Conectar
by Natalia Surzenko, Ashley Dominique, Taleen Hanania, Melville Osborne, Bassem F. El-Khodor
Polyamines (PAs), including spermidine, spermine and their precursor, putrescine, are ubiquitous molecules that are vital for a variety of physiological processes. Recently, PAs gained research attention because of their roles in promoting longevity and preventing age-related diseases. Circulating and tissue levels of PAs appear to decline with age, while higher intake of PAs in humans is correlated with better health during aging. Many foods, including plants and offal (organ meats), are good sources of dietary PAs, but are consumed much less in regions with prevailing Western diets. Elevating the circulating levels of PAs through dietary supplementation with PA-rich plant extracts or foods, on the other hand, has proven to be challenging, most likely due to their low bioavailability. In this study, we evaluated the effectiveness of nutritional supplements derived from bovine glandular tissues and/or plant material in elevating blood and tissue levels of spermidine, spermine and putrescine in adult rats. We detected appreciable amounts of PAs in the following materials: 1) spermidine-rich supplement (SRS), containing wheat germ, 2) a cytosolic fraction extract of bovine thymus gland (Thymus Cytosolic Fraction – TCF) and 3) a nuclear fraction extract of bovine thymus gland (Thymus Nuclear Fraction – TNF). We showed that all three PA-containing supplements also contain liposomes, with TNF displaying the largest amounts of liposomal PAs, as well as RNAs, among the tested supplements. We demonstrated that oral administration of SRS, TCF and TNF induce rapid changes in blood PA concentrations. Finally, we showed that TNF supplement is superior to SRS and TCF in elevating the levels of spermidine in the blood, liver and heart following a 28-day supplementation period. Considering the importance of PAs in prevention of age-related disease, supplementation with TNF could be a plausible approach towards the maintenance of proper cellular PA homeostasis during aging.Huge advances in rheumatoid arthritis (RA) treatment mean an increasing number of patients now achieve disease remission. However, long-term treatments can carry side effects and associated financial costs. In addition, some patients still experience painful and debilitating disease flares, the mechanisms of which are poorly understood. High rates of flare and a lack of effective prediction tools can limit attempts at treatment withdrawal. The BIOlogical Factors that Limit sustAined Remission in rhEumatoid arthritis (BIO-FLARE) experimental medicine study was designed to study flare and remission immunobiology. Here, we present the clinical outcomes and predictors of drug-free remission and flare, and develop a prediction model to estimate flare risk.
BIO-FLARE was a multicentre, prospective, single-arm, open-label experimental medicine study conducted across seven National Health Service Trusts in the UK. Participants had established RA in clinical remission (disease activity score in 28 joints with C reactive protein (DAS28-CRP)
The intervention was disease-modifying anti-rheumatic drug cessation, followed by observation for 24 weeks or until flare, with clinical and immune monitoring.
The primary outcome measure was the proportion of participants experiencing a confirmed flare, defined as DAS28-CRP≥3.2 or DAS28-CRP≥2.4 twice within 2 weeks, and time to flare. Exploratory predictive modelling was also performed using multivariable Cox regression to understand risk factors for flare.
121 participants were recruited between September 2018 and December 2020. Flare rate by week 24 was 52.3% (95% CI 43.0 to 61.7), with a median (IQR) time to flare of 63 (41–96) days. Female sex, baseline methotrexate use, anti-citrullinated peptide antibody level and rheumatoid factor level were associated with flare. An exploratory prediction model incorporating these variables allowed estimation of flare risk, with acceptable classification (C index 0.709) and good calibration performance.
The rate of flare was approximately 50%. Several baseline clinical parameters were associated with flare. The BIO-FLARE study design provides a robust experimental medicine model for studying flare and remission immunobiology.
ISRCTN registry 16371380
FreshRSS 