Use of recombinant factor VII in cardiac surgery.

The off-label use of recombinant human coagulation factor VIIa has been increasing to a number of different treatment areas since its original approval in 1999. Several US patents describe claims for FVIIa utilization in nonhemophilia patients, treatment of bleeding due to trauma, as a means to reverse major bleeding, including intracranial bleeding, induced from fibrinolytic therapy as well as a patent for using FVIIa in the treatment of bleeding for patients with bleeding disorders not caused by hemophilia, but rather bleeding disorders due to thrombocytopenia, platelet disorders, and von Willebrand's disease. Bleeding after cardiac surgery remains a serious complication that can increase both morbidity and mortality. We review the off-label usage of recombinant factor VIIa as a hemostatic agent that may help control bleeding following cardiac surgery.

Inhibition of PC-3 prostate cancer cell growth in vitro using both antisense oligonucleotides and taxol.

Antisense oligonucleotides (oligos) directed against mRNA-encoding transforming growth factor-alpha (TGF-alpha) and the epidermal growth factor receptor (EGFR) have demonstrated in vitro and in vivo efficacy against prostate cancer tumor models. However, many therapeutic agents have increased effectiveness when given in combination with other more established agents. We evaluated the effectiveness of two oligos (3.32 and 6.64 microM/L) known to have significant activity against the PC-3 prostate cell line in combination therapy with the chemotherapeutic agent paclitaxel (Taxol) (2.5 and 5.0 nm). Therapy was evaluated when oligos and Taxol were administered either as (1) single agents, (2) simultaneously in a combined therapy, or (3) sequentially, a form of combination therapy with both agents being administered in a series. We found that when either of the two oligos were given simultaneously with Taxol, no synergistic activity was noted. However, when sequentially administered in a series 1 d apart, a pretreatment with the antisense directed against TGF-alpha (6.64 microM/L) followed by Taxol (5 nm) had significantly greater activity than these agents similarly administered in the reverse order or simultaneously.>

Effect of relaxin in two models of renal mass reduction.

BACKGROUND: Relaxin (Rlx), a 6-kD protein hormone, belongs to the insulin growth factor family. We have previously shown that Rlx reduces interstitial fibrosis in a model of chronic papillary necrosis. HYPOTHESIS: The purpose of this study was to extend these observations to a model of renal injury induced by mass reduction. MATERIAL AND METHODS: Renal mass was reduced by either infarction or surgical excision of both poles, with removal of the contralateral kidney. Two weeks later, creatinine clearance was done and animals from both groups implanted with osmotic pumps delivering either Rlx (2 microg/h) or vehicle (Veh). Treatment was continued for 4 weeks. The severity of the glomerular injury was quantified by planimetric measurements. Renal function was assessed by creatinine clearance and plasma creatinine. RESULTS: Rlx significantly decreased systolic blood pressure in animals with infarction. This was accompanied by a decrease in serum creatinine and a slight improvement in creatinine clearance. The severity of the glomerular lesion was reduced by Rlx (sclerosis index, Veh 1.16 +/- 0.13 vs. Rlx 0.74 +/- 0.16, p = 0.037). In the excision group the animals were normotensive. In this group, Rlx treatment was accompanied by a decrease in serum creatinine (Veh 1.01 +/- 0.03 vs. Rlx 0.81 +/- 0.05 mg/dl, p = 0.02) and an increase in GFR (Veh 0.90 +/- 0.14 vs. Rlx 1.33 +/- 0.11 ml/min, p = 0.03). The sclerosis index was also reduced. CONCLUSION: Rlx decreases renal injury by at least two mechanisms, one by lowering blood pressure as seen in the infarction model, the other independent of blood pressure as seen in the normotensive excision model where there was also a significant functional improvement.