Endothelial nitric oxide synthase content in adipose tissue from obese and lean African American and white American women

It has been demonstrated that the enzyme endothelial nitric oxide synthase (eNOS) is present in adipose tissue, resulting in nitric oxide production and subsequent inhibition of lipolysis. A higher eNOS content has also been reported in the subcutaneous abdominal adipose tissue of obese than in that of lean white men. Furthermore, a lower lipolytic rate in obese than in lean women and a lower lipolytic rate in African American (AA) than in white American (WA) women have been demonstrated. The purpose of this study was to determine if eNOS protein content is higher in the subcutaneous and omental adipose tissues of obese than in those of lean women and if eNOS protein content is higher in the subcutaneous and omental adipose tissues of AA than in those of WA women. Whole tissue homogenates were prepared from frozen omental and subcutaneous adipose tissue samples obtained from lean and obese and AA and WA elective abdominal surgery patients and were analyzed for eNOS protein content using enzyme-linked immunosorbent assay. The adipose tissue eNOS protein content was approximately 40% higher in obese than in lean individuals (omental, 326.9 +/- 40.5 pg/mL lean and 445.3 +/- 38.0 pg/mL obese; subcutaneous, 246.8 +/- 20.8 pg/mL lean and 343.1 +/- 19.0 pg/mL obese; P < .05). There was no difference between the races for eNOS protein content in omental adipose tissue. In subcutaneous adipose tissue, there was a higher eNOS content in obese (417.1 +/- 78.9 pg/mg total protein) than in lean (216.7 +/- 29.9 pg/mg total protein) (P < .05) WA women, but there was no difference in subcutaneous adipose eNOS content between obese and lean AA women (250.7 +/- 47.4 and 294.1 +/- 42.2 pg/mg total protein, respectively). The higher eNOS content in the adipose tissue of obese than in that of lean WA women in the fasted state may contribute to the reduced lipolytic activity in WA women; however, eNOS protein content probably does not contribute to differences in lipolytic rates between AA and WA women.     

Human Disease/Clinical Medical Sciences in Dentistry: Current state and future directions of undergraduate teaching in the UK and Ireland

In March 2017, a group of teachers of human disease/clinical medical science (HD/CMSD) representing the majority of schools from around the UK and Republic of Ireland met to discuss the current state of teaching of human disease and also to discuss how the delivery of this theme might evolve to inform improved healthcare. This study outlines how the original teaching in medicine and surgery to dental undergraduate students has developed into the theme of HD/CMSD reflecting changing needs as well as guidance from the regulators, and how different dental schools have developed their approaches to reach their current state. Each school was also asked to share a strengths, weakness, opportunities and threats (SWOT) analysis of their programme and to outline how they thought their HD/CMSD programme may develop. The school representatives who coordinate the delivery and assessment of HD/CMSD in the undergraduate curriculum have extensive insight in this area and are well‐placed to shape the HD/CMSD development for the future.     

Overcoming the blood-brain barrier with high-dose enzyme replacement therapy in murine mucopolysaccharidosis VII

Enzyme replacement therapy (ERT) effectively reverses storage in several lysosomal storage diseases. However, improvement in brain is limited by the blood-brain barrier except in the newborn period. In this study, we asked whether this barrier could be overcome by higher doses of enzyme than are used in conventional trials. We measured the distribution of recombinant human beta-glucuronidase (hGUS) and reduction in storage by weekly doses of 0.3-40 mg/kg administered i.v. over 1-13 weeks to mucopolysaccharidosis type VII mice immunotolerant to recombinant hGUS. Mice given up to 5 mg/kg enzyme weekly over 3 weeks had moderate reduction in meningeal storage but no change in neo-cortical neurons. Mice given 20-40 mg/kg three times over 1 week showed no reduction in storage in any area of the CNS except the meninges. In contrast, mice receiving 4 mg/kg per week for 13 weeks showed clearance not only in meninges but also in parietal neocortical and hippocampal neurons and glia. Mice given 20 mg/kg once weekly for 4 weeks also had decreased neuronal, glial, and meningeal storage and averaged 2.5% of wild-type hGUS activity in brain. These results indicate that therapeutic enzyme can be delivered across the blood-brain barrier in the adult mucopolysaccharidosis type VII mouse if administered at higher doses than are used in conventional ERT trials and if the larger dose of enzyme is administered over a sufficient period. These results may have important implications for ERT for lysosomal storage diseases with CNS involvement.     

Clinical and hemodynamic results of mitral valve replacement with autologous fascia lata grafts. Studies in patients with competent prostheses.

Nine patients with severe mitral disease were studied before and six months after mitral valve replacement with a three-cusp stented prosthesis using fresh autologous fascia lata tissue. Only patients in whom there was no auscultatory and angiographic evidence of incompetence of the replaced valve were selected for restudy. All patients claimed a marked improvement in their exercise capacity after operation and there was a significant reduction in radiographic heart size. The cardiac output at rest and the response to exercise were both reduced before operation and were unchanged after valve replacement. The elevated pulmonary arterial and wedge pressures were significantly reduced after operation in all patients both at rest and during exercise, but in no instance were the postoperative exercise values within normal limits. Left ventricular end-diastolic pressure was within normal limits at rest and during exercise in all patients after valve replacement but the average pressure gradient across the fascia lata valve was 6+/-1 mm Hg at rest and 18+/-3 mm Hg during exercise. These findings indicate that altough replacement of the diseased mitral valve with a competent fascia lata prosthesis afforded substantial symptomatic relief, reduction of cardiac enlargement and a lowering of the pulmonary vascular pressures, this artificial valve offered a significant obstruction to left ventricular diastolic filling, particularly during exercise.     

Sharpness overconstancy: the roles of visibility and current context.

In a previous study we found that blurred edges presented in peripheral vision look sharper than when they are looked at directly, a phenomenon we have called peripheral sharpness overconstancy (Galvin et al. (1997). Vision Research, 37, 2035-2039). In the current study we show that when visibility of the stimulus edges is compromised by very brief presentations, we can demonstrate sharpness overconstancy for static, foveal viewing. We also test whether the degree of sharpening is a function of the current visual context, but find no difference between the peripheral sharpness overconstancy (at 24 degrees eccentricity) of edges measured in a blurred context and that measured in a sharp context. We conclude that if the visual system does carry a template for sharp edges which contributes to edge appearance when visibility is poor, then that template is resistant to changes in context.