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To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ajog.2005.02.084 Byline: Mervi Vaisanen-Tommiska, Tomi S. Mikkola, Olavi Ylikorkala Abstract: The cells of the human uterine cervix synthesize nitric oxide, which may be a factor in cervical ripening. We studied the effect of misoprostol on cervical nitric oxide release in nonpregnant and pregnant women. Author Affiliation: Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Helsinki, Finland Article History: Received 29 November 2004; Revised 8 February 2005; Accepted 8 February 2005

The effect of microprostol on cervical nitric oxide release in pregnant and nonpregnant women is studied. The results show that vaginal microprostol stimulates cervical nitric oxide release in pregnancy and further suggests a joint action of nitric oxide and prostaglandins in cervical ripening.

The authors have investigated nitric oxide metabolite concentrations in the cervical fluid in pregnant women. The results have demonstrated that cervical fluid nitric oxide metabolite level rises after cervical ripening, and that nitric oxide is important for cervical ripening.

Hormone therapy delivered through a skin patch may not have a consistently positive effect on blood pressure compared to oral hormone therapy. In a study of 73 postmenopausal women, both forms of hormone therapy lowered blood pressure, but only the oral form caused a long-term decrease that persisted for up to six months.

Doctors have shown for the first time that pregnant women with preeclampsia not only have increased blood levels of fetal DNA but also increased amounts of DNA from the woman's own body. Preeclampsia is a serious complication of pregnancy.

A nitroglycerine patch may be beneficial in pregnant women who develop preeclampsia. Preeclampsia is characterized by hypertension during pregnancy and protein in the urine. Researchers treated 17 pregnant women with preeclampsia with a transdermal nitroglycerine patch. Nitroglycerine relaxes blood vessels. The women experienced a drop in blood pressure and also a drop in resistance to blood flow in the uterus. When the patch was removed, blood pressure and resistance returned to the levels seen before the patch was used.

Byline: Bruno Cacciatore, Erja Halmesmaki, Risto Kaaja, Kari Teramo, Olavi Ylikorkala Keywords: Nitroglycerin; preeclampsia; Doppler ultrasonography; blood flow; fetus Abstract: OBJECTIVE: We studied whether transdermal nitroglycerin, a donor of nitric oxide, affects uterine, umbilical, and fetal cerebral blood flow in pregnancies complicated by preeclampsia and impaired uteroplacental blood flow. STUDY DESIGN: Seventeen patients with preeclampsia were treated with a nitroglycerin patch, 10 mg per 24 hours, for three consecutive days between 28 and 36 weeks' gestation. The uterine, umbilical, and fetal middle cerebral artery pulsatility index and resistance index were assessed by color Doppler ultrasonography before the start of treatment, daily during treatment, and on the first 2 days after the removal of the last patch. RESULTS: The nitroglycerin patch caused a significant fall in the mean uterine pulsatility index and resistance index that reached its maximum (18% [+ or -] 4% and 17% [+ or -] 3%, respectively, from baseline) on the last treatment day. After the removal of the last patch, uterine pulsatility index and resistance index rose to the pretreatment value within 12 hours. No significant changes in umbilical or middle cerebral artery pulsatility index and resistance index were observed during treatment. Maternal mean arterial pressure fell from 122 [+ or -] 8 to 117 [+ or -] 7 mm Hg (P = .05). CONCLUSION: Transdermal administration of nitroglycerin may offer a potential for treatment for patients with preeclampsia who have increased uteroplacental impedance. (Am J Obstet Gynecol 1998;179:140-5.) Author Affiliation: Helsinki, Finland Article History: Received 9 June 1997; Revised 20 November 1997; Accepted 10 December 1997 Article Note: (footnote) [star] From the Department of Obstetrics and Gynecology, Helsinki University Central Hospital., [star][star] Reprint requests: Bruno Cacciatore, MD, PhD, Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Haartmaninkatu 2, Helsinki, FIN-00290, Finland., a 0002-9378/98 $5.00 + 0 6/1/88118

Preeclampsia may not inhibit the ability of human umbilical vein cells to produce calcium-dependent nitric oxide. Preeclampsia is a serious complication of pregnancy involving high blood pressure and protein in the urine. Nitric oxide is produced by cells lining blood vessels and causes blood vessels to dilate. Researchers analyzed human umbilical vein samples from 11 preeclamptic and 10 normal pregnancies. Umbilical veins from preeclamptic pregnancies produced less nitric oxide overall, perhaps because fewer cells from these veins were obtained. Calcium-dependent nitric oxide production by preeclamptic umbilical veins was not considered deficient. Labetalol, a drug used to treat preeclampsia, did not impair nitric oxide production.

Byline: Arto K. Orpana, Kristiina Avela, Varpu Ranta, Lasse Viinikka, Olavi Ylikorkala Keywords: Endothelial cells; human; nitric oxide; pregnancy; preeclampsia Abstract: OBJECTIVE: Nitric oxide is an important vasodilator, and in this study we studied whether the calcium-dependent nitric oxide production capacity of human umbilical vein endothelial cells was affected by preeclampsia. STUDY DESIGN: Human umbilical vein endothelial cells were isolated from 11 preeclamptic and 10 normotensive pregnancies. The maximal calcium ionophore A23187-stimulated nitric oxide production capacity was measured as accumulation of nitrate and nitrite into the culture medium, and it was related to the number of viable endothelial cells by measurement of their mitochondrial dehydrogenase activity. RESULTS: The cell number - related nitric oxide production capacity was similar in preeclamptic and normotensive pregnancies. The total nitric oxide production of cells from preeclamptic pregnancies was significantly lower (p < 0.001). This difference, however, was mainly caused by larger amount of viable endothelial cells recovered from normotensive pregnancies. CONCLUSION: The maximal calcium-dependent nitric oxide production capacity of individual human umbilical vein endothelial cells is not affected by preeclampsia. (AM J OBSTET GYNECOL 1996;174:1056-60.) Author Affiliation: Helsinki, Finland Article History: Received 6 April 1995; Revised 17 July 1995; Accepted 25 July 1995 Article Note: (footnote) [star] From the Departments of Obstetrics and Gynecologya and Clinical Chemistry, b University of Helsinki. , [star][star] Supported by the Academy of Finland., a Reprint requests: Arto K. Orpana, PhD, Department of Obstetrics and Gynecology, University of Helsinki, Haartmaninkatu 2, SF-00290, Helsinki, Finland., aa 0002-9378/96 $5.00 + 0 6/1/68223

Sexual intercourse during pregnancy does not appear to increase the risk of premature birth in healthy women who have not previously delivered a live infant. A total of 407 pregnant women were tested for bacterial vaginosis when they were between eight and 17 weeks pregnant. The women then kept track of the number of times they had sexual intercourse each week until they delivered. Bacterial vaginosis was not associated with the frequency of sexual intercourse. Both women who had sexual intercourse during pregnancy and women who did not were equally likely to have bacterial vaginosis. A higher frequency of intercourse was associated with a lowered risk of premature delivery. More than 50% of the women who delivered prematurely had not had intercourse during the third trimester. Only three women who delivered prematurely reported having intercourse in the week before delivery.

OBJECTIVE: We studied the role of smooth muscle-relaxing prostacyclin and its endogenous antagonist, thromboxane [A.sub.2], in preterm labor by assessing the urinary output of the breakdown products of prostacyclin (6-keto-prostaglandin [F.sub.1[alpha]] and 2,3-dinor-6-keto-prostaglandin [F.sub.1[alpha]]) and those of thromboxane [A.sub.2] (thromboxane [B.sub.2], 2,3-dinor-thromboxane [B.sub.2]). STUDY DESIGN: Thirty-three women in preterm labor between 25 and 34 weeks of gestation were studied before, during, and after treatment with indomethacin (n = 16) or nylidrin (n = 17). Urinary prostanoid levels were determined by high-performance liquid chromatography followed by radioimmunoassay, and the excretion was expressed as nanograms of prostanoids per millimole of creatinine. Statistical analyses were done by paired and unpaired Student test, by Spearman's correlation, and by Wilcoxon signed-rank test. RESULTS: Preterm labor was accompanied by a median 32% higher output of prostacyclin and thromboxane [A.sub.2] metabolites as compared with those in 25 controls. At 8 hours after the start of treatment indomethacin induced maximal drops in 6-keto-prostaglandin [F.sub.1[alpha]] (70%), in dinor-6-keto-prostaglandin [F.sub.1[alpha]] (60%), in thromboxane [B.sub.2] (85%), and in dinor-thromboxane [B.sub.2] (95%) excretion. Within 1 week after the cessation of indomethacin, output of prostacyclin metabolites had recovered to pretreatment values, whereas output of thromboxane [A.sub.2] metabolites was yet lower than the pretreatment value. Nylidrin induced no change in the output of prostacyclin and thromboxane [A.sub.2] metabolites. CONCLUSION: Threatened preterm labor is associated with a use in prostacyclin and thromboxane [A.sub.2] synthesis. Indomethacin inhibits more thromboxane [A.sub.2] than does prostacyclin synthesis. These findings may explain the fetal vascular changes during maternal indomethacin treatment. (Am J Obstet Gynecol 1992; 166:150-4.)

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ajog.2007.10.804 Byline: Pauliina Tuomikoski (a), Kristiina Aittomaki (b), Tomi S. Mikkola (a), Anne Ropponen (a), Olavi Ylikorkala (a) Keywords: hormone therapy; hyaluronic acid; intrahepatic cholestasis of pregnancy; liver disease Abstract: Intrahepatic cholestasis of pregnancy predisposes women to liver disorders years after affected pregnancy. We compared the basal levels and responses of hyaluronic acid, a marker of liver fibrosis, and liver transaminases to postmenopausal hormone therapy in women with (n = 20) and without (n = 20) a history of intrahepatic cholestasis of pregnancy. Author Affiliation: (a) Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Helsinki, Finland (b) Department of Clinical Genetics, Helsinki University Central Hospital, Helsinki, Finland. Article History: Received 27 March 2007; Revised 3 July 2007; Accepted 13 October 2007 Article Note: (footnote) This study was supported by an unrestricted research grant from the Ida Montini Foundation and the Paivikki and Sakari Sohlberg Foundation., Cite this article as: Tuomikoski P, Aittomaki K, Mikkola TS, et al. Effect of oral and transdermal hormone therapy on hyaluronic acid in women with and without a history of intrahepatic cholestasis of pregnancy. Am J Obstet Gynecol 2008;198:375.e1-375.e5.

Background: Human milk, rich in cytokines, may contain the potent permeability- and angiogenesis-promoting agent vascular endothelial growth factor (VEGF). Objective: We wanted to study whether free or bound VEGF is present in human milk and whether it and its receptors (VEGFR-1 and -2) are expressed in lactating breast or newborn intestinal tissue. Design: The study had a longitudinal design with collection of human milk from healthy (n = 32) and diabetic (n = 5) women at 2, 7, and 30 d postpartum. Milk was analyzed for VEGF by enzyme-linked immunosorbent assay along with plasma samples collected 2 d postpartum. Immunohistochemistry was used to localize VEGF and its receptors in lactating breast and newborn intestine. Gel filtration with radiolabeled VEGF was performed to study whether human milk contains VEGF binding proteins. Results: Human milk VEGF concentrations in healthy (76 [+ or -] 19 [micro]g/L, [bar]x [+ or -] SD) and diabetic (75 [+ or -] 25 [micro]g/L) women did not differ at 2, 7 (23 [+ or -] 7 and 27 [+ or -] 8 [micro]g/L, respectively), or 30 d (14 [+ or -] 5 and 17 [+ or -] 7 [micro]g/L, respectively) postpartum. VEGF was undetectable in all but 3 plasma samples. Human milk was free of VEGF binding proteins. VEGFR-1 and -2 immunoreactivity was seen in the glandular epithelial cells of the newborn intestine and lactating breast, whereas VEGF was present only in breast glandular epithelium. Conclusions: The high concentrations of VEGF in human milk, especially colostrum, are not affected by maternal diabetes and may play a role in newborn nutrition. Am J Clin Nutr 2000;72:1196-201. KEY WORDS Colostrum, human milk, vascular endothelial growth factor, VEGF, VEGF receptors, lactating breast, intestinal villi, newborn intestine, type 1 diabetes mellitus