Glucocorticoid receptor binding characteristics in rat genetic models of hypertension and in normal subjects of known glucocorticoid receptor genotype

The evidence of a familial component in the development of hypertension has been discussed in its socio-economical, genetical and hormonal aspects. Of the endocrine influences, the activity of the adrenal cortex and the way in which both mineralocorticoids and glucocorticoids interact with their target tissues has been evaluated. It has been suggested that this interaction may vary in a genetically determined manner. Recent studies suggested that the restriction fragment length polymorphism (RFLP) of the glucocorticoid receptor (GR) is associated with differences of blood pressure. Subjects from the Ladywell district of Edinburgh who were homozygous for one GR genotype had higher blood pressure than those homozygous for the other. The hypothesis that the receptor genotype might be associated with phenotypic differences in glucocorticoid responsiveness, which in turn could contribute to the development of hypertension, was drawn. This hypothesis has been investigated in strains of rat prone to develop hypertension and in a group of normotensive male subjects characterised for GR RFLP genotype. The investigation first required the adaptation, validation and use of a number of biochemical and cell biology techniques. A new method of measuring glucocorticoid potency has been developed, based on the ability of glucocorticoids to inhibit the translation of the lysozyme gene. In addition, a large body of information on variables concerned with electrolyte homeostasis and the control of intermediary metabolism were collected. Many of the variables correlated independently of the receptor polymorphism. The results suggested a complex interaction of mineralocorticoid and glucocorticoid functions in the pathogenesis of hypertension. In conclusion, studies in rats with genetic hypertension and in patients strongly indicate that glucocorticoid sensitivity may be a contributory factor in essential hypertension. If this is the case, then hypertension - or predisposition to hypertension - should be associated with a constellation of glucocorticoid sensitivity-related changes. If sensitivity is impaired, mineralocorticoid-like changes may result. If sensitivity is increased, glucocorticoid-dependant variables should change. Although neither hypothesis has been absolutely established by the experiments described in this thesis, they have provided some valuable guidelines for future studies. (Abstract shortened by ProQuest.)

Vitamin K supplementation to improve vascular stiffness in CKD:The K4Kidneys randomized controlled trial

BACKGROUND:Vascular calcification, a risk factor for cardiovascular disease, is common among patients with CKD and is an independent contributor to increased vascular stiffness and vascular risk in this patient group. Vitamin K is a cofactor for proteins involved in prevention of vascular calcification. Whether or not vitamin K supplementation could improve arterial stiffness in patients with CKD is unknown. METHODS:To determine if vitamin K supplementation might improve arterial stiffness in patients in CKD, we conducted a parallel-group, double-blind, randomized trial in participants aged 18 or older with CKD stage 3b or 4 (eGFR 15-45 ml/min per 1.73 m2). We randomly assigned participants to receive 400 μg oral vitamin K2 or matching placebo once daily for a year. The primary outcome was the adjusted between-group difference in carotid-femoral pulse wave velocity at 12 months. Secondary outcomes included augmentation index, abdominal aortic calcification, BP, physical function, and blood markers of mineral metabolism and vascular health. We also updated a recently published meta-analysis of trials to include the findings of this study. RESULTS:We included 159 randomized participants in the modified intention-to-treat analysis, with 80 allocated to receive vitamin K and 79 to receive placebo. Mean age was 66 years, 62 (39%) were female, and 87 (55%) had CKD stage 4. We found no differences in pulse wave velocity at 12 months, augmentation index at 12 months, BP, B-type natriuretic peptide, or physical function. The updated meta-analysis showed no effect of vitamin K supplementation on vascular stiffness or vascular calcification measures. CONCLUSIONS:Vitamin K2 supplementation did not improve vascular stiffness or other measures of vascular health in this trial involving individuals with CKD. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER:Vitamin K therapy to improve vascular health in patients with chronic kidney disease, ISRCTN21444964 (www.isrctn.com)

The ViKTORIES trial: a randomised, double-blind, placebo-controlled trial of vitamin K supplementation to improve vascular health in kidney transplant recipients

Premature cardiovascular disease and death with a functioning graft are leading causes of death and graft loss respectively in kidney transplant recipients (KTR). Vascular stiffness and calcification are markers of cardiovascular disease that are prevalent in KTR and associated with subclinical vitamin K deficiency. We performed a single‐centre, phase II, parallel‐group, randomised, double‐blind, placebo‐controlled trial (ISRCTN22012044) to test whether vitamin K supplementation reduced vascular stiffness (MRI‐based aortic distensibility) or calcification (coronary artery calcium score on computed tomography) in KTR over 1 year of treatment. The primary outcome was between‐group difference in vascular stiffness (ascending aortic distensibility). KTR were recruited between September 2017 and June 2018, and randomised 1:1 to vitamin K (Menadiol diphosphate 5mg; n=45) or placebo (n=45) thrice‐weekly. Baseline demographics, clinical history and immunosuppression regimens were similar between groups. There was no impact of vitamin K on vascular stiffness (treatment effect ‐0.23 (95% CI ‐0.75 to 0.29) x10‐3 mmHg‐1; p=0.377), vascular calcification (treatment effect ‐141 (95% CI ‐320 to 38) units; p=0.124), nor any other outcome measure. In this heterogeneous cohort of prevalent KTR, vitamin K supplementation did not reduce vascular stiffness or calcification over 1 year. Improving vascular health in KTR is likely to require a multifaceted approach

Analysis and modelling of cholesterol and high-density lipoprotein cholesterol changes across the range of C-reactive protein levels in clinical practice as an aid to better understanding of inflammation-lipid interactions

Objectives: Raised total cholesterol (TC) and reduced high-density lipoprotein (HDL) cholesterol levels are established cardiovascular disease (CVD) risk factors. However, in autoimmune conditions the lipid–CVD association appears paradoxical, with inflammation as a potential confounding factor. We therefore sought to model the relationship between systemic inflammatory illness and lipid levels using C-reactive protein (CRP) as the prototypical marker of inflammation. Our hypothesis was that there would be an inverse association between raised CRP levels and both TC and HDL-cholesterol levels.<p></p> Methods: Results from samples analysed simultaneously for CRP and lipids in a 6-month period were collected retrospectively from a large city hospital laboratory database that collates results from both primary and secondary care. The relationships between CRP and lipids were determined using graphical techniques and empirical, non-parametric, best fit models.<p></p> Results: A total of 11 437 blood samples was included. We identified a significant (p<0.001) biphasic relationship between TC and CRP: TC increased within the healthy CRP range of less than 5 mg/l, but decreased with CRP levels above 10 mg/l. The two effects approximately cancelled each other out in the intermediate CRP range of 5–10 mg/l. There was an inverse relationship between HDL-cholesterol and CRP.<p></p> Conclusions: Lipid levels change significantly during inflammatory illness in a population with both acute and chronic conditions. These results provide a strong epidemiological basis for the better understanding of lipid changes in inflammatory conditions and with anti-inflammatory therapies

Increasing requests for vitamin D measurement: costly, confusing, and without credibility

No abstract available

Canne nel Medioevo tra memorie perdute e testimonianze ritrovate

Nel contributo sono analizzati una serie di manufatti scultorei e reperti in avorio provenienti dalla cittadella medievale di Canne. Alcune di queste opere sono inedite e conservate nel deposito del museo della cittadella, altre invece sono state esposte di recente nell'Antiquarium cannese. Lo scopo di questa ricerca è ricostruire un quadro della cultura artistica medievale della città abbandonata nel XV secolo. Allo scopo sono state prese in considerazione una serie di fonti quali documenti medievali, diari di scavo, memorie grafiche, fonti odeporiche, fonti bibliografiche settecentesche e ottocentesche. La maggior parte dei manufatti rinvenuti affonda le radici in una tradizione plastica fortemente ancorata al contesto territoriale: una cultura artistica estremamente articolata, coerente al multiforme contesto della Puglia romanica. Fa eccezione un piccolo frammento in avorio, fortunosamente rinvenuto nei pressi dell’area delle basiliche, in un contesto archeologico già compromesso, che presenta stringenti relazioni con gli avori di scuola anglo-normanna