Unintentional baclofen intoxication in the management of alcohol use disorder.

In recent years, there has been a growing interest in using baclofen for the management of alcohol use disorder. This off-label indication usually involves high doses of the medication. We report a case of severe baclofen overdose in a 66-year-old man. The patient was found severely agitated, and he presented with delirium and auditory hallucinations. At hospital admission, his daily dose was 180 mg baclofen. He was admitted to the intensive care unit for sedation and supportive care. When sedation was withdrawn, the patient presented with a normal neurological status. In this clinical context, baclofen intoxication was suspected. This was confirmed by measuring blood baclofen levels. This intoxication was probably mediated by a combination of risk factors including a high daily dose of baclofen and acute renal failure, conducive to drug accumulation.

Decrease in VEGF expression induces intussusceptive vascular pruning.

OBJECTIVE: The concept of vascular pruning, the "cuting-off" of vessels, is gaining importance due to expansion of angio-modulating therapies. The proangiogenic effects of vascular endothelial growth factor (VEGF) are broadly described, but the mechanisms of structural alterations by its downregulation are not known. METHODS AND RESULTS: VEGF(165)-releasing hydrogels were applied onto the chick chorioallantoic membrane on embryonic day 10. The hydrogels, designed to completely degrade within 2 days, caused high-level VEGF presentation followed by abrupt VEGF withdrawal. Application of VEGF resulted in a pronounced angiogenic response within 24 hours. The drastic decrease in level of exogenous VEGF-A within 48 hours was corroborated by enzyme-linked immunosorbent assay. Following this VEGF withdrawal we observed vasculature adaptation by means of intussusception, including intussusceptive vascular pruning. As revealed on vascular casts and serial semithin sections, intussusceptive vascular pruning occurred by emergence of multiple eccentric pillars at bifurcations. Time-lapse in vivo microscopy has confirmed the de novo occurrence of transluminal pillars and their capability to induce pruning. Quantitative evaluation corroborated an extensive activation of intussusception associated with VEGF withdrawal. CONCLUSIONS: Diminution of VEGF level induces vascular tree regression by intussusceptive vascular pruning. This observation may allude to the mechanism underlying the "normalization" of tumor vasculature if treated with antiangiogenic drugs. The mechanism described here gives new insights into the understanding of the processes of vasculature regression and hence provides new and potentially viable targets for antiangiogenic and/or angio-modulating therapies during various pathological processes.