Synthesis and Structural Study of Amidrazone Derived Pyrrole-2,5-Dione Derivatives: Potential Anti-Inflammatory Agents.

1H-pyrrole-2,5-dione derivatives are known for their wide range of pharmacological properties, including anti-inflammatory and antimicrobial activities. This study aimed to synthesize new 3,4-dimethyl-1H-pyrrole-2,5-dione derivatives 2a-2f in the reaction of N3-substituted amidrazones with 2,3-dimethylmaleic anhydride and evaluate their structural and biological properties. Compounds 2a-2f were studied by the 1H-13C NMR two-dimensional techniques (HMQC, HMBC) and single-crystal X-ray diffraction (derivatives 2a and 2d). The anti-inflammatory activity of compounds 2a-2f was examined by both an anti-proliferative study and a production study on the inhibition of pro-inflammatory cytokines (IL-6 and TNF-α) in anti-CD3 antibody- or lipopolysaccharide-stimulated human peripheral blood mononuclear cell (PBMC) cultures. The antibacterial activity of compounds 2a-2f against Staphylococcus aureus, Enterococcus faecalis, Micrococcus luteus, Esherichia coli, Pseudomonas aeruginosa, Yersinia enterocolitica, Mycobacterium smegmatis and Nocardia corralina strains was determined using the broth microdilution method. Structural studies of 2a-2f revealed the presence of distinct Z and E stereoisomers in the solid state and the solution. All compounds significantly inhibited the proliferation of PBMCs in anti-CD3-stimulated cultures. The strongest effect was observed for derivatives 2a-2d. The strongest inhibition of pro-inflammatory cytokine production was observed for the most promising anti-inflammatory compound 2a.

Small intestinal bacterial overgrowth in adult patients with type 1 diabetes: its prevalence and relationship with metabolic control and the presence of chronic complications of the disease.

INTRODUCTION Gastrointestinal symptoms may occur in 50% to 70% of patients with diabetes. OBJECTIVES The aim of this study was to evaluate the prevalence of small intestinal bacterial overgrowth (SIBO) in patients with diabetes, as well as the relationship between SIBO and metabolic control of diabetes and the presence of chronic complications of the disease. PATIENTS AND METHODS The study group included 148 patients with type 1 diabetes, treated in the years 2013-2015. The control group consisted of 41 healthy volunteers. The presence of SIBO was assessed with a noninvasive breath test using 20 g of lactulose suspended in 200 ml of water, with the assessment of exhaled hydrogen concentrations. The measurements were performed at 15-minute intervals in the first hour and at 30-minute intervals in the second hour of the test. A positive result was considered as the output value of exhaled hydrogen of 20 parts per million (ppm) or higher or an increase in the output value of the exhaled hydrogen of 12 ppm during the first 60 minutes of the test.  RESULTS We observed a lower prevalence of SIBO in the study group in comparison with controls (56 patients [37.8%] vs 30 healthy volunteers [73%]; P = 0.006). In the logistic regression model, this association was independent of age, sex, body mass index, cigarette smoking, serum C-reactive protein concentrations, and estimated glomerular filtration rate (odds ratio, 0.26; 95% confidence interval, 0.10-0.68; P = 0.006). CONCLUSIONS The prevalence of SIBO in patients with type 1 diabetes is lower than that in healthy subjects. One of the possible causes might be the beneficial effect of nutritional therapy in patients with diabetes.