Beiträge zur pathologischen Anatomie des Ohres

Ohne ZusammenfassungMit 5 Textabbildungen.     

Oppositional COMT Val158Met effects on resting state functional connectivity in adolescents and adults

Prefrontal dopamine levels are relatively increased in adolescence compared to adulthood. Genetic variation of COMT (COMT Val158Met) results in lower enzymatic activity and higher dopamine availability in Met carriers. Given the dramatic changes of synaptic dopamine during adolescence, it has been suggested that effects of COMT Val158Met genotypes might have oppositional effects in adolescents and adults. The present study aims to identify such oppositional COMT Val158Met effects in adolescents and adults in prefrontal brain networks at rest. Resting state functional connectivity data were collected from cross-sectional and multicenter study sites involving 106 healthy young adults (mean age 24 ± 2.6 years), gender matched to 106 randomly chosen 14-year-olds. We selected the anterior medial prefrontal cortex (amPFC) as seed due to its important role as nexus of the executive control and default mode network. We observed a significant age-dependent reversal of COMT Val158Met effects on resting state functional connectivity between amPFC and ventrolateral as well as dorsolateral prefrontal cortex, and parahippocampal gyrus. Val homozygous adults exhibited increased and adolescents decreased connectivity compared to Met homozygotes for all reported regions. Network analyses underscored the importance of the parahippocampal gyrus as mediator of observed effects. Results of this study demonstrate that adolescent and adult resting state networks are dose-dependently and diametrically affected by COMT genotypes following a hypothetical model of dopamine function that follows an inverted U-shaped curve. This study might provide cues for the understanding of disease onset or dopaminergic treatment mechanisms in major neuropsychiatric disorders such as schizophrenia and attention deficit hyperactivity disorder.     

Population pharmacokinetic modeling for enterohepatic recirculation in Rhesus monkey.

Enterohepatic recirculation (EHR) occurs via biliary excretion and intestinal reabsorption of a drug. Drug recycling through EHR can lead to a change in pharmacokinetic (PK) properties, such as reduced clearance (CL), extended half-life (T(1/2)) and increased plasma exposure (AUC). As a result, EHR may prolong the pharmacological effect of drugs. In the present study, the compound (Cpd A) was found to exhibit EHR in Rhesus monkeys associated with a reduction in CL (from 3.8 to 0.33 Lh(-1), IV; from 2.3 to 0.4 Lh(-1), PO), and an increase in T(1/2) (from 0.9 to 18 h, IV) and in AUC (from 1.5 to 17.4 microg h/mL, IV; from 2.8 to 16.3 microg h/mL, PO), by comparing the PK in the monkeys via the interruption of EHR (bile-duct cannulation) with that in the intact monkeys. A population four-compartment model was constructed based on recirculation loops incorporating all possible inputs (bile secretion, a lag-time model for gall bladder emptying, routes and amounts of a single dose administration) to fully evaluate the EHR of Cpd A. The plasma concentrations versus time profiles predicted from the model had a good fit to the values observed in the subjects and were further simulated with 90% confidence interval to demonstrate its utility. Thus, the model could be applied as a useful tool to evaluate the drugs or compounds that undergo EHR in different species.     

Conversion disorder (DSM-III 300.11): Symptomatology and course in childhood and adolescence

Summary The incidence, age and sex distribution, symptomatology, psychosocial stress factors and course of conversion symptoms in a child and adolescent psychiatric patient sample were studied. Under the age of 10 conversion symptoms are comparatively rare and consequently require careful diagnosis, particularly regarding visual and hearing defects. Predominant conversion symptoms are seizures, gait problems and paralysis.     

Heteroduplex analysis of Salmonella virulence plasmids and their prevalence in isolates of defined sources

Strains of the Salmonella serovars S. typhimurium, S. enteritidis, S. dublin, and S. choleraesuis harbour large plasmids which are required for extraintestinal colonization after oral infection of mice. Electron microscopic heteroduplex analysis showed that these virulence plasmids share large regions of homology. Nine hundred and eighty-six isolates of different origins were analysed for the presence of these plasmids by using a cloned fragment of a S. choleraesuis virulence plasmid as a gene probe. Virulence plasmids were detected in nearly 100% of strains isolated from animal organs or human blood. Frequencies of detection ranged from 48 to 87% in strains of faecal, food or environmental origin. These results suggest that Salmonella virulence plasmids are required for systemic infections in humans and livestock.     

Long-lived photoproducts of rhodopsin in the retina of the frog

We find that Baumann's (1972) model with appropriate values for the rate constants rather well describes the spectral changes observed after irradiation of frog retinas at varying temperatures (0–25°C) and pH-values (6·0–7·9). The rates of both reactions leading to retinal, i.e. the decay of metarhodopsin III and the direct conversion of metarhodopsin II into retinal, decrease with increasing pH, which explains the accumulation of large amounts of M III in slightly alkaline retinas     

Holoprosencephaly, ear abnormalities, congenital heart defect, and microphallus in a patient with 11q- mosaicism

We report on a newborn male with deletion of part of 11q, the 27th reported case. Our patient had some of the clinical characteristics of the 11q- syndrome, but his male gender, liveborn status, q21 breakpoint, and mosaicism were unusual. In addition, he demonstrated holoprosencephaly, with cyclopia and arhinencephaly, manifestations previously unreported in the 11q- syndrome. We discuss the above points and review the literature on 11q-.