Current overview of functions of FoxO proteins, with special regards to cellular homeostasis, cell response to stress, as well as inflammation and aging.

FoxO transcription factors act at the interconnections between metabolic pathways inducible by many important signal transducers and mediators, such as p53, Ikk-ß, NFKB, Akt, sirtuins, PTEN, and others. This may account for a crucial significance of disruptions in FoxO functions both in many kinds of diseases (including cancer, chronic inflammatory diseases, degenerative diseases, obesity, polymetabolic syndrome) and in some disease-like conditions (such as inflammaging, cachexia related to chronic inflammation, cancer-promotion by some chronic inflammatory responses, and the aging process itself). This paper reviews complex interactions between FoxOs and other signal transducers, trying to pinpoint how exactly disruptions of FoxO functions may occur, and how they may contribute to occurrence, development or complications of the conditions mentioned above.

Decrease in expression of histamine H2 receptors by human amniotic epithelial cells during differentiation into pancreatic beta-like cells.

OBJECTIVE AND DESIGN: Considering the role of histaminergic pathway in the differentiation of stem cells, we compared expression patterns of H(1) and H(2) receptors in the human amniotic epithelial cells (HAEC) culture at different stages of nicotinamide-induced differentiation into PBLC with the control HAEC. MATERIAL AND METHODS: HAEC isolated after term pregnancies (N = 12) were cultured in vitro. Altogether, 72 cultures were established. The culture medium in the studied group was supplemented on Day 5 with nicotinamide (10 mM). C-peptide concentration in the medium collected every 3 days for 15 days was determined immunoenzymatically as a marker of differentiation. At the same intervals the cultures were formalin-fixed and paraffinembedded for H(1) and H(2) receptors immunostaining. Quantitative immunohistochemistry was applied for evaluation of H(1) and H(2) expression. RESULTS: C-peptide was detected on Day 6 and the levels were kept gradually increased until Day 12, then stayed at almost the same level, 3.7-fold higher than initially. Expression of H(2) was unchanged until Day 9 after nicotinamide addition, then was significantly (p < 0.05) decreased and amounted (mean % value for the measurements performed on Day 12 and Day 15, +/-SEM) 49.73 +/- 11.03 of the reference value obtained in control HAEC. CONCLUSION: Variable expression of H(2) during nicotinamide-induced differentiation of HAEC into PBLC may define a time-point, indicating involvement of histamine at the earlier stages.

Histamine in pericarditis of children with congenital heart malformations.

INTRODUCTION: Congenital heart malformations are risk factors that make children susceptible to infections resulting in inflammation. MATERIAL AND METHODS: The concentration of histamine as a modulator of inflammation was quantified in pericardial fluid and expression of histamine H(4) receptor (H(4)R) and histamine-releasing factor (HRF) was determined at mRNA and protein levels. Samples of pericardium and pericardial fluid were obtained during cardiac reconstruction surgery in children. RESULTS: In children with pericarditis, increased levels of histamine were found and expression of H(4)R was localized on mast cells. Expression of HRF was independent of presence or absence of inflammation in pericardium and was localized within stationary epithelial cells. CONCLUSION: Results indicate that involvement of H4R in pericardial inflammation depends on penetration of mast cells into inflamed tissue, but HRF may not be directly involved in inflammatory reaction of the pericardium.

Cryotherapy decreases histamine levels in the blood of patients with rheumatoid arthritis.

INTRODUCTION: Conventional physiotherapy (electrotherapy, magnetic fields), kinesitherapy, and whole-body cryotherapy (plus kinesitherapy) are used to relieve pain and inflammation or to improve function in rheumatic diseases. The aim of this study was to investigate the effects of different physiotherapies and cryotherapy on biochemical blood parameters of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). MATERIALS AND METHODS: Twenty patients with RA and 17 patients with OA received whole-body cryotherapy at -140 to -160 degrees C for 2 to 3 min, once daily for 4 weeks. The second group of patients (24 with RA and 28 with OA) received conventional physiotherapy for 4 weeks. We measured the parameters of neutrophil activation (respiratory burst, calprotectin) and markers of cartilage metabolism [N-acetyl-beta-D-hexosaminidase (NAHase), ectonucleotide pyrophosphohydrolase (NTPPHase)] twice: before and 3 months after cryotherapy or physiotherapy. RESULTS: We showed, for the first time, that cryotherapy significantly reduced (P < 0.001) histamine levels in the blood of patients with RA. The effect was long-lasting (for at least 3 months). The levels of blood histamine in patients with OA were not changed significantly. Cryotherapy also downregulated the respiratory burst of PMNs and NAHase activity and upregulated calprotectin levels and the activity of NTPPHase. However, these changes were not statistically significant. In contrast, there were no significant changes in histamine levels or the other biochemical parameters measured in groups of patients treated only with physiotherapy and kinesitherapy. CONCLUSION: It may be concluded that the beneficial clinical effects of cryotherapy in RA patients are in part due to the action on the production, release, or degradation of histamine.