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J C Lavoie

Publications and source records attributed to J C Lavoie.

At least 19 recordsLinked to original sources

Increased urinary peroxides in newborn infants receiving parenteral nutrition exposed to light.

OBJECTIVES: To determine whether peroxide loads infused with total parenteral nutrition (TPN) are fully quenched by premature infants. STUDY DESIGN: After baseline urine peroxide levels were established, the effect of various parenteral regimens was correlated with urinary peroxide levels in 64 newborn infants </=32 weeks' gestation. This correlation was achieved with the properties of light and of various parenteral nutrient admixtures on the generation of peroxides. Peroxides were measured by the ferrous oxidation of xylenol orange. RESULTS: The level of urinary peroxides measured for infants given a fat-free TPN regimen unprotected from light (74.5 +/- 15.3 micromol/L) was similar to levels found in infants given a lipid-containing regimen (88.1 +/- 10.3 micromol/L). When photoprotected, the fat-free alimentation was associated with peroxide levels (28.8 +/- 2.8 micromol/L) similar to those measured before TPN (27.6 +/- 4.1 micromol/L). CONCLUSIONS: Because urine peroxide levels are changed by various nutritional procedures, antioxidant systems of premature infants are unable to fully quench the oxidant load associated with TPN.

Amino Acids↗

Contribution of multivitamins, air, and light in the generation of peroxides in adult and neonatal parenteral nutrition solutions.

OBJECTIVE: To compare the concentrations of peroxides between adult and neonatal total parenteral nutrition (TPN) solutions in response to protection against inducers of peroxidation such as multivitamins and exposure to light or air. METHODS: Peroxide concentrations were measured in freshly prepared adult and neonatal solutions of fat-free TPN in four settings: with or without an air inlet, and protected or unprotected from ambient light. An oxygen washout was performed by exposing a fat-free neonatal TPN solution to a continuous flow of nitrogen. RESULTS: Globally, light was the main inducer of peroxides in adult and neonatal solutions. However, in adult solutions the concentration of peroxides remained <15 micromol/L, while in neonatal solutions the peroxide concentration was as high as 300 micromol/L in ambient light. Although the oxygen washout did prevent the generation of peroxides, avoiding air inlet was not as effective as was photoprotection in decreasing the important peroxide load in the neonatal TPN solution. CONCLUSIONS: The higher concentration of peroxides found in neonatal solutions compared with adult solutions is explained by the differences in nutrient composition between the two solutions. Contamination of parenteral solutions by air during compounding accounts for the photoinduced generation of peroxides in TPN solutions. It is more convenient to protect TPN solutions from light exposure after the admixture of the multivitamin solution than to avoid contact with oxygen.

Adult↗

N-acetylcysteine in pig liver transplantation from non-heart-beating donors.

Lipid peroxidation due to oxygen free radicals (OFR) seems to play a major role in loss of liver graft viability after warm ischemia, preservation, and transplantation. N-acetylcysteine (NAC) is an antioxidant that has a direct effect on OFR, and is also a glutathione precursor, another antioxidant. This study was designed to evaluate the efficacy of NAC in preventing ischemia-reperfusion damage of liver grafts harvested from non-heart-beating donors. Liver transplantation was performed on pigs divided into five groups: group 1 (control group; n=5) received livers from heart-beating donors; livers were subjected to 30 min of warm ischemia in groups 2 (n=3, no NAC) and group 3 (n=3; NAC treatment); warm ischemia time lasted 60 min in groups 4 (n=4; no NAC) and 5 (n=5; NAC treatment). Studied parameters included graft survival for more than 3 days, aspartate aminotransferase plasma levels, liver histology, and hepatic total glutathione concentrations. Graft survival was 100% in groups 1, 2, and 3, 0% in group 4, and 20% in group 5. NAC treatment did not influence initial mean aspartate aminotransferase release which was greater in warm ischemic livers than in controls. NAC treatment had no effect on liver hepatic total glutathione after reperfusion of animals receiving warm ischemic grants. Finally, no effect on liver histology was observed with NAC treatment. Our study suggests that in liver transplantation from non-heart-beating donors, NAC has no effect in both graft viability and lipid peroxidation. The role of OFR in primary dysfunction of transplanted warm ischemic livers remains controversial.

Acetylcysteine↗

Glutathione synthetic activity in the lungs in newborn guinea pigs.

Depletion of glutathione, a key antioxidant, accelerates lung injury. Glutathione concentrations are reduced significantly in premature infants with respiratory distress syndrome, leaving them at greater risk of bronchopulmonary dysplasia. A study was designed to verify if the increased glutathione synthetic activity observed in oxygen-dependent and ventilated newborn infants was caused by their postsurgical state. Our objective was to evaluate the role of a general surgical procedure as a factor affecting lung glutathione. One-day-old guinea pig pups, a well characterized animal model for the study of neonatal lung disease, were divided between those undergoing a standardized surgical procedure and those that did not. The pups were fed by their mother. After 4 days the lungs were sampled to determine total glutathione content, activities of gamma-glutamyltranspeptidase, glutathione peroxidase, and reductase as well as the glutathione synthetic activity. The surgical procedure was associated with a specific stimulatory effect limited to glutathione synthetic activity (p < 0.02) leading to an increased (p < 0.02) pulmonary glutathione content. Glutathione concentration was significantly correlated (r2 = 0.67) with the synthetic activity. We concluded that in this animal model an invasive procedure such as a general surgical procedure affects lung glutathione metabolism in a fashion similar to that of hyperoxia. In the lungs, the synthetic activity is a stronger determinant of glutathione concentrations than the activities of the other enzymes involved in maintaining glutathione levels.

Animals↗

Survival of guinea pig pups in hyperoxia is improved by enhanced nutritional substrate availability for glutathione production.

The imbalance between high oxidant loads and immature antioxidant defenses is associated with long-term complications of prematurity. Glutathione is a central element among the antioxidants. Depletion of pulmonary glutathione accelerates the development of oxygen-induced lung injury in neonatal animal models. After the observation that newborn infants exposed to oxygen have low glutathione levels, a study was designed to test the hypothesis that in neonates from a species susceptible to oxygen toxicity, the lethal effect of hyperoxia is related to a low availability of substrates for glutathione production rather than an impairment in synthetic activity. One-day-old guinea pigs, randomly assigned to room air or oxygen (>95%), were fed by their mothers (n = 16) or i.v. by dextrose (n = 14) or by total parenteral nutrition (TPN, n = 20). After 3 d, glutathione and activities of enzymes involved in maintaining intracellular glutathione levels were determined in lungs and liver. The lethal effect of oxygen (p < 0.05) observed in animals without TPN was not related to glutathione depletion, as oxygen induced a 33% increase in lung glutathione, positively correlated (r2 = 0.35) with enhanced synthesis. With TPN, the animals were protected against the lethal effects of hyperoxia and lung glutathione increased by 67% in oxygen. The results suggest that the glutathione demand by the lungs in the presence of an oxidant stimulus was met by the increased (p < 0.001) hepatic production supported by TPN. Under hyperoxic conditions, early nutritional support is of vital importance.

Animals↗

Development of glutathione synthesis and gamma-glutamyltranspeptidase activities in tissues from newborn infants.

Following the observation that the level of glutathione in leukocytes from human newborn infants was lower in preterm and in male infants, a study was designed to document the level of activities of glutathione synthesis and gamma-glutamyltranspeptidase during the development of preterm and term newborn infants. Measurements were performed in leukocytes from tracheal aspirates of oxygen dependent infants, and in leukocytes from cord blood. Contrary to the common belief concerning the development of antioxidant activity, the biosynthesis of glutathione was active in leukocytes from preterm infants; and by two days of life the activity of gamma-glutamyltranspeptidase reached 3 times the level of that seen in cord blood. Our results suggest that the maturity of these enzymes was not the limiting step in maintaining cellular glutathione levels. This represents new information concerning the maturation of a central antioxidant in tissue derived from preterm and term human newborn infants at risk of oxidant stress. This implies that sources of cysteine crossing freely the cellular membrane could be used by tissues of term and preterm infants to produce glutathione.

Age Factors↗

Paradoxical role of ascorbic acid and riboflavin in solutions of total parenteral nutrition: implication in photoinduced peroxide generation.

In the presence of light, a multivitamin preparation is the main source of peroxides in solutions of total parenteral nutrition (TPN). This preparation contains two photosensitive products, 5'-phosphate flavin mononucleotide (FMN) and polysorbates (PS), as well as electron donors such as ascorbate (AH). We hypothesized that the admixture of FMN or PS with electron donors generates peroxides in TPN and alters the quality of nutrients. Using xylenol orange, peroxide concentrations were measured in solutions containing AH, FMN, and/or PS in water, a dextrose solution, an amino acid preparation, and a lipid emulsion. Thiol functions were evaluated by reduction of 5,5-dithiobis(2-nitrobenzoic acid) in the amino acid preparation. After 24-h light exposure, dextrose solutions with admixtures of AH + FMN or AH + FMN + PS generated peroxides at concentrations similar to those observed in a 1% multivitamin solution, and over three times higher than those observed with FMN, PS, or AH alone. However, in the presence of amino acids, FMN alone induced a generation of peroxides comparable to that observed with FMN + AH. In the lipid emulsion, peroxides increased over 3-fold in the presence of FMN or FMN + AH. The addition of catalase suggested that lipid peroxides and H2O2 were produced, and the loss of thiol function suggested that an oxidation of amino acids occurred. When exposed to light, FMN induces reactions with amino acids, polyunsaturated fatty acids, and even AH, altering the quality of nutrients. Paradoxically, AH without FMN has a protective effect on peroxide generation in TPN.

Ascorbic Acid↗

Gender and maturation affect glutathione status in human neonatal tissues.

Gender and maturation affect glutathione status in human neonatal tissues. The objective was to verify if human tissues derived from baby girls had a greater ability then tissues derived from males to stimulate the glutathione-reductase, when faced with an oxidative challenge. In vitro, the effect of a calibrated oxidative challenge was studied in endothelial cells. In vivo, the effect of a clinically relevant oxidative challenge was studied in cells from tracheal aspirates derived from oxygen-dependent newborn infants. In endothelial cells, the oxidant tert-butylhydroperoxide had a stimulating effect on GSSG-R activity in cells derived from females. The peroxide produced a time, concentration and gender-dependent cytotoxicity, with female-derived cells exhibiting a better viability. In vivo, the intracellular total glutathione content was higher in female-derived cells and in cells from more mature babies; postnatal age and gestational age had a positive effect on the activity of GSSG-R. Oxygen (FiO2 > or = 0.3) was associated with a lower activity of GSSG-R in boys, early in life. Considering that glutathione is a central element in the antioxidant defense, these results suggest that specific tissues derived from the baby girl are potentially better protected against an oxidative stress than those derived from the boy.

Female↗

Bound iron admixture prevents the spontaneous generation of peroxides in total parenteral nutrition solutions.

BACKGROUND: Parenteral administration of iron is a matter of controversy because it is feared that it could contribute to oxidative reactions. The aim of this study was to verify if irondextran participates in the redox reactions occurring in total parenteral nutrition (TPN) solutions. METHODS: Irondextran was compared with different forms of iron in the interaction with peroxides. Hydroperoxide levels were measured by a colorimetric technique in TPN solutions, in presence of varying sources (FeCl2, FeSO4, irondextran, iron sorbitol) and concentrations (0-0.8 mM) of iron. The consumption and inhibition of peroxide generation were tested by analyzing the effect of iron on different sources of peroxides (H2O2, tert-butyl and cumen hydroperoxide). The free radicals produced under conditions of a Fenton-like reaction were measured by the oxidation of scopoletin. And the proportion of Fe3+ freed by both bound-iron sources was counted by measuring the masking effect on the thiol function of cysteine. RESULTS: Free-iron admixture to parenteral nutrition induces the formation of free radicals, whereas sources of bound-iron inhibit the generation of peroxides in parenteral nutrition without implying a Fenton-like reaction. CONCLUSION: For patients requiring iron supplementation, bound-iron should be added during the preparation of TPN solutions, because it protects against the spontaneous generation of peroxides.

Colorimetry↗

Influence of bilirubin on the antioxidant capacity of plasma in newborn infants.

In vitro, bilirubin is a strong antioxidant, but in vivo its capacity to act as a scavenger of toxic oxygen radicals remains poorly documented. The aim of this study was to evaluate of bilirubin had antioxidant properties in jaundiced infants. The antioxidant capacity of neonatal plasma was measured in Trolox equivalents (TEAC, mmol/l) and correlated in vitro with plasma bilirubin concentrations (r2 = 0.99). Plasma TEAC was compared before and after exchange transfusions for neonatal hyperbilirubinemia (250-435 mumol/l). The antioxidant properties of the paired blood samples before and after exchange transfusions (TEAC: 1.67 +/- 0.12 vs. 1.37 +/- 0.09 mmol/l, n = 11) varied in proportion to the serum bilirubin levels. The changes in other antioxidants were not large enough to account for the magnitude of change in antioxidant capacity. Therefore, in vivo, the plasma antioxidant capacity of jaundiced newborn infants is related to the level of bilirubin.

Analysis of Variance↗

Admixture of a multivitamin preparation to parenteral nutrition: the major contributor to in vitro generation of peroxides.

BACKGROUND: Peroxides have been reported to contaminate lipid emulsions and amino acid solutions used in total parenteral nutrition (TPN). This is particularly disturbing in newborn infants who are prone to several diseases related to immature defense mechanisms against oxidative challenges. It is not clear whether the antioxidants in multivitamins help protect parenteral nutrients against the hazards of oxidation. OBJECTIVE: To evaluate the role of a multivitamin preparation (MVI) on the actual peroxide load received by patients on TPN. METHODOLOGY: The generation of peroxides in parenteral nutrition was tested first using test solutions. We compared the relative contribution of commercially available amino acid solutions, a lipid emulsion, and MVI on the level of peroxides in clinically relevant TPN solutions. Second, we measured the level of peroxides actually infused at the bedside. In both circumstances, the effects of time and light exposure were isolated. The level of peroxides was determined by a colorimetric technique and expressed as microM equivalents tert-butyl hydroperoxide (microM = TBH). RESULTS: Even when protected from light, the addition of MVI produced a 10-fold increase in peroxides (mean +/- SEM, n = 3, 19 +/- 4 to 189 +/- 8 microM = TBH at 4 h) in the fat-free TPN solution and a fourfold increase (64 +/- 6 to 244 +/- 8 microM = TBH at 4 h) in the lipid-containing TPN solution. A dose-response relationship was found between the concentration of MVI and peroxide levels. The effect of light was the strongest in the presence of multivitamins. The amino acid solutions had a relative inhibitory effect on the generation of peroxides by MVI, which varied (from 54 +/- 1% to 72 +/- 1%) all according to the amino acid blend. In parenterally fed premature infants, protecting the intravenous set from light decreased the load of infused peroxides (146 +/- 15 vs 215 +/- 24 microM = TBH). CONCLUSIONS: The lipid emulsion had a significant but minor additive effect compared with the multivitamin preparation, which was the major contributor to the generation of peroxides. Protection from photooxidation is not sufficient to prevent peroxidation of TPN solutions. Contrary to what one would expect, increasing the concentration of MVI will lead to a greater generation of peroxides, suggesting that the essential antioxidants in MVI do not have antiperoxide properties.

Amino Acids↗

[Intrahepatic glutathione and oxidative stress in liver transplantation in the pig].

OBJECT: To determine the loss of endogenous GSH from livers cold-stored and reperfused, using a model of liver transplantation in the pig. MATERIAL AND METHODS: Four female Yorkshire pigs weighing 19 to 40 kg received a liver allograft. Donor livers were cold-stored in the UW solution. Mean cold ischemic time was 6.5 hours. Malondialdehyde (MDA) levels were used as an index of oxidative stress. MDA plasma levels were measured following recipient laparotomy (H0), immediately (H1), and 90 minutes after liver reperfusion (H2). MDA and GSH levels in liver were measured following donor laparotomy (T0), at the end of cold ischemic period (T1), and at 90 minutes following liver reperfusion (T2). RESULTS: Three animals survived. MDA liver levels decreased of 44% between T0 and T1, then increased to 92% at T2. In contrast, in plasma, graft reperfusion was associated with an increase of MDA to 140% of the baseline values which reached 188% at H2. Intrahepatic GSH levels decreased of 49% at T1, then to 72% at T2. CONCLUSION: our study suggests that in liver transplantation: (1) Hepatic GSH is depleted to 49% during cold-storage, and an additional 23% is lost after reperfusion; (2) GSH contained in the UW solution does not prevent the loss of hepatocellular glutathione during preservation and reperfusion; (3) after short periods of cold ichemia, endogenous hepatic GSH may protect against oxydative stress in the transplanted liver.

Animals↗

Antiperoxide activity of sodium metabisulfite. A double-edged sword.

Sulfites are chemical substances that are used widely in the pharmaceutical industry to reduce or prevent oxidation. Sodium metabisulfite (Na2S2O5) is still present in several parenteral amino acid solutions. Since intravenous lipid emulsions are contaminated by hydroperoxides, we evaluated whether metabisulfite had an antioxidant activity against hydroperoxides. In vitro, Na2S2O5 inhibited the oxidant activity of H2O2, tert-butyl-, and cumene hydroperoxides. The antioxidant capacity of metabisulfite was supported in vivo by the lower (P < 0.01) excretion of malondialdehyde, a stable end product of lipid peroxidation, in babies receiving metabisulfite in their parenteral nutrition. However, for concentrations outside the range found in solutions for parenteral nutrition, the reduction of hydroperoxides by Na2S2O5 could transform this compound into an oxidant, like a sulfite radical. It is suggested that metabisulfite has antiperoxide properties that, under specific conditions, contribute to the generation of toxic oxidants.

Antioxidants↗

Gender-related response to a tert-butyl hydroperoxide-induced oxidation in human neonatal tissue.

Reports of gender-related differences in the activity of enzymes involved in the metabolism of intracellular antioxidants, led us to verify whether the prostaglandin response to tert-butyl hydroperoxide (TBH) differed according to the sex of infants. Segments of human umbilical veins were perfused in the presence or absence of TBH (0.25 mmol/l, and 1.0 mmol/l). Because TBH is quenched in the cell by glutathione peroxidase, total glutathione concentrations and production of glutathione-dependent prostaglandins (PGE2 and PGF2 alpha) as well as membrane-derived eicosanoids (PGI2 and thromboxane) were measured in the eluate. In veins from boys, TBH induced a sustained response for glutathione only, which was increased (p < 0.05). In female-derived tissue, the hydroperoxide induced a different response according to the dose of TBH. At 0.25 mmol/l, a drop (p < 0.005) in PGF2 alpha was associated with a rise (p < 0.001) in thromboxane. At 1.0 mmol/l, TBH had an opposite effect--there was a rise (p < 0.01) in PGE2 and PGI2. The prostaglandin concentration were not proportional to the oxidative stimulus, suggesting a critical level of TBH at which the oxidative state differs in tissues derived from boys or girls.

Dinoprost↗

The increase in vasomotor tone induced by a parenteral lipid emulsion is linked to an inhibition of prostacyclin production.

The aim of the study was to verify whether the infusion of a lipid emulsion causes a rise in vascular pressure related to an imbalance in the production of vasoconstricting and vasodilatating eicosanoids. Segments of umbilical veins were perfused with and without 1.5 microM indomethacin (cyclooxygenase inhibitor) in solutions differing only in their lipid content (control vs. lipid). The lipid-induced higher pressure (p < 0.05) was associated with an inhibition (p < 0.05) in the output of the vasodilatator PGI2, and an increase (p < 0.01) in the production of the vasoconstrictor PGF2 alpha. Indomethacin abolished differences in pressure, but produced a rise (p < 0.01) in vascular tone of both the control and lipid-containing solutions by inhibiting PGI2 synthesis. Prostacyclin was the only eicosanoid significantly correlated (p < 0.01) to vascular tone. The lipid emulsion was therefore linked to the inhibition of the conversion of PGH2 to PGI2. The ensuing greater PGH2 availability would result in vivo, in the increased synthesis of vasoconstricting eicosanoids. The lipid-containing solution produced vasoactive responses similar to those reported with tert-butyl hydroperoxide, suggesting that hydroperoxides contaminating commonly used lipid emulsions could be causing a prostanoid-dependent vasoconstriction.

Cesarean Section↗

Biologic effects of parenteral bisulfite on human vascular tissue.

Antioxidant properties of bisulfite are used to stabilize parenteral amino acid solutions. After reports of adverse reactions to dietary sulfites, we evaluated whether the infusion of bisulfite had biologic effects on human vascular tissue. Because an endothelial oxidative injury can affect mediators of vasoreactivity, vascular pressure and prostaglandin production were studied in an intact human vein model infused with clinically relevant amino acid solutions differing only by their metabisulfite content (0 versus 300 mg/L). The amino acid solution containing bisulfite presented higher venous pressure (p < 0.01) and prostaglandin production (6-keto-prostaglandin F1 alpha, p < 0.01; and prostaglandin E2, p < 0.05). A hydroxyl radical-generating system added to the solutions did not modify the pressure readings, but it resulted in an overall decrease in prostacyclin production (p < 0.05). Despite this known inhibitory effect on oxidative challenge on prostaglandin I2 production, prostaglandins remained higher in the presence of bisulfite. The results suggest that the effect of bisulfite takes place before prostaglandin H2 synthesis in the eicosanoid cascade, whereas the oxidative challenge affects specifically the synthesis of prostaglandin I2, after prostaglandin H2, indicating that there is no interaction between bisulfite and the hydroxyl generating system. Bisulfite has local vascular effects on endothelial mediators, separate from its antioxidant properties.

6-Ketoprostaglandin F1 alpha↗

Total parenteral nutrition in the newborn infant: energy substrates and respiratory gas exchange.

The hypothesis that a high-fat parenteral regimen was beneficial for respiratory gas exchanges, in comparison with a high-glucose regimen, was tested in a paired crossover design. Ten parenterally fed newborn infants with no respiratory problems received two 5-day isoenergetic and isonitrogenous regimens that differed in their nonprotein source of energy; the level of fat intake (low fat (LF) 1 gm.kg-1.day-1; high fat (HF) 3 gm.kg-1.day-1) varied inversely with that of glucose. Continuous transcutaneous PO2 (tcPO2) and PCO2 (tcPCO2), respiratory gas exchange (indirect calorimetry), and plasma arachidonate metabolites were measured at the end of each regimen. Oxygen consumption and resting energy expenditure were not affected by modification of the source of energy. However, carbon dioxide production (VCO2) was higher during LF than during HF (6.9 +/- 0.2 vs 6.2 +/- 0.1 ml.kg-1.min-1; p less than 0.01), as was the respiratory quotient (1.08 +/- 0.02 vs 0.96 +/- 0.02; p less than 0.001). Despite the differences in VCO2, the tcPCO2 was not affected, suggesting adequate pulmonary compensation during LF, as documented by the higher minute ventilation (160 +/- 7 vs 142 +/- 5 ml.kg-1.min-1; p less than 0.01). The lower tcPO2 during the HF regimen (73.8 +/- 2.8 vs 68.8 +/- 2.6 mm Hg; p less than 0.015) indicated a disturbance at the alveolocapillary level induced by the lipid emulsion. No differences were found in circulating levels of prostaglandins and thromboxanes. The substitution of glucose for lipid did not modify fat storage (2.1 +/- 0.3 vs 2.1 +/- 0.3 gm.kg-1.day-1). We conclude that the supposed beneficial effect of a fat emulsion on respiratory gas exchange is questionable.

Blood Gas Monitoring, Transcutaneous↗

Effects of glucocorticoids on prostaglandin formation by human amnion.

The human amnion may be an important source of prostaglandins involved in the onset of human labor and therefore it is important to define the factors that regulate their formation in this tissue. In the present study we demonstrate that glucocorticoids inhibit prostaglandin production by freshly isolated amnion cells. The inhibitory action of the glucocorticoids, however, changes to a stimulatory action when the cells are maintained in primary culture for a few days. For both inhibition and stimulation, concentrations of 10(-8) M dexamethasone or greater were required to give significant effects, and estradiol and progesterone had no effect on the prostaglandin output of the cells. Epidermal growth factor (EGF), which has previously been found to stimulate prostaglandin output by confluent amnion cells, did not alter prostaglandin output of cells initially placed in culture. Furthermore, the stimulatory action of EGF and dexamethasone appeared additive. The calcium ionophore A23187 stimulated prostaglandin output in freshly isolated cells and accentuated the inhibitory effect of dexamethasone. These studies indicate that prostaglandin formation by human amnion during pregnancy could be regulated by glucocorticoids. These steroids are easily available to the amnion by way of cortisone conversion to cortisol by the maternal decidua. The results also indicate that amnion is capable of responding to glucocorticoids in both a stimulatory and inhibitory fashion and whether one or both actions are of importance in vivo is a question that is as yet unresolved.

Amnion↗