Influence of iron on the gut microbiota in colorectal cancer

© 2020 The Authors. Published by MDPI. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.3390/nu12092512Perturbations of the colonic microbiota can contribute to the initiation and progression of colorectal cancer, leading to an increase in pathogenic bacteria at the expense of protective bacteria. This can contribute to disease through increasing carcinogenic metabolite/toxin production, inducing inflammation, and activating oncogenic signaling. To limit disease progression, external factors that may influence the colonic microbiota need to be considered in patients with colorectal cancer. One major factor that can influence the colonic microbiota is iron. Iron is an essential micronutrient that is required by both prokaryotes and eukaryotes for cellular function. Most pathogenic bacteria have heightened iron acquisition mechanisms and therefore tend to outcompete protective bacteria for free iron. Colorectal cancer patients often present with anemia due to iron deficiency, and thus they require iron therapy. Depending upon the route of administration, iron therapy has the potential to contribute to a procarciongenic microbiota. Orally administered iron is the common treatment for anemia in these patients but can lead to an increased gut iron concentration. This suggests the need to reassess the route of iron therapy in these patients. Currently, this has only been assessed in murine studies, with human trials being necessary to unravel the potential microbial outcomes of iron therapy.Published onlin

SARS-CoV-2 vaccines and donor recruitment for FMT

Non peer reviewe

The Gut Microbiota and the Hepatologist: Will Our Bugs Prove to be the Missing Link?

The advent of next-generation sequencing has enabled in-depth analysis to study the composition and function of the gut microbiota in a culture-independent manner. Consequently, this has led to rapid interest in understanding the pathogenesis and progression of chronic liver disease in relation to perturbations of the gut microbiota. Animal models and human studies have demonstrated its crucial role in contributing to disease mechanisms in alcoholic and non-alcoholic liver disease and more recently in primary sclerosing cholangitis. There is increasing evidence to suggest that the gut microbiota and its components influence the development and modulation of chronic liver damage through direct communication via the portal system, metabolite production, alterations in gut barrier integrity, liver/gut immune axis and bile acid metabolism. The impact of microbiota-directed therapies for liver disease is still in its infancy. Better understanding of its role in disease mechanisms will lead to a more targeted approach in modulation of gut microbiota to influence both progression and complications of liver disease. This review discusses the current evidence for the gut microbiota-liver axis and its role in the development, progression and treatment of liver disease

Development and Validation of an HPLC Method for the assay of Formoterol Using Electrochemical Detection System

A novel High performance liquid chromatography (HPLC) method for analysis of formoterol in dry powder inhaler has been developed and validated. A formulation containing formoterol and a carrier lactose with a target concentration of formoterol blend 0.266 % w/w was prepared and filled in an Airmax NB7/2 inhaler followed by pharmaceutical performance testing and analysed by HPLC with electrochemical detection. The validationand pharmaceutical performance testing was performed by FDA and ICH regulations for the validation of pharmaceutical samples. The samples were injected onto a reverse phase waters symmetry column maintained at 30 ⁰ C. The mobile phase consisted of potassium di-hydrogen orthophosphate buffer: acetonitrile (79:21, V/V) and the formoterol peak was detected at the following detector settings on the Decade digital electrochemical detector (ECD). Detector settings: working electrode potential (Eox): 0.65 V, Guard cell potential ( E twin ) : 0.70 V. Range select: nano amps, Range: 50 nano amps, Offset: 20%, Filter: 0.1 seconds. The mean blend strength was 0.269 % w/w. Recovery 101.1% and the blend homogeneity (RSD) / % was 0.9. The uniformity of the delivered dose for 6 µg product was DPA/µg: 5.6 ±0.5 and for 12 µg product was DPA/µg : 11.3 ± 08. The fine particle dose for 6 µg product was FPD/µg: 2.4 ± 0.1 and for 12 µg product was FPD/µg: 4.7 ± 0.2. The calibration curve was linear ( r2= 0.9968) over formoterol concentrations ranging from 0.1 to 0.7 µg/ml (n=7). Intra and inter day relative standard deviation (RSD) of variation between 0.3 and 4.1 and accuracy percentage recovery was between 92-108 %. Formoterol was stable over 3 day’s precision. Limit of quantification was 0.1 µg/ml and the limit of detection was 0.0625 µg/ml. The method is selective, reproducible and even though the linearity range is 0.1 µg/ml to 0.7 µg/ml the method has the capacity to be used for determination of formoterol in dry powder inhaler

Long term outcomes of initial infliximab therapy for inflammatory pouch pathology:a multi-Centre retrospective study

Background: Restorative proctocolectomy with ileal pouch-anal anastomosis is considered the procedure of choice in patients with ulcerative colitis refractory to medical therapy. Subsequent inflammation of the pouch is a common complication and in some cases pouchitis fails to respond to antibiotics, the mainstay of treatment. In such cases, corticosteroids, immunomodulatory or biologic treatments are options. However, our understanding of the efficacy of anti-tumour necrosis factor medications in both chronic pouchitis and Crohn’s-like inflammation are based on studies that include relatively small numbers of patients. Methods: This was an observational, retrospective, multi-centre study to assess the long-term effectiveness and safety of infliximab for inflammatory disorders related to the ileoanal pouch. The primary outcome was the development of infliximab failure defined by early failure to infliximab or secondary loss of response to infliximab. Results: Thirty-four patients met the inclusion criteria; 18/34 (53%) who were initiated on infliximab for inflammatory disorders of the pouch had infliximab failure, 3/34 (8%) had early failure, and 15/34 (44%) had secondary loss of response with a median follow-up of 280 days (range 3-47 months). In total, 24/34 (71%) avoided an ileostomy by switching to other medical therapies at a median follow-up of follow-up of 366 days (1-130 months). Conclusions: Initial infliximab therapy for pouch inflammatory conditions is associated with Infliximab failure in just over half of all patients. Despite a high failure rate, an ileostomy can be avoided in almost three quarters of patients at four years by using other medical therapies