Biomedical subjects

A Gulati

Publications and source records attributed to A Gulati.

At least 73 records · Page 4Linked to original sources

PubMed1994

Renal endothelin mechanism in altered thyroid states.

Endothelin (ET) mechanisms were studied in hyper- and hypo-thyroid states in rats. Hyperthyroidism was induced by daily administration of thyroxine (0.1 mg/kg, i.p.) for 8 weeks, while hypothyroidism was induced by daily administration of methimazole (10 mg/kg, i.p.) for 8 weeks. The concentration of endogenous ET-1 was determined in the kidneys using radioimmunoassay. Systemic hemodynamics and renal blood circulation was measured using a radioactive microsphere technique. A significant increase in systolic and diastolic blood pressure, heart rate and cardiac output was observed in hyperthyroid rats as compared to eu- and hypo-thyroid rats. Total peripheral resistance was found to be similar in eu-, hyper- and hypo-thyroid rats. The endogenous concentration of ET-1 in the kidneys was significantly lower in hyper- as compared to eu- and hypo-thyroid rats. The blood flow to the kidneys was significantly increased in hyper- as compared to eu- and hypo-thyroid rats. Infusion of ET-1 (100 ng/kg/min i.v. for 45 min) produced a significant decrease in blood flow to the kidneys of eu-, hyper- and hypo-thyroid rats. The decrease in blood flow was similar in eu-, hyper- and hypo-thyroid rats, indicating that the response of renal blood vessels to exogenous ET-1 is not altered during thyroid dysfunction. Since endogenous ET-1 is involved in the regulation of vascular tone, it may be concluded that in hyper-thyroid rats decrease in concentration of the renal ET-1 could be contributing to an increase in blood flow to the kidney.

Animals↗

PubMed1994

Altered endothelin 1 concentration in brain and peripheral regions during thyroid dysfunction.

Earlier studies have shown that plasma concentrations of endothelin 1 (ET-1) and the receptors for ET are altered during hyperthyroidism, while they are not affected during hypothyroidism. The present study was undertaken to determine the changes in concentration of endogenous ET-1 in various tissues of hyper- and hypothyroid rats. Hyperthyroidism was induced by daily administration of thyroxine (T4, 0.1 mg/kg, i.p.) for 8 weeks, while hypothyroidism was induced by daily administration of methimazole (10 mg/kg, i.p.) for 8 weeks. The concentration of endogenous ET-1 was determined in the brain regions (hypothalamus, corpus striatum, pituitary, hippocampus and spinal cord), heart, adrenals, kidneys and thoracic aorta using a radioimmunoassay procedure. Blood pressure and heart rate were significantly increased in hyperthyroid rats, while they were not affected in hypothyroid rats when compared with control (euthyroid) rats. Serum T4 and T3 levels were significantly increased in hyperthyroid rats, while they were significantly decreased in hypothyroid rats when compared with euthyroid rats. The concentrations of ET-1 in the hypothalamus, corpus striatum, hippocampus and spinal cord were not altered in hyper- or hypothyroid rats when compared with euthyroid rats. However, the pituitary showed a significant (p < 0.001) increase (104%) in ET-1 concentration in hyperthyroid rats when compared with euthyroid ones, while hypothyroid rats did not show any significant change in ET-1 concentration in the pituitary. In peripheral tissues ET-1 concentrations were not altered in the heart and adrenals of hyper- and hypothyroid rats when compared with euthyroid rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗

PubMed1994

Regional circulatory and systemic hemodynamic effects of diaspirin cross-linked hemoglobin in the rat.

Diaspirin cross-linked hemoglobin (DCLHb) (Baxter Healthcare Corporation) is a promising resuscitative fluid. The effect of DCLHb (400 mg/kg, i.v.), on regional circulation and systemic hemodynamics was studied in male Sprague-Dawley rats using a radioactive microsphere technique. Systemic hemodynamics, distribution of cardiac output, regional blood flow and vascular resistance were determined before (baseline) and 15, 30 and 60 min after the administration of DCLHb. Infusion of an equal volume of saline did not produce any significant change in systemic hemodynamics or regional circulation. DCLHb produced an increase (79%) in the mean blood pressure which lasted for more than 60 min. Heart rate, cardiac output and stroke volume were not significantly affected, while total peripheral resistance was increased after the administration of DCLHb. DCLHb produced significant increases in blood flow to the heart, gastrointestinal tract (GIT), portal system and skin. The blood flow to the kidney, brain and musculoskeletal system was not significantly affected by DCLHb. The vascular resistance was not altered in the heart, brain, GIT, portal system, kidney or skin, but there was a marked increase in the vascular resistance in the musculoskeletal system. There was a significant increase in the percentage of cardiac output to visceral organs like heart, GIT and portal system, while a marked decrease in the percent cardiac output to musculoskeletal system was observed with DCLHb. It is concluded that the blood flow to most of the organs is either increased or is not affected by DCLHb.

Animals↗

PubMed1994

Diaspirin cross-linked hemoglobin (DCLHB): involvement of adrenergic mechanisms in the pressor effect.

Diaspirin cross-linked Hemoglobin (DCLHb) (400 mg/kg, i.v.), a resuscitative solution, produces a pressor effect in rats and several other species. Studies were conducted to determine the role of the central nervous system and adrenal medulla in the pressor effect of DCLHb in rats. Intravenous administration of DCLHb produced an increase in blood pressure in cervical sectioned animals, which was comparable to that observed in normal rats. This indicates that the pressor effect of DCLHb was mediated through the peripheral vascular system rather than through the central nervous system. DCLHb produced a pressor effect in bilateral adrenal demedullated rats that was similar to normal rats, suggesting that the pressor effect is not through the release of catecholamines or other pressor substance from the adrenal medulla. The effects of DCLHb pretreatment on norepinephrine (0.5 microgram/kg), phenylephrine (5 micrograms/kg) and clonidine induced blood pressure and heart rate responses were also studied. DCLHb significantly potentiated the pressor response to norepinephrine and phenylephrine. Clonidine normally produces a fall in blood pressure by acting on the central alpha-adrenoceptors, and a rise in blood pressure by stimulating the peripheral vascular alpha-adrenoceptors. DCLHb produced a marked potentiation of the pressor response to clonidine (75 micrograms/kg, i.v.), that masked the central depressor effect. The specificity of the potentiation was confirmed by using phenoxybenzamine, prazosin, and yohimbine. In order to exclude the contribution of a centrally induced cardiovascular effect of clonidine, further studies were carried out in cervical sectioned rats. DCLHb markedly potentiated the pressor effect of clonidine (25 micrograms/kg, i.v.) in cervical sectioned rats. This potentiation could be attenuated by prazosin and yohimbine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Medulla↗

PubMed1994

Role of adrenergic mechanisms in the pressor effect of diaspirin cross-linked hemoglobin.

Diaspirin cross-linked hemoglobin (DCLHB; Baxter Healthcare Corp., Blood Substitutes Division) is a promising hemoglobin-based oxygen-carrying resuscitative solution. DCLHb (400 mg/kg, intravenously) produces an immediate increase in blood pressure when administered to conscious or anesthetized rats. To determine the role of the central nervous system and the peripheral vascular system in the pressor effect of DCLHb, experiments were performed in cervical-sectioned rats. Intravenous administration of DCLHb produced an increase in blood pressure in cervical-sectioned animals (41.2 +/- 2.5 mm Hg), which was similar to that observed in normal rats. To test whether the pressor effect was due to release of catecholamines or other pressor substances from the adrenal medulla, DCLHb was administered to bilateral adrenal demedullated rats. DCLHb was found to produce a pressor effect in bilateral adrenal demedullated rats (42.0 +/- 6.4 mm Hg) that was similar to normal rats. To determine whether DCLHb alters the responsiveness of peripheral vascular adrenoceptors, the effect of DCLHb pretreatment on the blood pressure and heart rate responses of adrenergic agonists was studied. DCLHb significantly potentiated (66.7%) the pressor response to norepinephrine (0.5 to 2.0 microgram/kg, intravenously) but did not affect the heart rate response to norepinephrine. Phenoxybenzamine completely blocked the DCLHb-induced potentiation of the norepinephrine responses. Phenylephrine produced a dose dependent (5 to 20 micrograms/kg, intravenously) pressor and reflex bradycardic effect. DCLHb significantly potentiated the pressor (40.6%) and bradycardiac (-22.8%) effect of phenylephrine, which were completely blocked by prazosin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Medulla↗

PubMed1994

Effect of diaspirin cross-linked hemoglobin and norepinephrine on systemic hemodynamics and regional circulation in rats.

Diaspirin cross-linked hemoglobin (DCLHb) (400 mg/kg, i.v.) produced a pressor effect that was equal to that produced by norepinephrine (NE) (25 micrograms/kg/min i.v. infusion). Total peripheral resistance was increased by DCLHb and more significantly by NE. Heart rate was not affected by DCLHb but was significantly increased by NE. The cardiac output and stroke volume were insignificantly increased by DCLHb but were significantly decreased by NE. DCLHb and NE produced a significant increase in blood flow to the heart. The vascular resistance in the heart was not affected by DCLHb but was decreased by NE. DCLHb did not affect the renal and brain circulation, but NE in kidneys decreased the blood flow and increased the vascular resistance, whereas in the brain it increased the blood flow and decreased the vascular resistance. DCLHb increased the blood flow to the stomach and small intestine. The vascular resistance was not affected by DCLHb in the gastrointestinal tract. NE did not affect the blood circulation in the gastrointestinal tract. Blood flow to the spleen was increased by DCLHb, and there was no change in the vascular resistance. NE insignificantly decreased the blood flow to the spleen and significantly increased the vascular resistance. The blood circulation to the mesentery and pancreas was not affected by DCLHb, whereas NE increased the blood flow without affecting the vascular resistance. DCLHb produced a significant increase in the blood flow to the skin without affecting the vascular resistance, whereas NE did not affect the blood flow but increased the vascular resistance. DCLHb did not affect the blood flow to the musculo-skeletal system but increased the vascular resistance, whereas NE decreased the blood flow and increased the vascular resistance. In summary, although the pressor effect of DCLHb and NE at the doses studied is equal, DCLHb did not decrease the blood flow to any organ, whereas NE produced significant decreases in blood flow to several organs. It is concluded that the blood flow to most of the organs is either increased or not affected by DCLHb.

Animals↗

PubMed1993

Endothelin mechanisms in altered thyroid states in the rat.

Endothelin (ET) and its receptor characteristics were studied in hyper- and hypo-thyroid states in the rats. Hyperthyroidism was induced by daily administration of thyroxine (0.1 mg/kg i.p.) for 8 weeks, while hypothyrodism was induced by daily administration of methimazole (10 mg/kg i.p.) for 8 weeks. The chronic administration of thyroxine to rats decreased their rate of gain of body weight, increased serum T3 and T4 concentration, blood pressure and heart rate. The chronic administration of methimazole decreased the rate of gain of body weight, serum T3 and T4 concentration, blood pressure and heart rate as compared to vehicle-treated control. Plasma ET-1 levels were found to be similar in control and methimazole-treated rats, while the levels were found to be significantly (P < 0.002) increased in thyroxine-treated rats as compared to control rats. Binding studies showed that [125I]ET-1 bound to a single, high affinity binding site in the cerebral cortex, hypothalamus and pituitary. The density (Bmax) and the affinity (Kd) of [125I]ET-1 binding in the cerebral cortex and hypothalamus were found to be similar in control, methimazole- and thyroxine-treated rats. The pituitary of thyroxine-treated rats showed a decrease in the binding (34.3% decrease in the density) of [125I]ET-1 as compared to control rats. No difference was observed in the binding of [125I]ET-1 to pituitary membranes from control and methimazole-treated rats. Competition studies showed that the IC50 and Ki values of ET-3 for [125]ET-1 binding were about 8 to 11 times higher than ET-1 in cerebral cortex, hypothalamus and pituitary.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

High-performance liquid chromatographic determination of morphine and its metabolites in plasma using diode-array detection.

An isocratic high-performance liquid chromatographic method has been developed for the determination of morphine, codeine, normorphine, morphine 3-glucuronide and morphine 6-glucuronide in plasma using a diol column and diode-array detection. Samples were extracted using solid-phase extraction with recoveries in excess of 90%. The limit of determination was 1 ng/ml for morphine, codeine and morphine 3-glucuronide, and 10 ng/ml for normorphine and morphine 6-glucuronide. Inter- and intra-day precision were better than 10%.

Chromatography, High Pressure Liquid↗

PubMed1993

Central serotonergic uptake mechanisms in hypertensive rats: effects of clonidine and centhaquin.

The binding of a highly specific ligand for serotonin (5-HT) uptake sites, [3H]paroxetine, was studied in brain regions of normotensive Wistar-Kyoto rats (WKY) and spontaneous hypertensive rats (SHR). [3H]Paroxetine bound to a single, high affinity binding site in the brain. In midbrain, the density (Bmax values) of [3H]paroxetine binding were significantly reduced (27.16%) in SHR as compared to WKY. The affinity (Kd values) were found to be similar in SHR and WKY. The Kd and Bmax values of [3H]paroxetine binding were found to be similar in spinal cord, pons and medulla and cerebral cortex of WKY and SHR. The effect of centrally acting hypotensive agents, clonidine and centhaquin, on [3H]paroxetine binding was also determined and compared with imipramine, a known 5-HT uptake inhibitor. Clonidine did not displace [3H]paroxetine binding at any concentration (10(-4) to 10(-7) M). On the other hand, centhaquin, which produces hypotension similar to clonidine, could displace [3H]paroxetine binding in a concentration dependent manner. In cerebral cortex and brainstem (midbrain, pons and medulla) membranes, the IC50 values of imipramine and centhaquin for [3H]paroxetine binding were found to be similar in WKY and SHR. The IC50 of centhaquin in displacing paroxetine from 5-HT uptake sites, was 10 times lower in the cerebral cortex and 4 times lower in the brainstem membranes when compared to imipramine. Clonidine had no effect on 5-HT uptake sites. The results indicate that (1) the density of 5-HT uptake sites is reduced in the midbrain of hypertensive rats, and (2) centhaquin, a centrally acting hypotensive agent, acts on 5-HT transporter sites.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Endothelin antagonizes the hypotension and potentiates the hypertension induced by clonidine.

Modification of clonidine-induced cardiovascular effects by endothelin-1 (ET-1) was studied in male Sprague-Dawley rats. A dose-dependent decrease in blood pressure and heart rate was produced by clonidine (100, 250 and 500 micrograms/kg i.v.). Lower doses produced only a fall in blood pressure (through central alpha-adrenoceptors) while higher doses of clonidine produced an initial hypertensive response (through peripheral alpha-adrenoceptors) and subsequent longer lasting hypotension and bradycardia. The hypotension and bradycardia induced by 100 and 250 micrograms/kg i.v. dose of clonidine were completely blocked by ET-1 (100 ng/kg i.v.) pretreatment. Conversely, the hypertensive response induced by high dose of clonidine (500 micrograms/kg i.v.) was significantly potentiated by ET-1 pretreatment. In cervical sectioned rats, i.v. administered clonidine failed to produce any hypotensive effect, indicating lack of central effect of clonidine. ET-1 significantly (P < 0.0005) potentiated the hypertensive response of a low dose (50 micrograms/kg i.v.) of clonidine in cervical-sectioned rats. I.c.v. administration of clonidine (1, 2, 4 and 6 micrograms) produced a dose-dependent decrease in blood pressure and heart rate. ET-1 pretreatment (25 ng i.c.v.) transiently blocked the clonidine-induced decrease in blood pressure and heart rate for about 10 min but the hypotension and bradycardia was observed subsequently. Since the major site of action of clonidine is the ventral surface of medulla, clonidine was applied directly to the ventral surface of medulla and produced a decrease in blood pressure and heart rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical↗

PubMed1993

Aging and 3H-paroxetine binding in rat brain: effect of imipramine and tetrahydroacridine.

3H-Paroxetine (PA) binding was studied in the frontal cortex (FC) and hippocampus (H) of 4 mos (young), 15 mos (adult) and 24 mos (aged) old Fischer 344 rats. Bmax (maximum number of binding sites) of PA binding was significantly higher in the H of adult rats compared with either young or old rats. There was no difference in Bmax between young and old rats. No change in Kd was observed in H and Kd or Bmax in FC with age. We also studied the effect of imipramine and tetrahydroacridine (THA) on PA binding in FC and H. Both drugs inhibited PA binding in FC and H but THA was 2000 times less potent than imipramine. There was no effect of age on IC50 values of imipramine and THA. These observations suggest that the number of 5-HT transporter sites in the hippocampus increases with brain maturity but then drops significantly during old age. This finding may have implications for age-related decrements in learning and memory, thought to be mediated by hippocampal structures.

Aging↗

PubMed1992

Evidence for antagonistic activity of endothelin for clonidine induced hypotension and bradycardia.

Effect of endothelin (ET) on clonidine induced cardiovascular effects was studied in male Sprague-Dawley rats. Clonidine (75 micrograms/kg, iv) produced significant decrease in blood pressure and heart rate. ET-1 (50 ng/kg, iv) pretreatment completely antagonized the hypotension and bradycardia induced by clonidine. ET-2 (50 ng/kg, iv) and ET-3 (50 ng/kg, iv) had similar antagonistic effect on clonidine induced hypotension and bradycardia. The antagonistic effect of ET lasted for several hours, however, 4 hours after ET pretreatment only partial blockade of clonidine induced hypotension and bradycardia was observed. This indicated that the antagonistic effect of ET was reversible. Initial hypertensive response induced by high dose of clonidine (750 micrograms/kg, iv) could not be antagonized by ET-1, ET-2 or ET-3, while phenoxybenzamine, an alpha adrenoceptor antagonist, blocked the hypertensive response of clonidine. Thus, ET has no antagonistic effect on the initial hypertensive response but antagonizes the hypotensive and bradycardic effect induced by clonidine. Clonidine induced hypotension and bradycardia are mediated through central alpha 2 adrenoceptors while hypertension is mediated through peripheral alpha 2 adrenoceptors. It is concluded that central alpha 2 adrenoceptors are different from peripheral alpha 2 adrenoceptors and ET antagonizes the effect of clonidine only on central alpha 2 adrenoceptors but has no antagonistic activity on peripheral alpha 2 adrenoceptors.

Animals↗

PubMed1992

Ontogeny of endothelin and its receptors in rat brain.

The ontogeny of endothelin (ET) system in rats was studied in preterm (18 days of gestation), term (21 days of gestation) and 1 week post term rats. Brains were dissected out and (1) processed for the estimation of endogenous ET-1 by RIA and (2) membranes were prepared for radioreceptor binding. Receptor characteristics, affinity (Kd) and density (Bmax) were determined using [125I] ET-1 and [125I] SRT 6b (which is structurally similar to ET) and cold ET-1 or SRT 6b as displacer. ET levels were found to be 25.66 +/- 3.18 pg/g protein in preterm, 47.37 +/- 5.31 pg/g protein in term and 48.30 +/- 1.90 pg/g protein in post term rats. ET levels were significantly lower in preterm as compared to term and post term rats. Preterm, term and post term rats showed single high affinity binding site for both [125I] ET-1 and [125I] SRT 6b. The Kd values for [125I] ET-1 and [125I] SRT 6b binding were similar in preterm, term and post term rats. The Bmax values of both [125I] ET-1 and [125I] SRT 6b binding were found to be similar in preterm and term rats while they were significantly higher in post term rats. In adult (4 month old) rats the Kd values were similar to neonatal rats while the Bmax values were significantly lower than the post term neonatal rats. It is concluded that ET and its receptors are developmentally regulated and there is a possibility that endogenous ET is involved in the regulation of ET receptor density.

Animals↗

PubMed1992

Down-regulation of central receptors for thyrotropin-releasing hormone in kappa opiate agonist-induced abstinence in the rat.

The effect of U-50,488H, a selective kappa opiate agonist, on tolerance-dependence and abstinence on the TRH receptors of the spinal cord and discrete regions of the brain of male Sprague-Dawley rats was determined. Rats were injected intraperitoneally twice daily with 25 mg/kg of U-50,488H for 4 days. Rats serving as controls were injected with the vehicle. On day 5, rats which were labeled as tolerant to U-50,488H were injected with U-50,488H (25 mg/kg) and sacrificed 1 hr later, whereas those labeled as abstinent were sacrificed without any injection. The above procedure has been previously shown to produce a high degree of tolerance to the analgesic and hypothermic effects of U-50,488H. The spinal cord and regions of the brain (hippocampus, cortex, midbrain, hypothalamus, corpus striatum, pons and medulla, and amygdala) were isolated for binding studies. The ligand [3H]MeTRH was used for TRH receptors. The binding constants, Bmax and Kd values, of [3H]MeTRH to bind to membranes prepared from various regions of the brain and spinal cord of rats tolerant-dependent on U-50,488H were unaffected. However, in rats abstinent to U-50,488H, the binding of [3H]MeTRH to membranes of the hypothalamus, and pons and medulla, was decreased. The decreased binding of [3H]MeTRH to hypothalamic membranes was due to changes in Bmax value, while in pons and medulla it was due to an increase in the Kd value.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed1992

Characteristics of endothelin receptors in the central nervous system of spontaneously hypertensive rats.

The binding of [125I]sarafotoxin 6b (SRT 6b) and [125I]endothelin-1 (ET-1) to endothelin (ET) receptors of neuronal membranes prepared, from regions of the brain and spinal cord of 8 week-old, spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats was determined. Spontaneously hypertensive rats had significantly higher blood pressure as compared to WKY rats. Heart rate was similar in SHR and WKY rats. [125I]SRT 6b and [125I]ET-1 bound to the membranes of the cerebral cortex, hypothalamus, ventrolateral medulla, dorsomedial medulla and spinal cord at a single, high affinity site. The Kd and Bmax values of the binding of [125I]SRT 6b were found to be similar to binding of [125I]ET-1 in all the regions. The concentration-dependent inhibition of binding of [125I]ET-1 by unlabeled ET-1, in spinal cord membranes showed an IC50 value of 2.66 +/- 0.59 nM and a Ki value of 2.35 +/- 0.52 nM in WKY rats and an IC50 value of 2.82 +/- 0.76 nM and a Ki value of 2.43 +/- 0.70 nM in SHR rats. On the other hand, the concentration-dependent inhibition of the binding of [125I]SRT 6b by unlabeled ET-1, in spinal cord membranes showed an IC50 value of 10.31 +/- 1.82 pM and a Ki value of 8.44 +/- 1.41 pM in WKY rats, while SHR rats showed an IC50 value of 10.28 +/- 1.94 pM and a Ki value of 8.89 +/- 2.00 pM. The binding of [125I]SRT 6b and [125I]ET-1 in the cerebral cortex, dorsomedial medulla and spinal cord membranes was found to be similar in SHR and WKY rats.(ABSTRACT TRUNCATED AT 250 WORDS) [corrected]

Animals↗

PubMed1992

Morphine metabolism in acutely ill preterm newborn infants.

To examine the manner in which morphine is metabolized in acutely ill premature infants, we measured the levels of morphine, morphine-3- and -6-glucuronides, and codeine in timed urine specimens and paired plasma specimens at 4 hours and 24 hours after a single dose of morphine in 16 preterm infants (less than 32 weeks of gestational age). A large amount of unmetabolized morphine was found in the urine in 13 (81.2%) of the 16 infants at 4 hours; in 12 of them, morphine was excreted even at 24 hours. Urinary morphine levels varied greatly; the coefficient of variation was 130% at 4 hours and 118% at 24 hours. Codeine was not found in any of the infants. In 10 (62.5%) of the 16 infants, at least one metabolite was found in either plasma or urine. Plasma and urinary levels of morphine conjugates also varied greatly among these 10 infants (coefficient of variation: 109% to 317%). All six infants (37.5%) who had no metabolites excreted large amounts of unmetabolized morphine in the urine for up to 24 hours. Birth weight, gestational age, postnatal age, systemic blood pressure, and other clinical or physiologic variables did not differ significantly between the 10 infants who had morphine conjugates and the six who did not. We conclude that (1) nearly two thirds of acutely ill preterm infants born at less than 32 weeks of gestational age conjugate morphine; (2) irrespective of their ability to produce morphine conjugates, preterm infants excrete large amounts of morphine unmetabolized, as late as 24 hours after a single dose; (3) morphine handling patterns are highly variable among premature infants, and no obvious factors account for the variability; and (4) such variability in morphine handling in general, and the production of the highly potent morphine-6-glucuronide in particular, could explain the variance in morphine pharmacokinetic measures and in the clinical responses to morphine during the newborn period.

Chromatography, High Pressure Liquid↗

PubMed1991

High-performance liquid chromatographic determination of morphine, morphine-3-glucuronide, morphine-6-glucuronide and codeine in biological samples using multi-wavelength forward optical detection.

An isocratic high-performance liquid chromatographic method has been developed for the determination of morphine, morphine-3-glucuronide, morphine-6-glucuronide and codeine in plasma, urine and cerebrospinal fluid. The use of an efficient solid-phase extraction procedure together with a forward optical scanning detector allows a detection limit of 500 pg/ml. The method was evaluated by examination of biological samples taken from newborn infants following the intravenous administration of morphine sulfate.

Chromatography, High Pressure Liquid↗

PubMed1991

Characteristics of endothelin binding sites in the spinal cord of spontaneously hypertensive rats.

The binding of [125I]sarafotoxin 6b (SRT 6b) and [125I]endothelin-1 (ET-1) to endothelin (ET) receptors of neuronal membranes prepared from cerebral cortex and spinal cord of 8-week-old spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) was determined. SHR had significantly higher blood pressure as compared to WKY. Heart rate was similar in SHR and WKY. [125I]SRT 6b and [125I] ET-1 bound to the membranes of cerebral cortex and spinal cord at a single, high affinity site. The binding of [125I]SRT 6b and [125I]ET-1 in the cerebral cortex and spinal cord membranes was found to be similar in SHR and WKY. Concentration-dependent inhibition of [125I]ET-1 binding in spinal cord membranes by unlabeled ET-1, ET-2 and ET-3 was performed. The Ki values were found to be 2.35 +/- 0.68, 0.29 +/- 0.08 and 24.10 +/- 5.90 nM for ET-1, ET-2 and ET-3, respectively in WKY. The Ki values of ET-1 and ET-2 were found to be similar in WKY and SHR. However, the Ki value of ET-3 were found to be significantly lower (P less than 0.004) in SHR as compared to WKY. Concentration-dependent inhibition of [125I]SRT 6b binding in spinal cord membranes by unlabeled ET-1, ET-2 and ET-3 were also performed. The Ki values were found to be 9.50 +/- 2.10 pM, 0.17 +/- 0.04 nM and 31.20 +/- 6.00 nM for ET-1, ET-2 and ET-3, respectively in WKY. The Ki values of ET-1 and ET-2 were found to be similar in WKY and SHR.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗