The dopamine D-2 antagonist, Ro 22-1319, inhibits the persistent behavioral syndrome induced by iminodipropionitrile (IDPN) in mice

Chronic administration of beta,beta'-iminodipropionitrile causes a persistent syndrome of excitement, choreoathetoid movements, and circling (the "ECC-syndrome") which persists indefinitely after termination of the IDPN injections. Ro 22-1319 is a specific D-2 dopamine receptor antagonist which was recently synthesized to fit a hypothetical model of the D-2 receptor. Ro 22-1319 inhibited several aspects of the ECC-syndrome, although some of its components, such as backward pedaling and forepaw treading reminiscent of the serotonin syndrome, were exacerbated. These results suggest that several neurotransmitter systems may be involved in the ECC-syndrome.     

Development of the Korea-Polyenvironmental Risk Score for Psychosis

Objective Comprehensive understanding of polyenvironmental risk factors for the development of psychosis is important. Based on a review of related evidence, we developed the Korea Polyenvironmental Risk Score (K-PERS) for psychosis. We investigated whether the K-PERS can differentiate patients with schizophrenia spectrum disorders (SSDs) from healthy controls (HCs). Methods We reviewed existing tools for measuring polyenvironmental risk factors for psychosis, including the Maudsley Environmental Risk Score (ERS), polyenviromic risk score (PERS), and Psychosis Polyrisk Score (PPS). Using odds ratios and relative risks for Western studies and the “population proportion” (PP) of risk factors for Korean data, we developed the K-PERS, and compared the scores thereon between patients with SSDs and HCs. In addition, correlation was performed between the K-PERS and Positive and Negative Syndrome Scale (PANSS). Results We first constructed the “K-PERS-I,” comprising five factors based on the PPS, and then the “K-PERS-II” comprising six factors based on the ERS. The instruments accurately predicted participants’ status (case vs. control). In addition, the K-PERS-I and -II scores exhibited significant negative correlations with the negative symptom factor score of the PANSS. Conclusion The K-PERS is the first comprehensive tool developed based on PP data obtained from Korean studies that measures polyenvironmental risk factors for psychosis. Using pilot data, the K-PERS predicted patient status (SSD vs. HC). Further research is warranted to examine the relationship of K-PERS scores with clinical outcomes of psychosis and schizophrenia.     

Migration of titanium dioxide microparticles and nanoparticles through the body and deposition in the gingiva: an experimental study in rats

The aim of this experimental work was to evaluate deposition of titanium dioxide (TiO₂) microparticles and nanoparticles, which could originate from titanium bioimplants, in the gingiva. Wistar rats were injected intraperitoneally (i.p.) with a suspension of TiO₂ particles of different sizes (150, 10, or 5 nm). The rats were killed 12 months post‐injection, and the buccal and lingual gingivae were resected and evaluated using light and scanning electron microscopy. Energy‐dispersive X‐ray spectroscopy (EDS) was used to confirm the presence of titanium in deposits of microparticles and nanoparticles, and the concentration of titanium in tissues was measured using inductively coupled plasma–mass spectrometry (ICP‐MS). Histological examination showed that all experimental groups exhibited agglomerates, in the gingiva, of titanium particles of micrometer size range, with no associated inflammatory response. Higher concentrations of titanium traces were shown, by ICP‐MS, in both buccal and lingual tissues of all experimental groups compared with their matched controls. Titanium concentrations were significantly higher in the buccal gingiva than in the lingual gingiva, and after injection with 5‐nm particles than with 10‐nm particles in both localizations. Titanium microparticles and nanoparticles deposit in the gingiva, and mostly on the buccal side. Gingival deposition of titanium could be considered a tissue indicator of tribocorrosion processes of titanium bioimplants.     

Comparison of three different forms of HLA-DR4Dw4 proteins

The biochemical behavior and peptide binding properties of a soluble form of the human class II DR4Dw4 molecule (PI-DR4Dw4) were compared to DR4Dw4 molecules containing the transmembrane and cytoplasmic domains that were purified both from B and transfected Chinese hamster ovary cells. Recombinant and B cell-derived DR4Dw4 molecules bound monoclonal anti-DR4Dw4 antibodies with different affinities and varied in their stability in the presence of sodium dodecyl sulfate. The three forms of DR4Dw4 bound peptides with a similar apparent affinity constant, but soluble class II molecules bound up to ten times more peptide than DR4Dw4 containing a transmembrane region. Peptide binding kinetics for soluble DR4Dw4 molecules were 10-20 times faster than for the other two forms of DR4Dw4 molecules. Finally, soluble PI-DR4Dw4/peptide complexes were shown to stimulate T cell proliferation.     

Results of phase II levetiracetam trial following acute head injury in children at risk for posttraumatic epilepsy

Posttraumatic seizures develop in up to 20% of children following severe traumatic brain injury (TBI). Children ages 6–17 years with one or more risk factors for the development of posttraumatic epilepsy, including presence of intracranial hemorrhage, depressed skull fracture, penetrating injury, or occurrence of posttraumatic seizure were recruited into this phase II study. Treatment subjects received levetiracetam 55 mg/kg/day, b.i.d., for 30 days, starting within 8 h postinjury. The recruitment goal was 20 treated patients. Twenty patients who presented within 8–24 h post‐TBI and otherwise met eligibility criteria were recruited for observation. Follow‐up was for 2 years. Forty‐five patients screened within 8 h of head injury met eligibility criteria and 20 were recruited into the treatment arm. The most common risk factor present for pediatric inclusion following TBI was an immediate seizure. Medication compliance was 95%. No patients died; 19 of 20 treatment patients were retained and one observation patient was lost to follow‐up. The most common severe adverse events in treatment subjects were headache, fatigue, drowsiness, and irritability. There was no higher incidence of infection, mood changes, or behavior problems among treatment subjects compared to observation subjects. Only 1 (2.5%) of 40 subjects developed posttraumatic epilepsy (defined as seizures >7 days after trauma). This study demonstrates the feasibility of a pediatric posttraumatic epilepsy prevention study in an at‐risk traumatic brain injury population. Levetiracetam was safe and well tolerated in this population. This study sets the stage for implementation of a prospective study to prevent posttraumatic epilepsy in an at‐risk population.     

Language abilities of siblings of children with autism

BACKGROUND: Language abilities of siblings of children with autism were examined to explore the possibility that language abilities are behavioral markers specific to the genetic liability for autism, as part of the broader phenotype. METHOD: Language abilities were compared among 27 siblings of children with autism, 23 siblings of children with mental retardation of unknown etiology (MR), and 22 siblings of children with developmental language disorders (DLD). Groups were matched by siblings' age, gender, birth order, family size, ethnicity, family income and by probands' gender and mental age. RESULTS: Siblings of children with autism achieved higher scores than siblings of children with DLD on receptive, expressive, and total language scales of the Children's Evaluation of Language Fundamentals and on verbal IQ. Moreover, within the DLD group, school problems in the domains of reading and arithmetic were more prevalent than within the other two groups. Only 2 siblings of children with autism received clinical diagnoses based on DSM-IV criteria compared to 3 siblings of children with MR and 7 siblings of children with DLD. CONCLUSIONS: After excluding data of the diagnosed siblings, no differences in language abilities could be discerned among the groups, except that more siblings in the DLD group were identified as having language difficulties. In summary, although language deficits characterize autism, siblings of children with autism were not found to demonstrate deficits in language skills assessed by formal language tests, IQ, or academic skills.