Cariprazine Safety in Adolescents and the Elderly: Analyses of Clinical Study Data.

Schizophrenia is a life-long mental disorder, affecting young adolescents to elderly patients. Antipsychotic treatment is indicated for all patients with schizophrenia, including the very young and old as well. Developmental issues in the young and decline in organ functioning in the elderly could influence reactions to the drug, and require different dosing regimens. The aim of the present article was to examine the safety profile and dosing requirements in adolescent (13 to less than 18) and elderly (65 and above) patients treated with cariprazine. Data from two clinical studies (one pharmacokinetic pediatric study and one phase III clinical trial) on 49 adolescent patients and 17 elderly patients (65 years of age or above) treated with cariprazine was examined. Safety measures included assessment of adverse events (AEs), clinical laboratory values, physical examinations, extrapyramidal symptom (EPS)-, depression-, and suicidality rating scales. Safety parameters were summarized using descriptive statistics. Results indicate that cariprazine was generally safe and well tolerated. Adverse events in the marginal age populations were comparable to the adult population, except for less insomnia in the young and no reports of akathisia in the elderly. Laboratory parameters, vital sign values and EEG parameters were comparable to previously published data in the adult population. In conclusion, cariprazine in the approved adult dose-range of 1.5-6 mg might be a safe treatment option also in adolescent and elderly patients with schizophrenia. Further studies are need to verify these preliminary findings.

Association between serum IL-16 levels and the degree of sensitization in patients with atopic dermatitis.

BACKGROUND: Interleukin (IL)-16 has been characterized as an immunomodulatory cytokine. Besides its chemotactic properties, IL-16 amplifies inflammatory processes and possesses immunoregulatory functions. Our aim was to investigate the association between serum IL-16 levels and the degree of allergic sensitization in patients with atopic dermatitis (AD). METHODS: The serum level of IL-16 was measured by immunoenzymatic assays. Eosinophil cell count, serum total and specific IgE levels were assessed; prick tests were also carried out. Based on specific IgE levels and prick tests, AD patients were divided into sensitized and nonsensitized subgroups, and correlations among serum IL-16, total IgE levels and eosinophil cell counts were measured in the total patient group and in subgroups. RESULTS: In the total patient group, significantly higher levels of IL-16 were found in the sera of patients with AD, compared to healthy individuals and patients with psoriasis. A significant correlation was detected between serum levels of IL-16 and total IgE, total IgE and eosinophil counts, but not between IL-16 and eosinophils. When sensitized and nonsensitized subgroups were compared, IL-16 levels showed a significant difference in subgroups that were divided based on specific IgE measurements, but not in those subgroups which were divided based on prick tests. On the other hand, serum total IgE levels showed a significant difference between sensitized and nonsensitized subgroups, assessed by the specific IgE method and also by prick test. CONCLUSION: Serum IL-16 levels of AD patients correlate to some extent with sensitization. This correlation is not as strong as the correlation between total IgE levels and allergic sensitization.

Analysis of components of the CD14/TLR system on leukocytes of patients with atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is frequently associated with skin infections that may be a consequence of an impaired function of the innate immune response. Conversely, the frequent bacterial colonization may also influence the systemic immune reactions, including the Toll-like receptor (TLR) system, through the translocation of bacterial components into the circulation. Therefore, we characterized phenotypic and functional properties of the TLR system in patients with extrinsic and intrinsic AD. METHODS: The absolute number of surface CD14, TLR2, TLR4 and CD180 and the CD14-mediated uptake of bodipy-labeled endotoxin and bacteria by whole blood leukocytes was studied by flow cytometry. We measured the serum soluble CD14 concentration by an inhibitory flow cytometric method. RESULTS: We observed a significant overexpression of TLR2 and TLR4 on monocytes, TLR2 and CD14 on granulocytes and CD180 on lymphocytes of intrinsic AD patients compared to healthy controls. The serum soluble CD14 was not different in the intrinsic AD patients, while it was diminished in the extrinsic AD group compared to the controls. The endotoxin and bacterium uptake showed no differences. CONCLUSIONS: The observed upregulation of CD14, TLR2, TLR4 and CD180 on peripheral leukocytes seems to be rather a consequence than the cause of the repeated bacterial infections in AD.

Distribution of 1000 sequenced T-DNA tags in the Arabidopsis genome.

Induction of knockout mutations by T-DNA insertion mutagenesis is widely used in studies of plant gene functions. To assess the efficiency of this genetic approach, we have sequenced PCR amplified junctions of 1000 T-DNA insertions and analysed their distribution in the Arabidopsis genome. Map positions of 973 tags could be determined unequivocally, indicating that the majority of T-DNA insertions landed in chromosomal domains of high gene density. Only 4.7% of insertions were found in interspersed, centromeric, telomeric and rDNA repeats, whereas 0.6% of sequenced tags identified chromosomally integrated segments of organellar DNAs. 35.4% of T-DNAs were localized in intervals flanked by ATG and stop codons of predicted genes, showing a distribution of 62.2% in exons and 37.8% in introns. The frequency of T-DNA tags in coding and intergenic regions showed a good correlation with the predicted size distribution of these sequences in the genome. However, the frequency of T-DNA insertions in 3'- and 5'-regulatory regions of genes, corresponding to 300 bp intervals 3' downstream of stop and 5' upstream of ATG codons, was 1.7-2.3-fold higher than in any similar interval elsewhere in the genome. The additive frequency of insertions in 5'-regulatory regions and coding domains provided an estimate for the mutation rate, suggesting that 47.8% of mapped T-DNA tags induced knockout mutations in Arabidopsis.