In vivo glycated low-density lipoprotein is not more susceptible to oxidation than nonglycated low-density lipoprotein in type 1 diabetes

It has been suggested that low-density lipoprotein (LDL) modified by glycation may be more susceptible to oxidation and thus, enhance its atherogenicity. Using affinity chromatography, LDL glycated in vivo (G-LDL) and relatively nonglycated. (N-LDL) subfractions can be isolated from the same individual. The extent of and susceptibility to oxidation of N-LDL compared with G-LDL was determined in 15 type 1 diabetic patients. Total LDL was isolated and separated by boronate affinity chromatography into relatively glycated (G-) and nonglycated (N-) subfractions. The extent of glycation, glycoxidation, and lipoxidation, lipid soluble antioxidant content, susceptibility to in vitro oxidation, and nuclear magnetic resonance (NMR)-determined particle size and subclass distribution were determined for each subfraction. Glycation, (fructose-lysine) was higher in G-LDL versus N-LDL, (0.28 +/- 0.08 v 0.13 +/- 0.04 mmol/mol lysine, P <.0001). However, levels of glycoxidation/lipoxidation products and of antioxidants were similar or lower in G-LDL compared with N-LDL and were inversely correlated with fructose-lysine (FL) concentrations in G-LDL, but positively correlated in N-LDL. In vitro LDL (CuCl2) oxidation demonstrated a longer lag time for oxidation of G-LDL than N-LDL (50 +/- 0.16 v 37 +/- 0.15 min, P <.01), but there was no difference in the rate or extent of lipid oxidation, nor in any aspect of protein oxidation. Mean LDL particle size and subclass distribution did not differ between G-LDL and N-LDL. Thus, G-LDL from well-controlled type 1 diabetic patients is not more modified by oxidation, more susceptible to oxidation, or smaller than relatively N-LDL, suggesting alternative factors may contribute to the atherogenicity of LDL from type 1 diabetic patients.

Age-dependent increase in ortho-tyrosine and methionine sulfoxide in human skin collagen is not accelerated in diabetes. Evidence against a generalized increase in oxidative stress in diabetes

The glycoxidation products Nepsilon-(carboxymethyl)lysine and pentosidine increase in skin collagen with age and at an accelerated rate in diabetes. Their age-adjusted concentrations in skin collagen are correlated with the severity of diabetic complications. To determine the relative roles of increased glycation and/or oxidation in the accelerated formation of glycoxidation products in diabetes, we measured levels of amino acid oxidation products, distinct from glycoxidative modifications of amino acids, as independent indicators of oxidative stress and damage to collagen in aging and diabetes. We show that ortho-tyrosine and methionine sulfoxide are formed in concert with Nepsilon-(carboxymethyl)lysine and pentosidine during glycoxidation of collagen in vitro, and that they also increase with age in human skin collagen. The age-adjusted levels of these oxidized amino acids in collagen was the same in diabetic and nondiabetic subjects, arguing that diabetes per se does not cause an increase in oxidative stress or damage to extracellular matrix proteins. These results provide evidence for an age-dependent increase in oxidative damage to collagen and support previous conclusions that the increase in glycoxidation products in skin collagen in diabetes can be explained by the increase in glycemia alone, without invoking a generalized, diabetes-dependent increase in oxidative stress.

Communicating with children in care: why it is important and how it is done

This paper details some emerging findings from an ESRC project whose focus is social workers talking with and listening to children.

A coiled-coil-repeat protein 'Ccrp' in Bdellovibrio bacteriovorus prevents cellular indentation, but is not essential for vibroid cell morphology

<p>Bdellovibrio bacteriovorus are small, vibroid, predatory bacteria that grow within the periplasmic space of a host Gram-negative bacterium. The intermediate-filament (IF)-like protein crescentin is a member of a broad class of IF-like, coiled-coil-repeat-proteins (CCRPs), discovered in Caulobacter crescentus, where it contributes to the vibroid cell shape. The B. bacteriovorus genome has a single ccrp gene encoding a protein with an unusually long, stutter-free, coiled-coil prediction; the inactivation of this did not alter the vibriod cell shape, but caused cell deformations, visualized as chiselled insets or dents, near the cell poles and a general 'creased' appearance, under the negative staining preparation used for electron microscopy, but not in unstained, frozen, hydrated cells. Bdellovibrio bacteriovorus expressing 'teal' fluorescent protein (mTFP), as a C-terminal tag on the wild-type Ccrp protein, did not deform under negative staining, suggesting that the function was not impaired. Localization of fluorescent Ccrp-mTFP showed some bias to the cell poles, independent of the cytoskeleton, as demonstrated by the addition of the MreB-specific inhibitor A22. We suggest that the Ccrp protein in B. bacteriovorus contributes as an underlying scaffold, similar to that described for the CCRP protein FilP in Streptomyces coelicolor, preventing cellular indentation, but not contributing to the vibroid shape of the B. bacteriovorus cells.</p>

Social Equality: On what it means to be equals

<br/>The first collected volume on social and relational equality.<br/>Addresses a gap in the literature - while many philosophers have pointed to the importance of social equality, it requires much more theoretical development, which this volume aims to provide.<br/>Offers a unique answer to the debate about whether or not equality is valuable.<br/>Features a foreword by eminent political theorist David Miller<br/>Includes new contributions by some of the most well-known contemporary moral and political philosophers, such as Samuel Scheffler and Jonathan Wolff.<br/>Is equality valuable? This question dominates many discussions of social justice, which tend to center on whether certain forms of distributive equality are valuable, such as the equal distribution of primary social goods. But these discussions often neglect what is known as social or relational equality. Social equality suggests that equality is foremost about relationships and interactions between people, rather than being primarily about distribution. <br/><br/>A number of philosophers have written about the significance of social equality, and it has also played an important role in real-life egalitarian movements, such as feminism and civil rights movements. However, as it has been relatively neglected in comparison to the debates about distributive equality, it requires much more theoretical attention. This volume brings together a collection of ten original essays which present new analyses of social and relational equality in philosophy and political theory. The essays analyze the nature of social equality, as well as its relationship to justice and politics.<br/><br/>Readership: The book is primarily aimed at professionals in the field - philosophers (especially in moral, social and political philosophy) and political theorists. It is also aimed at the academic library market. Moreover, the book should be of interest to advanced undergraduate and postgraduate students attending courses on theories of equality and/or social justice.

Unmasking the ���Elderly Mystique���: why it is time to make the personal political in ageing research

This article uses feminist scholarship to investigate ���the elderly mystique��� ��� which contends that the potential of old age is masked by a set of false beliefs about ageing (i.e. ageism) which permeate social, economic and political life (Cohen, 1988). <br/>The article presents a theoretical model which explores the extent to which institutionalised ageism shapes the trajectory of life after 60. The hypothesis under-pinning the model is simple: The challenge for ageing societies is not the average age of a given population but, rather, how age is used to structure economic, social and political life. An inter-disciplinary framework is used to examine how biological facts about ageing are used to segregate older from younger people, giving older people the status of ���other���; economically through retirement, politically through assumptions about ���the grey vote��� and socially through ageist stereotyping in the media and through denial and ridicule of the sexuality of older people. Each domain is informed by the achievements of feminist theory and research on sexism and how its successes and failures can inform critical investigations of ageism. <br/>The paper recognises the role of ageism in de-politicising the lived experience of ageing. The paper concludes that feminist scholarship, particularly work by feminists in their seventies, eighties and nineties has much to offer in terms of re-framing gerontology as an emancipatory project for current and future cohorts of older people.

Donor type microchimerism is an infrequent event following liver transplantation and is not associated with graft acceptance

<p>Donor-type microchimerism, the presence of a minority population of donor-derived haematopoietic cells following solid organ transplantation, has been postulated as a mechanism for induction of donor-specific graft tolerance. The stability, frequency, and relevance of microchimerism with respect to long-term outcome, however, remains uncertain. Using a polymerase chain reaction (PCR)-based method of microsatellite analysis of highly polymorphic short tandem repeat sequences (STRs) to detect donor-type cells, DNA from 11 patients was analyzed prospectively at specific time points for 12 months following liver transplantation, and from a further six patients retrospectively 2 years after liver transplantation. Using a panel of STRs, transient peripheral blood donor microchimerism was detected in 2 of 11 patients at a single time-point following transplantation, but persistent evidence of donor-derived cells was not observed during the study period. Analysis of DNA extracted from skin and duodenum in two patients likewise failed to show donor-type cells at these sites. None of the six patients in the retrospective arm showed donor microchimerism, resulting in an overall detection rate of 1.58%. These results suggest that donor microchimerism following liver transplantation is an infrequent event, and that the generation of graft tolerance is independent of microchimerism.</p>

Multigenerational Undernutrition Increases Susceptibility to Obesity and Diabetes that Is Not Reversed after Dietary Recuperation

<p>People in developing countries have faced multigenerational undernutrition and are currently undergoing major lifestyle changes, contributing to an epidemic of metabolic diseases, though the underlying mechanisms remain unclear. Using a Wistar rat model of undernutrition over 50 generations, we show that Undernourished rats exhibit low birth-weight, high visceral adiposity (DXA/MRI), and insulin resistance (hyperinsulinemic-euglycemic clamps), compared to age-/gender-matched control rats. Undernourished rats also have higher circulating insulin, homocysteine, endotoxin and leptin levels, lower adiponectin, vitamin B12 and folate levels, and an 8-fold increased susceptibility to Streptozotocin-induced diabetes compared to control rats. Importantly, these metabolic abnormalities are not reversed after two generations of unrestricted access to commercial chow (nutrient recuperation). Altered epigenetic signatures in insulin-2 gene promoter region of Undernourished rats are not reversed by nutrient recuperation, and may contribute to the persistent detrimental metabolic profiles in similar multigenerational undernourished human populations.</p>

The obligation to provide information where valid consent is not needed

Accounts of consent in medical ethics typically assume that consent plays the same role irrespective of the type of treatment. In this paper I argue that this assumption is false. Because of this, obligations to provide information to patients that stem from the need for consent to be valid will not apply to all types of treatment. This does not mean that there are no reasons to provide such information. The second part of the paper maps out what these reasons are and argues that they are grounded in the obligation of beneficence and a duty to warn, not in considerations of respect for autonomy.

Tacrolimus is not associated with gingival overgrowth in renal transplant patients

<p>BACKGROUND: Cyclosporin A is used extensively to prevent the rejection of allogenic renal transplants. However, it is associated with a variety of undesirable side effects including gingival overgrowth. Tacrolimus (FK506), has been marketed as an effective alternative immunosuppressant to cyclosporin A and recent subjective reports suggest patients taking it complain infrequently of gingival problems. This clinical investigation was undertaken to confirm whether or not tacrolimus adversely affected the gingival health of renal transplant recipients.</p><p>METHODS: Renal transplant patients (RTPs) under the care of the Renal Transplantation Service at the Manchester Royal Infirmary, who had received a renal allograft at least 18 months earlier, were recruited for this study. All but one of the RTPs had been taking tacrolimus since transplantation. The other had commenced tacrolimus therapy two months after receiving her allograft. A hospital based control group was recruited from non transplanted individuals attending the Turner Dental School, Manchester. Each patient underwent a detailed dental assessment and had dental impressions taken. The extent of gingival overgrowth was determined from plaster models.</p><p>RESULTS: 25 renal transplant recipients and 26 control patients were included in the study. None of the individuals in either the tacrolimus or control groups had clinically significant overgrowth. The patients in the tacrolimus group with the highest overgrowth scores were those also taking calcium antagonists as treatment for hypertension.</p><p>CONCLUSION: This study demonstrates that tacrolimus has no adverse effects on the gingival tissues and thus has potential as an alternative immunosuppressant for individuals susceptible to developing cyclosporin A-induced gingival overgrowth.</p>

Where the consumer is not a myth : letters from England describing economic and industrial conditions by Zach McGhee, Washington correspondent : speech of Hon. Wyatt Aiken in the House of Representatives, Tuesday, March 22, 1910

This document contains a speech of David Wyatt Aiken, representative of South Carolina, to the House of Representatives on Tuesday, March 22, 1910. Much of the speech is a letter from Zach McGhee, Washington correspondent of The State newspaper on industrial conditions in England and Europe.

Changing climate, changing decisions : understanding climate adaptation decision-making and the way science supports it

Tese de doutoramento, Ci��ncias do Ambiente, Universidade de Lisboa, Faculdade de Ci��ncias, Universidade Nova de Lisboa, 2015

Temperature-induced sex reversal is not responsible for sex-ratio distortions in grayling Thymallus thymallus or brown trout Salmo trutta.

On the basis of the experiments carried out over various years, it was concluded that (1) grayling Thymallus thymallus and brown trout Salmo trutta are resistant to temperature-induced sex reversal at ecologically relevant temperatures, (2) environmental sex reversal is unlikely to cause the persistent sex ratio distortion observed in at least one of the study populations and (3) sex-specific tolerance of temperature-related stress may be the cause of distorted sex ratios in populations of T. thymallus or S. trutta.