Збройні сили Гетьманщини та Запорожжя в боротьбі з Османською імперією в 1695-96 рр. за даними неопублікованих листів Івана Мазепи

Російський історик М.Богословський ще в 20-х рр. XX ст. слушно зауважив, що в історичній літературі зверталося порівняно мало уваги на завоювання дніпровських містечок в кінці XVII ст., оскільки вся увага була прикута до Азова, де діяв сам Петро І. Але зроблене тут мало не менше значення ніж взяття Азова, бо в результаті Росія наближалася до Чорного моря як зі східного, так і з західного боку. Під контролем з обох боків опинявся й Крим [1]. В 1695-1696 рр. збройні сили Російської держави та Війська Запорозького здійснили два походи на Азов та один на пониззя Дніпра, маючи на меті завоювання виходів до Азовського та Чорного морів. Похід на Азов у 1695 р., як відомо, був невдалим. Натомість похід російських військ на чолі з боярином Борисом Шереметєвим та українських сил, очолюваних гетьманом Іваном Мазепою, а також запорожців на пониззя Дніпра наприкінці липня – на початку серпня увінчався взяттям важливого плацдарму, де знаходилося чотири турецькі фортеці – Казикермен, Мустріткермен, Мубеуреккермен і Ісламкермен. В Мустріткермені (Таванську), котрий знаходився на острові Тавань, укріплення постраждали найменше. Тому тут було здійснено ремонтні роботи й залишено залогу. Досліджуючи неопубліковану епістолярну спадщину Мазепи в зібраннях Російського державного архіву давніх актів, ми виявили ряд листів, які стосуються участі Лівобережної України та Запорозької Січі у воєнних діях проти Османської імперії у згадані роки. Так, віднайдено чотири листи, котрі були написані напередодні походу 1695 р. Три з них адресувалися царям – від 26 березня, 1 квітня та 14 квітня, а один – боярину Леву Наришкіну від 26 березня. Отже, розглянемо їх зміст, з точки зору задекларованої теми. З першого з пропонованих документів дізнаємося, що перед походом гетьманський уряд вживав заходів для збору інформації щодо противника. Так, у листі до царів від 26 березня 1695 р. Мазепа повідомляв, що товариство Полтавського полку – понад сотня козаків на чолі з царичанським сотником і кількома польовими ватажками ходили на воєнні промисли з його відома. Поблизу Перекопа на шляху до Казикермена козаки захопили в полон 22 татарина і привели до Батурина. Мазепа відправляв “язиків” до Москви разом з козаками. Він висловлював сподівання, що полонених буде більше, бо під помешкання противника було послано й інші ватаги. Одну очолював колишній кошовий отаман Федько, другу – колишній кошовий Іван Гусак, третю – полковий осавул Іван Рубан, четверту – кінний сотник Гнат. У перших трьох ватагах нараховувалося по кілька сотень осіб та й четверта була “в немалому зібранні”. Крім того до Мазепи писав Семен Палій, повідомляючи, що його люди пішли на Очаківський шлях, який спрямовувався на Білгород, 6 тижнів тому. У зв’язку з цим гетьман хотів отримати царський указ про те, чи посилат

The Effect of Melatonin on Periodontitis

Background: Periodontitis is a chronic disease with a complex etiology that includes bacterial colonization, excessive inflammation, and oxidative stress. The hormone melatonin has antioxidant properties and might contribute to alleviating chronic conditions by reducing oxidative stress. The aim of this study was to analyze the effect of exogenous melatonin on periodontitis in an animal model of the disease as well as in patients with periodontitis. Methods: In rats with ligature-induced periodontitis, melatonin was administered in drinking water for two weeks. In the human study, patients with treatment-resistant periodontitis were asked to rinse their mouths with a solution containing melatonin or placebo every evening for two weeks. Periodontal status as well as salivary markers of oxidative stress were assessed at the end of the study. Results: Neither radiography nor μCT revealed any significant effects of melatonin on alveolar bone loss. Gum recession was the only improved macroscopic measure in rats (p < 0.05). Analysis of salivary markers of oxidative stress revealed no effects of treatment in rats or humans despite clearly elevated melatonin concentrations in melatonin treated groups. Conclusion: Our results do not support the use of melatonin for the treatment of periodontitis. However, the negative outcome is limited by the short duration of the study and the chosen route of application as well as the dose of melatonin.publishedVersio

Plasma Concentrations of Extracellular DNA in Acute Kidney Injury

Current diagnostic methods of acute kidney injury (AKI) have limited sensitivity and specificity. Tissue injury has been linked to an increase in the concentrations of extracellular DNA (ecDNA) in plasma. A rapid turnover of ecDNA in the circulation makes it a potential marker with high sensitivity. This study aimed to analyze the concentration of ecDNA in plasma in animal models of AKI. Three different fractions of ecDNA were measured—total ecDNA was assessed fluorometrically, while nuclear ecDNA (ncDNA) and mitochondrial DNA (mtDNA) were analyzed using quantitative real-time PCR. AKI was induced using four different murine models of AKI-bilateral ureteral obstruction (BUO), glycerol-induced AKI (GLY), ischemia–reperfusion injury (IRI) and bilateral nephrectomy (BNx). Total ecDNA was significantly higher in BUO (p < 0.05) and GLY (p < 0.05) compared to the respective control groups. ncDNA was significantly higher in BUO (p < 0.05) compared to SHAM. No significant differences in the concentrations of mtDNA were found between the groups. The plasma concentrations of different fractions of ecDNA are dependent on the mechanism of induction of AKI and warrant further investigation as potential surrogate markers of AKI.publishedVersio

Dynamics of Plasma and Urinary Extracellular DNA in Acute Kidney Injury

Early and reliable markers of acute kidney injury (AKI) are essential. One such candidate marker of tissue damage is extracellular DNA (ecDNA). The aim of our present study is to describe the unknown dynamics of ecDNA in an animal model of AKI. Glycerol-induced nephropathy was used to model AKI in adult male Wistar rats (n = 93). Blood and urine samples were collected 1, 3, and 24 h after model induction. Total ecDNA and its sub-cellular origin was assessed. In the plasma, total ecDNA and nuclear ecDNA were significantly increased in the AKI group already after 1 h (160% and 270%, respectively, p = 0.02 and p = 0.04). Both nuclear and mitochondrial ecDNA were higher after 3 h (180% and 170%, respectively, p = 0.002 and p = 0.005). Urinary ecDNA concentrations in the AKI group were significantly increased only 24 h after model induction (130% for total ecDNA, p = 0.009; 210% for nuclear ecDNA, p = 0.02; and 200% for mitochondrial ecDNA, p = 0.0009). Our results indicate that plasma ecDNA has the potential to serve as an early and sensitive, albeit non-specific marker of AKI. Further studies should elucidate the source of ecDNA and the dynamics of ecDNA in other animal models of AKI and patients with AKI.publishedVersio

Neutrophil extracellular traps in urinary tract infection

BackgroundUrinary tract infections (UTI) are common types of bacterial infection in children. UTI treatment is aimed to prevent complications including hypertension, proteinuria, and progression to chronic kidney disease. Activated neutrophils release chromatin-based structures associated with antimicrobial proteins called neutrophil extracellular traps (NETs). We aimed to describe the role of NET-associated markers in children with UTI as well as the role of NETs formation in a mouse model of UTI.Materials and methodsMarkers of NETs including extracellular DNA (ecDNA), myeloperoxidase (MPO) and cathelicidin were analyzed in children with febrile UTI caused by E.coli (n = 98, aged 0.3–1.3 years) and in healthy controls (n = 50, 0.5–5.2 years). Moreover, an acute experimental model of UTI was performed on PAD4 knock-out mice with diminished NETs formation (n = 18), and on wild-type mice (n = 15).ResultsChildren with UTI had significantly higher urinary NETs markers including total ecDNA, nuclear DNA and mitochondrial DNA, altogether with MPO and cathelicidin. The concentrations of MPO and cathelicidin positively correlated with ecDNA (r = 0.53, p ≤ 0.001; r = 0.56, p ≤ 0.001, respectively) and the number of leukocytes in the urine (r = 0.29, p ≤ 0.05; r = 0.27, p ≤ 0.05, respectively). Moreover, urinary MPO was positively associated with cathelicidin (r = 0.61, p ≤ 0.001). In the experimental model, bacterial load in the bladder (20-fold) and kidneys (300-fold) was significantly higher in PAD4 knock-out mice than in wild-type mice.ConclusionHigher urinary NETs makers—ecDNA, MPO and cathelicidin and their correlation with leukocyturia in children with UTI confirmed our hypothesis about the association between NETs and UTI in children. Higher bacterial load in mice with diminished NETs formation suggests that NETs are not only a simple consequence of UTI, but might play a direct role in the prevention of pyelonephritis and other UTI complications

Prenatal dietary load of Maillard reaction products combined with postnatal Coca-Cola drinking affects metabolic status of female Wistar rats.

AIM: To assess the impact of prenatal exposure to Maillard reaction products (MRPs) -rich diet and postnatal Coca-Cola consumption on metabolic status of female rats. Diet rich in MRPs and consumption of saccharose/fructose sweetened soft drinks is presumed to impose increased risk of development of cardiometabolic afflictions, such as obesity or insulin resistance. METHODS: At the first day of pregnancy, 9 female Wistar rats were randomized into two groups, pair-fed either with standard rat chow (MRP-) or MRPs-rich diet (MRP+). Offspring from each group of mothers was divided into two groups and given either water (Cola-) or Coca-Cola (Cola+) for drinking ad libitum for 18 days. Oral glucose tolerance test was performed, and circulating markers of inflammation, oxidative stress, glucose and lipid metabolism were assessed. RESULTS: MRP+ groups had higher weight gain, significantly so in the MRP+/Cola- vs MRP-/Cola-. Both prenatal and postnatal intervention increased carboxymethyllysine levels and semicarbazide-sensitive amine oxidase activity, both significantly higher in MRP+/Cola + than in MRP-/Cola-. Total antioxidant capacity was lower in MRP+ groups, with significant decrease in MRP+/Cola + vs MRP-/Cola+. Rats drinking Coca-Cola had higher insulin, homeostatic model assessment of insulin resistance, heart rate, advanced oxidation of protein products, triacylglycerols, and oxidative stress markers measured as thiobarbituric acid reactive substances compared to rats drinking water, with no visible effect of MRPs-rich diet. CONCLUSION: Metabolic status of rats was affected both by prenatal and postnatal dietary intervention. Our results suggest that combined effect of prenatal MRPs load and postnatal Coca-Cola drinking may play a role in development of metabolic disorders in later life

Sex differences in long-term effects of collagen-induced arthritis in middle-aged mice

Introduction: Rheumatoid arthritis (RA) is a chronic inflammatory disorder with high prevalence among middle-aged women. Collagen-induced arthritis (CIA) is the most widely used animal model of RA, however, sex differences and long-term effects of CIA in mice are poorly described in the literature.Aim: Therefore, the present study aimed to analyze the long-term effects of CIA on the joints of middle-aged mice of both sexes and to describe potential sex differences.Materials and methods: CIA was induced in middle-aged DBA/1J mice by immunization with bovine type II collagen and complete Freund’s adjuvant. Saline was administered to control mice. Arthritis score assessment, plethysmometry, and thermal imaging of the joints were performed weekly for 15 weeks. Locomotor activity, micro-computed tomography, joint histology and biochemical analyses were performed at the end of the experiment.Results: Our results indicate a similar prevalence of arthritis in both sexes of mice—67% (8/12) of females and 89% (8/9) males with an earlier onset in males (day 14 vs. day 35). After the arthritis scores peaked on day 56 for males and day 63 for females, they steadily declined until the end of the experiment on day 105. A similar dynamics was observed in paw volume and temperature analyzing different aspects of joint inflammation. Long-term consequences including higher proteinuria (by 116%), loss of bone density (by 33.5%) and joint damage in terms of synovial hyperplasia as well as bone and cartilage erosions were more severe in CIA males compared to CIA females. There were no significant differences in locomotor activity between CIA mice and CTRL mice of any sex.Conclusion: This is the first study to describe the long-term effects of the CIA model in terms of sex differences in DBA/1J mice. Our results indicate sex differences in the dynamics, but not in the extent of arthritis. An earlier onset of arthritis and more severe consequences on joints, bones and kidneys were found in males. The underlying immune pathomechanisms responsible for the limited duration of the arthritis symptoms and the opposite sex difference in comparison to RA patients require further investigation

Cognitive impairment and biomarkers of gut microbial translocation in testicular germ cell tumor survivors

BackgroundSurvivors of testicular germ cell tumors (GCT) may suffer from late cognitive impairment. We hypothesized that disruption of intestinal barrier during chemotherapy and/or radiotherapy may be a contributing factor of cognitive dysfunction within the gut-blood-brain axis.MethodsGCT survivors (N = 142) from National Cancer Institute of Slovakia completed the Functional Assessment of Cancer Therapy Cognitive Function questionnaires during their annual follow-up visit at 9-year median (range 4-32). Biomarkers of gut microbial translocation and dysbiosis high mobility group box-1 (HMGB-1), lipopolysaccharide, d-lactate and sCD14 were measured from peripheral blood obtained during the same visit. Each questionnaire score was correlated with biomarkers. Survivors were treated with orchiectomy only (N = 17), cisplatin-based chemotherapy (N = 108), radiotherapy to the retroperitoneum (N = 11) or both (N = 6).ResultsGCT survivors with higher sCD14 (above median) had worse cognitive function perceived by others (CogOth domain) (mean ± SEM; 14.6 ± 0.25 vs 15.4 ± 0.25, p = 0.019), lower perceived cognitive abilities (CogPCA domain) (20.0 ± 0.74 vs 23.4 ± 0.73, p = 0.025) and lower overall cognitive function score (109.2 ± 0.74 vs 116.7 ± 1.90, p = 0.021). There were no significant cognitive declines associated with HMGB-1, d-lactate and lipopolysaccharide. Survivors treated with ≥ 400mg/m2 vs &lt; 400mg/m2 of cisplatin-based chemotherapy had a higher lipopolysaccharide (567.8 μg/L ± 42.7 vs 462.9 μg/L ± 51.9, (p = 0.03).ConclusionssCD14 is a marker of monocytic activation by lipopolysaccharide and may also serve as a promising biomarker of cognitive impairment in long-term cancer survivors. While chemotherapy and radiotherapy-induced intestinal injury may be the underlying mechanism, further research using animal models and larger patient cohorts are needed to explore the pathogenesis of cognitive impairment in GCT survivors within the gut-brain axis