Background: Malnutrition due to insufficient intake of micronutrients, or due to impaired delivery of micronutrients to patients’ cells, is suppressing immune functions that are fundamental to host protection. Concurrently, an excessive triggering of patients’ immune reactions as the result of adverse responses to certain food antigens, can also lead to various chronic health conditions.Objective: To examine nutritional and immunological status in patients’ groups varying in age, dietary regimens and gastrointestinal condition; and explore a possible correlation between an impaired patients’ immune status and micronutrient deficiencies, food sensitivity and oxidative stress responses.Methods: This is a population-based study consisting of a American residents, age 13 and older, who completed the investigator’s provided questionnaires with application of cell-based individualized functional assays. Data for this paper were collected from 845 individuals between May and September 2019, as part of CSS CNA beta study. Micronutrient deficiencies, immune Redox status, antioxidative responses and food sensitivity profiles were assessed for each patient participating in this study.Results: The group of patients with low Redox status demonstrated significantly higher percent of immune reactivity (17%) to food antigens as compared to15% reactivity detected in the groups with the average and strong Redox response. An average number of identified micronutrient deficiencies, as well as beneficial anti-oxidative protective compounds, was also significantly higher in the group with the weak immune function as compared to other two groups.Conclusion: This study suggests that high food sensitivity is associated with a higher nutrient deficiency, a stronger oxidative stress response and a lower immune redox status.
Background. 5-fluorouracil (5-FU) is an effective chemotherapeutic agent used widely in the treatment of gastrointestinal and breast cancers. However its use is associated with severe (≥Grade 3) normal tissue toxicities, including mucositis. Although deleterious variants in DPYD have been associated with the development of these side effects, the sensitivity of DPYD genotyping tests is poor (<25%) and for many individuals the underlying cause of these adverse events is unknown. In addition, the transport processes mediate 5-FU influx and efflux in normal tissues are poorly understood. Methods. We have developed a functional assay to characterise 5-FU transport into primary human cells. Uptake of [2 -14C] 5-FU (μM, 37°C) into a) buccal mucosal cells (BMCs) and b) peripheral blood mononuclear cells (PBMCs) was assessed ex vivo in a cohort of healthy volunteers (n=25). BMC uptake was retested weekly and/or monthly for up to five months in a subset these participants (n=16) to determine intra-individual variability in 5-FU uptake. Results. Uptake of 5-FU into BMCs was temperature dependent and saturable. Significant (p<0.0001) inter-individual variability was observed at the initial test, with 5-FU uptake into BMCs ranging from 0.5 to 13.4 pmol.min -1 .10 5 live cells -1 across 25 healthy participants. Repeated phenotype testing demonstrated intra-individual variability in BMC 5-FU uptake in some participants (e.g. 5FU002, range 2.0-56.4 pmol.min -1 .10 5 live cells -1 ) but not in others (e.g. 5FU015, range 0.0-1.3 pmol.min -1 .10 5 live cells -1 . In contrast to the BMC data, no uptake of 5-FU into PBMCs was detected. Conclusions. 5-FU is highly muco-toxic, with the prevalence of mucositis reported to be between 20-50% following treatment with chemotherapeutic regimens that include this drug. To date there has been little focus on the mechanisms that mediate 5-FU accumulation into these cells. Our data show that transport of 5-FU into primary human BMCs, unlike PBMCs, is variable both between and within individuals. The impact of this process on the development of 5-FU induced normal tissue toxicities is worthy of further investigation.
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