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Biomedical subjects

Philippe Chessex

Publications and source records attributed to Philippe Chessex.

15 recordsLinked to original sources
PubMed2006

Photoprotection of parenteral nutrition enhances advancement of minimal enteral nutrition in preterm infants.

BACKGROUND: Light exposure of TPN generates peroxides which induce vasoconstriction. Mesenteric vasoconstriction may affect feeding tolerance. Since photo-protection of TPN decreases peroxide generation, we hypothesized that shielding TPN from light may improve the establishment of minimal enteral nutrition in preterm infants. METHODS: Infants were randomized to TPN being light exposed (LE) or protected (LP) from birth. Feeding volumes were monitored through 7 days of life in those initiated on minimal enteral nutrition (MEN). Comparisons between LP and LE were performed by ANOVA. RESULTS: Daily increments and cumulative volumes of enteral feeds (mL/kg birth weight/d) during the first week of life were significantly higher in LP (n = 18) than LE (n = 19). CONCLUSION: Photo-protection of parenteral nutrition enhances advancement of MEN in preterm infants. Further research is needed to substantiate these findings and determine whether this confers long-term nutritional advantages.

Enteral Nutrition↗
PubMed2006

Doubling calcium and phosphate concentrations in neonatal parenteral nutrition solutions using monobasic potassium phosphate.

BACKGROUND: Premature infants require high intakes of Ca and P to mimic fetal accretion rates. With the current phosphate salt used, adequate amounts cannot be provided due to the precipitation of Ca and P in TPN solutions. OBJECTIVE: To compare monobasic potassium phosphate (monobasic regimen) and monobasic plus dibasic potassium phosphate (dibasic regimen) on calcium phosphate solubility in 5 amino acid products, and to determine whether solubility differences observed in these products can be explained by buffering capacity. METHODS: TPN solutions were prepared according to standard clinical practice. The following amino acid products were used at 3% concentrations: Primene, Vamin N, TrophAmine, Aminosyn-PF, and Travasol. Dextrose 10%, standard electrolytes, heparin, vitamins and trace elements were added. Calcium (as gluconate) and phosphate (as monobasic or dibasic regimen) were added in one-to-one molar ratios from 0-45 mmol/L. Solutions were inspected macroscopically and microscopically for precipitation under three conditions: immediately, 24 h after preparation at room temperature, and 3 h later in a 37 degrees C water bath. Buffering capacity was determined for each amino acid product by titrating with standardized 0.1 M NaOH. RESULTS: Variations in Ca:P solubility and buffer capacity exist between amino acid solutions. With Primene and Vamin no macroscopic or microscopic precipitation was detected up to 45 mmol/L using monobasic regimen, compared to 25 mmol/L using dibasic regimen with Trophamine. Buffer capacity did not account for the solubility differences observed between the five amino acid products, which were related to the pH of the final solution. CONCLUSIONS: These data will allow clinicians to double the current concentrations of calcium and phosphate in neonatal TPN solutions using monobasic regimen. Although this is particularly relevant to situations when fluid intake is restricted, the effect of the acid load needs to be investigated in extremely low birth weight infants.

Amino Acids↗
PubMed2005

Association between hydrogen peroxide-dependent byproducts of ascorbic acid and increased hepatic acetyl-CoA carboxylase activity.

BACKGROUND: Parenteral multivitamin preparation (MVP) induces fatty liver in neonatal guinea pig pups; this is prevented by photoprotection. Photo-excited riboflavin present in MVP generates H(2)O(2) and molecules with masses of 136 and 208. We hypothesized that H(2)O(2) initiates the peroxidation of ascorbic acid (AA), producing biologically active byproducts affecting hepatic lipid metabolism. METHODS: Mass spectrometry (MS) documented the participation of H(2)O(2) and photo-excited riboflavin (Ribo) in the formation of AA byproducts. Sixteen 3-day-old guinea pig pups received an intravenous solution (50 g/L dextrose + 4.5 g/L NaCl + 1 kIU/L heparin) at 240 mL x kg(-1) x day(-1), enriched with control or test mixtures, for 4 days. The control mixture was photo-protected AA + Ribo (without byproducts or H(2)O(2)), and the test mixture was AA + Ribo treated to generate AA byproducts without H(2)O(2). Hepatic acetyl-CoA carboxylase (ACC) activity was determined after 4 days. Fourth-day urine samples were analyzed by MS. Data were treated by ANOVA (alpha = 0.05). RESULTS: H(2)O(2) did not influence the classic degradation of AA, as the generation of 2,3-diketogulonic acid was not affected. In contrast, the formation of molecules with masses of 136 and 208 was H(2)O(2) and time dependent. ACC activity was higher (P <0.01) in animals receiving high concentration of these molecules; its hepatic activation correlated (P <0.01) with the urinary concentration of molecule-208. CONCLUSIONS: H(2)O(2) at concentrations found in the clinical setting of total parenteral nutrition induce the transformation of dehydroascorbic acid into compounds that have the potential to affect lipid metabolism. These molecules have peroxide and aldehyde functions.

Acetyl-CoA Carboxylase↗
PubMed2005

Effect of coadministration of parenteral multivitamins with lipid emulsion on lung remodeling in an animal model of total parenteral nutrition.

Exposure of parenteral multivitamin solutions (MVP) to ambient light generates peroxides and vitamin loss, and induces initiation of fibrosis and a reduced alveolar count in an animal model of total parenteral nutrition (TPN). Adding MVP to the lipid moiety of TPN prevents lipid peroxidation and vitamin loss. The aim of the study was to compare modes of delivery of MVP on lung procollagen mRNA and alveolar counts. Three-day-old guinea pig pups were infused continuously with one of three intravenous solutions: 1) control = dextrose; 2) AA + MVP = MVP given with the dextrose + amino-acid moiety, in a "piggyback" setup with a lipid emulsion mixed close to the infusion site; and 3) LIP + MVP = same as AA + MVP, except that MVP is given with the lipid emulsion. After 4 days, lungs were prepared for alveolar count (intercept technique) and for quantification of the procollagen/beta-actin mRNA ratio (initial step of fibrosis). Data were compared by ANOVA. The procollagen mRNA was lower (P < 0.05) in animals receiving LIP + MVP than those with AA + MVP. But the two modes of admixture of MVP had the same effect on the alveolar counts, which were lower (P < 0.01) than controls. The mode of delivery of TPN affects lung remodeling. Although LIP + MVP protects against the initiation of lung fibrosis, the absence of a beneficial effect on alveolar counts suggests that these features of lung remodeling are not caused by a unique component of TPN. Specific roles of peroxides, components of MVP, and light exposure on lung remodeling need to be explored before LIP + MVP can be recommended as an alternative mode of parenteral vitamin delivery.

Amino Acids↗
PubMed2005

The mode of delivery of parenteral multivitamins influences nutrient handling in an animal model of total parenteral nutrition.

BACKGROUND: Very low birthweight preterm infants receive early total parenteral nutrition (TPN) to optimize protein balance. Adding multivitamins (MVP) to the lipid emulsion (MVP+LIP) rather than to the amino acid+dextrose moiety of TPN (AA+MVP) limits the effects of light exposure on lipid peroxidation and vitamin loss. AIM: Compare the effects of the mode of delivery of MVP on nutrient handling and indices of oxidant stress. METHODS: Three-day old guinea pig pups were assigned to TPN containing MVP+amino acids+dextrose+heparin and electrolytes, with lipids provided separately (AA+MVP). Solutions were light exposed (LE, n = 8) or light protected (LP, n = 9). In a further group (n = 7), MVP was co-administered with the lipid moiety and light exposed (LIP+MVP). Variables measured in urine (creatinine, nitrogen, vitamin C) and in liver (protein, glutathione, isoprostane, vitamins A, E, C) were compared by ANOVA. RESULTS: Urinary nitrogen and vitamin C were higher (P<0.05) during LE, while hepatic levels of vitamin C were higher (P<0.05) with LIP+MVP. These results were not related to total peroxide levels in TPN or to markers of oxidant stress. CONCLUSION. Co-administration of MVP with lipid or light protected amino acids offers comparable beneficial effects on nitrogen and vitamin C metabolism.

Analysis of Variance↗
PubMed2005

Iodine overload and severe hypothyroidism in a premature neonate.

Use of iodinated skin disinfectants in the perinatal period can result in significant iodine overload of the neonate and transient hypothyroidism. The authors report a case of unusually severe hypothyroidism requiring L-thyroxine (L-T4) replacement therapy in a premature neonate after prolonged use of iodinated skin disinfectants for a complex skin lesion. Neonatal iodine overload should be minimized, and in cases with significant iodine exposure, thyroid-stimulating hormone should be monitored, especially in preterm neonates who are exquisitely sensitive to the antithyroid effects of iodine excess.

Anti-Infective Agents, Local↗
PubMed2005

Reduced bile flow associated with parenteral nutrition is independent of oxidant load and parenteral multivitamins.

BACKGROUND: Reduction in bile flow is a characteristic of cholestasis related to parenteral nutrition. Light exposure of parenteral multivitamin preparations is the major source of peroxides contaminating parenteral nutrition solutions. They may contribute to local oxidative stress. Oxidants are reported to affect transport mechanisms across the hepatocyte membrane into bile. The authors hypothesize that an oxidant-antioxidant imbalance is involved in parenteral nutrition related cholestasis. The aim of this study was to investigate the roles of multivitamin preparations and peroxides on bile flow in newborn guinea pigs receiving parenteral nutrition. METHODS: Three-day-old guinea pigs were fed enterally or parenterally with solutions containing 8% dextrose/0.45% NaCl +/- multivitamin preparation +/- amino acids +/- lipids. The influence of the oxidant-antioxidant balance on bile flow was evaluated using 500 microM hydrogen peroxide and 1% and 3% multivitamin preparations +/- Na metabisulfite. Four days later, animals were anesthetized and bile flow was recorded over 2 hours. Glutathione determinations were performed on bile and liver samples. The percentage of oxidized glutathione, reflecting the redox status, was used as a marker of oxidative stress. Data were compared by analysis of variance with P < 0.05. RESULTS: Bile flow decreased first on initiating dextrose + NaCl infusion (a 25% decrease) and subsequently by adding amino acids (a further 30% decrease). Although antioxidant vitamins and peroxides modified the hepatic redox status, they did not influence bile flow. CONCLUSION: Although the composition of parenteral nutrition affects bile flow and the hepatic redox status, the oxidant-antioxidant imbalance in infused solutions is not the causal event in the installation of cholestasis.

Analysis of Variance↗
PubMed2004

Interaction between ascorbate and light-exposed riboflavin induces lung remodeling.

Light-exposed parenteral multivitamins induce in lungs peroxide-like oxidant responses as well as the initiation of fibrosis. We hypothesized that peroxides generated in light-exposed total parenteral nutrition (TPN) affect lung remodeling. The objective was to assess the specific roles of peroxides, multivitamin preparation (MVP), and light exposure on lung remodeling during TPN. Three-day-old guinea pigs fitted with an indwelling catheter were assigned to the following intravenous regimens: TPN or MVP +/- photoprotection, H(2)O(2)+/- glutathione, MVP +/- metabisulfite, or ascorbic acid +/- riboflavin. Fed animals served as controls. After 4 days, lungs were sampled to determine alveolarization (intercepts), beta-actin mRNA (protection assay), and apoptosis (terminal deoxynucleotidyl transferase dUTP nick-end labeling). Data were analyzed by analysis of variance. The infusion of light-exposed multivitamins induced a 20% lower (p < 0.01) alveolarization index than fed controls, and 3-fold higher (p < 0.01) apoptotic events. This was prevented by photoprotecting TPN. The effect of multivitamins on the alveolarization index was reproduced (p < 0.05) by infusion of light-exposed riboflavin in the presence of vitamin C. The alveolarization index correlated (r(2) = 0.35; p < 0.05) with beta-actin mRNA, suggesting alveolar disruption. Antiperoxides conferred no protection against decreased alveolarization. Lung remodeling induced by exposure of TPN to ambient light is not due to a direct effect of infused peroxides but rather to an interaction between vitamin C and peroxides generated by the exposure of riboflavin to light. It is speculated that this interaction may play a role in the development of chronic lung disease of premature infants who receive TPN and have immature antioxidant defenses.

Animals↗
PubMed2004

Light-induced byproducts of vitamin C in multivitamin solutions.

BACKGROUND: When solutions of multivitamin preparations (MVPs) are exposed to light, H(2)O(2) as well as organic peroxides are generated and the concentration of vitamin C decreases. The aim of this study was to determine, using mass spectrometry, whether the generation of oxidative byproducts of vitamin C, such as dehydroascorbate (DHA) and 2,3-diketogulonic acid (DKG), accounted for the reported decrease in ascorbic acid in MVPs exposed to light. METHODS: Mass spectrometry was used to document the formation of byproducts of ascorbic acid in solutions containing a MVP, vitamin C + riboflavin, and vitamin C + H(2)O(2) + Fe(2+). The involvement of ascorbic acid and H(2)O(2) in the formation of organic peroxides was tested by measuring peroxide concentrations in solutions containing H(2)O(2) with or without ascorbic acid and with or without Fe(2+) before and after addition of catalase. RESULTS: The loss of ascorbic acid in photo-exposed MVPs was associated with the concomitant generation of byproducts different from DHA and DKG. Among them, one mass fingerprint was particularly observed with solutions of vitamin C + riboflavin exposed to ambient light as well as with the solution of vitamin C + H(2)O(2) + Fe(2+), suggesting a Fenton-like reaction. This fingerprint was associated with the formation of catalase-resistant peroxides. CONCLUSION: Exposure of MVPs to light leads to the rapid loss of ascorbic acid and generation of specific byproducts that differ from DHA and DKG. The conversion of vitamin C into byproducts could be of biological importance in accounting for the decrease in ascorbic acid concentrations and the generation of organic peroxides in light-exposed MVPs.

2,3-Diketogulonic Acid↗
PubMed2003

Elevated umbilical cord ghrelin concentrations in small for gestational age neonates.

Ghrelin has orexigenic effects. It is present in umbilical cord plasma in full-term neonates, raising the prospect that ghrelin plays a role in fetal and neonatal energy balance. We measured ghrelin in small (SGA), appropriate (AGA), and large (LGA) for gestational age neonates and evaluated whether ghrelin levels are modulated by neonatal insulin and glucose concentrations. Plasma concentrations of ghrelin, insulin, and glucose were measured in cord blood sampled at birth in 123 SGA, AGA, and LGA neonates (gestational age, 24-41 wk) born to mothers with and without diabetes. Ghrelin was detected in samples from all infants. Its concentration was 40% higher in SGA neonates (mean +/- SD, 2436 +/- 657 pg/ml) compared with AGA (1738 +/- 380) and LGA (1723 +/- 269) neonates. There was a positive correlation between ghrelin and gestational age in AGA/LGA (r = 0.23; P < 0.05) and a negative correlation in SGA (r = -0.67; P < 0.005) neonates. Therefore, the difference in ghrelin between SGA and AGA/LGA neonates decreases with advancing gestational age. Birth weight z-score, maternal hypertension, and glucose concentrations were significant determinants of ghrelin concentrations. In conclusion, SGA neonates present with higher umbilical cord ghrelin plasma concentrations than AGA/LGA neonates. Ghrelin may play a physiological role in fetal adaptation to intrauterine malnutrition.

Anthropometry↗
PubMed2002

Photoprotection prevents TPN-induced lung procollagen mRNA in newborn guinea pigs.

BACKGROUND: Photo-exposed intravenous multivitamin solutions (MVP) carry a peroxide load. Peroxidation induces gene expression of procollagen. We hypothesized that photo exposure of the MVP solution might promote pulmonary fibrosis. The aim of the study was to assess the potential for MVP to increase procollagen mRNA. METHODS: Three day old guinea pigs were assigned to the following intravenous regimens, either: Control (C): 5% dextrose + 0.45% NaCl; C + 200 or 500 microM H(2)O(2); C + 500 microM H(2)O(2) + 10 microM GSSG; [C + 1% MVP +/- [amino acids + lipids]] +/- photoprotected. After 4 d, levels of pulmonary alpha1(I) procollagen mRNA and glutathione were determined. Results were compared by ANOVA. RESULTS: Photoprotection of MVP or TPN prevents light induction of procollagen mRNA. The effect of MVP + light was associated with a peroxide load coupled with a low glutathione level. This was also observed with the 500 microM H(2)O(2) group. The addition of GSSG prevented the increase of procollagen mRNA caused by H(2)O(2). CONCLUSION: An oxidant stress caused by the infusion of peroxides in an organism with a weak antiperoxide capacity induces the transcription of the gene encoding for procollagen alpha1(I). The results confirm the antiperoxide activity of lung glutathione. Parenteral nutrition could be a clinical condition favoring the initiation of lung fibrosis, especially in premature newborn infants who have low glutathione levels.

Amino Acid Sequence↗
PubMed2002

Multivitamin solutions for enteral supplementation: a source of peroxides.

OBJECTIVE: We investigated whether solutions of enteral vitamin supplementation are involved in the generation of peroxides and whether that contamination is biologically significant. METHODS: Peroxide contents of oral multivitamin preparations were measured over 3 wk after the initial opening of the containers. In selected premature infants (younger than 35 wk gestation), urinary peroxides were measured after initiating oral multivitamin supplementation. RESULTS: Peroxides in multivitamin solutions for enteral use are predominantly organic peroxides because they resist catalase. After the initial opening of the containers, there was a two-fold increase in total peroxides levels (P < 0.05) even in the preparation without riboflavin, a catalyst for the generation of peroxides. Initiation of oral vitamin supplementation was associated with increased (P < 0.05) urine peroxide levels. The high organic peroxide load did not correlate with its urinary excretion, mostly in the form of H(2)O(2). The excretion of H(2)O(2) corresponded to its oral intake from the multivitamin solution. CONCLUSIONS: Compared with parenteral multivitamin solutions, the enteral preparations contained higher organic peroxide levels starting with the initial opening of the bottles. The increased urinary excretion of H(2)O(2) after enteral multivitamin supplementation suggested a systemic diffusion of peroxides or of components of the multivitamin preparation responsible for the generation of peroxides. This oxidant load was not quenched by the immature antioxidant defenses of premature infants.

Drug Contamination↗
PubMed2002

Postnatal gender-dependent maturation of cellular cysteine uptake.

BACKGROUND: In view of the functional capacity of glutathione synthesis in premature infants, and because the availability of cysteine is one the rate limiting steps in glutathione synthesis, we hypothesized that the low glutathione levels in premature infants may be due to immaturity of the active cellular uptake of cysteine. OBJECTIVE: To document in cells from newborn infants the effect of maturity and gender on cysteine uptake and consequently on glutathione levels. METHODS: Incorporation of L-[35S] cysteine was measured in leukocytes from cord blood and from tracheal aspirates (TAC) of newborn infants of varying (gestational as well as postnatal) ages and gender. Cysteine uptake was correlated with glutathione in TAC. RESULTS: The maturity of newborn girls positively influences cysteine uptake, which is responsible for 78% of the variation in their glutathione content. However, in newborn boys, gestational and postnatal ages did not influence the cysteine uptake. DISCUSSION: Cysteine uptake appears to be the limiting step explaining the reported gender-related differences in glutathione as well as the low levels of this central antioxidant found in premature infants. The immature cysteine uptake found in cells from premature infants raises questions about the bioavailability of this conditionally essential amino acid in regimens of parenteral nutrition for human neonates.

Age Factors↗
PubMed2002

Photooxidation of parenteral multivitamins induces hepatic steatosis in a neonatal guinea pig model of intravenous nutrition.

Photooxidation of multivitamin solutions results in the generation of peroxides. Because peroxides are associated with hepatic steatosis and fibrosis as well as cholestasis, we questioned whether multivitamins are implicated in hepatic complications of parenteral nutrition. Guinea pig pups were assigned to groups receiving intravenously either total parenteral nutrition, photo-protected or not, or a control solution (5% dextrose + 0.45% NaCl) supplemented with either a) multivitamins; b) photo-protected multivitamins; c) multivitamins without riboflavin; or d) peroxides (H(2)O(2), tert-butylhydroperoxide). After 4 d, liver was sampled for histology and isoprostane-F(2alpha) levels, a marker of radical attack. Multivitamins as well as total parenteral nutrition were associated with steatosis (scored 0-4), the severity of which was reduced (p < 0.05) by photo protection. Although H(2)O(2) is the major peroxide contaminating multivitamins, it did not induce steatosis scores different than the controls. Compared with controls, hepatic isoprostane-F(2alpha) content increased in animals infused with H(2)O(2) (p < 0.05), but not in those infused with Multi-12 pediatric multivitamins or total parenteral nutrition. Results suggest that peroxides and/or free radicals are not mediators of the induction of steatosis observed with infusion of photo-exposed multivitamins, as there was no correspondence between histologic findings and hepatic levels of isoprostanes. It is suspected that a component of the multivitamin solution becomes hepato-toxic after photo-exposure, as indicated by the protective effect observed when withdrawing riboflavin. Photo-oxidation of multivitamins might be the common link between reports involving amino acids, lipids, and light exposure in the ethiology of hepatic complications of parenteral nutrition.

Animals↗