14 research outputs found
Early apoptosis of blood monocytes in the septic host: is it a mechanism of protection in the event of septic shock?
INTRODUCTION: Based on the central role of the triggering of monocytes for the initiation of the septic cascade, it was investigated whether apoptosis of blood monocytes in septic patients is connected to their final outcome. METHODS: Blood monocytes were isolated from 90 patients with septic syndrome due to ventilator-associated pneumonia on days 1, 3, 5 and 7 from the initiation of symptoms. Apoptosis was defined after incubation with annexin-V-fluorescein isothiocyanate and propidium iodine and reading by a flow cytometer. The function of first-day monocytes was evaluated from the concentrations of tumour necrosis factor alpha (TNFα) and IL-6 in supernatants of cell cultures after triggering with endotoxins. TNFα, IL-6 and IL-8 were estimated in serum by an enzyme immunoassay. RESULTS: Mortality rates of patients with apoptosis ≤50% compared with patients with apoptosis >50% were 49.12% and 15.15%, respectively (P < 0.0001). Kaplan-Meier analysis showed a 28-day survival benefit in patients with septic shock and monocyte apoptosis >50% compared with those patients with apoptosis ≤50% (P = 0.0032). Production of IL-6 by monocytes on the first day by patients with apoptosis ≤50% was similar compared with monocytes isolated from healthy controls. Serum concentrations of TNFα were higher in patients with monocyte apoptosis ≤50% and septic shock compared with patients with apoptosis >50% on day 7; similar findings occurred for serum IL-6 on days 1 and 7 and for serum IL-8 on days 1 and 5. CONCLUSION: Early apoptosis of monocytes upon presentation of clinical signs of sepsis is connected to a favourable outcome. These findings are of particular importance for the patient with septic shock, where they might constitute a mechanism of pathogenesis
Immunomodulatory intervention in sepsis by multidrug-resistant Pseudomonas aeruginosa with thalidomide: an experimental study
BACKGROUND: Thalidomide is an inhibitor of tumour necrosis factor-alpha (TNFα) that has been proven effective for the treatment of experimental sepsis by Escherichia coli. It was tested whether it might behave as an effective immunomodulator in experimental sepsis by multidrug-resistant (MDR) Pseudomonas aeruginosa. METHODS: Sepsis was induced by the intraperitoneal injection of 1 × 10(8 )cfu/kg inoculum of the test isolate in a total of 109 Wistar rats divided in three groups as follows: group A controls; group B administered seed oil 30 minutes before bacterial challenge; and group C administered 50 mg/kg of thalidomide diluted in seed oil 30 minutes before bacterial challenge. Blood was sampled for estimation of endotoxins (LPS), TNFα, interferon-gamma (IFNγ), nitric oxide (NO) and malondialdehyde (MDA). LPS was measured by the QCL-1000 LAL assay, TNFα and IFNγ by ELISA, NO by a colorimetric assay and MDA by the thiobarbiturate assay. RESULTS: Mean (± SE) survival of groups A, B and C were 18.60 ± 1.84, 12.60 ± 0.60 and 30.50 ± 6.62 hours (p of comparisons A to C equal to 0.043 and B to C equal to 0.002). Decreased TNFα and NO levels were found in sera of animals of group C compared to group A. Plasma levels of LPS, MDA and IFNγ did not differ between groups. CONCLUSION: Intake of thalidomide considerably prolonged survival in experimental sepsis by MDR P.aeruginosa an effect probably attributed to decrease of serum TNFα
Effect of Clarithromycin in Patients with Sepsis and Ventilator-Associated Pneumonia
Background. Because clarithromycin provided beneficiary nonantibiotic effects in experimental studies, its efficacy was tested in patients with sepsis and ventilator-associated pneumonia (VAP). Methods. Two hundred patients with sepsis and VAP were enrolled in a double-blind, randomized, multicenter trial from June 2004 until November 2005. Clarithromycin (1 g) was administered intravenously once daily for 3 consecutive days in 100 patients; another 100 patients were treated with placebo. Main outcomes were resolution of VAP, duration of mechanical ventilation, and sepsis-related mortality within 28 days. Results. The groups were well matched with regard to demographic characteristics, disease severity, pathogens, and adequacy of the administered antimicrobials. Analysis comprising 141 patients who survived revealed that the median time for resolution of VAP was 15.5 days and 10.0 days among placebo- and clarithromycin-treated patients, respectively (P=.011); median times for weaning from mechanical ventilation were 22.5 days and 16.0 days, respectively (P=.049). Analysis comprising all enrolled patients showed a more rapid decrease of the clinical pulmonary infection score and a delay for advent of multiple organ dysfunction in clarithromycin-treated patients, compared with those of placebo-treated patients (P=.047). Among the 45 patients who died of sepsis, time to death was significantly prolonged in clarithromycin-treated compared with placebo-treated patients (P=.004). Serious adverse events were observed in 0% and 3% of placebo- and clarithromycin-treated patients, respectively (P=.25). Conclusions. Clarithromycin accelerated the resolution of VAP and weaning from mechanical ventilation in surviving patients and delayed death in those who died of sepsis. The mortality rate at day 28 was not altered. Results are encouraging and render new perspectives on the management of sepsis and VA
Role of soluble triggering receptor expressed on myelold cells in inflammatory bowel disease
AIM: To investigate the probable role of soluble triggering receptor
expressed on myeloid cells-1 (sTREM-1) in the pathogenesis of
inflammatory bowel disease (IBD).
METHODS: Fifty-eight patients were enrolled; nineteen healthy volunteers
served as controls; 8 patients were diagnosed with Crohn’s disease, and
31 with ulcerative colitis. Clinical and endoscopic activity indexes of
patients with Crohn’s disease and ulcerative colitis respectively were
estimated. Upon admission blood was sampled; sTREM-1 and TNF alpha were
measured by an immunoassay and malondialdehyde (MDA) by the
thiobarbitourate assay, after passage through an HPLC system.
RESULTS: Median SE of TNFa of controls, patients with Crohn’s disease
and patients with ulcerative colitis were 6.02 +/- 3.94, 7.98 +/- 5.08
(P = NS vs controls), and 8.45 +/- 4.15 ng/L (P = 0.018 vs controls)
respectively. Respective values of sTREM-1 were 53.31 +/- 32.93, 735.10
+/- 197.17 (P = 0.008 vs controls) and 435.82 +/- 279.71 ng/L (P = 0.049
vs controls). sTREM-1 was positively correlated with Crohn’s disease
activity index and clinical and endoscopic activity indexes of
ulcerative colitis (P = 0.002, 0.001 and 0.009, respectively). sTREM-1
of patients with ulcerative colitis was positively correlated with TNF
alpha (P = 0.001).
CONCLUSION: sTREM-1 seems to behave as a novel mediator in IBD in
correlation with the degree of the :inflammatory reaction of the
intestinal mucosa. 2006 The WIG Press. All rights reserved
n-6 Polyunsaturated Fatty Acids Enhance the Activities of Ceftazidime and Amikacin in Experimental Sepsis Caused by Multidrug-Resistant Pseudomonas aeruginosa
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-α) 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-α. 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
Soluble triggering receptor expressed on myeloid cells (sTREM-1): a new mediator involved in the pathogenesis of peptic ulcer disease
Objectives Triggering receptor expressed on myeloid cells (TREM-1) is a
promoter of cytokine production triggered by microbial components. To
investigate the significance of its soluble counterpart, sTREM-1, for
the pathogenesis of peptic ulcer disease, sTREM-1 was compared with the
proinflammatory mediators and the pathology score of gastritis.
Methods Forty patients with dyspepsia were enrolled: 20 with peptic
ulcer and 20 controls without any macroscopic abnormalities. All
patients were examined by endoscopy; gastric juice was aspirated and
biopsy specimens were collected from the antrum and corpus of the
stomach. sTREM-1 was estimated by at hand-made enzyme immunoassay.
Interleukin-8 was estimated by enzyme-linked immunosorbent assay and
lipid peroxidation, indexed by malondialdehyde, by the thiobarbituric
assay, after passage through a high-performance liquid chromatography
system.
Results The median (+/- SE) of sTREM-1 of controls and patients with
ulcer was 3.91 +/- 0.57 and 44.27 +/- 241.55 R U, respectively
(P=0.006). The median (+/- SE) of interleukin-8 of controls and patients
with ulcer was 1802.97 +/- 122.10 and 2030.66 +/- 64.44 pg/ml,
respectively (P = 0.023). sTREM-1 was positively correlated with the
density of neutrophil and mononuclear infiltration scores and the total
Sydney score (P=0.029, 0.043 and 0.041, respectively). sTREM-1 was
positively correlated with interleukin-8 (P=0.042).
Conclusions sTREM-1 might be an independent factor involving with the
peptic ulcerative inflammatory process that is positively correlated
with histopathological abnormalities of gastritis
Immunomodulatory Clarithromycin Treatment of Experimental Sepsis and Acute Pyelonephritis Caused by Multidrug-Resistant Pseudomonas aeruginosa
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-α) 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-α 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
Can soluble triggering receptor expressed on myeloid cells (sTREM-1) be considered an anti-inflammatory mediator in the pathogenesis of peptic ulcer disease?
Soluble triggering receptor expressed on myeloid cells (sTREM-1) is a
novel mediator involved in the pathogenesis of peptic ulcer disease. To
investigate the potential role of sTREM-1 in the anti-inflammatory
response in chronic gastritis, sTREM-1 was compared with other
anti-inflammatory mediators of gastritis. Forty patients with dyspepsia
were enrolled: 20 with peptic ulcer and 20 controls without any
macroscopic abnormalities. All patients were examined by endoscopy;
gastric juice was aspirated and biopsy specimens were collected from the
antrum and corpus of the stomach. sTREM-1, interleukin (IL)-8, and IL-10
were estimated by enzyme immunoassays. Median sTREM-1 in patient
controls and in patients with peptic ulcer disease was 3.91 and 44.27
pg/ml, respectively (P=0.006). Respective values of IL-8 were 1856.97
and 2030.66 pg/ml (P=0.023); those of IL-10 were 16.92 and 18.43 pg/ml
(NS). The odds ratio for the presence of peptic ulcer in the event of a
concentration of sTREM-1 higher than 15 pg/ml was 23.22 (95% CI,
2.58-208.62; P=0.002). A positive correlation was found between the
ratios of IL-8/sTREM-1 and IL-8/IL-10 (r (s), + 0.365; P=0.021). In
conclusion, sTREM-1 is an independent factor for the generation of
peptic ulcer disease and might behave as an anti-inflammatory mediator
in chronic gastritis