No abstract

Ferulic acid (FA) is a polyphenol pertaining to the class of hydroxycinnamic acids present in numerous foods of a plant origin. Its dietary consumption leads to the formation of several phase I and II metabolites in vivo, which represent the largest amount of ferulates in the circulation and in the intestine in comparison with FA itself. In this work, we evaluated their efficacy against the proinflammatory effects induced by lipopolysaccharide (LPS) in intestinal Caco-2 cell monolayers, as well as the mechanisms underlying their protective action. LPS-induced overexpression of proinflammatory enzymes such as inducible nitric oxide synthase (iNOS) and the consequent hyperproduction of nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) were limited by physiological relevant concentrations (1 µM) of FA, its derivatives isoferulic acid (IFA) and dihydroferulic acid (DHFA), and their glucuronidated and sulfated metabolites, which acted upstream by limiting the activation of MAPK p38 and ERK and of Akt kinase, thus decreasing the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-ĸB) translocation into the nucleus. Furthermore, the compounds were found to promote the expression of Nrf2, which may have contributed to the downregulation of NF-ĸB activity. The overall data show that phase I/II metabolites retain the efficacy of their dietary free form in contrasting inflammatory response.

BackgroundProgression of radiographic damage in axial-spondyloarthropaties is related to higher functionality impairment in longstanding patients, resulting in poorer quality of life and autonomy. Its impact on gait has not been extensively studied yet. Time-up and go (TUG) test and GAIT analysis (GA) are currently used in neurological and musculoskeletal diseases to evaluate changes in patients gait and stance.ObjectivesThe aim of this study is to evaluate with standardized procedures modifications of gait in patients with inactive longstanding axSpa with radiographic damage, comparing them with a cohort of sex, age and BMI matched healthy controls.MethodsPatients followed at Rheumatology Unit of the University Hospital of Cagliari were enrolled. Inclusion criteria were: 1) having a diagnosis of axSpa, 2) having an inactive disease (BASDAI<4, PtGA<20, PhGA<20), 3) evidence of radiographic damage in the most recent spine x-ray available (mSASSS >20), 4) ability to walk autonomously. Exclusion criteria were: 1) deafness, 2) any medical condition that, according to investigators, could expose patients at any excess risk or interfere with the procedures of the study. Patients underwent a TUG test and a gait analysis at the Department of Mechanical, Chemical and Materials Engineering, University of Cagliari. For TUG Test the following parameters were recorded: TUG time, sit-to-stand time, first and second rotation time, stand-to-sit time, walking time. Walking speed and mean step length were recorded using GAIT analysis. Statistical analysis was performed with MANOVA (Pillai’s Trace, Wilk’s Lambda, Hotelling’s Trace, Roy’s Largest Roots). Level of statistical significance was set at<0,05.ResultsFifteen patients and fifteen HC were enrolled in this study. Mean age was 60,1±7,8 years for patients and 61,3±7,8 for HC. Weight and height were similar in both groups (axSpa 76,7 ± 16,8kg vs HC 72 ±7,2kg; axSpa 169,33 ± 8,8cm vs HC 170,4 ± 5,2cm). Disease duration was 27.61±9,67 years, mean mSASSS was 46,33±16,84. All patients were inactive, but showed clinical signs of disease progression (BASMI 5,9±1,19). Thirteen patients were on treatment with bDMARDs (TNF inhibitors), while 2 were off treatment. MANOVA revealed differences between axSPa patients and HC for TUG test (p<0,05). TUG time and walking time were significant longer in axSpa (TUG time 12,88±1,92s vs 10,44±2,18s, p=0,003; walking time 5,69±1,17s vs 3,68±0,8, p<0,001), while other parameters were not different between groups. Finally, axSpa patients were slower (0,95±0,16 m/s vs 1,18±0,17 m/s; p<0,05), and had a shorter step (0,52±0,65 m vs 0,65±0,69 m; p<0,05).ConclusionPatients with longstanding axSpa showed a different gait when compared with matched HC: we found that axSpa patients walk slower than HC, and with shorter steps. This could be interpreted as a compensatory behaviour as walking speed slower than 1 m/s has been reported as a risk factor for falling in elderly. In conclusion, we found that disease progression in axSpa patients could interfere with walking speed. Clinical relevance of these findings should be confirmed in future studies, as well as if some medical intervention (e.g. physical therapy) could minimize the impact of disease progression on posture control and walking.Reference[1]Verghese et al. Quantitative Gait Markers and Incident Fall Risk in Older Adults. Gerontol, 2009. Vol. 64A, No. 8, 896–901 doi:10.1093/gerona/glp033Table 1.Demographic and clinical features of patients and HC. Results of TUG and GA.axSpaHCpAge (years)60,1 ± 7,861,3 ± 7,8nsSex15 M15 MHeight (cm)169,33 ± 8,8170,4 ± 5,2nsWeight (kg)76,7 ± 16,872 ±7,2nsDisease duration27,6±9,67BASMI5,9±1,19mSASSS46,33±16,84TUG Test – Total time (s)12,88±1,9210,44±2,180,003Sit-stand time (s)1,53±0,421,38±0,34nsStand-sit time (s)1,26±0,371,36±0,62nsfirst turn time (s)2,49±0,532,22±0,65nssecond turn time (s)1,9±0,471,79±0,75nswalking time (s)5,69±1,173,68±0,8<0,001GA - walking speed (m/s)0,95±0,161,18±0,17<0,05Step length/m0,52±0,650,65±0,69<0,05Acknowledgements:NIL.Disclosure of InterestsNone Declared.