Glutamatergic changes with treatment in attention deficit hyperactivity disorder: a preliminary case series

Magnetic resonance spectroscopy, a noninvasive neuroimaging method, is a technique with the potential to measure in vivo neurochemical changes to different medication treatments. Symptoms of attention deficit hyperactivity disorder (ADHD) improved in two children treated with methylphenidate and two children treated with atomoxetine, for whom pre- and posttreatment proton magnetic resonance spectroscopy examinations were obtained to assess the relation between the neurochemical profiles in the striatum and prefrontal cortex among symptom severity and response to treatment. In the striatum, a striking decrease in the glutamate/creatine ratio (mean change 56.1%) was observed between 14 and 18 weeks of therapy in all four children with ADHD. In the prefrontal cortex, however, changes in the glutamate/creatine ratio were noted only in subjects receiving atomoxetine, not in those receiving methylphenidate. These data suggest that in vivo magnetic resonance spectroscopy measurement has the potential to assess response to psychopharmacological treatment in children with ADHD.     

Biological Transformation of Zearalenone by Some Bacterial Isolates Associated with Ruminant and Food Samples

Zearalenone (ZEA) is a secondary metabolite produced by Fusarium spp., the filamentous fungi. Food and feed contamination with zearalenone has adverse effects on health and economy. ZEA degradation through microorganisms is providing a promising preventive measure. The current study includes isolation of 47 bacterial strains from 100 different food and rumen samples. Seventeen isolates showed maximum activity of ZEA reduction. A bacterial isolate, RS-5, reduced ZEA concentration up to 78.3% through ELISA analysis and 74.3% as determined through HPLC. Ten of the most efficient strains were further selected for comparison of their biodegradation activity in different conditions such as incubation period, and different growth media. The samples were analyzed after 24 h, 48 h, and 72 h of incubation. De Man Rogosa Sharp (MRS) broth, Tryptic soy broth, and nutrient broth were used as different carbon sources for comparison of activity through ELISA. The mean degradation % ± SD through ELISA and HPLC were 70.77% ± 3.935 and 69.11% ± 2.768, respectively. Optimum reducing activity was detected at 72 h of incubation, and MRS broth is a suitable medium. Phylogenetic analysis based on 16S rRNA gene nucleotide sequences confirmed that one of the bacterial isolate RS-5 bacterial isolates with higher mycotoxin degradation is identified as Bacillus subtilis isolated from rumen sample. B05 (FSL-8) bacterial isolate of yogurt belongs to the genus Lactobacillus with 99.66% similarity with Lactobacillus delbrukii. Similarly, three other bacterial isolates, D05, H05 and F04 (FS-17, FSL-2 and FS-20), were found to be the sub-species/strains Pseudomonas gessardii of genus Pseudomonas based on their similarity level of (99.2%, 96% and 96.88%) and positioning in the phylogenetic tree. Promising detoxification results were revealed through GC-MS analysis of RS-5 and FSL-8 activity.     

Resveratrol supplementation confers neuroprotection in cortical brain tissue of nonhuman primates fed a high-fat/sucrose diet

Previous studies have shown positive effects of long-term resveratrol (RSV) supplementation in preventing pancreatic beta cell dysfunction, arterial stiffening and metabolic decline induced by high-fat/high-sugar (HFS) diet in nonhuman primates. Here, the analysis was extended to examine whether RSV may reduce dietary stress toxicity in the cerebral cortex of the same cohort of treated animals. Middle-aged male rhesus monkeys were fed for 2 years with HFS alone or combined with RSV, after which whole-genome microarray analysis of cerebral cortex tissue was carried out along with ELISA, immunofluorescence, and biochemical analyses to examine markers of vascular health and inflammation in the cerebral cortices. A number of genes and pathways that were differentially modulated in these dietary interventions indicated an exacerbation of neuroinflammation (e.g., oxidative stress markers, apoptosis, NF-κB activation) in HFS-fed animals and protection by RSV treatment. The decreased expression of mitochondrial aldehyde dehydrogenase 2, dysregulation in endothelial nitric oxide synthase, and reduced capillary density induced by HFS stress were rescued by RSV supplementation. Our results suggest that long-term RSV treatment confers neuroprotection against cerebral vascular dysfunction during nutrient stress.     

A homozygous splice site mutation in TRAPPC9 causes intellectual disability and microcephaly

Autosomal recessive intellectual disability is believed to be particularly prevalent in highly consanguineous populations and genetic isolates and may account for a quarter of all non-syndromic cases. Mutations in more than 50 genes have been reported to be involved in autosomal recessive intellectual disability, including TRAPPC9 (MIM 611966), mutations of which have been identified in six families from different geographical origins. We performed a clinical and molecular genetic study of a consanguineous Pakistani family segregating intellectual disability and microcephaly. SNP-array-based homozygosity mapping revealed suggestive linkage to four genomic regions including one on chromosome 8 that contained TRAPPC9. We detected a homozygous TRAPPC9 splice donor site mutation (c.1024+1G>T) that cosegregated with intellectual disability in the family and led to skipping of exon 3 and exons 3 and 4 in blood-derived patient RNA. We have thus identified a novel splice site mutation leading to exon skipping and premature termination of TRAPPC9 translation. These data further suggest that TRAPPC9 mutations –unlike mutations in the vast majority of the known intellectual disability-associated genes– constitute a more frequent cause of autosomal-recessive cognitive deficits, especially when microcephaly is also present.     

Metabolic responses to high-fat diets rich in n-3 or n-6 long-chain polyunsaturated fatty acids in mice selected for either high body weight or leanness explain different health outcomes

Background

Increasing evidence suggests that diets high in polyunsaturated fatty acids (PUFA) confer health benefits by improving insulin sensitivity and lipid metabolism in liver, muscle and adipose tissue.

Methods

The present study investigates metabolic responses in two different lines of mice either selected for high body weight (DU6) leading to rapid obesity development, or selected for high treadmill performance (DUhTP) leading to a lean phenotype. At 29 days of age the mice were fed standard chow (7.2% fat, 25.7% protein), or a high-fat diet rich in n-3 PUFA (n-3 HFD, 27.7% fat, 19% protein) or a high-fat diet rich in n-6 PUFA (n-6 HFD, 27.7% fat, 18.6% protein) for 8 weeks. The aim of the study was to determine the effect of these PUFA-rich high-fat diets on the fatty acid profile and on the protein expression of key components of insulin signalling pathways.

Results

Plasma concentrations of leptin and insulin were higher in DU6 in comparison with DUhTP mice. The high-fat diets stimulated a strong increase in leptin levels and body fat only in DU6 mice. Muscle and liver fatty acid composition were clearly changed by dietary lipid composition. In both lines of mice n-3 HFD feeding significantly reduced the hepatic insulin receptor β protein concentration which may explain decreased insulin action in liver. In contrast, protein kinase C ζ expression increased strongly in abdominal fat of n-3 HFD fed DUhTP mice, indicating enhanced insulin sensitivity in adipose tissue.

Conclusions

A diet high in n-3 PUFA may facilitate a shift from fuel deposition in liver to fuel storage as fat in adipose tissue in mice. Tissue specific changes in insulin sensitivity may describe, at least in part, the health improving properties of dietary n-3 PUFA. However, important genotype-diet interactions may explain why such diets have little effect in some population groups.     

Heritability of genetic variants of resistin gene in patients with coronary artery disease: a family-based study

ObjectiveThe resistin gene (RETN) ?420 C > G and + 299 G > A polymorphism was investigated in a case-control study from forty complex Pakistani families with coronary artery disease (CAD) history. Heritability of the susceptible/variant alleles was investigated from parent–offspring trios in these families.MethodResistin levels were determined from 239 individuals by enzyme-linked immunosorbent assay. Genotyping was performed using polymerase chain reaction and restriction fragment length polymorphism.ResultsElevated resistin levels were observed from CAD cases vs. controls (p < 0.0001). The RETN ? 420 C > G and + 299 G > A polymorphism was more prevalent in cases vs. controls (p < 0.0001). The transmission disequilibrium test revealed a significant association of the ? 420 and + 299 polymorphism with CAD (χ² = 34.4, p < 0.0001 and χ² = 31.6, p < 0.0001, respectively).ConclusionElevated resistin, and the RETN ?420 C > G and + 299 G > A polymorphism may contribute to familial CAD. The ? 420 and + 299 variant alleles are transmitted more frequently from parent to affected offspring. This is the first report on the association of the RETN + 299 G > A polymorphism with CAD.