Transport Form and Pathway from the Intestine to the Peripheral Tissues and the Intestinal Absorption and Metabolism Properties of Oleamide.

This study aimed to obtain information on the transport form and pathway from the intestine to the peripheral tissues and on the intestinal absorption and metabolism properties of oleamide (cis-9-octadecenamide). Oleamide was primarily transported via the portal vein. Density gradient centrifugation indicated that plasma oleamide was enriched in the fractions containing albumin in the portal and peripheral blood. Oleamide formed a complex with albumin in an endothermic reaction (apparent Kd = 4.4 µM). The CD36 inhibitor inhibited the oleamide uptake into the intestinal epithelial Caco-2 cells, and oleamide decreased the cell surface CD36 level. The fatty acid amide hydrolase (FAAH) inhibitor increased the transepithelial transport of oleamide across Caco-2 cells and the plasma oleamide concentration in mice intragastrically administered with oleamide. These results indicate that oleamide is transported primarily via the portal vein as a complex with albumin. Furthermore, we suggest that oleamide is taken up via CD36 in the small intestine and degraded intracellularly by FAAH.

Metals by Micro-Scale Additive Manufacturing: Comparison of Microstructure and Mechanical Properties.

Many emerging applications in microscale engineering rely on the fabrication of 3D architectures in inorganic materials. Small-scale additive manufacturing (AM) aspires to provide flexible and facile access to these geometries. Yet, the synthesis of device-grade inorganic materials is still a key challenge toward the implementation of AM in microfabrication. Here, a comprehensive overview of the microstructural and mechanical properties of metals fabricated by most state-of-the-art AM methods that offer a spatial resolution ≤10 µm is presented. Standardized sets of samples are studied by cross-sectional electron microscopy, nanoindentation, and microcompression. It is shown that current microscale AM techniques synthesize metals with a wide range of microstructures and elastic and plastic properties, including materials of dense and crystalline microstructure with excellent mechanical properties that compare well to those of thin-film nanocrystalline materials. The large variation in materials' performance can be related to the individual microstructure, which in turn is coupled to the various physico-chemical principles exploited by the different printing methods. The study provides practical guidelines for users of small-scale additive methods and establishes a baseline for the future optimization of the properties of printed metallic objects-a significant step toward the potential establishment of AM techniques in microfabrication.

Morphologic characteristics of the placental basal plate in in vitro fertilization pregnancies: a possible association with the amount of bleeding in delivery.

The aim of the present study was to investigate the relationship between assisted reproductive technology procedures, the morphology of the basal plate of placentas, and amount of bleeding in deliveries. Fifty-five whole placentas (fresh-embryo transfer in the in vitro fertilization cycle [n = 6], frozen-thawed embryo transfer in the natural cycle [n = 13] or in the hormonal cycle [n = 10], and age-matched spontaneously conceived pregnancies [n = 26]) were retrospectively enrolled and histologically analyzed. The whole placentas were stored in our pathological division among 512 singleton pregnancies with vaginal deliveries (34-41 weeks of gestation) at Hamamatsu University Hospital. The morphology of the placental basal plate was examined using Azan staining. A total of 20 digital images (each 0.53 mm(2)) of microscopic fields were analyzed per placenta to measure the mean values of the vertical maximum thickness of Rohr and Nitabuch fibrinoid layers and % loss of decidua. The thickness of Rohr fibrinoid layer and % loss of decidua were significantly higher in the frozen-thawed embryo transfer in the hormonal cycle group than in the frozen-thawed embryo transfer in the natural cycle and spontaneously conceived pregnancy groups (each P < .01). The z scores for both the thickness of Rohr fibrinoid layer and % loss of decidua positively correlated with those for the amount of bleeding in deliveries (P < .05 each). Assisted reproductive technology procedures changed the morphology of the placental basal plate, suggesting a possible association with an increase in the amount of bleeding in deliveries.

Rare form of extraovarian peritoneal serous papillary carcinoma with solitary tumor in the abdominal wall: a case report and literature review.

Cases of cancer presenting with microscopically confirmed metastatic malignancies for which no primary site can be detected are a challenge to stage clinically. Adenocarcinoma of unknown primary site is a subtype with high frequency that has no standard treatment and a poor prognosis. A 32-year-old female was found to have a tumor in the abdominal wall. Tumorectomy was conducted. A pathological examination indicated serous papillary adenocarcinoma, and peritoneal or ovarian cancer was suspected. Exploratory laparotomy and partial resection of the ovaries were carried out, but there were no malignant findings in the peritoneum, ovarian tissue or ascitic fluid. This is an extremely rare case of serous papillary adenocarcinoma with a cystic tumor that was categorized as extraovarian peritoneal serous papillary carcinoma (EPSPC) without other clinical findings.

Hypolipidemic effect of Shoyu polysaccharides from soy sauce in animals and humans.

Soy sauce (Shoyu) is a traditional Japanese fermented seasoning and is available worldwide. We investigated the effects of Shoyu polysaccharides (SPS) prepared from soy sauce on hyperlipidemia in vitro and in vivo. First, SPS inhibited pancreatic lipase. Second, in experiments with animals, it was found that SPS reduced serum triacylglycerol (TG) elevation induced by high-fat diets. Third, in a 2-week placebo-controlled parallel group study, healthy men (TG <150 mg/dl) were treated with 600 mg of SPS (n=5) or placebo (n=5) every day. After 2 weeks, serum TG elevation was significantly (P<0.05) lower in the SPS-treated group than in the placebo-treated group after 6 h of a high-fat diet. Fourth, in a 4-week randomized, double-blind, placebo-controlled parallel group study, hyperlipidemic men (TG >150 mg/dl) were treated with 600 mg of SPS (n=15) or placebo (n=15) daily. After 4 weeks, serum TG levels in the SPS-treated group were significantly (P<0.05) lower than the baseline (0 week). In conclusion, SPS of soy sauce reduce lipid absorption, and soy sauce is a potentially promising seasoning for the treatment of hyperlipidemia through food.

Natural IVF cycles may be desirable for women with repeated failures by stimulated IVF cycles.

PURPOSE: Although many reports support stimulated in vitro fertilization, several patients do not respond to it well. Furthermore, stimulated treatment could be associated with reduced ovarian response. We describe three successful cases involving patients of advanced age from whom dominant follicles were retrieved during the natural cycle. MATERIALS AND METHODS: All patients had failed to bear children through stimulated in vitro fertilization. In case 1, a follicle was retrieved after a gonadotropin-releasing hormone agonist was used to induce luteinizing hormone surge. In cases 2 and 3, pregnancy was achieved via completely natural cycles. RESULTS: One embryo was transferred every 16 cycles. Ongoing pregnancy--defined as pregnancy progressing beyond gestation week 9--was established in three cycles. The patients successfully delivered and had uneventful neonatal courses. CONCLUSION: Mature oocyte retrieval followed by natural rather than stimulated in vitro fertilization might be a potential treatment for patients of advanced age when stimulated in vitro fertilization has been repeatedly unsuccessful.

Modulation of the intestinal Ca2+ uptake by a cheese whey protein digest.

We have previously constructed a system which enables the search for factors that could modulate the intestinal calcium transporter, CaT1 (TRPV6; Takano et al., Cytotechnology, 43, 113 (2003)). This system evaluates the CaT1-mediated calcium uptake by using CHO cells stably expressing human CaT1 (CHO-hCaT1 cells). We found that a cheese whey protein digest (CWP-D) increased the calcium uptake by the CHO-hCaT1 cells. CWP-D also enhanced the calcium uptake in human intestinal Caco-2 cells. The in vivo effects of CWP-D were then measured by using rats with enteral feeding. Although enteral feeding decreased the portal calcium concentration, CWP-D partially suppressed the decrease, suggesting that CWP-D could be used for food to enhance calcium absorption.

Exogenous vascular endothelial growth factor can induce preeclampsia-like symptoms in pregnant mice.

It is reported that expression of vascular endothelial growth factor (VEGF) in trophoblasts increases in cases with preeclampsia. Recently, we demonstrated that the lack of cyclin-dependent kinase inhibitor, p57kip2, expression in the fetus and the placenta plays a role in the development of preeclampsia-like symptoms in pregnant mice. Furthermore, we observed that VEGF mRNA and protein levels, especially VEGF (164), were higher and its expression was stronger in placentas of p57kip2-null embryos than in placentas of wild-type embryos. In this study we investigated whether exogenous murine VEGF (164) induced preeclampsia-like symptoms in pregnant mice, and anti-VEGF neutralized antibody could suppress these symptoms. Administration of VEGF induced hypercoagulation in the placental circulation and a significant elevation of systolic blood pressure in pregnant mice. Furthermore, we demonstrated that treatment with anti-VEGF antibody could suppress the hypercoagulability in placenta and the elevation of systolic blood pressure. These data suggest that VEGF is related to the pathophysiology of preeclampsia.

[Suppression of glucose absorption by various health teas in rats].

The inhibitory effects on the intestinal digestion and absorption of sugar of health teas that claim beneficial dietary and diabetes-controlling effects were compared in rats using portal cannulae. The measured durations were the times during which the elevation of portal glucose levels resulting from continuous intragastric infusion of sucrose or maltose was suppressed by concentrated teas. The teas investigated included salacia oblonga, mulberry, guava, gymunema, taheebo, yacon, and banaba. The duration of the inhibitory effect on the sucrose load of salacia oblonga, mulberry, and guava were 110 min, 20 min, and 10 min, respectively. In contrast, gymunema, taheebo, yacon, and banaba had no significant effect on the continuous infusion of sucrose. These results suggest that there is considerable difference in the efficacy of commercial health teas in influencing glucose absorption.

Alteration of integrins under hypoxic stress in early placenta and choriocarcinoma cell line BeWo.

Invasion of the trophoblast into the decidua and the myometrium is very important for the establishment of a normal pregnancy. This invasion is regulated by the expression of integrins in the trophoblast. Recently, it has been shown that invasion of the trophoblast is impaired in preeclampsia. We report the effect of hypoxia on the expression of integrins and extracellular matrices at the mRNA level in early placenta and BeWo cells. Tissue RNA levels of fibronectin and integrin alpha5 were significantly higher in the hypoxic condition than under normoxic conditions. In contrast, tissue RNA levels of integrin alpha1 were significantly lower for the hypoxic condition than those under normoxic conditions. Alteration of the integrin components and increases in fibronectin expression were observed in early placenta and BeWo cells under hypoxic conditions. These results suggest that hypoxic stress regulates the synthesis of integrin and fibronectin mRNAs in early placenta.

Recombinant adenovirus vector bearing antisense macrophage migration inhibitory factor cDNA prevents acute lipopolysaccharide-induced liver failure in mice.

Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine involved in delayed hypersensitivity and cellular immunity. MIF also acts as a proinflammatory cytokine and counterregulates the anti-inflammatory effects of glucocorticoids. Exogenous gene transfer mediated by adenovirus is useful to study a particular molecular function as well as to develop gene therapy strategies. A recombinant adenovirus containing sense and antisense murine MIF (mMIF) cDNA inserts was constructed using a cosmid-terminal protein complex method. The sense mMIF adenovirus (AxCA-mMIFS) efficiently induced mMIF in COS-7 cells that endogenously lack mMIF in a dose-dependent manner. In contrast, the antisense mMIF adenovirus (AxCA-mMIFAS) inhibited the expression of mMIF in NIH3T3 cells in a dose-dependent manner. To assess the pathophysiologic role of MIF in acute liver failure, we induced acute onset of liver damage in mice (male Jcl:ICR) by a combined treatment of Bacille Calmette-Guerin (BCG) and lipopolysaccharide (LPS). mMIF level in the liver of mice infected with AxCA-mMIFAS showed a significant reduction in MIF production in response to BCG-LPS compared with mice treated without viral infection and with AxCA-mMIFS. In addition, the immunohistochemical staining demonstrated that F4/80 antigen on macrophage was enhanced in liver infected with AxCA-mMIFS but reduced in liver infected with AxCA-mMIFAS. The staining intensity is correlated with the mMIF antigen level in liver tissue. The survival rate of mice infected with AxCA-mMIFAS was significantly higher than that of mice treated with PBS and infected with AxCA-LacZ in BCG-LPS. These results suggest that inhibition of MIF production, using recombinant adenovirus bearing the antisense MIF gene, reduced the mortality rate in BCG-LPS-induced liver failure in mice. This finding might aid in the further development of gene therapy targeting MIF.

Anti-macrophage inhibitory factor antibody inhibits PMSG-hCG-induced follicular growth and ovulation in mice.

PURPOSE: To investigate the effect of an anti-MIF antibody on PMSG-hCG-induced murine follicular growth and ovulation and to determine whether MIF plays an essential role in this process. METHODS: Mice were primed with an intraperitoneal injection of pregnant mare serum gonadotropin (PMSG) and were treated with an anti-rat MIF antibody and human chorionic gonadotropin (hCG) to induce ovulation. After that, the ovulated ova were counted. The ovaries were studied using standard histological procedures. RESULTS: Ovaries treated with the anti-MIF antibody showed reduced numbers of growing follicles surrounded by granulosa cells and theca cells with a little proliferation compared with the control. The average numbers of ova collected from mice treated with the anti-MIF antibody were reduced compared with those collected from control mice. CONCLUSIONS: Anti-MIF antibody inhibits the follicular growth and ovulation in mice, and MIF may play an important role in the inflammatory reactions during follicle growth and ovulation.

Deficiency in p57Kip2 expression induces preeclampsia-like symptoms in mice.

p57Kip2, a potent inhibitor of several cyclin/cyclin dependent kinase complexes (CDK ), is a paternally imprinted gene in both humans and mice, and here we show that pregnant mice which are heterozygous for p57Kip2 deficiency display symptoms similar to preeclampsia. p57-/+ (heterozygotes for p57Kip2 ) female mice that were mated with p57-/+ males showed hypertension, proteinuria, thrombocytopenia, decreased anti-thrombin III activity, and increased endothelin levels during late pregnancy. In their kidneys, endotheliosis of glomeruli were recognized along with fibrinoid or hyalinoid deposits. These characteristics were also observed in pregnant p57-/+ females that were mated with wild type males, but not in pregnant wild type females mated with p57-/+ males or wild type males. The pregnant p57-/+ mice had conceptuses both with and without p57Kip2 expression. The conceptuses without p57Kip2 expression showed trophoblastic hyperplasia, which mimics the hallmark proliferation of intermediate trophoblasts in clinical preeclampsia. It is suggested that the preeclampsia-like symptoms of the pregnant p57-/+ mice might have been induced by the conceptus(es) without p57Kip2 expression. In addition, pregnant p57-/+ mice might serve as a new animal model for preeclampsia characterized by trophoblastic hyperplasia.

Increased expression of vascular endothelial growth factor in placentas of p57(Kip2) null embryos.

Placentas of mice lacking p57(Kip2) expression have trophoblastic hyperplasia. To elucidate the mechanism underlying this phenomenon, we studied expression of two angiogenic factors, vascular endothelial growth factor (VEGF) and placenta growth factor (PlGF). Immunohistochemical analysis with anti-VEGF antibodies indicated that VEGF expression was stronger and more clearly detectable in placentas of p57(Kip2) null embryos compared to wild-type placentas. PlGF showed no significant differences between placentas of p57(Kip2) null and wild-type embryos. In quantitative analysis, placentas of p57(Kip2) null embryos showed higher VEGF messenger (m)RNA and protein levels than did wild-type placentas. PlGF mRNA and protein levels were not significantly different. These findings suggest that VEGF is involved in the hyperplasia that occurs in placentas of p57(Kip2) null embryos.