у доношенных, р = 0,04; р = 0,01; ОТ/ОБ у девочек основной группы выше, чем у доношенных сверстниц, р < 0,0001. У недоношенных мальчиков выявлены следующие типы ПП: ограничительный (13,3%), эмоциогенный и экстернальный (по 50%), сочетание эмоциогенного и экстернального (33,3%). В контрольной группе обнаружены следующие типы ПП: ограничительный (5,7%), эмоциогенный (28,6%), экстернальный (32,3%), сочетание эмоциогенного и экстернального (10,8%), сочетание всех трех типов (5,7%). У девочек наблюдались следующие типы ПП: ограничительный в основной группе (7,1%) и контрольной (36,7%), р = 0,007; эмоциогенный – 10,7% против 36,6% из контроля (р = 0,02); экстернальный – 10,3% против 60% из контроля (р = 0,003). В контрольной группе отмечено сочетание эмоциогенного и экстернального (16,7%), в основной группе – 0, р = 0,02. У недоношенных мальчиков эмоциогенный и экстернальный тип ПП и их сочетание наблюдались чаще, чем у девочек (р = 0,001; р = 0,02; р = 0,001).Заключение. Дети и подростки, родившиеся недоношенными, ниже доношенных сверстников и имеют высокие z-score ИМТ. Мальчики реализуют нарушения экстернального и эмоциогенного типов и их сочетание.

Intrauterine Growth Restriction Is a Direct Consequence of Localized Maternal Uropathogenic Escherichia coli Cystitis

Despite the continually increasing rates of adverse perinatal outcomes across the globe, the molecular mechanisms that underlie adverse perinatal outcomes are not completely understood. Clinical studies report that 10% of pregnant women will experience a urinary tract infection (UTI) and there is an association of UTIs with adverse perinatal outcomes. We introduced bacterial cystitis into successfully outbred female mice at gestational day 14 to follow pregnancy outcomes and immunological responses to determine the mechanisms that underlie UTI-mediated adverse outcomes. Outbred fetuses from mothers experiencing localized cystitis displayed intrauterine growth restriction (20–80%) as early as 48 hours post-infection and throughout the remainder of normal gestation. Robust infiltration of cellular innate immune effectors was observed in the uteroplacental tissue following introduction of UTI despite absence of viable bacteria. The magnitude of serum proinflammatory cytokines is elevated in the maternal serum during UTI. This study demonstrates that a localized infection can dramatically impact the immunological status as well as the function of non-infected distal organs and tissues. This model can be used as a platform to determine the mechanism(s) by which proinflammatory changes occur between non-contiguous genitourinary organ

LEFT VENTRICULAR WALL THICKNESS AND AUTONOMIC REGULATION IN PATIENTS WITH HYPERTROPHIC CARDIOMYOPATHY

The study included 21 patients (mean age 35,86±10,01 years) with hypertrophic cardiomyopathy (HCMP) diagnosed according to the WHO criteria. All patients underwent in-hospital complex clinical and functional assessment, electrocardiography (QT dispersion, Sokolow-Lyon index, and Cornell voltage index analysis), Holter ECG monitoring (time and spectral parameter analysis), and echocardiography (EchoCG). Based on the interventricular septum thickness (IVST), all patients were divided into two groups: Group I with IVST <20 mm (n=13) and Group II with IVST >20 mm (n=8). Group II was characterised by left ventricular diastolic dysfunction, with a tendency towards the development of its restrictive variant. In addition, Group II patients demonstrated autonomic disbalance, sympathetic hyperactivity, and disturbed circadian patterns of heart rate

CLINICAL AND FUNCTIONAL CHARACTERISTICS OF PATIENTS AFTER Q-WAVE MYOCARDIAL INFARCTION DEPENDING ON THE METABOLIC SYNDROME PRESENCE OR ABSENCE

Aim. To study the clinical and functional parameters of patients after acute Q-wave myocardial infarction (Q-MI) depending on the concomitant metabolic syndrome (MS). Material and methods. Men after Q-MI (n=79; aged 51.7±8.9 years) were included into the study. Patients were divided into two groups depending on the MS presence or absence. Doppler echocardiography and determination of the serum C-reactive protein (CRP) level were performed in all patients on the 10-14 days after Q-MI, and treadmill test was performed in 25 patients.Results. Left ventricular ejection fraction was 12% lower and the CRP level was 2 times higher in MS patients versus these in non-MS patients (p&lt;0.01). The silent segment ST depression ≥1.0 mm were more often observed in MS patients compared with this in non-MS patients (40% vs 5%; respectively, p&lt;0.05).Conclusion. The MS presence complicates the post-infarction period by early heart failure progression, characterized by elevated CRP levels and more frequent occurrence of silent myocardial ischemia.</p

Antimicrobial susceptibility of Helicobacter pylori isolates in Smolensk in 2015-2016

Aim of investigation. To determine antimicrobial susceptibility of H. pylori in Smolensk in 2015-2016. Material and methods. Overall 248 adult patients with positive rapid urease test at the time of gastroscopy were included in the study. Antimicrobial susceptibility testing of H. pylori isolates to clarithromycin, amoxicillin, metronidazole, levofloxacin, rifampicin, tetracycline was performed by the agar dilution method. Results. H. pylori was isolated in 33% (n=82) of patients (24 isolates were nonviable after freezing). The rates of resistance among tested isolates of H. pylori were: 3,5% (2/58) for clarithromycin, 3,5% (2/58) for amoxicillin, 10.3% (6/58) for metronidazole, 27,6% (16/58) for levofloxacin, 8.6% (5/58) for rifampicin. No isolates showed resistance to tetracycline. Among 58 H. pylori isolates 29% (17 isolates) were resistant to one antimicrobial agent, 12,1% (7 isolates) were resistant to two antimicrobial agents. Associated resistance was observed for levofloxacin and metronidazole 3,5% (2 isolates), levofloxacin and rifampicin 5,2% (3 isolates), metronidazole and rifampicin 3,5% (2 isolates). Conclusions. Smolensk is the area of low clarithromycin resistance. So, clarithromycin-containing regimens are recommended for first-line empirical eradication therapy. Use of levofloxacin is questionable in relation to high levels of resistance H. pylori to levofloxacin. Use of rifabutin is questionable in relation to relatively high H. pylori rifampicin resistance rate

Remote consequences of prematurity: violations of physical development and eating behavior of children and adolescents

Aim. To characterize the physical development (PD) and eating behavior (EB) of children and adolescents born prematurely.Materials and methods. The study involved 123 people born in the period 1997-2008, 58 children born prematurely, age (12 ± 1.3) years, gestation period (33.07 ± 1.9) weeks (main group). The control group consisted of 65 full-term peers, age (12.7 ± 2.2) years, gestational age (39.5 ± 0.8) weeks. Participants were evaluated by PD (height, weight, body mass index (BMI), waist circumference (WC), throat circumference (TC)) under the WHO AnthroPlus program, and EB using the Dutch DEBQ questionnaire.Results. Growth and Z-score growth of boys and girls of the main group is lower than that of their fullterm peers, p = 0.04; 0.004 (p &lt; 0.0001 for Z-score growth). Z-score BMI in boys and girls of the main group is higher than in full-term, p = 0.04; 0.01. WC/TC the girls of the main group is higher than in fullterm peers, p &lt; 0.0001. In premature boys, the restrictive type is 13.3%, emotional and external – 50%, the combination of emotional and external – 33.3%. In the control restrictive – 5,7%, emotional – 28,6%, external – 32,3%, the combination of emotional and external – 10,8%, the combination of all three types – 5,7%. In the group of premature girls restrictive –7.1% against 36.7% in the control, (p = 0.007), emotsiogenic – 10.7% against 36.6% of the control (p = 0.02), external – 10.3% against 60% of the control (p = 0.003). In the control group the combination of external and emotiogenic – 16.7% (in the primary group is 0, p = 0.02). Preterm boys emotiogenic and external and their combination more often than girls (p = 0.001; 0.02; 0.001).Conclusion. Children and adolescents born prematurely are below full-term peers and have a high z-score of BMI. Boys realize violations of external and emotional types, and their combination