The reduction of serum soluble Flt-1 in patients with neovascular age-related macular degeneration

PURPOSE: To evaluate serum soluble Flt-1 (sFlt-1) in age-related degeneration (AMD) patients.

DESIGN: Case control study.

METHODS: Fifty-six non-AMD participants, fifty-three early AMD patients and ninety-seven neovascular AMD patients from Belfast in Northern Ireland. Serum samples were collected from each patient. Serum sFlt-1 was measured by human sVEGFR1/sFlt-1 ELISA kit. The results were analyzed by Excel and SPSS.

RESULTS: Serum sFlt-1 concentration of non-AMD, early AMD, and neovascular AMD were 90.8±2.9 pg/mL (±SEM), 88.2±2.6 pg/mL and 79.9±2.2 pg/mL. sFlt-1 from neovascular AMD patients was significantly decreased compared to non-AMD and early AMD patients (ANOVA, p<0.01). For each 10 point increase in sFlt-1, the odds for having neovascular AMD compared with non-AMD and neovascular AMD decreases by 27.8% OR=0.722 (95% CI: 0.588-0.888, p=0.002) and 27.0% OR=0.730 (95% CI: 0.594-0.898, p=0.003), respectively. In patients over 73 years of age, serum sFlt-1 <80 pg/mL was associated with a >6-fold higher risk of neovascular AMD.

CONCLUSIONS: Reduced serum sFlt-1 differentiates those patients with neovascular AMD from both early AMD and non-AMD participants. In those aged over 73, serum sFlt <80 pg/mL seems to indicate a particularly high risk of neovascular AMD. Our results indicate serum sFlt-1 could be a biomarker for development of neovascular AMD.

Choosing and using diversity indices: Insights for ecological applications from the German Biodiversity Exploratories

Biodiversity, a multidimensional property of natural systems, is difficult to quantify partly because of the multitude of indices proposed for this purpose. Indices aim to describe general properties of communities that allow us to compare different regions, taxa, and trophic levels. Therefore, they are of fundamental importance for environmental monitoring and conservation, although there is no consensus about which indices are more appropriate and informative. We tested several common diversity indices in a range of simple to complex statistical analyses in order to determine whether some were better suited for certain analyses than others. We used data collected around the focal plant Plantago lanceolata on 60 temperate grassland plots embedded in an agricultural landscape to explore relationships between the common diversity indices of species richness (S), Shannon's diversity (H'), Simpson's diversity (D1), Simpson's dominance (D2), Simpson's evenness (E), and Berger–Parker dominance (BP). We calculated each of these indices for herbaceous plants, arbuscular mycorrhizal fungi, aboveground arthropods, belowground insect larvae, and P. lanceolata molecular and chemical diversity. Including these trait-based measures of diversity allowed us to test whether or not they behaved similarly to the better studied species diversity. We used path analysis to determine whether compound indices detected more relationships between diversities of different organisms and traits than more basic indices. In the path models, more paths were significant when using H', even though all models except that with E were equally reliable. This demonstrates that while common diversity indices may appear interchangeable in simple analyses, when considering complex interactions, the choice of index can profoundly alter the interpretation of results. Data mining in order to identify the index producing the most significant results should be avoided, but simultaneously considering analyses using multiple indices can provide greater insight into the interactions in a system.

Comparative biochemical analysis of three members of the Schistosoma mansoni TAL family: Differences in ion and drug binding properties

The tegumental allergen-like (TAL) proteins from Schistosoma mansoni are part of a family of calcium binding proteins found only in parasitic flatworms. These proteins have attracted interest as potential drug or vaccine targets, yet comparatively little is known about their biochemistry. Here, we compared the biochemical properties of three members of this family: SmTAL1 (Sm22.6), SmTAL2 (Sm21.7) and SmTAL3 (Sm20.8). Molecular modelling suggested that, despite similarities in domain organisation, there are differences in the three proteins’ structures. SmTAL1 was predicted to have two functional calcium binding sites and SmTAL2 was predicted to have one. Despite the presence of two EF-hand-like structures in SmTAL3, neither was predicted to be functional. These predictions were confirmed by native gel electrophoresis, intrinsic fluorescence and differential scanning fluorimetry: both SmTAL1 and SmTAL2 are able to bind calcium ions reversibly, but SmTAL3 is not. SmTAL1 is also able to interact with manganese, strontium, iron(II) and nickel ions. SmTAL2 has a different ion binding profile interacting with cadmium, manganese, magnesium, strontium and barium ions in addition to calcium. All three proteins form dimers and, in contrast to some Fasciola hepatica proteins from the same family; dimerization is not affected by calcium ions. SmTAL1 interacts with the anti-schistosomal drug praziquantel and the calmodulin antagonists trifluoperazine, chlorpromazine and W7. SmTAL2 interacts only with W7. SmTAL3 interacts with the aforementioned calmodulin antagonists and thiamylal, but not praziquantel. Overall, these data suggest that the proteins have different biochemical properties and thus, most likely, different in vivo functions.

Nestor-Guillermo Progeria Syndrome: a biochemical insight into Barrier-to-Autointegration Factor 1, alanine 12 threonine mutation

Background: Premature aging syndromes recapitulate many aspects of natural aging and provide an insight into this phenomenon at a molecular and cellular level. The progeria syndromes appear to cause rapid aging through disruption of normal nuclear structure. Recently, a coding mutation (c.34G > A [p.A12T]) in the Barrier to Autointegration Factor 1 (BANF1) gene was identified as the genetic basis of Nestor-Guillermo Progeria syndrome (NGPS). This mutation was described to cause instability in the BANF1 protein, causing a disruption of the nuclear envelope structure.

Results: Here we demonstrate that the BANF1 A12T protein is indeed correctly folded, stable and that the observed phenotype, is likely due to the disruption of the DNA binding surface of the A12T mutant. We demonstrate, using biochemical assays, that the BANF1 A12T protein is impaired in its ability to bind DNA while its interaction with nuclear envelope proteins is unperturbed. Consistent with this, we demonstrate that ectopic expression of the mutant protein induces the NGPS cellular phenotype, while the protein localizes normally to the nuclear envelope.

Conclusions: Our study clarifies the role of the A12T mutation in NGPS patients, which will be of importance for understanding the development of the disease.

Comparison of functionally orientated tooth replacement and removable partial dentures on the nutritional status of partially dentate older patients: a randomised controlled clinical trial

OBJECTIVES: The aims of this study were to conduct a randomised controlled clinical trial (RCT) of partially dentate older adults comparing functionally orientated treatment based on the SDA concept with conventional treatment using RPDs to replace missing natural teeth. The two treatment strategies were evaluated according to their impact on nutritional status measured using haematological biomarkers.

METHODS: A randomised controlled clinical trial (RCT) was conducted of partially dentate patients aged 65 years and older (Trial Registration no. ISRCTN26302774). Each patient provided haematological samples which were screened for biochemical markers of nutritional status. Each sample was tested in Cork University Hospital for serum Albumin, serum Cholesterol, Ferritin, Folate, Vitamin B12 and 25-hydroxycholecalciferol (Vitamin D).

RESULTS: A mixed model analysis of covariance (ANCOVA) indicated that for Vitamin B12 (p=0.9392), serum Folate (p=0.5827), Ferritin (p=0.6964), Albumin (p=0.8179), Serum Total Cholesterol (p=0.3670) and Vitamin D (p=0.7666) there were no statistically significant differences recorded between the two treatment groups. According to the mixed model analysis of covariance (ANCOVA) for Vitamin D there was a significant difference between levels recorded at post-operative time points after treatment intervention (p=0.0470). There was an increase of 7% in 25-hydroxycholecalciferol levels recorded at 6 months compared to baseline (p=0.0172). There was no further change in recorded levels at 12 months (p=0.6482) and these increases were similar within the two treatment groups (p>0.05).

CONCLUSIONS: The only measure which illustrated consistent significant improvements in nutritional status for either group were Vitamin D levels. However no significant difference was recorded between the two treatment groups.

CLINICAL SIGNIFICANCE: Functionally orientated prosthodontic rehabilitation for partially dentate older patients was no worse than conventional removable partial dentures in terms of impact on nutritional status.

Characterisation of UK and Irish Cold-Pressed Rapeseed Oils in Relation to Quality Indices and Constituents.

Cold-pressed rapeseed oil (CPRSO) is produced when seeds from an oilseed rape crop are mechanically crushed whilst at a low temperature. CPRSO’s popularity is rapidly expanding and is now produced in most Northern European countries including both N.Ireland and ROI. The CPRSO industry is still relatively new and therefore not as widely researched as other high quality oils. Fifteen CPRSO from The UK, Ireland and France were examined to determine characteristic differences between the oils. Two samples of extra-virgin olive oil and two samples of refined rapeseed oil were also included in the investigation to assess performance against market competitors. The antioxidant potential of the oils was assessed using the ABTS and DPPH radical scavenging assays. Both unexpectedly showed that refined rapeseed oil had the highest potential whilst there was significant difference between many of the CPRSO’s. The acid value (ACOS method Cd 3d-63) ranged widely from 0.47-3.41. To predict the stability during storage, an accelerated oxidation test was carried out where the oils were placed in an oven (60°C) and peroxide value was monitored. The results showed extra-virgin olive oil underwent the least oxidation during the trial. The refined rapeseed oil suffered the worst levels of oxidation whilst the CPRSO’s performed similarly but with some variation. Fatty acid composition was investigated with GC-MS and some of the major fatty acids were found to differ significantly between producers. Minor compound analysis was achieved with extraction and identification through HPLC. All results are critically discussed and compared to relevant published studies.

A cross-sectional study demonstrating increased serum amyloid A-related inflammation in high density lipoproteins from subjects with type 1 diabetes mellitus and how this association was augmented by poor glycaemic control

Inflammatory atherosclerosis is increased in subjects with type 1 diabetes mellitus (T1DM). Normally high-density lipoproteins(HDL) protect against atherosclerosis; however, in the presence of serum amyloid-A- (SAA-) related inflammation this propertymay be reduced. Fasting blood was obtained from fifty subjects with T1DM, together with fifty age, gender and BMI matchedcontrol subjects. HDL was subfractionated into HDL2 and HDL3 by rapid ultracentrifugation. Serum-hsCRP and serum-, HDL2-,and HDL3-SAA were measured by ELISAs. Compared to control subjects, SAA was increased in T1DM subjects, nonsignificantly inserum (P = 0.088), and significantly in HDL2 (P  = 0.003) and HDL3 (P  = 0.005). When the T1DM group were separated accordingto mean HbA1c (8.34%), serum-SAA and HDL3-SAA levels were higher in the T1DM subjects with HbA1c ≥ 8.34%, compared towhen HbA1c was <8.34% (P  < 0.05). Furthermore, regression analysis illustrated, that for every 1%-unit increase in HbA1c, SAAincreased by 20% and 23% in HDL2 and HDL3, respectively, independent of BMI. HsCRP did not differ between groups (P  > 0.05).This cross-sectional study demonstrated increased SAA-related inflammation in subjects with T1DM that was augmented by poorglycaemic control. We suggest that SAA is a useful inflammatory biomarker in T1DM, which may contribute to their increasedatherosclerosis risk.

Polycystic ovary syndrome influences the level of serum amyloid A and activity of phospholipid transfer protein in HDL2 and HDL3

Endothelial function, antioxidant status and vascular compliance in newly diagnosed HFE C282Y homozygotes

Purpose: This pilot study was aimed to establish techniques for assessing and observing trends in endothelial function, antioxidant status and vascular compliance in newly diagnosed HFE haemochromatosis during the first year of venesection.

Patients/methods: Untreated newly diagnosed HFE haemochromatosis patients were tested for baseline liver function, iron indices, lipid profile, markers of endothelial function, anti-oxidant status and vascular compliance. Following baseline assessment, subjects attended at 6-weeks and at 3, 6, 9 and 12-months for follow-up studies.

Results: Ten patients were recruited (M = 8, F = 2, mean age = 51 years). Venesection significantly increased high density lipoproteins at 12-months (1.25 mmol/L vs. 1.37 mmol/L, p = 0.01). However, venesection did not significantly affect lipid hydroperoxides, intracellular and vascular cell adhesion molecules or high sensitivity C-reactive protein (0.57 mu mol/L vs. 0.51 mu mol/L, p = 0.45, 427.4 ng/ml vs. 307.22 ng/ml, p = 0.54, 517.70 ng/ml vs. 377.50 ng/ml, p = 0.51 and 290.75 mu g/dL vs. 224.26 mu g/dL, p = 0.25). There was also no significant effect of venesection on anti-oxidant status or pulse wave velocity (9.65 m/s vs. 8.74 m/s, p = 0.34).

Conclusions: Venesection significantly reduced high density lipoproteins but was not associated with significant changes in endothelial function, anti-oxidant status or vascular compliance. Larger studies using this established methodology are required to clarify this relationship further.