Evaluation of plasma tissue factor and tissue factor pathway inhibitor levels in childhood hemangiomas

BACKGROUND: The purpose of the study was to evaluate the plasma levels of tissue factor (TF), an angiogenic marker, and tissue factor pathway inhibitor (TFPI), an antiproliferative protein, in the childhood hemangiomas at proliferative and regressive stages. PROCEDURE: The study included 30 patients with hemangiomas and 30 healthy children. Localization, number, stage, type, duration of growth, and complications of the hemangiomas were determined. Venous blood samples from all individuals were collected into citrated tubes and centrifuged. Supernatant plasma was separated, aliquated, and stored at -70 degrees C until samples could be assayed. Plasma levels of TF and TFPI were measured with quantitative ELISA kits. RESULTS: Plasma TF and TFPI levels did not show any significant difference between the study and control groups. When plasma TF and TFPI levels of the children in the control group and in the study group who were in proliferative and regressive stage were compared to each other, no statistically significant difference could be detected. CONCLUSIONS: Plasma TF and TFPI levels of our patients with hemangiomas were not different from healthy children and they did not show any significant difference in proliferative and regressive stages.     

新生儿感染性黄疸血浆组织因子和组织因子途径抑制物含量的变化

目的　探讨新生儿感染性黄疸患儿血浆组织因子 (TF)和组织因子途径抑制物 (TFPI)含量的变化及其意义。方法　运用酶联免疫吸附法 (ELISA)测定 8例非感染性高胆红素血症新生儿 (对照组 )及 2 1例感染性黄疸新生儿 (感染组 )血浆TF和TFPI水平。结果　感染组的血浆TFPI含量和TF含量显著高于对照组 [TFPI( 2 1 0± 4 3 )、( 16 2± 1 9) μg/L ,P <0 0 1;TF ( 177± 79)、( 5 1± 2 4)ng/L ,P <0 0 1];TFPI/TF比值显著低于对照组 ( 13 7± 61、3 19± 67,P <0 0 1)。根据患儿血清胆红素 (SB)浓度 ,将 2 1例感染性黄疸新生儿分为胆红素重度增高感染组 (SB≥ 2 0 5 2 μmol/L ,n =10 )和胆红素轻度增高感染组 (SB <2 0 5 2 μmol/L ,n =11) ,两组间TFPI水平差异无显著性 (P >0 0 5 )。胆红素重度增高感染组TF水平高于胆红素轻度增高感染组 [( 2 16± 79)、( 141± 63 )ng/L ,P <0 0 1],而TFPI/TF低于胆红素轻度增高感染组 ( 10 0± 3 0、171± 74,P <0 0 1)。结论　感染可引起新生儿体内抗凝与促凝作用的平衡失调。黄疸可提高血浆TF水平 ,加重感染新生儿体内抗凝与促凝作用的失衡     

Oxidation and synthesis of fatty acids in human and rat placental and fetal tissues

The rat fetus (day 21 of pregnancy) covers its fatty acid (FA) demands at equal amounts both by maternal-fetal FA transfer and fetal FA synthesis. At the end of the first trimester the human fetal FA synthesis is too small to cover the fetal FA requirements. Therefore, the transfer of FA from the mother to the fetus seems to be the predominant source of fetal FA. The FA oxidation is greater than the FA synthesis in human and rat placenta as well as in the human fetus at the end of the first trimester, whereas the rat fetus (day 21 of pregnancy) oxidizes and synthesizes FA at equal amounts.     

组织因子途径抑制物及前降钙素在新生儿败血症诊断中的价值

目的 了解组织因子途径抑制物(TFPI)、前降钙素(PCT)在新生儿败血症诊断中的价值.方法 通过检测48例败血症新生儿及30例健康新生儿血TFPI、PCT、C-反应蛋白(CRP)浓度,比较各炎症指标对诊断败血症的灵敏度、特异度、阳性预测值、阴性预测值和约登指数,评价它们对该病的早期诊断价值.结果 (1)以TFPI≥30μg/L、CRP≥8 mg/L、PCT≥2 ng/ml为阳性标准,三指标对诊断败血症的灵敏度分别为86.92%、89.83%、87.50%,差异无显著性(P＞0.05),其中PCT的特异度96.67%、阳性预测值97.50%、阴性预测值83.32%、约登指数0.84;(2)在败血症组中,20例血培养阳性患儿的TFPI值为(35.5±4.5)μg/L,28例血培养阴性患儿的TFPI值为(34.3±3.2)μg/L,差异无显著性(P＞0.05);但是相对于正常对照组(26.9±5.24)μg/L,败血症组的TFPI值明显升高(P＜0.05).结论 TFP≥30μg/L对诊断新生儿败血症是一个具有较高灵敏度(86.92%)、中度特异度(59.3%)的指标;TFPI对新生儿败血症早期诊断有一定的价值,但均不及PCT及CRP,所有检测指标中PCT特异度、阳性预测值、阴性预测值、约登指数均最高.     

Mercury burden of human fetal and infant tissues

The total mercury concentrations in the liver (Hg-L), the kidney cortex (Hg-K) and the cerebral cortex (Hg-C) of 108 children aged 1 day-5 years, and the Hg-K and Hg-L of 46 fetuses were determined. As far as possible, the mothers were interviewed and their dental status was recorded. The results were compared to mercury concentrations in the tissues of adults from the same geographical area. The Hg-K (n = 38) and Hg-L (n = 40) of fetuses and Hg-K (n = 35) and Hg-C (n = 35) of older infants (11–50 weeks of life) correlated significantly with the number of dental amalgam fillings of the mother. The toxicological relevance of the unexpected high Hg-K of older infants from mothers with higher numbers of dental amalgam fillings is discussed.     

Sphingolipid composition and catabolism in human fetal tissues.

Human fetal tissues derived from prostaglandin-induced abortuses (9--18 wk fertilization age) have been utilized to evaluate sphingolipid composition and catabolism. Sphingolipid composition (lipid-hexose, sulfatide, and lipid-bound NANA) was assessed in fetal brain. Sphingolipid catabolism was evaluated in fetal lung and brain through the measurement of relevant acid hydrolases (arylsulfatase A, beta-galactosidase, and hexosaminidase). During the fetal period studied, the parameters of sphingolipid composition revealed variability but no consistent pattern of change. Each acid hydrolase was readily detected. Enzyme specific activities revealed no variation during the 9 fetal wk studied. Cellulose acetate electrophoresis yielded the anticipated isoenzyme patterns for each acid hydrolase with little variation during the period of study. The compositional values support current concepts of cerebral development during this period of fetal life. Together with the catabolic analyses, these studies provide normative data relative to the assessment of metabolic abnormalities during this period of fetal development.     

The roles of placental growth hormone and placental lactogen in the regulation of human fetal growth and development

The human growth hormone (hGH)/human placental lactogen (hPL) gene family, which consists of two GH and three PL genes, is important in the regulation of maternal and fetal metabolism and the growth and development of the fetus. During pregnancy, pituitary GH (hGH-N) expression in the mother is suppressed; and hGH-V, a GH variant expressed by the placenta, becomes the predominant GH in the mother. hPL, which is the product of the hPL-A and hPL-B genes, is secreted into both the maternal and fetal circulations after the sixth week of pregnancy. hGH-V and hPL act in concert in the mother to stimulate insulin-like growth factor (IGF) production and modulate intermediary metabolism, resulting in an increase in the availability of glucose and amino acids to the fetus. In the fetus, hPL acts via lactogenic receptors and possibly a unique PL receptor to modulate embryonic development, regulate intermediary metabolism and stimulate the production of IGFs, insulin, adrenocortical hormones and pulmonary surfactant. hGH-N, which is expressed by the fetal pituitary, has little or no physiological actions in the fetus until late in pregnancy due to the lack of functional GH receptors on fetal tissues. hGH-V, which is also a potent somatogenic hormone, is not released into the fetus. Taken together, studies of the hGH/hPL gene family during pregnancy reveal a complex interaction of the hormones with one another and with other growth factors. Additional investigations are necessary to clarify the relative roles of the family members in the regulation of fetal growth and development and the factors that modulate the expression of the genes.     

Ontogeny of human lysozyme. Distribution in fetal tissues

Using the immunoperoxidase method, major changes in the distribution of lysozyme (LZM) were found to occur during fetal development. At 10 weeks of gestation LZM was detected for the first time in the proximal tubules of the kidney. This generally coincides with the reported appearance of LZM in fetal blood and amniotic fluid. The enzyme was observed in lung macrophages and in mononuclear cells of the lamina propria of the small intestine in fetuses 12 and 16 weeks old, respectively. At about 18--20 weeks, LZM-positive mononuclear cells were detected in other tissues tested, such as liver, spleen and thymus. Paneth cells were found to be specifically stained at about 20 weeks of gestation. The timing of the appearance of LZM in the various tissues is discussed in relation to the functional maturation of each organ and the ontogeny of this enzyme in other species.     

组织因子基因沉默对胎盘早剥人脐静脉内皮细胞的影响

目的 利用RNA干扰技术对胎盘早剥(placental abruption,PA)和正常出生的新生儿脐静脉内皮细胞(human umbilical vein endothelial cell,HUVECs)组织因子(tissue factor,TF)的表达进行干预.方法 收集2008年11月至2010年2月胎盘早剥(placental abruption,PA)产妇分娩胎儿(足月或早产不限)6例的脐带(PA组)及6例同期正常产妇分娩胎儿的脐带(正常对照组).构建RNA干扰TF基因表达载体及RNA 干扰沉默PA胎儿HUVECs TF基因表达.两组分别进行以下处理:(1)空白未干扰对照;(2)假干扰对照;(3) RNA干扰TF基因表达.观察处理后HUVECs在基因沉默前后的mRNA表达、TF蛋白水平免疫荧光检测的变化.结果 将构建的pENTRTM/U6-TF-shRNA转染到正常对照组和PA组,正常对照组HUVECs在转染后TF mRNA水平较空白对照的0.657±0.097下降至0.220±0.030; PA组则由1.323±0.323下降至0.207±0.150.与正常对照组比较,TF mRNA表达在PA组空白对照处理(1.323±0.323 vs0.657±0.097,P=0.023)、假干扰处理(1.057 ±0.178 vs 0.540±0.079,P =0.01)后差异均有统计学意义,而RNA干扰处理后正常对照组和PA组之间TFmRNA的表达差异无统计学意义(0.220 ±0.030 vs 0.207 ±0.150,P＞0.05).在正常对照组及PA组内,各处理间差异均有统计学意义(F=27.657,P=0.001;F=19.299,p=0.002).结论 构建的pENTRTM/U6-TF-shRNA成功转染到HUVECs,显著抑制PA 产妇胎儿HUVECs中TF的表达.     

Transplacental effects of endotoxemia on fetal mouse brain, bone, and placental tissue

Pregnant mice were given 0.005 mg endotoxin on day 10 of gestation or 0.0025 mg endotoxin on days 10 and 12. Pregnant mice treated with normal saline served as controls. On day 18 of pregnancy, fetuses and placentas were removed for microscopic and histological examination. The treated placentas had fibrin thrombi and hemorrhages in the labyrinth and spongiosa. Glycogen cells in the spongiosa were swollen. The long bones of experimental animals had few metaphyseal trabeculae, which also were disorganized, with an increase in the number of metaphyseal and diaphyseal osteoclasts. An increase in the number of necrotic neurons was observed in coronal sections of brains of experimental fetuses at the level of the trigeminal ganglion. To correlate the degree of neuronal necrosis with long-term behavioral effects, a behavioral test was performed on pups whose mothers were treated with endotoxin. The pups were tested at the age of 28 days and for the next 3 days for their audiogenic seizure response. The pups of the experimental groups were more sensitive to high sounds than the controls. Escherichia coli endotoxins seemed to have a significant teratogenic effect on mice, being more severe when endotoxin was given in divided doses to the pregnant animals. The widespread endothelial damage or the elevation of prostaglandin levels caused by endotoxins may have been responsible for these teratogenic effects.     

Studies on human fetal tissues— I. Fetal weight and tissue weights in relation to gestational age,fetal size and maternal nutritional status

Studies were done on 130 human fetuses (including stillborns) varying in gestational age from 8 to 40 weeks, on fetal weight and tissue weights of selected fetal tissues, namely, liver, lung, heart small intestine and large intestine. As expected, fetal weight as well as tissue weights increased with the progress of gestation. Both fetal and tissue weights were found to be consistently higher in the high income group but the differences were statistically significant only around midpregnancy. The differences for subsequent gestational ages showed the same trend, but fell short of significance because of small sample size and large intragroup variations. Among the tissues studied, the lung apparently enjoys an ontogenetic priority while intestine appears to be the last to develop. Fetal growth retardation seems to be associated with decreased weights of liver, lung and large intestine. The small intestine is spared to some extent. These findings also suggest that because of smaller tissue weights, these fetuses are likely to have poor stores of critical nutrients.     

Vascular placental insufficiency in the rabbit. Changes in creatine kinase and adenylate kinase activities in fetal tissues

Vascular placental insufficiency is considered a common pathogenic factor in human intrauterine growth retardation. To mimic this condition, the rabbit, a 'perinatal brain developer' was utilized as an experimental model. Ischemic conditions were achieved by total ligation of approximately 30% of the uteroplacental vessels of half of the fetuses in each pregnant rabbit in the last third of gestation. The change in activity of the brain type isozyme of creatine kinase (CKBB), involved in energy regeneration and regulation, was assessed as a response marker to tissue ischemia in rabbit tissues: cerebellum, cerebrum, kidney, liver and placenta. A significant transient increase in CK-specific activity was found in the kidney and the cerebellum but not in the other organs tested, at 24 and 48 h after ligation. This increase was not seen with adenylate kinase, another enzyme involved in energy regeneration and regulation. It is proposed that an increase in CK-specific activity could serve as a metabolic marker of vascular insufficiency in rapidly developing tissues, representing part of a compensatory mechanism to overcome an energetic gap induced by ischemia.     

Enhanced tissue factor pathway inhibitor response as a defense mechanism against ongoing local microvascular events of Legg-Calve-Perthes disease

The precise pathogenetic basis of Legg-Calve-Perthes disease (LCPD) is currently unknown. Hemostatic abnormalities, i.e., hypercoagulability and/or hypofibrinolysis, were proposed in the genesis of the LCPD. Deficiency of tissue factor pathway inhibitor (TFPI), a critical natural anticoagulant molecule, may lead to a prothrombotic state in a wide variety of conditions. The aim of this study is to assess the circulating TFPI pool in the LCPD. Group I consisted of 44 patients with LCPD and group II comprised 38 healthy children. Median (IQR) TPFI concentration was significantly higher in the group I (p < .0001). Enhanced TFPI response could be regarded as a compensatory defense mechanism against ongoing local microvascular events of occlusion and revascularization of LCPD. TFPI molecule may be an important link between the crossroads of the LCPD genesis and pathogenetic microvascular changes in the disease course. Further investigations are needed to shed light on the endothelial anticoagulant kinetics, the unique microvascular compromise, and the self-limiting nature of the disease.     

Studies on human fetal tissues-II. Lipid composition of human fetal tissues in relation to gestational age,fetal size and maternal nutritional status

When lipids of different tissues were compared for the period 16–24 weeks of gest ation, the liver has the highest concentration of all the lipid components studied. The concentrations in the small intestine were close to that of the liver in the case of the neutral lipids. The lung and heart were found to have comparable concentrations of various lipids. Fetal growth retardation seems to be associated with a higher concentration of cholesterol in the liver, the lung and small intestine. Lower values for phospholipid concentration and phospholipid to cholesterol ratio were observed in the lung, heart and small intestine with such retardation. These studies suggest the delayed maturation of these tissues, as these lipids play an important role in the maintenance of cellular integrity, structure and function of plasma membrane as well as subcellular membranes.