Biomedical subjects

G J Quinlan

Publications and source records attributed to G J Quinlan.

At least 37 records · Page 2Linked to original sources

PubMed1998

Postoperative lung injury and oxidative damage in patients undergoing pulmonary resection.

Postpneumonectomy pulmonary oedema (PPO) complicates a significant number of thoracic surgical procedures involving lung resection and in its extreme form is indistinguishable from the acute respiratory distress syndrome. This study investigated the possibility that ischaemia-reperfusion (I-R) injury contributes to PPO via the production of damaging reactive oxygen species. In a prospective, observational, comparative study, patients undergoing pneumonectomy, lobectomy, or wedge resection or open lung biopsy were investigated for perioperative changes in lung function indicative of lung injury and changes in plasma indices of oxidative damage. Significant percentage perioperative falls in plasma protein thiol levels (-17.9+/-7.0% for pneumonectomy, -24.3+/-5.5% for two-lobe lobectomy and -10.2+/-2.2% for one-lobe lobectomy, p<0.05) and rises in plasma protein carbonyl levels (26.2+/-10.5% for pneumonectomy, p<0.05, 9.8+/-7.0% for two-lobe lobectomy and 5.0+/-2.7% for one-lobe lobectomy) were identified, but not in patients undergoing biopsy or wedge resection. Plasma myeloperoxidase levels rose in all groups, but not significantly. The carbon monoxide transfer coefficient (K(CO)) fell significantly in patients undergoing lobectomy (p<0.05) but not in those undergoing wedge resection, lung biopsy or pneumonectomy. Changes in markers of oxidative protein damage occurred in patients undergoing lung resection, although the gas transfer coefficient fell significantly only following lobectomy. Oxidative damage occurs during pulmonary resection, although associated effects on gas exchange are seen only after lobectomy.

Adult↗

PubMed1998

Hypothesis: are fatty acid patterns characteristic of essential fatty acid deficiency indicative of oxidative stress?

Several unrelated diseases show plasma and tissue fatty acid patterns characteristic of those seen in Essential Fatty Acid Deficiency Disease (EFADD). A common feature occurring in all these diseases is oxidative stress. We hypothesize that reactive oxygen species or products of oxidative damage, particularly those derived from lipids, act as signal molecules to alter desaturase enzymes and induce the fatty acid patterns characteristic of EFADD.

Animals↗

PubMed1998

Phagomimetic action of antimicrobial agents.

A wide variety of extracted and synthesised drug molecules have electron transfer capabilities which allow them to generate reactive oxygen species (ROS). In particular, many antibiotics that kill or inhibit bacteria, yeasts and cancer cells readily transfer electrons to oxygen making superoxide and hydrogen peroxide in the process. When suitable redox active forms of iron are available, Fenton chemistry occurs generating the highly damaging hydroxyl radical. This type of chemistry is very similar to that which evolved within phagocytic cells as part of their microbial killing armoury. Many antibiotics, when used in model systems, have well defined pharmacological actions against key cellular functions, but their clinical usefulness is also often demonstrable at concentrations in vivo well below their in vitro minimum inhibitory concentrations. These observations have led us to propose that a common mechanism exists whereby phagocytic cells and antibiotics exploit the use of ROS for microbial killing.

Anti-Bacterial Agents↗

PubMed1998

Administration of albumin to patients with sepsis syndrome: a possible beneficial role in plasma thiol repletion.

1. Albumin is often administered intravenously to critically ill patients as a volume expander, to combat hypoalbuminaemia, and to decrease hyperbilirubinaemia. There is, however, an ongoing debate concerning the therapeutic benefit of the former which is an expensive form of treatment.2. Albumin has several biological functions, in particular as a ligand binder. It also acts as an extracellular transition metal ion-binding and radical-scavenging antioxidant. These functions are influenced by the presence of an exposed thiol group (cys 34) on the surface of the albumin molecule. 3. The ability of infused albumin to influence the plasma thiol pool, and hence antioxidant potential, was investigated in patients with sepsis syndrome.4. Plasma thiol levels rose rapidly after albumin infusion and remained elevated even after plasma albumin levels had declined significantly, due to interstitial leakage. Data are suggestive of some form of thiol exchange in the plasma of these patients between albumin and molecules containing oxidized thiol groups.5. Administration of albumin to patients with sepsis syndrome leads to a sustained increase in plasma thiols. Thiols have several important antioxidant functions, and thiol repletion in these patients, who are known to suffer from oxidative stress, may have beneficial antioxidant effects. Antioxidant repletion may represent an important facet of clinically administered albumin.

Adult↗

PubMed1997

Is bleomycin-detectable iron present in the plasma of patients with septic shock?

OBJECTIVE: To assess plasma iron status in critically ill patients with septic shock. DESIGN: Observational, prospective study. SETTING: Adult intensive care units in teaching and tertiary referral hospitals. PATIENTS AND PARTICIPANTS: Fifteen adult patients with established septic shock. Normal control subjects (n = 10) were also investigated. Data from patients and controls were compared with previously published iron values in critical care patients. MEASUREMENTS AND RESULTS: The indices investigated and correlated with clinical scores of illness severity included bleomycin-detectable iron, non-haem iron; transferrin and its percentage iron saturation, and the iron binding (anti-oxidant) activity of transferrin. Bleomycin-detectable iron was not present in the plasma of patients with septic shock whilst the plasma transferrin remained unsaturated with iron. One patient in multi-organ failure displayed bleomycin-detectable iron in plasma (1.16 mumol/l) and had 100% iron-saturation of transferrin. The plasma non-haem iron levels (7.84 +/- 1.82 mumol/l) were the lowest of all critical care patient groups studied by us. The plasma transferrin levels were also low but resulted in a near normal percentage saturation of transferrin with iron (34.6 +/- 6.5%). The scores of clinical severity correlated with changes in plasma iron chemistry. CONCLUSIONS: Patients with septic shock rarely have iron saturated transferrin in their plasma leading to the presence of bleomycin-detectable iron.

APACHE↗

PubMed1997

Characterization of the vasodilator properties of peroxynitrite on rat pulmonary artery: role of poly (adenosine 5'-diphosphoribose) synthase.

1. The pulmonary vasculature is constantly exposed to oxygen and reactive oxygen species such as nitric oxide (NO) and superoxide anions which can combine at a near diffusion limited rate, to form the powerful, oxidant, peroxynitrite (ONOO-). When formed in large amounts, ONOO- is thought to contribute to tissue injury and vascular dysfunction seen in diseases such as the acute respiratory distress syndrome (ARDS) and septic shock. Recent studies have shown that ONOO- can cause vasodilatation and at higher concentrations can activate poly (adenosine 5'-diphosphoribose) synthase (PARS) leading to consumption of nicotinamide adenine dinucleotide (NAD+) and adenosine 5'-triphosphate (ATP). As the lung represents a prime site for ONOO- formation, we characterized its effects on pulmonary vascular tone and on endothelial function. In addition, we have assessed the role of PARS in producing the vasoactive properties of ONOO- on pulmonary artery rings. 2. Isolated pulmonary artery rings from rats were mounted in organ baths containing warmed and gassed (95% O2: 5% CO2) Krebs buffer. Force was measured with isometric force transducers. After equilibration, ONOO- (10 nM-100 microM) was added in a cumulative manner. In separate experiments designed to assess any vasodilator properties of ONOO-, tissues were pre-contracted with the thromboxane mimetic U46619 (1 microM). Once a stable base-line was achieved, ONOO- was added in a cumulative fashion. ONOO- had no significant effect on resting pulmonary artery tone but caused concentration-dependent relaxations of pre-contracted vessels in the range 1 microM to 100 microM. In some experiments the effects of freshly prepared ONOO- solutions were compared with those allowed to decay at 4 degrees C for 2 days. 3. In some experiments either vehicle or ONOO- (1, 10 or 100 microM) was added for 15 min before U46619 (1 microM). Concentration-response curves to the endothelium-dependent vasodilator, acetylcholine (10 nM-100 microM) were then constructed. In these experiments, ONOO- (1 microM or 10 microM) had no effect on the actions of acetylcholine. However, at the highest concentration tested (100 microM), ONOO- increased acetylcholine-induced relaxations. 4. The vasodilator actions of ONOO- were unaffected by the NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME; 100 microM) or by removal of superoxide anions with superoxide dismutase (SOD) (30 units ml-1). However, the relaxations induced by ONOO- were significantly inhibited by the PARS inhibitor, 3-aminobenzamide (10 microM). In contrast to its effects on ONOO-, 3-aminobenzamide had no effect on the relaxation caused by acetylcholine or sodium nitrite, but actually increased that induced by sodium nitroprusside. 5. These data show that ONOO- causes vasodilatation of rat pulmonary arteries, probably via activation of PARS. Moreover, at concentrations where relaxation was achieved, ONOO- did not affect the ability of pulmonary artery rings to relax to acetylcholine. We propose that ONOO-, but not endothelially derived NO, activates PARS resulting in the rapid depletion of ATP and a consequent reduction in contraction as well as other active processes of vascular smooth muscle. The finding that 3-aminobenzamide inhibited the actions of ONOO- but not acetylcholine, suggests that NO and ONOO- cause relaxation by independent mechanisms. It has been suggested that ONOO- is responsible for the vascular hyporesponsiveness to constrictor agents seen in experimental sepsis. This observation together with our current finding, that 3-aminobenzamide inhibits the relaxation induced by ONOO- but not by acetylcholine, suggests that inhibitors of PARS may reduce the persistent hypotension seen in sepsis without affecting the actions of endothelium-derived NO. Thus, the use of PARS inhibitors may represent a novel therapeutic approach to the treatment of septic shock.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed1997

Pulmonary vascular permeability after cardiopulmonary bypass and its relationship to oxidative stress.

OBJECTIVE: To assess the relationship between oxidative stress resulting from cardiopulmonary bypass and the onset of increased pulmonary vascular permeability. DESIGN: Prospective, controlled study. SETTING: Adult intensive care unit of a postgraduate teaching hospital. PATIENTS: Ten patients undergoing surgery requiring cardiopulmonary bypass, and seven normal subjects. INTERVENTIONS: Cardiopulmonary bypass in ten patients undergoing surgery. MEASUREMENTS AND MAIN RESULTS: Protein accumulation index was measured in patients after surgery and in normal subjects as a marker of increased pulmonary vascular permeability. Plasma markers of lipid peroxidation (lipid peroxides and thiobarbituric acid-reactivity), plasma chelatable iron, total non-heme iron, transferrin, and primary plasma proteinaceous antioxidant activities were measured before and after cardiopulmonary bypass, and compared with those values found in normal subjects. Protein accumulation index was significantly higher (1.79 +/- 0.54 [SEM]) in the postcardiopulmonary bypass patients compared with healthy subjects (0.33 +/- 0.07, p < .05). Concentrations of lipid peroxides precardiopulmonary bypass were similar to those concentrations in control patients (0.020 +/- 0.003 vs. 0.031 +/- 0.002 nmol/mg protein), but were significantly increased postcardiopulmonary bypass (0.114 +/- 0.010 nmol/mg protein, p < .01). Thiobarbituric acid-reactive substances were higher precardiopulmonary bypass than those in controls (0.052 +/- 0.01 vs. 0.019 +/- 0.01), and increased postcardiopulmonary bypass (0.072 +/- 0.012), although they did not reach significance. Bleomycin-chelatable iron, indicative of transient plasma iron-overload, was only found in one patient (6.5 mumol/L) postcardiopulmonary bypass. Total plasma non-heme iron concentrations before cardiopulmonary bypass were similar to those concentrations in normal control patients (0.19 +/- 0.03 vs. 0.22 +/- 0.015 nmol/mg of protein), and significantly increased postcardiopulmonary bypass (0.48 +/- 0.08, p < .01). Transferrin concentrations were lower in cardiopulmonary bypass patients (2.43 +/- 0.17 vs. 2.89 +/- 0.03 g/L) than in controls and significantly decreased postcardiopulmonary bypass (1.55 +/- 0.09 g/L, p < .01). High plasma iron concentrations with a lower level of transferrin, postcardiopulmonary bypass, gave significantly increased mean percentage iron-saturation of transferrin, increasing from 27.1% to 61.7% (p < .01). Proteinaceous primary antioxidant activities, measuring iron-binding and iron-oxidizing protection of peroxidizing lipid membranes, were both significantly decreased postcardiopulmonary bypass (83.7 +/- 3.71% pre and 26.6 +/- 8.42% post, p < .01, and 51.2 +/- 2.96% pre and 29.0 +/- 2.94% post, p < .01, respectively). In 90% of the cardiopulmonary bypass patients, there was a significant correlation between the percent increase in iron saturation of transferrin and the protein accumulation index. CONCLUSIONS: Pulmonary vascular permeability was significantly increased in patients postcardiopulmonary bypass compared with normal subjects. This patient population also had significantly increased plasma markers of lipid peroxidation compared with normal subjects. Cardiopulmonary bypass induced further increases in lipid peroxidation products but a substantial decrease in proteinaceous primary antioxidants. In the majority of patients, there was a significant correlation between the iron saturation of transferrin and the protein accumulation index.

Adult↗

PubMed1997

Plasma hypoxanthine levels in ARDS: implications for oxidative stress, morbidity, and mortality.

Acute respiratory distress syndrome in adults (ARDS) carries a high mortality. Patients with ARDS experience severe oxidative stress from neutrophil activation, and from treatment with high inspired oxygen concentrations (F(I)O2). Oxidative stress arises from an increased generation of reactive oxygen species (ROS) which overwhelm existing antioxidant defenses. Patients who do not survive ARDS sustain much greater levels of oxidative molecular damage, suggesting that they are less able to protect themselves against increased oxidative stress. We measured plasma levels of pro-oxidant substrates for xanthine oxidase, namely hypoxanthine and xanthine, and correlated them with the loss of plasma protein thiol groups. All patients with ARDS had higher levels of hypoxanthine (37.48 +/- 3.1 microM in nonsurvivors, 15.24 +/- 2.09 microM in survivors) compared with patients undergoing pulmonary resection (9.22 +/- 1.89 microM), patients in intensive care with sepsis but no lung injury (1.12 +/- 0.69 microM) and normal healthy control subjects (1.43 +/- 0.38 microM). The difference in plasma hypoxanthine levels between survivors and nonsurvivors of ARDS was highly significant (p < 0.001) and showed a negative correlation with loss of protein thiol groups. Xanthine levels were also higher in patients with ARDS but were not significantly different between ARDS survivors and nonsurvivors. Nonsurvivors of ARDS appear to experience higher levels of oxidative stress and damage than do survivors.

APACHE↗

PubMed1996

Pro-oxidant iron is present in human pulmonary epithelial lining fluid: implications for oxidative stress in the lung.

Bronchoalveolar lavage (BAL) provides a sample of lung surface lining fluid. Several pulmonary diseases appear to involve tissue damage caused by reactive oxygen species generated by inhaled oxidants or by phagocytic cells activated within the lung. We show that BAL from normal healthy controls contain chelatable redox active iron that is pro-oxidant towards free radical reactions. Adult patients with the acute respiratory distress syndrome (ARDS) are known to he under severe oxidative stress and to have high mortality rates. Patients who survived ARDS were found to have chelatable redox active iron in their lung fluid, whereas nonsurvivors had no such iron present. Severe lung leak in nonsurvivors was paradoxically associated with increased levels of transferrin and iron-binding antioxidant activity. We suggest that the presence of pro-oxidant iron in normal lung fluid is an important factor which makes the lung vulnerable to oxidative stress.

Adolescent↗

PubMed1996

Ischaemia--reperfusion injury in the rat is modulated by superoxide generation and leads to an augmentation of the hypoxic pulmonary vascular response.

1. The effects of the scavengers of reactive oxygen species superoxide dismutase and catalase, the iron chelator desferrioxamine and the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester and saline (control vehicle) on hypoxic pulmonary vasoconstriction, a measure of albumin flux and an index of lipid peroxidation (palmitic:linoleic acid ratio) were investigated after ischaemia-reperfusion in an isolated, blood-perfused rat lung model. 2. Lungs treated immediately before reperfusion with catalase (5,000 units), desferrioxamine (2 mg/kg), NG-nitro-L-arginine methyl ester (5 mmol/l) or saline showed a significant augmentation in pre-ischaemia-reperfusion hypoxic pulmonary vasoconstriction (57.7 +/- 6.0%, 82.7 +/- 28.8%, 95.2 +/- 36.6% and 45.95 +/- 10.53% respectively), an increase in albumin flux (0.35 +/- 0.04, 0.31 +/- 0.06, 0.29 +/- 0.04 and 0.33 +/- 0.02) and an increase in pre-ischaemia-reperfusion palmitic:linoleic acid ratio (0.64 +/- 0.08, 0.51 +/- 0.19, 0.5 +/- 0.04 and 0.17 +/- 0.07). Superoxide dismutase (2,750 i.u.) administered immediately before reperfusion prevented completely the changes in hypoxic pulmonary vasoconstriction (-0.3 +/- 5.4%), albumin flux (0.09 +/- 0.11) and palmitic:linoleic acid ratio (-0.06 +/- 0.12). In control lungs (2h of continuous perfusion), superoxide dismutase, catalase, desferrioxamine and saline did not affect hypoxic pulmonary vasoconstriction (5.5 +/- 4.9%, 1.0 +/- 3.1%, -5.1 +/- 1.8% and 3.0 +/- 6.6%). However, NG-nitro-L-arginine methyl ester significantly augmented hypoxic pulmonary vasoconstriction (275.1 +/- 39.3%). There was no effect of superoxide dismutase, catalase, desferrioxamine, NG-nitro-L-arginine methyl ester or saline in control lungs on albumin flux (0.10 +/- 0.04, 0.11 +/- 0.01, 0.1 +/- 0.01, 0.12 +/- 0.01 and 0.11 +/- 0.01 respectively) or palmitic:linoleic acid ratio (-0.08 +/- 0.08, 0.73 +/- 0.76, -0.03 +/- 0.12, 0.01 +/- 0.17 and 0.00 +/- 0.0 respectively). 3. We conclude that superoxide dismutase attenuates ischaemia-reperfusion-induced increases in albumin flux and hypoxic pulmonary vasoconstriction, and prevents consumption of linoleic acid in the isolated, blood-perfused rat lung.

Animals↗

PubMed1996

Plasma fatty acid changes and increased lipid peroxidation in patients with adult respiratory distress syndrome.

OBJECTIVE: There is a strong evidence that adult patients with acute respiratory distress syndrome (ARDS) are under severe oxidative stress, which leads to molecular damage. Using gas chromatography-mass spectrometry, our objective was to sequentially monitor changes, in intensive care unit (ICU) patients, characteristic of the oxidative loss of plasma unsaturated fatty acids and formation of the highly specific oxidation product of linoleic acid, 4-hydroxy-2-nonenal. DESIGN: Prospective, nonintervention, descriptive study. Limited statistics were applied to facilitate interpretation of the data. SETTING: ICU of a postgraduate teaching hospital. PATIENTS: Eighteen critically ill patients with an established diagnosis of ARDS requiring high FIO2 administered by mechanical ventilation were compared with ten normal, healthy controls and ten patients pre- and postcardiopulmonary bypass surgery at risk for developing ARDS. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Sixty percent of the patients with ARDS included in this study survived. Major changes in the plasma concentrations of fatty acids occurred in all patients during their stay in the ICU. Percentage decreases in plasma linoleic acid concentrations were accompanied by increases in plasma oleic and palmitoleic acid concentrations. Circulating linoleic acid concentrations were significantly (p = .0001) lower in patients with ARDS than in the two control groups. The patients with ARDS who did not survive had lower (p = .0056) plasma oleic acid values than normal healthy controls and patients at risk for ARDs as a consequence of undergoing cardiopulmonary bypass surgery. Changes in palmitoleic acid, however, did not reach significance within the different groups studied. Patients with ARDS showed higher plasma concentrations of 4-hydroxy-2-nonenal (0.433 +/- 0.048 vs. 0.523 +/- 0.069 nmol/mL plasma for survivors and nonsurvivors, respectively) when compared with normal healthy controls (0.205 +/- 0.03 nmol/mL, p = 0.0001) and cardiopulmonary bypass patients at risk for developing ARDS (0.279 +/- 0.027 nmol/mL, p = .034 prebypass). CONCLUSIONS: During intensive care treatment, patients with ARDS decrease their percentage plasma concentrations of total plasma linoleic acid, but increase their percentage concentrations of oleic and palmitoleic acids. As plasma linoleic acid concentrations decreased, there was usually an increase in plasma 4-hydroxy-2-nonenal values, one of its specific peroxidation products, suggestive of severe oxidative stress leading to molecular damage to lipids.

Adolescent↗

PubMed1995

The effect of cardiopulmonary bypass on intestinal and pulmonary endothelial permeability.

STUDY OBJECTIVE: To quantify simultaneously the pulmonary and gastrointestinal (GI) damage that occurs during uncomplicated surgery requiring cardiopulmonary bypass (CPB), and to examine the relationships between markers of such damage. DESIGN: Prospective, open. SETTING: Adult ICU of a national referral hospital. PATIENTS: Twenty patients undergoing elective CPB surgery. MEASUREMENTS AND RESULTS: Pulmonary vascular injury was assessed using the protein accumulation index (PAI), a double isotope technique specific for high permeability pulmonary edema. The relationships of the PAI with percent neutrophils in bronchoalveolar lavage (BAL), serum, and BAL myeloperoxidase (MPO), and bypass time were examined. Splanchnic vascular injury was assessed using tonometry to measure intramucosal pH (pHi) and the ratio of absorbed lactulose to L-rhamnose (L/R ratio) to determine gut mucosal permeability. Positive correlations were observed between bypass time and PAI (r = 0.64, p < 0.01), percent neutrophils in the postoperative BAL and PAI (r = 0.51, p < 0.05), and postoperative serum MPO and PAI (r = 0.77, p < 0.001). The L/R ratio rose significantly following CPB from 0.04 +/- 0.01 in controls to 0.48 +/- 0.05 (p < 0.0001). The L/R ratio in patients who developed a low pHi was 0.59 +/- 0.06 compared with 0.32 +/- 0.07 in those whose pHi remained normal (p < 0.05). No significant correlation between bypass time and pHi (r = -0.3, p = 0.33), bypass time and L/R ratio (r = 0.27, p = 0.26), PAI and L/R ratio (r = 0.2, p = 0.42), PAI and pHi (r = -0.34, p = 0.16), postoperative serum MPO and L/R ratio (r = 0.03, p = 0.90), or postoperative serum MPO and pHi (r = -0.10, p = 0.67) could be demonstrated. CONCLUSIONS: Pulmonary and GI injury are detectable following uncomplicated CPB. The absence of any relationship between the respective markers of dysfunction suggests that differing pathologic processes are responsible.

Aortic Valve↗

PubMed1994

Ferrous ion formation by ferrioxamine prepared from aged desferrioxamine: a potential prooxidant property.

The siderophore desferrioxamine (DEFOM) binds ferric ions in a 1:1 ratio resulting in a ferrioxamine (FOM) complex. When DEFOM is stored or heat degraded, the resulting FOMD undergoes an autoreduction with the transfer of electrons to the bound ferric ions forming ferrous ions which react with Ferrozine to yield a pink-coloured complex absorbing at 562 nm. Heat-aged DEFOM forms a FOMD complex with an absorption maxima changing from 432 nm to 441 nm. When the autoreduced FOMD complex is placed in a phosphate buffer at pH 7.4, ferrous ions autoxidise transferring electrons to molecular oxygen to form superoxide and hydrogen peroxide. Fenton chemistry leading to the formation of hydroxyl radicals can then occur. Studies with a variety of reactive oxygen scavengers support a role for the hydroxyl radical in damage to the detector molecule deoxyribose. However, when EDTA is present, damage to deoxyribose is decreased and the radicals causing deoxyribose degradation no longer appear to be characteristic of the hydroxyl radical.

Deferoxamine↗

PubMed1994

Iron-binding affinity of bacterial vaccine polysaccharides which contain phosphodiester linkages as part of the polymer chain and of other polyphosphates, including DNA.

The interaction of iron (II) with bacterial polysaccharides, possessing phosphodiester bonds as part of their polymer chain, has been studied by equilibrium binding dialysis using atomic absorption spectrophotometry. Ferrous ions were found to bind with a stoichiometry of one per two phosphates and with a binding constant of about 2.5 x 10(3) M-1. Similar results, but with larger (ca 1 x 10(4) M-1) binding constants were observed with DNA. This interaction helps explain the depolymerization of polyphosphates which has been observed in the presence of iron salts, and highlights the need to avoid iron contamination of vaccines (and other substances) which contain phosphodiester bonds. The interaction may also be a means of iron sequestration in bacteria which possess these cell-surface polyphosphates.

Bacterial Vaccines↗

PubMed1994

Transient iron overload with bleomycin detectable iron in the plasma of patients with adult respiratory distress syndrome.

BACKGROUND: A retrospective study was conducted to evaluate iron status in plasma samples collected from five patients with the adult respiratory distress syndrome (ARDS) who had bleomycin detectable iron in at least one sample. Ten patients with ARDS with no evidence of bleomycin detectable iron and 10 healthy individuals served as controls. METHODS: Evidence of iron overload was established by measuring the percentage saturation of plasma transferrin. In each case the bleomycin assay for redox active, chelatable iron was used to measure plasma levels of non-transferrin bound iron in the low micromolar range; assays for total plasma iron and transferrin were performed to establish a diagnosis of transient iron overload. The effect of this on the ability of transferrin to act as a plasma antioxidant was assessed using two different assay systems. RESULTS: The five patients with evidence of transient iron overload (mortality 4/5) represented 33% of the total population of patients with ARDS (mortality 5/10) managed by the unit during the study period. All had low molecular mass iron detectable in their plasma and had clinical and biochemical evidence of multiorgan system failure as well as liver impairment. Compared with the ARDS and normal control populations, transferrin and albumin levels were low and the former failed to act as a plasma antioxidant in preventing free radical mediated damage to detector molecules. CONCLUSIONS: Patients with ARDS are thought to be under severe oxidative stress from their disease and from treatment with high inspired oxygen concentrations. A subgroup of patients with ARDS has been identified who displayed evidence of transient iron overload as a result of which their plasma iron binding antioxidant protection was greatly compromised. This finding must be considered a serious additional risk factor for oxidative stress.

Adult↗

PubMed1994

4-hydroxy-2-nonenal levels increase in the plasma of patients with adult respiratory distress syndrome as linoleic acid appears to fall.

Gas chromatograph-mass spectrometry has been applied to the analysis of plasma linoleic acid and one of its oxidation products, 4-hydroxy-2-nonenal (HNE), in adult patients with the acute respiratory distress syndrome (ARDS). Peak areas of total ion chromatograms showed there to be negative correlations between loss of linoleic acid and formation of HNE (measured by selective ion monitoring) in 7 out 10 patients studied. When HNE was quantitated by selective ion monitoring, with reference to a pure standard of HNE and an internal standard of nonanoic acid, ARDS patients showed significantly increased levels of HNE (0.412 +/- 0.023 nmol/ml) compared with normal healthy controls (0.205 +/- 0.018 nmol/ml).

Adult↗

PubMed1994

Oxidative damage to plasma proteins in adult respiratory distress syndrome.

There is evidence that patients with adult respiratory distress syndrome are under severe oxidative stress that leads to molecular damage. Oxidative stress appears to be inherent in the disease process as well as an unfortunate complication of essential treatment with oxygen. Eight critically ill patients with an established diagnosis of adult respiratory distress syndrome requiring high inspired oxygen concentrations administered by ultra high frequency jet ventilation, were studied. Three patients survived (38%). For the group as a whole, there was evidence of increased protein damage, measured on serial plasma samples as an increase in protein carbonyls (mean +/- SEM, 1.41 +/- 0.09 nmol/mg protein), compared with Intensive Care Unit (ICU) controls (1.24 +/- 0.09 nmol/mg protein), and normal healthy controls (0.940 +/- 0.04 nmol/mg protein). Protein thiol groups were decreased in the ARDS group (4.56 +/- 0.50 nmol/mg protein) compared with ICU controls (5.5 +/- 0.27 nmol/mg protein), and the normal healthy controls (6.55 +/- 0.52 nmol/mg protein). However, when ARDS patients were grouped as survivors and non-survivors, total plasma protein levels were lower in survivors (53.9 +/- 2.15 mg/ml) compared with non-survivors (78.2 +/- 4.68 mg/ml); but the protein thiol content was significantly higher (p = < 0.001) in survivors (6.24 +/- 0.09 nmol/mg protein) compared with non-survivors (3.56 +/- 0.16 nmol/mg protein). Serial plasma measurements of protein damage indicated two different patterns. Survivors had higher total plasma thiol values (protein corrected), which increased as the lung injury resolved, and failing protein carbonyl values. By contrast, non-survivors had low and failing protein thiols often accompanying rising carbonyls.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Proteins↗

PubMed1994

Linoleic acid and protein thiol changes suggestive of oxidative damage in the plasma of patients with adult respiratory distress syndrome.

Patients with the acute lung injury syndrome ARDS are under oxidative stress from the disease and from treatment with high inspired oxygen concentrations. Oxidative stress can lead to molecular damage by a variety of reactive oxygen intermediates generated in the lung. In the present study we sequentially monitor changes in plasma total lipid linoleic acid fatty acid levels, using GC-MS, and express these as a function of changes in plasma protein thiol values. In nine out of eleven ARDS patients there was a relationship between loss of protein thiols and loss of total lipid linoleic acid. In three patients changes in protein thiols preceded changes in total lipid linoleic acid by several days. Parallel decreases in plasma total lipid fatty acid esters of linoleic acid and protein thiols are suggestive of oxidative stress leading to molecular damage.

Blood Proteins↗