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These results were in contrast with the findings of El-Far et al. The differences could be explained by different dosing of the drug.

Preeclampsia is a disorder of pregnancy characterized by high blood pressure and level of protein in urine, due to endothelial dysfunction and is a primary cause of maternal morbidity.

Complications include aspiration pneumonia, cerebral hemorrhage, kidney failure, and cardiac arrest. The vascular endothelial grow factors VEGFs family of proteins and their receptors are thought to be key contributors to this disease.

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The VEGF-receptor-1 is denoted as soluble fms-like tyrosine kinase-1 sFlt-1 as it belongs to fms related tyrosine kinase family.

Placenta of pregnant women with preeclampsia produces high levels of sFlt-1. Advanced glycation end-products AGEs represent the molecular complexes generated as a result of nonenzymatic reactions of carbohydrates and oxidized lipid with proteins.

These reactions lead to the irreversible cross-linking of proteins and, as a consequence, loss of protein structure and function.

Previous studies demonstrated that serum AGEs in preeclamptic women were significantly higher than in healthy women.


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The study of Jeong et al. The study was conducted on JEG-3 cell line established from choriocarcinoma that was shown to retain trophoblastic cell-like characteristics.

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Unexpected results of healing of one patient from B-cell chronic lymphocytic leukemia B-CLL treated only with sildenafil were reported by Sarfati et al. During a 3. In addition, sildenafil induced apoptosis of the B-CLL cells in caspase 3-dependent way in vitro.

It has been shown that IL-4 abrogated the effect of sildenafil.

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Interestingly, there was no killing effect of sildenafil on normal B-cells. Treon et al. One patient had complete remission of WM.


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WM tumor cells were also culture-sorted with sildenafil at pharmacologically relevant levels and apoptosis was demonstrated in tumor cells from all 5 patients.

Possibly, the modulating effect of sildenafil on lymphocyte subpopulations and humoral immune responses is also mediated by the synthesis and release of cytokines.

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The Rho GTPases are involved in numerous signal transduction pathways and act as regulators of the actin cytoskeleton, cell motility, and transcription.

They are associated with progression to malignancy in several types of cancer. The Rho GTPases are molecular switches which remain inactive when GDP bound and active when GTP bound, and they expand their signals through interaction with numerous downstream signaling effectors.

In this way it is possible that sildenafil affects oncogenesis.

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Guilluy et al. The inhibition of intracellular events downstream of RhoA thus participates in the beneficial effect of sildenafil in pulmonary hypertension.

Caravita et al.

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