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Biomedical subjects

C Lees

Publications and source records attributed to C Lees.

At least 37 records · Page 2Linked to original sources
PubMed2000

Increased fetal erythroblasts in women who subsequently develop pre-eclampsia.

In pregnancies complicated by pre-eclampsia (PET) and/or intrauterine growth restriction (IUGR) there is an increased number of fetal cells in the maternal circulation. The aim of this study was to investigate whether this increase in fetal cells precedes the onset of these pregnancy complications. Doppler ultrasound studies at 24 weeks gestation have shown that increased impedance to flow in the uterine arteries identifies pregnancies with impaired placental perfusion that subsequently develop PET and/or IUGR. We obtained maternal blood from 18 pregnancies with abnormal Doppler results at 22-24 weeks gestation and from 10 normal controls. Fetal erythroblasts were enriched from maternal blood by triple density gradient centrifugation and magnetic cell sorting with CD71 antibody, and the percentage of these erythroblasts was determined. The median proportion of fetal erythroblasts in the group with abnormal Doppler results was 4.5% (range 1-12%), which was significantly higher than in the control group [median 1% (range 0-3%; P < 0.001)]. Furthermore, within the group with abnormal Doppler the median proportion of fetal erythroblasts was higher in the 10 cases which subsequently developed PET and/or IUGR [median 5.5% (range 3-12%)], than in those with normal pregnancy outcome [median 2% (range 1-5%; P < 0.01)]. These findings suggest that impaired placental perfusion is associated with an increase in feto-maternal cell traffic, which precedes the onset of PET and/or IUGR by several weeks.

Adult↗
PubMed1999

Maternal and fetal cardiovascular effects of transdermal glyceryl trinitrate and intravenous ritodrine.

OBJECTIVE: To determine the maternal and fetal cardiovascular effects of transdermal glyceryl trinitrate compared with ritodrine for acute tocolysis. METHODS: Sixty women in preterm labor were enrolled in this study that was part of a multicenter study of glyceryl trinitrate. Once randomized, the women received transdermal glyceryl trinitrate or intravenous ritodrine for acute tocolysis. Measurements of maternal pulse, blood pressure (BP), and fetal heart rate (FHR) were recorded for up to 24 hours and compared over the treatment course. RESULTS: Changes from baseline in mean maternal heart rate, FHR, and maternal BP (mean arterial pressure [MAP]) were compared between the glyceryl trinitrate and ritodrine groups over the entire treatment course. The mean change from baseline in maternal heart rate was 21.1 beats per minute less (95% confidence interval [CI] 15.7, 26.5, P < .001), and the mean maternal heart rate was 21.8 beats per minute lower (95% CI 16.9, 26.7, P < .001) in the glyceryl trinitrate group. The mean change in FHR was 9.2 beats per minute less (95% CI 3.8, 14.6, P = .001) and the mean FHR significantly lower (6.9 beats per minute, 95% CI 1.9, 11.9, P = .008) during glyceryl trinitrate treatment. Ritodrine had a significantly hypotensive effect on MAP (95% CI -4.3, 0.0, P = .03). Mean arterial pressure was not significantly different over the treatment course. CONCLUSION: At doses required for acute tocolysis, transdermal glyceryl trinitrate had minimal effects on maternal pulse, BP, and FHR, and significantly fewer adverse cardiovascular effects than intravenous ritodrine. Thus, transdermal glyceryl trinitrate might be a safer treatment for women in preterm labor.

Administration, Cutaneous↗
PubMed1999

Assessment of umbilical arterial and venous flow using color Doppler.

OBJECTIVE: To estimate the umbilical artery and vein blood volume flow using B-mode and Doppler ultrasound in the second and third trimesters of pregnancy. DESIGN: This was a cross-sectional study of 129 singleton, healthy pregnancies at 23-33 weeks' gestation. The umbilical artery and vein cross-sectional area, time-averaged velocity and pulsatility index were measured in a free loop of cord, and the fetal weight was estimated. Ranges for each parameter were obtained; from these the blood flow for the vein and artery was calculated, and the average flow corrected for fetal weight was derived. RESULTS: The median time for examination was 6 min. The mean cross-sectional area and time-averaged velocity for both the vein and artery increased linearly with gestation. The umbilical artery flow correlated closely with the average vein flow (r = 0.9, p < 0.001). There was a significant, though poor, inverse correlation between the umbilical artery pulsatility index and the average umbilical flow (r = -0.25, p < 0.05). The average umbilical flow (calculated from the mean of arterial and venous flow), corrected for estimated fetal weight, decreased from 189.2 ml/kg per min at 23 weeks to 176.2 ml/kg per min at 33 weeks' gestation. CONCLUSION: The estimates of fetal umbilical flow obtained by this Doppler method are consistent with previously published data. Averaging the arterial and venous flow is theoretically advantageous in reducing the inherent errors in estimating either the arterial or the venous flow. This method of measuring umbilical flow may have clinical potential in assessing fetal health and disease processes.

Blood Flow Velocity↗
PubMed1999

The role of insulin-like growth factor binding protein-1 phosphoisoforms in pregnancies with impaired placental function identified by doppler ultrasound.

This study was performed to investigate the hypothesis that insulin-like growth factor binding protein-1 (IGFBP-1) is involved in the pathogenesis of trophoblast invasion and impaired placentation in human pregnancy. The role of total and non-phosphorylated IGFBP-1 in women with fetal growth restriction and in high risk pregnancies identified by uterine artery Doppler ultrasound screening was examined. This was a prospective study of women booked for antenatal care having second trimester anomaly scans and Doppler screening between 22-26 weeks gestation. Women were divided into three groups and compared: normal uterine artery Doppler and normal fetal growth (control group, n = 10); abnormal Doppler and normal fetal growth [bilateral uterine artery notches (BN; n = 16); abnormal Doppler and intrauterine growth restriction (IUGR; n = 8)]. Maternal serum was collected, stored and assayed simultaneously for total and non-phosphorylated IGFBP-1. There was elevated total and non-phosphorylated IGFBP-1 (mean 44.99 +/- 12.19 and 29.61 +/- 10.38 microg/l respectively) in the IUGR group compared with controls (mean 17.96 +/- 3.24 and 12.18 +/- 1.55 microg/l, P < 0.05). This finding suggests that the various IGFBP-1 isoforms, the degree of phosphorylation and the ratios of these different forms locally may be important during trophoblast invasion and may be implicated in clinical manifestations of impaired placentation later in the second trimester.

Female↗
PubMed1999

Vasa previa: an avoidable obstetric tragedy.

UNLABELLED: Vasa previa is a rarely reported condition in which the fetal blood vessels, unsupported by either the umbilical cord or placental tissue, traverse the fetal membranes of the lower segment of the uterus below the presenting part. The condition has a high fetal mortality due to fetal exsanguination resulting from fetal vessels tearing when the membranes rupture. Despite improvements in medical technology, vasa previa often remains unsuspected until this fatal fetal vessel rupture occurs. Significant reduction in the fetal mortality from this condition depends on a high index of suspicion leading to antenatal diagnosis, and elective delivery by cesarean. We believe transvaginal ultrasound in combination with color Doppler is the most effective tool in the antenatal diagnosis of vasa previa and should be utilized in patients at risk, specifically those with bilobed, succenturiate-lobed, and low-lying placentas, pregnancies resulting from in vitro fertilization, and multiple pregnancy. Where there has been antepartum or intrapartum hemorrhage, especially when associated with fetal heart irregularities, we also recommend a test to exclude fetal blood in the vaginal blood. Similarly, amnioscopy before amniotomy may help to diagnose this condition. Cesarean delivery is the method of delivery of choice, and aggressive resuscitation of the affected neonate may be life saving. With a high index of suspicion, antenatal diagnosis using transvaginal sonography in combination with color Doppler, elective delivery by cesarean, and aggressive resuscitation of the neonate where fetal vessel rupture has occurred, the mortality from this complication may be considerably reduced. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader will be able to identify the risk factors and associated conditions for vasa previa, to identify the various clinical presentations and management of vasa previa, and to be aware of the diagnostic tools available to make the antepartum diagnosis of vasa previa.

Cesarean Section↗
PubMed1998

Engraftment of severe combined immune deficient mice receiving allogeneic bone marrow via In utero or postnatal transfer.

Although in utero transplantation (IUT) has been shown to be effective in treating human severe combined immune deficiency (SCID), the relative merit of IUT as compared with postnatal bone marrow transplantation (BMT) for SCID is unknown. Therefore, comparative studies were undertaken in mice to determine the engraftment outcome in these two settings. Because T-cell depletion (TCD) reduces graft-versus-host disease (GVHD) severity but compromises alloengraftment, studies were performed with TCD or non-TCD BM and GVHD risk was assessed using a tissue scoring system and by the adoptive transfer of splenocytes from engrafted mice into secondary recipients. Non-SCID recipients received pre-BMT irradiation to simulate those circumstances in which conditioning is required for alloengraftment. IUT recipients of non-TCD and especially TCD BM cells in general had higher levels of donor T-cell and myeloid peripheral blood (PB) engraftment than nonconditioned SCID recipients. Increased TCD or non-TCD BM cell numbers in adult SCID recipients resulted in similar levels of PB engraftment as IUT recipients. However, under these conditions, mean GVHD scores were higher than in IUT recipients. The majority of adoptive transfer recipients of splenocytes from IUT recipients were GVHD-free, consistent with the in vitro evidence of tolerance to host alloantigens. Total body irradiation (TBI)-treated mice that had the highest engraftment had evidence of thymic damage as denoted by a higher proportion of thymic and splenic T cells with a memory phenotype as compared with IUT recipients. IUT mice had vigorous thymic reconstitution by 3 weeks of age. Our data indicate that IUT has a number of advantages as compared with postnatal BMT. Future studies examining the fine specificity of immunoreconstitution in IUT versus postnatal BMT are indicated.

Adoptive Transfer↗
PubMed1998

Mouse mucin 1 (MUC1) defined by monoclonal antibodies.

Mucins are highly expressed in many different human cancers and numerous murine monoclonal antibodies (MAbs) to human mucins, particularly Mucin 1 (MUC1), have been produced. However, no such antibodies to murine mucin 1 (muc1) have been described and we now describe 6 different antibodies produced to murine muc1 and to human MUC1 cytoplasmic tail, either by immunising rats, or muc1 o/o mice with synthetic peptides or a fusion protein composed of glutathione-s-transferase (GST) linked to the tandem repeat region of muc1. The antibodies to both the extracellular tandem repeat region and to the cytoplasmic tail were found to react with mucin-containing murine tissues such as breast, stomach, colon, ovary, kidney and pancreas, and the staining patterns were similar to those found in humans. The reagents reacted specifically with muc1 peptides and tissues; however, some cross reactivity with other mucin-derived peptides was noted, particularly those containing the amino acid sequence TSS. Three different epitopes (TSS, TAVLSGTS and LSGTSSP) of the M30, M70 and MFP25 MAbs were detected. Of interest was the finding that some of the antibodies reacted with murine lymphocytes; it was not clear whether these reactions were due to mucin 1 on mouse lymphocytes (MUC1 was considered to be absent from human lymphocyte), or due to cross reaction with a sialic adhesion molecule on lymphocytes. The antibodies should prove valuable reagents when studying differentiation and expression in murine glandular tissues and the ontogeny of mucin-secreting tumours.

Animals↗
PubMed1998

Oxidised mannan antigen conjugates preferentially stimulate T1 type immune responses.

It is desirable to be able to produce either T1 or T2 responses and we have found that, in mice, mannose--coupled antigens stimulated T2 type responses antibodies and CTLs, whereas if oxidized, mannose--coupled antigens stimulated T1 responses little antibody and a potent CTL response. In addition, the cytokine profiles support the T1rT2 differentiation with these immunizations, in that oxidized mannan antigen gives IFNg, IL-2 and IL-12 production, whereas in the absence of oxidization, IL-4 and not the other cytokines is produced. A number of antigens have been examined--particularly Mucin 1 and the delivery method using mannose may be applicable to the other antigens.

Animals↗
PubMed1998

Placental nitric oxide production and umbilical artery vascular impedance in early pregnancy.

OBJECTIVE: To evaluate whether the vasorelaxant molecule nitric oxide (NO) and its second messenger cyclic guanosine monophosphate (cGMP) modulate the reduction in resistance within the fetoplacental circulation that occurs during the first trimester of pregnancy. METHODS: We studied 27 women undergoing termination of pregnancy for psychosocial indications between 9 and 15 weeks' gestation. Each had ultrasound dating of the fetus and Doppler umbilical artery (UA) flow investigation immediately before the operation. Placental tissue was assayed for nitric oxide synthase (NOS) activity and cGMP content. RESULTS: Both UA pulsatility index (PI) and placental endothelial NOS activity decreased significantly with advancing gestation (r = -.52 and -.41, respectively). Umbilical PI correlated positively with endothelial NOS activity and cGMP level. Multiple linear regression analysis indicated that cGMP contributed most strongly to UA PI (P < .001). CONCLUSION: Our findings suggest somewhat paradoxically that NOS activity and cGMP levels are highest in the early gestations, when umbilical PI is also high, and decrease as umbilical PI decreases. Further studies are required to determine whether the predominant effect of NO is that of a vascular relaxant or a modulator of new villous vessel formation.

Blood Flow Velocity↗
PubMed1998

Unexpected effect of a nitric oxide donor on uterine artery Doppler velocimetry in oligomenorrheic women with polycystic ovaries.

We compared uterine artery vascular responses following administration of the nitric oxide donor glyceryl trinitrate to ten women with oligomenorrhea and ultrasound evidence of polycystic ovaries with those of nine women with a normal menstrual cycle and ultrasonically normal ovaries. Mean arterial blood pressure, pulse rate and uterine artery flow velocity waveforms were recorded before and 60-75 min after glyceryl trinitrate patch application. The pulsatility index and resistance index were calculated to describe changes in impedance to flow in the uterine artery. Peak systolic and time-averaged velocities were also measured. Pretreatment median arterial pressure was higher in women with polycystic ovaries (90 mmHg) compared to those with regular cycles (80 mmHg) (p < 0.05). No differences were found in pulse rate and uterine artery blood flow indices between the two groups. After glyceryl trinitrate patch administration, there was no change in blood pressure or pulse rate in either group. In women with polycystic ovaries, there was an increase in uterine artery resistance index (0.93 to 1.00; p < 0.05) and pulsatility index (3.77 to 4.99; p < 0.05) and a decrease in peak systolic (36.8 to 32.3 cm/s; p < 0.05) and time-averaged maximum (8.5 to 5.0 cm/s; p < 0.05) velocities. Uterine artery Doppler parameters remained unchanged in women with normal cycles. Uterine artery vascular responses to the nitric oxide donor glyceryl trinitrate are different in women with normal cycles compared to oligomenorrheic women with polycystic ovaries. This may be relevant to an understanding of the pathophysiology underlying the higher risk of cardiovascular morbidity and mortality associated with polycystic ovarian syndrome.

Adult↗
PubMed1998

The efficacy and fetal-maternal cardiovascular effects of transdermal glyceryl trinitrate in the prophylaxis of pre-eclampsia and its complications: a randomized double-blind placebo-controlled trial.

OBJECTIVES: Pre-eclampsia continues to be a major cause of maternal and perinatal mortality. A disorder of the nitric oxide system is implicated in the pathogenesis of this condition and preliminary studies have suggested a possible therapeutic role for nitric oxide donors in women with established pre-eclampsia. The aim of this study was to determine whether pre-eclampsia and its complications could be prevented by the long-term use of nitric oxide donors in a group of women identified to be at risk on the basis of abnormal uterine artery Doppler measurements. STUDY DESIGN: We enrolled 40 healthy normotensive women at high risk of pre-eclampsia selected on the basis of abnormal uterine artery Doppler waveforms at 24-26 weeks of gestation. Women were randomly allocated to receive transdermal glyceryl trinitrate 5 mg-patches or equivalent placebo patches in a double-blind randomized study. The primary outcome measures were pre-eclampsia, fetal growth restriction, preterm delivery or small for gestational age/fetal growth restriction rates. Patches were worn daily from recruitment for 10 weeks or until delivery. RESULTS: The primary outcomes were not significantly different in the placebo compared to the glyceryl trinitrate group. However, survival analysis of adverse events with gestation in both groups showed a significantly reduced risk of an adverse event in the glyceryl trinitrate group (p = 0.004), equating to a 73% reduction in hazard. There was no difference in maternal systolic and diastolic blood pressure, mean uterine artery resistance index and fetal umbilical and middle cerebral artery pulsatility indices between the groups. CONCLUSIONS: Low-dose prophylactic transdermal glyceryl trinitrate commenced late in the second trimester did not reduce the incidence of pre-eclampsia, preterm delivery or fetal growth restriction, but may increase the likelihood of a complication-free pregnancy. Transdermal glyceryl trinitrate (5 mg/day) did not affect maternal cardiovascular, uterine artery or fetal arterial Doppler parameters.

Administration, Cutaneous↗
PubMed1997

Transfer of inulin across the first-trimester human placenta.

OBJECTIVE: Our aim was to investigate the transfer of inulin from the mother to the first-trimester fetus. STUDY DESIGN: A bolus of inulin (5 mg/kg) was administered to nine healthy volunteers with pregnancies between 6 and 12 weeks of gestation scheduled for elective termination of pregnancy. Coelomic and amniotic fluid samples were obtained from the corresponding cavities between 8 and 25 minutes after the end of the bolus of inulin. Fetal fluid inulin concentrations were compared with those of matched samples of maternal blood and urine collected simultaneously. RESULTS: Inulin was detected in all fetal and maternal samples. A trend toward an increasing inulin concentration was noted in the exocoelomic cavity with advancing time. Coelomic and maternal serum inulin concentrations were similar within 20 minutes after injection. Amniotic inulin concentrations were always lower than coelomic concentrations irrespective of gestational age or advancing time after injection. CONCLUSIONS: Inulin crosses the first-trimester human placenta from 7 weeks of gestation in quantities that yield measurable concentrations in both coelomic and amniotic fluids. These results suggest that the study of drug transfer in the first trimester of human pregnancy is feasible with use of samples obtained from the exocoelomic cavity.

Female↗
PubMed1996

Preterm labour and delivery.

Preterm birth is a major cause of perinatal morbidity and mortality. It accounts for 5-10% of all births, and any treatment to prevent it could have a profound effect on neonatal outcome in both human and economic terms. The pathogenesis of both term and preterm birth remain poorly understood. Our ability to predict those at risk of preterm labour is also inaccurate, despite the creation of scoring systems, uterine activity monitoring, cervical ultrasound and several biochemical markers. Current drug therapies for preterm labour have not been shown in randomised controlled trials to significantly affect perinatal morbidity and mortality. Furthermore, most are associated with significant maternal or fetal side effects. Nitric oxide (NO) is a potent smooth muscle relaxant, produced when NO synthase acts on the amino acid L-arginine. Its presence has been demonstrated in human myometrium. We have conducted an observational study which has suggested that glyceryl trinitrate (GTN), and NO donor, may be effective in prolonging gestation. A randomised trial comparing GTN to intravenous ritodrine is currently recruiting patients; results will be available in the Spring of 1997. Few side effects have so far been encountered. Evidence suggests that GTN, an NO donor, should be a safe and effective tocolytic and early observations are encouraging; randomised trials currently underway should determine the significance of this breakthrough in the management of preterm labour.

Adrenergic beta-Agonists↗
PubMed1996

The effects of S-nitrosoglutathione on platelet activation, hypertension, and uterine and fetal Doppler in severe preeclampsia.

OBJECTIVE: To determine the effects of the platelet-specific nitric oxide donor S-nitrosoglutathione on women with severe preeclampsia. METHODS: Ten women with severe preeclampsia or preeclampsia with severe fetal compromise at 21-33 weeks' gestation each received a 60-90-minute intravenous infusion of 50-250 micrograms/minute of S-nitrosoglutathione. Each was hypertensive, despite conventional oral antihypertensive therapy in eight. Maternal blood pressure, heart rate, platelet activation, uterine artery, and fetal Doppler indices were measured during the infusion. RESULTS: A dose-dependent reduction in mean arterial pressure from 125 mmHg (95% confidence interval [CI] 117-133) to 103.5 (95% CI 97-111) (P < .005) and an increase in pulse rate from 73.7 beats per minute (95% CI 64.3-84.5) to 89.1 (95% CI 81.2-97.8) (P < .02) was observed during the infusion. Mean uterine artery resistance index fell from 0.76 (95% CI 0.73-0.81) to 0.70 (95% CI 0.65-0.75) (P < .009). Platelet activation measured by P-selectin expression was reduced from 3.02% (95% CI 2.09-4.36) to 1.22% (95% CI 0.94-1.58) (P < .01). Fetal Doppler indices (umbilical artery, middle cerebral artery, and thoracic aorta) showed no significant changes during the infusion. CONCLUSION: S-nitrosoglutathione infusion reduced material mean arterial pressure, platelet activation, and uterine artery resistance without further compromising fetal Doppler indices. This study suggests that platelet-specific nitric oxide donors may prove beneficial in the management of severe preeclampsia.

Adult↗
PubMed1996

Doppler ultrasound of the uterine arteries: the importance of bilateral notching in the prediction of pre-eclampsia, placental abruption or delivery of a small-for-gestational-age baby.

The use of Doppler studies of the uterine arteries in the prediction of pre-eclampsia and intrauterine growth retardation has had mixed success. The introduction of color Doppler imaging and the use of the "notch' to define an abnormal waveform have helped to improve the predictive value of uterine artery Doppler screening. The aim of this study was to evaluate the use of uterine artery Doppler in a group of women of mixed race and parity. This study was a prospective, cross-sectional analysis of 1326 unselected women who were screened with continuous wave uterine Doppler at 19-21 weeks, as part of a fetal anomaly/dating scan. A total of 214 women with abnormal uterine artery waveforms (notching) were referred for assessment at 24 weeks; 191 attended and had color Doppler imaging/pulsed Doppler studies of both uterine arteries. Data from 185 pregnancies were suitable for analysis. There were abnormal uterine Doppler findings (uni- or bilateral notching) in 110 patients at 24 weeks; 48 had bilateral notching. The sensitivity of notching for the prediction of proteinuric pregnancy-induced hypertension (PPIH) was similar in primiparas (76.9%), multiparas (77.7%), African-Caribbean women (82.6%) and Caucasian women (71.4%). The sensitivity of bilateral notching for the prediction of PPIH requiring delivery before 34 weeks was 81.2%, and 57.6% for babies small for gestational age (SGA), with positive predictive values of 27% (PPIH), 31.2% (SGA) and 37.5% (any complication). Patients with persistent bilateral notching are particularly at risk of developing PPIH or delivering an SGA baby before 34 weeks' gestation; they warrant increased surveillance, and may be a group that could benefit from prophylactic therapies.

Abruptio Placentae↗
PubMed1996

In-vivo study of diazepam transfer across the first trimester human placenta.

Diazepam transfer by the first trimester human placenta was investigated at pregnancy termination between 6 and 12 weeks of gestation. Fetal fluid samples were obtained from the exocoelomic and amniotic cavities of 65 pregnancies between 8 and 25 min following the i.v. administration of 0.1 mg/kg diazepam to the mother. Diazepam was detected in one-third of coelomic fluid samples and two-thirds of amniotic fluid samples. Maternal serum and urine diazepam concentrations correlated negatively and positively respectively, with time from drug injection to sampling. Individual diazepam concentrations were low on the fetal side, and the corresponding concentrations were independent of maternal serum concentrations and the time from drug injection to sampling. Amniotic fluid diazepam content increased significantly with advancing gestational age. A multiple regression analysis showed that the diazepam content of the coelomic fluid was not influenced by maternal serum diazepam concentration, the time from drug injection to sampling or gestational age, whereas only gestational age contributed to the diazepam content of amniotic fluid. These data demonstrate that the placental transfer of diazepam occurs from week 6 of gestation, indicate a preferential transfer of this drug to the amniotic cavity and suggest that diazepam may accumulate in fetal circulation and tissues during organogenesis.

Adult↗
PubMed1996

Effects of platelet-activating factor (PAF) receptor blockage on mucous glycoprotein secretion in cultured chinchilla middle ear epithelium.

Platelet-activating factor (PAF) is a naturally occurring phospholipid that acts as a pleiotropic mediator of inflammation via specific membrane receptors. It has been demonstrated in recent years that PAF is a strong secretagogue of mucous glycoprotein (MGP) in airways and middle ear epithelium. MGP secretion accompanies otitis media with effusion (OME) and prolongs the course of this disease by increasing the viscoelasticity of the fluid. It is important, therefore, to inhibit the pathological secretion of MGP in the treatment of otitis media. In the current study, we investigated the effects of PAF receptor inhibitor WEB 2170 BS on in vitro MGP secretion. At concentrations of 100 mu M, PAF significantly stimulated MGP secretion. WEB 2170 BS significantly inhibited this PAF-simulated MGP secretion at concentrations of 2000 mu M. The action of WEB 2170 BS was concentration-dependent. However, it did not affect MGP secretion stimulated by IL-1beta, suggesting that WEB 2170 BS inhibits PAF-stimulated MGP secretion, specifically. It was noted that WEB 2170 BS did not completely eliminate MGP secretion induced by PAF even though a high concentration was used. The fact that WEB 2170 BS alone does not exhibit an inhibitory or stimulatory effect on the secretion of MGP suggests that WEB 2170 BS competitively binds to PAF receptors and possesses less affinity to PAF receptors than PAF.

Animals↗