The effect of genetically-mediated taste acuity for 6-N-propylthiouracil (PROP) on food choice and diet-related disease

Taste acuity for the bitter taste of 6-n-propylthiouracil (PROP) is a heritable trait. Some individuals perceive concentrated levels of PROP to taste extremely bitter (supertasters) or moderately bitter (medium tasters), whereas others detect only a mild taste or none at all (non-tasters). Heightened PROP acuity has been reported to be associated with greater acuity for a variety of compounds found in ordinary foods, although there are some inconsistent findings. The extent to which these compounds are perceived may affect food likes/dislikes and dietary intake. The majority of studies have tended to measure food likes and intake using questionnaires or laboratory preparations of a single taste quality. The present study used food diaries and sensory responses to real foods to be better able to generalise to real eating situations. There was no substantial evidence that genetically mediated taste acuity for PROP had a direct influence on food likes/dislikes or intake, although there was evidence that dietary restraint could have influenced these findings among the female samples. However; investigation of PROP tasting among individuals with coronary heart disease (CHD) and a control group suggested that PROP acuity could function as a genetic taste marker for heart disease and potentially other diet-related conditions. CHD was associated with decreased PROP acuity among men. This is consistent with the findings that decreased PROP acuity tended to be associated with increased likelihood to be a smoker and higher body mass index. It is concluded that there is not a simple and direct relationship between PROP tasting ability and food choice. An interaction between PROP acuity and other mediating factors may be involved in a more complex model of food choice. The evidence that PROP taste acuity may function as a genetic taste marker for coronary heart disease could have wide implications for understanding the aetiology, and ultimately the prevention, of diet-related disease.

The hypocaloric diet in type 2 diabetes - déjà vu

Dietary modification is considered a cornerstone in the management of diabetes superimposed upon which are pharmacological therapies as required. The value of hypocaloric diets in reducing and eliminating glycosuria was extolled in the pre-insulin era. A common feature of the nutrient balance of these diets was restriction in the availability of carbohydrate. Herein we review the use of diet as therapy in the past and discuss the rationale for hypocaloric dietary management of type 2 diabetes in the 21st century, drawing comparisons with bariatric surgery and considering why weight loss is particularly difficult for overweight and obese individuals with type 2 diabetes. © SAGE Publications 2012.

Taking the biscuit? A discursive approach to managing diet in type 2 diabetes

Adopting and maintaining a healthy diet is pivotal to diabetic regimens. Behavioural research has focused on strategies to modify/maintain healthy behaviours; thus 'compliance' and 'non-compliance' are operationalized by researchers. In contrast, discursive psychology focuses on the actions different accounts accomplish-in this case regarding diets. Using thematic discourse analysis, we examine dietary management talk in repeat-interviews with 40 newly diagnosed type 2 diabetes patients. Women in our study tended to construct dietary practices as an individual concern, while men presented food consumption as a family matter. Participants accounted for 'cheating' in complex ways that aim to accomplish, for instance, a compliant identity. Discursive psychology may facilitate fluidity in our understandings of dietary management, and challenge fixed notions of 'compliant' and 'non-compliant' diabetes patients. Copyright © 2005 SAGE Publications.

Mass spectrometry-based methods for identifying oxidized proteins in disease:advances and challenges

Many inflammatory diseases have an oxidative aetiology, which leads to oxidative damage to biomolecules, including proteins. It is now increasingly recognized that oxidative post-translational modifications (oxPTMs) of proteins affect cell signalling and behaviour, and can contribute to pathology. Moreover, oxidized proteins have potential as biomarkers for inflammatory diseases. Although many assays for generic protein oxidation and breakdown products of protein oxidation are available, only advanced tandem mass spectrometry approaches have the power to localize specific oxPTMs in identified proteins. While much work has been carried out using untargeted or discovery mass spectrometry approaches, identification of oxPTMs in disease has benefitted from the development of sophisticated targeted or semi-targeted scanning routines, combined with chemical labeling and enrichment approaches. Nevertheless, many potential pitfalls exist which can result in incorrect identifications. This review explains the limitations, advantages and challenges of all of these approaches to detecting oxidatively modified proteins, and provides an update on recent literature in which they have been used to detect and quantify protein oxidation in disease.

Neuropathological differences between areas B17 and B18: implications for visual evoked responses in Alzheimer's disease

The density of senile plaques (SP) and neurofibrillary tangles (NFT) was estimated at post-mortem in areas B17 and B18 of the visual cortex in 18 Alzheimer’s disease (AD) cases which varied in disease onset and duration. The density of SP in B17 and NFT in B17 and B18 declined significantly with age at death of the patient. The density of SP and NFT was greater in B18 than B17 but only in cases of earlier onset and shorter duration. The pathological differences between B17 and B18 could explain the visual evoked responses (VER) that have been reported in AD. However, the differences were small, and changes in the afferent pathways remain the most likely explanation for the VER in AD. © 1994 S. Karger AG, Basel.

The visual cortex in Alzheimer disease:laminar distribution of the pathological changes in visual areas V1 and V2

Alzheimer’s disease (AD) is an important neurodegenerative disorder causing visual problems in the elderly population. The pathology of AD includes the deposition in the brain of abnormal aggregates of ?-amyloid (A?) in the form of senile plaques (SP) and abnormally phosphorylated tau in the form of neurofibrillary tangles (NFT). A variety of visual problems have been reported in patients with AD including loss of visual acuity (VA), colour vision and visual fields; changes in pupillary responses to mydriatics, defects in fixation and in smooth and saccadic eye movements; changes in contrast sensitivity and in visual evoked potentials (VEP); and disturbances in complex visual tasks such as reading, visuospatial function, and in the naming and identification of objects. In addition, pathological changes have been observed to affect the eye, visual pathway, and visual cortex in AD. To better understand degeneration of the visual cortex in AD, the laminar distribution of the SP and NFT was studied in visual areas V1 and V2 in 18 cases of AD which varied in disease onset and duration. In area V1, the mean density of SP and NFT reached a maximum in lamina III and in laminae II and III respectively. In V2, mean SP density was maximal in laminae III and IV and NFT density in laminae II and III. The densities of SP in laminae I of V1 and NFT in lamina IV of V2 were negatively correlated with patient age. No significant correlations were observed in any cortical lamina between the density of NFT and disease onset or duration. However, in area V2, the densities of SP in lamina II and lamina V were negatively correlated with disease duration and disease onset respectively. In addition, there were several positive correlations between the densities of SP and NFT in V1 with those in area V2. The data suggest: (1) NFT pathology is greater in area V2 than V1, (2) laminae II/III of V1 and V2 are most affected by the pathology, (3) the formation of SP and NFT in V1 and V2 are interconnected, and (4) the pathology may spread between visual areas via the feed-forward short cortico-cortical connections.

The relationship between high-sensitivity CRP and polyclonal Free Light Chains as markers of inflammation in chronic disease

Introduction: Serum concentrations of polyclonal free light chains (FLC) represent the activity of the adaptive immune system. This study assessed the relationship between polyclonal FLC and the established marker of innate immunity, C-reactive protein (CRP), in chronic and acute disease. Methods: We utilized four cross-sectional chronic disease patient cohorts: chronic kidney disease (CKD), diabetes, vasculitis and kidney transplantation; and a longitudinal intensive care case series to assess the kinetics of production in acute disease. Results: There was a weak association between polyclonal FLC and high-sensitivity CRP (hs-CRP) in the study cohorts. A longitudinal assessment in acute disease showed a gradual increase in FLC concentrations over time, often when CRP levels were falling, demonstrating clear differences in the response kinetics of CRP and FLC in this setting. Conclusion: Polyclonal FLC and hs-CRP provide independent information as to inflammatory status. Prospective studies are now required to assess the utility of hs-CRP and polyclonal FLC in combination for risk stratification in disease populations. © 2013 John Wiley & Sons Ltd.

Top-down lipidomics of low density lipoprotein reveal altered lipid profiles in advanced chronic kidney disease

This study compared the molecular lipidomic profi le of LDL in patients with nondiabetic advanced renal disease and no evidence of CVD to that of age-matched controls, with the hypothesis that it would reveal proatherogenic lipid alterations. LDL was isolated from 10 normocholesterolemic patients with stage 4/5 renal disease and 10 controls, and lipids were analyzed by accurate mass LC/MS. Top-down lipidomics analysis and manual examination of the data identifi ed 352 lipid species, and automated comparative analysis demonstrated alterations in lipid profi le in disease. The total lipid and cholesterol content was unchanged, but levels of triacylglycerides and N -acyltaurines were signifi cantly increased, while phosphatidylcholines, plasmenyl ethanolamines, sulfatides, ceramides, and cholesterol sulfate were signifi cantly decreased in chronic kidney disease (CKD) patients. Chemometric analysis of individual lipid species showed very good discrimination of control and disease sample despite the small cohorts and identifi ed individual unsaturated phospholipids and triglycerides mainly responsible for the discrimination. These fi ndings illustrate the point that although the clinical biochemistry parameters may not appear abnormal, there may be important underlying lipidomic changes that contribute to disease pathology. The lipidomic profi le of CKD LDL offers potential for new biomarkers and novel insights into lipid metabolism and cardiovascular risk in this disease. -Reis, A., A. Rudnitskaya, P. Chariyavilaskul, N. Dhaun, V. Melville, J. Goddard, D. J. Webb, A. R. Pitt, and C. M. Spickett. Topdown lipidomics of low density lipoprotein reveal altered lipid profi les in advanced chronic kidney disease. J. Lipid Res. 2015.

The visual cortex in alzheimer's disease:laminar distribution of the pathological changes in visual areas V1 and V2

Alzheimer's disease (AD) is an important neurodegenerative disorder causing visual problems in the elderly population. The pathology of AD includes the deposition in the brain of abnormal aggregates of β-amyloid (Aβ) in the form of senile plaques (SP) and abnormally phosphorylated tau in the form of neurofibrillary tangles (NFT). A variety of visual problems have been reported in patients with AD including loss of visual acuity (VA), colour vision and visual fields; changes in pupillary responses to mydriatics, defects in fixation and in smooth and saccadic eye movements; changes in contrast sensitivity and in visual evoked potentials (VEP); and disturbances in complex visual tasks such as reading, visuospatial function, and in the naming and identification of objects. In addition, pathological changes have been observed to affect the eye, visual pathway, and visual cortex in AD. To better understand degeneration of the visual cortex in AD, the laminar distribution of the SP and NFT was studied in visual areas V1 and V2 in 18 cases of AD which varied in disease onset and duration. In area V1, the mean density of SP and NFT reached a maximum in lamina III and in laminae II and III respectively. In V2, mean SP density was maximal in laminae III and IV and NFT density in laminae II and III. The densities of SP in laminae I of V1 and NFT in lamina IV of V2 were negatively correlated with patient age. No significant correlations were observed in any cortical lamina between the density of NFT and disease onset or duration. However, in area V2, the densities of SP in lamina II and lamina V were negatively correlated with disease duration and disease onset respectively. In addition, there were several positive correlations between the densities of SP and NFT in V1 with those in area V2. The data suggest: (1) NFT pathology is greater in area V2 than V1, (2) laminae II/III of V1 and V2 are most affected by the pathology, (3) the formation of SP and NFT in V1 and V2 are interconnected, and (4) the pathology may spread between visual areas via the feed-forward short cortico-cortical connections. © 2012 by Nova Science Publishers, Inc. All rights reserved.

Innovative biomarkers for predicting type 2 diabetes mellitus:relevance to dietary management of frailty in older adults

Type 2 diabetes mellitus (T2DM) increases in prevalence in the elderly. There is evidence for significant muscle loss and accelerated cognitive impairment in older adults with T2DM; these comorbidities are critical features of frailty. In the early stages of T2DM, insulin sensitivity can be improved by a “healthy” diet. Management of insulin resistance by diet in people over 65 years of age should be carefully re-evaluated because of the risk for falling due to hypoglycaemia. To date, an optimal dietary programme for older adults with insulin resistance and T2DM has not been described. The use of biomarkers to identify those at risk for T2DM will enable clinicians to offer early dietary advice that will delay onset of disease and of frailty. Here we have used an in silico literature search for putative novel biomarkers of T2DM risk and frailty. We suggest that plasma bilirubin, plasma, urinary DPP4-positive microparticles and plasma pigment epithelium-derived factor merit further investigation as predictive biomarkers for T2DM and frailty risk in older adults. Bilirubin is screened routinely in clinical practice. Measurement of specific microparticle frequency in urine is less invasive than a blood sample so is a good choice for biomonitoring. Future studies should investigate whether early dietary changes, such as increased intake of whey protein and micronutrients that improve muscle function and insulin sensitivity, affect biomarkers and can reduce the longer term complication of frailty in people at risk for T2DM.

The impact of bariatric surgery on estimated glomerular filtration rate in patients with type 2 diabetes:a retrospective cohort study

Background: Diabetes mellitus is the most common cause of end-stage renal disease, which is associated with increased morbidity and mortality. The impact of bariatric surgery on chronic kidney disease is unclear. Objectives: Our primary aim was to assess the impact of bariatric surgery on estimated glomerular filtration rate (eGFR) in type 2 diabetes (T2D) patients. Our secondary aim was to compare the impact of bariatric surgery versus routine care on eGFR in patients with T2D. Setting: University Hospital, United Kingdom. Methods: A retrospective cohort analysis of adults with T2D who underwent bariatric surgery at a single center between January 2005 and December 2012. Data regarding eGFR were obtained from electronic patients records. eGFR was calculated using the Modification of Diet in Renal Disease formula. Data regarding patients with T2D who did not undergo bariatric surgery ("routine care") were obtained from patients attending the diabetes clinic at the same center from 2009 to 2011. Results: One hundred sixty-three patients were included (mean age 48.5±8.8 yr; baseline body mass index 50.8±9.1 kg/m2) and were followed for 3.0±2.3 years. Bariatric surgery resulted in an improvement in eGFR (median [interquartile range] 86.0 [73.0-100.0] versus 92.0 [77.0-101.0] mL/min/1.73 m2 for baseline versus follow-up, respectively; P = .003), particularly in patients with baseline eGFR≤60 mL/min/1.73 m2 (48.0 [42.0-57.0] versus 61.0 [55.0-63.0] mL/min/1.73 m2; P = .004). After adjusting for baseline eGFR, glycated hemoglobin (HbA1C), body mass index, age, and gender, bariatric surgery was associated with higher study-end eGFR compared with routine care (B = 7.787; P< .001). Conclusion: Bariatric surgery results in significant improvements in eGFR in T2D patients, particularly those with an eGFR≤60 mL/min/1.73 m2, while routine care was associated with a decline in eGFR.

Carotenoids and ocular disease: a review

Background: Carotenoids are not considered to be essential nutrients, but their antioxidant and photoprotective properties have prompted interest in their potential role in disease prevention. Our aim is to review the evidence In relation to ocular disease. Method: Web of Science and Medline via PubMed database search. Results Lutein and zeaxanthin intake has been associated with a 22% reduced risk of cataract extraction in women (RR 0.78, p = 0.04), and a 19% lower risk of cataract in men (RR 0.8, p = 0, 03). A randomised controlled trial (RCT) found a significant improvement in visual acuity in cataract patients supplemented with lutein. Two RCTs investigating the effect of P-carotene, in combination with other nutrients, on cataract report conflicting results. Several studies show no inverse association between cataract and P-carotene. Lutein and zeaxanthin are the only carotenoids found in the human macula. RCTs have found beneficial effects of both lutein and beta-carotene supplementation, in combination with other antioxidants, on visual function age-related macular disease affected subjects. Evidence for a role of lutein in preventing deterioration of visual function in retinitis pigmentosa patients is conflicting. CONCLUSIONS: Further research into the role of lutein and zeaxanthin in prevention of onset and progression of ocular disease is warranted.

Does the neurodegeneration of Alzheimer’s disease spread between visual cortical regions B17 and B18 via the feedforward or feedback short cortico-cortical projections?

The laminar distribution of senile plaques (SP) and neurofibrillary tangles (NFT) was studied in areas B17 and B18 of the visual cortex in 18 cases of Alzheimer’s disease which varied in disease onset and duration. The objective was to test the hypothesis that SP and NFT could spread via either the feedforward or feedback short cortico-cortical projections. In area B17, the mean density of SP and NFT reached a maximum in lamina III and in laminae II and III respectively. In B18, mean SP density was maximal in laminae III and IV and NFT density in laminae II and III. No significant correlations were observed in any cortical lamina between the density of SP and patient age. However, the density of NFT in laminae III, IV and VI in B18 was negatively correlated with patient age. In addition, in B18, the density of SP in lamina II and lamina V was negatively correlated with disease duration and disease onset respectively. Although these results suggest that SP and NFT might spread between B17 and B18 via the feedforward short cortico-cortical projections, it is also possible that the longer cortico-cortical and cortico-subcortical connections may be involved.

Cadmium in the environment and high risk population groups

Cadmium has been widely used in various industries for the past fifty years, with current world production standing at around 16,755 tonnes per year. Very little cadmium is ever recycled and the ultimate fate of all cadmium is the environment. In view of reports that cadmium in the environment is increasing, this thesis aims to identify population groups 'at risk' of receiving dietary intakes of cadmium up to or above the current Food and Agricultural Organisation/World Health Organisation maximum tolerable intake of 70 ug/day. The study involves the investigation of one hundred households (260 individuals) who grow a large proportion of their vegetable diet in garden soils in the Borough of Walsall, part of an urban/industrial area in the United Kingdom. Measurements were made of the cadmium levels in atmospheric deposition, soil, house dust, diet and urine from the participants. Atmospheric deposition of cadmium was found to be comparable with other urban/industrial areas in the European Community, with deposition rates as high as 209 g ha-1 yr-1. The garden soils of the study households were found to contain up to 33 mg kg-1 total cadmium, eleven times the highest level usually found in agricultural soils. Dietary intakes of cadmium by the residents from food were calculated to be as high as 68 ug/day. It is suggested that with intakes from other sources, such as air, adventitious ingestion, smoking and occupational exposure, total intakes of cadmium may reach or exceed the FAO/WHO limit. Urinary excretion of cadmium amongst a non-smoking, non-occupationally exposed sub-group of the study population was found to be significantly higher than that of a similar urban population who did not rely on home-produced vegetables. The results from this research indicate that present levels of cadmium in urban/industrial areas can increase dietary intakes and body burdens of cadmium. As cadmium serves no useful biological function and has been found to be highly toxic, it is recommended that policy measures to reduce human exposure on the European scale be considered.

Physiological effects of oxidized phospholipids and their cellular signaling mechanisms in inflammation

Oxidized phospholipids, such as the products of the oxidation of 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine by nonenzymatic radical attack, are known to be formed in a number of inflammatory diseases. Interest in the bioactivity and signaling functions of these compounds has increased enormously, with many studies using cultured immortalized and primary cells, tissues, and animals to understand their roles in disease pathology. Initially, oxidized phospholipids were viewed largely as culprits, in line with observations that they have proinflammatory effects, enhancing inflammatory cytokine production, cell adhesion and migration, proliferation, apoptosis, and necrosis, especially in vascular endothelial cells, macrophages, and smooth muscle cells. However, evidence has emerged that these compounds also have protective effects in some situations and cell types; a notable example is their ability to interfere with signaling by certain Toll-like receptors (TLRs) induced by microbial products that normally leads to inflammation. They also have protective effects via the stimulation of small GTPases and induce up-regulation of antioxidant enzymes and cytoskeletal rearrangements that improve endothelial barrier function. Oxidized phospholipids interact with several cellular receptors, including scavenger receptors, platelet-activating factor receptors, peroxisome proliferator-activated receptors, and TLRs. The various and sometimes contradictory effects that have been observed for oxidized phospholipids depend on their concentration, their specific structure, and the cell type investigated. Nevertheless, the underlying molecular mechanisms by which oxidized phospholipids exert their effects in various pathologies are similar. Although our understanding of the actions and mechanisms of these mediators has advanced substantially, many questions do remain about their precise interactions with components of cell signaling pathways.