Tuesday, July 29, 2008
“Lorenzo’s Oil” Therapy for X-linked Adrenoleukodystrophy: Rationale and Current Assessment of Efficacy
Abstract X-linked adrenoleukodystrophy (X-ALD) is a genetic disorder that damages the nervous system and is associated with the accumulation of saturated very long chain fatty acids (SVLCFA). Oral administration of “Lorenzo’s oil” (LO), a 4:1 mixture of glyceryl trioleate and glyceryl trierucate, normalizes the SVLCFA levels in plasma, but its clinical efficacy and the clinical indications for its use have been controversial for more than 15 years. We review the biochemical effects of LO administration and the rationale for its use and present a current appraisal of its capacity to reduce the risk for the childhood cerebral phenotype when administered to asymptomatic boys and to slow progression of adrenomyeloneuropathy in patients without cerebral involvement. We also present current efforts to provide definitive evaluation of its clinical efficacy and discuss its possible role in the new therapeutic opportunities that will arise if newborn screening for X-ALD is validated and implemented.
“Good” and “bad” diatoms: development, growth and juvenile mortality of the copepod Temora longicornis on diatom diets
Abstract We measured development, growth and juvenile mortality of the common copepod Temora longicornis on 11 different monospecific diatom diets in order to estimate (1) how common the negative effects of diatoms are on the development of this copepod and (2) whether the arrested development is connected to deleterious polyunsaturated aldehydes (PUA) or food nutritional quality. Four diatom species (Thalassiosira weissflogii, Thalassiosira rotula CCMP1647, Leptocylindricus danicus CCPM469 and Skeletonema costatum CCMP1281) supported complete development, whereas development failed in or before metamorphosis on seven diatom species/strains (Chaetoceros affinis CCMP158, C. decipiens CCMP173, C. socialis, T. rotula CCMP1018, Thalassiosira pseudonana CCMP1010 and CCMP1335). However, four out of these seven species were not ingested by nauplii, either due to morphology (Chaetoceros spp.) or large size (T. pseudonana CCMP1010). The growth rate did not correlate with the ingestion rate of PUA, neither with ingestion of food mineral (nitrogen) nor with biochemical (polyunsaturated fatty acids, sterols) components. We show that, although some diatoms are of inferior food quality, this is unlikely to be connected to toxicity or due to a direct limitation by a single food nutritional compound.
‘Hybrid’ Bariatric Surgery: Bilio-pancreatic Diversion and Duodenal Switch - Preliminary Experience
Background: Hybrid, combined or mixed bariatric surgery is the combination of a degree of ‘malabsorption’ (as achieved by the intestinal bypass) with a ‘rrestriction’ (as achieved by gastric bypass or gastroplasty), thereby simultaneously reducing the absorption of fats in the small bowel and decreasing the intake of food. Methods: A modification of the bilio-pancreatic diversion (BPD) with a duodenal switch procedure, vertical lineal gastrectomy and preservation of the pylorus, has been used in 23 patients. The antropyloric pump and 4 cm of the duodenum are left intact to preserve physiologic gastric emptying and to prevent anastomotic ulcer. The use of staplers and continuous running sutures reduces surgical risks and operative time. Results: One patient, converted from a vertical gastroplasty, had an intrathoracic esophageal perforation and died of multisystemic organ failure, a mortality rate of 4.5%. One patient had a partial dehiscence of the laparotomy wound. Three patients developed subcutaneous seromas. Mean weight losses during the first 4 months were 13, 11, 6 and 5 kg, with a loss of 70% of excess weight in patients approaching 1 year. No patient needs treatment for diarrhea. No serious secondary side-effects have been detected. Conclusion: This operation appears to result in very satisfactory weight loss, improved quality of life, and a low incidence of complications.
‘Excesses of Responsibility? – Reconsidering Company Liability’
Abstract Several areas of expanding corporate responsibilities are evident from current practices. This article penetrates one such field, economic compensation through litigation, and discusses the possibility and desirability of reversing the trend. In court, companies are fined increasing amounts for an ever wider range of faults, or they settle out of court under this legal threat. This is not a local American problem, but European companies are increasingly involved because of globalization. The development in Europe is also driven by the same factors as in America – the mechanics of litigation and conventional ethics. The greed of plaintiffs and lawyers can mobilize the perceived virtue of sympathizing with a victim. Therefore it seems likely that a precondition for tort reform is an ethical reevaluation. Is it desirable and politically possible to make the individual more responsible for his own fate?
[3-13C] γ-linolenic acid: A new probe for 13C nuclear magnetic resonance studies of arachidonic acid synthesis in the suckling rat
Abstract Our objective was to develop a suitable probe to study metabolism of polyunsaturated fatty acids by 13C nuclear magnetic resonance (NMR) in the suckling rat pup. [3-13C] γ-Linolenic acid was chemically synthesized, and a 20 mg (Experiment 1) or 5 mg (Experiment 2) dose was injected into the stomachs of 6–10-day-old suckling rat pups that were then killed over a 192 h (8 d) time course. 13C NMR showed that 13C in γ-linolenate peaked in liver total lipids by 12-h post-dosing and that [5-13C]-arachidonic acid peaked in both brain and liver total lipids 48–96 h post-dosing. 13C enrichment in brain γ-linolenic acid was not detected by NMR, but gas chromatography-combustion-isotope ratio mass spectrometry showed that its mass enrichment in brain phospholipids at 48–96 h post-dosing was 1–2% of that in brain arachidonic acid. 13C was present in liver and brain cholesterol and in perchloric acid-extractable water-soluble metabolites in the brain, liver and carcass. We conclude that low but measurable amounts of exogenous γ-linolenic acid do access the suckling rat brain in vivo. The slow time course of [5-13C] arachidonic acid appearance in the brain suggests most of it was probably transported there after synthesis elsewhere, probably in the liver. Some carbon from γ-linolenic acid is also incorporated into lipid products other than n−6 long-chain polyunsaturated fatty acids.
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