Tumor Necrosis Factor-α and Muc2 Mucin Play Major Roles in Disease Onset and Progression in Dextran Sodium Sulphate-Induced Colitis

The sequential events and the inflammatory mediators that characterize disease onset and progression of ulcerative colitis (UC) are not well known. In this study, we evaluated the early pathologic events in the pathogenesis of colonic ulcers in rats treated with dextran sodium sulfate (DSS). Following a lag phase, day 5 of DSS treatment was found clinically most critical as disease activity index (DAI) exhibited an exponential rise with severe weight loss and rectal bleeding. Surprisingly, on days 1-2, colonic TNF-α expression (70-80-fold) and tissue protein (50-fold) were increased, whereas IL-1β only increased on days 7-9 (60-90-fold). Days 3-6 of DSS treatment were characterized by a prominent down regulation in the expression of regulatory cytokines (40-fold for IL-10 and TGFβ) and mucin genes (15-18 fold for Muc2 and Muc3) concomitant with depletion of goblet cell and adherent mucin. Remarkably, treatment with TNF-α neutralizing antibody markedly altered DSS injury with reduced DAI, restoration of the adherent and goblet cell mucin and IL-1β and mucin gene expression. We conclude that early onset colitis is dependent on TNF-α that preceded depletion of adherent and goblet cell mucin prior to epithelial cell damage and these biomarkers can be used as therapeutic targets for UC

diagnostic utility of procalcitonin in children with infectious complications during chemotherapy-induced neutropenia: single center experience, literature review

Background. Infectious complications cause significant mortality in children with oncological diseases during chemotherapy-induced neutropenia. The absence of sensitive and specific signs and symptoms of infectious conditions as well as its microbiological identification, leads to inappropriate antibiotic exposure. The use of laboratory biomarkers (procalcitonin (PCT) and C-reactive protein (CRP)) may be helpful for differential diagnostics of inflammatory conditions and for rational antimicrobial therapy.Objective: to assess the current value of PCT as an additional marker for differentiating inflammatory conditions in children with chemotherapy-induced neutropenia.Materials and methods. We presented the analysis of infectious complications in pediatric patients with oncological and onco- / hematological diseases between 2017–2020 (54 patients from 2 mnths – 17 years). PCT and CRP with clinical and instrumental diagnostic data were used for differential diagnosis of fever and development of antimicrobial therapy decision rules. Literature review concerning the discussed theme from 2006–2018 was done.Results. Eighty-five infectious episodes in 36 months were registered, among them 42 in pts with onco- / hematological diseases and 43 – with solid tumors. In the group of bacterial infectious complications mean CRP and PCT values were significantly higher than in group of nonbacterial, moreover the discriminative value was higher for PCT. We revealed the correlation between severity of infectious complications and values of markers of acute-phase reactions. In case of non-severe bacterial complications and other types of infections significant difference was revealed only for PCT mean values.Conclusion. Specificity of PCT concentration in bacterial infections exceeds that of CRP, which confirms the hypothesis of advantages in using PCT as differential marker of inflammatory conditions in children with malignancies

The microbiome role in pathogenesis of inflammatory and immune alterations of gastrointestinal tract in pediatric patients with cancer

Infectious complications remain one of the most significant problem associated with anticancer therapy in oncological patients. Cytotoxic, radiation and antibacterial therapy induce dysbiosis and gastrointestinal mucosal barrier injury. These changes lead to the mucositis, thereby increasing the risk of endogenous microflora translocation with following probable development of severe infectious and inflammatory diseases. In addition, current evidence suggests that there is a relationship between gut microbiome disturbances and post-transplant graft versus host disease development. The article presents the existing paradigms of determining the role of gastrointestinal tract functional condition in cancer patients in order to optimize prevention and antimicrobial treatment approaches

Hepatic injury and gluconeogenesis after subcutaneous injection of monochloroacetic acid in rats

Objective: Monochloroacetic acid (MCA) is corrosive to skin, and causes not only chemical injury but also fatal systemic poisoning. Little is known about the cause of death. We studied the acute toxicity of MCA before clinical symptoms appeared in fasting rats. Methods: Blood samples were analyzed 2 h after subcutaneous MCA injection (Ld90: 162 mg/ml kg body weight). Control rats were injected with saline. Results: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were about 1.5-fold higher than in the controls, and mitochondrial AST (mAST) was 2-fold higher. Blood urea nitrogen and creatinine were significantly increased, while serum glucose was significantly decreased in the treated group. Lactate was 6-fold higher and pyruvate was 13-fold higher than in the controls. Conclusions: MCA caused injury to the liver and kidneys but these injuries were slight. However, the larger increase in mAST indicated that hepatocellular mitochondria were selectively targeted. Hepatocellular mitochondrial injury decreased gluconeogenesis and caused hypoglycemia and extremely high levels of lactate and pyruvate. Hypoglycemia and lactic acidosis were insidious before the critical symptoms appeared and this combination accelerated to death, affecting other organs such as the heart and brain. Nosotropic therapy of these abnormalities up to the appearance of symptoms may help to establish an early therapy for skin exposure to MCA