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Biomedical subjects

J V Aranda

Publications and source records attributed to J V Aranda.

At least 19 recordsLinked to original sources
PubMed2006

Systematic review: intravenous Ibuprofen in preterm newborns.

Ibuprofen, a nonsteroidal antiinflammatory drug, widely used as antipyretic, antiinflammatory, and analgesic agent and for therapy of arthritis, exerts a dose-dependent constriction of the ductus arteriosus in newborn lambs. Two intravenous preparations, namely ibuprofen lysine and ibuprofen-THAM, have been studied in preterm newborns with patent ductus arteriosus. Clinical trials have compared IV ibuprofen to placebo, or to indomethacin. Pharmacodynamic effects of this drug before and after its administration have also been evaluated. Compared with placebo, IV ibuprofen effectively closed PDA with minimal effect on renal function. One study using intravenous ibuprofen-THAM showed decreased renal function and increased risk of NEC and PPHN. Compared with indomethacin, IV ibuprofen lysine exerted similar efficacy (75% to 93% closure). However, indomethacin increased abnormal renal function and decreased mesenteric and cerebral blood flow and bio-energetics. Two clinical trials showed that ibuprofen did not reduce the incidence of intraventricular hemorrhage compared with placebo. The drug has prolonged elimination (plasma half-life = ca 23 hours), suggesting that once daily dosing is appropriate. Dose finding studies indicate that a starting dose of 10 mg/kg followed by 5 mg/kg/d for 2 more days provides optimal efficacy with the least adverse effects. Neonatal data on ibuprofen and indomethacin indicate that, on the first day of life when IVH prevention is desired, indomethacin and not ibuprofen should be used since ibuprofen has no effect on IVH risk. On or after the second day of postnatal life, when early or therapeutic PDA closure is needed, ibuprofen and not indomethacin is probably the first choice due to its better adverse event profile.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2005

Analgesia and sedation during mechanical ventilation in neonates.

BACKGROUND: Endotracheal intubation and mechanical ventilation are major components of routine intensive care for very low birth weight newborns and sick full-term newborns. These procedures are associated with physiologic, biochemical, and clinical responses indicating pain and stress in the newborn. Most neonates receive some form of analgesia and sedation during mechanical ventilation, although there are marked variations in clinical practice. Clinical guidelines for pharmacologic analgesia and sedation in newborns based on robust scientific data are lacking, as are measures of clinical efficacy. OBJECTIVE: This article represents a preliminary attempt to develop a scientific rationale for analgesia sedation in mechanically ventilated newborns based on a systematic analysis of published clinical trials. METHODS: The current literature was reviewed with regard to the use of opioids (fentanyl, morphine, diamorphine), sedative-hypnotics (midazolam), nonsteroidal anti-inflammatory drugs (ibuprofen, indomethacin), and acetaminophen in ventilated neonates. Original meta-analyses were conducted that collated the data from randomized clinical comparisons of morphine or fentanyl with placebo, or morphine with fentanyl. RESULTS: The results of randomized trials comparing fentanyl, morphine, or midazolam with placebo, and fentanyl with morphine were inconclusive because of small sample sizes. Meta-analyses of the randomized controlled trials indicated that morphine and fentanyl can reduce behavioral and physiologic measures of pain and stress in mechanically ventilated preterm neonates but may prolong the duration of ventilation or produce other adverse effects. Randomized trials of midazolam compared with placebo reported significant adverse effects (P < 0.05) and no apparent clinical benefit; the findings of a meta-analysis suggest that there are insufficient data to justify use of IV midazolam for sedation in ventilated neonates. CONCLUSIONS: Despite ongoing research in this area, huge gaps in our knowledge remain. Well-designed and adequately powered clinical trials are needed to establish the safety, efficacy, and short- and long-term outcomes of analgesia and sedation in the mechanically ventilated newborn.

Analgesia↗
PubMed2005

Lidocaine 4% cream compared with lidocaine 2.5% and prilocaine 2.5% or dorsal penile block for circumcision.

This study evaluated the efficacy and safety of lidocaine 4% cream (LMX4), compared with lidocaine 2.5% and prilocaine 2.5% (EMLA) or dorsal penile block (DPNB) for analgesia during circumcision. Healthy, term males (n = 54), younger than 1 week old undergoing circumcision were randomly assigned to open-label pretreatment with LMX4, EMLA, or DPNB. Heart rate (HR; beats per minute [bpm]), respiratory rate (RR; breaths/minute), and arterial oxygen saturation as measured by pulse oximetry (Sp O2; %) were monitored at baseline, and during drug application, circumcision, and recovery. Mean differences were compared using the general linear model. At the end of drug application, mean HR for infants receiving LMX4 (146 bpm; standard error of mean [SEM], 8.0 bpm) was lower than that for DPNB (176 bpm; SEM, 8.3 bpm; p < 0.05). No significant difference in mean HR was observed between treatments during circumcision. Mean RR was higher during circumcision for EMLA compared with LMX4 (p < 0.05) and DPNB (p < 0.05). At lysis, mean RR was significantly lower in DPNB than LMX4 and EMLA. The number of Sp O2 samples was too small for comparison. Three infants (one receiving LMX4 and two receiving EMLA) experienced local reactions (p = 0.54). No adverse effects were observed with DPNB. No difference in analgesic efficacy was observed between treatments according to HR. Differences in RR may reflect a varying level of analgesia. The safety profile was similar for all treatments. LMX4 is an effective analgesic for newborn circumcision.

Administration, Cutaneous↗
PubMed2004

Pharmacogenomics and renal drug disposition in the newborn.

Genetic polymorphisms in the genes coding for drug metabolizing enzymes, drug transporters, and drug receptors are major determinants of an individual's response to drugs. The potential interactions of pharmacogenomics of renal drug transporters and drug receptors with renal drug disposition and the immature kidneys are briefly reviewed. Examples of gene polymorphisms seen in the RAAS (renin angiotensin system), beta-adrenergic receptors, dopamine receptors and cytochrome P450 and their potential clinical impact are discussed. The human newborn has deficient hepatic and renal drug metabolism and disposition. This immaturity in drug-handling capacity may potentially be superimposed to genetic polymorphisms determining drug metabolism and transport thereby substantially increasing interpatient variability in drug dose requirements and in drug responses in the newborn. Pharmacogenomics is a tool that can be used to individualize drug therapy in newborns to minimize adverse drug effects and to optimize efficacy.

Aldosterone↗
PubMed2004

Management of infiltration injury in neonates using duoderm hydroactive gel.

Neonates are at increased risk of injury from infiltration of intravenous fluids because of small vessel size and immature skin structure. Until recently, hyaluronidase injection was used to prevent tissue injury following the infiltration of intravenous solutions in neonates. The production of hyaluronidase injection was discontinued in 2001. The alternative, compounded hyaluronidase injection is not regulated by the U.S. Food and Drug Administration and is subject to variation in quality assurance practices. Amorphous hydrogels have been used as wound dressings for sloughy or necrotic wounds in a variety of clinical settings. Hydrogels facilitate autodebridement of the wound by rehydrating slough and enhancing the rate of autolysis. No adverse effects or increased infection rates have been associated with the use of hydrogel dressings. DuoDerm Hydroactive gel is a sterile, preservative-free, viscous, hydrating gel composed of natural hydrocolloids. We report our experience using DuoDerm Hydroactive gel for management of injury secondary to the infiltration of total parenteral nutrition solution and lipid emulsion in three neonates.

Autolysis↗
PubMed2001

Group B Streptococci and inducible nitric oxide synthase: modulation by nuclear factor kappa B and ibuprofen.

Group B Streptococci (GBS) neonatal infections cause a complex inflammatory process involving numerous biochemical mediators. Nitric Oxide (NO) is generated by many cell types in response to different inflammatory signals. Nuclear factor kappa B (NFkappaB) plays an important role in the inflammatory process and may induce a number of biochemical mediator genes, including the inducible nitric oxide synthase (iNOS). We tested the hypothesis that GBS induces iNOS gene expression through activation of NFkappaB. We also tested whether ibuprofen (IBU) will suppress iNOS expression by blocking NFkappaB activation. Cerebral microvascular endothelial cells isolated from newborn piglets were harvested for the determination of iNOS gene expression and activation of NFkappaB. GBS significantly induced iNOS mRNA expression (5- to 6-fold, P < .005) and iNOS protein (3- to 4-fold, P < .01) at 24 hours. DNA-NFkappaB binding activity was detected within 15 minutes of GBS treatment and reached a maximal effect at 3 hours. Treatment with IBU significantly suppressed GBS-induced iNOS mRNA expression at 24 hours, and NFkappaB activity at 3 hours, suggesting that suppression of GBS-induced iNOS mRNA expression by IBU occurs by blocking of NFkappaB activation. These data show that NFkappaB activation is an early step in the induction of iNOS gene expression by GBS and that this interaction may play a vital role in the pathogenesis of GBS neonatal infections.

Animals↗
PubMed2000

Nitric oxide, prostaglandins, and impaired cerebral blood flow autoregulation in group B streptococcal neonatal meningitis.

Impaired autoregulation of cerebral blood flow (CBF) contributes to CNS damage during neonatal meningitis. We tested (i) the hypothesis that cerebrovascular autoregulation is impaired during early onset group B streptococcal (GBS) meningitis, (ii) whether this impairment is regulated by vasoactive mediators such as prostaglandins and (or) nitric oxide (NO), and (iii) whether this impairment is preventable by specific and (or) nonspecific inhibitors: dexamethasone, ibuprofen, and Nomega-nitro-L-arginine, a NO inhibitor. Sterile saline or 10(9) colony-forming units (cfu) of heat-killed GBS was injected into the cerebral ventricle of newborn piglets. CBF autoregulation was determined by altering cerebral perfusion pressure (CPP) with balloon-tipped catheters placed in the aorta. GBS produced a narrow range of CBF autoregulation due to an impairment at the upper limit of CPP. We report that in vivo in the early stages (first 2 h) of induced GBS inflammation (i) GBS impairs the upper limit of cerebrovascular autoregulation; (ii) ibuprofen, dexamethasone, and Nomega-nitro-L-arginine not only prevent this GBS-induced autoregulatory impairment but improve the range of cerebrovascular autoregulation; (iii) these autoregulatory changes do not involve circulating cerebral prostanoids; and (iv) the observed changes correlate with the induction of NO synthase gene expression. Thus, acute early onset GBS-induced impairment of the upper limit of CBF autoregulation can be correlated with increases of NO synthase production, suggesting that NO is a vasoactive mediator of CBF.

Animals↗
PubMed1999

Deregulation of cyclooxygenase and nitric oxide synthase gene expression in the inflammatory cascade triggered by experimental group B streptococcal meningitis in the newborn brain and cerebral microvessels.

Group B Streptococcus (GBS) is the most common cause of neonatal sepsis and meningitis. Despite antibiotics, GBS in the newborn initiates a cascade of molecular and biological events leading to altered cerebral perfusion, blood-brain barrier disruption, cerebral edema, intracranial hypertension, neurological damage, and even death. Having previously shown that GBS infection impairs cerebral blood flow autoregulation and increases prostaglandin (PG) levels, we examined the regulation of some crucial inflammatory mediators (PGs, nitric oxide (NO), tumor necrosis factor-a) in the brain and cerebral microvessels (MVs) from newborn piglets. Cyclooxygenase (COX), the key enzyme in PG biosynthesis, exists in two isoforms, COX-1 and COX-2. Both may be directly induced by NO in a model of renal inflammation. Besides its neurotransmitter role, NO is a potent vasorelaxant whose production is catalyzed by at least three distinct nitric oxide synthases (NOS) (bNOS, ecNOS, iNOS). Western blot analyses showed that the newborn (4 day old) brain expressed lower levels of COX-1 (8-fold), COX-2 (20-fold), bNOS (12-fold), and ecNOS (5-fold) than in the 1 day old. MV showed approximately equal levels of COX-2, lower levels of COX-1 (4-fold), bNOS (5-fold), and higher levels of ecNOS (20-fold) in comparison to 4-day-old cerebral MV. A 4-day-old brain expressed lower levels of bNOS (5-fold), ecNOS (10-fold), and COX-1 (2-fold) than the 6-week-old pig. COX-2 protein was undetected in a 4-day-old pig brain, but present in great excess in MV. Purified MV showed lower ecNOS (14-fold), COX-1 (2-fold), and about equal levels of bNOS and COX-2 in comparison with MV from 6-week-old pigs. Reverse transcription polymerase chain reaction analyses confirmed these results. Treatment with noo-nitro-L-arginine (LNA), a NOS inhibitor, downregulated COX-1 expression in the newborn brain and both COX-1 and COX-2 cerebral MV expression. GBS infection (10(9) colony-forming units, 0.5 mL intracerebroventricular) of sedated newborn piglets induced the expression of tumor necrosis factor-alpha in the cerebrospinal fluid after 2 hours, upregulated bNOS expression in both brain and MVs, upregulated ecNOS in MVs, and downregulated COX-1, COX-2, and ecNOS in the brain. GBS did not trigger the expression of iNOS. Our data suggest that there is a net deficiency of NOS isoforms in the immature brain and microvasculature of the 4-day-old piglet and that the differences in expression lead to the immature control of NO and PG production, rendering newborns particularly susceptible to neurological damage because of the undeveloped nature of their response mechanisms. Moreover, the GBS-induced cascade deregulates the gene expression of interacting inflammatory mediators and may cause a net vasoconstrictor/vasodilator imbalance, leading to cerebral hypertension and edema in the early stages of infection. Pharmacological manipulations of the inflammatory cascade could lead to novel therapeutic approaches for the treatment of GBS meningitis.

Animals↗
PubMed1999

Plasma homocysteine concentrations of preterm infants.

Mild hyperhomocysteinemia in adults is associated with an increased risk of vascular disease. Although information is available about plasma homocysteine concentrations in childhood, data are entirely lacking for preterm infants despite their known abnormalities of sulfur amino acid metabolism. We measured plasma total homocysteine concentrations of 9 preterm infants (gestational age 23-31 weeks) within 48 h of birth and over the subsequent 14 days of life, and 4 term infants (gestational age 36-39 weeks) on a single occasion within 72 h of birth. As measured within 48 h of birth, average plasma homocysteine and cysteine concentrations of the preterm infants were 3.8 +/- 0.3 and 122 +/- 8 microM, both significantly less than those of the term infants (6.1 +/- 1.3 and 187 +/- 39) and of normal adults (8.2 +/- 0.5 and 232 +/- 6). Plasma homocysteine (but not cysteine) appeared to gradually increase during the first 2 weeks of life (p = 0.053). Our results indicate that hyperhomocysteinemia does not normally occur in preterm infants.

Adult↗
PubMed1997

Histamine release during cardiopulmonary bypass in neonates and infants.

PURPOSE: Histamine release has been previously documented in adults and children during cardiopulmonary bypass (CPB). It has not been studied in neonates nor during deep hypothermic circulatory arrest (DHCA). Histamine effects could explain many perioperative complications of congenital cardiac surgery such as dysrhythmias and massive oedema. Therefore, documentation of histamine release in the perioperative period is of clinical importance. The source of histamine can be determined by measurement of tryptase which is released with histamine from mast cells but not basophils. METHODS: Blood samples for histamine and tryptase were taken before and after specific events eg. cross-clamp removal, during anaesthesia and CPB in 14 infants and seven neonates undergoing complex congenital heart repairs and were analysed by commercial radioimmunoassays. Haemodynamic variables and pre and post-op weights were recorded to look for correlation between pathophysiological events and histamine release. RESULTS: Histamine concentration decreased at the start of bypass (0.69 to 0.38 ng.ml-1 at five minutes, (P < .005). There were no changes associated with DHCA and a small rise with reventilation (P < 0.02). Histamine concentration was lower in neonates than in infants (P < 0.05) during CPB. Plasma histamine and tryptase concentrations did not correlate, suggesting histamine release was from basophils and not from mast cells. Haemodynamic variables did not correlate with histamine concentrations. CONCLUSION: There was no major histamine release during CPB in infants and neonates. There was no relationship between histamine concentrations and clinical variables. Histamine released during CPB appears to come from basophils and may be a function of age.

Age Factors↗
PubMed1997

Pharmacokinetics and protein binding of intravenous ibuprofen in the premature newborn infant.

The elimination, disposition and protein binding of ibuprofen (IBU) in premature infants were studied for use in the prevention of intraventricular hemorrhage and closure of patent ductus arteriosus. The kinetic profile of i.v. IBU lysine (10 mg/kg bolus) given within the first 3 h after birth was studied in 21 premature neonates (mean birthweight = 944.7 g, range: 575-1450 g; gestational age: 26.8 weeks, range: 22-31 weeks). Blood samples (0.3 ml/sample) were obtained at time 0 and at 1, 3, 6, 12, 24, 48, and 72 h post-dose for IBU by high-performance liquid chromatography (HPLC). Kinetic analyses assumed applicability of one open-compartment model and calculations from the model-independent areas under the time concentration curve (AUC). Data (mean +/- SEM) show that apparent volume of distribution (AVd) was 62.1 +/- 3.9 ml/kg, plasma t1/2 beta was 30.5 +/- 4.2 h, elimination rate constant (Kel) was 0.032 +/- 0.004 h-1, plasma clearance was 2.06 +/- 0.33 ml/kg/h and plasma concentration (Cp) at 1 h was 180.6 +/- 11.1 mg/l. Gestational age and birthweight were not related to drug elimination. In 10 neonates, IBU maintenance dose of 5 mg/kg once daily on days 2 and 3 generated mean Cp of 116.6 +/- 54.5 mg/l and 113.6 +/- 58.2 mg/l, respectively. Protein binding by ultrafiltration and capillary electrophoresis showed that the percentage bound IBU was significantly lower in full term cord plasma (94.98 +/- 0.39%, n = 26) compared to adult plasma protein (mean +/- SE = 98.73 +/- 0.31%, n = 8, p < 0.0001). Compared to data from adults and older children, IBU elimination is markedly prolonged in neonates and protein binding is slightly lower. Thus, investigational and clinical therapeutic regimens should be adjusted to account for decreased drug disposition to ensure safe and effective therapy.

Age Factors↗
PubMed1996

Early ibuprofen administration to prevent patent ductus arteriosus in premature newborn infants.

OBJECTIVE: To test whether early postnatal (0 to 3 hours) intravenous administration of ibuprofen will prevent patent ductus arteriosus (PDA) in preterm neonates. DESIGN: Prospective sequential controlled trial with three treatment arms. SETTING: Level 3 perinatal-neonatal intensive care nursery. PATIENTS: Thirty-four premature newborn infants born from February to August 1993 with a mean birth weight of 913 g (range, 565 to 1460 g) and gestational age of 26.9 weeks (range, 22.4 to 31.0). INTERVENTION: Infants were consecutively assigned within 3 hours of age to treatment with either one dose of ibuprofen lysine (10 mg/kg intravenously) followed by 5 mg/kg per dose intravenously at 24 and 48 hours of age (n = 12), one dose of ibuprofen lysine (10 mg/kg intravenously; n = 11), or saline (n = 11). OUTCOME VARIABLES: Primary outcome variable was the presence of ductus arteriosus by echocardiography and clinical assessments at 3, 7, and 21 days of life. Secondary outcome variables included presence of intraventricular hemorrhage, renal function, ventilatory and oxygen needs, hematologic changes, gastrointestinal function, time to full enteral feeding, duration of hospitalization, and age at discharge. RESULTS: The three groups of patients were comparable in birth weight, gestational age, antenatal administration of betamethasone, and other perinatal characteristics. Ibuprofen treatment significantly reduced plasma levels of prostaglandins, and the levels remained low for 72 hours in newborns who received three doses of the drug. The incidence of PDA and other variables did not differ between patients who received a single dose of ibuprofen and those given saline. However, compared with the saline-treated newborns, babies who received three doses of ibuprofen had no PDA (0/12 vs 7/11 for saline; P < .02), had lower daily mean airway pressures (mean +/- SD, 5.2 +/- 1.1 cm H2O vs 8.3 +/- 2.8 cm H2O for saline; P < .02) and better oxygenation index (2.6 +/- 0.6 vs 4.7 +/- 1.8 for saline; P < .02) at the end of the first week of life, and required fewer days of ventilation (25 +/- 14 days vs 44 +/- 26 days for saline; P < .03). Babies given three doses of ibuprofen tended to tolerate full oral feedings earlier (35 +/- 19 days vs 56 +/- 34 days for saline; P = .09), had shorter duration of hospitalization (71.2 +/- 22.6 days vs 127.3 +/- 74.7 days for saline; P < .05), and were discharged to home at an earlier postconceptional age (37.8 +/- 2.0 weeks vs 44.8 +/- 9.8 weeks for saline; P < .05). ibuprofen treatment in this phase I trial was not associated with any apparent early neurological, intestinal, renal, hepatic, or hematologic complications. CONCLUSIONS: Administration of three doses of ibuprofen within 3 hours after birth in preterm neonates reduced the incidence of PDA without causing notable early adverse drug reactions in this phase I trial. Early closure of the ductus arteriosus was also associated with better respiratory outcome and earlier discharge from the hospital.

Analysis of Variance↗
PubMed1996

Changes in cerebrospinal fluid and cerebrovascular endothelin concentrations during hypotension and hypertension in newborn piglets with induced sterile meningitis.

The effects of sterile meningitis on endothelin-1 (ET-1) and big ET-1 concentrations during hypotension and hypertension were studied in the cerebrospinal fluid and plasma of newborn piglets. Cerebrospinal fluid was obtained via cisterna magna puncture, and blood was obtained from the sagittal sinus vein and left subclavian artery. The study group consisted of 14 newborn piglets injected with 0.5 mL heat-killed group B streptococcus (GBS) (10(9) colony forming unit (cfu) equivalents), into the right cerebral lateral ventricle; the control group consisted of 10 newborn piglets injected with sterile normal saline, in a similar fashion. Hypotension (mean arterial blood pressure (MABP) 20-59 mmHg; 1 mmHg = 133.3 Pa) and hypertension (MABP 110-140 mmHg) were induced 1.5-2 h apart in random sequence in each animal, by inflating balloon-tipped catheters placed at the aortic root and descending aorta, respectively. Cerebral blood flow (CBF) was measured using radiolabeled microspheres, 15 min before and after injection of GBS or saline (normotension), during the hypotension and hypertension episodes, and during recovery normotension, immediately prior to cerebrospinal fluid and blood sampling. ET-1 and big ET-1 concentrations (pg/mL) were measured using radioimmunoassay kits. The combined effect of induced sterile meningitis and induced hypotension resulted in a significant rise in the concentration of cerebrospinal fluid ET-1 (control, 5.1 +/- 0.1; GBS, 9.3 +/- 0.2 pg/mL; p < 0.01), cerebrospinal fluid big ET-1 (control, 0; GBS, 18.1 +/- 2.7 pg/mL; p < 0.01), and sagittal sinus (cerebrovascular) big ET-1 (control, 15.5 +/- 4.2; GBS, 47.5 +/- 9.6 pg/mL; p < 0.01). In contrast, the combined effect of induced sterile meningitis and induced hypertension resulted in a marked elevation in cerebrovascular ET-1 concentrations (control, 9.5 +/- 0.9; GBS, 28.5 +/- 6.1 pg/mL; p < 0.01), with no significant change in cerebrospinal fluid concentrations. In addition, cerebrovascular production of ET-1 increased dramatically during hypertension in the GBS group (control, 0; GBS, 161.7 +/- 13.2 pg.min-1.100 g-1; p < 0.001), and was maintained during the recovery period (133.7 +/- 10.8 pg.min-1.100 g-1). Cerebrovascular ET-1 concentrations correlated significantly with total CBF and MABP in both groups of animals (control, r = 0.49, p < 0.002; GBS, r = 0.64, p < 0.0001), but the response was of a much greater magnitude in the GBS group. There was an inverse relationship between cerebrovascular big ET-1 concentrations and total CBF (r = -0.53, p < 0.0001) and MABP (r = -0.71, p < 0.0001) in the GBS group. In the MABP range of 60-110 mmHg a positive relationship was observed between cerebrovascular ET-1 concentrations and cerebral vascular resistance, in the control group only (r = 0.59, p < 0.002). The combined insult of induced sterile meningitis and induced hypotension or hypertension may be associated with increased cerebrovascular ET-1 and (or) big ET-1 concentrations. Changes in these vasoactive agents may contribute to pressure passivity of CBF in the newborn with meningitis.

Animals↗
PubMed1995

Ascorbic acid during cerebral ischemia in newborn piglets.

We measured ascorbic acid (reduced and oxidized) in brain, CSF and blood, before, during and after cerebral ischemia in newborn piglets. Bilateral carotid ligation induced a 54% decrease in cerebral blood flow (p < 0.01) and a 43% decrease in the cerebral metabolic rate of oxygen (p < 0.01). After ischemia and reperfusion, we obtained a 60% decrease (p < 0.01) in total brain ascorbic acid content. CSF ascorbic acid increased during reperfusion: +60% at 30 min (p < 0.001) and +160% at 120 min (p < 0.05). Blood ascorbic acid content did not change. These changes and the absence of massive oxidation of ascorbic acid in brain tissue suggest release of ascorbic acid by the brain during ischemia.

Animals↗
PubMed1995

Ascorbic acid concentrations in umbilical cord veins and arteries of preterm and term newborns.

Ascorbic acid (AA) is a powerful antioxidant required for the defense against oxidative stress. At present it is not known whether AA may play a role in the developmental process of the fetus. We therefore determined the relationship of AA levels between the umbilical cord vein (UCV) and umbilical cord artery (UCA) of preterm ( < 37 weeks of gestation) and term ( > or = 37 weeks of gestation) infants and compared those levels to matched maternal venous AA levels. We also assessed the association between UCV plasma AA levels with birth weight and gestational age by measuring AA in 88 UCV plasma samples and 58 UCA plasma samples obtained from newborn infants ranging in gestational age from 24 to 42 weeks and birth weight from 675 to 5,020 g, by high pressure liquid chromatography. Maternal venous samples were collected at the time of delivery. The mean UCV plasma AA levels (mg/dl) were significantly lower in the preterm group than in the term group (0.43 +/- 0.59 and 1.16 +/- 0.97, respectively; p < 0.002); however, the mean UCA plasma AA levels did not differ between the groups. In contrast, mean maternal venous plasma AA levels of the preterm group (1.33 +/- 0.62) were significantly higher than those of the mothers in the term group (0.72 +/- 0.69; p < 0.01). A direct correlation was found between UCV levels and birth weight (r = 0.23, p < 0.05), and UCV levels and gestational age (r = 0.23, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Biochemical mediators of meningeal inflammatory response to group B streptococcus in the newborn piglet model.

The meningeal inflammatory response to a heat-killed mutant unencapsulated strain of type III group B Streptococcus (GBS) was studied in a newborn piglet model. GBS (10(9) colony-forming unit equivalents) or saline (control) was inoculated intraventricularly. Serial cerebrospinal fluid measurements were done at baseline and over the course of the next 24 h for cytochemical changes and production of tumor necrosis factor (TNF) and prostaglandins. In separate experiments, we defined the time course of early changes during the first 6 h and dose response relationship over a range of inocula 10(6) to 10(9) colony-forming unit equivalents. The intraventricular inoculation of the heat-killed unencapsulated GBS induced marked leukocytosis and increased protein by 6 h. These changes were preceded by a several hundredfold increase in TNF (maximum at 2 h) and prostaglandins (maximum at 2-4 h). The early and sharp rise in TNF suggests its pivotal role in initiating the inflammatory cascade. The magnitude of the inflammatory response increased with increasing bacterial dose over the range studied. To study the effect of encapsulation of GBS in the induction of meningeal inflammation, we compared the response to the unencapsulated mutant strain with that to the encapsulated parent strain. The encapsulated strain produced much smaller inflammatory changes, and only with high doses of bacteria. The GBS cell wall appeared to be the primary bacterial product triggering inflammation. Intraventricular injection of the heat-killed unencapsulated GBS with exposed cell wall can serve as a valid model for studying neonatal meningitis.

Animals↗