Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.1 (phosphodiesterase)
 18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this investigation was to identify those agents and combinations of agents that help convert murine melanoma cells to cells of differentiated (normal-like) phenotype in culture. The agents used were 4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone (R020-1724), which is an adenosine 3',5'-cyclic monophosphate (cAMP) phosphodiesterase inhibitor that has never been tested on melanoma cells in culture, and d-alpha tocopheryl succinate (vitamin E succinate), which has previously been shown to inhibit growth and induce morphological differentiation in melanoma cells. The results indicated that R020-1724 by itself inhibited growth, reduced survival, caused morphological differentiation and increased the melanin content (one of the biochemical differentiated functions) in melanoma cells. Vitamin E succinate had a similar effect on the melanoma cells, which supports past research on this vitamin. A combination of R20-1724 and vitamin E succinate had a significantly greater effect on the melanoma cells than either of the agents by themselves. The agents identified in this study may provide useful tools for studying the mechanisms of differentiation in melanoma cells.
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PMID:Induction of differentiated phenotypes in melanoma cells by a combination of an adenosine 3',5'-cyclic monophosphate stimulating agent and D-alpha tocopheryl succinate. 253 39

Effects of VA-045, a novel apovincaminic acid derivative, on neuronal damage induced by hypoxia or by excitatory amino acids (glutamate (Glu), N-methyl-D-aspartate and kainate) were examined in cultures of the rat cortices. The extent of cell injury was quantified by measuring lactic dehydrogenase activity released from the damaged cells into the culture medium. VA-045 at concentrations between 1 microM and 30 microM significantly attenuated this neuronal damage and exceeded those of vinpocetine. VA-045 had no significant binding affinity to Glu receptor subtypes. The cytoprotection of VA-045 does not seem to be the result of antagonism at Glu receptors. VA-045 inhibited lipid peroxide production in brain homogenates. Vitamin E also had this antioxidant effect, but did not attenuate the hypoxia-induced neuronal damage. A cAMP analogue and a phosphodiesterase (PDE) inhibitor also attenuated the hypoxia-induced neuronal damage. As VA-045 inhibits the activity of PDE, the effect of VA-045 may possibly relate to cAMP cascade. VA-045 may prove to be efficacious for the treatment of disorders related to cerebral neuronal injury.
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PMID:VA-045, a novel apovincamic acid derivative attenuates neuronal injury induced by hypoxia or by excitatory amino acids in cultures of rat cortices. 889 Sep 38

Oxidative stress is believed to affect the development of diabetic-associated vasculopathy, endothelial dysfunction, and neuropathy within erectile tissue. Our hypothesis is that, given adequate concentrations of the oxygen free radical scavenger vitamin E, enhanced levels of circulating nitric oxide (NO) should improve erectile function with the potential for a synergistic effect with a phosphodiesterase type 5 (PDE5) inhibitor. Twenty adult male Sprague-Dawley streptozotocin-induced (60 mg/kg intraperitoneally) diabetic rats were placed in 4 therapeutic groups (n = 5 per group) as follows: 1) peanut oil only (diabetic control), 2) 20 IU of vitamin E per day, 3) 5 mg/kg of sildenafil per day, and 4) vitamin E plus sildenafil using oral gavage for 3 weeks. In addition, 5 age-matched rats served as normal nondiabetic controls (normal). Erectile function was assessed by measuring the rise in intracavernous pressure (ICP) following cavernous nerve electrostimulation. Penile tissue was evaluated for neuronal NO synthase (nNOS), smooth muscle alpha-actin, nitrotyrosine, and endothelial cell integrity. Urine nitrite and nitrate (NOx) concentration was quantified, and electrolytes were tested by a serum biochemistry panel. A significant decrease in ICP was recorded in the diabetic animals, with improvement measured in the animals receiving PDE5 inhibitors either with or without vitamin E; the controls had a pressure of 54.8 +/- 5.3 cm H2O, the vitamin E group had a pressure of 73.5 +/- 6.6 cm H2O, the sildenafil group had a pressure of 78.4 +/- 10.77 cm H2O, and the vitamin E plus sildenafil group had a pressure of 87.9 +/- 5.5 cm H2O (P <.05), compared with the normal cohorts at 103.0 +/- 4.8 cm H2O. Histoexaminations showed improved nNOS, endothelial cell, and smooth muscle cell staining in the vitamin E plus sildenafil group compared to the control animals. Urine NOx increased significantly in all the diabetic groups but was blunted in the vitamin E and vitamin E plus sildenafil groups. A significant increase in positive staining for nitrotyrosine was observed in the vitamin E plus sildenafil group. Vitamin E enhanced the therapeutic effect of the PDE5 inhibitor in this study, supporting the potential use of oxygen free radical scavengers in salvaging erectile function in diabetic patients.
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PMID:Oxidative stress and antioxidant therapy: their impact in diabetes-associated erectile dysfunction. 1529 17