Fecal short-chain fatty acids at different time points after ceftriaxone administration in rats

Short-chain fatty acids (SCFAs) are major products of the microbial fermentation of dietary fiber in the colon. Recent studies suggest that these products of microbial metabolism in the gut act as signaling molecules, influence host energy homeostasis and play major immunological roles. In the present study, defined the long-term effects of ceftriaxone administration on the fecal SCFAs concentration in Wistar rats. Ceftriaxone (300 mg/kg, i.m.) was administered daily for 14 days. Rats were euthanized in 1, 15 and 56 days after ceftriaxone withdrawal. Caecal weight and fecal concentration of SCFAs by gas chromatography were measured. Ceftriaxone administration induced time-dependent rats’ caecal enlargement through accumulation of undigestable substances. In 1 day after ceftriaxone withdrawal, the concentrations of acetic, propionic, butyric acids and total SCFAs were decreased 2.9-, 13.8-, 8.5-, 4.8-fold (P < 0.05), respectively. Concentration of valeric, isovaleric and caproic acids was below the detectable level. That was accompanied by decreased 4.3-fold anaerobic index and increased the relative amount of acetic acid (P < 0.05). In 56 days, concentration of SCFAs was still below control value but higher than in 1 day (except propionic acid). Anaerobic index was lower 1.3-fold (P < 0.05) vs. control. Conclusion: antibiotic therapy induced long-term disturbance in colonic microbiota metabolic activity

The disturbance of oxidant-antioxidant balance in rat colonic mucosa after antibiotic therapy

Antibiotic treatment increases susceptibility to development of inflammatory bowel diseases (IBD) both in children and adults. Oxidative stress plays a prominent role in IBD pathogenesis. The aim of present study was to test an interrelationship between the morphological changes in rat colonic mucosa, the levels of antioxidant enzymes and redox sensitive transcription factors Egr-1 and Sp-1 after treatment with cephalosporin antibiotic ceftriaxone (Cf) with broad spectrum of action. Study was performed on male Wistar rats (180–230 g). Cf (50 mg/kg, i.m.) were injected daily for 5 days. The colonic levels of catalase and superoxide dismutase activity were measured by the colorimetric assays and zymography; levels of Egr-1 and Sp-1 – by Western-blot analysis; histological chan­ges – by morphometric analysis. Body weight and diarrhea were recorded. Systemic administration of the ceftriaxone induced morphological and functional changes in rat colonic mucosa associated with initial stages of the acute inflammation. These changes were accompanied by a decrease of activity of superoxide dismutase and catalase. Levels of redox-sensitive transcription factors Egr-1 and Sp1 were significantly increased, which shows a disturbance of homeostasis of the intestinal barrier

Досвід застосування діосмектиту гелю на тлі антибактеріальної терапії у дітей

Objective. To examine the effectiveness of the diosmectit gel in children due to the antibacterial therapy of acute infectious diseases. Patients and methods. A total of 60 children in the age from 3 to 17 years, who were hospitalized with acute infectious diseases were under observation. The study group consisted of 30 children who from the first day of appointment of an antibiotic additionally had received diosmectit gel. The control group consisted of 30 children who had received only conventional therapy. The duration of treatment ranged from 7 to 14 days, depending on the diagnosis and the severity of the patient's condition. On the first day of hospitalization and on the day after the last dose of the antibiotic was carried out biochemical blood, scatological study and determination of the level of sIgA. Results. Due to the application of the diosmectit gel the antibiotic-associated diarrhea was developed in six times less frequently. After the cancellation of antibiotics the number of patients with normal sIgA in feces in the study group was in 2.4 times more than the control group. Due to the application of diosmectit gel significantly was decreased the level of LDH, cholesterol and triglycerides. Conclusions. Application of diosmectit gel is effective in the prevention of antibiotic-associated diarrhea. Key words: antibacterial therapy, antibiotic-associated diarrhea, prevention, diosmectit gel.Цель: изучить эффективность применения диосмектита геля у детей на фоне антибактериальной терапии острых инфекционных заболеваний. Пациенты и методы. Под наблюдением находилось 60 детей в возрасте от 3 до 17 лет, госпитализированных по поводу острой инфекционной патологии. Основную группу составили 30 детей, которые с первого дня назначения антибиотика дополнительно получали диосмектита гель. Контрольную группу составили 30 детей, получавших только общепринятую терапию. Длительность терапии составила от 7 до 14 дней, в зависимости от диагноза и тяжести состояния больного. В первые сутки госпитализации и на следующий день после последней дозы антибиотика проводили биохимическое исследование крови, копрологическое исследование и определение уровня sIgA. Результаты. На фоне применения диосмектита геля антибиотик-ассоциированная диарея розвивалась в шесть раз реже. После отмены антибиотиков количество больных с нормальными показателями sIgA в фекалиях в основной группе было в 2,4 раза больше, чем в контрольной. На фоне применения диосмектита геля достоверно снижался уровень ЛДГ, холестерина, триглицеридов. Выводы. Применение диосмектита геля является эффективным в профилактике антибиотик-ассоциированной диареи. Ключевые слова: антибактериальная терапия, антибиотик-ассоциированная диарея, профилактика, диосмектита гель.Мета: вивчити ефективність застосування діосмектиту гелю у дітей на тлі антибактеріальної терапії гострих інфекційних захворювань. Пацієнти і методи. Під наглядом знаходилось 60 дітей віком від 3 до 17 років, госпіталізованих з приводу гострої інфекційної патології. Основну групу склали 30 дітей, які з першого дня призначення антибіотика додатково отримували діосмектиту гель. Контрольну групу склали 30 дітей, які отримували лише загальноприйняту терапію. Тривалість терапії становила від 7 до 14 днів, залежно від діагнозу та важкості стану хворого. У першу добу госпіталізації та на наступний день після останньої дози антибіотика проводили біохімічне дослідження крові, копрологічне дослідження та визначення рівня sIgA. Результати. На тлі застосування діосмектиту гелю антибіотик-асоційована діарея розвивалась у шість разів рідше. Після відміни антибіотиків кількість хворих з нормальними показниками sIgA у фекаліях в основній групі була в 2,4 разу більшою, ніж у контрольній. На тлі застосування діосмектиту гелю достовірно знижувався рівень ЛДГ, холестерину, тригліцеридів. Висновки. Застосування діосмектиту гелю є ефективним у профілактиці антибіотик-асоційованої діареї. Ключові слова: антибактеріальна терапія, антибіотик-асоційована діарея, профілактика, діосмектиту гель

Systemic inflammation biomarkers in 6-OHDA- and LPS-induced Parkinson’s disease in rats

Hematological and immunological markers of systemic inflammation were studied in 6-hydroxydopamine (6-OHDA)- and lipopolysaccharide (LPS)-induced models of Parkinson’s disease (PD). Experiments were carried out on adult male Wistar rats: 1 – intact animals; 2 – sham-operated animals and 3 – 6-OHDA- and LPS-lesioned animals. PD development was confirmed by the results of behavioral testing (apomorphine test, open field test) and immunohistochemical detection of the loss of dopaminergic neurons. Hematological indices (complete blood count and differential leukocyte count (DLC)) were examined using hematological analyser. Immunological indices included phenotypic (CD206 and CD80/86) and metabolic (oxidative metabolism and phagocytic activity) characteristics of circulating monocytes (Mo) and granulocytes (Gr), which were determined by flow cytometry, as well as plasma levels of C-reactive protein, which were determined by ELISA. LPS-induced PD was associated with neutrophilia, 1.9 times increased neutrophil-to-lymphocyte ratio, 3 times increased platelet-to-lymphocyte ratio, and 3 times increased systemic immune inflammation index as compared to intact animals. Functional profile of circulating phagocytes from LPS-lesioned animals was characterized by the pro-inflammtory metabolic shift, as was indicated by 5 times increased oxidative metabolism indices and up-regulated CD80/86 expression along with decreased phagocytic activity and CD206 expression. 6-OHDA-lesioned rats demonstrated decreased DLC indices as compared to intact and sham-operated rats. Functional profile of circulating phagocytes in this model was characterized by anti-inflammatory shift. The results obtained from this study demonstrated that stereotaxic LPS-induced PD is appropriate rodent model for the study of systemic inflammation which is inherent for the disease pathophysiology

Carbohydrate composition of rat intestine surface mucus layer after ceftriaxone treatment

The epidemiological studies have shown that antibiotic treatment increases the susceptibility to inflammatory bowel disease development. The disturbance of mucus layer integrity might be one of the possible mechanisms. The aim of the present study was to investigate the effect of antibiotic ceftriaxone treatment on glycoproteins level and its carbohydrate composition in surface mucus layer of rat intestine. The study was done on male Wistar rats (140-160 g). Ceftriaxone (300 mg/kg, i.m.) was administered once a day for 14 days. The surface mucus from terminal ileum and colon were collected on the 15th, 29th and 72nd days of the experiment. Total level of mucus glycoproteins, hexoses, hexosamines, fucose and sialic acids were measured. Ceftriaxone administration did not affect the levels of glycoproteins in rat ileum. In the colon, the levels of glycoprotein were 1.3-fold decreased (Р < 0.05) on the 72nd day of the experiment. These changes were accompanied by the 1.2-fold decrease of hexoses (Р < 0.05) and 3.1-fold (Р < 0.05) decrease of fucose level and 1.5-fold (Р < 0.05) increase of the levels of sialic acids in the surface mucus of the rat colon. Thus, ceftriaxone administration induces the long-term changes in the levels of glycoproteins and carbohydrates composition in the rat colon surface mucus. This could potentially explain the susceptibility to inflammatory bowel disea­ses development

МЕТОД ВИМІРЮВАННЯ ПРОНИКНОСТІ ЕПІТЕЛІЮ ТОВСТОЇ КИШКИ ЩУРІВ У РІЗНІ ТЕРМІНИ ЕКСПЕРИМЕНТАЛЬНОГО КОЛІТУ

It was analyzed existing studies of epithelial barrier function in inflammatory bowel diseases and adapted the method of the colonic epithelial permeability in Wistar rats by Evans blue permeation from intestine into the blood. It was concluded about greater sensitivity of the Wistar rats compared to Sprague-Dawley and toxic effect of the high concentrations of the EB (3%). It’s more advisable usage of 2-fold less concentration of EB. It was established that EB moved more slow along the intestinal tract during experimental colitis comparing to the control group after per-os administration of EB. Such way of administration of EB is not recommended for usage in the colonic epithelial permeability. The optimal conditions of the studies on the colonic epithelial permeability is usage of the 1,5% EB administrated into isolated colonic loop and blood sampling in 15, 30, 45 and 60 minutes after EB administration.Был проведен анализ существующих методов исследования барьерной функции эпителия толстой кишки при воспалительных заболеваниях кишечнику и адаптирован метод определения проницаемости эпителия толстой кишки для крыс линии Wistar за проникновением краски Эванс синий из кишечнику в кровь. Сделаны выводы о большей чувствительностью крыс линии Wistar, по сравнению с крысами линии Sprague-Dawley, к токсическим воздействиям больших количеств красок. Установлено, что при пероральном введении движение краски ЭВ вдоль пищеварительного канала более медленный у крыс с экспериментальным колитом, по сравнению с контрольными крысами, поэтому этот метод является ненадежным для исследования изменений эпителиальной проницаемости кишечнику.Использование 3% концентрации краски Эванса при пероральном и введении в изолированный участок кишки, приводит к летальному исходу в экспериментах на крысах линии Wistar и не может быть рекомендован к использованию.Оптимальными условиями проведения исследований изменений эпителиальной проницаемости толстой кишки на крысах линии Wistar является введение в изолированный участок толстой кишки 1,5% краски ЭВ и определения ее концентрации в образцах плазмы крови через 15, 30, 45 и 60 минут.Було проведено аналіз існуючих методів дослідження бар’єрної функції епітелію товстої кишки при запальних захворюваннях кишечнику та адаптовано метод визначення проникності епітелію товстої кишки для щурів лінії Wistar за проникненням фарби Еванс синій із кишечнику в кров. Зроблено висновки про більшу чутливість щурів лінії Wistar, порівняно з щурами лінії Sprague-Dawley, до токсичних впливів великих кількостей фарб. Встановлено, що при пероральному введенні рух фарби ЕВ вздовж травного каналу більш повільний у щурів з експериментальним колітом, порівняно з контрольними щурами, тому цей метод є ненадійним для дослідження змін епітеліальної проникності кишечнику.Використання 3% концентрації фарби Еванса при пероральному та введенні в ізольовану ділянку кишки, призводить до летальних наслідків в експериментах на щурах лінії Wistar та не може бути рекомендованим до використання.Оптимальними умовами проведення досліджень змін епітеліальної проникності товстої кишки на щурах лінії Wistar є введення в ізольовану ділянку товстої кишки 1,5% фарби ЕВ та визначення її концентрації в зразках плазми крові через 15, 30, 45 та 60 хвилин

Role of Dopamine and D2 Dopamine Receptor in the Pathogenesis of Inflammatory Bowel Disease

Background: VEGF-induced vascular permeability and blood vessels remodeling are key features of inflammatory bowel disease (IBD) pathogenesis. Dopamine through D2 receptor (D2R) inhibits VEGF/VPF-mediated vascular permeability and angiogenesis in tumor models. In this study, we tested the hypothesis that pathogenesis of IBD is characterized by the disturbance of dopaminergic system and D2R activity. Methods: IL-10 knockout (KO) mice and rats with iodoacetamide-induced ulcerative colitis (UC) were treated intragastrically with D2R agonists quinpirole (1&nbsp;mg/100&nbsp;g) or cabergoline (1 or 5&nbsp;µg/100&nbsp;g). Macroscopic, histologic, and clinical features of IBD, colonic vascular permeability, and angiogenesis were examined. Results: Although colonic D2R protein increased, levels of tyrosine hydroxylase and dopamine transporter DAT decreased in both models of IBD. Treatment with quinpirole decreased the size of colonic lesions in rats with iodoacetamide-induced UC (p&nbsp;&lt;&nbsp;0.01) and reduced colon wet weight in IL-10 KO mice (p&nbsp;&lt;&nbsp;0.05). Quinpirole decreased colonic vascular permeability (p&nbsp;&lt;&nbsp;0.001) via downregulation of c-Src and Akt phosphorylation. Cabergoline (5&nbsp;µg/100&nbsp;g) reduced vascular permeability but did not affect angiogenesis and improved signs of iodoacetamide-induced UC in rats (p&nbsp;&lt;&nbsp;0.05). Conclusions: Treatment with D2R agonists decreased the severity of UC in two animal models, in part, by attenuation of enhanced vascular permeability and prevention of excessive vascular leakage. Hence, the impairment dopaminergic system seems to be a feature of IBD pathogenesis

Hyperplasia of the female reproductive organs in Ukraine

The aim: To determine the role of infectious diseases as the cause of the Cervical, Ovarian and Breast hyperplasia in Ukraine. Materials and methods: We conducted a retrospective multicenter cohort study from January 1st, 2020 to December 31st, 2022. This study included patients aged 20-59 years with a diagnosis of hyperproliferative pathology of the women reproductive organs without atypia, who sought medical care for hyperplastic processes admitted to the 12 hospitals from 9 regions of Ukraine. Results: We had examined 4,713 women; out of which 81.1% met the clinical definition of female reproductive organs hyperplasia. Of all hyperplasia cases, most frequently recorded types were breast hyperplasia (41,7%), followed by cervical hyperplasia (31,1%) and ovarian hyperplasia (27,2%). History of Cervicitis (p<0.001), Vaginal cuff infection (p<0.001), Oophoritis (p<0.001), and Mastitis (p<0.001) were identified as independent risk factors of Cervical, Ovarian and Breast hyperplasia. Conclusions: This study showed that surgical site infections after obstetric and gynecological operations are is the cause of Cervical, Ovarian and Breast hyperplasia. Therefore, early detection and treatment SSIs can reduce the risk of hyperplasia these organs

Role of Dopamine and D2 Dopamine Receptor in the Pathogenesis of Inflammatory Bowel Disease

Background: VEGF-induced vascular permeability and blood vessels remodeling are key features of inflammatory bowel disease (IBD) pathogenesis. Dopamine through D2 receptor (D2R) inhibits VEGF/VPF-mediated vascular permeability and angiogenesis in tumor models. In this study, we tested the hypothesis that pathogenesis of IBD is characterized by the disturbance of dopaminergic system and D2R activity. Methods: IL-10 knockout (KO) mice and rats with iodoacetamide-induced ulcerative colitis (UC) were treated intragastrically with D2R agonists quinpirole (1&nbsp;mg/100&nbsp;g) or cabergoline (1 or 5&nbsp;µg/100&nbsp;g). Macroscopic, histologic, and clinical features of IBD, colonic vascular permeability, and angiogenesis were examined. Results: Although colonic D2R protein increased, levels of tyrosine hydroxylase and dopamine transporter DAT decreased in both models of IBD. Treatment with quinpirole decreased the size of colonic lesions in rats with iodoacetamide-induced UC (p&nbsp;&lt;&nbsp;0.01) and reduced colon wet weight in IL-10 KO mice (p&nbsp;&lt;&nbsp;0.05). Quinpirole decreased colonic vascular permeability (p&nbsp;&lt;&nbsp;0.001) via downregulation of c-Src and Akt phosphorylation. Cabergoline (5&nbsp;µg/100&nbsp;g) reduced vascular permeability but did not affect angiogenesis and improved signs of iodoacetamide-induced UC in rats (p&nbsp;&lt;&nbsp;0.05). Conclusions: Treatment with D2R agonists decreased the severity of UC in two animal models, in part, by attenuation of enhanced vascular permeability and prevention of excessive vascular leakage. Hence, the impairment dopaminergic system seems to be a feature of IBD pathogenesis