In Vitro And In Vivo Anti-angiogenic Effects Of Hydroxyurea.

Hydroxyurea (HU), or hydroxycarbamide, is used for the treatment of some myeloproliferative and neoplastic diseases, and is currently the only drug approved by the FDA for use in sickle cell disease (SCD). Despite the relative success of HU therapy for SCD, a genetic disorder of the hemoglobin β chain that results in red-cell sickling, hemolysis, vascular inflammation and recurrent vasoocclusion, the exact mechanisms by which HU actuates remain unclear. We hypothesized that HU may modulate endothelial angiogenic processes, with important consequences for vascular inflammation. The effects of HU (50-200 μM; 17-24 h) on endothelial cell functions associated with key steps of angiogenesis were evaluated using human umbilical vein endothelial cell (HUVEC) cultures. Expression profiles of the HIF1A gene and the miRNAs 221 and 222, involved in endothelial function, were also determined in HUVECs following HU administration and the direct in vivo antiangiogenic effects of HU were assessed using a mouse Matrigel-plug neovascularization assay. Following incubation with HU, HUVECs exhibited high cell viability, but displayed a significant 75% inhibition in the rate of capillary-like-structure formation, and significant decreases in proliferative and invasive capacities. Furthermore, HU significantly decreased HIF1A expression, and induced the expression of miRNA 221, while downregulating miRNA 222. In vivo, HU reduced vascular endothelial growth factor (VEGF)-induced vascular development in Matrigel implants over 7 days. Findings indicate that HU is able to inhibit vessel assembly, a crucial angiogenic process, both in vitro and in vivo, and suggest that some of HU's therapeutic effects may occur through novel vascular mechanisms.

Gastroprotective Effects (in Rodents) Of A Flavonoid Rich Fraction Obtained From Syngonanthus Macrolepsis.

Syngonanthus macrolepis, popularly known in Brazil as 'sempre-vivas', is a plant from the family Eriocaulaceae, it is found in the states of Minas Gerais and Bahia. The species contains a variety of constituents, including flavonoids with gastroprotective effect. In this work, a flavonoid-rich fraction (Sm-FRF) obtained from scapes of S. macrolepis was investigated for preventing gastric ulceration in mice and rats. The activity was evaluated in models of induced gastric ulcer (absolute ethanol, stress, non-steroidal anti-inflammatory drugs and pylorus ligation). The cytoprotective mechanisms of the Sm-FRF in relation to sulfhydryl (SH) groups, nitric oxide (NO) and antioxidant enzymes were also evaluated. The Sm-FRF (100 mg/kg, p.o.) significantly reduced gastric injury in all models, and did not alter gastric juice parameters after pylorus ligation. The results indicate significant gastroprotective activity for the Sm-FRF, which probably involves the participation of both SH groups and the antioxidant system. Both are integral parts of the gastrointestinal mucosa's cytoprotective mechanisms against aggressive factors.

Indicações para ceratoplastia penetrante no Hospital das Clínicas-UNICAMP

PURPOSE: To determine the main causes of penetrating keratoplasty indications at Hospital das Clínicas-UNICAMP (January, 1999 to December, 2003). METHODS: A non-comparative, retrospective series of case studies. The authors reviewed the files of 857 patients who underwent penetrating keratoplasty at Hospital das Clínicas-UNICAMP between 1999-2003 and classified them into different categories according to diagnostic indication for surgery. RESULTS: The age range was between 0-88 years (average 44 years ±1.2). The main causes of penetrating keratoplasty were: keratoconus in 427 cases (49.82%); 152 cases (17.74%) of corneal ulceration (perforated or not); corneal graft failure in 87 cases (10.15%); bullous keratopathy, 72 cases (8.40%); Fuchs dystrophy in 59 cases (6.88%); trachoma complications in 28 cases (3.27%); other causes, 32 (3.74%). In children under 10 years of age, the main cause of penetrating keratoplasty indications was infectious ulcer (77.78%) and between 11-50 years of age, keratoconus was the main cause (71.65%). CONCLUSION: This study was composed of a young population, and the main causes of penetrating keratoplasty were keratoconus and therapeutic keratoplasty.