Sitagliptin down-regulates retinol-binding protein 4 and reduces insulin resistance in gestational diabetes mellitus: a randomized and double-blind trial.

Gestational diabetes mellitus (GDM) is a condition that affects increasing number of pregnant women worldwide. Sitagliptin was reported to alleviate symptoms of type 2 diabetes mellitus by reducing serum levels of retinol-binding protein 4 (RBP-4). We investigated the effectiveness of sitagliptin on insulin sensitivity parameters in GDM patients. Pregnant GDM women in the 2nd trimester were recruited for this study. Participants were then assigned randomly to sitagliptin treatment group or placebo treatment group, and administered sitagliptin or placebo daily for 16 weeks. Glucose and insulin profiles, as well as serum RBP-4 level, were measured at both baseline and end of the study. After 16 weeks of treatment, participants in the STL group exhibited significantly improved levels of fasting plasma glucose and serum insulin, homeostasis model of assessment of ß cell function (HOMA-ß) and insulin resistance (HOMA-IR), compared with those in the placebo group. Serum levels of RBP-4 were also markedly decreased in the sitagliptin treatment group, and more importantly it was positively correlated with improved insulin resistance parameters. Our study supports a potentially promising role of sitagliptin in improving insulin resistance by decreasing RBP-4 in GDM-affected women.

Zinc protection in fetal rats for maternal mercury exposure-induced growth retardation is probably associated with S100B expression.

AIM: The study was conducted to investigate the effects of maternal mercury exposure on fetal rat development and zinc protection in mercury-exposed rats. METHODS: Pregnant rats were subjected to zinc sulfate pre-feeding, mercury exposure and zinc sulfate co-feeding. The control rats were administered distilled water. On day 19, the placental weight, overall weight, size and tail length of fetal rats, mercury content and S100B level in the placenta were determined using Western blot analysis. RESULTS: Compared with the control, mercury exposure at 2.0 mg/kg.d significantly reduced placental weight and fetal development, resulting in reduced fetal weight, size and tail length, while zinc pre-feeding increased placental weight and other fetal developmental parameters. Compared with mercury exposure, co-feeding with zinc significantly reduced mercury-induced injury in the fetal rats. S100B and mercury content levels were significantly elevated in rats maternally exposed to methylmercury chloride, compared with the unexposed control, while co-feeding with methylmercury chloride and zinc sulfate significantly reduced S100B and mercury levels in the placenta. CONCLUSION: Maternal exposure to mercury results in increased S100B in the placenta. Zinc sulfate feeding could reduce S100B and mercury levels, thereby protecting the rats from mercury damage. S100B level may be used to measure the antagonism between zinc and mercury during pregnancy.

Artemisia Extract Improves Insulin Sensitivity in Women With Gestational Diabetes Mellitus by Up-Regulating Adiponectin.

Gestational diabetes mellitus (GDM) has affected a great number of pregnant women worldwide. Artemisia extracts have been found to exhibit a potent antidiabetic effect in the treatment of type 2 diabetes mellitus. We aimed to examine the effects of Artemisia extract on insulin resistance and lipid profiles in pregnant GDM patients. Patients in their second trimester were randomly assigned to the Artemisia extract group (AE) or to a placebo group (PO). They were instructed to consume either AE or PO daily for a period of 10 weeks. Glucose and insulin profiles and adiponectin level were assessed at baseline (week 0) and after the treatment (week 10). Compared to the PO group, fasting plasma glucose, serum insulin levels, homeostasis model of assessment of insulin resistance (HOMA-IR), and ß-cell function (HOMA-B) were significantly reduced in the AE group participants. Moreover, levels of circulating adiponectin were also significantly up-regulated in the AE group, which also positively contributed to improved insulin sensitivity. Daily administration of Artemisia extract improves insulin sensitivity by up-regulating adiponectin in women with gestational diabetes mellitus.

[Expression of glucose regulated protein 78 and the pathogenesis of gestational diabetes mellitus].

OBJECTIVE: To investigate the relationship between the expression of glucose regulated protein 78 (GRP78) in the placental trophoblast cells and the pathogenesis of gestational diabetes mellitus (GDM). METHODS: All the patients were recruited from Qingdao Municipal Hospital from May 2013 to May 2014. Among them, fifty women with GDM were assigned to the GDM group, and fifty healthy women were defined as the control group. All of them received cesarean section because of breech presentation, contracted pelvis, scarred uterus or on mother's demand. Real-time PCR was conducted to analyze the expression of GRP78 mRNA in the trophoblasts. Immunohistochemistry was performed to detect the localization of GRP78 protein in the placentasl trophoblast cells. RESULTS: (1) GRP78 mRNA expressed in the cytoplasm of trophoblasts of both the GDM group and the control group. The GRP78 mRNA levels in the GDM group and the control group were 15.6±0.4 and 6.0±0.7, respectively. The relative expression level of GRP78 mRNA in the GDM group was 2.6 times of that in the control group, with statistically significant difference (P<0.01). (2) The expression of GRP78 protein was found in the cytoplasm of the trophoblasts of the GDM group. It showed in deep, light brown or yellow after staining, according to the expression degree. The expression of GRP78 protein was also found in the cytoplasm of the trophoblasts of the control group, but it mainly showed yellow color (38/50). The strong positive rate of GRP78 protein in the GDM group (96%, 48/50) was higher than that in the control group (22%, 11/50; P<0.01). CONCLUSION: The expression of GRP78 increased in the placental trophoblast cells of GDM patients. It might suggest that GRP78 had some effect on the pathogenesis of GDM.

[Relationship of S100B protein expression and the pathogenesis of early-onset and late-onset preeclampsia].

OBJECTIVE: To investigate the relationship of S100B protein expression and the pathogenesis of early-onset and late-onset preeclampsia. METHODS: Sixty patients with preeclampsia who received caesarean section at Qingdao Municipal Hospital from October 2010 to September 2011 were enrolled in this study. Thirty cases were early-onset preeclampsia (referred as early-onset preeclampsia group, < 34 weeks), and the other 30 cases were late-onset preeclampsia (referred as late-onset preeclampsia group, ≥ 34 weeks). Thirty women who received caesarean section because of pelvic structural deformities, breech presentation, macrosomia and social factors were included as the control group. The expression of S100B mRNA in the placenta was detected by reverse transcription (RT)-PCR. The expression of S100B protein in the placenta was detected by immunohistochemistry. RESULTS: (1) S100B mRNA was expressed in the trophoblasts of preeclampsia and control groups. The expression of S100B mRNA in early-onset preeclampsia group (0.73 ± 0.11) was significantly higher than the control group (0.58 ± 0.08) and late-onset preeclampsia group (0.64 ± 0.10, P < 0.05). There was no significant difference between late-onset preeclampsia group and the control group (P > 0.05). (2) S100B protein was expressed in the plasma membrane and cytoplasm of the trophoblasts, correlated positively with the brownish yellow and brown particles inside the cells. It was expressed in all the three groups. Immunohistochemistry revealed that the expression of S100B protein in the placenta of early-onset preeclampsia group was 100% (30/30), significantly higher than those of late-onset preeclampsia group and the control group, in which the positive rate were 70% (21/30) and 63% (19/30) respectively (P < 0.05). There was no difference between late-onset preeclampsia group and the control group (P > 0.05). CONCLUSION: Early-onset and late-onset preeclampsia may have different etiology and pathogenesis. S100B may be a factor in the pathogenesis of early-onset preeclampsia.

[Effects of transient receptor potential V6 silence on proliferation and apoptosis of trophoblasts].

OBJECTIVE: To investigate the effects of the transient receptor potential V6 (TRPV6) gene silencing on the proliferation and apoptosis of trophoblasts HTR-8/SVneo cells. METHODS: siRNA sequences targeting the TRPV6 gene were constructed and then transfected into HTR-8/SVneo cells mediated by liposome. The cells were divided three groups, including blank control (add the reagent of transfenction), negative control groups (transfecting nonspecific siRNA) and experimental groups (transfecting TRPV6-siRNA). Those cells in every group were collected at 24, 48, 72 hours after transfecting. The expression levels of TRPV6 mRNA were detected by reverse transcription (RT) PCR at different times after transfecting. The effects of siRNA on the proliferation and apoptosis of the cells were assayed by methyl thiagolyl tetragolium (MTT) and flow cytometry at different times after transfecting. RESULTS: siRNA TRPV6 transfection could inhibit the expression of TRPV6 mRNA in the HTR-8/SVneo cells. The expression was decreased with the extension of time, by 0.72 ± 0.02, 0.54 ± 0.02 and 0.29 ± 0.01 after 12, 48 and 72 hours of siRNA transfection as compared with the blank control and the negative control groups (P < 0.01). The rates of proliferation inhibition were (19.29 ± 1.23)%, (32.12 ± 1.35)% and (46.51 ± 1.42)% at 24, 48 and 72 hours respectively when compared with the blank control (2.12 ± 0.03)%, (2.42 ± 0.02)%, (3.13 ± 0.04)% and the negative control groups (2.37 ± 0.01)%, (2.61 ± 0.05)%, (2.93 ± 0.03)% (P < 0.01). The apoptosis rates of HTR-8/SVneo cells was 16.21% at 48 hours after transfected with siRNA TRPV6, which were significantly higher than 3.27% in the blank control and 5.34% in the negative control groups (P < 0.05). CONCLUSION: Silenceing of TRPV6 genen could inhibit the proliferation and increase the apoptosis of extravillous trophoblas of human placenta.

[Efficacy and delivery outcomes of women underwent double-catheter epidural block during labor].

OBJECTIVE: To investigate the efficacy and pregnancy outcomes of women receiving double-catheter epidural block in labor analgesia, and compare the results with single-catheter epidural block. METHODS: A double-blind clinical trial was conducted on 206 full-term singleton primiparas, aged 25 - 35 and at the 37 - 42 weeks of gestation who delivered at the Department of Obstetrics, Qingdao Municipal Hospital from August 2006 to December 2008, which were randomly divided into two groups: double-catheter epidural block (group D, n = 103) and single-catheter epidural-block (group S, n = 103). Women in group D were given mixture of 0.1% repivacaine hydrochloride and 0.5 mg/L sufentinil 4 - 6 ml as initial dose. Patient control epidural analgesia pump (PCEA) was connected with the upper catheter after 45 minutes. A bolus dose of 4 - 6 ml analgesia mixture was infused according to the condition through the lower catheter. Women in group S received analgesia mixture 10 - 15 ml as initial dose and PCEA pump was connected after 45 minutes. Oxytocin was infused in both groups according to uterine contraction after 30 minutes. The following indexes was observed: (1) visual analogue scales (VAS); (2)modified Bromage Scores; (3) the total dose of analgesia mixture, the percentage of oxytocin infusion, duration of labor and duration of the second stage of labor; (4) fetal birth weight and Apgar scores (1, 5 minutes); (5) mode of delivery; (6) the concentration of plasma cortisol and angiotension II at the beginning of regular uterine contraction and at the time when cervical dilated to 4 cm and 10 cm and fetal disengagement; (7) anesthesia-related complications. RESULTS: (1) The neonatal birth weight and Apgar scores (1, 5 minutes) of group D were (3456 ± 468) g, 9.8 ± 0.6 and 9.9 ± 0.7, respectively, while (3399 ± 569) g, 9.8 ± 0.5 and 9.9 ± 0.7 in group S (P > 0.05). No motor function block was reported in any group and the modified Bromage score was zero. (2) The total dose of analgesia mixture in group D was similar to that in group S [(57 ± 9) ml vs. (58 ± 11) ml, P > 0.05]. However, the percentage of women received oxytocin in group D was smaller [59.2% (61/103) vs. 81.6% (84/103), P < 0.01], and the total time of labor and the duration of second stage of labor in group D were shorter [(532 ± 140) minutes vs. (608 ± 150) minutes; (46 ± 31) minutes vs. (60 ± 34) minutes, P < 0.05]. (3) There were no significant differences in VAS at 30 minutes after initial dose and in the first stage of labor between group D and S (1.2 ± 1.1 vs 1.2 ± 1.1, 1.1 ± 1.1 vs. 1.2 ± 1.0, P > 0.05). VAS at the second stage of labor stage was lower in group D than in group S (1.2 ± 1.1 vs. 4.5 ± 2.2, P < 0.01). (4) The rate of cesarean section, instrumental delivery and episiotomy in group D were lower than in group S (7.8% vs. 17.5%, 7.8% vs. 15.5%, 10.7% vs. 18.4%, P < 0.05). The incidence of fetal distress and meconium-stained amniotic fluid as the indication of cesarean section were similar between the two groups (P > 0.05). Lower incidence of fetal malpresentation and arrested second stage of labor were shown in group D than in group S (2.9% vs. 9.7%, 1.0% vs. 5.8%, P < 0.05). (5) The concentration of plasma cortisol and angiotension II were lower in group D than in group S [(86 ± 25) ng/L vs. (100 ± 20) ng/L, (278 ± 53) nmol/L vs. (311 ± 53) nmol/L, P < 0.05] only at the end of second stage of labor, but not at any other times (P > 0.05). (6) No serious anesthesia-related complications were reported in any groups. Some light backache around the puncture point were complained by 29.1% (30/103) of the women in group D and 31.1% (32/103) in group S (P > 0.05). CONCLUSION: Double-catheter epidural block can provide better analgesia effect during labor than single-catheter epidural block, without any adverse influence on delivery outcomes.

[Study on the relation between concentration of circulating non-host fetal DNA in pregnant women and pre-eclampsia].

OBJECTIVE: To explore the diagnostic value of plasma fetal DNA level in preeclampsia. METHODS: Thirty cases of pregnant women with preeclampsia (at 33 weeks and 3 days) and 30 cases of normal pregnant women (at 34 weeks and 3 days) were selected. All the pregnant women carried a male fetus by B-ultrasound, and were sampled at gestational 20 weeks, third trimester and at 1 hour, 3 hours, 6 hours after delivery. SRY levels in maternal blood were quantitated by polymerase chain reaction (QF-PCR). The endotheliotoxin (ET) level was measured with RIA. RESULTS: (1) Mean fetal DNA level of patients with preeclampsia at 20 weeks of gestation was (316 +/- 61) copy/ml. They were (266 +/- 79) copy/ml, (396 +/- 91) copy/ml, (165 +/- 43) copy/ml for light and severe preeclampsia women and normal pregnant women, respectively. Maternal blood fetal DNA levels in pregnant women with preeclampsia at 20-weeks of gestation were significantly higher than those normal pregnant women (P < 0.01). (2) Mean fetal DNA level of patients with preeclampsia in third trimester was (970 +/- 413) copy/ml. They were (758 +/- 357) copy/ml, (1285 +/- 573) copy/ml, (319 +/- 99) copy/ml for light and severe preeclampsia and normal pregnant women, respectively. Maternal blood fetal DNA levels in pregnant women with preeclampsia in third trimester were significantly higher than those normal pregnant women (P < 0.01). (3) Maternal blood mean fetal DNA level of patients with preeclampsia were (139 +/- 45) copy/ml, (76 +/- 31) copy/ml, (44 +/- 13) copy/ml at 1 hour, 3 hours, and 6 hours after delivery, respectively. Mean fetal DNA level was (102 +/- 42) copy/ml, (57 +/- 25) copy/ml, (36 +/- 12) copy/ml for patients with light preeclampsia, (209 +/- 51) copy/ml, (97 +/- 40) copy/ml, (52 +/- 17) copy/ml for patients with severe preeclampsia, and (33 +/- 13) copy/ml, (9 +/- 5) copy/ml, 0 copy/ml for normal pregnant women. Significant difference was found between preeclampsia and control groups (P < 0.01). (4) The mean endotheliotoxin level for preeclampsia women was (80 +/- 18) ng/L. For light preeclampsia, severe preeclampsia and normal pregnant women ET levels were (74 +/- 14) ng/L, (89 +/- 32) ng/L, (50 +/- 11) ng/L, respectively. ET levels in pregnant women with preeclampsia were significantly higher than those normal pregnant women (P < 0.01). (5) A positive correlation was found between fetal DNA levels and ET levels in preeclampsia group (r = 0.748, P < 0.01). CONCLUSION: The fetal DNA determination may help diagnose preeclampsia.

[Study on the time selection of pregnancy and delivery in women with systemic lupus erythematosus].

OBJECTIVE: To analyze the appropriate time selection of pregnancy and delivery in women with systemic lupus erythematosus (SLE). METHODS: Twenty-nine pregnancies in women with SLE in our hospital from 1998 to 2003 were retrospectively analyzed regarding the selection of appropriate time of pregnancy and delivery. RESULTS: All patients did not take any cytotoxic medicine for at least 6 months before pregnancy. Twenty-three conceptions occurred when SLE was inactive for at least 1 year. Two conceptions occurred when SLE was active without doctors' agreement. SLE was diagnosed during pregnancy in the remaining 4 cases. The condition of all patients fluctuated and the gestational time at delivery ranged from 30 to 38 weeks after we modified the doses of glucocorticoid (prednisone). Among totally 29 living neonates, eight were premature neonates, three were FGR and one had serious congenital heart disease. Two neonates died of complications in early stage of neonatal period. None of the 29 neonates from all patients had neonatal lupus. CONCLUSION: Pregnancy safety will be improved obviously if the condition of SLE is controlled and the patients are given reasonable doses of glucocorticoid and intensive monitoring. If pharmacotherapy does not work well and the condition threatens the safety of mother and fetus, or the fetus has matured, termination of pregnancy should be done on time, which reduces maternal complications and improves the perinatal mortality rate. The gestational time should be 34 to 38 weeks.

Clinical study on labor pain relief using the combined spinal-epidural analgesia and inhaling nitrous oxide.

OBJECTIVE: To study the pain relief effectiveness of the combined spinal-epidural analgesia (CSEA) and the inhalation of nitrous oxide, and the influences on the mothers and infants. METHODS: The 300 cases of pregnant women were randomly divided into 3 groups: CSEA group, nitrous oxide group and control group. The nitrous oxide group was that pregnant women inhaled nitrous oxide premixed with oxygen (50%:50%), the pregnant women of the CSEA group were injected fentanyl and bupivacaine in the subarachnoid and epidural space, analgesic was not used in the control group. The degree of labor pain, duration of the labor, way of delivery, bleeding volume, rate of anoxia of newborn, blood gas analysis to maternal radius artery and fetal umbilical blood among 3 groups were observed. RESULTS: The effect for analgesia labor of the CSEA group was much better than that of the nitrous oxide group (P < 0.01). In the first stage of labor and total stage of labor, the CSEA group was shorter than the others (P < 0.05), but there was no difference between the nitrous oxide group and the control group (P > 0.05). In the second stage of labor, the 3 groups were alike to each other. The bleeding volume of caesarean section (373 +/- 77) ml in the nitrous oxide group was much more than the other 2 groups, there was no difference between the CSEA group (259 +/- 78) ml and the control group (239 +/- 89) ml. The rate of obstetric forceps of CSEA group was higher than the control group (P < 0.01), and the rate of caesarean section of the nitrous oxide group was much higher than the CSEA group. The blood gas analysis to maternal radius artery and fetal umbilical blood and the rate of anoxia of newborn of 3 groups revealed no significant difference. CONCLUSIONS: The effectiveness of the combined spinal-epidural analgesia CSEA for analgesia labor is confirmed and has rarely side-effect, and it can be the first choice, and the inhalation of nitrous oxide can safely provide effective labor analgesia, too.