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Biomedical subjects

J Caroff

Publications and source records attributed to J Caroff.

At least 19 recordsLinked to original sources

Changes in cerebrospinal fluid monoamine metabolites, tryptophan, and gamma-aminobutyric acid during the 1st year of life in normal infants. comparison with victims of sudden infant death syndrome.

Cerebrospinal fluid (CSF) levels of 3-methoxy-4-hydroxyphenylglycol, 5-hydroxyindoleacetic acid, homovanillic acid, tryptophan, and gamma-aminobutyric acid were measured using high-performance liquid chromatography in 102 infants during the 1st year of life (preterm and term neonates included). CSF levels are expressed versus corrected age (postnatal days - preterm days) which reflects the stage of maturity of the central nervous system. These results are compared to those obtained in CSF of 53 victims of sudden infant death syndrome (SIDS). All components were significantly higher in SIDS than in the age-matched control group. This increase does not seem to be an artefact related to death. Indeed, under the same conditions concerning postmortem time interval before CSF sampling and analysis, the levels are not significantly higher in infants who died from a known pathology than in living infants. Moreover, in living infants as regards a pathology such as asphyxia or hypoventilation in comparison with SIDS, similar profiles are observed in some neurotransmitters or metabolites. Other studies are necessary to explore further neurotransmission systems in SIDS.

Age Factors↗

Simultaneous measurement of monoamines, their metabolites and 2,3- and 2,5-dihydroxybenzoates by high-performance liquid chromatography with electrochemical detection. Application to rat brain dialysates.

A reversed-phase chromatographic method with electrochemical detection was developed for the simultaneous determination of 2,3- and 2,5-dihydroxybenzoates, indicators of in vivo hydroxyl free radical formation, monoamines (NE, DA, 5-HT) and their metabolites (MHPG, DOPAC, HVA, 3MT, 5-HIAA). Linearity was observed from 10 pg to 10 ng injected. Reproducibility is correct (C.V. about 9%) except for 3MT and 5-HT. The limit of detection for almost all products was about 20 pg injected on the column. An application of this method in the study of the neurotoxicity of high pressure oxygen in rat is described. The limit of quantification for all compounds was 5 ng/ml except for HVA (10 ng/ml). Some basal levels DA, 5-HT, 5-HIAA, HVA, DOPAC, 3MT, 2,5-DHBA and 2,3-DHBA in microdialysates coming from striatum of normoxic restrained rats are given.

3,4-Dihydroxyphenylacetic Acid↗

gamma-Aminobutyric acid concentrations in the cerebrospinal fluid of newborn infants determined by high performance liquid chromatography.

gamma-Aminobutyric acid (GABA), a major inhibitory amino acid, has a central role in cardiorespiratory regulation. Its measurement in the cerebrospinal fluid (CSF) complements the study of neurotransmission systems. Forty-one children were studied (postnatal age < 1 year). For each child, date of birth, date of sampling and current treatments were collated and their postnatal (days) and postconception (weeks) ages were calculated. CSF samples were studied using reverse phase high performance liquid chromatography (HPLC) with o-phthaldialdehyde derivation and spectro-fluorimetric measurement. A clear increase in levels of GABA was observed around 41 weeks postconception, followed by a progressive decrease, with levels stabilizing after 57 weeks postconception. GABA-regulated neuromodulation therefore appears to be mature at 41 weeks postconception and not at birth. The data could be used in further studies investigating amino acid metabolism in relation to brain function in various neurological disorders.

Age Factors↗

Amino acids and ammonia in the cerebral cortex, the corpus striatum and the brain stem of the mouse prior to the onset and after a seizure induced by hyperbaric oxygen.

The contents of amino acids (AA) and ammonia (NH3) were measured in corpus striatum, brain stem and cerebral cortex of two strains of mice exposed to hyperbaric oxygen (HBO). Mice of the HBO-sensitive strain (CD1) were exposed to 600 kPa O2 for 24 min versus 90 min for mice of the normal C57 strain, so that 50% of the mice in both strains developed a generalized convulsion. In the cortex of exposed but unconvulsed (EXUN) C57 mice, the contents of taurine, glutamine and NH3 increased while that of GABA decreased when compared to control mice. In the CD1 mice, NH3 content was increased while that of Asp decreased. After a convulsion, NH3 was increased in both strains, the AA contents returned to normal in C57 but Asp remained low in CD1 mice. Somewhat similar changes occurred in the striatum except that NH3 levels were less affected while GABA ones were significantly decreased in the CD1 mice exposed to HBO, whether convulsed or not. In the EXUN brain stem, Asp and Glu contents decreased. These decreases were greater in C57 on a percentage basis than in CD1 mice. GABA content was decreased in the C57 strain. After a convulsion, Asp and Glu levels remained low and NH3 accumulated in CD1 whereas in C57 only the Glu level was decreased. The cortical and striatal changes may indicate a lesser GABA supply in C57 strain and some Asp release in CD1 strain. In the brain stem of both strains, Asp and Glu release is possible in addition to GABA in C57 strain.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗

Effect of one hyperbaric oxygen-induced convulsion on cortical polyamine content in two strains of mice.

In rat striatum, after one hyperbaric oxygen (HBO)-induced convulsion, polyamine changes are found that could promote N-methyl-D-aspartate (NMDA) activation. In the HBO-sensitive CD1 mouse, unlike in the common C57 strain, there is some support for NMDA activation after the HBO seizure. We measured PA cortical content before and after the first HBO-induced convulsion (about 608 kPa O2) in CD1 and C57 strains. Putrescine, spermidine and spermine were dansyl derived and analysed by HPLC. Exposure to HBO significantly increased putrescine content only in CD1 though a similar trend was observed in C57. No further increase was observed after convulsion whatever the strain. There were no significant changes in spermidine or spermine to support NMDA activation. Therefore, putrescine increase in CD1 cortex could reflect the free radical formation that is known to be greater in CD1 than in C57 mouse. Attempts to increase putrescine levels before HBO exposure hastened HBO-induced convulsion, less than spermidine or spermine. Because of physiological polyamine interconversion, additional experiments with indirect manipulation of putrescine levels and study of their time-course would precise these preliminary reports on putrescine and HBO.

Animals↗

[Activity of plasma dopamine-beta-hydroxylase in newborn infants. Implication in prematurity, maternal pathology and growth].

The aim of the study was to determine plasma dopamine-beta-hydroxylase activity (DBH) in newborn infants and possible changes with maturation, mode of delivery and maternal disease: pregnancy-induced hypertension and gestational diabetes. DBH activity was determined by high performance liquid chromatography from 82 neonates divided in 2 groups: group I: 27 neonates (age: 1 to 8 days) including 6 preterm and 21 full-term neonates; group II: 55 full-term neonates divided in 5 classes: A: vaginal delivery; B: forceps; C: elective caesarean section; D: vaginal delivery and maternal hypertension; E: vaginal delivery and gestational diabetes. The plasma DBH activity was low in neonates and not influenced by prematurity. Significantly lower DBH activity was found after caesarean section. Hypertension and gestational diabetes did not affect umbilical cord plasma DBH activity.

Adult↗

Standardization in the determination of red blood cell polyamines by high-performance liquid chromatography.

The choice of the standardization method in the high-performance liquid chromatographic determination of dansyl polyamines (spermidine and spermine) in red blood cell extracts is discussed. 1,6-Hexanediamine, commonly used as an internal standard, is unsuitable for the quantification of spermidine and spermine in red blood cells because their percentage recoveries are significantly different (100% for 1,6-hexanediamine, and 70% for spermidine and spermine). The external standard method and the standard addition method are better suited. The procedure for the preparation of the standard mixture before dansylation has an influence on the values of red blood cell polyamines. Two procedures are compared and the corresponding percentages of variation were found to be high for spermidine and spermine. Thus the procedure in which the standard is treated in a strictly similar way as the red blood cells is certainly the most appropriate one for the quantification.

Chromatography, High Pressure Liquid↗

[Neurotransmission and sudden infant death. Study of cerebrospinal fluid].

The study of 33 cerebrospinal fluids of infants victims of sudden death shows a very significant increase of the metabolites of dopamine and serotonin. These determinations, compared to a control group, indicate a failure, concerning these two neurotransmitters, which could induce a cardiorespiratory seizure. This failure has likely a multifactorial origin.

Heart Arrest↗

Catecholamine release controlled by blood oxygen tension during deep hypoxia in trout: effect on red blood cell Na/H exchanger activity.

Changes in plasma catecholamine levels were measured in trout exposed to acute hypoxia, in order to correlate with acid-base disturbances due to activation of the cAMP-dependent Na+/H+ antiporters of red blood cells, as previously described (Fiévet B., Respir. Physiol. 74, 99-114, 1988). The extracellular acidosis corresponding with the stimulation of the exchangers, occurred when arterial oxygen partial pressure (PaO2) reached around 15 Torr (Thomas S., Respir. Physiol. 74, 77-90, 1988). This blood pH drop coincided with a marked increase in plasma catecholamine levels. The catecholamine secretion was transient and the hormones were cleared provided PaO2 remained above 10 Torr. On the other hand, when PaO2 remained below 10 Torr, there was a persistent secretion of catecholamines. This is in agreement with the fact that the exchangers are 'turned off' or sustained when PaO2 remains above or below 10 Torr respectively, as previously described. Following the transient hormone peak when PaO2 stabilized above 10 Torr, it was possible to trigger the second pattern of continuous catecholamine secretion by controlling water PO2 so that PaO2 declined below 10 Torr. We conclude that the blood oxygen level controls catecholamine secretion during deep hypoxia.

Acid-Base Imbalance↗

Ammonia and monoamine concentrations in two brain areas in rats after one hyperoxic seizure.

Monoamines (catecholamines, serotonin, and metabolites) and ammonia were studied within two areas of the rat brain--the frontal cortex (FC) and the striatum (SA)--after exposure to hyperbaric oxygen (HBO) at 6 ATA up to the first seizure. An increase of norepinephrine (NE), dopamine (DA), and metabolites (HVA, DOPAC) measured by the HPLC/EC method were found in SA with a parallel increase of ammonia at variance with the FC where no monoamine changes, but a slight increase of ammonia, were found. Blood ammonia did not change with HBO. So, 20 min after one HBO seizure, there are regional differences in the brain, which are consistent with the previous findings of an SA start of electrocortical abnormalities at the onset of a seizure. Elevated DA, and possibly NE, levels may contribute to the accumulation of ammonia in the brain. During prolonged HBO exposure, this rise of ammonia could be one of the mechanisms involved in the relapse of seizures. It might also be implicated in initiation of the first seizure. By their situations and contents, SA glial cells could play an important role in brain HBO susceptibility.

Ammonia↗

Effects of breathing an O2-H2 (20%-80%) mixture on the energy metabolism of the eel at 1 ATA.

The hypothesis of a specific effect of hydrogen on living organisms was investigated. Three tissues were studied: brain, muscle, and liver. Nucleotide concentrations (ATP, ADP, AMP, IMP, NAD) were determined using an HPLC method, and energy charge (EC) was calculated. These measurements were performed at atmospheric pressure for 50 or 132 h. Experiments were carried out using 15 control eels that breathed aerated water and 15 eels that breathed water saturated with oxygen (20%) and hydrogen (80%). No significant variation was found of the measured concentrations in muscle or liver, irrespective of the exposure duration to H2. In contrast, hydrogen induced in brain tissue a significant increase of AMP (p less than 0.005) and significant decreases of ATP (p less than 0.005) and EC (p less than 0.001). It should be noted that the EC decrease is already significant (p less than 0.05) after 50 h of exposure to H2. These modifications in energetic nucleotides were coupled with a small decrease of NAD (NS) in the three tissues explored. From the present results, obtained from eels at atmospheric pressure, it appeared that hydrogen could induce a perturbation of energy metabolism at the brain level. Its origin could be a partial saturation of respiratory chain carriers with exogen H2.

Adenosine Monophosphate↗

Effects of hydrostatic pressure (HP = 101 ATA) on nucleotides and pyridine dinucleotides tissue contents in trout.

Tissue concentrations of energetic nucleotides and coenzymes, and oxygen consumption (MO2), have been measured in trout, exposed for 30 min in normoxic conditions (PwO2 congruent to 150 Torr), to 101 ATA (Atmosphere Absolute) of hydrostatic pressure (HP) and compared with results obtained at atmospheric pressure (1 ATA). The results show that in trout exposed to HP, there is an increase in MO2 accompanied by a decrease in ATP and energy charge (EC) in the three tissues explored (brain, liver, and muscle). Moreover, the fall of EC in muscle is accompanied by an increase in inosine 5' monophosphate (IMP). These results are in agreement with the hypothesis of an histotoxic hypoxia induced by HP, which can act at the Krebs cycle level and/or at the respiratory chain level, possibly by uncoupling the respiratory chain from oxidative phosphorylation processes.

Adenine Nucleotides↗

Effects of hydrostatic pressure per se (101 ATA) on energetic processes in fish.

Nucleotides concentrations (ATP, ADP, AMP) have been measured in brain and muscle of eels exposed to 101 ATA of hydrostatic pressure (HP) for 3 hr. Survival times (ST) and oxygen arterial content (CaO2) have been measured in trouts exposed to HP = 101 ATA. The results show that at HP = 101 ATA, AMP increases (P less than 0.05) and ATP decreases (-12%; NS) in muscle but are not modified in brain; ST values are similar in normoxic and hyperoxic conditions, and CaO2 are similar at 1 ATA and 101 ATA of HP. It is concluded that HP tends to decrease aerobic production of energy. This phenomenon is not due to a failure in O2 transport from ambient medium to the cell but to a possible perturbation of the aerobic cellular processes leading to energy production (Krebs cycle and/or respiratory chain coupled to oxidative phosphorylation.

Adenine Nucleotides↗

Brain and plasma biogenic amines analysis by the EC-HPLC technique: application to fish.

A HPLC technique has been developed for the analysis of biogenic amines (noradrenaline, NA; dopamine, DA; adrenaline, A; serotonin, 5-HT) in tissues and blood and then applied to fish. It appears that when compared to classical methods, HPLC is more rapid and reliable with a lower variation in the results. This technique showed that in eel blood, 5-HT and DA (and their metabolites) are missing or at least are present at very low concentrations.

Anguilla↗

Catecholamine content (as measured by the HPLC method) in brain and blood plasma of the eel: effects of 101 ATA hydrostatic pressure.

The catecholamine content (noradrenaline, NA; adrenaline, A; dopamine, DA, and its metabolite, DOPAC) was measured, by the HPLC method, in brain and blood plasma of eels studied at atmospheric pressure (1 ATA) or at 101 ATA of hydrostatic pressure (HP). In the brain, HP induces a slight but significant increase (P less than 0.05) in A and DA contents but NA and DOPAC levels are not modified at 101 ATA when compared to 1 ATA. In the plasma, only A and NA are detected, adrenaline being the predominant amine. In eels exposed to 101 ATA HP, A and NA are strongly increased (+100%; P less than 0.01). The significance of the catecholamine increase in brain and plasma of the eels under HP is discussed.

3,4-Dihydroxyphenylacetic Acid↗

Perinatal assessment of glycaemic control in newborn infants of diabetic mothers.

The glycaemic control of infants and of their mothers was studied at delivery and on day 7 after birth in 11 control and 20 insulin-dependent diabetic women. At delivery, venous blood glucose was lower in infants of diabetic mothers compared with control infants (p less than 0.02). Seven days after birth, no significant difference in blood glucose could be found between control and infants of diabetic mothers. C-peptide levels were higher in infants of diabetic mothers compared with control infants (p less than 0.01). On day 7 after birth, the C-peptide levels remained higher only in infants of Class B, C, D diabetic mothers. Glycosylated haemoglobin was lower in the venous blood of infants than of their mothers (p less than 0.001). Glycosylated haemoglobin was lower in control mothers than in diabetic mothers (p less than 0.05), but it was higher in the venous blood samples from control infants compared with infants of diabetic mothers at delivery (p less than 0.05) and 7 days after (p less than 0.01). At delivery infants' glycaemia and infants' glycosylated haemoglobin correlated (r = 0.44, p less than 0.02). C-Peptide and glycosylated haemoglobin levels in infants at delivery also correlated (r = -0.42, p less than 0.05).

Blood Glucose↗