Improving Antioxidant Capacity in Children With Autism: A Randomized, Double-Blind Controlled Study With Cysteine-Rich Whey Protein.

Previous studies indicate that children with autism spectrum disorder (ASD) have lower levels of glutathione. Nutritional interventions aim to increase glutathione levels suggest a positive effect on ASD behaviors, but findings are mixed or non-significant. A commercially available nutritional supplement comprising a cysteine-rich whey protein isolate (CRWP), a potent precursor of glutathione, was previously found to be safe and effective at raising glutathione in several conditions associated with low antioxidant capacity. Therefore, we investigated the effectiveness of a 90-day CRWP intervention in children with ASD and examined whether intracellular reduced and oxidized glutathione improvements correlated with behavioral changes. We enrolled 46 (of 81 screened) 3-5-year-old preschool children with confirmed ASD. Using a double-blind, randomized, placebo-controlled design, we evaluated the effectiveness of daily CRWP (powder form: 0.5 g/kg for children <20 kg or a 10-g dose for those >20 kg), compared with placebo (rice protein mimicking the protein load in the intervention group), on glutathione levels and ASD behaviors assessed using different behavioral scales such as Childhood Autism Rated Scale, Preschool Language Scale, Social Communication Questionnaire, Childhood Behavioral Checklist and the parent-rated Vineland Adaptive Behavior Scale, 2nd edition (VABS-II). Forty children (CRWP, 21; placebo, 19) completed the 90-day treatment period. Improvements observed in some behavioral scales were comparable. However, the VABS-II behavioral assessment, demonstrated significant changes only in children receiving CRWP compared to those observed in the placebo group in the composite score (effect size 0.98; 95% confidence intervals 1.42-4.02; p = 0.03). Further, several VABS-II domain scores such as adaptive behavior (p = 0.03), socialization (p = 0.03), maladaptive behavior (p = 0.04) and internalizing behavior (p = 0.02) also indicated significant changes. Children assigned to the CRWP group showed significant increases in glutathione levels (p = 0.04) compared to those in the placebo group. A subanalysis of the VABS-II scale results comparing responders (>1 SD change from baseline to follow up) and non-responders in the CRWP group identified older age and higher levels of total and reduced glutathione as factors associated with a response. CRWP nutritional intervention in children with ASD significantly improved both glutathione levels and some behaviors associated with ASD. Further studies are needed to confirm these results. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/study/NCT01366859, identifier: NCT01366859.

A community-based pilot study of a diabetes pharmacist intervention in Latinos: impact on weight and hemoglobin A1c.

Type 2 diabetes disproportionately affects Latinos increasing their risk of diabetes-related complications. This study used a randomized controlled design with a community-based approach to evaluate the impact of a culturally tailored pharmacist intervention on clinical outcomes in Latino diabetics. The intervention included a focused discussion and two individual pharmacist counseling sessions on medication, nutrition, exercise, and self-care to promote behavior changes. Sessions were culturally adapted for language, diet, family participation, and cultural beliefs. Clinical outcomes were measured at baseline and three months. Nineteen intervention and 24 control participants completed the study. Mean BMI reduction was greater for intervention than for control group participants (-0.73 ± 0.07 kg/m2 versus + 0.37 ± 0.02 kg/m2 p<.009 respectively). Hemoglobin A1c was significantly reduced by 0.93 ± 0.45% in the intervention group only. There was no significant difference in blood glucose, blood pressure, or lipid levels. An innovative culturally-sensitive pharmacist intervention improved selected clinical outcomes among Latino diabetics.

Regulation of c-fos, c-jun and c-myc gene expression by angiotensin II in primary cultured rat astrocytes: role of ERK1/2 MAP kinases.

We have previously shown that angiotensin II (Ang II) stimulates astrocyte growth through activation of ERK1/2 mitogen activated protein (MAP) kinases. In the current study, we determined whether Ang II stimulates the expression of c-fos, c-jun and c-myc in brainstem astrocyte cultures. Reverse transcriptase-PCR analysis showed c-fos, c-jun, and c-myc mRNAs were induced by Ang II. The EC50 values for Ang II stimulation of c-fos, c-jun and c-myc were 1.3, 1.68 and 1.4 nM, respectively. Ang II (100 nM) induced peak stimulation for all genes by 45 min followed by a gradual decline. Inhibition of ERK1/2 by PD98059 attenuated Ang II-induced c-fos and c-myc mRNA expression (by 75% and 100%, respectively) but was ineffective in preventing Ang II induction of c-jun. These studies show for the first time in brainstem astrocytes that Ang II induces the expression of c-fos, c-myc and c-jun, and showed that ERK1/2 mediate Ang II stimulation of c-fos and c-myc. These data implicate the ERK1/2 MAP kinase pathway as a divergent point in controlling Ang II stimulation of immediate early response genes in the central nervous system.