115 research outputs found

    Characteristics and Treatments of Patients with Peripheral Arterial Disease Referred to UK Vascular Clinics: Results of a Prospective Registry

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    BackgroundPeripheral arterial disease (PAD) is often associated with risk factors including cigarette smoking, hypertension and hypercholesterolaemia, and patients have a high risk of future vascular events. Good medical management results in improved outcomes and quality of life, but previous studies have documented sub-optimal treatment of risk factors. We assessed the management of cardiovascular risk factors in patients with PAD referred to specialist vascular clinics.MethodsThis was a prospective, protocol driven registry carried out in UK vascular clinics. Patients who were first-time referrals for evaluation of PAD were eligible if they had claudication plus ankle-brachial pressure index (ABPI) ≤0.9. Statistical associations between key demographic and treatment variables were explored using a chi-squared test.ResultsWe enrolled 473 patients from 23 sites. Mean age was 68 years (SD 10) and 66% were male. Mean estimated claudication distance was 100m, and ABPI was 0.74. Mean systolic blood pressure (SBP) was 155mmHg, and 42% had a SBP >160mmHg. Forty percent were current smokers and half had tried to give up in the prior 6 months, but there was no evidence of a systematic method of smoking cessation. Mean total cholesterol was 5.4 (SD1.2) mmol/l and 30% had levels >6mmol/l. Antiplatelet therapy had been given to 70% and statins to 44%. Prior CHD was present in 29% and these patients had significantly higher use of antiplatelet therapy, statins and ACE-inhibitors.ConclusionsIn spite of attempts to raise awareness about PAD as an important marker of cardiovascular risk, patients are still poorly treated prior to referral to a vascular clinic. In particular, the use of evidence-based treatments is sub-optimal, while hypertension and cigarette smoking are poorly managed. More work needs to be done to educate health professionals about the detection and optimal medical management of PAD

    Does Reduced IGF-1R Signaling in Igf1r+/− Mice Alter Aging?

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    Mutations in insulin/IGF-1 signaling pathway have been shown to lead to increased longevity in various invertebrate models. Therefore, the effect of the haplo- insufficiency of the IGF-1 receptor (Igf1r+/−) on longevity/aging was evaluated in C57Bl/6 mice using rigorous criteria where lifespan and end-of-life pathology were measured under optimal husbandry conditions using large sample sizes. Igf1r+/− mice exhibited reductions in IGF-1 receptor levels and the activation of Akt by IGF-1, with no compensatory increases in serum IGF-1 or tissue IGF-1 mRNA levels, indicating that the Igf1r+/− mice show reduced IGF-1 signaling. Aged male, but not female Igf1r+/− mice were glucose intolerant, and both genders developed insulin resistance as they aged. Female, but not male Igf1r+/− mice survived longer than wild type mice after lethal paraquat and diquat exposure, and female Igf1r+/− mice also exhibited less diquat-induced liver damage. However, no significant difference between the lifespans of the male Igf1r+/− and wild type mice was observed; and the mean lifespan of the Igf1r+/− females was increased only slightly (less than 5%) compared to wild type mice. A comprehensive pathological analysis showed no significant difference in end-of-life pathological lesions between the Igf1r+/− and wild type mice. These data show that the Igf1r+/− mouse is not a model of increased longevity and delayed aging as predicted by invertebrate models with mutations in the insulin/IGF-1 signaling pathway

    The Exopolysaccharide Matrix Modulates the Interaction between 3D Architecture and Virulence of a Mixed-Species Oral Biofilm

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    Virulent biofilms are responsible for a range of infections, including oral diseases. All biofilms harbor a microbial-derived extracellular-matrix. The exopolysaccharides (EPS) formed on tooth-pellicle and bacterial surfaces provide binding sites for microorganisms; eventually the accumulated EPS enmeshes microbial cells. The metabolic activity of the bacteria within this matrix leads to acidification of the milieu. We explored the mechanisms through which the Streptococcus mutans-produced EPS-matrix modulates the three-dimensional (3D) architecture and the population shifts during morphogenesis of biofilms on a saliva-coated-apatitic surface using a mixed-bacterial species system. Concomitantly, we examined whether the matrix influences the development of pH-microenvironments within intact-biofilms using a novel 3D in situ pH-mapping technique. Data reveal that the production of the EPS-matrix helps to create spatial heterogeneities by forming an intricate network of exopolysaccharide-enmeshed bacterial-islets (microcolonies) through localized cell-to-matrix interactions. This complex 3D architecture creates compartmentalized acidic and EPS-rich microenvironments throughout the biofilm, which triggers the dominance of pathogenic S. mutans within a mixed-species system. The establishment of a 3D-matrix and EPS-enmeshed microcolonies were largely mediated by the S. mutans gtfB/gtfC genes, expression of which was enhanced in the presence of Actinomyces naeslundii and Streptococcus oralis. Acidic pockets were found only in the interiors of bacterial-islets that are protected by EPS, which impedes rapid neutralization by buffer (pH 7.0). As a result, regions of low pH (<5.5) were detected at specific locations along the surface of attachment. Resistance to chlorhexidine was enhanced in cells within EPS-microcolony complexes compared to those outside such structures within the biofilm. Our results illustrate the critical interaction between matrix architecture and pH heterogeneity in the 3D environment. The formation of structured acidic-microenvironments in close proximity to the apatite-surface is an essential factor associated with virulence in cariogenic-biofilms. These observations may have relevance beyond the mouth, as matrix is inherent to all biofilms

    Bio-analytical Assay Methods used in Therapeutic Drug Monitoring of Antiretroviral Drugs-A Review

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