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Biomedical subjects

C Marie

Publications and source records attributed to C Marie.

At least 37 records · Page 2Linked to original sources
PubMed2000

Ex vivo T-lymphocyte derived cytokine production in SIRS patients is influenced by experimental procedures.

Ex vivo production of interleukin-2 (IL-2), IL-4, IL-5, and IL-10 by peripheral blood mononuclear cells (PBMC) was studied in 13 septic patients with infectious systemic inflammatory response syndrome (SIRS) and 13 patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) (noninfectious SIRS). We have investigated the levels of cytokines after activation by either concanavalin A (ConA), phytohemagglutinin (PHA), or anti-CD3 antibodies. In whole blood assays, ConA-induced IL-10 was significantly reduced in both groups of patients compared with healthy controls. In sepsis patients, IL-2, IL-5, and IL-10 productions by isolated PBMC were diminished on ConA-induced activation but not in response to PHA and anti-CD3; in CPB patients, only anti-CD3-induced IL-10 production was significantly reduced. Our data indicate that subtle modifications of the reactivity of circulating cells occur during infectious and noninfectious SIRS. Production of both Th1 and Th2 cytokines can be down-regulated; however, the nature of the SIRS, of the cell population, and of the activator may influence the observation.

Adult↗
PubMed2000

Antihypertensive effects of fasidotril, a dual inhibitor of neprilysin and angiotensin-converting enzyme, in rats and humans.

The aim of this study was to assess the antihypertensive activity of fasidotril, a dual inhibitor of neprilysin (NEP) and angiotensin I-converting enzyme (ACE), in various models of hypertension in rats (spontaneously hypertensive rats [SHR]; renovascular Goldblatt 2-kidney, 1-clip rats; and deoxycorticosterone acetate [DOCA]-salt hypertensive rats) and in patients with mild-to-moderate essential hypertension. Fasidotril treatment (100 mg/kg PO twice daily for 3 weeks) resulted in a progressive and sustained decrease in systolic blood pressure (-20 to -30 mm Hg) in SHR and Goldblatt rats compared with vehicle-treated rats and prevented the progressive rise in blood pressure in DOCA-salt hypertensive rats. After a 4-week placebo run-in period, 57 patients with essential hypertension were included in a randomized double-blind, placebo-controlled, parallel-group study and received orally either fasidotril (100 mg twice daily) or placebo for 6 weeks. Blood pressure was measured during the 6 hours after the first intake and then at trough (12 hours after the last intake) on days 7, 28, and 42. The first dose of fasidotril had no significant effect on blood pressure. After 42 days, compared with placebo, fasidotril lowered supine systolic and diastolic blood pressures by 7.4/5.4 mm Hg and standing blood pressure by 7.6/6.8 mm Hg. Fasidotril, a dual NEP/ACE inhibitor, was an effective oral antihypertensive agent during chronic treatment in high-renin renovascular rats, normal-renin SHR, and low-renin DOCA-salt hypertensive rats and in patients with essential hypertension.

Alanine↗
PubMed1999

Heterologous expression of the avirulence gene product, NIP1, from the barley pathogen Rhynchosporium secalis.

NIP1, the product of the avirulence gene AvrRrs1 from Rhynchosporium secalis, a fungal pathogen of barley, is a small secreted cysteine-rich protein. This protein is essential for the specific recognition of the fungus by host plants carrying the complementary resistance gene Rrs1. Different heterologous expression systems were tested to produce sufficient quantities of NIP1 to allow its utilization in receptor identification and isolation. In addition, protein amounts higher than those produced in fungal cultures are required to determine its 3D structure and to analyze its interaction with a receptor. The most efficient method, the synthesis of a His-tag fusion protein in Escherichia coli combined with a refolding procedure, yielded up to 3 mg of recombinant NIP1 from a 1-liter bacterial culture. After removal of the His-tag, the recombinant protein showed the same physicochemical characteristics as the native NIP1 and, most importantly, full biological activity.

Animals↗
PubMed1999

Effect of long-term therapy with fasidotril, a mixed inhibitor of neprilysin and angiotensin-converting enzyme (ACE), on survival of rats after myocardial infarction.

OBJECTIVE: Two hormonal systems with opposite effects are activated in congestive heart failure: the renin-angiotensin system that promotes vasoconstriction, cardiac hypertrophy and salt retention, and the atrial natriuretic factor (ANF), which has vasorelaxant and natriuretic effects. It could be of therapeutic interest to associate prevention of angiotensin II formation, by inhibition of angiotensin I-converting enzyme (ACE), with potentiation of the ANF effects, by inhibition of neprilysin (NEP). METHODS: The effects of long-term therapy with fasidotril, a mixed NEP/ACE inhibitor, were assessed in rats submitted to coronary artery ligation. Twenty-four hours after ligation, 172 rats were assigned to either placebo or fasidotril therapy (180 mg/kg/day, orally) for 40 weeks. The date of spontaneous death was recorded, myocardial infarct size was determined and rats were classified as having small, moderate or large infarcts. RESULTS: In rats with moderate infarcts, fasidotril prolonged survival, 50% of the control rats dying during the 40-week observation period compared with 30% of treated rats (P = 0.04, log-rank test)). In rats with large infarcts, mortality was significantly reduced during the initial 25 weeks of therapy, during which 23.5% of animals died compared to 53.8% in untreated rats (P = 0.015). Cardiac hypertrophy was significantly attenuated by fasidotril for the three infarct sizes. Plasma renin activity was not increased by therapy, which presumably reflected the inhibition of renal renin secretion by endogenous ANF. Fasidotril therapy had no significant effects on arterial blood pressure and heart rate. CONCLUSION: In addition to its beneficial effects on survival and cardiac hypertrophy, the lack of hypotensive effect of fasidotril is of interest by reducing the risk of renal hypoperfusion and differentiates the mixed inhibitor from selective ACE inhibitors.

Alanine↗
PubMed1999

Paradoxical priming effects of IL-10 on cytokine production.

IL-10 is a well-known immunosuppressive and/or anti-inflammatory cytokine. However, we report in vitro experimental studies in which IL-10 primed leukocytes and led to an enhanced production of tumor necrosis factor (TNF) upon further stimulation by lipopolysaccharide (LPS). Monocytes and peripheral blood mononuclear cells (PBMC) prepared from whole blood maintained for 20 h at 37 degrees C in the presence of recombinant human IL-10 had an enhanced capacity to produce TNF in response to LPS. In addition to TNF, LPS-induced IL-6 and spontaneous IL-1ra production were also enhanced. When isolated PBMC were first cultured for 20 h in the presence of IL-10 on Teflon to prevent adherence, washed to remove IL-10 and then further cultured in plastic dishes for an additional 20 h in the presence of LPS or IL-1beta, an enhanced release of TNF was observed. This was not the case when PBMC were pre-cultured in plastic multidishes in the presence of IL-10. TNF mRNA expression induced by LPS was decreased when the pre-treatment of PBMC with IL-10 was performed on plastic, whereas this was not the case when cells were pre-cultured with IL-10 on Teflon. Furthermore, NFkappaB translocation following LPS activation was higher after IL-10 pre-treatment on Teflon than on plastic. Interestingly, an enhanced frequency of CD16 and CD68(+) cells among the CD14(+) cells was observed in the presence of IL-10, independently of the pre-culture conditions of the PBMC. Altogether, these results indicate that the IL-10-induced up-regulation of cytokine production depends on the prevention of monocyte adherence by red cells in the whole blood assays or by cultures of PBMC on Teflon. In contrast, the adherence parameter has no effect on the IL-10-induced modulation of some monocyte surface markers.

Antigens, CD↗
PubMed1999

Involvement of mitogen-activated protein kinase pathways in interleukin-8 production by human monocytes and polymorphonuclear cells stimulated with lipopolysaccharide or Mycoplasma fermentans membrane lipoproteins.

Interleukin-8 (IL-8) is a chemokine that belongs to the alpha-chemokine or CXC subfamily and is produced by a wide variety of human cells, including monocytes and polymorphonuclear cells (PMN). IL-8 is secreted in response to inflammatory stimuli, notably bacterial products such as lipopolysaccharide (LPS), but little is known about the mechanisms by which these agents mediate IL-8 induction. In this report, we show that Mycoplasma fermentans lipid-associated membrane proteins (LAMPf) induce the production of high levels of IL-8 by THP-1 (human monocyte) cells and PMN at the same extent as LPS. It was previously demonstrated that stimulation of monocytic cells with either LPS or LAMPf led to a series of common downstream signaling events, including the activation of protein tyrosine kinase and of mitogen-activated protein kinase cascades. By using PD-98059 and SB203580, two potent and selective inhibitors of MEK1 (a kinase upstream of ERK1/2) and p38, respectively, we have demonstrated that both ERK1/2 and p38 cascades play a key role in the production of IL-8 by monocytes and PMN stimulated with bacterial fractions.

Bacterial Proteins↗
PubMed1998

Structural studies of the O-antigenic polysaccharide from Escherichia coli O139.

The structure of the O-antigenic polysaccharide from Escherichia coli O139 has been investigated with the aid of NMR spectroscopy, and sugar and methylation analyses. The sequence of the sugar residues was determined by NOESY and heteronuclear-multiple-bond-connectivity NMR experiments. The polysaccharide is composed of heptasaccharide repeating units containing 0.6 mol O-acetyl groups/repeating unit. The following structure is concluded, where Rha represents rhamnose. [structure in text]

Acetylation↗
PubMed1998

Reduced ex vivo interleukin-8 production by neutrophils in septic and nonseptic systemic inflammatory response syndrome.

Ex vivo cytokine production by circulating lymphocytes and monocytes is reduced in patients with infectious or noninfectious systemic inflammatory response syndrome. Very few studies have addressed the reactivity of polymorphonuclear cells (PMN). To analyze further the relative contribution of systemic inflammatory response syndrome alone or in combination with infection we studied the interleukin-8 (IL-8) production by PMN isolated from patients who had undergone cardiac surgery with cardiopulmonary bypass (CPB) and patients with sepsis. Cells were activated with either lipopolysaccharide (LPS) or heat-killed streptococci. Compared with healthy controls, the release of IL-8 by PMN in both groups of patients was significantly reduced whether activated by LPS, independently of its concentration and origin, or by heat-killed streptococci. These observations suggest that stressful conditions related to inflammation, independently of infection, rapidly dampened the reactivity of circulating PMN. We investigated whether the observed diminished reactivity of PMN might reflect an endotoxin tolerance phenomenon. Our in vitro experiments with PMN from healthy controls indicated that PMN could not be rendered tolerant stricto sensu. However, our data suggested that LPS-induced mediators such as IL-10 may be responsible for the observed anergy in patients.

Adult↗
PubMed1998

[Stromal tumors in the digestive tract. A case of duodenal localization].

BACKGROUND: Stromal tumors of the digestive tract are undifferentiated connective tissue tumors which are difficult to characterize even with immunohistochemistry. CASE REPORT: A stromal tumor of the duodenum (the most frequently encountered location) was resected entirely. Histochemistry was unable to provide a precise identification of the histological nature. The tumor was considered to be low grade due to the low mitosis index despite its large size and the presence of necrosis. Careful surveillance was indicated. DISCUSSION: The risk of these tumors is uncertain and may be assessed on the basis of histological prognosis factors such as tumor size, mitosis index and ploidy. Echoendoscopy can be particularly useful for diagnostic purposes providing information on location in the duodenal musculosa.

Duodenal Neoplasms↗
PubMed1998

Acute natriuretic effect of fasidotrilat, a mixed inhibitor of neutral endopeptidase and angiotensin I-converting enzyme, in rats with heart failure.

The acute diuretic and natriuretic effects of fasidotrilat, a mixed inhibitor of neutral endopeptidase (NEP) and angiotensin I-converting enzyme (ACE) were evaluated in control and myocardial-infarcted rats. Fasidotrilat injection (10 mg/kg i.v.) had no significant effect on arterial blood pressure and led to significant elevations in urine volume (+57% in control rats and +114% in infarcted rats) and of urinary sodium excretion (+81% in control rats and +225% in infarcted rats). Comparison between control and infarcted rats showed that fasidotrilat-induced changes in diuresis and natriuresis were higher in infarcted rats (2.4-fold for diuresis and 4.7-fold for natriuresis, p < 0.05), despite a lower perfusion pressure (-10 mm Hg) in infarcted rats. These data show the potential therapeutic interest of mixed NEP/ACE inhibitors in congestive heart failure.

Alanine↗
PubMed1997

Presence of high levels of leukocyte-associated interleukin-8 upon cell activation and in patients with sepsis syndrome.

In inflammatory and infectious diseases, the presence of circulating cytokines in plasma strongly suggests, following their exacerbated production, that saturation of specific binding sites has occurred or that an equilibrium between receptor-bound and free cytokines has been reached. In this report, we demonstrate that in addition to circulating interleukin-8 (IL-8), high levels of cell-associated IL-8 were detected in blood samples from patients with sepsis syndrome. The following analysis will reveal that in addition to erythrocytes, which have been dubbed a "sink" for IL-8, peripheral blood mononuclear cells (PBMC) and polymorphonuclear cells (PMN) contributed to the detection of cell-associated IL-8. On a per cell basis, 2,000 to 7,000 times the amount of IL-8 was found associated with PMN than with erythrocytes. In addition, circulating cells may well be the source of the leukocyte-associated form of IL-8. Similarly, in vitro experiments, such as whole-blood stimulation assays or the addition of exogenous IL-8 in blood samples, demonstrated that a large proportion of the IL-8 was associated with leukocytes. This suggests that the trapping of free cytokines onto the cell surface and the internalization of the IL-8 bound to its receptor, occurring both in vitro and in vivo, allows the detection of this cell-associated form. This analysis of cell-associated cytokines was extended to IL-1ra, another component of the inflammatory response, which, in contrast to IL-8, has been demonstrated to exist as an intracellular form. Indeed, cell-associated IL-1ra was also detected in septic patients. The measurement of cell-associated proinflammatory and anti-inflammatory cytokines in patients is clearly a more reliable reflection of their production than is the simple measurement in plasma and may provide useful indication to further understand the inflammatory process.

Adult↗
PubMed1997

Cytokines and soluble cytokine receptors in pleural effusions from septic and nonseptic patients.

The balance between proinflammatory cytokines and their inhibitors has rarely been investigated in pleural effusions of nonmalignant or noninfectious origin. To evaluate the impact of a lung and/or intrathoracic infection in such a circumstance, we compared the levels of proinflammatory cytokines (interleukin-8 [IL-8]); tumor necrosis factor-alpha (TNF-alpha); the cytokine antagonists and inhibitors (IL-1 receptor antagonist [IL-1ra]) and soluble TNF receptors Types I and II (sTNFRI, sTNFRII); and antiinflammatory cytokines (transforming growth factor-beta [TGF-beta]) in pleural effusion and plasma from septic (n = 15) and nonseptic (n = 9) patients. In addition, we analyzed the levels of IL-6 and its soluble receptor (sIL-6R). Bronchoalveolar lavage fluids (BALFs) were also studied in a few septic patients. High and nonsignificantly different levels of cytokines and inhibitors were detected in both groups of patients. The levels of IL-6 and sTNFRI and sTNFRII in pleural effusion were higher than in plasma, whereas the levels of IL-1ra and sIL-6R were higher in plasma. The levels of sIL-6R influenced the bioactivity of IL-6. There was no correlation between the levels of cytokines in plasma and in pleural effusion. In contrast, a significant correlation was observed for the soluble receptors sIL-6R (r = 0.67, p < 0.001), sTNFRI (r = 0.76, p < 0.001) and sTNFRII (r = 0.66, p = 0.001). Furthermore, a high correlation was found between the levels of both forms of sTNFRs in plasma (r = 0.95, p < 0.001) and in pleural effusion (r = 0.79, p < 0.001). In addition, a correlation was observed between the levels of TGF-beta in pleural effusion and in BALF. The highest levels of some markers in plasma and of others in pleura argue in favor of both a systemic and a compartmentalized response, independently of the presence of infection. Because cytokines can be trapped by the surrounding cells in their environment, measurable levels of cytokines in biologic fluids represent the "tip of the iceberg," which is not the case for soluble receptors. The correlations of these latter markers between plasma and pleura strongly suggest that exchanges between both compartments can occur in both directions.

Adult↗
PubMed1997

Variations of cytokine levels and production in CAPD patients.

Macrophages, predominant cells in dialysates of patients on CAPD without peritonitis, produce a wide variety of substances including cytokines. The aim of this study was to examine the cytokine production in five uninfected patients. This work investigated the presence in dialysates of interleukin-1beta, interleukin-6, interleukin-8, tumor necrosis factor alpha and the ability of peritoneal macrophages to produce these cytokines. These results were compared with values obtained from control group in non-uremic conditions (peritoneal lavage with isotonic saline or dialysis fluid). All cytokines were detectable in dialysates. Interindividual variations in cytokine concentration in dialysates were wider than variations of production of cytokines ex vivo by stimulated and unstimulated cells. In control group, dialysis fluid inhibited the cytokine production and with isotonic saline, cells produced less cytokines than dialysis patients' cells. The highest levels of interleukin-1 and tumor necrosis factor in dialysates and the highest capacity to respond to LPS were observed in patients having the shortest duration of dialysis. The variability observed did not seem to be due to cells themselves but to their environment.

Adult↗
PubMed1996

IL-10 and IL-4 synergize with TNF-alpha to induce IL-1ra production by human neutrophils.

The anti-inflammatory properties of IL-4, IL-10, IL-13 and TGF-beta are associated with their ability to repress the production of pro-inflammatory cytokines and to favour the release of interleukin-1 receptor antagonist (IL-1ra). Here, we investigate their actions on activated human polymorphonuclear cells (PMN). IL-4 and TGF-beta were able to increase the production of IL-1ra, however only IL-4 were able to further increase IL-1ra production in the presence of LPS. When IL-1ra production by PMN was induced by tumour necrosis factor-alpha (TNF-alpha), IL-10 and IL-4 both amplified its release and its presence as a cell-associated form. In conclusion, IL-10 which was unable to induce IL-1ra by itself or to amplify the LPS-induced production by PMN, was able to increase its release when TNF-alpha, is the triggering signal. IL-4 was active in the different combinations tested; IL-13 and TGF-beta did not further modulate LPS- and TNF-alpha-induced IL-1ra production by PMN.

Cells, Cultured↗
PubMed1996

Effects of increasing intracellular reactive iron level on cardiac function and oxidative injury in the isolated rat heart.

Elevation of cell iron content was produced by use of a lipophilic iron ligand, 8-hydroxyquinoline (HQ), capable of transferring catalytically active iron into cells. The Fe(3+)-HQ complex labeled with 59Fe was avidly taken up by isolated perfused hearts contrary to the hydrophilic complex Fe(3+)-citrate. Hearts perfused in aerobic conditions with Krebs-Henseleit buffer were exposed for 15 min to the iron complexes, Fe(3+)-HQ (5 microM/10 microM and 10 microM/20 microM), or Fe(3+)-citrate (10 microM), and then perfused for 30 min with normal buffer. Exposure to the high dose of Fe(3+)-HQ (10 microM/20 microM) resulted in early and irreversible decreases in coronary flow and heart rate (-48% and -33%, respectively), initial increases followed by decreases in left ventricular systolic pressure and +dP/dt, and increase in left ventricular end-diastolic pressure (+80%). The low dose of Fe(3+)-HQ (5 microM/10 microM) mimicked with a lower magnitude the effects of the high dose, whereas Fe(3+)-citrate had no effects on cardiac parameters. Only hearts exposed to the high dose of Fe(3+)-HQ exhibited a significant increase (+60%) in thiobarbituric acid-reactive substance level, an index of lipid peroxidation. The production of hydroxyl radicals was investigated by measuring 2,3-dihydroxybenzoic acid level in the coronary effluent after addition of salicylic acid (1 mM) in the perfusate. An immediate and high increase (x6) was seen during heart exposure to Fe(3+)-HQ (10 microM/20 microM) and to Fe(3+)-citrate (10 microM). Considering Fe(3+)-citrate had no effect on cardiac function and lipid peroxidation it was concluded that this hydroxyl radical formation occurring in the extracellular space was not implicated in Fe(3+)-HQ-induced cardiac dysfunction. These results demonstrate the deleterious effect of increasing intracellular reactive iron level in non-ischemic hearts.

Animals↗
PubMed1996

Effect on prolonged inhibition of neutral endopeptidase on cardiac hypertrophy in rats with myocardial infarction.

Myocardial infarction was induced by rats by ligation of the left coronary artery. Treatment with TM1, a prodrug of SQ 28,603, an inhibitor of neutral endopeptidase (NEP, EC 3.4.24.11), was started 18-20 hours after ligation and was continued for 4 weeks (100 mg/kg, orally, twice daily). Morphological and biochemical parameters were assessed at the endo of therapy. The treatment resulted in a significant reduction of heart hypertrophy, which was restricted to the parts of myocardium hemodynamically upstream of the infarcted left ventricle. The weights of the right ventricle and atria were reduced by 15-20%, whereas the treatment had no effect on the left ventricle and septum weights. Treatment led to an almost complete inhibition of plasma NEP activity and to a slight decrease (-14%, p < 0.05) in plasma ACE activity. Plasma ANF level increased 3.8-fold after ligation, and treatment resulted in a slight ( + 29%) and nonsignificant additional increase in the ANF level. The amount of hydroxyproline in the right ventricle was enhanced by + 207% in control ligated rats and by +140% (NS) in treated rats. These data indicated that prolonged NEP inhibition exerts a favorable effect in heart failure by reducing the development of right ventricular and atrial hypertrophy. These effects may result from an improvement in hemodynamic conditions, leading to a reduction in cardiac preload.

Alanine↗
PubMed1996

Effect of intracellular iron loading on lipid peroxidation of brain slices.

The effect of artificially elevated cell iron content on oxygen-derived free radical production was assessed in brain slices by use of an iron ligand, 8-hydroxyquinoline (HQ). The iron complex Fe(3+)-HQ exhibited a high lipid solubility evidenced by n-octanol/water partition coefficient and was avidely taken up by brain slices. The catalytically active form of Fe3+ within the complex was evidenced by measuring the rate of ascorbate oxidation. Lipid peroxidation was assessed by measuring the thiobarbituric acid-reactive substances (TBARS) in brain homogenates or slices exposed to two doses of Fe(3+)-HQ (10 microM/20 microM, 100 microM/200 microM) or Fe(3+)-citrate (10 microM, 100 microM). Addition of the iron complexes to homogenates or slices resulted in a dose-dependent increase in lipid peroxidation. In homogenates, the effects were grossly similar with both complexes, whereas in slices the effects of Fe-HQ were significantly higher than those of Fe-citrate. Lipid peroxidation persisted in washed slices preexposed to Fe-HQ, but not in slices preexposed to the hydrophilic iron complex Fe-citrate. Fe-HQ-induced lipid peroxidation in slices was enhanced in the presence of H2O2, an effect that was not seen using Fe-citrate. Addition of Fe-HQ to brain homogenates in the presence of salicylic acid resulted in the production of 2,3-dihydroxybenzoic acid and the effect was potentiated in the presence of H2O2. This model of iron cell loading may be useful for evaluating the efficacy of antioxidant drugs.

Animals↗