[Familial occurrence of a congenital defect of the keratinisation of the skin in German Angus calves]. / Familiäres Auftreten einer angeborenen Verhornungsstörung der Haut bei zwei Kälbern der Rasse Deutsche Angus.

Congenital dysfunction of the keratinisation of the epithelium was diagnosed in two female German Angus calves born on the same farm. The relationship coefficient between the two affected Angus calves was 34.38%. The clinical findings were similar to ichthyosis congenita as the alterations of the skin were present at birth and the levels of zinc in the blood were not decreased. However, parakeratosis could not be completely excluded as skin alterations were partly parakeratotic. On account of the close relationship between the two affected calves a genetic cause is likely for the present cases.

[Case report: congenital myoclonus in a German Holstein calf]. / Fallbericht. Kongenitale Myoklonie bei einem Kalb der Rasse Deutsche Holsteins.

A female German Holstein calf was not able to stand up after birth. Resting the animal was lying in normal position and could lift its head. Sensory stimuli like auditory or tactile impulses induced myoclonic jerking of the whole body. Afterwards it calmed down quickly. The signs observed correspond to the clinical findings of congenital myoclonus in poll Hereford calves. The pathological examination revealed no indications for changes in organs. The inbreeding coefficient of the calf was 1.56 %. The present type of congenital myoclonus in the calf examined is likely to be genetically determined, even if the point mutation in exon 2 of the glycin receptor alpha 1 gene was not confirmed.

Detection of hepatotoxicity potential with metabolite profiling (metabolomics) of rat plasma.

While conventional parameters used to detect hepatotoxicity in drug safety assessment studies are generally informative, the need remains for parameters that can detect the potential for hepatotoxicity at lower doses and/or at earlier time points. Previous work has shown that metabolite profiling (metabonomics/metabolomics) can detect signals of potential hepatotoxicity in rats treated with doxorubicin at doses that do not elicit hepatotoxicity as monitored with conventional parameters. The current study extended this observation to the question of whether such signals could be detected in rats treated with compounds that can elicit hepatotoxicity in humans (i.e., drug-induced liver injury, DILI) but have not been reported to do so in rats. Nine compounds were selected on the basis of their known DILI potential, with six other compounds chosen as negative for DILI potential. A database of rat plasma metabolite profiles, MetaMap(®)Tox (developed by metanomics GmbH and BASF SE) was used for both metabolite profiles and mode of action (MoA) metabolite signatures for a number of known toxicities. Eight of the nine compounds with DILI potential elicited metabolite profiles that matched with MoA patterns of various rat liver toxicities, including cholestasis, oxidative stress, acetaminophen-type toxicity and peroxisome proliferation. By contrast, only one of the six non-DILI compounds showed a weak match with rat liver toxicity. These results suggest that metabolite profiling may indeed have promise to detect signals of hepatotoxicity in rats treated with compounds having DILI potential.