Large-for-Gestational-Age, Leptin, and Adiponectin in Infancy.

CONTEXT: Fetal overgrowth "programs" an elevated risk of obesity and type 2 diabetes in adulthood. Plausibly, adipokines may be involved in programming metabolic health. OBJECTIVE: This work aimed to evaluate whether large-for-gestational-age (LGA), an indicator of fetal overgrowth, is associated with altered circulating leptin and adiponectin levels in infancy, and assess the determinants. METHODS: In the Canadian 3D birth cohort, we studied 70 LGA (birth weight > 90th percentile) and 140 optimal-for-gestational-age (OGA, 25th-75th percentiles) infants matched by maternal ethnicity, smoking, and gestational age at delivery. The primary outcomes were fasting leptin, and total and high-molecular-weight (HMW) adiponectin concentrations at age 2 years. RESULTS: LGA infants had higher body mass index (BMI) than OGA infants. However, there were no significant differences in leptin, and total and HMW adiponectin concentrations. Leptin concentrations were positively associated with female sex, weight (z score) gain 0 to 24 months, current BMI, and the sum of triceps and subscapular skinfold thickness, and negatively associated with maternal age and White ethnicity. Female sex was associated with lower total and HMW adiponectin concentrations. Weight (z score) gain 0 to 24 months and current BMI were positively correlated with total and HMW adiponectin concentrations in LGA infants only. CONCLUSION: This study is the first to demonstrate that LGA does not matter for circulating leptin and adiponectin concentrations in infancy, and there may be LGA-specific positive associations between weight gain or current BMI and adiponectin concentrations in infancy, suggesting dysfunction in establishing the adiposity-adiponectin negative feedback loop in LGA individuals.

Large birth size, infancy growth pattern, insulin resistance and ß-cell function.

OBJECTIVE: Large birth size programs an elevated risk of type 2 diabetes in adulthood, but data are absent concerning glucose metabolic health impact in infancy. We sought to determine whether the large birth size is associated with insulin resistance and ß-cell function in infancy and evaluate the determinants. DESIGN AND PARTICIPANTS: In the Canadian 3D birth cohort, we conducted a nested matched (1:2) study of 70 large-for-gestational-age (LGA, birth weight >90th percentile) and 140 optimal-for-gestational-age (OGA, 25th-75th percentiles) control infants. The primary outcomes were homeostasis model assessment of insulin resistance (HOMA-IR) and beta-cell function (HOMA-ß) at age 2-years. RESULTS: HOMA-IR and HOMA-ß were similar in LGA and OGA infants. Adjusting for maternal and infant characteristics, decelerated growth in length during early infancy (0-3 months) was associated with a 25.8% decrease (95% confidence intervals 6.7-41.0%) in HOMA-ß. During mid-infancy (3-12 months), accelerated growth in weight was associated with a 25.5% (0.35-56.9%) increase in HOMA-IR, in length with a 69.3% increase (31.4-118.0%) in HOMA-IR and a 24.5% (0.52-54.3%) increase in HOMA-ß. Decelerated growth in length during late infancy (1-2 years) was associated with a 28.4% (9.5-43.4%) decrease in HOMA-IR and a 21.2% (3.9-35.4%) decrease in HOMA-ß. Female sex was associated with higher HOMA-ß, Caucasian ethnicity with lower HOMA-IR, and maternal smoking with lower HOMA-ß. CONCLUSIONS: This study is the first to demonstrate that large birth size is not associated with insulin resistance and ß-cell function in infancy but infancy growth pattern matters. Decelerated infancy growth may be detrimental to beta-cell function.

Insecticidal effect of aconitine on the rice brown planthoppers.

The brown planthopper, Nilaparvata lugens (Stål), severely damages rice production and develops high level resistance to several classes of insecticides. To find potential insecticidal resources is always important. As an environmentally friendly compound, aconitine exhibits potential pesticide features. In the present study, the pesticide and knockdown effects of aconitine were first tested on the brown planthopper. The results showed that the knockdown rates for an aconitine concentration of 200 ppm was 83.6%. The insecticidal LD50 was 22.68 ng/pest (95% CI, 17.75-28.99). The molecular mechanisms responding to aconitine application were analyzed through transcriptional sequencing. Compared to that of the knockdown nymphs of the brown planthoppers, the enzymes CYP3A4, UDP-glucuronosyltransferase (UGT), GST, carboxylesterase (EC3.1.1.1), and GABAergic synapse were up-regulated. We inferred that aconitine might be neurotoxic to the brown planthoppers, and the conscious nymphs resist the drug neurotoxicity through the upregulation of CYP3A4, UGT, and GABA receptor mutation. Although aconitine is not safe for mammals, it may be a leading compound to develop novel insecticides.

Large-for-Gestational-Age May Be Associated With Lower Fetal Insulin Sensitivity and ß-Cell Function Linked to Leptin.

Context: Fetal overgrowth is associated with increased risk for type 2 diabetes in adulthood. It is unclear whether there are alterations in insulin sensitivity and ß-cell function in early life. Objective: To determine whether large-for-gestational-age (LGA) (birth weight > 90th percentile), an indicator of fetal overgrowth, is associated with altered fetal insulin sensitivity and ß-cell function. Study Design, Population, and Outcomes: In the Design, Development, and Discover birth cohort in Canada, we studied 106 pairs of LGA and optimal-for-gestational-age (OGA; birth weight, 25th to 75th percentiles) infants matched by maternal ethnicity, smoking status, and gestational age. Cord plasma glucose-to-insulin ratio was used as an indicator of fetal insulin sensitivity, and proinsulin-to-insulin ratio was used as an indicator of ß-cell function. Cord plasma leptin and high-molecular-weight (HMW) adiponectin concentrations were measured. Results: Comparisons of infants who were born LGA vs OGA, adjusted for maternal and newborn characteristics, showed that cord blood insulin, proinsulin, and leptin concentrations were significantly higher, whereas HWM adiponectin concentrations were similar. Glucose-to-insulin ratios were significantly lower (15.4 ± 28.1 vs 22.0 ± 24.9; P = 0.004), and proinsulin-to-insulin ratios significantly higher (0.73 ± 0.82 vs 0.60 ± 0.78; P = 0.005) in LGA vs OGA newborns, indicating lower insulin sensitivity and ß-cell function in LGA newborns. These significant differences were almost unchanged after further adjustment for cord blood adiponectin levels but disappeared upon additional adjustment for cord blood leptin levels. Conclusions: This study demonstrates that LGA may be associated with decreases in both fetal insulin sensitivity and ß-cell function. The alterations appear to be linked to elevated leptin levels.

Plasma cotinine indicates an increased risk of preeclampsia in previous and passive smokers.

OBJECTIVE: Self-reported tobacco smoking in pregnancy has been consistently associated with a decreased risk of developing preeclampsia, but the evidence has been limited and inconsistent for previous and passive smokers. Misclassifications and inaccuracies of self-reported tobacco exposure may disguise the true relationship. This study aimed to assess the association of gestational hypertension and preeclampsia with maternal smoking status as ascertained by plasma cotinine. STUDY DESIGN: This was a prospective study of 605 pregnant women without chronic hypertension. Maternal smoking status at 24-26 weeks' gestation was defined by plasma cotinine: >3.0 ng/mL "current smokers," 0.20-3.00 ng/mL "previous and passive smokers," and <0.20 ng/mL "nonsmokers." RESULTS: Compared to nonsmokers, the risk of developing preeclampsia did not change significantly for current smokers, but increased significantly (adjusted odds ratio, 6.06; 95% confidence interval, 2.32-15.85; P < .001) for previous and passive smokers. There were no significant differences in the risk of developing gestational hypertension only. CONCLUSION: Previous and passive smoking may increase the risk of preeclampsia. Avoidance of exposure to environmental tobacco smoke in pregnancy may decrease the risk of preeclampsia.

Maternal plasma 25-hydroxyvitamin D levels, angiogenic factors, and preeclampsia.

OBJECTIVE: The objective of the study was to examine the associations of maternal plasma levels of 25-hydroxyvitamin D [25(OH)D] with angiogenesis and endothelial dysfunction indicators: soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), intercellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1), and risk of preeclampsia. STUDY DESIGN: In this prospective cohort study (n = 697), maternal plasma 25(OH)D levels were measured at 12-18 and 24-26 weeks; sFlt-1, PlGF, ICAM-1, and VCAM-1 levels were measured at 24-26 weeks. RESULTS: Maternal PlGF levels were significantly lower in women with 25(OH)D less than 50 nmol/L at 12-18 weeks (median, 449.5 vs 507.9 pg/mL, P = 0.04) and 24-26 weeks (median, 450.4 vs 522.5 pg/mL, P = 0.007). Both maternal 25(OH)D and PlGF levels were inversely associated with the risk of preeclampsia (both P < .05). However, based on a test of interaction, there was no evidence that the association between vitamin D and preeclampsia depended on the level of PlGF. CONCLUSION: Maternal vitamin D deficiency is associated with low PlGF levels and increased preeclampsia risk. However, our data do not support the hypothesis that the association between vitamin D deficiency and preeclampsia is mediated by impaired angiogenesis.

Risks for preeclampsia and small for gestational age: predictive values of placental growth factor, soluble fms-like tyrosine kinase-1, and inhibin A in singleton and multiple-gestation pregnancies.

OBJECTIVE: To determine the accuracy of placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1), and inhibin A in singleton and multiple-gestation pregnancies for predicting preeclampsia (PE) and small for gestational age (SGA). STUDY DESIGN: A prospective cohort nested in a randomized controlled trial of antioxidant supplementation for the prevention of PE. Plasma biomarkers were evaluated at 12 to 18 (visit 1) and 24 to 26 (visit 2) weeks' gestation and expressed as adjusted multiples of the median. RESULTS: Multiple-gestation pregnancy (74/772) had a significant impact on all biomarkers' levels. PlGF was the best predictor of PE and SGA. At a 10% false-positive rate, PlGF at visit 1 had 21% sensitivity for predicting PE in singleton versus 60% in multiple-gestation pregnancies. PlGF at visit 1 had a 31% sensitivity in singleton and 27% in multiple-gestation pregnancies for SGA prediction. CONCLUSION: PlGF level was a good predictor of subsequent PE as early as 12 to 18 weeks in multiple-gestation pregnancies but was not clinically useful enough to be used as a single marker.

Intravitreal versus subtenon triamcinolone acetonide injection for diabetic macular edema: a systematic review and meta-analysis.

OBJECTIVE: To compare the efficacy of intravitreal (IV) triamcinolone acetonide (IVTA) versus subtenon (ST) triamcinolone acetonide (STTA) injection for the treatment of diabetic macular edema (DME). METHODS: Searches for randomized clinical trials published between 1 January 1950 and 15 March 2011 were conducted using PubMed, MEDLINE, EMBASE, and the Cochrane Library included in the present meta-analysis are five randomized controlled trials, each with a minimum follow-up of 3 mo. All included studies evaluated the efficacy of TA for the treatment of refractory DME, and compared IVTA with STTA by measuring visual acuity (VA), central macular thickness (CMT), and intraocular pressure (IOP). RESULTS: One mo post-injection, treatment with IVTA had significantly improved VA (MD, -0.14 logMAR; 95% CI = -0.16 to -0.13) and reduced CMT (MD = -174.02 µm; 95% CI = -249.97 to -98.08) compared with STTA. At 3 mo post-injection, treatment with IVTA had significantly improved VA (MD = -0.07 logMAR; 95% CI = -0.09 to -0.05) and reduced CMT (MD = -119.46 µm; 95% CI = -176.55 to -62.36) compared with STTA. The benefits of either treatment were no longer significant at 6 mo, and patients had to be retreated. Compared with STTA, IVTA injections produced no difference in IOPs at 1 mo, higher IOPs at 3 mo, and lower IOP values at 6 months CONCLUSIONS: Within 3 mo, IVTA is more effective than is STTA in improving VA and reducing CMT in patients with refractory DME. However, the benefits of either regimen were no longer evident at 6 mo.

IL-6-174 G/C and -572 C/G polymorphisms and risk of Alzheimer's disease.

Associations between interleukin 6 (IL-6) polymorphisms and Alzheimer's disease (AD) remain controversial and ambiguous. The aim of this meta-analysis is to explore more precise estimations for the relationship between IL-6-174 G/C and -572 C/G polymorphisms and risk for AD. Electronic searches for all publications in databases PubMed and EMBASE were conducted on the associations between IL-6 polymorphisms and risk for AD until January 2012. Odds ratio (OR) and 95% confidence intervals (CIs) were calculated using fixed and random effects models. Twenty-seven studies were included with a total of 19,135 individuals, involving 6,632 AD patients and 12,503 controls. For IL-6-174 G/C polymorphism, the combined results showed significant differences in recessive model (CC vs. CG+GG: OR = 0.65, 95%CI = 0.52-0.82). As regards IL-6-572 C/G polymorphism, significant associations were shown in dominant model (CG+GG vs. CC: OR= 0.73, 95% CI = 0.62-0.86) and in additive model (GG vs. CC, OR= 0.66, 95% CI = 0.46-0.96). In conclusion, genotype CC of IL-6-174 G/C and genotype GG plus GC of IL-6-572 C/G could decrease the risk of AD.

Ursodeoxycholic acid prevents selenite-induced oxidative stress and alleviates cataract formation: In vitro and in vivo studies.

OBJECTIVE: To evaluate the antioxidative and anticataractogenic potential effect of ursodeoxycholic acid (UDCA) on selenite-induced cataract in vitro and in vivo. METHODS: Enucleated rat lenses were incubated in M199 medium alone (Group I), with 200 µM selenite (Group II), or with 200 µM selenite and 500 µM UDCA (Group III). Selenite was administered on the third day and UDCA treatment was from the second to the fifth day. The development of cataracts was observed under an inverted microscope. Total antioxidative capabilities (T-AOC), mean activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (Gpx), glutathione reductase (GR) and glutathione S-transferase (GST), levels of reduced glutathione (GSH), malondialdehyde (MDA), and total sulfhydryl content were analyzed in lenticular samples. In vivo, cataracts were induced in 12-day-old pups by single subcutaneous injections of sodium selenite. The test groups received 180 mg/kg bodyweight/day of UDCA intraperitoneally on postpartum days 11-16 or 0.5% UDCA drops four times daily on postpartum days 11-25. RESULTS: In vitro, morphological examination of the lenses revealed dense vacuolization and opacification in Group II, minimal vacuolization in 12.5% of Group III, and no opacification in 87.5% of Group III. In Group I, all lenses were clear. UDCA significantly (p<0.05) restored GSH and total sulfhydryl, and decreased MDA levels. T-AOC and the mean activities of the antioxidant enzymes were elevated following treatment with UDCA. In vivo, 0.5% UDCA drops resulted in only 20% nuclear cataract development and 180 mg/kg of UDCA intraperitoneally led to 50% development, compared to 100% in the control group (p<0.05). CONCLUSIONS: UDCA prevents selenite toxicity and cataractogenesis by maintaining antioxidant status and GSH, protecting the sulfhydryl group, and inhibiting lipid peroxidation in lenses.

Inflammatory cytokines and spontaneous preterm birth in asymptomatic women: a systematic review.

OBJECTIVE: To estimate the association between inflammatory cytokines and the risk of spontaneous preterm birth in asymptomatic women. DATA SOURCES: We searched electronic databases of the human literature in PubMed, EMBASE, and the Cochrane Library up to February 2010 using the following key words: "preterm/pre-term + (birth/delivery)" and "cytokine" or "inflammation/inflammatory + marker/biomarker." METHODS OF STUDY SELECTION: We included observational studies that reported the association between common inflammatory cytokines and spontaneous preterm birth as an outcome in asymptomatic women. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using fixed and random effects models. TABULATION, INTEGRATION, AND RESULTS: Seventeen primary studies comprising 6,270 participants met the inclusion criteria. Spontaneous preterm birth was strongly associated with increased levels of interleukin-6 (IL-6) in midtrimester cervicovaginal fluid (OR 3.05, 95% CI 2.00-4.67) (number needed to treat=7 for identifying an additional preterm delivery) and amniotic fluid (OR 4.52, 95% CI 2.67-7.65) (number needed to treat=7), but there was no association in plasma specimen (OR 1.5, 95% CI 0.7-3.0). Spontaneous preterm birth was strongly associated with increased C-reactive protein (CRP) levels in midtrimester amniotic fluid (OR 7.85, 95% CI 3.88-15.87) (number needed to treat=3), but the association was weak in plasma specimen (OR 1.53, 95% CI 1.22-1.90). There were insufficient data (fewer than three studies) for meta-analysis in other inflammatory cytokines. CONCLUSION: Inflammatory cytokine IL-6 in cervicovaginal fluid and IL-6 and CRP in amniotic fluid but not in plasma are strongly associated with spontaneous preterm birth in asymptomatic women, suggesting that inflammation at the maternal-fetal interface, rather than systemic inflammation, may play a major role in the etiology of such spontaneous preterm births.

An international trial of antioxidants in the prevention of preeclampsia (INTAPP).

OBJECTIVE: We sought to investigate whether prenatal vitamin C and E supplementation reduces the incidence of gestational hypertension (GH) and its adverse conditions among high- and low-risk women. STUDY DESIGN: In a multicenter randomized controlled trial, women were stratified by the risk status and assigned to daily treatment (1 g vitamin C and 400 IU vitamin E) or placebo. The primary outcome was GH and its adverse conditions. RESULTS: Of the 2647 women randomized, 2363 were included in the analysis. There was no difference in the risk of GH and its adverse conditions between groups (relative risk, 0.99; 95% confidence interval, 0.78-1.26). However, vitamins C and E increased the risk of fetal loss or perinatal death (nonprespecified) as well as preterm prelabor rupture of membranes. CONCLUSION: Vitamin C and E supplementation did not reduce the rate of preeclampsia or GH, but increased the risk of fetal loss or perinatal death and preterm prelabor rupture of membranes.

[Experimental therapy of survivin antisense oligonucleotide for human ovarian cancer cell SKOV3].

BACKGROUND & OBJECTIVE: Survivin abnormally overexpresses in a variety of human tumors, it may play an important role in the development of tumor. This study was designed to investigate the inhibitory effects of survivin antisense oligonucleotide (ASODN) on human ovarian carcinoma cell SKOV3 in vivo and its mechanism. METHODS: SKOV3 cells were transfected with survivin ASODN mediated by DOTAP liposome reagent, MTT method was used to observe the inhibitory rate, Western blot analysis was used to determine relating gene expression. Flow cytometry, DNA ladder analysis, and DAPI staining were used to examine cell apoptosis. Kinase activity test was used to examine the changes of caspase-3 activity. RESULTS: The expression of survivin in SKOV3 cells decreased after transfected with survivin ASODN. Survivin ASODN has obviously inhibited the growth of SKOV3 cells after transfection. The inhibitory rate of 1000 ng/ml ASODN transfection group was (60.30+/-2.95)%, which is obviously higher than control group (P< 0.05). Survivin ASODN transfection induced cell cycle arrest in G1 phrase, while the apoptotic rate increased from 0.65% to 32.10%. Caspase-3 activity (0.998+/-0.001) increased significantly after transfected with survivin ASODN (P< 0.01). CONCLUSION: Survivin ASODN,which can inhibit human ovarian carcinoma SKOV3 cells proliferation and induce apoptosis, is a prospective anti-cancer drug.

Role of ERK1/2 kinase in cisplatin-induced apoptosis in human ovarian carcinoma cells.

OBJECTIVE: To investigate the role of extracellular regulated kinase (ERK1/2) pathway in cisplatin-induced apoptosis in human ovarian carcinoma cells. METHODS: Cisplatin-induced apoptosis were stained with DAPI and was assessed microscopically in human epithelial adenocarcinoma ovarian cell line SKOV3 cells. ERK activation was determined by Western blotting using an anti-phospho-ERK antibody to detect ERK activity. The effect of PD98059 on ERK activity induced by cisplatin was detected by MTT assay. RESULTS: Marked apoptosis of SKOV3 cells resulted from 48 hours treatment with 20 microg/mL cisplatin. Strong activation of ERK was led to by 15 microg/mL cisplatin. Dose response and time course of cisplatin induced apoptosis in SKOV3 cells. Cisplatin-induced ERK activation occurred at 12 hours and increased to highest induction at 24 hours by Western blotting. The effect of PD 98059 on ERK activity induced by cisplatin at the concentration of 100 micromol/L PD 98059. Statistically significant decreased in cell survival were observed with 100 micromol/L PD 98059 at 15 and 20 microg/mL cisplatin (P < 0.05). CONCLUSIONS: Cisplatin activates the ERK signaling pathway in ovarian cancer cell line SKOV3. Inhibition of ERK activity enhances sensitivity to cisplatin cytotoxity in ovarian cancer cell line SKOV3. Evaluation of ERK activity could be useful in predicting which ovarian cancer will response most favorably to cisplatin therapy.