Repeated elements coordinate the spatial organization of the yeast genome.

The spatial organization of the chromosomes is crucial for gene expression and development. Inter- and intrachromosomal interactions form a crucial part of this epigenomic regulatory system. Here we use circular chromosome conformation capture-on-chip (4C) to identify interactions between repetitive and non-repetitive loci within the yeast genome. The interacting regions occur in non-randomly distributed clusters. Furthermore, the SIR2 histone deacetylase has opposing roles in the organization of the inter- or intrachromosomal interactions. These data establish a dynamic domain model for yeast genome organization. Moreover, they point to the repeated elements playing a central role in the dynamic organization of genome architecture.

How long after drug ingestion is activated charcoal still effective?

OBJECTIVE: The recent American Academy of Clinical Toxicology/European Association of Poisons Centres and Clinical Toxicologists position statement on activated charcoal stated "there are insufficient data to support or exclude its use after 1 hour of ingestion.'' The purpose of this study was to determine the effectiveness of activated charcoal administered 1, 2, and 3 hours after drug ingestion. METHODS: This was a human volunteer, randomized crossover study. Ten volunteers ingested 4 g of acetaminophen on four occasions at least 1 week apart. One ingestion served as a control and the other three as experimental ingestions with charcoal being administered at 1, 2, and 3 hours after acetaminophen dosing. Eight blood specimens were obtained over the initial 8 hours for serum acetaminophen concentrations that were used for calculation of routine pharmacokinetic parameters. Repeated measures of ANOVA and Tukey's HSD test were used for statistical analysis. RESULTS: Pharmacokinetic parameters for acetaminophen in our volunteers were consistent with literature values. The mean area under the curve (AUC+/-SD) for the control and the 1-, 2-, and 3-hour groups were 221 +/- 54, 154 +/- 71, 206 +/- 67 and 204 +/- 58 mg/L/h, respectively. The 1-hour group was the only one differing from control (p < 0.01). The decrease of bioavailability at 1 hour was 30.3%, which is similar to previous studies. CONCLUSION: Our data do not support the administration of activated charcoal as a gastrointestinal decontamination strategy beyond 1 hour after drug overdose.

Gastric lavage for liquid poisons.

STUDY OBJECTIVE: This study was conducted to determine whether gastric lavage reduces the absorption of ingested liquids. METHODS: The study design was a randomized controlled human volunteer crossover study in 10 subjects. On 2 separate occasions 2 weeks apart, the volunteers ingested a solution of 4.0 g of acetaminophen in 60 mL of water. Eight blood specimens were obtained over the initial 8 hours for determination of serum acetaminophen concentrations, which were used to calculate routine pharmacokinetic parameters. One hour after 1 drug ingestion, gastric lavage was performed through a 34-F orogastric tube. Serum acetaminophen concentrations were measured by high-performance liquid chromatography and a 2-tailed t test was used for statistical analysis. RESULTS: The mean values for area under the concentration curve (+/-SD) for the control and gastric lavage groups were 195+/-31 and 154+/-52 mg/L.hour, respectively (P <.05). The mean reduction in acetaminophen bioavailability because of gastric lavage was 20%+/-28% (95% confidence interval 3 to 37). CONCLUSION: In this experimental model for the ingestion of liquids, gastric lavage at 1 hour resulted in a significant decrease in the mean serum bioavailability of acetaminophen. Nonetheless, this treatment effect is unlikely to be of clinical value because of its modest extent, unreliable performance, and the availability of a more effective, less risky alternative, activated charcoal.