Parkinson's - is time on your side? : temporal enhancement of motor performance using sensory guides

The basal ganglia system is directly involved in functions of habitual motor control, organisation and initiation of movement (Redgrave et al., 2010). As decreased dopamine levels debilitate normal motor function, people with Parkinson's disease tend to move 30-40% slower than healthy adults, with a movement range that is often compromised (Stelmach, Teasdale, Philips, & Worringham, 1989). There is lack of consistent evidence as to how well Parkinson's Disease patients are able to temporally control their movements. This thesis reports on work exploring the underpinnings of temporal control of movement in healthy brains and Parkinson's disease patients. Initial investigations suggest that basal ganglia play an important role in sensorimotor synchronisation through error correction and temporal anticipation processes. We demonstrate that progression of the disease has a debilitating impact on the ability to time the movement with regards to an external temporal framework in intercepting beat task and is independent from underscaling of the movement. We further explore ways of enhancement of temporal control in Parkinson's disease by providing an extrinsic kinematic template for the movement. We present novel evidence that enhancement of motor performance in Parkinson's disease (paradoxical kinesia) is triggered by the dynamic temporal information in the environment (moving object, visual and auditory arrays of information). We demonstrate that both healthy controls and patients can exploit the characteristics of specially engineered sensory guides (visual and acoustic) to improve the timing of their movement (finger tracking and ball catching). The findings from this report have both theoretical and practical implications. We propose that ability for sensorimotor synchronisation could be a behavioural marker of Parkinson's disease progression. Finally, we point towards the use of dynamic guides based on biological motion to aid motor planning in daily activities and facilitate exercise in Parkinson's disease.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Dual Stimulus-Dependent Effect of Oenothera paradoxa

Although a growing body of evidence suggests that plant polyphenols can modulate human immune responses, their simultaneous action on monocyte and neutrophil oxidative burst is currently poorly understood. Based on the hypothesis that various polyphenols contained in plant extracts might affect the oxidative burst of phagocytes, we evaluated the effects of ethanolic O. paradoxa extract polyphenols on monocyte and neutrophil oxidative burst in vitro activated by different stimuli, including opsonized bacteria E. coli, phorbol 12-myristate 13-acetate (PMA), and formyl-methionyl-leucyl-phenylalanine (fMLP). Samples were analyzed by the dihydrorhodamine flow cytometry assay. Our results showed that the extract repressed significantly and dose-dependently reactive oxygen species production in both cell types stimulated with E. coli and PMA (P < 0.05) and its inhibitory efficiency was stimulus- and cell-type-dependent. Interestingly, there was significant stimulatory effect of the extract on bursting phagocytes induced by fMLP (P < 0.05). Additionally, several flavonoids and phenolic compounds as well as penta-galloyl-β-(D)-glucose (PGG), the representative of hydrolyzable tannins, were identified in the 60% extract by high-performance liquid chromatography (HPLC) coupled to electrospray ionization in negative ion mode. In summary, the ethanolic O. paradoxa extract, rich in flavonoids and phenolic compounds, exhibits dual stimulus-dependent effect on the respiratory burst in human leukocytes; hence, it might affect immune responses in humans

Positive correlation between serum omentin and thrombospondin-1 in gestational diabetes despite lack of correlation with insulin resistance indices

Gestational Diabetes (GDM) is characterized by insulin resistance and a pro-inflammatory state, both factors possible related to adipokine expression. Subjects and Methods: The study included 20 women with GDM, diagnosed according to the WHO criteria, and 23 matched for age and BMI women with normal glucose tolerance. Omentin and TSP-1 were measured by ELISA assays. Insulin resistance was assessed by NOMA and Insulin Resistance Index (IRI). Results: There were no significant differences in omen tin and TSP-1 levels between subjects with GDM and controls (48.0 +/- 12.0ng/ml versus 50.2 +/- 7.9ng/ml and 2150 +/- 1661ng/ml versus 1569 +/- 1160ng/ml, p=0.64 and p=0.29, for omentin and TSP-1 in GDM and control subjects, respectively). There was no significant correlation between either omen tin or TSP-1 with HOMA or IRI, however there was a significant positive correlation between thrombospondin-1 and omentin (r=0.49, p=0.010). There was also a positive correlation between serum omentin and glucose levels at 60 and 90 minutes of OGTT, however in the control group only (p<0.05). Conclusions: Concentrations of omen tin and thrombospondin-1 seem to be inter-related in pregnancy however there are no differences in serum levels between women with normal glucose tolerance and those with glucose intolerance. These observations suggest that regulation of concentrations of these adipokines in pregnancy might be mediated though different mechanisms than in non-pregnant subjects

Elevated concentrations of retinol-binding protein-4 (RBP-4) in gestational diabetes mellitus : negative correlation with soluble vascular cell adhesion molecule-1 (sVCAM-1)

Background. Retinol-binding protein-4 (RBP-4) may increase insulin resistance (IR) in animals, with elevated levels reported in humans with obesity and type 2 diabetes. There are, however, few data on concentrations of RBP-4 in gestational diabetes mellitus (GDM). Methods. We measured fasting serum levels of RBP-4, soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) in 50 women at 28 weeks of gestation, divided according to the results of a 50g glucose challenge test (GCT) and a 75g oral glucose tolerance test (OGTT): (1) controls (n=20), normal responses to both GCT and OGTT; (2) intermediate group (IG) (n=15): false positive GCT, but normal OGTT; and (3) GDM group (n=15), both GCT and OGTT abnormal. IR was assessed by homeostasis model assessment (HOMA-IR) and by insulin resistance index (IRI) based on glycemia and insulinemia during OGTT. Results. All groups were matched for age and body mass index (BMI). RBP-4 levels (g/ml, meanstandard deviation) were higher in women with GDM vs. controls (53.917.9 vs. 29.713.9, p0.001), with a trend towards higher RBP-4 in GDM compared with IG (38.019.3, p=0.07). There was no significant correlation between RBP-4 and age, BMI, insulin, IRI or HOMA-IR, but there was a moderate, significant negative correlation between RBP-4 and sVCAM-1 (r2=0.20, p=0.001). Conclusions. RBP-4 levels are elevated in women with GDM, but do not correlate with IR indices and correlate negatively with sVCAM-1. The physiological significance of RBP-4 rise in women with GDM remains to be elucidated