Hormesis, cellular stress response, and redox homeostasis in autism spectrum disorders.

In the United States, 1.1-1.5% of children have been diagnosed with autism spectrum disorders (ASD), corresponding to a 30% increase in incidence and prevalence. Social and communication impairments are the main signs and symptoms of ASD, and currently available medications have been ineffective in reducing these core deficits. Observational studies have indicated that children with ASD tend to show improved cognition and behavior after febrile illness, which is associated with alteration of metabolic pathways, leading to cellular stress responses and increased expression of heat shock proteins (Hsps). Sulforaphane and hydroxytyrosol, phytochemicals derived from cruciferous vegetables and extra virgin olive oil, respectively, can induce metabolic effects in cellular stress responses that are similar to those produced by fever. Thus, modulation of endogenous cellular defense mechanisms may be an innovative approach for therapeutic intervention in ASD and other disorders associated with neuroinflammation and neurodegeneration. This Review introduces the hormetic dose-response concept and presents possible mechanisms and applications for neuroprotection. We address the emerging role of Hsps in the neuroprotective network of redox stress-responsive mechanisms and propose the potential therapeutic utility of the nutritional antioxidants sulforaphane and hydroxytyrosol against particular signs and symptoms of ASD. We argue that such research findings must be approached with pragmatism and prudence. It is vital to capitalize on recent and ongoing investments in brain science research and to refine neuroscientific knowledge and capability for more accurate diagnosis and safe, effective, and ethically sound treatment of ASD and other neuropsychiatric spectrum disorders. © 2016 Wiley Periodicals, Inc.

Palifermin reduces infection rate and hyperfibrinogenemia in patients treated with high-dose chemotherapy based on beam or BU-thiothepa.

We performed a retrospective study in patients who underwent high-dose chemotherapy and auto-SCT because of haematological malignancies. Forty patients were treated with palifermin while 80 were controls selected after being matched for diagnosis and length of neutropenia. Patients treated with BEAM or BU-CY or THIO-CY (BEAM/BUS) displayed, after palifermin, a lower rate of severe oral mucositis (P=0.03). This beneficial effect of palifermin was not evident in the stratum of patients treated with high-dose melphalan (HD-PAM). After palifermin, we observed in the whole treated population a reduced rate of 'fever of unknown origin' (FUO, P=0.02) and of severe infections not related to Gram-positive bacteria (FUO, Gram-negative bacteremia or pneumonia) (P=0.003). This effect of palifermin on infections not related to Gram-positive bacteria was evident only in patients receiving BEAM/BUS (P=0.01) and not in patients treated with HD-PAM (P=0.11). Fibrinogen peak in plasma was found to be reduced after palifermin in the whole population (P=0.01) and in the stratum who received BEAM/BUS (P=0.02) but not in the stratum of HD-PAM. In conclusion, anti-infectious beneficial effects of palifermin are more evident in BEAM/BUS-treated patients and toward some types of infections. Reduction of fibrinogen level after palifermin suggests that this agent reduces not only the rate of infections but also their severity.