Vitamin C in premature and full-term human neonates

Summary

Plasma concentrations of vitamin C (ascorbic acid, AA) are known to be higher in full-term human neonates than their mothers. Immaturity of placental AA transport could result in low plasma AA concentrations in pre-term infants. We found that plasma AA concentrations in umbilical cord blood of 25 full-term neonates (38–42 weeks gestation) and 33 pre-term neonates (24–36 weeks gestation) were always significantly higher than in the corresponding maternal blood (P < 0.0001). However, plasma AA levels were significantly higher in pre-term than in full-term infants (146 ± 93 vs 102 ± 27 μM, respectively; P = 0.03). Furthermore, a rapid and sharp decrease in plasma AA concentrations from 229 ± 166 μM to 45 ± 18 μM (P < 0.0001) over the first 3 days of life was observed in eight very low birth weight infants (460–1090 g, 24–28 weeks gestation). These findings raise important questions about the in utero functions of AA in the developing fetus and the adequacy of postnatal vitamin C supplementation of the premature infant.     

正常顺产儿与早产儿人巨细胞病毒和风疹病毒脐带血清抗体检测分析

通过间接酶联免疫法检测178份新生儿(正常顺产儿为114例,早产儿64例)脐带血血清中人巨细胞病毒(human cytomegalovirus,HCMV)和风疹病毒(rubella virus,RV)IgG和IgM抗体,并分析所测结果与临床表现的相关性。结果表明,178例新生儿脐带血血清中HCMV-IgG阳性标本为168例(94.38%),HCMV-IgM阳性标本为1例(0.56%);RV-IgG阳性标本为119例(66.85%);RV-IgM阳性标本为1例(0.56%)。其中,正常顺产儿脐带血中HCMV-IgM和RV-IgM阳性率均为0.87%(1/114),HCMV-IgG阳性率为94.73%(108/114),RV-IgG阳性率为61.40%(70/114),HCMV和RV IgG两者均阳性者为55.26%(63/114);早产儿HCMV-IgM和RV-IgM均为阴性(0/64),HCMV-IgG阳性率为93.75%(60/64),RV-IgG阳性率为76.56%(49/64),HCMV和RV IgG两者均阳性者为70.31%(45/64)。早产儿与正常顺产儿比较,早产儿的RV-IgG阳性率和HCMV和RV-IgG两者均阳性者均高于正常顺产儿,且差异有统计学意义(P<0.05)。可见,HCMV感染率较高,至今仍无有效的HCMV疫苗,应加大疫苗研发力度。所查新生儿RV-IgG阳性率为66.48%,提示中国33%以上的育龄期妇女有在孕早期暴露感染的机率,国家有必要加大该种疫苗的接种力度。     

Identification of diagnostic biomarkers for infection in premature neonates

Infection is a leading cause of neonatal morbidity and mortality worldwide. Premature neonates are particularly susceptible to infection because of physiologic immaturity, comorbidity, and extraneous medical interventions. Additionally premature infants are at higher risk of progression to sepsis or severe sepsis, adverse outcomes, and antimicrobial toxicity. Currently initial diagnosis is based upon clinical suspicion accompanied by nonspecific clinical signs and is confirmed upon positive microbiologic culture results several days after institution of empiric therapy. There exists a significant need for rapid, objective, in vitro tests for diagnosis of infection in neonates who are experiencing clinical instability. We used immunoassays multiplexed on microarrays to identify differentially expressed serum proteins in clinically infected and non-infected neonates. Immunoassay arrays were effective for measurement of more than 100 cytokines in small volumes of serum available from neonates. Our analyses revealed significant alterations in levels of eight serum proteins in infected neonates that are associated with inflammation, coagulation, and fibrinolysis. Specifically P- and E-selectins, interleukin 2 soluble receptor alpha, interleukin 18, neutrophil elastase, urokinase plasminogen activator and its cognate receptor, and C-reactive protein were observed at statistically significant increased levels. Multivariate classifiers based on combinations of serum analytes exhibited better diagnostic specificity and sensitivity than single analytes. Multiplexed immunoassays of serum cytokines may have clinical utility as an adjunct for rapid diagnosis of infection and differentiation of etiologic agent in neonates with clinical decompensation.     

Bleomycin-detectable iron in the plasma of premature and full-term neonates.

The bleomycin assay measures non-transferrin-bound iron, able to catalyze free radical reactions, in human plasma. No bleomycin-detectable iron is present in plasma from healthy adults. However, plasma from 3/15 premature babies was positive in this assay. Plasma from 52 apparently-healthy term babies was analyzed and 11 were positive in the bleomycin assay. Hence not only some premature but also some full-term apparently-healthy babies may be at risk of severe oxidative damage.     

Isolation of Robinsoniella peoriensis from the feces of premature neonates

Robinsoniella peoriensis is a recently described anaerobic, spore-forming, Gram positive bacillus originally recovered from swine-manure and clinical human samples. In this study, R. peoriensis was isolated from the feces of one set of twin premature neonates. It suggests that this anaerobic bacillus may be a commensal bacterium of human gut.     

Amino acids do not suppress proteolysis in premature neonates

To determine whether increased amino acid availability can reduce proteolysis in premature neonates and to assess the capacity of infants born prematurely to acutely increase the irreversible catabolism of the essential amino acids leucine (via oxidation) and phenylalanine (via hydroxylation to form tyrosine), leucine and phenylalanine kinetics were measured under basal conditions and in response to a graded infusion of intravenous amino acids (1.2 and 2.4 g. kg(-1). day(-1)) in clinically stable premature (approximately 32 wk gestation) infants in the 1st wk of life. In contrast to the dose-dependent suppression of proteolysis seen in healthy full-term neonates, the endogenous rates of appearance of leucine and phenylalanine (reflecting proteolysis) were unchanged in response to amino acids (297 +/- 21, 283 +/- 19, and 284 +/- 31 micromol. kg(-1). h(-1) for leucine and 92 +/- 6, 92 +/- 4, and 84 +/- 7 micromol. kg(-1). h(-1) for phenylalanine). Similar to full-term neonates, leucine oxidation (40 +/- 5, 65 +/- 6, and 99 +/- 7 micromol. kg(-1). h(-1)) and phenylalanine hydroxylation (12 +/- 1, 16 +/- 1, and 20 +/- 2 micromol. kg(-1). h(-1)) increased in a stepwise fashion in response to graded amino acids. This capacity to increase phenylalanine hydroxylation may be crucial to meet tyrosine needs when exogenous supply is limited. Finally, to determine whether amino acids stimulate glucose production in premature neonates, glucose rate of appearance was measured during each study period. In response to amino acid infusion, rates of endogenous glucose production were unchanged (and near zero).     

Dapsone for the treatment of doxorubicin extravasation injury in the rat

Doxorubicin is the most common antitumor drug implicated in serious extravasation injuries. Progressive tissue necrosis may lead to intense pain, chronic ulceration, and disfiguring tissue loss. This progressive necrosis is analogous to that seen with brown recluse spider bites, where dapsone is an established mode of therapy, minimizing the area of tissue loss by a proposed antiinflammatory mechanism. The backs of 50 Lewis rats were injected intradermally with 1 mg of doxorubicin in 1 cc of saline to simulate an extravasation injury. The rats were divided into five groups for treatment with oral dapsone 50 mg/kg/day: 10 were controls (no treatment), 10 were started the day before injury, 10 were started the day of injury, 10 were started the day after injury, and 10 were started 1 week after injury. The area of ulceration was calculated by planimetry. The data suggest that dapsone has little positive effect on healing extravasation ulcers.     

Nonspecific killer cells in premature and mature neonates and infants

K (killer) and natural killer (NK) cells were investigated in peripheral blood of 76 children, preterm small for date babies (n = 8), preterm babies (n = 15), fullterm small for date babies (n = 6) fullterm babies (n = 7) and infants up to 12 months age (n = 40). The K and NK cell activity of human leukocytes was analysed as compared with those cells of the K 562 cell line and murine cells covered by xenologous antibodies in Graffi erythroblast leukemia by means of the 51Cr release test. K cell activities were significantly lower in preterm small for date babies to infants with 1-12 months of age. In our results it is shown that NK capacity of preterm or term newborns and infants up to 6 months age does not differ significantly from each other. Children who are 6-12 months old will have significantly higher NK cell activities. It can be concluded that K cell activities are fully developed during pregnancy and NK cell activities later when the children are between 6 and 12 months of age.     

Aberrant gut-microbiota-immune-brain axis development in premature neonates with brain damage

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Influence of recombinant human erythropoietin on neutrophil function in premature neonates

The in vivo influence of recombinant human erythropoietin (rhEpo) and iron on human neutrophil (PMN) antimicrobial function was assessed. A total of 21 preterm infants were randomized to receive either 200 U/kg/other day of rHuEPO+12 mg/kg/day of iron (EPO+high Fe, seven infants) or 200 U/kg/other day of rhEPO+4 mg/kg/day of iron (EPO+standard Fe, 9 infants) or 4 mg/kg/day of iron only (standard Fe, five infants). PMNs were isolated from blood of these infants 60+/-5 days after birth and from eight healthy adults. No differences between infants and adults were found in PMN random migration and chemotactic activity to N-formylmethionyl leucyl phenylalanine (FMLP), superoxide anion production in response to FMLP and phagocytosis of Staphylococcus aureus. In contrast, percentage phagocytosis was significantly lower in EPO+standard Fe as compared to both EPO+high Fe and standard Fe groups (P<0.01). This modest impairment of phagocytic activity of neonatal PMNs found in association with administration of rhEPO and standard iron may be related to consumption of iron during rhEPO-enhanced erythropoiesis.     

Factors affecting the premature induction of phosphopyruvate carboxylase in neonatal rat liver

1. Phosphopyruvate carboxylase activity rapidly appears in the liver of prematurely delivered rats and development of activity is prevented by injection of actinomycin D just before delivery. 2. The activity is considerably decreased by puromycin and amino acid analogues and thus appears to be due to enzyme synthesis. 3. Newborn or premature animals show a transient intense phase of hypoglycaemia after delivery. 4. When the hypoglycaemic phase is prevented by glucose injection little phosphopyruvate carboxylase activity appears in the liver, but galactose, mannose and fructose, which have no effect on the blood glucose concentration, also repress enzyme development. 5. Lactate, pyruvate and glycerol injections repress the premature development of phosphopyruvate carboxylase. 6. Injections of glucagon, adrenalin and noradrenalin into the rat foetus in utero result in development of phosphopyruvate carboxylase activity. 7. These findings are discussed in relation to the mechanism of initiation of enzyme synthesis in neonatal rat liver.     

Factors affecting the premature induction of tyrosine aminotransferase in foetal rat liver

1. Premature delivery of foetal rats by uterine section results in the rapid appearance of tyrosine aminotransferase activity in foetal liver, after an initial lag period of 3-6hr. 2. The premature induction of activity is completely repressible by actinomycin D given soon after delivery and partially repressible by puromycin and amino acid analogues. 3. Glucagon injections into foetal rats in utero lead to production of tyrosine aminotransferase in the foetal liver, but adrenalin and nor-adrenalin are without effect. 4. Injections of glucose, galactose, fructose and mannose into prematurely delivered rats repress the development of tyrosine aminotransferase activity about 50% when they are given 2hr. after delivery, but glucose has no significant effect when injected at delivery. 5. The results are discussed in relation to current hypotheses on the role of hormones in enzyme induction in foetal development.     

The use of ethyl methanesulfonate for the induction of mutants inMycobacterium phlei PA

The mutagenic effect of ethyl methanesulfonate in a concentration of 0.2m on a prototrophic, acid-fast strainMycobacterium phlei PA was studied by following the induction of changes of three genetic markers: prototrophy to auxotrophy and sensitivity to two antituberculosis drugs (INH and STM) to resistence. Ethylmethanesulfonate was found to be a very effective mutagen in all three cases. Thirty auxotrophic strains were obtained, out of which eight exhibited a low frequency of spontaneous reversions and could hence be used for further studies. Of the phenotypes induced the glycine⁻ (serine⁻) type was most frequently isolated and represented more than half of all auxotrophs obtained. Requirements for lysine and purines were also observed. The EMS treatment (1% survival of the basic suspension) resulted in a 74-fold increase of the frequency of INH-resistant mutants and a frequency of STM-resistant mutants about 1.1/2 to almost 2 orders of magnitude higher than the spontaneous values     

Levels of soluble ICAM-1 in premature and full-term neonates with infection

BACKGROUND: Infection in the neonatal period is an extremely serious condition and diagnosis is difficult. C-reactive protein (CRP) is widely used as a marker of infection; however, its usefulness is limited in the early phase. The role of soluble intracellular adhesion molecule-1 (sICAM-1), an adhesion molecule, has been examined in recent studies as an early marker of neonatal infection with controversial results. AIM: Assessment of sICAM-1 concentrations and correlation with CRP, which is the currently used marker of infection, in order to use sICAM as an early diagnostic tool in neonates suspected for infection METHODS: Blood samples and blood cultures were obtained from two groups of pre-term and full-term neonates with clinical suspicion of infection prior to the initiation of antibiotics. The sICAM-1 and CRP values were compared with the corresponding noninfected ones (n = 10 each). RESULTS: The sICAM-1 levels were found increased in the group of both premature and term neonates with infection compared with the corresponding healthy ones (P < 0.0001). Prematurity combined with infection resulted in excessive increase of the levels of sICAM-1 in comparison with full-term infected newborns (p < 0.001). CRP values were normal in all samples except one in both full-term and premature infected neonates on day 1 of clinically suspected infection. Serial detection of CRP values on days 2 and 4 of infection revealed a pattern according to which CRP values in premature neonates continued rising, while in the group of full terms these values, after rising on the second day, lowered on day 4. CONCLUSIONS: Increased sICAM-1 levels can be detected early in both full-term and premature neonates with sepsis while CRP levels are within normal range at the same time. Assessment of sICAM-1 concentrations may be used as a diagnostic tool in neonates suspected for infection, resulting in earlier initiation of antibiotic therapy and therefore improving their outcome.     

The significance of extravasation in oncological care

The treatment of cancer may be associated with various chemotherapy-induced mucocutaneous reactions. One of the mucocutaneous adverse effects of antineoplastic drugs is the toxic local tissue reaction, the extravasation, which occurs in less than 1-2% of cytotoxic infusions. The standard management of vesicant extravasation includes: discontinuing all local infusions, aspiration of any residual drug, elevating the involved limb, local cooling or warm compresses, local anesthesia, antidotes (sodium thiosulfate for alkylating agents, dimethylsulfoxide (DMSO) for anthracyclines and mitomycin, and hyaluronidase for the vinca alkaloids), and finally surgical debridement with plastic surgery reconstruction. Because the anthracyclines are topoisomerase II poisons that are antagonized by topoisomerase II catalytic inhibitors such as dexrazoxane, it seems to be the treatment of choice immediately after extravasation of doxorubicin, epirubicin, daunorubicin, etc. One systemic dose of dexrazoxane after the accident may significantly reduce the toxic tissue lesions. Repeated intralesional injections of GM-CSF may accelerate the wound healing without the need of skin grafts.     

VEP's in normal full-term and premature neonates: longitudinal versus cross-sectional data

VEPs have been shown to change with CNS maturation in children, yet few studies had documented maturational changes in the premature infant. Using LED goggles, VEPs were studied in 75 neurologically normal infants of 22–42 weeks gestational age (GA) within the first 3 days of life. Twenty of these (22–32 weeks GA) were also followed longitudinally.The 22–23 week GA neonates had no identifiable waves. In all infants >24 weeks a large negative wave is seen with a latency around 300 msec (N300). After 27 weeks GA a late positive wave was present (P400), but with more variable latency and morphology. Between 30 and 35 weeks GA a small positive wave (P200) was seen in over one-third of the neonates; this component was present in all infants > 36 weeks GA.The consistency of the N300 across the ages studied suggests that it might arise from the basilar dendrites in the visual cortex, which are well developed by 24 weeks GA and undergo relatively little further development between 24 weeks and term. The P200 is suggested to arise from the apical dendrites which develop in the last trimester, explaining the emergence of P200 after 30 weeks GA.The infants followed longitudinally showed the same components, emerging in the same order, but with more rapid development (particularly of P200) compared to the cross-sectional studies. These data suggest that there are differences in the maturation of the visual system in the extrauterine versus intrauterine environment.     

Effect of lung inflation on the respiratory frequency and heart rate of premature neonates

Changes in the respiratory frequency and heart rate in response to 10 seconds' inflation of the lungs with oxygen by the CPAP method were studied in 32 premature neonates. Elevation of the pressure in the airways and lungs of 0.25, 0.49, 0.73 and 0.98 kPa led to a slower respiration rate or to apnoea. The incidence of apnoea rose in proportion to the pressure. When inflation was started, forced inspiratory efforts (a gasp reflex) occurred. The incidence of the efforts was higher at higher inflation pressures, but their intensity was not correlated to the size of the pressure. They were manifested in a drop in oesophageal pressure to a mean -2.0 +/- 0.2 kPa and their mean duration was 169 +/- 8 ms. The administration of oxygen without an increase in pressure produced neither apnoea nor forced inspiratory reactions. Neither an increase in the pressure in the airways and lungs to the above values, nor the plain administration of oxygen, produced any significant changes in the instantaneous heart rate.