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Charis Roussos

Publications and source records attributed to Charis Roussos.

At least 73 records · Page 4Linked to original sources
PubMed2004

Hypoxemic reperfusion after 120 mins of intestinal ischemia attenuates the histopathologic and inflammatory response.

OBJECTIVE: It has been suggested that reactive oxygen species play a pivotal role in the initial organ-tissue injury during reperfusion, eliciting inflammatory reaction and multiple organ failure. It was investigated if hypoxemic reperfusion attenuates tissue injury and inflammatory response. DESIGN: Randomized animal study. SETTING: Medical school laboratory. SUBJECTS: Twenty-five male pigs weighing 25-28 kg. INTERVENTIONS: Pigs were subjected to 120 mins of intestinal ischemia by clamping the superior mesenteric artery. Upon declamping, the animals were randomly assigned to receive either hypoxemic reperfusion (HR group, n = 9) reperfused with a Pao2 = 30-35 or normoxemic reperfusion (control group, n = 16) reperfused with a Pao2 = 100 mm Hg for 120 mins. Fluids without inotropes were given to combat circulatory shock during reperfusion. MEASUREMENTS AND MAIN RESULTS: Portal blood and intestinal and lung biopsies were collected at baseline, end of ischemia, and end of reperfusion. Histopathologic changes were scored, and interleukin-1beta, qualitative Limulus amebocyte, lysate test, and Pao2/Fio2 were measured. Eight of 16 animals of the control group and seven of nine of the HR group survived (p = .22). At the end of reperfusion, the intestinal (p = .004) and lung (p = .028) pathologic scores were lower in the HR group compared with controls. The only significant difference in concentration of interleukin-1beta in the portal blood between the two animal groups occurred 120 mins after reperfusion (p = .006). The number of HR animals with a positive Limulus test was significantly smaller compared with controls at 60 (p = .041) and 120 (p = .07) mins of reperfusion. During the period of ischemia, the Pao2/Fio2 decreased similarly in the control and HR group, whereas after 120 mins of reperfusion the rate was significantly higher in the HR group. CONCLUSIONS: Hypoxemic reperfusion represents an intervention that may attenuate the triggering of multifactorial cascade and organ tissue injury.

Animals↗
PubMed2004

Health-related quality of life and disability in survivors of multiple trauma one year after intensive care unit discharge.

OBJECTIVE: To evaluate health-related quality of life and disability in multiple-trauma patients requiring intensive care unit management. DESIGN: A total of 87 survivors of multiple trauma, with a median age of 31 yrs and a median Injury Severity Score of 22, were enrolled in the present study. The Nottingham Health Profile, Glasgow Outcome Scale, and Rosser Disability Scale were used to assess the functional consequences of trauma 1 yr after intensive care unit discharge. RESULTS: A total of 64 of 87 patients had a problem in at least one of the six domains related to subjective health status. The most prevalent complaint was related to somatic subdimensions, but emotional functioning was also affected. Nottingham Health Profile part 2 showed that 63 of the survivors experienced problems in at least one of the daily activities. Of particular importance, inability to work was reported by 47% of the patients. Fifty-nine percent experienced moderate-to-severe disability as evaluated by Glasgow Outcome Scale and Rosser Disability Scale. High aggregate injury severity score along with severe head trauma were independent predictors of poor health-related quality of life and disability. CONCLUSIONS: The majority of survivors of major trauma exhibit considerable levels of disability and impairment in health-related quality of life. Global injury severity score and degree of brain trauma determine functional limitations. This information may help in organizing long-term rehabilitation of multiple-trauma patients.

Adolescent↗
PubMed2004

Sputum carcinoembryonic antigen, neuron-specific enolase and cytokeratin fragment 19 levels in lung cancer diagnosis.

OBJECTIVE: The aim of the present study was to examine the impact of sputum carcinoembryonic antigen (CEA), neuron-specific enolase (NSE) and cytokeratin fragment 19 (CYFRA 21-1) levels in lung cancer diagnosis and to compare the diagnostic usefulness of sputum assays with that of serum assays. METHODOLOGY: Forty-seven patients with lung cancer and 62 with benign lung disease were studied. Tumour marker levels in sputum (sp.) and serum (ser) were measured by immunoradiometric assays. RESULTS: Sputum and serum tumour marker levels were significantly higher in lung cancer than in benign disease. When the specificity was 95%, the sensitivity was 57%, 43%, 36%, 30%, 28% and 19%, for spCEA, serCYFRA 21-1, spCYFRA 21-1, serCEA, serNSE, and spNSE, respectively. Bayesian analysis showed that the best predictive values correspond to spCEA and serCYFRA 21-1. The maximum overall gain was obtained in pretest probability of 0.35 for both spCEA and serCYFRA 21-1, with predictive values of 84% and 80% for spCEA and serCYFRA 21-1, respectively. CONCLUSION: Sputum tumour marker levels were no more useful than the serum levels in lung cancer diagnosis. SpCEA offered the best predictive values but these were still not sufficiently satisfactory for spCEA to be proposed for routine use.

Adult↗
PubMed2004

Effects of modulation of the NO/cGMP pathway in tumor cell lines derived from the upper airway tract.

Nitric oxide (NO) is known to be expressed in a variety of cell types and exert its effects through autocrine and paracrine mechanisms. To characterize the NO/cGMP pathway in tumor cells of the upper airway tract, we studied the cell lines Detroit 562, FaDu and FAT7. Using isoform-specific antibodies, we were unable to detect expression of NO synthases in the above-mentioned cells lines. To evaluate whether tumor cells respond to NO, we exposed cells to the NO donor sodium nitroprusside (SNP). Stimulation of Detroit 562 and FaDu with SNP (10 micromol/l to 1 mmol/l) led to a concentration-dependent increase in cGMP accumulation. In addition, incubation of cells with SNP, but not 8 Br-cGMP, reduced Detroit 562 cell number. As exposure of cells to SNP decreased (3)H-thymidine incorporation without inducing DNA fragmentation, we attributed the observed decrease in cell number to inhibition of cell proliferation rather than induction of apoptosis. On the other hand, exposure of Detroit 562 to high concentrations of SNP (1 mmol/l) led to apoptosis and increased the release of vascular endothelial growth factor. We conclude that, although human cell lines derived from the upper airway tract do not produce NO, they respond to NO released by neighboring cells and that exposure to NO exerts an anti-proliferative/apoptotic effect that is independent of cGMP generation.

Animals↗
PubMed2003

Relationship of thyroid function to post-traumatic S-100b serum levels in survivors of severe head injury: preliminary results.

OBJECTIVE: To assess thyroid function abnormalities in survivors of severe head trauma and to examine their relationship with indices of brain injury severity. DESIGN: Prospective study. SETTING: General intensive care unit (ICU) in a university hospital. PATIENTS AND PARTICIPANTS: Twenty-two (21 men) head-injured patients, with a median age of 25.5 years at the time of injury, were investigated. Severity of brain trauma was assessed by Glasgow Coma Scale (GCS) score, Marshall Computerized Tomographic Classification, intracranial pressure levels and serum S-100b concentrations measured over a 6-day period. INTERVENTIONS: Thyroid function testing was performed 1 year after ICU discharge and included the measurement of free thyroxine, triiodothyronine and thyrotropin. MEASUREMENTS AND RESULTS: On admission to the ICU, GCS ranged from 3 to 8. Peak S-100b was 1.49 microg/l (range: 0.37-5.26 microg/l). Median triiodothyronine and thyrotropin were 123 ng/dl and 1.60 microIU/ml, respectively. Free thyroxine was 1.08+/-0.22 ng/dl (range: 0.7-1.5 ng/dl). Overall, 7 of the 22 patients (32%) had thyroid dysfunction. Four patients had central hypothyroidism and three patients had subclinical hypothyroidism. Peak S-100b correlated negatively with free thyroxine (r=-0.47, p=0.02). There were no correlations between other brain injury severity indices and thyroid hormone levels. CONCLUSIONS: A significant subset of brain injury patients presents with changes in thyroid function 1 year after ICU discharge; these depend upon biochemical serum markers of head trauma severity.

Adolescent↗
PubMed2003

Prediction of prolonged ventilatory support in blunt thoracic trauma patients.

OBJECTIVE: To identify predictors of prolonged (>7 days) mechanical ventilation (MV) in patients with blunt thoracic trauma. DESIGN: Prospective analysis of consecutive patients. SETTING: Adult intensive care unit (ICU) in a teaching, tertiary-care hospital. PATIENTS AND PARTICIPANTS: Sixty-nine patients (53 men, 16 women) with thoracic trauma having a median age of 35 (range 17-85) years and a median injury severity score (ISS) of 29 (range 14-41) were enrolled in the present study. Associated injuries included head-neck (77%), extremities (72%), external (67%), abdomen-pelvis (67%), and face (55%). INTERVENTIONS: Patient surveillance and data collection. MEASUREMENTS AND RESULTS: Thirty-three (48%) of the 69 patients required prolonged ventilatory support, ranging in duration from 8 to 38 (median 18) days. Logistic regression analysis revealed that advancing age (odds ratio=1.04, p=0.04), severity of head injury (odds ratio=1.92, p=0.008), and bilateral thoracic injuries (odds ratio=12.80, p<0.0001) were significant and independent predictors of long-lasting MV. In contrast, gender, injuries affecting the other body regions (face, abdomen-pelvis, extremities, and external), laparotomy in patients with abdominal injury, or PaO(2)/FIO(2) on admission in the ICU, were unrelated to prolonged MV. CONCLUSIONS: In thoracic trauma patients admitted in the ICU, prolonged mechanical ventilation was primarily determined by presence of bilateral chest injuries, age, and degree of neurotrauma. This information may help in planning the long-term care of such patients.

Adolescent↗
PubMed2003

Angiopoietin-1 inhibits endothelial permeability, neutrophil adherence and IL-8 production.

1 Angiopoietin-1 (Ang1) is an angiogenic growth factor that binds to the Tie2 receptor on vascular endothelium, promoting blood vessel maturation and integrity. In the present study, we have investigated whether Ang1 also possesses anti-inflammatory properties by determining its effects on endothelial barrier function, neutrophil (PMN) adherence to endothelial cells (EC) and production of the PMN chemotactic factor interleukin-8 (IL-8). 2 Pretreatment of endothelial monolayers with Ang1 attenuated the permeability increase induced by thrombin in both lung microvascular cells and a human endothelial cell line. Similarly, Ang1 prevented the permeability-inducing effects of platelet-activating factor, bradykinin and histamine. 3 Pretreatment of EC with Ang1 also reduced the adherence of PMN to EC stimulated by thrombin. In contrast to its ability to counteract the increase in monolayer permeability brought about by various inflammatory agents, Ang1 did not affect the ability of histamine, PAF, or tumor necrosis factor-alpha to stimulate PMN adherence to EC. 4 In addition to its ability to inhibit PMN adherence, Ang1 diminished IL-8 production from EC challenged with thrombin in a concentration-dependent manner. 5 When EC were preincubated with the specific Rho kinase (ROCK) inhibitor Y-27632, we observed a reduction in PMN adherence in response to thrombin, as well as a decrease in thrombin-stimulated IL-8 production. Coincubation of monolayers with Y-27632 and Ang1 did not further attenuate the above-mentioned responses. However, Ang-1 failed to inhibit the activation of RhoA in response to thrombin, suggesting that inhibition of EC adhesiveness for PMN and IL-8 production by Ang1 does not result from reduced ROCK activation. 6 We conclude that Ang1 can counteract several aspects of the inflammatory response, including endothelial permeability, PMN adherence to EC as well as inhibition of IL-8 production by EC.

Amides↗
PubMed2003

High prevalence of decreased cortisol reserve in brain-dead potential organ donors.

OBJECTIVE: To investigate the adrenocortical function in brain-dead patients, potential organ donors. DESIGN: Prospective study. SETTING: Intensive care units in two teaching hospitals. PATIENTS: A total of 37 patients (28 men, nine women) with severe brain injury, having a mean age of 42 +/- 18 yrs, were included in the study. Group A consisted of 20 brain-injured patients who did not deteriorate to brain death. Group B included 17 brain-injured patients who were brain dead; of these, ten patients developed brain death during ICU stay and seven patients were admitted to the ICU after clinical brain death. INTERVENTIONS: In all patients (group A and group B), a morning blood sample was obtained at admission to the ICU to determine baseline plasma cortisol. Subsequently, 1 microg of corticotropin (adrenocorticotropic hormone, Synacthen) was administered intravenously, and a blood sample was taken 30 mins after the injection. In group B patients who became brain dead while being treated in the ICU (n = 10), the same procedure was repeated the morning after the confirmation of brain death. Patients having a cortisol level of at least 18 microg/dL after the administration of adrenocorticotropic hormone were defined as responders. MEASUREMENTS AND MAIN RESULTS: After the occurrence of brain death, group B patients had significantly lower values for baseline (8.5 +/- 6.2 vs. 17.0 +/- 6.6 microg/dL, p <.001) and stimulated (16.9 +/- 6.3 vs. 23.9 +/- 5.7 microg/dL, p =.001) plasma cortisol compared with group A patients. Thirteen group B patients (76%) and two group A patients (10%) were nonresponders to adrenocorticotropic hormone (p <.001). In group B patients, baseline and stimulated cortisol concentrations were significantly related (r =.71, p =.001), whereas there was no correlation between baseline cortisol and the increment in cortisol (r = -.37, p =.15). Mean hormonal data of the ten brain-dead patients studied at admission in the ICU and after the occurrence of brain death were the following: baseline plasma cortisol (23.5 +/- 11.4 vs. 6.8 +/- 4.2 microg/dL, p =.003) and stimulated serum cortisol (28.8 +/- 9.9 vs. 16.3 +/- 4.3 microg/dL, p =.008). CONCLUSIONS: Adrenal cortisol secretion after dynamic stimulation is deficient in a substantial proportion of brain-dead potential organ donors.

Adolescent↗
PubMed2003

Myocardial ischemia in intestinal postischemic shock: the effect of hypoxemic reperfusion.

OBJECTIVE: The circulatory shock following intestinal ischemia-reperfusion injury has been attributed to hypovolemia. The purpose of the current study is to clarify the pathophysiology of this type of shock and to test the hypothesis that hypoxemic compared with normoxemic reperfusion improves hemodynamics. DESIGN: Randomized animal study. SETTING: Medical school laboratory. SUBJECTS: Twenty-one pigs. INTERVENTIONS: Pigs were subjected to 120 mins of intestinal ischemia by clamping the superior mesenteric artery. Upon declamping, the animals were randomized into two groups: a group that received hypoxemic reperfusion (HR group, n = 8) with a PaO2 = 30-35 and a control group reperfused with PaO2 = 100 mm Hg (control group, n = 13). MEASUREMENTS AND MAIN RESULTS: Measurements included mean arterial pressure, cardiac index, pulmonary artery occlusion pressure, and requirements for fluids and epinephrine. Biopsies from the terminal ileal mucosa were taken for malondialdehyde measurements at baseline, at 120 mins of ischemia, and at 30 and 60 mins of reperfusion. A piece of left ventricle was obtained after 120 mins of reperfusion for histologic studies. Five of 13 animals of the control group died in intractable shock; no animal of the HR group died (p =.11). The decrease in the mean arterial pressure during reperfusion was more pronounced in the control group (p <.008) despite the larger doses of epinephrine administered, compared with the HR group (p <.02). During reperfusion, both groups exhibited a decrease in cardiac index; this was more pronounced in the control group (p =.0007). Pulmonary artery occlusion pressure increased during reperfusion in both groups and was more pronounced in the control group (p =.04 at 60 mins). Although mixed venous blood oxygen saturation of the control animals was higher at 30 mins of reperfusion (p =.005), it declined after 60 mins and became lower than that of HR animals at the end of reperfusion (p <.02). The myocardial histopathologic injury score was higher in the control group (2.0 +/- 0.69 and 3.4 +/- 0.89 for the HR and control groups, respectively; p <.03). The concentrations of intestinal mucosa malondialdehyde were significantly higher in the control group at 60 mins of reperfusion (p <.03). CONCLUSIONS: Acute myocardial ischemia and left heart failure significantly contribute to the circulatory shock that follows intestinal ischemia/reperfusion injury and are attenuated by hypoxemic reperfusion.

Animals↗
PubMed2003

Resting lung function and hemodynamic parameters as predictors of exercise capacity in patients with chronic heart failure.

STUDY OBJECTIVES: The aim of this study was to examine the role of resting pulmonary function and hemodynamic parameters as predictors of exercise capacity in patients with chronic heart failure. MEASUREMENTS AND RESULTS: Fifty-one patients with chronic heart failure underwent resting pulmonary function testing, including inspiratory capacity (IC) and symptom-limited, treadmill cardiopulmonary exercise testing (CPET). Right-heart catheterization and radionuclide ventriculography were performed within 2 days of CPET. Mean (+/- SD) left ventricular ejection fraction was 31 +/- 12% and cardiac index was 2.34 +/- 0.77 L/min/m(2). Percentage of predicted FEV(1) was 92 +/- 14%, percentage of predicted FVC was 94 +/- 15%, FEV(1)/FVC was 81 +/- 4%, and percentage of predicted IC was 84 +/- 18%. Mean peak oxygen uptake (peak O(2)) was 17.9 +/- 5.4 mL/kg/min. Analysis of variance among the three functional Weber classes showed statistically significant differences for pulmonary capillary wedge pressure (PCWP) and IC. Specifically, the more severe the exercise intolerance, the lower was IC and the higher was PCWP. In a multivariate stepwise regression analysis, using peak O(2) (liters per minute) as the dependent variable and the pulmonary function test measurements as independent variables, the only significant predictor selected was IC (r = 0.71, p < 0.0001). In a final stepwise regression analysis including all the independent variables of the resting pulmonary function tests and hemodynamic measurements, the two predictors selected were IC and PCWP (r(2) = 0.58). CONCLUSIONS: In patients with chronic heart failure, IC is inversely related to PCWP and is a strong independent predictor of functional capacity.

Cardiac Output↗
PubMed2002

Antioxidants attenuate the plasma cytokine response to exercise in humans.

Exercise increases plasma TNF-alpha, IL-1beta, and IL-6, yet the stimuli and sources of TNF-alpha and IL-1beta remain largely unknown. We tested the role of oxidative stress and the potential contribution of monocytes in this cytokine (especially IL-1beta) response in previously untrained individuals. Six healthy nonathletes performed two 45-min bicycle exercise sessions at 70% of Vo(2 max) before and after a combination of antioxidants (vitamins E, A, and C for 60 days; allopurinol for 15 days; and N-acetylcysteine for 3 days). Blood was drawn at baseline, end-exercise, and 30 and 120 min postexercise. Plasma cytokines were determined by ELISA and monocyte intracellular cytokine level by flow cytometry. Before antioxidants, TNF-alpha increased by 60%, IL-1beta by threefold, and IL-6 by sixfold secondary to exercise (P < 0.05). After antioxidants, plasma IL-1beta became undetectable, the TNF-alpha response to exercise was abolished, and the IL-6 response was significantly blunted (P < 0.05). Exercise did not increase the percentage of monocytes producing the cytokines or their mean fluorescence intensity. We conclude that in untrained humans oxidative stress is a major stimulus for exercise-induced cytokine production and that monocytes play no role in this process.

Acetylcysteine↗
PubMed2002

Strenuous resistive breathing induces plasma cytokines: role of antioxidants and monocytes.

Inspiratory resistive breathing increases plasma cytokines, yet the stimulus (or stimuli) and source(s) remain unknown. We tested the role of reactive oxygen species as stimuli and of monocytes as sources of resistive breathing-induced cytokines. Six healthy subjects performed two resistive breathing sessions at 75% of maximum inspiratory pressure before and after a combination of antioxidants (vitamin E 200 mg, vitamin A 50,000 IU, and vitamin C 1,000 mg per day for 60 days, allopurinol 600 mg/day for 15 days, and N-acetylcysteine 2 g/day for 3 days before the second session). Blood was drawn before, at the end, and at 30 and 120 minutes after resistive breathing. Before antioxidants, plasma cytokine levels (determined by enzyme-linked immunosorbent assay) increased secondary to resistive breathing (tumor necrosis factor-alpha and interleukin [IL]-6 by twofold and IL-1beta by threefold). After antioxidants, plasma IL-1beta became undetectable. The tumor necrosis factor-alpha response to resistive breathing was abolished, and the IL-6 response was significantly blunted. Intracellular cytokine detection (by flow cytometry) showed no change in either the percentage of monocytes producing the cytokines or their mean fluorescence intensity both before and after antioxidants. We conclude that oxidative stress is a major stimulus for the resistive breathing-induced cytokine production and that monocytes play no role in this process.

Adult↗
PubMed2002

Adrenal function in non-septic long-stay critically ill patients: evaluation with the low-dose (1 micro g) corticotropin stimulation test.

OBJECTIVE: To investigate the adrenal function in non-septic, long-stay critically ill patients. DESIGN: Prospective, consecutive study. SETTING: General intensive care unit in a university hospital. PATIENTS: Forty-three non-septic patients with protracted critical illness. INTERVENTIONS: A morning blood sample was first obtained to measure baseline plasma cortisol. Subsequently, 1 micro g of corticotropin (ACTH, Synacthene) was injected intravenously and 30 min later a second blood sample was drawn to determine stimulated plasma cortisol. Patients having a stimulated cortisol level of at least 18 micro g/dl were defined as responders. In 36 patients, morning interleukin-6 (IL-6) was also measured. MEASUREMENTS AND RESULTS: Baseline and stimulated plasma cortisol were 16.8+/-4.1 micro g/dl and 21.2+/-5.1 micro g/dl, respectively. Interleukin-6 was high (median 39.3 pg/ml, interquartile range 24.9-86.6 pg/ml) and correlated negatively with stimulated plasma cortisol (r=-0.40, p<0.05). Of the 43 patients studied, 31 patients (72%) were responders and 12 patients (28%) were non-responders to the ACTH stimulation test. Overall, 18 patients died and 25 patients survived to hospital discharge. Non-responders had significantly higher IL-6 levels compared to responders (106+/-73 versus 48+/-42 pg/ml, p<0.05), whereas mortality rate was comparable in the two groups (50% versus 38%, p=0.74). CONCLUSIONS: Circulating plasma IL-6 levels are high during protracted critical illness, and are partially responsible for the relative adrenal insufficiency found in a subset of severely ill patients.

Adrenal Insufficiency↗
PubMed2002

Luteolin reduces lipopolysaccharide-induced lethal toxicity and expression of proinflammatory molecules in mice.

Luteolin is a flavonoid that has been shown to reduce proinflammatory molecule expression in vitro. In the present study, we have tested the ability of luteolin to inhibit lipopolysaccharide (LPS)- induced lethal toxicity and proinflammatory molecule expression in vivo. Mice receiving LPS (Salmonella enteriditis LPS, 32 mg/kg, intraperitoneally) exhibited high mortality with only 4.1% of the animals surviving seven days after the LPS challenge. On the contrary, mice that had received luteolin (0.2 mg/kg, intraperitoneally) before LPS showed an increased survival rate with 48% remaining alive on Day 7. To investigate the mechanism by which luteolin affords protection against LPS toxicity we measured intercellular adhesion molecule-1 (ICAM-1) and tumor necrosis factor-alpha (TNF-alpha) production in response to LPS in the presence or absence of luteolin pretreatment. Treatment of animals with LPS increased serum TNF-alpha levels in a time-dependent manner. The increase in peak serum TNF-alpha levels was sensitive to luteolin pretreatment. Luteolin pretreatment also reduced LPS-stimulated ICAM-1 expression in the liver and abolished leukocyte infiltration in the liver and lung. We conclude that luteolin protects against LPS-induced lethal toxicity, possibly by inhibiting proinflammatory molecule (TNF-alpha, ICAM-1) expression in vivo and reducing leukocyte infiltration in tissues.

Analysis of Variance↗
PubMed2002

A prospective study of pulmonary function in patients treated with paclitaxel and carboplatin.

BACKGROUND: Adverse effects of paclitaxel and carboplatin have been well described; however, pulmonary toxicity after patients receive this regimen has not been investigated extensively. METHODS: To clarify this issue, 33 consecutive patients who were treated with paclitaxel and carboplatin underwent prospective evaluation of respiratory function, which included pulmonary symptoms, pulmonary function tests (PFTs), arterial blood gas levels, and radiographic studies. Assessment was performed before and after completion of chemotherapy in all patients. Patients with substantial declines in PFTs, defined as a decline > or = 20 percent in forced expiratory volume in 1 second (FEV1), total lung capacity (TLC), or diffusion capacity for carbon monoxide (DLCO), were reassessed 5 months later. RESULTS: After chemotherapy, there were no significant changes in forced vital capacity (FVC; 111%+/-21% of the predicted value before chemotherapy vs. 111+/-20% of the predicted value after chemotherapy), FEV1 (108%+/-24% of the predicted value before chemotherapy vs. 107%+/-22% of the predicted value after chemotherapy), FEV1/FVC ratio (79%+/-8% before chemotherapy vs. 78%+/-6% after chemotherapy), alveolar volume (VA; 95%+/-14% of the predicted value before chemotherapy vs. 96%+/-14% of the predicted value after chemotherapy), or TLC (96%+/-14% of the predicted value before chemotherapy vs. 97%+/-13% of the predicted value after chemotherapy). In contrast, there was a significant decline in DLCO (101%+/-20% of the predicted value before chemotherapy vs. 96+/-21% of the predicted value after chemotherapy; P < 0.05). Arterial blood gas levels did not change after treatment. No patient had decreased FEV1 or TLC levels by > or = 20%, whereas 4 of 33 patients (12%) exhibited a substantial decline (> or = 20%) in DLCO that persisted 5 months after treatment (DLCO at baseline, immediately after chemotherapy, and 5 months after the completion of chemotherapy, respectively: 99%+/-36% of the predicted value vs. 75%+/-28% of the predicted value vs. 74%+/-31% of the predicted value; P < 0.05). None of the 33 patients developed respiratory symptoms or had radiologic signs suggestive of lung toxicity. Among the various risk factors examined, baseline DLCO and FEV1 levels were associated with changes in DLCO post-treatment. CONCLUSIONS: This prospective analysis showed that the combination of paclitaxel with carboplatin induced an isolated decrease in DLCO level in the absence of clinical or radiologic evidence of toxicity. Further studies are needed to clarify whether this reduction in DLCO is predictive of subsequent pulmonary impairment.

Aged↗
PubMed2002

Inhibition of LPS-stimulated pathways in macrophages by the flavonoid luteolin.

1: We have previously shown that the flavonoid luteolin inhibits the expression of pro-inflammatory molecules induced by LPS. In the present study we tested the ability of luteolin to block signalling pathways implicated in LPS-induced inflammatory gene expression in macrophages. 2: Exposure of the murine macrophage cell line RAW 264.7 to LPS increased phosphorylation of the mitogen-activated protein kinase family members ERK1/2, p38 and JNK1/2 in a time-dependent manner. Pretreatment of RAW 264.7 with luteolin inhibited the LPS-induced ERK1/2 and p38, but not JNK1/2, phosphorylation, and blocked the LPS-induced TNF-alpha release. 3: To investigate which of these pathways contribute to the inhibitory effects of luteolin on TNF-alpha release, cells were pretreated with pharmacological inhibitors of these pathways; PD98059 and SB203580 when used alone failed to inhibit TNF-alpha release, whereas pretreatment with both agents attenuated TNF-alpha release. 4: We have previously shown that luteolin blocks Akt phosphorylation in response to LPS in RAW 264.7 macrophages. To determine the role of Akt in TNF-alpha release, cells were transiently transfected with a dominant negative form of Akt (K179M). Overexpression of K179M Akt did not alter LPS-induced TNF-alpha release, suggesting that inhibition of this kinase does not mediate the inhibitory action of luteolin. 5: In addition, DRB (a pharmacological inhibitor of CK2) blocked TNF-alpha release in a concentration-dependent manner, whereas co-treatment of cells with luteolin and DRB did not have an additive effect. 6: We conclude that luteolin interferes with LPS signalling by reducing the activation of several MAPK family members and that its inhibitory action on TNF-alpha release correlates with inhibition of ERK, p38 and CK2 activation.

Animals↗