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.

The effect of Antithrombin-III on routine hematological and biochemical parameters in an experimental animal model of skeletal muscle ischemia-reperfusion injury.

BACKGROUND: Antithrombin III (AT-III) has been shown to attenuate the local and systemic harmful effects of skeletal muscle ischemia-reperfusion (I-R) injury. The aim of the present study was to monitor the fluctuation of routine hematological and biochemical parameters in an experimental animal model of tourniquet-induced skeletal muscle I-R injury and to investigate how these are influenced by the protective administration of AT-III. METHODS: Sixty male Wistar rats were submitted to a 6-hour, tourniquet-induced, complete ischemia of the right hind-limb. Animals were divided into those receiving AT-III (dose, 250 IU/kg) 30 minutes before the reperfusion (group A, n=30) and those receiving placebo (group B, n =30). Another 10 animals were sham-operated (group C). White blood cell (WBC) and platelet (PLT) count, aspartate and alanine aminotransferases (AST and ALT), alkaline phosphatase (ALP), and γ-glutamyl transferase (γ-GT) were estimated in blood samples taken from the inferior vena cava at 3 different time points post-reperfusion (at baseline, at 30 minutes and at 4 hours) and groups A and B were compared using the Mann-Whitney U test. RESULTS: There were no statistically significant differences between the AT-III and the placebo groups at 0, 30 minutes and 4 hours with regard to the WBC, ALT and γ-GT levels, however, there was a significant decrease of AST levels 4 hours post-reperfusion in the AT-III group compared to the placebo group (p=0.002). An increased PLT count and ALP levels 30 minutes post-reperfusion were also noted in the AT-III group compared to placebo (p<0.001; and p=0.001, respectively). CONCLUSIONS: Of the routine hematological and biochemical parameters tested, AST was found to be significantly suppressed at 4 hours in the AT-III-treated animals, suggesting a possible beneficial effect of AT-III in mouse skeletal muscle I-R injury. The effect of AT-III on PLTs and ALP levels merits further investigation. Hippokratia 2014; 18 (3): 234-239.

Conservative management of canine tracheal collapse with stanozolol: a double blinded, placebo control clinical trial.

The objective of this study is to determine the efficacy of stanozolol in the treatment of tracheal collapse (TC) in dogs, which is the analogous disease to tracheomalacia (TM) in humans. Twenty-two dogs with endoscopically confirmed and graded TC were enrolled into five groups. Groups S1 (n=5), S2 (n=5) and S3 (n=4) with grade 1, 2 and 3 TC, respectively, received stanozolol orally for 75 days, while groups P1 (n=4) and P2 (n=4) with grade 1 and 2 TC, respectively, received placebo. The clinical score was evaluated every 15 days, whereas TC grade was reassessed at the end of the experiment. Clinical improvement was detected from the 30th day in S2 and S3 group dogs and from the 45th day in S1 group dogs and continued until the end of the experiment. Also, statistically significant differences were seen between S2 and P2 dogs from the 30th day, and between S1 and P1 dogs from the 60th day, and continued until the end of the study. Amelioration of the TC grade was seen in 13 of 14 (92.9%) dogs, which received stanozolol. Of the 14 dogs, 57.1% were cured and 35.8% demonstrated a less severe TC grade, while only one dog (7.1%) did not improve at all. Stanozolol seems to be an effective drug in the management of canine TC and it may have potential for use in humans with TM.

Factors associated with the occurrence of epistaxis in natural canine leishmaniasis (Leishmania infantum).

BACKGROUND: Canine leishmaniasis (CanL) is a common cause of epistaxis in dogs residing in endemic areas. The pathogenesis of CanL-associated epistaxis has not been fully explored because of the limited number of cases reported so far. HYPOTHESIS: Epistaxis in CanL could be attributed to more than 1 pathomechanism such as hemostatic dysfunction, biochemical abnormalities, chronic rhinitis, and coinfections occurring in various combinations. ANIMALS: Fifty-one dogs with natural CanL. METHODS: The allocation of 51 dogs in this cross-sectional study was based on the presence (n = 24) or absence (n = 27) of epistaxis. The potential associations among epistaxis and concurrent infections (Ehrlichia canis, Bartonella spp., and Aspergillus spp.), biochemical and hemostatic abnormalities, and nasal histopathology were investigated. RESULTS: Hypergammaglobulinemia (P= .044), increased serum viscosity (P= .038), decreased platelet aggregation response to collagen (P= .042), and nasal mucosa ulceration (P= .039) were more common in the dogs with epistaxis than in those without epistaxis. The other significant differences between the 2 groups involved total serum protein (P= .029) and gamma-globulin (P= .013) concentrations, which were higher, and the percentage platelet aggregation to collagen, which was lower (P= .012) in the epistaxis dogs. CLINICAL IMPORTANCE: CanL-associated epistaxis appears to be the result of multiple and variable pathogenetic factors such as thrombocytopathy, hyperglobulinemia-induced serum hyperviscosity, and nasal mucosa ulceration.

Short-term exogenous glucocorticosteroidal effect on iron and copper status in canine leishmaniasis (Leishmania infantum).

Prednisolone was administered as an anti-inflammatory for 7 consecutive days in 11 dogs with leishmaniasis (CL group) and 5 clinically normal dogs (control group). After a 15-day wash-out phase, the same medication was given as an immunosuppressive for another 7-day period. In both animal groups and experimental periods an overall significant increase of serum iron and transferrin saturation was noted. Serum copper showed a significant increase during the anti-inflammatory period in the control group and a significant decrease during the immunosuppressive period in the CL group. No differences or changes of any kind regarding bone marrow hemosiderin were found between the 2 groups either before or after the end of both experimental periods. The only change noticed in the hematocrit values was a significant decrease in the control group after the end of the anti-inflammatory period. Based on these findings the use of prednisolone cannot be recommended and, if contemplated, should be carefully monitored, especially at an immunosuppressive dosage, because it may promote parasite replication through the induction of increased serum iron levels and hypocupremia.