Comparative metabolism of 1,2,4-trichlorobenzene in the rat and rhesus monkey

1,2,4-Trichloro[14C]benzene (TCB) was administered po (10 mg/kg) and iv (10 mg/kg) to rats and rhesus monkeys. Urine was collected at 24 hr and the major urinary metabolites were quantified and identified. By 24 hr, the monkey had excreted 22% of the iv dose and roughly 40% of the po dose in the urine. Less than 1% of the radioactivity was found in the monkey's feces. An isomeric pair of 3,4,6-trichloro-3,5-cyclohexadiene-1,2-diol glucuronides accounted for between 48 and 61% of the urinary metabolites. Glucuronides of 2,4,5- and 2,3,5-trichlorophenol (TCP) accounted for 14 to 37%, and unconjugated TCP's accounted for 1-37% of the monkey's urinary metabolites. For the rat, 84% of the po dose and 78% of the iv dose were collected in the urine by 24 hr; 11% and 7%, respectively, were the amounts collected in the feces. Two isomers, 2,4,5- and 2,3,5-, of N-acetyl-S-(trichlorophenyl)-L-cysteine accounted for 60-62% of the rat's urinary metabolites. Free 2,4,5- and 2,3,5-isomers of trichlorothiophenol amounted to 33% of the urinary metabolites in the po dosed rats and 28% in the iv dosed rats; free 2,4,5- and 2,3,5-TCP's amounted to 1% and 10%, respectively. These results show that there is a sharp division in the types of conjugates formed in the metabolism of 1,2,4-TCB by the rat and rhesus monkey.     

Computertomographische Spongiosadichtebestimmungen bei prä- und postmenopausalen Frauen

Ohne Zusammenfassung     

Interactions of carboxypeptidase G2 with 6S-leucovorin and 6R-leucovorin in vitro: implications for the application in case of methotrexate intoxications

Carboxypeptidase G₂ (CPG₂) is used when unexpected toxicity or renal failure occurs during high-dose methotrexate therapy. Leucovorin is also administered to antagonise the effects of methotrexate on purine anabolism. To investigate the effects of CPG₂ on leucovorin rescue, we incubated the enzyme with both stereoisomers and analysed the degradation. A method for separating the stereoisomers of leucovorin, the internal standard aminopterin and the degradation products by capillary electrophoresis with 2.6-dimethyl--cyclodextrin as a chiral selector has been developed. The active 6S-leucovorin is degraded much faster than the inactive 6R-isomer. The maximum observed degradation velocity was 31 M/min for 6S-leucovorin and 20 M/min for 6R-leucovorin, respectively, with an initial concentration of each stereoisomer of 250 M. Similar results were obtained at lower concentrations of leucovorin isomers. Thus, the selectivity of CPG₂ for methotrexate in comparison to leucovorin is not as high as anticipated in the literature as only the active 6S-leucovorin and not the mixture of the diastereomers should be taken into account. We conclude that the protective effects of leucovorin are antagonized by CPG₂. Therefore, CPG₂ should be administered to patients with caution.     

Zotepine in the treatment of acute hospitalized schizophrenic episodes

The atypical antipsychotic zotepine was studied in an open, multicentre uncontrolled, post-marketing surveillance study in 108 schizophrenic patients hospitalized in 12 trial centres in Austria. Within the dosage range of 50-450 mg (mean at the end of the study, 207 +/- 125 mg/day), a significant reduction of positive as well as negative symptoms was noted. There was no increase in extrapyramidal side-effects during the study and a significant decrease in akathisia scores. The medication was well tolerated during the 42-day observation period. Zotepine improved both positive and negative symptoms and was not accompanied by extrapyramidal side-effects, justifying its classification as an atypical antipsychotic.     

Evidence for superior neurobiological and behavioral inhibitory control abilities in non‐offending as compared to offending pedophiles

Neurobehavioral models of pedophilia and child sexual offending suggest a pattern of temporal and in particular prefrontal disturbances leading to inappropriate behavioral control and subsequently an increased propensity to sexually offend against children. However, clear empirical evidence for such mechanisms is still missing. Using a go/nogo paradigm in combination with functional magnetic resonance imaging (fMRI) we compared behavioral performance and neural response patterns among three groups of men matched for age and IQ: pedophiles with (N = 40) and without (N = 37) a history of hands‐on sexual offences against children as well as healthy non‐offending controls (N = 40). As compared to offending pedophiles, non‐offending pedophiles exhibited superior inhibitory control as reflected by significantly lower rate of commission errors. Group‐by‐condition interaction analysis also revealed inhibition‐related activation in the left posterior cingulate and the left superior frontal cortex that distinguished between offending and non‐offending pedophiles, while no significant differences were found between pedophiles and healthy controls. Both areas showing distinct activation pattern among pedophiles play a critical role in linking neural networks that relate to effective cognitive functioning. Data therefore suggest that heightened inhibition‐related recruitment of these areas as well as decreased amount of commission errors is related to better inhibitory control in pedophiles who successfully avoid committing hands‐on sexual offences against children. Hum Brain Mapp 38:1092–1104, 2017. © 2016 Wiley Periodicals, Inc.     

Differenzialdiagnose rheumatischer Erkrankungen

QUESTION TO ANSWER: Which imaging modalities are appropriate for the Differential diagnosis of Rheumatic diseases. METHODS AND RESULTS: MRI has far most the highest sensitivity and is unequaled in its brilliant presentation of anatomy and pathology. But it is sometimes forgotten, that this is at least in part the result of carefully selected sequences, dedicated to the expected result. CONCLUSION: Plain X-ray offers high specificity in the differential diagnoses of rheumatic diseases, it is well standardised and it is a device, to use independent from any suspected findings.