妊娠期糖尿病患者体内铁负荷状态及氧化应激水平的研究

为了探讨铁代谢在妊娠期糖尿病(GDM)发病中的作用,对GDM患者体内铁负荷状态、氧化应激水平及抗氧化状态进行分析研究.在912例孕24～28周产前检查的孕妇中,按血糖筛查和糖耐量试验筛选出GDM孕妇32例为实验组,随机选择糖耐量正常孕妇26例作为对照组,分别测定两组孕妇的血红蛋白(Hb)等指标,以评价机体铁代谢状况;测...     

Association of IGF-I and the IGF-I/IGFBP-3 ratio with plasma aldosterone levels in the general population

Several studies in patients with acromegaly or growth hormone (GH) deficiency suggest a stimulatory effect of the growth hormone (GH)/insulin-like growth factor I (IGF-I) axis on the renin-angiotensin-aldosterone system (RAAS). We analyzed the association of serum IGF-I with plasma aldosterone and the aldosterone-to-renin ratio in a large sample from the general population. In addition to serum IGF-I levels, we also considered the IGF-I-to-IGF binding protein (IGFBP)-3 ratio. A total of 1 504 men and 1 566 women aged 25-88 were selected from the first follow-up of the population-based Study of Health in Pomerania. Plasma aldosterone and renin concentrations, as well as serum IGF-I and IGFBP-3 levels were determined with immunoassays. Analyses of variance and linear regression analyses were performed. We found positive associations between serum IGF-I or the IGF-I/IGFBP-3 ratio with plasma aldosterone in women but not in men. Plasma aldosterone levels increased by 2.91 ng/l per IGF-I standard deviation (SD) and by 2.17 ng/l per IGF-I/IGFBP-3 SD. The associations remained significant after exclusion of subjects taking RAAS-altering medication and of subjects with serum IGF-I levels and aldosterone-to-renin ratios outside the reference range. We conclude that, serum IGF-I and the IGF-I/IGFBP-3 ratio are associated with plasma aldosterone levels in women but not in men from the general population.     

Purification from human pregnancy serum of a low molecular weight mitogen similar to placental lactogen and growth hormone

Recently, we isolated from the serum of pregnant women a factor that induced rapid proliferation of a lactogen-dependent rat lymphoma cell line (Nb2). This mitogenic factor is reasonably specific to pregnancy, since it was present in serum samples from second trimester as well as term-pregnant women, but not in those of adult men or cycling females. It is unlikely that this mitogenic activity (referred to as pregnancy mitogen [PM]) is due to contamination by classical lactogens, since acetone fractionation of serum yielded a preparation devoid of placental lactogen and prolactin, as determined by radioimmunoassays. Further purification of acetone precipitates from term-pregnant serum by ion exchange chromatography and gel filtration yielded a mitogenic activity with a relative mol wt of approximately 10,000. PM activity in the NB2 cell bioassay was not affected by the presence of prolactin antiserum. However, its activity was immunoneutralized by coincubation with anti-placental lactogen serum and, to a lesser extent, anti-growth hormone serum. It appears that PM was not generated by our extraction procedure, since gel filtration of whole serum also yielded a bioactive fraction of approximately 10 kDa. PM was further purified to homogeneity by high-performance liquid chromatography. Examination of the preliminary amino acid composition of PM revealed differences from that of a bioactive fragment of growth hormone and a corresponding portion of placental lactogen, suggesting that PM could be either a molecular variant of these hormones or a novel protein.     

Is epidermal growth factor present in human blood? Interference with the radioreceptor assay for epidermal growth factor

Human whole blood serum reduces the binding of [125I]labeled mouse epidermal growth factor to cultured human fibroblasts as well as does 70-100 ng/ml mouse epidermal growth factor. However, at most 1-2% of the binding inhibitor detected in human whole blood serum is related to epidermal growth factor--the remaining consists of other factors released during preparation of serum, predominantly the platelet-derived growth factor, which are capable of altering the binding properties of the epidermal growth factor receptor. This accounts for much of the differences between values reported for epidermal growth factor concentration in blood by investigators using different assay procedures.     

Circulating anti-heat-shock-protein antibodies in normal pregnancy and preeclampsia

It has been previously reported that circulating anti-heat-shock-protein (Hsp) antibody levels are elevated in cardiovascular disorders. The aim of the present study was to determine circulating antihuman Hsp60, antimycobacterial Hsp65, and antihuman Hsp70 antibody levels in healthy pregnant women and preeclamptic patients and to investigate their relationship to the clinical characteristics of the study subjects, as well as to the markers of inflammation (C-reactive protein (CRP)), endothelial activation (von Willebrand factor antigen), or endothelial injury (fibronectin), oxidative stress (malondialdehyde) and to serum Hsp70 levels. Ninety-three preeclamptic patients and 127 normotensive healthy pregnant women were involved in this case control study. Serum anti-Hsp60, anti-Hsp65, anti-Hsp70, and Hsp70 levels were measured with enzyme-linked immunosorbent assay (ELISA). Serum CRP levels were determined by an autoanalyzer using the manufacturer’s kit. Plasma von Willebrand factor antigen levels were quantified by ELISA, while plasma fibronectin concentration by nephelometry. Plasma malondialdehyde levels were measured by the thiobarbituric-acid-based colorimetric assay. For statistical analyses, nonparametric methods were applied. Anti-Hsp60, anti-Hsp65, and anti-Hsp70 antibodies were detected in all of our serum samples. There were no significant differences in serum anti-Hsp60, anti-Hsp65, and anti-Hsp70 antibody levels between the control and preeclamptic groups. Serum levels of Hsp70 and CRP, as well as plasma levels of VWF antigen, fibronectin, and malondialdehyde, were significantly higher in preeclamptic patients than in normotensive healthy pregnant women. Serum anti-Hsp60 antibody levels showed significant correlations with serum anti-Hsp65 antibody levels both in the control and the preeclamptic groups (Spearman R = 0.55 and 0.59; p < 0.001, respectively). However, no other relationship was found between clinical features (maternal age, smoking status, parity, body mass index, gestational age at blood draw, systolic and diastolic blood pressure, gestational age at delivery, and fetal birth weight) and measured laboratory parameters of the study subjects and serum anti-Hsp antibody levels in either study group. In conclusion, anti-Hsp60 and anti-Hsp70 antibodies as naturally occurring autoantibodies are present in the peripheral circulation of healthy pregnant women. Nevertheless, humoral immunity against heat shock proteins was not associated with preeclampsia. Further studies are warranted to explore the role of heat shock proteins and immune reactivity to them in the immunobiology of normal pregnancy and preeclampsia.     

Circulating levels of insulin-like growth factors increase and molecular forms of their serum binding proteins change with human pregnancy.

Insulin-like growth factors (IGF) and binding proteins were measured in serum from pregnant and nonpregnant women. IGF-I determined by immunoassay after acid-ethanol extraction was increased by pregnancy (p less than 0.005) and was highest in the third trimester (p less than 0.01). Size exclusion chromatography of serum in acid before assay (i) gave a very similar IGF-I pattern, (ii) showed that IGF-II was much higher than IGF-I and (iii) revealed less serum IGF-binding protein activity in pregnancy and lactation. All IGF-binding proteins except binding protein-1 were markedly reduced by pregnancy. This indicates a major change in the main carrier protein for IGFs in the circulation and suggests that tissue targetting of IGFs may be altered during pregnancy.     

Prevalence and avidity of human herpesvirus-6 specific IgG antibodies in pregnant women in Hungary

The prevalence, the level and the avidity of human herpesvirus-6 (HHV-6) specific IgG were examined in pregnant women and age-matched female blood donors. The study group consisted of 180 women (age 14-45); 60 women with normal pregnancy, 60 pregnant women with fetuses suspected of having any viral infection and 60 healthy blood donors with no history of pregnancy. Plasma or serum samples were tested for HHV-6 IgG antibodies by an immunofluorescence assay. Ninety-eight percent of blood donors and 97% of 120 pregnant women had IgG antibodies to HHV-6. The rate of seropositivity in women with normal pregnancies and women with fetuses suspected to have viral infection was the same. Pregnant women (n = 120) had significantly lower antibody titer than blood donors. No significant differences were found in the same respect between the two groups of pregnant women. Low avidity of IgG antibodies to HHV-6 was detected in 5% of pregnant women.     

Mechanisms of diminished natural killer cell activity in pregnant women and neonates

Because alterations in natural killer (NK) activity in the perinatal period may be important in the maintenance of a healthy pregnancy, we examined the mechanisms by which these alterations are mediated in neonates and in pregnant and postpartum women. NK activity, as measured in a 4-hr 51Cr-release assay and compared with adult controls, is significantly diminished in all three trimesters of pregnancy and in immediately postpartum women. In postpartum women, NK activity appears to be higher than in pregnant women, although this does not reach statistical significance. Pregnant and postpartum women have normal numbers of large granular lymphocytes and normal target cell binding in an agarose single cell assay but decreased lysis of the bound target cells. NK activity of mononuclear cells from postpartum women, in addition, demonstrate a shift in distribution to higher levels of resistance to gamma-irradiation. Further, sera from postpartum women cause a similar shift to increased radioresistance in mononuclear cells from adult controls. Because radioresistance is a property of interleukin 2-stimulated NK, the shift to radioresistance may represent lymphokine-mediated stimulation occurring during parturition. In contrast, cord blood cells have a more profound decrease in NK activity as determined by 51Cr-release assay and decreases in both binding and lysis of bound target cells in the single cell assay. The resistance of NK activity in cord cells to gamma-irradiation is also increased, as seen in postpartum women. Cord blood serum, however, did not alter radioresistance or inhibit NK activity. The results suggest that the observed diminished NK activity in pregnant women and neonates arise by different mechanisms: an absence of mature NK cells in the neonate and an alteration of the NK cell in pregnancy leading to decreased killing.     

Prevalence of antibodies to Chlamydia trachomatis in healthy population groups in Manitoba.

The prevalence of antibodies to Chlamydia trachomatis was determined in 1877 serum samples from healthy population groups of Caucasians, native Indians and recent Vietnamese immigrants in Manitoba. Testing was done with a commercially available immunofluorescence kit containing C. trachomatis antigen. The presence of antibodies was age-related; a progressive increase in prevalence was observed in children aged 1 to 15 years, and the overall prevalence was higher in female Caucasian blood donors and female Vietnamese immigrants than in males in both groups. However, there was no sex-related difference in prevalence among the subjects undergoing premarital testing or among the native Indians. Antibodies were more prevalent (p less than 0.001) in pregnant than in nonpregnant women matched for race and age, and a relatively high prevalence (66.6%) was found in the cord serum of newborns. The overall prevalence rate of antibodies in all Manitobans was 48.8% (44.9% in men, 55.9% in women and 35.3% in children.     

Bioactive and immunoactive prolactin levels after TRH-stimulation in the sera of normal women.

The availability of an improved microbioassay for lactogenic hormone measurement has enabled comparison of basal and dynamic prolactin bioactivity (BA) and immunoactivity (IRMA) in normal human serum. Serum from 16 normal females aged 22-74 years was assayed and revealed a mean BA/IRMA prolactin ratio of 1.6 for basal and 1.8 for peak TRH-stimulated levels. Basal prolactin levels in postmenopausal women measured by bioassay were lower than in premenopausal women showing a relative and absolute decrease in prolactin bioactivity with age, but there was no significant difference in dynamic levels. There was also no significant difference in BA or IRMA levels following the stress of venepuncture. These findings indicate that, as previously described for basal levels, there is a good correlation between dynamic prolactin bioactivity and immunoactivity in human serum.     

Fetal Endoxins and Complications of Pregnancy

Maternal endoxin (digoxinlike substance) is proposed as arising in the fetal area of the fetal adrenal cortex. Its function may be to sensitize the uterus for labor, much as does cortisol in the sheep fetus. Because endoxin is a sodium-potassium-adenosine triphosphatase inhibitor, however, it may also induce maternal vasoconstriction. On our service, normal pregnant women have detectable endoxin after 35 weeks with increasing amounts at term. Specimens of cord blood often have “digoxin” in the therapeutic range. We find that about 40% of women in premature labor and 65% of pregnant women with hypertension have elevated levels of serum endoxin. Postdate gravid women sometimes have very low endoxin levels. Pregnant women with complications and elevated digoxin (endoxin) levels could have specific antidigoxin therapy if endoxin proves to be a modulator of their symptoms. Digoxinlike substances are also sometimes elevated in ill nonpregnant persons, such as those with renal, liver, or heart failure, or hypertension.     

Immunoregulatory factors derived from human tumors. II. Partial purification and further immunobiochemical characterization of a human sarcoma-derived immunosuppressive factor expressing HLA-DR and immunoglobulin-related determinants

An immunoregulatory factor (IRF) that suppresses Con A-mediated peripheral blood mononuclear cell (PBM) proliferative responses was partially purified by DEAE anion exchange chromatography and affinity chromatography from a 3 M KCl extract of a human liposarcoma. The factor (m.w. = 70K) co-purified with albumin, monitored by two-dimensional gel electrophoresis, and demonstrated a heterogeneous isoelectric point (pI 7.6-7.8). Xenoantisera produced against the DEAE-purified fraction and coupled to Affigel 10 removed suppressive activity that could subsequently be eluted by glycine-HCl, pH 3.5. An anti-albumin column partially removed activity, but the unbound 70K factor could still be detected in the column effluent. A xenoantiserum to this 70K effluent coupled to acrylamide beads completely removed the immunosuppressive activity in immunodepletion experiments. Further direct binding enzyme-linked immunoassays (ELISA) and solid-phase immunoabsorption experiments with monoclonal antibodies to human anti-HLA-DR framework determinants and a constant region of the IgM mu-chain demonstrated determinants on the 70K factor recognized by these antibodies.     

重度子痫前期患者外周血NK 细胞功能的研究*

目的:探讨重度子痫前期患者外周血中NK细胞数量、杀伤功能以及相关细胞因子的变化。方法:选择重度子痫前期患者25例(研究组)以及正常妊娠妇女25例(对照组),流式细胞术测定外周血中NK细胞数量,细胞毒实验测定NK细胞的杀伤活性,ELISA法测定血清IFN-γ及IL-2的浓度。结果:研究组患者外周血中NK细胞的数量以及杀伤活性显著高于对照组;研究组外周血中IFN-γ、IL-2的浓度也显著高于对照组。结论:重度子痫前期患者外周血NK细胞数量增多,杀伤活性增强,血清中NK细胞相关细胞因子也增加。这些改变可能参与重度子痫前期的发病机制。     

Dynamics of antibody nuclease activity in blood of women during pregnancy and lactation

In human milk we previously found catalytic antibodies (abzymes) catalyzing hydrolysis of DNA, RNA, NMP, NDP, and NTP and also phosphorylation of proteins and lipids. In the present study we have analyzed nuclease activities of antibodies in blood of women during pregnancy and lactation. Blood of healthy male and female volunteers lacked catalytically active antibodies, whereas antibodies from blood of pregnant women hydrolyzed DNA and RNA and their relative activity varied over a wide range. Relative blood abzyme activities significantly increased after delivery and at the beginning of lactation. The highest abzyme activity was observed in blood of parturient women. Although the dynamics of changes in antibody DNase activity during pregnancy was rather individual for each woman, there was a common trend in the increase in antibody activity in the first and/or third trimester of the pregnancy. The DNase activity of IgG and IgM from blood of healthy pregnant women was 4-5 times less than that from pregnant women with pronounced autoimmune thyroiditis.     

Identification of luteinizing hormone releasing hormone-like immunoactivity in ovine cotyledons

Luteinizing hormone releasing hormone (LHRH)-like immunoactivity has been identified in cotyledonary extracts prepared from pregnant ewes. This activity displayed similar physico-chemical properties as synthetic LHRH, as determined by reverse-phase HPLC and size-exclusion HPLC. Under reverse-phase conditions, cotyledonary LHRH-like immunoactivity displayed a retention time (10.5 +/- 0.1 min) which was not significantly different from that of synthetic LHRH. When subjected to size-exclusion HPLC, cotyledonary LHRH-like immunoactivity eluted in fractions which corresponded to a molecular weight range of 1100-1200 Da, which was not significantly different from the elution profile observed for synthetic LHRH. The cotyledonary tissue content of LHRH-like immunoactivity averaged 94 +/- 24 pg/mg (n = 6). The results of this study demonstrate the presence of LHRH-like immunoactivity in ovine cotyledons. Although placental synthesis of LHRH-like immunoactive material has been demonstrated in other species, it remains to be established whether this activity, demonstrated in ovine placenta, is the consequence of de novo placental synthesis or represents uptake from the maternal (and/or fetal) circulation.     

孕期妇女钙含量与妊娠期高血压的相关性分析

目的：探讨孕期妇女钙含量与妊娠期高血压的相关性。方法：选取235例妊娠期高血压孕妇为观察组研究对象,抽取母体血清样本检测血清中微量元素钙的含量。另外选取200例正常妊娠孕妇为对照组,同样检测母血中钙的含量。比较两组孕妇的血钙含量,且对观察组孕妇进行补钙治疗后,检测其血压值的变化,探讨孕期妇女钙含量与妊娠期高血压的相关性。结果：观察组中轻度妊娠期高血压孕妇钙离子的平均浓度为（2．11±0．24）mmol／L,中度妊娠期高血压孕妇钙离子的平均浓度为（2．03±0．21）mmol／L,重度妊娠期高血压孕妇钙离子的平均浓度为（1．98±0．25）mmol／L。观察组中孕妇平均钙离子浓度为（2．05±0．22）mmol／L,而对照组中孕妇钙离子的平均浓度为（2．40±0．28）mmol／L。对照组孕妇钙离子浓度明显高于观察组孕妇（P〈0．05）。在观察组孕妇随着血压值的上升,血清钙离子浓度呈下降趋势（P〈0．05）。补钙治疗后的原轻度妊娠期高血压孕妇收缩压与舒张压较治疗前有所下降（P〈0．05）。中度及重度妊娠期高血压孕妇治疗后收缩压与舒张压较治疗前有明显下降（P〈0．01）。结论：妊娠期高血压的发生,可能与孕妇血钙含量有关,加强孕期微量元素钙的摄取,为控制妊娠期高血压的发生和发展提供了新的思路。     

Effects of Renal Function on Plasma Digoxin Levels in Elderly Ambulant Patients in Domiciliary Practice

An investigation into the relations between the daily dose of digoxin, drug regimen, serum digoxin concentration, and creatinine and digoxin clearance was carried out in a group of elderly ambulant patients in domiciliary practice. Moderate to severe impairment of renal function was found both in patients taking digoxin and in elderly control subjects. Plasma digoxin levels were not related to blood urea concentrations or creatinine clearance. Digoxin clearance was less than creatinine clearance. Now that plasma digoxin levels can be measured relatively easily their estimation should become part of clinical practice.     

Effect of acetylsalicylic acid on prostacyclin production in trophoblast

In attempt to elucidate whether acetylsalicylic acid (ASA) has an in vivo effect on prostacyclin (PGI2)-like activity released from trophoblast we have evaluated PGI2-like activity in pregnant women scheduled for pregnancy termination after ASA ingestion. Following subjects were studied: Group I: 7 healthy pregnant women who were treated with 1.5 g ASA for two days; Group II: 18 control pregnant women who received placebo for two days. Trophoblast specimens were obtained by legal abortions; PGI2-like activity in trophoblast was measured by the method of Moncada. In normal pregnant women (8-10 weeks gestation) treated with ASA the mean PGI2-like activity of trophoblast significantly decreased compared to the controls. These data indicate that treatment with ASA of early pregnant women might have a harmful effect on trophoblast and the problem should be further explored before allowing the administration of cyclooxygenase inhibiting drugs during early pregnancy.     

Lead Accumulation as Possible Risk Factor for Primary Open-Angle Glaucoma

The objective of this study was to investigate the relationship between preeclampsia and iodine levels and magnesium concentration in the blood of subjects in the northeast Anatolia region where iodine deficiency is common. Blood specimens were obtained from 24 preeclamptic and 16 healthy pregnant women. Iodine levels in blood were determined by the Foss method based on the Sandell–Kolthoff reaction. Serum protein-bound iodine (PBI) levels and magnesium concentration in maternal blood were lower in patients with severe preeclampsia compared to normal pregnant women (8.46?±?1.22 vs. 11.46?±?1.71 μg/dL, p?<?0.001, 1.63?±?0.05 vs. 1.86?±?0.05 mg/dL, p?<?0.001, respectively). Serum PBI levels and magnesium concentration in umbilical cord blood were higher in patients with severe preeclampsia than in normal pregnant women (8.84?±?1.9 vs. 7.33?±?1.07 μg/dL, p?<?0.05, 2.48?±?0.03 vs. 2.02?±?0.01 mg/dL, p?<?0.001, respectively). There was a positive correlation between the serum PBI levels in maternal blood and magnesium concentration in maternal blood in patients with severe preeclampsia (r?=?0.41, p?<?0.05). Thus, iodine may be one factor contributing to the pathophysiology of preeclampsia. Iodine supplementation may be effective therapy in preeclamptic in pregnant women.     

Serum digoxin in patients with thyroid disease.

Serum digoxin concentrations were measured by radioimmunoassay in 17 hyperthyroid and 16 hypothyroid patients after a seven-day course of oral digoxin. The significantly higher levels of serum digoxin in patients with hypothyroidism and lower levels in those with hyperthyroidism were closely related to the measured changes of glomerular filtration rate and digoxin serum half time in these two groups. Differences in serum digoxin concentration contribute to the altered sensitivity to digoxin shown by patients with thyroid disease.