Smiling by five Down's syndrome and seven nonhandicapped infants was recorded longitudinally during face-to-face interactions with their mothers over the first 6 months of the infants' lives. Two conditions, 'mobile' (mothers were asked to talk to the baby as naturally as possible) and 'immobile' (silent and maintain an impassive face), were contrasted. Between-group comparisons confirmed previous findings of significantly delayed emergence and less frequent smiling by the infants with Down's syndrome. Their smiles were also found to be shorter, and less discriminative between the two face-to-face conditions. The non-handicapped infants showed significantly more cry/distress vocalizations in the immobile than in the mobile condition, while the reverse was found for the Down's syndrome infants. A close temporal association between smiling and eye contact with mothers was found for both groups of infants. In a free interaction condition, mothers of the Down's syndrome babies showed a stronger tendency to use kinaesthetic and tactile stimulation than mothers of the non-handicapped infants.

The changes in mitochondrial phospholipid metabolism and energy-linked functions have been followed as coupled mitochondria are allowed to age in isotonic sucrose at 18 degrees C. Analysis of the aging process has provided an approach for studying the structure--function relationships within the mitochondrion without adding external agents to perturb the membrane structure. The initial event observed in this process of deterioration is a loss of respiratory control which is paralleled by diminishing levels of ATP. As ATP levels decline, so do the rates of reacylation of monoacyglycerophosphorylethanolamine and fatty acid oxidation. In most cases the previously inactive phospholipase A2 (EC 3.1.1.4, phosphatide-2-acyl-hydrolase) begins rapid hydrolysis of membrane phosphatidylethanolamine as ATP levels approach zero. The final energy-linked phenomenon observed to decline is the anilinonaphthalenesulfonic acid fluorescence response. Evidence is presented which suggests strongly that the activity of the mitochondrial phospholipase A2 on endogenous phospholipids is suppressed in tightly coupled mitochondria. This suppression is temporally linked to ATP levels in the mitochondria. Furthermore, this study demonstrates that mitochondria which are only slightly damaged have the potential to effect membrane repair through reacylation of monoacyl phospholipids.

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Career situation of first and presenting authorPost-doctoral fellow.IntroductionRheumatoid Arthritis (RA) and Psoriatic Arthritis (PsA) share common features such as synovial hyperplasia, cartilage degradation and subchondral bone remodelling, however, there are distinct pathologic differences, which aid their diagnosis, and may account for the differential responses to specific treatments. Increased proliferation and angiogenesis transforms the synovium into an aggressive, tumour-like ‘pannus’ which contributes to disease pathogenesis. Hypoxia, resulting from dysregulated angiogenesis, can cause cells to switch from mitochondrial respiration to anaerobic glycolysis in order to meet the cellular energy demand. The RA synovium is more hyperplastic and invasive than that of PsA, while a more abnormal vasculature is observed in the PsA synovium and correlates with a reduction in tissue pO2 levels.ObjectivesThe aim of this study was to compare the metabolic profiles of RA and PsA synovial fibroblast cells (SFC) and to determine whether there is a correlation between dysregulated metabolism, cell function and disease pathogenesis.MethodsThe metabolic profiles of RA and PsA SFC were analysed using the XF96 Extracellular Flux Analyzer. Gene expression was determined by quantitative-PCR. SFC migration and invasion were observed by microscopy following wound-scratch and transwell invasion assays.ResultsRA SFC displayed increased migratory capacity and invasiveness compared to PsA SFC. Expression of IL-6, IL-8 and the glycolytic markers, GLUT1/3, HK2, PKM1/2, PDK2 and LDHA is higher in RA SFC compared to PsA SFC and is upregulated following TNF-α treatment. PsA SFC displayed higher baseline oxygen consumption rate (OCR), baseline extracellular acidification rate (ECAR) and ECAR:OCR ratio than RA SFC. Treatment with TNF-α increases the ECAR:OCR ratio in both RA and PsA SFC.ConclusionsConsistent with clinical observations, RA SFC have a greater migratory and invasive capacity than PsA SFC. Despite the lower expression of glycolytic markers, PsA SFC display a more glycolytic phenotype than RA SFC, as indicated by a higher ECAR:OCR ratio. Interestingly, however, RA SFC display a higher glycolytic reserve, possibly due to the higher expression of glycolytic markers, which can be called upon in response to increases in cellular ATP demand. Preliminary data suggest a positive correlation between the ECAR:OCR ratio and DAS28 in RA but a negative correlation in PsA. Further investigation is required to determine the precise role of metabolism in specific pathogenic processes.Disclosure of InterestNone declared.