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R Stocker

Publications and source records attributed to R Stocker.

At least 127 records · Page 7Linked to original sources
PubMed1996

[Added work of breathing, respiratory pattern and determination of ventilator weaning readiness in inspiratory pressure support and and automatic tube compensation].

We measured the ventilatory pattern and additional work of breathing (WOBadd) at three different levels of inspiratory pressure support [IPS 5, 10, 15 mbar above positive end-expiratory pressure (PEEP)] and in a new ventilatory mode, automatic tube compensation (ATC), in nine operative patients without lung injury nine patients ventilated for several following acute respiratory insufficiency (ARI). In ATC, endotracheal tube resistance is compensated automatically by means of closed-loop control of the calculated tracheal pressure. Pressure support in this mode, i.e. airway pressure above PEEP, is equal to the actual flow-dependent pressure drop across the endotracheal tube (ETT). Airway pressure rises at the beginning of inspiration and falls towards the end. As the tube resistance of ETT seriously hinders expiration and can cause desynchronization between ventilator and patient, airway pressure is reduced below PEEP during expiration in the same way as it is increased during inspiration. The result is a near-constant tracheal pressure at PEEP both during inspiration and during expiration. This mode could be best termed as "electronic extubation". The most striking difference between the postoperative patients and the ARI patients was their minute ventilation (17.8 +/- 1.85 l/min in ARI patients vs 7.3 +/- 3.1 l/min in the postoperative patients). In the postoperative patients augmentation of IPS from 5 to 15 mbar induced a steady increase in tidal volume (VT) and a consecutive decrease in respiratory rate (rr) compared with ATC (VTATC,postop = 463 +/- 78 ml; rrATC,postop = 16 +/- 4 min-1; VTIPS5.postop = 505 +/- 79 ml; rrIPS5,postop = 15 +/- 4 min-1; VTIPS10,postop = 562 +/- 86 ml; rrIPS15,postop = 14 +/- 4 min-1; VTIPS15.postop = 660 +/- 151 ml; rrTPS15,postop = 12 +/- 4 min-1), whereas the augmentation of IPS of 5 and 10 mbar in the ARI patients could not compensate for the increase in rr and the decrease in VT, after switching from ATC to IPS (VTATC,ARI 724 +/- 308 ml, rrATC,ARI = 24 +/- 6 min-1; VTIPS5,ARI = 649 +/- 315 ml; rrIPS5,ARI = 27 +/- 8 min-1; VTIPS10,ARI = 653 +/- 353 ml; rrIPS10,ARI = 25 +/- 8 min-1: Even IPS 15 was not able to reestablish VT at the values observed during ATC (VTIPS15,ARI = 680 +/- 312 ml). During ATC WOBadd was small in both postoperative and ARI patients (WOBadd,ATC,postop = 93 +/- 36 mJ/l, WOBadd,ATC,ARI = 116 +/- 72 mJ/l). In the postoperative patients, an inspiratory pressure support of 5 mbar was not sufficient to compensate WOBadd compared with ATC. However, IPS 10 and 15 mbar were able to compensate for WOBadd (WOBadd,ATC5.postop WOBadd,IPS5,postop = 189 +/- 77 mJ/l; WOBadd,IPS10,postop = 55 +/- 30 mJ/l; WOBadd,IPS15,postop = 21 +/- 11 mJ/l). In the ARI patients an IPS 5, 10 or 15 mbar was not sufficient to compensate for WOBadd (WOBadd,IPS 5,ARI = 1126 +/- 262 mJ/l; WOBadd,IPS 10,ARI 863 +/- 253 mJ/l; WOBadd,IPS15,ARI 763 +/- 298 mJ/l). Under ATC, WOBadd was only 15% of WOBadd under IPS of 15 mbar. All but two patients were successfully extubated after the investigation. These two patients were not extubated because they were dependent on an FIO2 > 0.5. Our results strongly indicate that ventilatory dependence in ARI patients may be caused by the ETT rather than by mechanical dysfunction of the lung. ATC is a very helpful mode to use in distinguishing between ventilatory failure caused by ETT and real ventilatory dependence.

Adult↗
PubMed1996

Radical-initiated lipid peroxidation in low density lipoproteins: insights obtained from kinetic modeling.

We present kinetic models of various complexity for radical-initiated lipid peroxidation in low density lipoproteins (LDL). The models, comprised of simultaneous differential equations programmed in Mathematica, were used to evaluate the concentration profiles of the reactants of interest. Single-phase reaction schemes describing lipid peroxidation and antioxidation according to the "conventional" and tocopherol-mediated peroxidation (TMP) model were simulated for conditions of low and high radical fluxes produced by thermolabile azo initiators. The results show that the particular dependencies of the rates of lipid peroxidation (Rp) on the rates of initiation (Ri) for the two reaction schemes were accurately predicted by the simulations. Both models qualitatively predicted inhibition of lipid peroxidation in the presence of alpha-tocopherol (alpha-TOH) under high radical flux conditions, suggesting that both can describe inhibited lipid peroxidation in solution under these conditions. TMP, but not the conventional model, could also predict the experimentally observed complex behavior of LDL lipid peroxidation induced with different concentrations of azo initiators. Specifically, TMP faithfully reproduced the observed kinetic chain length of lipid peroxidation of > > 1 at low and < < 1 at high concentration of the initiator (i.e., 0.2 and 10 mM, respectively for LDL at 1 mumol apoB-100/L) during the alpha-TOH-containing period of oxidation. It also demonstrated the experimentally observed nondependence of RpTMP on Ri. Kinetic analysis of radical generation and initiation of lipid peroxidation in an extended, two-compartment model of TMP showed that phase separation of bimolecular reactions in a suspension of LDL particles can lead to a approximately 400-fold increase in the rate of lipid hydroperoxide formation. The experimentally observed co-antioxidant action of water-soluble ascorbate and lipid-soluble ubiquinol-10 were verified using this model. A simple biophysical model constituting the reactions of TMP and incorporating the compartmental nature of an LDL suspension is proposed. Together, the results demonstrate that TMP is the only model that fits the experimental data describing the early stages of LDL lipid peroxidation under various oxidizing conditions. The implications of our findings are discussed in relation to atherogenesis and a recently proposed alternative model of LDL lipid peroxidation (Abuja and Esterbauer (1995) Chem. Res. Toxicol. 8, 753).

Antioxidants↗
PubMed1996

Different pattern of local and systemic release of proinflammatory and anti-inflammatory mediators in severely injured patients with chest trauma.

BACKGROUND: Excessive release of proinflammatory cytokines has been involved in pathogenesis of acute respiratory distress syndrome. DESIGN: Since injured patients with chest trauma reveal a high risk for posttraumatic acute respiratory distress syndrome, local and systemic release of proinflammatory cytokines and their naturally occurring inhibitors were determined in the early posttraumatic period. MATERIALS AND METHODS: Proinflammatory and anti-inflammatory mediators were measured in plasma and bronchoalveolar lavage fluid (BALF) from 16 patients with multiple injuries including severe chest injury (Injury Severity Score of 34.4 +/- 2.3 points) and compared with healthy volunteers (n = 17). RESULTS: Tumor necrosis factor-alpha was detectable neither in plasma nor in BALF. Interleukin-1beta and interleukin-8 were significantly increased in BALF from injured patients, while plasma levels were similar in both groups. Soluble tumor necrosis factor receptors p55 and p75 and interleukin-1ra were markedly elevated in plasma (p < or = 0.01) and BALF (p < or = 0.001) from injured patients compared with controls. CONCLUSION: Highly increased concentrations of proinflammatory cytokines in BALF, but not in circulation, indicate a strong local inflammatory response early after multiple injuries combined with chest injury rather than severe systemic inflammation. In contrast, anti-inflammatory mechanisms seem to be activated locally and systemically.

Adult↗
PubMed1996

Cosupplementation with coenzyme Q prevents the prooxidant effect of alpha-tocopherol and increases the resistance of LDL to transition metal-dependent oxidation initiation.

There is considerable interest in the ability of antioxidant supplementation, in particular with vitamin E, to attenuate LDL oxidation, a process implicated in atherogenesis. Since vitamin E can also promote LDL lipid peroxidation, we investigated the effects of supplementation with vitamin E alone or in combination with coenzyme Q on the early stages of the oxidation of isolated LDL. Isolated LDL was obtained from healthy subjects before and after in vitro enrichment with vitamin E (D-alpha-tocopherol, alpha-TOH) or dietary supplementation with D-alpha-TOH (1 g/d) and/or coenzyme Q (100 mg/d). LDL oxidation initiation was assessed by measurement of the consumption of alpha-TOH and cholesteryl esters containing polyunsaturated fatty acids and the accumulation of cholesteryl ester hydroperoxides during incubation of LDL in the transition metal-containing Ham's F-10 medium in the absence and presence of human monocyte-derived macrophages (MDMs). Native LDL contained 8.5 +/- 2 molecules of alpha-TOH and 0.5 to 0.8 molecules of ubiquinol-10 (CoQ10H2, the reduced form of coenzyme Q) per lipoprotein particle. Incubation of this LDL in Ham's F-10 medium resulted in a time-dependent loss of alpha-TOH with concomitant stoichiometric conversion of the major cholesteryl esters to their respective hydroperoxides. MDMs enhanced this process. LDL lipid peroxidation occurred via a radical chain reaction in the presence of alpha-TOH, and the rate of this oxidation decreased on alpha-TOH depletion. In vitro enrichment of LDL with alpha-TOH resulted in an LDL particle containing sixfold to sevenfold more alpha-TOH, and such enriched LDL was more readily oxidized in the absence and presence of MDMs compared with native LDL. In vivo alpha-TOH-deficient LDL, isolated from a patient with familial isolated vitamin E deficiency, was highly resistant to Ham's F-10-initiated oxidation, whereas dietary supplementation with vitamin E restored the oxidizability of the patient's LDL. Oral supplementation of healthy individuals for 5 days with either alpha-TOH or coenzyme Q increased the LDL levels of alpha-TOH and CoQ10H2 by two to three or three to four times, respectively. alpha-TOH-supplemented LDL was significantly more prone to oxidation, whereas CoQ10H2-enriched LDL was more resistant to oxidation initiation by Ham's F-10 medium than native LDL. Cosupplementation with both alpha-TOH and coenzyme Q resulted in LDL with increased levels of alpha-TOH and CoQ10H2, and such LDL was markedly more resistant to initiation of oxidation than native or alpha-TOH-enriched LDL. These results demonstrate that oral supplementation with alpha-TOH alone results in LDL that is more prone to oxidation initiation, whereas cosupplementation with coenzyme Q not only prevents this prooxidant activity of vitamin E but also provides the lipoprotein with increased resistance to oxidation.

Cell Line↗
PubMed1996

[Percutaneous tracheostomy: a minimally invasive procedure on the intensive care unit].

INTRODUCTION: In 1985 Ciaglia [2] introduced percutaneous tracheostomy as a minimal invasive procedure. Since October 1991 percutaneous tracheostomy has been performed in 40 patients at the University Hospital in Zürich. This paper compares our complication rate using the Cook-system with the conventional open technique in the literature. MATERIALS AND METHODS: 40 patients, mean 53.6 years of age, 26 male, 14 female. Indications were: inability to perform sufficient bronchial suction, recurrent atelectasis, long term ventilation, difficult or prolonged weaning (i.e. neurotrauma). The tracheal tube is introduced following stepwise dilatation after making skin incision, according to the Seldinger technique. RESULTS: In all patients tracheostomy was carried out as an elective procedure in the Intensive Care Unit. Time between primary intubation and tracheostomy varied between O and 51 days, mean 15.9 days. Complications occurred in 5/40 cases (12.5%), with only one serious complication: the tracheostoma was misplaced, requiring intubation. Beside that we have seen 2 minor hematomas, 1 bradycardia and 1 subcutaneous emphysema. CONCLUSIONS: Percutaneous tracheostomy can be safely performed at bedside in the ICU. The method is simple and has a lower complication rate compared to the conventional open technique as reported by Hazard [7] and Griggs [8].

Adult↗
PubMed1996

A rapid and simple screening test for potential inhibitors of tocopherol-mediated peroxidation of LDL lipids.

We report a rapid and convenient method for screening potential inhibitors of the initiation of low density lipoprotein (LDL) lipid peroxidation. The method uses positively and negatively charged micelles of either cetyltrimethyl ammonium chloride or sodium dodecyl sulfate with added alpha-tocopherol. It is based on the capacity of an antioxidant to attenuate alpha-tocopheroxyl radicals, generated by irradiation of the alpha-tocopherol-containing micelles with UV light, and measured directly by electron spin resonance spectroscopy. To establish the reliability of the method, we compared the alpha-to-copheroxyl radical attenuating ability (TRAA) of 53 natural and synthetic potential antioxidants with their respective ability to inhibit the early stages of LDL lipid peroxidation initiated by a low flux of water-soluble peroxyl radicals. The relationship between the measured TRAA and corresponding LDL antioxidation activity was highly significant (P < 0.00005, Rank test). Thus, the potency of a co-antioxidant for LDLs alpha-tocopherol could be predicted with > 98% probability by the TRAA test alone. The results suggest that this relatively simple method represents an effective and simple screening test that can be used for large numbers of potential inhibitors of the early stages of LDL lipid oxidation.

Adult↗
PubMed1996

Oxidation of LDL by recombinant human 15-lipoxygenase: evidence for alpha-tocopherol-dependent oxidation of esterified core and surface lipids.

Various lipoxygenases (LO) oxidize low density lipoprotein (LDL) in vitro and 15-LO has been implicated in the development of atherosclerosis in vivo. Direct oxidation of phospholipids (PL) and cholesteryl esters (CE) by LO has been proposed as a mechanism whereby these enzymes cause or contribute to LDL lipid peroxidation. Herein we show that the extent to which recombinant human 15-LO (rhLO) caused peroxidation of LDL's esterified core and surface lipids depended on, and directly related to, the alpha-tocopherol (alpha-TOH) content of the lipoprotein. Thus, CE and PL of in vivo alpha-TOH-depleted LDL, isolated from a patient with familial isolated vitamin E deficiency, were resistant to oxidation by rhLO, whereas those in alpha-TOH-containing LDL from the same patient receiving vitamin E supplements readily oxidized. The extent to which rhLO caused oxidation of CE and PL directly and linearly correlated with LDL's content of vitamin E, as demonstrated by studies with in vitro alpha-TOH-depleted lipoproteins. The geometric isomers of oxidized cholesteryl linoleate formed in LDL during oxidation initiated by rhLO, matched those obtained during non-enzymic, peroxyl radical-initiated oxidation of LDL whilst alpha-TOH was present. Ascorbate, an efficient co-antioxidant for alpha-TOH, completely prevented rhLO-initiated oxidation of LDL's CE, but did not inhibit rhLO-mediated oxidation of unesterified linoleate. These results are inconsistent with direct oxidation of LDL esterified lipids by rhLO. Isolated LDL contained free fatty acids (FFA), and its exposure to rhLO caused a rapid formation of linoleate hydroperoxide. To reconcile these data, we propose that during rhLO-initiated oxidation of LDL, enzymic oxidation of FFA preceeds the oxidation of CE and PL, which occurs largely via a tocopherol-dependent process.

Arachidonate 15-Lipoxygenase↗
PubMed1995

Inverse deuterium kinetic isotope effect for peroxidation in human low-density lipoprotein (LDL): a simple test for tocopherol-mediated peroxidation of LDL lipids.

alpha-Tocopherol (alpha-TOH) can act as a pro- or antioxidant for isolated ubiquinol-10-free human low density lipoprotein (LDL). We demonstrate that alpha-TOH is a more potent pro-oxidant than other forms of vitamin E for LDL peroxidation initiated by mild fluxes of aqueous peroxyl radicals and low concentrations of Cu2+. A simple deuterium exchange test shows that alpha-TOH switches from pro- to anti-oxidant at Cu2+:LDL ratios > 2.5. The results suggest that this test may be useful to distinguish 'inhibited' peroxidation of emulsion lipids propagated via the lipid peroxyl radical from that mediated via the antioxidant radical.

Adult↗
PubMed1995

[Isolated lung transplantation--evaluation of patients and initial results].

Between November 1992 and May 1994 we performed 10 single and 5 double lung transplants in patients with end-stage lung diseases due to lymphangioleiomyomatosis (4), cystic fibrosis (3), pulmonary hypertension (3), pulmonary fibrosis (3) and chronic obstructive lung disease (2). In the 13 patients (87%) surviving for median 245 (19-567) days, FEV1 improved from median 640 ml to 1410 ml and the 12-minute walk distance from median 315 to 1100 meters. 10 patients (77%) enjoy a good or even excellent quality of life. 2 patients died 11 and 62 days postoperatively, due to multi-organ failure and invasive pulmonary aspergillosis respectively. The main postoperative problems are fungal and cytomegalovirus infections and chronic rejection in the form of bronchiolitis obliterans. In Switzerland as elsewhere, lung transplantation has become an established modality for the management of end-stage diseases of the lung and pulmonary circulation.

Adolescent↗
PubMed1995

Prevention of tocopherol-mediated peroxidation in ubiquinol-10-free human low density lipoprotein.

Oxidation of low density lipoprotein (LDL) may be involved in the development of atherosclerosis. It has recently been shown that alpha-tocopherol (alpha-TOH) can act either as an antioxidant or prooxidant for isolated low density lipoprotein (LDL). In the absence of an effective co-antioxidant, alpha-TOH is a prooxidant and this activity is evidently due to reaction of the alpha-tocopheroxyl radical (alpha-TO.) with the LDL's polyunsaturated lipids (Bowry, V. B., and Stocker, R. (1993) J. Am. Chem. Soc. 115, 6029-6045). Herein we examined the effectiveness of selected natural and synthetic radical scavengers as co-antioxidants for inhibiting peroxyl radical-induced peroxidation in LDL that is devoid of ubiquinol-10 (an effective endogenous co-antioxidant) but still contains most of its natural complement of alpha-TOH. Various quinols, catechols, and aminophenols, as well as ascorbate, 6-palmityl ascorbate, and bilirubin, were very effective co-antioxidants under our test conditions, whereas ordinary phenolic antioxidants, including short-tailed alpha-TOH homologues, were less effective. Reduced glutathione, urate, and Probucol were ineffective. These findings confirm that the prooxidant activity of alpha-TOH in LDL relies heavily on the segregation of water-insoluble radicals (particularly alpha-TO.) into individual LDL particles, since it was those compounds that are expected to either irreversibly reduce alpha-TO. or accelerate the diffusion of radicals between particles which most effectively inhibited the tocopherol-mediated phase of peroxidation. Theoretical and practical implications of these findings are discussed, as is their relevance to the "LDL oxidation" hypothesis of atherogenesis.

Bilirubin↗
PubMed1995

[Isolated lung transplantation].

Over the last 10 years, single and bilateral lung transplantation has developed from an experimental technique to a valid therapy for patients with end-stage pulmonary or pulmonary-vascular disease. The main reasons for this progress are better defined selection criteria, improved operative technique and organ preservation, optimized peri- and postoperative management and more precise immunosuppressive and antiinfective therapy. Since 1983 more than 3000 lung transplantations have been performed worldwide with a 1- and 3-year survival rate of 70-90% and 60-70% respectively. In Switzerland 41 lung transplantations have been performed since 1992 with a 1-year survival rate of more than 80%. Indications, technique, treatment and results are discussed.

Adult↗
PubMed1995

[An unusual case of gunshot wound to the head].

We are going to present a special case of head injury caused by a gunshot. In this case it resulted in a fracture of the skull, but the bullet did not penetrate the skull. It was deflected by the bone, leaving the body at an angle. But bone fragments, acting as secondary bullets, penetrated the brain. In spite of a massive cerebral trauma and brain injury, no retrograde amnesia could be diagnosed. The patient recovered to such an extent, that he could return to his former job. Special characteristics of head injuries caused by bullets will be referred to.

Adult↗
PubMed1995

Cholesterylester hydroperoxide reducing activity associated with isolated high- and low-density lipoproteins.

Exposure of isolated high-(HDL) and low-density lipoproteins (LDL) to aqueous peroxyl radicals generated from a thermo-labile azo-compound resulted in immediate formation of cholesteryllinoleate hydroxide (Ch18:2-OH) in addition to hydroperoxides of cholesteryllinoleate (Ch18:2-OOH) and phospholipids. Ch18:2-OH was also formed in peroxyl radical-oxidizing human plasma devoid of ascorbate or low molecular weight compounds or isolated lipoproteins in the presence of desferrioxamine. In contrast, peroxyl radical-mediated oxidation of HDL or LDL lipid extracts or detergent-solubilized lipoproteins resulted in the formation of Ch18:2-OOH without concomitant formation of Ch18:2-OH. Heat treatment of the isolated lipoproteins prior to oxidation greatly reduced Ch18:2-OH formation. Compared to the concentrations of Ch18:2-OOH accumulating, formation of Ch18:2-OH was more pronounced in oxidizing HDL than LDL isolated from the same blood donor. The levels of Ch18:2-OH detected after prolonged oxidation periods were independent of the radical flux to which the lipoproteins were exposed. In the absence of peroxyl radical generator, [3H]Ch18:2-OOH associated with HDL was converted readily and in a biphasic manner into [3H]Ch18:2-OH upon incubation at 37 but not 4 degrees C. LDL-associated [3H]Ch18:2-OOH were also reduced, albeit with an initial reaction rate approximately 10 times slower than that observed with labelled HDL. Together, the results show that cholesterylester hydroxides are formed during (peroxyl) radical-mediated oxidation of isolated intact HDL and LDL under transition metal-free conditions. The findings suggest the presence of a hydroperoxide reducing activity in isolated human lipoproteins, particularly HDL.

Cholesterol Esters↗
PubMed1995

Vitamin C redox reactions in blood of normal and malaria-infected mice studied with isoascorbate as a nonisotopic marker.

It has been suggested that the host antimalarial response depends in part on phagocyte-derived oxidants and that the parasite itself exerts an oxidative stress on its erythrocytic environment. Intraerythrocytic malaria parasites are particularly susceptible to being damaged by oxidative drugs, several of which are under development as chemotherapeutic agents. Thus the antioxidant status and associated regulatory mechanisms of the blood during malaria infection are of great interest. The important antioxidant ascorbate (AH-) and isoascorbate (IAH-), an isomer that does not occur naturally in animals, were found to have similar redox properties. We therefore assessed the usefulness of IAH- as a marker for studies of AH- handling in vivo and in vitro under normal conditions and in murine malaria infection. DHIA added to whole blood from normal or Plasmodium vinckei-infected mice in vitro was rapidly taken up into blood cells and reduced to IAH-. Intracellular IAH- derived from the exogenous DHIA was released into the plasma by blood cells from malaria-infected mice but not those from normal mice. Uptake and reduction of DHIA had no effect on plasma or cellular levels of AH- under these conditions. IAH- injected i.v. into either normal or P. vinckei-infected mice was rapidly cleared in both cases and led to an increase in plasma levels of AH-; this suggested displacement of the latter from some intracellular site, presumably not associated with blood cells. DHIA administered as an intravascular bolus into either normal or malaria-infected mice was rapidly reduced. However, in contrast to the in vitro situation, the concentration of plasma IAH- derived from the injected DHIA was approximately the same in both the infected and control animals. The IAH- so formed disappeared quickly from the plasma. Intravenous injection of DHIA into malaria-infected mice caused a rapid, prolonged increase in the proportion of plasma vitamin C in the form of DHA, whereas in uninfected mice there was a transient decrease in plasma DHA followed by normalisation. The changes in plasma AH- and DHA following IV injection of a single dose of DHA closely paralleled those seen after DHIA administration. These observations indicate that: (i) blood cells from normal and malaria-infected mice take up and reduce DHIA in a similar fashion, but they have different ways of handling the resulting IAH-; (ii) cells other than blood cells are important in the reduction of plasma DHIA and DHA in vivo; (iii) malaria-infected mice are less capable of handling oxidative challenge than normal ones; (iv) in some circumstances IAH- and DHIA may be useful nonisotopic markers for studies of vitamin C handling in vitro and in vivo.

Animals↗
PubMed1995

Is alpha-tocopherol a reservoir for alpha-tocopheryl hydroquinone?

The products of oxidation of the alpha-tocopherol model compound, 2,2,5,7,8-pentamethyl-6-chromanol (PH) by t-butyl hydroperoxide in chloroform varied with the amount of water present. In the presence of a trace of water, the main products were the spirodimer (PSD) and spirotrimer (PST). As the content of water increased, the main product became 2-(3-hydroxy-3-methylbutyl)-3,5,6-trimethyl-1,4-benzoquinone (PQ). Oxidation of PH in aqueous liposome suspension also produced PQ as the major product. These results suggested that, in aqueous solutions, the major oxidation product of PH would be PQ and of alpha-tocopherol (TH) would be alpha-tocopheryl quinone (TQ). The ease of reduction of PQ and TQ was studied in chemical and biological systems. PQ, TQ, and ubiquinone-10 (UQ) were rapidly reduced to their respective hydroquinones (PQH2, TQH2, and UQH2) at pH 7.3 by NADH plus FAD. Whole blood reduced PQ rapidly at 37 degrees C to PQH2 but did not reduce TQ to TQH2. Human peripheral blood mononuclear cells took up TQ from a bovine serum albumin complex and reduced it to TQH2. Ingestion of TQ (350 mg) by one of us (PSK) resulted in the formation of TQH2 during a 5 h period. These results demonstrate that several biological systems are able to reduce TQ to TQH2 and that it is a reaction that may occur normally in vivo.

Blood↗
PubMed1995

Oxidation of parenteral lipid emulsion by ambient and phototherapy lights: potential toxicity of routine parenteral feeding.

Vitamin E can be a prooxidant in isolated lipoprotein suspensions. Because lipid emulsions used in parenteral nutrition are lipoprotein-like suspensions rich in polyunsaturated fatty acids and vitamin E, we hypothesized that vitamin E may act as a prooxidant in lipid emulsions, as it is in lipoprotein suspensions. We therefore exposed an intravenously administered lipid emulsion (Intralipid) to a single spotlight commonly used in the treatment of neonatal jaundice, and measured the formation of triglyceride hydroperoxides by using high-performance liquid chromatography with postcolumn chemiluminescence detection. Concentrations of these hydroperoxides in different batches of fresh intralipid were usually approximately 10 mumol/L but increased up to 60 times after exposure to phototherapy light for a period of 24 hours, even though significant amounts of vitamin E were present at the end of the exposure. Triglyceride hydroperoxides were formed during phototherapy light exposure whether the intralipid was in plastic tubing used routinely for infusion or in glass containers. Ambient light also caused significant peroxidation of the formula lipids, although to a much lesser extent than observed with phototherapy light. For infants in the neonatal intensive care unit who were receiving intralipid but not phototherapy, solutions being infused at the end of 24 hours contained a mean of 40 mumol/L hydroperoxides. For infants receiving phototherapy, the mean was 97 mumol/L. Phototherapy light-induced formation of triglyceride hydroperoxides was prevented by covering the intralipid with aluminum foil or supplementation with sodium ascorbate before light exposure. We conclude that intralipid is highly susceptible to oxidation and that elevated levels of oxidized lipids can be formed during its clinical use, especially when intralipid infusion is combined with phototherapy. Because lipid hydroperoxides are cytotoxic and can cause adverse effects, inadvertent infusion of rancid intralipid may add to the numerous problems encountered by premature neonates.

Aluminum↗