Epidemiological studies revealed that antibiotics exposure increases a risk of inflammatory bowel diseases (IBD) development. It remained largely unknown how antibiotic-induced dysbiosis confers the risk for enhanced inflammatory response. The aim of the present study was to test the hypothesis that SCFAs, their receptors and transporters mediate the antibiotic long-term effects on the functional state of colonic mucosa and susceptibility to the experimental colitis. Male Wistar rats were treated daily for 14 days with antibiotic ceftriaxone (300 mg/kg, i.m.) or vehicle; euthanized by CO 2 inhalation followed by cervical dislocation in 1, 14 or 56 days after antibiotic withdrawal. We found increased cecum weight and sustained changes in microbiota composition after ceftriaxone treatment with increased number of conditionally pathogenic enterobacteria, E . coli , Clostridium , Staphylococcus spp . and hemolytic bacteria even at 56 days after antibiotic withdrawal. The concentration of SCFAs was decreased after ceftriaxone withdrawal. We found decreased immunoreactivity of the FFA2, FFA3 receptors, SMCT1 and increased MCT1 & MCT4 transporters of SCFAs in colon mucosa. These changes evoked a significant shift in colonic mucosal homeostasis: the disturbance of oxidant-antioxidant balance; activation of redox-sensitive transcription factor HIF1α and ERK1/2 MAP kinase; increased colonic epithelial permeability and bacterial translocation to blood; morphological remodeling of the colonic tissue. Ceftriaxone pretreatment significantly reinforced inflammation during experimental colitis 56 days after ceftriaxone withdrawal, which was confirmed by increased histopathology of colitis, Goblet cell dysfunction, colonic dilatation and wall thickening, and increased serum levels of inflammatory cytokines (TNF-α and IL-10). Since the recognition of the importance of microbiota metabolic activity rather than their composition in the development of inflammatory disorders, e.g. IBD, the present study is the first report on the role of the SCFA system in the long lasting side effects of antibiotic treatment and its implication in IBD development.

Short-chain fatty acids (SCFAs) T he interchange of low molecular weight metabolites between gut microorganisms and macroorganism have attracted a lot of attention during last years [1][2][3]. The gut microbiota affects predominantly host physiology by the production of short-chain fatty acids (SCFAs). SCFAs are saturated aliphatic organic acids that consist of one to six carbons of which acetate (C2), propionate (C3), and butyrate (C4) are most abundant (≥95%). Acetate, propionate, and butyrate are present in an approximate molar ratio of 60:20:20 in the colon and stool [4]. Depending on the diet, the total maximum concentration of SCFAs decreases from 70 to 140 mM in the proximal colon from 20 to 70 mM in the distal colon [5].These metabolites, especially butyrate, serve as an important source of energy for the intestinal epithelial cells, providing about 60-70% of their ener gy demand. Colonocytes from germ-free mice are in an energy-deprived state and exhibit decreased expression of enzymes that catalyze key steps in intermediary metabolism including the tricarboxylic acid cycle. Consequently, there is a marked decrease in NADH/NAD + , oxidative phosphorylation, and ATP levels, that results in AMP-activated protein kinase activation, cyclin-dependent kinase inhibitor 1B phosphorylation and autophagy. When butyrate is added to germ-free colonocytes, it rescues their deficit in mitochondrial respiration and prevents them from undergoing autophagy [6].

Cryptococcosis is an infrequent but treatable opportunistic infection of HIV-infected children. The diagnosis of HIV in this case was not clear at admission but clinical history was consisted of several typical signs like body weight loss, recurrent temperature, episode of severe bacterial disease. In all patients with fever, headache, meningismus and CD4 + T-lymphocyte deficiency should be suspected cryptococcosis.

Резюме. В статті описані етіологія, патогенез, клініка, діагностика та лікування герпетичних енцефалітів. Наведені дані власних спостережень за дітьми з герпетичним енцефалітом. Рання діагностика захворювання з використанням ацикловіру значно покращує перебіг хвороби та знижує летальність.

Due to the growing resistance of bacteria to antibacterial drugs, the treatment of pneumonia remains topical medical issue. The article provides international recommendations on the use of antibiotics in the treatment of community-acquired pneumonia in children. Numerous experimental and clinical studies have revealed high efficacy of azithromycin even in the presence of resistant strains. This is due to the peculiarities of pharmacokinetics, pharmacodynamics and the versatility of the mechanisms of action of the drug. To date, azithromycin has not lost its position in the treatment of community-acquired pneumonia, especially in the children.