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  • Article: Hypertonic saline and reduced peroxynitrite formation in experimental pancreatitis.
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    ABSTRACT: In this study, we tested the hypothesis that hypertonic saline exerts anti-inflammatory effects by modulating hepatic oxidative stress in pancreatitis. The incidence of hepatic injury is related to severe pancreatitis, and hypertonic saline reduces pancreatic injury and mortality in pancreatitis. Wistar rats were divided into four groups: control (not subjected to treatment), untreated pancreatitis (NT, pancreatitis induced by a retrograde transduodenal infusion of 2.5% sodium taurocholate into the pancreatic duct with no further treatment administered), pancreatitis with normal saline (NS, pancreatitis induced as described above and followed by resuscitation with 0.9% NaCl), and pancreatitis with hypertonic saline (HS, pancreatitis induced as described above and followed by resuscitation with 7.5% NaCl). At 4, 12, and 24 h after pancreatitis induction, liver levels of inducible nitric oxide synthase (iNOS), heat-shock protein 70, nitrotyrosine (formation of peroxynitrite), nitrite/nitrate production, lipid peroxidation, and alanine aminotransferase (ALT) release were determined. Twelve hours after pancreatitis induction, animals in the HS group presented significantly lower iNOS expression (P<0.01 vs. NS), nitrite/nitrate levels (P<0.01 vs. NS), lipid peroxidation (P<0.05 vs. NT), and ALT release (P<0.01 vs. NS). Twenty-four hours after pancreatitis induction, nitrotyrosine expression was significantly lower in the HS group than in the NS group (P<0.05). The protective effect of hypertonic saline was related to the establishment of a superoxide-NO balance that was unfavorable to nitrotyrosine formation. Hypertonic saline decreases hepatic oxidative stress and thereby minimizes liver damage in pancreatitis.
    Clinics (São Paulo, Brazil) 01/2011; 66(3):469-76. · 1.59 Impact Factor
  • Article: Human cholesteryl ester transfer protein expression enhances the mouse survival rate in an experimental systemic inflammation model: a novel role for CETP.
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    ABSTRACT: Mice expressing human cholesteryl ester transfer protein (huCETP) are more resistant to Escherichia coli bacterial wall LPS because death rates 5 days after intraperitoneal inoculation of LPS were higher in wild-type than in huCETP+/+ mice, whereas all huCETP+/+ mice remained alive. After LPS inoculation, plasma concentrations of TNF-alpha and IL-6 increased less in huCETP+/+ than in wild-type mice. LPS in vitro elicited lower TNF-alpha production by CETP expressing than by wild-type macrophages. In addition, TNF-alpha production by RAW 264.7 murine macrophages increased on incubation with LPS but decreased in a dose-dependent manner when human CETP was added to the medium. Human CETP in vitro enhanced the LPS binding to plasma high-density lipoprotein/low-density lipoprotein. The liver uptake of intravenous infused 14C-LPS from Salmonella typhimurium was greater in huCETP+/+ than in wild-type mice. Present data indicate for the first time that CETP is an endogenous component involved in the first line of defense against an exacerbated production of proinflammatory mediators.
    Shock (Augusta, Ga.) 05/2008; 30(5):590-5. · 2.87 Impact Factor
  • Article: The adenosine A3 receptor agonist, N6-(3-iodobenzyl)-adenosine-5'-N-methyluronamide, is protective in two murine models of colitis.
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    ABSTRACT: This study evaluated the effects of the adenosine A(3) receptor agonist, N(6)-(3-iodobenzyl)-adenosine-5'-N-methyluronamide (IB-MECA), in two murine models of colitis, the dextran sodium sulphate-induced colitis and the spontaneous colitis found in interleukin-10 gene deficient mice. IB-MECA was given orally twice a day at a dose of either 1 or 3 mg/kg/day. Evaluation of colon damage and inflammation was determined grossly (body weight, rectal bleeding) and biochemically (colon levels of myeloperoxidase, malondialdehyde, chemokines and cytokines). There was significantly increased inflammatory cell infiltration into the colon associated with an increase in colon levels of cytokines and chemokines; with subsequent free radical related damage in both dextran sodium sulphate-induced colitis and 10-week-old interleukin-10(-/-) mice. IB-MECA protected in both models against the colitis induced inflammatory cell infiltration and damage and attenuated the increases in colon inflammatory cytokine and chemokine levels. Thus activation of the adenosine A(3) receptor is effective in protecting against colitis.
    European Journal of Pharmacology 05/2003; 466(3):323-9. · 2.52 Impact Factor
  • Article: APACHE and Brazilian intensive care units
    Soriano Francisco Garcia
    Sao Paulo Medical Journal. 01/2003;
  • Article: Positive end-expiratory pressure and renal function influence B-type natriuretic peptide in patients with severe sepsis and septic shock.
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    ABSTRACT: Myocardial dysfunction is a complication associated with a poor prognosis in septic patients. A biomarker of cardiac function providing prognostic information is of paramount interest. We sought to determine the value of B-type natriuretic peptide in patients with severe sepsis/septic shock. We performed a prospective study in patients with severe sepsis/septic shock in a medical intensive care unit. B-type natriuretic peptide level was determined within 24 hours after the diagnosis of severe sepsis/septic shock. We also analyzed mortality, and presence of association between B-type natriuretic peptide and clinical, hemodynamic and respiratory variables. 23 (9 women; 14 men) patients with ages ranging from 20-79 (mean 51.3+/-18.6) years old and APACHE score of 22.6+/-11.8 were included; 15 (65.2%) patients received pulmonary artery catheters, and 20 (87%) were mechanically ventilated. Multivariate analysis disclosed inverse association between B-type natriuretic peptide values with positive end-expiratory pressure values, and direct association with creatinine (beta 0.548 and 0.377, p 0.02 and 0.002, respectively), but not with mortality, clinical and hemodynamic parameters. This is the first report on an inverse association between positive end-expiratory pressure and BNP levels in patients with severe sepsis and septic shock. BNP and creatinine levels should be taken into consideration when analyzing B-type natriuretic peptide levels in this setting.
    Arquivos brasileiros de cardiologia 09/2008; 91(2):107-12. · 1.32 Impact Factor

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