Purpose: Translational studies suggest that excess perioperative release of catecholamines and prostaglandins may facilitate metastasis and reduce disease-free survival. This trial tested the combined perioperative blockade of these pathways in breast cancer patients.Experimental Design: In a randomized placebo-controlled biomarker trial, 38 early-stage breast cancer patients received 11 days of perioperative treatment with a β-adrenergic antagonist (propranolol) and a COX-2 inhibitor (etodolac), beginning 5 days before surgery. Excised tumors and sequential blood samples were assessed for prometastatic biomarkers.Results: Drugs were well tolerated with adverse event rates comparable with placebo. Transcriptome profiling of the primary tumor tested a priori hypotheses and indicated that drug treatment significantly (i) decreased epithelial-to-mesenchymal transition, (ii) reduced activity of prometastatic/proinflammatory transcription factors (GATA-1, GATA-2, early-growth-response-3/EGR3, signal transducer and activator of transcription-3/STAT-3), and (iii) decreased tumor-infiltrating monocytes while increasing tumor-infiltrating B cells. Drug treatment also significantly abrogated presurgical increases in serum IL6 and C-reactive protein levels, abrogated perioperative declines in stimulated IL12 and IFNγ production, abrogated postoperative mobilization of CD16- "classical" monocytes, and enhanced expression of CD11a on circulating natural killer cells.Conclusions: Perioperative inhibition of COX-2 and β-adrenergic signaling provides a safe and effective strategy for inhibiting multiple cellular and molecular pathways related to metastasis and disease recurrence in early-stage breast cancer. Clin Cancer Res; 23(16); 4651-61. ©2017 AACR.

A 9-week feeding experiment was conducted to evaluate the effects of dietary vitamin E (VE) supplementation on growth performance, liver fatty acid composition, lipid peroxidation and peroxisome proliferator-activated receptors (PPAR) genes expressions in blunt snout bream juveniles. Fish (average initial weight: 0.59 g) were fed diet supplemented with 0, 50, 100, 300 and 500 mg α-tocopherol acetate/kg in triplicates, which were found to, respectively, contain 11.2, 56.3, 114.6, 306.5 and 588.4 mg α-tocopherol/kg diet. Results showed that final weight, body weight gain and specific growth rate significantly increased with increasing dietary VE supplemented level from 11.2 to 56.3 mg/kg. When the broken-line model was employed to estimate the adequate requirement of vitamin E based on body weight gain, the optimal level was 55.5 mg/kg in diet. Hepatosomatic index value significantly decreased with incremental dietary VE levels. However, liver VE concentration showed a direct relationship with the dietary VE level. The percentages of 20:5n-3, 22:6n-3 and total n-3 long chain polyunsaturated fatty acids in liver increased with increasing dietary VE supplementation. Meanwhile, the expressions of PPAR-α, PPAR-β and PPAR-γ in liver were down-regulated by supplementation of dietary VE level from 56.3 to 588.4 mg/kg. In conclusion, supplementation of more than 55.5 mg/kg vitamin E may improve growth and increase n-3 LC-PUFA content in blunt snout bream, which is beneficial to human consumer.

Short-term bed rest in older adults is characterized by significant loss in leg lean mass and strength posing significant health consequences. The purpose of this study was to determine in healthy older adults if the daily combination of neuromuscular electrical stimulation and protein supplementation (NMES+PRO) would protect muscle mass and function after 5 days of bed rest. Twenty healthy older adults (∼70 years) were subjected to 5 days of continuous bed rest and were randomized into one of two groups: NMES+PRO (n = 10) or control (CON) (n = 10). The NMES+PRO group received bilateral NMES to quadriceps (40 minutes/session, 3 × /day; morning, afternoon, and evening) followed by an interventional protein supplement (17 g). The CON group received an isocaloric equivalent beverage. Before and after bed rest, vastus lateralis biopsies occurred before and after acute essential amino acid (EAA) ingestion for purposes of acutely stimulating mechanistic target of rapamycin (mTORC1) signaling, a major regulator of muscle protein synthesis, in response to bed rest and NMES+PRO. Baseline (pre and post bed rest) muscle samples were also used to assess myofiber characteristics and gene expression of muscle atrophy markers. Thigh lean mass and muscle function were measured before and after bed rest. Five days of bed rest reduced thigh lean mass, muscle function, myofiber cross-sectional area, satellite cell content, blunted EAA-induced mTORC1 signaling, and increased myostatin and MAFbx mRNA expression. Interestingly, NMES+PRO during bed rest maintained thigh lean mass, but not muscle function. Thigh muscle preservation during bed rest with NMES+PRO may partly be explained by attenuation of myostatin and MAFbx mRNA expression rather than restoration of nutrient-induced mTORC1 signaling. We conclude that the combination of NMES and protein supplementation thrice a day may be an effective therapeutic tool to use to preserve thigh muscle mass during periods of short-term hospitalization in older adults. However this combined intervention was not effective to prevent the loss in muscle function.

Migraine is a destabilizing neuroinflammatory disorder characterized by recurrent headache attacks. Evidences show tumor necrosis factor (TNF)-α play a role in neuroimmunity pathogenesis of migraine. TNF-α increase prostanoid production, hyperexcitability of neurons, and nociceptor activation resulted in neuroinflammation and neurogenic pain. ω-3 fatty acids and curcumin exert neuroprotective and anti-inflammatory effects via several mechanisms including suppression of TNF-α gene expression and its serum levels. The aim of this study is an evaluation of synergistic effects of ω-3 fatty acids and nano-curcumin on TNF-α gene expression and serum levels in migraine patients. The present study performed as a clinical trial over a 2 month period included 74 episodic migraine patients in 4 groups and received ω-3 fatty acids, nano-curcumin, and combination of them or placebo. At the start and the end of the study, the gene expression of TNF-α and TNF-α serum levels was measured by real-time PCR and ELISA method, respectively. Our results showed that the combination of ω-3 fatty acids and nano-curcumin downregulated TNF-α messenger RNA (mRNA) significantly in a synergistic manner (P < 0.05). As relative to gene expression, a significant greater reduction in serum levels of TNF-α were observed in the combination group, but no significant differences in other groups. Supplementation with ω-3 fatty acids or nano-curcumin alone did not show significant reduction either in mRNA or serum levels of TNF-α. In addition, a much greater reduction in attack frequency was found in the combination group (P < 0.001). These findings indicated that ω-3 fatty acids and curcumin supplementation can be considered as a new promising approach in migraine management.

Selenium and coenzyme Q10 is essential for important cellular functions. A low selenium intake is reported from many European countries, and the endogenous coenzyme Q10 production is decreasing in the body with increasing age. Supplementation with selenium and coenzyme Q10 in elderly have shown reduced cardiovascular mortality and reduced levels of markers of inflammation. However, microRNA analyses could give important information on the mechanisms behind the clinical effects of supplementation.

Bone turnover markers (BTMs) are used to evaluate bone health together with bone mineral density and fracture assessment. Vitamin D supplementation is widely used to prevent and treat musculoskeletal diseases but existing data on vitamin D effects on markers of bone resorption and formation are inconsistent. We therefore examined the effects of vitamin D supplementation on bone-specific alkaline phosphatase (bALP), osteocalcin (OC), C-terminal telopeptide (CTX), and procollagen type 1 N-terminal propeptide (P1NP). This is a post-hoc analysis of the Styrian Vitamin D Hypertension Trial, a single-center, double-blind, randomized, placebo-controlled trial (RCT) performed at the Medical University of Graz, Austria (2011-2014). Two hundred individuals with arterial hypertension and 25-hydroxyvitamin D (25[OH]D) levels <75 nmol/L were randomized to 2800 IU of vitamin D daily or placebo for eight weeks. One hundred ninety-seven participants (60.2 ± 11.1 years; 47% women) were included in this analysis. Vitamin D had no significant effect on bALP (mean treatment effect (MTE) 0.013, 95% CI -0.029 to 0.056 µg/L; p = 0.533), CTX (MTE 0.024, 95% CI -0.163 to 0.210 ng/mL, p = 0.802), OC (MTE 0.020, 95% CI -0.062 to 0.103 ng/mL, p = 0.626), or P1NP (MTE -0.021, 95% CI -0.099 to 0.057 ng/mL, p = 0.597). Analyzing patients with 25(OH)D levels <50 nmol/L separately (n = 74) left results largely unchanged. In hypertensive patients with low 25(OH)D levels, we observed no significant effect of vitamin D supplementation for eight weeks on BTMs.

Vilazodone is a novel antidepressant agent that combines selective serotonin (5-HT) reuptake inhibitor (SSRI) activity and 5-HT(1A) receptor partial agonist activity. A pilot study was conducted to compare vilazodone (novel compound) and paroxetine (gold standard) on antidepressant effects, tolerability, and inflammation and immune modulation. A 12-week, double-blind, randomized clinical trial was conducted with 56 nondemented older adults diagnosed with major depressive disorder (MDD). Between-group differences in mood, tolerability, and safety, as well as genomic markers of inflammation and immune modulation, were examined. Both treatment groups demonstrated similar improvement in depressed mood. Leukocyte gene expression profiles demonstrated reduction of specific proinflammatory gene transcripts and bioinformatic indications of reduced nuclear factor kappa B (NF-κB), activator protein (AP)-1, and cAMP response element binding (CREB) activity in the vilazodone group compared to the paroxetine group. Transcript origin analyses implicated monocytes and dendritic cells as the primary cellular origins of transcript reductions in the vilazodone-treated group. Vilazodone's antidepressant effects may be associated with reduction of proinflammatory gene expression and immune modulation. Further research is required.

The effects of dietary folic acid on biochemical parameters and gene expression of three heat shock proteins (HSPs) of blunt snout bream (Megalobrama amblycephala) fingerling under acute high temperature stress. Six dietary folic acid groups (0.0, 0.5, 1.0, 2.0, 5.0, and 10.0) mg/kg diets were designed and assigned into 18 tanks in three replicates each (300 l/tank) and were administered for 10 weeks in a re-circulated water system. The fingerlings with an initial weight of 27.0 ± 0.03 g were fed with their respective diets four times daily. At the end of the experiment, samples were collected before challenge, 0, 24, 72 h, and 7 days. Serum total protein (TP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), cortisol, glucose, complement C3 (C3), complement C4 (C4, immunoglobulin M (IgM) hepatic superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), and the expression of heat shock protein 60 (HSP60), 70 (HSP70), and 90 (HSP90) were studied. The results showed that fish fed with dietary folic acid between 1.0, 2.0, and 5.0 mg/kg significantly (P < 0.05) increased serum TP, C3, C4 hepatic SOD, CAT, and the expression of HSP60, HSP70, and HSP90 before and after temperature challenge of 32 °C. Also, serum ALP, cortisol, glucose, and hepatic MDA were significantly (P < 0.05) reduced by supplementation of dietary folic acid level 1.0, 2.0, and 5.0 mg/kg before and after the same temperature challenge of 32 °C. Before stress, 0, 24, 72 h, and 7 days significantly (P < 0.05) affects serum biochemical parameters, immune and antioxidant capacities, and expression level of three HSPs. Furthermore, there was no statistical evidence to show that dietary folic acid inclusion level and temperature duration have significant interactive effect on serum biochemical parameters, antioxidant parameters, and gene expression level (P > 0.05) of the three HSPs. However, there were statistical significant interactive effect between dietary folic acid inclusion level and temperature duration on serum C3 and C4 (P < 0.05) except IgM (P > 0.05). The present results indicate that supplementation of basal diet from 1.0 mg/kg; 2.0 and 5.0 mg/kg can enhance acute high temperature resistance ability in M. amblycephala fingerling to some degree and improve physiological response, immune and antioxidant capacities, and expression level of three HSPs.

This experiment evaluated the dose and payout pattern of trenbolone acetate (TBA) and estradiol-17β (E) on LM mRNA expression of adenosine monophosphate-activated protein kinase-ɑ (-ɑ), β, G protein-coupled receptor 41(), G protein-coupled receptor 43 (), γ, and stearoyl CoA desaturase () in finishing feedlot steers as indicators of adipogenesis and marbling development. British × Continental steers (n = 168; 14 pens/treatment; initial BW = 362 kg) were used in a randomized complete block design. Treatments included: no implant (NI), Revalor-S (REV-S; 120 mg TBA + 24 mg E), or Revalor-XS (REV-X; delayed release implant: 80 mg TBA + 16 mg E [uncoated], 120 mg TBA + 24 mg E [coated], 200 mg TBA + 40 mg E [total]). Steers were fed 1 time daily for an average of 164 d. The LM biopsies were collected (1 steer/pen) on d -1, 27, 55, and 111 relative to timing of implant. Total RNA was isolated from each sample and real-time quantitative PCR was used to measure quantity of -ɑ, β, , ,it, γ, and mRNA. No implant × day interactions were detected ( ≥ 0.19) in this experiment. Day impacted the mRNA expression of all adipogenic genes ( ≤ 0.02). The main effect of implant tended ( = 0.09) to influence expression of -ɑ, REV-X had an 8.8% increase over NI and an 18.7% increase over REV-S. Implant influenced ( = 0.03) mRNA expression of , expression of for the REV-X treatment was not different ( > 0.10) from NI, and both were greater ( ≤ 0.05) than REV-S (1.13, 1.00, and 0.67 ± 0.224 arbitrary units) for REV-X, NI, and REV-S, respectively. Implant also influenced ( = 0.02) expression of , expression of for REV-X was not different ( > 0.10) from NI, and both were greater ( ≤ 0.05) than REV-S (1.27, 1.07, and 0.72 ± 0.234 arbitrary units) for REV-X, NI, and REV-S, respectively. Implant influenced ( = 0.02) mRNA expression of γ in LM tissue, expression of γ for REV-X was not different ( > 0.10) from NI, and both were greater ( ≤ 0.05) than REV-S (1.09, 1.02, and 0.69 ± 0.195 arbitrary units) for REV-X, NI, and REV-S, respectively. The REV-X steers received the greatest anabolic dose of TBA + E without detriment to marbling scores. The increased mRNA expression of adipogenic genes for REV-X steers suggest that the delayed and gradual release of anabolic stimulants associated with REV-X might have mitigated decreases in marbling generally attributed to multiple combined TBA + E implants.

Vitamin D is hydroxylated in the liver and kidneys to its active form, which can bind to the vitamin D receptor (VDR). The VDR is present in a wide variety of different cells types and tissues and acts as a transcription factor. Although activation of the VDR is estimated to regulate expression of up to 5% of the human genome, our study is the first analysing gene expression after supplementation in more than 10 subjects. Subjects of a randomized controlled trial (RCT) received either vitamin D3 (n=47) in a weekly dose of 20,000 IU or placebo (n=47) for a period of three to five years. For this study, blood samples for preparation of RNA were drawn from the subjects and mRNA gene expression in blood was determined using microarray analysis. The two study groups were similar regarding gender, age, BMI and duration of supplementation, whereas the mean serum 25-hydroxyvitamin D (25(OH)D) level as expected was significantly higher in the vitamin D group (119 versus 63nmol/L). When analysing all subjects, nearly no significant differences in gene expression between the two groups were found. However, when analysing men and women separately, significant effects on gene expression were observed for women. Furthermore, when only including subjects with the highest and lowest serum 25(OH)D levels, additional vitamin D regulated genes were disclosed. Thus, a total of 99 genes (p≤0.05, log2 fold change ≥|0.2|) were found to be regulated, of which 72 have not been published before as influenced by vitamin D. These genes were particularly involved in the interleukin signaling pathway, oxidative stress response, apoptosis signaling pathway and gonadotropin releasing hormone receptor pathway. Thus, our results open the possibility for many future studies.

Our aim was to evaluate whether the cell of origin (COO) as defined by the Hans algorithm and MYC/BCL2 coexpression, which are the two main biological risk factors in elderly patients treated with rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisolone (R-CHOP), maintain their prognostic value in a large prospective clinical trial.

β-Aminoisobutyric acid (BAIBA) has shown to modulate uncoupling protein (UCP)-1 expression, which is mainly expressed in white adipose tissue; however, no studies to date have analyzed its potential effect on the main uncoupling protein of skeletal muscle, UCP-3. The main goal of this study was to assess the potential effect of acute aerobic exercise on serum BAIBA and skeletal muscle UCP-3. The secondary goal was to assess the potential involvement of the transcription factors proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and peroxisome proliferator-activated receptor alpha (PPARα), as well as free fatty acids (FFAs) in UCP-3 expression. A tertiary goal of the study was to evaluate the potential effect of consuming a preexercise meal on the outcome of the first 2 objectives.

Heat stress (HS) disrupts redox balance and insulin-related metabolism. Supplementation with supranutritional amounts of selenium (Se) may enhance glutathione peroxidase (GPX) activity and reduce oxidative stress, but may trigger insulin resistance. Therefore, the aim of this experiment was to investigate the effects of a short-term high Se supplementation on physiology, oxidative stress and insulin-related metabolism in heat-stressed pigs. Twenty-four gilts were fed either a control (0.20 ppm Se) or a high Se (1.0 ppm Se yeast, HiSe) diet for 2 weeks. Pigs were then housed in thermoneutral (20°C) or HS (35°C) conditions for 8 days. Blood samples were collected to study blood Se and oxidative stress markers. An oral glucose tolerance test (OGTT) was conducted on day 8 of thermal exposure. The HS conditions increased rectal temperature and respiration rate (both p < .001). The HiSe diet increased blood Se by 12% (p < .05) and ameliorated the increase in rectal temperature (p < .05). Heat stress increased oxidative stress as evidenced by a 48% increase in plasma advanced oxidized protein products (AOPPs; p < .05), which may be associated with the reductions in plasma biological antioxidant potential (BAP) and erythrocyte GPX activity (both p < .05). The HiSe diet did not alleviate the reduction in plasma BAP or increase in AOPPs observed during HS, although it tended to increase erythrocyte GPX activity by 13% (p = .068). Without affecting insulin, HS attenuated lipid mobilization, as evidenced by a lower fasting NEFA concentration (p < .05), which was not mitigated by the HiSe diet. The HiSe diet increased insulin AUC, suggesting it potentiated insulin resistance, although this only occurred under TN conditions (p = .066). In summary, HS induced oxidative stress and attenuated lipid mobilization in pigs. The short-term supranutritional Se supplementation alleviated hyperthermia, but did not protect against oxidative stress in heat-stressed pigs.

These negative phase II results for parsatuzumab highlight the challenges of developing an agent intended to enhance the efficacy of vascular endothelial growth factor inhibition without the benefit of validated pharmacodynamic biomarkers or strong predictive biomarker hypotheses.Any further clinical development of anti-EGFL7 is likely to require new mechanistic insights and biomarker development for antiangiogenic agents.

Liver metabolism is affected by nutrients. The aim of this study was to explore the effects of low-protein diets (17% crude protein, CP) supplemented with branched-chain amino acids (BCAAs), including leucine (Leu), isoleucine (Ile) and valine (Val), on hepatic amino acid profile and lipid metabolism in growing pigs. The ratio of Leu : Ile : Val in all groups was 1 : 0.51 : 0.63 (20% crude protein, CP), 1 : 1 : 1 (17% CP), 1 : 0.75 : 0.75 (17% CP), 1 : 0.51 : 0.63 (17% CP) and 1 : 0.25 : 0.25 (17% CP) respectively. Results revealed that compared to the positive control group (1 : 0.51 : 0.63, 20% CP), the low-protein diets significantly augmented the concentrations of most essential amino acids and non-essential amino acids (p < .05), with the greatest values observed in the 1 : 0.25 : 0.25 group. Moreover, relative to the control, the low-protein diets with the Leu : Ile : Val ratio ranging from 1 : 0.75 : 0.75 to 1 : 0.25 : 0.25 markedly downregulated the mRNA abundance of acetyl-CoA carboxylase (ACC), lipoprotein lipase (LPL) and fatty acid-binding protein 4 (FABP-4) (p < .05), and upregulated the mRNA expression of hormone-sensitive lipase (HSL), peroxisome proliferator-activated receptor-g coactivator-1α (PGC-1α), uncoupling protein 3 (UCP3) and liver carnitine palmitoyltransferase 1 (L-CPT-1) (p < .05). Therefore, our data suggest that protein-restricted diets supplemented with optimal BCAA ratio, that is, 1 : 0.75 : 0.75-1 : 0.25 : 0.25, induce a shift from fatty acid synthesis to fatty acid oxidation in the liver of growing pigs. These effects may be associated with increased mitochondrial biogenesis.

Limited data are available evaluating the effects of omega-3 fatty acids supplementation on gene expression involved in the insulin and lipid-signaling pathway in women with polycystic ovary syndrome (PCOS). This study was conducted to evaluate the effects of omega-3 fatty acids supplementation on gene expression involved in the insulin and lipid signaling pathway in women with PCOS. This randomized double blind, placebo-controlled trial was done among 60 women aged 18-40 years old and diagnosed with PCOS according to the Rotterdam criteria. Participants were randomly assigned into 2 groups to receive either 1 000 mg omega-3 fatty acids from flaxseed oil containing 400 mg α-linolenic acid (n=30) or placebo (n=30) twice a day for 12 weeks. Gene expressions involved in the insulin and lipid-signaling pathway were quantified in blood samples of PCOS women with RT-PCR method. Quantitative results of RT-PCR demonstrated that compared with the placebo, omega-3 fatty acids supplementation upregulated peroxisome proliferator-activated receptor gamma (PPAR-γ) mRNA (p=0.005) in peripheral blood mononuclear cells of women with PCOS. In addition, compared to the placebo, omega-3 fatty acids supplementation downregulated expressed levels of oxidized low-density lipoprotein receptor (LDLR) mRNA (p=0.002) in peripheral blood mononuclear cells of women with PCOS. We did not observe any significant effect of omega-3 fatty acids supplementation on expressed levels of glucose transporter 1 (GLUT-1) and lipoprotein(a) [Lp(a)] genes in peripheral blood mononuclear cells. Overall, omega-3 fatty acids supplementation for 12 weeks in PCOS women significantly improved gene expression of PPAR-γ and LDLR.

Background: Vitamin D deficiency, defined as a serum 25-hydroxyvitamin D [25(OH)D] concentration <20 ng/mL, is correlated with a more atherogenic lipid profile. However, oral vitamin D supplementation does not lower LDL-cholesterol concentrations or raise HDL-cholesterol concentrations. This uncoupling between association and causation may result from a failure of oral vitamin D to mimic the effect of dermally synthesized vitamin D in response to ultraviolet type B (UVB) light.Objective: We tested the hypothesis that, in vitamin D-deficient adults, the replenishment of vitamin D with UVB exposure would lower LDL-cholesterol concentrations compared with the effect of oral vitamin D3 supplementation.Design: We performed a randomized clinical trial in vitamin D-deficient adults and compared vitamin D replenishment between subjects who received oral vitamin D3 (n = 60) and those who received narrow-band UVB exposure (n = 58) ≤6 mo.Results: There was no difference in the change from baseline LDL-cholesterol concentrations between oral vitamin D3 and UVB groups (difference in median of oral vitamin D3 minus that of UVB: 1.5 mg/dL; 95% CI: -5.0, 7.0 mg/dL). There were also no differences within groups or between groups for changes in total or HDL cholesterol or triglycerides. Transcriptional profiling of skin and blood, however, revealed significant upregulation of immune pathway signaling with oral vitamin D3 but significant downregulation with UVB.Conclusions: Correcting vitamin D deficiency with either oral vitamin D3 or UVB does not improve the lipid profile. Beyond cholesterol, these 2 modalities of raising 25(OH)D have disparate effects on gene transcription. This trial was registered at clinicaltrials.gov as NCT01688102.

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 β cell function (HOMA-β) 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.

A recent dose-finding study showed no significant differences in number of mature oocytes, embryos and top-quality embryos when triptorelin doses of 0.2, 0.3 or 0.4 mg were used to trigger final oocyte maturation in oocyte donors co-treated with a gonadotropin-releasing hormone (GnRH) antagonist. This analysis investigated whether triptorelin dosing for triggering final oocyte maturation in oocyte donors induced differences in follicular fluid (FF) hormone levels and granulosa cell gene expression.

Recent studies report an increased risk of enteric infections in patients treated with proton pump inhibitors (PPIs). Polymorphonuclear neutrophils (PMNs) play a key role in host response to bacterial infection. We evaluated the effect of omeprazole and pantoprazole treatment on the PMN function. Fifteen patients were treated with omeprazole 20 mg daily and 15 patients with pantoprazole 40 mg daily for 7 days. Treatment with omeprazole or pantoprazole had no effect on spontaneous nitroblue tetrazolium (NBT) test results. Significant increase in the percentage of phagocytes in the omeprazole group in stimulated NBT test (by 69%) was found. Treatment with omeprazole or pantoprazole had no effect on nitric oxide (NO) concentration in the PMN culture supernatant and serum, cyclic guanosine monophosphate concentration in the PMN culture supernatant and serum, as well as inducible nitric oxide synthase (iNOS) protein expression and p38 mitogen-activated protein kinase activity in PMNs. In conclusion, treatment with PPI has no effect on NO production and p38 mitogen-activated protein kinase activity in PMNs. Interestingly, short-term treatment with omeprazole but not with pantoprazole enhances PMN reactive oxygen species production.