The effect of cholecalciferol supplementation on vitamin D levels and insulin sensitivity is dose related in vitamin D-deficient HIV-1-infected patients.

OBJECTIVE: The aim of this study was to explore the effects of cholecalciferol supplementation on vitamin D levels, bone mineral density (BMD), body fat distribution and insulin sensitivity in vitamin D-deficient HIV-1-infected patients. METHODS: Twenty vitamin D-deficient HIV-1-infected patients were prospectively treated with 2000 IU cholecalciferol/day for 14 weeks, whereafter treatment was continued with half this dosage until 48 weeks. BMD, body fat distribution, 1,25-dihydroxy vitamin D(3) (1,25(OH)2D3), fasting glucose, insulin, adiponectin, leptin, interleukin (IL)-6 and tumour necrosis factor (TNF)-alpha were measured at baseline, and at 24 and 48 weeks. Parathyroid hormone (PTH), 25-hydroxy vitamin D(3) [25(OH)D(3)], cholesterol and triglycerides were measured at baseline, and at 12, 24 and 48 weeks. RESULTS: After 24 weeks, cholecalciferol supplementation significantly increased 25(OH)D3 and 1,25(OH)2D3 levels and decreased PTH and insulin sensitivity. After 48 weeks, however, only 25(OH)D3 levels remained significantly different from baseline, while the other parameter levels returned to baseline, suggesting a dose-response effect. Cholecalciferol had no effect on BMD, adipokines and triglycerides. CONCLUSIONS: The effect of cholecalciferol treatment in this cohort appears to be dose dependent. Cholecalciferol dosages of > or =2000 IU are necessary to achieve 1,25(OH)2D3 levels that significantly decrease PTH, but also negatively affect insulin sensitivity. The results of this hypothesis-driven explorative study need to be confirmed in larger clinical trials.

Cumulative exergy extraction from the natural environment (CEENE): a comprehensive life cycle impact assessment method for resource accounting.

The objective of the paper is to establish a comprehensive resource-based life cycle impact assessment (LCIA) method which is scientifically sound and that enables to assess all kinds of resources that are deprived from the natural ecosystem, all quantified on one single scale, free of weighting factors. The method is based on the exergy concept. Consistent exergy data on fossils, nuclear and metal ores, minerals, air, water, land occupation, and renewable energy sources were elaborated, with well defined system boundaries. Based on these data, the method quantifies the exergy "taken away" from natural ecosystems, and is thus called the cumulative exergy extraction from the natural environment (CEENE). The acquired data set was coupled with a state-of-the art life cycle inventory database, ecoinvent. In this way, the method is able to quantitatively distinguish eight categories of resources withdrawn from the natural environment: renewable resources, fossil fuels, nuclear energy, metal ores, minerals, water resources, land resources, and atmospheric resources. Third, the CEENE method is illustrated for a number of products that are available in ecoinvent, and results are compared with common resource oriented LCIA methods. The application to the materials in the ecoinvent database showed that fossil resources and land use are of particular importance with regard to the total CEENE score, although the other resource categories may also be significant.

Visual acuity scored by the letter-by-letter or probit methods has lower retest variability than the line assignment method.

PURPOSE: The optimal method for scoring visual acuity measures is unknown. Our goal was to determine, in a clinical setting, the method of scoring visual acuity with the lowest test-retest variability. METHODS: We investigated the effect of three different scoring methods using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart comparing 32 patients with macular disease and 38 age-matched normal subjects. All subjects completed six repetitions of ETDRS charts. Three scoring methods were then used (line assignment, ETDRS or letter-by-letter and probit), the results were converted to log MAR values and the test-retest variabilities analysed. RESULTS: We found significant differences in variability among the three scoring methods (p < 0.0001). The variability was greatest with the line assignment method and less with the ETDRS and probit methods. The ETDRS and probit methods had similar variabilities. The difference in variability between normals and patients was not statistically significant. There were no differences in the calculated visual acuities among the three methods, only the variabilities. Using the ETDRS or probit methods, the within-test standard deviation was about 0.04 log MAR units (two letters). CONCLUSION: Test-retest variability of visual acuity measurements is lower using the ETDRS or probit methods than the traditional line assignment method.

Antisense oligonucleotides, a novel tool for the control of cytokine effects on human cartilage. Focus on interleukins 1 and 6 and proteoglycan synthesis.

OBJECTIVE: To prevent the negative effects of interleukin-1 (IL-1) and IL-1-induced IL-6 on cartilage proteoglycan (PG) synthesis, we used an antisense oligonucleotide (ASO) specific for IL-6 messenger RNA (mRNA) to inhibit IL-6 production. METHODS: Explants of human articular cartilage were cultured in the presence or absence of IL-6-ASO, IL-1, and exogenous IL-6. As metabolic parameters, cartilage production of IL-6 was determined in the B9 bioassay and PG as incorporation of 35SO4. RESULTS: The IL-6-ASO prevented IL-1-induced production of IL-6 in the cartilage explants, as well as IL-1-induced inhibition of PG synthesis. This inhibition was restored, despite the presence of IL-6-ASO, when exogenous IL-6 was added. A control ASO (not specific for IL-6 mRNA) was not effective. CONCLUSION: The IL-6-ASO used can penetrate the extracellular matrix of articular cartilage, enter the chondrocytes, and inhibit the IL-1-induced production of IL-6. Furthermore, IL-6-ASO can prevent the IL-1-induced inhibition of cartilage PG synthesis. The effect of exogenous IL-6 shows that IL-1 requires IL-6 for inhibition of PG synthesis.