Tamao Yamamoto

Reduced function of endothelial prostacyclin in human omental resistance arteries in pre‐eclampsia

It remains unclear in pre‐eclampsia whether or not a functional change occurs in the role played by prostacyclin in endothelium‐dependent relaxation in resistance arteries. We examined this using human omental resistance arteries (obtained from pre‐eclamptic or normotensive pregnant women) in the presence of NG‐nitro‐l‐arginine (l‐NNA, an inhibitor of nitric oxide synthase). In endothelium‐intact strips from both groups, 9,11‐epithio‐11,12‐methano‐thromboxane A2 (STA2, a thromboxane A2 mimetic) produced a contraction. Diclofenac (an inhibitor of cyclooxygenase) enhanced the STA2 contraction only in the normotensive pregnant group (1.4 times control, P < 0.01). In the presence of STA2, bradykinin (0.1 μm) produced an endothelium‐dependent relaxation in both groups, the relaxation being significantly smaller for the pre‐eclamptic group (P < 0.002). Diclofenac significantly attenuated the bradykinin‐induced relaxation only for the normotensive pregnant group (31 % inhibition, P < 0.001). The bradykinin‐induced membrane hyperpolarization consisted of diclofenac‐sensitive and ‐insensitive components. The former, but not the latter, was significantly smaller in pre‐eclampsia (‐4.3 vs.−2.6 mV, P < 0.05). The concentrations of 6‐keto‐PGF1α (a stable metabolite of prostacyclin) in these arteries were significantly lower in pre‐eclampsia in both the absence and presence of bradykinin (about 0.2‐0.4 times the normotensive pregnant value in each case, P < 0.01). By contrast, both the relaxation and the membrane hyperpolarization in response to beraprost (10 nm, a stable analogue of prostacyclin) were similar between the two groups. We conclude that, in pre‐eclampsia, a reduced part is played by prostaglandins in the endothelium‐dependent relaxation seen in resistance arteries and that this may be due to a reduced production of prostacyclin by the endothelium.

Involvement of H2O2 in superoxide-dismutase-induced enhancement of endothelium-dependent relaxation in rabbit mesenteric resistance artery.

The mechanism underlying the enhancement by superoxide dismutase (SOD) of endothelium‐dependent relaxation was investigated in rabbit mesenteric resistance arteries. SOD (200 U ml−1) increased the production of H2O2 in smooth muscle cells (as indicated by the use of an H2O2‐sensitive fluorescent dye). Neither SOD nor catalase (400 U ml−1) modified either the resting membrane potential or the hyperpolarization induced by acetylcholine (ACh, 1 μM) in smooth muscle cells. In arteries constricted with noradrenaline, the endothelium‐dependent relaxation induced by ACh (0.01–1 μM) was enhanced by SOD (200 U ml−1) (P<0.01). This action of SOD was inhibited by L‐NG‐nitroarginine (nitric oxide (NO)‐synthase inhibitor) but not by either charybdotoxin+apamin (Ca2+‐activated‐K+‐channel blockers) or diclofenac (cyclooxygenase inhibitor). Neither ascorbate (50 μM) nor tiron (0.3 mM), superoxide scavengers, had any effect on the ACh‐induced relaxation, but each attenuated the enhancing effect of SOD on the ACh‐induced relaxation. Similarly, catalase (400 U ml−1) inhibited the effect of SOD without changing the ACh‐induced relaxation. In endothelium‐denuded strips constricted with noradrenaline, SOD enhanced the relaxation induced by the NO donor 1‐hydroxy‐2‐oxo‐3‐(N‐methyl‐3‐aminopropyl)‐3‐methyl‐1‐triazene (NOC‐7) (P<0.05). Ascorbate and catalase each attenuated this effect of SOD. H2O2 (1 μM) enhanced the relaxation on the noradrenaline contraction induced by NOC‐7 and that induced by 8‐bromo‐cGMP, a membrane‐permeable analogue of guanosine 3′,5′ cyclic monophosphate (cGMP). SOD had no effect on cGMP production, whether measured in endothelium‐intact strips following an application of ACh (0.1 μM) or in endothelium‐denuded strips following an application of NOC‐7 (0.1 μM). It is suggested that in rabbit mesenteric resistance arteries, SOD increases the ACh‐induced, endothelium‐dependent relaxation by enhancing the action of NO in the smooth muscle via its H2O2‐producing action (rather than via a superoxide‐scavenging action).

Evaluation Levels of Cytokines in Amniotic Fluid of Women with Intrauterine Infection in the Early Second Trimester

Amniotic fluid was obtained from 180 patients by amniocentesis at 16–22 weeks of gestation and assayed for the levels of interleukin (IL)-6, IL-8, leukocyte elastase (LE), and glucose. Ten of cases had clinical symptoms, such as uterine contraction, genital bleeding, and cervical ripening, and the other 170 were assessed for fetal chromosomal features. Four of the ten cases with uterine contraction developed abortion, while 10 of those screened had findings of fetal chromosomal anomalies, and 7 cases then underwent induced abortion artificially. In the cases of abortion, levels of IL-6, IL-8 and LE were higher than in the samples from the 160 pregnant women without clinical symptoms and a normal karyotype, while glucose in amniotic fluid was lower. Of 6 cases with clinical symptoms, but not developing abortion, 4 developed preterm labor, and in these IL-6 and IL-8 also were significantly elevated, with LE being slight high compared to normal. The results suggest that IL-6, IL-8, LE, and glucose in amniotic fluid at early second trimester can be used as markers of severe infection in the uterus, and with the first two being particularly sensitive.

Prenatal Diagnosis of Lissencephaly (Type II) by Ultrasound and Fast Magnetic Resonance Imaging

We report a case of lissencephaly which could be diagnosed by detailed examination during pregnancy. We first found bilateral enlarged ventricles in the fetus by routine abdominal ultrasonography at mid-pregnancy. Fast scanning MRI subsequently allowed confirmation of a diagnosis of lissencephaly during pregnancy.

Reduced hyperpolarization in endothelial cells of rabbit aortic valve following chronic nitroglycerine administration

This study was undertaken to determine whether long‐term in vivo administration of nitroglycerine (NTG) downregulates the hyperpolarization induced by acetylcholine (ACh) in aortic valve endothelial cells (AVECs) of the rabbit and, if so, whether antioxidant agents can normalize this downregulated hyperpolarization. ACh (0.03–3 μM) induced a hyperpolarization through activations of both apamin‐ and charybdotoxin‐sensitive Ca2+‐activated K+ channels (KCa) in rabbit AVECs. The intermediate‐conductance KCa channel (IKCa) activator 1‐ethyl‐2‐benzimidazolinone (1‐EBIO, 0.3 mM) induced a hyperpolarization of the same magnitude as ACh (3 μM). The ACh‐induced hyperpolarization was significantly weaker, although the ACh‐induced [Ca2+]i increase was unchanged, in NTG‐treated rabbits (versus NTG‐untreated control rabbits). The hyperpolarization induced by 1‐EBIO was also weaker in NTG‐treated rabbits. The reduced ACh‐induced hyperpolarization seen in NTG‐treated rabbits was not modified by in vitro application of the superoxide scavengers Mn‐TBAP, tiron or ascorbate, but it was normalized when ascorbate was coadministered with NTG in vivo. Superoxide production within the endothelial cell (estimated by ethidium fluorescence) was increased in NTG‐treated rabbits and this increased production was normalized by in vivo coadministration of ascorbate with the NTG. It is suggested that long‐term in vivo administration of NTG downregulates the ACh‐induced hyperpolarization in rabbit AVECs, possibly through chronic actions mediated by superoxide.

Characteristic changes in coronary artery at the early hyperglycaemic stage in a rat type 2 diabetes model and the effects of pravastatin

Background and purpose:  Diabetes is a risk factor for the development of coronary artery disease but it is not known whether the functions of endothelium‐derived nitric oxide (NO) and endothelium‐derived hyperpolarizing factor (EDHF) in coronary arteries are altered in the early stage of diabetes. Such alterations and the effects of pravastatin were examined in left anterior descending coronary arteries (LAD) from Otsuka Long‐Evans Tokushima Fatty (OLETF) rats (type 2 diabetes model) at the early hyperglycaemic stage [vs. non‐diabetic Long‐Evans Tokushima Otsuka (LETO) rats].

Use of aspirin and low-molecular-weight heparin to prevent recurrence of maternal floor infarction in women without evidence of antiphospholipid antibody syndrome.

During pregnancy, maternal floor infarction (MFI) and massive perivillous fibrin deposition (MFD) often cause fetal growth restriction and death, both being markedly increased by occlusion of the maternal intravenous circulation. Incident rates have been reported to be in the range of 0.09–0.5% and recurrent MFI/MFD might be more frequent in early-onset cases. Thus, prevention measures are necessary for high-risk women who have had MFI/MFD as complications in a previous pregnancy. In this report, the use of oral low-dose aspirin at the early trimester and low-molecular-weight heparin drip infusion from the mid-second trimester was examined for this purpose.

Increase in serum concentrations of inhibin in early onset pre‐eclampsia with intrauterine growth restriction

Aim:  Recently, it has been hypothesized that reduced placental blood flow in early pregnancy causes changes in endothelial function, leading to pre‐eclampsia. To clarify this clinically, we assessed serum concentrations of inhibin and uric acid in pre‐eclamptic women compared with those of normotensive pregnant women.

Cardiac failure caused by severe pre-eclampsia with placental abruption, and its treatment with anti-hypertensive drugs.

Pre‐eclampsia is the abnormality of blood circulation in late pregnancy, often caused by renal failure, hemolysis, elevated liver enzyme, low platelet syndrome, and eclampsia. We present a case of severe pre‐eclampsia with placental abruption in a 24‐year‐old woman, pregnant for the first time. The patient was diagnosed with congestive heart failure, which came as a result of pre‐eclampsia. Anti‐hypertensive drugs were used for its treatment.

Establishment of a Polymerase Chain Reaction Method for Detection of Escherichia coli in Amniotic Fluid in Patients with Chorioamnionitis

Objective: We investigated whether Escherichia coli could be detected by E. coli of reference (ECOR) grouping and virulence factors (VFs) in amniotic fluid using polymerase chain reaction (PCR). Method: From 18 patients with clinical symptoms, such as cyclic uterine contraction, genital bleeding and cervical ripening, who subsequently developed abortion or labor before term, and from 40 normal pregnant women undergoing diagnostic amniocentesis, amniotic fluid was obtained. All samples were negative for standard culture. Six patients with symptoms were classified into the ECOR group, and with VFs, E. coli was detected in 6 patients. Thus, 4 patients were positive for both tests. Conclusion: We could establish a detection method for E. coli in amniotic fluid using both ECOR grouping and VFs with PCR.