0
selected
-
1.
Effects of fucoidan from Fucus vesiculosus in reducing symptoms of osteoarthritis: a randomized placebo-controlled trial.
Myers, SP, Mulder, AM, Baker, DG, Robinson, SR, Rolfe, MI, Brooks, L, Fitton, JH
Biologics : targets & therapy. 2016;:81-8
Abstract
PURPOSE Preliminary investigation of a fucoidan with demonstrated reduction in the symptoms of osteoarthritis (OA) of the hip and knee. PATIENTS AND METHODS A double-blind randomized controlled trial was carried out to determine the safety and efficacy of a 300 mg dose of a Fucus vesiculosus extract (85% fucoidan) over a 12-week period in a population (n=122) with mild-to-moderate OA of the hip and knee as measured by the validated instrument "Comprehensive Osteoarthritis Test." Safety was measured by assessing cholesterol, liver function, renal function, and hematopoietic function, and closely monitoring adverse events. RESULT Ninety-six participants completed the study. The reduction in symptoms of OA was not significantly different from the placebo response. There were no changes in the blood measurements that were of any clinical significance during the course of the study. CONCLUSION The F. vesiculosus fucoidan extract was safe and well tolerated. At a dose of 300 mg, the extract showed no difference in reduction of OA symptoms from the placebo.
-
2.
Cognitive impairment in coeliac disease improves on a gluten-free diet and correlates with histological and serological indices of disease severity.
Lichtwark, IT, Newnham, ED, Robinson, SR, Shepherd, SJ, Hosking, P, Gibson, PR, Yelland, GW
Alimentary pharmacology & therapeutics. 2014;40(2):160-70
-
-
-
Free full text
-
Plain language summary
Coeliac disease (CD) is an inflammatory autoimmune disorder caused by the ingestion of gluten. While CD is known to primarily affect the bowel, there is reported evidence of potential neurological side effects. Cognition may be impaired in undiagnosed CD patients because of nutrient deficiencies, systemic inflammation and changes in the gut microbiome. CD patients often report a mild cognitive impairment, brain fog, characterised by difficulty concentrating, short-term memory and confusion. The aim of this study was to investigate the relationship between gut mucosal healing and cognitive function in eleven patients recently diagnosed with CD commencing a strict gluten-free diet. The findings of this study showed that in newly diagnosed CD patients, cognitive functioning improved with a gluten-free diet and was correlated with mucosal healing. Based on this study, the authors conclude that cognition is impaired in people with untreated coeliac disease and may affect the performance of everyday tasks. This finding also introduces the possibility of using cognitive tests to provide a marker of intestinal healing.
Abstract
BACKGROUND Mild impairments of cognition or 'Brain fog' are often reported by patients with coeliac disease but the nature of these impairments has not been systematically investigated. AIM: This longitudinal pilot study investigated relationships between cognitive function and mucosal healing in people with newly diagnosed coeliac disease commencing a gluten-free diet. METHODS Eleven patients (8 females, 3 males), mean age 30 (range 22-39) years, were tested with a battery of cognitive tests at weeks 0, 12 and 52. Information processing efficacy, memory, visuospatial ability, motoric function and attention were tested. Small bowel biopsies were collected via routine gastroscopy at weeks 12 and 52 and were compared to baseline Marsh scores. Cognitive performance was compared to serum concentrations of tissue transglutaminase antibodies, biopsy outcomes and other biological markers. RESULTS All patients had excellent adherence to the diet. Marsh scores improved significantly (P = 0.001, Friedman's test) and tissue transglutaminase antibody concentrations decreased from a mean of 58.4 at baseline to 16.8 U/mL at week 52 (P = 0.025). Four of the cognitive tests assessing verbal fluency, attention and motoric function showed significant improvement over the 12 months and strongly correlated with the Marsh scores and tissue transglutaminase antibody levels (r = 0.377-0.735; all P < 0.05). However, no meaningful patterns of correlations were found for nutritional or biochemical markers, or markers of intestinal permeability. CONCLUSIONS In newly diagnosed coeliac disease, cognitive performance improves with adherence to the gluten-free diet in parallel to mucosal healing. Suboptimal levels of cognition in untreated coeliac disease may affect the performance of everyday tasks.
-
3.
Hemin toxicity: a preventable source of brain damage following hemorrhagic stroke.
Robinson, SR, Dang, TN, Dringen, R, Bishop, GM
Redox report : communications in free radical research. 2009;(6):228-35
Abstract
Hemorrhagic stroke is a common cause of permanent brain damage, with a significant amount of the damage occurring in the weeks following a stroke. This secondary damage is partly due to the toxic effects of hemin, a breakdown product of hemoglobin. The serum proteins hemopexin and albumin can bind hemin, but these natural defenses are insufficient to cope with the extremely high amounts of hemin (10 mM) that can potentially be liberated from hemoglobin in a hematoma. The present review discusses how hemin gets into brain cells, and examines the multiple routes through which hemin can be toxic. These include the release of redox-active iron, the depletion of cellular stores of NADPH and glutathione, the production of superoxide and hydroxyl radicals, and the peroxidation of membrane lipids. Important gaps are revealed in contemporary knowledge about the metabolism of hemin by brain cells, particularly regarding how hemin interacts with hydrogen peroxide. Strategies currently being developed for the reduction of hemin toxicity after hemorrhagic stroke include chelation therapy, antioxidant therapy and the modulation of heme oxygenase activity. Future strategies may be directed at preventing the uptake of hemin into brain cells to limit the opportunity for toxic interactions.
-
4.
Anti-AGEing defences against Alzheimer's disease.
Münch, G, Kuhla, B, Lüth, HJ, Arendt, T, Robinson, SR
Biochemical Society transactions. 2003;(Pt 6):1397-9
Abstract
Accumulation of insoluble protein deposits and their cross-linking by AGEs (advanced glycation end products) in the brain is a feature of aging and neurodegeneration, especially in AD (Alzheimer's disease). In AD, two types of fibrillar protein aggregates are present: extracellular deposits (plaques) consisting mainly of Abeta (beta-amyloid peptide), and intracellular deposits (tangles) composed predominantly of microtubule-associated protein tau. Both plaques and tangles are modified by AGEs, which occurs particularly at lysine and arginine residues. Interaction of a synthetic amyloid plaque (fibrillar Abeta) with microglia leads to a strong pro-inflammatory response, indicating that priming of immune cells with beta-amyloid potentiates their response to secondary stimuli such as AGE and cytokines such as interferon-gamma. Formation of hyperphosphorylated and cross-linked microtubule-associated protein tau aggregates, especially tau dimers as the first step in tangle formation, can be induced in vitro by the combination of okadaic acid, a PP2A phosphatase inhibitor, and methylglyoxal. These results suggest that excess production of reactive carbonyl compound ("carbonyl stress") and subsequent AGE formation can contribute to cross-linking of protein fibrils and to pathological pro-inflammatory signalling, which all contribute to pathological changes and dementia progression in AD. However, the human brain has developed the glyoxalase system, a most effective defence system to scavenge small dicarbonyl compounds such as glyoxal and methylglyoxal. Very importantly, this system needs GSH as a rate-limiting cofactor. Since GSH is limited under conditions of oxidative stress and inflammation, supplementation with antioxidants such as lipoic acid, vitamin E or flavonoids could indirectly strengthen the anti-glycation defence system in AD. In addition, synthetic carbonyl scavengers and anti-inflammatory drugs could also be valuable drugs for the "anti-glycation" treatment of AD.
-
5.
Iron: a pathological mediator of Alzheimer disease?
Bishop, GM, Robinson, SR, Liu, Q, Perry, G, Atwood, CS, Smith, MA
Developmental neuroscience. 2002;(2-3):184-7
Abstract
Brains from patients with Alzheimer disease (AD) show a disruption in the metabolism of iron, such that there is an accumulation of iron in senile plaques, and an altered distribution of iron transport and storage proteins. One of the earliest events in AD is the generation of oxidative stress, which may be related to the generation of free radicals by the excess iron that is observed in the disease. Iron has also been shown to mediate the in vitro toxicity of amyloid-beta peptide, and the presence of iron in most in vitro systems could underlie the toxicity that is normally attributed to amyloid-beta in these studies. In contrast, several recent studies have suggested that amyloid-beta may decrease oxidative stress and decrease the toxicity of iron. Continued examination of the complex interactions that occur between iron and amyloid-beta may assist in the elucidation of the mechanisms that underlie the neurodegeneration that leads to dementia in AD.