The impairment of endothelium-dependent relaxations in isolated rabbit aorta and coronary arteries by low-density lipoproteins and oxidised fatty acids

Vasodilation mediated by endothelium-derived relaxing factor (EDRF) is accounted for by the release of nitric oxide from the endothelium in response to acetylcholine and other agents. In isolated arteries from atherosclerotic and hypercholesterolaemic animals endothelium-dependent responses are attenuated. This dysfunction may result from the accumulation of oxidised low-density lipoproteins (OXLDL) within the vessel wall, a process known to contribute to the pathogenesis of atherosclerosis. Previous studies have shown that LDL oxidised by Cu2+ inhibits endothelium-dependent relaxation in isolated rabbit aorta and porcine coronary arteries. This study investigated the effects of Cu2+-oxidised LDL on relaxations in rabbit large coronary arteries and small resistance vessels which do not exhibit overt signs of atherosclerosis. The effects of lipoxygenase metabolites of linoleic and arachidonic acid, which are present in OXLDL, on vascular reactivity of rabbit aorta were also investigated. Oxidised, but not native, LDL caused a reversible inhibition of endothelium-dependent relaxations evoked by ACh in isolated rabbit coronary arteries precontracted with either PGF2α or KC1. Furthermore, the extent of the inhibitory effect was similar in both large and small coronary arteries. Relaxations evoked by the nitrovasodilator SNP were unaffected by the presence of OXLDL. Hydroperoxy and hydroxy derivatives of linoleic and arachidonic acid, which have been identified in OXLDL, caused an immediate and reversible attenuation of ACh-evoked relaxations in isolated rabbit aorta. The inhibition was prevented by the addition of the protein kinase C inhibitor chelerythrine chloride suggesting the inhibition is mediated through a mechanism involving the activation of protein kinase C. Metabolites of arachidonic but not linoleic acid inhibited endothelium-independent relaxations evoked by GTN. In addition, arachidonic acid oxidation products caused a direct contraction of rabbit aortic rings which was not altered by the presence of the endothelium. LDL modified by treatment with lipoxygenase (LO-LDL) also inhibited endothelium-dependent relaxations in rabbit aorta by a mechanism involving protein kinase C and not dependent on uptake via the scavenger receptor. Relaxations evoked by GTN were reversibly attenuated by the presence of LO-LDL. In conclusion, the inhibitory effect of OXLDL in coronary vessels suggests that the effects of atherosclerosis on vascular function may extend into the microcirculation. Products of fatty acid peroxidation may contribute, with other constituents of OXLDL, to the impairment of coronary vasodilation observed in atherosclerosis and hypercholesterolaemia. Arachidonic acid metabolites may also be involved in enhanced vasoconstrictor responses and vasospasm

Photography: 'Story Behind the Picture' Interview and Photograph: Journalist Magazine June 2017

Garry Clarkson interviewed by Christine Buckley (Editor Journalist Magazine) in the National Union of Journalists Journal. Clarkson explains the process behind his first published picture the 'Satanic Verses' in Bradford which was the Guardian 1989 Picture of the Year

Pathogenesis and control of Senecavirus A in swine

Senecavirus A (SVA) is a nonenveloped, single-stranded, positive-sense RNA virus in the family Picornaviridae. It was first discovered as a cell culture contaminant in 2002 but had been identified in US swine samples dating back to the late 1980s. Since swine were presumed to be the natural host, pigs were experimentally inoculated, but did not develop any specific clinical disease. Prior to 2015, SVA was sporadically detected in US swine associated with various clinical histories. In 2015, cases of vesicular disease and increased neonatal mortality were observed in Brazil and subsequently in the US. SVA was consistently detected in affected animals. Although previous attempts to reproduce disease with SVA in the past were unsuccessful, experimental inoculation studies performed with contemporary isolates demonstrated SVA was a causative agent for vesicular disease in swine. SVA is now included in the differential list of etiologic agents that can cause vesicular disease in swine. This list includes foot-and-mouth disease virus (FMDV), which is a notifiable disease, so when vesicular lesions are observed in FMDV-free countries an investigation must be initiated to rule out FMDV. SVA has now been found across the Americas and Asia, and it appears the ecology of this virus has changed from sporadic infections to an endemic disease that does not induce severe clinical disease; but, its presence does have a significant impact since each case needs to be investigated as if it was a FMDV case. Thus, control and prevention measures are critical to reducing the spread of SVA in the global swine industry. Due to the difficulty of reproducing clinical disease in past experimental challenges and the timing of SVA outbreaks in the field with stressful situations, there was speculation that stress may be a factor in the development of vesicular lesions. To study the impact of stress, an immunosuppressive dexamethasone regime prior to SVA inoculation was administered. Clinical presentation and infection dynamics were similar in pigs treated with dexamethasone and those not treated prior to challenge. Another hypothesis for the lack of lesions in early experimental challenges was older isolates were less pathogenic than contemporary isolates. Vesicular lesion development and viral shedding in swine were compared between three SVA strains isolated prior to the 2015 outbreak and three strains isolated during 2015. The majority of animals in all groups developed vesicular lesions, and serum had cross neutralizing titers against all viruses. Sequencing and analysis of isolates used in the study found amino acid differences between the isolates in prominent loop structures of the capsid that may be involved with virus receptor binding and host immune response. Due to the clinical similarities between SVA and FMDV, control and prevention of SVA infections are a priority. Understanding the minimum infectious dose (MID) of SVA could provide insights into the infectivity of virus found in the environment and how the virus is spread. Finishing pigs and neonates were used to determine the MID of a 2011 SVA isolate using intranasal and oral challenge routes respectively. In this study, finishing pigs had a MID of 103.1 TCID50/mL and neonates 102.5 TCID50/mL. Although there were differences in infectious dose, fewer dilutions were tested in finishing pigs, which may provide a less precise estimate compared to the neonates. Another control measure for SVA could be vaccination. An inactivated vaccine was tested in weaned pigs and mature sows. The vaccine prevented the development of clinical signs and viremia as well as reduced rectal shedding in pigs. In addition, piglets suckling immunized dams had sterilizing immunity against SVA challenge. Overall, a better understanding of the pathogenesis of SVA in swine can help improve control and prevention measures to reduce the burden of SVA infection on the swine industry

Low density lipoprotein cholesterol is inversely correlated with abdominal visceral fat area: a magnetic resonance imaging study

Background: Visceral Fat Area (VFA) is an independent predictor of coronary disease. While low density lipoprotein cholesterol (LDL-C) is used to determine risk and guide therapy, its accuracy fails in obese patients who may have low LDL-C despite high VFA. Objective: We sought to describe the relationship between VFA, LDL-C and to describe shifting cholesterol metabolism with increasing VFA

Testing the Persistence of Phenotypic Plasticity After Incubation in the Western Fence Lizard, Sceloporus Occidentalis

Hypothesis: Phenotypic variation in traits induced by different incubation temperatures does not persist into the lifetime of young lizards, and therefore contributes little to variation in long-term fitness. Organism: Western fence lizard (Sceloporus occidentalis). Methods: Split-clutch laboratory incubation experiment including eggs from two different populations under two different incubation regimes, measurement of morphological traits at hatching, and tracking of morphology and temperature preference behaviour for 7 weeks after hatching. Results: Several morphological traits, including body mass, hindlimb length, inter-limb length, and tail length, initially differed between the two incubation treatments, but only the difference in tail length persisted to age 7 weeks. Thermal preference was relatively conserved, with juveniles showing no difference in mean selected body temperatures across treatments; however, warm-incubated lizards thermoregulated more precisely than their cool-incubated counterparts. Conclusion: Studies of incubation effects can reveal changes in animal phenotypes post-hatching, but if these effects do not persist, they may not be subject to natural selection and consequently be of little ecological relevance

SPR Perspectives: scientific opportunities in the Environmental influences on Child Health Outcomes Program

Drawing upon extant data from existing pediatric cohorts and new follow-up of a diverse set of pediatric cohorts from across the United States, the Environmental influences on Child Health Outcomes (ECHO) Program creates the opportunity for novel and innovative investigations of many previously inaccessible scientific questions in the area of child health. We describe how the large sample size, diversity of participants, emphasis on team science, and infrastructure for improving research methodology make the ECHO Program a major research resource for improving our understanding of early life determinants of childhood health and well-being. Pediatric researchers leverage the unique features of the ECHO Program to address research questions with the potential to yield far-reaching and long-term impacts on child health. IMPACT: The ECHO Program unites pediatric cohorts from across the United States, allowing for investigations of compelling research questions that were previously infeasible due to limited sample sizes or lack of participant diversity. The focus of the ECHO Program on team science, solution-oriented research, and methodological innovation propels novel scientific investigations that are responsive to the needs of a wide range of stakeholders. Features of the ECHO program\u27s infrastructure poise its investigators to rapidly launch research endeavors that are responsive to time-sensitive and critical needs within the realm of pediatric research

Enhancing predicted fluoride varnish efficacy and post-treatment compliance by means of calcium-containing gummy bears

Objectives This study determined whether consumption of calcium-containing gummies prior to fluoride varnish application enhances plaque fluoride retention and compliance with post-varnish application instructions. Methods The present study followed a multi-center, parallel, randomized, and laboratory analyst-blind design. Following IRB approval, parent consent and child assent, 44 subjects (7–12 years), were randomized to either gummy or no-gummy study groups. A baseline plaque sample was obtained after a wash-out period. Fluoride varnish (5% NaF) was applied; subjects in the gummy group received two calcium-containing gummies prior to varnish application. Subjects were given two questionnaires to complete (subject and parent) to investigate adherence to post-treatment instructions. Three days later, a second plaque sample was obtained. Plaque was analyzed for plaque fluid and solid fluoride concentrations. Fluoride data were analyzed using Wilcoxon Rank Sum tests, questionnaire data using Pearson chi-square tests. Results Plaque fluid fluoride did not change pre- to post-treatment in the gummy group (mean ± sd: 8.8 ± 5.7 μmol/l vs. 10.0 ± 6.3 μmol/l; p = 0.265) or in the no-gummy group (8.1 ± 4.4 μmol/l vs. 16.1 ± 20.0 μmol/l; p = 0.058). Groups were not different for plaque fluid fluoride pre-treatment (p = 1.000), post-treatment (p = 0.904), or change (p = 0.904). Plaque solid fluoride did not change pre- to post-treatment in the gummy group (0.89 ± 1.10 μmol/g vs. 1.37 ± 1.77 μmol/g; p = 0.073) or in the no-gummy group (0.68 ± 0.77 μmol/g vs. 2.01 ± 5.00 μmol/g; p = 0.190). Groups were not different for plaque solid fluoride pre-treatment (p = 1.000), post-treatment (p = 0.466), or change (p = 0.874). No significant differences were found between groups for questionnaire responses. Conclusion This study failed to demonstrate an effect of calcium-containing gummies in enhancing plaque fluoride retention

Relationship between enamel fluorosis severity and fluoride content

OBJECTIVES: Enamel fluorosis is a hypomineralization caused by chronic exposure to high levels of fluoride during tooth development. Previous research on the relationship between enamel fluoride content and fluorosis severity has been equivocal. The current study aimed at comparing visually and histologically assessed fluorosis severity with enamel fluoride content. METHODS: Extracted teeth (n=112) were visually examined using the Thylstrup and Fejerskov Index for fluorosis. Eruption status of each tooth was noted. Teeth were cut into 100 μm slices to assess histological changes with polarized light microscopy. Teeth were categorized as sound, mild, moderate, or severe fluorosis, visually and histologically. They were cut into squares (2 × 2 mm) for the determination of fluoride content (microbiopsy) at depths of 30, 60 and 90 μm from the external surface. RESULTS: Erupted teeth with severe fluorosis had significantly greater mean fluoride content at 30, 60 and 90 μm than sound teeth. Unerupted teeth with mild, moderate and severe fluorosis had significantly greater mean fluoride content than sound teeth at 30 μm; unerupted teeth with mild and severe fluorosis had significantly greater mean fluoride content than sound teeth at 60 μm, while only unerupted teeth severe fluorosis had significantly greater mean fluoride content than sound teeth at 90 μm. CONCLUSIONS: Both erupted and unerupted severely fluorosed teeth presented higher mean enamel fluoride content than sound teeth. CLINICAL SIGNIFICANCE: Data on fluoride content in enamel will further our understanding of its biological characteristics which play a role in the management of hard tissue diseases and conditions

Ethics roundtable debate: Withdrawal of tube feeding in a patient with persistent vegetative state where the patients wishes are unclear and there is family dissension

The decision to withdraw or withhold life supporting treatment in moribund patients is difficult under any circumstances. When the patient becomes incompetent to clarify their wishes regarding continued maintenance in long-term facilities, surrogates sometimes cannot agree, further clouding the issue. We examine a case where the State's interests come into play, forcing a controversial resolution