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Biomedical subjects

O Carrier

Publications and source records attributed to O Carrier.

At least 19 recordsLinked to original sources
PubMed1989

Maturation of AFMU excretion in infants.

The maturation of the N-acetyltransferase-dependent AFMU production from caffeine was studied during infancy. The group of children (N = 14) consisted of 4 premature newborn infants and ten 1-19 month-old infants who received caffeine citrate solution for the treatment and prevention of apnea. Caffeine, AFMU, 1X and 9 other metabolites were measured in urine using HPLC. The AFMU/1X ratio did not vary significantly in this population with increasing age. In one of the infants serially studied, the AFMU/1X ratio increased dramatically between 6 and 12 months of age. This observation suggests that the maturation of N-acetyltransferase activity is not completed before 1 year of age implying that acetylator status cannot reliably be determined before that age. Patients studied before 1 year of age whose AFMU/1X ratio was below 0.4 may be either true slow acetylators or still immature fast acetylators.

Acetylation↗
PubMed1988

Maturation of caffeine metabolic pathways in infancy.

The maturation of the different pathways of caffeine metabolism was studied during infancy. The group of children (n = 14) consisted of four premature newborn infants and 10 older infants who received caffeine citrate solution. Caffeine and 11 of its metabolites were measured by HPLC. Total demethylation and N3- and N7-demethylation increase exponentially with postnatal age; the plateau is reached by 120 days and accounts for 58.6%, 90.5%, and 79.3%, respectively. N1-demethylation shows no variation with postnatal age. It is suggested that N3-demethylation is more important in young infants than in adults and that maturation of N1-demethylation occurs later than 19 months of age. 8-Hydroxylation is mature as early as 1 month of age and may be higher in infants than in adults. Acetylation is not mature before at least 1 year of age. Differences in maturation rate of acetylation may be related in part to genetic acetylator status.

Acetylation↗
PubMed1988

Developmental changes of caffeine elimination in infancy.

Five neonates (4 premature) and 16 infants (6 prematurely born), 15-588 days old, received caffeine as citrate salt for apnea. Plasma samples were collected 0, 2, 4, 6 h after a dose and before the next scheduled one. Patients 8 and 9 were serially studied. Caffeine plasma concentrations were determined using HPLC. The caffeine elimination half-life and clearance varied linearly with gestational age and exponentially with postnatal age, the plateau being reached during the second trimester of life. Dose regimen guidelines as a function of postnatal age were derived from individually calculated doses and dosing intervals in order to achieve, at steady state, a caffeine mean plasma concentration of 11 mg/l with a minimum of 7.5 mg/l and a maximum of 14.5 mg/l. We suggest dosing intervals for infants before 1 month, 1-2 months, 2-4 months and after 4 months to be equal to 24, 12, 8 and 6 h, respectively. The individual recommended dose varies from 2 to 10 mg/kg (as caffeine base) making caffeine monitoring mandatory in infants.

Aging↗
PubMed1988

Maturation of caffeine N-demethylation in infancy: a study using the 13CO2 breath test.

Four premature neonates and eight infants 1-19 months old received caffeine for apnea. The usual morning oral dose was substituted by 1,3,7 13C-trimethylxanthine (13C-tri CAF) as the citrate salt. Five breath samples were collected the day before (day 1) and the day of 13C-tri CAF administration (day 2). Plasma (after each breath collection) and urine were collected on day 2. 13C-CO2 exhalation was determined by isotope ratio mass spectrometry. Caffeine and its metabolites were measured using high-pressure liquid chromatography. Assessment of the labeled CO2 in the breath revealed no detectable 13C-tri CAF N-demethylation activity in infants before 45 wk postconceptional age. However, demethylation (as urinary metabolites) has been detected before that age. Two-, 4-, and 6-h cumulative excretion of 13C-tri CAF as 13C-CO2 increased with postnatal age and correlated with caffeine plasma clearance (r = 0.840, p less than 0.01). These results were consistent with those obtained for urinary metabolites. In one infant (19 months old) the cumulative excretion of 13C-CO2 while crying was 65% of the value observed during quiet breathing. The measurement of caffeine demethylation using the caffeine CO2 breath test is feasible in infants and is a safe and noninvasive method to determine age related changes in P4501-dependent N-demethylase activity.

Apnea↗
PubMed1984

[Premedication using intrarectal midazolam. Study of effective dosage in pediatric anesthesia].

The object of this study was to determine the optimal dose of midazolam given per rectum which would produce sedation adequate for inducing inhalational anaesthesia in paediatric practice. Five doses were studied: 0.15, 0.25, 0.30, 0.35 and 0.40 mg X kg-1. The criteria used to appreciate the effectiveness of the sedation at 30 min were the change in the child's behaviour, with a scale of 6 levels, and the acceptance of the mask and anaesthetic vapours. There was a significant correlation between the dose administered and the degree of sedation, as well as between the dose administered and the lack of reaction to the mask. Significantly better results were found with the higher doses of 0.35 and 0.40 mg X kg-1, when compared with the children who had received 0.15 and 0.25 mg X kg-1. Only in the groups who received 0.35 and 0.40 mg X kg-1 were the degrees of sedation and acceptance of induction considered as adequate. The dose of 0.35 mg X kg-1 seemed to be the best dose for adequately premedicating a child.

Age Factors↗
PubMed1978

The role of calcium in supersensitivity to the inotropic effects of norepinephrine.

Experiments using electrically stimulated rabbit left atria have demonstrated that supersensitivity to the inotropic effects of norepinephrine can be induced by either chronic reserpine pretreatment or hypothermia (lowering the temperature of the bathing medium). These two experimental conditions for inducing supersensitivity were not additive implying that they shared a common mechanism of action. Norepinephrine had no significant effect on the amplitude of a potentiated contraction of the rabbit atrium when the temperature was reduced from 37 to 30 degrees C or following pretreatment with reserpine (30 or 37 degrees C). Under these same conditions the ED50 of norepinephrine on the normal contraction was reduced. It is concluded that both reserpine pretreatment and hypothermia induce supersensitivity to the inotropic effects of norepinephrine by enhancing the cellular store of activator calcium while not affecting the ability of norepinephrine to release activator calcium.

Animals↗
PubMed1978

Identification of hydrallazine and hydrallazine hydrazone metabolites in human body fluids and quantitative in vitro comparisons of their smooth muscle relaxant activity.

1 Serum and urine from hypertensive subjects on chronic oral hydrallazine therapy were studied using gas chromatographic/mass spectrometry techniques. 2 Metabolites resulting from acetylation, hydrolysis and conjugation reactions were detected. The acetone, pyruvate and alpha-ketoglutarate hydrazone were identified. 3 The activity of the pyruvate and alpha-ketoglutarate hydrazones were compared with that of hydrallazine using isolated rabbit aortic strips. 4 Both hydrazones were active under in vitro conditions, producing smooth muscle relaxant effects equal to those of hydrallazine. 5 It is concluded that hydrazone metabolites will contribute to the hypotensive effects of hydrallazine therapy in proportion to their relative abundance, persistence in vascular tissues and intrinsic activity.

Animals↗
PubMed1978

Specific alpha-adrenergic receptor desensitization in vascular smooth muscle.

Specific desensitization of vascular tissue to norepinephrine was studied using an open-ring-type strip preparation of rabbit aorta. Aortae were taken from untreated, reserpine-pretreated (0.1 mg/kg/day; 3, 5, or 7 days) and 6-hydroxydropamine-pretreated (50 mg/kg; 3 or 7 days before sacrifice) rabbits. Aortic strips from the pretreated rabbits were supersensitive to norepinephrine. Subsequent to obtaining the first dose-response curve for norepinephrine, aortic strips were less sensitive to norepinephrine. It was found that desensitization to norepinephrine occurred following 10 min preincubation with 10(-6)m norepinephrine, and 20 min preincubation with 10(-7)m norepinephrine. The desensitization of supersensitive strips was significantly greater than in controls. Dopamine and isoproterenol desensitized both untreated and pretreated strips to norepinephrine. Phenylephrine desensitized strips to norepinephrine from 6-hydroxydopamine-pretreated rabbits. Acetylcholine and potassium did not desensitize strips to norepinephrine; however, acetylcholine desensitized strips to acetylcholine. It is concluded from these studies that norepinephrine desensitization in a specific alpha-adrenergic-related event.

Acetylcholine↗
PubMed1978

Reserpine-induced supersensitivity to the chronotropic and inotropic effects of calcium in rabbit atria.

Supersensitivity to the chronotropic and inotropic effects of calcium was demonstrated in spontaneously beating paired atria from reserpine-pretreated (0.1 mg/kg/day, 7 days) rabbits. Supersensitivity to the inotropic effects of calcium in electrically driven left atria was also demonstrated. Atria were driven at 80, 100 and 120 beats/min. At each frequency the reserpine-pretreated atria were more sensitive than controls. Atria were tested under diastolic tensions of 1,2 and 4 g. As the tension was increased the sensitivity to calcium increased. The sensitivity of reserpine-pretreated atria was greater at each tension than that of control atria. Atria tested at 37 degrees C were less sensitive than those tested at 30 degrees C; however, the reserpine-pretreated atria were more sensitive than control atria at both temperatures. This study demonstrates that reserpine-induced supersensitivity to the inotropic effects of calcium can be obtained and that the ability to demonstrate this phenomenon does not appear to be altered by the frequency, diastolic tension or temperature at which each experiment is performed.

Animals↗
PubMed1978

Interaction of hydralazine and hydrazone derivatives with contractile mechanisms in rabbit aortic smooth muscle.

The mechanism of action and relative potency of hydralazine (H) and tow hydrazone derivatives were investigated using isolated rabbit aortic strips. H, hydralazine acetone hydrazone (HA) and hydralazine butanone hydrazone (HBH) relaxed established K+ and norepinephrine (NE) contractures, and inhibited the development of contractures to these two agents on preincubation. H, HA and HBH increased the threshold to Ca++ and decreased the maximum tension responses during K+-Ca++-contractures (HA greater than H, P less than .05; HBH greater than H P less than .01). The Ca++-dependent and Ca++-independent components of NE contractures were both inhibited by H, HA and HBH. NE contractures were more sensitive to the effects of H than K+ contractures. These results are consistent with the conclusion that H and hydrazone derivatives produce effects on vascular muscle both by interactions with the fluxes of Ca++ from the extracellular space and effects on release from cell stores. However, other possibilities need to be assessed experimentally.

Animals↗
PubMed1978

Tension development and associated calcium influx of control and reserpine pretreated rabbit aortae in response to norepinephrine, isoproterenol and acetylcholine.

The influence of reserpine (3mg/kg) pretreatment on phasic and tonic components of the contractile responses of rabbit aortae to maximally effective concentrations of norepinephrine, acetylcholine, and isoproterenol and on agonists-induced movements of 45Ca during these responses were studied. Four hours after reserpine administration, there were no histological changes, in extracellular space, and no change in tissue water, sodium, calcium or magnesium. Potassium contents were slightly decreased and the catecholamine content was depleted by 95%. The responses to the three agonists were enhanced in the reserpine pretreated tissues. The absence of calcium eliminated the slow tonic componenet of the responses. Reserpine induced an increase in lanthanum (La3+) resistant 45Ca uptake. The three agonists induced an increase in La3+ resitant 45Ca uptake of equal magnitude in both reserpine pretreated and control tissues. Lanthanum ion affected 45Ca efflux similarly in both reserpine pretreated and untreated tissues. The results suggest that a major portion of the enhanced responsiveness of rabbit aortic strips following reserpien administration is the result of a change in calcium retention in those tissue stores mobilized by these agonists to initiate the fast, phasic componenet, and is, therefore, a reflection of an increased agonist intrinsic activity.

Acetylcholine↗
PubMed1978

Study of in vitro effects of hydralazine metabolites--comparative evaluation of products of hydroxylation, hydrolysis and conjugation.

K+ contractures were induced in paired strips of rabbit aortic smooth muscle. The relationship between relaxant effects and the bath concentration of hydralazine acetone hydrazone (HA), 4-OH-hydralazine (HH) and phthalazine (P) was studied over the concentration range 10(-5)-10(-3)M. All compounds were active, HA = HH greater than P (p less than 0.05; n = 6) at concentrations in the range 10(-4)-10(-3M, HA greater than HH at a concentration of 10(-3M (pgreater than 0.01). The activity of HA did not depend on significant reconversion to hydralazine (H) in the bath ( less than 0.5%). A range of H derivatives may contribute to the hypotensive effects of administered H.

Animals↗
PubMed1977

Comparative evaluation of the in vitro effects of hydralazine and hydralazine acetonide on arterial smooth muscle.

1. Dose-response relationships to K+ were determined in isolated strips of rabbit aorta. 2. K+ contractures were induced by 30 mM K+ in paired strips from individual animals. The effects of hydralazine and hydralazine acetone hydrazone (hydralazine acetonide) on these contractures were studied. 3. Hydralazine and hydralazine acetonide both produced dose-dependent decreases of K+-induced tone. Threshold concentrations for hydralazine were 11.89 +/- 4.5 X 10(-5) M (mean +/- s.d.) and for hydralazine actonide 9.7 +/- 4.6 X 10(-5) M (0.5 less than P less than 0.4). 4. The magnitude of the effect of hydralazine acetonide was greater than that of hydralazine at all concentrations above threshold, as reflected in a significant difference (P less than 0.05) in the slopes of dose-response curves to the two treatments. The vasodilator effects of hydralazine and the acetonide were terminated by washout of the bath. 5. The differences in effect were not due to instability of hydralazine under in vitro conditions. 6. It is concluded that hydralazine acetonide has intrinsic activity on vascular smooth muscle which differs significantly from that of the parent compound and that this may contribute to the hypotensive effects which follow administration of the parent compound.

Animals↗
PubMed1977

Sensitivity of different segments of rabbit aorta to acetylcholine and isoproterenol.

In order to determine whether or not reserpine-induced supersensitivity was affected or reflected in differences in sensitivities to acetylcholine and isoproterenol in different segments of the rabbit aorta, segments of aorta, taken at two different distances from the arch, were tested for their sensitivities to these two agonists. Sensitivity and maximum responses to acetylcholine were lower in the more distal segment. Sensitivity to isoproterenol of the segments was not different while the maximum responses were lower in the more distal segment. Reserpine-induced supersensitivity to both agonists was similar in both aortic segments.

Acetylcholine↗
PubMed1976

The relationship between calcium and increased sensitivity of rabbit aortae four hours after reserpine.

1 Four hours after reserpine, rabbit aortic strips were supersensitive to acetylcholine, isoprenaline and noradrenaline. The threshold concentration of the drugs necessary to induce a response was less and the maximum tension developed by the tissues was greater than in control strips. 2 Reserpine-treatment potentiated the contractile responses to CaCl2. 3 Reserpine-treatment resulted in an increase in calcium uptake and an increase in the slow component of 45Ca2+ efflux. 4 After resperine-treatment, the rate of relaxation from a potassium-induced contraction was decreased. 5 It is concluded that reserpine-induced supersensitivity is related to an enhanced ability of the tissue to retain and utilize calcium.

Acetylcholine↗
PubMed1976

Role of calcium in different layers of vascular smooth muscle in norepinephrine contraction.

The role of calcium present in adventitial and media-intimal layers of rabbit aorta in the fast (F-) and the slow (S-) components of norepinephrine (10(-5) M) contraction was evaluated in this study. An increased sensitivity and decreased maximum tension to response to norepinephrine was observed in adventitia-free aorta as compared to whole aorta. Incubation in calcium-free Ringer solution with or without EDTA decreased the F-component of norepinephrine contraction of the adventitia-free aorta, whereas the F-component of the whole aorta was not affected. The S-component of both preparations was abolished in calcium-free Ringer solution. Norepinephrine increased calcium uptake into whole and adventitia-free aortic strips. An increase in calcium uptake induced by norepinephrine during the F-component of norepinephrine contraction was also observed. 45Ca efflux studies revealed the presence of an exchangeable calcium fraction in the adventitial layer. These data suggest that F-component of norepinephrine contraction is partially dependent on the extracellular calcium distributed in the adventitial layer of rabbit aorta.

Animals↗
PubMed1976

Influence of magnesium on calcium- and potassium-related responses in vascular smooth muscle.

The influence of Mg on Ca- and K-related responses of rabbit aortic strips was studied. Aortic strips bathed in either a K-free or 60.0 mM K solution were less sensitive to Ca in the presence of 1.2 mm Mg. Ca induced greater maximum tension in the aortic strips in the presence of Mg when bathed in 60.0 mM K. Addition of K to a K-free medium induced a slight relaxation at low concentrations (is less than 1.0 mm) which was Ca dependent. The relaxation was less in the presence of Mg. Wiolution were less sensitive to Ca in the presence of 1.2 mm Mg. Ca induced greater maximum tension in the aortic strips in the presence of Mg when bathed in 60.0 mm K. Addition of K to a K-free medium induced a slight relaxation at low concentrations (is less thth Mg in the medium throughout the experiment (90 min), the threshold concentration of K, including a contractile response, was increased as was the maximum tension. Acute addition of Mg decreased the maximum response to K. When K was lowered from 5.4 to 0.0 mm a contractile response, absent in the presence of Mg, occurred. When the K was increased, the tension returned to baseline. At 25-30 mm K, the tension again increased, reaching a maximum at 40-50 mm K. Ca uptake was stimulated at all K concentrations producing a contraction. Mg depressed this increase in uptake. 45Ca efflux was more rapid into a 50.0 mm than into 0.0 mm K solution. Mg delayed Ca efflux. It is concluded from these data that Mg has two components in its effect on the Ca associated with K responses. One is a competition with Ca at extracellular sites probably at the membrane, and the other is intracellular, probably a competition with Ca at sequestration sites.

Animals↗