Suppression of plasminogen activator inhibitor-1 (PAI-1) activity by crocin ameliorates lipopolysaccharide-induced thrombosis in rats.

The imbalance between clot formation and fibrinolysis is mainly attributed to increased levels of plasminogen activator inhibitor type 1 (PAI-1), an inhibitor of fibrinolysis closely involved in inflammatory responses such as septic shock. This increase is mediated by many factors, including reactive oxygen species (ROS). The present study was designed to evaluate the prophylactic effect of crocin, a potent natural antioxidant, on PAI-1 in the rat model of endotoxic shock. Lipopolysaccharide-infused rats (500 µg/kg) showed significant changes in thrombosis-related haematological parameters such as decrease of platelet blood counts and increase (7 fold) of PAI-1 concentration in blood plasma. No effect on t-PA activity was observed. Crocin administration in two different doses (10 mg/kg and 100 mg/kg) 30 min prior to the injection of LPS, inhibited the reduction of platelet counts and ameliorated the concentration of PAI-1 in the liver and the brain. Moreover, crocin inhibited the deposition of fibrin in the renal glomeruli. No significant changes were recorded in the healthy groups of crocin (10 mg/kg and 100 mg/kg) compared to the control group. These data demonstrate the potential of crocin to prevent LPS-induced organ injury and suggest it is worthwhile to investigate the use of antioxidants for the treatment of septicemia.

Mycotic encephalitis and nephritis in a dog due to infection with Cladosporium cladosporioides.

The dematiaceous fungus Cladosporium cladosporioides is a widely distributed saprophyte that is reported to occasionally infect the lung, skin, eye and brain of humans. This report describes a German shepherd dog with granulomatous encephalitis and nephritis due to C. cladosporioides infection. Although the fungal organisms appeared non-pigmented in haematoxylin and eosin stained sections, they were readily identified with histochemical stains. Semi-nested polymerase chain reaction using universal fungal primers amplified fungal DNA from fixed tissue that had identity to that of C. cladosporioides on sequencing.

Natural and lesion-induced apoptosis in the rat striatum during development.

We evaluated the pattern of apoptosis in the rat striatum during normal development and in two models of lesion-induced cell death. Lesions included i) unilateral ablations of the cerebral cortex at different postnatal ages, and ii) early postnatal lesions of the catecholaminergic afferent systems of the striatum with 6-hydroxydopamine (6-OHDA). Dying cells were identified as apoptotic using the TUNEL (terminal deoxynucleotidyl-transferase-mediated dUTP-biotin nick end labeling) method at the light and electron microscopic levels. Moreover, we used immunohistochemistry for the apoptotic markers active caspase-3 and fractin. TUNEL+ cells were present in the striatum during the first four postnatal weeks. Their frequency was high during the first postnatal week and peaked at postnatal day (P)5. Cortical lesions at birth, in contrast to those performed at later stages, induced a significant increase in the frequency of TUNEL+ cells in the ipsilateral striatum, which peaked at seven days postlesion. 6-OHDA lesions resulted in a similar and significant increase in the frequency of TUNEL+ cells in the striatum, which also peaked at P7. We also showed that cortical lesions at P0 and 6-OHDA lesions resulted in a reduction in the frequency, as well as in alterations of the morphology of gamma-aminobutyric acid (GABA)-immunoreactive (ir) neurons in the striatum. We suggest that: i) apoptosis in the striatum is temporally coordinated with maturation events in this area and ii) early developmental lesions of major afferent pathways to the striatum affect both the survival and phenotype of striatal neurons.