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Biomedical subjects

M Permezel

Publications and source records attributed to M Permezel.

At least 19 recordsLinked to original sources
PubMed2006

15-Deoxy-Delta(12,14)-prostaglandin J(2) and troglitazone regulation of the release of phospholipid metabolites, inflammatory cytokines and proteases from human gestational tissues.

Phospholipid-derived mediators, inflammatory cytokines and extracellular matrix remodelling enzymes are all involved in the initiation of human labour and delivery. We have previously demonstrated that natural and synthetic PPAR-gamma ligands regulate LPS-stimulated pro-inflammatory cytokine release from human gestational tissues, however, the effect of these ligands on the basal and/or LPS-induced expression of prostaglandins and proteases is not known. Therefore, the aim of this study was to determine the effects of 15d-PGJ(2) and troglitazone on the expression of basal and LPS-stimulated inflammatory mediators in human gestational tissues. Human placenta, amnion and choriodecidua (n=5) were incubated in the presence or absence of 15 microM 15d-PGJ(2) and 30 microM troglitazone under basal and LPS-stimulated (10 microg/ml) conditions. Treatment of placenta, amnion and choriodecidua with both 15d-PGJ(2) and troglitazone decreased basal and LPS-stimulated IL-1beta, IL-6, IL-10 and TNF-alpha release. Basal type II PLA(2) release from placental tissues was also significantly decreased by 15d-PGJ(2) and troglitazone. There was no effects of 15d-PGJ(2) and troglitazone on cPLA(2) protein expression. Both 15d-PGJ(2) and troglitazone significantly decreased basal and LPS-stimulated PGE(2) and PGF(2alpha) release from placenta and amnion. However, in choriodecidua, although 15d-PGJ(2) decreased basal and/or LPS-stimulated PGE(2) and PGF(2alpha) release, there was an increase in PGE(2) and PGF(2alpha) release in the presence of troglitazone. 15d-PGJ(2) and troglitazone inhibited MMP-9 release from human amnion. NF-kappaB DNA binding activity and NF-kappaB p65 protein expression was inhibited by treatment with 15d-PGJ(2) in human amnion. There was no effect of 15d-PGJ(2) or troglitazone on PPAR-gamma protein, and GW9662 failed to alleviate 15d-PGJ(2) and troglitazone inhibition of IL-6 and TNF-alpha release in placenta, amnion and choriodecidua. The data demonstrated in this study suggest that the 15d-PGJ(2) and troglitazone exhibit anti-inflammatory properties in human gestational tissues via PPAR-gamma independent actions.

Anilides↗
PubMed2005

Lipopolysaccharide and TNF-alpha activate the nuclear factor kappa B pathway in the human placental JEG-3 cells.

Up-regulation of pro-inflammatory cytokines, cyclooxygenase (COX-2) and prostaglandins is a critical factor driving human term labour and inflammation-associated preterm labour. Nuclear factor kappa B (NF-kappaB) is activated in response to a number of inflammatory mediators, including cytokines and lipopolysaccharide (LPS). The aim of this study was (i) to investigate if TNF-alpha and LPS activate the NF-kappaB pathway; and (ii) to use short interfering RNA (siRNA) against inhibitor kappaB kinase (IKK)-beta to confirm the role of the NF-kappaB pathway in the regulation of pro-inflammatory mediators in human placental JEG-3 cells. JEG-3 cells (3 independent experiments) were (i) incubated in the presence or absence of 10 microg/ml LPS or 20 ng/ml TNF-alpha, or (ii) transfected with 100 nM IKK-beta siRNA. Incubation of JEG-3 cells with LPS and TNF-alpha increased the expression of cytoplasmic IKK-beta and phosphorylated IkappaB-alpha, and nuclear NF-kappaB proteins p50 and p65. This was associated with a concurrent increase in COX-2 protein, and IL-6 and PGF2alpha release from JEG-3 cells. Treatment of cells with BAY 11-7082 at 50 microM significantly inhibited basal, LPS- and TNF-alpha-induced NF-kappaB and COX-2 expression, and IL-6 and PGF2alpha release. Transfection of JEG-3 cells with IKK-beta siRNA significantly decreased IL-6 and PGF2alpha release. The data presented in this study demonstrate that pro-inflammatory mediators regulate the NF-kappaB transcription pathway in human JEG-3 cells, and the IKK-beta/NF-kappaB pathway is a regulator of inflammatory mediators in placental JEG-3 cells.

Cell Line, Tumor↗
PubMed2004

Factors affecting umbilical venous perfusion during experimental cord knotting.

The aim was to determine experimentally the factors that increase the risk of venous occlusion by applying a standardised tightening force to isolated perfused umbilical cords tied in a true knot in vitro. Umbilical cords were collected from patients undergoing Caesarean section. Cords were clamped, isolated and studied within 15 min. The umbilical vein was cannulated, the cord tied in a true knot and traction was applied using standard weights. The umbilical vein was perfused with modified Krebs solution at a constant pressure of 40 mmHg and the attached weight increased until perfusion ceased. The cord mass index (weight/length), hydration index/100-[(dry weight/wet weight)x100], and coiling index (coils/length) were determined. Cord morphometric analysis was performed on 193 cords. Intra uterine growth restriction was associated with decreased cord mass index (p=0.002) and increased coiling index (p=0.002). Venous perfusion experiments were performed on 75 cords. Using multivariate regression analysis, cord morphometric factors that increased the risk of cord occlusion were decreased cord mass index (p=0.008), decreased cord hydration index (p=0.004), and low venous flow capacity (p=0.001). During experimental cord knotting with applied traction, the susceptibility to venous occlusion was increased with low cord mass index, low cord hydration index and low venous flow capacity. These cord characteristics were associated with low fetal body weight and intrauterine growth restriction. An increased susceptibility to cord occlusion may contribute to the higher perinatal morbidity and mortality in growth restricted pregnancies.

Female↗
PubMed2004

Altered placental oxidative stress status in gestational diabetes mellitus.

Oxidative stress has been clearly linked to type 2 diabetes mellitus, however, limited data are available on the involvement of oxidative stress in gestational diabetes mellitus (GDM), a disease of similar pathophysiology. The aim of this study was to investigate the status of placental oxidative stress in healthy pregnant women and women with GDM. The hypothesis to be tested was that tissue markers of oxidative stress are significantly increased in GDM compared to normal placental tissues. Markers of oxidative stress measured were the release of 8-isoprostane (8-epi-prostaglandin F(2alpha)) from human term placental explants (n=11), the activity of the antioxidant enzymes superoxide dismutase and glutathione peroxidase (n=10), and protein carbonyl content (n=12). Placental release of 8-isoprostane was 2-fold greater from women with GDM (P<0.001) compared to healthy pregnant women. Superoxide dismutase activity and protein carbonyl content were elevated in placentae obtained from women with GDM (P<0.04 and P<0.004 respectively), whilst there was no significant difference in the activity of glutathione peroxidase. These data demonstrate the presence of oxidative stress in the placenta from women with GDM, in addition to the induction of a key antioxidant, collectively indicating a state of existing oxidative stress in this condition.

Biomarkers↗
PubMed2001

Blood pressure in late pregnancy and work outside the home.

OBJECTIVE: To assess maternal blood pressure (BP) responses to working outside the home in late pregnancy, using 24-hour ambulatory BP monitoring. METHODS: Our paired observational study involved 24-hour ambulatory BP monitoring of 100 normotensive women (51 primiparas, 49 multiparas) on work and nonwork days. Mean BP differences were calculated for working, postworking, sleeping, and 24-hour periods on both days. Main outcome measures were BP differences between work and nonwork days and subsequent pregnancy hypertension. Comparisons in BP between work and nonwork days were done with Student paired t test. Comparisons between study subgroups were done with unpaired t test. Potential predictors of change in BP were examined using multiple linear regression. RESULTS: During job time, BP was significantly higher on work days than on nonwork days. The mean increase in BP associated with work was 2.6 mmHg (systolic BP, P <.001), 2.8 mmHg (diastolic BP, P <.001), and 2.9 mmHg (mean arterial BP, P <.001). Those observations were independent of parity. More than 10% of our subjects had increased mean arterial BP of 10 mmHg or more during job time on work days compared with nonwork days. Higher absolute BP levels (regression coefficient 0.21, P =.04) and greater perceived job stress (regression coefficient 1.34, P =.04) correlated positively with BP increases at work. Twelve women developed hypertension. Those women had a larger increase on work days in mean systolic (6.6 mmHg compared with 2.1 mmHg, P =.013), mean diastolic (6.4 mmHg compared with 2.3 mmHg, P =.014), and mean arterial (7.4 mmHg compared with 2.3 mmHg, P =.002) BP compared with normotensive women. The magnitude of BP responses to work was a significant predictor of pregnancy hypertension, independent of absolute BP level. CONCLUSION: Blood pressure increased in women when they worked outside the home. The effect of maternal work is important when treating pregnancy hypertension. Ambulatory BP monitoring makes assessment of maternal BP responses to work a practical clinical option.

Adult↗
PubMed2001

Type II phospholipase A2 in preterm human gestational tissues.

Maternal genital tract infections and the associated inflammatory response may contribute to the onset of many cases of preterm labour. Type II phospholipase A(2)(PLA2) hydrolyses glycerophospholipids, releasing free fatty acid for conversion into potent biological mediators, such as prostaglandins, which play a significant role in both the onset and progression of human labour and the activation of inflammatory reactions. The aim of this study was to quantify immunoreactive (ir) Type II PLA2 in placenta, amnion and choriodecidua collected from women delivering prematurely or due to histological chorioamnionitis, and to compare levels to those at term. Tissues were assayed for ir Type II PLA2 by ELISA and expressed as ng/mg tissue protein. Ir Type II PLA2 tissue content was significantly higher in preterm (n=26) amnion and choriodecidua, but not in the placenta when compared to tissues obtained at term (n=42). When the data were stratified with respect to labour status, ir Type II PLA2 content was significantly higher in the preterm not-in-labour group (NIL, n=17) than the preterm in labour group (IL, n=9) in the amnion. When the NIL group was analysed with respect to membrane rupture, women who had spontaneously ruptured membranes (n=6) expressed significantly greater ir Type II PLA2 than those that had intact membranes (n=11) in both the amnion and choriodecidua but not in the placenta. No significant difference was observed between the preterm IL group (n=9) and the group with histological chorioamnionitis (n=14). The data obtained in this study support a role for Type II PLA2 in association with spontaneous rupture of membranes.

Adult↗
PubMed2001

The effect of vascular coiling on venous perfusion during experimental umbilical cord encirclement.

OBJECTIVE: The aim of these studies was to compare venous perfusion in umbilical cords subjected to a standardized tight encirclement force. Comparisons were made between cords from normal pregnancies and those complicated by gestational diabetes mellitus and intrauterine growth restriction. STUDY DESIGN: The cannulated cord segment was wrapped around a plastic container, which in turn was attached with nylon string to a hanging graduated measuring cylinder in which known volumes of water could be applied for weight. The cord was perfused with Krebs solution to a constant venous perfusion pressure of 40 mm Hg. Weights of 100-g increments were applied until total cessation of venous perfusion was observed. The weight, length, number of vascular coils, and degree of hydration were recorded for each cord. The coiling index was defined as the number of vascular coils per 10 cm of cord. RESULTS: Regression analysis of 34 cords (normal, n = 16; gestational diabetes mellitus, n = 12; intrauterine growth restriction, n = 6) identified a significant inverse correlation (P =.0003, Spearman rank correlation) between coiling index and the minimum weight required to occlude venous perfusion. Cords from pregnancies complicated by intrauterine growth restriction displayed a higher frequency of vascular coiling and were more easily occluded (median weight, 350 g) than were cords from pregnancies complicated by gestational diabetes mellitus, which were less coiled and tended to resist occlusion (median weight, 1100 g). CONCLUSION: During experimental cord encirclement there was a significant inverse relationship between vascular coiling and susceptibility to cord venous occlusion when traction was applied to the encirclement.

Biomechanical Phenomena↗
PubMed2001

Is there an interaction between cervical length and cervical microbiology in the pathogenesis of preterm labour?

Transvaginal ultrasound of the cervix is increasingly used to estimate cervical length during pregnancy. Initially used to determine a possible need for cervical suture, the technique has been shown to be of value in the prediction of preterm delivery In addition, bacterial vaginosis has been shown to be associated with an increased risk of preterm delivery. We hypothesised that shortening of the cervix and potential cervical pathogens, in particular the presence of bacterial vaginosis, act synergistically in the pathogenesis of premature labour. Three hundred and sixteen women were recruited for prospective longitudinal follow-up, with both transvaginal ultrasound and cervical bacteriology performed at approximately 18 and 28 weeks gestation. A strong correlation was found between a shortened cervix and preterm delivery (p<0.02 at 18 weeks; p<0.001 at 28 weeks). Women with both a short cervix and cervical pathogens had the highest risk of preterm delivery (43%), although not significantly greater than a short cervix with normal cervical flora (31% preterm delivery). In the presence of a normal cervical length, preterm delivery rates in the presence of normal flora and potential cervical pathogens were much lower (9% and 5% respectively).

Cervix Uteri↗
PubMed2001

Elevated interleukin-8 concentrations in cervical secretions are associated with preterm labour.

The aim of this study was to assess the potential clinical utility of interleukin-8 (IL-8) present in cervical secretions as a marker of preterm labour and delivery. Samples of cervical mucus from 91 pregnant women were assessed for the presence and concentration of IL-8. Two samples were collected (at 18 +/- 2 and 28 +/- 2.5 weeks of gestation) and correlated with cervicovaginal microbiology and cervical length, as measured by transvaginal ultrasound. The IL-8 concentration at 28/40 was significantly higher in women who went on to deliver preterm (p < 0.01), and there was a greater than five-fold increase from 18 to 28 weeks in 6/7 of these women.

Cervix Mucus↗
PubMed2001

Successful pregnancy outcome after preterm premature rupture of membranes at < 20 weeks. A report of three cases.

BACKGROUND: Spontaneous preterm premature rupture of the membranes occurring before 20 weeks' gestation carries a perinatal mortality of approximately 82% and potential for considerable morbidity for mother and fetus. This is in contrast to amniotic fluid leakage after second-trimester amniocentesis, when the prognosis is usually good. CASES: We report three cases of spontaneous rupture of the membranes before 20 weeks' gestation, all associated with reaccumulation of amniotic fluid and satisfactory neonatal outcomes. CONCLUSION: Our cases may represent a subgroup with a relatively good prognosis. The existence of such subgroups would better be determined in a prospective, cohort study, and it might need to be a multicenter one. It requires well-defined entry criteria, management protocols and neonatal follow-up as well as information about pregnancies where termination, rather than continuation, is chosen.

Adolescent↗
PubMed2000

Knowledge and attitudes about vaginal birth after Caesarean section in Australian hospitals. VBAC Study Group. Vaginal Birth After Caesarean.

A survey of staff attitudes and knowledge about vaginal birth after Caesarean section (VBAC) was undertaken in Australian hospitals. There was a high response rate (67%), and over 900 responses were analysed. Generally, there was a high level of awareness about outcomes and the relative importance of many issues in considering VBAC. Registrars, consultants and midwives differed significantly in some aspects of their knowledge and attitudes to VBAC. There was also a wide range of opinion within each group. Approximately half (53%) of respondents believed patients should be actively encouraged to consider VBAC, whereas 47% felt it should be simply presented as an option.

Attitude of Health Personnel↗
PubMed2000

Vaginal birth after Caesarean section: an Australian multicentre study. VBAC Study Group.

Retrospective analysis of medical records and individual case review was undertaken at 11 major obstetric hospitals for a 5 year period from July 1992 to June 1997 to investigate rates of vaginal birth after Caesarean section (VBAC), the occurrences of uterine rupture, and the outcomes for mother and infant following rupture. Total deliveries were 234,015, of which 21,452 or 9.2% were associated with one or more previous Caesarean sections. Within this scar group, 5419 patients or 25.3% were delivered vaginally. There were 62 cases of significant uterine rupture with no maternal deaths. Perinatal mortality with rupture was 25% and serious maternal complications (usually hysterectomy) occurred in 25% of those with uterine rupture. In women attempting vaginal delivery after a previous lower segment Caesarean section, the uterine rupture rate was estimated at 0.3%, with 0.05% experiencing a perinatal death and 0.05% requiring a hysterectomy. Although VBAC rates in Australia remain lower than many overseas reported series, rates are increasing. While rupture continues to be associated with serious adverse outcomes, the incidence of rupture during trial of labour is low and appears to be associated with a better outcome than rupture of an unscarred uterus.

Australia↗
PubMed2000

Parathyroid hormone-related protein(1-34) in gestational fluids and release from human gestational tissues.

Parathyroid hormone-related protein (PTHrP) is present in fetal and gestational tissues, in which its proposed roles include stimulation of epithelial growth and differentiation, vasodilatation of the uteroplacental vasculature, relaxation of uterine muscle and stimulation of placental calcium transport. The aim of this study was to determine whether the release of PTHrP from gestational tissue explants was tissue specific. In addition, PTHrP concentrations were measured in maternal plasma, umbilical artery and vein plasma, and amniotic fluid from term, uncomplicated pregnancies before the onset of labour. PTHrP was detected in low concentrations in the mother, fetus and placental tissue. Amniotic fluid had ten times the PTHrP concentration compared with that in the maternal or fetal circulations. Using late pregnant human gestational tissues in an in vitro explant system, we found that amnion over placenta, choriodecidua, reflected amnion, and placenta released PTHrP into culture medium in progressively greater amounts over 24 h (P<0.05). This release was not associated with a loss of cell membrane integrity, as indicated by measurement of the intracellular enzyme, lactate dehydrogenase, in the incubation media. After 24 h incubation, the fetal membranes released significantly (P<0.05) greater amounts of PTHrP than did the placenta (placenta 3. 7+/-0.5 pmol PTHrP/g protein). Amnion over placenta released significantly more PTHrP (139.3+/- 43.1 pmol PTHrP/g protein) than did reflected amnion (29.0+/-8.3 pmol PTHrP/g protein) (P<0.05). This study unequivocally demonstrated that human gestational tissues release PTHrP and it was concluded that the main contributors to PTHrP in amniotic fluid were the human fetal membranes, particularly amnion over placenta. Fetal membrane-derived and amniotic fluid PTHrP are proposed to have stimulatory effects on epithelial growth and differentiation in fetal lung, gut, skin and hair follicles and paracrine effects on placental vascular tone and calcium transport.

Amnion↗
PubMed1999

A trial of simple versus intensified dietary modification for prevention of progression to diabetes mellitus in women with impaired glucose tolerance.

Women with impaired glucose tolerance are at high risk of developing noninsulin dependent diabetes mellitus (NIDDM). The Mercy Hospital for Women has a long-term follow-up programme for women with gestational diabetes, which identifies many women with impaired glucose tolerance. Two hundred of these women were entered into a randomized controlled trial of intensive versus routine dietary advice. Seven women were lost to follow-up. The annual incidence rates of diabetes mellitus for the 2 groups were 6.1% (intervention) and 7.3% (control), an incident rate ratio of 0.83, 95% confidence interval 0.47-1.48, p = 0.50. Overall, there was a return to normal glucose tolerance in 44% of patients. Multivariate analysis showed that body mass index, fasting and 2-hour plasma glucose levels at trial entry were significantly associated with an increased risk of diabetes mellitus. Impaired glucose tolerance is an important condition that should be treated with advice about lifestyle modification (diet and/or exercise). We consider that future trials in the management of women with previous gestational diabetes who have impaired glucose tolerance should investigate the effect of pharmacological intervention in addition to diet and/or exercise, the latter providing a therapy that it would be unethical to exclude on the evidence presently available.

Adult↗