Recombinant gamma interferon induces hypertriglyceridemia and inhibits post-heparin lipase activity in cancer patients.

Animals suffering from malignancy or chronic infection develop characteristic metabolic abnormalities, including a well-defined hypertriglyceridemic state. These abnormalities have been attributed to release of one or more mediators from activated macrophages. We report that cancer patients receiving RIFN-gamma, a potent macrophage activator, at doses of greater than or equal to 0.25 mg/m2/d i.m. show marked increases in triglyceride but not in cholesterol levels (pretreatment triglyceride level of 180 +/- 190 mg/dl [mean +/- SD] vs. a day-14 level of 370 +/- 242 mg/dl, n = 23, p less than 0.001 by the paired t test). This hypertriglyceridemia was characterized by an increase in very low-density lipoproteins and a decrease in plasma post-heparin lipase activity, consistent with defective triglyceride clearance (mean pretreatment lipase level of 2.1 mumol/ml/h vs. a day-14 level of 1.2 mumol/ml/h, n = 6, p = 0.02 by the paired t test). rIFN-gamma did not directly inhibit lipoprotein lipase enzymatic activity in vitro. Other possible mechanisms of action, such as suppression of lipase by an rIFN-gamma-induced mediator released from activated macrophages, or a direct effect of interferon on lipase biosynthesis, require further investigation. Our observations provide evidence that factors produced by the immune system can regulate lipid metabolism in man

The magnitude of educational disadvantage amongst indigenous minority groups in Australia.

Indigenous groups are amongst the most disadvantaged minority groups in the developed world. This paper examines the educational disadvantage of indigenous Australians by assessing academic performance at a relatively early age. We find that, by the age of 10, indigenous Australians are substantially behind non-indigenous Australians in academic achievement. Their relative performance deteriorates further over the next 2 years. School and locality do not appear to be important determinants of the indigenous to non-indigenous achievement gap. However, geographic remoteness, indigenous ethnicity and language use at home have a marked influence on educational achievement. A current focus of Australian indigenous policy is to increase school resources. Our results suggest that this will not eliminate indigenous educational disadvantage on its own

Efficacy of High Dose Vitamin D Supplements for Elite Athletes.

PURPOSE: Supplementation with dietary forms of vitamin D is commonplace in clinical medicine, elite athletic cohorts and the general population, yet the response of all major vitamin D metabolites to high doses of vitamin D is poorly characterized. We aimed to identify the responses of all major vitamin D metabolites to moderate and high dose supplemental vitamin D3. METHODS: A repeated measures design was implemented in which 46 elite professional European athletes were block randomized based on their basal 25[OH]D concentration into two treatment groups. Athletes received either 35,000 or 70,000 IU.week vitamin D3 for 12 weeks and 42 athletes completed the trial. Blood samples were collected over 18 weeks to monitor the response to supplementation and withdrawal from supplementation. RESULTS: Both doses led to significant increases in serum 25[OH]D and 1,25[OH]2D3. 70,000 IU.week also resulted in a significant increase of the metabolite 24,25[OH]2D at weeks 6 and 12 that persisted following supplementation withdrawal at week 18, despite a marked decrease in 1,25[OH]2D3. Intact PTH was decreased in both groups by week 6 and remained suppressed throughout the trial. CONCLUSIONS: High dose vitamin D3 supplementation (70,000 IU.week) may be detrimental for its intended purposes due to increased 24,25[OH]2D production. Rapid withdrawal from high dose supplementation may inhibit the bioactivity of 1,25[OH]2D3 as a consequence of sustained increases in 24,25[OH]2D that persist as 25[OH]D and 1,25[OH]2D concentrations decrease. These data imply that lower doses of vitamin D3 ingested frequently may be most appropriate and gradual withdrawal from supplementation as opposed to rapid withdrawal may be favorable

Evaluation of a Commercial Enzyme Linked Immunosorbent Assay (ELISA) for the Determination of the Neurotoxin BMAA in Surface Waters

The neurotoxin ß-N-methylamino-L-alanine (BMAA) is suspected to play a role in Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis. Because BMAA seems to be produced by cyanobacteria, surface waters are screened for BMAA. However, reliable analysis of BMAA requires specialized and expensive equipment. In 2012, a commercial enzyme-linked immunosorbent assay (ELISA) for determination of BMAA in surface waters was released. This kit could enable fast and relatively cheap screening of surface waters for BMAA. The objective of this study was to determine whether the BMAA ELISA kit was suitable for the determination of BMAA concentrations in surface waters. We hypothesised that the recovery of spiked samples was close to 100% and that the results of unspiked sample analysis were comparable between ELISA and liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis. However, we found that recovery was higher than 100% in most spiked samples, highest determined recovery was over 400%. Furthermore, the ELISA gave a positive signal for nearly each tested sample while no BMAA could be detected by LC-MS/MS. We therefore conclude that in its current state, the kit is not suitable for screening surface waters for BMAA

Degenerate fermion gas heating by hole creation

Loss processes that remove particles from an atom trap leave holes behind in the single particle distribution if the trapped gas is a degenerate fermion system. The appearance of holes increases the temperature and we show that the heating is (i) significant if the initial temperature is well below the Fermi temperature $T_{F}$, and (ii) increases the temperature to $T \geq T_{F}/4$ after half of the system's lifetime, regardless of the initial temperature. The hole heating has important consequences for the prospect of observing Cooper-pairing in atom traps.Comment: to be published in PR

Phase I/II study of DHA–paclitaxel in combination with carboplatin in patients with advanced malignant solid tumours

DHA–paclitaxel is a conjugate of paclitaxel and the fatty acid, docosahexaenoic acid. Preclinical studies have demonstrated increased activity, relative to paclitaxel, with the potential for an improved therapeutic ratio. We conducted a phase I study to determine the maximum tolerated doses of DHA–paclitaxel and carboplatin when administered in combination. Two cohorts of patients were treated: carboplatin AUC 5 with DHA–paclitaxel 660 mg m-2 and carboplatin AUC 5 with DHA–paclitaxel 880 mg m-2. Both drugs were given on day 1 every 21 days. A total of 15 patients were enrolled with a median age of 59 years (range 33–71). All patients had advanced cancer refractory to standard treatment, performance status 0–2 and were without major organ dysfunction. A total of 54 cycles of treatment were delivered. No dose-limiting toxicity (DLT) was seen in the first cohort of three patients. In an expanded second cohort, neutropenia was the main DLT, occurring in the first cycle of treatment in five of 12 patients: three of these patients and one additional patient also experienced dose-limiting grade 3 transient rises in liver transaminases. No alopecia was seen and one patient developed clinically significant neuropathy. One partial response was seen in a patient with advanced adenocarcinoma of the oesophago-gastric junction and 12 patients had stable disease with a median time to progression of 184 days (range 60–506 days). The recommended phase II dose in pretreated patients is Carboplatin AUC 5 and DHA–paclitaxel 660 mg m-2 given every 21 days. Further studies with Carboplatin AUC 5 and DHA-paclitaxel 880 mg m-2, given every 28 days, are warranted in chemo-naive patients