CCL

Összesen 5 találat.
#/oldal:
Részletezés:
Rendezés:

1.

001-es BibID:BIBFORM014258
Első szerző:Goldfarb, R. D.
Cím:Protective effect of a novel, potent inhibitor of poly(adenosine 5'-diphosphate-ribose) synthetase in a porcine model of severe bacterial sepsis / Goldfarb, R. D., Marton, A., Szabo, E., Virag, L., Salzman, A. L., Glock, D., Akhter, I., McCarthy, R., Parrillo, J. E., Szabo, C.
Dátum:2002
ISSN:0090-3493 (Print)
Megjegyzések:To determine whether activation of the nuclear enzyme poly(adenosine 5'-diphosphate [ADP]-ribose) synthetase (PARS) contributes to mortality rate, myocardial dysfunction, and cardiovascular collapse in a porcine model of sepsis induced by implantation of an infected clot. DESIGN: Prospective, random animal study. SETTING: Research laboratory at Rush Presbyterian St. Luke's Medical Center. SUBJECTS: Twenty pigs were chronically instrumented with intracardiac transducers to measure left ventricular pressure, sonomicrometer crystals in the left ventricle to measure short axis diameter, an ultrasonic flow meter to measure cardiac output, and catheters in the pulmonary artery and aorta to measure blood pressures and collect samples. INTERVENTIONS: By using a randomized study design, we administered either the novel potent PARS inhibitor PJ34 (10 mg/kg for 1 hr, 2 mg x kg(-1) x hr(-1) for 96 hrs) or vehicle to pigs immediately before intraperitoneal implantation of Escherichia coli 0111.B4 (2.3 +/- 0.1 x 10(10) colony-forming units/kg)-laden fibrin clots to produce peritonitis and bacteremia. MEASUREMENTS AND MAIN RESULTS: In vehicle-treated pigs, 12% survival was recorded at 24 hrs, whereas 83% and 66% survival was recorded in the PJ34-treated animals at 24 and 96 hrs, respectively (p <.05). PJ34 treatment attenuated bacteremia-induced increases in systemic and pulmonary vascular resistances. In controls, peritonitis induced rapid increase in plasma tumor necrosis factor-alpha. PJ34 treatment significantly attenuated this cytokine response. The formation of peroxynitrite and the activation of PARS were confirmed in hearts and lungs of the septic pigs by the immunohistochemical detection of nitrotyrosine and poly(ADP-ribose), respectively. Inhibition of PARS with PJ34 abolished poly(ADP-ribose) formation in septic animals. CONCLUSIONS: Treatment with a potent PARS inhibitor improved survival and cardiovascular status and attenuated an important mediator component of the inflammatory response in a lethal porcine model of sepsis.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Animals
Bacterial Infections
Disease Models, Animal
Enzyme Inhibitors
Escherichia coli Infections
Hemodynamics
Peritonitis
Phenanthrenes
Poly(ADP-ribose) Polymerases
Prospective Studies
Random Allocation
Swine
Tumor Necrosis Factor-alpha
külföldön készült közlemény
Megjelenés:Critical care Medicine. - 30 : 5 (2002), p. 974-980. -
További szerzők:Marton, A. Szabó Éva (1965-) (bőrgyógyász, kozmetológus) Virág László (1965-) (biokémikus, sejtbiológus, farmakológus) Salzman, Andrew L. Glock, D. Akhter, I. McCarthy, R. Parrillo, J. E. Szabó Csaba
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:BIBFORM028387
Első szerző:Kirov, Mikhail Y.
Cím:Aerosolized linear polyethylenimine-nitric oxide/nucleophile adduct attenuates endotoxin-induced lung injury in sheep / Mikhail Y. Kirov, Oleg V. Evgenov, Vladimir N. Kuklin, László Virág, Pál Pacher, Garry J. Southan, Andrew L. Salzman, Csaba Szabó, Lars J. Bjertnaes
Dátum:2002
ISSN:1073-449X
Megjegyzések:Pulmonary hypertension and edema are mainstays of acute lung injury (ALI). We synthesized linear polyethylenimine-nitric oxide/nucleophile adduct (DS-1), a water-soluble nitric oxide donor, and demonstrated that it is a potent relaxant of precontracted rat aortic rings without inducing desensitization. Moreover, DS-1 does not suppress the viability of human pulmonary epithelial cells in vitro. We also tested whether DS-1 counteracts ALI in endotoxemic sheep. Animals were instrumented for a chronic study. In 16 awake, spontaneously breathing sheep, Escherichia coli endotoxin (10 ng/kg/minute) was infused for 8 hours. From 2 hours of endotoxemia, sheep received either nebulized DS-1 (1 mg/kg/hour) or isotonic saline. DS-1 reduced endotoxin-induced rises in pulmonary arterial and microwedge pressures and vascular resistance index by 40-70%. In parallel, DS-1 decreased the accumulation of extravascular lung water by 60-70% and reduced the increment in right ventricle stroke work index and the falls in right ventricle ejection fraction, stroke volume, and left ventricle stroke work indices. Furthermore, DS-1 reduced venous admixture and improved arterial oxygen saturation. In four healthy animals, DS-1 alone slightly increased arterial oxygenation but had no other effects. Thus, aerosolized DS-1 attenuates endotoxin-induced ALI in sheep by reducing pulmonary hypertension and edema and improving myocardial function and gas exchange.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
acute lung injury
pulmonary circulation
extravascular lung water
nitric oxide donor
endotoxin
külföldön készült közlemény
Megjelenés:American Journal Of Respiratory And Critical Care Medicine 166 : 11 (2002), p. 1436-1442. -
További szerzők:Evgenov, Oleg V. Kuklin, Vladimir N. Virág László (1965-) (biokémikus, sejtbiológus, farmakológus) Pacher Pál Southan, Garry J. Salzman, Andrew L. Szabó Csaba (1967-) (orvos) Bjertnaes, Lars J.
Internet cím:Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:

4.

001-es BibID:BIBFORM028378
Első szerző:Liaudet, Lucas
Cím:Activation of poly(ADP-Ribose) polymerase-1 is a central mechanism of lipopolysaccharide-induced acute lung inflammation / Lucas Liaudet, Pál Pacher, Jon G. Mabley, László Virág, Francisco G. Soriano, György Haskó, Csaba Szabó
Dátum:2002
ISSN:1073-449X
Megjegyzések:Recent studies demonstrated that activation of the nuclear enzyme poly(ADP-ribose) polymerase-1 (PARP-1) by oxidant-mediated DNA damage is an important pathway of tissue injury in conditions associated with oxidative stress. Using a dual approach of PARP-1 suppression, by genetic deletion or pharmacological inhibition with the phenanthridinone PARP inhibitor PJ-34, we now demonstrate an essential role of PARP-1 in the development of pulmonary inflammation induced by lipopolysaccharide (LPS). PARP-1+/+ and PARP-1-/- mice received an intratracheal instillation of LPS (50 microg), followed after 24 h by bronchoalveolar lavage to measure the cytokines TNF-alpha, IL-1beta, and IL-6, the chemokines MIP-1alpha and MIP-2, leukocyte counts and myeloperoxidase activity (neutrophil accumulation), protein content (high permeability edema), and nitrite/ nitrate (nitric oxide production). Malondialdehyde (an index of lipid peroxidation) was measured in lung tissue. Similar experiments were conducted in BALB/c mice treated with PJ-34 or vehicle. The absence of functional PARP-1 reduced LPS-induced increases of cytokines and chemokines, alveolar neutrophil accumulation, lung hyperpermeability, NO production, and lipid peroxidation. Histological analysis revealed attenuated lung damage after PARP inhibition. Our findings support a mechanistic role of PARP-1 in the regulation of LPS-induced lung inflammation. Pharmacological inhibition of PARP may be useful in clinical conditions associated with overwhelming lung inflammation.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
lung
ARDS
lipopolysaccharide
poly(ADP-ribose) polymerase
chemokines
külföldön készült közlemény
Megjelenés:American Journal Of Respiratory And Critical Care Medicine 165 : 3 (2002), p. 372-377. -
További szerzők:Pacher Pál Mabley, Jon G. Virág László (1965-) (biokémikus, sejtbiológus, farmakológus) Soriano, Francisco Garcia Haskó György (1967-) (biokémikus) Szabó Csaba (1967-) (orvos)
Internet cím:Intézményi repozitóriumban (DEA) tárolt változat
Borító:

5.

001-es BibID:BIBFORM040070
Első szerző:Soejima, Kazutaka
Cím:Role of nitric oxide in vascular permeability after combined burns and smoke inhalation injury / Soejima, K., Traber, L. D., Scghmalstieg, F. C., Hawkins, H., Jodoin, J. M., Szabó, Cs., Szabó, É., Virag, L., Salzman, A., Traber, D. L.
Dátum:2001
Megjegyzések:Patients with severe burn and/or smoke inhalation injury suffer both systemic and pulmonary vascular hyperpermeability. We hypothesized that nitric oxide (NO) produced by inducible nitric oxide synthase (iNOS) plays a role in the changes in microvascular permeability seen with this injury. To test the hypothesis, we administered mercaptoethylguanidine (MEG), a selective iNOS inhibitor, to conscious sheep subjected to a combined smoke inhalation and third-degree burn injury to 40% of total body surface area. The sheep were surgically prepared for chronic study with lung and prefemoral lymph fistulas in order to estimate microvascular permeability. Both the groups and a control group of animals showed an increase in iNOS protein and message in their lungs. The control animals showed significant increases in either plasma or lymph NO2-/NO3- (NOx) concentration at 24 h after injury, with associated cardiac depression and hemoconcentration. The airway epithelium stained for nitrotyrosine. In the treatment group, NOx did not increase significantly in plasma or lymph throughout the experiment, there was no nitrotyrosine staining, hemodynamic depression was not observed, and the fluid requirement was significantly less than in the control group. Changes in pulmonary microvascular permeability were significantly suppressed by inhibition of iNOS. However, there was no significant difference between the two study groups in the microvascular permeability of burned tissue. These data suggest that NO produced by iNOS plays an important role in the changes in systemic and pulmonary microvascular permeability in combined smoke inhalation/third-degree burn injury, but does not affect the vascular permeability of third-degree-burned tissue in this type of injury.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:American Journal of Respiratory and Critical Care Medicine 163 : 3 Pt1 (2001), p. 745-752. -
További szerzők:Traber, Lilliand D. Scghmalstieg, Frank C. Hawkins, Hal Jodoin, Jeffrey M. Szabó Cs. Szabó Éva (1965-) (bőrgyógyász, kozmetológus) Virág László (1965-) (biokémikus, sejtbiológus, farmakológus) Salzman, Andrew L. Traber, Daniel L.
Internet cím:Szerző által megadott URL
Intézményi repozitóriumban (DEA) tárolt változat
Borító:
Rekordok letöltése1