The Experts below are selected from a list of 9741 Experts worldwide ranked by ideXlab platform
Helen Giamarellou - One of the best experts on this subject based on the ideXlab platform.
-
Immunomodulatory effect of three-day continuous administration of clarithromycin for Experimental Sepsis due to multidrug-resistant Pseudomonas aeruginosa.
Journal of chemotherapy (Florence Italy), 2008Co-Authors: Fotini Baziaka, Evangelos J. Giamarellos-bourboulis, Michael Chrisofos, Pantelis Koutoukas, Labros Sabracos, Vassiliki Tziortzioti, Theodoros Adamis, Helen Giamarellou, Maria Raftogiannis, Emmanuel E. DouzinasAbstract:Abstract Based on former animal studies showing the effect of clarithromycin in Experimental Sepsis by multidrug-resistant Pseudomonas aeruginosa following administration of single doses, the significance of its administration for three consecutive days was evaluated. Acute pyelonephritis was induced in 20 rabbits after inoculation of the test isolate in the renal pelvis. Therapy was administered upon signs of Sepsis in group B; A served as control. Survival was recorded; monocytes were isolated for determination of ex vivo TNFα secretion. Quantitative cultures of organs were performed after death. Mean survival of groups A and B was 2.65 and 7.95 days respectively. At 24 hours, serum malondialdehyde of group B, which is an index of the oxidant status in serum, was lower than A. ex vivo release of TNFα by the isolated monocytes of group B was lower than A at 3.5 and 48 hours. Tissue bacterial load was similar in two groups after animal death. It is concluded that clarithromycin possessed considerable immu...
-
Early apoptosis of blood monocytes is a determinant of survival in Experimental Sepsis by multi-drug-resistant Pseudomonas aeruginosa.
Clinical and experimental immunology, 2007Co-Authors: Anastasia Antonopoulou, Evangelos J. Giamarellos-bourboulis, Pantelis Koutoukas, Labros Sabracos, Ira Tzepi, Maria Mouktaroudi, Theodoros Adamis, Helen Giamarellou, Maria Raftogiannis, Emmanuel E. DouzinasAbstract:Apoptosis of blood monocytes was studied in Experimental Sepsis by multi-drug-resistant Pseudomonas aeruginosa. Thirty-six rabbits were used, divided into the following groups: A (n = 6), sham; B (n = 6), administered anaesthetics; and C (n = 24), acute pyelonephritis induced after inoculation of the test isolate in the renal pelvis. Blood was sampled at standard time intervals for estimation of tumour necrosis factor (TNF)-alpha and isolation of monocytes. Half the monocytes were incubated and the other half was lysed for estimation of the cytoplasmic activity of caspase-3 by a kinetic chromogenic assay. No animal in groups A and B died; those in group C were divided into two subgroups, CI (n = 8) with present activity of caspase-3 of blood monocytes at 3.5 h and CII (n = 16) with absent activity. Their median survival was 2.0 and 3.5 days, respectively (P = 0.0089). Ex vivo secretion of TNF-alpha from monocytes was higher by monocytes of subgroup CII than subgroup CI at 3.5 h (P = 0.039) and of group A than CII at 48 h (P = 0.010). Median change of caspase-3 activity between 3.5 and 24 h of sampling was 56.1 and -5.8 pmol/min per 10(4) cells for subgroups CI and CII (P = 0.040), respectively. Respective changes between 3.5 and 48 h were 28 981.0 and 0 pmol/min per 10(4) cells (P = 0.036). Early induction of apoptosis in blood monocytes is of prime importance for the survival of the septic host and might be connected to changes of monocyte potential for the secretion of TNF-alpha.
-
Clarithromycin co-administered with amikacin attenuates systemic inflammation in Experimental Sepsis with Escherichia coli.
International journal of antimicrobial agents, 2005Co-Authors: Evangelos J. Giamarellos-bourboulis, Pantelis Koutoukas, Labros Sabracos, Fotini Baziaka, Despina Perrea, Anastasia Antonopoulou, Vassilios Kousoulas, Charalambos Panagou, Helen GiamarellouAbstract:Abstract To assess the efficacy of clarithromycin as an immunomodulator in Experimental Sepsis with Escherichia coli, acute pyelonephritis was induced after ligation of the right ureter and injection of the test isolate into the renal pelvis in 40 rabbits. Four groups of treatment were applied with administration of therapy on advent of Sepsis-associated pulmonary oedema, as follows: A: controls; B: clarithromycin; C: amikacin, D: both agents. Survival was recorded along with estimation of serum levels of endotoxins (LPS), of tumour necrosis factor-alpha (TNFα), malondialdehyde (MDA) and of bacterial counts. Mean survival of groups A, B, C and D was 2.51, 7.60, 10.25 and 11.40 days, respectively. Serum levels of TNFα and of MDA of group A increased over-time. Pulmonary oedema at 6 h after bacterial challenge was accompanied by increase of TNFα and MDA; administration of clarithromycin decreased their values. It is concluded that intravenous clarithromycin might constitute a promising immunomodulatory agent for the management of Sepsis since its efficacy was proved after administration on presentation of Sepsis-associated pulmonary oedema. The presented findings emphasise the need for further clinical research of the use of clarithromycin for the therapy of Gram-negative Sepsis.
-
The significance of oxidant/antioxidant balance for the pathogenesis of Experimental Sepsis by multidrug-resistant Pseudomonas aeruginosa.
Prostaglandins leukotrienes and essential fatty acids, 2005Co-Authors: Vassilios Koussoulas, Evangelos J. Giamarellos-bourboulis, Labros Sabracos, Maria Mouktaroudi, Theodoros Adamis, Despina Perrea, Helen Giamarellou, Amalia Dionyssiou-asteriouAbstract:Abstract Objective : The significance of lipid peroxidation as an independent factor leading to Sepsis by multidrug-resistant Pseudomonas aeruginosa . Design Experimental study Methods : Twenty-six rabbits were applied. They were divided into two groups; A ( n = 6 ) comprising controls, and B ( n = 20 ) comprising animals infected by the injection of 1×10 8 cfu/kg inoculum of the test pathogen into the left inner jugular vein. Six rabbits of group B were followed-up to estimate survival; all of the remaining were sacrificed. Blood was sampled for the determination of serum malondialdehyde (MDA) by the thiobarbiturate assay, total antioxidant status (TAS) by a chromogenic assay, tumor necrosis factor alpha by a bioassay on fibrosarcoma L929 cell line, and endotoxins (LPS) by the QCL-1000 LAL assay. Results : Mean survival of group B was 60.0±15.8h. MDA was significantly higher in group B compared to group A at 30, 60, 120 and 150min. TAS was statistically decreased in group B compared to group A at 30 and 60min. Increases of MDA in group B were followed by reciprocal decreases of TAS ( P of correlation Conclusions : Early alterations of oxidant/antioxidant balance occur in Experimental Sepsis by multidrug-resistant P. aeruginosa followed by hemodynamic instability. Results highlight the perspective of the administration of antioxidants as immunomodulatory treatment of Sepsis in animal studies.
-
n-6 Polyunsaturated Fatty Acids Enhance the Activities of Ceftazidime and Amikacin in Experimental Sepsis Caused by Multidrug-Resistant Pseudomonas aeruginosa
Antimicrobial agents and chemotherapy, 2004Co-Authors: Evangelos J. Giamarellos-bourboulis, Maria Mouktaroudi, Theodoros Adamis, Vassilios Koussoulas, Fotini Baziaka, Despina Perrea, Panayotis E. Karayannacos, Helen GiamarellouAbstract:Recent in vitro and ex vivo studies disclosed an enhancement of the activity of antimicrobials on multidrug-resistant Pseudomonas aeruginosa by n-6 polyunsaturated fatty acids (PUFAS); therefore their effect was evaluated in Experimental Sepsis in 60 rabbits. Solutions of gamma-linolenic acid (GLA) and arachidonic acid (AA) were administered intravenously with ceftazidime and amikacin in rabbits with Sepsis caused by one multidrug-resistant isolate. Therapy was started after bacterial challenge in five groups comprising 12 animals in each group: A, normal saline; B, antimicrobials; C, 99% ethanol and antimicrobials; D, GLA and antimicrobials; and E, AA and antimicrobials. Blood was sampled for the estimation of levels of endotoxins in serum (lipopolysaccharide), leukocytes, tumor necrosis factor alpha (TNF-alpha) and antimicrobials. Animals were sacrificed 210 min after bacterial challenge for tissue cultures. All animals had considerable endotoxemia and evolved leukopenia. The number of viable cells in blood, lung, and mesenteric lymph nodes was significantly reduced in groups D and E compared to that in other groups. Levels of antimicrobials in serum were inadequate to achieve bacterial killing due to the level of resistance. n-6 PUFAs did not influence TNF-alpha. It is concluded that intravenous coadministration of n-6 PUFAs and antimicrobials enhanced antimicrobial bacterial killing in Experimental Sepsis caused by multidrug-resistant P. aeruginosa.
Evangelos J. Giamarellos-bourboulis - One of the best experts on this subject based on the ideXlab platform.
-
Angiopoietin-2 Enhances Survival in Experimental Sepsis Induced by Multidrug-Resistant Pseudomonas aeruginosa
The Journal of pharmacology and experimental therapeutics, 2012Co-Authors: Ira Tzepi, Evangelos J. Giamarellos-bourboulis, Thomas Tsaganos, Dionyssia Pinelopi Carrer, Ralf A. Claus, Ilia Vaki, Aimilia Pelekanou, Antigone Kotsaki, Vassiliki Tziortzioti, Stavros TopouzisAbstract:Levels of circulating angiopoietin-2 (Ang-2) increase in Sepsis, raising the possibility that Ang-2 acts as a modulator in the Sepsis cascade. To investigate this, Experimental Sepsis was induced in male C57BL6 mice by a multidrug-resistant isolate of Pseudomonas aeruginosa; survival was determined along with neutrophil tissue infiltration and release of proinflammatory cytokines. Survival was significantly increased either by pretreatment with recombinant Ang-2 2 h before or treatment with recombinant Ang-2 30 min after bacterial challenge. Likewise, Ang-2 pretreatment protected against Sepsis-related death elicited by Escherichia coli; however, Ang-2 failed to provide protection in lipopolysaccharide (LPS)-challenged mice. The survival advantage of Ang-2 in response to P. aeruginosa challenge was lost in tumor necrosis factor (TNF)-deficient mice or neutropenic mice. Infiltration of the liver by neutrophils was elevated in the Ang-2 group compared with saline-treated animals. Serum TNF-α levels were reduced by Ang-2, whereas those of interleukin (IL)-6 and IL-10 remained unchanged. This was accompanied by lower release of TNF-α by stimulated splenocytes. When applied to U937 cells in vitro, heat-killed P. aeruginosa induced the secretion of IL-6 and TNF-α; low levels of exogenous TNF-α synergized with P. aeruginosa. This synergistic effect was abolished after the addition of Ang-2. These results put in evidence a striking protective role of Ang-2 in Experimental Sepsis evoked by a multidrug-resistant isolate of P. aeruginosa attributed to modulation of TNF-α production and changes in neutrophil migration. The protective role of Ang-2 is shown when whole microorganisms are used and not LPS, suggesting complex interactions with the host immune response.
-
Immunomodulatory effect of three-day continuous administration of clarithromycin for Experimental Sepsis due to multidrug-resistant Pseudomonas aeruginosa.
Journal of chemotherapy (Florence Italy), 2008Co-Authors: Fotini Baziaka, Evangelos J. Giamarellos-bourboulis, Michael Chrisofos, Pantelis Koutoukas, Labros Sabracos, Vassiliki Tziortzioti, Theodoros Adamis, Helen Giamarellou, Maria Raftogiannis, Emmanuel E. DouzinasAbstract:Abstract Based on former animal studies showing the effect of clarithromycin in Experimental Sepsis by multidrug-resistant Pseudomonas aeruginosa following administration of single doses, the significance of its administration for three consecutive days was evaluated. Acute pyelonephritis was induced in 20 rabbits after inoculation of the test isolate in the renal pelvis. Therapy was administered upon signs of Sepsis in group B; A served as control. Survival was recorded; monocytes were isolated for determination of ex vivo TNFα secretion. Quantitative cultures of organs were performed after death. Mean survival of groups A and B was 2.65 and 7.95 days respectively. At 24 hours, serum malondialdehyde of group B, which is an index of the oxidant status in serum, was lower than A. ex vivo release of TNFα by the isolated monocytes of group B was lower than A at 3.5 and 48 hours. Tissue bacterial load was similar in two groups after animal death. It is concluded that clarithromycin possessed considerable immu...
-
Early apoptosis of blood monocytes is a determinant of survival in Experimental Sepsis by multi-drug-resistant Pseudomonas aeruginosa.
Clinical and experimental immunology, 2007Co-Authors: Anastasia Antonopoulou, Evangelos J. Giamarellos-bourboulis, Pantelis Koutoukas, Labros Sabracos, Ira Tzepi, Maria Mouktaroudi, Theodoros Adamis, Helen Giamarellou, Maria Raftogiannis, Emmanuel E. DouzinasAbstract:Apoptosis of blood monocytes was studied in Experimental Sepsis by multi-drug-resistant Pseudomonas aeruginosa. Thirty-six rabbits were used, divided into the following groups: A (n = 6), sham; B (n = 6), administered anaesthetics; and C (n = 24), acute pyelonephritis induced after inoculation of the test isolate in the renal pelvis. Blood was sampled at standard time intervals for estimation of tumour necrosis factor (TNF)-alpha and isolation of monocytes. Half the monocytes were incubated and the other half was lysed for estimation of the cytoplasmic activity of caspase-3 by a kinetic chromogenic assay. No animal in groups A and B died; those in group C were divided into two subgroups, CI (n = 8) with present activity of caspase-3 of blood monocytes at 3.5 h and CII (n = 16) with absent activity. Their median survival was 2.0 and 3.5 days, respectively (P = 0.0089). Ex vivo secretion of TNF-alpha from monocytes was higher by monocytes of subgroup CII than subgroup CI at 3.5 h (P = 0.039) and of group A than CII at 48 h (P = 0.010). Median change of caspase-3 activity between 3.5 and 24 h of sampling was 56.1 and -5.8 pmol/min per 10(4) cells for subgroups CI and CII (P = 0.040), respectively. Respective changes between 3.5 and 48 h were 28 981.0 and 0 pmol/min per 10(4) cells (P = 0.036). Early induction of apoptosis in blood monocytes is of prime importance for the survival of the septic host and might be connected to changes of monocyte potential for the secretion of TNF-alpha.
-
Oleuropein: a novel immunomodulator conferring prolonged survival in Experimental Sepsis by Pseudomonas aeruginosa.
Shock (Augusta Ga.), 2006Co-Authors: Evangelos J. Giamarellos-bourboulis, Taxiarchis Geladopoulos, Michael Chrisofos, Pantelis Koutoukas, John Vassiliadis, Ioannis Alexandrou, Thomas Tsaganos, Labros Sabracos, Vassiliki Karagianni, Emilia PelekanouAbstract:Oleuropein, a novel immunomodulator derived from olive tree, was assessed in vitro and in Experimental Sepsis by Pseudomonas aeruginosa. After addition in monocyte and neutrophil cultures, malondialdehyde, TNF-!, IL-6, and bacterial counts were estimated in supernatants. Acute pyelonephritis was induced in 70 rabbits after inoculation of pathogen in the renal pelvis. Intravenous therapy was administered in four groups postchallenge by one multidrug- resistant isolate (A, controls; B, oleuropein; C, amikacin; D, both agents) and in three groups postchallenge by one susceptible isolate (E, controls; F, oleuropein; G, amikacin). Survival was recorded; bacterial growth in blood and organs was counted; endotoxins (LPS), malondialdehyde, total antioxidant status, and TNF-! in serum were estimated. TNF-! and IL-6 of cell supernatants were not increased compared with controls when triggered by LPS and P. aeruginosa. Counts of multidrug-resistant P. aeruginosa were decreased in monocyte supernatants. Median survival of groups A, B, C, D, E, F, and G were 3.00, 6.00, 2.00, 10.00, 1.00, 5.00, and 1.00 days, respectively. Bacteria in blood were lower at 48 h in groups B and D compared with A and in groups F and G compared with E. Total antioxidant status decreased steadily over time in groups A, C, D, and G, but not in groups B and F. TNF-! of groups B, C, and D was lower than A at 48 h. Tissue bacteria decreased in group F compared with E. Oleuropein prolonged survival in Experimental Sepsis probably by promoting phagocytosis or inhibiting biosynthesis of proinflammatory cytokines. KEYWORDS—Sepsis, Pseudomonas, antioxidants, immunomodulation
-
Clarithromycin co-administered with amikacin attenuates systemic inflammation in Experimental Sepsis with Escherichia coli.
International journal of antimicrobial agents, 2005Co-Authors: Evangelos J. Giamarellos-bourboulis, Pantelis Koutoukas, Labros Sabracos, Fotini Baziaka, Despina Perrea, Anastasia Antonopoulou, Vassilios Kousoulas, Charalambos Panagou, Helen GiamarellouAbstract:Abstract To assess the efficacy of clarithromycin as an immunomodulator in Experimental Sepsis with Escherichia coli, acute pyelonephritis was induced after ligation of the right ureter and injection of the test isolate into the renal pelvis in 40 rabbits. Four groups of treatment were applied with administration of therapy on advent of Sepsis-associated pulmonary oedema, as follows: A: controls; B: clarithromycin; C: amikacin, D: both agents. Survival was recorded along with estimation of serum levels of endotoxins (LPS), of tumour necrosis factor-alpha (TNFα), malondialdehyde (MDA) and of bacterial counts. Mean survival of groups A, B, C and D was 2.51, 7.60, 10.25 and 11.40 days, respectively. Serum levels of TNFα and of MDA of group A increased over-time. Pulmonary oedema at 6 h after bacterial challenge was accompanied by increase of TNFα and MDA; administration of clarithromycin decreased their values. It is concluded that intravenous clarithromycin might constitute a promising immunomodulatory agent for the management of Sepsis since its efficacy was proved after administration on presentation of Sepsis-associated pulmonary oedema. The presented findings emphasise the need for further clinical research of the use of clarithromycin for the therapy of Gram-negative Sepsis.
Christian Lehmann - One of the best experts on this subject based on the ideXlab platform.
-
The novel iron chelator, DIBI, attenuates inflammation and improves outcome in colon ascendens stent peritonitis-induced Experimental Sepsis
Clinical hemorheology and microcirculation, 2020Co-Authors: Danielle Fokam, Juan Zhou, Bruce E. Holbein, Maral Aali, Kayle Dickson, Cassidy Scott, Christian LehmannAbstract:BACKGROUND Sepsis is the result of a dysregulated host immune response to an infection. An ideal therapy would target both the underlying infection and the dysregulated immune response. DIBI, a novel iron-binding polymer, was specifically developed as an antimicrobial agent and has also demonstrated in vivo anti-inflammatory properties. OBJECTIVE This study aimed to further investigate the effects of DIBI with and without the antibiotic imipenem (IMI) in colon ascendens stent peritonitis (CASP)-induced Experimental Sepsis. METHODS Vehicle, DIBI and/or IMI were administered in C57BL/6 mice after CASP surgery. Intestinal leukocyte activation and capillary perfusion was evaluated by intravital microscopy. Moreover, bacterial load in peritoneal lavage fluid and blood, and plasma cytokine levels were assessed. In a second series of experiments, surgery to repair the colon was performed at 5 hr and these mice were followed for long-term survival over 7 days. RESULTS DIBI reduced leukocyte adhesion, improved capillary blood flow, and decreased key plasma cytokines levels. DIBI also improved survival of infected mice and greatly improved IMI efficacy. Survivors treated with IMI and DIBI were found to be free of systemic infection. CONCLUSIONS DIBI has promising potential for Sepsis treatment including its use as a sole or an adjunct therapeutic with antibiotics.
-
Inhibition of GPR 55 improves dysregulated immune response in Experimental Sepsis.
Clinical hemorheology and microcirculation, 2019Co-Authors: Juan Zhou, Hyewon Yang, Christian LehmannAbstract:Sepsis is a medical condition caused by dysregulated systemic inflammatory response against infection, resulting in high mortality. Despite intensive research over the last few decades, the results from multiple clinical trials targeting specific inflammatory mediators have been disappointing. In the present study, we investigated the role of G protein-coupled receptor GPR55 modulation on immune response in an Experimental Sepsis model (endotoxemia). Immune response was evaluated by analyzing leukocyte-endothelial interactions and capillary perfusion in the intestinal microcirculation using intravital microscopy. In addition, the levels of plasma inflammatory cytokines were measured. The results demonstrated that GPR55 inhibition using antagonists, CID16020046 or O-1918, significantly reduced leukocyte adherence in intestinal submucosal venules and decreased proinflammatory cytokine TNF-α and IL-6 production. These data suggest that GPR55 inhibition may be a novel therapeutic target for attenuating hyperinflammation during Sepsis.
-
Impact of lipid modulation on the intestinal microcirculation in Experimental Sepsis.
Microvascular research, 2018Co-Authors: Annette Wegner, Dragan Pavlovic, Sebastian Haußmann-vopel, Christian LehmannAbstract:Abstract It has been observed, that patients who were treated medically for dyslipoproteinemia had a potentially lower risk of complications during infection and Sepsis, regarding both morbidity and mortality. Aim of this study in Experimental Sepsis was to elucidate the impact of lipid metabolism modulation by simvastatin, HDL, or bezafibrate, respectively, on the intestinal microcirculation which plays a crucial role in the development of multiple organ failure in Sepsis. Experimental Sepsis was induced in Lewis rats by intravenous lipopolysaccharide (LPS) administration. Animals were treated with simvastatin, HDL or bezafibrate. By means of intestinal intravital microscopy (IVM), the inflammatory response in the microcirculation was studied by leukocyte adherence assessment (LA) and functional capillary density (FCD) measurements. In addition, plasma levels of pro-inflammatory cytokines were determined. Bezafibrate treatment led to a reduction in leukocyte adherence, improved functional capillary density (FCD), and a reduction in interleukin-1α (IL-1α), tumour necrosis factor α (TNF-α) and granulocyte macrophage colony stimulating factors (GM-CSF) plasma levels in Experimental Sepsis. Contrary to this, the administration of HDL increased leukocyte adherence as well as the number of rolling leukocytes. Only IL-1α plasma levels were decreased by HDL. No significant changes were observed following simvastatin treatment. In summary, only bezafibrate showed anti-inflammatory effects in endotoxemia. This effect cannot be explained by the HDL-enhancing effect of the bezafibrate, since the direct administration of HDL showed opposite effects. Bezafibrate induced reduction of inflammation in Sepsis should be investigated in further studies.
-
Anti-inflammatory and anti-bacterial effects of iron chelation in Experimental Sepsis
The Journal of surgical research, 2015Co-Authors: Sufia Islam, Juan Zhou, Stefan Jarosch, Maria Del Carmen Parquet, James T. Toguri, Patricia Colp, Bruce E. Holbein, Christian LehmannAbstract:Abstract Background Sepsis is the systemic inflammatory response to an infection. Generation of reactive oxygen species represents an important part of the inflammatory cascade in Sepsis. Dysregulation of iron homeostasis can further promote the generation of radicals and amplify the damage caused by systemic immune activation. This can potentially be suppressed or prevented by iron chelation. Therefore, this study was designed to examine the effects of a novel iron chelator (DIBI) with or without standard antibiotic treatment in colon ascendens stent peritonitis (CASP)-induced Experimental Sepsis. Methods Six groups of animals (n = 7–10) were included in the study: sham surgery; untreated CASP animals; CASP and subcutaneous (sc) or intraperitoneal DIBI administration, respectively; CASP and imipenem sc; and combination of DIBI and imipenem sc. Results We observed a 55% reduction in leukocyte adhesion in V1 venules after sc administration of DIBI and a 40% reduction after imipenem treatment, when compared to untreated CASP animals ( P P = 0.0065). The bacterial count in the peritoneal lavage fluid was also significantly reduced in the sc imipenem group and the sc DIBI and imipenem combination group ( P = 0.0021 and P = 0.0001, respectively) when compared to untreated CASP animals. Conclusions These findings suggest a potential role of iron chelators in the treatment of Sepsis.
-
Combination of dehydroepiandrosterone and orthovanadate administration reduces intestinal leukocyte recruitment in models of Experimental Sepsis
Microvascular research, 2014Co-Authors: Nadia Al-banna, Dragan Pavlovic, Nivin Sharawi, Vo Hoai Bac, Mathis Jaskulski, Claudius Balzer, Stefan Weber, Vladimir Nedeljkov, Christian LehmannAbstract:Abstract Background Dehydroepiandrosterone (DHEA) was shown to improve the immune function and survival in Experimental Sepsis. This study examined the effect of DHEA on intestinal leukocyte recruitment during Experimental Sepsis, considering factors of gender (male, female and ovariectomized female animals) and combined treatment using orthovanadate (OV) in two models of Sepsis. Methodology/findings Male rats underwent colon ascendens stent peritonitis (CASP) or endotoxemia. DHEA was administered after induction of Experimental Sepsis. Changes in leukocyte adherence and capillary perfusion (measured as intestinal functional capillary density — FCD) were assessed using intravital microscopy. While DHEA increased baseline leukocyte adherence in control animals, DHEA reduced leukocyte adherence and increased FCD in male animals with CASP. These effects were also observed in DHEA-treated ovariectomized female rats with CASP. Similarly, the administration of DHEA reduced the number of adherent leukocytes to intestinal venules by 30% in the endotoxemia model. The combined treatment of DHEA and OV significantly reduced adherence of leukocytes to intestinal venules and improved FCD. Conclusions Our results indicate that DHEA is able to reduce intestinal leukocyte recruitment induced by Experimental Sepsis. Combination of DHEA with OV inhibits leukocyte adherence to intestinal endothelium, similar to what is achieved by the single administration of DHEA but with significantly improved FCD. These findings suggest a potential role for DHEA and OV in clinical Sepsis.
Labros Sabracos - One of the best experts on this subject based on the ideXlab platform.
-
Immunomodulatory effect of three-day continuous administration of clarithromycin for Experimental Sepsis due to multidrug-resistant Pseudomonas aeruginosa.
Journal of chemotherapy (Florence Italy), 2008Co-Authors: Fotini Baziaka, Evangelos J. Giamarellos-bourboulis, Michael Chrisofos, Pantelis Koutoukas, Labros Sabracos, Vassiliki Tziortzioti, Theodoros Adamis, Helen Giamarellou, Maria Raftogiannis, Emmanuel E. DouzinasAbstract:Abstract Based on former animal studies showing the effect of clarithromycin in Experimental Sepsis by multidrug-resistant Pseudomonas aeruginosa following administration of single doses, the significance of its administration for three consecutive days was evaluated. Acute pyelonephritis was induced in 20 rabbits after inoculation of the test isolate in the renal pelvis. Therapy was administered upon signs of Sepsis in group B; A served as control. Survival was recorded; monocytes were isolated for determination of ex vivo TNFα secretion. Quantitative cultures of organs were performed after death. Mean survival of groups A and B was 2.65 and 7.95 days respectively. At 24 hours, serum malondialdehyde of group B, which is an index of the oxidant status in serum, was lower than A. ex vivo release of TNFα by the isolated monocytes of group B was lower than A at 3.5 and 48 hours. Tissue bacterial load was similar in two groups after animal death. It is concluded that clarithromycin possessed considerable immu...
-
Early apoptosis of blood monocytes is a determinant of survival in Experimental Sepsis by multi-drug-resistant Pseudomonas aeruginosa.
Clinical and experimental immunology, 2007Co-Authors: Anastasia Antonopoulou, Evangelos J. Giamarellos-bourboulis, Pantelis Koutoukas, Labros Sabracos, Ira Tzepi, Maria Mouktaroudi, Theodoros Adamis, Helen Giamarellou, Maria Raftogiannis, Emmanuel E. DouzinasAbstract:Apoptosis of blood monocytes was studied in Experimental Sepsis by multi-drug-resistant Pseudomonas aeruginosa. Thirty-six rabbits were used, divided into the following groups: A (n = 6), sham; B (n = 6), administered anaesthetics; and C (n = 24), acute pyelonephritis induced after inoculation of the test isolate in the renal pelvis. Blood was sampled at standard time intervals for estimation of tumour necrosis factor (TNF)-alpha and isolation of monocytes. Half the monocytes were incubated and the other half was lysed for estimation of the cytoplasmic activity of caspase-3 by a kinetic chromogenic assay. No animal in groups A and B died; those in group C were divided into two subgroups, CI (n = 8) with present activity of caspase-3 of blood monocytes at 3.5 h and CII (n = 16) with absent activity. Their median survival was 2.0 and 3.5 days, respectively (P = 0.0089). Ex vivo secretion of TNF-alpha from monocytes was higher by monocytes of subgroup CII than subgroup CI at 3.5 h (P = 0.039) and of group A than CII at 48 h (P = 0.010). Median change of caspase-3 activity between 3.5 and 24 h of sampling was 56.1 and -5.8 pmol/min per 10(4) cells for subgroups CI and CII (P = 0.040), respectively. Respective changes between 3.5 and 48 h were 28 981.0 and 0 pmol/min per 10(4) cells (P = 0.036). Early induction of apoptosis in blood monocytes is of prime importance for the survival of the septic host and might be connected to changes of monocyte potential for the secretion of TNF-alpha.
-
Oleuropein: a novel immunomodulator conferring prolonged survival in Experimental Sepsis by Pseudomonas aeruginosa.
Shock (Augusta Ga.), 2006Co-Authors: Evangelos J. Giamarellos-bourboulis, Taxiarchis Geladopoulos, Michael Chrisofos, Pantelis Koutoukas, John Vassiliadis, Ioannis Alexandrou, Thomas Tsaganos, Labros Sabracos, Vassiliki Karagianni, Emilia PelekanouAbstract:Oleuropein, a novel immunomodulator derived from olive tree, was assessed in vitro and in Experimental Sepsis by Pseudomonas aeruginosa. After addition in monocyte and neutrophil cultures, malondialdehyde, TNF-!, IL-6, and bacterial counts were estimated in supernatants. Acute pyelonephritis was induced in 70 rabbits after inoculation of pathogen in the renal pelvis. Intravenous therapy was administered in four groups postchallenge by one multidrug- resistant isolate (A, controls; B, oleuropein; C, amikacin; D, both agents) and in three groups postchallenge by one susceptible isolate (E, controls; F, oleuropein; G, amikacin). Survival was recorded; bacterial growth in blood and organs was counted; endotoxins (LPS), malondialdehyde, total antioxidant status, and TNF-! in serum were estimated. TNF-! and IL-6 of cell supernatants were not increased compared with controls when triggered by LPS and P. aeruginosa. Counts of multidrug-resistant P. aeruginosa were decreased in monocyte supernatants. Median survival of groups A, B, C, D, E, F, and G were 3.00, 6.00, 2.00, 10.00, 1.00, 5.00, and 1.00 days, respectively. Bacteria in blood were lower at 48 h in groups B and D compared with A and in groups F and G compared with E. Total antioxidant status decreased steadily over time in groups A, C, D, and G, but not in groups B and F. TNF-! of groups B, C, and D was lower than A at 48 h. Tissue bacteria decreased in group F compared with E. Oleuropein prolonged survival in Experimental Sepsis probably by promoting phagocytosis or inhibiting biosynthesis of proinflammatory cytokines. KEYWORDS—Sepsis, Pseudomonas, antioxidants, immunomodulation
-
Clarithromycin co-administered with amikacin attenuates systemic inflammation in Experimental Sepsis with Escherichia coli.
International journal of antimicrobial agents, 2005Co-Authors: Evangelos J. Giamarellos-bourboulis, Pantelis Koutoukas, Labros Sabracos, Fotini Baziaka, Despina Perrea, Anastasia Antonopoulou, Vassilios Kousoulas, Charalambos Panagou, Helen GiamarellouAbstract:Abstract To assess the efficacy of clarithromycin as an immunomodulator in Experimental Sepsis with Escherichia coli, acute pyelonephritis was induced after ligation of the right ureter and injection of the test isolate into the renal pelvis in 40 rabbits. Four groups of treatment were applied with administration of therapy on advent of Sepsis-associated pulmonary oedema, as follows: A: controls; B: clarithromycin; C: amikacin, D: both agents. Survival was recorded along with estimation of serum levels of endotoxins (LPS), of tumour necrosis factor-alpha (TNFα), malondialdehyde (MDA) and of bacterial counts. Mean survival of groups A, B, C and D was 2.51, 7.60, 10.25 and 11.40 days, respectively. Serum levels of TNFα and of MDA of group A increased over-time. Pulmonary oedema at 6 h after bacterial challenge was accompanied by increase of TNFα and MDA; administration of clarithromycin decreased their values. It is concluded that intravenous clarithromycin might constitute a promising immunomodulatory agent for the management of Sepsis since its efficacy was proved after administration on presentation of Sepsis-associated pulmonary oedema. The presented findings emphasise the need for further clinical research of the use of clarithromycin for the therapy of Gram-negative Sepsis.
-
The significance of oxidant/antioxidant balance for the pathogenesis of Experimental Sepsis by multidrug-resistant Pseudomonas aeruginosa.
Prostaglandins leukotrienes and essential fatty acids, 2005Co-Authors: Vassilios Koussoulas, Evangelos J. Giamarellos-bourboulis, Labros Sabracos, Maria Mouktaroudi, Theodoros Adamis, Despina Perrea, Helen Giamarellou, Amalia Dionyssiou-asteriouAbstract:Abstract Objective : The significance of lipid peroxidation as an independent factor leading to Sepsis by multidrug-resistant Pseudomonas aeruginosa . Design Experimental study Methods : Twenty-six rabbits were applied. They were divided into two groups; A ( n = 6 ) comprising controls, and B ( n = 20 ) comprising animals infected by the injection of 1×10 8 cfu/kg inoculum of the test pathogen into the left inner jugular vein. Six rabbits of group B were followed-up to estimate survival; all of the remaining were sacrificed. Blood was sampled for the determination of serum malondialdehyde (MDA) by the thiobarbiturate assay, total antioxidant status (TAS) by a chromogenic assay, tumor necrosis factor alpha by a bioassay on fibrosarcoma L929 cell line, and endotoxins (LPS) by the QCL-1000 LAL assay. Results : Mean survival of group B was 60.0±15.8h. MDA was significantly higher in group B compared to group A at 30, 60, 120 and 150min. TAS was statistically decreased in group B compared to group A at 30 and 60min. Increases of MDA in group B were followed by reciprocal decreases of TAS ( P of correlation Conclusions : Early alterations of oxidant/antioxidant balance occur in Experimental Sepsis by multidrug-resistant P. aeruginosa followed by hemodynamic instability. Results highlight the perspective of the administration of antioxidants as immunomodulatory treatment of Sepsis in animal studies.
Theodoros Adamis - One of the best experts on this subject based on the ideXlab platform.
-
Immunomodulatory effect of three-day continuous administration of clarithromycin for Experimental Sepsis due to multidrug-resistant Pseudomonas aeruginosa.
Journal of chemotherapy (Florence Italy), 2008Co-Authors: Fotini Baziaka, Evangelos J. Giamarellos-bourboulis, Michael Chrisofos, Pantelis Koutoukas, Labros Sabracos, Vassiliki Tziortzioti, Theodoros Adamis, Helen Giamarellou, Maria Raftogiannis, Emmanuel E. DouzinasAbstract:Abstract Based on former animal studies showing the effect of clarithromycin in Experimental Sepsis by multidrug-resistant Pseudomonas aeruginosa following administration of single doses, the significance of its administration for three consecutive days was evaluated. Acute pyelonephritis was induced in 20 rabbits after inoculation of the test isolate in the renal pelvis. Therapy was administered upon signs of Sepsis in group B; A served as control. Survival was recorded; monocytes were isolated for determination of ex vivo TNFα secretion. Quantitative cultures of organs were performed after death. Mean survival of groups A and B was 2.65 and 7.95 days respectively. At 24 hours, serum malondialdehyde of group B, which is an index of the oxidant status in serum, was lower than A. ex vivo release of TNFα by the isolated monocytes of group B was lower than A at 3.5 and 48 hours. Tissue bacterial load was similar in two groups after animal death. It is concluded that clarithromycin possessed considerable immu...
-
Early apoptosis of blood monocytes is a determinant of survival in Experimental Sepsis by multi-drug-resistant Pseudomonas aeruginosa.
Clinical and experimental immunology, 2007Co-Authors: Anastasia Antonopoulou, Evangelos J. Giamarellos-bourboulis, Pantelis Koutoukas, Labros Sabracos, Ira Tzepi, Maria Mouktaroudi, Theodoros Adamis, Helen Giamarellou, Maria Raftogiannis, Emmanuel E. DouzinasAbstract:Apoptosis of blood monocytes was studied in Experimental Sepsis by multi-drug-resistant Pseudomonas aeruginosa. Thirty-six rabbits were used, divided into the following groups: A (n = 6), sham; B (n = 6), administered anaesthetics; and C (n = 24), acute pyelonephritis induced after inoculation of the test isolate in the renal pelvis. Blood was sampled at standard time intervals for estimation of tumour necrosis factor (TNF)-alpha and isolation of monocytes. Half the monocytes were incubated and the other half was lysed for estimation of the cytoplasmic activity of caspase-3 by a kinetic chromogenic assay. No animal in groups A and B died; those in group C were divided into two subgroups, CI (n = 8) with present activity of caspase-3 of blood monocytes at 3.5 h and CII (n = 16) with absent activity. Their median survival was 2.0 and 3.5 days, respectively (P = 0.0089). Ex vivo secretion of TNF-alpha from monocytes was higher by monocytes of subgroup CII than subgroup CI at 3.5 h (P = 0.039) and of group A than CII at 48 h (P = 0.010). Median change of caspase-3 activity between 3.5 and 24 h of sampling was 56.1 and -5.8 pmol/min per 10(4) cells for subgroups CI and CII (P = 0.040), respectively. Respective changes between 3.5 and 48 h were 28 981.0 and 0 pmol/min per 10(4) cells (P = 0.036). Early induction of apoptosis in blood monocytes is of prime importance for the survival of the septic host and might be connected to changes of monocyte potential for the secretion of TNF-alpha.
-
The significance of oxidant/antioxidant balance for the pathogenesis of Experimental Sepsis by multidrug-resistant Pseudomonas aeruginosa.
Prostaglandins leukotrienes and essential fatty acids, 2005Co-Authors: Vassilios Koussoulas, Evangelos J. Giamarellos-bourboulis, Labros Sabracos, Maria Mouktaroudi, Theodoros Adamis, Despina Perrea, Helen Giamarellou, Amalia Dionyssiou-asteriouAbstract:Abstract Objective : The significance of lipid peroxidation as an independent factor leading to Sepsis by multidrug-resistant Pseudomonas aeruginosa . Design Experimental study Methods : Twenty-six rabbits were applied. They were divided into two groups; A ( n = 6 ) comprising controls, and B ( n = 20 ) comprising animals infected by the injection of 1×10 8 cfu/kg inoculum of the test pathogen into the left inner jugular vein. Six rabbits of group B were followed-up to estimate survival; all of the remaining were sacrificed. Blood was sampled for the determination of serum malondialdehyde (MDA) by the thiobarbiturate assay, total antioxidant status (TAS) by a chromogenic assay, tumor necrosis factor alpha by a bioassay on fibrosarcoma L929 cell line, and endotoxins (LPS) by the QCL-1000 LAL assay. Results : Mean survival of group B was 60.0±15.8h. MDA was significantly higher in group B compared to group A at 30, 60, 120 and 150min. TAS was statistically decreased in group B compared to group A at 30 and 60min. Increases of MDA in group B were followed by reciprocal decreases of TAS ( P of correlation Conclusions : Early alterations of oxidant/antioxidant balance occur in Experimental Sepsis by multidrug-resistant P. aeruginosa followed by hemodynamic instability. Results highlight the perspective of the administration of antioxidants as immunomodulatory treatment of Sepsis in animal studies.
-
n-6 Polyunsaturated Fatty Acids Enhance the Activities of Ceftazidime and Amikacin in Experimental Sepsis Caused by Multidrug-Resistant Pseudomonas aeruginosa
Antimicrobial agents and chemotherapy, 2004Co-Authors: Evangelos J. Giamarellos-bourboulis, Maria Mouktaroudi, Theodoros Adamis, Vassilios Koussoulas, Fotini Baziaka, Despina Perrea, Panayotis E. Karayannacos, Helen GiamarellouAbstract:Recent in vitro and ex vivo studies disclosed an enhancement of the activity of antimicrobials on multidrug-resistant Pseudomonas aeruginosa by n-6 polyunsaturated fatty acids (PUFAS); therefore their effect was evaluated in Experimental Sepsis in 60 rabbits. Solutions of gamma-linolenic acid (GLA) and arachidonic acid (AA) were administered intravenously with ceftazidime and amikacin in rabbits with Sepsis caused by one multidrug-resistant isolate. Therapy was started after bacterial challenge in five groups comprising 12 animals in each group: A, normal saline; B, antimicrobials; C, 99% ethanol and antimicrobials; D, GLA and antimicrobials; and E, AA and antimicrobials. Blood was sampled for the estimation of levels of endotoxins in serum (lipopolysaccharide), leukocytes, tumor necrosis factor alpha (TNF-alpha) and antimicrobials. Animals were sacrificed 210 min after bacterial challenge for tissue cultures. All animals had considerable endotoxemia and evolved leukopenia. The number of viable cells in blood, lung, and mesenteric lymph nodes was significantly reduced in groups D and E compared to that in other groups. Levels of antimicrobials in serum were inadequate to achieve bacterial killing due to the level of resistance. n-6 PUFAs did not influence TNF-alpha. It is concluded that intravenous coadministration of n-6 PUFAs and antimicrobials enhanced antimicrobial bacterial killing in Experimental Sepsis caused by multidrug-resistant P. aeruginosa.
-
Immunomodulatory Clarithromycin Treatment of Experimental Sepsis and Acute Pyelonephritis Caused by Multidrug-Resistant Pseudomonas aeruginosa
Antimicrobial agents and chemotherapy, 2004Co-Authors: Evangelos J. Giamarellos-bourboulis, Labros Sabracos, Maria Mouktaroudi, Theodoros Adamis, Vassilios Koussoulas, Despina Perrea, Panayotis E. Karayannacos, George Laoutaris, Helen GiamarellouAbstract:Clarithromycin was administered intravenously to 55 rabbits to evaluate its effect on Experimental Sepsis caused by multidrug-resistant Pseudomonas aeruginosa. Acute pyelonephritis was induced after ligation of the right ureter and injection of 10(8) CFU of the test isolate per kg of body weight into the renal pelvis. The animals were divided into six groups: group A, controls; group B, rabbits that received one intravenous dose of 80 mg of clarithromycin per kg concomitantly with bacterial challenge; group C, rabbits that received two doses of clarithromycin, the second one of which was given 2 h after the first one; group D, rabbits that received 15 mg of amikacin per kg; group E, rabbits that received one dose of clarithromycin and amikacin; and group F, rabbits that received two doses of clarithromycin and amikacin. Serum endotoxin levels were estimated by the QCL-1000 Limulus amoebocyte lysate assay, tumor necrosis factor alpha (TNF-alpha) levels were measured by a bioassay, and malondialdehyde (MDA) levels were measured by the thiobarbiturate assay. Viable bacterial counts in various tissue samples were also assessed. The mean survival times of the animals in groups A, B, C, D, E, and F were 4.50, 7.69, 4.07, 4.55, 11.55, and 11.60 days, respectively (P = 0.033 for group D versus group F, P = 0.006 for group D versus group E, P = not significant for group B versus group E, P = 0.042 for group C versus group F). Serum endotoxin levels were similar between groups at all sampling times; TNF-alpha and MDA levels in groups B, C, E, and F decreased significantly over follow-up. The numbers of viable bacterial cells in the infected kidney were similar among the groups; those in the liver, spleen, lungs, and mesenteral lymph nodes were significantly decreased in groups B, E, and F compared to those in groups A and D. It is concluded that a prolongation of survival in animals with Experimental Sepsis caused by multidrug-resistant P. aeruginosa was achieved after coadministration of clarithromycin and amikacin and that the increased survival was probably attributable to the immunomodulatory properties of clarithromycin.
