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José Such - One of the best experts on this subject based on the ideXlab platform.

  • Bacterial DNA translocation is associated with systemic circulatory abnormalities and intrahepatic endothelial dysfunction in patients with cirrhosis
    Hepatology (Baltimore Md.), 2010
    Co-Authors: Pablo Bellot, Rubén Francés, Miguel Pérez-mateo, José Such, Juan Carlos García-pagán, Juan G. Abraldes, Miguel Navasa, Jaime Bosch
    Abstract:

    Presence of Bacterial DNA in noninfected patients with cirrhosis and ascites is associated with a marked inflammatory response including activation of the inducible form of nitric oxide synthase and release of nitric oxide, similar to that observed in patients with spontaneous Bacterial peritonitis. Although presence of Bacterial DNA is associated with an impaired prognosis, no information is available regarding its hemodynamic consequences. Systemic and hepatic hemodynamics before and after a liquid test meal were assessed in a series of 75 noninfected patients with cirrhosis (55 with ascites). Bacterial DNA was measured by polymerase chain reaction. Bacterial DNA was detected only in patients with ascites. Clinical data and liver function were similar in ascitic patients with presence (n = 21) or absence of Bacterial DNA (n = 34). Bacterial-DNA(+) patients had significantly lower mean arterial pressure (P = 0.002) and systemic vascular resistance (P = 0.03) than Bacterial-DNA(−) patients. Cardiac output, cardiopulmonary pressures, hepatic venous pressure gradient (HVPG), and hepatic blood flow were similar in both groups. Thirty minutes after the test meal, in response to increased blood flow caused by postprandial hyperemia, there was a significantly greater increase in HVPG and impaired hepatic vasorelaxation in Bacterial-DNA(+) as compared with Bacterial-DNA(−) patients, which indicates hepatic endothelial dysfunction. Indeed, the increase in HVPG after the test meal significantly correlated with serum Bacterial DNA concentration. Conclusion: Presence of Bacterial DNA, a marker of Bacterial translocation, is associated with aggravation of peripheral vasodilation and with worsening of intrahepatic endothelial dysfunction. (HEPATOLOGY 2010;.)

  • Presence of Bacterial-DNA in cirrhosis identifies a subgroup of patients with marked inflammatory response not related to endotoxin
    Journal of hepatology, 2007
    Co-Authors: José M. González-navajas, Rubén Francés, Miguel Pérez-mateo, Pedro Zapater, Carlos Munoz, Pablo Bellot, Juan Carlos García-pagán, Sonia Pascual, J. Bosch, José Such
    Abstract:

    Background/Aims Serum lipopolysaccharide-binding protein and Bacterial-DNA have been proposed as markers of Bacterial translocation and this study aimed to evaluate the immune response registered by Bacterial-DNA from Gram-positive and Gram-negative microorganisms and the effect on lipopolysaccharide-binding protein, to further investigate both markers. Methods Thirty-two patients were distributed into two groups according to the presence of Bacterial-DNA, determined by broad-range PCR of 16SrRNA gene. Serum endotoxin, lipopolysaccharide-binding protein, cytokines and nitric oxide products were measured by ELISA. Results Serum endotoxin and lipopolysaccharide-binding protein were non-significantly higher in patients with Bacterial-DNA than in those without Bacterial-DNA. Regarding patients with Bacterial-DNA from Gram-positive microorganisms ( n =8), these levels were similar to those in patients without Bacterial-DNA ( n =16), and significantly lower than in patients with Bacterial-DNA from Gram-negative bacteria. Tumour necrosis factor-alpha and interleukin-6 were significantly increased in patients with vs without Bacterial-DNA (324.93±70.76 vs 134.91±34.58μg/mL; p p Conclusions Patients with translocation of Bacterial-DNA from Gram-positive microorganisms showed increased proinflammatory cytokines unrelated to endotoxin, which would not be detected by serum lipopolysaccharide-binding protein measurement.

  • Bacterial DNA induces the complement system activation in serum and ascitic fluid from patients with advanced cirrhosis.
    Journal of clinical immunology, 2007
    Co-Authors: Rubén Francés, Miguel Pérez-mateo, Pedro Zapater, Carlos Munoz, José M. González-navajas, Sonia Pascual, Rocío Caño, Dorkas Márquez, Francia Santana, José Such
    Abstract:

    Translocation of intestinal bacteria to ascitic fluid is, probably, the first step in the development of spontaneous Bacterial peritonitis in patients with cirrhosis. Proteins of the complement system are soluble mediators implicated in the host immune response to Bacterial infections and its activation has been traditionally considered to be an endotoxin-induced phenomenon. The aim of this study was to compare the modulation of these proteins in response to the presence of Bacterial DNA and/or endotoxin in patients with advanced cirrhosis and ascites in different clinical conditions. Groups I and II consisted of patients without/with Bacterial DNA. Group III included patients with spontaneous Bacterial peritonitis and Group IV with patients receiving norfloxacin as secondary long-term prophylaxis of spontaneous Bacterial peritonitis. Serum and ascitic fluid levels of endotoxin and truncated residues of the complement system were measured by ELISA. The complement system is triggered in response to Bacterial DNA, as evidenced by significantly increased levels of C3b, membrane attack complex, and C5a in patients from Groups II and III compared with patients without Bacterial DNA (Group I) and those receiving norfloxacin (Group IV). Gram classification did not further differentiate the immune response between patients within groups II and III, even though endotoxin levels were, as expected, significantly higher in patients with Bacterial DNA from gram-negative microorganisms. The complement protein activation observed in patients with Bacterial DNA in blood and ascitic fluid is indistinguishable from that observed in patients with spontaneous Bacterial peritonitis and may occur in an endotoxin-independent manner.

  • Detection and identification of Bacterial DNA in serum from patients with acute pancreatitis.
    Gut, 2005
    Co-Authors: E. De Madaria, Rubén Francés, José Such, Juan Martínez, Beatriz Lozano, Laura Sempere, Susana Benlloch, Francisco Uceda, Miguel Pérez-mateo
    Abstract:

    Background and aims: Bacterial infections are common complications in patients with acute pancreatitis, and translocation of bacteria from the intestinal lumen is probably the first step in the pathogenesis of these infections. As blood cultures in afebrile patients are usually negative, more sensitive methods to investigate this hypothesis in patients are needed. Our group has recently developed a method to detect the presence of Bacterial DNA in biological fluids, and we aimed to detect Bacterial DNA in patients with acute pancreatitis, as molecular evidences of Bacterial translocation. Methods: Samples of blood were obtained on three consecutive days within the first six days after admission. Bacterial DNA was detected using a polymerase chain reaction based method, and an automated DNA nucleotide sequencing process allowed identification of bacteria species. Results: Thirty one consecutively admitted patients with acute pancreatitis were studied. Bacterial DNA was detected in six patients (19.3%), and the sequencing process allowed identification of Citrobacter freundii and Pseudomonas aeruginosa. In two patients the same bacteria detected at admission was detected 24 hours later (above 99.9% homology of nucleotide sequence). Basic clinical and biochemical characteristics were similar among patients with or without the presence of Bacterial DNA. Conclusion: Detection of gram negative bacteria derived Bacterial DNA in our series supports the contention that Bacterial translocation is a systemic process in approximately 20% of patients with acute pancreatitis that does not seem to be related to the severity of the episode or immediate development of infection.

  • Intracellular cytokine expression in peritoneal monocyte/macrophages obtained from patients with cirrhosis and presence of Bacterial DNA
    European Journal of Gastroenterology and Hepatology, 2005
    Co-Authors: Rubén Francés, Ma Luz De La Sen, Miguel Pérez-mateo, Enrique Rodriguez, Moises Ndongo, Pedro Zapater, Carlos Munoz, José Such
    Abstract:

    BACKGROUND: The detection of Bacterial DNA in serum and ascitic fluid from patients with cirrhosis and ascites is interpreted as molecular evidence of intestinal Bacterial translocation and considered sufficient to activate the cellular immune response. In vitro studies on ascitic fluid culture have shown a close relationship between the synthesis of several cytokines and nitric oxide and the presence of Bacterial DNA. Since different cell types give rise to cytokines, flow cytometry becomes a powerful tool to discriminate between populations involved in a Bacterial challenge.\n\nOBJECTIVE: To study the pre-activation status of macrophage/monocyte population ex vivo according to the presence of Bacterial DNA.\n\nPATIENTS: Patients with cirrhosis and culture-negative, non-neutrocytic ascites, with or without the presence of Bacterial DNA in blood and ascitic fluid were studied.\n\nMETHODS: Flow cytometry analysis of intracellular cytokine expression in monocyte/macrophages from ascitic fluid was performed in basal conditions and after 12 h of cell stimulation adding lypopolysaccharide.\n\nRESULTS: Monocyte/macrophages from patients with Bacterial DNA showed a significantly higher production of interleukin-6 and tumor necrosis factor alpha in basal conditions than that in cells from patients without the presence of Bacterial DNA. The addition of lipopolysaccharide produced a non-significant increment in the expression of these cytokines in patients with the presence of Bacterial DNA, while this increment became significant in the other group of patients.\n\nCONCLUSIONS: Bacterial translocation in patients with cirrhosis and ascites increases the basal intracellular cytokine expression, reducing its functional reserve capability.

Rubén Francés - One of the best experts on this subject based on the ideXlab platform.

  • Identification of Bacterial DNA in the peripheral blood of patients with active hidradenitis suppurativa
    Archives of Dermatological Research, 2019
    Co-Authors: Patricia Hispán, Rubén Francés, Oscar Murcia, Iris Gonzalez-villanueva, Paula Giménez, Jorge Riquelme, Isabel Betlloch, José Carlos Pascual
    Abstract:

    Bacterial translocation may have a role in the pathogenesis of several inflammatory conditions. A prospective analytical case–control study was designed to assess the presence of Bacterial DNA in the peripheral blood of patients with hidradenitis suppurativa (HS). An age- and gender-matched control population was recruited from healthy blood donors. Demographic and HS-related data were also collected. We took fasting blood samples from each participant and determined the presence of Bacterial DNA (including Bacterial species identification) and levels TNF-α, IL-1β, and IL-17A. We included 50 patients with HS and 50 healthy controls. Bacterial DNA was present in 17 (34.0%) cases vs. 2 (4.0%) controls ( P  

  • Treatment with non-selective beta-blockers affects the systemic inflammatory response to Bacterial DNA in patients with cirrhosis.
    Liver international : official journal of the International Association for the Study of the Liver, 2018
    Co-Authors: Paula Giménez, Rubén Francés, José M. González-navajas, José María Palazón, Irma Garcia-martinez, Montserrat Mauri, Rocío Alfayate, Susana Almenara, Cayetano Miralles, F. Carnicer
    Abstract:

    Background & aims The use of non-selective beta-blockers has been associated with lower rates of infection and reduced infection-associated morbidity in patients with cirrhosis. However, it is unknown if these drugs modify the systemic inflammatory response to circulating Bacterial DNA. Methods Sixty-three patients with cirrhosis were included during an episode of decompensation by ascites. Thirty of those patients were on beta-blockers. Blood samples were obtained after each patient had been in the supine position for at least 30 minutes in a quiet atmosphere. Bacterial DNA, serum cytokines, nitric oxide, and LPS were determined. Phagocytic and oxidative burst activities were determined in polymorphonuclear cells from the patients. Results The detection rate of Bacterial DNA in the blood was the same (33%) for patients not treated and treated with non-selective beta-blockers. Patients naive to non-selective beta-blockers showed significantly higher serum levels of IL6, IFN-gamma and IL10 in response to the presence of Bacterial DNA. Patients treated with non-selective beta-blockers showed higher basal inflammatory activity that did not change with the presence of Bacterial DNA. Monocytes and granulocytes from patients treated with non-selective beta-blockers showed a significantly increased phagocytic capacity in the presence of Bacterial DNA. Conclusions In patients with cirrhosis, chronic treatment with beta-blockers is associated with a higher unstimulated production of serum cytokines and an increased phagocytic activity in the presence of Bacterial DNA.

  • Bacterial DNA translocation is associated with systemic circulatory abnormalities and intrahepatic endothelial dysfunction in patients with cirrhosis
    Hepatology (Baltimore Md.), 2010
    Co-Authors: Pablo Bellot, Rubén Francés, Miguel Pérez-mateo, José Such, Juan Carlos García-pagán, Juan G. Abraldes, Miguel Navasa, Jaime Bosch
    Abstract:

    Presence of Bacterial DNA in noninfected patients with cirrhosis and ascites is associated with a marked inflammatory response including activation of the inducible form of nitric oxide synthase and release of nitric oxide, similar to that observed in patients with spontaneous Bacterial peritonitis. Although presence of Bacterial DNA is associated with an impaired prognosis, no information is available regarding its hemodynamic consequences. Systemic and hepatic hemodynamics before and after a liquid test meal were assessed in a series of 75 noninfected patients with cirrhosis (55 with ascites). Bacterial DNA was measured by polymerase chain reaction. Bacterial DNA was detected only in patients with ascites. Clinical data and liver function were similar in ascitic patients with presence (n = 21) or absence of Bacterial DNA (n = 34). Bacterial-DNA(+) patients had significantly lower mean arterial pressure (P = 0.002) and systemic vascular resistance (P = 0.03) than Bacterial-DNA(−) patients. Cardiac output, cardiopulmonary pressures, hepatic venous pressure gradient (HVPG), and hepatic blood flow were similar in both groups. Thirty minutes after the test meal, in response to increased blood flow caused by postprandial hyperemia, there was a significantly greater increase in HVPG and impaired hepatic vasorelaxation in Bacterial-DNA(+) as compared with Bacterial-DNA(−) patients, which indicates hepatic endothelial dysfunction. Indeed, the increase in HVPG after the test meal significantly correlated with serum Bacterial DNA concentration. Conclusion: Presence of Bacterial DNA, a marker of Bacterial translocation, is associated with aggravation of peripheral vasodilation and with worsening of intrahepatic endothelial dysfunction. (HEPATOLOGY 2010;.)

  • Presence of Bacterial-DNA in cirrhosis identifies a subgroup of patients with marked inflammatory response not related to endotoxin
    Journal of hepatology, 2007
    Co-Authors: José M. González-navajas, Rubén Francés, Miguel Pérez-mateo, Pedro Zapater, Carlos Munoz, Pablo Bellot, Juan Carlos García-pagán, Sonia Pascual, J. Bosch, José Such
    Abstract:

    Background/Aims Serum lipopolysaccharide-binding protein and Bacterial-DNA have been proposed as markers of Bacterial translocation and this study aimed to evaluate the immune response registered by Bacterial-DNA from Gram-positive and Gram-negative microorganisms and the effect on lipopolysaccharide-binding protein, to further investigate both markers. Methods Thirty-two patients were distributed into two groups according to the presence of Bacterial-DNA, determined by broad-range PCR of 16SrRNA gene. Serum endotoxin, lipopolysaccharide-binding protein, cytokines and nitric oxide products were measured by ELISA. Results Serum endotoxin and lipopolysaccharide-binding protein were non-significantly higher in patients with Bacterial-DNA than in those without Bacterial-DNA. Regarding patients with Bacterial-DNA from Gram-positive microorganisms ( n =8), these levels were similar to those in patients without Bacterial-DNA ( n =16), and significantly lower than in patients with Bacterial-DNA from Gram-negative bacteria. Tumour necrosis factor-alpha and interleukin-6 were significantly increased in patients with vs without Bacterial-DNA (324.93±70.76 vs 134.91±34.58μg/mL; p p Conclusions Patients with translocation of Bacterial-DNA from Gram-positive microorganisms showed increased proinflammatory cytokines unrelated to endotoxin, which would not be detected by serum lipopolysaccharide-binding protein measurement.

  • Bacterial DNA induces the complement system activation in serum and ascitic fluid from patients with advanced cirrhosis.
    Journal of clinical immunology, 2007
    Co-Authors: Rubén Francés, Miguel Pérez-mateo, Pedro Zapater, Carlos Munoz, José M. González-navajas, Sonia Pascual, Rocío Caño, Dorkas Márquez, Francia Santana, José Such
    Abstract:

    Translocation of intestinal bacteria to ascitic fluid is, probably, the first step in the development of spontaneous Bacterial peritonitis in patients with cirrhosis. Proteins of the complement system are soluble mediators implicated in the host immune response to Bacterial infections and its activation has been traditionally considered to be an endotoxin-induced phenomenon. The aim of this study was to compare the modulation of these proteins in response to the presence of Bacterial DNA and/or endotoxin in patients with advanced cirrhosis and ascites in different clinical conditions. Groups I and II consisted of patients without/with Bacterial DNA. Group III included patients with spontaneous Bacterial peritonitis and Group IV with patients receiving norfloxacin as secondary long-term prophylaxis of spontaneous Bacterial peritonitis. Serum and ascitic fluid levels of endotoxin and truncated residues of the complement system were measured by ELISA. The complement system is triggered in response to Bacterial DNA, as evidenced by significantly increased levels of C3b, membrane attack complex, and C5a in patients from Groups II and III compared with patients without Bacterial DNA (Group I) and those receiving norfloxacin (Group IV). Gram classification did not further differentiate the immune response between patients within groups II and III, even though endotoxin levels were, as expected, significantly higher in patients with Bacterial DNA from gram-negative microorganisms. The complement protein activation observed in patients with Bacterial DNA in blood and ascitic fluid is indistinguishable from that observed in patients with spontaneous Bacterial peritonitis and may occur in an endotoxin-independent manner.

Carlos Munoz - One of the best experts on this subject based on the ideXlab platform.

  • Presence of Bacterial-DNA in cirrhosis identifies a subgroup of patients with marked inflammatory response not related to endotoxin
    Journal of hepatology, 2007
    Co-Authors: José M. González-navajas, Rubén Francés, Miguel Pérez-mateo, Pedro Zapater, Carlos Munoz, Pablo Bellot, Juan Carlos García-pagán, Sonia Pascual, J. Bosch, José Such
    Abstract:

    Background/Aims Serum lipopolysaccharide-binding protein and Bacterial-DNA have been proposed as markers of Bacterial translocation and this study aimed to evaluate the immune response registered by Bacterial-DNA from Gram-positive and Gram-negative microorganisms and the effect on lipopolysaccharide-binding protein, to further investigate both markers. Methods Thirty-two patients were distributed into two groups according to the presence of Bacterial-DNA, determined by broad-range PCR of 16SrRNA gene. Serum endotoxin, lipopolysaccharide-binding protein, cytokines and nitric oxide products were measured by ELISA. Results Serum endotoxin and lipopolysaccharide-binding protein were non-significantly higher in patients with Bacterial-DNA than in those without Bacterial-DNA. Regarding patients with Bacterial-DNA from Gram-positive microorganisms ( n =8), these levels were similar to those in patients without Bacterial-DNA ( n =16), and significantly lower than in patients with Bacterial-DNA from Gram-negative bacteria. Tumour necrosis factor-alpha and interleukin-6 were significantly increased in patients with vs without Bacterial-DNA (324.93±70.76 vs 134.91±34.58μg/mL; p p Conclusions Patients with translocation of Bacterial-DNA from Gram-positive microorganisms showed increased proinflammatory cytokines unrelated to endotoxin, which would not be detected by serum lipopolysaccharide-binding protein measurement.

  • Bacterial DNA induces the complement system activation in serum and ascitic fluid from patients with advanced cirrhosis.
    Journal of clinical immunology, 2007
    Co-Authors: Rubén Francés, Miguel Pérez-mateo, Pedro Zapater, Carlos Munoz, José M. González-navajas, Sonia Pascual, Rocío Caño, Dorkas Márquez, Francia Santana, José Such
    Abstract:

    Translocation of intestinal bacteria to ascitic fluid is, probably, the first step in the development of spontaneous Bacterial peritonitis in patients with cirrhosis. Proteins of the complement system are soluble mediators implicated in the host immune response to Bacterial infections and its activation has been traditionally considered to be an endotoxin-induced phenomenon. The aim of this study was to compare the modulation of these proteins in response to the presence of Bacterial DNA and/or endotoxin in patients with advanced cirrhosis and ascites in different clinical conditions. Groups I and II consisted of patients without/with Bacterial DNA. Group III included patients with spontaneous Bacterial peritonitis and Group IV with patients receiving norfloxacin as secondary long-term prophylaxis of spontaneous Bacterial peritonitis. Serum and ascitic fluid levels of endotoxin and truncated residues of the complement system were measured by ELISA. The complement system is triggered in response to Bacterial DNA, as evidenced by significantly increased levels of C3b, membrane attack complex, and C5a in patients from Groups II and III compared with patients without Bacterial DNA (Group I) and those receiving norfloxacin (Group IV). Gram classification did not further differentiate the immune response between patients within groups II and III, even though endotoxin levels were, as expected, significantly higher in patients with Bacterial DNA from gram-negative microorganisms. The complement protein activation observed in patients with Bacterial DNA in blood and ascitic fluid is indistinguishable from that observed in patients with spontaneous Bacterial peritonitis and may occur in an endotoxin-independent manner.

  • Intracellular cytokine expression in peritoneal monocyte/macrophages obtained from patients with cirrhosis and presence of Bacterial DNA
    European Journal of Gastroenterology and Hepatology, 2005
    Co-Authors: Rubén Francés, Ma Luz De La Sen, Miguel Pérez-mateo, Enrique Rodriguez, Moises Ndongo, Pedro Zapater, Carlos Munoz, José Such
    Abstract:

    BACKGROUND: The detection of Bacterial DNA in serum and ascitic fluid from patients with cirrhosis and ascites is interpreted as molecular evidence of intestinal Bacterial translocation and considered sufficient to activate the cellular immune response. In vitro studies on ascitic fluid culture have shown a close relationship between the synthesis of several cytokines and nitric oxide and the presence of Bacterial DNA. Since different cell types give rise to cytokines, flow cytometry becomes a powerful tool to discriminate between populations involved in a Bacterial challenge.\n\nOBJECTIVE: To study the pre-activation status of macrophage/monocyte population ex vivo according to the presence of Bacterial DNA.\n\nPATIENTS: Patients with cirrhosis and culture-negative, non-neutrocytic ascites, with or without the presence of Bacterial DNA in blood and ascitic fluid were studied.\n\nMETHODS: Flow cytometry analysis of intracellular cytokine expression in monocyte/macrophages from ascitic fluid was performed in basal conditions and after 12 h of cell stimulation adding lypopolysaccharide.\n\nRESULTS: Monocyte/macrophages from patients with Bacterial DNA showed a significantly higher production of interleukin-6 and tumor necrosis factor alpha in basal conditions than that in cells from patients without the presence of Bacterial DNA. The addition of lipopolysaccharide produced a non-significant increment in the expression of these cytokines in patients with the presence of Bacterial DNA, while this increment became significant in the other group of patients.\n\nCONCLUSIONS: Bacterial translocation in patients with cirrhosis and ascites increases the basal intracellular cytokine expression, reducing its functional reserve capability.

  • intracellular cytokine expression in peritoneal monocyte macrophages obtained from patients with cirrhosis and presence of Bacterial DNA
    European Journal of Gastroenterology & Hepatology, 2005
    Co-Authors: Rubén Francés, Enrique Rodriguez, Moises Ndongo, Pedro Zapater, Carlos Munoz, Miguel Perezmateo, José Such
    Abstract:

    BACKGROUND: The detection of Bacterial DNA in serum and ascitic fluid from patients with cirrhosis and ascites is interpreted as molecular evidence of intestinal Bacterial translocation and considered sufficient to activate the cellular immune response. In vitro studies on ascitic fluid culture have shown a close relationship between the synthesis of several cytokines and nitric oxide and the presence of Bacterial DNA. Since different cell types give rise to cytokines, flow cytometry becomes a powerful tool to discriminate between populations involved in a Bacterial challenge. OBJECTIVE: To study the pre-activation status of macrophage/monocyte population ex vivo according to the presence of Bacterial DNA. PATIENTS: Patients with cirrhosis and culture-negative, non-neutrocytic ascites, with or without the presence of Bacterial DNA in blood and ascitic fluid were studied. METHODS: Flow cytometry analysis of intracellular cytokine expression in monocyte/macrophages from ascitic fluid was performed in basal conditions and after 12 h of cell stimulation adding lypopolysaccharide. RESULTS: Monocyte/macrophages from patients with Bacterial DNA showed a significantly higher production of interleukin-6 and tumor necrosis factor alpha in basal conditions than that in cells from patients without the presence of Bacterial DNA. The addition of lipopolysaccharide produced a non-significant increment in the expression of these cytokines in patients with the presence of Bacterial DNA, while this increment became significant in the other group of patients. CONCLUSIONS: Bacterial translocation in patients with cirrhosis and ascites increases the basal intracellular cytokine expression, reducing its functional reserve capability.

  • A sequential study of serum Bacterial DNA in patients with advanced cirrhosis and ascites
    Hepatology (Baltimore Md.), 2004
    Co-Authors: Rubén Francés, Pedro Zapater, Carlos Munoz, Beatriz Lozano, Susana Benlloch, Francisco Uceda, Sonia Pascual, José M. González, Juan Antonio Casellas, José María Palazón
    Abstract:

    Bacterial translocation is currently considered the main pathogenic mechanism leading to spontaneous Bacterial peritonitis in patients with advanced cirrhosis and ascites. However, to the authors' knowledge there is no information regarding the characteristics of this process in humans. The goals of the current study were to pursue partially identified Bacterial DNA in blood (what the authors consider molecular evidence of Bacterial translocation) through its relative quantification in a 72-hour study period by using real-time polymerase chain reaction (PCR). A consecutive series of 17 patients with advanced cirrhosis and culture-negative, nonneutrocytic ascites were studied. Therapeutic paracentesis was performed at the time of admission, and blood samples were obtained at baseline and every 8 hours in a 3-day period. Bacterial DNA was detected by a PCR-based method, relatively quantified by real-time PCR, and identified by automated nucleotide sequencing. Seven of 17 patients demonstrated the simultaneous presence of Bacterial DNA in blood and ascitic fluid at the time of admission. After therapeutic paracentesis was performed, Bacterial DNA persisted in the blood for a minimum of 24 hours, and was reported to last as long as 72 hours in some patients. In addition, different patterns of Bacterial DNA appearance and clearance from the blood were identified. The nucleotide sequencing process demonstrated that bacteria detected in the first sample were identical to those noted in subsequent detections over time. In conclusion, Bacterial translocation is a single-species, dynamic process that appears to develop in a subgroup of patients with advanced cirrhosis.

Pedro Zapater - One of the best experts on this subject based on the ideXlab platform.

  • Presence of Bacterial-DNA in cirrhosis identifies a subgroup of patients with marked inflammatory response not related to endotoxin
    Journal of hepatology, 2007
    Co-Authors: José M. González-navajas, Rubén Francés, Miguel Pérez-mateo, Pedro Zapater, Carlos Munoz, Pablo Bellot, Juan Carlos García-pagán, Sonia Pascual, J. Bosch, José Such
    Abstract:

    Background/Aims Serum lipopolysaccharide-binding protein and Bacterial-DNA have been proposed as markers of Bacterial translocation and this study aimed to evaluate the immune response registered by Bacterial-DNA from Gram-positive and Gram-negative microorganisms and the effect on lipopolysaccharide-binding protein, to further investigate both markers. Methods Thirty-two patients were distributed into two groups according to the presence of Bacterial-DNA, determined by broad-range PCR of 16SrRNA gene. Serum endotoxin, lipopolysaccharide-binding protein, cytokines and nitric oxide products were measured by ELISA. Results Serum endotoxin and lipopolysaccharide-binding protein were non-significantly higher in patients with Bacterial-DNA than in those without Bacterial-DNA. Regarding patients with Bacterial-DNA from Gram-positive microorganisms ( n =8), these levels were similar to those in patients without Bacterial-DNA ( n =16), and significantly lower than in patients with Bacterial-DNA from Gram-negative bacteria. Tumour necrosis factor-alpha and interleukin-6 were significantly increased in patients with vs without Bacterial-DNA (324.93±70.76 vs 134.91±34.58μg/mL; p p Conclusions Patients with translocation of Bacterial-DNA from Gram-positive microorganisms showed increased proinflammatory cytokines unrelated to endotoxin, which would not be detected by serum lipopolysaccharide-binding protein measurement.

  • Bacterial DNA induces the complement system activation in serum and ascitic fluid from patients with advanced cirrhosis.
    Journal of clinical immunology, 2007
    Co-Authors: Rubén Francés, Miguel Pérez-mateo, Pedro Zapater, Carlos Munoz, José M. González-navajas, Sonia Pascual, Rocío Caño, Dorkas Márquez, Francia Santana, José Such
    Abstract:

    Translocation of intestinal bacteria to ascitic fluid is, probably, the first step in the development of spontaneous Bacterial peritonitis in patients with cirrhosis. Proteins of the complement system are soluble mediators implicated in the host immune response to Bacterial infections and its activation has been traditionally considered to be an endotoxin-induced phenomenon. The aim of this study was to compare the modulation of these proteins in response to the presence of Bacterial DNA and/or endotoxin in patients with advanced cirrhosis and ascites in different clinical conditions. Groups I and II consisted of patients without/with Bacterial DNA. Group III included patients with spontaneous Bacterial peritonitis and Group IV with patients receiving norfloxacin as secondary long-term prophylaxis of spontaneous Bacterial peritonitis. Serum and ascitic fluid levels of endotoxin and truncated residues of the complement system were measured by ELISA. The complement system is triggered in response to Bacterial DNA, as evidenced by significantly increased levels of C3b, membrane attack complex, and C5a in patients from Groups II and III compared with patients without Bacterial DNA (Group I) and those receiving norfloxacin (Group IV). Gram classification did not further differentiate the immune response between patients within groups II and III, even though endotoxin levels were, as expected, significantly higher in patients with Bacterial DNA from gram-negative microorganisms. The complement protein activation observed in patients with Bacterial DNA in blood and ascitic fluid is indistinguishable from that observed in patients with spontaneous Bacterial peritonitis and may occur in an endotoxin-independent manner.

  • Intracellular cytokine expression in peritoneal monocyte/macrophages obtained from patients with cirrhosis and presence of Bacterial DNA
    European Journal of Gastroenterology and Hepatology, 2005
    Co-Authors: Rubén Francés, Ma Luz De La Sen, Miguel Pérez-mateo, Enrique Rodriguez, Moises Ndongo, Pedro Zapater, Carlos Munoz, José Such
    Abstract:

    BACKGROUND: The detection of Bacterial DNA in serum and ascitic fluid from patients with cirrhosis and ascites is interpreted as molecular evidence of intestinal Bacterial translocation and considered sufficient to activate the cellular immune response. In vitro studies on ascitic fluid culture have shown a close relationship between the synthesis of several cytokines and nitric oxide and the presence of Bacterial DNA. Since different cell types give rise to cytokines, flow cytometry becomes a powerful tool to discriminate between populations involved in a Bacterial challenge.\n\nOBJECTIVE: To study the pre-activation status of macrophage/monocyte population ex vivo according to the presence of Bacterial DNA.\n\nPATIENTS: Patients with cirrhosis and culture-negative, non-neutrocytic ascites, with or without the presence of Bacterial DNA in blood and ascitic fluid were studied.\n\nMETHODS: Flow cytometry analysis of intracellular cytokine expression in monocyte/macrophages from ascitic fluid was performed in basal conditions and after 12 h of cell stimulation adding lypopolysaccharide.\n\nRESULTS: Monocyte/macrophages from patients with Bacterial DNA showed a significantly higher production of interleukin-6 and tumor necrosis factor alpha in basal conditions than that in cells from patients without the presence of Bacterial DNA. The addition of lipopolysaccharide produced a non-significant increment in the expression of these cytokines in patients with the presence of Bacterial DNA, while this increment became significant in the other group of patients.\n\nCONCLUSIONS: Bacterial translocation in patients with cirrhosis and ascites increases the basal intracellular cytokine expression, reducing its functional reserve capability.

  • intracellular cytokine expression in peritoneal monocyte macrophages obtained from patients with cirrhosis and presence of Bacterial DNA
    European Journal of Gastroenterology & Hepatology, 2005
    Co-Authors: Rubén Francés, Enrique Rodriguez, Moises Ndongo, Pedro Zapater, Carlos Munoz, Miguel Perezmateo, José Such
    Abstract:

    BACKGROUND: The detection of Bacterial DNA in serum and ascitic fluid from patients with cirrhosis and ascites is interpreted as molecular evidence of intestinal Bacterial translocation and considered sufficient to activate the cellular immune response. In vitro studies on ascitic fluid culture have shown a close relationship between the synthesis of several cytokines and nitric oxide and the presence of Bacterial DNA. Since different cell types give rise to cytokines, flow cytometry becomes a powerful tool to discriminate between populations involved in a Bacterial challenge. OBJECTIVE: To study the pre-activation status of macrophage/monocyte population ex vivo according to the presence of Bacterial DNA. PATIENTS: Patients with cirrhosis and culture-negative, non-neutrocytic ascites, with or without the presence of Bacterial DNA in blood and ascitic fluid were studied. METHODS: Flow cytometry analysis of intracellular cytokine expression in monocyte/macrophages from ascitic fluid was performed in basal conditions and after 12 h of cell stimulation adding lypopolysaccharide. RESULTS: Monocyte/macrophages from patients with Bacterial DNA showed a significantly higher production of interleukin-6 and tumor necrosis factor alpha in basal conditions than that in cells from patients without the presence of Bacterial DNA. The addition of lipopolysaccharide produced a non-significant increment in the expression of these cytokines in patients with the presence of Bacterial DNA, while this increment became significant in the other group of patients. CONCLUSIONS: Bacterial translocation in patients with cirrhosis and ascites increases the basal intracellular cytokine expression, reducing its functional reserve capability.

  • A sequential study of serum Bacterial DNA in patients with advanced cirrhosis and ascites
    Hepatology (Baltimore Md.), 2004
    Co-Authors: Rubén Francés, Pedro Zapater, Carlos Munoz, Beatriz Lozano, Susana Benlloch, Francisco Uceda, Sonia Pascual, José M. González, Juan Antonio Casellas, José María Palazón
    Abstract:

    Bacterial translocation is currently considered the main pathogenic mechanism leading to spontaneous Bacterial peritonitis in patients with advanced cirrhosis and ascites. However, to the authors' knowledge there is no information regarding the characteristics of this process in humans. The goals of the current study were to pursue partially identified Bacterial DNA in blood (what the authors consider molecular evidence of Bacterial translocation) through its relative quantification in a 72-hour study period by using real-time polymerase chain reaction (PCR). A consecutive series of 17 patients with advanced cirrhosis and culture-negative, nonneutrocytic ascites were studied. Therapeutic paracentesis was performed at the time of admission, and blood samples were obtained at baseline and every 8 hours in a 3-day period. Bacterial DNA was detected by a PCR-based method, relatively quantified by real-time PCR, and identified by automated nucleotide sequencing. Seven of 17 patients demonstrated the simultaneous presence of Bacterial DNA in blood and ascitic fluid at the time of admission. After therapeutic paracentesis was performed, Bacterial DNA persisted in the blood for a minimum of 24 hours, and was reported to last as long as 72 hours in some patients. In addition, different patterns of Bacterial DNA appearance and clearance from the blood were identified. The nucleotide sequencing process demonstrated that bacteria detected in the first sample were identical to those noted in subsequent detections over time. In conclusion, Bacterial translocation is a single-species, dynamic process that appears to develop in a subgroup of patients with advanced cirrhosis.

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  • Bacterial DNA translocation is associated with systemic circulatory abnormalities and intrahepatic endothelial dysfunction in patients with cirrhosis
    Hepatology (Baltimore Md.), 2010
    Co-Authors: Pablo Bellot, Rubén Francés, Miguel Pérez-mateo, José Such, Juan Carlos García-pagán, Juan G. Abraldes, Miguel Navasa, Jaime Bosch
    Abstract:

    Presence of Bacterial DNA in noninfected patients with cirrhosis and ascites is associated with a marked inflammatory response including activation of the inducible form of nitric oxide synthase and release of nitric oxide, similar to that observed in patients with spontaneous Bacterial peritonitis. Although presence of Bacterial DNA is associated with an impaired prognosis, no information is available regarding its hemodynamic consequences. Systemic and hepatic hemodynamics before and after a liquid test meal were assessed in a series of 75 noninfected patients with cirrhosis (55 with ascites). Bacterial DNA was measured by polymerase chain reaction. Bacterial DNA was detected only in patients with ascites. Clinical data and liver function were similar in ascitic patients with presence (n = 21) or absence of Bacterial DNA (n = 34). Bacterial-DNA(+) patients had significantly lower mean arterial pressure (P = 0.002) and systemic vascular resistance (P = 0.03) than Bacterial-DNA(−) patients. Cardiac output, cardiopulmonary pressures, hepatic venous pressure gradient (HVPG), and hepatic blood flow were similar in both groups. Thirty minutes after the test meal, in response to increased blood flow caused by postprandial hyperemia, there was a significantly greater increase in HVPG and impaired hepatic vasorelaxation in Bacterial-DNA(+) as compared with Bacterial-DNA(−) patients, which indicates hepatic endothelial dysfunction. Indeed, the increase in HVPG after the test meal significantly correlated with serum Bacterial DNA concentration. Conclusion: Presence of Bacterial DNA, a marker of Bacterial translocation, is associated with aggravation of peripheral vasodilation and with worsening of intrahepatic endothelial dysfunction. (HEPATOLOGY 2010;.)

  • Presence of Bacterial-DNA in cirrhosis identifies a subgroup of patients with marked inflammatory response not related to endotoxin
    Journal of hepatology, 2007
    Co-Authors: José M. González-navajas, Rubén Francés, Miguel Pérez-mateo, Pedro Zapater, Carlos Munoz, Pablo Bellot, Juan Carlos García-pagán, Sonia Pascual, J. Bosch, José Such
    Abstract:

    Background/Aims Serum lipopolysaccharide-binding protein and Bacterial-DNA have been proposed as markers of Bacterial translocation and this study aimed to evaluate the immune response registered by Bacterial-DNA from Gram-positive and Gram-negative microorganisms and the effect on lipopolysaccharide-binding protein, to further investigate both markers. Methods Thirty-two patients were distributed into two groups according to the presence of Bacterial-DNA, determined by broad-range PCR of 16SrRNA gene. Serum endotoxin, lipopolysaccharide-binding protein, cytokines and nitric oxide products were measured by ELISA. Results Serum endotoxin and lipopolysaccharide-binding protein were non-significantly higher in patients with Bacterial-DNA than in those without Bacterial-DNA. Regarding patients with Bacterial-DNA from Gram-positive microorganisms ( n =8), these levels were similar to those in patients without Bacterial-DNA ( n =16), and significantly lower than in patients with Bacterial-DNA from Gram-negative bacteria. Tumour necrosis factor-alpha and interleukin-6 were significantly increased in patients with vs without Bacterial-DNA (324.93±70.76 vs 134.91±34.58μg/mL; p p Conclusions Patients with translocation of Bacterial-DNA from Gram-positive microorganisms showed increased proinflammatory cytokines unrelated to endotoxin, which would not be detected by serum lipopolysaccharide-binding protein measurement.

  • Bacterial DNA induces the complement system activation in serum and ascitic fluid from patients with advanced cirrhosis.
    Journal of clinical immunology, 2007
    Co-Authors: Rubén Francés, Miguel Pérez-mateo, Pedro Zapater, Carlos Munoz, José M. González-navajas, Sonia Pascual, Rocío Caño, Dorkas Márquez, Francia Santana, José Such
    Abstract:

    Translocation of intestinal bacteria to ascitic fluid is, probably, the first step in the development of spontaneous Bacterial peritonitis in patients with cirrhosis. Proteins of the complement system are soluble mediators implicated in the host immune response to Bacterial infections and its activation has been traditionally considered to be an endotoxin-induced phenomenon. The aim of this study was to compare the modulation of these proteins in response to the presence of Bacterial DNA and/or endotoxin in patients with advanced cirrhosis and ascites in different clinical conditions. Groups I and II consisted of patients without/with Bacterial DNA. Group III included patients with spontaneous Bacterial peritonitis and Group IV with patients receiving norfloxacin as secondary long-term prophylaxis of spontaneous Bacterial peritonitis. Serum and ascitic fluid levels of endotoxin and truncated residues of the complement system were measured by ELISA. The complement system is triggered in response to Bacterial DNA, as evidenced by significantly increased levels of C3b, membrane attack complex, and C5a in patients from Groups II and III compared with patients without Bacterial DNA (Group I) and those receiving norfloxacin (Group IV). Gram classification did not further differentiate the immune response between patients within groups II and III, even though endotoxin levels were, as expected, significantly higher in patients with Bacterial DNA from gram-negative microorganisms. The complement protein activation observed in patients with Bacterial DNA in blood and ascitic fluid is indistinguishable from that observed in patients with spontaneous Bacterial peritonitis and may occur in an endotoxin-independent manner.

  • Detection and identification of Bacterial DNA in serum from patients with acute pancreatitis.
    Gut, 2005
    Co-Authors: E. De Madaria, Rubén Francés, José Such, Juan Martínez, Beatriz Lozano, Laura Sempere, Susana Benlloch, Francisco Uceda, Miguel Pérez-mateo
    Abstract:

    Background and aims: Bacterial infections are common complications in patients with acute pancreatitis, and translocation of bacteria from the intestinal lumen is probably the first step in the pathogenesis of these infections. As blood cultures in afebrile patients are usually negative, more sensitive methods to investigate this hypothesis in patients are needed. Our group has recently developed a method to detect the presence of Bacterial DNA in biological fluids, and we aimed to detect Bacterial DNA in patients with acute pancreatitis, as molecular evidences of Bacterial translocation. Methods: Samples of blood were obtained on three consecutive days within the first six days after admission. Bacterial DNA was detected using a polymerase chain reaction based method, and an automated DNA nucleotide sequencing process allowed identification of bacteria species. Results: Thirty one consecutively admitted patients with acute pancreatitis were studied. Bacterial DNA was detected in six patients (19.3%), and the sequencing process allowed identification of Citrobacter freundii and Pseudomonas aeruginosa. In two patients the same bacteria detected at admission was detected 24 hours later (above 99.9% homology of nucleotide sequence). Basic clinical and biochemical characteristics were similar among patients with or without the presence of Bacterial DNA. Conclusion: Detection of gram negative bacteria derived Bacterial DNA in our series supports the contention that Bacterial translocation is a systemic process in approximately 20% of patients with acute pancreatitis that does not seem to be related to the severity of the episode or immediate development of infection.

  • Intracellular cytokine expression in peritoneal monocyte/macrophages obtained from patients with cirrhosis and presence of Bacterial DNA
    European Journal of Gastroenterology and Hepatology, 2005
    Co-Authors: Rubén Francés, Ma Luz De La Sen, Miguel Pérez-mateo, Enrique Rodriguez, Moises Ndongo, Pedro Zapater, Carlos Munoz, José Such
    Abstract:

    BACKGROUND: The detection of Bacterial DNA in serum and ascitic fluid from patients with cirrhosis and ascites is interpreted as molecular evidence of intestinal Bacterial translocation and considered sufficient to activate the cellular immune response. In vitro studies on ascitic fluid culture have shown a close relationship between the synthesis of several cytokines and nitric oxide and the presence of Bacterial DNA. Since different cell types give rise to cytokines, flow cytometry becomes a powerful tool to discriminate between populations involved in a Bacterial challenge.\n\nOBJECTIVE: To study the pre-activation status of macrophage/monocyte population ex vivo according to the presence of Bacterial DNA.\n\nPATIENTS: Patients with cirrhosis and culture-negative, non-neutrocytic ascites, with or without the presence of Bacterial DNA in blood and ascitic fluid were studied.\n\nMETHODS: Flow cytometry analysis of intracellular cytokine expression in monocyte/macrophages from ascitic fluid was performed in basal conditions and after 12 h of cell stimulation adding lypopolysaccharide.\n\nRESULTS: Monocyte/macrophages from patients with Bacterial DNA showed a significantly higher production of interleukin-6 and tumor necrosis factor alpha in basal conditions than that in cells from patients without the presence of Bacterial DNA. The addition of lipopolysaccharide produced a non-significant increment in the expression of these cytokines in patients with the presence of Bacterial DNA, while this increment became significant in the other group of patients.\n\nCONCLUSIONS: Bacterial translocation in patients with cirrhosis and ascites increases the basal intracellular cytokine expression, reducing its functional reserve capability.