Background Eosinophilic esophagitis (EoE) is an emerging chronic inflammatory disease mediated by immune hypersensitization to multiple foods and strongly associated with atopy and esophageal remodeling. Objective We provide clinical and molecular evidence indicating a high prevalence of EoE in patients with inherited connective tissue disorders (CTDs). Methods We examined the rate of EoE among patients with CTDs and subsequently analyzed esophageal mRNA transcript profiles in patients with EoE with or without CTD features. Results We report a cohort of 42 patients with EoE with a CTD-like syndrome, representing 0.8% of patients with CTDs and 1.3% of patients with EoE within our hospital-wide electronic medical record database and our EoE research registry, respectively. An 8-fold risk of EoE in patients with CTDs (relative risk, 8.1; 95% confidence limit, 5.1-12.9; χ21 = 112.0; P < 10−3) was present compared with the general population. Esophageal transcript profiling identified a distinct subset of genes, including COL8A2, in patients with EoE and CTDs. Conclusion There is a remarkable association of EoE with CTDs and evidence for a differential expression of genes involved in connective tissue repair in this cohort. Thus, we propose stratification of patients with EoE and CTDs into a subset referred to as EoE-CTD.

Previous research has indicated that the blockade of H 3 -type histamine receptors may improve attention and memory in normal rodents. The purpose of this study was to determine if ciproxifan, an H 3 receptor antagonist, could alleviate the hyperactivity and cognitive deficits observed in a transgenic mouse model (APP Tg2576 ) of Alzheimer's disease. APP Tg2576 mice displayed significantly greater locomotor activity than wild-type mice, but APP Tg2576 mice provided with daily ciproxifan treatment showed activity levels that did not differ from wild-type mice. In the swim maze, APP Tg2576 mice exhibited significantly longer escape latencies, but the APP Tg2576 mice treated daily with ciproxifan had latencies that were indistinguishable from controls. In probe trials conducted one hour after the last training trial, ciproxifan-treated APP Tg2576 mice spent more time near the previous platform location and made more crossings of this area than did saline-treated APP Tg2576 mice. APP Tg2576 mice also demonstrated a significant impairment in the object recognition task that was reversed by acute treatment with ciproxifan (3.0 mg/kg). These data support the idea that modulation of H 3 receptors represents a novel and viable therapeutic strategy in the treatment of Alzheimer's disease.

Risperidone is an antipsychotic drug approved for use in children, but little is known about the long-term effects of early-life risperidone treatment. In animals, prolonged risperidone administration during development increases forebrain dopamine receptor expression immediately upon the cessation of treatment. A series of experiments was performed to ascertain whether early-life risperidone administration altered locomotor activity, a behavior sensitive to dopamine receptor function, in adult rats. One additional behavior modulated by forebrain dopamine function, spatial reversal learning, was also measured during adulthood. In each study, Long-Evans rats received daily subcutaneous injections of vehicle or one of two doses of risperidone (1.0 and 3.0 mg/kg per day) from postnatal days 14 – 42. Weight gain during development was slightly yet significantly reduced in risperidone-treated rats. In the first two experiments, early-life risperidone administration was associated with increased locomotor activity at one week post-administration through approximately nine months of age, independent of changes in weight gain. In a separate experiment, it was found that the enhancing effect of early-life risperidone on locomotor activity occurred in males and female rats. A final experiment indicated that spatial reversal learning was unaffected in adult rats administered risperidone early in life. These results indicate that locomotor activity during adulthood is permanently modified by early-life risperidone treatment. The findings suggest that chronic antipsychotic drug use in pediatric populations (e.g., treatment for the symptoms of autism) could modify brain development and alter neural set-points for specific behaviors during adulthood.

The C57BL/6 (B6) mouse is the background strain most frequently used for genetically-modified mice. Previous studies have found significant behavioral and genetic differences between the B6J (The Jackson Laboratory) and B6N substrains (National Institutes of Health); however, most studies employed only male mice. We performed a comprehensive battery of motor function and learning and memory tests on male and female mice from both substrains. The B6N male mice had greater improvement in the rotarod test. In contrast, B6J female mice had longer latencies to falling from the rotarod. In the Morris water maze (MWM), B6J males had significantly shorter latencies to finding the hidden platform. However, B6N females had significantly shorter path lengths in the reversal and shifted-reduced phases. In open field locomotor activity, B6J males had higher activity levels, whereas B6N females took longer to habituate. In the fear conditioning test, B6N males had a significantly longer time freezing in the new context compared with B6J males, but no significant differences were found in contextual or cued tests. In summary, our findings demonstrate the importance of testing both males and females in neurobehavioral studies. Both factors (sex and substrain) must be taken into account when designing developmental neurotoxicology studies.