Metabolomic response to coffee consumption: application to a three-stage clinical trial.

BACKGROUND: Coffee is widely consumed and contains many bioactive compounds, any of which may impact pathways related to disease development. OBJECTIVE: To identify individual metabolite changes in response to coffee. METHODS: We profiled the metabolome of fasting serum samples collected from a previously reported single-blinded, three-stage clinical trial. Forty-seven habitual coffee consumers refrained from drinking coffee for 1 month, consumed four cups of coffee/day in the second month and eight cups/day in the third month. Samples collected after each coffee stage were subject to nontargeted metabolomic profiling using UPLC-ESI-MS/MS. A total of 733 metabolites were included for univariate and multivariate analyses. RESULTS: A total of 115 metabolites were significantly associated with coffee intake (P < 0.05 and Q < 0.05). Eighty-two were of known identity and mapped to one of 33 predefined biological pathways. We observed a significant enrichment of metabolite members of five pathways (P < 0.05): (i) xanthine metabolism: includes caffeine metabolites, (ii) benzoate metabolism: reflects polyphenol metabolite products of gut microbiota metabolism, (iii) steroid: novel but may reflect phytosterol content of coffee, (iv) fatty acid metabolism (acylcholine): novel link to coffee and (v) endocannabinoid: novel link to coffee. CONCLUSIONS: The novel metabolites and candidate pathways we have identified may provide new insight into the mechanisms by which coffee may be exerting its health effects.

Dose-dependent induction of IL-6 by plant-derived proteases in vitro.

Oral administration of proteases such as bromelain and papain is commonly used in patients with a wide range of inflammatory conditions, but their molecular and cellular mechanisms of action are still poorly understood. The aim of our study was to investigate the impact of these proteases on the release of interleukin-6 (IL-6) and other cytokines in the recently described modified mixed lymphocyte culture (MMLC) test system which is based on the mutual interaction of cells of the innate and adaptive immunity. Bromelain and papain enhanced IL-6 production dose-dependently up to 400-fold in MMLC before and up to 30-fold after neutralization of LPS content of proteases using polymyxin B, indicating that IL-6 induction by protease treatment was attributable to both protease action and LPS content of enzyme preparations. The production of IFNgamma and IL-10 was not altered by bromelain or papain, indicating a selective and differential immune activation. Both proteases impaired cytokine stability, cell proliferation and expression of cell surface molecules like CD14 only marginally, suggesting no impact of these mechanisms on protease-mediated cytokine release. These findings might provide the mechanistic rationale for the current use of proteases in wound healing and tissue regeneration since these processes depend on IL-6 induction.

[Surgical treatment of obstructive sleep-apnoea syndrome]. / Chirurgische behandeling van obstructief slaapapneusyndroom.

5 patients, 4 males aged 41, 32, 52 and 49 years and 1 female aged 57 years, suffered from socially unacceptable snoring and hypersomnolence in the daytime. They were evaluated for obstructive sleep-apnoea syndrome. After polysomnography and sleep endoscopy was performed to establish the severity of the sleep-apnoea syndrome and the level(s) of upper airway obstruction, a patient-specific treatment was performed. Conservative therapy with continuous positive airway pressure (CPAP) was refused by 4 patients, while 1 patient discontinued therapy after complaints of nose obstruction. This patient underwent radiofrequency thermotherapy (RFTT) of the inferior turbinates. The other patients underwent uvulopalatopharyngoplasty (UPPP), RFTT of the soft palate, hyoidthyroidpexia (HTP) and 'multilevel' surgery: UPPP, HTP and RFTT of the tongue base, respectively. All patients showed improvement after surgery. Although its longterm effects are not yet known, surgical treatment is an option for patients with obstructive sleep-apnoea syndrome who cannot or will not undergo CPAP.