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1.
Ned Tijdschr Geneeskd ; 160: D491, 2016.
Article in Dutch | MEDLINE | ID: mdl-27848906

ABSTRACT

BACKGROUND: Barbiturate intoxication is potentially lethal. With the availability of the newer anticonvulsants the use of barbiturates in treating epilepsy has decreased significantly, with a concurrent decrease in the incidence of overdose with these medications. There have, however, been recent alarm signals from governmental sources concerning the increase in the Internet purchase of illegal medications, including barbiturates, for use in attempted suicide. CASE DESCRIPTION: Here we describe two patient cases involving barbiturate intoxication with amobarbital and thiopental, respectively. They had both obtained the barbiturates via the Internet. Both patients were comatose and showed signs of respiratory depression; one of them was also haemodynamically unstable. Both patients recovered fully following intensive supportive therapy. CONCLUSION: In patients with coma, respiratory depression, absence of brainstem reflexes and shock with no evident cause one should be aware of the possibility of barbiturate intoxication, even when there is no indication that these have been prescribed or that the patient has direct or indirect access to barbiturates. Prompt, optimal supportive therapy will give a good chance of full somatic recovery.


Subject(s)
Anticonvulsants/poisoning , Barbiturates/poisoning , Coma/chemically induced , Suicide, Attempted , Amobarbital/adverse effects , Amobarbital/poisoning , Anticonvulsants/administration & dosage , Barbiturates/administration & dosage , Barbiturates/adverse effects , Drug Overdose , Female , Humans , Male , Respiratory Insufficiency/chemically induced , Thiopental/poisoning
2.
Biochim Biophys Acta ; 1839(11): 1273-82, 2014 Nov.
Article in English | MEDLINE | ID: mdl-24878542

ABSTRACT

GATA4 is expressed in the proximal 85% of small intestine where it promotes a proximal intestinal ('jejunal') identity while repressing a distal intestinal ('ileal') identity, but its molecular mechanisms are unclear. Here, we tested the hypothesis that GATA4 promotes a jejunal versus ileal identity in mouse intestine by directly activating and repressing specific subsets of absorptive enterocyte genes by modulating the acetylation of histone H3, lysine 27 (H3K27), a mark of active chromatin, at sites of GATA4 occupancy. Global analysis of mouse jejunal epithelium showed a statistically significant association of GATA4 occupancy with GATA4-regulated genes. Occupancy was equally distributed between down- and up-regulated targets, and occupancy sites showed a dichotomy of unique motif over-representation at down- versus up-regulated genes. H3K27ac enrichment at GATA4-binding loci that mapped to down-regulated genes (activation targets) was elevated, changed little upon conditional Gata4 deletion, and was similar to control ileum, whereas H3K27ac enrichment at GATA4-binding loci that mapped to up-regulated genes (repression targets) was depleted, increased upon conditional Gata4 deletion, and approached H3K27ac enrichment in wild-type control ileum. These data support the hypothesis that GATA4 both activates and represses intestinal genes, and show that GATA4 represses an ileal program of gene expression in the proximal small intestine by inhibiting the acetylation of H3K27.


Subject(s)
GATA4 Transcription Factor/physiology , Histone Acetyltransferases/antagonists & inhibitors , Histones/metabolism , Ileum/metabolism , Acetylation , Animals , Cells, Cultured , Down-Regulation/genetics , Gene Expression Regulation , Histone Acetyltransferases/metabolism , Intestine, Small/metabolism , Lysine/metabolism , Mice , Mice, Transgenic
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