HDlive imaging of vertical, bridging uterine synechia during pregnancy.

We present a case of vertical, bridging uterine synechia in the central part of the uterine cavity diagnosed by conventional two-dimensional (2D) sonography and HDlive at 29 weeks and 5 days of gestation. 2D sonography showed a uterine synechia located vertically in the central part of the uterine cavity, dividing the lower uterine cavity into two parts. HDlive clearly revealed triangular, vertical, and bridging uterine synechia with foot protrusion and umbilical cord prolapse in the lower uterine cavity. The low, liquor-filled amniotic cavity was divided by a thin membrane. MRI confirmed the vertical structure dividing the uterus with umbilical cord prolapse. Emergency cesarean section was performed at 37 weeks and 1 day of gestation because of onset of labor, and a female infant weighing 2,380 g was delivered with an umbilical artery pH of 7.25, and Apgar score of 6/9 at 1 and 5 min, respectively. The vertical, bridging synechia in the central part of uterine cavity was confirmed during the operation.

Concurrent chemoradiotherapy with nedaplatin in patients with stage IIA to IVA cervical carcinoma.

The present study aimed to evaluate the efficacy and toxicities of nadaplatin-based concurrent chemoradiotherapy (CCRT) in patients with stage IIA to IVA cervical carcinoma. Patients with an International Federation of Gynecology and Obstetrics (FIGO) stage IIA to IVA cervical carcinoma were treated with nadaplatin-based CCRT, using high-dose rate intracavitary brachytherapy (HDR-ICBT) or radiotherapy (RT) alone, in patients with FIGO stage IIA to IVA cervical carcinoma. CCRT with nedaplatin (80 mg/m2) was administered on Days 1 and 29. The records of 17 women treated either with nadaplatin-based CCRT using HSR-ICBT (n=8) or RT alone (n=9), for stage IIA to IVA cervical carcinoma were retrospectively reviewed. The activity and toxicity were compared in the two treatment groups. Progression-free survival (PFS) and overall survival (OS) were the main endpoints. The 5-year overall survival rates in the CCRT and RT groups were 68.6 and 77.8%, respectively. The median OS of the CCRT and RT groups was 38.5 and 27.3 months, respectively. There was no significant difference in either PFS (P=0.618) or OS (P= 0.231). The most common grade 3-4 or higher toxicities in the CCRT groups were leuko-/neutropenia (37.5%). The frequency of acute grade 3-4 toxicity was higher in the CCRT compared to the RT group. However, no statistically significant difference was observed. Nedaplatin-based CCRT was safely performed. Although the prognosis of patients with FIGO stage IIA to IVA cervical carcinoma was not significantly improved, fewer distant relapses were observed in this treatment. Consequently, nedaplatin-based CCRT may be considered as a potential alternative to cisplatin-based CCRT in this patient population.

Nitric oxide production and blood corpuscle dynamics in response to the endocrine status of female rats.

INTRODUCTION: Menopause is associated with marked changes in the endocrine profile, and increases the risk of vascular disease. However, the effect of hormones on the vascular system is still unclear. Therefore, the aim of this study was to examine the effects of endocrine status in female rats on nitric oxide (NO) production, inflammatory reactions and thrombus organization potency in the mesenteric microcirculation. MATERIALS AND METHODS: Female Wistar rats were divided into four groups: proestrus, metestrus, ovariectomized (OVX) and OVX plus estradiol treatment (OVX+E2). NO was imaged using an NO-sensitive dye. The leukocyte and platelet velocities relative to the erythrocyte velocity (VW/VRC and VP/VRE, respectively) and thrombi sizes created by laser radiation were measured as thrombogenesis indices. RESULTS: Changes in endocrine status did not affect vascular function in the arterioles. However, in venules, NO production, VW/VRC and VP/VRE were decreased in the OVX group compared with the proestrus and metestrus states. Thrombus size was significantly greater in the OVX group than in the proestrus and metestrus states. Administration of E2 for 2 weeks restored NO production, VW/VRC and VP/VRE to control levels. CONCLUSIONS: Changes in endocrine status did not affect arterioles. In contrast, in venules, reduced estrogen levels led to a decrease in NO production, thereby increasing thrombogenesis. Estrogen replacement restored NO production and leukocyte and platelet velocities, reducing thrombus formation relative to OVX. Although it is unclear how E2 reduces thrombus formation, our results indicate that leukocyte and platelet adhesion to the endothelium is a target for E2 via NO.

Effect of dienogest administration on angiogenesis and hemodynamics in a rat endometrial autograft model.

BACKGROUND: We aimed to establish an endometrial autograft model in rats that would allow for repetitive in vivo analyses of angiogenesis. Dienogest (DNG) is an orally active progestin used for the treatment of endometriosis. We investigated whether DNG would affect angiogenesis of the ectopic endometrium in our model. METHODS: Mechanically isolated endometrial fragments were transplanted into dorsal skinfold chambers in rats. We analyzed the effect of DNG on angiogenesis of the ectopic endometrium on Days 0, 2, 4, 7, 10 and 14 after transplantation using intravital fluorescence microscopy. RESULTS: The DNG-administered group showed significant suppression of angiogenesis of endometrial autografts, as indicated by the reduced size of the microvascular network and decreased microvessel density compared with those of control animals. The newly formed microvessels of the DNG-administered group showed consistently elevated diameters and centerline red blood cell velocity was decreased. Immunohistochemistry revealed a significant reduction in the level of perivascular α-smooth muscle actin within endometrial grafts of the DNG-administered group. CONCLUSIONS: DNG inhibited angiogenesis of the ectopic endometrium, with confirmed structural changes in the microvessels.

Role of nitric oxide and reactive oxygen species in the pathogenesis of preeclampsia.

AIM: Preeclampsia is characterized by a disruption of general vascular dilatation, which is mainly mediated by nitric oxide (NO) and disturbed by reactive oxygen species (ROS). The present study investigated the roles of NO and ROS in the pathogenesis of preeclampsia. METHODS: Serum samples were obtained prospectively. Serum levels of NO(2)/NO(3) (NOx) and creatol (CTL), the oxidized metabolite of creatine, and flow-mediated dilatation (FMD) of brachial artery were measured in normal pregnant women and preeclamptic patients. To evaluate the effect of circulating factors that control vascular function NO synthase (NOS) and NAD(P)H oxidase mRNA expression was evaluated in cultured human umbilical vein endothelial cells using reverse transcriptase polymerase chain reaction. RESULTS: Serum NOx concentration was decreased and CTL concentration was increased in preeclamptic patients relative to healthy controls during the first trimester of pregnancy. Further, preeclamptic patients exhibited disrupted FMD, which was regulated in part by NO. Immunohistochemistry demonstrated strong expression of nitrotyrosine in the vasculature of preeclamptic placentas. Treatment with sera derived from preeclamptic patients increased endothelial expression of inducible NOS (iNOS) mRNA, and this increase was inhibited by angiotensin II (Ang II) receptor type 2 (AT2) blocker. Endothelial NAD(P)H oxidase subunit gp91(phox) expression was increased by treatment with sera from preeclamptic patients and this increase was attenuated by Ang II receptor type 1 (AT1) blocker. CONCLUSION: The present findings suggest that NO and ROS play important roles in the pathogenesis of preeclampsia and that these roles involve Ang II.

In vivo visualization of nitric oxide and interactions among platelets, leukocytes, and endothelium following hemorrhagic shock and reperfusion.

OBJECTIVES: We examined changes in nitric oxide (NO) distribution in the mesenteric microcirculation after hemorrhagic shock and reperfusion (H/R), and correlated NO production to leukocyte and platelet behavior. MATERIALS AND METHODS: The behavior of leukocytes and platelets in mesenteric venules was observed by intravital microscopy at 0.5 and 24 h after H/R in male Wistar rats. Transvascular leakage of fluorescein isothiocyanate-labeled albumin was assessed by epi-illumination. The NO-sensitive dye, 4,5-diaminofluorescein diacetate, was used for imaging NO release. RESULTS: H/R significantly increased vascular albumin leakage and adhesion of leukocytes and platelets (P < 0.05). In H/R 0.5 h rats, NO production in the venular endothelium declined. However, NO production was elevated in H/R 24 h rats in mast cells (P < 0.05). Leukocyte adherence, platelet adherence, and venular permeability were attenuated by iNOS inhibition. CONCLUSION: Mesenteric endothelial cell dysfunction after H/R 0.5 h is associated with reduced NO, whereas after H/R 24 h is related to increase NO in mast cells.

Prenatal diagnosis of persistent cloaca associated with VATER (vertebral defects, anal atresia, tracheo-esophageal fistula, and renal dysplasia).

The cloaca is a single canal from which the urinary, genital, and intestinal tracts arise around gestational weeks 5-6. Persistent cloaca can result from cystic mass formation within the pelvis, which is commonly association with multiple developmental defects. VATER association, which is a spectrum of anomalies, manifested by vertebral defects, anal atresia, tracheo-esophageal fistula with esophageal atresia, and renal dysplasia, arises from abnormalities in mesodermal differentiation. Recently, both conditions have been proposed to represent a continuous spectrum of anomalies, but the pathophysiology concerning the continuity of the development and the clinical condition are still unclear. Since renal failure becomes a serious problem after birth, timely infant delivery is essential to avoid loss of renal function. We report a patient, in whom the overlap between these two conditions was identified, and renal function was lost from one kidney. A polycystic mass was found in the fetal abdomen at 26 weeks of gestation. By ultrasonography, we detected a polycystic left kidney, a single umbilical artery, a ventricular septal defect, an esophageal atresia, ascites, an anal atresia, and a cystic mass with debris behind the bladder. The left kidney was non-functioning and the right kidney showed signs of hydronephrosis at 30 weeks of gestation. We measured the size and the blood flow of renal artery sequentially, and could deliver the fetus before the function was lost from the right kidney. Our observations will help inform future patients where prompt intervention can help improve renal function and infant health.

Ranking the contributing risk factors in venous thrombosis in terms of therapeutic potential: Virchow's triad revisited.

AIM: Thromboemoblism is an attendant feature of a variety of pathological conditions. We reconsidered Virchow's pathogenetic triad of stasis, humoral factors and vascular wall pathologies in the light of platelet behavior in vivo. METHODS: Rat mesenteric microcirculation was examined by intravital microscopy. After isolated rat platelets had been injected i.v. into rats, their behavior in venules was examined under the following conditions: stasis from pressure, hemoconcentration from erythropoietin injections, or endothelial damage from tumor necrosis factor-alpha. RESULTS: In the endothelial damage group, platelets displayed transient adhesion and rolling, while some platelets exhibited stationary adhesion to venular endothelium. The stasis and hemoconcentration groups exhibited only a slight change in adhesive response. CONCLUSION: Endothelial dysfunction appears to be the most important contributing factor in the development of venous thrombosis. As such, targeting this dysfunction is suggested for therapeutic intervention.

Effects of oxidized low-density lipoprotein on leukocyte-endothelial interactions in the rat mesenteric microcirculation during pregnancy.

OBJECTIVE: The accumulation of evidence implicates oxidized lipoproteins in atherosclerosis. Treatment of endothelial cells with these lipoproteins stimulates monocyte binding and the production of chemotactic factors that contribute to inflammation and endothelial injury and dysfunction. In preeclampsia, circulating low-density lipoprotein particles, which are susceptible to oxidation, are increased. We studied leukocyte-endothelial interactions that were related to oxidized lipoproteins in pregnant rats. STUDY DESIGN: We examined oxidized low-density lipoprotein-induced leukocyte behavior and uptake of fluorescent-labeled oxidized low-density lipoprotein in rat mesenteric venules during pregnancy, with the use of intravital microscopy with a video imager. RESULTS: The administration of oxidized low-density lipoprotein significantly reduced rolling velocities of leukocytes in venules and increased the numbers of leukocytes that adhered to endothelium in both nonpregnant and pregnant rats. These interactions were attenuated in pregnancy, when uptake of labeled oxidized low-density lipoprotein into leukocytes and endothelial cells also was decreased. CONCLUSION: Pregnancy may be associated with antioxidant effects.

Leukocyte behaviour and permeability in the rat mesenteric microcirculation following induction of ovulation.

BACKGROUND: Ovarian hyperstimulation syndrome (OHSS), a highly dangerous and incompletely understood complication of ovulation induction with exogenous gonadotrophins, can include haemoconcentration, hypovolaemia, hypotension, acute renal insufficiency, thromboembolism and ultimately death. Using intravital microscopy, we examined microvascular permeability and leukocyte-endothelial cell interactions in the rat mesenteric microcirculation associated with induction of ovulation. METHODS: In female rats treated with hMG and hCG, mesenteric venules were observed by intravital microscopy assisted by a video imager. Erythrocyte velocity was monitored, and rolling and adhesion of leukocytes were studied by transmission video images. Transvascular leakage of fluorescein isothiocyanate-labelled albumin was assessed by epi-illumination. RESULTS: Administration of hMG and hCG significantly increased vascular protein leakage within a few hours, and also reduced rolling velocities of leukocytes in venules and increased numbers of leukocytes adherent to endothelium at 16 h following hCG injection. The administration of antibodies against intracellular adhesion molecule (ICAM)-1 inhibited these reactions. CONCLUSION: By induction of ovulation, vascular permeability is increased not only at the surface of the ovary but also in the mesentery. Alteration of leukocyte behaviour in the microcirculation through mechanisms involving ICAM-1 is one likely cause of the protein leakage.

Carbon monoxide modulates endotoxin-induced microvascular leukocyte adhesion through platelet-dependent mechanisms.

BACKGROUND: Although precise mechanisms remain to be determined, recent studies show that heme oxygenase-1 (HO-1), providing endogenous carbon monoxide (CO) and bilirubin, serves as an antiinflammatory enzyme. This study aimed to clarify roles of CO in regulation of microvascular adhesion of platelets and leukocytes in endotoxemia. METHODS: Rats pretreated with or without hemin were anesthetized with pentobarbital and received continuous infusion of endotoxin. Platelets labeled with carboxyfluorescein diacetate succinimidyl ester and leukocyte behavior in mesenteric venules were visualized using intravital ultra-high-speed intensified fluorescence videomicroscopy. To examine the mechanisms for the effects of HO-1 on platelet and leukocyte behavior during endotoxemia, these studies were repeated with superfusion of either CO, bilirubin, or zinc protoporphyrine-IX. RESULTS: Endotoxin caused a marked depression of platelet velocity traversing along periendothelial regions, accompanied by augmented rolling and adhesion of leukocytes in venules. The endotoxin-elicited changes were attenuated by the HO-1 induction with hemin and restored by blockade of the enzyme activity with zinc protoporphyrine-IX, a potent inhibitor of HO-1. Such an inhibitory action of HO-1 on microvascular cell adhesion was reproduced by local superfusion of the buffer containing CO at micromolar concentrations. Such antiadhesive actions of CO on leukocytes disappeared under immunoneutralization of glycoprotein Ibalpha, an adhesion molecule against platelets, but not against leukocytes. Platelets isolated from hemin-treated rats increased their ability to generate CO and displayed lesser sensitivity of agonist-induced aggregation than those from controls. CONCLUSIONS: These results suggest that CO desensitizes endotoxin-induced adhesive responses of leukocytes, mainly through its ability to ameliorate platelet activation.