Alpha-lipoic acid does not acutely affect resistance and conduit artery function or oxidative stress in healthy men

AIMS: Alpha-lipoic acid (ALA) is a thiol compound with antioxidant properties used in the treatment of diabetic polyneuropathy. ALA may also improve arterial function, but there have been scant human trials examining this notion. This project aimed to investigate the effects of oral and intra-arterial ALA on changes in systemic and regional haemodynamics, respectively. METHODS: In study 1, 16 healthy older men aged 58 +/- 7 years (mean +/- SD) received 600 mg of ALA or placebo, on two occasions 1 week apart, in a randomized cross-over design. Repeated measures of peripheral and central haemodynamics were then obtained for 90 min. Central blood pressure and indices of arterial stiffness [augmentation index (AIx) and estimated aortic pulse wave velocity] were recorded non-invasively using pulse wave analysis. Blood samples obtained pre- and post-treatments were analysed for erythrocyte antioxidant enzyme activity, plasma nitrite and malondialdehyde. In study 2 the effects of incremental cumulative doses (0.5, 1.0, 1.5 and 2.0 mg ml(-1) min(-1)) of intra-arterial ALA on forearm blood flow (FBF) were assessed in eight healthy subjects (aged 31 +/- 5 years) by conventional venous occlusion plethysmography. RESULTS: There were no significant changes on any of the central or peripheral haemodynamic measures after either oral or direct arterial administration of ALA. Plasma ALA was detected after oral supplementation (95% confidence intervals 463, 761 ng ml(-1)), but did not alter cellular or plasma measures of oxidative stress. CONCLUSIONS: Neither oral nor intra-arterial ALA had any effect on regional and systemic haemodynamics or measures of oxidative stress in healthy men.     

Comparison of a very low-carbohydrate and low-fat diet on fasting lipids, LDL subclasses, insulin resistance, and postprandial lipemic responses in overweight women

OBJECTIVE: Very low-carbohydrate diets are widely used for weight loss yet few controlled studies have determined how these diets impact cardiovascular risk factors compared to more traditional low-fat weight loss diets. The primary purpose of this study was to compare a very low-carbohydrate and a low-fat diet on fasting blood lipids, LDL subclasses, postprandial lipemia, and insulin resistance in overweight and obese women. METHODS: Thirteen normolipidemic, moderately overweight (body fat >30%) women were prescribed two hypocaloric (-500 kcal/day) diets for 4 week periods, a very low-carbohydrate (<10% carbohydrate) and a low-fat (<30% fat) diet. The diets were consumed in a balanced and randomized fashion. Two fasting blood draws were performed on separate days and an oral fat tolerance test was performed at baseline, after the very low-carbohydrate diet, and after the low-fat diet. RESULTS: Compared to corresponding values after the very low-carbohydrate diet, fasting total cholesterol, LDL-C, and HDL-C were significantly (p < or = 0.05) lower, whereas fasting glucose, insulin, and insulin resistance (calculated using the homeostatic model assessment) were significantly higher after the low-fat diet. Both diets significantly decreased postprandial lipemia and resulted in similar nonsignificant changes in the total cholesterol/HDL-C ratio, fasting triacylglycerols, oxidized LDL, and LDL subclass distribution. CONCLUSIONS: Compared to a low-fat weight loss diet, a short-term very low-carbohydrate diet did not lower LDL-C but did prevent the decline in HDL-C and resulted in improved insulin sensitivity in overweight and obese, but otherwise healthy women. Small decreases in body mass improved postprandial lipemia, and therefore cardiovascular risk, independent of diet composition.     

Dietary melatonin selectively reverses age-related changes in cortical cytokine mRNA levels,and their responses to an inflammatory stimulus

The basal levels of expression of mRNA of cytokines, interleukin-6 (IL-6) and tumor necrosis factor (TNF-alpha), in the cerebral cortex of 5 and 26 month-old male B6C3F1 mice have been compared. In addition, the responsivity of animals of differing age to an inflammatory stimulus (lipopolysaccharide, LPS) has been studied. Basal levels of both of these cytokine mRNAs were elevated in aged animals relative to the younger group. However LPS administration led to a robust increase in cytokine mRNA levels in the younger animals but in aged mice, there was either an unchanged (IL-6) or a depressed (TNF-alpha) response. Administration of dietary melatonin (200 ppm) to aged mice for 6 weeks prior to sacrifice, resulted in reduction of basal levels of cytokine mRNA to values found in the younger animals. Furthermore, following administration of LPS to melatonin fed animals, cerebral cytokine mRNA levels were significantly elevated rather than being unchanged or depressed. Taken together these findings reflect a trend in the cortices of melatonin-treated aged mice, to more closely approximate the status of younger mice. For comparative purposes, parallel studies were carried out using an immunologically active organ (spleen) and a non-neural organ with a low rate of cell turnover (heart muscle). In both these tissues, basal levels of cytokine mRNAs of animals of either age were very low, and there was a marked positive response to LPS. Dietary melatonin had no effect on the responses of TNF-alpha mRNA to LPS but attenuated the reaction of splenic IL-6 mRNA, thus bringing the response closer to that of the younger mice.     

Macrophages contribute to the maintenance of stable regenerating neurites following peripheral nerve injury

Normal adult uninjured nerve is unable to support axonal regeneration. We have studied the mechanisms underlying the regeneration of peripheral nerve by culturing adult mouse dorsal root ganglia (DRG) explants on unfixed, longitudinal cryosections of either the uninjured sciatic nerve or the distal segment of the transected sciatic nerve. We found that, initially, DRG grew vigorously on cryosections of both uninjured and postinjury sciatic nerves. However, the neurites began to degenerate shortly after contact with the uninjured nerve, whereas those growing on postinjury nerve substrate remained healthy for up to 9 days in culture. This ability to support stable outgrowth peaked at 8 days, gradually decreased by 10 days, and disappeared by 20 days after injury. Macrophages appeared in the distal segment by 4 days postinjury and had infiltrated its entire length by 8 days. Uninjured nerve cryosections could be rendered supportive of stable outgrowth by preincubation with macrophage-conditioned medium or by brief trypsinization. The activity of the macrophage-conditioned medium was augmented upon activation of macrophages. Together these findings suggest that the environment of the sciatic nerve undergoes a transformation during Wallerian degeneration such that it becomes transiently supportive of the stable outgrowth of neurites. This transformation may be mediated by a proteolytic activity, generated by activated macrophages, that removes a putative "degeneration signal" protein normally present in the adult nerve and thus contributes to the maintenance of stable regenerating neurites.     

The antibody response in pigs inoculated with attenuated African swine fever virus.

Pigs were inoculated with a modified isolate of African swine fever virus (ASFV). Complement-fixing (CF) and agar gel diffusion precipitin (AGDP) antibodies could be detected in the serums of most pigs from 14-days postinoculation (DPI) until their immunity was challenged with virulent ASFV at 117 DPI.Reductive cleavage with 2-mercaptoethanol showed that serums collected at 14 to 35 DPI contained 19S antibody, but that the 7S antibody was dominant at 35 and 117 DPI. This distribution of antibody was confirmed by sucrose-gradient centrifugation. Nearly all of the early serums also contained 7S antibodies which fixed complement and reacted in the AGDP test. Pigs whose serums contained both CF and AGDP antibodies at time of challenge failed to develop acute disease while pigs without CF antibodies were usually not protected.Pigs surviving challenge with virulent virus showed no increase in antibody titers, or reversion to 19S antibody.     

Controlled trial of calcitriol in hemodialysis patients

We report on a 5-year, prospective, double-blind trial of 1,25 dihydroxycholecalciferol (calcitriol) versus placebo in 76 hemodialysis patients without biochemical or radiological evidence of bone disease. Calcitriol, 1 microgram daily, regularly induced hypercalcemia. Doses of 0.25 microgram daily or less proved satisfactory in most patients. During calcitriol treatment, plasma calcium concentration was significantly higher and serum parathyroid hormone concentration significantly lower than on placebo. There was no difference in the rates of development or of progression of vascular calcification in the two groups. Significantly more patients on placebo (17 vs. 6, p less than 0.05) developed a sustained elevation of plasma alkaline phosphatase concentration. Calcitriol appeared to protect against the development of histological evidence of osteitis fibrosa but not of osteomalacia, but accumulation of aluminum in bone occurred during the study. We conclude that calcitriol delays and may prevent the development of osteitis fibrosa in patients receiving regular hemodialysis and may reasonably be prescribed routinely in hemodialysis patients without biochemical or radiological abnormality, unless there is a substantial prospect of early renal transplantation.     

Variability in the elimination of mianserin in elderly patients.

1. Two studies of the elimination of mianserin are reported. 2. In the first study, the oral clearance of mianserin was measured in 15 elderly patients at steady state. In a sub-group of eight patients who completed studies at two different doses there was evidence of enhanced oral clearance at the higher dose. 3. In the second study, the elimination half-life was estimated in 12 patients who were observed to have disproportionately high mianserin concentrations with respect to dose. All had half-lives greater than or equal to 2.5 days with a mean of 6 +/- 2.8 (s.d.) days. In six of the patients the profile of elimination was suggestive of saturable elimination. 4. The sparteine oxidation status was measured in seven of the patients showing slow mianserin elimination. Only one was a 'poor oxidiser' of sparteine, suggesting no concordance with this phenotype. 5. It is concluded that there is marked variability in the elimination of mianserin in elderly patients.     

“Meaningful Use” of ambulatory EMR: Does it improve the quality and efficiency of health care?

The US government has initiated incentive programs to encourage the adoption of Electronic Medical Records (EMR). To qualify for the incentive payment, healthcare providers need to demonstrate “meaningful use” of EMR systems, which requires the use of certified EMRs and the implementation of a set of standard functionalities. In this paper, we examine how the meaningful use of EMRs would affect health care outcomes in outpatient settings. Our results show that the use of core functionalities required by “meaningful use” criteria and the use of certified EMRs have a positive impact on the quality and efficiency of health care. In addition, we find the relationship between the meaningful use and quality of care is moderated by the length of use. The implications of this study are also discussed.