Perioperative outcomes of goal-directed versus conventional fluid therapy in radical cystectomy with enhanced recovery protocol

International Urology and Nephrology - The aim of this study is to evaluate the intra/perioperative fluid management and early postoperative outcomes of patients who underwent radical cystectomy...     

Shiva-1: in vitro and in vivo tests of the effects of a novel,synthetic, lytic peptide on ocular cells

An investigation was undertaken to determine the toxicity of an intravitreal injection of a novel peptide drug, Shiva-1, in rabbits. The drug, a synthetic peptide modeled after lytic peptides secreted by certain insects, has antiproliferative and antibacterial properties. Initial in vitro experiments showed that the drug, at a concentration of 100 M, was toxic to both Y-79 retinoblastoma cells and human retinal pigment epithelial cells. A wide range of doses (6–1200 g) was injected into the rabbit vitreous in an attempt to determine the maximum tolerated dose. Retinal toxicity was evaluated clinically, by electroretinography, and by light microscopy. Some localized toxicity was evident at 200 g; all doses of 240 g and above were toxic. While the drug appears to exhibit a narrow range between effective and toxic doses, the results suggest that this and other peptides of similar design merit further investigation for the treatment of proliferative and infectious diseases of the eye.Supported in part by U.S. Public Health Service grants EY07541 and EY02377 from the National Eye Institute, the National Institutes of Health Services, Bethesda, MD, USA     

Novel Derivatives of Tetrahydrobenzo (g) Imidazo[α-1,2] Quinoline Induce Apoptosis Via ROS Production in the Glioblastoma Multiforme Cells,U-87MG

Background:Despite newer therapeutic approaches against glioblastoma multiforme (GBM), the severely poor prognosis and treatment resistance are still disadvantages that slow down the patient’s recovery process. Consistent with the need to develop more effective and optimized therapies to control GBM cell growth, the effects of a new series of tetrahydrobenzo(g)imidazo[α-1,2]quinolone derivatives on GBM cell growth and the underlying mechanism is investigated in the current study. Methods:U-87MG cell line, glioblastoma multiforme and normal skin fibroblast cell line, AGO1522 were used to study the anticancer effects of 5 derivatives of tetrahydrobenzo(g)imidazo[α-1,2]quinolone and paclitaxel as a standard drug. The cytotoxic effect on cell growth was assessed using the MTT assay. Annexin V FITC staining and PI staining were applied to detect apoptosis and cell cycle distribution using flow cytometry. The extent of reactive oxygen species (ROS) formation was assessed using the fluorescent probe 7-dichlorofluorescin diacetate and caspase-3 activity using the colorimetric assay kit. Results:Among the 5 derivatives of tetrahydrobenzo(g)imidazo[α-1,2]quinolone, the 5c derivative (5-(6-bromo-2-chloroquinolin-3-yl)-9a-hydroxy-8,8-dimethyl-4-Nitro-2,3,5,5a,7,8,9,9a-octahydroimidazo[α-1,2]quinoline-6(1H)) showed the strongest cytotoxic effect on U-87MG cells in a time and Dose-dependent manner compared to the other derivatives and paclitaxel. The IC₅₀ (11.91 M) of the 5c derivative induced apoptosis accompanied by a significant increase in sub-G1 and super-G2 phases of U-87MG cells. The increased level of cellular ROS and caspase 3 activity after treatment of U-87MG cells with 5c derivative was significant compared to untreated cells. Conclusion:Our data provide insights into the potent anticancer effects of the 5c-derivative of tetrahydrobenzo(g)imidazo[α-1,2]quinolone on GBM cells via the caspase-dependent apoptotic pathway, which may merit further attention.Key Words: Glioblastoma multiforme, imidazoquinoline, apoptosis, ROS, reactive oxygen species     

Connexins regulate calcium signaling by controlling ATP release

Forced expression of gap junction proteins, connexins, enables gap junction-deficient cell lines to propagate intercellular calcium waves. Here, we show that ATP secretion from the poorly coupled cell lines, C6 glioma, HeLa, and U373 glioblastoma, is potentiated 5- to 15-fold by connexin expression. ATP release required purinergic receptor-activated intracellular Ca²⁺ mobilization and was inhibited by Cl⁻ channel blockers. Calcium wave propagation also was reduced by purinergic receptor antagonists and by Cl⁻ channel blockers but insensitive to gap junction inhibitors. These observations suggest that cell-to-cell signaling associated with connexin expression results from enhanced ATP release and not, as previously believed, from an increase in intercellular coupling.