A Antonucci

Sapienza University of Rome, Roma, Latium, Italy

Are you A Antonucci?

Claim your profile

Publications (19)39.65 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: We examined lymphocyte apoptosis, activity of caspases-1, -3, -8 and -9 and the relationship between those two events and inflammation response in septic shock. Blood samples were obtained within 24 h after diagnosis of septic shock from 16 patients to measure apoptosis, caspases-3, -8, -9 expression, changes in mitochondrial transmembrane potential and expression of Fas/FasL system of peripheral blood mononuclear cells (PBMCs). Moreover, serum levels of caspase-1 and blood concentrations of IL-6, IL-12, IL-15 and IL-18 were assessed. PBMCs from patients with septic shock compared to control individuals exhibited a greatly increased frequency of apoptosis (39.10 +/- 7.33% vs 4.19 +/- 1.13%; p < 0.001), an over expression of caspases-3, -8, and -9 (p < 0.01, p < 0.05, p < 0.001 for caspases-3, -8 and -9, respectively) as well as of Fas/FasL system (p < 0.05) and significant changes in mitochondrial transmembrane potential. Blood levels of caspase-1 (101.5 +/- 18.2 pg/ml vs 9.09 +/- 2.7 pg/ml, p < 0.001) and of IL-6, IL-12, IL-15 and IL-18 were significantly higher in septic patients vs control (p < 0.0001, p < 0.05, p < 0.05 and p < 0.0001, respectively). Furthermore, a correlation linking IL-6 blood level with both the apoptotic rate (r(2) = 0.75; p = 0.001) and caspase-9 expression (r(2) = 0.92; p = 0.0001) of PBMCs was observed.
    Infection 10/2008; 36(5):485-7. · 2.44 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To determine the effect of alpha-tocopherol in patients receiving hypotensive anesthesia with propofol-remifentanil. Prospective, randomized study. University hospital. 66 ASA physical status I and II patients, aged 32 to 56 years, scheduled for nasal polypectomy. Patients were allocated into two groups, the treatment and the control groups (T group and C group). T group received alpha-tocopherol 300 mg orally 5 to 6 hours before surgery. Sampling times and measurements were done before hypotension (t0), 45 minutes after starting hypotension (t1), 90 minutes after starting hypotension (t2), 45 minutes after recovery of normotension (t3), and 24 hours after surgery (t4). Renal function was assessed by testing glomerular and tubular functions: glomerular filtration rate, fractional excretion of sodium (FENA); fractional excretion of urea (FEUN); and urinary N-acetyl-1-beta-D-glucosoaminidase (NAG) index (NAGi). Glomerular filtration rate values remained unchanged in all patient populations. Fractional excretion of sodium was within reference ranges in both groups at times t0, t1, and t2. At time t3, a significant FE(NA) peak was observed. At this time, FENA was significantly higher in C group than T group (P < 0.001). FEUN time course was similar to the FENA trend. At time t4, FENA and FEUN returned to basal values. At time t3, NAGi was also increased without significant intergroup differences (P < 0.01, P < 0.001, and P < 0.01 vs times t0, t1, t2 in C group, respectively; P < 0.01, P < 0.01, and P < 0.001 vs times t0, t1, and t2 in T group, respectively). In patients without any renal disease, hypotensive anesthesia with propofol and remifentanil results in a transient tubular dysfunction, which appears to be minimized by the preoperative administration of alpha-tocopherol.
    Journal of Clinical Anesthesia 05/2008; 20(3):164-9. · 1.15 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Intraoperative fluid administration is considered an important factor in the management of metabolic acidosis following surgical procedures. The aim of this study was to compare three types of intraoperative infusional models in order to evaluate their effect on acid-base changes in the immediate postoperative period as calculated by both the Henderson-Hasselbach equation and the Stewart approach. Forty-seven patients undergoing left hemicolectomy were enrolled in the study and assigned randomly to receiving 0.9% saline alone (Group A, n=16), lactated Ringer's solution alone (Group B, n=16) or 0.9% saline and Ringer's solution, 1:1 ratio (Group C, n=15). Arterial blood samples were taken before operation (t0) and 30 min after extubation (t1) in order to measure the acid-base balance. The results showed a metabolic acidosis status in Group A patients, whereas Group B exhibited metabolic alkalosis only by means of the Stewart method. No difference was found in Group C between the time points t0 and t1 when using either the Henderson-Hasselbach equation or using the Stewart model. We conclude that saline solution in association with Ringer's solution (1:1 ratio) appears to be the most suitable form of intraoperative fluid management in order to guarantee a stable acid-base balance in selected surgical patients during the immediate postoperative period.
    Chirurgia italiana 01/2008; 60(1):33-40.
  • [Show abstract] [Hide abstract]
    ABSTRACT: An alteration in production of both interleukin-10 (IL-10) and nitric oxide (NO) has been found following surgical/anaesthesia trauma. It is also suggested that IL-10 could be an important factor in regulating NO metabolism during the postoperative period. Furthermore, NO seems to play a crucial role in the anaesthetic state. The purpose of this study was to investigate plasma levels of IL-10 and NO following surgery, any possible correlation between these two variables and whether anaesthesia technique could influence NO and IL-10 circulating concentrations. Thirty-two patients scheduled to undergo elective major surgery were enrolled in the study and allocated into two groups to receive two different techniques of anaesthesia, total intravenous (i.v.) anaesthesia (Group I) and inhalational anaesthesia (Group II). Blood samples were drawn before (t0), at the end (t1) of operation and after 24 h (t2). Plasma IL-10 and NO levels were measured by using an enzyme-linked-immunosorbent assay (ELISA) and a total NO assay kit, respectively. In both patient groups there was a significant decrease of plasma NO levels at the end of surgery (30.35 +/- 2.70 mmol L(-1) at t0 to 13.76 +/- 1.51 mmol L(-1) at t1 in Group I, P < 0.0001; 28.23 +/- 2.50 mmol L(-1) at t0 to 11.38 +/- 0.95 mmol L(-1) at t1 in Group II, P < 0.0001). This reduction remained at 24 h postoperatively (14.33 +/- 1.52 mmol L(-1) in Group I, P < 0.0001; 12.52 +/- 1.11 mmol L(-1) in Group II, P < 0.0001, both vs. t0). There was an increase in IL-10 concentrations (26.35 +/- 3.42 pg mL(-1) and 75.39 +/- 8.33 pg mL(-1) at t1 and t2, respectively, vs. 4.93 +/- 0.31 pg mL(-1) at t0, P = 0.03 and P < 0.0001, respectively, in Group I; 26.18 +/- 3.22 pg mL(-1) and 69.91 +/- 7.33 pg mL(-1) at t1 and t2, respectively, vs. 5.50 +/- 0.33 pg mL(-1) at t0, P = 0.02 and P < 0.0001, respectively, in Group II). No relationship was found between circulating IL-10 and NO. During the postoperative period, IL-10 overproduction does not correlate with the decrease in systemic NO concentration.
    European Journal of Anaesthesiology 06/2005; 22(6):462-6. · 2.79 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The aim of the study was to determine whether intrathecal sufentanil alone provides an adequate analgesia for patients undergoing transurethral resection of the bladder (TURB) and to compare it to standard spinal bupivacaine anesthesia in terms of motor and sensory blockade, discharge time and side effects. Sixty-two patients were blindly and randomly assigned to receive either intrathecal bupivacaine (10 mg of 0.5% hyperbaric bupivacaine) or intrathecal sufentanil (15 microg). Motor and sensory blockade was evaluated using a modified Bromage scale as well as cold and pinprick tests. Severity of pain was assessed by means of a 10-point verbal analog scale. We found that the mean duration of sensory blockade was similar for both sufentanil and bupivacaine patients but the quality of analgesia induced by sufentanil alone was poor as compared with spinal bupivacaine anesthesia. The subarachnoid administration of sufentanil 15 mg seems to be inadequate for TURB surgery. In addition, the advantage of a faster recovery we observed in sufentanil patients is minimized by the occurrence of a troublesome symptom such as pruritus. On the other hand, spinal bupivacaine produces an undesirable motor blockade exceeding, in our opinion, the requirement for TURB procedure.
    Minerva anestesiologica 04/2005; 71(3):83-91. · 2.82 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Genomic instability is recognized as a cause of cellular apoptosis and certain drugs that exhibit a proapoptotic effect are also able to induce chromosome damage. Since we found in recent experiments that drugs such as pancuronium and fentanyl exerted an apoptogenic effect on T cells, we studied the capacity of those agents to promote chromosome instability, i.e. chromosome aberrations (CA) and telomeric associations (tas) in peripheral blood lymphocytes. Lymphocytes from healthy donors were cultured with pancuronium or fentanyl, using two different concentrations for each drug: 20 and 200 ng/ml for pancuronium and 10 and 30 ng/ml for fentanyl, respectively. Cells were exposed to each concentration of these drugs either for 24 or 48 h. The higher concentration chosen was the same at which we detected the proapoptotic effect in our previous works. Cytogenetic analysis was performed by means of a standard technique and chromosome aberrations or telomeric associations were blindly evaluated by two independent observers. The chromosome aberrations we observed in treated cells were not significantly different from control lymphocytes. However, an unusual rate of telomeric associations (P < 0.001) was detected in cells exposed to both pancuronium and fentanyl, at each concentration tested and at each exposure time of the study. Fentanyl and pancuronium do not have a direct clastogenic effect on T cultures, but at the same concentrations at which we demonstrated their apoptogenic power, these drugs are able to increase genomic instability through inducing an elevated rate of telomeric associations. Such a capacity could exploit in peripheral T cells the same mitochondrion-mediated signal pathway of apoptosis death.
    Acta Anaesthesiologica Scandinavica 09/2004; 48(8):968-72. · 2.36 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Opioids may trigger the apoptotic death of widely ranging cell types, and apoptosis contributes to the immune deficiency of critically ill patients and subjects experiencing surgical trauma. There is evidence that an altered mitochondrial membrane potential constitutes an early and irreversible step in the death-signaling pathway of apoptosis. This study investigated whether fentanyl, a opioid widely used in the management of these patients, may induce apoptosis of T cells by altering their mitochondrial membrane potential. Peripheral blood lymphocytes were cultured in the presence of 30 ng fentanyl for 60 (time 1), 90 (time 2), and 120 (time 3) minutes, respectively. The cells then were processed for assessment of mitochondrial membrane potential by means of flow cytometry and confocal scanning microscopy. Furthermore, production of reactive oxygen species, expression of the Fas-Fas L pro-apoptotic pathway, and apoptosis frequency were measured by means of flow cytometry. Control cells were incubated for the same times in the complete culture medium without the drug. Flow cytometry analysis showed a significantly increased rate (p < 0.05) of lymphocytes with disrupted mitochondrial membrane potential after incubation with fentanyl for 90 and 120 minutes, as compared with both control cells and lymphocytes cultured in the presence of fentanyl for 60 minutes. In addition, as early as 60 minutes after exposure to fentanyl, cells displayed a disrupted mitochondrial membrane potential when this was assayed by means of confocal laser scanning. These findings were associated with increased production of reactive oxygen species. The frequency of apoptotic lymphocytes was markedly increased (p < 0.05) after 120 minutes of incubation, as compared with untreated cells and cells exposed to fentanyl for only 60 and 90 minutes. Expression of Fas-FasL was not substantially affected by exposure to fentanyl. Fentanyl may induce a time-dependent apoptosis of lymphocytes by altering their mitochondrial redox metabolism.
    The Journal of trauma 07/2004; 57(1):75-81. · 2.35 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To evaluate the potential of compounds commonly used in anesthesia practice to affect the intracellular oxidant-antioxidant homeostasis of peripheral blood lymphocytes at clinically relevant concentrations; and to study the changes in reactive oxygen species production and measure the mitochondrial glutathione content. Prospective, in vitro study. Experimental medical research laboratory at a University Hospital. Lymphocytes were isolated from the peripheral blood of 15 healthy donors and incubated for 12 hours at 37 degrees C with the following drug concentrations: thiopental sodium 20 mmoL/mL, droperidol 130 micromol/mL, propofol 60 mmoL/mL, and succinylcholine 17 mmoL/mL. Reactive oxygen species (ROS) generation was determined by hydroethidine and 2',7'-dichlorofluorescein diacetate methods. Mitochondrial glutathione level was assessed using monobromobimane staining. Thiopental-treated lymphocytes exhibited an overgeneration of ROS, but no change was detected in mitochondrial glutathione quantity. Propofol and droperidol could not induce any perturbative effect on the oxidative state of T cells, whereas succinylcholine was found to markedly affect lymphocyte oxidative state both by impairing glutathione content and promoting exaggerated production of ROS. Drugs commonly used in anesthesia practice may significantly alter the oxidative state of peripheral T cells. This mechanism could contribute to the immune suppression that occurs transiently in the early postoperative period.
    Journal of Clinical Anesthesia 06/2004; 16(3):189-94. · 1.15 Impact Factor
  • European Journal of Anaesthesiology - EUR J ANAESTH. 01/2004; 21.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Several compounds used in anesthesia practice have demonstrated to impair immune function and to influence the process of apoptotic death in T cell population following surgical trauma. We designed this study to test in vitro the impact of neuromuscular blocker, such as pancuronium, at clinically relevant concentration on lymphocyte apoptosis, death factor expression and mitochondrial function. Following isolation, lymphocytes were incubated with pancuronium bromide at a clinically relevant concentration (0.136 micro mol l-1) for 3 h at 37 C in a 5% carbon-dioxide-humidified atmosphere and the frequency of apoptotic lymphocytes was then measured. We also investigated crucial steps in the apoptotic process, including Fas/Fas ligand (FasL) phenotype, intracellular expression of the interleukin-1beta-converting enzyme (ICE) p20, mitochondrial membrane potential (DeltaPsim), generation of mitochondrial reactive oxygen species, and glutathione (GSH) levels. Control experiments were performed incubating cells in the complete culture medium added with the dilution medium of the drug without addition of the drug. Expression of Fas, FasL and ICEp20 was six-fold, four-fold, and five-fold increased, respectively, among pancuronium-treated lymphocytes with respect to control cultures (P = 0.0001). The percentage of cells exhibiting either dissipation of mitochondrial membrane potential or increased production of reactive oxygen species was seven-fold increased following exposure to pancuronium compared with untreated lymphocytes (P = 0.0001). These findings were associated with a decrease in GSH level. In addition, the frequency of apoptotic cells was 10-fold greater among lymphocytes cultured in the presence of the drug with respect to control cultures. (P = 0.0001). Our data suggest an apoptogenic effect of pancuronium in vitro at clinically relevant concentration on peripheral blood lymphocytes. This could be implicated in the transient immune suppression following a surgical operation.
    Acta Anaesthesiologica Scandinavica 11/2003; 47(9):1138-44. · 2.36 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Previous studies have shown that a profound suppression of immune function transiently occurs in patients who undergo surgery under general anesthesia. The decline in the absolute counts of peripheral blood lymphocytes constitutes a major factor accounting for this immune defect, and recent evidence indicates that apoptosis plays a crucial role in determining postsurgical lymphocytopenia. An altered oxidation-reduction status of mitochondria may contribute through apoptosis to the loss of lymphocytes following surgical trauma and general anesthesia. We studied 16 patients with American Society of Anesthesiologists' physical status I or II who underwent elective surgery under general anesthesia. The data were collected prospectively. University hospital. Samples of peripheral blood were drawn on the day before surgery and at 24 and 96 hours after the operation. Following lymphocyte isolation, the mitochondrial transmembrane potential was assessed by flow cytometry using 3,3'-dihexylocarbo-cyanine iodide, and stains with hydroethidine and 2'-7'-dichlorofluorescein diacetate were used to determine the generation of reactive oxygen species. The labeling of lymphocytes with monobromobimane was used to assess the presence of reduced glutathione. At 24 hours after surgery, we detected a significantly elevated frequency of peripheral blood lymphocytes (P =.002), which incorporated low levels of 3,3'-dihexylocarbo-cyanine iodide, compared with the preoperative period. At this same time point, the frequency of lymphocytes with the hydroethidine- and 2'-7'-dichlorofluorescein diacetate-positive phenotype was elevated compared with baseline levels. Conversely, at 24 hours after surgery, the frequency of cells that stained positive for glutathione was strongly decreased compared with preoperative values. Overall measurements returned to the baseline levels at 96 hours after surgery. The strict association we observed between the overproduction of reactive oxygen species and the disruption of the mitochondrial transmembrane potential supports the view that alterations in mitochondrial energy metabolism, paralleled by the presence of a pro-oxidant oxidation-reduction status, could be involved in the accelerated apoptotic loss of lymphocytes following surgical trauma and general anesthesia.
    Archives of Surgery 11/2001; 136(10):1190-6. · 4.10 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To examine the relationship between circulating interleukin-10 (IL-10) and the occurrence of lymphocyte apoptosis after surgical/anesthesia trauma. Data were collected prospectively on 18 adult patients undergoing elective major surgery. Blood sampling for assessment of lymphocyte apoptosis and IL-10 levels was performed on the day before surgery (t(0)) and at 24 and 96 hours after operation (t(1) and t(2), respectively). After lymphocyte isolation, quantification of apoptosis was made by staining apoptotic cells with 7-amino-actinomycin D. Plasma IL-10 concentrations were measured using enzyme-linked immunosorbent assay. A significantly increased frequency of apoptotic CD4(+) and CD8(+) cells (p < 0.05) was observed at t1 measurement (8.10% +/- 0.58% and 12.21% +/- 1.47% for CD4(+) and CD8(+), respectively) compared with preoperative values (1.53% +/- 0.38% and 1.32% +/- 0.45% for CD4(+) and CD8(+), respectively). Plasma IL-10 levels showed a significant elevation at both t(1) and t(2) times, peaking at t(1). At t(1), IL-10 levels were correlated with the frequency of CD4(+) and CD8(+) apoptotic lymphocytes (r = 0.78, p = 0.0005 for IL-10 vs. apoptotic CD4(+); r = 0.71, p = 0.003 for IL-10 vs. apoptotic CD8(+)). Surgical trauma is associated with a significant but transient increase in lymphocyte commitment to apoptosis and IL-10 production. The exact relationship linking the overproduction of IL-10 with lymphocyte apoptosis after a surgical operation is still elusive and requires further investigation.
    The Journal of trauma 08/2001; 51(1):92-7. · 2.35 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective: To examine the relationship between circulating interleukin-10 (IL-10) and the occurrence of lymphocyte apoptosis after surgical/anesthesia trauma. Methods: Data were collected prospectively on 18 adult patients undergoing elective major surgery. Blood sampling for assessment of lymphocyte apoptosis and IL-10 levels was performed on the day before surgery (t0) and at 24 and 96 hours after operation (t1 and t2, respectively). After lymphocyte isolation, quantification of apoptosis was made by staining apoptotic cells with 7-amino-actinomycin D. Plasma IL-10 concentrations were measured using enzyme-linked immunosorbent assay. Results: A significantly increased frequency of apoptotic CD4+ and CD8+ cells (p < 0.05) was observed at t1 measurement (8.10% ± 0.58% and 12.21% ± 1.47% for CD4+ and CD8+, respectively) compared with preoperative values (1.53% ± 0.38% and 1.32% ± 0.45% for CD4+ and CD8+, respectively). Plasma IL-10 levels showed a significant elevation at both t1 and t2 times, peaking at t1. At t1, IL-10 levels were correlated with the frequency of CD4+ and CD8+ apoptotic lymphocytes (r = 0.78, p = 0.0005 for IL-10 vs. apoptotic CD4+;r = 0.71, p = 0.003 for IL-10 vs. apoptotic CD8+). Conclusion: Surgical trauma is associated with a significant but transient increase in lymphocyte commitment to apoptosis and IL-10 production. The exact relationship linking the overproduction of IL-10 with lymphocyte apoptosis after a surgical operation is still elusive and requires further investigation.
    The Journal of Trauma and Acute Care Surgery 06/2001; 51(1):92-97. · 2.35 Impact Factor
  • The Journal of Trauma Injury Infection and Critical Care 01/2001; 51(1):92-97.
  • European Journal of Anaesthesiology - EUR J ANAESTH. 01/2001; 18.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Evidence suggests that apoptosis plays a main role in the postoperative changes detected in the polymorphonuclear neutrophil (PMN) population. Furthermore, recent studies have demonstrated that mitochondrial alterations constitute critical events of the apoptotic cascade. In this study we investigated whether apoptosis among neutrophils taken from patients undergoing surgical trauma could be associated with perturbation of mitochondrial transmembrane potential (deltapsim) and/or exaggerated production of mitochondrial reactive oxygen species (ROS). Twenty-seven patients undergoing elective surgery under general anaesthesia were enrolled in the study. Peripheral blood samples were drawn one day before the operation and at 12 and 24 h after surgery. Apoptosis rate was assessed by staining neutrophils with 7-amino-actinomycin D (7-AAD) and by analysis by a FACScan flow cytometer. In order to evaluate deltapsim, cells were exposed to 3,3-dihexyloxacarbocyanine iodide [DiOC6(3)]; intracellular ROS was measured by means of hydroethidine (HE) and 2,7-diclorofluorescein diacetate (DCFH-DA), followed by analysis on a cytofluorometer. At 12 h following surgery we observed a significantly (P<0.05) increased frequency of apoptotic PMNs compared to that preoperatively (30.79+/-3.68% vs 7.40+/-0.69%). At this same time-point, the rate of neutrophils stained with HE, DCFH-DA and [DiOC6(3)] were significantly (P<0.05) higher compared to baseline (51.05+/-5.44%, 50.58+/-5.84% and 55.31+/-4.33% vs 20.17+/-2.38%, 19.59+/-2.03 and 25.43+/-2.71% respectively). Overall measurements returned to the preoperative values 24 h after surgery. These data suggest that surgery under general anaesthesia triggers in the immediate postoperative period pathways of PMN accelerated apoptosis associated with significant alterations in mitochondrial function.
    Acta Anaesthesiologica Scandinavica 01/2001; 45(1):87-94. · 2.36 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Surgery and anesthesia cause depression of cell-mediated immunity in the postoperative period, including a reduction in the numbers of circulating lymphocytes. It has been claimed that this immunosuppression is associated with an increased incidence of postoperative infections. Lymphocytopenia following surgical trauma depends on a dysregulated expression of death/and survival factors associated with apoptosis that, in turn, interferes with the occurrence of postsurgical infections. Fifteen subjects undergoing elective surgery under general anesthesia entered the study. The data of the patients who had infections during the postoperative outcome were compared with the data of those who did not. The data were collected prospectively. Peripheral blood samples were drawn before the operation, and 24 hours and 96 hours after the operation. Lymphocytes were isolated and examined for quantification and phenotypic analysis of apoptosis using the 7-amino-actinomycin D method, as well as for Fas and Fas ligand, interleukin 1-converting enzyme p20/caspase-1, Bcl-2, and p35 expression. The rate of apoptotic cells was correlated with the incidence of postoperative infections. University hospital. Twenty-four hours after surgery, CD4(+) and CD8(+) cells exhibited a significantly higher frequency of apoptosis as well as of Fas and Fas ligand and interleukin 1-converting enzyme p20/caspase-1 expressions than preoperatively. This increase was paralleled by a significant down-regulation of antiapoptotic factors such as Bcl-2. However, the expression of the proapoptotic factor p35 was reduced. In addition, we found a relationship between the rate of the apoptotic CD8(+) subset and the occurrence of infectious complications during the postoperative course. At 96 hours after surgery, the variables studied returned to the baseline levels. In the early postoperative period, surgical trauma under general anesthesia induces an intracellular perturbation on peripheral lymphocytes, resulting in both up-regulation of death-signaling factors and down-regulation of survival-signaling factors. The increased apoptosis of CD8(+) lymphocytes, but not of CD4(+) cells, seemed to be associated with a greater risk of postsurgical infections.
    Archives of Surgery 11/2000; 135(10):1141-7. · 4.10 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To verify the impact on stress response and the influence of anesthesia on endocrine/immunologic changes, we have investigated the plasma level of norepinephrine, cortisol, TNFalpha, and IL-6 in 46 patients scheduled for laparotomy and laparoscopic cholecystectomy at 2, 6, 12, and 24 h after the operation. Among subjects who underwent open approach, 9 received fentanyl anesthesia and 13 received isoflurane anesthesia. In the laparoscopy group, 14 patients were given fentanyl anesthesia and 10 were given isoflurane anesthesia. The results obtained confirmed that laparoscopic cholecystectomy is associated with a lesser immunoendocrine response, and the two anesthesia models do not interfere with plasma changes of the assessed hormones and cytokines.
    Surgical laparoscopy, endoscopy & percutaneous techniques 11/1999; 9(5):326-32. · 0.88 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To investigate the concentrations of mononuclear cell-associated ceramide and serum tumor necrosis factor-alpha (TNF-alpha) in patients with sepsis and to assess their predictive value for the development of multiple organ dysfunction syndrome (MODS). Prospective, cohort study. Intensive care unit and two research laboratories at a university hospital. Twenty-three adult patients admitted to an intensive care unit meeting the criteria for diagnosis of sepsis. Blood samples were collected at the time when diagnosis of sepsis was made. Mononuclear cell-associated ceramide and serum TNF-alpha were significantly elevated in the samples from the septic patients compared with the control individuals (318.01+/-270.15 pmol/10(6) cells vs. 99.90+/-52.75 pmol/10(6) cells; p<.001, and 28.52+/-18.77 pg/mL vs. 10.43+/-3.37 pg/mL; p<.0001, respectively), and a direct correlation linked ceramide and TNF-alpha concentrations (r2 = .90, p<.00001). In the septic patients who went on to develop MODS, ceramide and TNF-alpha were significantly higher compared with the no MODS patients (489.22+/-264.93 pmol/10(6) cells vs. 131.23+/-99.02 pmol/10(6) cells; p<.0001, and 40.96+/-18 pg/mL vs. 14.95+/-5.60 pg/mL; p<.001, respectively). The receiver operating characteristic curves demonstrated that both TNF-alpha and ceramide were prognostic of MODS, but ceramide concentrations were more efficient predictors. These observations suggest that mononuclear cells of peripheral blood from patients with sepsis are committed to undergo apoptosis, because there is evidence that ceramide acts as an endogenous mediator of apoptosis. The strong correlation we found between cell-associated ceramide and serum TNF-alpha supports the hypothesis that this cytokine plays an important role in activating the sphingomyelin pathway and ceramide generation in patients with sepsis. In addition, this study provides evidence that consistent concentrations of mononuclear cell-associated ceramide may predict progression toward MODS in septic patients.
    Critical Care Medicine 11/1999; 27(11):2413-7. · 6.12 Impact Factor