Vorinostat in the acute neuroinflammatory form of X-linked adrenoleukodystrophy.

OBJECTIVE: To identify a pharmacological compound targeting macrophages, the most affected immune cells in inflammatory X-linked adrenoleukodystrophy (cerebral X-ALD) caused by ABCD1 mutations and involved in the success of hematopoietic stem cell transplantation and gene therapy. METHODS: A comparative database analysis elucidated the epigenetic repressing mechanism of the related ABCD2 gene in macrophages and identified the histone deacetylase (HDAC) inhibitor Vorinostat as a compound to induce ABCD2 in these cells to compensate for ABCD1 deficiency. In these cells, we investigated ABCD2 and pro-inflammatory gene expression, restoration of defective peroxisomal ß-oxidation activity, accumulation of very long-chain fatty acids (VLCFAs) and their differentiation status. We investigated ABCD2 and pro-inflammatory gene expression, restoration of defective peroxisomal ß-oxidation activity, accumulation of very long-chain fatty acids (VLCFA) and differentiation status. Three advanced cerebral X-ALD patients received Vorinostat and CSF and MRI diagnostics was carried out in one patient after 80 days of treatment. RESULTS: Vorinostat improved the metabolic defects in X-ALD macrophages by stimulating ABCD2 expression, peroxisomal ß-oxidation, and ameliorating VLCFA accumulation. Vorinostat interfered with pro-inflammatory skewing of X-ALD macrophages by correcting IL12B expression and further reducing monocyte differentiation. Vorinostat normalized the albumin and immunoglobulin CSF-serum ratios, but not gadolinium enhancement upon 80 days of treatment. INTERPRETATION: The beneficial effects of HDAC inhibitors on macrophages in X-ALD and the improvement of the blood-CSF/blood-brain barrier are encouraging for future investigations. In contrast with Vorinostat, less toxic macrophage-specific HDAC inhibitors might improve also the clinical state of X-ALD patients with advanced inflammatory demyelination.

[Dementia and Nutrition - a brief overview].

The continued ageing of our society results in an increased prevalence of dementia. It is therefore of interest to question possible effects of a balanced right diet in the prevention of dementia as well as focus on the specific dietary needs of patients suffering from dementia. Epidemiologic studies have linked a Mediterranean diet to a decreased risk of developing dementia. Various current studies are being done to determine which nutritional components are causing the effect and whether single food components can cause similar outcomes. Malnutrition, Sarcopenia and Frailty are frequent co morbidities in moderate to severe dementia resulting in an increased care-dependency as well as a higher mortality rate. To prevent this, a timely intervention with a suitable diet is required.

[Feasibility of consultation - liaison psychiatry in a large general hospital: quantitative description of services and personnel expenditure]. / Möglichkeiten der psychosozialen Konsiliarversorgung im Schwerpunktkrankenhaus. Quantitative Leistungsdarstellung und Personalaufwand.

BACKGROUND: The integration of psychiatric departments in general hospitals lead to an increasing demand of psychiatric consultation, which often overstrains personnel resources of short staffed psychiatric services. To provide consulting service, as it is demanded by guidelines, a multidisciplinary consulting team could be a possible solution. METHODS: A retrospective descriptive analysis of all consultations made by the psychosocial consultation and liaison service at the general hospital Wels-Grieskirchen in the years 2012 and 2013. RESULTS: There was an increase in referrals overall of 22 % from 2012 to 2013. The largest increase was observed in the group of psychiatrists, who carried out 33.1 % of all consultations. Most consultations, 39.5 %, were done by the group of clinical psychologists, partly substituting medical attendance. Taking together both occupational groups, the expected number of consultations of at least 3 % of all admissions could be achieved. CONCLUSION: A multidisciplinary consulting team consisting of psychiatrists, psychologists, psychosomatic physicians and social workers staffed with 5.11-6.79 full-time personnel is able to provide psychosocial consultation service at a quantitative level required by international guidelines.

Perinatal use of aripiprazole: plasma levels, placental transfer, and child outcome in 3 new cases.

The use of new agents of second-generation antipsychotics in childbearing women is increasing and poses an unknown risk to the fetus; thus, information of pregnancy and child outcome are urgently needed. We reviewed the literature of 12 patients, 3 of them were exposed during the first trimester, and added 3 new cases of peripartum use of aripiprazole. No teratogenesis was observed despite all 3 women having received the substance during part or full first trimester. All 3 pregnancies were uncomplicated with spontaneous birth. Dosage had to be changed during the course of gestation from 2.5 to 15 mg and plasma levels (PL) were below recommended levels, although all 3 women remained in stable remission throughout pregnancy and postpartum period.The extent of placental transfer of aripiprazole (mean ratio of 56.2%) is comparable with that of other second-generation antipsychotics.Our observations have clinical implications: antipsychotic PLs show large-scale decreases, which may require dose adjustments during pregnancy. Pregnant women may require lower PLs. In our cases, a PL of one third of the previous effective PL was effective and safe. Repeated therapeutic drug monitoring during late gestation based on individual, previous effective PLs seems to be a feasible way for safe and effective antipsychotic therapy in unplanned pregnancy.