CCL

Összesen 4 találat.
#/oldal:
Részletezés:
Rendezés:

1.

001-es BibID:BIBFORM014257
Első szerző:Faro, R.
Cím:Myocardial protection by PJ34, a novel potent poly (ADP-ribose) synthetase inhibitor / Faro, R., Toyoda, Y., McCully, J. D., Jagtap, P., Szabo, E., Virag, L., Bianchi, C., Levitsky, S., Szabo, C., Sellke, F. W.
Dátum:2002
ISSN:0003-4975 (Print)
Megjegyzések:The activation of poly (ADP-ribose) synthetase plays an important role in the pathogenesis leading to myocardial ischemia-reperfusion injury. The aim of this study was to determine if a novel potent inhibitor of poly (ADP-ribose) synthetase, PJ34, provides myocardial protection. METHODS: Pigs were subjected to 60 minutes of regional ischemia followed by 180 minutes of reperfusion. Ten mg/kg of PJ34 (PJ34; n = 6) was administrated intravenously (treated group) from 15 to 5 minutes before reperfusion followed by 3 mg/kg/hour of PJ34 from 5 minutes before reperfusion to the end of 180 minutes reperfusion. Control pigs (n = 7) received vehicle only. Arterial and left ventricular pressure and coronary flow were monitored. RESULTS: The PJ34 showed significant reduction on infarct size (37.5%+/-4.5% and 50.5%+/-4.8% of the area at risk) for PJ34 and control pigs groups, respectively, (p < 0.05). Significant reduction in postsystolic shortening, as well as improvement on segment shortening, and positive first derivative of pressure over time (+dP/dt) maximum were also observed in PJ34 versus control pigs (p < 0.05). CONCLUSIONS: Our results suggest that PJ34 provides cardioprotection by decreasing myocardial infarct size and enhancing postischemic regional and global functional recovery.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Animals
Blood Pressure
Coronary Circulation
Enzyme Inhibitors
Female
Hemodynamics
Male
Myocardial Contraction
Myocardial Infarction
Myocardial Reperfusion Injury
Myocardium
külföldön készült közlemény
Phenanthrenes
Poly(ADP-ribose) Polymerases
Swine
Megjelenés:The Annals of Thoracic Surgery. - 73 : 2 (2002), p. 575-581. -
További szerzők:Toyoda, Y. McCully, J. D. Jagtap, Prakash Szabó Éva (1965-) (bőrgyógyász, kozmetológus) Virág László (1965-) (biokémikus, sejtbiológus, farmakológus) Bianchi, C. Levitsky, S. Szabó Csaba Sellke, F. W.
Internet cím:elektronikus változat
Intézményi repozitóriumban (DEA) tárolt változat
Borító:

2.

001-es BibID:BIBFORM014259
Első szerző:Jagtap, Prakash
Cím:Novel phenanthridinone inhibitors of poly (adenosine 5'-diphosphate-ribose) synthetase: potent cytoprotective and antishock agents / Jagtap, P., Soriano, F. G., Virag, L., Liaudet, L., Mabley, J., Szabo, E., Hasko, G., Marton, A., Lorigados, C. B., Gallyas, F., Jr., Sumegi, B., Hoyt, D. G., Baloglu, E., VanDuzer, J., Salzman, A. L., Southan, G. J., Szabo, C.
Dátum:2002
ISSN:0090-3493 (Print)
Megjegyzések:To synthesize novel inhibitors of the nuclear enzyme poly(adenosine 5'-diphosphate [ADP]-ribose) synthetase (PARS), also known as poly(ADP-ribose) polymerase (PARP), and to test them in in vitro models of oxidant-induced cytotoxicity and in endotoxin and splanchnic occlusion-reperfusion-induced shock. DESIGN: Randomized, prospective laboratory study. SETTING: Research laboratory. SUBJECTS: Murine macrophages, thymocytes, and endothelial cells; Balb/c mice and Wistar rats. INTERVENTIONS: Macrophages and endothelial cells were treated with peroxynitrite and bleomycin to induce PARS activation, and thymocytes were treated with peroxynitrite to induce cell necrosis. Novel PARS inhibitors were synthesized and used to reduce PARS activation and to reverse cytotoxicity. Balb/c mice were subjected to splanchnic occlusion and reperfusion and were pretreated with various doses (1-10 mg/kg intraperitoneally) of PJ34, a selected, potent, water-soluble PARS inhibitor. The passage of fluorescein isothiocyanate-conjugated dextran (4 kDa) was analyzed in everted gut ileal sacs incubated ex vivo as an index of gut permeability. Wistar rats were subjected to Escherichia coli bacterial lipopolysaccharide (40 mg/kg intraperitoneally). PJ34 was also used at 10 mg/kg intraperitoneally, 1 hr before lipopolysaccharide or at 25 mg/kg intraperitoneally 1 hr after lipopolysaccharide treatment. Serum concentrations of indicators or multiple organ injury, concentrations of various proinflammatory mediators, and tissue concentrations of myeloperoxidase and malondialdehyde were measured. In addition, survival rates and vascular contractile and relaxant responses were recorded. MEASUREMENTS AND MAIN RESULTS: Appropriate modifications of the phenanthridinone core structure yielded significant increases in the potency of the compounds, both as PARS inhibitors and as cytoprotective agents. The compound N-(6-oxo-5,6-dihydro-phenanthridin-2-yl) -N,N-dimethylacetamide (designated as PJ34) was one of the potent PARS inhibitors of the series, and it dose-dependently protected against thymocyte necrosis, with a half-maximal restoration of cell viability of 35 nM and complete protection at 200 nM. PARS activation also was visualized by immunohistochemistry and was dose-dependently suppressed by PJ34. The effect of PJ34 was dose-dependently reversed by excess nicotinamide adenine dinucleotide (oxidized). The PARS inhibitors dose-dependently suppressed proinflammatory cytokine and chemokine production and restored viability in immunostimulated macrophages. PJ34 was selected for the subsequent in vivo studies. PJ34 significantly protected against splanchnic reperfusion-induced intestinal hyperpermeability in the mouse. PJ34 reduced peak plasma concentrations of tumor necrosis factor-alpha, interleukin-1beta, and nitrite/nitrate in the plasma of lipopolysaccharide-treated rats. PJ34 ameliorated the lipopolysaccharide-induced increases in indexes of liver and kidney failure and concentrations of myeloperoxidase and malondialdehyde in the lung and gut. Lipopolysaccharide elicited vascular dysfunction, which was normalized by PJ34. Lipopolysaccharide-induced mortality was reduced by PJ34 (both pre- and posttreatment). CONCLUSIONS: The novel series of phenanthridinone PARS inhibitors have potent cytoprotective effects in vitro and significant protective effects in shock and reperfusion injury in rodent models in vivo.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Animals
Bleomycin/pharmacology
Cells, Cultured
*Cytoprotection
Dose-Response Relationship, Drug
Enzyme Activation
Enzyme Inhibitors/*pharmacology
külföldön készült közlemény
Interleukin-1/blood
Kidney/chemistry
Lipopolysaccharides/pharmacology
Lung/chemistry
Malondialdehyde/analysis
Mice
Mice, Inbred BALB C
Nitrates/blood
Nitrites/blood
Peroxidase/analysis
Peroxynitrous Acid/pharmacology
Phenanthrenes/*pharmacology
Poly(ADP-ribose) Polymerases/*antagonists & inhibitors
Rats
Rats, Wistar
Shock/*prevention & control
Tumor Necrosis Factor-alpha/analysis
Megjelenés:Critical Care Medicine. - 30 : 5 (2002), p. 1071-1082. -
További szerzők:Soriano, Francisco Garcia Virág László (1965-) (biokémikus, sejtbiológus, farmakológus) Liaudet, Lucas Mabley, Jon G. Szabó Éva (1965-) (bőrgyógyász, kozmetológus) Haskó György (1967-) (biokémikus) Marton, A. Lorigados, Clara Batista Gallyas Ferenc Jr Sümegi Balázs Hoyt, Dale G. Baloglu, Erkan VanDuzer, John Salzman, Andrew L. Southan, Garry J. Szabó Csaba
Internet cím:elektronikus változat
Intézményi repozitóriumban (DEA) tárolt változat
Borító:

3.

001-es BibID:BIBFORM040009
Első szerző:Mabley, Jon G.
Cím:Anti-inflammatory effects of a novel, potent inhibitor of poly (ADP-ribose) polymerase / Mabley, J. G., Jagtap, P., Perretti, M., Getting, S. J., Salzman, A. L., Virág, L., Szabó, É., Soriano, F. G., Liaudet, L., Abdelkarim, G. E., Haskó, G., Marton, A., Southan, G. J., Szabó, C.
Dátum:2001
ISSN:1023-3830
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Inflammation Research. - 50 : 11 (2001), p. 561-569. -
További szerzők:Jagtap, Prakash Perretti, Mauro Getting, S. J. Salzman, Andrew L. Virág László (1965-) (biokémikus, sejtbiológus, farmakológus) Szabó Éva (1965-) (bőrgyógyász, kozmetológus) Soriano, Francisco Garcia Liaudet, Lucas Abdelkarim, G. Haskó György (1967-) (biokémikus) Marton, A. Southan, Garry J. Szabó Csaba
Internet cím:Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:

4.

001-es BibID:BIBFORM040071
Első szerző:Soriano, Francisco Garcia
Cím:Diabetic endothelial dysfunction : the role of poly(ADP-ribose) polymerase activation / Soriano G. F., Virág L., Jagtap P., Szabó E., Mabley J. G., Liaudet L., Marton A., Hoyt D. G., Murthy K. G., Salzman A. L., Southan G. J., Szabó C.
Dátum:2001
ISSN:1078-8956
Megjegyzések:Diabetic patients frequently suffer from retinopathy, nephropathy, neuropathy and accelerated atherosclerosis. The loss of endothelial function precedes these vascular alterations. Here we report that activation of poly(ADP-ribose) polymerase (PARP) is an important factor in the pathogenesis of endothelial dysfunction in diabetes. Destruction of islet cells with streptozotocin in mice induced hyperglycemia, intravascular oxidant production, DNA strand breakage, PARP activation and a selective loss of endothelium-dependent vasodilation. Treatment with a novel potent PARP inhibitor, starting after the time of islet destruction, maintained normal vascular responsiveness, despite the persistence of severe hyperglycemia. Endothelial cells incubated in high glucose exhibited production of reactive nitrogen and oxygen species, consequent single-strand DNA breakage, PARP activation and associated metabolic and functional impairment. Basal and high-glucose-induced nuclear factor-kappaB activation were suppressed in the PARP-deficient cells. Our results indicate that PARP may be a novel drug target for the therapy of diabetic endothelial dysfunction.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Nature Medicine. - 7 : 1 (2001), p. 108-113. -
További szerzők:Virág László (1965-) (biokémikus, sejtbiológus, farmakológus) Jagtap, Prakash Szabó Éva (1965-) (bőrgyógyász, kozmetológus) Mabley, Jon G. Liaudet, Lucas Marton Anita Hoyt, Dale G. Murthy, Kanneganti G. Salzman, Andrew L. Southan, Garry J. Szabó Csaba
Internet cím:Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:
Rekordok letöltése1