Perioperative Dexamethasone for Patients With Diabetes and Its Effect on Blood Glucose After Surgery.

PURPOSE: P Perioperative administration of single-dose dexamethasone helps reduce postoperative nausea and vomiting, inflammation, and pain. However, it is unclear which dose achieves these effects while minimizing the hyperglycemic impact in patients with diabetes. The purpose of this review was to elucidate the most appropriate perioperative dose of dexamethasone for diabetic patients, and whether it is necessary to withhold it in patients with poor glycemic control. DESIGN: A systematic review. METHODS: A literature search using PubMed and Cochrane Database of Systematic Reviews revealed 17 potential evidence sources. Eight sources met the inclusion criteria. Sources included one systematic review with meta-analysis, one randomized control trial, and six observational studies. FINDINGS: Evidence suggests diabetic patients who receive dexamethasone perioperatively are more likely to develop postoperative hyperglycemia, with a maximum blood glucose increase of 30 to 45 mg/dL in the first 24 hours following a single dose. One study described increased blood glucose levels with escalating doses, but no other sources have supported that finding. The available studies were markedly heterogeneous in both design and proportion of diabetic subjects included, and most were of low quality. CONCLUSIONS: There is not enough evidence to quantify the hyperglycemic effect of commonly used dexamethasone doses, and rigorous studies are needed to inform practice.

FM19G11, a new hypoxia-inducible factor (HIF) modulator, affects stem cell differentiation status.

The biology of the alpha subunits of hypoxia-inducible factors (HIFalpha) has expanded from their role in angiogenesis to their current position in the self-renewal and differentiation of stem cells. The results reported in this article show the discovery of FM19G11, a novel chemical entity that inhibits HIFalpha proteins that repress target genes of the two alpha subunits, in various tumor cell lines as well as in adult and embryonic stem cell models from rodents and humans, respectively. FM19G11 inhibits at nanomolar range the transcriptional and protein expression of Oct4, Sox2, Nanog, and Tgf-alpha undifferentiating factors, in adult rat and human embryonic stem cells, FM19G11 activity occurs in ependymal progenitor stem cells from rats (epSPC), a cell model reported for spinal cord regeneration, which allows the progression of oligodendrocyte cell differentiation in a hypoxic environment, has created interest in its characterization for pharmacological research. Experiments using small interfering RNA showed a significant depletion in Sox2 protein only in the case of HIF2alpha silencing, but not in HIF1alpha-mediated ablation. Moreover, chromatin immunoprecipitation data, together with the significant presence of functional hypoxia response element consensus sequences in the promoter region of Sox2, strongly validated that this factor behaves as a target gene of HIF2alpha in epSPCs. FM19G11 causes a reduction of overall histone acetylation with significant repression of p300, a histone acetyltransferase required as a co-factor for HIF-transcription activation. Arrays carried out in the presence and absence of the inhibitor showed the predominant involvement of epigenetic-associated events mediated by the drug.