Biomedical subjects

H M Berger

Publications and source records attributed to H M Berger.

At least 19 recordsLinked to original sources

PubMed1997

Uric acid and ascorbic acid redox ratios in plasma and tracheal aspirate of preterm babies with acute and chronic lung disease.

This study compared plasma redox ratios of uric acid and ascorbic acid in well preterm babies with those with respiratory distress syndrome (RDS) and chronic lung disease (CLD), and investigated the relationship between these ratios and their respective measurements in tracheal aspirate. On day 1 after birth, plasma allantoin and allantoin/uric acid ratio were elevated in CLD (p < .05), and both markers of oxidative stress enabled early prediction of development of CLD (sensitivity and specificity: 54 and 83%, respectively). The relation between allantoin production and oxidative stress is supported by the correlation between the allantoin level and oxygen therapy in both RDS and CLD (p < .05). Reduced and oxidize ascorbic acid in plasma decreased postnatally in all groups and their redox ratio remained stable. Uric acid and ascorbic acid redox ratios were significantly elevated in tracheal aspirates compared to plasma samples (p < .05), and there was a strong positive correlation between both ratios (p < .005). These markers may be useful in monitoring babies with respiratory distress.

Antioxidants↗

PubMed1997

Oxidative stress during post-hypoxic-ischemic reperfusion in the newborn lamb: the effect of nitric oxide synthesis inhibition.

Post-hypoxic-ischemic (HI) reperfusion induces endothelium and neurons to produce excessive amounts of nitric oxide and superoxide, leading to peroxynitrite formation, release of protein-bound metal ions (i.e. iron), and cytotoxic oxidants. We produced severe HI in 18 newborn lambs and serially determined plasma prooxidants (non-protein-bound iron), lipid peroxidation (malondialdehyde), and antioxidative capacity [ratio of ascorbic acid/dehydroascorbic acid (AA/DHA), alpha-tocopherol, sulfhydryl groups, allantoin/uric acid ratio, and vitamin A] in blood effluent from the brain before and at 15, 60, 120, and 180 min after HI. The lambs were divided in three groups: six received a placebo (CONT), six received low dose (10 mg/kg/i.v.) N omega-nitro-L-arginine (NLA-10) to block nitric oxide production, and six received high dose NLA (40 mg/kg/i.v.; NLA-40), immediately after completion of HI. Non-protein-bound iron increased in all groups after HI but was significantly lower in both NLA groups at 180 min post-HI (p < 0.05), the AA/DHA ratio showed a consistent decrease in CONT (at 60 min post-HI, p < 0.05), but remained stable in NLA lambs. alpha-Tocopherol decreased steadily in the CONT, but not in the NLA lambs [180 post-H: 1.9 +/- 0.9 versus 4.2 +/- 0.7 microM (NLA-40), p < 0.05). Malondialdehyde was significantly higher in CONT lambs 120 min post-H compared with NLA groups [0.61 +/- 017 versus 0.44 +/- 0.05 microM (NLA-40), p < 0.05]. Vitamin A and sulfhydryl groups did not differ among groups. We conclude that post-H inhibition of nitric oxide synthesis diminishes non-protein-bound iron increment and preserves antioxidant capacity.

Animals↗

PubMed1996

Influence of plasma preparations and donor red blood cells on the antioxidant capacity of blood from newborn babies: an in vitro study.

We investigated in an in vitro transfusion model the early effects of plasma preparations and donor red blood cells on the antioxidant capacity of the cord blood from babies. Addition of pasteurized plasma protein solution to plasma from babies decreased the peroxyl radical trapping capacity (p < 0.02). In contrast, fresh frozen plasma did not lower this capacity. Addition of adult donor red blood cells to the babies' red blood cells did not significantly decrease the glutathione-recycling capacity of the blood. On the basis of these in vitro results we hypothesize that the use of resuscitation fluids with low antioxidant capacity may temporarily decrease the ability of the baby to catabolize reactive oxygen species.

Adult↗

PubMed1996

Inhalation of nitric oxide: effect on cerebral hemodynamics and activity, and antioxidant status in the newborn lamb.

Ventilation with nitric oxide (NO) is increasingly being used to treat pulmonary hypertension in the newborn. In the brain, NO has vasoactive properties and is involved in neurotransmission. However, the effect of inhaled NO on the cerebral blood flow (CBF) and on the cerebral activity is not known. Furthermore, there is little information on the influence of this free radical gas on the redox status in pulmonary vessels. We therefore investigated the effect of inhaled NO (2-60 ppm) on CBF, cerebral activity and redox status in blood effluent from the pulmonary circulation in 6 ventilated newborn lambs before and during group B streptococci (GBS)-induced pulmonary hypertension. Blood pressure in the pulmonary artery (P(ap)) and aorta (Pao), carotid artery blood flow (Qcar) to assess changes in CBF, and electrocortical activity were measured. Blood gases, indices of free radical status and methemoglobin were determined in blood samples obtained from the left ventricle. Inhalation of NO, before and during GBS-induced pulmonary hypertension, decreased P(ap) and PCO2 and increased PO2. Multiple linear regression revealed that Qcar was positively related to PCO2, but not to inhaled NO or PO2 before or during GBS conditions. Electrocortical activity and indices of antioxidative capacity and lipid peroxidation did not change significantly. Methemoglobin was not detected. In conclusion, inhalation of NO (up to 60 ppm) lowered P(ap) without directly affecting CBF, electrocortical activity, and redox status in the pulmonary vessels. CBF, however, can indirectly be influenced by NO-mediated changes in PCO2.

Administration, Inhalation↗

PubMed1996

Influence of long chain unsaturated fatty acids in formula feeds on lipid peroxidation and antioxidants in preterm infants.

The influence of long chain polyunsaturated fatty acids (LCP) in formula feeds on lipid peroxidation and antioxidants was studied in 35 healthy preterm infants (gestational age 30-35 wk) during the first 6 postnatal weeks. Infants received a preterm formula supplemented with n-3 LCP (LCP group, n = 13), or standard preterm formula (NO-LCP group, n = 15); 7 infants fed human milk served as a reference group. With LCP supplementation, erythrocyte C22:6n-3 levels were stable; without supplementation, the levels declined (difference p < 0.001). LCP supplementation did not decrease vitamin E or C levels, or increase lipid peroxidation products (thiobarbituric acid-reactive substances) in plasma. In erythrocytes, LCP supplementation did not markedly influence the reduced/oxidized glutathione ratio; however, the susceptibility to H2O2-induced oxidative stress was reduced. Our results suggest that healthy preterm infants are able to cope with any extra peroxidative stress produced by n-3 LCP supplementation. However, these findings might not be generally applicable to other formulas containing LCP supplements.

Antioxidants↗

PubMed1996

Nonprotein-bound iron in postasphyxial reperfusion injury of the newborn.

OBJECTIVE: To investigate if the availability of nonprotein-bound iron after birth asphyxia is related to the severity of the postasphyxial injury and neurodevelopmental outcome. METHODS: Nonprotein-bound iron (bleomycin assay) and thiobarbituric-acid-reactive species, an index of oxidative lipid damage, were measured in plasma of 50 newborn infants (gestational age > 34 weeks) between 0 to 8 hours, 8 to 16 hours, and 16 to 24 hours after birth. Three groups were compared: healthy infants (n = 20), moderately asphyxiated infants (n = 15), who were neurologically normal during the first 24 hours after birth and severely asphyxiated infants (n = 15), who developed abnormal neurological signs in the first 24 hours after birth. RESULTS: In the severely asphyxiated infants, liver enzymes, creatinine, urea, and uric acid concentrations were significantly elevated. Eleven severely asphyxiated infants were brain-damaged, 9 of them died during the neonatal period. Nonprotein-bound iron was detectable in 30% of the control, 60% of the moderately asphyxiated, and 80% of the severely asphyxiated infants. During the whole study period nonprotein-bound iron concentration was significantly elevated in severely asphyxiated infants as compared with controls. Three of the four severely asphyxiated infants who had a normal outcome at 1 year of age, had no detectable nonprotein-bound iron during the study period. Stepwise logistic regression analysis with neurodevelopmental outcome at 1 year of age (normal versus adverse/death) as dependent variable and all the measured parameters for organ damage as independent variables revealed that the nonprotein-bound iron concentration at 0 to 8 hours after birth was the most significant variable and at the same time the only variable that entered the model, in relation to neurodevelopmental outcome. Thiobarbituric-acid-reactive species tended to be higher in severely asphyxiated infants, suggesting oxidative lipid damage. CONCLUSION: Nonprotein-bound iron may play an important role in oxidative damage-mediated postasphyxial brain injury and subsequent neurodevelopmental outcome.

Asphyxia Neonatorum↗

PubMed1995

Influence of low dose allopurinol on ischaemia--reperfusion injury during abdominal aortic surgery.

OBJECTIVES: To ascertain whether surgery causes ischaemia-reperfusion (I-R) related injury, if this injury is augmented by preoperative shock, and reduced with low dose allopurinol. DESIGN: Randomised blind placebo controlled trial. SETTING: Surgical laboratory. MATERIAL AND METHODS: 22 pigs were randomly allocated to four groups; OP = operation/placebo, OA = operation/ allopurinol, SOP = shock + operation/placebo, SOA = shock + operation/allopurinol. An aortic tube prosthesis was inserted in all. In groups SOP and SOA preoperative shock was induced by exsanguination. Allopurinol was administered in group OA on the preoperative day and peroperatively, in group SOA during shock and peroperatively. CHIEF OUTCOME MEASURES: Perioperative blood concentrations of thiobarbituric acid reactive species (TBARS), ascorbic acid (AA), albumin, 99mTc-albumin and creatine phosphokinase (CPK) as indicators of oxidative membrane damage, antioxidant activity, microvascular permeability changes and muscular cell damage respectively. MAIN RESULTS: In the OP and OA groups TBARS gradually increased, while AA, 99mTc-albumin and CPK remained unchanged and albumin decreased. No effect of allopurinol was observed in these groups. In the SOP group TBARS and AA were not significantly different from groups OP and OA. Yet, albumin, 99mTc-albumin and CPK decreased significantly more in the SOP group. Compared with the SOP group, allopurinol treatment (SOA) produced lower TBARS and higher AA levels, and reduced the effect of shock on albumin, 99mTc-albumin and CPK concentrations. CONCLUSIONS: Aortic surgery causes no I-R related damage. Pre-operative shock produces I-R related damage, which is reduced by allopurinol.

Allopurinol↗

PubMed1995

Measured versus calculated latent iron binding capacity in plasma of newborns.

Iron overload as well as iron deficiency may play a role in the pathogenesis of diseases in the newborn and infant and therefore knowledge of the iron status is essential. Using an automated method for the determination of plasma latent iron-binding capacity (LIBC) we measured the LIBC in 20 full term and 20 preterm babies and 20 adults. LIBC was also calculated from transferrin and iron concentration.

Adult↗

PubMed1995

Ferrous ions detected in iron-overloaded cord blood plasma from preterm and term babies: implications for oxidative stress.

Redox active iron chelatable to bleomycin is often present in the plasma of cord blood samples taken from preterm and term babies. The low caeruloplasmin and high ascorbate levels in plasma at birth may allow this iron to exist in the reduced ferrous state. In support of this postulate thirteen cord blood samples showing the presence of low molecular mass iron were able to degrade DNA in the presence of bleomycin and plasma.

Bleomycin↗

PubMed1994

Postnatal changes in plasma chain-breaking antioxidants in healthy preterm infants fed formula and/or human milk.

Concentrations of chain-breaking antioxidants were studied in the first 6 postnatal weeks in 29 healthy preterm infants (gestational age 30-35 wk). Vitamin C, uric acid, and sulfhydryl groups declined, whereas vitamin E rose and bilirubin followed its typical biphasic postnatal course. The influence of these changes on the plasma peroxyl radical trapping capacity was assessed in vitro (TRAP assay). The trapping capacity decreased postnatally and this appeared to be related to the coincident fall in uric acid concentrations. Results did not differ between babies fed with only preterm formula (n = 12) and those fed predominantly with human milk (n = 6), except for higher bilirubin and TRAP values in the breast-fed infants. There are major postnatal changes in the concentrations of the plasma chain-breaking antioxidants and this may influence the susceptibility of the preterm baby to oxygen toxicity.

Aging↗

PubMed1994

Protein nutrition, faecal flora and iron metabolism: the role of milk-based formulae.

This paper explores the role of milk-based formulae in achieving four aspects of nutritional health in infants and toddlers: in the suckling, to mimic the amino acid metabolism and the faecal flora of a breast-fed baby; in the weanling, to achieve adequate protein intakes in later infancy and beyond and to achieve satisfactory haemoglobin concentrations in the early toddler years. Milk-based formulae have two roles in infant nutrition: as so-called breast milk substitutes and as a safety net during the weaning period; the latter role may be the more important.

Animals↗

PubMed1993

[Continuation or withdrawal of life-sustaining procedures in newborn infants: a study in 4 centers for neonatal intensive care].

OBJECTIVE: To provide data about continuation or withdrawal of life sustaining therapy in the critical ill newborn. METHOD: Retrospective examination of the histories of all 185 patients who died during the year 1990 (17% of total admissions) in 4 out of the 10 neonatal intensive care units in the Netherlands. RESULTS: The mean gestational age was 31.9 weeks (range 23-43; SD 5.5) and the mean birth weight 1827 g (455-5820; SD 1105). 136 infants were prematurely born, 49 full term. Intensive care was not started in 17 (9%) of the 185 patients and intensive care was withdrawn in 58 patients (31%) because there was no chance of survival. Therapy was withdrawn because of the poor prognosis for the quality of later life in 35 patients (19%). Intensive therapy was continued until death occurred in 74 infants (40%). Respiratory and circulatory problems, infections and severe acquired neurological damage were the main causes of death (32%, 17%, 19% and 24% of the cases respectively). In the cases of death due to respiratory and circulatory failure treatment was continued as long as possible. In infants who died with neurological damage as the main diagnosis, treatment was withdrawn because of the poor prognosis for the quality of life in 25 out of 44 infants. CONCLUSION: Life sustaining therapy was withdrawn or not started in 5% of the patients admitted because there was no chance of survival and in 3% because of a poor prognosis for the quality of later life.

Birth Weight↗

PubMed1993

Induction of lipid peroxidation of pulmonary surfactant by plasma of preterm babies.

Respiratory distress syndrome of the preterm baby is believed to be caused by a deficiency of pulmonary surfactant and leakage of plasma into the alveolar spaces. Since the two pathogenetic factors seem to be inter-related, we postulated that peroxidation of surfactant by plasma iron could be the linking mechanism. We obtained cord blood samples from 22 preterm babies (mean gestational age 32.2 [SD 2.7] weeks) and 24 term babies (40.1 [1.6] weeks), and venous blood samples from 18 healthy adults. No adult had detectable non-protein-bound iron in the plasma, but 10/21 (48%) preterm babies and 6/24 (25%) term babies had detectable concentrations (rate difference 23% [95% Cl -5 to 51%], p = 0.20). Transferrin and haptoglobin concentrations were higher and free haemoglobin concentrations lower in adults than in babies (p < 0.005). Only transferrin differed significantly between term and preterm babies. Plasma from all 18 adults and from 23 (96%) term babies inhibited iron-catalysed lipid peroxidation of pulmonary surfactant liposomes. By contrast, plasma from 11 (50%) preterm babies stimulated such peroxidation (difference in stimulation rate 46% [20-71%], p < 0.005 for preterm vs term babies); the ability to stimulate peroxidation was related to the presence of non-protein-bound iron (p < 0.001). Peroxidation decreased in the babies when apotransferrin was added to plasma and in all subjects when alpha-tocopherol was incorporated into the surfactant liposomes. Lipid peroxidation of surfactant may contribute to the pathogenesis of respiratory distress syndrome. Possible therapeutic approaches are increasing babies' iron-binding capacity by plasma transfusions and increasing the antioxidant capacity of commercial surfactant.

Adult↗

PubMed1993

Lipid peroxidation in human milk and infant formula: effect of storage, tube feeding and exposure to phototherapy.

Preformed lipid peroxidation products present in the feed may contribute to the total reactive oxygen radical load infants have to deal with and may play a role in the pathogenesis of necrotizing enterocolitis and bronchopulmonary dysplasia. In this study, the occurrence of lipid peroxidation in human milk and feeding formulas for preterm babies was evaluated in vitro. Free linoleic acid (18:2) and its hydroperoxide (18:2OOH) were measured by gas chromatography-mass spectrometry and the concentration of 18:2OOH and the 18:2OOH/18:2 ratio were used as indices of peroxidation. In all feeds peroxidation products were present, but the proportion of peroxidized 18:2 was greater in infant formula. Storage of human milk (+4 degrees C for four days) increased lipid peroxidation. Exposure to light during tube feeding increased peroxidation in infant formula but not in human milk. Different procedures for preparation, storage and feeding may decrease the concentration of these potentially toxic peroxidized lipids in human milk and infant formula.

Enteral Nutrition↗

PubMed1993

Is there a relationship between indomethacin-induced reduction in neonatal cerebral blood flow velocity and prostaglandin production?

Indomethacin lowers neonatal cerebral perfusion immediately after intravenous administration. It is important to elucidate whether this reduction is mediated by inhibition of production of prostaglandins, especially prostacyclin, which plays an important role in the autoregulation of the neonatal cerebral vascular bed. We studied changes in cerebral blood flow by serial measurements of temporal mean flow velocity in the anterior cerebral artery (TMFV-ACA), relative cerebral vascular resistance (R-cer), and prostaglandins (measured as changes in thiobarbituric acid reactive substances concentration; TBARS) after a therapeutic dose of 0.1 mg/kg indomethacin administered intravenously for noninvasive closure of patent ductus arteriosus. TMFV-ACA decreased and R-cer increased immediately after the indomethacin administration with a sustained recovery to pre-indomethacin values. The TBARS concentrations, however, did not change during the study period. We conclude that the present study suggests that a therapeutic dose of 0.1 mg/kg of indomethacin has no impact on prostaglandin metabolism.

Blood Flow Velocity↗

PubMed1993

Changes in cerebral hemodynamics and oxygenation in the first 24 hours after birth asphyxia.

OBJECTIVE: To investigate whether or not postasphyctic cerebral hypoperfusion and decreased cerebral metabolism occur in the perinatally asphyxiated neonate, as has been reported in adults and newborn animals. METHODS: Using near-infrared spectroscopy, we monitored changes in oxyhemoglobin (HbO2), deoxyhemoglobin (HbR), total hemoglobin (HbO2 + HbR, which represents changes in cerebral blood volume [CBV]), and cytochrome oxidase (Cytaa3, which indicates changes in oxidation level of this intracerebral mitochondrial enzyme). Thirty-one neonates (gestational age > 34 weeks), divided into three groups, were monitored between 2 and 12 hours or between 12 and 24 hours of life. Group I consisted of healthy newborns: N = 8 (2 to 12 hours) and N = 5 (12 to 24 hours). Patients in group II were moderately asphyxiated newborns but neurologically normal in the first 24 hours of life: N = 6 (2 to 12 hours) and N = 3 (12 to 24 hours). Group III consisted of severely asphyxiated newborns with an abnormal neurologic behavior within 24 hours after birth: N = 5 (2 to 12 hours) and N = 4 (12 to 24 hours). RESULTS: From 2 to 12 h, CBV levels in groups I and II were stable. In group III CBV decreased in all infants. This decrease in CBV was associated with a drop in both HbO2 and HbR. Cytaa3 was stable in groups I and II, but showed a marked decrease in two of the five infants of group III. There was a positive relationship between CBV and mean arterial blood pressure in groups II and III. Between 12 and 24 hours, all groups showed stable CBV and Cytaa3 patterns. A positive relation existed now between transcutaneous PCO2 and CBV in groups II and III. CONCLUSIONS: CBV, HbO2, HbR, and Cytaa3 decreased in the first 12 hours of life in severely asphyxiated neonates who subsequently developed neurologic abnormalities. We therefore suggest that posthypoxic-ischemic reperfusion injury of the brain during early neonatal life occurs in neonates with severe birth asphyxia.

Asphyxia Neonatorum↗

PubMed1992

Recycling of glutathione during oxidative stress in erythrocytes of the newborn.

The ability of erythrocytes from newborn babies and adults to maintain reduced glutathione levels during oxidative stress was studied. In vitro incubation of erythrocytes with H2O2, with or without inactivation of catalase, caused a rapid depletion of reduced glutathione (GSH) and concomitant accumulation of oxidized glutathione followed by recovery of GSH and fall of oxidized glutathione to initial values in all subjects. Inactivation of catalase resulted in a 50% loss of intracellular glutathione (p less than 0.005), a larger maximum GSH depletion (p less than 0.05), and a longer GSH recovery time (p less than 0.005). Erythrocytes from newborn babies showed a smaller maximum GSH depletion (p less than 0.05) and a shorter GSH recovery time (p less than 0.005) compared with those from adults. These differences between the newborn and adult groups persisted after inactivation of catalase. An increase in maximum GSH depletion and GSH recovery time (p less than 0.005) was observed when a lower hematocrit was used for these GSH recovery studies. Effective glutathione recycling in erythrocytes may protect immature tissues of the newborn baby from peroxidative damage.

Adult↗

PubMed1992

Limited protection against iron-induced lipid peroxidation by cord blood plasma.

The ability of plasma from newborn babies (cord blood) and adults to inhibit iron-induced lipid peroxidation was compared. The caeruloplasmin and transferrin concentrations, and latent iron-binding capacity were lower in the babies (p less than 0.001). The plasma of many of the babies had no latent iron-binding capacity and contained non-protein-bound iron (measured by the bleomycin assay). The in vitro ability of plasma to inhibit iron-induced liposome peroxidation by either ferroxidase antioxidant activity (caeruloplasmin) or iron-binding antioxidant activity (transferrin) was measured. The antioxidant activity in both assays was decreased in the babies (p less than 0.001). The percentage inhibition of peroxidation in the iron-binding antioxidant assay correlated positively with the latent iron-binding capacity (p less than 0.001) and negatively with the presence of bleomycin-detectable iron (p less than 0.02) in the babies. This assay produced stimulation of peroxidation in 42% of the babies but none of the adults. The diminished capacity of cord blood plasma to prevent iron-induced lipid peroxidation may predispose the newborn baby to the toxic effects of oxygen.

Adult↗