Development of LOX-1 Antibody Modified Immuno-liposomes as Drug Carriers to Macrophages in Atherosclerotic Lesions.

We developed a drug delivery system for atherosclerotic lesions using immuno-liposomes. We focused on enhancing the delivery efficiency of the liposomes to macrophages in atherosclerotic lesions by antibody modification of lectinlike oxidized low-density lipoproteins (LDL) receptor 1 (LOX-1). The cellular accumulation of the liposomes in foam cells induced by oxidized LDL (oxLDL) in Raw264 mouse macrophages was evaluated. The cellular accumulation of LOX-1 antibody modified liposomes in oxLDL-induced foam cells and untreated Raw264 cells was significantly higher compared with that of unmodified liposomes. The liposomes were also administered intravenously to Apoeshl mice as an atherosclerosis model. Frozen sections were prepared from the mouse aortas and observed by confocal laser microscopy. The distribution of LOX-1 antibody modified liposomes in the atherosclerotic regions of Apoeshl mice was significantly greater compared with that of unmodified liposomes. The results suggest that LOX-1 antibody modified liposomes can target foam cells in atherosclerotic lesions, providing a potential route for delivering various drugs with pharmacological effects or detecting atherosclerotic foci for the diagnosis of atherosclerosis.

Differences in fetal fractional limb volume changes in normal and gestational diabetic pregnancies: an exploratory observational study.

OBJECTIVE: Fetal fractional limb volume has been proposed as a useful measure for quantifying fetal soft tissue development. The aim of this study was to investigate the growth of fractional arm volume (AVol) and fractional thigh volume (TVol) of fetuses with maternal gestational diabetes (GDM) compared with those of fetuses with normal glucose tolerance (NGT). We hypothesised fetal fractional limb volume would be larger in the GDM group than in the NGT group in late gestation. DESIGN: Exploratory observational study. SETTING: Saitama Municipal Hospital. SAMPLE: A total of 165 (125 NGT and 40 GDM) singleton Japanese pregnant women. METHODS: AVol and TVol were assessed between 20 and 37 weeks' gestation as cylindrical limb volumes based on 50% of the fetal humeral or femoral diaphysis length. Women were diagnosed as GDM based on the criteria of the Japan Society of Obstetrics and Gynecology. MAIN OUTCOME MEASURES: AVol and TVol were compared between women with NGT and those with GDM at each gestational age period (2-week intervals from 20 to 37 weeks' gestation). RESULTS: Overall, 287 ultrasound scans were performed (NGT group, 205 scans; GDM group, 82 scans). There was no significant difference of AVol between the groups before 32 weeks' gestation. AVol was significantly larger in the GDM group than in the NGT group after 32 weeks' gestation (P < 0.05). TVol was not statistically different between the groups across gestation. CONCLUSIONS: Detection of variations in fetal AVol may provide greater insight into understanding the origins of altered fetal body proportion in GDM. TWEETABLE ABSTRACT: AVol, but not TVol, is significantly larger in fetuses with GDM than in those with NGT after 32 weeks' gestation.

Mid-trimester residual cervical length and the risk of preterm birth in pregnancies after abdominal radical trachelectomy: a retrospective analysis.

OBJECTIVE: To investigate the association between mid-trimester residual cervical length (CL) and the risk of preterm birth in pregnancies after abdominal radical trachelectomy (RT). DESIGN: Retrospective cohort study. SETTING: University hospital. POPULATION: A total of 33 deliveries after 22 weeks' gestation in 30 women who underwent abdominal RT including prophylactic cervical cerclage and perinatal care between January 2002 and May 2016. METHODS: The association between mid-trimester residual CL (the distance between the cerclage and the external cervical os) and gestational age at delivery was investigated. Receiver-operating characteristics (ROC) curve analysis was performed to estimate the optimal cut-off values of the mid-trimester residual CL for the prediction of preterm birth. MAIN OUTCOME MEASURES: Preterm birth before 34 weeks' gestation. RESULTS: Mid-trimester residual CL showed a significant correlation with gestational age at delivery (r = 0.36, P < 0.05). There was a significant difference in residual CL between women who did and those who did not give birth before 34 weeks (P < 0.05). Mid-trimester residual CL < 13 mm was a good predictor of birth before 34 weeks, with a sensitivity of 67%, specificity of 75%, positive predictive value of 55% and negative predictive value of 86% (area under ROC curve, 0.75). CONCLUSIONS: Mid-trimester residual CL is significantly correlated with gestational age at delivery. Residual CL assessment could be used to reassure physicians and women that there is only a small chance of preterm birth in pregnancies after abdominal RT. TWEETABLE ABSTRACT: Mid-trimester residual cervical length is a good predictor of preterm birth after radical trachelectomy.

Prenatal ultrasound diagnosis of small-bowel torsion.

BACKGROUND: We report a case of congenital small-bowel torsion detected by prenatal ultrasonographic examination. CASE: A 27-year-old primigravida was found to have a fetus with a small-bowel obstruction by ultrasound examination during the third trimester. At 35 weeks of gestation, she complained of absence of fetal activity. A nonstress test showed a nonreactive pattern with reduced baseline variability. Sonographic examination revealed heterogeneous echogenicity within the dilated bowel, and loss of peristalsis. Also noted was a small amount of fetal ascites. After birth, torsion of the dilated small bowel associated with ileal atresia was found at exploratory laparotomy. CONCLUSION: Serial sonographic examinations with special attention to changes in the dilated bowel are useful in the management of prenatally diagnosed small-bowel obstruction.

[An operative case of congenital fistula of the right coronary artery to the left ventricle with congestive heart failure].

We reported an extremely rare case of congenital fistula of the right coronary artery to the left ventricle in a 71-year-old man who suffered from difficulty in breathing and palpitation. The diagnosis was confirmed by the right coronary angiography. The fistula was closed by Symbas's operation under cardiopulmonary bypass. Postoperative recovery was uneventful. Coronary angiography performed one year after the operation revealed that the right coronary artery was completely occluded by thrombus. But there were no signs of myocardial ischemia or infarction. And so we suspected that the dilated right coronary artery had not work as functional vessel.

[Lateral femoral circumflex artery as a free graft for coronary artery bypass grafting to an 85-year-old man; report of a case].

An 85-year-old man had a 2 vessel coronary disease. Preoperative echogram showed the lateral femoral circumflex artery (LFCA) had enough diameter and length. We performed coronary artery bypass grafting (OPCAB) with the left internal thoracic artery (LITA) and LFCA. Postoperative coronary angiogram showed that the LFCA bypass graft was patent and supplied sufficient blood to the anastomosed vessel.

Prediction of smallness for gestational age by maternal serum human chorionic gonadotropin levels and by uterine artery Doppler study.

OBJECTIVES: To compare the utility of maternal serum human chorionic gonadotropin (MShCG) levels with that of uterine artery Doppler study in predicting small for gestational age (SGA) birth and pregnancy-induced hypertension (PIH). METHODS: MShCG assay and uterine artery Doppler study were performed in 359 consecutive pregnant women with singleton pregnancies. MShCG levels > or =2.0 multiples of the median at 15-18 weeks' gestation were considered to be elevated. An abnormal uterine artery Doppler velocimetry at 21-24 weeks' gestation was defined as a mean pulsatility index above the 95th percentile or the presence of an early diastolic notch in either uterine artery. The predictive values of MShCG levels and uterine artery Doppler velocimetry were evaluated for the risk of SGA birth and PIH. RESULTS: Forty-one subjects gave birth to SGA infants, and 20 developed PIH. Patients with MShCG elevation or abnormal uterine artery Doppler velocimetry showed a significantly higher incidence of SGA infants than the controls. The sensitivity and specificity of MShCG elevation for SGA birth were 17.1 and 93.4%, respectively, compared with abnormal uterine artery Doppler velocimetry, which had 24.4 and 94.3%, respectively. There was no significant difference between these methods. Elevated levels of MShCG and abnormal uterine artery Doppler velocimetry were not associated with PIH. CONCLUSION: Elevated levels of second-trimester MShCG were as sensitive and specific in predicting SGA births as abnormal uterine artery Doppler velocimetry.

Effects of a thromboxane synthetase inhibitor (OKY-046) in an ischemia-reperfusion model of intrauterine growth retardation in Sprague-Dawley rats.

We investigated the effects of thromboxane (TX) A2 in rats with ischemia-reperfusion-induced intrauterine growth retardation. A saline solution or OKY-046, a selective TXA2 synthetase inhibitor, was injected into the caudal vein of pregnant rats on gestation day 17 before the induction of 60-min uteroplacental ischemia. The fetuses and placentas were delivered and examined on gestation day 21. Blood from the uterine vein of the occluded horn shortly after uteroplacental ischemia was collected, and plasma concentrations of TXB2 and 6-keto-prostaglandin (PG) F1 alpha were determined in the other rats on gestation day 17. Treatment with OKY-046 prevented the ischemia-induced reduction in the fetal body and placental weights. The ratio of 6-keto-PGF1 alpha to TXB2 was significantly increased in the OKY-046-treated group. We conclude that the action of TXA2 might play a salient role in our model.

Prenatal diagnosis of midgut volvulus by sonography and magnetic resonance imaging.

We present a case of congenital midgut volvulus detected by prenatal sonography and ultrafast magnetic resonance (MR) imaging. At 34 weeks of gestation, enlarged hyperechogenic loops without peristalsis was identified by sonographic examination. On ultrafast T2-weighted single-shot fast-spin echo MR imaging, enlarged loops exhibited a lower signal intensity than the surrounding bowel loops, suggesting intraluminal hemorrhage. At explorative laparotomy following delivery, midgut volvulus causing hemorrhagic necrosis was found. Combined use of sonography and ultrafast MR imaging is useful to identify fetal midgut volvulus with hemorrhagic change.

Power and colour Doppler ultrasonography for the evaluation of the vasculature of the human corpus luteum.

We used power Doppler imaging to examine neovascularization in the corpus luteum (CL) in 12 healthy volunteers. We also investigated whether CL blood flow reflected luteal function. The ratio of the area of vessels in the CL to the area of a sectional plane at the maximum diameter of the CL observed by power Doppler (FA ratio) was used as a quantitative index of the vascularity of the CL. The pulsatility index (PI) was significantly lower in ovarian arteries with CL than without CL (P < 0.05). Changes in ovarian arterial and intra-luteal PI appeared to reflect physiological changes in the vasculature of the CL. There was no correlation between the volume of the CL or the FA ratio and the concentration of progesterone. The pattern of changes in the product of the FA ratio and the CL volume and in the progesterone concentration was similar. The progesterone concentration was positively correlated with this product (r = 0.74, P < 0.01). The product of the FA ratio and the CL volume plateaued during the mid- to late luteal phase, suggesting the presence of functional and structural luteolysis. These findings suggest that colour Doppler ultrasonography, including power Doppler imaging, can detect physiological changes in the blood flow of the ovary in the luteal phase, and may be a useful noninvasive tool for evaluating CL function.

Participation of reactive oxygen species in PGF2alpha-induced apoptosis in rat luteal cells.

Prostaglandin F(2alpha) (PGF(2alpha)) is implicated in the process of luteal regression in many species. Treatment of rat luteal tissue with PGF(2alpha) increases the generation of reactive oxygen species. Since reactive oxygen species have been implicated in apoptosis, the present study was undertaken to determine whether reactive oxygen species play a role in the PGF(2alpha)-induced apoptosis of rat luteal cells. Rat luteal cells were loaded with 6-carboxy-2, 7'-dichlorodihydro-fluorescein (CDCFH) diacetate, di (acetomethyl ester), which can be oxidized by reactive oxygen species to yield CDCF, a fluorescent molecule, and the cells were treated with different doses of PGF(2alpha). Incubation with 100 micromol PGF(2alpha) l(-1) induced an increase in CDCF fluorescence (P < 0. 05). Treatment of cells with PGF(2alpha) for 48 h in serum-free medium induced a dose-dependent increase in cell death, and these cells exhibited the morphological characteristics typical of apoptosis, including condensed or fragmented nuclei and fragmentation of internucleosomal DNA. Pretreatment of these cells with ascorbic acid, N,N'-dimethylthiourea, or superoxide dismutase, which acts as an antioxidant or a radical scavenger, prevented the PGF(2alpha)-induced apoptosis. These results demonstrate that PGF(2alpha) produces reactive oxygen species and induces apoptosis in rat luteal cells, indicating that the reactive oxygen species may induce apoptotic cell death during luteolysis.

Role of leukocytes in uterine hypoperfusion and fetal growth retardation induced by ischemia-reperfusion.

We investigated leukocyte involvement in uterine hypoperfusion and intrauterine fetal growth retardation (IUGR) induced by ischemia-reperfusion (I/R) in Sprague-Dawley rats. On day 17 of gestation, leukocyte accumulation in the uterus and placenta subjected to 30 min of ischemia, followed by reperfusion, was assessed by measuring myeloperoxidase (MPO) activity. Uterine MPO activity was significantly higher after 1 h of reperfusion than it was before ischemia (P < 0.05), without any increase in placental MPO activity. Immunohistochemical staining showed leukocyte accumulation in the uterus subjected to I/R. The effects of treatment with monoclonal antibodies against CD11a (WT1) and CD18 (WT3) at a dose of 0.8 mg/kg on uterine blood flow and IUGR were investigated. Laser-Doppler flowmetry demonstrated that uterine hypoperfusion at 2 h after ischemia (blood flow, -51.7 +/- 1.2%; P < 0.01) was inhibited by WT1 and WT3 treatment. I/R-induced IUGR at full term (P < 0.05 vs. nonischemic horn) was prevented by WT1 and WT3 treatment on day 17. These results indicate that leukocyte accumulation may play an important role in the pathogenesis of uterine hypoperfusion and IUGR induced by I/R in pregnant rats.

Role of beta 1 integrins in human endometrium and decidua during implantation.

The present study was undertaken to investigate the expression and function of beta 1 integrins in human endometrium and decidua. Fluorescence-activated flow cytometry demonstrated the greater expression of the beta 1, alpha 1, alpha 2, and alpha 5 subunits of the beta 1 integrin family in cultured stromal cells from the midsecretory phase than in those of the early proliferative phase. The addition of estradiol (E2) and progesterone (P) to cultured stromal cells in the early proliferative phase increased the expression of beta 1 integrins in vitro. The immunohistochemical distribution of beta 1 integrins demonstrated predominantly glandular epithelial staining in the proliferative phase, and stromal and glandular staining in the midsecretory phase. Flow cytometry also demonstrated the expression of beta 1, alpha 1, alpha 2, alpha 3, alpha 5, and alpha 6 subunits of beta 1 integrin family in cultured decidual cells. Immunohistochemistry confirmed the beta 1 integrin cell surface phenotypes in cultured decidual cells observed by flow cytometry. In the subsequent experiment, the effects of antibodies against specific beta 1 integrin heterodimers on mouse embryo attachment and spreading were tested to identify the role of beta 1 integrins in early implantation. We developed assays for the attachment of mouse embryos and for trophoblastic spreading on cultured human decidual cells. The addition of antibodies directed against beta 1 and alpha integrin subunits to cultured decidual cells did not affect the rates of hatching or attachment of the blastocysts, whereas the outgrowth of embryos on the decidual cells was inhibited by their antibodies in a dose-dependent manner. Thus, beta 1 integrin in human endometrium and decidua may be important in mediating the organization of extracelllar matrix proteins derived from embryos during the early stage of implantation.