Predictive value of cystatin C and beta-2 microglobulin in preeclampsia

The purpose of this study was to determine whether the levels of cystatin C and beta-2 microglobulin (B2M) are altered during the second trimester in the plasma of women who subsequently develop preeclampsia.Study designWe performed a case control study to compare the levels of cystatin C and B2M in women in whom preeclampsia ultimately developed (n = 30) and in pregnant women who remained normotensive throughout gestation (n = 60). The maternal plasma levels of cystatin C and B2M were measured by enzyme-linked immunosorbent assay. Blood samples were collected between 15 and 20 weeks’ gestation for fetal aneuploidy screening and frozen at ?20 °C until assay after groups had been selected.ResultsThe median concentrations of cystatin C and B2M were significantly higher in those who subsequently developed preeclampsia when compared to those of normal pregnancy (median 668.6 ng/ml and 418.3 μg/ml vs 413.7 ng/ml and 321.2 μg/ml, respectively).ConclusionsIn this study, the maternal plasma levels of cystatin C and B2M were significantly elevated in pregnant women who subsequently developed preeclampsia as compared with normotensive women. Alterations of these proteins antedate clinical symptoms and, thus, they may be useful for early identification of patients at the risk of developing preeclampsia.     

Identification of new potent inhibitor of aldose reductase from Ocimum basilicum

Recent efforts to develop cure for chronic diabetic complications have led to the discovery of potent inhibitors against aldose reductase (AKR1B1, EC 1.1.1.21) whose role in diabetes is well-evident. In the present work, two new natural products were isolated from the ariel part of Ocimum basilicum; 7-(3-hydroxypropyl)-3-methyl-8-β-O-d-glucoside-2H-chromen-2-one (1) and E-4-(6′-hydroxyhex-3′-en-1-yl)phenyl propionate (2) and confirmed their structures with different spectroscopic techniques including NMR spectroscopy etc. The isolated compounds (1, 2) were evaluated for in vitro inhibitory activity against aldose reductase (AKR1B1) and aldehyde reductase (AKR1A1). The natural product (1) showed better inhibitory activity for AKR1B1 with IC₅₀ value of 2.095 ± 0.77 µM compare to standard sorbinil (IC₅₀ = 3.14 ± 0.02 µM). Moreover, the compound (1) also showed multifolds higher activity (IC₅₀ = 0.783 ± 0.07 µM) against AKR1A1 as compared to standard valproic acid (IC₅₀ = 57.4 ± 0.89 µM). However, the natural product (2) showed slightly lower activity for AKR1B1 (IC₅₀ = 4.324 ± 1.25 µM). Moreover, the molecular docking studies of the potent inhibitors were also performed to identify the putative binding modes within the active site of aldose/aldehyde reductases.     

Chromene-3-carboxamide derivatives discovered from virtual screening as potent inhibitors of the tumour maker,AKR1B10

A human aldose reductase-like protein, AKR1B10 in the aldo-keto reductase (AKR) superfamily, was recently identified as a therapeutic target in the treatment of several types of cancer. In order to identify potential leads for new inhibitors of AKR1B10, we adopted the virtual screening approach using the automated program icm, which resulted in the discovery of several chromene-3-carboxamide derivatives as potent competitive inhibitors. The most potent (Z)-2-(4-methoxyphenylimino)-7-hydroxy-N-(pyridin-2-yl)-2H-chromene-3-carboxamide inhibited the reductase activity of AKR1B10 with a K_i value of 2.7 nM, and the metabolism of farnesal and 4-hydroxynonenal in the AKR1B10-overexpressed cells from 0.1 μM with an IC₅₀ value equal to 0.8 μM.     

Transgenic barley expressing the Arabidopsis AKR4C9 aldo-keto reductase enzyme exhibits enhanced freezing tolerance and regenerative capacity

Aldo-keto reductase (AKR) enzymes contribute to reactive aldehyde detoxifying capacity and to osmotic stress protection of various plant species. The protective effects of these enzymes have already been well characterised but only limited information has been gained on the role of AKRs in frost tolerance. The approach to study frost tolerance was based on transgenic barley (Hordeum vulgare L.) carrying and expressing the Arabidopsis thaliana At2g37770.2 gene (coding AKR4C9) under constitutive regulation. We demonstrated that the osmoprotective sugar alcohol sorbitol was present in both non-transgenic (WT) and transgenic barley plants. The increase of the sorbitol concentration was around 2- and 4-fold higher in the low (line C2) and in the high (line C1) AKR4C9-expressing transgenic line, respectively, compared to WT. Furthermore by applying three subsequent, identical − 20 °C treatments 94.7% of all the leaves of WT plants had died, but only 80% in the case of transgenic line C1. The average electrolyte leakage of the transgenic plants (line C1) was lower than that of WT plants. Line C1 plant also had significantly higher fresh weight than the WT after 6 days of recovery following frost-treatment. Transgenic line C2 had an intermediate freezing tolerance based on the same physiological parameters. The results indicate that AKR-overexpression may lead to higher frost tolerance and higher post-frost regenerative capacity.     

The adipokine preadipocyte factor-1 is downregulated in preeclampsia and expressed in placenta

BackgroundAdipokines contribute to the development of preeclampsia (PE), a severe pregnancy complication which increases the future risk for cardiovascular and metabolic disease in both mother and newborn. Pre-adipocyte factor-1 (Pref-1) was recently introduced as a novel antiangiogenic and antiadipogenic adipokine.Material and methodsPref-1 was quantified in patients with PE (n = 51) and healthy pregnant controls (n = 51) during pregnancy, as well as 6 months after delivery (study population 1). Furthermore, Pref-1 was investigated in the immediate peripartal period and the placenta in 40 healthy pregnant women undergoing elective cesarean section (study population 2).ResultsIn study population 1, median Pref-1 serum concentrations during pregnancy were significantly lower in women with PE (0.5 μg/l) as compared to healthy pregnant controls (0.7 μg/l) (p < 0.001). Furthermore, Pref-1 serum concentrations were independently predicted by PE, leptin levels, and gestational age in this population. In both study populations, Pref-1 serum levels significantly decreased after delivery as compared to prepartal levels. Moreover, significant expression of Pref-1 was detected in placental tissue.ConclusionMaternal Pref-1 serum concentrations are significantly decreased in PE. The pathophysiological significance of this regulation needs to be studied in more detail in future experiments.     

Does emotional dysregulation mediate the relationship between disability and depressive symptoms in older people?

BackgroundEmotion dysregulation has been consistently linked to psychopathology, and the relationship between disability and depressive symptomatology in old age is well-known.ObjectiveTo examine the mediational role of emotional dysregulation in the relationship between perceived disability and depressive symptomatology in older adults.MethodsTwo hundred eighty-three participants, aged 60–96 years (M ± SD = 74.22 ± 8.69; 62.9% women; 29.0% with long-term care support [LTC-S] and 71.0% community residents without LTC-S), were assessed with the Geriatric Depression Scale-8 (GDS-8), the World Health Organization Disability Assessment Schedule-2 (WHODAS-2), and the Difficulties in Emotion Regulation Scale-16 (DERS-16).ResultsA mediation model was established, which revealed: (1) a moderate association between WHODAS-2 and GDS-8 (β = 0.20; p < .001); (2) DERS-16 partially and weakly mediated the relationship between WHODAS-2 and GDS-8 (β = 0.003; p < .01). The model explained 31.9% of the variance of depressive symptoms. An inconsistent mediation model was obtained in the LTC-S group.ConclusionsGlobally, our findings indicate that disability has an indirect relationship with depressive symptomatology through emotional dysregulation (except for those in the LTC-S). Accordingly, we present suggestions for the treatment of depressive symptoms and for the inclusion of other emotion regulation variables in the study of the disability-depressive symptom link in future studies with older people in the LTC-S.     

Correlations among antiangiogenic factors and trace elements in hypertensive disorders of pregnancy

Although a number of studies have measured circulating levels of some trace elements in preeclampsia (PE) and compared to healthy pregnant (HP), there is no consensus yet about the deficiency of some metals and development of hypertensive disorders in pregnancy. The aim of this study was to compare plasmatic levels of Zn, Mn, Co, Cu, Se and Sr among non-pregnant (NP), healthy pregnant (HP), gestational hypertensive (GH) and preeclamptic (PE) women and to correlate these levels with plasma soluble endoglin (sENG) and soluble fms-like tyrosine kinase-1 (sFLT-1), two important antiangiogenic proteins related to PE. A total of 184 women were enrolled in this study (NP = 35, GH = 51, PE = 37 and HP = 61). Trace element analyses were carried out with an inductively coupled plasma mass spectrometer (ICPMS). sENG and sFLT-1 plasma concentrations were measured by commercial ELISA kits. The most interesting result is that Sr is higher in PE (63%, P < 0.001) compared to HP and their levels are positively correlated with sENG in all three groups of pregnant women. Moreover, we found a negative correlation between Zn and sENG in HP (r = −0.43, P = 0.003). Regarding other elements, we found similar levels among pregnant groups. In conclusion, this study showed that Sr may has a role in physiopathology of PE.     

Concentrations of preptin,salusins and hepcidins in plasma and milk of lactating women with or without gestational diabetes mellitus

This study was undertaken to ascertain whether human milk contains preptin, salusin-alpha (salusin-α) and -beta (salusin-β) and pro-hepcidin and hepcidin-25, and whether there are relationships between plasma and milk preptin, salusin-α and -β and pro-hepcidin and hepcidin-25 concentrations in lactating mothers with and without gestational diabetes mellitus (GDM). Blood was obtained from non-lactating women (n = 12), non-diabetic lactating women (n = 12), and GDM lactating women (n = 12). Colostrum, transitional milk, and mature milk samples were collected just before suckling from healthy and GDM lactating women. Peptides concentrations were determined by ELISA and EIA. Mammary gland tissues were screened immunohistochemically for these peptides. Women with GDM had significantly higher plasma and colostum preptin concentrations than healthy lactating women during the colostral and transitional milk period. Salusin-alpha and -beta levels in milk and plasma were lower in women with GDM. Salusin-α and -β were significantly lower in both plasma and colostrums of GDM than of healthy lactating women. Women with GDM had significantly higher colostum prohepcidin and hepcidin-25 concentrations than healthy lactating women during the colostral period. Plasma prohepcidin was also higher in women with GDM than in healthy lactating women during the colostral period, but plasma prohepcidin and hepcidin-25 levels decreased during mature milk period. Transitional milk pro-hepcidin and hepcidin-25 levels in women with GDM were higher than in healthy lactating women. All these results revealed that the mammary gland produces those peptides, which were present in milk at levels correlating with plasma concentrations.     

Primary alveolar echinococcosis: Course of larval development and antibody responses in intermediate host rodents with different genetic backgrounds after oral infection with eggs of Echinococcus multilocularis

We investigated parasite establishment, subsequent larval development and antibody responses in gerbils, cotton rats and 4 inbred mouse strains until 16 weeks post inoculation (p.i.) with 200 eggs of Echinococcus multilocularis. The rate of parasite establishment in the liver determined at 4 weeks p.i. was highest in DBA/2, followed by AKR/N, C57BL/10 and C57BL/6 mice, whereas gerbils harboured few parasite foci. The accurate number of liver lesions in cotton rats could not be determined due to rapid growth and advanced multivesiculation of the parasite observed at 2 weeks p.i. The course of larval development was most advanced in DBA/2 mice with mature protoscolex formation at 16 weeks p.i., followed by AKR/N harbouring metacestodes with sparsely distributed immature protoscoleces. On the other hand, C57BL/6 and C57BL/10 mice had infertile metacestodes without any protoscolex formation. The parasite growth in mice was totally slower than those in gerbils and cotton rats. Specific IgG and IgM responses against 3 types of native crude antigens of larval E. multilocularis were evaluated using somatic extracts of and vesicle fluid of metacestode, and somatic extracts from purified protoscoleces. The 4 mouse strains demonstrated basically similar kinetics with apparent IgG and IgM increases at 9 weeks p.i. and thereafter, except C57BL/10, exhibited higher levels of IgM against crude antigens at some time point of infection. On the other hand, a follow-up determination of specific IgG and IgM levels against recombinant antigens from larval E. multilocularis revealed that each mouse strain showed different antibody-level kinetics. The findings in the present study demonstrate that the course of host–parasite interactions in primary alveolar echinococcosis, caused by larval E. multilocularis, clearly varies among intermediate host rodents with different genetic backgrounds.     

Cord blood nesfatin-1 in large for gestational age pregnancies

ObjectiveTo investigate possible alterations in cord blood levels of adipokine nesfatin-1 (secreted by adipose tissue and pancreatic β-cells and implicated in glucose metabolism and insulin resistance), as well as insulin, in large (LGA) and appropriate for gestational age (AGA) pregnancies, granted that these groups differ in body fat mass and metabolic/endocrine mechanisms.Materials and methodsCord blood nesfatin-1 and insulin concentrations were prospectively measured in 40 LGA (9 born from diabetic and 31 from non-diabetic mothers) and 20 AGA singleton full-term infants as well as their mothers.ResultsCord blood nesfatin-1 concentrations were significantly lower in LGA compared to AGA neonates (b = ?0.206, SE 0.07, p = 0.005). However, cord blood nesfatin-1 concentrations were elevated in infants born from mothers with gestational diabetes mellitus (GDM), compared to those born from non-diabetic mothers, after controlling for group (b = 0.190, SE 0.10, p = 0.05). Finally, cord blood nesfatin-1 concentrations were lower in cases of vaginal delivery (b = 0.11, SE 0.05, p = 0.042). Insulin levels were significantly elevated, as customized centiles increased (b = 0.004, SE = 0.002, p = 0.016). No significant correlation was found between insulin and nesfatin-1 in maternal and umbilical cord levels.ConclusionsIn this study nesfatin-1 levels are decreased in LGA compared to AGA fetuses. Fetal nesfatin-1 concentrations are higher in cases of GDM and cord blood nesfatin-1 concentrations are lower in cases of vaginal delivery.     

Role of IL6, IL12B and VDR gene polymorphisms in Plasmodium vivax malaria severity,parasitemia and gametocytemia levels in an Amazonian Brazilian population

ObjectiveTo investigate the influence of IL6, IL12B and VDR single nucleotide polymorphisms (SNPs) in uncomplicated Plasmodium vivax infection symptoms intensity, parasitemia and gametocytemia levels in a Brazilian Amazonian population.MethodsA total of 167 malaria patients infected by P. vivax have parasitemia and gametocytemia levels estimated before treatment. Fourteen clinical symptoms were evaluated and included in a principal component analysis to derive a clinical symptom index. Patients were genotyped for IL6-174C > G, IL12B 735T > C, 458A > G, 159A > C, and VDR FokI, TaqI, BsmI SNPs by Taqman 5’ nuclease assays. A General Linear Model analysis of covariance with age, gender, exposure period and infection history and genetic ancestry was performed to investigate the association of genotypes with parasitemia and gametocytemia levels and with a clinical symptom index.ResultsHigher parasitemia levels were observed in IL6-174C carriers (p = 0.02) whereas IL12B CGT haplotype carriers presented lower parasitemia levels (p = 0.008). VDR TaqIC/BsmIA haplotype carriers showed higher gametocyte levels than non-carriers (p = 0.013). Based on the clinical index values the IL6-174C > G polymorphism was associated with malaria severity. The IL6-174C carriers presented a more severe clinical index when compared to GG homozygotes (p = 0.001).ConclusionThe present study suggests that IL6, IL12 and VDR influence severity, parasitemia and gametocytemia clearance in P. vivax infections, and highlights their potential role in malaria immune response in an Amazonian population.     

Antioxidant treatment reduces matrix metalloproteinase-2-induced vascular changes in renovascular hypertension

Mounting evidence indicates that structural and functional vascular changes associated with two-kidney, one-clip (2K-1C) hypertension result, at least in part, from altered activity of matrix metalloproteinases (MMPs). Because MMPs are upregulated by increased formation of reactive oxygen species (ROS), we hypothesized that antioxidant approaches could attenuate the increases in MMP-2 expression/activity and the vascular dysfunction and remodeling associated with 2K-1C hypertension. Sham-operated or 2K-1C hypertensive rats were treated with tempol 18 mg/kg/day or apocyanin 25 mg/kg/day (or vehicle). Systolic blood pressure was monitored weekly. After 8 weeks of treatment, aortic rings were isolated to assess endothelium-dependent and -independent relaxation. Quantitative morphometry of structural changes in the aortic wall was studied in hematoxylin/eosin sections. Aortic and systemic ROS levels were measured using dihydroethidine and thiobarbituric acid-reactive substances, respectively. Aortic MMP-2 levels and activity were determined by gelatin and in situ zymography, fluorimetry, and immunohistochemistry. Tempol and apocyanin attenuated 2K-1C hypertension (181 ± 20.8 and 192 ± 17.6 mm Hg, respectively, versus 213 ± 18 mm Hg in hypertensive controls; both p < 0.05) and prevented the reduction in endothelium-dependent vasorelaxation found in 2K-1C rats. Tempol, but not apocyanin (p > 0.05), prevented the vascular remodeling found in 2K-1C rats (all p < 0.01). Tempol was more effective than apocyanin in attenuating hypertension-induced increases in oxidative stress (both p < 0.05), MMP-2 levels, and MMP-2 activity in hypertensive rats (all p < 0.05). Our results suggest that antioxidant approaches decrease MMP-2 upregulation and attenuate the vascular dysfunction and remodeling during 2K-1C hypertension.     

1,5-Anhydroglucitol and Neonatal Complications in Pregnancy Complicated by Diabetes

Objective: To determine the association of 1,5-anhydroglucitol (1,5-AG) with neonatal birth weight (NBW) and neonatal hypoglycemia (+NH) in pregnancies complicated by diabetes.Methods: We assessed a retrospective cohort of 102 females, 17 with gestational diabetes (GDM), 48 with type 1 diabetes mellitus (T1DM), and 37 with type 2 diabetes mellitus (T2DM). 1,5-AG and glycated hemoglobin A1C (A1C) values throughout pregnancy were extracted. Linear regression was used to assess their association with NBWs z-scores adjusting for maternal age, ethnicity and body mass index (BMI). +NH was defined by a note in the infant record, glucose <1.7 mmol/L in the first 24 h, or <2.5 mmol/L in the first 48 h after birth. A t test or Welch's approximate t test was used to compare the mean 1,5-AG and A1C of mothers with +NH versus those without (-NH), adjusted for gestational age and analyzed by diabetes type and across trimesters.Results: Mean 1,5-AG significantly differed across groups: T1DM 3.77 ± 2.82 μg/mL, T2DM 5.73 ± 4.38 μg/mL, GDM 8.89 ± 4.39 μg/mL (P<.0001), suggesting less glucose exposure in GDM relative to T1DM or T2DM. A negative linear association was found between mean 1,5-AG and z-scores (R= -0.28, P = .005. In contrast, the association between mean A1C and z-scores was weaker (R = 0.15, P = .14). The mean 1,5-AG tended to be lower in the +NH cohort versus -NH (P = .08), and this was statistically significant (P = .01) among subjects with GDM.Conclusion: The association of 1,5-AG with complications related to glycemic exposure supports the notion of its utility as an adjunct glycemic biomarker in pregnancies complicated by diabetes and across trimesters.Abbreviations: 1,5-AG = 1,5-anhydroglucitol A1C = glycated hemoglobin A1C BMI = body mass index CGM = continuous glucose monitoring GDM = gestational diabetes mellitus LGA = large for gestational age MICC = maternal and infant care unit NBW = neonatal birth weight NH = neonatal hypoglycemia PPH = postprandial hyperglycemia SMBG = self-monitoring of blood glucose T1DM = type 1 diabetes mellitus T2DM = type 2 diabetes mellitus     

Effects of flooding on photosynthesis and root respiration in saltcedar (Tamarix ramosissima), an invasive riparian shrub

The introduced shrub Tamarix ramosissima invades riparian zones, but loses competitiveness under flooding. Metabolic effects of flooding could be important for T. ramosissima, but have not been previously investigated. Photosynthesis rates, stomatal conductance, internal (intercellular) CO₂, transpiration, and root alcohol dehydrogenase (ADH) activity were compared in T. ramosissima across soil types and under drained and flooded conditions in a greenhouse. Photosynthesis at 1500 μmol quanta m⁻² s⁻¹ (A₁₅₀₀) in flooded plants ranged from 2.3 to 6.2 μmol CO₂ m⁻² s⁻¹ during the first week, but A₁₅₀₀ increased to 6.4–12.7 μmol CO₂ m⁻² s⁻¹ by the third week of flooding. Stomatal conductance (g_s) at 1500 μmol quanta m⁻² s⁻¹ also decreased initially during flooding, where g_s was 0.018 to 0.099 mol H₂O m⁻² s⁻¹ during the first week, but g_s increased to 0.113–0.248 mol H₂O m⁻² s⁻¹ by the third week of flooding. However, photosynthesis in flooded plants was reduced by non-stomatal limitations, and subsequent increases indicate metabolic acclimation to flooding. Root ADH activities were higher in flooded plants compared to drained plants, indicating oxygen stress. Lower photosynthesis and greater oxygen stress could account for the susceptibility of T. ramosissima at the onset of flooding. Soil type had no effect on photosynthesis or on root ADH activity. In the field, stomatal conductance, leaf water potential, transpiration, and leaf δ¹³C were compared between T. ramosissima and other flooded species. T. ramosissima had lower stomatal conductance and water potential compared to Populus deltoides and Phragmites australis. Differences in physiological responses for T. ramosissima could become important for ecological concerns.     

Colesevelam Hydrochloride to Treat Hypercholesterolemia and Improve Glycemia in Prediabetes: A Randomized,Prospective Study

ObjectiveTo assess the effect of the bile acid sequestrant colesevelam hydrochloride in patients with hypercholesterolemia and prediabetes.MethodsIn this 16-week, randomized, double-blind study, adults with untreated prediabetes (2-hour postoral glucose tolerance test [OGTT] glucose ≥ 140 to 199 mg/dL, fasting plasma glucose [FPG] ≥ 110 to 125 mg/ dL, or both), low-density lipoprotein cholesterol (LDL-C) ≥ 100 mg/dL, and triglycerides < 500 mg/dL were randomly assigned to receive colesevelam (3.75 g/d) or placebo. The primary end point was percent change in LDL-C from baseline to week 16 with last observation carried forward. Secondary end points included change in FPG, hemoglobin A1c (A1C), and 2-hour post-OGTT glucose level from baseline to week 16 and attainment of LDL-C and FPG targets.ResultsIn total, 216 patients were randomized (colesevelam, 108; placebo, 108). In comparison with placebo, colesevelam significantly reduced LDL-C (mean treatment difference, -15.6%), non-high-density lipoprotein cholesterol (-9.1%), total cholesterol (-7.2%), apolipoprotein B (-8.1%) (P < .001 for all the foregoing), FPG (median, -2.0 mg/dL; P = .02), and A1C (mean, -0.10%; P = .02). Colesevelam did not significantly change 2-hour post-OGTT glucose (-1.9 mg/dL; P = .75) or high-density lipoprotein cholesterol (-0.5%; P = .80). In addition, colesevelam significantly increased triglyceride levels relative to placebo (median, 14.3%; P < .001). The proportion of patients achieving target levels with colesevelam versus placebo, respectively, was as follows: LDL-C < 100 mg/dL (29% versus 11%; P < .001), A1C < 6.0% (37% versus 25%; P = .05), FPG < 110 mg/dL (48% versus 56%; P = .97), and normalization of glucose (FPG < 100 mg/dL [40% versus 23%; P = .06]). Colesevelam had a weight-neutral effect and was well tolerated.ConclusionColesevelam is an option for managing the lipid profile and normalizing glucose levels in patients with hypercholesterolemia and prediabetes. Further study is warranted to determine whether colesevelam slows or prevents progression of prediabetes to type 2 diabetes. (Endocr Pract. 2010;16:617-628)     

Serum chemerin levels during normal human pregnancy

During gestation there are important changes in maternal metabolism and an increase in insulin resistance, coinciding with an increase in adiposity. Chemerin is an adipocytokine which is expressed and secreted in various tissues, including placenta, and may play an important role in metabolic regulation during pregnancy. The aim of this study was to determine serum levels of chemerin during gestation and compare them to other indicators of insulin resistance. A cross-sectional study was carried out analyzing serum chemerin levels of 20 pregnant women during three gestational periods, early, middle, and late (between the 10th and 14th, the 23rd and 26th, and the 34th and 37th week) and 20 non-pregnant women were used as a control group. An analysis of chemerin levels during the menstrual cycle was performed in an eumenorrheic group (n = 16) in the early follicular (cycle day 4 ± 1) and the midluteal phase (cycle day 22 ± 1), demonstrating that serum chemerin levels did not fluctuate significantly. Serum levels of chemerin were significantly elevated during late gestation when compared to early (P < 0.001) and middle (P = 0.001) gestation and a negative correlation between serum chemerin and adiponectin levels (r = −0.1643) became more significant when the non-pregnant group was included in the calculations (r = −0.2471). There was no significant association of triglycerides, total cholesterol, LDL, HDL, insulin, and HOMA levels with chemerin. Although chemerin rose significantly and is negatively associated with adiponectin levels, it is not correlated with other markers of insulin sensitivity, suggesting that more study is needed to determine whether chemerin is useful in predicting insulin resistance during gestation.     

Initial Combination Therapy with Metformin and Colesevelam for Achievement of Glycemic and Lipid Goals Min Early Type 2 Diabetes

ObjectiveTo evaluate the efficacy and safety of initial combination therapy with metformin plus colesevelam in patients with early type 2 diabetes.MethodsIn this 16-week, randomized, double-blind, placebo-controlled study, adults with type 2 diabetes (hemoglobin A1c [A1C] values of 6.5% to 10.0%) and hypercholesterolemia (low-density lipoprotein cholesterol [LDL-C] levels ≥ 100 mg/dL) were randomly assigned (1:1) to colesevelam (3.75 g/d) or placebo in combination with open-label metformin (850 mg/d; uptitrated at week 2 to 1, 700 mg/d). The primary efficacy evaluation was change in A1C from baseline to study end (week 16 with last observation carried forward).ResultsIn total, 286 patients were randomized: metformin/colesevelam (n = 145) or metformin/placebo (n = 141). Mean A1C was reduced by 1.1% with metformin/ colesevelam (from 7.8% at baseline to 6.6% at study end) and by 0.8% with metformin/placebo (from 7.5% to 6.7%), resulting in a treatment difference of -0.3% at study end (P = .0035). In addition, metformin/colesevelam significantly reduced LDL-C (-16.3%), total cholesterol (-6.1%), non-high-density lipoprotein cholesterol (-8.3%), apolipoprotein B (-8.0%), and high-sensitivity C-reactive protein (-17%) and increased apolipoprotein A-I (+ 4.4%) and triglycerides (+ 18.6%) versus metformin/placebo (P < .01 for all). The proportions of patients who achieved recommended goals with metformin/colesevelam versus metformin/placebo, respectively, were as follows: A1C < 7.0% (67% versus 56% [P = .0092]), LDL-C < 100 mg/dL (48% versus 18% [P < .0001]), and composite A1C < 7.0% + LDL-C < 100 mg/dL (40% versus 12% [P < .0001]). Safety and tolerability were similar between the treatment groups.ConclusionMetformin plus colesevelam may be a valid option for initial therapy to achieve glycemic and lipid goals safely in early type 2 diabetes. (Endocr Pract. 2010;16:629-640)     

Recreational physical activity and risk of papillary thyroid cancer among women in the California Teachers Study

Purpose: Little is known about the relationship between physical activity and thyroid cancer risk, and few cohort data on this association exist. Thus, the present study aimed to prospectively examine long-term activity and risk of papillary thyroid cancer among women. Methods: 116,939 women in the California Teachers Study, aged 22–79 years with no history of thyroid cancer at cohort entry, were followed from 1995–1996 through 2009; 275 were diagnosed with invasive papillary thyroid cancer. Cox proportional-hazards regression provided relative risk (RR) estimates and 95% confidence intervals (CI) for associations between thyroid cancer and combined strenuous and moderate recreational physical activity both in the long-term (high school through age 54 years or current age if younger than 54 years) and recently (during the three years prior to joining the cohort). Results: Overall, women whose long-term recreational physical activity averaged at least 5.5 MET-hours/week (i.e. were active) had a non-significant 23% lower risk of papillary thyroid cancer than inactive women (RR = 0.77, 95% CI: 0.57, 1.04). RR estimates were stronger among normal weight or underweight women (body mass index, BMI < 25.0 kg/m², trend p = 0.03) than among overweight or obese women (trend p = 0.35; homogeneity-of-trends p = 0.03). A similar pattern of risk was observed for recent activity (BMI < 25 kg/m², trend p = 0.11; BMI ≥ 25 kg/m², trend p = 0.16; homogeneity-of-trends p = 0.04). Associations for long-term activity did not appear to be driven by activity in any particular life period (e.g. youth, adulthood). Conclusions: Long-term physical activity may reduce papillary thyroid cancer risk among normal weight and underweight women.     

Serum zinc levels of cord blood: Relation to birth weight and gestational period

BackgroundZn-deficiency has been associated with numerous alterations during pregnancy including low birth weight; however, the research relating neonatal zinc status and birth weight has not produced reliable results.ObjectiveTo compare the serum Zn-levels of cord blood in healthy newborns and low birth weight newborns, and to assess a possible relationship between zinc concentration and neonatal birth weight and gestational age.Material and methods123 newborns divided in “study group” (n = 50) with <2500 g birth weight neonates and “control group” (n = 73) with ≥2500 g birth weight neonates were enrolled. Study group was subdivided according to gestational age in preterm (<37 weeks) and full-term (≥37 weeks). Serum cord blood samples were collected and the Zn-levels were analyzed using flame Atomic Absorption Spectrophotometry method and the result was expressed in μmol/L. The Zn-levels were compared between the groups (Mann–Whitney-U test) and the Zn-levels were correlated with the birth weight and gestational age (Spearman's rank correlations).ResultsStatistically significant low positive correlation between Zn-levels and birth weight (ρ = 0.283; p = 0.005) was found. No statistically significant difference between Zn-levels of study and control groups [17.00 ± 0.43 vs. 18.16 ± 0.32 (p = 0.053)] was found. Statistically significant low positive correlation between Zn-levels and gestational age (ρ = 0.351; p = 0.001) was found. No statistically significant difference between Zn-levels of preterm as compare to full-term newborns [16.33 ± 0.42 vs. 18.43 ± 0.93 (p = 0.079)] was found. Zn-level of preterm subgroup was significantly lower compared to control group (p = 0.001).ConclusionsDespite low birth weight preterm neonates had significantly lower serum zinc levels of cord blood than healthy term neonates, the correlation between cord blood zinc levels and birth weight and gestational age was lower. The results are not enough to relate the change in cord blood zinc concentration to the birth weight values or gestational period. In relation to complicated pregnancies, further studies regarding zinc levels in blood in our population are required.     

Synthesis of non-prenyl analogues of baccharin as selective and potent inhibitors for aldo-keto reductase 1C3

Inhibitors of a human member (AKR1C3) of the aldo-keto reductase superfamily are regarded as promising therapeutics for the treatment of prostatic and breast cancers. Baccharin [3-prenyl-4-(dihydrocinnamoyloxy)cinnamic acid], a component of propolis, was shown to be both potent (K_i 56 nM) and highly isoform-selective inhibitor of AKR1C3. In this study, a series of derivatives of baccharin were synthesized by replacing the 3-prenyl moiety with aryl and alkyl ether moieties, and their inhibitory activities for the enzyme were evaluated. Among them, two benzyl ether derivatives, 6m and 6n, showed an equivalent inhibitory potency to baccharin. The molecular docking of 6m in AKR1C3 has allowed the design and synthesis of (E)-3-{3-[(3-hydroxybenzyl)oxy]-4-[(3-phenylpropanoyl)oxy]phenyl}acrylic acid (14) with improved potency (K_i 6.4 nM) and selectivity comparable to baccharin. Additionally, 14 significantly decreased the cellular metabolism of androsterone and cytotoxic 4-oxo-2-nonenal by AKR1C3 at much lower concentrations than baccharin.