Increased risk of colorectal cancer (CRC) in inflammatory bowel disease (IBD) patients has been attributed to long-standing chronic inflammation, with the contribution of genetic alterations and environmental factors such as the microbiota. Moreover, accumulating data indicate that IBD-associated CRC (IBD-CRC) may initiate and develop through a pathway of tumorigenesis distinct from that of sporadic CRC. This mini-review summarizes the current knowledge of IBD-CRC, focusing on the main mechanisms underlying its pathogenesis, and on the important role of immunomodulators and biologics used to treat IBD patients in interfering with the inflammatory process involved in carcinogenesis.

A mutualistic relationship between the composition, function and activity of the gut microbiota (GM) and the host exists, and the alteration of GM, sometimes referred as dysbiosis, is involved in various immune-mediated diseases, including inflammatory bowel disease (IBD). Accumulating evidence suggests that the GM is able to influence the efficacy of the pharmacological therapy of IBD and to predict whether individuals will respond to treatment. Additionally, the drugs used to treat IBD can modualate the microbial composition. The review aims to investigate the impact of the GM on the pharmacological therapy of IBD and vice versa. The GM resulted in an increase or decrease in therapeutic responses to treatment, but also to biotransform drugs to toxic metabolites. In particular, the baseline GM composition can help to predict if patients will respond to the IBD treatment with biologic drugs. On the other hand, drugs can affect the GM by incrementing or reducing its diversity and richness. Therefore, the relationship between the GM and drugs used in the treatment of IBD can be either beneficial or disadvantageous.

Diseases affecting the immune system, such as inflammatory bowel disease (IBD), juvenile idiopathic arthritis (JIA), and acute lymphoblastic leukemia (ALL), are pathological conditions affecting the pediatric population and are often associated with alterations in the intestinal microbiota, such as a decrease in bacterial diversity. Growing evidence suggests that gut microbiota can interfere with chemotherapeutic and immunosuppressant drugs, used in the treatment of these diseases, reducing or facilitating drug efficacy. In particular, the effect of intestinal microflora through translocation, immunomodulation, metabolism, enzymatic degradation, and reduction of bacterial diversity seems to be one of the reasons of interindividual variability in the therapeutic response. Although the extent of the role of intestinal microflora in chemotherapy and immunosuppression remains still unresolved, current evidence on bacterial compositional shifts will be taken in consideration together with clinical response to drugs for a better and personalized therapy. This review is focused on the effect of the intestinal microbiota on the efficacy of pharmacological therapy of agents used to treat IBD, JIA, and ALL.

Purpose In the era of antibiotic resistance, there is an increased interest in antiseptic solutions that might represent a reliable option for ocular surface disinfection. The objective of this study is to compare for the first time three different antiseptic ophthalmic preparations to assess their in vitro antimicrobial activity. Methods The antiseptic activity of three commercial ophthalmic solutions, IODIM (povidone-iodine 0.6% in hyaluronic acid vehicle—Medivis, Catania, Italy), OZODROP (nanoemulsion with ozonated oil—concentration not specified—FBVision, Ophthalmic Pharmaceuticals, Rome, Italy), and DROPSEPT (chlorhexidine 0.02% and vitamin E 0.5% Tocopherol Polyethylene Glycol 1000 Succinate—TPGS, Sooft Italia, Montegiorgio, Italy), was tested in vitro on six reference strains by time-killing assays. Viable cells were evaluated after 1, 15, 30 min; 2, 6, and 24 h exposure by seeding 100 µl of the suspension (or appropriate dilutions) on LB agar or Sabouraud-dextrose agar. All plates were incubated at 37 °C for 24 h and evaluated by manually counting the colonies. Results IODIM solution showed a very rapid microbicidal activity: the number of viable cells for all the tested strains was under the detection limit (less than 10 CFU/ml) already after 1 min exposure, and this result was maintained at every incubation time. The rapid antimicrobial activity of povidone-iodine was not replicated when testing the other two antiseptics. Conclusions The study reports the great efficacy in reducing bacterial load in a very short time of povidone-iodine 0.6% compared with other antiseptic preparations.

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PACSIN2 variants are associated with gastrointestinal effects of thiopurines and thiopurine methyltransferase activity through an uncharacterized mechanism that is postulated to involve autophagy. This study aims to clarify the role of PACSIN2 in autophagy and in thiopurine cytotoxicity in leukemic and intestinal models. Higher autophagy and lower PACSIN2 levels were observed in inflamed compared with non-inflamed colon biopsies of inflammatory bowel disease pediatric patients at diagnosis. PACSIN2 was identified as an inhibitor of autophagy, putatively through inhibition of autophagosome formation by a protein–protein interaction with LC3-II, mediated by a LIR motif. Moreover, PACSIN2 resulted a modulator of mercaptopurine-induced cytotoxicity in intestinal cells, suggesting that PACSIN2-regulated autophagy levels might influence thiopurine sensitivity. However, PACSIN2 modulates cellular thiopurine methyltransferase activity via mechanisms distinct from its modulation of autophagy.

Background To date, measurement of intracellular cystine is used for the therapeutic monitoring of patients affected by cystinosis in treatment with cysteamine. Since this method is time and sample consuming, development of a faster method to quantify cysteamine would be extremely useful in order to help clinicians to adjust dosages of cysteamine and to define better the pharmacokinetic profile of this drug. The aim of the study was to develop a liquid chromatography tandem mass spectrometry method for the quantification of cysteamine in plasma samples and to test its applicability on plasma samples derived from patients with nephropathic infantile cystinosis in treatment with cysteamine. Results The percentage of accuracy of the developed method varied between 97.80 and 106.00% and CV% between 0.90 and 6.93%. There was no carry over. The calibration curves were built from 2.5 to 50 µM. The limit of detection and the lower limit of quantification occurred at 0.25 and 1.25 µM respectively. Cysteamine was stable up to 2 months at -20 °C. Concentrations of cysteamine and intracellular cystine of 4 patients were in line with data previously reported. Conclusion The proposed method showed an appropriate selectivity, specificity, linearity, sensibility, accuracy, precision and good applicability to samples.

Background A general consensus exists that patients with inflammatory bowel disease (IBD) present compositional changes in the gut microbiota (dysbiosis), including an increase in the abundance of Enterobacteriaceae. Thiopurine drugs are commonly used in the maintenance of remission in IBD. In this context, the purpose of the project is to explore the role of candidate bacterial strains in mediating the effects of thiopurines in vitro. Methods Azathioprine (AZA), mercaptopurine (MP) and thioguanine (TG) (400 µM) were incubated in minimal salts medium (M9) in presence or not of E. coli, S. enterica and K. pneumoniae and of their growth phase broths (GPB) for 4 h at 37°C. The viability of NALM6 (B cells) and JURKAT (T cells) exposed to serial dilution of drugs (ranging from 0.2 to 15 μM of AZA, from 0.3 to 20 μM of MP, from 0.08 to 5 μM of TG) previously incubated or not with bacteria and with their GPB was determined by the MTT assay. Absorbance peaks of thiopurines were analysed by UV spectrophotometry. Statistical significance was assessed by two-way ANOVA and Bonferroni’s post-test for MTT tests and by one-way ANOVA for UV spectra. Results In NALM6 cells, the cytotoxic effects of 15 μM of AZA, 2.5 μM of MP and 1.25 μM of TG decreased significantly (p < 0.001) after incubation with K. pneumoniae (respectively 45 ± 2.9%; 34 ± 2.5%% and 21 ± 0.6%) and its GPB (respectively 41 ± 7.7%; 41 ± 5.1% and 27 ± 3.5%) compared with the drugs not previously exposed (respectively 76 ± 2.3%; 69 ± 1.7% and 43 ± 3.8%). In JURKAT cells, the cytotoxic effects of 15 μM of AZA, 2.5 μM of MP and 1.25 μM of TG decreased significantly (p < 0.001) after incubation with K. pneumoniae (respectively 46 ± 2.8%; 38 ± 1.29% and 19 ± 3.3%) and its GPB (respectively 49 ± 9.4%; 38 ± 1.5% and 26 ± 1.5%) in comparison with the drugs not exposed (respectively 75 ± 4.0%; 50 ± 3.5% and 54 ± 4.0%). E. coli and S. enterica did not affect the cytotoxicity of the thiopurines. UV analysis evidenced a reduction of absorbance peaks of AZA (21 ± 0.05%), MP (32 ± 0.015%) and TG (30 ± 0.03%) after incubation with K. pneumoniae but not with its growth phase broth (GPB). Conclusion The activity of thiopurines decreased after incubation with both K. pneumoniae and its GPB. UV analysis suggested that the lower cytotoxicity of thiopurines exposed to the bacterial strain is due to the reduction of the concentration of the drugs exposed to K. pneumoniae. Moreover, the reduction of drug availability after the exposure to GPB could be explained with a possible interaction between thiopurines and capsular polysaccharides released by the bacteria.