Papers by Shaun Brennecke
Frontiers in epidemiology, Oct 15, 2023
The Journal of Physiology, 1981
ABSTRACT
Obstetric Anesthesia Digest, Mar 1, 2013
Bjog: An International Journal Of Obstetrics And Gynaecology, Aug 1, 1982
Using a n enzyme incubation-radioimmunoassay technique. we have tested the hypothesis that an inc... more Using a n enzyme incubation-radioimmunoassay technique. we have tested the hypothesis that an increase in a maternal plasma factor(s) that inhibits prostaglandin synthase (EC 1.14.99. I) is responsible for the suppression of decidual prostaglandin production that occurs in early human pregnancy. Measurements made on serial maternal samples failed to reveal any significant increase in plasma inhibitory activity at this time, and it was concluded that the conceptus achieves the reduction in prostaglandin synthesis by a mechanism other than a systemically mediated direct inhibition of decidual prostaglandin synthase.
Journal of Obstetrics and Gynaecology, 1983
ABSTRACT
Obstetrical & Gynecological Survey, Oct 1, 1998
ABSTRACT
Best Practice & Research: Clinical Obstetrics & Gynaecology, Mar 1, 1998
ABSTRACT
Obstetrics & Gynecology, Aug 1, 2016
American Journal of Obstetrics and Gynecology, Dec 1, 1999
This study was undertaken to investigate in human tissue samples the mechanisms underlying sponta... more This study was undertaken to investigate in human tissue samples the mechanisms underlying spontaneous and prostaglandin F(2)(alpha)-induced contractions during the final trimester of pregnancy and labor. Membrane potential and cytoplasmic calcium were recorded simultaneously with contraction in uterine strips obtained from the lower segment during cesarean delivery. Between week 28 of gestation and term there was a progressive increase in the frequency of spontaneous contractions and a decrease in the negative potential of the membrane. The response to prostaglandin F(2alpha) was biphasic. The initial excitatory component remained stable toward term. A later inhibitory component, which was underpinned by increased activity of the sodium-potassium adenosine triphosphatase pump, decreased at the time of labor. There is a gradual increase in excitability in uterine muscle throughout the third trimester of human pregnancy. The initial component of the prostaglandin response is a large contraction that is kept brief by a subsequent inhibitory component of the response, which ensures that full relaxation occurs between contractions.
Pregnancy Hypertension, Jul 1, 2012
G28 fetal weight was significantly lower in the L-NAME group than in the control group (27.40 ± 0... more G28 fetal weight was significantly lower in the L-NAME group than in the control group (27.40 ± 0.55 g vs 33.14 ± 0.62 g, p < 0.0001). In the L-Name group the vascularization index (VI) was significantly lower than in the control group (2.6 [1.4; 6.0] vs 7.6 [3.5; 12.6], p < 0.05). Similar results were obtained for the Flow Index (FI) and the Vascularization Flow Index (VFI). The number of fetuses considered as small for gestational age (SGA; weight < 10th centile) was significantly higher in the L-NAME group than in the control group (47/108 vs 7/72, p < 0.0001). The VI was significantly lower in the SGA group than in the eutrophic group (3.
PubMed, 1992
Peripheral plasma concentrations of immunoreactive phospholipase A2 (irPLA2) (Type II, non-pancre... more Peripheral plasma concentrations of immunoreactive phospholipase A2 (irPLA2) (Type II, non-pancreatic) were determined in 110 women during pregnancy. The concentration of irPLA2 did not significantly change during pregnancy (5.7 +/- 0.6 ng/ml, n = 72) until the onset of labour. When compared with non-labouring women, irPLA2 concentrations were significantly elevated in association with both preterm labour (13.3 +/- 2.4 ng/ml, n = 15, p less than 0.02) and labour at term (10.4 +/- 1.7, n = 23, p less than 0.02). These data suggest that maternal plasma irPLA2 may be reflective of the mechanism(s) underlying the labour-associated increase in human gestational tissue eicosanoid formation.
Prostaglandins, Dec 1, 1987
The release and absorption profiles from the vagina of PGE2 in different vehicles used for cervic... more The release and absorption profiles from the vagina of PGE2 in different vehicles used for cervical ripening and labour induction have been studied observing changes in concentrations of PGE metabolite (PGEM) and PGF metabolite (PGFM). In all groups a rise in PGEM concentration occurred over the 6 hour observation time but with wide variation. The profiles obtained differed markedly between the preparations under investigation correlating with the uterine contractions generated. PGFM generally showed little change. The model used could be explored further to enable modification of the vehicles used for PGE2 incorporation to achieve improved clinical results.
Gynecologic and Obstetric Investigation, 2000
In European and Japanese but not in Australian, American, and South African women, the C677T meth... more In European and Japanese but not in Australian, American, and South African women, the C677T methylenetetrahydrofolate reductase (MTHFR) polymorphism has been reported to be a genetic risk factor pre-eclampsia/eclampsia (PE/E). The recently described A1298C MTHFR gene polymorphism also results in reduced MTHFR enzyme activity, although to a lesser extent than the previously described C677T polymorphism. Heterozygotes for both polymorphisms are reported to have an even lower MTHFR enzymatic activity than seen in homozygotes for the C677T genotype. In this current study we determined the allele frequency of the A1298C MTHFR gene polymorphism in an Australian population and examined this polymorphism alone and in combination with the C677T MTHFR polymorphism for an association with PE/E. Neither the A1298C polymorphism alone nor a combination of both polymorphisms showed an association with PE/E in our population of Australian women.
Molecular human reproduction, Jul 1, 2005
The role of progesterone withdrawal in human parturition continues to provoke controversy. One po... more The role of progesterone withdrawal in human parturition continues to provoke controversy. One possible mechanism by which functional progesterone withdrawal may be achieved is by a decrease in the circulating concentration of its bioactive metabolites. The progesterone metabolite 5-dihydroprogesterone (5DHP) has been shown to be a potent tocolytic in vitro. We quantified plasma concentrations of 5DHP in association with the onset of spontaneous labour in women at term and steroid 5-reductase mRNA expression in placenta, myometrium, chorion and amnion in relation to parturition, using real time RT-PCR. Serial blood samples were obtained from patients late in pregnancy, before term labour, during term labour and within the first 24 h postpartum. Following organic solvent extraction, steroids including 5DHP were separated by high-performance liquid chromatography (HPLC) and then quantified by radioimmunoassay (RIA). 5DHP concentration decreased twofold (P = 0.00001, n = 25) from 0.317 ± 0.039 nmol/ml to 0.178 ± 0.017nmol/ml in association with active labour. Tissue 5-reductase mRNA-relative abundance was determined in placenta, myometrium, chorion and amnion obtained from labouring and non-labouring women. In placenta and myometrium, relative expression decreased significantly in association with labour, by about twofold and 10-fold, respectively. These data are consistent with a possible role for 5DHP in the onset of spontaneous human labour. Further studies exploring this hitherto unrecognized endocrinological pathway are indicated.
Geburtshilfe Und Frauenheilkunde, Apr 14, 2015
Eine prazise Vorhersage der Praeklampsie (PE) kann dazu beitragen, mutterliche und kindliche Morb... more Eine prazise Vorhersage der Praeklampsie (PE) kann dazu beitragen, mutterliche und kindliche Morbiditat und Mortalitat zu reduzieren. Der Quotient aus loslicher fms-like Tyrosinkinase 1 (sFlt-1) und plazentarem Wachstumsfaktor (PlGF) ist bei Frauen, die eine PE entwickeln, erhoht. In dieser Studie wurde der sFlt-1/PlGF-Quotient als Vorhersagemarker untersucht. In dieser doppelblinden, nicht-interventionellen Studie wurde der sFlt-1/PlGF-Quotient bei Frauen mit klinischem Verdacht auf PE (24 bis 36+6 Schwangerschaftswochen) bestimmt. Der primare Endpunkt der Studie war erstens zu zeigen, dass ein sFlt-1/PlGF-Quotient unterhalb des ermittelten Trennwerts das Auftreten von PE innerhalb von einer Woche ausschliest. Zweitens, dass ein sFlt-1/PlGF-Quotient oberhalb des Trennwerts das Auftreten von PE innerhalb von vier Wochen vorhersagt. Sekundare Endpunkte waren die Assoziation von sFlt-1/PlGF Quotient mit mutterlichen oder kindlichen Komplikationen. In einer Kohorte von 500 Patientinnen wurde ein sFlt-1/PlGF-Quotient Trennwert von 38 fur die Vorhersage der PE ermittelt. Dieser Trennwert wurde in einer Kohorte von 550 weiteren Patienten validiert. Fur die Gesamtkohorte konnte gezeigt werden, dass das Auftreten einer PE innerhalb einer Woche mit einem negativen Vorehrsagewert von 99,1% (95% Konfidenzintervall [CI], 98,2 bis 99,6), mit einer Sensitivitat von 85,7% (95% CI, 72,8 to 94,1) und einer Spezifitat von 79,1% (95% CI, 76,5 bis 81,6) ausgeschlossen werden kann. Das Auftreten einer PE innerhalb vier Wochen konnte mit einem positiven Vorhersagewert von 38,6% (95% CI, 32,6 bis 45,0), mit einer Sensitivitat von 70,3% (95% CI, 61,9 bis 77,8) und einer Spezifitat von 83,1% (95% CI, 80,5 bis 85,5) vorhergesagt werden. Hohe sFlt-1/PlGF Quotienten waren mit fetalen Komplikationen vergesellschaftet. Ein sFlt-1/PlGF Quotient < 38 kann das Auftreten einer PE innerhalb von einer Woche bei Patientinnen mit klinischem Verdacht auf Praeklampsie sicher ausschliesen.
Reproduction, Fertility and Development, 2010
Pre-eclampsia is a multisystem disorder of human pregnancy that involves abnormal placentation vi... more Pre-eclampsia is a multisystem disorder of human pregnancy that involves abnormal placentation via insufficient trophoblast cell invasion of the maternal spiral arteries and widespread maternal endothelial cell dysfunction. Factors in plasma of pre-eclamptic women affect both trophoblast and endothelial cell functions during in vitro culture (1). The calcium-binding protein calreticulin is elevated in peripheral blood with pre-eclampsia compared to normotensive pregnancy (2). The aim of this study was to determine the effects of exogenous calreticulin at concentrations relevant to normotensive pregnancy (2 µg/mL) and to pre-eclampsia (5 µg/mL) on human trophoblast cell (HTR8) and microvascular endothelial cell (myometrial) numbers and migratory activity. Cell migration was measured by scratch assay; changes in cell number were measured by MTS assay (Promega). The results showed that calreticulin at 5µg/mL did not affect HTR8 cell number (control 68044+24542 cells, with calreticulin 72810 + 30673 cells, n = 3, P &gt; 0.05) after 48 hours, but significantly inhibited migration of the cells by 48+11% compared to the control at 26 hours (n = 4, P &lt; 0.02). Calreticulin at 5 µg/mL and under conditions that did not change cell number significantly increased migration of the myometrial endothelial cells by 39+7% (n = 4, P &lt; 0.01) at 20 hours. Calreticulin at 5 µg/mL, however, significantly reduced endothelial cell numbers after 3–5 days (control 6213 + 1937 cells, with calreticulin 1937+728 cells, n = 6, P &lt; 0.05). There was no significant change to the functions of either cell type with 2 µg/mL of calreticulin. In conclusion, exogenous calreticulin at a concentration consistent with that found in maternal blood with pre-eclampsia was shown to alter trophoblast and endothelial cell migratory activity and reduce endothelial cell numbers during in vitro culture. These results indicate that elevated circulating calreticulin may contribute to the cellular mechanisms that underlie the development of pre-eclampsia. (1) Harris et al, Reprod Sci, 2009, 16: 1082–90.(2) Gu et al, Molec Human Repro, 2008, 14: 309–15.
Australian & New Zealand Journal of Obstetrics & Gynaecology, May 1, 1999
Obstetric Anesthesia Digest, Sep 1, 2016
Pregnancy Hypertension, Jul 1, 2012
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Papers by Shaun Brennecke