[Aorto-iliac thrombosis in a gelding: treatment with the anticoagulant Phenprocoumon (Marcoumar)]. / Aortenthrombose bei einem Wallach: Behandlung mit dem Antikoagulans Phenprocoumon (Marcoumar).

A 14-year old Swiss warmblood gelding was presented to the equine hospital of the University of Zurich because of therapy-resistant fever. An intermittent lameness suggested the presence of an intravascular aorto-iliac thrombus which was confirmed sonographically. Subsequently, treatment was initiated with Heparin s.c. and continued for 7 months with Phenprocoumon (Marcoumar). The dosage was monitored and adjusted according to the prothrombin time, which was initially measured every week, and later maximally biweekly. The lameness improved and the regression of the thrombus could be followed sonographically. Seven months later the horse had to be euthanized due to acute colic.

[Drug interactions of phenylbutazone and phenprocoumon in a warmblood gelding]. / Arzneimittelinteraktionen von Phenylbutazon und Phenprocoumon bei einem Warmblutpferd.

A 15 year old Oldenburger gelding was treated during 3 weeks for laminitis with the anticoagulant phenprocoumone (27 mg orally, once daily) and concurrent administration of phenylbutazone (2-4 g orally, twice daily). After this treatment the animal was presented to the Equine Clinic University of Zurich with a history of acute colic and advanced symptoms of shock. On the basis of the clinical signs and laboratory values, a diagnosis of combined drug induced coagulopathy was made. The horse was treated with the antidote Vitamine-K1 (0.5 mg/kg, subcutaneously). Eventually, the general condition of the animal worsened and it was therefore euthanized. Necropsy revealed profound, multifocal hemorrhagic diathesis of the serosal surface of the viscera, as well as bleeding into the visceral cavities. This case shows that concurrent administration of phenprocoumone and phenylbutazone may lead to drug interactions that increase the anticoagulation effect of the coumarine-derivative. Simultaneous use of coumarine-derivatives and phenylbutazone is therefore contraindicated due to the higher risk of bleeding. A reasonable treatment of horses with anticoagulants requires regular monitoring with constant evaluation of coagulation status and special attention to potential drug interactions.

The roles of poly(ADP-ribose)-metabolizing enzymes in alkylation-induced cell death.

Poly(ADP-ribose) (PAR) has been identified as a DNA damage-inducible cell death signal upstream of apoptosis-inducing factor (AIF). PAR causes the translocation of AIF from mitochondria to the nucleus and triggers cell death. In living cells, PAR molecules are subject to dynamic changes pending on internal and external stress factors. Using RNA interference (RNAi), we determined the roles of poly(ADP-ribose) polymerases-1 and -2 (PARP-1, PARP-2) and poly(ADP-ribose) glycohydrolase (PARG), the key enzymes configuring PAR molecules, in cell death induced by an alkylating agent. We found that PARP-1, but not PARP-2 and PARG, contributed to alkylation-induced cell death. Likewise, AIF translocation was only affected by PARP-1. PARP-1 seems to play a major role configuring PAR as a death signal involving AIF translocation regardless of the death pathway involved.