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Biomedical subjects

L Wilson

Publications and source records attributed to L Wilson.

At least 253 records · Page 14Linked to original sources
PubMed1991

Design of potent oxytocin antagonists featuring D-tryptophan at position 2.

We prepared nine analogues (1-9) of MCPA-D-Phe-Phe-Ile-Asn-Cys-Pro-Arg-Gly-NH2, [MCPA1, D-Phe2, Phe3, Ile4, Arg8]oxytocin (MCPA = beta-mercapto-beta,beta-pentamethylenepropionic acid), a potent antagonist of the rat uterotonic action of oxytocin (OT). We replaced D-Phe with D-Trp and made [MCPA1,D-Trp2,Phe3,Ile4,Arg8]OT (1), which had OT pA2 of 7.51, somewhat higher than that of the D-Phe2 antagonist which has OT pA2 = 7.35 in our rat uterotonic assay. Both compounds are equipotent as antagonists of [Arg8]vasopressin in the rat antidiuretic assay, with pA2 = 8.1. Other substitutions gave [MCPA1,D-Trp2,4-Cl-Phe3,Ile4,Arg8]OT, (2), OT pA2 7.44; [MCPA1,D-Trp2,Phe3,Ile4,3,4-dehydro-Pro7,Arg8]OT (3), OT pA2 = 7.42; [MCPA1,D-Trp2,Phe3,Arg8]OT (4), OT pA2 = 7.58; [MCPA1,D-Trp2,Phe3,Arg8,Gly9-NHEt]OT (5), OT pA2 = 7.49; [MCPA1,D-Trp2,Ile4,Arg8]OT (6), OT pA2 = 7.46; [MCPA1,D-Trp2,Val4,Arg8]OT (7), OT pA2 = 7.58; [MCPA1,D-Trp2,Thr4,Arg8]OT (8), OT pA2 = 7.48; and finally, [MCPA1,D-Trp2,Arg8]OT (9), which was a more potent and more selective OT antagonist, with OT pA2 = 7.77 in the uterotonic assay and ADH pA2 less than 5.9 in the antidiuretic assay and hence is an important lead for the design of OT antagonists.

Animals↗
PubMed1991

Improvement in potency of an oxytocin antagonist after systematic substitutions with L-tryptophan.

We report twelve analogues of [Pmp1,D-Trp2,Arg8]oxytocin, ANTAG (Pmp = beta, beta-pentamethylene-beta-mercaptopropionic acid), which is a potent antagonist (pA2 = 7.77) of the uterotonic effect of oxytocin (OT) in rats, as measured in a uterotonic assay. Nine of the following analogues were designed by replacement of each of the nine residues in ANTAG with an L-tryptophan residue: [Ac-Trp1,D-Trp2,Val6,Arg8]OT, [Pmp1,Trp2,Arg8]OT, [Pmp1,D-Trp2,Trp3,Arg8]OT, [Pmp1,D-Trp2,Trp4,Arg8]OT, [Pmp1,D-Trp2,Trp5,Arg8]OT, [Aaa1,D-Trp2,Trp6,Arg8]OT, [Aaa1,D-Trp2,Val6,Arg8]OT, [Pmp1,D-Trp2,Ica7,Arg8]OT, [Pmp1,D-Trp2,Trp7,Arg8]OT, [Pmp1,D-Trp2,Trp8]OT, [Pmp1,D-Trp2,Arg8,Trp9]OT (11), [Pmp1,D-Trp2,Arg8,Trp(For)9]OT (12). In these analogues Aaa = 1-adamantaneacetic acid, and Ica = indoline-2-carboxylic acid. All linear analogues and analogues featuring Trp substitutions in the ring sequence of ANTAG were OT antagonists of lower potency than the parent peptide. All the analogues featuring Trp substitutions in the tail sequence of ANTAG were OT antagonists of equal or better potency than the parent peptide. Replacement with Ica7 gave analogue 8, equipotent with ANTAG, but replacement with Trp7 gave analogue 9, which shows almost a two-fold increase in potency (pA2 = 8.06). Replacement with Trp9 gave analogue 11 (pA2 = 8.03) which is about 1.8 times more potent than the parent antagonist, although Trp(For)9 had lower potency. Of great interest is that substitution with Trp8 leads to a more potent analogue, 10 (pA2 = 8.22), which, unlike most antidiuretic hormone antagonists, lacks any cationic charge in the molecule. The antidiuretic assay shows antagonists 9-11 to be weak antagonists of [Arg8]vasopressin, the antidiuretic hormone, with pA2 less than or equal to 6.0; hence, they may be interesting leads for future design of more potent and specific OT antagonists.

Amino Acid Sequence↗
PubMed1991

Dose-response characteristics of a ferrous-sulphate-doped gelatin system for determining radiation absorbed dose distributions by magnetic resonance imaging (Fe MRI).

The nuclear magnetic resonance (NMR) longitudinal relaxation rate R1 dose-response characteristics of a ferrous-sulphate-doped chemical dosimeter system (Fe MRI) immobilized in a gelatin matrix were explored. Samples containing various concentrations of the FeSO4 dosimeter were irradiated to absorbed doses of 0-150 Gy. R1 relaxation rates were determined by imaging the samples at a field strength of 1.5T(1H Lamor frequency of 63.8 MHz). The response of the system was found to be approximately linear up to doses of 50 Gy for all FeSO4 concentrations studied (0.1-2.0 mM). Changing concentrations in the range of 0.1-0.5 mM affected both the slope and intercept of the dose-response curve. For concentrations of 0.5-2.0 mM, the slope of the dose-response curves remained constant at approximately 0.0423 s-1 Gy-1 in the dose range of 0-50 Gy. However, the intercept of the curve continued to increase in that region, as expected, because of the additional paramagnetic ions. The reproducibility of the absorbed dose estimates for measurements made over a 22 cm field of view was found to be 5% in the range of 20-50 Gy (an uncertainty of 0.81 Gy on average), decreasing to approximately 10% in the dose range of 5-10 Gy.

Dose-Response Relationship, Radiation↗
PubMed1991

In vitro effects of progesterone and estradiol on uterine prostaglandin production in the pregnant rat.

Uterine prostaglandin (PG) levels increase markedly at the end of pregnancy in the rat and steroid hormones appear to be important regulators of this augmentation. The purpose of the present study was to examine the in vitro effects of progesterone (P) and estradiol (E2) on uterine PGE and PGF production in the pregnant rat. Uterine tissue was removed at Days 19 and 21 of pregnancy and incubated with P or E2 (0.1, 1, 10, 100, and 1,000 ng/ml) for 48 h in Ham's F-10 medium at 37 degrees C. P significantly (p less than 0.05) inhibited PGE and PGF production in a dose-dependent manner at Day 19, but not at Day 21 of pregnancy. In contrast, E2 had no effect (p greater than 0.05) at either day of pregnancy. In a second study, P was found to inhibit uterine PGE production at Days 15 and 19, but not at Day 21 or at delivery. A third study determined that the levels of P were greatly reduced in media containing uterine tissue from delivery when compared to media containing tissue from day 15 of pregnancy (p less than 0.05). In a fourth experiment, no difference in tritium-labeled P uptake was detected between media containing uterine tissue from Day 15 of pregnancy and media containing uterine tissue removed at delivery. This observation in association with data from the literature suggests that the disappearance of P from the media in experiment 3 might be due to enhanced P metabolism rather than to differential uptake of P by the tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Hormonal regulation of uterine secretion of prostaglandin F2 alpha during luteolysis in ruminants.

In recent years, considerable progress has been made in our understanding of the endocrine mechanisms that control the pattern and timing of uterine secretion of prostaglandin F2 alpha (PGF2 alpha) during luteolysis in ruminants. Oxytocin may be important in establishing a pulsatile pattern of secretion. Neurohypophyseal oxytocin appears to be released in a pulsatile fashion and may initiate each episode of PGF2 alpha secretion from the uterus. Uterine PGF2 alpha stimulates release of oxytocin from the corpus luteum. Luteal oxytocin further stimulates secretion of PGF2 alpha from the uterus and may induce a transient refractoriness of the uterus to subsequent stimulation with oxytocin. Uterine refractoriness subsides after approximately 6 h. A similar desensitization phenomenon occurs in response to PGF2 alpha at the level of the corpus luteum. Together, uterine and luteal refractoriness may account for the interval between pulses of PGF2 alpha observed during luteolysis. Uterine secretory responsiveness to oxytocin increases at luteolysis, when endogenous, pulsatile secretion of PGF2 alpha normally begins. Thus, the acquisition by the uterus of responsiveness to oxytocin may determine when endogenous secretion of PGF2 alpha occurs during the estrous cycle. Uterine secretory responsiveness to oxytocin develops slowly, in the presence of progesterone. Progesterone exerts two types of effects that contribute to the regulation of PGF2 alpha secretion. First, prolonged exposure to progesterone appears to promote uterine accumulation of arachidonic acid, prostaglandin endoperoxide synthase, and other substances needed for synthesis of PGF2 alpha. Second, progesterone exerts a suppressive effect on secretion, which wanes after prolonged exposure. Together, these effects of progesterone ensure that PGF2 alpha is secreted only at the appropriate time to induce luteolysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

POU-domain proteins Pit-1 and Oct-1 interact to form a heteromeric complex and can cooperate to induce expression of the prolactin promoter.

Two members of the POU-domain family of transcriptional activators, Pit-1 and Oct-1, are coexpressed in cells of the anterior pituitary gland. We demonstrate that the pituitary-specific developmental regulator Pit-1 can bind as a heterodimer with the widely expressed 100-kD Oct-1 protein to critical tissue-specific cis-active elements in the rat prolactin gene. Pit-1 and Oct-1 can also associate, in the absence of DNA, via their POU domains. Coexpression of Pit-1 and Oct-1 in a heterologous cell type results in reproducible 2- to 2.5-fold synergistic transcriptional effects on genes under control of the native prolactin promoter or of a single Pit-1 response element. These results suggest that a combinatorial pattern of heterodimeric and homodimeric interactions between different members of the POU-domain gene family can result when members of this large family are coexpressed in cells of developing and established organ systems, potentially regulating differential developmental gene activation.

Animals↗
PubMed1991

Some pharmacological properties of cyclic and linear analogs obtained by substituting each residue of an oxytocin antagonist with D-tryptophan.

We synthesized 10 analogs (1-10) derived from the sequence of [Pmp1,D-Trp2,Arg8]oxytocin, (parent antagonist or PA), (Pmp = beta,beta-pentamethylene-beta-mercaptopropionic acid) which is a potent antagonist (pA2 = 7.77) of the uterotonic effect of oxytocin (OT) in rats, as determined in our uterotonic assay. Eight of the following analogs were designed by replacement of each residue in the PA sequence, other than the residue at position 2, with D-tryptophan: Ac-D-Trp-D-Trp-Ile-Gln-Asn-Val-Pro- Arg-Gly-NH2, (1); [Pmp1,D-Trp(For)2,Arg8] OT, (2); [Pmp1,D-Trp2,D-Trp3,Arg8] OT, (3); [Pmp1,D-Trp2,D-Trp4,Arg8] OT, (4); [Pmp1,D-Trp2,D-Trp5,Arg8] OT, (5); Aaa-D-Trp-Ile-Gln-Asn-D-Trp-Pro-Arg- Gly-NH2, (6); [Pmp1,D-Trp2,D-Trp7,Arg8] OT, (7); [Pmp1,D-Trp2,D-Trp8] OT, (8); [Pmp1,D-Trp2,Arg8,D-Trp9] OT, (9); [Pmp1,D-Trp2,Arg8,D-Trp(For)9] OT, (10). To avoid free mercaptan groups, Val6 was chosen in analog 1 instead of Cys and Aaa1 (Aaa = 1-adamantaneacetic acid) in analog 6 instead of Pmp1. Of the linear analogs, 1 was inactive as an OT antagonist and 6 was a very poor antagonist, with a pA2 = 5.66, but it was more potent than Aaa-D-Trp-Ile-Gln-Asn-Val-Pro-Arg-Gly-NH2, which has a pA2 = 5.33, as we had previously reported. Analog 2, featuring D-Trp(For)2, pA2 = 7.37, was weaker than PA, indicating that the formyl group lowers potency. Analogs 3 and 4 were much weaker than PA, and analog 5 was inactive. Hence, other than at position 2, D-Trp is undesirable in the ring sequence of PA.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1991

Commentary on a national invitational seminar on quality assurance in health services.

This paper is a slightly modified version of a paper presented at a quality assurance seminar at Royal North Shore Hospital, Sydney on 7 December 1990. The paper uses the seminar given by Professor Avedis Donabedian in Sydney 13-17 August 1990, to emphasize two issues. First, while there are claims from many hospitals that they are conducting quality assurance, such activity demands the use of explicit criteria in one form or another and, in the author's view, few if any hospitals are, in fact, using this technology. What, then, of their claims to be conducting quality assurance? The second point is that Australian efforts at quality assurance have been focused on projects, ignoring the need for a program or system in the hospital, and a program or system is essential if efforts at ensuring effective quality assurance are to succeed.

Australia↗
PubMed1991

Monoclonal antibodies to human embryonal carcinoma cells: antigenic relationships of germ cell tumors.

Fifteen monoclonal antibodies (mAb) that show specificity for human embryonal carcinoma cells are described. C57BL/6 mice were immunized with Tera-2 embryonal carcinoma cells, and hybridomas were isolated and tested versus a set of human developmental tumor cell lines. The antigens exhibit relatively restricted and unique distributions on normal tissues as shown by immunohistochemistry. The mAbs recognize a series of differentiation antigens since their expression changes when teratocarcinoma stem cells are induced to differentiate in vitro. The expression of these molecules in germ cell and related tumors is consistent with the data obtained from in vitro cell studies. Seven of these mAbs immunoprecipitate molecules from surface labeled Tera-2 cells that show distinct molecular weights on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The antigenic phenotypes defined by the set of mAbs can be used to investigate possible pathogenetic relationships of the various testicular tumors.

Animals↗
PubMed1990

Glutathione S-transferase. Novel vaccine against Fasciola hepatica infection in sheep.

The potential of GST as a vaccine candidate against liver fluke infection in ruminants was studied by vaccinating sheep (n = 9) with GST purified from adult worms of Fasciola hepatica and challenging with 500 F. hepatica metacercariae. The immunization induced a high antibody response to GST in contrast to the poor or undetectable response to this Ag observed in naturally infected sheep. Throughout the trial, the progress of the fluke infection was monitored by measuring RBC hemoglobin levels, the extent of liver damage and the fecal egg output in the sheep. This analysis indicated that a subpopulation (n = 4) of the GST vaccinated animals exhibited no anemia, reduced liver damage and a lower mean fecal egg count relative to the infected control group suggesting a lower fluke burden in these animals. Worm burdens in the livers of the GST vaccine group (107 +/- 22) were 57% lower than in the infected control group (250 +/- 25). The subpopulation of the GST vaccine group demonstrated a 78% reduction in mean worm burdens relative to the control group. These results show that GST of adult F. hepatica is a novel Ag that can significantly protect sheep against liver fluke infection. The results suggest that the immune response to GST is directed to the juvenile worm reducing the number of worms that can establish in the liver of the vaccinated animals.

Animals↗
PubMed1990

Trial of brief intermittent neuroleptic prophylaxis for selected schizophrenic outpatients: clinical and social outcome at two years.

OBJECTIVE: To evaluate a novel approach to the prophylaxis of schizophrenic relapse characterised by administration of brief courses of neuroleptic for the earliest non-psychotic signs of relapse (prodromal symptoms). DESIGN: Two year follow up of subjects randomised, double blind, to receive either active (control group) or placebo (intermittent group) depot neuroleptic medication. Both groups received brief courses of oral neuroleptic when prodromal symptoms or relapse occurred. SETTING: Psychiatric outpatient department, Charing Cross Hospital, London. SUBJECTS: 54 Stable patients in remission who met the American Psychiatric Association's DSM-III criteria for schizophrenia on the basis of case notes. MAIN OUTCOME MEASURES: Survival without relapse, survival without hospitalisation, point prevalence of extrapyramidal side effects and tardive dyskinesia, structured assessment of social functioning (social adjustment scale II), and frequency of prodromal symptoms. RESULTS: Of 19 relapses recorded over two years, 10 (53%) were preceded by non-psychotic prodromal signs. Survival rates for both relapse and hospitalisation were worse with intermittent treatment than continuous treatment over the two year follow up: 92% of controls and only 54% of patients given intermittent treatment survived the two year period without hospitalisation. Prolonged or frequent relapses as well as episodes of prodromal symptoms were more frequent with intermittent treatment. Lower scores for extrapyramidal side effects were recorded in the intermittent treatment group, but periodic assessments of social functioning failed to show any social advantages from this. CONCLUSION: The findings are at variance with a previous report of one year follow up in this cohort and attest to the superiority of continuous depot neuroleptic prophylaxis in preventing both psychotic and neurotic or dysphoric morbidity in schizophrenia.

Administration, Oral↗
PubMed1990

Autoregulation of pit-1 gene expression mediated by two cis-active promoter elements.

The pit-1 gene is a member of a large family of genes that encode proteins which are involved in development and which contain a highly homologous region, referred to as the POU domain. Pit-1, a pituitary-specific transcription factor, can activate the transcription of the growth hormone and prolactin promoters. It is expressed in mature thyrotroph, somatotroph and lactotroph cell types of the anterior pituitary which arise sequentially during development; somatotrophs and lactotrophs, which secrete growth hormone and prolactin, respectively, are the last to arise. Intriguingly, during ontogeny, pit-1 transcripts are observed in the rat neural tube and neural plate (embryonic day 10-11) and disappear thereafter (day 13), only to reappear exclusively in the anterior lobe of the pituitary gland (day 15) just before activation of prolactin and growth hormone. This biphasic pattern suggests a complex mechanism of initial activation of pit-1 gene expression. Transcription and transfection analyses in vitro using wild-type and mutated promoters indicate that Pit-1 can positively autoregulate the expression of the pit-1 promoter as a consequence of binding to two Pit-1-binding elements. Mutation of the 5' Pit-1-binding site abolished positive autoregulation, whereas mutation of the element located immediately 3' of the cap site markedly increased expression of the pit-1 promoter. These data are consistent with a positive, attenuated autoregulatory loop that seems to function in maintaining pit-1 gene expression.

Animals↗
PubMed1990

Role of GTP hydrolysis in microtubule polymerization: evidence for a coupled hydrolysis mechanism.

The relationship between GTP hydrolysis and microtubule assembly has been investigated by using a rapid filtration method. Microtubules assembled from phosphocellulose-purified tubulin, double-labeled with [gamma-32P]- and [3H]GTP, were trapped and washed free of unbound nucleotide on glass fiber filters. The transient accumulation of microtubule-bound GTP predicted by uncoupled GTP hydrolysis models [Carlier & Pantaloni (1981) Biochemistry 20, 1918-1924; Carlier et al. (1987) Biochemistry 26, 4428-4437] during the rapid assembly of microtubules was not detectable under our experimental conditions. By calculating hypothetical time courses for the transient accumulation of microtubule-bound GTP, we demonstrate that microtubule-bound GTP would have been detectable even if the first-order rate constant for GTP hydrolysis were 4-5 times greater than the pseudo-first-order rate constant for tubulin subunit addition to microtubules. In a similar manner, we demonstrate that if GTP hydrolysis were uncoupled from microtubule assembly but were limited to the interface between GTP subunits and GDP subunits (uncoupled vectorial hydrolysis), then microtubule-bound GTP would have been detectable if GTP hydrolysis became uncoupled from microtubule assembly at less than 50 microM free tubulin, 5 times the steady-state tubulin concentration of our experimental conditions. In addition, during rapid microtubule assembly, we have not detected any microtubule-bound Pi, which has been proposed to form a stabilizing cap at the ends of microtubules [Carlier et al. (1988) Biochemistry 27, 3555-3559]. Also, several conditions that could be expected to increase the degree of potential uncoupling between GTP hydrolysis and microtubule assembly were examined, and no evidence of uncoupling was found. Our results are consistent with models that propose cooperative mechanisms that limit GTP hydrolysis to the terminal ring of tubulin subunits [e.g., O'Brien et al. (1987) Biochemistry 26, 4148-4156]. The results are also consistent with the hypothesis that a slow conformational change in tubulin subunits after GTP hydrolysis and Pi release occurs that results in destabilized microtubule ends when such subunits become exposed at the ends.

Animals↗
PubMed1990

The POU-specific domain of Pit-1 is essential for sequence-specific, high affinity DNA binding and DNA-dependent Pit-1-Pit-1 interactions.

Pit-1 is a member of a family of transcription factors sharing two regions of homology: a highly conserved POU-specific (POUS) domain and a more divergent homeodomain (POUHD). Analysis of mutant Pit-1 proteins suggests that, while the POUHD is required and sufficient for low affinity DNA binding, the POUS domain is necessary for high affinity binding and accurate recognition of natural Pit-1 response elements. Pit-1 is monomeric in solution but associates as a dimer on its DNA response element, exhibiting DNA-dependent protein-protein interactions requiring the POUS domain. Analysis of alpha-helical domains and conserved structures in Pit-1 suggests that POU domain proteins interact with their DNA recognition sites differently than classic homeodomain proteins, with both the POUHD and the POUS domain contacting DNA. Transcriptional activity of Pit-1 on enhancer elements is conferred primarily by a Ser- and Thr-rich N-terminal region unrelated to other known transcription-activating motifs.

Algorithms↗
PubMed1990

Kinetic analysis of tubulin exchange at microtubule ends at low vinblastine concentrations.

We have investigated the effects of vinblastine at micromolar concentrations and below on the dynamics of tubulin exchange at the ends of microtubule-associated-protein-rich bovine brain microtubules. The predominant behavior of these microtubules at polymer-mass steady state under the conditions examined was tubulin flux, i.e., net addition of tubulin at one end of each microtubule, operationally defined as the assembly or A end, and balanced net loss at the opposite (disassembly or D) end. No dynamic instability behavior could be detected by video-enhanced dark-field microscopy. Addition of vinblastine to the microtubules at polymer-mass steady state resulted in an initial concentration-dependent depolymerization predominantly at the A ends, until a new steady-state plateau at an elevated critical concentration was established. Microtubules ultimately attained the same stable polymer-mass plateau when vinblastine was added prior to initiation of polymerization as when the drug was added to already polymerized microtubules. Vinblastine inhibited tubulin exchange at the ends of the microtubules at polymer-mass steady state, as determined by using microtubules differentially radiolabeled at their opposite ends. Inhibition of tubulin exchange occurred at concentrations of vinblastine that had very little effect on polymer mass. Both the initial burst of incorporation that occurs in control microtubule suspensions following a pulse of labeled GTP and the relatively slower linear incorporation of label that follows the initial burst were inhibited in a concentration-dependent manner by vinblastine. Both processes were inhibited to the same extent at all vinblastine concentrations examined. If the initial burst of label incorporation represents a low degree of dynamic instability (very short excursions of growth and shortening of the microtubules at one or both ends), then vinblastine inhibits both dynamic instability and flux to similar extents. The ability of vinblastine to inhibit tubulin exchange at microtubule ends in the micromolar concentration range appeared to be mediated by the reversible binding of vinblastine to tubulin binding sites exposed at the polymer ends. Determination by dilution analysis of the effects of vinblastine on the apparent dissociation rate constants for tubulin loss at opposite microtubule ends indicated that a principal effect of vinblastine is to decrease the dissociation rate constant at A ends (i.e., it produces a kinetic cap at A ends), whereas it has no effect on the D-end dissociation rate constant.

Animals↗
PubMed1990

Inhibition of spontaneous uterine contractions during the last trimester in pregnant baboons by an oxytocin antagonist.

The effect of a potent oxytocin antagonist, produced in our laboratories, on spontaneous uterine contractions in the pregnant baboon was examined. Three types of uterine contractions were studied: immediately after operation, during the nocturnal period, and near or at labor. Bolus intravenous injections of oxytocin antagonist were given and uterine activity was examined +/- 1 hour after the injection. The oxytocin antagonist caused a precipitate decrease (approximately 70%) in contractile force (mean amplitude x frequency) in the first 15 minutes after injection (p less than 0.05); this force diminished to approximately 90% at the end of 1 hour for both nocturnal and labor contractions. In contrast, uterine contractions immediately after operation were diminished by only 60% within 60 minutes after the oxytocin antagonist. These results indicate that the oxytocin antagonist is a potent inhibitor and suggest that oxytocin is a primary regulator of spontaneous nocturnal and labor uterine contractions in the pregnant baboon.

Analysis of Variance↗
PubMed1990

Cocaine use and its effect on umbilical artery prostacyclin production.

Cocaine's association with adverse perinatal outcome has been attributed to its inhibition of norepinephrine uptake. This study examined the effect of cocaine on umbilical artery prostacyclin (PGI2) production. Umbilical arteries from pregnant cocaine users and controls were incubated in vitro and PGI2 levels in the media determined by measuring its stable metabolite, 6-keto-PGF1 alpha, by RIA. Cocaine users showed a significant decrease (p less than .05) in PGI2 production from their umbilical arteries when compared to controls. This appears to be through a direct effect of cocaine, as it decreases PGI2 production when added in vitro to umbilical arteries from controls. In addition, in vitro phospholipase A2 activity is inhibited by cocaine in a dose-dependent manner. These results suggest that the adverse perinatal outcome associated with cocaine use may be due in part to reduced vascular PGI2 production in the fetus.

Cocaine↗