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Biomedical subjects

M A Ledingham

Publications and source records attributed to M A Ledingham.

7 recordsLinked to original sources
PubMed2001

Cell adhesion molecule expression in the cervix and myometrium during pregnancy and parturition.

OBJECTIVE: To determine the expression and localization of cell adhesion molecules intercellular adhesion molecule-1 (ICAM-1), E-selectin, platelet-endothelial cell adhesion molecule (PECAM), and vascular cell adhesion molecule (VCAM) in the cervix and myometrium during pregnancy and labor. METHODS: Biopsies of myometrium and cervix were obtained from non-pregnant women and from pregnant women before and after onset of spontaneous labor at term. Cell adhesion molecule mRNA expression was quantified using Northern blotting and cell adhesion molecule protein was localized using immunohistochemistry. RESULTS: ICAM-1 mRNA was upregulated in the cervix (10-fold increase, P <.01) and myometrium (10.5-fold increase, P <.01) during labor. ICAM-1 was localized in the vascular endothelium and in leukocytes in the cervix and myometrium from all three groups of women. VCAM mRNA was upregulated in the cervix (2.5-fold increase, P <.01) during pregnancy and there was no further change during labor. VCAM localized weakly to the vascular endothelium in cervical and myometrial biopsies from pregnant and non-pregnant women. PECAM mRNA was significantly upregulated in myometrium during pregnancy (ninefold increase, P <.01) and did not change with the onset of labor. PECAM localized to the vascular endothelium in all cervical and myometrial biopsies and was identified on leukocytes. There were no significant changes in E-selectin mRNA expression in either tissue with pregnancy or parturition. CONCLUSION: Cell adhesion molecule expression changes in human cervix and myometrium during pregnancy and parturition. At least part of these changes are attributable to expression by leukocytes infiltrating these tissues.

Adult↗
PubMed2001

A comparison of isosorbide mononitrate, misoprostol and combination therapy for first trimester pre-operative cervical ripening: a randomised controlled trial.

OBJECTIVE: To determine whether a combined therapy with isosorbide mononitrate (40mg) and misoprostol (400 microg) for pre-operative cervical ripening in the first trimester would result in improved clinical effectiveness, and fewer side effects compared with each agent used alone. DESIGN: Randomised controlled trial. SETTING: Glasgow Royal Infirmary. POPULATION: Sixty-six primigravid women scheduled for suction termination of pregnancy. METHODS: Women were randomly assigned to receive before surgery, per vaginam, isosorbide mononitrate 40 mg (n = 22), misoprostol 400 microg (n = 22) or both agents together [isosorbide mononitrate 40 mg and misoprostol 400 microg] (n = 22). MAIN OUTCOME MEASURES: 1. To assess the cumulative force required to dilate the cervix to 8 mm; 2. the onset of new symptoms before termination of pregnancy. RESULTS: The cervical resistance following combination therapy with isosorbide mononitrate and misoprostol was not significantly different than following misoprostol alone [24.5N vs 18.5N; median difference (95% CI) 19N (-22 to 49)]. Pre-treatment with misoprostol used alone resulted in a lower cervical resistance than isosorbide mononitrate alone (18.5N vs 39N, P = 0.04, Mann-Whitney U test). There was no difference in the number of women remaining asymptomatic following either isosorbide mononitrate or misoprostol or combination therapy [14/22 (64%) vs 11/21 (52%) vs 11/22 (50%), Fisher's exact test]. CONCLUSIONS: We have not shown any advantage of combining misoprostol with the nitric oxide donor isosorbide mononitrate compared with misoprostol alone for pre-operative cervical ripening in the first trimester.

Abortifacient Agents, Nonsteroidal↗
PubMed2000

Changes in the expression of nitric oxide synthase in the human uterine cervix during pregnancy and parturition.

Nitric oxide (NO) has been proposed as a mediator of cervical ripening. We investigated the expression, using Western blotting, and localization, using immunohistochemistry, of the nitric oxide synthase (NOS) enzymes, inducible NOS (iNOS), endothelial NOS (eNOS) and neuronal NOS (bNOS) in the human cervix during pregnancy and parturition. Cervical biopsies were obtained from non-pregnant women, women in the first trimester of pregnancy, and pregnant women at term before and after the onset of labour. Each of the NOS isoforms was localized in the cervices of both non-pregnant and pregnant subjects using immunohistochemistry. iNOS expression was significantly greater in early pregnancy compared with the non-pregnant state (P: < 0.005). iNOS expression was up-regulated further in samples obtained in the third trimester compared with the first trimester. bNOS expression was greater in samples from the first trimester of pregnancy than in non-pregnant samples (P: < 0. 005), but showed no additional increase in late pregnancy or with the onset of labour. eNOS expression was increased in samples obtained in the third trimester both before (P: = 0.002) and after the onset of labour (P: < 0.002) when compared with non-pregnant samples. The increased expression of NOS isoforms in late pregnancy supports the hypothesis that NO is involved in the process of cervical ripening.

Blotting, Western↗
PubMed1999

Matrix metalloproteinases-2 and -9 and their inhibitors are produced by the human uterine cervix but their secretion is not regulated by nitric oxide donors.

We have investigated the presence of matrix metalloproteinases (MMP)-2 and -9 and their tissue inhibitors (TIMP) in the human uterine cervix. We postulate that during the process of cervical ripening, there is an increase in the activity of MMP in order to facilitate cervical connective tissue change. We have previously demonstrated that nitric oxide (NO) donors induce cervical ripening in vivo. A secondary hypothesis is that NO donors regulate MMP activity within the human uterine cervix. Cervical tissue biopsies were obtained from both pregnant and non-pregnant subjects. Cervical fibroblasts were cultured from the non-pregnant tissue. MMP-2 was present in conditioned media from pregnant and non-pregnant cervical explants and non-pregnant cervical fibroblasts. MMP-9 secretion was only detected in explants from non-pregnant women. TIMP-1, -2 and -4 were released by all cervical explants and fibroblast preparations. Pregnant women, in the first trimester, were treated with an NO donor (isosorbide mononitrate) in vivo. Cervical explants and fibroblasts from non-pregnant women were treated with the NO donor spermine nonoate in vitro. Treatment with an NO donor either in vivo or in vitro had no effect on the secretion of the MMP or TIMP studied. Further studies evaluating the mechanisms involved in cervical ripening are required.

Cells, Cultured↗
PubMed1999

Nitric oxide donors stimulate prostaglandin F(2alpha) and inhibit thromboxane B(2) production in the human cervix during the first trimester of pregnancy.

Nitric oxide (NO) donors are capable of ripening the human cervix during pregnancy. The purpose of this study was to examine how NO donors may be involved in this process. Cervical biopsies were obtained from pregnant women randomized to receive isosorbide mononitrate (n = 10) or no treatment (n = 10) prior to suction termination. Enzyme-linked immunosorbent assays (ELISA) were performed on culture supernatant for interleukin (IL)-1, IL-6, IL-8, IL-10, IL-15, tumour necrosis factor-alpha, monocyte chemoattractant protein-1 and prostaglandin metabolites. Immunohistochemistry was performed to localize these cytokines, cyclooxygenase (COX)-1, COX-2 and prostaglandin dehydrogenase in cervical tissue and reverse transcription-polymerase chain reaction (RT-PCR) to identify COX-1 and COX-2 expression. Biopsies treated with the NO donor isosorbide mononitrate (IMN) produced significantly greater amounts of prostaglandin F(2alpha) in culture and lower amounts of thromboxane B(2) than controls (572.8 versus 34.9 pg/ml, P < 0.05; 53.3 pg/ml versus 530.9 pg/ml, P < 0.01 respectively). The release of other prostaglandins and of cytokines was not affected by treatment with NO. Inflammatory mediators were localized to cervical tissue and COX-1 and COX-2 expression was confirmed by RT-PCR. In conclusion, the mechanism of NO donor-induced cervical ripening during pregnancy may be mediated in part via increased prostaglandin F(2alpha) synthesis.

Base Sequence↗