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Sample records for binding protein-3 luteinizing

  1. Structure of the lutein-binding domain of human StARD3 at 1.74 Å resolution and model of a complex with lutein.

    Science.gov (United States)

    Horvath, Martin P; George, Evan W; Tran, Quang T; Baumgardner, Kody; Zharov, Gabe; Lee, Sarah; Sharifzadeh, Hassan; Shihab, Saeed; Mattinson, Ty; Li, Binxing; Bernstein, Paul S

    2016-08-01

    A crystal structure of the lutein-binding domain of human StARD3 (StAR-related lipid-transfer protein 3; also known as MLN64) has been refined to 1.74 Å resolution. A previous structure of the same protein determined to 2.2 Å resolution highlighted homology with StARD1 and shared cholesterol-binding character. StARD3 has since been recognized as a carotenoid-binding protein in the primate retina, where its biochemical function of binding lutein with specificity appears to be well suited to recruit this photoprotective molecule. The current and previous structures correspond closely to each other (r.m.s.d. of 0.25 Å), especially in terms of the helix-grip fold constructed around a solvent-filled cavity. Regions of interest were defined with alternate conformations in the current higher-resolution structure, including Arg351 found within the cavity and Ω1, a loop of four residues found just outside the cavity entrance. Models of the complex with lutein generated by rigid-body docking indicate that one of the ionone rings must protrude outside the cavity, and this insight has implications for molecular interactions with transport proteins and enzymes that act on lutein. Interestingly, models with the ℇ-ionone ring characteristic of lutein pointing towards the bottom of the cavity were associated with fewer steric clashes, suggesting that steric complementarity and ligand asymmetry may play a role in discriminating lutein from the other ocular carotenoids zeaxanthin and meso-zeaxanthin, which only have β-ionone rings. PMID:27487925

  2. Lutein

    Science.gov (United States)

    ... this eye disease. Eye problems in premature infants (retinopathy of prematurity). Early research suggests that lutein does not decrease the risk or severity of retinopathy of prematurity. Other conditions. More evidence is needed to rate ...

  3. Radioiodination of chicken luteinizing hormone without affecting receptor binding potency

    Energy Technology Data Exchange (ETDEWEB)

    Kikuchi, M.; Ishii, S. (Waseda Univ., Tokyo (Japan))

    1989-12-01

    By improving the currently used lactoperoxidase method, we were able to obtain radioiodinated chicken luteinizing hormone (LH) that shows high specific binding and low nonspecific binding to a crude plasma membrane fraction of testicular cells of the domestic fowl and the Japanese quail, and to the ovarian granulosa cells of the Japanese quail. The change we made from the original method consisted of (1) using chicken LH for radioiodination that was not only highly purified but also retained a high receptor binding potency; (2) controlling the level of incorporation of radioiodine into chicken LH molecules by employing a short reaction time and low temperature; and (3) fractionating radioiodinated chicken LH further by gel filtration using high-performance liquid chromatography. Specific radioactivity of the final {sup 125}I-labeled chicken LH preparation was 14 microCi/micrograms. When specific binding was 12-16%, nonspecific binding was as low as 2-4% in the gonadal receptors. {sup 125}I-Labeled chicken LH was displaced by chicken LH and ovine LH but not by chicken follicle-stimulating hormone. The equilibrium association constant of quail testicular receptor was 3.6 x 10(9) M-1. We concluded that chicken LH radioiodinated by the present method is useful for studies of avian LH receptors.

  4. Somatomedin-1 binding protein-3: insulin-like growth factor-1 binding protein-3, insulin-like growth factor-1 carrier protein.

    Science.gov (United States)

    2003-01-01

    Somatomedin-1 binding protein-3 [insulin-like growth factor-1 binding protein-3, SomatoKine] is a recombinant complex of insulin-like growth factor-1 (rhIGF-1) and binding protein-3 (IGFBP-3), which is the major circulating somatomedin (insulin-like growth factor) binding protein; binding protein-3 regulates the delivery of somatomedin-1 to target tissues. Somatomedin-1 binding protein-3 has potential as replacement therapy for somatomedin-1 which may become depleted in indications such as major surgery, organ damage/failure and traumatic injury, resulting in catabolism. It also has potential for the treatment of osteoporosis; diseases associated with protein wasting including chronic renal failure, cachexia and severe trauma; and to attenuate cardiac dysfunction in a variety of disease states, including after severe burn trauma. Combined therapy with somatomedin-1 and somatomedin-1 binding protein-3 would prolong the duration of action of somatomedin-1 and would reduce or eliminate some of the undesirable effects associated with somatomedin-1 monotherapy. Somatomedin-1 is usually linked to binding protein-3 in the normal state of the body, and particular proteases clip them apart in response to stresses and release somatomedin-1 as needed. Therefore, somatomedin-1 binding protein-3 is a self-dosing system and SomatoKine would augment the natural supply of these linked compounds. Somatomedin-1 binding protein-3 was developed by Celtrix using its proprietary recombinant protein production technology. Subsequently, Celtrix was acquired by Insmed Pharmaceuticals on June 1 2000. Insmed and Avecia, UK, have signed an agreement for the manufacturing of SomatoKine and its components, IGF-1 and binding protein-3. CGMP clinical production of SomatoKine and its components will be done in Avecia's Advanced Biologics Centre, Billingham, UK, which manufactures recombinant-based medicines and vaccines with a capacity of up to 1000 litres. In 2003, manufacturing of SomatoKine is

  5. Insulin-like growth factor binding protein 3 in inflammatory bowel disease

    DEFF Research Database (Denmark)

    Kirman, Irena; Whelan, Richard Larry; Jain, Suvinit;

    2005-01-01

    Epithelial cell growth regulation has been reported to be altered in inflammatory bowel disease (IBD) patients. The cell growth regulatory factor, insulin-like growth factor binding protein 3 (IGFBP-3), may be partly responsible for this phenomenon. So far, IGFBP-3 levels have been assessed...

  6. Functional modulation of insulin-like growth factor binding protein-3 expression in melanoma

    OpenAIRE

    Dar, Altaf A.; Majid, Shahana; Nosrati, Mehdi; deSemir, David; Federman, Scot; Kashani-Sabet, Mohammed

    2010-01-01

    Insulin-like growth factor binding protein-3 (IGFBP3) is a member of the IGFBP family, which regulates mitogenic and anti-apoptotic effects of insulin-like growth factors. In this report we evaluated the role of IGFBP3 in melanoma. Quantitative real-time PCR (qRT-PCR), western and ELISA analysis indicated a significant downregulation of IGFBP3 expression in melanoma cell lines as compared to a normal melanocyte cell line. Melanoma cell lines treated with the demethylating agent 5-AZA-2′ deoxy...

  7. Insulin-like growth factor binding protein 3 in inflammatory bowel disease

    DEFF Research Database (Denmark)

    Kirman, Irena; Whelan, Richard Larry; Jain, Suvinit;

    2005-01-01

    Epithelial cell growth regulation has been reported to be altered in inflammatory bowel disease (IBD) patients. The cell growth regulatory factor, insulin-like growth factor binding protein 3 (IGFBP-3), may be partly responsible for this phenomenon. So far, IGFBP-3 levels have been assessed...... as values of total protein, which is a sum of bioactive intact 43- to 45-kDa protein and its inactive proteolytic cleavage fragments. We aimed to assess the levels of intact IGFBP-3 and its cleaving protease MMP-9 in IBD. Patients with IBD and controls were included. Total plasma IGFBP-3 concentration...... and MMP-9 levels were determined in ELISA. The concentration of intact IGFBP-3 was significantly decreased in patients with moderate to severe IBD activity compared to those in remission or controls. Of note, a dramatic depletion of intact IGFBP-3 was found in 7.4% of patients with IBD. Zymography...

  8. Insulin-like growth factor binding protein-3 in preterm infants with retinopathy of prematurity

    Directory of Open Access Journals (Sweden)

    Manizheh Mostafa Gharehbaghi

    2012-01-01

    Full Text Available Background: Retinopathy of prematurity (ROP is the main cause of visual impairment in preterm newborn infants. Objective: This study was conducted to determine whether insulin-like growth factor binding protein -3 (IGFBP-3 is associated with proliferative ROP and has a role in pathogenesis of the disease in premature infants. Materials and Methods: A total of 71 preterm infants born at or before 32 weeks of gestation participated in this study. Studied patients consisted of 41 neonates without vaso-proliferative findings of ROP as the control group and 30 preterm infants with evidence of severe ROP in follow up eye examination as the case group. Blood samples obtained from these infants 6-8 weeks after birth and blood levels of IGFBP-3 were measured using enzyme-linked immunosorbent assay (ELISA. Results: The mean gestation age and birth weight of the studied patients were 28.2±1.6 weeks and 1120.7±197 gram in the case group and 28.4±1.6 weeks and 1189.4±454 gram in the control group (P=0.25 and P=0.44 respectively. The infants in the case group had significantly lower Apgar score at first and 5 min after birth. Insulin-like growth factor binding protein -3 (IGFBP-3 was significantly lower in the patients with proliferative ROP than the patients without ROP [592.5±472.9 vs. 995.5±422.2 ng/ml (P=0.009]. Using a cut-off point 770.45 ng/ml for the plasma IGFBP-3, we obtained a sensitivity of 65.9% and a specificity of 66.7% in the preterm infants with vasoproliferative ROP. Conclusion: Our data demonstrated that the blood levels IGFBP-3 was significantly lower in the patients with ROP and it is suspected that IGFBP-3 deficiency in the premature infants may have a pathogenetic role in proliferative ROP.

  9. Ability of luteinizing hormone releasing hormone-Pseudomonas aeruginosa exotoxin 40 binding to LHRH receptor on human liver cancer cells

    Institute of Scientific and Technical Information of China (English)

    Shou-Liang Gong; Gang Zhao; Hong-Guang Zhao; Wen-Tian Lü; Guang-Wei Liu; Ping Zhu

    2004-01-01

    AIM: To explore the ability of recombinant toxin luteinizing hormone releasing hormone-Pseudomonas aeruginosa exotoxin 40 (LHRH-PE40) anH binding to LHRH receptor(LHRHR) on the membrane surfa ogf hman liver cancer HEPG cells.METHODS: LHRH was beled by using 125I with enzymatic reaction. The affinity and receptor volume of LHRH-PE40and LHRH binding to LHRHR on the membrane surface of human liver cancer cells were measured with radioligand receptor assay.RESULTS:The specific activity of LHRH labeled with 125I was 2.7×104 kBq/μL, and its radiochemical purity reached to 99.2-99.7%. The binding of 125I to LHRH was maximal for 240 min in the warm cultivation, and this binding was stabilized. The inhibiting rates of 125I-LHRH and LHRH on the proliferation of human liver cancer HEPG cells were not significantly different. On the basis of the saturation curve of 125I-LHRH binding to the membrane LHRHR of HEPG cells, 125I-LHRH of 1×105 cpm was selected for radioligand receptor assay. The affinity constants (Kd) of LHRH-PE40and LHRH bively,and their receptor volumes were 0.37±0.15 μmol/g and0.42±0.13 μmol/g, respectively. The binding of LHRH-PE40to the membrane proteinof normal liver cells was not observed.CONCLUSION: The recombinant toxin LHRH-PE40 binding to the membrane surface of LHRHR of human liver cancer HEPG cells was very strong, while the specific binding of it to normal liver cells was not observed. The results provide an important experimental basis for the clinical application of LHRH-PE.

  10. Nuclear actions of insulin-like growth factor binding protein-3.

    Science.gov (United States)

    Baxter, Robert C

    2015-09-10

    In addition to its actions outside the cell, cellular uptake and nuclear import of insulin-like growth factor binding protein-3 (IGFBP-3) has been recognized for almost two decades, but knowledge of its nuclear actions has been slow to emerge. IGFBP-3 has a functional nuclear localization signal and interacts with the nuclear transport protein importin-β. Within the nucleus IGFBP-3 appears to have a role in transcriptional regulation. It can bind to the nuclear receptor, retinoid X receptor-α and several of its dimerization partners, including retinoic acid receptor, vitamin D receptor (VDR), and peroxisome proliferator-activated receptor-γ (PPARγ). These interactions modulate the functions of these receptors, for example inhibiting VDR-dependent transcription in osteoblasts and PPARγ-dependent transcription in adipocytes. Nuclear IGFBP-3 can be detected by immunohistochemistry in cancer and other tissues, and its presence in the nucleus has been shown in many cell culture studies to be necessary for its pro-apoptotic effect, which may also involve interaction with the nuclear receptor Nur77, and export from the nucleus. IGFBP-3 is p53-inducible and in response to DNA damage, forms a complex with the epidermal growth factor receptor (EGFR), translocating to the nucleus to interact with DNA-dependent protein kinase. Inhibition of EGFR kinase activity or downregulation of IGFBP-3 can inhibit DNA double strand-break repair by nonhomologous end joining. IGFBP-3 thus has the ability to influence many cell functions through its interactions with intranuclear pathways, but the importance of these interactions in vivo, and their potential to be targeted for therapeutic benefit, require further investigation. PMID:26074086

  11. Acromegaly: the significance of serum total and free IGF-I and IGF-binding protein-3 in diagnosis

    NARCIS (Netherlands)

    A-J. van der Lely (Aart-Jan); W.W. de Herder (Wouter); J.A.M.J.L. Janssen (Joop); S.W.J. Lamberts (Steven)

    1997-01-01

    textabstractWe have studied the physiological and clinical relevance of measurements of serum total and free IGF-I and IGF-binding protein-3 (IGFBP-3) in 57 previously untreated patients with active acromegaly (32 males, 25 females; mean age 47 years) as compared with sex- and age-

  12. Aggravation of post-ischemic liver injury by overexpression of insulin-like growth factor binding protein 3

    OpenAIRE

    Lu Zhou; Hyoung-Won Koh; Ui-Jin Bae; Byung-Hyun Park

    2015-01-01

    Insulin-like growth factor-1 (IGF-1) is known to inhibit reperfusion-induced apoptosis. IGF-binding protein-3 (IGFBP-3) is the major circulating carrier protein for IGF-1 and induces apoptosis. In this study, we determined if IGFBP-3 was important in the hepatic response to I/R. To deliver IGFBP-3, we used an adenovirus containing IGFBP-3 cDNA (AdIGFBP-3) or an IGFBP-3 mutant devoid of IGF binding affinity but retaining IGFBP-3 receptor binding ability (AdIGFBP-3GGG). Mice subjected to I/R in...

  13. Differential expression of the RNA-binding motif protein 3 in human astrocytoma

    Institute of Scientific and Technical Information of China (English)

    ZHANG Hai-tao; ZHANG Zhi-wen; XUE Jing-hui; KONG Hai-bo; LIU Ai-jun; LI Shou-chun; LIU Yu-xiao

    2013-01-01

    Background The RNA-binding motif protein 3 (RBM3),which is transcriptionally induced by low temperature and hypoxia,has recently been found to be upregulated in human tumors.However,its expression status in human astrocytoma is not well defined.This article focuses on the differential expression of RBM3 in human astrocytomas of different grades and normal brain tissues.Methods RBM3 was detected in astrocytomas and normal brain tissues by quantitative real-time PCR,immunohistochemistry,and Western blotting.Analysis of variance was performed on the data from quantitative real-time PCR.The Fisher's exact test was used to analyze the immunohistochemistry results.A P-value of less than 0.05 indicates a statistically significant difference.Results On one hand,the mRNA expression levels of three X-chromosome-related RBM genes (RBMX,RBM3,and RBM10) were detected by quantitative real-time PCR.The results showed that there were no significant differences in RBMX and RBM10 mRNA expression levels in human astrocytomas of different grades and normal brain tissues.However,RBM3 mRNA expression levels were elevated in high-grade (World Health Organization (WHO) Grade Ⅲ-Ⅳ) astrocytomas versus low-grade (WHO Grade Ⅰ-Ⅱ) astrocytomas (5.06±0.66 vs.1.60±0.58; P <0.05) or normal controls (5.06±0.66 vs.1.03±0.22; P <0.05) as determined by quantitative real-time PCR analysis.On the other hand,immunohistochemistry showed an increased RBM3 labeling index in astrocytomas of different grades and normal brain tissues (positive staining rate:astrocytoma Grade Ⅳ,92.9%; astrocytoma Grade Ⅲ,81.8%; astrocytoma Grade Ⅰ-Ⅱ,50%;normal brain tissues,37.5%; high-grade astrocytoma versus normal brain tissues,P <0.05; high-grade astrocytoma versus low-grade astrocytoma,P <0.05).The higher protein levels of RBM3 were also validated in high-grade astrocytomas and low-grade astrocytomas compared with normal brain tissues by Western blotting.Conclusions These

  14. Interaction of Insulin-like Growth Factor-binding Protein-3 and BAX in Mitochondria Promotes Male Germ Cell Apoptosis

    OpenAIRE

    Jia, Yue; Lee, Kuk-Wha; Swerdloff, Ronald; Hwang, David; Cobb, Laura J.; Sinha Hikim, Amiya; Lue, Yan He; Cohen, Pinchas; Wang, Christina

    2009-01-01

    Germ cell apoptosis is crucial for spermatogenesis and can be triggered by various stimuli, including intratesticular hormone deprivation. This study proposes a role for insulin-like growth factor binding protein-3 (IGFBP-3) in male germ cell apoptosis. Groups of adult Sprague-Dawley male rats received one of the following treatments for 5 days: (i) daily intratesticular (IT) injections with saline (control); (ii) a single subcutaneous injection of the gonadotropin-releasing hormone antagonis...

  15. Identification of StARD3 as a Lutein-binding Protein in the Macula of the Primate Retina†

    OpenAIRE

    Li, Binxing; Vachali, Preejith; Frederick, Jeanne M.; Bernstein, Paul S

    2011-01-01

    Lutein, zeaxanthin and their metabolites are the xanthophyll carotenoids that form the macular pigment of the human retina. Epidemiological evidence suggests that high levels of these carotenoids in the diet, serum and macula are associated with decreased risk of age-related macular degeneration (AMD), and the AREDS2 study is prospectively testing this hypothesis. Understanding the biochemical mechanisms underlying the selective uptakes of lutein and zeaxanthin into the human macula may provi...

  16. ADAM 12, a disintegrin metalloprotease, interacts with insulin-like growth factor-binding protein-3

    DEFF Research Database (Denmark)

    Shi, Z; Xu, Wei; Loechel, F;

    2000-01-01

    Insulin-like growth factor-binding protein (IGFBP)-3 binds the insulin-like growth factors with high affinity and modulates their actions. Proteolytic cleavage of IGFBP-3 may regulate insulin-like growth factor bioavailability. IGFBP-3 is extensively degraded in serum during pregnancy; however, a...

  17. Role of insulin-like growth factor binding protein-3 in glucose and lipid metabolism

    OpenAIRE

    Kim, Ho-Seong

    2013-01-01

    Insulin-like growth factor binding protein (IGFBP)-3 has roles in modulating the effect of IGFs by binding to IGFs and inhibiting cell proliferation in an IGF-independent manner. Although recent studies have been reported that IGFBP-3 has also roles in metabolic regulation, their exact roles in adipose tissue are poorly understood. In this review, we summarized the studies about the biological roles in glucose and lipid metabolism. IGFBP-3 overexpression in transgenic mice suggested that IGFB...

  18. Enthalpy/entropy compensation effects from cavity desolvation underpin broad ligand binding selectivity for rat odorant binding protein 3.

    Science.gov (United States)

    Portman, Katherine L; Long, Jed; Carr, Stephen; Briand, Loïc; Winzor, Donald J; Searle, Mark S; Scott, David J

    2014-04-15

    Evolution has produced proteins with exquisite ligand binding specificity, and manipulating this effect has been the basis for much of modern rational drug design. However, there are general classes of proteins with broader ligand selectivity linked to function, the origin of which is poorly understood. The odorant binding proteins (OBPs) sequester volatile molecules for transportation to the olfactory receptors. Rat OBP3, which we characterize by X-ray crystallography and NMR, binds a homologous series of aliphatic γ-lactones within its aromatic-rich hydrophobic pocket with remarkably little variation in affinity but extensive enthalpy/entropy compensation effects. We show that the binding energetics are modulated by two desolvation processes with quite different thermodynamic signatures. Ligand desolvation follows the classical hydrophobic effect; however, cavity desolvation is consistent with the liberation of "high energy" water molecules back into bulk solvent with a strong, but compensated, enthalpic contribution, which together underpin the origins of broad ligand binding selectivity.

  19. Insulin-like growth factor-binding protein-3 inhibition of prostate cancer growth involves suppression of angiogenesis.

    Science.gov (United States)

    Liu, B; Lee, K-W; Anzo, M; Zhang, B; Zi, X; Tao, Y; Shiry, L; Pollak, M; Lin, S; Cohen, P

    2007-03-15

    Insulin-like growth factor-binding protein-3 (IGFBP-3) is a multifunctional protein that induces apoptosis utilizing both insulin-like growth factor receptor (IGF)-dependent and -independent mechanisms. We investigated the effects of IGFBP-3 on tumor growth and angiogenesis utilizing a human CaP xenograft model in severe-combined immunodeficiency mice. A 16-day course of IGFBP-3 injections reduced tumor size and increased apoptosis and also led to a reduction in the number of vessels stained with CD31. In vitro, IGFBP-3 inhibited both vascular endothelial growth factor- and IGF-stimulated human umbilical vein endothelial cells vascular network formation in a matrigel assay. This action is primarily IGF independent as shown by studies utilizing the non-IGFBP-binding IGF-1 analog Long-R3. Additionally, we used a fibroblast growth factor-enriched matrigel-plug assay and chick allantoic membrane assays to show that IGFBP-3 has potent antiangiogenic actions in vivo. Finally, overexpression of IGFBP-3 or the non-IGF-binding GGG-IGFBP-3 mutant in Zebrafish embryos confirmed that both IGFBP-3 and the non-IGF-binding mutant inhibited vessel formation in vivo, indicating that the antiangiogenic effect of IGFBP-3 is an IGF-independent phenomenon. Together, these studies provide the first evidence that IGFBP-3 has direct, IGF-independent inhibitory effects on angiogenesis providing an additional mechanism by which it exerts its tumor suppressive effects and further supporting its development for clinical use in the therapy of patients with prostate cancer. PMID:16983336

  20. Nuclear magnetic resonance structure of the nucleic acid-binding domain of severe acute respiratory syndrome coronavirus nonstructural protein 3.

    Science.gov (United States)

    Serrano, Pedro; Johnson, Margaret A; Chatterjee, Amarnath; Neuman, Benjamin W; Joseph, Jeremiah S; Buchmeier, Michael J; Kuhn, Peter; Wüthrich, Kurt

    2009-12-01

    The nuclear magnetic resonance (NMR) structure of a globular domain of residues 1071 to 1178 within the previously annotated nucleic acid-binding region (NAB) of severe acute respiratory syndrome coronavirus nonstructural protein 3 (nsp3) has been determined, and N- and C-terminally adjoining polypeptide segments of 37 and 25 residues, respectively, have been shown to form flexibly extended linkers to the preceding globular domain and to the following, as yet uncharacterized domain. This extension of the structural coverage of nsp3 was obtained from NMR studies with an nsp3 construct comprising residues 1066 to 1181 [nsp3(1066-1181)] and the constructs nsp3(1066-1203) and nsp3(1035-1181). A search of the protein structure database indicates that the globular domain of the NAB represents a new fold, with a parallel four-strand beta-sheet holding two alpha-helices of three and four turns that are oriented antiparallel to the beta-strands. Two antiparallel two-strand beta-sheets and two 3(10)-helices are anchored against the surface of this barrel-like molecular core. Chemical shift changes upon the addition of single-stranded RNAs (ssRNAs) identified a group of residues that form a positively charged patch on the protein surface as the binding site responsible for the previously reported affinity for nucleic acids. This binding site is similar to the ssRNA-binding site of the sterile alpha motif domain of the Saccharomyces cerevisiae Vts1p protein, although the two proteins do not share a common globular fold.

  1. FOXA1 promotes tumor progression in prostate cancer via the insulin-like growth factor binding protein 3 pathway.

    Directory of Open Access Journals (Sweden)

    Yusuke Imamura

    Full Text Available Fork-head box protein A1 (FOXA1 is a "pioneer factor" that is known to bind to the androgen receptor (AR and regulate the transcription of AR-specific genes. However, the precise role of FOXA1 in prostate cancer (PC remains unknown. In this study, we report that FOXA1 plays a critical role in PC cell proliferation. The expression of FOXA1 was higher in PC than in normal prostate tissues (P = 0.0002, and, using immunohistochemical analysis, we found that FOXA1 was localized in the nucleus. FOXA1 expression levels were significantly correlated with both PSA and Gleason scores (P = 0.016 and P = 0.031, respectively. Moreover, FOXA1 up-regulation was a significant factor in PSA failure (P = 0.011. Depletion of FOXA1 in a prostate cancer cell line (LNCaP using small interfering RNA (siRNA significantly inhibited AR activity, led to cell-growth suppression, and induced G0/G1 arrest. The anti-proliferative effect of FOXA1 siRNA was mediated through insulin-like growth factor binding protein 3 (IGFBP-3. An increase in IGFBP-3, mediated by depletion of FOXA1, inhibited phosphorylation of MAPK and Akt, and increased expression of the cell cycle regulators p21 and p27. We also found that the anti-proliferative effect of FOXA1 depletion was significantly reversed by simultaneous siRNA depletion of IGFBP-3. These findings provide direct physiological and molecular evidence for a role of FOXA1 in controlling cell proliferation through the regulation of IGFBP-3 expression in PC.

  2. DIAGNOSTIC VALUE OF SERUM INSULIN-LIKE GROWTH FACTOR BINDING PROTEIN-3 IN CHILDREN WITH OR WITHOUT GROWTH HORMONE DEFICIENCY

    Institute of Scientific and Technical Information of China (English)

    覃舒文; 史轶蘩; 邓洁英

    2002-01-01

    Objective. To study the value of serum insulin-like growth factor binding protein-3 (IGFBP-3) levels in differential diagnosis of growth hormone deficiency (GHD). Methods. To measure serum IGFBP-3 levels by RIA in normal children and adolescents, GHD children and short-stature children without GHD. Results. Serum level of IGFBP-3 in 129 children with untreated GHD and with no pubertal development was 1.6± 0.9 mg/L, which was less than that in normal group of the same age, but overlapped with the normal children in Tanner stage I. After six -month treatment with recombinant human growth hormone (rhGH), serum level of IGFBP-3 in 59 GHD significantly increased from 1.3± 0.7 mg/L to 2.7± 0.9 mg/L, accompanied by an increase of body heights, growth velocities and serum level of IGF-1. Serum level of IGFBP-3 in 55 short-stature children without GHD was 3.3± 2.2 mg/L, which was not significantly different from that in normal group. Conclusion. Serum IGFBP-3 level can reflect the status of GH secretion in children with GHD and is a useful marker for differential diagnosis of GHD.

  3. Insulin-like growth factor binding protein-3 affects osteogenic efficacy on dental implants in rat mandible

    International Nuclear Information System (INIS)

    Insulin like growth factor binding protein-3 (IGFBP-3) in bone cells and its utilization in dental implants have not been well studied. The aim of this study was to determine the osteogenic efficacy of chitosan gold nanoparticles (Ch-GNPs) conjugated with IGFBP-3 coated titanium (Ti) implants. Ch-GNPs were conjugated with IGFBP-3 plasmid DNA through a coacervation process. Conjugation was cast over Ti surfaces, and cells were seeded on coated surfaces. For in vitro analysis the expression of different proteins was analyzed by immunoblotting. For in vivo analysis, Ch-GNP/IGFBP-3 coated implants were installed in rat mandibles. Four weeks post-implantation, mandibles were examined by microcomputed tomography (μCT), immunohistochemistry, hematoxylin & eosin and tartrate resistance acid phosphatase staining. In vitro overexpressed Ch-GNP/IGFBP-3 coated Ti surfaces was associated with activation of extracellular signal related kinase (ERK), inhibition of the stress activated protein c-Jun N-terminal kinase (JNK) and enhanced bone morphogenetic protein (BMP)-2 and 7 compared to control. Further, in vivo, Ch-GNP/IGFBP-3 coated implants were associated with inhibition of implant induced osteoclastogenesis molecules, receptor activator of nuclear factor kappa-B ligand (RANKL) and enhanced expression of osteogenic molecules including BMP2/7 and osteopontin (OPN). The μCT analysis demonstrated that IGFBP-3 increased the volume of newly formed bone surrounding the implants compared to control (n = 5; p < 0.05). These results support the view that IGFBP-3 overexpression diminishes osteoclastogenesis and enhances osteogenesis of Ti implants, and can serve as a potent molecule for the development of good implantation. - Highlights: • Chitosan gold nanoparticles were conjugated with IGFBP-3 and coated onto surface of the titanium implants for gene delivery to bone. • Implants were inserted in rat mandible for 4 weeks. • Parameters studied: histopathology and radiology.

  4. Insulin-like growth factor binding protein-3 affects osteogenic efficacy on dental implants in rat mandible

    Energy Technology Data Exchange (ETDEWEB)

    Bhattarai, Govinda; Lee, Young-Hee [Department of Oral Biochemistry, Institute of Oral Bioscience, School of Dentistry, Chonbuk National University, Jeonju (Korea, Republic of); Lee, Min-Ho [Department of Dental Materials, Institute of Oral Bioscience, School of Dentistry, Chonbuk National University, Jeonju (Korea, Republic of); Park, Il-Song [Division of Advanced Materials Engineering, Research Center for Advanced Materials, Development and Institute of Biodegradable Materials, Chonbuk National University, Jeonju 561-756 (Korea, Republic of); Yi, Ho-Keun, E-mail: yihokn@chonbuk.ac.kr [Department of Oral Biochemistry, Institute of Oral Bioscience, School of Dentistry, Chonbuk National University, Jeonju (Korea, Republic of)

    2015-10-01

    Insulin like growth factor binding protein-3 (IGFBP-3) in bone cells and its utilization in dental implants have not been well studied. The aim of this study was to determine the osteogenic efficacy of chitosan gold nanoparticles (Ch-GNPs) conjugated with IGFBP-3 coated titanium (Ti) implants. Ch-GNPs were conjugated with IGFBP-3 plasmid DNA through a coacervation process. Conjugation was cast over Ti surfaces, and cells were seeded on coated surfaces. For in vitro analysis the expression of different proteins was analyzed by immunoblotting. For in vivo analysis, Ch-GNP/IGFBP-3 coated implants were installed in rat mandibles. Four weeks post-implantation, mandibles were examined by microcomputed tomography (μCT), immunohistochemistry, hematoxylin & eosin and tartrate resistance acid phosphatase staining. In vitro overexpressed Ch-GNP/IGFBP-3 coated Ti surfaces was associated with activation of extracellular signal related kinase (ERK), inhibition of the stress activated protein c-Jun N-terminal kinase (JNK) and enhanced bone morphogenetic protein (BMP)-2 and 7 compared to control. Further, in vivo, Ch-GNP/IGFBP-3 coated implants were associated with inhibition of implant induced osteoclastogenesis molecules, receptor activator of nuclear factor kappa-B ligand (RANKL) and enhanced expression of osteogenic molecules including BMP2/7 and osteopontin (OPN). The μCT analysis demonstrated that IGFBP-3 increased the volume of newly formed bone surrounding the implants compared to control (n = 5; p < 0.05). These results support the view that IGFBP-3 overexpression diminishes osteoclastogenesis and enhances osteogenesis of Ti implants, and can serve as a potent molecule for the development of good implantation. - Highlights: • Chitosan gold nanoparticles were conjugated with IGFBP-3 and coated onto surface of the titanium implants for gene delivery to bone. • Implants were inserted in rat mandible for 4 weeks. • Parameters studied: histopathology and radiology.

  5. IGF-1 receptor and IGF binding protein-3 might predict prognosis of patients with resectable pancreatic cancer

    International Nuclear Information System (INIS)

    The present study aimed to elucidate the clinicopathologic role of insulin-like growth factor-1 receptor (IGF1R) and IGF binding protein-3 (IGFBP3) in patients with pancreatic cancer. The function of IGFBP3 is controversial, because both inhibition and facilitation of the action of IGF as well as IGF-independent effects have been reported. In this study, IGF1R and IGFBP3 expression was examined, and their potential roles as prognostic markers in patients with pancreatic cancer were evaluated. Clinicopathological features of 122 patients with curatively resected pancreatic cancer were retrospectively reviewed, and expression of IGF1R and IGFBP3 was immunohistochemically analyzed. Expression of IGF1R and IGFBP3 was observed in 50 (41.0%) and 37 (30.3%) patients, respectively. IGF1R expression was significantly associated with histological grade (p = 0.037). IGFBP3 expression had a significant association with tumor location (p = 0.023), and a significant inverse association with venous invasion (p = 0.037). Tumors with IGF1R-positive and IGFBP3-negative expression (n = 32) were significantly frequently Stage II and III (p = 0.011). The prognosis for IGF1R positive patients was significantly poorer than that for IGF1R negative patients (p = 0.0181). IGFBP3 protein expression did not correlate significantly with patient survival. The subset of patients with both positive IGF1R and negative IGFBP3 had worse overall survival (8.8 months versus 12.6 months, respectively, p < 0.001). IGF1R signaling might be associated with tumor aggressiveness, and IGFBP3 might show antiproliferative effects in pancreatic cancer. Both high IGF1R expression and low IGFBP3 expression represent useful prognostic markers for patients with curatively resected pancreatic cancer

  6. Excessive gestational weight gain and obesity contribute to altered expression of maternal insulin-like growth factor binding protein-3

    Directory of Open Access Journals (Sweden)

    Ferraro ZM

    2013-10-01

    0.01. However, serum IGFBP-3 expression in the EXCEED mothers was greater than that in the ADHERE group (P ≤ 0.05. Conclusion: These findings provide preliminary evidence suggesting that small deviations in IGFBP-regulated IGF bioavailability arising from excessive GWG/positive energy balance may affect adipocyte differentiation through subclinical insulin resistance. Keywords: gestational weight gain, insulin-like growth factors, insulin-like growth factor binding protein-3, pregnancy, insulin sensitivity

  7. Protection of blood retinal barrier and systemic vasculature by insulin-like growth factor binding protein-3.

    Directory of Open Access Journals (Sweden)

    Yagna P R Jarajapu

    Full Text Available Previously, we showed that insulin growth factor (IGF-1 binding protein-3 (IGFBP-3, independent of IGF-1, reduces pathological angiogenesis in a mouse model of the oxygen-induced retinopathy (OIR. The current study evaluates novel endothelium-dependent functions of IGFBP-3 including blood retinal barrier (BRB integrity and vasorelaxation. To evaluate vascular barrier function, either plasmid expressing IGFBP-3 under the regulation of an endothelial-specific promoter or a control plasmid was injected into the vitreous humor of mouse pups (P1 and compared to the non-injected eyes of the same pups undergoing standard OIR protocol. Prior to sacrifice, the mice were given an injection of horseradish peroxidase (HRP. IGFBP-3 plasmid-injected eyes displayed near-normal vessel morphology and enhanced vascular barrier function. Further, in vitro IGFBP-3 protects retinal endothelial cells from VEGF-induced loss of junctional integrity by antagonizing the dissociation of the junctional complexes. To assess the vasodilatory effects of IGFBP-3, rat posterior cerebral arteries were examined in vitro. Intraluminal IGFBP-3 decreased both pressure- and serotonin-induced constrictions by stimulating nitric oxide (NO release that were blocked by L-NAME or scavenger receptor-B1 neutralizing antibody (SRB1-Ab. Both wild-type and IGF-1-nonbinding mutant IGFBP-3 (IGFBP-3NB stimulated eNOS activity/NO release to a similar extent in human microvascular endothelial cells (HMVECs. NO release was neither associated with an increase in intracellular calcium nor decreased by Ca(2+/calmodulin-dependent protein kinase II (CamKII blockade; however, dephosphorylation of eNOS-Thr(495 was observed. Phosphatidylinositol 3-kinase (PI3K activity and Akt-Ser(473 phosphorylation were both increased by IGFBP-3 and selectively blocked by the SRB1-Ab or PI3K blocker LY294002. In conclusion, IGFBP-3 mediates protective effects on BRB integrity and mediates robust NO release to stimulate

  8. Radioimmunoassay of human insulin-like growth factor binding protein-3 in serum and its clinical application

    International Nuclear Information System (INIS)

    Objective: To establish a specific radioimmunoassay (RIA) for serum level of human insulin-like growth factor binding protein-3 (IGFBP-3) and study serum IGFBP-3 levels in normal adults and some pathophysiological states. Methods: IGFBP-3 antibody was raised and iodinated IGFBP-3 was made with lactoperoxidase as a tracer, then set up the RIA for human serum IGFBP-3. Serum levels of normal adults, patients suffered from acromegaly, growth hormone deficiency (GHD), liver cirrhosis and chronic renal failure (CRF) were tested. Results: The minimal detectable range of this IGFBP-3 RIA was (16.9 +- 2.4) μg/L. The affinity constant is 7.9 x 1010 L/mol, without cross-reactivity with IGFBP-1, IGFBP-2, insulin-like growth factor-1 (IGF-1) and human growth hormone (hGH). The mean rate of recovery was 98.7%, and the mean coefficients of variation for intra- and inter batch-assay were (7.8 +- 3.5)% and (10.8 +- 3.1)% respectively. The mean serum levels of IGFBP-3 in 88 normal adults were (3.1+- 0.5) mg/L (range 2.0-4.0 mg/L), while that in 49 active acromegalics were (16.8 +- 9.9) mg/L (range 5.6-42.8 mg/L) and in 19 CRF were (13.2 +- 3.6) mg/L (range 9.8-25.0 mg/L), none of them was overlapping the normal adult levels. The mean serum IGFBP-3 levels of 129 GHD and 18 liver cirrhosis were (1.6 +-0.9) mg/L (range 0.4-3.7 mg/L) and (2.4+-0.7) mg/L (range 1.2-3.7 mg/L) respectively, all of them were overlapping the lower level of serum IGFBP-3 of normal adults. Conclusions: This RIA is easy to use, can detect wide range of serum IGFBP-3, has high specificity and good reproducibility. Serum IGFBP-3 assay is very useful in diagnosis of the hyper-, normal and hypo-secretory state of hGH

  9. The Association between Insulin-like Growth Factor-1 and Insulin-like Growth Factor Binding Protein-3 Levels and Clinical Prognosis in Patients with Ischemic Stroke

    Directory of Open Access Journals (Sweden)

    Hasan Yaşar

    2015-04-01

    Full Text Available OBJECTIVE: Recent studies report that the insulin-like growth factor system may be involved in stroke pathogenesis, and is reported to increase myelination, maturation, cell proliferation and neuronal sprouting of the central nervous system. The aim of the present study is to demonstrate the role of insulin-like growth factor system in ischemic stroke pathogenesis and its association with the prognosis by investigating insulin-like growth factor-1 and insulin-like growth factor binding protein-3 levels in patients diagnosed with acute ischemic stroke. METHODS: : Sixty-eight patients and 20 healthy individuals were included to this study. Clinical evaluation of the patients was performed according to National Institute of Health Stroke Scale and functional outcomes were graded according to Modified Rankin Scale. Bamford classification was used for the clinical classification of ischemic strokes, and the TOAST system for etiological classification. Each patient's levels of insulin-like growth factor-1 and insulin-like growth factor binding protein-3 were measured on the first, fifth and thirtieth day of ischemic stroke. RESULTS: Only the levels of insulin-like growth factor binding protein-3 on the day of 5 were significantly decreased compared to the control group. The decrease in IGF-1 values was associated with an increased risk of death and was accompanied by clinical worsening and decreased functionality. CONCLUSION: It has been concluded that the levels of investigating insulin-like growth factor-1 and insulin-like growth factor binding protein-3 may affect mortality risk, clinical condition and functionality outcomes in patients presenting with ischemic stroke, and further studies are needed for the investigation of different effects of insulin-like growth factor-1 in future.

  10. Insulin-like growth factor binding protein-3 is required for the regulation of rat oval cell proliferation and differentiation in the 2AAF/PHX model

    OpenAIRE

    Steiger-Luther, Nicole C; Darwiche, Houda; Oh, Seh-Hoon; Williams, Jennifer M.; PETERSEN, BRYON E.

    2010-01-01

    Oval cell-mediated liver regeneration is a highly complex process that involves the coordination of several signaling factors, chemokines and cytokines to allow for proper maintenance of the liver architecture. When hepatocyte proliferation is inhibited, an hepatic stem cell population, often referred to as “oval cells”, is activated to aid in liver regeneration. The function of insulin-like growth factor binding protein-3 (IGFBP-3) during this process of oval cell activation is of particular...

  11. Enhancing the Apoptotic Potential of Insulin-Like Growth Factor-Binding Protein-3 in Prostate Cancer by Modulation of CK2 Phosphorylation

    OpenAIRE

    Cobb, Laura J.; Mehta, Hemal; Cohen, Pinchas

    2009-01-01

    IGF-binding protein 3 (IGFBP-3) promotes apoptosis by both IGF-dependent and -independent mechanisms. We have previously reported that phosphorylation of IGFBP-3 (S156) by DNA-dependent protein kinase enhances its nuclear accumulation and is essential for its ability to interact with retinoid X receptor-α and induce apoptosis in cultured prostate cancer cells. Using specific chemical inhibitors and small interfering RNA, we demonstrate that preventing casein kinase 2 (CK2) activation enhanced...

  12. Immunohistochemical expression of insulin-like growth factor binding protein-3 in invasive breast cancers and ductal carcinoma in situ: implications for clinicopathology and patient outcome

    OpenAIRE

    Vestey, Sarah B; Perks, Claire M.; Sen, Chandan; Calder, Caroline J; Holly, Jeff MP; Winters, Zoe E

    2004-01-01

    Introduction Insulin-like growth factor binding protein-3 (IGFBP-3) differentially modulates breast epithelial cell growth through insulin-like growth factor (IGF)-dependent and IGF-independent pathways and is a direct (IGF-independent) growth inhibitor as well as a mitogen that potentiates EGF (epidermal growth factor) and interacts with HER-2. Previously, high IGFBP-3 levels in breast cancers have been determined by enzyme-linked immunosorbent assay and immunoradiometric assay methods. In v...

  13. Analysis of the cellular uptake and nuclear delivery of insulin-like growth factor binding protein-3 in human osteosarcoma cells

    OpenAIRE

    Laich, A; Matscheski, A.; Mück, C.; Ferrando-May, E.; H. Pircher; Ebner, H L; Micutkova, L.; Huber, L A; M. Hermann; Offerdinger, M.; Hess, M. W.; Jansen-Dürr, P; Zwerschke, W.

    2010-01-01

    Insulin-like growth factor (IGF) binding protein-3 (IGFBP-3) is an important regulator of cell proliferation and survival, which plays an important role in a variety of epithelial cancers, including prostate cancer, cervical cancer and breast cancer. IGFBP-3 was described as a tumor suppressor in the prostate and identified as a functional cellular target for the E7 oncoprotein of human papillomaviruses. IGFBP-3 interacts with IGF-I outside the cell; however, IGF-independent actions of IGFBP...

  14. Effects of Hibiscus sabdariffa Linn. on insulin-like growth factor binding protein 3 (IGFBP-3) to prevent overtraining syndrome

    OpenAIRE

    Ermita I.I. Ilyas; Neng T. Kartinah; Trinovita Andraini; Roman A. Goenarjo; Donna N. Kahandjak

    2015-01-01

    Background: Excessive physical exercises (overtraining) can increase the production of reactive oxygen species (ROS). One of the indicators of overtraining syndrome is a decrease in insulin-like growth factor binding protein 3 (IGFBP-3). Administration of Hibiscus sabdariffa Linn., a powerful antioxidant, is expected to boost endogenous antioxidants, and thus prevents overtraining. The aim of this study is to determine the effect of H. sabdariffa on IGFBP-3 levels in rats under ”overtraining ...

  15. Interaction between the Alzheimer's survival peptide humanin and insulin-like growth factor-binding protein 3 regulates cell survival and apoptosis

    OpenAIRE

    Ikonen, Maaria; LIU, BINGRONG; Hashimoto, Yuichi; Ma, Liqun; Lee, Kuk-Wha; Niikura, Takako; Nishimoto, Ikuo; Cohen, Pinchas

    2003-01-01

    Insulin-like growth factor-binding protein-3 (IGFBP-3) regulates IGF bioactivity and also independently modulates cell growth and survival. By using a yeast two-hybrid screen to identify IGFBP-3-interacting proteins, we cloned humanin (HN) as an IGFBP-3-binding partner. HN is a 24-aa peptide that has been shown to specifically inhibit neuronal cell death induced by familial Alzheimer's disease mutant genes and amyloid-β (Aβ). The physical interaction of HN with IGFBP-3 was determined to be of...

  16. Potentiation of Growth Factor Signaling by Insulin-like Growth Factor-binding Protein-3 in Breast Epithelial Cells Requires Sphingosine Kinase Activity*

    OpenAIRE

    Martin, Janet L; Mike Z. Lin; Eileen M. McGowan; Baxter, Robert C.

    2009-01-01

    We have investigated the mechanism underlying potentiation of epidermal growth factor receptor (EGFR) and type 1 insulin-like growth factor receptor (IGFR1) signaling by IGF-binding protein-3 (IGFBP-3) in MCF-10A breast epithelial cells, focusing on a possible involvement of the sphingosine kinase (SphK) system. IGFBP-3 potentiated EGF-stimulated EGF receptor activation and DNA synthesis, and this was blocked by inhibitors of SphK activity or small interference RNA-mediated silencing of SphK1...

  17. Serum insulin-like growth factor I (IGF-I) and IGF-binding protein 3 levels are increased in central precocious puberty

    DEFF Research Database (Denmark)

    Juul, A; Scheike, Thomas Harder; Nielsen, C T;

    1995-01-01

    Central precocious puberty (CPP) is characterized by early activation of the pituitary-gonadal axis, which leads to increased growth velocity and development of secondary sexual characteristics. It is generally believed that gonadal sex steroids stimulate pulsatile GH secretion, which, in turn......, stimulates insulin-like growth factor I (IGF-I) and IGF-binding protein 3 (IGFBP-3) production. However, little is known about GH, IGF-I, and IGFBP-3 serum levels in children with precocious puberty. Treatment of CPP by GnRH agonists has become the treatment of choice. However, the effect of long term...

  18. Total and free insulin-like growth factor I, insulin-like growth factor binding protein 3 and acid-labile subunit reflect clinical activity in acromegaly

    DEFF Research Database (Denmark)

    Sneppen, S B; Lange, Merete Wolder; Pedersen, L M;

    2001-01-01

    The aim was to evaluate, markers of disease activity in acromegaly in relation to perceived disease activity. Thirty-seven consecutively treated, acromegalic patients, classified by clinical symptoms as inactive (n=16), slightly active (n=10) and active (n=11), entered the study. When evaluating......-like growth factor binding protein-3 (IGFBP-3) with PV(pos) of 0.69 and 0.71 and PV(neg) of 0.91 and 0.92 respectively. We conclude that free IGF-I is more closely related than total IGF-I to perceived disease activity and is as such useful when evaluating previously treated acromegaly for disease activity...

  19. Isolation of complexes formed between insulin-like growth factor-binding protein-3 and transferrin from the human serum

    Directory of Open Access Journals (Sweden)

    Miljuš Goran

    2012-01-01

    Full Text Available Insulin-like growth factors (IGFs play an important role in the regulation of cell growth, differentiation and metabolism. The amount of free, biologically active IGFs is regulated by the IGF-binding proteins (IGFBPs. IGFBP-3 is the most abundant binding protein and it is known to interact with other circulating proteins, including transferrin (Tf. In order to elucidate the possible role of IGF/IGFBP-3 in the iron metabolism, it is necessary to isolate IGFBP-3/Tf complexes. Several affinity-based techniques were employed. Results have shown that only double immunoprecipitation method with anti-Tf and anti-IGFBP-3 antibodies selectively separated complexes from other molecular forms, such as monomers, oligomers or fragments of IGFBP-3 and Tf. Isolated complexes can now be used to investigate the relationship between IGF/IGFBP-3 and iron, both in structural and metabolic tеrms.

  20. Epidermal Growth Factor Receptor Regulates Aberrant Expression of Insulin-Like Growth Factor-Binding Protein 3

    OpenAIRE

    TAKAOKA, MUNENORI; Harada, Hideki; Andl, Claudia D; Oyama, Kenji; Naomoto, Yoshio; Dempsey, Kelly L.; Klein-Szanto, Andres J.; El-Deiry, Wafik S; GRIMBERG, ADDA; Nakagawa, Hiroshi

    2004-01-01

    Epidermal growth factor receptor (EGFR) is frequently overexpressed in esophageal carcinoma and its precursor lesions. To gain insights into how EGFR overexpression affects cellular functions in primary human esophageal cells, we performed gene expression profiling and identified insulin-like growth factor-binding protein (IGFBP)-3 as the most up-regulated gene. IGFBP-3 regulates cell proliferation through both insulin-like growth factor-dependent and independent mechanisms. We found that IGF...

  1. PPARγ induces growth inhibition and apoptosis through upregulation of insulin-like growth factor-binding protein-3 in gastric cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Kim, S.Y. [Department of Pediatrics, Chonbuk National University Hospital, Jeonju (Korea, Republic of); Biomedical Research Institute, School of Medicine, Chonbuk National University Hospital, Jeonju (Korea, Republic of); Kim, M.S.; Lee, M.K. [Department of Pediatrics, Chonbuk National University Hospital, Jeonju (Korea, Republic of); Kim, J.S.; Yi, H.K. [Department of Biochemistry, School of Dentistry, Chonbuk National University, Jeonju (Korea, Republic of); Nam, S.Y. [Department of Alternative Therapy, Jeonju University, Jeonju (Korea, Republic of); Lee, D.Y.; Hwang, P.H. [Department of Pediatrics, Chonbuk National University Hospital, Jeonju (Korea, Republic of); Biomedical Research Institute, School of Medicine, Chonbuk National University Hospital, Jeonju (Korea, Republic of)

    2015-01-13

    Peroxisome proliferator activator receptor-gamma (PPARγ) is a ligand-activated transcriptional factor involved in the carcinogenesis of various cancers. Insulin-like growth factor-binding protein-3 (IGFBP-3) is a tumor suppressor gene that has anti-apoptotic activity. The purpose of this study was to investigate the anticancer mechanism of PPARγ with respect to IGFBP-3. PPARγ was overexpressed in SNU-668 gastric cancer cells using an adenovirus gene transfer system. The cells in which PPARγ was overexpressed exhibited growth inhibition, induction of apoptosis, and a significant increase in IGFBP-3 expression. We investigated the underlying molecular mechanisms of PPARγ in SNU-668 cells using an IGFBP-3 promoter/luciferase reporter system. Luciferase activity was increased up to 15-fold in PPARγ transfected cells, suggesting that PPARγ may directly interact with IGFBP-3 promoter to induce its expression. Deletion analysis of the IGFBP-3 promoter showed that luciferase activity was markedly reduced in cells without putative p53-binding sites (-Δ1755, -Δ1795). This suggests that the critical PPARγ-response region is located within the p53-binding region of the IGFBP-3 promoter. We further demonstrated an increase in PPARγ-induced luciferase activity even in cells treated with siRNA to silence p53 expression. Taken together, these data suggest that PPARγ exhibits its anticancer effect by increasing IGFBP-3 expression, and that IGFBP-3 is a significant tumor suppressor.

  2. The impact of obesity, fat distribution, and energy restriction on insulin-like growth factor-1 (IGF-1), IGF-binding protein-3, insulin, and growth hormone

    DEFF Research Database (Denmark)

    Rasmussen, M H; Frystyk, Jan; Andersen, T;

    1994-01-01

    The aim of this study was to characterize the association between serum insulin-like growth factor-1 (IGF-1) and obesity, as well as fat distribution, before and during moderate energy restriction (1,200 kcal/d). In 51 females and nine males having a body mass index (BMI) between 27 and 39 kg/m2......, relationships between serum IGF-1, IGF-binding protein-3 (IGFBP-3), insulin, growth hormone (GH), blood glucose, and anthropometric measurements of body fat were examined. The patients were studied before treatment and again after 8 and 16 weeks of dieting. Visceral adipose tissue (AT) was estimated...... = .02) weeks of dietary treatment. Both serum IGF-1 and insulin levels were positively correlated with serum IGFBP-3 levels (r = .34, P = .009 and r = .34, P = .008, respectively). We conclude that IGF-1 levels in obese females reflect the intraabdominal fat mass rather than obesity per se. IGF-1...

  3. Total and free insulin-like growth factor I, insulin-like growth factor binding protein 3 and acid-labile subunit reflect clinical activity in acromegaly

    DEFF Research Database (Denmark)

    Sneppen, S B; Lange, Merete Wolder; Pedersen, L M;

    2001-01-01

    insulin-like growth factor binding protein-3 (IGFBP-3) with PV(pos) of 0.69 and 0.71 and PV(neg) of 0.91 and 0.92 respectively. We conclude that free IGF-I is more closely related than total IGF-I to perceived disease activity and is as such useful when evaluating previously treated acromegaly for disease...... activity. Total IGF-I, IGFBP-3 and ALS possess a higher PV(neg) for the clinical disease activity. None of the parameters can at present be claimed to be superior to the others and thus all the measured parameters are recommended to be part of the evaluation of acromegalic patients....

  4. Insulin-like growth factor-1 and binding protein-3 in a 2-year soya intervention among premenopausal women.

    Science.gov (United States)

    Maskarinec, Gertraud; Takata, Yumie; Murphy, Suzanne P; Franke, Adrian A; Kaaks, Rudolph

    2005-09-01

    Soya foods may protect against the development of breast cancer. Insulin-like growth factor (IGF)-1 is under investigation as a possible link between nutrition and cancer. We examined the effect of soya foods on circulating IGF-1 and IGF binding protein (BP)-3 levels among 196 healthy premenopausal women in a 2-year randomised nutritional trial. The intervention group consumed two daily servings of soya foods including tofu, soya milk, soya nuts and soya protein powder (equivalent to 50 mg isoflavones and 5-22 g soya protein per serving); the controls maintained their regular diet. Five serum samples at baseline, 3, 6, 12, and 24 months were collected in the morning during the luteal phase and analysed for IGF-1 and IGFBP-3 by double-antibody ELISA. We applied mixed models to investigate the intervention effect and predictors of serum levels while considering the repeated measurement design. Adherence with the study regimen was high and dropout rates were acceptable. Randomisation resulted in similar mean IGF-1 and IGFBP-3 levels by group. We did not observe a significant intervention effect on IGF-1, IGFBP-3, and their molar ratio during the entire study period. However, urinary isoflavone excretion during the study period was positively associated with IGF-1 (P=0.04) and the IGF-1:IGFBP-3 ratio (P=0.06). The effect was consistent over time. Adding soya foods to the diet of premenopausal women does not appear to lower serum levels of IGF-1 and IGFBP-3; if anything, the greater protein intake from soya may lead to a small increase in IGF-1 serum levels.

  5. Is Lutein a Physiologically Important Ligand for Transthyretin in Humans?

    Energy Technology Data Exchange (ETDEWEB)

    Liwei Chen

    2003-05-31

    Lutein and zeaxanthin are the only carotenoids accumulated in the macula of the human retina and are known as the macular pigments (MP). These pigments account for the yellow color of the macula and appear to play an important role in protecting against age-related macular degeneration (AMD). The uptake of lutein and zeaxanthin in human eyes is remarkably specific. It is likely that specific transport or binding proteins are involved. The objective is to determine whether transthyretin (TTR) is a transport protein in human plasma and could thus deliver lutein from the blood to the retina. In this study, they used a biosynthetic {sup 13}C-lutein tracer and gas chromatography-combustion interfaced-isotope ratio mass spectrometry (GCC-IRMS) to gain the requisite sensitivity to detect the minute amounts of lutein expected as a physiological ligand for human transthyretin. The biosynthetic {sup 13}C-labeled lutein tracer was purified from algae. Healthy women (n = 4) each ingested 1 mg of {sup 13}C-labeled lutein daily for 3 days and a blood sample was collected 24 hours after the final dose. Plasma TTR was isolated by retinol-binding protein (RBP)-sepharose affinity chromatography and extracted with chloroform. The {sup 13}C/{sup 12}C ratio in the TTR extract was measured by GCC-IRMS. There was no {sup 13}C-lutein enrichment in the pure TTR extract. This result indicated that lutein is not associated with TTR in human plasma after ingestion in physiological amounts. Some hydrophobic compounds with yellow color may bind to human TTR in the plasma. However, this association needs to be further proved by showing specificity. The study provides a new approach for carotenoid-binding protein studies using a stable isotope tracer method combined with the high precision of GCC-IRMS. The mechanism of selective transport, uptake, and accumulation of lutein in human macula remain to be determined.

  6. The Effects of Combined Antioxidant Supplementation on Antioxidant Capacity, DNA Single-Strand Breaks and Regulation of Insulin Growth Factor-1/IGF-Binding Protein 3 in the Ferret Model of Lung Cancer

    Science.gov (United States)

    Purpose: Insulin-like growth factor 1 (IGF-1) and its major binding protein, IGF binding protein 3 (IGFBP-3) are implicated in lung cancer and other malignancies. We have previously shown that the combination of three major antioxidants [beta-carotene (BC), alpha-tocopherol (AT) and ascorbic acid (...

  7. Nuclear Magnetic Resonance Structure of the Nucleic Acid-Binding Domain of Severe Acute Respiratory Syndrome Coronavirus Nonstructural Protein 3

    Science.gov (United States)

    Serrano, Pedro; Johnson, Margaret A.; Chatterjee, Amarnath; Neuman, Benjamin W.; Joseph, Jeremiah S.; Buchmeier, Michael J.; Kuhn, Peter; Wüthrich, Kurt

    2009-01-01

    The nuclear magnetic resonance (NMR) structure of a globular domain of residues 1071 to 1178 within the previously annotated nucleic acid-binding region (NAB) of severe acute respiratory syndrome coronavirus nonstructural protein 3 (nsp3) has been determined, and N- and C-terminally adjoining polypeptide segments of 37 and 25 residues, respectively, have been shown to form flexibly extended linkers to the preceding globular domain and to the following, as yet uncharacterized domain. This extension of the structural coverage of nsp3 was obtained from NMR studies with an nsp3 construct comprising residues 1066 to 1181 [nsp3(1066-1181)] and the constructs nsp3(1066-1203) and nsp3(1035-1181). A search of the protein structure database indicates that the globular domain of the NAB represents a new fold, with a parallel four-strand β-sheet holding two α-helices of three and four turns that are oriented antiparallel to the β-strands. Two antiparallel two-strand β-sheets and two 310-helices are anchored against the surface of this barrel-like molecular core. Chemical shift changes upon the addition of single-stranded RNAs (ssRNAs) identified a group of residues that form a positively charged patch on the protein surface as the binding site responsible for the previously reported affinity for nucleic acids. This binding site is similar to the ssRNA-binding site of the sterile alpha motif domain of the Saccharomyces cerevisiae Vts1p protein, although the two proteins do not share a common globular fold. PMID:19828617

  8. Insulin-Like Growth Factor II mRNA-Binding Protein 3 Expression Correlates with Poor Prognosis in Acral Lentiginous Melanoma.

    Directory of Open Access Journals (Sweden)

    Yi-Shuan Sheen

    Full Text Available Insulin-like growth factor-II mRNA-binding protein 3 (IMP-3 is an RNA-binding protein expressed in multiple cancers, including melanomas. However, the expression of IMP-3 has not been investigated in acral lentiginous melanoma (ALM. This study sought to elucidate its prognostic value in ALMs. IMP-3 expression was studied in 93 patients diagnosed with ALM via immunohistochemistry. Univariate and multivariate analyses for survival were performed, according to clinical and histologic parameters, using the Cox proportional hazard model. Survival curves were graphed using the Kaplan-Meier method. IMP-3 was over-expressed in 70 out of 93 tumors (75.3%. IMP-3 expression correlated with thick and high-stage tumor and predicted poorer overall, melanoma-specific, recurrence-free and distant metastasis-free survivals (P = 0.002, 0.006, 0.008 and 0.012, respectively. Further analysis showed that patients with tumor thickness ≤ 4.0 mm and positive IMP-3 expression had a significantly worse melanoma-specific survival than those without IMP-3 expression (P = 0.048. IMP-3 (hazard ratio 3.67, 95% confidence intervals 1.35-9.97, P = 0.011 was confirmed to be an independent prognostic factor for melanoma-specific survival in multivariate survival analysis. Positive IMP-3 expression was an important prognostic factor for ALMs.

  9. NKX3.1 activates expression of insulin-like growth factor binding protein-3 to mediate insulin-like growth factor-I signaling and cell proliferation.

    Science.gov (United States)

    Muhlbradt, Erin; Asatiani, Ekaterina; Ortner, Elizabeth; Wang, Antai; Gelmann, Edward P

    2009-03-15

    NKX3.1 is a homeobox gene that codes for a haploinsufficient prostate cancer tumor suppressor. NKX3.1 protein levels are down-regulated in the majority of primary prostate cancer tissues. NKX3.1 expression in PC-3 cells increased insulin-like growth factor binding protein-3 (IGFBP-3) mRNA expression 10-fold as determined by expression microarray analysis. In both stably and transiently transfected PC-3 cells and in LNCaP cells, NKX3.1 expression increased IGFBP-3 mRNA and protein expression. In prostates of Nkx3.1 gene-targeted mice Igfbp-3 mRNA levels correlated with Nkx3.1 copy number. NKX3.1 expression in PC-3 cells attenuated the ability of insulin-like growth factor-I (IGF-I) to induce phosphorylation of type I IGF receptor (IGF-IR), insulin receptor substrate 1, phosphatidylinositol 3-kinase, and AKT. The effect of NKX3.1 on IGF-I signaling was not seen when cells were exposed to long-R3-IGF-I, an IGF-I variant peptide that does not bind to IGFBP-3. Additionally, small interfering RNA-induced knockdown of IGFBP-3 expression partially reversed the attenuation of IGF-IR signaling by NKX3.1 and abrogated NKX3.1 suppression of PC-3 cell proliferation. Thus, there is a close relationship in vitro and in vivo between NKX3.1 and IGFBP-3. The growth-suppressive effects of NKX3.1 in prostate cells are mediated, in part, by activation of IGFBP-3 expression. PMID:19258508

  10. Evaluation of androgen receptor and GATA binding protein 3 as immunohistochemical markers in the diagnosis of metastatic breast carcinoma to the lung.

    Science.gov (United States)

    Hattori, Yukinori; Yoshida, Akihiko; Yoshida, Masayuki; Takahashi, Masahide; Tsuta, Koji

    2015-06-01

    Differentiating metastatic breast carcinoma in the lungs from primary lung tumors and mesotheliomas is important for determining prognosis and treatment. We evaluated novel breast specific markers, androgen receptor (AR) and GATA binding protein 3 (GATA3) immunohistostaining, for this differential, and compare to other traditional markers. The specimens comprised 33 metastatic breast carcinomas to the lung, 566 primary lung tumors (170 adenocarcinomas, 157 squamous cell carcinomas, 31 pleomorphic carcinomas, 115 large cell neuroendocrine carcinomas, 43 small cell carcinomas, and 49 typical carcinoids) and 42 malignant mesotheliomas. They were analyzed by immunohistochemistry using antibodies to AR, GATA3, estrogen receptor (ER), progesterone receptor (PgR), mammaglobin, gross cystic disease fluid protein-15 (GCDFP-15). Of the metastatic breast carcinomas, immunohistostaining of AR, GATA3, ER, PgR, mammaglobin, GCDFP-15 were positive in 27 cases (81.8%), 24 cases (72.7%), 26 cases (78.8%), 13 cases (39.4%), 12 cases (36.4%), 9 cases (27.3%), respectively. Of primary lung tumors and mesotheliomas, staining of AR, GATA3, ER, PgR, mammaglobin, GCDFP-15 were positive in 18 cases (3%), 3 cases (0.5%), 4 cases (0.7%), 2 cases (0.3%), 0 case (0%), 2 cases (0.3%), respectively. Immunohistochemistry of AR and GATA3 are reliable for differentiating metastatic breast carcinoma from primary lung tumors and mesotheliomas. PMID:25727644

  11. Identification of polymorphism in fatty acid binding protein 3 (FABP3) gene and its association with milk fat traits in riverine buffalo (Bubalus bubalis).

    Science.gov (United States)

    Dubey, Praveen Kumar; Goyal, Shubham; Mishra, Shailendra Kumar; Arora, Reena; Mukesh, Manishi; Niranjan, Saket Kumar; Kathiravan, Periasamy; Kataria, Ranjit Singh

    2016-04-01

    The fatty acid binding protein 3 (FABP3) gene, known to be associated with fat percentage of milk and meat in bovines, was screened among swamp and riverine buffaloes for polymorphism detection and further association with milk fat contents. An SNP g.307C > T was identified in the intron 2 (+53 exon 2) region of FABP3 gene of Indian buffaloes. The SNP identified was genotyped in 692 animals belonging to 15 riverine, swamp and hybrid (riverine × swamp) buffalo populations of diverse phenotypes and utilities, by PCR-RFLP. A marked contrast was observed between the C and T allele frequencies in three types of buffaloes. The frequency of C allele ranged from 0.67 to 0.96 in pure swamp buffalo populations, with the highest in Mizoram (0.96). Whereas the frequency of T allele was high across all the Indian riverine buffalo breeds, ranging from 0.57 to 0.96. None of the genotypes at FABP3 g.307C > T locus was found to have significant association with milk fat and other production traits in Mehsana dairy buffalo breed. Our study revealed marked differences in the allele frequencies between riverine and swamp buffaloes at FABP3 g.307C > T locus, without any significant association with different milk traits in riverine buffaloes.

  12. Time dependent impact of perinatal hypoxia on growth hormone, insulin-like growth factor 1 and insulin-like growth factor binding protein-3.

    Science.gov (United States)

    Kartal, Ömer; Aydınöz, Seçil; Kartal, Ayşe Tuğba; Kelestemur, Taha; Caglayan, Ahmet Burak; Beker, Mustafa Caglar; Karademir, Ferhan; Süleymanoğlu, Selami; Kul, Mustafa; Yulug, Burak; Kilic, Ertugrul

    2016-08-01

    Hypoxic-ischemia (HI) is a widely used animal model to mimic the preterm or perinatal sublethal hypoxia, including hypoxic-ischemic encephalopathy. It causes diffuse neurodegeneration in the brain and results in mental retardation, hyperactivity, cerebral palsy, epilepsy and neuroendocrine disturbances. Herein, we examined acute and subacute correlations between neuronal degeneration and serum growth factor changes, including growth hormone (GH), insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) after hypoxic-ischemia (HI) in neonatal rats. In the acute phase of hypoxia, brain volume was increased significantly as compared with control animals, which was associated with reduced GH and IGF-1 secretions. Reduced neuronal survival and increased DNA fragmentation were also noticed in these animals. However, in the subacute phase of hypoxia, neuronal survival and brain volume were significantly decreased, accompanied by increased apoptotic cell death in the hippocampus and cortex. Serum GH, IGF-1, and IGFBP-3 levels were significantly reduced in the subacute phase of HI. Significant retardation in the brain and body development were noted in the subacute phase of hypoxia. Here, we provide evidence that serum levels of growth-hormone and factors were decreased in the acute and subacute phase of hypoxia, which was associated with increased DNA fragmentation and decreased neuronal survival. PMID:26943480

  13. Syndecan-2 is a novel target of insulin-like growth factor binding protein-3 and is over-expressed in fibrosis.

    Directory of Open Access Journals (Sweden)

    Ximena D Ruiz

    Full Text Available Extracellular matrix deposition and tissue scarring characterize the process of fibrosis. Transforming growth factor beta (TGFβ and Insulin-like growth factor binding protein-3 (IGFBP-3 have been implicated in the pathogenesis of fibrosis in various tissues by inducing mesenchymal cell proliferation and extracellular matrix deposition. We identified Syndecan-2 (SDC2 as a gene induced by TGFβ in an IGFBP-3-dependent manner. TGFβ induction of SDC2 mRNA and protein required IGFBP-3. IGFBP-3 independently induced production of SDC2 in primary fibroblasts. Using an ex-vivo model of human skin in organ culture expressing IGFBP-3, we demonstrate that IGFBP-3 induces SDC2 ex vivo in human tissue. We also identified Mitogen-activated protein kinase-interacting kinase (Mknk2 as a gene induced by IGFBP-3. IGFBP-3 triggered Mknk2 phosphorylation resulting in its activation. Mknk2 independently induced SDC2 in human skin. Since IGFBP-3 is over-expressed in fibrotic tissues, we examined SDC2 levels in skin and lung tissues of patients with systemic sclerosis (SSc and lung tissues of patients with idiopathic pulmonary fibrosis (IPF. SDC2 levels were increased in fibrotic dermal and lung tissues of patients with SSc and in lung tissues of patients with IPF. This is the first report describing elevated levels of SDC2 in fibrosis. Increased SDC2 expression is due, at least in part, to the activity of two pro-fibrotic factors, TGFβ and IGFBP-3.

  14. Lutein and brain function

    Science.gov (United States)

    Lutein is one of the most prevalent carotenoids in nature and in the human diet. Together with zeaxanthin, it is highly concentrated in macular pigment in the foveal retina of primates, attenuating blue light exposure, providing protection from photo-oxidation and enhancing visual performance. Rece...

  15. Growth hormone (GH) provocative retesting of 108 young adults with childhood-onset GH deficiency and the diagnostic value of insulin-like growth factor I (IGF-I) and IGF-binding protein-3

    DEFF Research Database (Denmark)

    Juul, A; Kastrup, K W; Pedersen, S A;

    1997-01-01

    Serum levels of total insulin-like growth factor I (IGF-I) and IGF-binding protein-3 (IGFBP-3) reflect the endogenous GH secretion in healthy children and exhibit little diurnal variation, which makes them good diagnostic markers for screening of GH deficiency (GHD) in short children, although so...

  16. Potentiation of growth factor signaling by insulin-like growth factor-binding protein-3 in breast epithelial cells requires sphingosine kinase activity.

    Science.gov (United States)

    Martin, Janet L; Lin, Mike Z; McGowan, Eileen M; Baxter, Robert C

    2009-09-18

    We have investigated the mechanism underlying potentiation of epidermal growth factor receptor (EGFR) and type 1 insulin-like growth factor receptor (IGFR1) signaling by IGF-binding protein-3 (IGFBP-3) in MCF-10A breast epithelial cells, focusing on a possible involvement of the sphingosine kinase (SphK) system. IGFBP-3 potentiated EGF-stimulated EGF receptor activation and DNA synthesis, and this was blocked by inhibitors of SphK activity or small interference RNA-mediated silencing of SphK1, but not SphK2, expression. Similarly, IGFR1 phosphorylation and DNA synthesis stimulated by LR3-IGF-I (an IGF-I analog not bound by IGFBP-3), were enhanced by IGFBP-3, and this was blocked by SphK1 silencing. SphK1 expression and activity were stimulated by IGFBP-3 approximately 2-fold over 24 h. Silencing of sphingosine 1-phosphate receptor 1 (S1P1) or S1P3, but not S1P2, abolished the effect of IGFBP-3 on EGF-stimulated EGFR activation. The effects of IGFBP-3 could be reproduced with exogenous S1P or medium conditioned by cells treated with IGFBP-3, and this was also blocked by inhibition of S1P1 and S1P3. These data indicate that potentiation of growth factor signaling by IGFBP-3 in MCF-10A cells requires SphK1 activity and S1P1/S1P3, suggesting that S1P, the product of SphK activity and ligand for S1P1 and S1P3, is the "missing link" mediating IGF and EGFR transactivation and cell growth stimulation by IGFBP-3. PMID:19633297

  17. Urinary bladder cancer risk in relation to a single nucleotide polymorphism (rs2854744) in the insulin-like growth factor-binding protein-3 (IGFBP3) gene.

    Science.gov (United States)

    Selinski, Silvia; Lehmann, Marie-Louise; Blaszkewicz, Meinolf; Ovsiannikov, Daniel; Moormann, Oliver; Guballa, Christoph; Kress, Alexander; Truss, Michael C; Gerullis, Holger; Otto, Thomas; Barski, Dimitri; Niegisch, Günter; Albers, Peter; Frees, Sebastian; Brenner, Walburgis; Thüroff, Joachim W; Angeli-Greaves, Miriam; Seidel, Thilo; Roth, Gerhard; Volkert, Frank; Ebbinghaus, Rainer; Prager, Hans-Martin; Lukas, Cordula; Bolt, Hermann M; Falkenstein, Michael; Zimmermann, Anna; Klein, Torsten; Reckwitz, Thomas; Roemer, Hermann C; Hartel, Mark; Weistenhöfer, Wobbeke; Schöps, Wolfgang; Rizvi, S Adibul Hassan; Aslam, Muhammad; Bánfi, Gergely; Romics, Imre; Ickstadt, Katja; Hengstler, Jan G; Golka, Klaus

    2012-02-01

    Currently, twelve validated genetic variants have been identified that are associated with urinary bladder cancer (UBC) risk. However, those validated variants explain only 5-10% of the overall inherited risk. In addition, there are more than 100 published polymorphisms still awaiting validation or disproval. A particularly promising of the latter unconfirmed polymorphisms is rs2854744 that recently has been published to be associated with UBC risk. The [A] allele of rs2854744 has been reported to be associated with a higher promoter activity of the insulin-like growth factor-binding protein-3 (IGFBP3) gene, which may lead to increased IGFBP-3 plasma levels and cancer risk. Therefore, we investigated the association of rs2854744 with UBC in the IfADo case-control series consisting of 1,450 cases and 1,725 controls from Germany, Hungary, Venezuela and Pakistan. No significant association of rs2854744 with UBC risk was obtained (all study groups combined: unadjusted P = 0.4446; adjusted for age, gender and smoking habits P = 0.6510), besides a small effect of the [A] allele in the Pakistani study group opposed to the original findings (unadjusted P = 0.0508, odds ratio (OR) = 1.43 for the multiplicative model) that diminished after adjustment for age, gender and smoking habits (P = 0.7871; OR = 0.93). Associations of rs2854744 with occupational exposure to urinary bladder carcinogens and smoking habits were also not present. A meta-analysis of all available case-control series including the original discovery study resulted in an OR of 1.00 (P = 0.9562). In conclusion, we could not confirm the recently published hypothesis that rs2854744 in the IGFBP3 gene is associated with UBC risk.

  18. Potentiation of growth factor signaling by insulin-like growth factor-binding protein-3 in breast epithelial cells requires sphingosine kinase activity.

    Science.gov (United States)

    Martin, Janet L; Lin, Mike Z; McGowan, Eileen M; Baxter, Robert C

    2009-09-18

    We have investigated the mechanism underlying potentiation of epidermal growth factor receptor (EGFR) and type 1 insulin-like growth factor receptor (IGFR1) signaling by IGF-binding protein-3 (IGFBP-3) in MCF-10A breast epithelial cells, focusing on a possible involvement of the sphingosine kinase (SphK) system. IGFBP-3 potentiated EGF-stimulated EGF receptor activation and DNA synthesis, and this was blocked by inhibitors of SphK activity or small interference RNA-mediated silencing of SphK1, but not SphK2, expression. Similarly, IGFR1 phosphorylation and DNA synthesis stimulated by LR3-IGF-I (an IGF-I analog not bound by IGFBP-3), were enhanced by IGFBP-3, and this was blocked by SphK1 silencing. SphK1 expression and activity were stimulated by IGFBP-3 approximately 2-fold over 24 h. Silencing of sphingosine 1-phosphate receptor 1 (S1P1) or S1P3, but not S1P2, abolished the effect of IGFBP-3 on EGF-stimulated EGFR activation. The effects of IGFBP-3 could be reproduced with exogenous S1P or medium conditioned by cells treated with IGFBP-3, and this was also blocked by inhibition of S1P1 and S1P3. These data indicate that potentiation of growth factor signaling by IGFBP-3 in MCF-10A cells requires SphK1 activity and S1P1/S1P3, suggesting that S1P, the product of SphK activity and ligand for S1P1 and S1P3, is the "missing link" mediating IGF and EGFR transactivation and cell growth stimulation by IGFBP-3.

  19. Association between serum insulin-like growth factor I or IGF-binding protein 3 and estimated glomerular filtration rate: results of a population-based sample

    Directory of Open Access Journals (Sweden)

    Dittmann Kathleen

    2012-12-01

    Full Text Available Abstract Background Insulin-like growth factor I (IGF-I, which is mostly carried in blood by IGF-binding protein 3 (IGFBP-3, was associated to the glomerular filtration rate and chronic kidney disease in a multiethnic study among US adults. The aim of the present study was to investigate whether serum IGF-I or IGFBP-3 are associated with estimated glomerular filtration rate (eGFR in a population-based study of Caucasian adults. Methods Data from 4028 subjects (2048 women aged 20 to 81 years from the Study of Health in Pomerania (SHIP were analyzed. Total serum IGF-I and IGFBP-3 concentrations were determined by chemiluminescence immunoassays and categorized into sex- and age-specific quartiles. Results After adjusting for age, waist circumference and type 2 diabetes mellitus, analysis of variance (ANOVA revealed inverse associations between serum IGF-I concentrations and eGFR in men as well as between serum IGFBP-3 concentrations and eGFR in men and women. Logistic regression analyses confirmed these findings and showed that high IGF-I or IGFBP-3 concentrations were associated with an increased risk of decreased eGFR (2 in men or women. These relations became stronger when lower eGFR cut-offs were used for the analyses. Conclusion Our data revealed associations of increased serum IGF-I concentrations and decreased eGFR in men but not in women and an association of increased serum IGFBP-3 concentrations and decreased eGFR in both sexes.

  20. Changes in the level of growth hormone, insulin like growth factor-1 and insulin like growth factor binding proteine-3 in young males 24 hours after submaximaltraining

    Directory of Open Access Journals (Sweden)

    Hakkı Çoknaz

    2011-04-01

    Full Text Available Normal 0 21 false false false MicrosoftInternetExplorer4 The study was accomplished as a control study, under the question whether 6-weeks endurance training affects the growth hormone (GH, insulin like growth factor-1 (IGF-1 and the IGF bindings protein-3 (IGFBP-3 levels. Sixty male subjects participated in the study. The subjects were separated into 2 groups as control (n=30; mean age=21,13±1,16 years and study (n=30; mean age=21,53±1,61 years randomly, prior to the runtest. Blood samples were drawn before breakfast and analyzed in the laboratory of the medical faculty of Abant Izzet Baysal University concerning GH, IGF-1and IGFBP-3. VO2max was measured in all individuals. The individuals experimental group trained 3 times a week (Monday, Wednesday, and Friday for 6 weeks, on the other hand the control group had rest/rested for 6 weeks. Trainings included 30-40 minutes submaximal run on the treadmill, per day. After the last session of training, blood samples were drawn from all subjects following day before breakfast, and were analyzed similar to the first measurements. Then, all subjects (experimental and control groups were subjected to VO2max measurement again. There were no differences within groups and between the groups in GH, IGF-1, IGFBP-3levels before (p>0.05 and after the test (p>0.05. VO2max was found to be significantly higher in the study group compare to controls (p<0.05. We conclude that submaximal training does not affect the production of growth hormones, although it may increase oxygen consumption. 

  1. The joint effects of arsenic and risk diplotypes of insulin-like growth factor binding protein-3 in renal cell carcinoma.

    Science.gov (United States)

    Huang, Chao-Yuan; Huang, Ya-Li; Pu, Yeong-Shiau; Shiue, Horng-Sheng; Chen, Wei-Jen; Chen, Shih-Shan; Lin, Ying-Chin; Su, Chien-Tien; Hsueh, Yu-Mei

    2016-07-01

    The association between renal cell carcinoma (RCC) and diabetes mellitus (DM), alcohol consumption, insulin-like growth factor binding protein-3 (IGFBP-3) gene, and arsenic exposure, has been the subject of independent studies. However, few studies have examined the combined effect of these factors on RCC risk. The aim of this study was to examine the association between these risk factors and the odds ratio (OR) of RCC. A hospital-based case-control study was conducted in 398 RCC patients and 756 age- and gender-matched non-cancer controls. Genomic DNA was used to examine the genotype of IRS-1 (Gly972Arg), PI3-K (Met362Ile), IGFBP-3 (A[-202]C), and IGFBP-3 (C[-1590]A) by PCR-RFLP. Profiles of urinary arsenic were measured by high performance liquid chromatography linked with hydride generator and atomic absorption spectrometry. Participants who had never consumed alcohol and who had high total levels of urinary arsenic and DM had a high OR of RCC. IGFBP-3 (A[-202]C) and IGFBP-3 (C[-1590]A) were in linkage disequilibrium. Participants carrying high-risk IGFBP-3 diplotypes A-C/C-C, A-A/A-C, and C-A/C-A had a significantly higher odds ratio (OR) and 95% confidence interval (2.80, 1.91-4.12) of RCC compared to those carrying other IGFBP-3 diplotypes. This is the first study to show that borderline significant interaction of high total levels of urinary arsenic and IGFBP-3 high-risk diplotypes significantly enhanced the OR of RCC. Our data also provide evidence that subjects with more risk factors (e.g., high total levels of urinary arsenic, never consumed alcohol, IGFBP-3 high-risk diplotypes) may experience a higher OR of RCC. PMID:27038904

  2. Serum levels of free and total insulin-link growth factor (IGF)-1 and (IGF) binding protein-3 in normal and growth hormone deficient children

    International Nuclear Information System (INIS)

    Serum levels of total insulin-like growth factor- 1 (IGF-1) and IGF-binding protein-3 (IGFBP-3) reflect endogenous GH secretion in healthy children, which makes them good diagnostic markers for screening GH deficiency (GHD) in short children, although some controversy still exists. Only a minor fraction of the total IGF-1 circulates in its free form, which is believed to be the biologically active form. Serum levels of free IGF-1, total IGF-I and IGFBP-3 were measured in 144 healthy children (72 boys and 72 girls, aged from 0 to 16 years) and in 12 prepubertal GH. deficient (GHD) children to study correlation between the age and free IGF-1, total IGF-1 and IGFBP-3 levels. In healthy subjects (both sexes), serum free IGF-1, total IGF-1 and IGFBP-3 levels were low in infancy, increasing during puberty and declining thereafter. Free IGF-1 in serum occupied about 0.97. 1.45 % of the total IGF-1 values, and the ratios of free IGF-1 to total IGF-1 were significantly increased in the pubertal age groups than in the prepubertal age groups. Serum levels of free IGF-1 showed significant positive correlation with those of total IGF-I and IGFBP-3. Serum free IGF-1, total IGF-1 and IGFBP-3 levels in patients with GHD decreased significantly with increasing degree of hypopituitarism. These observations suggest that the increase in serum free IGF-1 level during puberty was caused by a dramatic increase in total IGF-1 rather than IGFBP-3. Also, high levels of these hormones may play an important role in pubertal growth spurt and may become a useful tool for diagnosing GHD and predicting growth response to long term GH therapy

  3. Mecasermin rinfabate: insulin-like growth factor-I/insulin-like growth factor binding protein-3, mecaserimin rinfibate, rhIGF-I/rhIGFBP-3.

    Science.gov (United States)

    2005-01-01

    Insmed is developing mecasermin rinfabate, a recombinant complex of insulin-like growth factor-I (rhIGF-I) and binding protein-3 (rhIGFBP-3) [insulin-like growth factor-I/insulin-like growth factor binding protein-3, rhIGF-I/rhIGFBP-3, SomatoKine], for a number of metabolic and endocrine indications. In the human body, IGF-I circulates in the blood bound to a binding protein-3 (IGFBP-3), which regulates the delivery of IGF-I to target tissues, and particular proteases clip them apart in response to stresses and release IGF-I as needed. IGF-I, a naturally occurring hormone, is necessary for normal growth and metabolism. For the treatment of IGF-I deficiency, it is desirable to administer IGF-I bound to IGFBP-3 to maintain the normal equilibrium of these proteins in the blood. Mecasermin rinfabate (rhIGF-I/rhIGFBP-3) mimics the effects of the natural protein complex in the bloodstream and would augment the natural supply of these linked compounds. The most advanced indication in development of mecasermin rinfabate is the treatment of severe growth disorders due to growth hormone insensitivity syndrome (GHIS), also called Laron syndrome. GHIS is a genetic condition in which patients do not produce adequate quantities of IGF because of a failure to respond to the growth hormone signal. This results in a slower growth rate and short stature. Mecasermin rinfabate also has potential as replacement therapy for IGF-I, which may become depleted in indications such as major surgery, organ damage/failure, traumatic injury, cachexia and severe burn trauma. It also has potential for the treatment of osteoporosis. Mecasermin rinfabate was developed by Celtrix using its proprietary recombinant protein production technology. Subsequently, Celtrix was acquired by Insmed Pharmaceuticals on 1 June 2000. Insmed and Avecia of the UK have signed an agreement for manufacturing mecasermin rinfabate and its components, rhIGF-1 and rhIGFBP-3. CGMP clinical production of mecasermin rinfabate

  4. Immunohistochemical expression of insulin-like growth factor binding protein-3 in invasive breast cancers and ductal carcinoma in situ: implications for clinicopathology and patient outcome

    International Nuclear Information System (INIS)

    Insulin-like growth factor binding protein-3 (IGFBP-3) differentially modulates breast epithelial cell growth through insulin-like growth factor (IGF)-dependent and IGF-independent pathways and is a direct (IGF-independent) growth inhibitor as well as a mitogen that potentiates EGF (epidermal growth factor) and interacts with HER-2. Previously, high IGFBP-3 levels in breast cancers have been determined by enzyme-linked immunosorbent assay and immunoradiometric assay methods. In vitro, IGFBP-3's mechanisms of action may involve cell membrane binding and nuclear translocation. To evaluate tumour-specific IGFBP-3 expression and its subcellular localisation, this study examined immunohistochemical IGFBP-3 expression in a series of invasive ductal breast cancers (IDCs) with synchronous ductal carcinomas in situ (DCIS) in relation to clinicopathological variables and patient outcome. Immunohistochemical expression of IGFBP-3 was evaluated with the sheep polyclonal antiserum (developed in house) with staining performed as described previously. IGFBP-3 was evaluable in 101 patients with a variable pattern of cytoplasmic expression (positivity of 1+/2+ score) in 85% of invasive and 90% of DCIS components. Strong (2+) IGFBP-3 expression was evident in 32 IDCs and 40 cases of DCIS. A minority of invasive tumours (15%) and DCIS (10%) lacked IGFBP-3 expression. Nuclear IGFBP-3 expression was not detectable in either invasive cancers or DCIS, with a consistent similarity in IGFBP-3 immunoreactivity in IDCs and DCIS. Positive IGFBP-3 expression showed a possible trend in association with increased proliferation (P = 0.096), oestrogen receptor (ER) negativity (P = 0.06) and HER-2 overexpression (P = 0.065) in invasive tumours and a strong association with ER negativity (P = 0.037) in DCIS. Although IGFBP-3 expression was not an independent prognosticator, IGFBP-3-positive breast cancers may have shorter disease-free and overall survivals, although these did not reach

  5. Latent transforming growth factor β-binding protein-3 and fibulin-1C interact with the extracellular domain of the heparin-binding EGF-like growth factor precursor

    Directory of Open Access Journals (Sweden)

    Eidels Leon

    2002-01-01

    Full Text Available Abstract Background The membrane-bound cell-surface precursor and soluble forms of heparin-binding epidermal growth factor-like growth factor (HB-EGF contribute to many cellular developmental processes. The widespread occurrence of HB-EGF in cell and tissue types has led to observations of its role in such cellular and tissue events as tumor formation, cell migration, extracellular matrix formation, wound healing, and cell adherence. Several studies have reported the involvement of such extracellular matrix proteins as latent transforming growth factor β-binding protein, TGF-β, and fibulin-1 in some of these processes. To determine whether HB-EGF interacts with extracellular matrix proteins we used the extracellular domain of proHB-EGF in a yeast two-hybrid system to screen a monkey kidney cDNA library. cDNA clones containing nucleotide sequences encoding domains of two proteins were obtained and their derived amino acid sequences were evaluated. Results From ≈ 3 × 106 screened monkey cDNA clones, cDNA clones were recovered that contained nucleotide sequences encoding domains of the monkey latent transforming growth factor-β binding protein-3 (MkLTBP-3 and fibulin-1C protein. The amino acid sequence derived from the MkLTBP-3 gene shared 98.6% identity with human LTBP-3 and 86.7% identity with mouse LTBP-3 amino acid sequences. The amino acid sequence derived from the monkey fibulin-1C gene shared 97.2% identity with human fibulin-1C. Yeast two-hybrid screens indicate that LTBP-3 and fibulin-1C interact with proHB-EGF through their calcium-binding EGF-like modules. Conclusions The interactions of the extracellular domain of proHB-EGF with LTBP-3 and fibulin-1C suggest novel functions for HB-EGF between cell and tissue surfaces.

  6. Insulin-like growth factor 2 mRNA-binding protein-3 as a marker for distinguishing between cutaneous squamous cell carcinoma and keratoacanthoma.

    Science.gov (United States)

    Kanzaki, Akiko; Kudo, Mitsuhiro; Ansai, Shin-Ichi; Peng, Wei-Xia; Ishino, Kousuke; Yamamoto, Tetsushi; Wada, Ryuichi; Fujii, Takenori; Teduka, Kiyoshi; Kawahara, Kiyoko; Kawamoto, Yoko; Kitamura, Taeko; Kawana, Seiji; Saeki, Hidehisa; Naito, Zenya

    2016-03-01

    In the histopathological diagnosis of cutaneous tumors, the differential diagnosis of squamous cell carcinoma (SCC) with crateriform architecture and keratoacanthoma (KA) is often difficult so an accurate understanding of the biological features and the identification of reliable markers of SCC and KA are crucial issues. Insulin-like growth factor 2 mRNA-binding protein-3 (IGF2BP3, also known as IMP3) is thought of as a bona fide oncofetal protein, which is overexpressed and is involved in cell proliferation, migration, and invasion in several kinds of tumors. However, the role of IMP3 in cutaneous SCC and KA has not been well studied. Therefore, we focused on studying the biological functions of IMP3 in SCC and KA. In human skin SCC cell lines, HSC-1 and HSC-5, and the human keratinocyte cell line, HaCaT, IMP3 mRNA levels were significantly higher than that of normal human skin. The knockdown of IMP3 expression reduced the proliferation of HSC-1, and significantly reduced invasion by HSC-1 and HSC-5. In contrast, the knockdown of IMP3 did not significantly affect invasion by HaCaT cells. In immunohistochemical studies of SCC and KA tissues, the Ki-67 labeling index (LI) of the suprabasal cell layer was significantly higher in SCC, compared with KA tissues and the tumor-free margin (TFM) adjacent to SCC and KA. Most SCC tissues stained strongly positive for IMP3, but KA tissues and TFM were mostly negative for IMP3. The Ki-67 LI of the IMP3-positive group was significantly higher than that of the IMP3-negative group in the suprabasal cell layer of SCC. These results suggest that IMP3 plays an important role in proliferation and, more significantly, in the invasion of SCC, and may be a suitable marker for the histopathological diagnosis of SCC with a crateriform architecture and KA. Furthermore, IMP3 may potentially be a new therapeutic target for SCC. PMID:26782292

  7. Re-evaluation of the significance of penicillin binding protein 3 in the susceptibility of Listeria monocytogenes to β-lactam antibiotics

    Directory of Open Access Journals (Sweden)

    Krawczyk-Balska Agata

    2012-04-01

    Full Text Available Abstract Background Penicillin binding protein 3 (PBP3 of L. monocytogenes has long been thought of as the primary lethal target for β-lactam antibiotics due to the excellent correlation between the MICs of different β-lactams and their affinity for this protein. The gene encoding PBP3 has not yet been directly identified in this gram-positive bacterium, but based on in silico analysis, this protein is likely to be encoded by lmo1438. However, studies examining the effects of mutations in genes encoding known and putative L. monocytogenes PBPs have demonstrated that inactivation of lmo1438 does not affect sensitivity to β-lactams. Results In this study, overexpression of lmo1438 was achieved using an inducible (nisin-controlled expression system. This permitted the direct demonstration that lmo1438 encodes PBP3. PBP3 overexpression was accompanied by slightly elevated PBP4 expression. The recombinant strain overexpressing PBP3 displayed significant growth retardation and greatly reduced cell length in the stationary phase of growth in culture. In antibiotic susceptibility assays, the strain overexpressing PBP3 displayed increased sensitivity to subinhibitory concentrations of several β-lactams and decreased survival in the presence of a lethal dose of penicillin G. However, the MIC values of the tested β-lactams for this recombinant strain were unchanged compared to the parent strain. Conclusions The present study allows a reevaluation of the importance of PBP3 in the susceptibility of L. monocytogenes to β-lactams. It is clear that PBP3 is not the primary lethal target for β-lactams, since neither the absence nor an excess of this protein affect the susceptibility of L. monocytogenes to these antibiotics. The elevated level of PBP4 expression observed in the recombinant strain overexpressing PBP3 demonstrates that the composition of the L. monocytogenes cell wall is subject to tight regulation. The observed changes in the morphology of

  8. Insulin-like growth factor binding protein-3 is required for the regulation of rat oval cell proliferation and differentiation in the 2AAF/PHX model

    Directory of Open Access Journals (Sweden)

    Nicole C Steiger-Luther

    2010-02-01

    Full Text Available Nicole C Steiger-Luther1, Houda Darwiche1, Seh-Hoon Oh1, Jennifer M Williams1, Bryon E Petersen1,21Department of Pathology, Immunology and Laboratory Medicine, 2Program in Stem Cell Biology and Regenerative Medicine, College of Medicine, University of Florida, Gainesville, FL, USAAbstract: Oval cell-mediated liver regeneration is a highly complex process that involves the coordination of several signaling factors, chemokines and cytokines to allow for proper maintenance of the liver architecture. When hepatocyte proliferation is inhibited, an hepatic stem cell population, often referred to as “oval cells”, is activated to aid in liver regeneration. The function of insulin-like growth factor binding protein-3 (IGFBP-3 during this process of oval cell activation is of particular interest because it is produced in liver and has been shown to induce migration and differentiation of other stem cell populations both in vitro and in vivo. Additionally, IGFBP-3 production has been linked to the transforming growth factor-β (TGF-β superfamily, a pathway known to be induced during oval cell proliferation. In this study, we set out to determine whether IGFBP-3 plays a role in oval cell proliferation, migration and differentiation during this specific type of regeneration. Through activation of the oval cell-mediated liver regeneration in a rat model, we found that IGFBP-3 is elevated in the liver and serum of animals during peak days of oval cell activation and proliferation. Furthermore, in vitro assays found that WB-344 cells, a liver stem cell line similar to oval cells, were induced to migrate in the presence of IGFBP-3. When expression of IGFBP-3 was knocked down during oval cell activation in vivo, we found that oval cell proliferation was increased and observed the appearance of numerous atypical ductular structures, which were OV-6 and Ki67-positive. Finally, quantitative realtime PCR analysis of liver tissue from IGFBP-3 small interfering

  9. Genetic variants in insulin-like growth factor binding protein-3 are associated with prostate cancer susceptibility in Eastern Chinese Han men

    Directory of Open Access Journals (Sweden)

    Zhang G

    2015-12-01

    Full Text Available Guiming Zhang,1–3 Yao Zhu,1,2 Fang Liu,4,5 Chengyuan Gu,1,2 Haitao Chen,4,5 Jianfeng Xu,4–6 Dingwei Ye1,2 1Department of Urology, Fudan University Shanghai Cancer Center, 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 3Department of Urology, The Affiliated Hospital of Qingdao University, Shandong, 4Fudan Institute of Urology, Huashan Hospital, Fudan University, 5State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, People’s Republic of China; 6Center for Cancer Genomics, Wake Forest School of Medicine, Winston-Salem, NC, USA Background: Growing evidence has indicated that insulin-like growth factor binding protein-3 (IGFBP-3 polymorphisms are associated with altered risk of prostate cancer (PCa. However, few studies have been conducted in Chinese population to validate this association. Materials and methods: Herein, we examined the association between genetic variants in the IGFBP-3 gene and PCa risk in the Chinese Han population based on a genome-wide association study (1,417 cases and 1,008 controls, and replicated three genetic variants loci in an independent case-control study (1,755 cases and 1,523 controls using Sequenom platform. Logistic regression analyses were performed to estimate odds ratios (ORs and 95% confidence intervals (95% CIs. Results: We found that in the discovery stage, rs9691259 (OR =0.691, 95% CI: 0.587–0.814, P<0.001 and rs6950179 (OR =1.420, 95% CI: 1.201–1.677, P<0.001 were significantly associated with PCa risk, whereas rs2854744 showed a marginal association with PCa risk. In the replication stage, the association between rs9691259 and rs6950179 and PCa risk was not replicated, whereas rs2854744 conferred a significant association with PCa risk (OR =1.399, 95% CI: 1.010–1.937, P=0.043. After combining the two stages, we found that rs9691259, rs6950179, and rs2854744 were all significantly associated with PCa risk. Conclusion

  10. Insulin-like Growth Factor-binding Protein-3 (IGFBP-3) Blocks the Effects of Asthma by Negatively Regulating NF-κB Signaling through IGFBP-3R-mediated Activation of Caspases*♦

    OpenAIRE

    Lee, Yong-Chul; Jogie-Brahim, Sherryline; Lee, Dae-Yeol; Han, Jinfeng; Harada, Aki; Murphy, Liam J.; Oh, Youngman

    2011-01-01

    Insulin-like growth factor-binding protein-3 (IGFBP-3) is a multifunctional protein known for modulating mitogenic and metabolic actions of IGFs as well as exerting a variety of biological actions not involving IGFs. Here, we show that IGFBP-3 blocks specific physiological consequences of asthma in an IGF-independent manner in vitro and in vivo. IGFBP-3 treatment effectively reduced all physiological manifestations of asthma examined in vivo (airway hyper-responsiveness, cellular and patholog...

  11. Mecasermin rinfabate: insulin-like growth factor-I/insulin-like growth factor binding protein-3, mecaserimin rinfibate, rhIGF-I/rhIGFBP-3.

    Science.gov (United States)

    2005-01-01

    Insmed is developing mecasermin rinfabate, a recombinant complex of insulin-like growth factor-I (rhIGF-I) and binding protein-3 (rhIGFBP-3) [insulin-like growth factor-I/insulin-like growth factor binding protein-3, rhIGF-I/rhIGFBP-3, SomatoKine], for a number of metabolic and endocrine indications. In the human body, IGF-I circulates in the blood bound to a binding protein-3 (IGFBP-3), which regulates the delivery of IGF-I to target tissues, and particular proteases clip them apart in response to stresses and release IGF-I as needed. IGF-I, a naturally occurring hormone, is necessary for normal growth and metabolism. For the treatment of IGF-I deficiency, it is desirable to administer IGF-I bound to IGFBP-3 to maintain the normal equilibrium of these proteins in the blood. Mecasermin rinfabate (rhIGF-I/rhIGFBP-3) mimics the effects of the natural protein complex in the bloodstream and would augment the natural supply of these linked compounds. The most advanced indication in development of mecasermin rinfabate is the treatment of severe growth disorders due to growth hormone insensitivity syndrome (GHIS), also called Laron syndrome. GHIS is a genetic condition in which patients do not produce adequate quantities of IGF because of a failure to respond to the growth hormone signal. This results in a slower growth rate and short stature. Mecasermin rinfabate also has potential as replacement therapy for IGF-I, which may become depleted in indications such as major surgery, organ damage/failure, traumatic injury, cachexia and severe burn trauma. It also has potential for the treatment of osteoporosis. Mecasermin rinfabate was developed by Celtrix using its proprietary recombinant protein production technology. Subsequently, Celtrix was acquired by Insmed Pharmaceuticals on 1 June 2000. Insmed and Avecia of the UK have signed an agreement for manufacturing mecasermin rinfabate and its components, rhIGF-1 and rhIGFBP-3. CGMP clinical production of mecasermin rinfabate

  12. Changes of insulin-like growth factor-Ⅱ and insulin-like growth factor binding protein-3 in cerebrospinal fluid of children with tuberculous meningitis

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    BACKGROUND: Recent studies have found that insulin-like growth factors (IGFs) and insulin-like growth factor binding protein-3 (IGFBP-3) have stronger neurotrophic and neuroprotective effects. But whether their levels in cerebrospinal fluid could be used as an auxiliary indicator in differentially diagnosing tuberculous meningitis and viral encephalitis is not yet clear.OBJECTIVE: To explore the changes of insulin-like growth factor-Ⅱ (IGF-Ⅱ ) and IGFBP-3 in cerebrospinal fluid (CSF) of children with tuberculous meningitis and the significance of the changes.DESIGN: A non-randomized concurrent controlled study.SETTING: Department of Pediatric Internal Medicine, the First Affiliated Hospital of Xinxiang Medical College.PARTICIPANTS: Thirty children with tuberculous meningitis (14 males and 16 females) were selected from the Department of Pediatric Internal Medicine, the First Affiliated Hospital of Xinxiang Medical College from January 2005 to December 2006. Tuberculous meningitis was diagnosed according to their clinical manifestations, the history of close contact with tuberculosis, typical cerebrospinal fluid changes of tuberculous meningitis, positive tuberculosis antibody and effective antituberculosis treatment. There were 30 children (13 males and 17 females) with viral encephalitis, and viral encephalitis was diagnosed according to epidemiological history, clinical manifestations, conventional and biochemical changes of cerebrospinal fluid, and negative bacteriology judgment. Meanwhile, 30 children (13 males and 17 females) without infectious and central nervous system disease were selected as the control group. Informed consent was obtained from the parents of all the enrolled children.METHODS: ① The lumbar puncture operation was implemented immediately to obtain cerebrospinal fluid (3 mL). The contents of IGF-Ⅱ and IGFBP-3 were detected with immunoradiometric assay. The concentrations of glucose and protein in cerebrospinal fluid were determined

  13. Structure of the human-heart fatty-acid-binding protein 3 in complex with the fluorescent probe 1-anilinonaphthalene-8-sulphonic acid

    Energy Technology Data Exchange (ETDEWEB)

    Hirose, Mika; Sugiyama, Shigeru, E-mail: sugiyama@chem.eng.osaka-u.ac.jp [Lipid Active Structure Project, 1-1 Machikaneyama-cho, Toyonaka 560-0043 (Japan); Osaka University, 1-1 Machikaneyama-cho, Toyonaka 560-0043 (Japan); Ishida, Hanako; Niiyama, Mayumi [Lipid Active Structure Project, 1-1 Machikaneyama-cho, Toyonaka 560-0043 (Japan); Osaka University, 2-1 Yamadaoka, Suita 565-0871 (Japan); Matsuoka, Daisuke; Hara, Toshiaki [Lipid Active Structure Project, 1-1 Machikaneyama-cho, Toyonaka 560-0043 (Japan); Osaka University, 1-1 Machikaneyama-cho, Toyonaka 560-0043 (Japan); Mizohata, Eiichi [Osaka University, 2-1 Yamadaoka, Suita 565-0871 (Japan); Murakami, Satoshi [Tokyo Institute of Technology, Nagatsuta, Midori-ku, Yokohama, Kanagaw 226-8501 (Japan); Inoue, Tsuyoshi [Osaka University, 2-1 Yamadaoka, Suita 565-0871 (Japan); Matsuoka, Shigeru; Murata, Michio [Lipid Active Structure Project, 1-1 Machikaneyama-cho, Toyonaka 560-0043 (Japan); Osaka University, 1-1 Machikaneyama-cho, Toyonaka 560-0043 (Japan)

    2013-11-01

    The crystal structure of human-heart-type fatty-acid-binding protein in complex with anilinonaphthalene-8-sulfonate was solved at 2.15 Å resolution revealing the detailed binding mechanism of the fluorescent probe 1-anilinonaphthalene-8-sulfonate. Heart-type fatty-acid-binding protein (FABP3), which is a cytosolic protein abundantly found in cardiomyocytes, plays a role in trafficking fatty acids throughout cellular compartments by reversibly binding intracellular fatty acids with relatively high affinity. The fluorescent probe 1-anilinonaphthalene-8-sulfonate (ANS) is extensively utilized for examining the interaction of ligands with fatty-acid-binding proteins. The X-ray structure of FABP3 was determined in the presence of ANS and revealed the detailed ANS-binding mechanism. Furthermore, four water molecules were clearly identified in the binding cavity. Through these water molecules, the bound ANS molecule forms indirect hydrogen-bond interactions with FABP3. The adipocyte-type fatty-acid-binding protein (FABP4) exhibits 67% sequence identity with FABP3 and its crystal structure is almost the same as that of FABP3. However, FABP4 can bind with a higher affinity to ANS than FABP3. To understand the difference in their ligand specificities, a structural comparison was performed between FABP3–ANS and FABP4–ANS complexes. The result revealed that the orientation of ANS binding to FABP3 is completely opposite to that of ANS binding to FABP4, and the substitution of valine in FABP4 to leucine in FABP3 may result in greater steric hindrance between the side-chain of Leu115 and the aniline ring of ANS.

  14. Structure of the human-heart fatty-acid-binding protein 3 in complex with the fluorescent probe 1-anilinonaphthalene-8-sulphonic acid

    International Nuclear Information System (INIS)

    The crystal structure of human-heart-type fatty-acid-binding protein in complex with anilinonaphthalene-8-sulfonate was solved at 2.15 Å resolution revealing the detailed binding mechanism of the fluorescent probe 1-anilinonaphthalene-8-sulfonate. Heart-type fatty-acid-binding protein (FABP3), which is a cytosolic protein abundantly found in cardiomyocytes, plays a role in trafficking fatty acids throughout cellular compartments by reversibly binding intracellular fatty acids with relatively high affinity. The fluorescent probe 1-anilinonaphthalene-8-sulfonate (ANS) is extensively utilized for examining the interaction of ligands with fatty-acid-binding proteins. The X-ray structure of FABP3 was determined in the presence of ANS and revealed the detailed ANS-binding mechanism. Furthermore, four water molecules were clearly identified in the binding cavity. Through these water molecules, the bound ANS molecule forms indirect hydrogen-bond interactions with FABP3. The adipocyte-type fatty-acid-binding protein (FABP4) exhibits 67% sequence identity with FABP3 and its crystal structure is almost the same as that of FABP3. However, FABP4 can bind with a higher affinity to ANS than FABP3. To understand the difference in their ligand specificities, a structural comparison was performed between FABP3–ANS and FABP4–ANS complexes. The result revealed that the orientation of ANS binding to FABP3 is completely opposite to that of ANS binding to FABP4, and the substitution of valine in FABP4 to leucine in FABP3 may result in greater steric hindrance between the side-chain of Leu115 and the aniline ring of ANS

  15. Insulin-like growth factors, insulin-like growth factor-binding proteins, insulin-like growth factor-binding protein-3 protease, and growth hormone-binding protein in lipodystrophic human immunodeficiency virus-infected patients

    DEFF Research Database (Denmark)

    Haugaard, Steen B; Andersen, Ove; Hansen, Birgitte Rønde;

    2004-01-01

    Human immunodeficiency virus (HIV)-lipodystrophy is associated with impaired growth hormone (GH) secretion. It remains to be elucidated whether insulin-like growth factors (IGFs), IGF-binding proteins (IGFBPs), IGFBP-3 protease, and GH-binding protein (GHBP) are abnormal in HIV-lipodystrophy....... These parameters were measured in overnight fasting serum samples from 16 Caucasian males with HIV-lipodystrophy (LIPO) and 15 Caucasian HIV-infected males without lipodystrophy (NONLIPO) matched for age, weight, duration of HIV infection, and antiretroviral therapy. In LIPO, abdominal fat mass and insulin...... of bioactive IGF-I in HIV-lipodystrophy....

  16. Nonparallel changes of growth hormone (GH) and insulin-like growth factor-I, insulin-like growth factor binding protein-3, and GH-binding protein, after craniospinal irradiation and chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Nivot, S.; Adan, L.; Souberbielle, J.; Rappaport, R.; Brauner, R.; Benelli, C.; Clot, J.P.; Saucet, C. [Hopital des Enfants-Malades, Paris (France); Zucker, J.M. [Institut Curie, Paris (France)

    1994-03-01

    The authors studied the GH-insulin-like growth factor-I (IGF-I) axis serially over 24-36 months in six patients with medulloblastoma who underwent surgical removal of the tumor followed by craniospinal irradiation therapy for 6 weeks and then chemotherapy for 42 weeks. Eighteen and 24 months after beginning irradiation there was a decline in the peak GH secretory response to acute stimulation with arginine/insulin hypoglycemia. Six months after irradiation and during chemotherapy there was a transient decline in IGF-I, IGF binding protein-3 (IGFBP-3), and GH-BP values (respective mean values of 56.1 {+-} 9.0 ng/mL, 1.1 {+-} 0.2 {mu}g/mL, and 7.6 {+-} 3.3% of radioactivity as compared to time 0 values: 139 {+-} 15 ng/mL, 2.2 {+-} 0.2 {mu}g/mL, and 20.0 {+-} 4.0%, P < 0.001), although provoked GH secretion was normal at this time. The IGF-I, IGFBP-3, and GH-BP returned to pretreatment ranges by 12-36 months after initiation of the study. There was also a decline in body mass index and serum protein values at 6 months after irradiation in ligand and immunoblot analysis there was a decline in IGFBP-3 and an abnormal electrophoretic mobility of IGFBP-2 that were both normalized at 36 months. In one patient they observed a high level of IGFBP-3 proteolysis at this time. This study demonstrates that before the decrease of GH secretion in patients receiving cranial irradiation there is a transient phase of GH insensitivity that may be characteristic of the acute therapeutic phase including the chemotherapy. This partial insensitivity may explain the early growth retardation observed in these patients. 28 refs., 4 figs., 1 tab.

  17. Nonparallel changes of growth hormone (GH) and insulin-like growth factor-I, insulin-like growth factor binding protein-3, and GH-binding protein, after craniospinal irradiation and chemotherapy

    International Nuclear Information System (INIS)

    The authors studied the GH-insulin-like growth factor-I (IGF-I) axis serially over 24-36 months in six patients with medulloblastoma who underwent surgical removal of the tumor followed by craniospinal irradiation therapy for 6 weeks and then chemotherapy for 42 weeks. Eighteen and 24 months after beginning irradiation there was a decline in the peak GH secretory response to acute stimulation with arginine/insulin hypoglycemia. Six months after irradiation and during chemotherapy there was a transient decline in IGF-I, IGF binding protein-3 (IGFBP-3), and GH-BP values (respective mean values of 56.1 ± 9.0 ng/mL, 1.1 ± 0.2 μg/mL, and 7.6 ± 3.3% of radioactivity as compared to time 0 values: 139 ± 15 ng/mL, 2.2 ± 0.2 μg/mL, and 20.0 ± 4.0%, P < 0.001), although provoked GH secretion was normal at this time. The IGF-I, IGFBP-3, and GH-BP returned to pretreatment ranges by 12-36 months after initiation of the study. There was also a decline in body mass index and serum protein values at 6 months after irradiation in ligand and immunoblot analysis there was a decline in IGFBP-3 and an abnormal electrophoretic mobility of IGFBP-2 that were both normalized at 36 months. In one patient they observed a high level of IGFBP-3 proteolysis at this time. This study demonstrates that before the decrease of GH secretion in patients receiving cranial irradiation there is a transient phase of GH insensitivity that may be characteristic of the acute therapeutic phase including the chemotherapy. This partial insensitivity may explain the early growth retardation observed in these patients. 28 refs., 4 figs., 1 tab

  18. Luteinizing hormone (LH) blood test

    Science.gov (United States)

    ICSH - blood test; Luteinizing hormone - blood test; Interstitial cell stimulating hormone - blood test ... medicines you take. These include: Birth control pills Hormone therapy Testosterone DHEA (a supplement) If you are ...

  19. Prediction of the outcome of growth hormone provocative testing in short children by measurement of serum levels of insulin-like growth factor I and insulin-like growth factor binding protein 3

    DEFF Research Database (Denmark)

    Juul, A; Skakkebaek, N E

    1997-01-01

    Serum levels of insulin-like growth factor I (IGF-I) and insulin-like growth factor binding protein 3 (IGFBP-3) reflect the secretion of endogenous growth hormone (GH) in healthy children and exhibit little diurnal variation, which makes them potential candidates for screening of GH deficiency (GHD......). We evaluated serum IGF-I and IGFBP-3 levels in relation to the outcome of GH provocative testing in 203 children and adolescents (111 boys and 92 girls) in whom GHD was suspected. A total of 1030 children served as control subjects. In children less than 10 years of age, IGF-I levels were below...

  20. Serum levels of insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) in healthy infants, children, and adolescents

    DEFF Research Database (Denmark)

    Juul, A; Dalgaard, P; Blum, W F;

    1995-01-01

    Circulating IGF-I and -II are bound to specific insulin-like growth factor (IGF)-binding proteins (IGFBPs), of which IGFBP-3 binds the majority of the IGFs. IGFBP-3 levels are regulated by GH and have been suggested to provide additional information on GH secretory capacity compared to IGF...... in puberty. We found that IGFBP-3 levels increase with age in children, with maximal levels in puberty; girls experience peak values approximately 1 yr earlier than boys. Age, sex, height, BMI, and pubertal maturation were all important factors in determining the circulating levels of IGFBP-3, whereas IGF...

  1. Cloning and expression of full-length human insulin-like growth factor binding protein 3 (IGFBP3) in the Escherichia coli

    OpenAIRE

    Emad Khodadadi; Mojtaba Panjepour; Mahdi Abbasian; Zahra Khalili Broujeni; Mohammad Reza Mofid

    2015-01-01

    Background: The effect of the growth hormone on target cells is mediated by the insulin-like growth factor 1 (IGF-1). IGF-1 binds to the insulin-like growth factor binding proteins (IGFBPs) in blood and biological fluids. Considering the important application of IGBP3 as a drug component, in this research we cloned and expressed the full-length IGFBP3 in the pET-11a vector and BL21 (DE3) expression host. Materials and Methods: First the sequence encoding of IGFBP3 was designed based on th...

  2. Serum levels of insulin-like growth factor-1 and insulin-like growth factor binding protein-3 in relapsing and primary progressive multiple sclerosis

    NARCIS (Netherlands)

    Wilczak, N; Ramsaransing, GSM; Mostert, J; Chesik, D; De Keyser, J

    2005-01-01

    Using radioimmunoassay we measured serum levels of insulin- like growth factor ( IGF)- 1 and IGF binding protein ( IGFBP)- 3 in patients with relapsing multiple sclerosis ( MS) and a benign course ( Expanded Disability Status Scale ( EDSS) less than or equal to 3 despite > 10 years disease duration)

  3. Growth hormone (GH) secretory dynamics in a case of acromegalic gigantism associated with hyperprolactinemia: nonpulsatile secretion of GH may induce elevated insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 levels.

    Science.gov (United States)

    Yoshida, T; Shimatsu, A; Sakane, N; Hizuka, N; Horikawa, R; Tanaka, T

    1996-01-01

    We describe a case of pituitary gigantism with low levels of growth hormone (GH), elevated insulin-like growth factor-I (IGF-I), and IGF-binding protein-3 (IGF-BP-3). The patient had characteristic clinical features of gigantism and acromegaly. The basal serum GH levels ranged from 1.2-1.9 micrograms/L, which were considered to be within normal limits. Serum GH response to either insulin-induced hypoglycemia or GH-releasing hormone was blunted. Frequent blood samplings during daytime and at night showed nonpulsatile GH secretion. Serum prolactin, IGF-I and IGF-binding protein-3 levels were elevated. After unsuccessful surgery, bromocryptine treatment normalized serum prolactin without affecting serum GH and IGF-I levels. Combined administration of octreotide and bromocryptine reduced serum GH and IGF-I levels. GH bioactivity as measured by Nb2 cell proliferation assay was within reference range. In the present case, nonpulsatile GH secretion and enhanced tissue sensitivity to GH may induce hypersecretion of IGF-I and IGF-BP-3 and cause clinical acromegalic gigantism. PMID:8550769

  4. Histone Deacetylase Inhibitors Enhance the Apoptotic Activity of Insulin-Like Growth Factor Binding Protein-3 by Blocking PKC-Induced IGFBP-3 Degradation

    OpenAIRE

    Oh, Seung Hyun; Whang, Young Mi; Min, Hye-Young; Han, Seung Ho; Kang, Ju-Hee; Song, Ki-Hoon; Glisson, Bonnie S.; Kim, Yeul Hong; Lee, Ho-Young

    2012-01-01

    Overexpression of insulin-like growth factor binding protein (IGFBP)-3 induces apoptosis of cancer cells. However, preexisting resistance to IGFBP-3 could limit its antitumor activities. This study characterizes the efficacy and mechanism of the combination of recombinant IGFBP-3 (rIGFBP-3) and HDAC inhibitors to overcome IGFBP-3 resistance in a subset of non-small cell lung cancer (NSCLC) and head and neck squamous cell carcinoma (HNSCC) cells. The effects of the combination of rIGFBP-3 and ...

  5. Bioavailability and biodistribution of nanodelivered lutein.

    Science.gov (United States)

    Kamil, Alison; Smith, Donald E; Blumberg, Jeffrey B; Astete, Carlos; Sabliov, Cristina; Oliver Chen, C-Y

    2016-02-01

    The aim of the study was to evaluate the ability of poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NP) to enhance lutein bioavailability. The bioavailability of free lutein and PLGA-NP lutein in rats was assessed by determining plasma pharmacokinetics and deposition in selected tissues. Lutein uptake and secretion was also assessed in Caco-2 cells. Compared to free lutein, PLGA-NP increased the maximal plasma concentration (Cmax) and area under the time-concentration curve in rats by 54.5- and 77.6-fold, respectively, while promoting tissue accumulation in the mesenteric fat and spleen. In comparison with micellized lutein, PLGA-NP lutein improved the Cmax in rat plasma by 15.6-fold and in selected tissues by ⩾ 3.8-fold. In contrast, PLGA-NP lutein had a lower uptake and secretion of lutein in Caco-2 cells by 10.0- and 50.5-fold, respectively, compared to micellized lutein. In conclusion, delivery of lutein with polymeric NP may be an approach to improve the bioavailability of lutein in vivo. PMID:26304429

  6. Analysis of circulating insulin-like growth factor-1 (IGF-1 and IGF binding protein-3 (IGFBP-3 in tobacco smokers and non-smokers

    Directory of Open Access Journals (Sweden)

    Palmer RM

    2002-06-01

    Full Text Available Abstract Background IGF-1 and the major serum IGF-1 binding protein, IGFBP-3, are under extensive investigation as potential prognostic markers of specific malignancies and vascular diseases. However, there is conflicting evidence that tobacco smoking may influence systemic concentrations of IGF-1 and IGFBP-3. Subjects and methods Serum concentrations of IGF-1 and IGFBP-3 were measured in 20 smokers and 20 non-smokers, matched for age and gender. Serum concentrations of cotinine, the major metabolite of nicotine, and ICAM-1, known to exhibit a dose-dependent relationship with cotinine, were also assayed. Results There was no difference between the systemic concentrations of IGF-1 or IGFBP-3 found in smokers and non-smokers (IGF-1: mean [s.d]; 104 29 vs 101 24 ng ml-1, respectively; and IGFBP-3: 2562 [522] vs 2447 [570] ng ml-1, respectively. Similarly, there was no correlation between serum cotinine and IGF-1 or IGFBP-3 concentrations in smokers. Soluble ICAM-1 concentrations were significantly increased in smokers, compared to non-smokers (mean [s.d]; 258 [60] vs 194 [50] ng ml-1, respectively; p = 0.002. Conclusion There was no relationship noted between tobacco smoking and either IGF-1 or IGFBP-3. These data suggest that smoking would not appear to be a major confounder of the reported clinical associations between IGF-1, IGFBP-3, or IGF-1/IGFBP-3 ratios and specific disease entities.

  7. Targeting insulin-like growth factor-I and insulin-like growth factor-binding protein-3 signaling pathways. A novel therapeutic approach for asthma.

    Science.gov (United States)

    Lee, Hyun; Kim, So Ri; Oh, Youngman; Cho, Seong Ho; Schleimer, Robert P; Lee, Yong Chul

    2014-04-01

    Insulin-like growth factor (IGF)-I has been recognized to play critical roles in the pathogenesis of asthma, whereas IGF-binding protein (IGFBP)-3 blocks crucial physiologic manifestations of asthma. IGF-I enhances subepithelial fibrosis, airway inflammation, airway hyperresponsiveness, and airway smooth muscle hyperplasia by interacting with various inflammatory mediators and complex signaling pathways, such as intercellular adhesion molecule-1, and the hypoxia-inducible factor/vascular endothelial growth factor axis. On the other hand, IGFBP-3 decreases airway inflammation and airway hyperresponsiveness through IGFBP-3 receptor-mediated activation of caspases, which subsequently inhibits NF-κB signaling pathway. It also inhibits the IGF-I/hypoxia-inducible factor/vascular endothelial growth factor axis via IGF-I-dependent and/or IGF-I-independent mechanisms. This Translational Review summarizes the role of IGF-I and IGFBP-3 in the context of allergic airway disease, and discusses the therapeutic potential of various strategies targeting the IGF-I and IGFBP-3 signaling pathways for the management of asthma. PMID:24219511

  8. Antiproliferative action of tumor necrosis factor-alpha on MCF-7 breastcancer cells is associated with increased insulin-like growth factor binding protein-3 accumulation.

    Science.gov (United States)

    Rozen, F; Zhang, J; Pollak, M

    1998-10-01

    Tumor necrosis factor-alpha (TNF-alpha) is a multifunctional cytokine involved in host response to neoplasia. TNF-alpha has been shown to inhibit proliferation and induce apoptosis of MCF-7 breast carcinoma cells. Insulin-like growth factors I and II (IGF-I and IGF-II) are potent mitogens involved in growth regulation of breast epithelial cells and are implicated in the pathophysiology of breast cancer. Their bioactivity is strongly influenced by specific IGF-binding proteins (IGFBPs). We report that accumulation of IGFBP-3 in the conditioned media of MCF-7 cells is increased over control values in the presence of TNF-alpha. The increased IGFBP-3 accumulation induced by TNF-alpha is correlated with increased IGFBP-3 mRNA abundance. TNF-alpha also decreases IGF-I receptor levels in MCF-7 cells. Estradiol-stimulated MCF-7 cell proliferation is associated with reduced IGFBP-3 accumulation, and we show that TNF-alpha attenuation of estradiol-stimulated proliferation is associated with increased IGFBP-3 accumulation. Finally, we demonstrate that an IGFBP-3 antisense oligodeoxynucleotide antagonizes TNF-alpha-induced inhibition of cell proliferation and TNF-alpha-induced IGFBP-3 accumulation. These data strongly suggest that IGFBP-3 plays a role in modulation of breast cancer cell proliferation by TNF-alpha.

  9. Effect of recombinant porcine IGF-binding protein-3 on proliferation of embryonic porcine myogenic cell cultures in the presence and absence of IGF-I.

    Science.gov (United States)

    Pampusch, M S; Kamanga-Sollo, E; White, M E; Hathaway, M R; Dayton, W R

    2003-02-01

    IGF-binding protein (IGFBP)-3 is produced by cultured porcine embryonic myogenic cell (PEMC) cultures and is secreted into the medium. Levels of secreted IGFBP-3 and IGFBP-3 mRNA are significantly reduced during differentiation and increase after differentiation is complete, suggesting that IGFBP-3 may play some role in myogenesis and/or in changes in myogenic cell proliferation that accompany differentiation. IGFBP-3 reportedly may either suppress or stimulate proliferation of cultured cells depending on cell type. Additionally, IGFBP-3 has been shown to affect proliferation via both IGF-dependent and IGF-independent mechanisms in some cell types but not all. Currently, the effect, if any, of IGFBP-3 on myogenic cell proliferation is not known. Consequently, the goal of this study was to assess the IGF-I-dependent and IGF-I-independent actions of recombinant porcine IGFBP-3 on proliferation of cultured porcine myogenic cells. To facilitate these investigations, we have expressed porcine IGFBP-3 in the baculovirus system, purified and characterized the expressed recombinant porcine IGFBP-3 (rpIGFBP-3), and produced and characterized an anti-porcine IGFBP-3 antibody that neutralizes the biological activity of porcine IGFBP-3. rpIGFBP-3 suppressed IGF-I-stimulated proliferation of PEMCs in a concentration-dependent manner with equimolar concentrations of IGF-I and rpIGFBP-3, resulting in complete suppression of IGF-I-stimulated proliferation. rpIGFBP-3 also suppressed Long-R3-IGF-I-stimulated proliferation of PEMC, indicating that rpIGFBP-3 possesses IGF-independent activity in this cell system. These data have established that IGFBP-3 has the potential to affect proliferation of PEMCs during critical periods of muscle development that may impact ultimate muscle mass achievable postnatally. PMID:12553871

  10. Increased placental fatty acid transporter 6 and binding protein 3 expression and fetal liver lipid accumulation in a mouse model of obesity in pregnancy.

    Science.gov (United States)

    Díaz, Paula; Harris, Jessica; Rosario, Fredrick J; Powell, Theresa L; Jansson, Thomas

    2015-12-15

    Obesity in pregnancy is associated with increased fetal growth and adiposity, which, in part, is determined by transplacental nutrient supply. Trophoblast uptake and intracellular trafficking of lipids are dependent on placental fatty acid transport proteins (FATP), translocase (FAT/CD36), and fatty acid binding proteins (FABP). We hypothesized that maternal obesity in mice leads to increased placental expression of FAT/CD36, FATPs, and FABPs, and lipid accumulation in the fetal liver. C57/BL6J female mice were fed either a control (C; n = 10) or an obesogenic (OB; n = 10) high-fat, high-sugar diet before mating and throughout pregnancy. At E18.5, placentas and fetal livers were collected. Trophoblast plasma membranes (TPM) were isolated from placental homogenates. Expression of FAT/CD36 and FATP (TPM) and FABP (homogenates) was determined by immunoblotting. Gene expression was assessed by RT-quantitative PCR. Sections of fetal livers were stained for Oil Red O, and lipid droplets were quantified. TPM protein expression of FAT/CD36, FATP 2, and FATP 4 was comparable between C and OB groups. Conversely, TPM FATP 6 expression was increased by 35% in OB compared with C placentas without changes in mRNA expression. FABPs 1, 3-5 and PPARγ were expressed in homogenates, and FABP 3 expression increased 27% in OB compared with C placentas; however, no changes were observed in mRNA expression. Lipid droplet accumulation was 10-fold higher in the livers of fetuses from OB compared with C group. We propose that increased lipid transport capacity in obese mice promotes transplacental fatty acid transport and contributes to excess lipid accumulation in the fetal liver.

  11. Lutein and lutein esters in marigold flowers by high performance chromatography

    Institute of Scientific and Technical Information of China (English)

    JIANG Xin-yu; CHEN Long-sheng; ZHOU Chun-shan

    2005-01-01

    Lutein and lutein esters in marigold flowers was quantitatively determined by high performance chromatography (HPLC) with ODS-C18 column. A mixture of CH3CN - CH3OH - CH3COOCH2CH3 with volume ratio of 55: 1: 44 was used as mobile phase at a flow rate of 1.0 mL/min and detection was carried out at 460 nm. The column temperature was about 20 ℃. The contents of lutein and lutein esters were determined by analytical curve of lutein since lutein and lutein esters have the same spectral characteristics. Determination results of hexane extracts and saponified samples of lutein show that the saponification transforms the esters into free lutein. The increase of the content of dipalmitate and palmitate stearate reveals that the reaction includes transesterifications.

  12. Vitreoscilla hemoglobin gene ( vgb) improves lutein production in Chlorella vulgaris

    Science.gov (United States)

    Ma, Ruijuan; Lin, Xiangzhi

    2014-03-01

    Vitreoscilla hemoglobin is an oxygen-binding protein that promotes oxygen delivery and reduces oxygen consumption under low oxygen conditions to increase the efficiency of cell respiration and metabolism. In this study, we introduced a Vitreoscilla hemoglobin gene ( vgb) into Chlorella vulgaris by Agrobacterium tumefaciens -mediated transformation (ATMT). PCR analysis confirmed that the vgb gene was successfully integrated into the Chlorella vulgaris genome. Analysis of biomass obtained in shake flasks revealed transformant biomass concentrations as high as 3.28 g/L, which was 38.81% higher than that of the wild-type strain. Lutein content of transformants also increased slightly. Further experiments recovered a maximum lutein yield of 2.91 mg/L from the transformants, which was 36.77% higher than that of the wild-type strain. The above results suggest that integrated expression of the vgb gene may improve cell growth and lutein yield in Chlorella vulgaris, with applications to lutein production from Chlorella during fermentation.

  13. Stimulation of the 150-kilodalton insulin-like growth factor-binding protein-3 ternary complex by continuous and pulsatile patterns of growth hormone (GH) administration in GH-deficient patients

    DEFF Research Database (Denmark)

    Laursen, Torben; Flyvbjerg, Allan; Jørgensen, Jens Otto Lunde;

    2000-01-01

    Abstract In the circulation insulin-like growth factor I (IGF-I), IGF-binding protein 3 (IGFBP-3), and the acid-labile subunit (ALS) form a 150-kDa ternary complex that is of importance for the regulation of IGF-I bioactivity. GH administration is known to increase each of the single components of...... GH dose (2 IU/m2-24 h) was administered iv randomly as 1) continuous infusion or 2) eight bolus injections to five GH-deficient patients over a period of 24 h. GH administration significantly increased serum IGF-I and IGFBP-3 levels and the IGF-I/IGFBP-3 ratio. IGF-I levels increased most......, formation of the ternary complex was unaffected by the pattern of GH delivery. In conclusion, short-term GH administration increased all components of the 150-kDa ternary complex. Higher levels of IGF-I after constant GH exposure could indicate an increased bound fraction. However, the GH pattern did not...

  14. Inhibition of human MCF-7 breast cancer cells and HT-29 colon cancer cells by rice-produced recombinant human insulin-like growth binding protein-3 (rhIGFBP-3.

    Directory of Open Access Journals (Sweden)

    Stanley C K Cheung

    Full Text Available BACKGROUND: Insulin-like growth factor binding protein-3 (IGFBP-3 is a multifunctional molecule which is closely related to cell growth, apoptosis, angiogenesis, metabolism and senescence. It combines with insulin-like growth factor-I (IGF-I to form a complex (IGF-I/IGFBP-3 that can treat growth hormone insensitivity syndrome (GHIS and reduce insulin requirement in patients with diabetes. IGFBP-3 alone has been shown to have anti-proliferation effect on numerous cancer cells. METHODOLOGY/PRINCIPAL FINDINGS: We reported here an expression method to produce functional recombinant human IGFBP-3 (rhIGFBP-3 in transgenic rice grains. Protein sorting sequences, signal peptide and endoplasmic reticulum retention tetrapeptide (KDEL were included in constructs for enhancing rhIGFBP-3 expression. Western blot analysis showed that only the constructs with signal peptide were successfully expressed in transgenic rice grains. Both rhIGFBP-3 proteins, with or without KDEL sorting sequence inhibited the growth of MCF-7 human breast cancer cells (65.76 ± 1.72% vs 45.00 ± 0.86%, p < 0.05; 50.84 ± 1.97% vs 45.00 ± 0.86%, p < 0.01 respectively and HT-29 colon cancer cells (65.14 ± 3.84% vs 18.01 ± 13.81%, p < 0.05 and 54.7 ± 9.44% vs 18.01 ± 13.81%, p < 0.05 respectively when compared with wild type rice. CONCLUSION/SIGNIFICANCE: These findings demonstrated the feasibility of producing biological active rhIGFBP-3 in rice using a transgenic approach, which will definitely encourage more research on the therapeutic use of hIGFBP-3 in future.

  15. Mitogenic properties of insulin-like growth factors I and II, insulin-like growth factor binding protein-3 and epidermal growth factor on human breast stromal cells in primary culture.

    Science.gov (United States)

    Strange, Karen S; Wilkinson, Darcy; Edin, Glenn; Emerman, Joanne T

    2004-03-01

    Insulin-like growth factors I and II (IGF-I and IGF-II) are growth factors implicated in both normal mammary gland development and breast cancer. We have previously reported on the effects of components of the IGF system on breast epithelial cells. Since data suggests that stromal-epithelial interactions play a crucial role in breast cancer, we have now investigated the mitogenic properties of IGF-I, IGF-II, insulin-like growth factor binding protein-3 (IGFBP-3) and epidermal growth factor (EGF) on human breast stromal cells in primary culture. We show that, under serum-free conditions, stromal cells are stimulated to grow in response to IGF-I and IGF-II in a dose-dependent manner. IGF-I and EGF, a potent stimulator of human breast epithelial cell growth in primary culture and also associated with breast cancer, appear to stimulate stromal cell growth in a synergistic manner. IGFBP-3 does not inhibit the stimulation of growth by IGF-I, or IGF-I plus EGF. However, IGFBP-3 does inhibit the stimulation of growth by IGF-II. In contrast to our previous results with human breast epithelial cells, IGFBP-3 does not have an IGF-independent inhibitory effect on stromal cell growth. This study is the first to address the effects of IGF-I, IGF-II and IGFBP-3 alone and in combination with EGF on human breast stromal cell growth in primary culture. Characterizing the role of the IGF system in both normal breast epithelial cells and stromal cells will aid in our understanding of the mechanisms behind the role of the IGF system in breast cancer.

  16. Mitogenic properties of insulin-like growth factors I and II, insulin-like growth factor binding protein-3 and epidermal growth factor on human breast epithelial cells in primary culture.

    Science.gov (United States)

    Strange, Karen S; Wilkinson, Darcy; Emerman, Joanne T

    2002-10-01

    Insulin-like growth factor-I (IGF-I) and insulin-like growth factor-II (IGF-II) are growth factors implicated in mammary gland development and are believed to be involved in breast cancer. However, the interactions between components of the IGF system and breast epithelial cells, which give rise to breast cancer, are not well understood. We have investigated the mitogenic properties of IGF-I, IGF-II, IGF binding protein-3 (IGFBP-3) and epidermal growth factor (EGF) on human breast epithelial cells (HBEC) in primary culture. We show that, under serum-free conditions, HBEC are stimulated to grow in response to IGF-I and IGF-II in a dose-dependent manner. IGF-I and EGF, a potent stimulator of HBEC growth in primary culture and also associated with breast cancer, appear to stimulate HBEC in a synergistic manner. IGFBP-3 inhibits the stimulation by IGF-I, IGF-II and IGF-I plus EGE In addition, it appears that IGFBP-3 has an inhibitory effect on HBEC growth that is IGF-independent. This study is the first to address the effects of IGF-I, IGF-II and IGFBP-3 alone and in combination with EGF on HBEC growth in primary culture. Characterizing the role of the IGF system in normal breast biology is significant because the system has been implicated in breast cancer and a number of the anti-estrogens used in treatment are believed to function through the IGF system.

  17. Human immunodeficiency virus type 1 enhancer-binding protein 3 is essential for the expression of asparagine-linked glycosylation 2 in the regulation of osteoblast and chondrocyte differentiation.

    Science.gov (United States)

    Imamura, Katsuyuki; Maeda, Shingo; Kawamura, Ichiro; Matsuyama, Kanehiro; Shinohara, Naohiro; Yahiro, Yuhei; Nagano, Satoshi; Setoguchi, Takao; Yokouchi, Masahiro; Ishidou, Yasuhiro; Komiya, Setsuro

    2014-04-01

    Human immunodeficiency virus type 1 enhancer-binding protein 3 (Hivep3) suppresses osteoblast differentiation by inducing proteasomal degradation of the osteogenesis master regulator Runx2. In this study, we tested the possibility of cooperation of Hivep1, Hivep2, and Hivep3 in osteoblast and/or chondrocyte differentiation. Microarray analyses with ST-2 bone stroma cells demonstrated that expression of any known osteochondrogenesis-related genes was not commonly affected by the three Hivep siRNAs. Only Hivep3 siRNA promoted osteoblast differentiation in ST-2 cells, whereas all three siRNAs cooperatively suppressed differentiation in ATDC5 chondrocytes. We further used microarray analysis to identify genes commonly down-regulated in both MC3T3-E1 osteoblasts and ST-2 cells upon knockdown of Hivep3 and identified asparagine-linked glycosylation 2 (Alg2), which encodes a mannosyltransferase residing on the endoplasmic reticulum. The Hivep3 siRNA-mediated promotion of osteoblast differentiation was negated by forced Alg2 expression. Alg2 suppressed osteoblast differentiation and bone formation in cultured calvarial bone. Alg2 was immunoprecipitated with Runx2, whereas the combined transfection of Runx2 and Alg2 interfered with Runx2 nuclear localization, which resulted in suppression of Runx2 activity. Chondrocyte differentiation was promoted by Hivep3 overexpression, in concert with increased expression of Creb3l2, whose gene product is the endoplasmic reticulum stress transducer crucial for chondrogenesis. Alg2 silencing suppressed Creb3l2 expression and chondrogenesis of ATDC5 cells, whereas infection of Alg2-expressing virus promoted chondrocyte maturation in cultured cartilage rudiments. Thus, Alg2, as a downstream mediator of Hivep3, suppresses osteogenesis, whereas it promotes chondrogenesis. To our knowledge, this study is the first to link a mannosyltransferase gene to osteochondrogenesis.

  18. Inhibition of Human MCF-7 Breast Cancer Cells and HT-29 Colon Cancer Cells by Rice-Produced Recombinant Human Insulin-Like Growth Binding Protein-3 (rhIGFBP-3)

    Science.gov (United States)

    Liu, Lizhong; Liu, Qiaoquan; Lan, Linlin; Tong, Peter C. Y.; Sun, Samuel S. M.

    2013-01-01

    Background Insulin-like growth factor binding protein-3 (IGFBP-3) is a multifunctional molecule which is closely related to cell growth, apoptosis, angiogenesis, metabolism and senescence. It combines with insulin-like growth factor-I (IGF-I) to form a complex (IGF-I/IGFBP-3) that can treat growth hormone insensitivity syndrome (GHIS) and reduce insulin requirement in patients with diabetes. IGFBP-3 alone has been shown to have anti-proliferation effect on numerous cancer cells. Methodology/Principal Findings We reported here an expression method to produce functional recombinant human IGFBP-3 (rhIGFBP-3) in transgenic rice grains. Protein sorting sequences, signal peptide and endoplasmic reticulum retention tetrapeptide (KDEL) were included in constructs for enhancing rhIGFBP-3 expression. Western blot analysis showed that only the constructs with signal peptide were successfully expressed in transgenic rice grains. Both rhIGFBP-3 proteins, with or without KDEL sorting sequence inhibited the growth of MCF-7 human breast cancer cells (65.76 ± 1.72% vs 45.00 ± 0.86%, p < 0.05; 50.84 ± 1.97% vs 45.00 ± 0.86%, p < 0.01 respectively) and HT-29 colon cancer cells (65.14 ±3.84% vs 18.01 ± 13.81%, p < 0.05 and 54.7 ± 9.44% vs 18.01 ± 13.81%, p < 0.05 respectively) when compared with wild type rice. Conclusion/Significance These findings demonstrated the feasibility of producing biological active rhIGFBP-3 in rice using a transgenic approach, which will definitely encourage more research on the therapeutic use of hIGFBP-3 in future. PMID:24143239

  19. Associations of serum insulin-like growth factor-I and insulin-like growth factor-binding protein 3 levels with biomarker-calibrated protein, dairy product and milk intake in the Women's Health Initiative.

    Science.gov (United States)

    Beasley, Jeannette M; Gunter, Marc J; LaCroix, Andrea Z; Prentice, Ross L; Neuhouser, Marian L; Tinker, Lesley F; Vitolins, Mara Z; Strickler, Howard D

    2014-03-14

    It is well established that protein-energy malnutrition decreases serum insulin-like growth factor (IGF)-I levels, and supplementation of 30 g of whey protein daily has been shown to increase serum IGF-I levels by 8 % after 2 years in a clinical trial. Cohort studies provide the opportunity to assess associations between dietary protein intake and IGF axis protein levels under more typical eating conditions. In the present study, we assessed the associations of circulating IGF axis protein levels (ELISA, Diagnostic Systems Laboratories) with total biomarker-calibrated protein intake, as well as with dairy product and milk intake, among postmenopausal women enrolled in the Women's Health Initiative (n 747). Analyses were carried out using multivariate linear regression models that adjusted for age, BMI, race/ethnicity, education, biomarker-calibrated energy intake, alcohol intake, smoking, physical activity and hormone therapy use. There was a positive association between milk intake and free IGF-I levels. A three-serving increase in milk intake per d (approximately 30 g of protein) was associated with an estimated average 18·6 % higher increase in free IGF-I levels (95 % CI 0·9, 39·3 %). However, total IGF-I and insulin-like growth factor-binding protein 3 (IGFBP-3) levels were not associated with milk consumption and nor were there associations between biomarker-calibrated protein intake, biomarker-calibrated energy intake, and free IGF-I, total IGF-I or IGFBP-3 levels. The findings of the present study carried out in postmenopausal women are consistent with clinical trial data suggesting a specific relationship between milk consumption and serum IGF-I levels, although in the present study this association was only statistically significant for free, but not total, IGF-I or IGFBP-3 levels.

  20. Association of sterol regulatory element binding protein 2 and insulin-like growth factor binding protein 3 genetic polymorphisms with avascular necrosis of the femoral head in the Chinese population

    Institute of Scientific and Technical Information of China (English)

    SONG Yang; DU Zhen-wu; LI Qiu-ju; ZHANG Gui-zhen; WANG Ling-ling; WU Ning; WANG Jin-cheng; GAO Zhong-li

    2012-01-01

    Background Sterol regulatory element binding protein(SREBP)-2 plays a key role in lipid homeostasis by stimulating gene expression of cholesterol biosynthetic pathways.The insulin-like growth factor binding protein(IGFBP)family regulates growth and metabolism,especially bone cell metabolism,and correlates with osteonecrosis.However,association of their gene polymorphisms with risk of avascular necrosis of the femoral head(ANFH)has rarely been reported.We determined whether SREBP-2 and IGFBP-3 gene polymorphisms were associated with increased ANFH risk in the Chinese population.Methods Two single nucleotide polymorphisms of SREBP2 gene,rs2267439 and rs2267443,and one of IGFBP-3 gene,rs2453839,were selected and genotyped in 49 ANFH patients and 42 control individuals by direct sequencing assay.Results The frequencies of rs2267439 TT and rs2267443 GA of SREBP2 and rs2453839 TT and CT of IGFBP-3 in the ANFH group showed increased and decreased tendencies(against normal control group),respectively.Interaction analysis of genes revealed that the frequency of carrying rs2267439 TT and rs2267443 GA genctypes of SREBF-2 in ANFH patients was significantly higher than in the control group(P<0.05).Association analysis between polymorphisms and clinical phenotype demonstrated that the disease course in ANFH patients with the rs2453839 TT genotype of IGFBP-3 was significantly shorter than that of CT+CC carriers(P<0.01).CT+CC genotype frequency in patients with stage Ⅲ/Ⅳ?bilateral hip lesions was significantly higher than in those with stage Ⅲ/Ⅳ?unilateral lesions and stage Ⅱ/Ⅲ?bilateral lesions(P<0.05-0.02).Conclusions Our results suggested that interaction of SREBP-2 gene polymorphisms and the relationship between the polymorphisms and clinical phenotype of IGFBP-3 were closely related to increased ANFH risk in the Chinese population.The most significant finding was that the CT+CC genotype carriers of IGFBP-3 rs2453839 were highly associated with the

  1. An Open-Label Trial of Recombinant Human Insulin-Like Growth Factor-I/Recombinant Human Insulin-Like Growth Factor Binding Protein-3 (rhIGF-1/rhIGFBP-3) in Myotonic Dystrophy Type 1

    Science.gov (United States)

    Heatwole, Chad R.; Eichinger, Katy J.; Friedman, Deborah I.; Hilbert, James E.; Jackson, Carlayne E.; Logigian, Eric L.; Martens, William B.; McDermott, Michael P.; Pandya, Shree K.; Quinn, Christine; Smirnow, Alexis M.; Thornton, Charles A.; Moxley, Richard T.

    2012-01-01

    Objective To evaluate the safety and tolerability of recombinant human insulin-like growth factor-1 (rhIGF-1) complexed with IGF binding protein-3 (rhIGF-1/rhIGFBP-3) in patients with myotonic dystrophy type 1 (DM1). Design Open-label dose-escalation clinical trial. Setting University medical center. Participants Fifteen moderately affected ambulatory participants with genetically-proven DM1. Intervention Participants received escalating dosages of subcutaneous rhIGF-1/rhIGFBP-3 over 24 weeks followed by a 16 week washout period. Outcome Measures Serial assessments of safety, muscle mass, muscle function, and metabolic state were performed. The primary outcome variable was the ability of participants to complete 24 weeks on rhIGF-1/rhIGFBP-3 treatment. Results All participants tolerated rhIGF-1/rhIGFBP-3. There were no significant changes in muscle strength or functional outcomes measures. Lean body muscle mass measured by dual energy x-ray absorptiometry increased by 1.95 kg (p=0.0007) after treatment. Participants also experienced a mean reduction in triglyceride levels of 47 mg/dL (p=0.002), a mean increase in HDL levels of 5.0 mg/dL (p=0.03), a mean reduction in HbA1c of 0.15% (p=0.03), and a mean increase in testosterone level (in men) of 203 ng/dL (p=0.002) while on rhIGF-1/rhIGFBP-3. Mild reactions at the injection site occurred (n=9 participants), as did mild transient hypoglycemia (n=3), lightheadedness (n=2), and transient papilledema (n=1). Conclusions rhIGF-1/rhIGFBP-3 treatment was generally well tolerated in DM1. rhIGF-1/rhIGFBP-3 was associated with increased lean body mass and improvements in metabolism, but not with increased muscle strength or function. Larger randomized controlled trials would be needed to further evaluate the efficacy and safety of this medication in patients with neuromuscular disease. PMID:20837825

  2. Toxicity profile of lutein and lutein ester isolated from marigold flowers (Tagetes erecta).

    Science.gov (United States)

    Harikumar, Kuzhuvelil Bhaskarannair; Nimita, Chittikappil Venugopal; Preethi, Korengath Chandran; Kuttan, Ramadasan; Shankaranarayana, Madapura Lingappiah; Deshpande, Jayant

    2008-01-01

    Lutein is a carotenoid with antioxidant properties and is commonly present in many fruits, vegetables, and egg yolk. Lutein affords protection against the development of the two common eye diseases of aging: cataract and macular degeneration. As the dietary lutein concentration is much lower compared to the actual requirement to reduce macular degeneration, supplementation of lutein is under consideration. There are very few data on the toxicity of lutein. In the present study, the authors have evaluated the short-term and long-term toxicity profile of lutein and its esterified form isolated from marigold flowers (Tagetes erecta) in young adult male and female Wistar rats. Lutein and its ester form administered orally at doses of 4, 40, and 400 mg/kg body weight for 4 weeks for short-term toxicity study and 13 weeks for a subchronic toxicity study did not produced any mortality, change in body weight, food consumption pattern, organ weight, and other adverse side reactions. Administration of lutein and ester form did not alter the hepatic and renal function, and did not produce any change in the hematological parameters and in lipid profile. Histopathological analysis of the organs supported the nontoxicity of lutein and its ester form. PMID:18293208

  3. 胰岛素样生长因子结合蛋白3和特发性肺纤维化%Insulin-like growth factor binding protein-3 and idiopathic pulmonary fibrosis

    Institute of Scientific and Technical Information of China (English)

    叶琳; 赵洪文

    2008-01-01

    Idiopathic pulmonary fibrosis(IPF)is a fibrous degeneration disease whose etiopathogenisis is unclear,but incidence and case fatality is prominent.During the fibrous degeneration,a lot of cytokines take part in cell regulation.Insulin-like growth factor binding Protein-3(IGFBP-3)is discovered to be related with IPF.But its concrete mechanism of action is unclear.Many scholars have discovered IGFBP-3 can bind with IGF by dependent or non-dependent mode,but the concrete IGFBP-3 signal transduction pathway has not been elucidated completely.More and more studies have shown IGFBP-3 exerts very important role in many body organs and scholars put emphasis on the pulmonary fibrosis study in recent years.But the concrete mechanism of this action is not so clear,according to relative reports,maybe it iS relative to aspects below:①growth inhibiting of IGFBP-3 and apoptosis;②IGFBP-3 and IGF-1;③IGFBP-3 and TGF-β1;④IGF-1 and TGF-β1;⑤IGFBP-3 and extracellular matrix.So potential and inevitable association exists between IGFBP-3 and IPF,IGFBP-3 has important role in pulmonary fibrosis.%特发性肺纤维化(IPF)是原因不明但发病率和病死率明显的纤维变性疾病,在肺纤维化过程中,众多细胞因子参与了细胞调控,其中胰岛素样生长因子结合蛋白3(IGFBP-3)被发现与IPF有关,但其具体作用机制还不明了.许多学者发现IGFBP-3可以通过依赖性和非依赖性地方式结合IGF,但具体的IGFBP-3信号传导通路还没完全阐明.越来越多的研究显示出IGFBP-3这种蛋白在人体多器官中的重要作用,近年来研究者们把目光聚焦在肺上,而且有关纤维化的相关研究逐渐浮出水面.但其作用机制尚不清楚,阅览国内外有关报道,可能与以下内容相关:①IGFBP-3的生长抑制和细胞凋亡作用;②IGFBP-3与IGF-1;③IGFBP-3与TGF-β1;④IGF-1与TGF-β1;⑤IGFBP-3与细胞外基质.由此可见,IGFBP-3与IPF有着潜在的必然关系,IGFBP-3在促IPF的形成扮演着重要角色.

  4. Lutein and cataract: from bench to bedside.

    Science.gov (United States)

    Manayi, Azadeh; Abdollahi, Mohammad; Raman, Thiagarajan; Nabavi, Seyed Fazel; Habtemariam, Solomon; Daglia, Maria; Nabavi, Seyed Mohammad

    2016-10-01

    Cataract is one of the most important leading causes of blindness in the world. Extensive research showed that oxidative stress may play an important role in the initiation and progression of a cataract and other age-related eye diseases. Extra-generation of reactive oxygen and nitrogen species in the eye tissue has been shown as one of the most important risk factors for cataracts and other age-related eye diseases. With respect to this, it can be hypothesized that dietary antioxidants may be useful in the prevention and/or mitigation of cataract. Lutein is an important xanthophyll which is widely found in different vegetables such as spinach, kale and carrots as well as some other foods such as eggs. Lutein is concentrated in the macula and suppresses the oxidative stress in the eye tissues. A plethora of literature has shown that increased lutein consumption has a close correlation with reduction in the incidence of cataract. Despite this general information, there is a negligible number of review articles considering the beneficial effects of lutein on cataracts and age-related eye diseases. The present review is aimed at discussing the role of oxidative stress in the initiation and progression of a cataract and the possible beneficial effects of lutein in maintaining retinal health and fighting cataract. We also provide a perspective on the chemistry, sources, bioavailability and safety of lutein. PMID:26042352

  5. Detection of serum level of insulin-like growth factor binding protein-3 of normal children aged 2-6 years%2~6岁正常儿童血清IGFBP-3含量的探讨

    Institute of Scientific and Technical Information of China (English)

    蒋新液; 陈雅芬; 于亮; 古桂雄

    2011-01-01

    Objective To detect serum level of insulin-like growth factor binding protein-3 (IGFBP-3) of normal children aged 2-6 years. Methods The serum IGFBP-3 level of 41 healthy children aged 2-6 years in one kindergarten in Wuxi city was detected by using immunoradiometric assay(IRMA). Results The mean serum level of IGFBP-3 of normal children aged 2-6 years was 2 260. 89 ±850. 15ng/mL and there were no significant difference between the two genders ( t = 0. 7970, P > 0. 05 ) and among 5 age groups ( F = 1. 3773, P >0.05 ). The serum level of IGFBP-3 was not related to intelligence quotient(IQ) of the child (the correlation coefficients between IGFBP3 and verbal intelligence quotient, performance intelligence quotient, full intelligence quotient were O. 1297,0.0661,0. 1153 respectively,t =0. 6797, O. 3452, 0. 6071 respectively, all P > 0.05 ). Conclusion 2 260.89 ± 850. 15ng/mL of serum level of IGFBP-3 can be regarded as normal reference range of 2-6 years aged children in clinic, which could be referred by colleagues as an index to evaluate growth and development of the children and to study diseases in growth and development of them.%目的 探讨2~6岁正常儿童血清胰岛素生长因子结合蛋白-3(IGFBP-3)的正常值.方法 对无锡某幼儿园41名健康儿童,应用免疫放射分析法测定血清胰岛素样生长因子结合蛋白-3(IGFBP-3)水平.结果 2~6岁儿童血清中胰岛素样生长因子结合蛋白-3含量为2 260.89±850.15ng/mL,无性别(t=0.7970,P>0.05)和年龄(F=1.3773,P>0.05)差异,血清胰岛素样生长因子结合蛋白-3含量与智商无显著相关性(语言智商、操作智商、总智商与胰岛素样生长因子结合蛋白-3的相关系数分别为0.1297、0.0661、0.1153,t值分别为0.6797、0.3452、0.6071,均P>0.05).结论 血清胰岛素样生长因子结合蛋白-3含量为2 260.89±850.15ng/mL可作为2~6岁儿童的正常参考值用于其生长发育评价及生长发育障碍的研究.

  6. Characterization of Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) interaction with the Bovine Aortic Endothelial (BAE) cell surface : Examination of the Role of Heparan Sulfate Proteoglycans (HSPG).

    OpenAIRE

    Parghi, Nirav

    1998-01-01

    Insulin-like growth factor binding proteins (IGFBPs) are known to be important modulators of the insulin-like growth factor (IGF-I). However, their precise role is as yet unclear. Further, recent studies have indicated that IGFBP-3 has a receptor mediated growth inhibitory response of its own. In the present study, we quantified the binding characteristics of IGFBP-3 to bovine aortic endothelial (BAE) cells. Binding studies at 4 oC were conducted and a specific binding curve for IGFB...

  7. Bioavailability of lutein from a lutein-enriched egg-yolk beverage and its dried re-suspended versions

    NARCIS (Netherlands)

    Bunger, M.; Quataert, M.C.J.; Kamps, L.M.; Versloot, P.; Hulshof, P.J.M.; Togtema, K.A.; Amerongen, van A.; Mensink, M.R.

    2014-01-01

    Drying a fresh lutein-enriched egg-yolk beverage would extend its shelf life, however, functional properties should not be affected. It was investigated whether consumption of a dried beverage containing lutein-enriched egg-yolk significantly increases serum lutein. One-hundred healthy young subject

  8. The Impact of Polymeric Nanoencapsulation on the Bioavailability of Lutein

    Science.gov (United States)

    Kamil, Alison

    Lutein, a fat-soluble xanthophyll, contributes partially to the health benefits from consuming plant foods. Like all dietary carotenoids, lutein has a low bioavailability. In addition to increasing the intake of lutein-rich foods to enhance lutein status, delivery of lutein in polymeric nanoparticles (NP) presents a novel approach to enhancing lutein bioavailability. The overall research objective of this project was to investigate, in rats, the impact of nanoencapsulation using poly(lactic-co-glycolic acid) (PLGA) on the pharmacokinetics of lutein. We also used an in vitro cell culture approach utilizing human epithelial colorectal adenocarcinoma (Caco-2) cells grown in both conventional (CONV) and permeable support (PS) systems to investigate the impact of PLGA-NP on the absorption of lutein in intestinal cells. In chapter one, we compared the efficacy of lutein absorption in vitro using Caco-2 cells grown in both CONV and PS systems. We further examined the role of the micelle, the physiological vehicle for lutein within the small intestine, on its intestinal absorption in vitro compared to an organic solvent, ethanol, which is safe and consumed by humans. The finding from this study demonstrated that the CONV system displayed a larger efficacy of lutein uptake by Caco-2 cells. Further, in the PS system, micelle components appeared to facilitate more effective intestinal secretion of lutein. These findings suggest that lutein uptake by Caco-2 cells is subject to the influence of culturing system (CONV vs. PS) and delivery vehicle (ethanol vs. micelle). Chapter two examined the impact of PLGA-NP in rats on lutein pharmacokinetics in plasma and distribution in selected tissues as compared to free lutein. We also investigated the effect of nanoencapsulation on the absorption of lutein in intestinal cells compared to a more physiological vehicle, the micelle, using the PS method. In addition, we explored the need of additional micelles for the ultimate absorption of

  9. Luteinizing hormone and human chorionic gonadotropin: origins of difference.

    Science.gov (United States)

    Choi, Janet; Smitz, Johan

    2014-03-01

    Luteinizing hormone (LH) and human chorionic gonadotropin (hCG) are widely recognized for their roles in ovulation and the support of early pregnancy. Aside from the timing of expression, however, the differences between LH and hCG have largely been overlooked in the clinical realm because of their similar molecular structures and shared receptor. With technologic advancements, including the development of highly purified and recombinant gonadotropins, researchers now appreciate that these hormones are not as interchangeable as once believed. Although they bind to a common receptor, emerging evidence suggests that LH and hCG have disparate effects on downstream signaling cascades. Increased understanding of the inherent differences between LH and hCG will foster more effective diagnostic and prognostic assays for use in a variety of clinical contexts and support the individualization of treatment strategies for conditions such as infertility.

  10. Insulin-like growth factor-binding protein-3 promotes transforming growth factor-β1-mediated epithelial-to-mesenchymal transition and motility in transformed human esophageal cells

    OpenAIRE

    Natsuizaka, Mitsuteru; Ohashi, Shinya; Wong, Gabrielle S; Ahmadi, Azal; Kalman, Ross A.; Budo, Daniela; Klein-Szanto, Andres J.; Herlyn, Meenhard; Diehl, J. Alan; Nakagawa, Hiroshi

    2010-01-01

    Insulin-like growth factor-binding protein (IGFBP)-3 is overexpressed frequently in esophageal squamous cell carcinoma. Yet, the role of IGFBP3 in esophageal tumor biology remains to be elucidated. We find that IGFBP3 facilitates transforming growth factor (TGF)-β1-mediated epithelial-to-mesenchymal transition (EMT) in transformed human esophageal epithelial cells, EPC2–hTERT–EGFR–p53R175H. In organotypic 3D culture, a form of human tissue engineering, laser-capture microdissection revealed c...

  11. Low serum levels of free and total insulin-like growth factor I (IGF-I) in patients with anorexia nervosa are not associated with increased IGF-binding protein-3 proteolysis

    DEFF Research Database (Denmark)

    Støving, R K; Flyvbjerg, A; Frystyk, J;

    1999-01-01

    Patients with anorexia nervosa (AN) are GH resistant, with elevated GH levels and low serum levels of total insulin-like growth factor I (IGF-I). IGF-I action is modulated by IGF-binding proteins (IGFBPs), and a variety of catabolic states has been characterized by the presence of increased IGFBP-3...... for the adaption of the GH-IGF-IGFBP axis in AN may be different from other catabolic conditions, because the low levels of free and total IGF-I in AN are not associated with increased IGFBP-3 proteolysis....

  12. The Photobiology of Lutein and Zeaxanthin in the Eye

    OpenAIRE

    Roberts, Joan E.; Jessica Dennison

    2015-01-01

    Lutein and zeaxanthin are antioxidants found in the human retina and macula. Recent clinical trials have determined that age- and diet-related loss of lutein and zeaxanthin enhances phototoxic damage to the human eye and that supplementation of these carotenoids has a protective effect against photoinduced damage to the lens and the retina. Two of the major mechanisms of protection offered by lutein and zeaxanthin against age-related blue light damage are the quenching of singlet oxygen and o...

  13. Abnormal sex chromosome constitution and longitudinal growth: serum levels of insulin-like growth factor (IGF)-I, IGF binding protein-3, luteinizing hormone, and testosterone in 109 males with 47,XXY, 47,XYY, or sex-determining region of the Y chromosome (SRY)-positive 46,XX karyotypes

    DEFF Research Database (Denmark)

    Aksglaede, L.; Skakkebaek, N.E.; Juul, A.

    2008-01-01

    CONTEXT: Growth is a highly complex process regulated by the interaction between sex steroids and the GH IGF-axis. However, other factors such as sex chromosome-related genes play independent roles. AIM: The aim of the study was to evaluate the role of abnormal chromosome constitution for longitu...

  14. Epidermal growth factor suppresses insulin-like growth factor binding protein 3 levels in human papillomavirus type 16-immortalized cervical epithelial cells and thereby potentiates the effects of insulin-like growth factor 1.

    Science.gov (United States)

    Hembree, J R; Agarwal, C; Eckert, R L

    1994-06-15

    Human ectocervical epithelial cells are a primary target for infection by oncogenic papillomaviruses, which are strongly implicated as causative agents in the genesis of cervical cancer. Growth factors have been implicated as agents that stimulate proliferation and enhance the possibility of malignant transformation. In the present study we utilize several human papillomavirus (HPV) type 16-immortalized ectocervical epithelial cell lines to investigate the effects of epidermal growth factor (EGF) and insulin-like growth factor I (IGF-I) on cell proliferation and the production of IGF binding proteins (IGFBPs). ECE16-1 cells, an HPV16-immortalized/nontumorigenic cell line, maintained in defined medium, produce and release high levels of IGFBP-3 (38/42 kDa) as well as smaller amounts of a 24-kDa IGFBP. Supplementation of defined medium with EGF causes a dose-dependent increase in cell growth and a concomitant decrease in the levels of IGFBP-3 released into the culture medium. EGF suppression of IGFBP-3 is maintained even when EGF-stimulated cell growth is suppressed 67% due to the simultaneous presence of 3 ng/ml of TGF beta 1, indicating that EGF suppression of IGFBP-3 levels is independent of EGF effects on cell growth. EGF suppression of IGFBP-3 production is correlated with a reduction in IGFBP-3 mRNA level. In the presence of EGF, the growth response of the cells to ng amounts of IGF-I is significantly enhanced. Moreover, the simultaneous presence of both EGF and IGF-I reduces the level of IGFBP-3 more efficiently than EGF alone. We also observe that the IGFBP-3 level is decreased and the 24-kDa IGFBP level is increased in HPV16-positive tumorigenic versus nontumorigenic cell lines. This is the first report of EGF acting as a positive regulator of IGF-I action via the IGFBPs. On the basis of these findings, we propose that EGF stimulates ECE16-1 cell growth via a dual-action mechanism by (a) stimulating growth directly via the EGF mitogenic pathway and (b

  15. Changes in Macular Pigment Optical Density and Serum Lutein Concentration in Japanese Subjects Taking Two Different Lutein Supplements.

    Directory of Open Access Journals (Sweden)

    Akira Obana

    Full Text Available To investigate macular pigment optical density (MPOD and serum concentration changes of lutein in Japanese subjects participating in a clinical trial in which two formulations of lutein and zeaxanthin supplements with different physiochemical properties are used.Thirty-six healthy volunteers were recruited into this prospective, randomized, parallel-group, double-masked comparative study at a single institute. Two products were used, FloraGLO® (Kemin Japan and XanMax® (Katra Phytochem. The lutein particle size and zeaxanthin concentrations differed between the formulations. The subjects consumed one of the two supplements for a duration of up to 6 months. MPOD levels were measured by resonance Raman spectrometry at baseline and once a month until the end of the study. Serum lutein concentration was measured at baseline, month 3, and month 6. The subjects were also tested for contrast sensitivity, glare sensitivity, visual acuity, and in addition had a focal electroretinogram measured.The mean serum lutein concentrations increased significantly after the first three months, but the mean MPOD levels in either supplement group did not show any statistically significant increase. A detailed analysis, however, revealed three response patterns in both groups for the increase of MPOD levels and serum lutein concentration, i.e. "retinal responders", who had an increase of both MPOD levels and serum lutein concentrations (n = 13, "retinal non-responders", who had only increased serum concentrations and no change in MPOD levels (n = 20, and "retinal and serum non-responders", who had neither MPOD level nor plasma concentration increases (n = 3. The subjects with low MPOD levels at baseline appeared to show increased MPOD levels at the 6 month time point upon lutein supplementation (r = -0.4090, p = 0.0133. Glare sensitivity improved in retinal responders in both supplement groups, while there were no remarkable changes in contrast sensitivity

  16. The study on the role of transcription factor GATA binding protein 3 in familial Alzheimer's disease pathogenesis%转录因子GATA结合蛋白3在家族性阿尔茨海默病发病机制中的作用

    Institute of Scientific and Technical Information of China (English)

    秦伟; 周爱红; 左秀美; 王芬; 程哲; 贾建平

    2011-01-01

    Objective To investigate the mechanisms of decreasing insulin degrading enzyme (IDE) level by mutation V97L in the gene presenilin 1 (PS-1).Methods Transcription factor GATA binding protein 3 (GATA-3) activity was assessed by protein/DNA array and verified by Western blot in SH-SY5Y cells transfected by PS-1 mutation V97L.Results Protein/DNA array and Western blot revealed that there was increased transcript factor activity (5.5 times high) and protein level of GATA-3 in V97L-PS-1 transfected SH-SY5Y cells.Transcription factor GATA-3 can bind to the IDE promoter and negatively control the IDE transcription level.Conclusion PS-1 mutation V97L may regulate the transcription of IDE via GATA-3, and subsequently involve in deposition of Aβ42 and development of Alzheimer's disease.%目的 探讨家族性阿尔茨海默病(Alzheimer's disease,AD)相关的早老素1(presenilin-1,PS-1)V97L突变引起胰岛素降解酶(insulin degrading enzyme,IDE)降低的机制.方法 应用转录因子活性芯片技术检测转录因子活性的差异,再用Western b1ot法验证芯片结果.结果 芯片结合MatInspector软件分析发现,上调了5.5倍的转录因子GATA结合蛋白3(GATA binding protein 3,GATA-3)在IDE启动子上有结合位点,并对IDE起负性调控作用.Westem b1ot也证实稳定转染PS-1 V97L细胞系中GATA-3蛋白表达明显增高.结论 PS-1 V97L突变可能通过上调转录因子GATA-3抑制IDE的表达,影响β-淀粉样蛋白42含量进而参与AD的发生.

  17. Possible degradation/biotransformation of lutein in vitro and in vivo: isolation and structural elucidation of lutein metabolites by HPLC and LC-MS (atmospheric pressure chemical ionization).

    Science.gov (United States)

    Lakshminarayana, Rangaswamy; Aruna, Gorusupudi; Sangeetha, Ravi Kumar; Bhaskar, Narayan; Divakar, Sounder; Baskaran, Vallikannan

    2008-10-01

    Metabolites of lutein are highly concentrated in the human macula and are known to provide protection against age-related macular degeneration. The aim of this investigation was to characterize the in vitro oxidation products of lutein obtained through photo-oxidation and to compare them with biologically transformed dietary lutein in intestine, plasma, liver, and eyes of rats. In vivo studies involved feeding rats a diet devoid of lutein for 2 weeks to induce deficiency. Rats were divided into two equal groups (n=6/group) and received either micellar lutein by gavage for 10 days or diet supplemented with fenugreek leaves as a lutein source for 4 weeks. Lutein metabolites/oxidation products obtained from in vivo and in vitro studies were characterized by HPLC and LC-MS (APCI) techniques to elucidate their structure. The characteristic fragmented ions resulting from photo-oxidation of lutein were identified as 523 (M(+)+H(+)-3CH(3)), 476 (M(+)+H(+)-6CH(3)), and 551 (M(+)+H(+)-H(2)O). In the eyes, the fragmented molecules resulting from lutein were 13-Z lutein, 13'-Z lutein, 13-Z zeaxanthin, all-E zeaxanthin, 9-Z lutein, 9'-Z lutein, and 3'-oxolutein. Epoxycarotenoids were identified in liver and plasma, whereas anhydrolutein was identified in intestine. This study emphasizes the essentiality of dietary lutein to maintain its status in the retina. PMID:18640265

  18. Comparison of lutein bioavailability from vegetables and supplement.

    Science.gov (United States)

    Riso, Patrizia; Brusamolino, Antonella; Ciappellano, Salvatore; Porrini, Marisa

    2003-05-01

    Lutein is a carotenoid present in dark green leafy vegetables and it may be involved in the prevention of several diseases related to oxidative stress. The aim of this study was to evaluate bioavailability of lutein from different food sources (150 g spinach and 200 g broccoli) and a supplement in oil (300 mg VEGEX), all providing about 9 mg lutein. Eight healthy females were instructed to eat a low-carotenoid diet for the period of experimentation. On three different occasions, three weeks apart, volunteers ate the lutein sources together with 10 g olive oil and 40 g bread. Blood samples were collected just before eating, every two hours for 12 hours, and at 24, 32, 56, 80 and 104 hours. Lutein concentration increased significantly after six to eight hours and peaked after 10-12 hours, with the highest concentration reached after VEGEX intake. Lutein concentration remained significantly elevated for up to 80 hours (VEGEX and spinach). On the whole, our results suggest that the intake of one single dose of lutein from different sources is able to bring about a significant plasma response in the short term.

  19. Lutein as protective agent against neonatal oxidative stress

    Directory of Open Access Journals (Sweden)

    Giuseppe Buonocore

    2014-06-01

    Full Text Available Free radicals (FR are important for a correct development of neonatal organs and tissues. However, newborn and fetus have profoundly impaired antioxidant system. In these subjects, oxidative stress (OS may be detrimental by activating deleterious cellular processes. Decreasing FR and restoring oxidative imbalance certainly appear to be beneficial in perinatal period. Among the therapeutic antioxidant approaches in newborns, lutein, a compound belonging to the xanthophyll family of carotenoids, is one of the emerging strategies. Humans cannot synthesize lutein, hence the intake primarily depends on diet. In the neonatal period, fresh, non-processed human milk is the main dietary source of lutein, while infant formula is lacking it. Lutein has antioxidant and anti-inflammatory properties. Lutein supplementation in human newborns during the first days of life has been demonstrated to decrease plasma biomarkers of OS and increase antioxidant capacities. Numerous experimental study have demonstrated that lutein effectively neutralizes oxidants and modulates inflammatory processes, showing particular protective effects on macula and photoreceptors against phototoxicity and oxidative injury. Only few clinical studies evaluated the effectiveness of lutein in reducing preterm and term infant morbidity, reporting no definitive results. The challenge for the future is to better clarify the timing, the optimal dose and the duration of lutein intervention in perinatal period and to verify its impact on infants’ health. Proceedings of the 10th International Workshop on Neonatology · Cagliari (Italy · October 22nd-25th, 2014 · The last ten years, the next ten years in Neonatology Guest Editors: Vassilios Fanos, Michele Mussap, Gavino Faa, Apostolos Papageorgiou

  20. Why lutein is important for the eye and the brain

    Directory of Open Access Journals (Sweden)

    Ramirez Maria

    2016-01-01

    Full Text Available Lutein and zeaxanthin are carotenoids that accumulate in the macula. The macula is a yellow spot near the center of the retina that is responsible of high resolution vision. Macular pigment acts as a natural blue light filter and protects the eye from damage. Macular pigment optical density (MPOD increases with lutein administration and is related to visual function and to the prevention of age-related macular degeneration. MOPD can be measured non-invasively and has been related to better cognitive performance. Moreover, compositional analyses of centenarian brains have shown that lutein is the main carotenoid in the brain although not in plasma, indicating a preferential accumulation in neural tissues, and that carotenoids status is correlated with some functional outcomes. Carotenoids are present in human milk with higher concentration in colostrum than in transitional and mature milk. Formula fed-infants have less plasma lutein concentration than breast fed infants. Analyses of brain from infants who died during the first year of life showed that lutein is also the predominant carotenoid of brain. Studies in non-human primates revealed that carotenoids are determinant in the formation of the retinal epithelia. In vitro studies showed that lutein stimulates the differentiation of human stem cells to neural progenitor cells. All this findings together, mostly the presence of lutein in breast milk, plasma concentration in breast-fed infants vs. formula fed infants, preferential accumulation in the brain and evidences of influence on the retina and the functionality of the brain signal the importance of the role of lutein and zeaxanthin on visual maturation and brain development.

  1. Nutritional and clinical relevance of lutein in human health.

    Science.gov (United States)

    Granado, F; Olmedilla, B; Blanco, I

    2003-09-01

    Lutein is one of the most widely found carotenoids distributed in fruits and vegetables frequently consumed. Its presence in human tissues is entirely of dietary origin. Distribution of lutein among tissues is similar to other carotenoids but, along with zeaxanthin, they are found selectively at the centre of the retina, being usually referred to as macular pigments. Lutein has no provitamin A activity in man but it displays biological activities that have attracted great attention in relation to human health. Epidemiological studies have shown inconsistent associations between high intake or serum levels of lutein and lower risk for developing cardiovascular disease, several types of cancer, cataracts and age-related maculopathy. Also, lutein supplementation has provided both null and positive results on different biomarkers of oxidative stress although it is effective in increasing macular pigment concentration and in improving visual function in some, but not all, subjects with different eye pathologies. Overall, data suggest that whereas serum levels of lutein have, at present, no predictive, diagnostic or prognostic value in clinical practice, its determination may be very helpful in assessing compliance and efficacy of intervention as well as potential toxicity. In addition, available evidence suggests that a serum lutein concentration between 0.6 and 1.05 micromol/l seems to be a safe, dietary achievable and desirable target potentially associated with beneficial impact on visual function and, possibly, on the development of other chronic diseases. The use of lutein as a biomarker of exposure in clinical practice may provide some rationale for assessing its relationship with human health as well as its potential use within the context of evidence-based medicine. PMID:14513828

  2. Several insulin-like growth factor-I analogues and complexes of insulin-like growth factors-I and -II with insulin-like growth factor-binding protein-3 fail to mimic the effect of growth hormone upon lactation in the rat.

    Science.gov (United States)

    Flint, D J; Tonner, E; Beattie, J; Gardner, M

    1994-02-01

    Lactation was suppressed in rats using a combined treatment of bromocriptine (to reduce prolactin concentrations) and a specific antiserum to rat GH administered twice daily for 2 days. When milk production had ceased, as determined by litter weight loss and the absence of milk in the stomachs of pups, attempts were made to reinitiate lactation using prolactin, GH, insulin-like growth factor-I (IGF-I) precomplexed to recombinant human IGF-binding protein-3 (hIGFBP-3) or IGF-I plus IGF-II precomplexed to hIGFBP-3. Despite the fact that all treatments except prolactin led to increases in serum IGFs and IGFBP-3, only prolactin and GH provoked the reinitiation of milk production as determined by increased litter weight gain, milk in the stomach of pups and a significant increase in the weight of the mammary glands. Since the mammary gland has been shown to produce IGFBPs which may inhibit IGF action we also tested three IGF-I analogues, R3-IGF-I, Long-IGF-I and Long-R3-IGF-I. R3-IGF-I has a single amino acid substitution (Glu to Arg) at position 3 whereas Long-IGF-I has a 13 amino acid N-terminal extension. These modifications dramatically reduce the ability of these analogues to bind to IGFBPs although they remain active at the IGF-I receptor. Such IGF analogues would therefore be expected to be active irrespective of the production of inhibitory IGFBPs. However, none was effective in reinitiating lactation, even at doses which have been shown to be biologically effective in terms of nitrogen retention.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7513341

  3. Lutein Inhibits the Migration of Retinal Pigment Epithelial Cells via Cytosolic and Mitochondrial Akt Pathways (Lutein Inhibits RPE Cells Migration

    Directory of Open Access Journals (Sweden)

    Ching-Chieh Su

    2014-08-01

    Full Text Available During the course of proliferative vitreoretinopathy (PVR, the retinal pigment epithelium (RPE cells will de-differentiate, proliferate, and migrate onto the surfaces of the sensory retina. Several studies have shown that platelet-derived growth factor (PDGF can induce migration of RPE cells via an Akt-related pathway. In this study, the effect of lutein on PDGF-BB-induced RPE cells migration was examined using transwell migration assays and Western blot analyses. We found that both phosphorylation of Akt and mitochondrial translocation of Akt in RPE cells induced by PDGF-BB stimulation were suppressed by lutein. Furthermore, the increased migration observed in RPE cells with overexpressed mitochondrial Akt could also be suppressed by lutein. Our results demonstrate that lutein can inhibit PDGF-BB induced RPE cells migration through the inhibition of both cytoplasmic and mitochondrial Akt activation.

  4. Changes in Macular Pigment Optical Density and Serum Lutein Concentration in Japanese Subjects Taking Two Different Lutein Supplements

    OpenAIRE

    Akira Obana; Masaki Tanito; Yuko Gohto; Shigetoshi Okazaki; Werner Gellermann; Bernstein, Paul S

    2015-01-01

    Purpose To investigate macular pigment optical density (MPOD) and serum concentration changes of lutein in Japanese subjects participating in a clinical trial in which two formulations of lutein and zeaxanthin supplements with different physiochemical properties are used. Methods Thirty-six healthy volunteers were recruited into this prospective, randomized, parallel-group, double-masked comparative study at a single institute. Two products were used, FloraGLO® (Kemin Japan) and XanMax® (Katr...

  5. Serum free and total insulin-like growth factor-1, insulin-like growth factor binding protein-1 and insulin-like growth factor binding protein-3 levels in healthy elderly individuals - Relation to self-reported duality of health and disability

    NARCIS (Netherlands)

    Janssen, JAMJL; Stolk, RP; Pols, HAP; Grobbee, DE; Lamberts, SWJ

    1998-01-01

    Background: Little is known about the influence of the free insulin-like growth factor-I/insulin-like growth factor binding protein (IGF-I/IGFBP) system on the quality of health and on disability in the elderly population. Design: In a cross-sectional population based study of 218 healthy elderly su

  6. Expression and Localization of Uncoupling Protein 3 and Heart Fatty Acid-binding Protein in Skeletal Muscle Cells of Nuogu Pig%糯谷猪解耦联蛋白3和心脏型脂肪酸结合蛋白在骨骼肌中的表达和定位

    Institute of Scientific and Technical Information of China (English)

    王阳; 冉雪琴; 王嘉福; 冯诚诚; 胡倩

    2011-01-01

    Uncoupling protein 3 (UCP3) and heart fatty acid-binding protein (H-FABP) are pivotal in the regulation of fat metabolism in skeletal muscle cells. Taking binary crossbreed pig of Large White pig and Landrace as control, the expression and localization of UCP3 and H-FABP genes and proteins are detected in the skeletal muscle cells by reverse transcription polymerase chain reaction (RT-PCR) and histological and immunohistochemistry methods. The results show that both of UCP3 and H-FABP are detected in the cytoplasm of muscle cells from Nuogu pig and crossbreed pig. Compared with crossbreed pig,however, the expressions of UCP3 and H-FABP in Nuogu pig breed are significantly lower based on the scan results of mean optical density (mOD) of positive pellets in the muscle cells. And the content of serum free fatty acids and intramuscular fat (IMF) of skeletal muscle are much higher in Nuogu pig breeds together with larger muscle cells and intracellular spaces. It sounds that the absorption of fatty acids from blood is less because of the lower H-FABP in muscle cells of Nuogu pig. And the production of adenosine triphosphate (ATP) is much more effective in Nuogu pig due to the lower expression of UCP3, which seems to be compensation to the less intake of fatty acids for energy supply in muscle cells of Nuogu pig.As a result, the excessive fatty acids would turn to synthesize triglyceride deposited in fat cells inside of muscle and fat tissue, which results in higher intramuscular fat (IMF) and backfat in Nuogu pig breed.It suggests that both of UCP3 and H-FABP genes and the expression in the muscle cells are contributed to the meat quality and backfat traits in Nuogu pig breed.%为了探索解耦联蛋白3(uncoupling protein 3,UCP3)和心脏型脂肪酸结合蛋白(heart fatty acid-binding protein,H.FABP)对骨骼肌细胞中脂肪代谢的调节作用,采用RT-PCR和免疫组织化学方法,研究了地方猪品种糯谷猪骨骼肌细胞中UCP3和H.FABP基因的表达

  7. The Photobiology of Lutein and Zeaxanthin in the Eye.

    Science.gov (United States)

    Roberts, Joan E; Dennison, Jessica

    2015-01-01

    Lutein and zeaxanthin are antioxidants found in the human retina and macula. Recent clinical trials have determined that age- and diet-related loss of lutein and zeaxanthin enhances phototoxic damage to the human eye and that supplementation of these carotenoids has a protective effect against photoinduced damage to the lens and the retina. Two of the major mechanisms of protection offered by lutein and zeaxanthin against age-related blue light damage are the quenching of singlet oxygen and other reactive oxygen species and the absorption of blue light. Determining the specific reactive intermediate(s) produced by a particular phototoxic ocular chromophore not only defines the mechanism of toxicity but can also later be used as a tool to prevent damage. PMID:26798505

  8. The Photobiology of Lutein and Zeaxanthin in the Eye

    Directory of Open Access Journals (Sweden)

    Joan E. Roberts

    2015-01-01

    Full Text Available Lutein and zeaxanthin are antioxidants found in the human retina and macula. Recent clinical trials have determined that age- and diet-related loss of lutein and zeaxanthin enhances phototoxic damage to the human eye and that supplementation of these carotenoids has a protective effect against photoinduced damage to the lens and the retina. Two of the major mechanisms of protection offered by lutein and zeaxanthin against age-related blue light damage are the quenching of singlet oxygen and other reactive oxygen species and the absorption of blue light. Determining the specific reactive intermediate(s produced by a particular phototoxic ocular chromophore not only defines the mechanism of toxicity but can also later be used as a tool to prevent damage.

  9. Lutein and Zeaxanthin Isomers in Eye Health and Disease.

    Science.gov (United States)

    Mares, Julie

    2016-07-17

    Current evidence suggests lutein and its isomers play important roles in ocular development in utero and throughout the life span, in vision performance in young and later adulthood, and in lowering risk for the development of common age-related eye diseases in older age. These xanthophyll (oxygen-containing) carotenoids are found in a wide variety of vegetables and fruits, and they are present in especially high concentrations in leafy green vegetables. Additionally, egg yolks and human milk appear to be bioavailable sources. The prevalence of lutein, zeaxanthin, and meso-zeaxanthin in supplements is increasing. Setting optimal and safe ranges of intake requires additional research, particularly in pregnant and lactating women. Accumulating evidence about variable interindividual response to dietary intake of these carotenoids, based on genetic or metabolic influences, suggests that there may be subgroups that benefit from higher levels of intake and/or alternate strategies to improve lutein and zeaxanthin status. PMID:27431371

  10. Methylation of insulin-like growth factor binding protein 3 gene in neonates with intrauterine growth restriction%胰岛素样生长因子结合蛋白3在宫内生长受限儿中的甲基化研究

    Institute of Scientific and Technical Information of China (English)

    苏爱玲; 蒋犁; 葛芹玉

    2011-01-01

    Objective To study the role of promoter methylation of insulin-like growth factor binding protein 3 (ICFBP3) in intrauterine growth restriction (IUGR). Methods Fifty neonates with IUCR and 30 healthy neonates were enrolled. The promoter methylation status of 1GFBP3 in peripheral blood was evaluated by methylation-specific PCR (MSP) and high resolution melting (HRM) techniques. Results The complete methylation rate, partial methylation rate and non-methylation rate of IGFBP3 promoter in the IUGR group was 4% (2/50) , 40% (20/50) and 56% (28/50) , respectively. The partial methylation rate and non-methylation rate of IGFBP3 promoter in the control group were 13% (4/30) and 87% (26/30) , respectively. There were significant differences in the promoter methylation rate of IGFBP3 between the two groups ( P < 0. 01 ). Conclusions The promoter methylation of IGFBP3 gene is associated with the pathogenesis of IUGR.%目的 探讨胰岛素样生长因子结合蛋白3(IGFBP3)启动子区甲基化状态在胎儿宫内生长受限(IUGR)中的作用.方法 选取IUGR新生儿50例及正常新生儿30例,应用甲基化特异性PCR(MSP)及高分辨率溶解(HRM)技术检测外周血中IGFBP3基因的甲基化状态.结果 IUGR组中IGFBP3启动子区完全甲基化比例为4%(2/50),部分甲基化比例为40%(20/50),未甲基化比例为56%(28/50);对照组中部分甲基化比例为13%(4/30),未甲基化比例为87%(26/30),两组甲基化率差异有统计学意义(P<0.01).结论 IGFBP3基因启动子区的甲基化程度与IUGR的发生有关.

  11. Antioxidant activity of carotenoid lutein in vitro and in vivo.

    Science.gov (United States)

    Sindhu, Edakkadath R; Preethi, Korengath C; Kuttan, Ramadasan

    2010-08-01

    Carotenoid lutein was evaluated for its antioxidant potential both in vitro and in vivo. Lutein was found to scavenge superoxide radicals, hydroxyl radicals and inhibited in vitro lipid peroxidation. Concentrations needed for 50% inhibition (IC50) were 21, 1.75 and 2.2 microg/mL respectively. It scavenged 2,2-diphenyl-1-picryl hydrazyl (IC50 35 microg/mL) and nitric oxide radicals (IC50 3.8 microg/mL) while 2,2-azobis-3-ethylbenzthiozoline-6-sulfonic acid radicals were inhibited at higher concentration. Ferric reducing power (50%) of lutein was found to be equal 0.3 micromols/mL of FeSO4.7H2O. Its oral administration inhibited superoxide generation in macrophages in vivo by 34.18, 64.32 and 70.22% at doses of 50, 100 and 250 mg/kg body weight. The oral administration of lutein in mice for 1 month significantly increased the activity of catalase, superoxide dismutase, glutathione reductase and glutathione in blood and liver while the activity of glutathione peroxidase and glutathione-S-transferase were found to be increased in the liver tissue. Implication of these results in terms of its role in reducing degenerative diseases is discussed. PMID:21341544

  12. Isolation and purification of lutein from the microalga Chlorella vulgaris by extraction after saponification.

    Science.gov (United States)

    Li, Hua-Bin; Jiang, Yue; Chen, Feng

    2002-02-27

    A simple and efficient method for the isolation and purification of lutein from the microalga Chlorella vulgaris was developed. Crude lutein was obtained by extraction with dichloromethane from the microalga after saponification. Partition values of lutein in the two-phase system of ethanol-water-dichloromethane at different ratios were measured by HPLC so as to assist the determination of an appropriate condition for washing water-soluble impurities in the crude lutein. Partition values of lutein in another two-phase system of ethanol-water-hexane at different ratios were also measured by HPLC for determining the condition for removing fat-soluble impurities. The water-soluble impurities in the crude lutein were removed by washing with 30% aqueous ethanol, and the fat-soluble impurities were removed by extraction with hexane. The final purity of lutein obtained was 90-98%, and the yield was 85-91%.

  13. 非霍奇金淋巴瘤患者血清胰岛素样生长因子-1及其结合蛋白-3表达水平的初步观察%Observation on the expressions of insulin-like growth factor-1 and insulin-like growth factor binding protein-3 in non-Hodgkin's lymphoma

    Institute of Scientific and Technical Information of China (English)

    李康保; 刘国龙; 朱志刚; 朱园; 朱国栋

    2012-01-01

    To investigate the expressions of serum insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) in patients with non-Hodgkin's lymphoma (NHL) and its clinical significance. Methods:Twenty-eight cases with newly diagnosed NHL and 28 cases of healthy volunteers were involved in the study. Serum levels of IGF-1 and IGFBP-3 were determined by the method of chemical luminescence,and ratio of IGF-l/IGFBP-3 was counted. The differences were compared between two groups. Results: Serum levels of IGF-1 and IGFBP-3 were significantly lower in NHL group than those in control group (P 0.05); and there were no differences in serum levels of IGF-1, IGFBP-3 and the ratio of IGF-l/IGFBP-3 among different (ypes of non-Hodgkin's lymphoma ( P > 0. 05 ). Conclusions ; Serum levels of IGF-1 and IGFBP-3 significantly decreased in patients with NHL,and might relate with NHL. The ratio of IGF-l/IGFBP-3 has no obvious correlation with NHL. Serum levels of IGF-1 and IGFBP-3 have no obvious correlation with types of NHL.%目的:探讨非霍奇金淋巴瘤(NHL)患者血清胰岛素样生长因子-1(IGF-1)及其结合蛋白-3(IGFBP-3)表达水平及其临床意义.方法:选择28例诊断初发NHL患者(淋巴瘤组)及28例健康志愿者(对照组),化学发光法测定血清IGF-1及IGFBP-3水平并计算IGF- 1/IGFBP-3值,分析组间的差异.结果:血清IGF-1及IGFBP-3水平淋巴瘤组显著低于正常对照组(均P<0.01);IGF-1/IGFBP-3淋巴瘤组与正常对照组差异无统计学意义(P>0.05);不同亚型的淋巴瘤组的血清IGF-1、IGFBP-3水平及IGF-1/IGFBP-3比值的差异均未达到统计学意义(P>0.05).结论:N HL患者血清IGF-I及IGFBP-3水平明显降低,可能与NHL相关.IGF-1/IGFBP-3比值与NHL无明显相关性,IGF-1及IGFBP-3水平与NHL的分型无明显相关.

  14. Determination of Lutein from Fruit and Vegetables Through an Alkaline Hydrolysis Extraction Method and HPLC Analysis.

    Science.gov (United States)

    Fratianni, Alessandra; Mignogna, Rossella; Niro, Serena; Panfili, Gianfranco

    2015-12-01

    A simple and rapid analytical method for the determination of lutein content, successfully used for cereal matrices, was evaluated in fruit and vegetables. The method involved the determination of lutein after an alkaline hydrolysis of the sample matrix, followed by extraction with solvents and analysis by normal phase HPLC. The optimized method was simple, precise, and accurate and it was characterized by few steps that could prevent loss of lutein and its degradation. The optimized method was used to evaluate the lutein amounts in several fruit and vegetables. Rich sources of lutein were confirmed to be green vegetables such as parsley, spinach, chicory, chard, broccoli, courgette, and peas, even if in a range of variability. Taking into account the suggested reference values these vegetables can be stated as good sources of lutein. PMID:26540023

  15. The role for runt related transcription factor 2 (RUNX2) as a transcriptional repressor in luteinizing granulosa cells.

    Science.gov (United States)

    Park, Eun-Sil; Park, Jiyeon; Franceschi, Renny T; Jo, Misung

    2012-10-15

    Transcription factors induced by the LH surge play a vital role in reprogramming the gene expression in periovulatory follicles. The present study investigated the role of RUNX2 transcription factor in regulating the expression of Runx1, Ptgs2, and Tnfaip6 using cultured granulosa cells isolated from PMSG-primed immature rats. hCG or forskolin+PMA induced the transient increase in Runx1, Ptgs2, and Tnfaip6 expression, while the expression of Runx2 continued to increase until 48 h. The knockdown of the agonist-stimulated Runx2 expression increased Runx1, Ptgs2, and Tnfaip6 expression and PGE(2) levels in luteinizing granulosa cells. Conversely, the over-expression of RUNX2 inhibited the expression of these genes and PGE(2) levels. The mutation of RUNX binding motifs in the Runx1 promoter enhanced transcriptional activity of the Runx1 promoter. The knockdown and overexpression of Runx2 increased and decreased Runx1 promoter activity, respectively. ChIP assays revealed the binding of RUNX2 in the Runx1 and Ptgs2 promoters. Together, these novel findings provide support for the role of RUNX2 in down-regulation of Runx1, Ptgs2, and Tnfaip6 during the late ovulatory period to support proper ovulation and/or luteinization.

  16. Lutein acts via multiple antioxidant pathways in the photo-stressed retina.

    Science.gov (United States)

    Kamoshita, Mamoru; Toda, Eriko; Osada, Hideto; Narimatsu, Toshio; Kobayashi, Saori; Tsubota, Kazuo; Ozawa, Yoko

    2016-01-01

    Lutein slows the progression of age-related macular degeneration (AMD), a leading cause of blindness in ageing societies. However, the underlying mechanisms remain elusive. Here, we evaluated lutein's effects on light-induced AMD-related pathological events. Balb/c mice exposed to light (2000 lux, 3 h) showed tight junction disruption in the retinal pigment epithelium (RPE) at 12 h, as detected by zona occludens-1 immunostaining. Substantial disruption remained 48 h after light exposure in the vehicle-treated group; however, this was ameliorated in the mice treated with intraperitoneal lutein at 12 h, suggesting that lutein promoted tight junction repair. In the photo-stressed RPE and the neighbouring choroid tissue, lutein suppressed reactive oxygen species and increased superoxide dismutase (SOD) activity at 24 h, and produced sustained increases in sod1 and sod2 mRNA levels at 48 h. SOD activity was induced by lutein in an RPE cell line, ARPE19. We also found that lutein suppressed upregulation of macrophage-related markers, f4/80 and mcp-1, in the RPE-choroid tissue at 18 h. In ARPE19, lutein reduced mcp-1 mRNA levels. These findings indicated that lutein promoted tight junction repair and suppressed inflammation in photo-stressed mice, reducing local oxidative stress by direct scavenging and most likely by induction of endogenous antioxidant enzymes. PMID:27444056

  17. Transference of lutein during cheese making, color stability, and sensory acceptance of prato cheese

    Directory of Open Access Journals (Sweden)

    Mirian Tiaki Kaneiwa Kubo

    2013-02-01

    Full Text Available The consumption of lutein is associated with the prevention and reduction of age-related macular degeneration. Its incorporation into Prato cheese as a yellowish food coloring is a valid alternative to increase the daily intake of this compound. However, part of the lutein added may be lost in the whey during the cheese making, or it can be degraded by light during storage, resulting in color changes reducing the sensory acceptance of the cheese. The objectives of this study were to determine the transference of the lutein (dye, added to the milk, in the whey, and cheese, to evaluate the effect of the lutein addition, light exposure, and storage time on the cheese color, and to verify the sensory acceptance of Prato cheese with addition of lutein. The lutein recovery of cheese was 95.25%. Color saturation (chrome increased during storage time resulting in a cheese with more intense color, but there were no changes in the hue of the cheese. Adjusting the amount of lutein added to Prato cheese may lead to greater acceptance. The high recovery of lutein in the cheese and the fact that the hue remained unchanged during storage under light showed that the incorporation of lutein into Prato cheese is feasible from a technical point of view.

  18. Phase II enzyme induction by a carotenoid, lutein, in a PC12D neuronal cell line

    Energy Technology Data Exchange (ETDEWEB)

    Miyake, Seiji [Laboratory of Retinal Cell Biology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582 (Japan); Department of Ophthalmology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582 (Japan); Wakasa Seikatsu Co., Ltd., 134 Chudoujiminami-cho, Shimogyo-ku, Kyoto 600-8813 (Japan); Kobayashi, Saori [Wakasa Seikatsu Co., Ltd., 134 Chudoujiminami-cho, Shimogyo-ku, Kyoto 600-8813 (Japan); Tsubota, Kazuo [Laboratory of Retinal Cell Biology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582 (Japan); Ozawa, Yoko, E-mail: ozawa@a5.keio.jp [Laboratory of Retinal Cell Biology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582 (Japan); Department of Ophthalmology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582 (Japan)

    2014-04-04

    Highlights: • Lutein reduced ROS levels in a PC12D neuronal cell line. • Lutein induced mRNAs of phase II antioxidative enzymes in PC12D neuronal cells. • Lutein increased protein levels of HO-1, SOD2, and NQO-1 in PC12D neuronal cells. • Lutein had no effect on intranuclear Nrf2 levels in PC12D neuronal cells. • Lutein did not activate potential upstream Nrf2 nuclear translocation pathways. - Abstract: The mechanism by which lutein, a carotenoid, acts as an antioxidant in retinal cells is still not fully understood. Here, lutein treatment of a neuronal cell line (PC12D) immediately resulted in reduced intracellular ROS levels, implying that it has a direct role in ROS scavenging. Significantly, lutein treatment also induced phase II antioxidative enzyme expression, probably via a nuclear factor-like 2 (Nrf2) independent pathway. This latter mechanism could explain why lutein acts diversely to protect against oxidative/cytotoxic stress, and why it is physiologically involved in the human neural tissue, such as the retina.

  19. Differentiation between lutein monoester regioisomers and detection of lutein diesters from marigold flowers (Tagetes erecta L.) and several fruits by liquid chromatography-mass spectrometry.

    Science.gov (United States)

    Breithaupt, Dietmar E; Wirt, Ursula; Bamedi, Ameneh

    2002-01-01

    Liquid chromatography-atmospheric pressure chemical ionization mass spectrometry (LC-APCIMS) was employed for the identification of eight lutein monoesters, formed by incomplete enzymatic saponification of lutein diesters of marigold (Tagetes erecta L.) by Candida rugosa lipase. Additionally, the main lutein diesters naturally occurring in marigold oleoresin were chromatographically separated and identified. The LC-MS method allows for characterization of lutein diesters occurring as minor components in several fruits; this was demonstrated by analysis of extracts of cape gooseberry (Physalis peruviana L.), kiwano (Cucumis metuliferus E. Mey. ex Naud.), and pumpkin (Cucurbita pepo L.). The assignment of the regioisomers of lutein monoesters is based on the characteristic fragmentation pattern: the most intense daughter ion generally results from the loss of the substituent (fatty acid or hydroxyl group) bound to the epsilon-ionone ring, yielding an allylic cation. The limit of detection was estimated at 0.5 microg/mL with lutein dimyristate as reference compound. This method provides a useful tool to obtain further insight into the biochemical reactions leading to lutein ester formation in plants. PMID:11754543

  20. Relationship between insulin-like growth factor binding protein-3 and intelligence development of children with congenital hypothyroidism%IGFBP-3与先天性甲状腺功能减低症儿童智力发育的关系

    Institute of Scientific and Technical Information of China (English)

    蒋新液; 古桂雄; 裴晶晶; 于亮; 朱敏敏; 许飞; 陶晓红

    2011-01-01

    Objective: To explore the relationship between insulin - like growth factor binding protein - 3 ( IGFBP - 3 ) and intelligence development of children with congenital hypothyroidism (CH).Methods: Immunoradiometric assay was used to detect the expression level of IGFBP - 3, CDCC and C - WYCSI we re used to determine the levels of intelligence of children aged 2 ~ years old and 3 ~ 7 years old.Results: The intelligence quotients of the two groups were within normal range, but the intelligence quotient in case group was lower than that in control group (P < 0.05).Among the children aged 2 ~ years old, there was no significant difference in expression level of IGFBP - 3 between case group and control group ( P > 0.05 ); among the children aged 3 ~ 7 years old, the expression level of IGFBP - 3 in case group was lower than that in control group (P < 0.05 ).Among the children aged 2 ~ years old, there was no correlation between IGFBP - 3 and intelligence quotient (P > 0.05 ); among the children aged 3 ~ 7 years old, there was a positive correlation between IGFBP - 3 and linguistic IQ, Verbal intelligence quotient (P < 0.05).IGFBP - 3 level was selected as dependent variable, the scores of various tests in C - WYCSI were selected as independent variable, multivariate regression analysis was carried out, among intelligent factors, the first six effect factors of IGFBP -3 level were picture vocabulary, understanding, memory inverse order, maze, visual analysis and reciting orderly.Conclusion: For the children with CH, early diagnosis and timely treatment can avoid disorder of intelligence development, but injury of cognition exists; after early treatment, the serum level of IGFBP - 3 in the children with CH is still lower than that in normal children; the level of IGFBP - 3 is related to development of linguistic IQ in children; CH may induce low expression of IGFBP - 3 and affect the development of intelligence in children.%目的:探讨胰岛

  1. Radioimmunological and clinical studies with luteinizing hormone releasing hormone (LRH)

    International Nuclear Information System (INIS)

    Radioimmunoassay for Luteinizing Hormone Releasing Hormone (LRH) has been established, tested and applied. Optimal conditions for the performance with regards to incubation time, incubation temperature, concentration of antiserum and radiolabelled LRH have been established. The specificity of the LRH immunoassay was investigated. Problems with direct measurement of LRH in plasmas of radioimmunoassay are encountered. The LRH distribution in various tissues of the rat are investigated. By means of a system for continuous monitoring of LH and FSH in women the lowest effective dose of LRH causing a significant release of LH and FSH could be established. (Auth.)

  2. The Relationship between Lutein and Zeaxanthin Status and Body Fat

    OpenAIRE

    Hammond, Billy R.; Lewis, Richard D.; Emily R. Bovier

    2013-01-01

    The objective of this project was to investigate the relationships between total and regional distribution of body fat and tissue lutein (L) and zeaxanthin (Z) status. Healthy men and women (N = 100; average age: 22.5 year, average BMI: 23.4 kg/m2) were evaluated. Total body and regional fat mass were assessed by dual-energy X-ray absorptiometry (Hologic Delphi A). Serum LZ was measured using reverse phase high-performance liquid chromatography, and retinal LZ (referred to as macular pigment ...

  3. Lutein and Age-Related Ocular Disorders in the Older Adult: A Review

    Science.gov (United States)

    Lutein, a carotenoid found in dark green, leafy vegetables, has been implicated as being protective against the acquired ocular diseases, such as cataracts and age-related macular degeneration. In the eye, lutein may act as an antioxidant and as a blue light filter to protect the underlying tissues ...

  4. Optimization of culture media for large-scale lutein production by heterotrophic Chlorella vulgaris.

    Science.gov (United States)

    Jeon, Jin Young; Kwon, Ji-Sue; Kang, Soon Tae; Kim, Bo-Ra; Jung, Yuchul; Han, Jae Gap; Park, Joon Hyun; Hwang, Jae Kwan

    2014-01-01

    Lutein is a carotenoid with a purported role in protecting eyes from oxidative stress, particularly the high-energy photons of blue light. Statistical optimization was performed to growth media that supports a higher production of lutein by heterotrophically cultivated Chlorella vulgaris. The effect of media composition of C. vulgaris on lutein was examined using fractional factorial design (FFD) and central composite design (CCD). The results indicated that the presence of magnesium sulfate, EDTA-2Na, and trace metal solution significantly affected lutein production. The optimum concentrations for lutein production were found to be 0.34 g/L, 0.06 g/L, and 0.4 mL/L for MgSO4 ·7H2 O, EDTA-2Na, and trace metal solution, respectively. These values were validated using a 5-L jar fermenter. Lutein concentration was increased by almost 80% (139.64 ± 12.88 mg/L to 252.75 ± 12.92 mg/L) after 4 days. Moreover, the lutein concentration was not reduced as the cultivation was scaled up to 25,000 L (260.55 ± 3.23 mg/L) and 240,000 L (263.13 ± 2.72 mg/L). These observations suggest C. vulgaris as a potential lutein source. PMID:24550199

  5. Lutein acts via multiple antioxidant pathways in the photo-stressed retina

    Science.gov (United States)

    Kamoshita, Mamoru; Toda, Eriko; Osada, Hideto; Narimatsu, Toshio; Kobayashi, Saori; Tsubota, Kazuo; Ozawa, Yoko

    2016-01-01

    Lutein slows the progression of age-related macular degeneration (AMD), a leading cause of blindness in ageing societies. However, the underlying mechanisms remain elusive. Here, we evaluated lutein’s effects on light-induced AMD-related pathological events. Balb/c mice exposed to light (2000 lux, 3 h) showed tight junction disruption in the retinal pigment epithelium (RPE) at 12 h, as detected by zona occludens-1 immunostaining. Substantial disruption remained 48 h after light exposure in the vehicle-treated group; however, this was ameliorated in the mice treated with intraperitoneal lutein at 12 h, suggesting that lutein promoted tight junction repair. In the photo-stressed RPE and the neighbouring choroid tissue, lutein suppressed reactive oxygen species and increased superoxide dismutase (SOD) activity at 24 h, and produced sustained increases in sod1 and sod2 mRNA levels at 48 h. SOD activity was induced by lutein in an RPE cell line, ARPE19. We also found that lutein suppressed upregulation of macrophage-related markers, f4/80 and mcp-1, in the RPE-choroid tissue at 18 h. In ARPE19, lutein reduced mcp-1 mRNA levels. These findings indicated that lutein promoted tight junction repair and suppressed inflammation in photo-stressed mice, reducing local oxidative stress by direct scavenging and most likely by induction of endogenous antioxidant enzymes. PMID:27444056

  6. Ultrasound assisted extraction in quantifying lutein from chicken liver using high-performance liquid chromatography.

    Science.gov (United States)

    Sun, Ting; Xu, Zhimin; Godber, J Samuel

    2006-01-01

    Four sample preparation methods, (1) solvent (SOL), (2) saponification and solvent (SP), (3) ultrasound assisted solvent (UA), and (4) saponification and ultrasound assisted solvent (SP-UA), were used for quantifying lutein in chicken liver samples by HPLC. The lutein concentrations obtained by using SOL, UA, SP, and SP-UA were significantly different with values from 10.4 microg/g (UA) to undetected (SOL). Efficiency of the four different methods for extracting lutein from high to low were the UA, SP, SP-UA, and SOL method. The measured value of lutein in the liver sample using the UA method was approximately two and three times higher than that obtained from the SP and SP-UA method, respectively. The methods with saponification significantly affected the stabilities of lutein in liver samples. The lutein concentration measured with the solvent only method was either much lower than any of the other extraction methods or undetectable. This indicated that little lutein in those samples was in a form that could be extracted directly by solvent. Compared with the saponification method, the ultrasound assisted solvent method could effectively extract lutein from sample matrix and thus avoid chemical degradation reactions, which would be especially important for complex biological tissue such as liver.

  7. Production, extraction and stabilization of lutein from microalga Chlorella sorokiniana MB-1.

    Science.gov (United States)

    Chen, Chun-Yen; Jesisca; Hsieh, Chienyan; Lee, Duu-Jong; Chang, Chien-Hsiang; Chang, Jo-Shu

    2016-01-01

    The efficiencies of extraction and preservation of lutein from microalgae are critical for the success of its commercialization. In this study, lutein was produced by Chlorella sorokiniana MB-1 via semi-batch mixotrophic cultivation. The microalgal biomass with a lutein content of 5.21mg/g was pretreated by bead-beating and high pressure cell disruption methods, and the lutein content was harvested by a reduced pressure extraction method. The effect of pretreatment, pressure, solvent type, extraction time and temperature on lutein recovery was investigated. Using high pressure pretreatment followed by extraction with tetrahydrofuran (THF) as solvent resulted in high lutein recovery efficiencies of 87.0% (20min) and 99.5% (40min) at 850mbar and 25°C. In contrast, using ethanol as the solvent, 86.2% lutein recovery was achieved under 450mbar, 35°C and 40min extraction. The extracted lutein was stabilized in olive oil or sunflower oil with half-lives of 53.1 and 63.8days, respectively.

  8. Antioxidant properties of lutein contribute to the protection against lipopolysaccharide-induced uveitis in mice

    Directory of Open Access Journals (Sweden)

    Yao Xin-Sheng

    2011-10-01

    Full Text Available Abstract Background Lutein is an important eye-protective nutrient. This study investigates the protective effects and mechanisms of lutein on lipopolysaccharides (LPS-induced uveitis in mice. Methods Lutein, suspended in drinking water at a final concentration of 12.5 and 25 mg/mL, was administered to mice at 0.1 mL/10 g body weight for five consecutive days. Control and model group received drinking water only. Uveitis was induced by injecting LPS (100 mg per mouse into the footpad in the model and lutein groups on day 5 after the last drug administration. Eyes of the mice were collected 24 hours after the LPS injection for the detection of indicators using commercial kits and reverse transcription-polymerase chain reaction. Results LPS-induced uveitis was confirmed by significant pathological damage and increased the nitric oxide level in eye tissue of BALB/C mice 24 hours after the footpad injection. The elevated nitric oxide level was significantly reduced by oral administration of lutein (125 and 500 mg/kg/d for five days before LPS injection. Moreover, lutein decreased the malondialdehyde content, increased the oxygen radical absorbance capacity level, glutathione, the vitamin C contents and total superoxide dismutase (SOD and glutathione peroxidase (GPx activities. Lutein further increased expressions of copper-zinc SOD, manganese SOD and GPx mRNA. Conclusion The antioxidant properties of lutein contribute to the protection against LPS-induced uveitis, partially through the intervention of inflammation process.

  9. Exploratory metabolomic analyses reveal compounds correlated with lutein concentration in frontal cortex, hippocampus, and occipital cortex of human infant brain

    Science.gov (United States)

    Lutein is a dietary carotenoid well known for its role as an antioxidant in the macula and recent reports implicate a role for lutein in cognitive function. Lutein is the dominant carotenoid in both pediatric and geriatric brain tissue. In addition, cognitive function in older adults correlated with...

  10. Lutein, zeaxanthin, and meso-zeaxanthin: The basic and clinical science underlying carotenoid-based nutritional interventions against ocular disease.

    Science.gov (United States)

    Bernstein, Paul S; Li, Binxing; Vachali, Preejith P; Gorusupudi, Aruna; Shyam, Rajalekshmy; Henriksen, Bradley S; Nolan, John M

    2016-01-01

    The human macula uniquely concentrates three carotenoids: lutein, zeaxanthin, and meso-zeaxanthin. Lutein and zeaxanthin must be obtained from dietary sources such as green leafy vegetables and orange and yellow fruits and vegetables, while meso-zeaxanthin is rarely found in diet and is believed to be formed at the macula by metabolic transformations of ingested carotenoids. Epidemiological studies and large-scale clinical trials such as AREDS2 have brought attention to the potential ocular health and functional benefits of these three xanthophyll carotenoids consumed through the diet or supplements, but the basic science and clinical research underlying recommendations for nutritional interventions against age-related macular degeneration and other eye diseases are underappreciated by clinicians and vision researchers alike. In this review article, we first examine the chemistry, biochemistry, biophysics, and physiology of these yellow pigments that are specifically concentrated in the macula lutea through the means of high-affinity binding proteins and specialized transport and metabolic proteins where they play important roles as short-wavelength (blue) light-absorbers and localized, efficient antioxidants in a region at high risk for light-induced oxidative stress. Next, we turn to clinical evidence supporting functional benefits of these carotenoids in normal eyes and for their potential protective actions against ocular disease from infancy to old age. PMID:26541886

  11. Establishment and validation of a model for non-luteinized human mural granulosa cell culture.

    Science.gov (United States)

    Ophir, L; Yung, Y; Maman, E; Rubinstein, N; Yerushalmi, G M; Haas, J; Barzilay, E; Hourvitz, A

    2014-03-25

    Cell culture techniques of human mural granulosa cells (MGCs) serve as a major in vitro tool. However, the use of luteinized MGCs has major limitations due to their luteinized state. Our aim was to establish a standardized protocol for the culture of MGCs as a model for different stages of folliculogenesis. We showed that early-non-luteinized, preovulatory-non-luteinized and luteal-MGCs have distinct gene expression pattern. After 4 days of incubation of luteinized-MGCs, ovulatory genes mRNA's achieve expression levels similar to the early non-luteinized follicles. FSH stimulation for 48 h of these 4 days cultured MGCs showed ovulatory genes mRNA's expression similar to the pre-ovulatory non-luteinized follicles. These FSH-stimulated cells responded to hCG stimulation in a pattern similar to the response of pre-ovulatory follicles. This novel model may provide a standardized research tool for delineation of the molecular processes occurring during the latter stages of follicular development in the human ovary.

  12. Radioimmunoassay of bovine, ovine and porcine luteinizing hormone with a monoclonal antibody and a human tracer

    International Nuclear Information System (INIS)

    A radioimmunoassay for bovine (bLH), ovine (oLH) and porcine (pLH) luteinizing hormone was developed using a human 125ILH tracer from a commercial kit and a monoclonal antibody (518B7) specific for LH but with low species specificity. Standard curves demonstrated similar binding kinetics when bLH, oLH and pLH were incubated with tracer and antibody for 2 h at room temperature. A 30-min delay in the addition of the tracer gave sufficient sensitivity when analysing pLH. Separation of antibody-bound LH from free hormone was achieved by using second antibody-coated micro Sepharose beads. The assay was validated and the performance compared with that of an RIA currently in use for determination of bLH (coefficient of correlation: 0.99 and 0.98). Regardless of the standards used, intra-assay coefficients of variation were <10% for LH concentrations exceeding 1 μg/L. The inter-assay coefficients of variation were <15%. The assay was used for clinical evaluation demonstrating the pre-ovulatory LH surge in two cyclic cows, LH pulsatility in an oophorectomized ewe and LH response to GnRH injection in a boar. (au) (7 refs.)

  13. Enhancement of Lutein Production in Chlorella sorokiniana (Chorophyta by Improvement of Culture Conditions and Random Mutagenesis

    Directory of Open Access Journals (Sweden)

    Maria Angeles Vargas

    2011-09-01

    Full Text Available Chlorella sorokiniana has been selected for lutein production, after a screening of thirteen species of microalgae, since it showed both a high content in this carotenoid and a high growth rate. The effects of several nutritional and environmental factors on cell growth and lutein accumulation have been studied. Maximal specific growth rate and lutein content were attained at 690 µmol photons m−2 s−1, 28 °C, 2 mM NaCl, 40 mM nitrate and under mixotrophic conditions. In general, optimal conditions for the growth of this strain also lead to maximal lutein productivity. High lutein yielding mutants of C. sorokiniana have been obtained by random mutagenesis, using N-methyl-N′-nitro-nitrosoguanidine (MNNG as a mutagen and selecting mutants by their resistance to the inhibitors of the carotenogenic pathway nicotine and norflurazon. Among the mutants resistant to the herbicides, those exhibiting both high content in lutein and high growth rate were chosen. Several mutants exhibited higher contents in this carotenoid than the wild type, showing, in addition, either a similar or higher growth rate than the latter strain. The mutant MR-16 exhibited a 2.0-fold higher volumetric lutein content than that of the wild type, attaining values of 42.0 mg L−1 and mutants DMR-5 and DMR-8 attained a lutein cellular content of 7.0 mg g−1 dry weight. The high lutein yield exhibited by C. sorokiniana makes this microalga an excellent candidate for the production of this commercially interesting pigment.

  14. Elevation of lutein content in tomato: a biochemical tug-of-war between lycopene cyclases.

    Science.gov (United States)

    Giorio, Giovanni; Yildirim, Arzu; Stigliani, Adriana Lucia; D'Ambrosio, Caterina

    2013-11-01

    Lutein is becoming increasingly important in preventive medicine due to its possible role in maintaining good vision and in preventing age-related maculopathy. Average daily lutein intake in developed countries is often below suggested daily consumption levels, and lutein supplementation could be beneficial. Lutein is also valuable in the food and feed industries and is emerging in nutraceutical and pharmaceutical markets. Currently, lutein is obtained at high cost from marigold petals, and synthesis alternatives are thus desirable. Tomato constitutes a promising starting system for production as it naturally accumulates high levels of lycopene. To develop tomato for lutein synthesis, the tomato Red Setter cultivar was transformed with the tomato lycopene ε-cyclase-encoding gene under the control of a constitutive promoter, and the HighDelta (HD) line, characterised by elevated lutein and δ-carotene content in ripe fruits, was selected. HD was crossed to the transgenic HC line and to RS(B) with the aim of converting all residual fruit δ-carotene to lutein. Fruits of both crosses were enriched in lutein and presented unusual carotenoid profiles. The unique genetic background of the crosses used in this study permitted an unprecedented analysis of the role and regulation of the lycopene cyclase enzymes in tomato. A new defined biochemical index, the relative cyclase activity ratio, was used to discern post-transcriptional regulation of cyclases, and will help in the study of carotenoid biosynthesis in photosynthetic plant species and particularly in those, like tomato, that have been domesticated for the production of food, feed or useful by-products. PMID:24141052

  15. Synthesis and in vitro anti-cancer evaluation of luteinizing hormone-releasing hormone-conjugated peptide.

    Science.gov (United States)

    Deng, Xin; Qiu, Qianqian; Ma, Ke; Huang, Wenlong; Qian, Hai

    2015-11-01

    Luteinizing hormone-releasing hormone (LHRH) is a decapeptide hormone released from the hypothalamus and shows high affinity binding to the LHRH receptors. It is reported that several cancer cells also express LHRH receptors such as breast, ovarian, prostatic, bladder and others. In this study, we linked B1, an anti-cancer peptide, to LHRH and its analogs to improve the activity against cancer cells with LHRH receptor. Biological evaluation revealed that TB1, the peptide contains triptorelin sequence, present favorable anti-cancer activity as well as plasma stability. Further investigations disclosed that TB1 trigger apoptosis by activating the mitochondria-cytochrome c-caspase apoptotic pathway, it also exhibited the anti-migratory effect on cancer cells. PMID:26058357

  16. Management of Ocular Diseases Using Lutein and Zeaxanthin: What Have We Learned from Experimental Animal Studies?

    Directory of Open Access Journals (Sweden)

    Chunyan Xue

    2015-01-01

    Full Text Available Zeaxanthin and lutein are two carotenoid pigments that concentrated in the retina, especially in the macula. The effects of lutein and zeaxanthin on the prevention and treatment of various eye diseases, including age-related macular degeneration, diabetic retinopathy and cataract, ischemic/hypoxia induced retinopathy, light damage of the retina, retinitis pigmentosa, retinal detachment, and uveitis, have been studied in different experimental animal models. In these animal models, lutein and zeaxanthin have been reported to have beneficial effects in protecting ocular tissues and cells (especially the retinal neurons against damage caused by different etiological factors. The mechanisms responsible for these effects of lutein and zeaxanthin include prevention of phototoxic damage by absorption of blue light, reduction of oxidative stress through antioxidant activity and free radical scavenging, and their anti-inflammatory and antiangiogenic properties. The results of these experimental animal studies may provide new preventive and therapeutic procedures for clinical management of various vision-threatening diseases.

  17. Transference of lutein during cheese making, color stability, and sensory acceptance of prato cheese

    OpenAIRE

    Mirian Tiaki Kaneiwa Kubo; Diogo Maus; Ana Augusta Odorissi Xavier; Adriana Zerlotti Mercadante; Walkiria Hanada Viotto

    2013-01-01

    The consumption of lutein is associated with the prevention and reduction of age-related macular degeneration. Its incorporation into Prato cheese as a yellowish food coloring is a valid alternative to increase the daily intake of this compound. However, part of the lutein added may be lost in the whey during the cheese making, or it can be degraded by light during storage, resulting in color changes reducing the sensory acceptance of the cheese. The objectives of this study were to determine...

  18. Enhanced production of lutein in heterotrophic Chlorella protothecoides by oxidative stress

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    The fast growing unicellular green microalgae Chlorella protothecoides has attracted interest as a promising organism for commercial production of a high-value carotenoid, lutein, by heterotrophic fermentation. Effects of two oxidant-forming reactive oxygen species (ROS) on the biomass concen-tration, and yield and content of lutein in batch culture of heterotrophic Chlorella protothecoides were investigated in this study. The addition of 0.1 mmol/L H2O2 and 0.01 mmol/L NaClO plus 0.5 mmol/L Fe2+ to the culture led to the generation of ·OH and enhanced the lutein content from 1.75 to 1.90 and 1.95 mg/g, respectively. The lutein content further increased to 1.98 mg/g when 0.01 mmol/L H2O2 and 0.5 mmol/L NaClO were added to generate 1O2. The maximum yield of lutein (28.5, 29.8 and 31.4 mg/L) and a high biomass concentration (15.0, 15.3 and 15.9 g/L) were also achieved through the above treatments. The results indicated that 1O2 could promote lutein formation and enhance lutein production in hetero-trophic Chlorella protothecoides. Moreover, 1O2 produced from the reaction of H2O2 and NaClO was more effective in enhancing lutein production and reducing biomass loss than ·OH from the reaction of H2O2 or NaClO plus Fe2+.

  19. Endogenous opiates modulate the pulsatile secretion of biologically active luteinizing hormone in man.

    OpenAIRE

    Veldhuis, J D; Rogol, A D; Johnson, M. L.

    1983-01-01

    We studied the secretion of physiological pools of immunoreactive and biologically active luteinizing hormone in response to endogenous pulses of gonadotropin-releasing hormone (GNRH) in eugonadal men. Concentrations of immunoactive and bioactive luteinizing hormone (LH) were determined in blood drawn at 20-min intervals for 8 h in eight normal men under two conditions: (a) after placebo, in order to evaluate spontaneous LH pulsations in the basal state, and (b) after administration of the op...

  20. Enhanced production of lutein in heterotrophic Chlorella protothecoides by oxidative stress

    Institute of Scientific and Technical Information of China (English)

    WEI Dong; CHEN Feng; CHEN Gu; ZHANG XueWu; LIU LongJun; ZHANG Hao

    2008-01-01

    The fast growing unicellular green microalgae Chlorella protothecoides has attracted interest as a promising organism for commercial production of a high-value carotenoid, lutein, by heterotrophic fermentation. Effects of two oxidant-forming reactive oxygen species (ROS) on the biomass concentration, and yield and content of lutein in batch culture of heterotrophic Chlorella protothecoides were investigated in this study. The addition of 0.1 mmol/L H2O2 and 0.01 mmol/L NaClO plus 0.5 mmol/L Fe2+ to the culture led to the generation of OH and enhanced the lutein content from 1.75 to 1.90 and 1.95 mg/g, respectively. The lutein content further increased to 1.98 mg/g when 0.01 mmol/L H2O2 and 0.5 mmol/L NaClO were added to generate 1O2. The maximum yield of lutein (28.5, 29.8 and 31.4 mg/L) and a high biomass concentration (15.0, 15.3 and 15.9 g/L) were also achieved through the above treatments. The results indicated that 1O2 could promote lutein formation and enhance lutein production in heterotrophic Chlorella protothecoides. Moreover, 1O2 produced from the reaction of H2O2 and NaClO was more effective in enhancing lutein production and reducing biomass loss than OH from the reaction of H2O2 or NaClO plus Fe2+.

  1. Extraction of lutein from Marigold flower petals - Experimental kinetics and modelling

    OpenAIRE

    Hojnik, Maša; Škerget, Mojca; Knez, Željko

    2012-01-01

    The extraction kinetics behaviour of lutein from Marigold flower petals and simultaneous alkali hydrolysis has been studied. Extraction was carried out by varying following operating conditions: type of organic solvent, temperature, ratio liquid: material, concentration of alkali solution, and particle size of plant material. Experimental extraction curves were analysed with a mathematical model derived from Fick's second law. The extraction of lutein appeared to be governed by slow and fast ...

  2. Solitary luteinized follicle cyst of pregnancy complicated with persistent postpartum vaginal bleeding: case report

    Institute of Scientific and Technical Information of China (English)

    ZHANG Song-ying; HUANG He-feng; TONG Xiao-mei

    2007-01-01

    @@ Solitary luteinized follicle cyst, a rare cause of ovarian enlargement during pregnancy and puerperium, is a self-limited disease that can regress spontaneously after labor. The complications of the disease include ovarian torsion, intracystic hemorrhage, and rupture; endocrine disturbances have not been reported.1-4 Here we report a case of solitary luteinized follicle cyst of pregnancy,which required surgical intervention owing to persistent postpartum vaginal bleeding.

  3. Exploratory Metabolomic Analyses Reveal Compounds Correlated with Lutein Concentration in Frontal Cortex, Hippocampus, and Occipital Cortex of Human Infant Brain.

    Directory of Open Access Journals (Sweden)

    Jacqueline C Lieblein-Boff

    Full Text Available Lutein is a dietary carotenoid well known for its role as an antioxidant in the macula, and recent reports implicate a role for lutein in cognitive function. Lutein is the dominant carotenoid in both pediatric and geriatric brain tissue. In addition, cognitive function in older adults correlated with macular and postmortem brain lutein concentrations. Furthermore, lutein was found to preferentially accumulate in the infant brain in comparison to other carotenoids that are predominant in diet. While lutein is consistently related to cognitive function, the mechanisms by which lutein may influence cognition are not clear. In an effort to identify potential mechanisms through which lutein might influence neurodevelopment, an exploratory study relating metabolite signatures and lutein was completed. Post-mortem metabolomic analyses were performed on human infant brain tissues in three regions important for learning and memory: the frontal cortex, hippocampus, and occipital cortex. Metabolomic profiles were compared to lutein concentration, and correlations were identified and reported here. A total of 1276 correlations were carried out across all brain regions. Of 427 metabolites analyzed, 257 were metabolites of known identity. Unidentified metabolite correlations (510 were excluded. In addition, moderate correlations with xenobiotic relationships (2 or those driven by single outliers (3 were excluded from further study. Lutein concentrations correlated with lipid pathway metabolites, energy pathway metabolites, brain osmolytes, amino acid neurotransmitters, and the antioxidant homocarnosine. These correlations were often brain region-specific. Revealing relationships between lutein and metabolic pathways may help identify potential candidates on which to complete further analyses and may shed light on important roles of lutein in the human brain during development.

  4. Ultrasound-Enhanced Subcritical CO2 Extraction of Lutein from Chlorella pyrenoidosa.

    Science.gov (United States)

    Fan, Xiao-Dan; Hou, Yan; Huang, Xing-Xin; Qiu, Tai-Qiu; Jiang, Jian-Guo

    2015-05-13

    Lutein is an important pigment of Chlorella pyrenoidosa with many beneficial functions in human health. The main purpose of this study was to extract lutein from C. pyrenoidosa using ultrasound-enhanced subcritical CO2 extraction (USCCE). Effects of operating conditions on the extraction, including extraction pretreatment, temperature, pressure, time, CO2 flow rate, and ultrasonic power, were investigated, and an orthogonal experiment was designed to study the effects of extraction pressure, temperature, cosolvent amount, and time on the extraction yields. The USCCE method was compared with other extraction methods in terms of the yields of lutein and the microstructure of C. pyrenoidosa powder by scanning electron microscopy. A maximal extraction yield of 124.01 mg lutein/100 g crude material was achieved under optimal conditions of extraction temperature at 27 °C, extraction pressure at 21 MPa, cosolvent amount at 1.5 mL/g ethanol, and ultrasound power at 1000 W. Compared to other methods, USCCE could significantly increase the lutein extraction yield at lower extraction temperature and pressure. Furthermore, the kinetic models of USCCE and subcritical CO2 extraction (SCCE) of lutein from C. pyrenoidosa were set as E = 130.64 × (1 - e(-0.6599t)) and E = 101.82 × (1 - e(-0.5683t)), respectively. The differences of parameters in the kinetic models indicate that ultrasound was able to enhance the extraction process of SCCE.

  5. Dietary effects of lutein-fortified chlorella on milk components of Holstein cows.

    Science.gov (United States)

    Jeon, Jin-Young; Park, Keun-Kyu; Lee, Kyung-Woo; Jang, Seung-Wan; Moon, Byung-Hern; An, Byoung-Ki

    2016-01-01

    This study was conducted to investigate the dietary effect of conventional or lutein-fortified chlorella on milk production and lutein incorporation in milk. Fifteen Holstein cows in mid-lactation were used in a 3 × 3 Latin square design each with a 21-day period. Cows were top-dressed daily with 30 g of conventional or lutein-fortified chlorella for 3 weeks. Cows without chlorella served as the control. The feed intake and milk yield were not affected by dietary treatments. The concentrations of milk protein and solids non-fat in groups fed diets containing both conventional and lutein-fortified chlorella were significantly higher than those of the control group (P chlorella as compared with those of conventional chlorella and control, respectively (P chlorella has positive effects on milk components and the use of lutein-fortified chlorella in a dairy diet is effective in the production of milk enriched with lutein. PMID:27386352

  6. 重组人生长激素对特发性矮小患儿症血清胰岛素样生长因子1与胰岛素样生长因子结合蛋白3水平的影响%Effect of recombinant human growth hormone on serum levels of insulin like growth factor 1 and insulin-like growth factor binding protein 3 in children with idiopathic short stature

    Institute of Scientific and Technical Information of China (English)

    干冬梅; 石小军

    2015-01-01

    目的:探讨重组人生长激素对特发性矮小症患儿血清胰岛素样生长因子1(insulin-like growth factor-1,IGF-1)与胰岛素样生长因子结合蛋白3(insulin-like growth factor binding protein-3,IGFBP-3)水平的影响。方法收集宁波市妇女儿童医院儿5科收治的特发性矮小症患儿48例,随机分为对照组和实验组,每组各24例,对照组患儿给予营养治疗,实验组在对照组基础上给予重组人生长激素治疗,均治疗12个月。治疗结束后,对所有患儿的血清胰岛素样生长因子1、胰岛素样生长因子结合蛋白3水平及身高进行检测。结果与对照组治疗后比较,实验组患儿的血清IGF-1水平较高( P<0.05);实验组患儿的血清IGFBP-3水平较高( P<0.05);实验组患儿的身高较高(P<0.05)。结论重组人生长激素能够显著提高特发性矮小症患儿血清IGF-1、IGFBP-3水平,促进患儿生长,对临床有指导意义。%Objective To investigate the effect of recombinant human growth hormone on serum levels of insulin like growth factor 1(IGF-1) and insulin-like growth factor binding protein 3(IGFBP-3)in children with short stature.Methods 48 children were diagnosed with idiopathic short stature were collected.All children were randomly divided into control group and experimental group ,24 cases in each group.Children in control group received nutritional therapy, children in experimental group were given recombinant human growth hormone on the basis of control group treatment, both group were treated for 12 month.After the treatment, the serum levels of IGF-1,IGFBP-3 and the height were detected in all children.Results Compared with control group post-treatment,,the serum level of IGF-1 was higher in experimental group ( P<0.05 );the serum level of IGFBP-3 was higher in experimental group ( P<0.05 );the height was higher in experimental group ( P<0.05 ) .Conclusion

  7. The Relationship between Lutein and Zeaxanthin Status and Body Fat

    Directory of Open Access Journals (Sweden)

    Billy R. Hammond

    2013-03-01

    Full Text Available The objective of this project was to investigate the relationships between total and regional distribution of body fat and tissue lutein (L and zeaxanthin (Z status. Healthy men and women (N = 100; average age: 22.5 year, average BMI: 23.4 kg/m2 were evaluated. Total body and regional fat mass were assessed by dual-energy X-ray absorptiometry (Hologic Delphi A. Serum LZ was measured using reverse phase high-performance liquid chromatography, and retinal LZ (referred to as macular pigment optical density; MPOD was measured using heterochromatic flicker photometry. Body fat percentage (total and regional was inversely related to MPOD (p < 0.01 but no significant relationship was found for serum LZ. Higher body fat percentage, even within relatively healthy limits, is associated with lower tissue LZ status. The results indicate that adiposity may affect the nutritional state of the retina. Such links may be one of the reasons that obesity promotes age-related degenerative conditions of the retina.

  8. Substantial expression of luteinizing hormone-releasing hormone (LHRH) receptor type I in human uveal melanoma

    Science.gov (United States)

    Schally, Andrew V.; Block, Norman L; Dezso, Balazs; Olah, Gabor; Rozsa, Bernadett; Fodor, Klara; Buglyo, Armin; Gardi, Janos; Berta, Andras; Halmos, Gabor

    2013-01-01

    Uveal melanoma is the most common primary intraocular malignancy in adults, with a very high mortality rate due to frequent liver metastases. Consequently, the therapy of uveal melanoma remains a major clinical challenge and new treatment approaches are needed. For improving diagnosis and designing a rational and effective therapy, it is essential to elucidate molecular characteristics of this malignancy. The aim of this study therefore was to evaluate as a potential therapeutic target the expression of luteinizing hormone-releasing hormone (LHRH) receptor in human uveal melanoma. The expression of LHRH ligand and LHRH receptor transcript forms was studied in 39 human uveal melanoma specimens by RT-PCR using gene specific primers. The binding charachteristics of receptors for LHRH on 10 samples were determined by ligand competition assays. The presence of LHRH receptor protein was further evaluated by immunohistochemistry. The expression of mRNA for type I LHRH receptor was detected in 18 of 39 (46%) of tissue specimens. mRNA for LHRH-I ligand could be detected in 27 of 39 (69%) of the samples. Seven of 10 samples investigated showed high affinity LHRH-I receptors. The specific presence of full length LHRH receptor protein was further confirmed by immunohistochemistry. A high percentage of uveal melanomas express mRNA and protein for type-I LHRH receptors. Our results support the merit of further investigation of LHRH receptors in human ophthalmological tumors. Since diverse analogs of LHRH are in clinical trials or are already used for the treatment of various cancers, these analogs could be considered for the LHRH receptor-based treatment of uveal melanoma. PMID:24077773

  9. Optimization by response surface methodology of lutein recovery from paprika leaves using accelerated solvent extraction.

    Science.gov (United States)

    Kang, Jae-Hyun; Kim, Suna; Moon, BoKyung

    2016-08-15

    In this study, we used response surface methodology (RSM) to optimize the extraction conditions for recovering lutein from paprika leaves using accelerated solvent extraction (ASE). The lutein content was quantitatively analyzed using a UPLC equipped with a BEH C18 column. A central composite design (CCD) was employed for experimental design to obtain the optimized combination of extraction temperature (°C), static time (min), and solvent (EtOH, %). The experimental data obtained from a twenty sample set were fitted to a second-order polynomial equation using multiple regression analysis. The adjusted coefficient of determination (R(2)) for the lutein extraction model was 0.9518, and the probability value (p=0.0000) demonstrated a high significance for the regression model. The optimum extraction conditions for lutein were temperature: 93.26°C, static time: 5 min, and solvent: 79.63% EtOH. Under these conditions, the predicted extraction yield of lutein was 232.60 μg/g. PMID:27006224

  10. Dietary Sources of Lutein and Zeaxanthin Carotenoids and Their Role in Eye Health

    Directory of Open Access Journals (Sweden)

    Rashida Ali

    2013-04-01

    Full Text Available The eye is a major sensory organ that requires special care for a healthy and productive lifestyle. Numerous studies have identified lutein and zeaxanthin to be essential components for eye health. Lutein and zeaxanthin are carotenoid pigments that impart yellow or orange color to various common foods such as cantaloupe, pasta, corn, carrots, orange/yellow peppers, fish, salmon and eggs. Their role in human health, in particular the health of the eye, is well established from epidemiological, clinical and interventional studies. They constitute the main pigments found in the yellow spot of the human retina which protect the macula from damage by blue light, improve visual acuity and scavenge harmful reactive oxygen species. They have also been linked with reduced risk of age-related macular degeneration (AMD and cataracts. Research over the past decade has focused on the development of carotenoid-rich foods to boost their intake especially in the elderly population. The aim of this article is to review recent scientific evidences supporting the benefits of lutein and zexanthin in preventing the onset of two major age-related eye diseases with diets rich in these carotenoids. The review also lists major dietary sources of lutein and zeaxanthin and refers to newly developed foods, daily intake, bioavailability and physiological effects in relation to eye health. Examples of the newly developed high-lutein functional foods are also underlined.

  11. Biodegradable Poly (Lactic-co-Glycolic Acid)-Polyethylene Glycol Nanocapsules: An Efficient Carrier for Improved Solubility, Bioavailability, and Anticancer Property of Lutein.

    Science.gov (United States)

    Arunkumar, Ranganathan; Prashanth, Keelara Veerappa Harish; Manabe, Yuki; Hirata, Takashi; Sugawara, Tatsuya; Dharmesh, Shylaja Mallaiah; Baskaran, Vallikannan

    2015-06-01

    Lutein bioavailability is limited because of its poor aqueous solubility. In this study, lutein-poly (lactic-co-glycolic acid) (PLGA)-polyethylene glycol (PEG) nanocapsules were prepared to improve the solubility, bioavailability, and anticancer property of lutein. The scanning electron microscopy and dynamic light scattering examination revealed that the nanocapsules are smooth and spherical with size ranging from 80 to 500 nm (mean = 200 nm). In vitro lutein release profile from nanocapsules showed controlled sustainable release (66%) up to 72 h. Aqueous solubility of lutein nanocapsules was much higher by 735-fold than the lutein. Fourier transform infrared spectroscopy analyses showed no chemical interaction among PLGA, PEG, and lutein, indicating possible weak intermolecular forces like hydrogen bonds. X-ray diffraction revealed lutein is distributed in a disordered amorphous state in nanocapsules. Postprandial plasma kinetics (area under the curve) of an oral dose of lutein from nanocapsules was higher by 5.4-fold compared with that of micellar lutein (control). The antiproliferative effect of lutein from nanocapsules (IC50 value, 10.9 μM) was higher (43.6%) than the lutein (IC50 value, 25 μM). Results suggest that PLGA-PEG nanocapsule is an efficient carrier for enhancing hydrophilicity, bioavailability, and anticancer property of lipophilic molecules such as lutein.

  12. Interfacial properties of Quillaja saponins and its use for micellisation of lutein esters.

    Science.gov (United States)

    Tippel, Janine; Lehmann, Maren; von Klitzing, Regine; Drusch, Stephan

    2016-12-01

    Natural food colourants, colouring foods and bioactive food ingredients need to be solubilised for their incorporation in food. Aim of the present study was to investigate the micelle-forming properties of saponins from Quillaja saponaria Mollina (QS) in order to solubilise a lutein ester extract for its incorporation in food matrices. QS showed a high surface activity and functionality with respect to micellisation as derived from interfacial tension measurements and subsequent data fitting to the classical Frumkin model. The composition of the aqueous phase affected the lutein ester incorporation as revealed by particle size, zeta potential and colour measurements. In terms of morphology of lutein ester loaded saponin micelles (LMS), cryo-TEM micrographs showed depending on the composition of the medium both, spherical and elongated branched micelles. PMID:27374503

  13. THE EFFECT OF LUTEIN ADDITIVES ON BIOCHEMICAL PARAMETERS IN BLOOD OF LAYING HENS

    Directory of Open Access Journals (Sweden)

    Manuela Grčević

    2016-06-01

    Full Text Available The aim of this study was to present the performance and some biochemical parameters in the blood of hens fed feed mixtures with different levels of lutein. The study involved a total of 291 Tetra SL hybrid laying hens, divided into 3 groups (O0 with 0 mg/kg lutein added, O200 with 200 mg/kg lutein added and O400 with 400 mg/kg lutein added, and lasted for 5 weeks. The O0 group included 93 hens, whereas experimental groups 98 and 100 hens, respectively. The highest egg production and the best feed consumption per egg were recorded in O400 group with a total of 3367 pieces of eggs produced and 128.60 g of feed consumed. The best laying intensity (96.68% and number of eggs per laying hen (34.19 as well as the highest feed consumption per day (129.01 g, was recorded in O200 group. Lutein added to feed mixtures for laying hens did not significantly affect the values of biochemical parameters in blood (P>0.05. An increase in total cholesterol (CHOL and HDL cholesterol content as well as the decrease of total protein (PROT and albumin (ALB content in the experimental groups can be observed. The content of glucose (GUK and urea was similar between the experimental groups, while the highest content of triglycerides (TGC was recorded in O200 group. It can be concluded that different levels of lutein added to the feed mixtures for laying hens did not have negative effect on the performance and blood biochemical parameters of laying hens.

  14. Macular pigment density in relation to serum and adipose tissue concentrations of lutein and serum concentrations of zeaxanthin

    NARCIS (Netherlands)

    Broekmans, WMR; Berendschot, TTJM; Klopping-Ketelaars, IAA; de Vries, AJ; Goldbohm, RA; Tijburg, LBM; Kardinaal, AFM; van Poppel, G

    2002-01-01

    Background: Macular pigment (MP), concentrated in the central area of the retina, contains the carotenoids lutein and zeaxanthin. A low MP density could be a risk factor for age-related macular degeneration. Little information is available regarding MP density in relation to serum lutein and zeaxant

  15. Structural and spectroscopic features of lutein/butanoyl-β-cyclodextrin nanoassemblies

    DEFF Research Database (Denmark)

    Stancanelli, R.; Løjkner, L.D.; Larsen, Kim Lambertsen;

    2012-01-01

    ) represent a drawback for bioavailability. To circumvent these unfavorable characteristics, in this work lutein (Lut) have been encapsulated in amphiphilic cyclodextrin (ACyD) by following the well-established strategy of entrapping a lipophilic drug in CyD carriers. Primary face butyrate modified β-cyclodextrins......–vis measurements revealed that electronic properties of lutein were maintained when interact with ACyD nanoaggregates. The monitoring of the entapped carotenoid leaking from ACyD nanostructures was investigated suggesting the potential of Lut/ACyD nanoassemblies in drug delivery....

  16. PGR: A Graph Repository of Protein 3D-Structures

    OpenAIRE

    Dhifli, Wajdi; Diallo, Abdoulaye Baniré

    2016-01-01

    Graph theory and graph mining constitute rich fields of computational techniques to study the structures, topologies and properties of graphs. These techniques constitute a good asset in bioinformatics if there exist efficient methods for transforming biological data into graphs. In this paper, we present Protein Graph Repository (PGR), a novel database of protein 3D-structures transformed into graphs allowing the use of the large repertoire of graph theory techniques in protein mining. This ...

  17. Single nucleotide polymorphism in Egyptian cattle insulin-like growth factor binding protein-3 gene

    Directory of Open Access Journals (Sweden)

    Othman E. Othman

    2014-12-01

    It is concluded that the IGFBP-3/HaeIII polymorphism may be utilized as a good marker for genetic differentiation between cattle animals for different body functions such as growth, metabolism, reproduction, immunity and energy balance. The nucleotide sequences of Egyptian cattle IGFBP-3 A and C alleles were submitted to GenBank with the accession numbers KF899893 and KF899894, respectively.

  18. Enhanced Productivity of a Lutein-Enriched Novel Acidophile Microalga Grown on Urea

    NARCIS (Netherlands)

    Casal, C.; Cuaresma, M.; Vega, J.M.; Vilchez, C.

    2011-01-01

    Coccomyxa acidophila is an extremophile eukaryotic microalga isolated from the Tinto River mining area in Huelva, Spain. Coccomyxa acidophila accumulates relevant amounts of b-carotene and lutein, well-known carotenoids with many biotechnological applications, especially in food and health-related i

  19. Protein 3-nitrotyrosine formation during Trypanosoma cruzi infection in mice

    Directory of Open Access Journals (Sweden)

    M. Naviliat

    2005-12-01

    Full Text Available Nitric oxide (·NO is a diffusible messenger implicated in Trypanosoma cruzi resistance. Excess production of ·NO and oxidants leads to the generation of nitrogen dioxide (·NO2, a strong nitrating agent. Tyrosine nitration is a post-translational modification resulting from the addition of a nitro (-NO2 group to the ortho-position of tyrosine residues. Detection of protein 3-nitrotyrosine is regarded as a marker of nitro-oxidative stress and is observed in inflammatory processes. The formation and role of nitrating species in the control and myocardiopathy of T. cruzi infection remain to be studied. We investigated the levels of ·NO and protein 3-nitrotyrosine in the plasma of C3H and BALB/c mice and pharmacologically modulated their production during the acute phase of T. cruzi infection. We also looked for protein 3-nitrotyrosine in the hearts of infected animals. Our results demonstrated that C3H animals produced higher amounts of ·NO than BALB/c mice, but their generation of peroxynitrite was not proportionally enhanced and they had higher parasitemias. While N G-nitro-arginine methyl ester treatment abolished ·NO production and drastically augmented the parasitism, mercaptoethylguanidine and guanido-ethyl disulfide, at doses that moderately reduced the ·NO and 3-nitrotyrosine levels, paradoxically diminished the parasitemia in both strains. Nitrated proteins were also demonstrated in myocardial cells of infected mice. These data suggest that the control of T. cruzi infection depends not only on the capacity to produce ·NO, but also on its metabolic fate, including the generation of nitrating species that may constitute an important element in parasite resistance and collateral myocardial damage.

  20. Positive effect of dietary lutein and cholesterol on the undirected song activity of an opportunistic breeder

    Science.gov (United States)

    Pinxten, Rianne; Zaid, Erika; Eens, Marcel

    2016-01-01

    Song is a sexually selected trait that is thought to be an honest signal of the health condition of an individual in many bird species. For species that breed opportunistically, the quantity of food may be a determinant of singing activity. However, it is not yet known whether the quality of food plays an important role in this respect. The aim of the present study was to experimentally investigate the role of two calorie-free nutrients (lutein and cholesterol) in determining the expression of a sexually selected behavior (song rate) and other behaviors (locomotor activity, self-maintenance activity, eating and resting) in male zebra finches (Taeniopygia guttata). We predicted that males supplemented with lutein and cholesterol would sing at higher rates than controls because both lutein and cholesterol have important health-related physiological functions in birds and birdsong mirrors individual condition. To control for testosterone secretion that may upregulate birdsong, birds were exposed to a decreasing photoperiod. Our results showed that control males down-regulated testosterone in response to a decreasing photoperiod, while birds treated with lutein or cholesterol maintained a constant singing activity. Both lutein- and cholesterol-supplemented groups sang more than control groups by the end of the experiment, indicating that the quality of food can affect undirected song irrespective of circulating testosterone concentrations. None of the other measured behaviors were affected by the treatment, suggesting that, when individuals have full availability of food, sexually selected song traits are more sensitive to the effect of food quality than other behavioral traits. Overall the results support our prediction that undirected song produced by male zebra finches signals access to high-quality food.

  1. Plasma and macular responses to lutein supplement in subjects with and without age-related maculopathy: a pilot study.

    Science.gov (United States)

    Koh, Hui-Hiang; Murray, Ian J; Nolan, Daniel; Carden, Dave; Feather, Jim; Beatty, Stephen

    2004-07-01

    There is a growing body of evidence which suggests that macular pigment (MP), which is entirely of dietary origin, protects against age-related maculopathy. We evaluated the effect of a daily 20 mg lutein ester (equivalent of 10 mg/day free lutein) supplement in patients with early age-related maculopathy (ARM), in terms of macular pigment optical density (MPOD) and plasma concentrations of lutein. MPOD was measured using a flicker photometric technique in seven ARM sufferers and six age-matched controls over a period of supplementation which lasted 18-20 weeks. Plasma lutein increased from a mean (SD) baseline concentration of 182 (127)ng ml(-1) to a peak of 1077 (165)ng ml(-1) in ARM patients, and from 152 (57) to 1110 (605)ng ml(-1) in control subjects. Mean MPOD had increased significantly from baseline of 0.24 to a peak of 0.31 in ARM sufferers. This mean increment of 0.07 was the same for the age-matched controls (baseline: 0.20; peak: 0.27). The augmentation of MP, and plasma concentrations of lutein, following supplementation in subjects with ARM provides the first evidence the disease is not associated with intestinal malabsorption of the relevant macular carotenoids, and that a diseased macula can accumulate and stabilise lutein and/or zeaxanthin. Furthermore, these results suggest that the beneficial effects of lutein supplementation, if any, may be extended to subjects with established ARM. PMID:15183097

  2. Employing Response Surface Methodology for the Optimization of Ultrasound Assisted Extraction of Lutein and β-Carotene from Spinach

    Directory of Open Access Journals (Sweden)

    Ammar Altemimi

    2015-04-01

    Full Text Available The extraction of lutein and β-carotene from spinach (Spinacia oleracea L. leaves is important to the dietary supplement industry. A Box-Behnken design and response surface methodology (RSM were used to investigate the effect of process variables on the ultrasound-assisted extraction (UAE of lutein and β-carotene from spinach. Three independent variables, extraction temperature (°C, extraction power (% and extraction time (min were studied. Thin-layer chromatography (TLC followed by UV visualization and densitometry was used as a simple and rapid method for both identification and quantification of lutein and β-carotene during UAE. Methanol extracts of leaves from spinach and authentic standards of lutein and β-carotene were separated by normal-phase TLC with ethyl acetate-acetone (5:4 (v/v as the mobile phase. In this study, the combination of TLC, densitometry, and Box–Behnken with RSM methods were effective for the quantitative analysis of lutein and β-carotene from spinach extracts. The resulting quadratic polynomial models for optimizing lutein and β-carotene from spinach had high coefficients of determination of 0.96 and 0.94, respectively. The optimal UAE settings for output of lutein and β-carotene simultaneously from spinach extracts were an extraction temperature of 40 °C, extraction power of 40% (28 W/cm3 and extraction time of 16 min. The identity and purity of each TLC spot was measured using time-of-flight mass spectrometry. Therefore, UAE assisted extraction of carotenes from spinach can provide a source of lutein and β-carotene for the dietary supplement industry.

  3. Development and validation of a dissolution test for lutein tablets and evaluation of intestinal permeability.

    Science.gov (United States)

    Anselmo, Carina de Souza; Mendes, Thamara de Carvalho; Honorio, Thiago da Silva; do Carmo, Flávia Almada; Cabral, Lucio Mendes; de Sousa, Valeria Pereira

    2016-11-01

    Lutein is a carotenoid with antioxidant activity that is present in various dosage forms. The bioavailability of carotenoid from oral dosage formulations depends on their release, dissolution and its permeability through the gastrointestinal tract. Here, a dissolution test was developed for evaluating formulations and the bioavailability was assessed. The test utilized a USP-apparatus II with rotations of 50, 75 and 100rpm in water with P80 at 1, 2 and 5% (w/v). A non-everted rat intestinal sac model was used in conjunction to assess the intestinal permeability. The most discriminative conditions were 100rpm in water with 2% polysorbate 80, which showed profile differences between two formulations. The intestinal permeation studies showed a lag-time and apparent permeability coefficient that were characteristic of highly permeable drugs. We suggest that a dissolution test can be an essential quality control tool for formulations containing compounds as lutein, although not mandatory by the regulation agencies. PMID:27211621

  4. Metabolic alterations of lutein, β-carotene and chlorophyll a during germination of two soybean sprout varieties.

    Science.gov (United States)

    Lee, Jinwook; Hwang, Young-Sun; Lee, Jeong-Dong; Chang, Woo-Suk; Choung, Myoung-Gun

    2013-12-01

    The metabolic changes of lutein, β-carotene and chlorophyll a during germination of the soybean (Glycine max (L.) Merr.) sprout varieties, 'Pungsannamulkong' and 'Bosug', have been studied. Seeds were germinated at 20 °C with 80% humidity in the darkness and sampled at 2 day intervals for 10 days. Partial least squares (PLS) scores plot showed that the responses of three metabolites during germination were linearly linked with each other except for day 2 in both varieties. PLS loading plots indicated that lutein content in whole sprout and cotyledon was closely associated with germination in 'Pungsannamulkong' while the chlorophyll a content in whole sprouts was highly linked with germination in 'Bosug'. Heatmap analyses revealed that lutein and β-carotene levels, but not those of chlorophyll a, accumulated in whole soybean sprouts and cotyledon. While hypocotyls did not accumulate lipophilic pigments during germination, the accumulation of lutein and β-carotene in the cotyledons was greater in 'Pungsannamulkong' than in 'Bosug' sprouts. In addition, the contents of lutein, β-carotene and chlorophyll a increased from those in the seeds. Overall, the metabolic changes of lutein, β-carotene and chlorophyll a during germination are affected not only by variety but also by organ type.

  5. Macular pigment optical density and its relationship with serum and dietary levels of lutein and zeaxanthin

    OpenAIRE

    BEATTY, S; Nolan, John; Kavanagh, H.; O'Donovan, O. M.

    2004-01-01

    Observational evidence is accumulating that the onset of age-related maculopathy, the leading cause of legal blindness in the Western World, could be delayed, or even averted, with antioxidant supplements. Lutein (L) and zeaxanthin (Z) are two hydroxycarotenoids with antioxidant activity which accumulate at the macula, where they are collectively known as macular pigment (MP). It has been shown that MP is entirely of dietary origin, and that L and Z levels in serum, diet, and retina correlate...

  6. A single extraction and HPLC procedure for simultaneous analysis of phytosterols, tocopherols and lutein in soybeans.

    Science.gov (United States)

    Slavin, Margaret; Yu, Liangli Lucy

    2012-12-15

    A saponification/extraction procedure and high performance liquid chromatography (HPLC) analysis method were developed and validated for simultaneous analysis of phytosterols, tocopherols and lutein (a carotenoid) in soybeans. Separation was achieved on a phenyl column with a ternary, isocratic solvent system of acetonitrile, methanol and water (48:22.5:29.5, v/v/v). Evaporative light scattering detection (ELSD) was used to quantify β-sitosterol, stigmasterol, campesterol, and α-, δ- and γ-tocopherols, while lutein was quantified with visible light absorption at 450 nm. Peak identification was verified by retention times and spikes with external standards. Standard curves were constructed (R(2)>0.99) to allow for sample quantification. Recovery of the saponification and extraction was demonstrated via analysis of spiked samples. Also, the accuracy of results of four soybeans using the described saponification and HPLC analytical method was validated against existing methods. This method offers a more efficient alternative to individual methods for quantifying lutein, tocopherols and sterols in soybeans.

  7. Mutations in a novel, cryptic exon of the luteinizing hormone/chorionic gonadotropin receptor gene cause male pseudohermaphroditism.

    Directory of Open Access Journals (Sweden)

    Nina Kossack

    2008-04-01

    Full Text Available BACKGROUND: Male pseudohermaphroditism, or Leydig cell hypoplasia (LCH, is an autosomal recessive disorder in individuals with a 46,XY karyotype, characterized by a predominantly female phenotype, a blind-ending vagina, absence of breast development, primary amenorrhea, and the presence of testicular structures. It is caused by mutations in the luteinizing hormone/chorionic gonadotropin receptor gene (LHCGR, which impair either LH/CG binding or signal transduction. However, molecular analysis has revealed that the LHCGR is apparently normal in about 50% of patients with the full clinical phenotype of LCH. We therefore searched the LHCGR for novel genomic elements causative for LCH. METHODS AND FINDINGS: In the present study we have identified a novel, primate-specific bona fide exon (exon 6A within the LHCGR gene. It displays composite characteristics of an internal/terminal exon and possesses stop codons triggering nonsense-mediated mRNA decay (NMD in LHCGR. Transcripts including exon 6A are physiologically highly expressed in human testes and granulosa cells, and result in an intracellular, truncated LHCGR protein of 209 amino acids. We sequenced exon 6A in 16 patients with unexplained LCH and detected mutations in three patients. Functional studies revealed a dramatic increase in the expression of the mutated internal exon 6A transcripts, indicating aberrant NMD. These altered ratios of LHCGR transcripts result in the generation of predominantly nonfunctional LHCGR isoforms, thereby preventing proper expression and functioning. CONCLUSIONS: The identification and characterization of this novel exon not only identifies a new regulatory element within the genomic organization of LHCGR, but also points toward a complex network of receptor regulation, including events at the transcriptional level. These findings add to the molecular diagnostic tools for LCH and extend our understanding of the endocrine regulation of sexual differentiation.

  8. High affinity human antibody fragments to dengue virus non-structural protein 3.

    Directory of Open Access Journals (Sweden)

    Nicole J Moreland

    Full Text Available BACKGROUND: The enzyme activities catalysed by flavivirus non-structural protein 3 (NS3 are essential for virus replication. They are distributed between the N-terminal protease domain in the first one-third and the C-terminal ATPase/helicase and nucleoside 5' triphosphatase domain which forms the remainder of the 618-aa long protein. METHODOLOGY/PRINCIPAL FINDINGS: In this study, dengue full-length NS3 protein with residues 49 to 66 of NS2B covalently attached via a flexible linker, was used as bait in biopanning with a naïve human Fab phage-display library. Using a range of truncated constructs spanning the NS2B cofactor region and the full-length NS3, 10 unique Fab were identified and characterized. Of these, monoclonal Fab 3F8 was shown to bind α3″ (residues 526 through 531 within subdomain III of the helicase domain. The antibody inhibits the ATPase and helicase activites of NS3 in biochemical assays and reduces DENV replication in HEK293 cells that were previously transfected with Fab 3F8 compared with mock transfected cells. CONCLUSIONS/SIGNIFICANCE: Antibodies such as 3F8 are valuable tools for studying the molecular mechanisms of flaviviral replication and for the monospecific detection of replicating dengue virus in vivo.

  9. The role of uncoupling protein 3 regulating calcium ion uptake into mitochondria during sarcopenia

    Science.gov (United States)

    Nikawa, Takeshi; Choi, Inho; Haruna, Marie; Hirasaka, Katsuya; Maita Ohno, Ayako; Kondo Teshima, Shigetada

    Overloaded mitochondrial calcium concentration contributes to progression of mitochondrial dysfunction in aged muscle, leading to sarcopenia. Uncoupling protein 3 (UCP3) is primarily expressed in the inner membrane of skeletal muscle mitochondria. Recently, it has been reported that UCP3 is associated with calcium uptake into mitochondria. However, the mechanisms by which UCP3 regulates mitochondrial calcium uptake are not well understood. Here we report that UCP3 interacts with HS-1 associated protein X-1 (Hax-1), an anti-apoptotic protein that is localized in mitochondria, which is involved in cellular responses to calcium ion. The hydrophilic sequences within the loop 2, matrix-localized hydrophilic domain of mouse UCP3 are necessary for binding to Hax-1 of the C-terminal domain in adjacent to mitochondrial innermembrane. Interestingly, these proteins interaction occur the calcium-dependent manner. Indeed, overexpression of UCP3 significantly enhanced calcium uptake into mitochondria on Hax-1 endogenously expressing C2C12 myoblasts. In addition, Hax-1 knock-down enhanced calcium uptake into mitochondria on both UCP3 and Hax-1 endogenously expressing C2C12 myotubes, but not myoblasts. Finally, the dissociation of UCP3 and Hax-1 enhances calcium uptake into mitochondria in aged muscle. These studies identify a novel UCP3-Hax-1 complex regulates the influx of calcium ion into mitochondria in muscle. Thus, the efficacy of UCP3-Hax-1 in mitochondrial calcium regulation may provide a novel therapeutic approach against mitochondrial dysfunction-related disease containing sarcopenia.

  10. Torsion theca lutein cyst in association with invasive mole presenting as acute abdomen: a rare case

    Directory of Open Access Journals (Sweden)

    Radhamani S.

    2015-08-01

    Full Text Available Gestational trophoblastic neoplasias (GTN are rare tumours that constitute less than 1% of all gynaecological malignancies. Invasive mole is a distinct subgroup of GTN, which if not diagnosed and treated early, can result in serious complications like uterine perforation and haemoperitoneum. We present a rare case of torsion theca lutein cyst in association with invasive mole of the uterus, which developed following the evacuation of a molar pregnancy with features of continued irregular vaginal bleeding, persistently high betaHcg levels along with acute abdomen. [Int J Reprod Contracept Obstet Gynecol 2015; 4(4.000: 1237-1240

  11. Effect of supplemental light on growth, prolactin, progesterone and luteinizing hormone in water buffalo ( Bubalus bubalis)

    Science.gov (United States)

    Perera, K. S.; Gwazdauskas, F. C.; Akers, R. M.; McGilliard, M. L.

    1989-06-01

    Fifty non-pregnant Surti buffalo heifers aged between 17 and 42 months ( n=24, 24 months) were randomly assigned to groups subject to either natural daylight +4h supplemental light ( n=25) or natural day light ( n=25), to study changes in growth, serum prolactin (Prl), progesterone (P4) and luteinizing hormone (LH) to supplemental lighting. Ambient temperatures (T) and relative humidity (RH) generally were >27° C and buffaloes under similar planes of nutrition. While light supplementation did not have a positive effect on body wieght during the 10 week study, body weight and endocrine changes due to supplemental light may be important factors for initiation of reproductive cyclicity.

  12. Organophosphorus insecticide induced decrease in plasma luteinizing hormone concentration in white-footed mice

    Science.gov (United States)

    Rattner, B.A.; Michael, S.D.

    1985-01-01

    Oral intubation of 50 and 100 mg/kg acephate inhibited brain acetylcholinesterase (AChE) activity by 45% and 56%, and reduced basal luteinizing hormone (LH) concentration by 29% and 25% after 4 h in white-footed mice (Peromyscus leucopus noveboracensis). Dietary exposure to 25, 100, and 400 ppm acephate for 5 days substantially inhibited brain AChE activity, but did not affect plasma LH concentration. These preliminary findings suggest that acute exposure to organophosphorus insecticides may affect LH secretion and possibly reproductive function.

  13. Lutein inhibits the function of the transient receptor potential A1 ion channel in different in vitro and in vivo models.

    Science.gov (United States)

    Horváth, Györgyi; Szoke, Éva; Kemény, Ágnes; Bagoly, Teréz; Deli, József; Szente, Lajos; Pál, Szilárd; Sándor, Katalin; Szolcsányi, János; Helyes, Zsuzsanna

    2012-01-01

    Transient receptor potential (TRP) ion channels, such as TRP vanilloid 1 and ankyrin repeat domain 1 (TRPV1 and TRPA1), are expressed on primary sensory neurons. Lutein, a natural tetraterpene carotenoid, can be incorporated into membranes and might modulate TRP channels. Therefore, the effects of the water-soluble randomly methylated-β-cyclodextrin (RAMEB) complex of lutein were investigated on TRPV1 and TRPA1 activation. RAMEB-lutein (100 μM) significantly diminished Ca(2+) influx to cultured rat trigeminal neurons induced by TRPA1 activation with mustard oil, but not by TRPV1 stimulation with capsaicin, as determined with microfluorimetry. Calcitonin gene-related peptide release from afferents of isolated tracheae evoked by mustard oil, but not by capsaicin, was inhibited by RAMEB-lutein. Mustard oil-induced neurogenic mouse ear swelling was also significantly decreased by 100 μg/ml s.c. RAMEB-lutein pretreatment, while capsaicin-evoked edema was not altered. Myeloperoxidase activity indicating non-neurogenic granulocyte accumulation in the ear was not influenced by RAMEB-lutein in either case. It is concluded that lutein inhibits TRPA1, but not TRPV1 stimulation-induced responses on cell bodies and peripheral terminals of sensory neurons in vitro and in vivo. Based on these distinct actions and the carotenoid structure, the ability of lutein to modulate lipid rafts in the membrane around TRP channels can be suggested.

  14. Lutein and zeaxanthin: Role as macular pigment and factors that control bioavailability from egg yolks and nanoemulsions

    Science.gov (United States)

    Vishwanathan, Rohini

    Lutein and zeaxanthin, two oxygenated carotenoids, exclusively accumulate in the macula, protecting the underlying photoreceptors and retinal pigment epithelial cells from damaging blue radiation of sunlight. As macular pigment, lutein and zeaxanthin are also potent antioxidants protecting the vulnerable regions of retina from free radical injury. Oxidative stress and cumulative light damage play an important role in pathogenesis of age-related macular degeneration (AMD), the leading cause of vision loss in the elderly population. Antioxidant and lutein supplementation has been shown to decrease the risk and prevent the progression of AMD. The egg yolk is a highly bioavailable source of lutein and zeaxanthin and thus a possible contender for AMD prevention and treatment. Consumption of 2 egg yolks/d for 5 weeks was shown herein to significantly increase serum lutein and zeaxanthin concentration and clinically improve macular pigment concentrations at 0.5° retinal eccentricity in an older adult population taking cholesterol-lowering statins. Four egg yolks/d not only raised serum lutein and zeaxanthin significantly but also macular pigment densities at 0.25°, 0.5° and 1° retinal eccentricity. A positive outcome of the 2 egg yolk consumption was the significant increase in serum HDL-C with a tendency of serum LDL-C to decrease, although not significantly. Four egg yolks/d seemed to cross the threshold for dietary cholesterol tolerance as serum LDL-C tended to increase, although not significantly, despite the significant increase in serum HDL-C. There is a strong possibility that greater build up of lutein and zeaxanthin in the macula may have been observed with 2 egg yolks/d if the intervention period was longer than 5 weeks. Addition of up to 2 eggs a day to the diet is suggested to benefit an older adult population, especially those who are already taking cholesterol-lowering statins by (a) building their macular pigment and possibly protect against AMD and (b

  15. Local Production of Luteinizing Hormone Antisera to Be Used In Radioimmunoassay Technique

    International Nuclear Information System (INIS)

    Luteinizing hormone (LH) is a glycoprotein hormone. It is one of the coordinate pituitary regulators of gonadal function (2). Serum LH concentration increase in polycystic ovary syndrome (PCOS) which is the most common cause of infertility among infertile women. (3). The expensive imported LH kits lead us to think seriously to develop our local reagents. The antibody is a backbone of RIA reagents and this study is describing how to raise LH antibody and how to use it for a local LH kit production. Human LH was emulsified to Freunds adjuvant and acted as an immunogen Local Sudanese sheep was used to raise anti-LH antisera. The obtained antisera were adsorbed physically onto polystyrene beads with a dilution of 1/100.000 in order to develop an RIA kit. Optimization of LH assay conditions including incubation temperature and reaction time were performed. Assay validation tests including specificity, sensitivity, linearity, recovery, reproducibility and comparability for the local kit were performed. The polystyrene beads RIA LH system showed a minimum detectable dose of 0.04 m U/L. For the linearity and recovery tests, the regression coefficients were found to be 0.99, 0.997 respectively. The assay was found to be reproducible where the coefficients of variation within and between assays were less than 10%. Comparison between local and Chinese reagents for Luteinizing hormone determination in serum showed high correlation where r=0.96. (Authors)

  16. Local production of luteinizing hormone antisera to be used in radioimmunoassay technique

    International Nuclear Information System (INIS)

    Luteinizing hormone (LH) is a glycoprotein hormone. It is one of the coordinate pituitary regulators of gonadal function (2). Serum LH concentration increase in polycystic ovary syndrome (PCOS) which is the most common cause of infertility among infertile women (3). The expensive imported LH kits lead us to think seriously to develop our local reagents. The antibody is a backbone of RIA reagents and this study is describing how to raise LH antibody and how to use it for a local LH kit production. Human LH was emulsified to Freunds adjuvant and acted as an immunogen local Sudanese sheep was used to raise anti-LH antisera. The obtained antisera were adsorbed physically onto polystyrene beads with a dilution of 1/100.000 in order to develop an RIA kit. Optimization of LH assay conditions including incubation temperature and reaction time were performed. Assay validation tests including specificity, sensitivity, linearity, recovery, reproducibility and comparability for the local kit were performed. The polystyrene beads RIA LH system showed a minimum detectable dose of 0.04 m U/L. For the linearity and recovery tests, the regression coefficients were found to be 0.99, 0.997 respectively. The assay was found to be reproducible where the coefficients of variation within and between assays were less than 10%. Comparison between local and Chinese reagents for luteinizing hormone determination in serum showed high correlation where r=0.96. (Author)

  17. Lutein in selected Canadian crops and agri-food processing by-products and purification by high-speed counter-current chromatography.

    Science.gov (United States)

    Tsao, Rong; Yang, Raymond

    2006-04-21

    This study mainly focused on lutein content in several selected crops grown in southern Ontario, Canada. Marigold flower, a good rotation crop for the control of nematodes in tobacco fields was found to contain 0.77% lutein (after saponification, on dry basis). A high-speed counter-current chromatography (HSCCC) method using a two-phase solvent system consisting of hexane-ethanol-water (6:4.5:1.5, v/v/v) was developed for the purification of lutein from the saponification mixture of marigold flower extract. The purity of lutein prepared using this HSCCC method was 97%. Free lutein was found to be the predominant form in three squash varieties, and it was mostly found in the peel rather than the commonly consumed flesh. Sweet Mamma, Buttercup and Pepper squash varieties contained 25.4, 18.4 and 30.1mg/100g fresh weigh (FW) of lutein in the peels, respectively. These concentrations were significantly higher than that in spinach and kale (3.7 and 12.3 mg/100 g FW). beta-Carotene was found most in the peel of Sweet Mamma squash at 13.6 mg/100g FW, whereas it was below 2mg/100g FW in all other samples. Cooking increased extractable free lutein by 22-65% in squash peels. Lutein in Yukon Gold potato was at ca. 0.4 mg/100 g FW. Certain Yukon Gold was also found to contain violaxanthin (0.35 mg/100 g FW). Structures of lutein, beta-carotene and violaxanthin were identified by LC-atmospheric pressure chemical ionization MS in positive ion mode, and by comparing the retention time and UV-vis spectral data with standards. Results from this study suggest the selected crops and agri-food industrial processing by-products of these can be a good source of free lutein. PMID:16242702

  18. Modulation of DNA-induced damage and repair capacity in humans after dietary intervention with lutein-enriched fermented milk.

    Directory of Open Access Journals (Sweden)

    Carmen Herrero-Barbudo

    Full Text Available Dietary factors provide protection against several forms of DNA damage. Additionally, consumer demand for natural products favours the development of bioactive food ingredients with health benefits. Lutein is a promising biologically active component in the food industry. The EFSA Panel on Dietetic Products, Nutrition and Allergies considers that protection from oxidative damage may be a beneficial physiological effect but that a cause and effect relationship has not been established. Thus, our aim was to evaluate the safety and potential functional effect of a lutein-enriched milk product using the Comet Assay in order to analyze the baseline, the induced DNA-damage and the repair capacity in the lymphocytes of 10 healthy donors before and after the intake of the mentioned product. Our data suggest that the regular consumption of lutein-enriched fermented milk results in a significant increase in serum lutein levels and this change is associated with an improvement in the resistance of DNA to damage and the capacity of DNA repair in lymphocytes. Our results also support the lack of a genotoxic effect at the doses supplied as well as the absence of interactions and side effects on other nutritional and biochemicals markers.

  19. Modulation of DNA-induced damage and repair capacity in humans after dietary intervention with lutein-enriched fermented milk.

    Science.gov (United States)

    Herrero-Barbudo, Carmen; Soldevilla, Beatriz; Pérez-Sacristán, Belén; Blanco-Navarro, Inmaculada; Herrera, Mercedes; Granado-Lorencio, Fernando; Domínguez, Gemma

    2013-01-01

    Dietary factors provide protection against several forms of DNA damage. Additionally, consumer demand for natural products favours the development of bioactive food ingredients with health benefits. Lutein is a promising biologically active component in the food industry. The EFSA Panel on Dietetic Products, Nutrition and Allergies considers that protection from oxidative damage may be a beneficial physiological effect but that a cause and effect relationship has not been established. Thus, our aim was to evaluate the safety and potential functional effect of a lutein-enriched milk product using the Comet Assay in order to analyze the baseline, the induced DNA-damage and the repair capacity in the lymphocytes of 10 healthy donors before and after the intake of the mentioned product. Our data suggest that the regular consumption of lutein-enriched fermented milk results in a significant increase in serum lutein levels and this change is associated with an improvement in the resistance of DNA to damage and the capacity of DNA repair in lymphocytes. Our results also support the lack of a genotoxic effect at the doses supplied as well as the absence of interactions and side effects on other nutritional and biochemicals markers. PMID:24040187

  20. Effect of naloxone treatment on luteinizing hormone and testosterone concentrations in boars with high and low libido

    Science.gov (United States)

    The objective was to determine the effects of naloxone, an opioid peptide receptor antagonist on circulating concentrations of luteinizing hormone (LH) and testosterone in boars characterized as having high (n = 8) or low libido (n = 8) based on the willingness to mount an artificial sow and allow s...

  1. Luteinizing hormone-releasing hormone induces thyroxine release together with testosterone in the neotenic axolotl Ambystoma mexicanum.

    Science.gov (United States)

    Jacobs, G F; Kühn, E R

    1988-09-01

    In male neotenic axolotls Ambystoma mexicanum plasma concentrations of thyroxine (T4) and testosterone were increased following intravenous injection of 10 micrograms luteinizing hormone-releasing hormone. A dose of 50 micrograms influenced only plasma T4 levels. This observation suggests for the first time that a hypothalamic hormone is capable of stimulating the thyroidal axis in the neotenic axolotl.

  2. Cysteine-rich secretory protein 3 is a ligand of alpha1B-glycoprotein in human plasma

    DEFF Research Database (Denmark)

    Udby, Lene; Sørensen, Ole E; Pass, Jesper;

    2004-01-01

    -like substances found in lizard saliva or snake venom. Human CRISP-3 is present in exocrine secretions and in secretory granules of neutrophilic granulocytes and is believed to play a role in innate immunity. On the basis of the relatively high content of CRISP-3 in human plasma and the small size of the protein...... (28 kDa), we hypothesized that CRISP-3 in plasma was bound to another component. This was supported by size-exclusion chromatography and immunoprecipitation of plasma proteins. The binding partner was identified by mass spectrometry as alpha(1)B-glycoprotein (A1BG), which is a known plasma protein of......Human cysteine-rich secretory protein 3 (CRISP-3; also known as SGP28) belongs to a family of closely related proteins found in mammals and reptiles. Some mammalian CRISPs are known to be involved in the process of reproduction, whereas some of the CRISPs from reptiles are neurotoxin...

  3. Radical Scavenging Activity-Based and AP-1-Targeted Anti-Inflammatory Effects of Lutein in Macrophage-Like and Skin Keratinocytic Cells

    Directory of Open Access Journals (Sweden)

    Jueun Oh

    2013-01-01

    Full Text Available Lutein is a naturally occurring carotenoid with antioxidative, antitumorigenic, antiangiogenic, photoprotective, hepatoprotective, and neuroprotective properties. Although the anti-inflammatory effects of lutein have previously been described, the mechanism of its anti-inflammatory action has not been fully elucidated. Therefore, in the present study, we aimed to investigate the regulatory activity of lutein in the inflammatory responses of skin-derived keratinocytes or macrophages and to elucidate the mechanism of its inhibitory action. Lutein significantly reduced several skin inflammatory responses, including increased expression of interleukin-(IL- 6 from LPS-treated macrophages, upregulation of cyclooxygenase-(COX- 2 from interferon-γ/tumor necrosis-factor-(TNF- α-treated HaCaT cells, and the enhancement of matrix-metallopeptidase-(MMP- 9 level in UV-irradiated keratinocytes. By evaluating the intracellular signaling pathway and the nuclear transcription factor levels, we determined that lutein inhibited the activation of redox-sensitive AP-1 pathway by suppressing the activation of p38 and c-Jun-N-terminal kinase (JNK. Evaluation of the radical and ROS scavenging activities further revealed that lutein was able to act as a strong anti-oxidant. Taken together, our findings strongly suggest that lutein-mediated AP-1 suppression and anti-inflammatory activity are the result of its strong antioxidative and p38/JNK inhibitory activities. These findings can be applied for the preparation of anti-inflammatory and cosmetic remedies for inflammatory diseases of the skin.

  4. Physicochemical stability, microrheological properties and microstructure of lutein emulsions stabilized by multilayer membranes consisting of whey protein isolate, flaxseed gum and chitosan.

    Science.gov (United States)

    Xu, Duoxia; Aihemaiti, Zulipiya; Cao, Yanping; Teng, Chao; Li, Xiuting

    2016-07-01

    The impact of chitosan (CTS) on the physicochemical stability, microrheological property and microstructure of whey protein isolate (WPI)-flaxseed gum (FG) stabilized lutein emulsions at pH 3.0 was studied. A layer-by-layer electrostatic deposition method was used to prepare multilayered lutein emulsions. Droplet size, zeta-potential, instability index, microstructure and microrheological behavior of lutein emulsions were measured. The influences of interfacial layer, metal chelator and free radical scavenger on the chemical stability of lutein emulsions were also investigated. It was found that multilayer emulsions had better physical stability showing the pronounced effect of 1wt% CTS. The mean square displacement analysis demonstrated that CTS led to increases of macroscopic viscosity and elasticity index for WPI-FG stabilized lutein emulsions due to CTS embedding in the network. CTS also helped to chemically stabilize the lutein emulsions against degradation. The combination of interfacial membrane and prooxidative metal chelator or free radical scavenger was an effective method to control lutein degradation. PMID:26920280

  5. Immunoreactive luteinizing hormone-releasing hormone in the seminal plasma and human semen parameters

    International Nuclear Information System (INIS)

    A luteinizing hormone-releasing hormone (LH-RH)-like substance has been detected in human seminal plasma by a radioimmunoassay (RIA) with a highly specific anti-LH-RH antiserum. The seminal samples - not only the plasma itself but also the sample extracted by an acid/alcohol method - showed satisfactory displacement curves in our RIA system. The relationship between fertility and the LH-RH values in the seminal plasma was studied by comparing the peptide levels with sperm concentration and motility. By these two parameters, 103 samples were divided into four groups. In the low-concentration groups (oligozoospermic patients), the hormonal concentrations differed significantly between those specimens demonstrating good and poor motility. These data suggest that this immunoreactive LH-RH may play a role in human spermatogenesis

  6. Depression of plasma luteinizing hormone concentration in quail by the anticholinesterase insecticide parathion

    Science.gov (United States)

    Rattner, B.A.; Clarke, R.N.; Ottinger, M.A.

    1986-01-01

    To examine the effects of parathion on basal plasma luteinizing hormone (LH) concentration, male Japanese quail (Coturnix japonica) were orally intubated with 0, 5 or 10 mg/kg parathion and sacrificed after 4, 8 and 24 hr. At the 5 mg/kg dose, plasma LH levels were reduced at 4 and 8 hr, but returned to control values by 24 hr. Brain acetylcholinesterase activity was substantially reduced by 10 mg/kg parathion (52, 75 and 37% inhibition at 4, 8 and 24 hr, respectively) and plasma LH concentration remained depressed through the 24-hr period. These findings suggest that the organophosphorus insecticide parathion may alter plasma LH concentration in a manner which might impair reproductive activity, and provide indirect evidence for a cholinergic component in the regulation of LH secretion in quail.

  7. effect of luteinizing hormone-releasing hormone analogue on the sexual behavior of sacalia quadriocellata

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    luteinizing hormone-releasing hormone (lhrh) is known to influence sexual behavior in many vertebrate taxa,but there have been no systematic studies on the role of lhrh in sexual behavior of turtles.we tested the hypotheses that exogenous lhrh analogues would induce sexual behavior of male four-eyed turtle,sacalia quadriocellata.we examined this by challenging males with intramuscular injections of mammalian luteinizing hormone-releasing hormone analogue (lhrh-a),human chorionic gonadotropin (hcg),or a combination of the two,and subsequently exposing them to sexually receptive females for behavioral observation.our data show that the injection of only hcg could not,while that of only lhrh-a could,facilitate sexual behavior along with testicular recrudescence and spermatogenesis in s.quadriocellata.the injection of both lhrh-a and hcg would induce more drastic sexual behavior of the animals than that of lhrh-a alone,indicating hcg enhances the effects of lhrh-a induced sexual behavior.however,different pharmacological dosages of lhrh-a (0.5 μg,1 μg,2 μg per 100 g bodyweight) did not correspond to different activity levels.though the mechanism of lhrh effect was not determined,this study may support that the sexual behavior ofs.quadriocellata which occurs at the beginning of the injection despite regression of the gonads.this is the first report on the exogenous lhrh-a induced sexual behavior for this species.

  8. Enhanced productivity of a lutein-enriched novel acidophile microalga grown on urea.

    Science.gov (United States)

    Casal, Carlos; Cuaresma, Maria; Vega, Jose Maria; Vilchez, Carlos

    2011-01-01

    Coccomyxa acidophila is an extremophile eukaryotic microalga isolated from the Tinto River mining area in Huelva, Spain. Coccomyxa acidophila accumulates relevant amounts of β-carotene and lutein, well-known carotenoids with many biotechnological applications, especially in food and health-related industries. The acidic culture medium (pH cultivation from non-desired microorganism growth is one of the main advantages of acidophile microalgae production. Conversely, acidophile microalgae growth rates are usually very low compared to common microalgae growth rates. In this work, we show that mixotrophic cultivation on urea efficiently enhances growth and productivity of an acidophile microalga up to typical values for common microalgae, therefore approaching acidophile algal production towards suitable conditions for feasible outdoor production. Algal productivity and potential for carotenoid accumulation were analyzed as a function of the nitrogen source supplied. Several nitrogen conditions were assayed: nitrogen starvation, nitrate and/or nitrite, ammonia and urea. Among them, urea clearly led to the best cell growth (~4 × 10(8) cells/mL at the end of log phase). Ammonium led to the maximum chlorophyll and carotenoid content per volume unit (220 μg·mL(·1) and 35 μg·mL(·1), respectively). Interestingly, no significant differences in growth rates were found in cultures grown on urea as C and N source, with respect to those cultures grown on nitrate and CO(2) as nitrogen and carbon sources (control cultures). Lutein accumulated up to 3.55 mg·g(·1) in the mixotrophic cultures grown on urea. In addition, algal growth in a shaded culture revealed the first evidence for an active xanthophylls cycle operative in acidophile microalgae. PMID:21339944

  9. Enhanced Productivity of a Lutein-Enriched Novel Acidophile Microalga Grown on Urea

    Directory of Open Access Journals (Sweden)

    Carlos Vilchez

    2010-12-01

    Full Text Available Coccomyxa acidophila is an extremophile eukaryotic microalga isolated from the Tinto River mining area in Huelva, Spain. Coccomyxa acidophila accumulates relevant amounts of b-carotene and lutein, well-known carotenoids with many biotechnological applications, especially in food and health-related industries. The acidic culture medium (pH < 2.5 that prevents outdoor cultivation from non-desired microorganism growth is one of the main advantages of acidophile microalgae production. Conversely, acidophile microalgae growth rates are usually very low compared to common microalgae growth rates. In this work, we show that mixotrophic cultivation on urea efficiently enhances growth and productivity of an acidophile microalga up to typical values for common microalgae, therefore approaching acidophile algal production towards suitable conditions for feasible outdoor production. Algal productivity and potential for carotenoid accumulation were analyzed as a function of the nitrogen source supplied. Several nitrogen conditions were assayed: nitrogen starvation, nitrate and/or nitrite, ammonia and urea. Among them, urea clearly led to the best cell growth (~4 ´ 108 cells/mL at the end of log phase. Ammonium led to the maximum chlorophyll and carotenoid content per volume unit (220 mg·mL-1 and 35 mg·mL-1, respectively. Interestingly, no significant differences in growth rates were found in cultures grown on urea as C and N source, with respect to those cultures grown on nitrate and CO2 as nitrogen and carbon sources (control cultures. Lutein accumulated up to 3.55 mg·g-1 in the mixotrophic cultures grown on urea. In addition, algal growth in a shaded culture revealed the first evidence for an active xanthophylls cycle operative in acidophile microalgae.

  10. Stress and the timing of breeding: glucocorticoid-luteinizing hormones relationships in an arctic seabird.

    Science.gov (United States)

    Goutte, Aurélie; Angelier, Frédéric; Chastel, Céline Clément; Trouvé, Colette; Moe, Børge; Bech, Claus; Gabrielsen, Geir W; Chastel, Olivier

    2010-10-01

    In birds, stressful environmental conditions delay the timing of breeding but the underlying mechanisms are poorly understood. The stress hormone corticosterone appears to be a good candidate for mediating the decision to breed and when to start egg-laying, via a possible inhibition of luteinizing hormone (LH) and sex-steroids production. We used luteinizing hormone releasing hormone (LHRH) challenge in pre-laying male and female Black-legged kittiwakes (Rissa tridactyla) to test whether LH and testosterone secretion were depressed by elevated corticosterone levels. Females bearing high baseline corticosterone levels showed reduced baseline LH levels and a low ability to release LH, following LHRH challenge. Further, females bearing low baseline LH levels and elevated baseline corticosterone levels were more likely to skip breeding. However, non-breeding females were physiologically primed for breeding, since they mounted high LHRH-induced LH release. Egg-laying date was advanced in good body condition females but was unaffected by hormones secretion. In males, corticosterone levels had no effect on LH and/or testosterone secretion and did not affect their decision to breed. Interestingly, males with high LHRH-induced testosterone release bred early. Our study highlights clear sex-differences in the HPG sensitivity to stress hormones in pre-laying kittiwakes. Because females have to store body reserves and to build up the clutch, they would be more sensitive to stress than males. Moreover, intrasexual competition could force male kittiwakes to acquire reproductive readiness earlier in the season than females and to better resist environmental perturbations. We suggest that high testosterone releasing ability would mediate behavioural adjustments such as courtship feeding, which would stimulate early egg-laying in females.

  11. Mutations in the latent TGF-beta binding protein 3 (LTBP3) gene cause brachyolmia with amelogenesis imperfecta.

    Science.gov (United States)

    Huckert, Mathilde; Stoetzel, Corinne; Morkmued, Supawich; Laugel-Haushalter, Virginie; Geoffroy, Véronique; Muller, Jean; Clauss, François; Prasad, Megana K; Obry, Frédéric; Raymond, Jean Louis; Switala, Marzena; Alembik, Yves; Soskin, Sylvie; Mathieu, Eric; Hemmerlé, Joseph; Weickert, Jean-Luc; Dabovic, Branka Brukner; Rifkin, Daniel B; Dheedene, Annelies; Boudin, Eveline; Caluseriu, Oana; Cholette, Marie-Claude; Mcleod, Ross; Antequera, Reynaldo; Gellé, Marie-Paule; Coeuriot, Jean-Louis; Jacquelin, Louis-Frédéric; Bailleul-Forestier, Isabelle; Manière, Marie-Cécile; Van Hul, Wim; Bertola, Debora; Dollé, Pascal; Verloes, Alain; Mortier, Geert; Dollfus, Hélène; Bloch-Zupan, Agnès

    2015-06-01

    Inherited dental malformations constitute a clinically and genetically heterogeneous group of disorders. Here, we report on four families, three of them consanguineous, with an identical phenotype, characterized by significant short stature with brachyolmia and hypoplastic amelogenesis imperfecta (AI) with almost absent enamel. This phenotype was first described in 1996 by Verloes et al. as an autosomal recessive form of brachyolmia associated with AI. Whole-exome sequencing resulted in the identification of recessive hypomorphic mutations including deletion, nonsense and splice mutations, in the LTBP3 gene, which is involved in the TGF-beta signaling pathway. We further investigated gene expression during mouse development and tooth formation. Differentiated ameloblasts synthesizing enamel matrix proteins and odontoblasts expressed the gene. Study of an available knockout mouse model showed that the mutant mice displayed very thin to absent enamel in both incisors and molars, hereby recapitulating the AI phenotype in the human disorder.

  12. Mutations in the latent TGF-beta binding protein 3 (LTBP3) gene cause brachyolmia with amelogenesis imperfecta

    Science.gov (United States)

    Huckert, Mathilde; Stoetzel, Corinne; Morkmued, Supawich; Laugel-Haushalter, Virginie; Geoffroy, Véronique; Muller, Jean; Clauss, François; Prasad, Megana K.; Obry, Frédéric; Raymond, Jean Louis; Switala, Marzena; Alembik, Yves; Soskin, Sylvie; Mathieu, Eric; Hemmerlé, Joseph; Weickert, Jean-Luc; Dabovic, Branka Brukner; Rifkin, Daniel B.; Dheedene, Annelies; Boudin, Eveline; Caluseriu, Oana; Cholette, Marie-Claude; Mcleod, Ross; Antequera, Reynaldo; Gellé, Marie-Paule; Coeuriot, Jean-Louis; Jacquelin, Louis-Frédéric; Bailleul-Forestier, Isabelle; Manière, Marie-Cécile; Van Hul, Wim; Bertola, Debora; Dollé, Pascal; Verloes, Alain; Mortier, Geert; Dollfus, Hélène; Bloch-Zupan, Agnès

    2015-01-01

    Inherited dental malformations constitute a clinically and genetically heterogeneous group of disorders. Here, we report on four families, three of them consanguineous, with an identical phenotype, characterized by significant short stature with brachyolmia and hypoplastic amelogenesis imperfecta (AI) with almost absent enamel. This phenotype was first described in 1996 by Verloes et al. as an autosomal recessive form of brachyolmia associated with AI. Whole-exome sequencing resulted in the identification of recessive hypomorphic mutations including deletion, nonsense and splice mutations, in the LTBP3 gene, which is involved in the TGF-beta signaling pathway. We further investigated gene expression during mouse development and tooth formation. Differentiated ameloblasts synthesizing enamel matrix proteins and odontoblasts expressed the gene. Study of an available knockout mouse model showed that the mutant mice displayed very thin to absent enamel in both incisors and molars, hereby recapitulating the AI phenotype in the human disorder. PMID:25669657

  13. Binding Procurement

    Science.gov (United States)

    Rao, Gopalakrishna M.; Vaidyanathan, Hari

    2007-01-01

    This viewgraph presentation reviews the use of the binding procurement process in purchasing Aerospace Flight Battery Systems. NASA Engineering and Safety Center (NESC) requested NASA Aerospace Flight Battery Systems Working Group to develop a set of guideline requirements document for Binding Procurement Contracts.

  14. Clinical Observations on Electroacupuncture-induced Ovulation in Patients with Luteinized Unruptured Follicle Syndrome

    Institute of Scientific and Technical Information of China (English)

    连方; 李海仙; 张建伟; 张宁; 孙振高; 刘海萍; 辛明蔚; 曾颖筠; 朱函亭

    2006-01-01

    To investigate the curative effect of electroacupuncture on luteinized unruptured follicle syndrome(LUFS) and its mechanism. Methods:Sixty LUFS patients were randomly allocated to treatment (electroacupuncture) group and control (hCG) group. The follicular condition and ovarian arterial flow under color Doppler ultrasonogaphy and a change in reproductive endocrine level were observed in the patients before and after treatments. The ovulation rates and pregnancy rates were compared between the two groups,and the mechanism was investigated. Results:Both ovulation rate and pregnancy rate were significantly higher in the treatment group than in the control group (P<0.01). There was a significant difference in the improvement in ovarian arterial flow between the treatment and control groups (P<0.01). The improvement in endocrine level was significantly more marked in the treatment group than in the control group(P<0.01). Conclusion:Electroacupuncture has a good effect on luteinized unrupture follicle syndrome. Its mechanism may be related to the improvement in ovarian arterial blood supply and the regulation of endocrine level.%目的:观察电针治疗LUFS的临床疗效,并探讨其作用机理.方法:将60例LUFS患者随机分为治疗组(电针组)和对照组(hCG组),观察患者治疗前后彩色多普勒超声下卵泡的排出情况和卵巢动脉血流,生殖内分泌水平的变化,比较两组排卵率,妊娠率,并探讨其作用机理.结果:治疗组的排卵率与妊娠率均显著高于对照组(P<0.01);治疗组在改善卵巢动脉血流方面较对照组差异有极显著性(P<0.01);治疗组在改善内分泌水平方面显著优于对照组(P<0.01).结论:电针治疗未破裂卵泡黄素化综合征有较好的疗效,其机理可能与改善卵巢动脉血供和调节内分泌水平有关.

  15. Endogenous opiates modulate the pulsatile secretion of biologically active luteinizing hormone in man.

    Science.gov (United States)

    Veldhuis, J D; Rogol, A D; Johnson, M L

    1983-12-01

    We studied the secretion of physiological pools of immunoreactive and biologically active luteinizing hormone in response to endogenous pulses of gonadotropin-releasing hormone (GNRH) in eugonadal men. Concentrations of immunoactive and bioactive luteinizing hormone (LH) were determined in blood drawn at 20-min intervals for 8 h in eight normal men under two conditions: (a) after placebo, in order to evaluate spontaneous LH pulsations in the basal state, and (b) after administration of the opiate-receptor antagonist, naltrexone, which is believed to amplify the pulsatile release of endogenous GNRH. Spontaneous and naltrexone-stimulated secretion of LH occurred in pulses of high biological activity, as measured in the RICT (rat interstitial cell testosterone bioassay), i.e., bioactive:immunoactive LH ratios within both spontaneous and naltrexone-stimulated LH pulses were higher than corresponding interpulse ratios (P less than 0.001). Quantitative characterization of the pulsatile release of bioactive LH revealed the following specific effects of opiate-receptor blockade: increased 8-h mean and integrated serum concentrations of bioactive LH (P less than 0.002), enhanced pulse frequency of bioactive LH release (P less than 0.001), and augmented peak amplitude of bio-LH pulses (P less than 0.01). Moreover, this increase in episodic secretion of bioactive LH was associated with increased 8-h mean and integrated serum testosterone concentrations in these men (P less than 0.05). We conclude the following: (a) LH is normally released in spontaneous pulses of high biological activity in men; (b) when the endogenous GNRH signal is amplified by opiate-receptor blockade, the pituitary gland releases more frequent bioactive LH pulses, which are of high amplitude and contain a high bioactive:immunoactive LH ratio. This increase in pulsatile release of bioactive LH quantitated in the RICT assay in vitro is reflected by acutely increased serum testosterone concentrations in vivo

  16. Luteinizing hormone-releasing hormone receptor-mediated delivery of mitoxantrone using LHRH analogs modified with PEGylated liposomes

    OpenAIRE

    Sun, Hongfan

    2010-01-01

    Yingna He, Linhua Zhang, Cunxian SongKey Laboratory of Biomedical Material of Tianjin, Institute of Biomedical Engineering, Peking Union Medical College and Chinese Academy of Medical Sciences, Tianjin, ChinaAbstract: A sterically stabilized, mitoxantrone-loaded liposome, tailored to target luteinizing hormone-releasing hormone (LHRH) receptor overexpressing cells, was developed to promote the efficiency of intracellular delivery of mitoxantrone through receptor-mediated endocytosis. Liposome...

  17. Significance of monoclonal antibodies against the conserved epitopes within non-structural protein 3 helicase of hepatitis C virus.

    Directory of Open Access Journals (Sweden)

    Yixin Bian

    Full Text Available Nonstructural protein 3 (NS3 of hepatitis C virus (HCV, codes for protease and helicase carrying NTPase enzymatic activities, plays a crucial role in viral replication and an ideal target for diagnosis, antiviral therapy and vaccine development. In this study, monoclonal antibodies (mAbs to NS3 helicase were characterized by epitope mapping and biological function test. A total of 29 monoclonal antibodies were produced to the truncated NS3 helicase of HCV-1b (T1b-rNS3, aa1192-1459. Six mAbs recognized 8/29 16mer peptides, which contributed to identify 5 linear and 1 discontinuous putative epitope sequences. Seven mAbs reacted with HCV-2a JFH-1 infected Huh-7.5.1 cells by immunofluorescent staining, of which 2E12 and 3E5 strongly bound to the exposed linear epitope (1231PTGSGKSTK(1239 (EP05 or core motif (1373IPFYGKAI(1380 (EP21, respectively. Five other mAbs recognized semi-conformational or conformational epitopes of HCV helicase. MAb 2E12 binds to epitope EP05 at the ATP binding site of motif I in domain 1, while mAb 3E5 reacts with epitope EP21 close to helicase nucleotide binding region of domain 2. Epitope EP05 is totally conserved and EP21 highly conserved across HCV genotypes. These two epitope peptides reacted strongly with 59-79% chronic and weakly with 30-58% resolved HCV infected blood donors, suggesting that these epitopes were dominant in HCV infection. MAb 2E12 inhibited 50% of unwinding activity of NS3 helicase in vitro. Novel monoclonal antibodies recognize highly conserved epitopes at crucial functional sites within NS3 helicase, which may become important antibodies for diagnosis and antiviral therapy in chronic HCV infection.

  18. Plasma levels of luteinizing hormone and gonadal maturation of lambari females under different photoperiods

    Directory of Open Access Journals (Sweden)

    Fernanda Keley Silva Pereira Navarro

    2013-08-01

    Full Text Available The objective of this work was to evaluate the effect of photoperiod on luteinizing hormone (LH plasma levels and gonadal maturation of lambari females. One hundred and twenty adult lambaris, distributed into 12 aquaria of 20 L each, were randomly subjected to three different treatments, in a completely randomized design, and four replicates. Treatments were photoperiods in hours of light (L and darkness (D: T1, 0 L:24 D; T2, 12 L:12 D; T3, 24 L:0 D. After 40 days, fish were subjected to fasting for 24 hours and, then, anesthetized. Immediately after slaughter, fish were weighed, and their gonads and livers were removed and weighed. Ovaries were weighed and immersed in Bouin's fixative solution for 24 hours and, then, kept in 70% alcohol until processing the material. Subsequently, the oocyte developmental stage was determined. No significant differences were observed between treatments for final weight, ovary weight, gonadosomatic index (GSI, hepatosomatic index (HSI and LH levels. In all treatments, lambari females showed maturing ovaries with prevalence of vitellogenic oocytes. Photoperiod does not affect the LH levels and ovarian maturation in lambari females.

  19. Thecal cell sensitivity to luteinizing hormone and insulin in polycystic ovarian syndrome.

    Science.gov (United States)

    Cadagan, David; Khan, Raheela; Amer, Saad

    2016-03-01

    This study examined whether a defect of steroid synthesis in ovarian theca cells may lead to the development of PCOS, through contributions to excess androgen secretion. Polycystic ovarian syndrome (PCOS) is one of the leading causes of infertility worldwide affecting around 1 in 10 of women of a reproductive age. One of the fundamental abnormalities in this syndrome is the presence of hormonal irregularities, including hyperandrogenemia, hyperinsulinemia and hypersecretion of luteinizing hormone (LH). Studies suggest that insulin treatment increases progesterone and androstenedione secretion in PCOS theca cells when compared to insulin treated normal theca cells. Furthermore the augmented effects of LH and insulin have been seen to increase ovarian androgen synthesis in non-PCOS theca cultures whilst also increasing the expression of steroidogenic enzymes specific to the PI3-K pathway. Our examination of primary thecal cultures showed an increase in both the expression of the steroidogenic enzyme CYP17 and androgen secretion in PCOS theca cells under basal conditions, when compared to non-PCOS cells. This was increased significantly under treatments of LH and insulin combined. Our results support the previous reported hypothesis that a dysfunction may exist within the PI3-K pathway. Specifically, that sensitivity exists to physiological symptoms including hyperinsulinemia and hyper secretion of LH found in PCOS through co-stimulation. The impact of these findings may allow the development of a therapeutic target in PCOS. PMID:26952754

  20. Cerebral white matter in early puberty is associated with luteinizing hormone concentrations.

    Science.gov (United States)

    Peper, Jiska S; Brouwer, Rachel M; Schnack, Hugo G; van Baal, G Caroline M; van Leeuwen, Marieke; van den Berg, Stéphanie M; Delemarre-Van de Waal, Henriëtte A; Janke, Andrew L; Collins, D Louis; Evans, Alan C; Boomsma, Dorret I; Kahn, René S; Hulshoff Pol, Hilleke E

    2008-08-01

    Puberty is a period in which cerebral white matter grows considerably, whereas gray matter decreases. The first endocrinological marker of puberty in both boys and girls is an increased secretion of luteinizing hormone (LH). Here we investigated the phenotypic association between LH, global and focal gray and white matter in 104 healthy nine-year-old monozygotic and dizygotic twins. Volumetric MRI and voxel-based morphometry were applied to measure global gray and white matter and to estimate relative concentrations of regional cerebral gray and white matter, respectively. A possible common genetic origin of this association (genetic correlation) was examined. Results showed that higher LH levels are associated with a larger global white matter proportion and with higher regional white matter density. Areas of increased white matter density included the cingulum, middle temporal gyrus and splenium of the corpus callosum. No association between LH and global gray matter proportion or regional gray matter density was found. Our data indicate that a common genetic factor underlies the association between LH level and regional white matter density. We suggest that the increase of white matter growth during puberty reported earlier might be directly or indirectly mediated by LH production. In addition, genes involved in LH production may be promising candidate genes in neuropsychiatric illnesses with an onset in early adolescence.

  1. Genetic dissection of epidermal growth factor receptor signaling during luteinizing hormone-induced oocyte maturation.

    Directory of Open Access Journals (Sweden)

    Minnie Hsieh

    Full Text Available Recent evidence that luteinizing hormone (LH stimulation of ovulatory follicles causes transactivation of the epidermal growth factor receptor (EGFR has provided insights into the mechanisms of ovulation. However, the complete array of signals that promote oocyte reentry into the meiotic cell cycle in the follicle are still incompletely understood. To elucidate the signaling downstream of EGFR involved in oocyte maturation, we have investigated the LH responses in granulosa cells with targeted ablation of EGFR. Oocyte maturation and ovulation is disrupted when EGFR expression is progressively reduced. In granulosa cells from mice with either global or granulosa cell-specific disruption of EGFR signaling, LH-induced phosphorylation of MAPK3/1, p38MAPK, and connexin-43 is impaired. Although the LH-induced decrease in cGMP is EGFR-dependent in wild type follicles, LH still induces a decrease in cGMP in Egfr(delta/f Cyp19-Cre follicles. Thus compensatory mechanisms appear activated in the mutant. Spatial propagation of the LH signal in the follicle also is dependent on the EGF network, and likely is important for the control of signaling to the oocyte. Thus, multiple signals and redundant pathways contribute to regulating oocyte reentry into the cell cycle.

  2. Effects of Estrogen and/or Progesterone on Morphology of Pituitary Luteinizing Hormone Cells

    Institute of Scientific and Technical Information of China (English)

    周寿康; 任惠民; 王健; 赵伟; 顾敦瑜; 谢衷明

    2001-01-01

    Objective To identify the morphological characteristics of pituitary luteinizing hormone (LH) cells after exogenous gonadal hormone treatment Methods Effects of various doses of estrogen, progesterone and their combination on morphological parameters, including the size and shape of pituitary LH cells, the size of endocellular vacuoles, were observed and measured by immuno-histochemistry and computer image analysis.Results Different kinds of gonadal hormones could recover the magnified LH cells to the normal level in ovariectomized rats. However, their final effects on the gonadotrophin levels and the cellular morphological characters of the LH cells were different. The low dose of estrogen elicited abundant hormone stored in the LH cells to an easy released status with a lot of different size of vacuoles. On the contrary, the high dose of estrogen inhibited the storage of LH, and the LH cells were filled with secretory granules and few vacuoles. The progesterone could promote the storage of LH in an uneasy released status. The administration of estrogen-progesterone combina tion not only inhibited the storage of LH, but also the release of LH. In this group,the LH cells containing a large amount of secretory granules and a few vacuoles showed a better uniform shape compared with those administrated with high dose of estrogen.Conclusion: Different kinds of gonadal hormones could reverse the excessive secretion of LH and recover the morphological change of LH cells to the normally physiological condition.

  3. Biosynthesis and the conjugation of magnetite nanoparticles with luteinizing hormone releasing hormone (LHRH).

    Science.gov (United States)

    Obayemi, J D; Dozie-Nwachukwu, S; Danyuo, Y; Odusanya, O S; Anuku, N; Malatesta, K; Soboyejo, W O

    2015-01-01

    This paper presents the results of an experimental study of the biosynthesis of magnetite nanoparticles (BMNPs) with particle sizes between 10 nm and 60 nm. The biocompatible magnetic nanoparticles are produced from Magnetospirillum magneticum (M.M.) bacteria that respond to magnetic fields. M.M. bacteria were cultured and used to synthesize magnetite nanoparticles. This was done in an enriched magnetic spirillum growth medium (EMSGM) at different pH levels. The nanoparticle concentrations were characterized with UV-Visible (UV-Vis) spectroscopy, while the particle shapes were elucidated via transmission electron microscopy (TEM). The structure of the particles was studied using X-ray diffraction (XRD), while the hydrodynamic radii, particle size distributions and polydispersity of the nanoparticles were characterized using dynamic light scattering (DLS). Carbodiimide reduction was also used to functionalize the BMNPs with a molecular recognition unit (luteinizing hormone releasing hormone, LHRH) that attaches specifically to receptors that are over-expressed on the surfaces of most breast cancer cell types. The resulting nanoparticles were examined using Fourier Transform Infrared (FTIR) spectroscopy and quantitative image analysis. The implications of the results are then discussed for the potential development of magnetic nanoparticles for the specific targeting and treatment of breast cancer.

  4. Macular pigment optical density and its relationship with serum and dietary levels of lutein and zeaxanthin.

    Science.gov (United States)

    Beatty, Stephen; Nolan, John; Kavanagh, Heather; O'Donovan, Orla

    2004-10-01

    Observational evidence is accumulating that the onset of age-related maculopathy, the leading cause of legal blindness in the Western World, could be delayed, or even averted, with antioxidant supplements. Lutein (L) and zeaxanthin (Z) are two hydroxy-carotenoids with antioxidant activity which accumulate at the macula, where they are collectively known as macular pigment (MP). It has been shown that MP is entirely of dietary origin, and that L and Z levels in serum, diet, and retina correlate. However, the nature of the relationships between L and Z in foodstuffs, blood, and macula is confounded by many variables including processes which influence digestion, absorption, and transport of the compounds in question, and accumulation and stabilization of the carotenoids in the tissues. If macular pigment is protective for age-related maculopathy, a clear understanding of the mechanisms whereby L and Z arrive at the target tissue (retina) from their source (foodstuff) is essential. In this paper, we review the literature germane to this growing area of interest. PMID:15325913

  5. Expression of Leptin Long-form Receptor mRNA in Luteinized Granulosa Cells of Obese Women with Polycystic Ovary Syndrome

    Institute of Scientific and Technical Information of China (English)

    YIN Jie; LIU Yi; LV Liqun; WANG Donghua; GONG Cheng; XIAO Wei; SHENG Hui

    2007-01-01

    To investigate the expression of mRNA of leptin long-form receptor (OB-Rb) in luteinized granulosa cells of obese women with polycystic ovary syndrome (PCOS), and to determine the role of leptin in the physiopathology of PCOS, luteinized granulosa cells were collected from the follicle fluid of 10 obese women who met the diagnostic criteria for PCOS and their BMI was equal to or greater than 25 kg/m2, and at the same time, granulosa cells were collected from 10 normal women undergoing IVF-ET who served as the control group. Some luteinized granulosa cells were taken from normal women for in-vitro culture, into which human leptin of different concentrations was added (0, 10, 100 and 1000 ng/mL). After stimulation with leptin for 48 h, RT-PCR was employed for the detection of the expression of OB-RLmRNA in the luteinized granulosa cells. Our results showed that the level of OB-RLmRNA in luteinized granulosa cells of obese PCOS women was higher than those in the control (P<0.05). In luteinized granulosa cells cultured in vitro and stimulated by human leptin for 48 h, the level of OB-RLmRNA was higher than those without leptin stimulation (P<0.01), and when leptin concentration was at 100 ng/mL, and the level of OB-RLmRNA reached a peak. It is concluded that in obese PCOS women, the level of serum leptin is increased, which promotes the expression of OB-RL in luteinized granulosa cells and increases the sensitivity of the granulosa cells to leptin. Leptin may contribute to anovulation in obese women with PCOS.

  6. Uncoupling Protein 3 Content Is Decreased in Skeletal Muscle of Patients With Type 2 Diabetes

    NARCIS (Netherlands)

    Schrauwen, P.; Hesselink, M.K.C.; Blaak, E.E.; Borghouts, L.B.; Schaart, G.; Saris,; Keizer,

    2001-01-01

    Recently, a role for uncoupling protein-3 (UCP3) in carbohydrate metabolism and in type 2 diabetes has been suggested. Mice overexpressing UCP3 in skeletal muscle showed reduced fasting plasma glucose levels, improved glucose tolerance after an oral glucose load, and reduced fasting plasma insulin l

  7. Calcineurin B homologous protein 3 negatively regulates cardiomyocyte hypertrophy via inhibition of glycogen synthase kinase 3 phosphorylation.

    Science.gov (United States)

    Kobayashi, Soushi; Nakamura, Tomoe Y; Wakabayashi, Shigeo

    2015-07-01

    Cardiac hypertrophy is a leading cause of serious heart diseases. Although many signaling molecules are involved in hypertrophy, the functions of some proteins in this process are still unknown. Calcineurin B homologous protein 3 (CHP3)/tescalcin is an EF-hand Ca(2+)-binding protein that is abundantly expressed in the heart; however, the function of CHP3 is unclear. Here, we aimed to identify the cardiac functions of CHP3. CHP3 was expressed in hearts at a wide range of developmental stages and was specifically detected in neonatal rat ventricular myocytes (NRVMs) but not in cardiac fibroblasts in culture. Moreover, knockdown of CHP3 expression using adenoviral-based RNA interference in NRVMs resulted in enlargement of cardiomyocyte size, concomitant with increased expression of a pathological hypertrophy marker ANP. This same treatment elevated glycogen synthase kinase (GSK3α/β) phosphorylation, which is known to inhibit GSK3 function. In contrast, CHP3 overexpression blocked the insulin-induced phosphorylation of GSK3α/β without affecting the phosphorylation of Akt, which is an upstream kinase of GSK3α/β, in HEK293 cells, and it inhibited both IGF-1-induced phosphorylation of GSK3β and cardiomyocyte hypertrophy in NRVMs. Co-immunoprecipitation experiments revealed that GSK3β interacted with CHP3. However, a Ca(2+)-binding-defective mutation of CHP3 (CHP3-D123A) also interacted with GSK3β and had the same inhibitory effect on GSK3α/β phosphorylation, suggesting that the action of CHP3 was independent of Ca(2+). These findings suggest that CHP3 functions as a novel negative regulator of cardiomyocyte hypertrophy via inhibition of GSK3α/β phosphorylation and subsequent enzymatic activation of GSK3α/β.

  8. Action of luteinizing hormone-releasing hormone in rat ovarian cells: Hormone production and signal transduction

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jian.

    1989-01-01

    The present study was conducted to investigate the hypothesis that the breakdown of membrane phosphoinositides may participate in the actions of luteinizing hormone-releasing hormone (LHRH) on hormone production in rat granulosa cells. In cells prelabeled with ({sup 3}H)inositol or ({sup 3}H)arachidonic acid (AA), treatment with LHRH increased the formation of radiolabeled inositol 1,4,5-trisphosphate (IP{sub 3}) and diacylglycerol (DG), and the release of radiolabeled AA. Since IP{sub 3} induces intracellular Ca{sup 2+} mobilization, changes in the cytosolic free calcium ion concentrations ((Ca{sup 2+})i) induced by LHRH were studied in individual cells using fura-2 microspectrofluorimetry. Alterations in (Ca{sup 2+})i induced by LHRH were rapid and transient, and could be completely blocked by a LHRH antagonist. Sustained perifusion of LHRH resulted in a desensitization of the (Ca{sup 2+})i response to LHRH. LHRH treatment accelerated (Ca{sup 2+})i depletion in the cells perifused with Ca{sup 2+} free medium, indicating the involvement of intracellular Ca{sup 2+} pool(s) in (Ca{sup 2+})i changes. The actions of LHRH on the regulation of progesterone (P{sub 4}) and prostaglandin E{sub 2} (PGE{sub 2}) production were also examined. LHRH increased basal P{sub 4} production and attenuated FSH induced P{sub 4} production. Both basal and FSH stimulated PGE{sub 2} formation were increased by LHRH. Since LHRH also increased the formation of DG that stimulates the activity of protein kinase C, an activator of protein kinase C (12-0-tetradecanolyphorbol-13-acetate: TPA) was used with the Ca{sup 2+} ionophore A23187 and melittin (an activator of phospholipase A{sub 2}) to examine the roles of protein kinase C, Ca{sup 2+} and free AA, respectively, in LHRH action.

  9. Biosynthesis and the conjugation of magnetite nanoparticles with luteinizing hormone releasing hormone (LHRH)

    International Nuclear Information System (INIS)

    This paper presents the results of an experimental study of the biosynthesis of magnetite nanoparticles (BMNPs) with particle sizes between 10 nm and 60 nm. The biocompatible magnetic nanoparticles are produced from Magnetospirillum magneticum (M.M.) bacteria that respond to magnetic fields. M.M. bacteria were cultured and used to synthesize magnetite nanoparticles. This was done in an enriched magnetic spirillum growth medium (EMSGM) at different pH levels. The nanoparticle concentrations were characterized with UV–Visible (UV–Vis) spectroscopy, while the particle shapes were elucidated via transmission electron microscopy (TEM). The structure of the particles was studied using X-ray diffraction (XRD), while the hydrodynamic radii, particle size distributions and polydispersity of the nanoparticles were characterized using dynamic light scattering (DLS). Carbodiimide reduction was also used to functionalize the BMNPs with a molecular recognition unit (luteinizing hormone releasing hormone, LHRH) that attaches specifically to receptors that are over-expressed on the surfaces of most breast cancer cell types. The resulting nanoparticles were examined using Fourier Transform Infrared (FTIR) spectroscopy and quantitative image analysis. The implications of the results are then discussed for the potential development of magnetic nanoparticles for the specific targeting and treatment of breast cancer. - Highlights: • Biosynthesis of MNPs with clinically relevant sizes between 10 and 60 nm. • New insights into the effects of pH and processing time on nanoparticle shapes and sizes. • Successful conjugation of biosynthesized magnetite nanoparticles to LHRH ligands. • Conjugated BMNPs that are monodispersed with potential biomedical relevance. • Magnetic properties of biosynthesized MNPs suggest potential for MRI enhancement

  10. MicroRNA expression and regulation in human ovarian carcinoma cells by luteinizing hormone.

    Directory of Open Access Journals (Sweden)

    Juan Cui

    Full Text Available BACKGROUND: MicroRNAs have been widely-studied with regard to their aberrant expression and high correlation with tumorigenesis and progression in various solid tumors. With the major goal of assessing gonadotropin (luteinizing hormone, LH contributions to LH receptor (LHR-positive ovarian cancer cells, we have conducted a genome-wide transcriptomic analysis on human epithelial ovarian cancer cells to identify the microRNA-associated cellular response to LH-mediated activation of LHR. METHODS: Human ovarian cancer cells (SKOV3 were chosen as negative control (LHR- and stably transfected to express functional LHR (LHR+, followed by incubation with LH (0-20 h. At different times of LH-mediated activation of LHR the cancer cells were analyzed by a high-density Ovarian Cancer Disease-Specific-Array (DSA, ALMAC™, which profiled ∼ 100,000 transcripts with ∼ 400 non-coding microRNAs. FINDINGS: In total, 65 microRNAs were identified to exhibit differential expression in either LHR expressing SKOV3 cells or LH-treated cells, a few of which have been found in the genomic fragile regions that are associated with abnormal deletion or amplification in cancer, such as miR-21, miR-101-1, miR-210 and miR-301a. By incorporating the dramatic expression changes observed in mRNAs, strong microRNA/mRNA regulatory pairs were predicted through statistical analyses coupled with collective computational prediction. The role of each microRNA was then determined through a functional analysis based on the highly-confident microRNA/mRNA pairs. CONCLUSION: The overall impact on the transcriptome-level expression indicates that LH may regulate apoptosis and cell growth of LHR+ SKOV3 cells, particularly by reducing cancer cell proliferation, with some microRNAs involved in regulatory roles.

  11. Luteinizing hormone reduction by the male potency herb, Butea superba Roxb.

    Directory of Open Access Journals (Sweden)

    S. Malaivijitnond

    2010-09-01

    Full Text Available To determine if Butea superba Roxb., a traditional Thai male potency herb, has androgenic activity in 60-day-old male Wistar rats, we measured its effects on the pituitary-testicular axis and sex organs. Intact and orchidectomized adult male rats were subdivided into five groups (10 rats/group: distilled water, Butea superba (BS-10, BS-50, BS-250, and testosterone propionate (TP. They received 0, 10, 50, and 250 mg·kg body weight-1·day-1 BS in distilled water by gavage and 6 mg·kg body weight-1·day-1 TP sc, respectively, during the 30-day treatment period. Blood was collected every 15 days and luteinizing hormone (LH, follicle-stimulating hormone (FSH and testosterone were measured. Changes of weight and histological appearance of sex organs were determined at the end of the 30-day treatment and 15-day post-treatment periods. TP treatment reduced serum FSH and LH levels and significantly increased the weight of the seminal vesicles and epididymis, in accordance with histopathological changes, in both intact and orchidectomized rats. No changes in serum testosterone, LH, and FSH levels were observed in any of the intact rats treated with BS, but a significant increase in seminal vesicle weight was observed only in the BS-250 group. Although a significant reduction in serum LH was detected in the BS-50 and BS-250 groups of orchidectomized rats, no significant change in weight or histology of sex organs was observed. Thus, we conclude that B. superba needs endogenous testosterone to work synergistically to stimulate the accessory sex organ of intact animals and can potentially exhibit an LH reduction effect in orchidectomized animals.

  12. Annual cycle of plasma luteinizing hormone and sex hormones in male and female mallards (Anas platyrhynchos)

    Science.gov (United States)

    Donham, R.S.

    1979-01-01

    Comparisons between 'wild'and 'game farm' mallards (Anas platyrhynchos) were made to assess the differences in the temporal changes of plasma hormones. Seasonal variation in the levels of immunoreactive luteinizing hormone (LH), testosterone, 5 -dihydrotestosterone (DHT), estrone, estradiol-17i?? and progesterone were measured in male and female mallards. In all birds there was a vernal increase in the concentrations of LH and testosterone in plasma which were correlated with the development of the testes and ovaries prior to and during the nesting season. The concentrations of estrogens in the plasma of the females were, in general, slightly higher during the nesting season but were much lower than the levels of testosterone. The highest levels of LH and testosterone in the females coincided precisely with the period of egg laying which occurred approximately one month earlier in game farm females than in wild females. The concentrations of LH and testosterone in the plasma of females decreased rapidly during incubation. In wild males, the decline in levels of these hormones temporally coincided with that of females. In contrast, plasma levels of LH and testosterone of males of the game farm stock remained elevated after the beginning of incubation in females to which they were paired. On the basis of these results and an examination of the literature, it appears that domestication results in: 1) increased reproductive potential through earlier initiation of nesting and by delay of the termination of reproduction until later in the summer; and 2) a decrease in the synchronization of the hormonal events supporting reproduction between the male and female of a pair. Testicular weights and plasma levels of testosterone become higher in game farm and domestic males than in the wild stock but levels of LH are similar.

  13. Lutein alleviates arsenic-induced reproductive toxicity in male mice via Nrf2 signaling.

    Science.gov (United States)

    Li, S G; Xu, S Z; Niu, Q; Ding, Y S; Pang, L J; Ma, R L; Jing, M X; Wang, K; Ma, X M; Feng, G L; Liu, J M; Zhang, X F; Xiang, H L; Li, F

    2016-05-01

    This study aims to investigate the mechanisms involved in the action of lutein (LU) alleviating arsenic-induced reproductive toxicity using mice model. Forty male Kunming mice were received following treatments by gavage: normal saline solution (control), arsenic trioxide (ATO; 5 mg/kg/day), LU (40 mg/kg/day), and ATO + LU (5 mg/kg/day + 40 mg/kg/day). At the end, the mice were killed by cervical dislocation and weighed. Pathological examination was done on the testis. The biomedical parameters including superoxide dismutase (SOD), glutathione (GSH), total antioxidative capability, malondialdehyde (MDA), 8-hydroxydeoxyguanosine (8-OHdG), and reproductive indexes were analyzed. The messenger RNA (mRNA) and protein expression of Nrf2, heme oxygenase 1 (HO-1), glutathione S-transferase (GST), nicotinamide adenine dinucleotide phosphate dehydrogenase, quinone 1 (NQO1) in testis were detected by real-time polymerase chain reaction and Western blot. We found that there was a decrease in sperm count; testis somatic index; the activities of SOD, GSH, total antioxidative capacity (p treated mice, while there was an increase in the levels of sperm abnormalities, MDA, and 8-OHdG than control (p treated with ATO + LU showed recovery of the measured parameters between those of ATO or saline-treated group. The antagonized interaction between ATO and LU was statistically significant (p treated with ATO + LU also showed greater mRNA expression of Nrf2, HO-1, NQO1, and GST than ATO or saline-treated groups. These findings suggest that LU alleviates reproductive toxicity induced by arsenic in male mice via Nrf2 signaling, which implicates a possible mechanism of LU in preventing the reproductive injury, and elucidates that consuming the rich plant sources of LU will alleviate the reproductive toxicity induced by chemicals.

  14. Melatonin effects on luteinizing hormone in postmenopausal women: a pilot clinical trial NCT00288262

    Directory of Open Access Journals (Sweden)

    Kline Lawrence E

    2006-05-01

    Full Text Available Abstract Background In many mammals, the duration of the nocturnal melatonin elevation regulates seasonal changes in reproductive hormones such as luteinizing hormone (LH. Melatonin's effects on human reproductive endocrinology are uncertain. It is thought that the same hypothalamic pulse generator may both trigger the pulsatile release of GnRH and LH and also cause hot flashes. Thus, if melatonin suppressed this pulse generator in postmenopausal women, it might moderate hot flashes. This clinical trial tested the hypothesis that melatonin could suppress LH and relieve hot flashes. Methods Twenty postmenopausal women troubled by hot flashes underwent one week of baseline observation followed by 4 weeks of a randomized controlled trial of melatonin or matched placebo. The three randomized treatments were melatonin 0.5 mg 2.5–3 hours before bedtime, melatonin 0.5 mg upon morning awakening, or placebo capsules. Twelve of the women were admitted to the GCRC at baseline and at the end of randomized treatment for 24-hour sampling of blood for LH. Morning urine samples were collected twice weekly to measure LH excretion. Subjective responses measured throughout baseline and treatment included sleep and hot flash logs, the CESD and QIDS depression self-ratings, and the SAFTEE physical symptom inventory. Results Urinary LH tended to increase from baseline to the end of treatment. Contrasts among the 3 randomized groups were statistically marginal, but there was relative suppression combining the groups given melatonin as contrasted to the placebo group (p Conclusion The data are consistent with the hypothesis that melatonin suppresses LH in postmenopausal women. An effect related to the duration of nocturnal melatonin elevation is suggested. Effects of melatonin on reproductive endocrinology should be studied further in younger women and in men. Larger studies of melatonin effects on postmenopausal symptoms would be worthwhile.

  15. Biosynthesis and the conjugation of magnetite nanoparticles with luteinizing hormone releasing hormone (LHRH)

    Energy Technology Data Exchange (ETDEWEB)

    Obayemi, J.D. [Department of Materials Science and Engineering, African University of Science and Technology (AUST) Abuja, Federal Capital Territory (Nigeria); Department of Materials Science and Engineering, Kwara State University, Malete, Kwara State (Nigeria); Dozie-Nwachukwu, S. [Department of Materials Science and Engineering, African University of Science and Technology (AUST) Abuja, Federal Capital Territory (Nigeria); Sheda Science and Technology Complex (SHESTCO) Abuja, Federal Capital Territory (Nigeria); Danyuo, Y. [Department of Materials Science and Engineering, African University of Science and Technology (AUST) Abuja, Federal Capital Territory (Nigeria); Department of Electronics and Electricals Engineering, Nigerian Turkish Nile University, Abuja (Nigeria); Odusanya, O.S. [Department of Materials Science and Engineering, African University of Science and Technology (AUST) Abuja, Federal Capital Territory (Nigeria); Sheda Science and Technology Complex (SHESTCO) Abuja, Federal Capital Territory (Nigeria); Anuku, N. [Department of Chemistry, Bronx Community College, New York, NY 10453 (United States); Princeton Institute of Science and Technology of Materials (PRISM), Princeton, NJ 08544 (United States); Malatesta, K. [Princeton Institute of Science and Technology of Materials (PRISM), Princeton, NJ 08544 (United States); Department of Mechanical and Aerospace Engineering, Princeton University, NJ 08544 (United States); Soboyejo, W.O., E-mail: soboyejo@princeton.edu [Department of Materials Science and Engineering, African University of Science and Technology (AUST) Abuja, Federal Capital Territory (Nigeria); Princeton Institute of Science and Technology of Materials (PRISM), Princeton, NJ 08544 (United States); Department of Mechanical and Aerospace Engineering, Princeton University, NJ 08544 (United States)

    2015-01-01

    This paper presents the results of an experimental study of the biosynthesis of magnetite nanoparticles (BMNPs) with particle sizes between 10 nm and 60 nm. The biocompatible magnetic nanoparticles are produced from Magnetospirillum magneticum (M.M.) bacteria that respond to magnetic fields. M.M. bacteria were cultured and used to synthesize magnetite nanoparticles. This was done in an enriched magnetic spirillum growth medium (EMSGM) at different pH levels. The nanoparticle concentrations were characterized with UV–Visible (UV–Vis) spectroscopy, while the particle shapes were elucidated via transmission electron microscopy (TEM). The structure of the particles was studied using X-ray diffraction (XRD), while the hydrodynamic radii, particle size distributions and polydispersity of the nanoparticles were characterized using dynamic light scattering (DLS). Carbodiimide reduction was also used to functionalize the BMNPs with a molecular recognition unit (luteinizing hormone releasing hormone, LHRH) that attaches specifically to receptors that are over-expressed on the surfaces of most breast cancer cell types. The resulting nanoparticles were examined using Fourier Transform Infrared (FTIR) spectroscopy and quantitative image analysis. The implications of the results are then discussed for the potential development of magnetic nanoparticles for the specific targeting and treatment of breast cancer. - Highlights: • Biosynthesis of MNPs with clinically relevant sizes between 10 and 60 nm. • New insights into the effects of pH and processing time on nanoparticle shapes and sizes. • Successful conjugation of biosynthesized magnetite nanoparticles to LHRH ligands. • Conjugated BMNPs that are monodispersed with potential biomedical relevance. • Magnetic properties of biosynthesized MNPs suggest potential for MRI enhancement.

  16. Uncoupling clutch size, prolactin, and luteinizing hormone using experimental egg removal.

    Science.gov (United States)

    Ryan, Calen P; Dawson, Alistair; Sharp, Peter J; Williams, Tony D

    2015-03-01

    Clutch size is a key avian fitness and life history trait. A physiological model for clutch size determination (CSD), involving an anti-gonadal effect of prolactin (PRL) via suppression of luteinizing hormone (LH), was proposed over 20 years ago, but has received scant experimental attention since. The few studies looking at a PRL-based mechanistic hypothesis for CSD have been equivocal, but recent experiments utilizing a pharmacological agent to manipulate PRL in the zebra finch (Taeniopygia guttata) found no support for a role of this hormone in clutch size determination. Here, we take a complementary approach by manipulating clutch size through egg removal, examining co-variation in PRL and LH between two breeding attempts, as well as through experimentally-extended laying. Clutch size increased for egg removal females, but not controls, but this was not correlated with changes in PRL or LH. There were also no differences in PRL between egg removal females and controls, nor did PRL levels during early, mid- or late-laying of supra-normal clutches predict clutch size. By uncoupling PRL, LH and clutch size in our study, several key predictions of the PRL-based mechanistic model for CSD were not supported. However, a positive correlation between PRL levels late in laying and days relative to the last egg (clutch completion) provides an alternative explanation for the equivocal results surrounding the conventional PRL-based physiological model for CSD. We suggest that females coordinate PRL-mediated incubation onset with clutch completion to minimize hatching asynchrony and sibling hierarchy, a behavior that is amplified in females laying larger clutches.

  17. Generation of Monoclonal Antibodies against Non-structural Protein 3AB of Foot-and-Mouth Disease Virus

    Institute of Scientific and Technical Information of China (English)

    Tong Lin; Junjun Shao; Huiyun Chang; Shandian Gao; Guozheng Cong; Junzheng Du

    2012-01-01

    To identify linear epitopes on the non-structural protein 3AB of foot-and-mouth disease virus (FMDV),BABL/c mice were immunized with the 3AB protein and splenocytes of BALB/c mice were fused with myeloma Sp2/0 cells.Two hybridoma monoclonal antibodies (mAbs) cell lines against the 3AB protein of foot-and-mouth disease virus (FMDV) were obtained,named C6 and E7 respectively.The microneutralization titer was 1∶1024 for mAb C6,and 1∶512 for E7.Both mAbs contain kappa light chains,and were of subclass IgG2b.In order to define the mAbs binding epitopes,the reactivity of these mAbs against FMDV were examined by indirect ELISA.The results showed that both mAbs can react with FMDV,but had no cross-reactivity with Swine Vesicular Disease (SVD) antigens.The titers in abdomen liquor were 1∶5×106 for C6 and 1∶2×106 for E7.In conclusion,the mAbs obtained from this study are specific for the detection of FMDV,can be used for etiological and immunological researches on FMDV,and have potential use in diagnosis and future vaccine designs.

  18. Hepatitis C virus non-structural protein 3 interacts with cytosolic 5'(3'-deoxyribonucleotidase and partially inhibits its activity.

    Directory of Open Access Journals (Sweden)

    Chiu-Ping Fang

    Full Text Available Infection with hepatitis C virus (HCV is etiologically involved in liver cirrhosis, hepatocellular carcinoma and B-cell lymphomas. It has been demonstrated previously that HCV non-structural protein 3 (NS3 is involved in cell transformation. In this study, a yeast two-hybrid screening experiment was conducted to identify cellular proteins interacting with HCV NS3 protein. Cytosolic 5'(3'-deoxyribonucleotidase (cdN, dNT-1 was found to interact with HCV NS3 protein. Binding domains of HCV NS3 and cellular cdN proteins were also determined using the yeast two-hybrid system. Interactions between HCV NS3 and cdN proteins were further demonstrated by co-immunoprecipitation and confocal analysis in cultured cells. The cellular cdN activity was partially repressed by NS3 protein in both the transiently-transfected and the stably-transfected systems. Furthermore, HCV partially repressed the cdN activity while had no effect on its protein expression in the systems of HCV sub-genomic replicons and infectious HCV virions. Deoxyribonucleotidases are present in most mammalian cells and involve in the regulation of intracellular deoxyribonucleotides pools by substrate cycles. Control of DNA precursor concentration is essential for the maintenance of genetic stability. Reduction of cdN activity would result in the imbalance of DNA precursor concentrations. Thus, our results suggested that HCV partially reduced the cdN activity via its NS3 protein and this may in turn cause diseases.

  19. A double-blind, placebo-controlled study on the effects of lutein and zeaxanthin on neural processing speed and efficiency.

    Directory of Open Access Journals (Sweden)

    Emily R Bovier

    Full Text Available Lutein and zeaxanthin are major carotenoids in the eye but are also found in post-receptoral visual pathways. It has been hypothesized that these pigments influence the processing of visual signals within and post-retina, and that increasing lutein and zeaxanthin levels within the visual system will lead to increased visual processing speeds. To test this, we measured macular pigment density (as a biomarker of lutein and zeaxanthin levels in brain, critical flicker fusion (CFF thresholds, and visual motor reaction time in young healthy subjects (n = 92. Changes in these outcome variables were also assessed after four months of supplementation with either placebo (n = 10, zeaxanthin only (20 mg/day; n = 29 or a mixed formulation containing 26 mg/day zeaxanthin, 8 mg/day lutein, and 190 mg/day mixed omega-3 fatty acids (n = 25. Significant correlations were found between retinal lutein and zeaxanthin (macular pigment and CFF thresholds (p<0.01 and visual motor performance (overall p<0.01. Supplementation with zeaxanthin and the mixed formulation (considered together produced significant (p<0.01 increases in CFF thresholds (∼12% and visual motor reaction time (∼10% compared to placebo. In general, increasing macular pigment density through supplementation (average increase of about 0.09 log units resulted in significant improvements in visual processing speed, even when testing young, healthy individuals who tend to be at peak efficiency.

  20. Research progress on extraction, function and application of lutein%叶黄素的提取、功效和应用研究进展

    Institute of Scientific and Technical Information of China (English)

    王彦博; 石燕; 唐慧安

    2011-01-01

    叶黄素属于类胡萝卜素色素之一,功效独特,具有多种生物活性,应用广泛,为当今国际上研究的热点之一.叶黄素的提取技术较多,主要有溶剂抽提法、微波提取法、超声波提取法、超临界CO2萃取法、酶介质有机溶剂提取等.随着进一步的深入研究,对于相关机理的认识将不断加深、技术手段迅速进步,叶黄素的功效作用机制将逐步被揭示,为更好地应用叶黄素而奠定基础.%Lutein, which has biological activities and is widely used, is one of carotenoid pigments. Study about lutein is one of the hottest research points in the world. The extraction methods of lutein mainly include solvent extraction, microwave assistant extraction, ultrasonic assistant extraction, supercritical CO, extraction and enzymatic medium organic solvent extraction, etc. With further study and technical progress, mechanism of lutein function will be revealed and this will be helpful for better application of lutein.

  1. Discussion on Improved Determination Methods for Lutein%改进叶黄素测定方法的探讨

    Institute of Scientific and Technical Information of China (English)

    黄秋婵; 许元明; 韦友欢; 黄敏敏; 黄晓云

    2012-01-01

    [目的]为改进叶黄素的测定方法.[方法]采用丙酮和酒精混合液(体积比1∶1)进行萃取,用分光光度法在不同的萃取时间对胡萝卜、黄槐决明花和柑橘皮中的叶黄素含量进行测定.[结果]胡萝卜萃取12 h时其叶黄素含量达最高(0.315 5 mg/gFW),可见12h是胡萝卜中叶黄素的最佳萃取时间;黄槐决明花萃取14 h时其叶黄素含量最高(0.818 5 mg/gFW),说明14 h是黄槐花中叶黄素的最佳萃取时间;柑橘皮萃取8h时其叶黄素含量达最高(0.001 9 mg/gFW),可知8h是柑橘皮中叶黄素的最佳萃取时间.[结论]为改进叶黄素的测定方法提供了理论依据.%[Objective] To improve determination method for lutein. [Method] By using acetone and alcohol volume ratio (1:1) to extract, the lutein content in Daucus carrot, Senna surattensis and Citrus reticulata Banco at different extraction time were determined with spectropho-tometry method. [ Result] The results showed that lutein content in Daucus carrot was up to the highest at 12 h (0.315 5 mg/gFW) , and Senna sumttensisn at 14 h(0. 818 5 mg/gFW) , Citrus reticulata Banco at 8 h(0. 001 9 mg/gFW). [ Conclusion] The study will provide theoretical basis for improving lutein determination method.

  2. Determination of beta-carotene and lutein available from green leafy vegetables by an in vitro digestion and colonic fermentation method.

    Science.gov (United States)

    Serrano, José; Goñi, Isabel; Saura-Calixto, Fulgencio

    2005-04-20

    Green leafy vegetables (Spinacea oleracea, Cnidoscolus aconitifolius, and Solanum americanum) contain a high amount of beta-carotene (27-52 mg/100 g of dry sample) and lutein (140-193 mg/100 g of dry sample). The amount of beta-carotene and lutein released from the food matrix by the action of digestive enzymes ranged from 22 to 67% and from 27 to 77%, respectively. There was a significant correlation between the enzymatic release of carotenoids (lutein + beta-carotene) and the content of Klason lignin, nonstarch polysaccharides, and resistant protein. The carotenoids released by the in vitro colonic fermentation ranged from 2 to 11%, and part of them (0.251-4.03 mg/100 g of original dry sample) remained intact in the fermentation media and could be potentially absorbed in the colon. A significant part of carotenoids seems to be unavailable in the intestinal tract (16% in S. oleracea to 58% in C. aconitifolius). PMID:15826042

  3. Increased uncoupling protein 3 content does not affect mitochondrial function in human skeletal muscle in vivo

    OpenAIRE

    Hesselink, M.K.C.; Greenhaff, P L; Constantin-Teodosu, D.; Hultman, E; Saris, W. H. M.; Nieuwlaat, R.; Schaart, G.; Kornips, C.F.P.; P. Schrauwen

    2003-01-01

    Phosphocreatine (PCr) resynthesis rate following intense anoxic contraction can be used as a sensitive index of in vivo mitochondrial function. We examined the effect of a diet-induced increase in uncoupling protein 3 (UCP3) expression on postexercise PCr resynthesis in skeletal muscle. Nine healthy male volunteers undertook 20 one-legged maximal voluntary contractions with limb blood flow occluded to deplete muscle PCr stores. Exercise was performed following 7 days consumption of low-fat (L...

  4. Seasonal variation in plasma testosterone, luteinizing hormone concentrations and LH-RH responsiveness in mature, male rusa deer (Cervus rusa timorensis).

    Science.gov (United States)

    van Mourik, S; Stelmasiak, T; Outch, K H

    1986-01-01

    Plasma testosterone and luteinizing hormone (LH) concentrations in immobilized or yarded rusa stags (Cervus rusa timorensis) were investigated over a two-year period. Testosterone concentrations showed a minor elevation in autumn (May) and reached maximal levels in late winter-early spring (August) coinciding with the rut. Luteinizing hormone in plasma was only detectable from January to May. Maximal responsiveness of the pituitary-gonadal axis to LH-RH stimulation was recorded in August. The combination of Fentaz (fentanylcitrate and azaperone) and Rompun (xylazine hydrochloride) for immobilizing deer influences hypothalamic function. PMID:2869876

  5. Secondary Analyses of the Effects of Lutein/Zeaxanthin on Age-Related Macular Degeneration Progression AREDS2 Report No.3

    OpenAIRE

    Emily Y Chew; Clemons, Traci E.; SanGiovanni, John Paul; Danis, Ronald P; Ferris, Frederick L.; Elman, Michael J.; Antoszyk, Andrew; Ruby, Alan; Orth, David; Bressler, Susan B.; Fish, Gary; Hubbard, Baker; Klein, Michael; Chandra, Suresh; Blodi, Barbara

    2014-01-01

    The Age-Related Eye Disease Study (AREDS) formulation for treatment of age-related macular degeneration contains vitamins C, E, beta-carotene and zinc with copper. Age-Related Eye Disease Study 2 (AREDS2) assessed the value of substituting lutein/zeaxanthin in the AREDS formulation because of the demonstrated risk of lung cancer from beta-carotene in smokers and former smokers. As previously reported in a secondary analysis, AREDS2 participants taking lutein/zeaxanthin with or without omega-3...

  6. Identification, cDNA Cloning, and Characterization of Luteinizing Hormone Beta Subunit (lhb) Gene in Catla catla.

    Science.gov (United States)

    Rather, Mohd Ashraf; Bhat, Irfan Ahmad; Sharma, Rupam

    2016-01-01

    Reproductive hormones play a significant role in the gonadal development and gametogenesis process of animals. In the present study luteinizing hormone beta, (lhb) subunit gene was cloned and characterized from the brain of Catla catla. The lhb full-length of cDNA sequence is 629 bp which consists of 43bp 5'-UTR (untranslated region) 447bp, ORF(open reading frame) and 139 bp of 3'-UTR respectively. The coding region of lhb gene encoded a peptide of 148 amino acids. The coding sequence of lhb gene consist of a single N-linked glycosylation site (NET) and 12 cysteine knot residues. Phylogenetic analysis of C. catla Lhβ deduced amino acid sequence showed high similarity with Carassius auratus followed by Gobiocypris rarus. 3D structure Lhβ protein comprises of five β-sheets and six coils/loops. The qPCR results revealed lhb mRNA is mainly expressed in the pituitary, ovary while moderate expression was observed in brain and testis. To best our knowledge, this is the first report on the identification, molecular characterization and structural information regarding luteinizing hormone in Indian major carp. PMID:26980432

  7. Lutein, a Natural Carotenoid, Induces α-1,3-Glucan Accumulation on the Cell Wall Surface of Fungal Plant Pathogens.

    Science.gov (United States)

    Otaka, Junnosuke; Seo, Shigemi; Nishimura, Marie

    2016-01-01

    α-1,3-Glucan, a component of the fungal cell wall, is a refractory polysaccharide for most plants. Previously, we showed that various fungal plant pathogens masked their cell wall surfaces with α-1,3-glucan to evade plant immunity. This surface accumulation of α-1,3-glucan was infection specific, suggesting that plant factors might induce its production in fungi. Through immunofluorescence observations of fungal cell walls, we found that carrot (Daucus carota) extract induced the accumulation of α-1,3-glucan on germlings in Colletotrichum fioriniae, a polyphagous fungal pathogen that causes anthracnose disease in various dicot plants. Bioassay-guided fractionation of carrot leaf extract successfully identified two active substances that caused α-1,3-glucan accumulation in this fungus: lutein, a carotenoid widely distributed in plants, and stigmasterol, a plant-specific membrane component. Lutein, which had a greater effect on C. fioriniae, also induced α-1,3-glucan accumulation in other Colletotrichum species and in the phylogenetically distant rice pathogen Cochliobolus miyabeanus, but not in the rice pathogen Magnaporthe oryzae belonging to the same phylogenetic subclass as Colletotrichum. Our results suggested that fungal plant pathogens reorganize their cell wall components in response to specific plant-derived compounds, which these pathogens may encounter during infection. PMID:27483218

  8. Peripheral serum progesterone and luteinizing hormone concentrations of goats during synchronization of estrus and ovulation with prostaglandin F2 alpha.

    Science.gov (United States)

    Ott, R S; Nelson, D R; Hixon, J E

    1980-09-01

    Prostaglandin F2 alpha (PGF2 alpha) (2 doses, 11 days apart) was given to 20 mixed-breed dairy does to synchronize estrus and ovulation. The dose of PGF2 alpha used was the free-acid equivalent of 8 mg which was divided between 2 injections at 0800 and 1200 hours. At the initiation of treatments, does were from day 0 (estrus) to day 18 of the estrous cycle. Seventeen of the doses exhibited estrus within a mean (+/- SE) interval of 53 +/- 2 hours after the first 0800-hour injection. Peripheral progesterone concentrations determined at daily intervals indicated that PGF2 alpha was luteolytic as early as day 4 of the cycle. Does were in the 8th to 12th days of the cycle at the time of the 2nd treatments with PGF2 alpha. Estrus was observed in all 20 does at 50 +/- 1 hour after the 0800-hour injections. Serum progesterone concentrations confirmed that luteolysis occurred in all of the does. In 19 does, concentrations of luteinizing hormone characteristic of a preovulatory peak were observed 55 +/- 2 hours after the 2nd 0800-hour injection. One doe did not demonstrate a luteinizing hormone peak within the 72-hour period. Laparotomies were performed 6 days after estrus, and ovaries were examined for corpora lutea. The mean number of corpora lutea was 2.0 +/- 1.0. PMID:7192524

  9. Lycopene, Lutein and Zeaxanthin May Reduce Faecal Blood, Mucus and Pus but not Abdominal Pain in Individuals with Ulcerative Colitis

    Science.gov (United States)

    Głąbska, Dominika; Guzek, Dominika; Zakrzewska, Paulina; Włodarek, Dariusz; Lech, Gustaw

    2016-01-01

    Background: The main symptom of ulcerative colitis is diarrhoea, which is often accompanied by painful tenesmus and faecal blood and mucus. It sometimes co-occurs with abdominal pain, fever, feeling of fatigue, loss of appetite and weight loss. Some dietary factors have been indicated as important in the treatment of ulcerative colitis. The aim of the study was to analyse the association between retinoid intake (total vitamin A, retinol, β-carotene, α-carotene, β-cryptoxanthin, lycopene, lutein and zeaxanthin) and ulcerative colitis symptoms (abdominal pain, faecal blood, faecal mucus, faecal pus) in individuals with ulcerative colitis in remission. Methods: Assessment of diet was based on self-reported data from each patient’s dietary records taken over a period of three typical, random days (2 weekdays and 1 day of the weekend). Results: A total of 56 individuals with ulcerative colitis in remission (19 males and 37 females) were recruited for the study. One in every four individuals with ulcerative colitis in remission was characterised as having inadequate vitamin A intake. Higher lycopene, lutein and zeaxanthin intakes in individuals with ulcerative colitis in remission were associated with lower faecal blood, mucus and pus but not with lower incidence of abdominal pain. Higher carotene intake in individuals with ulcerative colitis in remission may contribute to higher incidence of faecal mucus. Conclusions: Optimising intake of specific retinoids may enhance disease control in individuals with ulcerative colitis. Prospective studies, including patient reported and objective outcomes, are required to confirm this. PMID:27706028

  10. The adhesion of mussel foot protein-3 to TiO2 surfaces: the effect of pH

    Science.gov (United States)

    Yu, Jing; Wei, Wei; Menyo, Matthew S.; Masic, Admir; Waite, J. Herbert; Israelachvili, Jacob N.

    2013-01-01

    The underwater adhesion of marine mussels relies on mussel foot proteins (mfps) rich in the catecholic amino acid 3, 4-dihydroxyphenylalanine (Dopa). As a side-chain, Dopa is capable of strong bidentate interactions with a variety of surfaces, including many minerals and metal oxides. Titanium is among the most widely used medical implant material and quickly forms a TiO2 passivation layer under physiological conditions. Understanding the binding mechanism of Dopa to TiO2 surfaces is therefore of considerable theoretical and practical interest. Using a surface forces apparatus, we explored the force-distance profiles and adhesion energies of mussel foot protein 3 (mfp-3) to TiO2 surfaces at three different pHs (pH3, 5.5 and 7.5). At pH3, mfp-3 showed the strongest adhesion force on TiO2, with an adhesion energy of ~ −7.0 mJ/m2. Increasing the pH gives rise to two opposing effects: (1) increased oxidation of Dopa, thus decreasing availability for the Dopa-mediated adhesion, and (2) increased bidentate Dopa-Ti coordination, leading to the further stabilization of the Dopa group and thus an increasing of adhesion force. Both effects were reflected in the resonance-enhanced Raman spectra obtained at the three deposition pHs. The two competing effects give rise to a higher adhesion force of mfp-3 on TiO2 surface at pH 7.5 than at pH 5.5. Our results suggest that Dopa-containing proteins and synthetic polymers have great potential as coating materials for medical implant materials, particularly if redox activity can be controlled. PMID:23452271

  11. Membrane-association properties of avian encephalomyelitis virus protein 3A

    International Nuclear Information System (INIS)

    Avian encephalomyelitis virus (AEV) protein 3A is a membrane-interacting protein containing a stretch of 21 hydrophobic amino acid residues. Membrane-association property was assayed using chick embryo brain (CEB) cells transfected with the fusion GFP-3A and its various deletion mutants demonstrate that 3A is integrally interacted with membranes by its hydrophobic domain and further defines that the motif of amino acid residues 45-51, the most C-terminal hydrophobic domain essential for this feature. Expression of 3A in transfected CEB cells results in membrane permeability modifications through association of the third motif with membranes, which can be demonstrated by release of lactate dehydrogenase (LDH) into the medium. Furthermore, the localization of the protein 3A in transfected CEB and Cos-7 cells exhibited an overlapping staining pattern with an endoplasmic reticulum (ER) and involved in the disassembly of the Golgi apparatus under double-staining and confocal microscopic observations, whereas the 3A mutants lacking amino acids 45-51 could not localize to the ER and display an intact Golgi morphology as seen in the mutant devoid of the complete hydrophobic domain after transfection. Taken together, our results demonstrate that the motif (aa 45-51) of the transmembrane domain might be fundamental for the stable interaction of the protein 3A with the ER membrane regardless of the cell types. Although this motif was deleted, the resultant protein did not localize to the ER, which directly results in the loss of the ability to block the ER-to-Golgi transport by 3A protein and hence makes the morphology of the Golgi apparatus return to normal

  12. Genetic analysis on 3'-terminal flanking region of uncoupling protein 3 in different pig breeds

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    The 3′-terminal flanking region of porcine uncoupling protein 3 (UCP3) was cloned, the sequence data revealed 15 nucleotide substitutions among Landrace and three Chinese native pig breeds named Neijiang, Minpig and Erhualian. The continuous 9 polymorphic sites were checked by PCR-RFLP, the results indicatedthat Erhualian had extraordinary gene frequency, presented most significant difference by χ2 test compared with Landrace, Largewhite, Neijiang and Minpig respectively, significant level compared with Meishan; and Meishan also had significant difference compared with Landrace and Minpig respectively. These results canbe concluded that Taihu pigs have special genetic characteristics among pig breeds.

  13. Cold Shock Domain Protein 3 Regulates Freezing Tolerance in Arabidopsis thaliana*

    OpenAIRE

    Kim, Myung-Hee; Sasaki, Kentaro; Imai, Ryozo

    2009-01-01

    In response to cold, Escherichia coli produces cold shock proteins (CSPs) that have essential roles in cold adaptation as RNA chaperones. Here, we demonstrate that Arabidopsis cold shock domain protein 3 (AtCSP3), which shares a cold shock domain with bacterial CSPs, is involved in the acquisition of freezing tolerance in plants. AtCSP3 complemented a cold-sensitive phenotype of the E. coli CSP quadruple mutant and displayed nucleic acid duplex melting activity, suggesting that AtCSP3 also fu...

  14. Vasoactive intestinal polypeptide and peptide histidine methionine. Presence in human follicular fluid and effects on DNA synthesis and steroid secretion in cultured human granulosa/lutein cells

    DEFF Research Database (Denmark)

    Gräs, S; Ovesen, P; Andersen, A N;

    1994-01-01

    Vasoactive intestinal polypeptide (VIP) and peptide histidine methionine (PHM) originate from the same precursor molecule, prepro VIP. In the present study we examined the concentrations of VIP and PHM in human follicular fluid and their effects on cultured human granulosa/lutein cells. Follicular...

  15. Bilateral vanished testes diagnosed with a single blood sample showing very high gonadotropins (follicle-stimulating hormone and luteinizing hormone) and very low inhibin B

    DEFF Research Database (Denmark)

    Thorup, Jørgen Mogens; Petersen, Bodil Laub; Kvist, Kolja;

    2011-01-01

    Objective. In boys with cryptorchidism median serum values of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) are higher and median serum values of inhibin B lower than in normal controls. Serum values of inhibin B reflect the state of germinative epithelium in cryptorchid testes....

  16. Expression of receptors for gastric-inhibitory polypeptide, luteinizing hormone, and vasopressin in normal adrenals and cortisol-secreting adrenocortical tumors in dogs

    NARCIS (Netherlands)

    Galac, S.; Kars, V.J.; Klarenbeek, S.; Teerds, K.J.; Mol, J.A.; Kooistra, H.S.

    2010-01-01

    Domest Anim Endocrinol. 2010 Jul;39(1):63-75. Epub 2010 Mar 11. Expression of receptors for luteinizing hormone, gastric-inhibitory polypeptide, and vasopressin in normal adrenal glands and cortisol-secreting adrenocortical tumors in dogs. Galac S, Kars VJ, Klarenbeek S, Teerds KJ, Mol JA, Kooistra

  17. Supression of the steroid-primed luteinizing hormone surge in the female rat by sodium dimethyldithiocarbamate: Relationship to hypothalamic catecholamines and GnRH neuronal activation

    Science.gov (United States)

    In female rodents, hypothalamic norepinephrine (NE) has a role in stimulating the secretion of gonadotropin-releasing hormone (GnRH) that triggers the ovulatory surge of luteinizing hormone (LH). NE synthesis from dopamine requires the presence of dopamine--hydroxylase (DH) an...

  18. Quick method for the determination of the luteinizing hormone (LH). Eine schnelle Methode der radioimmunologischen Bestimmung des luteinisierenden Hormons (LH)

    Energy Technology Data Exchange (ETDEWEB)

    Koch, R.

    1985-01-17

    A radioimmunological determination method for luteinizing hormone (LH) was developed, whose time requirement could be reduced from 2 days down to 2 hours. All of the parameters influenced by the test were studied and for the test correspondingly optimized. The biggest advantages of this method are the accuracy in the nanogram area, the non-dependence on the cooperation and discipline of the patients (immunological LH-measurements in urine), and the lack of time-consuming preparations and increasing costs in large treatment centers, where, for example, a large number of patients for insemination or in vitro fertilization would need to be observed at the same time. The results were tested for correctness against clinical and clinical-chemical criteria and compared with results of recently used methods. (TRV).

  19. Leucine-enkephalin-like immunoreactivity is localized in luteinizing hormone-producing cells in the axolotl (Ambystoma mexicanum) pituitary.

    Science.gov (United States)

    Suzuki, Hirohumi; Yamamoto, Toshiharu

    2014-02-01

    In this study, we used immunohistochemical techniques to determine the cell type of leucine-enkephalin (Leu-ENK)-immunoreactive cells in the axolotl (Ambystoma mexicanum) pituitary. Immunoreactive cells were scattered throughout the pars distalis except for the dorso-caudal portion. These cells were immuno-positive for luteinizing hormone (LH), but they were immuno-negative for adrenocorticotrophic, growth, and thyroid-stimulating hormones, as well as prolactin. Immunoelectron microscopy demonstrated that Leu-ENK-like substance and LH co-localized within the same secretory granules. Leu-ENK secreted from gonadotrophs may participate in LH secretion in an autocrine fashion, and/or may participate in the release of sex steroids together with LH. PMID:24034715

  20. Global but not gonadotrope-specific disruption of Bmal1 abolishes the luteinizing hormone surge without affecting ovulation

    DEFF Research Database (Denmark)

    Chu, Adrienne; Zhu, Lei; Blum, Ian D;

    2013-01-01

    While there is evidence for a circadian regulation of the preovulatory luteinizing hormone (LH) surge, the contributions of individual tissue clocks to this process remain unclear. We studied female mice deficient in the Bmal1 gene (Bmal1(-/-)), which is essential for circadian clock function...... pituitaries rhythmically express clock components throughout all cycle-stages. To determine the role of the gonadotrope clock in the preovulatory LH and FSH surge process, we generated mice that specifically lack BMAL1 in gonadotropes (GBmal1KO). GBmal1KO females exhibited a modest elevation in both proestrus...... and baseline LH levels across all estrous stages. BMAL1 elimination from gonadotropes also led to increased variability in estrous cycle length, yet GBmal1KO animals were otherwise reproductively normal. Together our data suggest that the intrinsic clock in gonadotropes is dispensable for LH surge regulation...

  1. Leucine-enkephalin-like immunoreactivity is localized in luteinizing hormone-producing cells in the axolotl (Ambystoma mexicanum) pituitary.

    Science.gov (United States)

    Suzuki, Hirohumi; Yamamoto, Toshiharu

    2014-02-01

    In this study, we used immunohistochemical techniques to determine the cell type of leucine-enkephalin (Leu-ENK)-immunoreactive cells in the axolotl (Ambystoma mexicanum) pituitary. Immunoreactive cells were scattered throughout the pars distalis except for the dorso-caudal portion. These cells were immuno-positive for luteinizing hormone (LH), but they were immuno-negative for adrenocorticotrophic, growth, and thyroid-stimulating hormones, as well as prolactin. Immunoelectron microscopy demonstrated that Leu-ENK-like substance and LH co-localized within the same secretory granules. Leu-ENK secreted from gonadotrophs may participate in LH secretion in an autocrine fashion, and/or may participate in the release of sex steroids together with LH.

  2. Luteinizing hormone-releasing hormone receptor-mediated delivery of mitoxantrone using LHRH analogs modified with PEGylated liposomes

    Directory of Open Access Journals (Sweden)

    Yingna He

    2010-09-01

    Full Text Available Yingna He, Linhua Zhang, Cunxian SongKey Laboratory of Biomedical Material of Tianjin, Institute of Biomedical Engineering, Peking Union Medical College and Chinese Academy of Medical Sciences, Tianjin, ChinaAbstract: A sterically stabilized, mitoxantrone-loaded liposome, tailored to target luteinizing hormone-releasing hormone (LHRH receptor overexpressing cells, was developed to promote the efficiency of intracellular delivery of mitoxantrone through receptor-mediated endocytosis. Liposomes were prepared by lipid film hydration and an ultrasound dispersion process. Thiolated gonadorelin with affinity for the LHRH receptor was chemically coupled to N-[(3-maleimide-1-oxopropyl aminopropyl polyethylene glycol-carbamyl] distearoyl-l-phosphatidyl-ethanolamine via a thioether bond and subsequently inserted into polyethylene glycol-grafted liposomes. The liposome was characterized in terms of its size, ligand density, drug loading, and leakage properties. The targeting nature and antitumor effects of the liposomes were evaluated in vitro using cultured MCF-7 breast cancer cells. A protein assay of ligand coupling to the liposomal surface indicated that more than 60% of the LHRH peptides were inserted into the liposome bilayer. Up to 1.0 mg/mL of stable liposomal mitoxantrone loading was achieved, with approximately 98% of this being entrapped within the liposomes. In vitro cell culture studies revealed that the gonadorelin-modified liposomes bound to their target cells had significantly higher affinity and better antitumor efficiency than generic drug-loaded liposomes. These events were presumed to occur through specific interactions of the LHRH with its cognate receptors on the cell surface. It was concluded that the targeting properties of the delivery system would potentially improve the therapeutic benefits of mitoxantrone, as compared with nontargeted liposomes.Keywords: mitoxantrone, liposome, luteinizing hormone-releasing hormone receptor

  3. Radioautographic identification of lactogen binding sites in rat median eminence using 125I-human growth hormone

    International Nuclear Information System (INIS)

    The binding characteristics of human growth hormone were exploited to identify radioautographically lactogen binding sites in the rat median eminence following systemic injection 125I-human growth hormone bound preferentially to the lateral palisade zone, a region of median eminence rich in dopamine and LHRH. Coinjection of 125I-human growth hormone with an excess of unlabeled human growth hormone or ovine prolactin, but not bovine growth hormone, competitively blocked 125I-human growth hormone binding to the external median eminence. These observations provide direct evidence of recognition sites for lactogenic hormones in a discrete region of the median eminence associated with hypothalamic regulation of hypophyseal prolactin and luteinizing hormone secretion. Median eminence lactogen binding sites may mediate presumed direct effects of lactogenic hormones on the reproductive functions of the hypophysiotropic hypothalamus. (orig.)

  4. Identification of a group of Haemophilus influenzae penicillin-binding proteins that may have complementary physiological roles

    Energy Technology Data Exchange (ETDEWEB)

    Malouin, F.; Parr, T.R. Jr.; Bryan, L.E. (Eli Lilly Company, Indianapolis, IN (USA))

    1990-02-01

    (35S)penicillin bound to different Haemophilus influenzae proteins in assays performed at 20, 37, or 42{degrees}C. Penicillin-binding proteins 3a, 3b, 4, and 4' formed a group characterized by their affinity for moxalactam, cefotaxime, and piperacillin. Penicillin-binding protein 4' showed specific properties that may reflect its complementary role in septation.

  5. Expression of Nonfusion Extracellular Porcine Zona Pellucida Protein 3β in E. coli

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Objective To obtain the recombinant nonfusion extracellular porcine zona pellucida protein 3β (pZP3β ) in E. coliMethods By modificated the transition initiation region (TIR) in primers, synthetic nucleotide was gained by PCR. Such gene was cloned into pET-3c vector and trans-formed into E. coli BL21(DE3)pLysS.Results The recombinant nonfusion extracellular pZP3β was expressed in E. coli to 10% of total cellular proteins, and identified by the Western blot method.Conclusion Modification of nucleotide without changing amino acid sequences is an effective means to increase non fusion expression rate of recombinant proteins, such as pZP3β in E. coli.

  6. Sushi Domain-Containing Protein 3: A Potential Target for Breast Cancer.

    Science.gov (United States)

    Yu, Zhenghong; Jiang, Enze; Wang, Xinxing; Shi, Yaqin; Shangguan, Anna Junjie; Zhang, Luo; Li, Jie

    2015-06-01

    Aromatase inhibitors (AIs) are the most effective endocrine treatment for estrogen receptor α-positive (ERα+) postmenopausal breast cancer. Identification of biomarkers that are able to predict AIs responsiveness of patients is a key for successful treatment. The currently used biomarkers for tamoxifen responsiveness, which including ERα as well as progesterone receptor can only predict part of the potential responders to AIs treatment. Sushi domain-containing protein 3 (SUSD3) is a potential novel biomarker of AIs responsiveness. The lack of SUSD3 expression in breast cancer tissue can be an important predictor for non-responsiveness to AI. Here we reviewed the property and function of SUSD3, its usage as a biomarker and the practicability for SUSD3 to become a target for immune therapy. We suggest this protein can be potentially measured or targeted for prevention, diagnostic, and therapeutic purposes for estrogen or progesterone-dependent disorders including breast cancer in women. PMID:25556073

  7. Structural and biochemical analysis of nuclease domain of clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein 3 (Cas3).

    Science.gov (United States)

    Mulepati, Sabin; Bailey, Scott

    2011-09-01

    RNA transcribed from clustered regularly interspaced short palindromic repeats (CRISPRs) protects many prokaryotes from invasion by foreign DNA such as viruses, conjugative plasmids, and transposable elements. Cas3 (CRISPR-associated protein 3) is essential for this CRISPR protection and is thought to mediate cleavage of the foreign DNA through its N-terminal histidine-aspartate (HD) domain. We report here the 1.8 Å crystal structure of the HD domain of Cas3 from Thermus thermophilus HB8. Structural and biochemical studies predict that this enzyme binds two metal ions at its active site. We also demonstrate that the single-stranded DNA endonuclease activity of this T. thermophilus domain is activated not by magnesium but by transition metal ions such as manganese and nickel. Structure-guided mutagenesis confirms the importance of the metal-binding residues for the nuclease activity and identifies other active site residues. Overall, these results provide a framework for understanding the role of Cas3 in the CRISPR system.

  8. Analyzing binding data.

    Science.gov (United States)

    Motulsky, Harvey J; Neubig, Richard R

    2010-07-01

    Measuring the rate and extent of radioligand binding provides information on the number of binding sites, and their affinity and accessibility of these binding sites for various drugs. This unit explains how to design and analyze such experiments.

  9. Induction of chemokines and prostaglandin synthesis pathways in luteinized human granulosa cells: potential role of luteotropin withdrawal and prostaglandin F2α in regression of the human corpus luteum.

    Science.gov (United States)

    Luo, Wenxiang; Salih, Sana M; Bormann, Charles L; Wiltbank, Milo C

    2015-12-01

    Our objective was to determine the effects of prostaglandin F2α (PGF2α) and withdrawal of luteotropic stimulants (forskolin or hCG) on expression of chemokines and prostaglandin-endoperoxide synthase 2 (PTGS2) in luteinized human granulosa cells. Human granulosa cells were collected from 12 women undergoing oocyte retrieval and were luteinized in vitro with forskolin or hCG. In first experiment, granulosa-lutein cells were treated with PGF2α, the primary luteolytic hormone in most species. In second experiment, granulosa cells that had been luteinized for 8 d had luteotropins withdrawn for 1, 2, or 3 d. Treatment with PGF2α induced mRNA for chemokine (c-x-c motif) ligand 2 (CXCL2) and CXC ligand 8 (CXCL8; also known as interleukin-8) in granulosa cells luteinized for 8 d but not in cells that were only luteinized for 2 d. Similarly, luteinization of human granulosa cells for 8 d with forskolin or hCG followed by withdrawal of luteotropic stimulants, not only decreased P4 production, but also increased mRNA concentrations for CXCL8, CXCL-2 (after forskolin withdrawal), and PTGS2. These results provide evidence for two key steps in differentiation of luteolytic capability in human granulosa cells. During 8 d of luteinization, granulosa cells acquire the ability to respond to luteolytic factors, such as PGF2α, with induction of genes involved in immune function and PG synthesis. Finally, a decline in luteotropic stimuli triggers similar pathways leading to induction of PTGS2 and possibly intraluteal PGF2α production, chemokine expression, leukocyte infiltration and activation, and ultimately luteal regression. PMID:26679166

  10. β-Microseminoprotein binds CRISP-3 in human seminal plasma

    OpenAIRE

    Udby, Lene; Lundwall, Åke; Johnsen, Anders H.; Fernlund, Per; Valtonen-André, Camilla; Blom, Anna M.; Lilja, Hans; Borregaard, Niels; Kjeldsen, Lars; Bjartell, Anders

    2005-01-01

    β -Microseminoprotein (MSP) and cysteine-rich secretory protein 3 (CRISP-3) are abundant constituents of human seminal plasma. Immunoprecipitation and gel filtration of seminal plasma proteins combined with examination of the proteins in their pure form showed that MSP and CRISP-3 form stable, non-covalent complexes. CRISP-3 binds MSP with very high affinity, as evidenced by surface plasmon resonance. Due to far higher abundance of MSP in prostatic fluid, it manifests large overcapacity for C...

  11. Characterization of recombinant DNA derived-human luteinizing hormone in vitro and in vivo: efficacy in ovulation induction and corpus luteum support

    International Nuclear Information System (INIS)

    The present data are the first, to the authors knowledge, to demonstrate the production feasibility of a commercially available medication of pure human luteinizing hormone from recombinant DNA technology (rechLH). The rechLH preparation achieved ovulation induction and corpus luteum support in the primate menstrual cycle. The observations described herein indicate the opportunity for significant improvement in the treatment of infertile women and men who require gonadal stimulation. Recombinant DNA-derived gonadotropin products, rechLH in this case, will have several therapeutic advantages compared with current medications extracted from urine. These advantages include (1) better reliability of an available supply of hormone and (2) improved treatment flexibility in determining the optimal dose ratio of follicle-stimulating hormone and luteinizing hormone or avoidance of the long-acting effects of human chorionic gonadotropin, as the needs of individual patients may dictate

  12. Characterization of recombinant DNA derived-human luteinizing hormone in vitro and in vivo: efficacy in ovulation induction and corpus luteum support

    Energy Technology Data Exchange (ETDEWEB)

    Simon, J.A.; Danforth, D.R.; Hutchison, J.S.; Hodgen, G.D.

    1988-06-10

    The present data are the first, to the authors knowledge, to demonstrate the production feasibility of a commercially available medication of pure human luteinizing hormone from recombinant DNA technology (rechLH). The rechLH preparation achieved ovulation induction and corpus luteum support in the primate menstrual cycle. The observations described herein indicate the opportunity for significant improvement in the treatment of infertile women and men who require gonadal stimulation. Recombinant DNA-derived gonadotropin products, rechLH in this case, will have several therapeutic advantages compared with current medications extracted from urine. These advantages include (1) better reliability of an available supply of hormone and (2) improved treatment flexibility in determining the optimal dose ratio of follicle-stimulating hormone and luteinizing hormone or avoidance of the long-acting effects of human chorionic gonadotropin, as the needs of individual patients may dictate.

  13. Selective induction of apoptosis by the cytotoxic analog AN-207 in cells expressing recombinant receptor for luteinizing hormone-releasing hormone

    OpenAIRE

    Danila, Daniel C; Schally, Andrew V.; Nagy, Attila; Alexander, Joseph M

    1999-01-01

    The selectivity of ligands specific for certain cells can be used to preferentially target chemotherapeutic compounds to neoplastic cells. Human breast, ovarian, endometrial, and prostatic cancers express receptors that can mediate the delivery of targeted cytotoxic compounds to neoplastic cells. Recently, a potent derivative of 2-pyrrolinodoxorubicin (AN-201) conjugated to [d-Lys6] luteinizing hormone-releasing hormone (LH-RH) (AN-207), was demonstrated to be less toxic than the nonconjugate...

  14. Rheological characterization of coloured oil-in-water food emulsions with lutein and phycocyanin added to the oil and aqueous phases

    OpenAIRE

    Sousa, Isabel; Batista, Ana Paula; Raymundo, Anabela; Empis, José

    2006-01-01

    The use of natural colourings in food products presents nutritional advantages, and certain pigments are associated with functional properties, e.g. antioxidant effects. This can be very advantageous in food products with high fat contents like mayonnaises. The aim of this work was to study the effect of adding natural pigments, lutein and phycocyanin, to the water and oil phases, respectively, of oil-in-water pea protein-stabilized emulsions, beyond the desirable and expected develo...

  15. Hubungan Kadar βHCG Praevakuasi, Gambaran Histopatologi, dan Kista Lutein dengan Performa βHCG pada Penderita Mola Hidatidosa yang Berkembang Menjadi PTG dan Kembali Normal

    Directory of Open Access Journals (Sweden)

    Yudi Mulyana Hidayat

    2014-12-01

    Full Text Available The incidence of trophoblastic diseases in Indonesia and developing countries is relatively high compared to the developed countries. The incidence of gestational trophoblast tumors (GTT after the evacuation of a hydatidiform mole ranges from 10% to 20%. Several clinical variables have been studied as the risk factors for malignancy, including the pre-evacuation level of beta human chorionic gonadotropin (βHCG, histopathological appearance, and the presence of lutein cysts. The purpose of this study was to determine the relationship between βHCG decline and pre-evacuation βHCG levels, histopathological features, and the lutein cysts status in patients with moles. This study was a case control study of patients with complete hydatidiform mole in Dr. Hasan Sadikin General Hospital during the period of 2007-2011. The results revealed that there was a significant correlation between the level of βHCG ≥100,000 mIU/mL and post-molar malignancy (p<0.05. There was also a significant relationship between the histopathologic feature of excessive post-molar cell proliferation and malignancy (p<0.05 and between the presence of lutein cyst and post-molar malignancy (p<0.05. This study concludes that the pre-evacuation βHCG level ≥100.000 mIU/mL, excessive proliferation, and the presence of lutein cysts are correlated with malignancy after molar evacuation. These risk factors are useful to differentiate whether a complete hydatidiform mole will become malignant or remain benign.

  16. Estradiol feedback effects on the alpha-subunit mRNA in the sheep pituitary gland: correlation with serum and pituitary luteinizing hormone concentrations.

    OpenAIRE

    Landefeld, T; Kepa, J.; Karsch, F.

    1984-01-01

    The effects of estradiol feedback on pituitary luteinizing hormone (LH) content, serum LH concentration, and in vitro-translated alpha subunit was examined in the ewe. Three animal models were used representing positive, negative, and no estradiol feedback. Two experiments were carried out: (i) anestrous ewes were treated acutely with five Silastic estradiol implants to induce a LH surge (positive feedback) and (ii) ovariectomized ewes were treated chronically with an estradiol implant (negat...

  17. Role of endogenous opiates in the expression of negative feedback actions of androgen and estrogen on pulsatile properties of luteinizing hormone secretion in man.

    OpenAIRE

    Veldhuis, J D; Rogol, A D; Samojlik, E; Ertel, N H

    1984-01-01

    We have tested the participation of endogenous opiate pathways in the negative feedback actions of gonadal steroids on pulsatile properties of luteinizing (LH) hormone release in normal men. To this end, sex steroid hormones were infused intravenously at dosages that under steady state conditions selectively suppressed either the frequency or the amplitude of the pulsatile LH signal. The properties of pulsatile LH secretion were assessed quantitatively by computerized analysis of LH series de...

  18. Plasma lutein and zeaxanthin and other carotenoids as modifiable risk factors for age-related maculopathy and cataract: the POLA Study.

    OpenAIRE

    Delcourt, Cécile; Carrière, Isabelle; Delage, Martine; Barberger-Gateau, Pascale; Schalch, Wolfgang

    2006-01-01

    PURPOSE: To assess the associations of plasma lutein and zeaxanthin and other carotenoids with the risk of age-related maculopathy (ARM) and cataract in the population-based Pathologies Oculaires Li? ?'Age (POLA) Study. METHODS: Retinal photographs were graded according to the international classification. ARM was defined by the presence of late ARM (neovascular ARM, geographic atrophy) and/or soft indistinct drusen (>125 microm) and/or soft distinct drusen (>125 microm) associated with pigme...

  19. Impairment of dendritic cell functions in patients with adaptor protein-3 complex deficiency.

    Science.gov (United States)

    Prandini, Alberto; Salvi, Valentina; Colombo, Francesca; Moratto, Daniele; Lorenzi, Luisa; Vermi, William; De Francesco, Maria Antonia; Notarangelo, Lucia Dora; Porta, Fulvio; Plebani, Alessandro; Facchetti, Fabio; Sozzani, Silvano; Badolato, Raffaele

    2016-06-30

    Hermansky-Pudlak syndrome type 2 (HPS2) is a primary immunodeficiency due to adaptor protein-3 (AP-3) complex deficiency. HPS2 patients present neutropenia, partial albinism, and impaired lysosomal vesicles formation in hematopoietic cells. Given the role of dendritic cells (DCs) in the immune response, we studied monocyte-derived DCs (moDCs) and plasmacytoid DCs (pDCs) in two HPS2 siblings. Mature HPS2 moDCs showed impaired expression of CD83 and DC-lysosome-associated membrane protein (LAMP), low levels of MIP1-β/CCL4, MIG/CXCL9, and severe defect of interleukin-12 (IL-12) secretion. DCs in lymph-node biopsies from the same patients showed a diffuse cytoplasm reactivity in a large fraction of DC-LAMP(+) cells, instead of the classical dot-like stain. In addition, analysis of pDC-related functions of blood-circulating mononuclear cells revealed reduced interferon-α secretion in response to herpes simplex virus-1 (HSV-1), whereas granzyme-B induction upon IL-3/IL-10 stimulation was normal. Finally, T-cell costimulatory activity, as measured by mixed lymphocyte reaction assay, was lower in patients, suggesting that function and maturation of DCs is abnormal in patients with HPS2.

  20. Effects of dietary supplementation with a combination of fish oil, bilberry extract, and lutein on subjective symptoms of asthenopia in humans.

    Science.gov (United States)

    Kawabata, Fuminori; Tsuji, Tomoko

    2011-12-01

    The aim of this study was to determine the effects of dietary supplementation with a combination of fish oil, bilberry extract, and lutein on subjective symptoms of asthenopia in humans by a double- blind, randomized, parallel-group, and placebo-controlled trial. In the Active group, eleven subjects ingested a supplement containing omega-3 fatty acid-rich fish oil (docosahexaenoic acid 783 mg/day, eicosapentaenoic acid 162 mg/day), bilberry extract (anthocyanidin 59 mg/day), and lutein (17.5 mg/day) in soft gel capsule form, every day for 4 weeks. In the Placebo group, nine subjects ingested placebo capsules. Before and after supplementation, subjects completed a questionnaire to determine their asthenopia symptoms and were also assessed for mental fatigue symptom by the visual analog scale (VAS) test. Asthenopia symptoms such as "stiff shoulder, low back pain", "frustration", "dry-eye", and "stuffy head" were improved in the Active group. Furthermore, a score of mental fatigue was improved after 4 weeks of supplementation, and no side effects were observed after the 4-week supplementation and a 2-week washout period in the Active group. These results suggest that dietary supplementation with the combination of omega-3 fatty acid-rich fish oil, bilberry extract, and lutein may safely improve subjective symptoms of asthenopia and mental fatigue in humans.

  1. Inhibin A, inhibin B, follicle-stimulating hormone, luteinizing hormone, estradiol, and sex hormone-binding globulin levels in 473 healthy infant girls

    DEFF Research Database (Denmark)

    Chellakooty, M; Schmidt, I M; Haavisto, A M;

    2003-01-01

    The early postnatal regulation of reproductive hormones seems to be more complex in girls than in boys. The aim of this study was to describe inhibins A and B, FSH, LH, estradiol, and SHBG in a large prospective cohort of 473 unselected, healthy, 3-month-old girls. In full term, appropriate...

  2. Inhibin A, inhibin B, follicle-stimulating hormone, luteinizing hormone, estradiol, and sex hormone-binding globulin levels in 473 healthy infant girls

    DEFF Research Database (Denmark)

    Chellakooty, M; Schmidt, I M; Haavisto, A M;

    2003-01-01

    The early postnatal regulation of reproductive hormones seems to be more complex in girls than in boys. The aim of this study was to describe inhibins A and B, FSH, LH, estradiol, and SHBG in a large prospective cohort of 473 unselected, healthy, 3-month-old girls. In full term, appropriate......-for- gestational-age girls (n = 355) hormones showed a marked interindividual variation, with concentrations up to pubertal values [medians (95% confidence intervals): inhibin B, 82 pg/ml (...

  3. Corpus luteum derived copper, zinc-superoxide dismutase serves as a luteinizing hormone-release inhibiting factor in sheep.

    Science.gov (United States)

    Al-Gubory, Kaïs H; Huet, Jean-Claude; Pernollet, Jean-Claude; Martal, Jacques; Locatelli, Alain

    2003-01-31

    In the present study, we report the purification and characterization of a polypeptide from the sheep corpus luteum of pregnancy with a potent luteinizing hormone-release inhibiting factor (LH-RIF) bioactivity that stained as a single band in SDS-PAGE with an apparent molecular mass of 16000 Da. The amino acid sequences obtained after sequence analysis of peptides derived from the trypsin digestion of LH-RIF were subjected to a protein data bank search and were found to be identical with regions of sheep copper, zinc-superoxide dismutase (Cu,Zn-SOD). The measured mass of LH-RIF (15604.2+/-1.9 Da) was found to be similar to the theoretical mass of sheep Cu,Zn-SOD (15603.5 Da), with a disulfide bond and N acetylated alanine at the N-terminus. The inhibitory action of Cu,Zn-SOD on pulsatile LH secretion would suggest that this antioxidant may play an important role, either independently or in concert with some neurotransmitters, in the neuroendocrine regulation of sheep female reproductive function.

  4. Heterodimers and homodimers of inhibin subunits have different paracrine action in the modulation of luteinizing hormone-stimulated androgen biosynthesis

    International Nuclear Information System (INIS)

    Inhibin, a gonadal hormone capable of preferential suppression of pituitary follicle-stimulating hormone (FSH) secretion, has recently been purified. The major form of this protein is an αβ heterodimer encoded by two separate genes. In contrast to the FSH-suppressing action of the αβ heterodimer, the ββ homodimer stimulates FSH secretion. Luteinizing hormone (LH)-secreting pituitary cells and gonadal androgen-producing cells have long been shown to form a closed-loop feedback axis. Based on recent studies demonstrated the FSH stimulation of inhibin biosynthesis by ovarian granulosa and testis Sertoli cells, an additional closed-loop feedback axis exists between pituitary FSH- and gonadal inhibin-producing cells. Because uncharacterized Sertoli cell factors have been suggested to either stimulate or inhibit androgen production by testicular Leydig cells, the authors have tested the intragonadal paracrine actions of heterodimers and homodimers of inhibin subunits. In primary cultures of testis cells, the αβ heterodimer of inhibin enhances Leydig cell androgen biosynthesis stimulated by LH, whereas the ββ homodimer suppresses androgen production. The data indicate that the inhibin-related gene products synthesized by Sertoli and granulosa cells may form heterodimers or homodimers to serve as intragonadal paracrine signals in the modulation of LH-stimulated androgen biosynthesis and allow cross-communication between the two feedback loops

  5. A controlled study of human chorionic gonadotrophin induced ovulation versus urinary luteinizing hormone surge for timing of intrauterine insemination.

    Science.gov (United States)

    Martinez, A R; Bernadus, R E; Voorhorst, F J; Vermeiden, J P; Schoemaker, J

    1991-10-01

    Forty-eight patients in a programme of intrauterine insemination (IUI) were randomized in a cross-over study. All were stimulated with clomiphene citrate (CC) and inseminated either after follicular rupture induced by human chorionic gonadotrophin (HCG) or after a spontaneous urinary luteinizing hormone (LH) surge. The HCG was administered when follicles of 18-22 mm in diameter were observed on ultrasound and IUI was performed 37-40 h thereafter. The monitoring of a urinary LH peak was carried out using a rapid urinary LH test. IUI took place approximately 22 h after detection of the LH surge. Overall, the pregnancy rates were 9.3% (4/43) after HCG induced ovulation and 20.5% (9/44) after spontaneous ovulation (P = 0.12). Analysis of mid-cycle events showed that following sonographic criteria, the HCG injection was performed significantly earlier in the cycle compared with the spontaneous LH surge. In addition, the mean diameter of the preovulatory follicles was significantly smaller and insemination was substantially earlier in the HCG induced cycles. These findings suggest that a beneficial effect arises from allowing the natural process of final follicular maturation to occur. PMID:1752926

  6. Ablation of GalNAc-4-sulfotransferase-1 enhances reproduction by altering the carbohydrate structures of luteinizing hormone in mice.

    Science.gov (United States)

    Mi, Yiling; Fiete, Dorothy; Baenziger, Jacques U

    2008-05-01

    Luteinizing hormone (LH), produced in the anterior lobe of the pituitary, is a member of the hypothalamic-pituitary-gonad axis that is required for production of the sex hormones estradiol, progesterone, and testosterone. Perturbations in levels of hormones associated with this axis can result in defects in sexual development and maturity. LH bears unique N-linked carbohydrate units that terminate with a sulfated N-acetylgalactosamine structure (GalNAc-4-SO(4)) that mediates its clearance from the blood. To determine the significance of this terminal structure, we ablated the gene encoding the sulfotransferase responsible for sulfate addition to GalNAc on LH, GalNAc-4-sulfotransferase-1 (GalNAc-4-ST1) in mice. Mice lacking GalNAc-4-ST1 exhibited increased levels of circulating LH. In male mice, this resulted in elevated levels of testosterone and precocious maturation of testis and seminal vesicles. Female mice lacking GalNAc-4-ST1 demonstrated elevated estrogen levels and exhibited precocious sexual maturation and increased fecundity. Female mice remained in estrus for prolonged periods and produced almost 50% more litters per mouse than wild-type mice over the same period of time. Thus, sulfate modification of the terminal glycosylation of LH plays a central role in regulating the hypothalamic-pituitary-gonad axis in vivo.

  7. Isolation and characterization of testis-specific cDNAs for luteinizing hormone beta-subunit in the rat.

    Science.gov (United States)

    Zhang, F P; Rannikko, A; Huhtaniemi, I

    1995-05-25

    To study further the unexpected expression of the luteinizing hormone (LH) beta-subunit in the rat testis, we identified in a rat testicular cDNA library three LH beta clones with lengths of 3.2, 2.4 and 0.86 kb (TLH beta 1, TLH beta 2 and TLH beta 3). The clones were identified using a 32P-labeled cDNA probe complimentary to the known rat pituitary LH beta mRNA. Clone TLH beta 2 corresponds in size to the main LH beta mRNA species (2.7 kb) detected by Northern hybridization in the rat testis. Sequence analysis indicated that the different sizes of the three clones are due to alternative RNA splicing and differences at the 5' ends of transcripts. The sequence of one open reading frame deduced from TLH beta 1 is almost identical with the pituitary LH beta peptide, differing only in three amino acids in the putative signal peptide. It might encode a functional testis-specific LH beta peptide. Shorter transcripts from clones TLH beta 2 and TLH beta 3 may correspond to short testicular LH beta peptides. The present findings provide further evidence in the rat for expression of testis-specific mRNA variants of the LH beta gene. Their translation products may form a novel class of testicular para/autocrine factors. PMID:7763258

  8. Adrenocortical Production Is Associated with Higher Levels of Luteinizing Hormone in Nonobese Women with Polycystic Ovary Syndrome

    Directory of Open Access Journals (Sweden)

    Luciana Tock

    2014-01-01

    Full Text Available Objective. Insulin resistance (IR and ovarian and adrenal hyperandrogenism are a common finding in women with polycystic ovary syndrome (PCOS. The aim of the present study was to access possible differences in insulin resistance, gonadotropins, and androgens production in obese and nonobese PCOS women. Study Design. We studied 37 PCOS women (16 nonobese and 21 obese and 18 nonobese controls. Fasting glucose, insulin, androgens, and gonadotropins levels were determined. Salivary cortisol was measured basal and in the morning after dexamethasone (DEX 0.25 mg. Results. Nonobese PCOS women showed higher basal salivary cortisol and serum dehydroepiandrosterone sulfate and luteinizing hormone (LH levels than controls and obese PCOS. These hormones levels did not differ between the obese and control groups. After DEX administration no differences were found between the three groups. In PCOS women, salivary cortisol levels showed negative correlation with BMI (r=-0.52; P=0.001 and insulin (r=-0.47; P=0.003 and positive correlation with LH (r=0.40; P=0.016. Conclusion. Our results show an increased adrenocortical production in nonobese PCOS women, not related to IR and associated with a normal hypothalamic-pituitary-adrenal suppression. Higher LH levels might be involved in this event.

  9. Role of Serum Follicle Stimulating Hormone, Luteinizing Hormone, Testosterone and Prolactin Levels in Azoospermic Male Partner of Subfertile Couple.

    Science.gov (United States)

    Begum, N; Anwary, S A; Alfazzaman, M; Mahzabin, Z; Nahar, K; Rahman, M M; Mostafa, M A

    2016-04-01

    This cross sectional study was carried out in the Infertility Unit, Department of Obstetrics and Gynaecology, Bangabandhu Sheikh Mujib Medical University (BSMMU) from January 2011 and June 2013. Eighty one (81) consecutive azoospermic male partner of married couple, aged 20-50 years with at least two years of subfertility and no known endocrinopathy and ejaculatory dysfunction were included in this study to find out their abnormal hormonal pattern. None of them had received any form of treatment within the last 3 months prior to hormonal evaluation. Men with hypertension, recent fever, chemo or radiation exposure were excluded from the study. Eight weeks interval two semen analyses were done in the Andrology Laboratory of above department following standard WHO guideline, 2004. Using standard ELISA technique, serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone and prolactin were measured/assayed/estimated. The results of this study demonstrated that 40 (49.4%) men had normal endocrine pattern against 51 (50.6%) with endocrinopathy. The former may be related to obstructive azoospermia, which needs further analyses. Both the increased FSH (>11.1mIU/ml) and LH (>7.6mIU/ml) were observed in 25 (30.9%) men, only elevated FSH (>11.1mIU/ml) in 9(11.1%), and only elevated LH (>7.6mIU/ml) in 7(8.6%). Low testosterone level (prolactin (<2.5ng/dl) in 5(6.2%).

  10. Protective role of ginger on lead induced derangement in plasma testosterone and luteinizing hormone levels of male sprague dawley rats

    International Nuclear Information System (INIS)

    Background: Lead is one of the most serious environmental threats to human health especially in developing countries. It damages multiple body systems including the reproductive system. Ginger's antioxidant and androgenic activity is reported in multiple animal studies. The aim of this study was to investigate the ameliorative effect of Zingiber officinale (ginger) on lead induced derangement in plasma testosterone and luteinizing hormone (LH) levels of male rats. Methods: Sixty adult male Sprague Dawley rats were used in this study in four groups. Group A served as normal control, Group B received 0.3% lead acetate in drinking water, Group C and group D received supplementary 0.5 and 1 gm/Kg bodyweight of ginger respectively along with lead acetate in drinking water. Five rats from each group were sacrificed at the end of 2nd, 4th and 6th weeks. Serum testosterone and LH levels were analysed using ELISA technique. Results: After co administration with different doses of ginger, serum testosterone level which was significantly decreased in lead treated group, showed a significant rise as compared to lead treated group. LH levels which had exhibited no significant change by lead treatment, after co administration with different doses of ginger, again showed no significant change. Conclusion: Oral administration of ginger ameliorated lead induced testicular toxicity in male rats by increasing serum testosterone level at all durations which might be a product of both its androgenic and antioxidant properties. (author)

  11. Transforming growth factor-β1 increases lysyl oxidase expression by downregulating MIR29A in human granulosa lutein cells.

    Science.gov (United States)

    Fang, Ying; Chang, Hsun-Ming; Cheng, Jung-Chien; Klausen, Christian; Leung, Peter C K; Yang, Xiaokui

    2016-09-01

    Lysyl oxidase (LOX), a key enzyme in the formation and stabilization of the extracellular matrix, is expressed in granulosa cells and plays a critical role in the regulation of granulosa cell differentiation, oocyte maturation and ovulation. To date, the regulation of LOX expression in human granulosa cells remains largely unknown. In this study, using primary and immortalized human granulosa lutein cells, we demonstrated that transforming growth factor (TGF)-β1 (TGFB1) upregulated LOX expression and downregulated microRNA-29a (MIR29A) expression via a TGF-β type I receptor-mediated signaling pathway. Additionally, we showed that MIR29A downregulated the expression of LOX in both types of cells. Furthermore, the downregulation of MIR29A contributed to the TGFB1-induced increase in LOX expression because the inhibition of MIR29A with a MIR29A inhibitor not only reversed the MIR29A-induced downregulation of LOX but also enhanced the TGFB1-induced upregulation of LOX. Our findings suggest that TGFB1 and MIR29A may play essential roles in the regulation of extracellular matrix remodeling during the periovulatory phase. PMID:27335131

  12. 超临界流体抗溶剂法制备叶黄素/羟丙甲纤维素邻苯二甲酸酯纳米微胶囊%Nanoencapsulation of Lutein with Hydroxypropylmethyl Cellulose Phthalate by Supercritical Antisolvent

    Institute of Scientific and Technical Information of China (English)

    金鹤阳; 夏菲; 江翠兰; 赵亚平; 何琳

    2009-01-01

    Lutein was nano-encapsuled with hydroxypropylmethyl cellulose phthalate (HPMCP) to maintain its bioactivity and to avoid thermal/light degradation. Supercritical antisolvent precipitation was applied to prepare lutein/HPMCP nano-capsule. The effects of several operating parameters on the yield, lutein loading, encapsulation efficiency, particle size and particle size distribution of the nanocapsule were investigated. The mean diameter of nanocapsules ranged from 163 nm to 219 nm under appropriate experimental conditions. The result of scanning electron microscope showed that the nanocapsules were nearly spherical. The highest yield reached 95.35% when the initial concentration of lutein was saturated. The highest lutein loading of 15.80% and encapsulation efficiency of 88.41% were obtained under the conditions of 11 MPa, 40℃ and CHPMCP:Clutein=5:1. The results may pro-mote the application of lutein in food industry.

  13. Insulin-like growth factors, insulin-like growth factor-binding proteins, insulin-like growth factor-binding protein-3 protease, and growth hormone-binding protein in lipodystrophic human immunodeficiency virus-infected patients

    DEFF Research Database (Denmark)

    Haugaard, Steen B; Andersen, Ove; Hansen, Birgitte R;

    2004-01-01

    concentration were increased (>90%, P II, IGFBP-3, and IGFBP-3 protease were similar between groups (all P > .5), whereas, in LIPO, IGFBP-1 and IGFBP-2 were reduced (-36%, P ...). In pooled groups, total IGF-I, free IGF-I, total IGF-II, and IGFBP-3, respectively, correlated inversely with age (all P ... study groups, including suppressed GH, and increased GHBP in LIPO, argue against GH resistance of GH-sensitive tissues in LIPO compared with NONLIPO; however, this notion awaits examination in dose-response studies. Furthermore, our data suggest that IGFBP-3 protease is a significant regulator...

  14. Nucleoside triphosphatase and RNA helicase activities associated with GB virus B nonstructural protein 3.

    Science.gov (United States)

    Zhong, W; Ingravallo, P; Wright-Minogue, J; Skelton, A; Uss, A S; Chase, R; Yao, N; Lau, J Y; Hong, Z

    1999-09-01

    GB virus B (GBV-B) is a positive-stranded RNA virus that belongs to the Flaviviridae family. This virus is closely related to hepatitis C virus (HCV) and causes acute hepatitis in tamarins (Saguinus species). Nonstructural protein 3 (NS3) of GBV-B contains sequence motifs predictive of three enzymatic activities: serine protease, nucleoside triphosphatase (NTPase), and RNA helicase. The N-terminal serine protease has been characterized and shown to share similar substrate specificity with the HCV NS3 protease. In this report, a full-length GBV-B NS3 protein was expressed in Escherichia coli and purified to homogeneity. This recombinant protein was shown to possess polynucleotide-stimulated NTPase and double-stranded RNA (dsRNA) unwinding activities. Both activities were abolished by a single amino acid substitution, from the Lys (K) residue in the conserved walker motif A (or Ia) "AXXXXGK(210)S" to an Ala (A), confirming that they are intrinsic to GBV-B NS3. Kinetic parameters (K(m) and k(cat)) for hydrolysis of various NTPs or dNTPs were obtained. The dsRNA unwinding activity depends on the presence of divalent metal ions and ATP and requires an RNA duplex substrate with 3' unpaired regions (RNAs with 5' unpaired regions only or with blunt ends are not suitable substrates for this enzyme). This indicates that GBV-B NS3 RNA helicase unwinds dsRNA in the 3' to 5' direction. Direct interaction of the GBV-B NS3 protein with a single-stranded RNA was established using a gel-based RNA bandshift assay. Finally, a homology model of GBV-B NS3 RNA helicase domain based on the 3-dimensional structure of the HCV NS3 helicase that shows a great similarity in overall structure and surface charge distribution between the two proteins was proposed. PMID:10497107

  15. Role of Multidrug Resistance Protein 3 in Antifungal-Induced Cholestasis.

    Science.gov (United States)

    Mahdi, Zainab M; Synal-Hermanns, Uta; Yoker, Aylin; Locher, Kaspar P; Stieger, Bruno

    2016-07-01

    Drug-induced liver injury is an important clinical entity resulting in a considerable number of hospitalizations. While drug-induced cholestasis due to the inhibition of the bile salt export pump (BSEP) is well investigated, only limited information on the interaction of drugs with multidrug resistance protein 3 (MDR3) exists and its role in the pathogenesis of drug-induced cholestasis is poorly understood. Therefore, we aimed to study the interaction of drugs with MDR3 and the effect of drugs on canalicular lipid secretion in a newly established polarized cell line system that serves as a model of canalicular lipid secretion. LLC-PK1 cells were stably transfected with human Na(+)-taurocholate cotransporting polypeptide, BSEP, MDR3, and ABCG5/G8 and grown in the Transwell system. Apical phospholipid secretion and taurocholate transport were assayed to investigate the effect of selected drugs on MDR3-mediated phospholipid secretion as well as inhibition of BSEP. The established cell line displayed vectorial bile salt transport and specific phosphatidylcholine secretion into the apical compartment. The antifungal azoles, posaconazole, itraconazole, and ketoconazole, significantly inhibited MDR3-mediated phosphatidylcholine secretion. In contrast, amoxicillin clavulanate and troglitazone did not interfere with MDR3 activity. Drugs interfering with MDR3 activity did not display a parallel inhibition of BSEP. Our in vitro model for MDR3-mediated phospholipid secretion facilitates parallel screening for MDR3 and BSEP inhibitors. Our data demonstrate that the cholestatic potential of certain drugs may be aggravated by simultaneous inhibition of BSEP and MDR3. PMID:27112167

  16. Quantitative and qualitative changes in serum luteinizing hormone after injectable testosterone undecanoate treatment in hypogonadal men

    Institute of Scientific and Technical Information of China (English)

    Yi-QunGU; Zheng-YanGE; Gui-YuanZHANG; WilliamJ.Bremner

    2000-01-01

    Aim: To clarify the immuno-active LH (i-LH) and bioactive LH (b-LH) responses and qualitative changes in the circulating LH to testosterone undecanoate (TU) injection. Methods: Eight men with Klinefelter's syndrome were recruited for the study. They received crossover injections of TU at doses of 500 and 1000 mg. Serum i-LH and b-LH levels before and at various time intervals after TU injection were measured and the serum i-LH, b-LH, b-LH/i-LH (B/I) and testosterone/sex hormone-binding globulin (T/SHBG) ratio in LH-responders and LH non-responders were compared. Results: A parallel suppression of serum i-LH and b-LH was consistent with their overall high correlation between each other (r = 0.84, P < 0. 001). Mean serum i-FSH levels were decreased by TU injection at both doses without dose-response effects. LH-responders had lower baseline serum i-LH and b-LH, and higher E2 levels and T/SHBG ratio. There was a quantitative change in serum LH as induced by TU without qualitative change within LH-responders os LH-non-responders. Conclusion: A high loading dose (1000 mg) of TU is important for the initial suppression of LH. With the lower dose (500 mg), repeated injections will be required to attain such LH suppression for the purpose of fertility regulation. The lower baseline serum i-LH level may be an intrinsic characteristic of LH-responders. ( Asian J Androl 2000 ; 2 : 65 - 71 )

  17. A partial deletion in non-structural protein 3A can attenuate foot-and-mouth disease virus in cattle

    Science.gov (United States)

    The role of non-structural protein 3A in foot-and-mouth disease virus (FMDV) on the virulence in cattle has received significant attention. Particularly, a characteristic 10–20 amino acid deletion has been implicated as being responsible for virus attenuation in cattle: a 10 amino acid deletion in t...

  18. Expression patterns of Wnt signaling component, secreted frizzled-related protein 3 in astrocytoma and glioblastoma

    Science.gov (United States)

    PEĆINA-ŠLAUS, NIVES; KAFKA, ANJA; VAROŠANEC, ANA MARIA; MARKOVIĆ, LEON; KRSNIK, ŽELJKA; NJIRIĆ, NIKO; MRAK, GORAN

    2016-01-01

    Secreted frizzled-related protein 3 (SFRP3) is a member of the family of soluble proteins, which modulate the Wnt signaling cascade. Novel research has identified aberrant expression of SFRPs in different types of cancer. In the present study the expression intensities and localizations of the SFRP3 protein across different histopathological grades of astrocytic brain tumors were investigated by immunohistochemistry, digital scanning and image analysis. The results demonstrated that the differences between expression levels and malignancy grades were statistically significant. Tumors were classified into four malignancy grades according to the World Health Organization guidelines. Moderate (P=0.014) and strong (P=0.028) nuclear expression levels were significantly different in pilocytic (grade I) and diffuse (grade II) astrocytomas demonstrating higher expression values, as compared with anaplastic astrocytoma (grade III) and glioblastoma (grade IV). When the sample was divided into two groups, the moderate and high cytoplasmic expression levels were observed to be significantly higher in glioblastomas than in the group comprising astrocytoma II and III. Furthermore, the results indicated that high grade tumors were associated with lower values of moderate (P=0.002) and strong (P=0.018) nuclear expression in comparison to low grade tumors. Analysis of cytoplasmic staining demonstrated that strong cytoplasmic expression was significantly higher in the astrocytoma III and IV group than in the astrocytoma I and II group (P=0.048). Furthermore, lower grade astrocytomas exhibited reduced membranous SFRP3 staining when compared with higher grade astrocytomas and this difference was statistically significant (P=0.036). The present results demonstrated that SFRP3 protein expression levels were decreased in the nucleus in higher grade astrocytoma (indicating the expected behavior of an antagonist of Wnt signaling), whereas when the SFRP3 was located in the cytoplasm an

  19. Expression patterns of Wnt signaling component, secreted frizzled‑related protein 3 in astrocytoma and glioblastoma.

    Science.gov (United States)

    Pećina-Šlaus, Nives; Kafka, Anja; Varošanec, Ana Maria; Marković, Leon; Krsnik, Željka; Njirić, Niko; Mrak, Goran

    2016-05-01

    Secreted frizzled-related protein 3 (SFRP3) is a member of the family of soluble proteins, which modulate the Wnt signaling cascade. Novel research has identified aberrant expression of SFRPs in different types of cancer. In the present study the expression intensities and localizations of the SFRP3 protein across different histopathological grades of astrocytic brain tumors were investigated by immunohistochemistry, digital scanning and image analysis. The results demonstrated that the differences between expression levels and malignancy grades were statistically significant. Tumors were classified into four malignancy grades according to the World Health Organization guidelines. Moderate (P=0.014) and strong (P=0.028) nuclear expression levels were significantly different in pilocytic (grade I) and diffuse (grade II) astrocytomas demonstrating higher expression values, as compared with anaplastic astrocytoma (grade III) and glioblastoma (grade IV). When the sample was divided into two groups, the moderate and high cytoplasmic expression levels were observed to be significantly higher in glioblastomas than in the group comprising astrocytoma II and III. Furthermore, the results indicated that high grade tumors were associated with lower values of moderate (P=0.002) and strong (P=0.018) nuclear expression in comparison to low grade tumors. Analysis of cytoplasmic staining demonstrated that strong cytoplasmic expression was significantly higher in the astrocytoma III and IV group than in the astrocytoma I and II group (P=0.048). Furthermore, lower grade astrocytomas exhibited reduced membranous SFRP3 staining when compared with higher grade astrocytomas and this difference was statistically significant (P=0.036). The present results demonstrated that SFRP3 protein expression levels were decreased in the nucleus in higher grade astrocytoma (indicating the expected behavior of an antagonist of Wnt signaling), whereas when the SFRP3 was located in the

  20. The pro-apoptotic protein death-associated protein 3 (DAP3) interacts with the glucocorticoid receptor and affects the receptor function.

    Science.gov (United States)

    Hulkko, S M; Wakui, H; Zilliacus, J

    2000-08-01

    The yeast two-hybrid system was used to isolate cDNAs encoding proteins that interact with the glucocorticoid receptor (GR) ligand-binding domain in a ligand-dependent manner. One isolated cDNA encoded a fragment of death-associated protein 3 (DAP3), which has been implicated as a positive mediator of apoptosis. In vitro experiments showed that the full-length DAP3 also interacted with GR. The main interaction domain was mapped to the N-terminal region of DAP3 that had previously been shown to function in a dominant-negative fashion, protecting cells from apoptosis. Co-transfection experiments in COS-7 cells showed that DAP3 had a stimulatory effect on the ligand-induced transcriptional activation by GR and also increased the steroid-sensitivity. Furthermore, DAP3 formed a complex with several other nuclear receptors and some basic helix-loop-helix/Per-Arnt-Sim proteins, as well as with heat-shock protein 90 (hsp90) (Arnt is the aryl-hydrocarbon-receptor nuclear translocator, and Per and Sim are the Drosophila proteins Period and Single-minded). The results suggest that DAP3 could have an important role in GR action, possibly by modulating the cytoplasmic GR-hsp90 complex. Since glucocorticoids can induce apoptosis, the pro-apoptotic DAP3 protein may be involved in this function of GR. PMID:10903152

  1. Intracerebroventricular Infusion of Vasoactive Intestinal Peptide (VIP Rescues the Luteinizing Hormone Surge in Middle-Aged Female Rats

    Directory of Open Access Journals (Sweden)

    Yan eSun

    2012-02-01

    Full Text Available Reproductive aging is characterized by delayed and attenuated luteinizing hormone (LH surges apparent in middle-aged rats. The suprachiasmatic nucleus (SCN contains the circadian clock that is responsible for the timing of diverse neuroendocrine rhythms. Electrophysiological studies suggest vasoactive intestinal peptide (VIP originating from the SCN excites gonadotropin-releasing hormone (GnRH neurons and affects daily patterns of GnRH-LH release. Age-related LH surge dysfunction correlates with reduced VIP mRNA expression in the SCN and fewer GnRH neurons with VIP contacts expressing c-fos, a marker of neuronal activation, on the day of the LH surge. To determine if age-related LH surge dysfunction reflects reduced VIP availability or altered VIP responsiveness under estradiol positive feedback conditions, we assessed the effect of intracerebroventricular (icv VIP infusion on c-fos expression in GnRH neurons and on LH release in ovariohysterectomized, hormone-primed young and middle-aged rats. Icv infusion of VIP between 1300 and 1600 h significantly advanced the time of peak LH release, increased total and peak LH release, and increased the number of GnRH neurons expressing c-fos on the day of the LH surge in middle-aged rats. Surprisingly, icv infusion of VIP in young females significantly reduced the number of GnRH neurons expressing c-fos and delayed and reduced the LH surge. These observations suggest that a critical balance of VIP signaling is required to activate GnRH neurons for an appropriately timed and robust LH surge in young and middle-aged females. Age-related LH surge changes may, in part, result from decreased availability and reduced VIP-mediated neurotransmission under estradiol positive feedback conditions.

  2. First attempt to monitor luteinizing hormone and reproductive steroids in urine samples of the Amazonian manatee (Trichechus inunguis).

    Science.gov (United States)

    Amaral, Rodrigo S; Rosas, Fernando C W; Graham, Laura H; da Silva, Vera M F; Oliveira, Claudio A

    2014-12-01

    The aims of this study were to validate an enzyme immunoassay (EIA) for the measurement of luteinizing hormone (LH) in urine samples of Amazonian manatees (Trichechus inunguis; Mammalia: Sirenia) and to monitor urinary LH and reproductive steroids during the ovarian cycle in this species. Urine samples were collected from two captive males following a hormonal challenge with a gonadotropin-releasing hormone (GnRH) analogue. The urinary LH results from hormonal challenge were compared with urinary androgens for the purpose of EIA validation. Furthermore, urine samples were collected daily, over a 12-wk period, from two captive adult females, for 2 consecutive yr. The urinary LH pattern from females was compared with the patterns of urinary progestagens and estrogen conjugates throughout the ovarian cycle. An LH peak was observed in both male Amazonian manatees after the hormonal challenge, occurring prior to or together with peak androgen levels. In the females, the ovarian cycle ranged from 40 to 48 days (mean of 43.7 days). Two distinct peaks of estrogen conjugates were observed across all cycles analyzed, and the urinary LH peaks observed were accompanied by peaks of urinary estrogen conjugates. The EIA was validated as a method for the quantification of urinary LH from Amazonian manatees, as it was able to detect variations in the levels of LH in urine samples. These results suggest that T. inunguis exhibits a peculiar hormonal pattern during the ovarian cycle. Therefore, further studies are desirable and necessary to clarify the relationship between this hormonal pattern and morphological changes, as well as mating behavior, in Amazonian manatee. PMID:25632672

  3. Altered regulation of luteinizing hormone secretion in 2,3,7,8-tetrachlorodibenzo-p-dioxin-treated male rats

    Energy Technology Data Exchange (ETDEWEB)

    Bookstaff, R.C.

    1989-01-01

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) severely decreases plasma androgen concentrations, yet plasma luteinizing hormone (LH) concentrations remain unchanged. The mechanism by which TCDD prevents the expected compensatory increase in plasma LH was investigated. No effect on the plasma disappearance rate of LH or on pituitary capacity to synthesize or secrete LH was detected. Rather, TCDD altered the regulation of LH secretion by substantially increasing the potency of both androgens and estrogens as feedback inhibitors of LH secretion. The mechanism by which TCDD alters androgen-regulated LH secretion was further investigated. Seven days after dosing, TCDD decreased plasma testosterone concentrations but prevented the expected compensatory increases in pituitary gonadotropin-releasing hormone (GnRH) receptor number, pituitary responsiveness to GnRH, and plasma LH concentrations as seen in similarly hypoandrogenic vehicle dosed rats. Furthermore, the TCDD dose-response relationships for preventing the compensatory increases in pituitary GnRH receptor number and plasma LH concentration were similar. However, in the absence of gonadal steroids (7 days after castration) TCDD did not affect the compensatory increases in pituitary GnRH receptor number, pituitary responsiveness to GnRH, or plasma LH concentration. All of these parameters increased substantially relative to intact TCDD treated rats, and to levels virtually identical to those seen in castrated control rats. Treatment of castrated rats with testosterone restored the ability of TCDD to prevent these compensatory increases. Taken together, these results demonstrate that the presence of androgens is required for TCDD to alter the regulation of pituitary GnRH receptors.

  4. Kisspeptin signaling is required for the luteinizing hormone response in anestrous ewes following the introduction of males.

    Directory of Open Access Journals (Sweden)

    Julie-Ann P De Bond

    Full Text Available The introduction of a novel male stimulates the hypothalamic-pituitary-gonadal axis of female sheep during seasonal anestrus, leading to the resumption of follicle maturation and ovulation. How this pheromone cue activates pulsatile secretion of gonadotropin releasing hormone (GnRH/luteinizing hormone (LH is unknown. We hypothesised that pheromones activate kisspeptin neurons, the product of which is critical for the stimulation of GnRH neurons and fertility. During the non-breeding season, female sheep were exposed to novel males and blood samples collected for analysis of plasma LH profiles. Females without exposure to males served as controls. In addition, one hour before male exposure, a kisspeptin antagonist (P-271 or vehicle was infused into the lateral ventricle and continued for the entire period of male exposure. Introduction of a male led to elevated mean LH levels, due to increased LH pulse amplitude and pulse frequency in females, when compared to females not exposed to a male. Infusion of P-271 abolished this effect of male exposure. Brains were collected after the male effect stimulus and we observed an increase in the percentage of kisspeptin neurons co-expressing Fos, by immunohistochemistry. In addition, the per-cell expression of Kiss1 mRNA was increased in the rostral and mid (but not the caudal arcuate nucleus (ARC after male exposure in both aCSF and P-271 treated ewes, but the per-cell content of neurokinin B mRNA was decreased. There was also a generalized increase in Fos positive cells in the rostral and mid ARC as well as the ventromedial hypothalamus of females exposed to males. We conclude that introduction of male sheep to seasonally anestrous female sheep activates kisspeptin neurons and other cells in the hypothalamus, leading to increased GnRH/LH secretion.

  5. Control of luteinizing hormone and testosterone secretion in a flexibly breeding male passerine, the Rufous-winged Sparrow, Aimophila carpalis.

    Science.gov (United States)

    Deviche, Pierre; Small, Thomas; Sharp, Peter; Tsutsui, Kazuyoshi

    2006-12-01

    Rufous-winged Sparrows, Aimophila carpalis, reside in the Sonoran desert and although testicular development is initiated in the spring under the influence of increasing day length, breeding occurs opportunistically in summer in association with heavy rainfall or "monsoon". The aim of this study in free-living male Rufous-winged Sparrows was to establish the relationship between concentrations of plasma luteinizing hormone (LH) and testosterone (T), and breeding associated with heavy rainfall, and to investigate whether breeding is mediated by changes in pituitary gland sensitivity to gonadotropin releasing hormone-I (GnRH) and the recently discovered avian gonadotropin-inhibitory hormone (GnIH). Concentrations of plasma LH and T were relatively low until mid-summer, but increased rapidly and transiently immediately prior to the monsoon which occurred after the summer solstice, when day lengths were decreasing. At this time the birds came into full breeding condition. An injection of chicken GnRH (10 ng) increased plasma LH within 2 min when given before or during the monsoon. An injection of GnIH (1 microg) did not affect plasma LH within 2 min during the monsoon and did not decrease GnRH-elicited LH secretion before or during the monsoon. No experimental treatment affected plasma T concentrations. The data suggest in male Rufous-winged Sparrows that the seasonal increase in plasma LH associated with summer monsoon results from increased stimulation of the pituitary gland by GnRH, rather than from a change in the responsiveness of the gland to GnRH, and that GnIH does not play an acute role in this mechanism. However, a possible chronic role for GnIH in the seasonal control of LH synthesis and secretion through an inhibitory effect on the hypothalamic GnRH system remains to be investigated.

  6. Age-related mercury contamination and relationship with luteinizing hormone in a long-lived Antarctic bird.

    Directory of Open Access Journals (Sweden)

    Sabrina Tartu

    Full Text Available Seabirds, as long-lived top predators, accumulate contaminants such as mercury (Hg, an established endocrine disruptor. In long lived species hormonal secretion varies with age; therefore, Hg-induced endocrine disruption may be exacerbated in some age classes. Here we investigated relationships between blood total Hg and luteinizing hormone (LH, a key pituitary hormone for the onset of breeding, in pre-laying known-age (11-45 years old snow petrels (Pagodroma nivea from Adélie Land, Antarctica. We predicted that 1 blood Hg would increase with advancing age as a consequence of bio-accumulation; and that 2 increasing blood Hg would be related to decreased concentrations of LH in the most Hg-contaminated individuals. Hg concentrations were higher in females than in males (p<0.001, and contrary to our prediction, decreased with advancing age in males (p = 0.009 and tended to do so in females (p = 0.06. The analysis of stable isotopes (δ13C and δ15N suggested that this unexpected pattern could originate from age and sex-related variations in trophic niche, and hence Hg exposure. Regarding LH, our prediction was only supported in young birds (≤23 years where baseline LH was inversely correlated with Hg concentrations (p = 0.04. Hg burden did not predict baseline LH or GnRH-induced LH in birds that were more than 23 years old. These results show that age and contaminants may interfere with major endocrine mechanisms and, together with other recent studies, support the view that Hg could be connected to LH secretion and could then impair the fitness of long-lived birds.

  7. Cloning and expression of full-length human insulin-like growth factor binding protein 3 (IGFBP3 in the Escherichia coli

    Directory of Open Access Journals (Sweden)

    Emad Khodadadi

    2015-01-01

    Conclusion: DNA fragment encoding the full-length IGFBP3 protein was accurately cloned in the pET-11a expression vector and the recombinant plasmid transformed to E. coli BL21 (DE3 expression host. Results of the SDS-PAGE analysis verified that recombinant IGFBP3 (31.6 kDa are successfully expressed under the control of T7 promoter. As we shown pET-11a can be successfully used for expression of the IGFBP3 protein.

  8. Prognostic value of insulin-like growth factor 1 and insulin-like growth factor binding protein 3 blood levels in breast cancer.

    NARCIS (Netherlands)

    Hartog, H.; Boezen, H.M.; Jong, M.M. de; Schaapveld, M.; Wesseling, J.; Graaf, W.T.A. van der

    2013-01-01

    High circulating insulin-like growth factor 1 (IGF-1) levels are firmly established as a risk factor for developing breast cancer, especially estrogen positive tumors. The effect of circulating IGF-1 on prognosis once a tumor is established is unknown. The authors explored the effect of IGF-1 blood

  9. c-myb stimulates cell growth by regulation of insulin-like growth factor (IGF) and IGF-binding protein-3 in K562 leukemia cells

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Min-Sun; Kim, Sun-Young; Arunachalam, Sankarganesh [Department of Pediatrics, School of Medicine, Chonbuk National University, Jeonju 561-712 (Korea, Republic of); Hwang, Pyoung-Han [Department of Pediatrics, School of Medicine, Chonbuk National University, Jeonju 561-712 (Korea, Republic of); Research Institute of Clinical Medicine, School of Medicine, Chonbuk National University, Jeonju 561-712 (Korea, Republic of); Yi, Ho-Keun [Department of Biochemistry, School of Dentistry, Chonbuk National University, Jeonju 561-712 (Korea, Republic of); Nam, Sang-Yun [Department of Alternative Therapy, School of Alternative Medicine and Health Science, Jeonju University, Jeonju 561-712 (Korea, Republic of); Lee, Dae-Yeol, E-mail: leedy@chonbuk.ac.kr [Department of Pediatrics, School of Medicine, Chonbuk National University, Jeonju 561-712 (Korea, Republic of); Research Institute of Clinical Medicine, School of Medicine, Chonbuk National University, Jeonju 561-712 (Korea, Republic of)

    2009-07-17

    c-myb plays an important role in the regulation of cell growth and differentiation, and is highly expressed in immature hematopoietic cells. The human chronic myelogenous leukemia cell K562, highly expresses IGF-I, IGF-II, IGF-IR, and IGF-induced cellular proliferation is mediated by IGF-IR. To characterize the impact of c-myb on the IGF-IGFBP-3 axis in leukemia cells, we overexpressed c-myb using an adenovirus gene transfer system in K562 cells. The overexpression of c-myb induced cell proliferation, compared to control, and c-myb induced cell growth was inhibited by anti-IGF-IR antibodies. c-myb overexpression resulted in a significant increase in the expression of IGF-I, IGF-II, and IGF-IR, and a decrease in IGFBP-3 expression. By contrast, disruption of c-myb function by DN-myb overexpression resulted in significant reduction of IGF-I, IGF-II, IGF-IR, and elevation of IGFBP-3 expression. In addition, exogenous IGFBP-3 inhibited the proliferation of K562 cells, and c-myb induced cell growth was blocked by IGFBP-3 overexpression in a dose-dependent manner. The growth-promoting effects of c-myb were mediated through two major intracellular signaling pathways, Akt and Erk. Activation of Akt and Erk by c-myb was completely blocked by IGF-IR and IGFBP-3 antibodies. These findings suggest that c-myb stimulates cell growth, in part, by regulating expression of the components of IGF-IGFBP axis in K562 cells. In addition, disruption of c-myb function by DN-myb may provide a useful strategy for treatment of leukemia.

  10. Low levels of the 150-kD insulin-like growth factor binding protein 3 ternary complex in patients with anorexia nervosa: effect of partial weight recovery

    DEFF Research Database (Denmark)

    Støving, René K; Hangaard, Jørgen; Hagen, Claus;

    2003-01-01

    on the ternary complex formation. Despite GH hypersecretion, serum IGF-I, IGFBP-3, and ALS levels have all been reported to be low in patients with anorexia nervosa (AN), while the degree of ternary complex formation in AN is unknown. METHODS: Serum ALS and 150-kD ternary complex formation were measured in 6...

  11. Insulin-like growth factor I (IGF-I) and IGF-binding protein 3 as diagnostic markers of growth hormone deficiency in infancy

    DEFF Research Database (Denmark)

    Jensen, Rikke Beck; Jeppesen, Katrine Arp; Vielwerth, Signe;

    2005-01-01

    The diagnosis of growth hormone deficiency (GHD) in infancy is difficult, and no specific cutoff value during GH provocative testing is recommended in early life.......The diagnosis of growth hormone deficiency (GHD) in infancy is difficult, and no specific cutoff value during GH provocative testing is recommended in early life....

  12. Serum insulin-like growth factor I (IGF-I) and IGF-binding protein 3 levels are increased in central precocious puberty

    DEFF Research Database (Denmark)

    Juul, A; Scheike, Thomas Harder; Nielsen, C T;

    1995-01-01

    Central precocious puberty (CPP) is characterized by early activation of the pituitary-gonadal axis, which leads to increased growth velocity and development of secondary sexual characteristics. It is generally believed that gonadal sex steroids stimulate pulsatile GH secretion, which, in turn...

  13. Total iron binding capacity

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/003489.htm Total iron binding capacity To use the sharing features on this page, please enable JavaScript. Total iron binding capacity (TIBC) is a blood test to ...

  14. Plant Hormone Binding Sites

    OpenAIRE

    Napier, Richard

    2004-01-01

    • Aims Receptors for plant hormones are becoming identified with increasing rapidity, although a frustrating number remain unknown. There have also been many more hormone‐binding proteins described than receptors. This Botanical Briefing summarizes what has been discovered about hormone binding sites, their discovery and descriptions, and will not dwell on receptor functions or activities except where these are relevant to understand binding.

  15. Analysis of binding heterogeneity.

    NARCIS (Netherlands)

    Nederlof, M.M.

    1992-01-01

    Binding heterogeneity, due to different functional groups on a reactive surface, plays an important role in the binding of small molecules or ions to many adsorbents, both in industrial processes and in natural environments. The binding heterogeneity is described by a distribution of affinity consta

  16. Luteinizing hormone and progesterone concentrations and induction of estrus after use of norgestomet ear implants or constant infusion of gonadotropin-releasing hormone in anestrous, nonlactating dairy goats.

    Science.gov (United States)

    Bretzlaff, K N; Nuti, L C; Scarfe, A D; Elmore, R G; Capehart, J; Varner, D D; Weston, P G

    1991-09-01

    Plasma luteinizing hormone and progesterone concentrations, time to onset of estrus, and pregnancy rates were determined in nonlactating anestrous does given 1 of 4 treatments: subcutaneous ear implants containing 3 mg of norgestomet for 9 days (NOR; n = 6); subcutaneous administration, using osmotic minipumps, of 250 ng of gonadotropin-releasing hormone (GnRH)/h for 48 hours (GnRH; n = 6); 3 mg of NOR for 9 days, followed immediately by 250 ng of GnRH/h for 48 hours (NOR + GnRH; n = 6); or no treatment (control; n = 6). During the 72-hour period after removal of NOR or insertion of GnRH pumps, 6 of 6, 0 of 6, 6 of 6, and 3 of 6 does were observed in estrus at a mean (+/- 13.8) hours in groups NOR, GnRH, NOR + GnRH, and control, respectively. Time from end of treatment to peak concentrations of luteinizing hormone were 56 +/- 4.0, 28 +/- 4.7, 34 +/- 4.3, and 41 +/- 9.7 hours (mean +/- SE) for NOR, GnRH, NOR +/- GnRH, and control, respectively. Peak concentrations of luteinizing hormone were significantly greater and occurred significantly later in does given NOR. Progesterone concentrations in does that became pregnant increased to concentrations greater than or equal to 1.0 ng/ml 3 to 5 days after breeding and remained high. Functional corpora lutea (CL) was found in 6 does that did not become pregnant, 1 CL was associated with pseudopregnancy and 1 CL was associated with ovulation prior to placement of the GnRH pumps. Functional CL failed to form in 10 of the 12 doses in groups GnRH and control.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1952326

  17. 木糖醇叶黄素固体饮料的研制%Preparation of Xylitol-Lutein Solid Beverage

    Institute of Scientific and Technical Information of China (English)

    王成福

    2014-01-01

    以木糖醇、叶黄素为主要原料,经粉碎混合、造粒、整粒、干燥包袋等工艺制成木糖醇叶黄素固体饮料,确定产品的最佳工艺配方为木糖醇的添加量为76%,叶黄素的添加量为10%,甜菊糖的添加量为1%,维生素C的添加量为10%,香精的添加量为0.5%,粘合剂麦芽糖醇浆的添加量为2.5%。其产品的外观呈松散颗粒状,大小均匀一致,溶化后溶液呈透明的黄色,即冲即饮,具有携带、运输方便的优点,具有非常好的市场发展前景。%Xylitol-lutein solid beverage was made through crushing,mixing,granulating,drying processes,and packaging with xylitol and lutein as the main raw materials. The optimum formula as follows: xylitol is 76%;lutein is 10%;stevioside is 1%;vitamin C is 10%;essence is 0.5%;and adhesive maltitol syrup is 2.5%;The product has the appearance of a loose granular and of uniform size.The aqueous solution is bright yellow. It is a kind of instant drink with the advantages of convenient carrying and transportation and it has the very good market prospects.

  18. D-Tryptophan-6 analog of luteinizing hormone-releasing hormone as a protective agent against testicular damage caused by cyclophosphamide in baboons.

    OpenAIRE

    Lewis, R W; Dowling, K J; Schally, A V

    1985-01-01

    Possible protective effects of the agonist [D-Trp6]LH-RH (the D-tryptophan-6 analog of luteinizing hormone-releasing hormone) against testicular damage caused by cyclophosphamide (Cytoxan) were investigated in subhuman primates. Three adult male baboons (Papio anubis) were first subjected to normal semen evaluation by using electroejaculation. The average baseline count for the animals ranged from 95.7 X 10(6) to 585.7 X 10(6) sperm per ml with 90% normal forms and 85% motility with excellent...

  19. Research on high lutein content microencapsulate by nano-disperse%纳米分散高含量叶黄素微囊化的研究

    Institute of Scientific and Technical Information of China (English)

    周迪; 邵斌; 许新德; 周玉春; 刘爱琴; 代志凯

    2012-01-01

    叶黄素不溶于水,微溶于植物油,有限的溶解性和对氧化的高敏感性,阻碍了合成得到的粗产品在食品和饲料染色中的直接使用,为增加得色量并增加可吸收性和生物利用率,必须将活性物质的粒径减小到10μm以下,甚至有的达到了纳米级,因为叶黄素的着色效力和生物利用率与其在介质中的粒径和分散性直接相关,为此本文研究了以叶黄素为原料,通过单因素实验,分析了油、溶解温度、时间、喷雾干燥工艺对微囊化叶黄素产品的影响,确定了瞬时高温油溶和喷雾冷凝法微囊化叶黄素新工艺;并通过正交实验,从产品感观质量和稳定性入手,确定了合理的水溶性5%叶黄素微囊化产品配方,解决了高含量叶黄素产品的稳定性、异构和高脂溶难吸收的三大难题.%Lutein' s insolubility in water, slight solubility in vegetable oils, and high sensitivity to oxidation inhibit its crude products from being directly applied as dyes in the food and feed industry. Research showed that if the size of the active substance is reduced to 10 microns or to the nanometer level, the coloring effect and absorbance all increased. This is because the coloring effects of lutein and its bioavailability are correlated with its particle size. By a single factor experiment and analysis, oil, solution temperature, time, and spray -drying process are selected as the main factors. By orthogonal experiment, combined with sensory quality and stability, the formula for 5% water - soluble lutein microencapsulated products is optimized. It solved three major problems of high concentrated lutein products; stability, heterogeneous and difficult solubility in fat.

  20. 万寿菊中叶黄素的提取皂化工艺研究%Extraction and Saponification Technology of Lutein from Marigold

    Institute of Scientific and Technical Information of China (English)

    赵洁; 尹俊涛; 郭亚可; 李超鹏; 陈文

    2011-01-01

    In this paper, Extraction and Saponification technology of Lutein esters in Tagetes erecta L.particle were investigated systemically.The mixed solvent of THF and Alc is main extraction solvent.The affecting factors such as the ratio of THF and Alc, reaction time , the ratio of reaction solution to material(mL/g), the addition of water, the addition of KOH in reaction solution and reaction temperature were investigate in singe factor experiments.An orthogonal test table L9 (34 ) was used to optimized the affecting factors on the base of singe factor experiments.The content of free Lutein in the end product was determined by HPLC.The results showed that the optimal Extraction and Saponification parameter was: 1.6g KOH, 4h, the ratio of 1∶20 (mL/g) ,ratio of THF and Alc is 2∶8.Under this condition,the yield of Free Lutein reach 1.14% and the content of Free Lutein reach 10.32 % in extracta sicca.%该文以四氢呋喃和乙醇的二元混合溶剂为主要提取剂,对万寿菊颗粒中叶黄素的提取皂化工艺进行了研究.实验分别考察了加入四氢呋喃与乙醇的比例、反应时间、料液比、加水体积、加碱量、反应温度对叶黄素得率的影响.在单因素试验的基础上,选取影响较大的4个因素采用L9(34)正交试验考察对叶黄素得率的影响,以得率为指标,确定最佳工艺条件为A1 B2 C2 D3,即料液比为1∶20,加碱质量1.6 g,反应时间4 h,THF∶乙醇=2∶8.由此可知:此条件下叶黄素得率为1.14%,所得浸膏中叶黄素的含量达到10.32%.

  1. Effect of foliar calcium chloride treatment on the level of chlorogenic acid, β-carotene, lutein and tocopherols in lettuce (Lactuca sativa L.)

    OpenAIRE

    Irena Perucka; Katarzyna Olszówka

    2012-01-01

    The aim of the presented study was to determine the effect of foliar application of CaCl2 on the level of β-carotene, lutein, tocopherols and phenolic compounds in the leaves of lettuce cv. Omega (Lactuca sativa L.). The experiments were conducted in the greenhouse of the Faculty of Cultivation and Fertilisation of Horticultural Plants, University of Life Sciences in Lublin. During the growing period, 7 and 14 days before harvest, the plants were treated with a solution of CaCl2 with concentr...

  2. THE RELATIONSHIP BETWEEN LUTEINIZING HORMONE LEVELS AND RECURRENT MISCARRIAGE%促黄体生成素水平与复发性流产的关系

    Institute of Scientific and Technical Information of China (English)

    商微; 王蔼明; 舒明明; 汤晓蓉; 李敏; 闫玲

    2012-01-01

    目的 测定复发性流产患者黄体期促黄体生成素的水平,探讨促黄体生成素与复发性流产的关系.方法 选择有复发性流产史患者43例为试验组,选择有正常生育史组妇女30例为对照组.监测卵泡发育,于排卵后第3天和第5天测定血清中促黄体生成素水平并进行比较.结果 对照组排卵后第3天和第5天促黄体生成素水平均明显高于试验组,差异有统计学意义(P<0.05).结论 黄体早期低促黄体生成素水平与复发性流产直接相关,改善黄体早期低促黄体生成素水平可降低复发性流产的发生.%Objective To discuss the relationship between luteinizing hormone ( LH ) level and recurrent miscarriage by measuring the luteinizing hormone levels of patients with recurrent miscarriage in luteal phase. Methods : Forty - three patients with recurrent miscarriage were selected as experimental group and thirty patients without recurrent miscarriage history and with secondary infertility of pure oviduct factors at the same time as control group. Results The LH concentrations of control group on the third day and the fifth day after ovulation were higher than those of the experimental group, which had statistical significance ( P <0. 05 ). Conclusion In early luteal phase,low luteinizing hormone level has close relationship with recurrent miscarriage. Timely increasing luteinizing hormone level in early luteal phase may decrease the occurrence of recurrent miscarriage.

  3. Analyzing radioligand binding data.

    Science.gov (United States)

    Motulsky, Harvey; Neubig, Richard

    2002-08-01

    Radioligand binding experiments are easy to perform, and provide useful data in many fields. They can be used to study receptor regulation, discover new drugs by screening for compounds that compete with high affinity for radioligand binding to a particular receptor, investigate receptor localization in different organs or regions using autoradiography, categorize receptor subtypes, and probe mechanisms of receptor signaling, via measurements of agonist binding and its regulation by ions, nucleotides, and other allosteric modulators. This unit reviews the theory of receptor binding and explains how to analyze experimental data. Since binding data are usually best analyzed using nonlinear regression, this unit also explains the principles of curve fitting with nonlinear regression.

  4. Biological insights from topology independent comparison of protein 3D structures.

    Science.gov (United States)

    Nguyen, Minh N; Madhusudhan, M S

    2011-08-01

    Comparing and classifying the three-dimensional (3D) structures of proteins is of crucial importance to molecular biology, from helping to determine the function of a protein to determining its evolutionary relationships. Traditionally, 3D structures are classified into groups of families that closely resemble the grouping according to their primary sequence. However, significant structural similarities exist at multiple levels between proteins that belong to these different structural families. In this study, we propose a new algorithm, CLICK, to capture such similarities. The method optimally superimposes a pair of protein structures independent of topology. Amino acid residues are represented by the Cartesian coordinates of a representative point (usually the C(α) atom), side chain solvent accessibility, and secondary structure. Structural comparison is effected by matching cliques of points. CLICK was extensively benchmarked for alignment accuracy on four different sets: (i) 9537 pair-wise alignments between two structures with the same topology; (ii) 64 alignments from set (i) that were considered to constitute difficult alignment cases; (iii) 199 pair-wise alignments between proteins with similar structure but different topology; and (iv) 1275 pair-wise alignments of RNA structures. The accuracy of CLICK alignments was measured by the average structure overlap score and compared with other alignment methods, including HOMSTRAD, MUSTANG, Geometric Hashing, SALIGN, DALI, GANGSTA(+), FATCAT, ARTS and SARA. On average, CLICK produces pair-wise alignments that are either comparable or statistically significantly more accurate than all of these other methods. We have used CLICK to uncover relationships between (previously) unrelated proteins. These new biological insights include: (i) detecting hinge regions in proteins where domain or sub-domains show flexibility; (ii) discovering similar small molecule binding sites from proteins of different folds and (iii

  5. Influence of leptin on luteinizing hormone and follicle stimulating hormone secreted from cultured rat anterior pituitary cells

    Institute of Scientific and Technical Information of China (English)

    Yuebing Qiao; Xiuyan Ma; Huixian Cui

    2008-01-01

    BACKGROUND: Leptin may regulate reproductive function via release of hypothalamic neuropeptide Y. However, it is unknown whether this regulatory effect is limited to the hypothalamus. OBJECTIVE: To detect the effect of different dosages of leptin on luteinizing hormone (LH) and follicle stimulating hormone (FSH) secretion from in vitro cultured rat anterior pituitary cells. DESIGN: Contrast study based on cells. SETTING: This study was performed in the Basic Institute of Chengde Medical College, Chengde City, Hebei Province, China from March to June 2007. MATERIALS: Eighteen female Wistar rats of three months of age, weighing 200-220 g, and of clean grade were used. Leptin was provided by Peprotech Company, DMEM culture medium by Invitrogen Company, and the radioimmunological kit by Beijing Zhongshan Jinqiao Biotechnology Co., Ltd. METHODS: Three glandular organs were regarded as one group for culture of anterior pituitary cells. In the control group, saline was added to the culture medium instead of leptin. In the leptin group, leptin was prepared into different concentrations of 1×10-12, 1×10-11, 1×10-9, 1×10-7, and 1×10-6 mol/L for stimulation of cultured cells. The culture supernatant was obtained at three hours after additional of saline/leptin. MAIN OUTCOME MEASURES: Contents of LH and FSH were detected by radioimmunology. RESULTS: Following leptin stimulation, LH release increased with increasing concentrations of leptin up to 1×10-9 mol/L, where LH release peaked. LH release then progressively decreased with increasing leptin concentrations (P<0.01). LH release in the leptin (1×10-12, 1×10-11, 1×10-7, and 1×10-6 mol/L) groups was significantly higher than that in the control group (P<0.01). FSH content in the leptin (1×10-11, 1×10-9, and 1×10-7 mol/L) groups was significantly higher than that in the control group (P<0.01). CONCLUSION: Leptin can directly affect pituitary tissue to promote the secretion of LH and FSH in a dose-dependent manner.

  6. Episodic variations of prolactin, thyroid-stimulating hormone, luteinizing hormone, melatonin and cortisol in infertile women with subclinical hypothyroidism.

    Science.gov (United States)

    Bals-Pratsch, M; De Geyter, C; Müller, T; Frieling, U; Lerchl, A; Pirke, K M; Hanker, J P; Becker-Carus, C; Nieschlag, E

    1997-05-01

    Preliminary data have suggested that female infertility due to corpus luteum insufficiency may be caused by subclinical hypothyroidism [exaggerated thyroid-stimulating hormone (TSH) response to thyrotrophin-releasing hormone (TRH) stimulation]. L-Thyroxine supplementation has been recommended to achieve pregnancies in subclinical hypothyroid women. This controlled study was carried out in order to investigate the biochemical diagnosis of subclinical hypothyroidism as a possible infertility factor. Five infertile patients (aged 25-36 years) with subclinical hypothyroidism (n = 4, stimulated TSH >20 microU/ml) or primary hypothyroidism (n = 1) and five healthy controls (aged 22-39 years) with normal thyroid function (stimulated TSH infertility were studied in the early follicular phase. In the pre-study evaluation, eight of 23 volunteers (34.8%) had to be excluded because of subclinical hypothyroidism with stimulated TSH values (TSHs) >15 microU/ml. Cycle function of patients and controls was compared by the method of LH pulse pattern analysis. Therefore blood samples were drawn every 10 min during a 24 h period. Sleep was recorded from midnight to 7 a.m. Repetition of the TRH tests at the end of the 24 h blood sampling period confirmed the difference in stimulated TSH values of the two study groups. Pulse analysis for luteinizing hormone (LH), TSH and prolactin showed no differences between patients and controls for pulse frequency, amplitude, height, length, area under curve (AUC) and the 24 h mean. Even the hypothyroid patient had a normal LH pulse pattern. Additional measurement of melatonin in pooled sera every 30 min gave the well-documented diurnal profiles during day and night for both groups. Patients had significantly higher melatonin values at seven time points during the night. Peaks for LH, TSH, prolactin and cortisol were correlated with the sleep stages wake, rapid eye movement, 1 + 2 and 3 + 4. We concluded that corpus luteum insufficiency in female

  7. Study on technologies of extracting and saponifying lutein ester from marigold%万寿菊花中叶黄素酯的提取及皂化工艺

    Institute of Scientific and Technical Information of China (English)

    刘洪海; 杜平; 梁红兵; 张希波; 张晓丽

    2009-01-01

    Lutein can be used to improve human immune system and prevent cataract and senile maculutea degeneration.It can be obtained by saponification of lutein ester,which is the major extracts from Marigold.Lutein is widely used in food,food additive,drugs and feed industries.In this paper,extraction of lutein ester from marigold is conducted with n-hexane as extractant.The best condition for saponifying lutein ester was chosen by the orthogonal experiments of L9 (34).It is found that using 20% KOH methanol as the extracting solution,with saponification reaction time of 40 minutes,at a temperature of 50℃,Lutein ester can be thoroughly sponified.Lutein can then be recrystallized in the solvent of acetone and methanol(v : v 1 : 1).The purity of lutein crystal is 97.2%.%叶黄素具有调节人体的免疫能力、防治老年性视黄斑退化和白内障等作用,目前天然叶黄素的提取原料主要为万寿菊花,万寿菊花的有机溶剂提取物含有大量叶黄素酯,经皂化后可转变为叶黄素,广泛用于食品、食品添加剂、药品及饲料等工业.本文采用甲醇处理万寿菊鲜花后直接用正己烷提取叶黄素酯,并通过L9 (34)正交实验选择了叶黄素酯皂化的最佳条件,即KOH/甲醇浓度为20%,提取液﹕KOH为4 : 1,时间为40min,温度为50℃时,叶黄素酯皂化进行的比较完全.皂化得到的叶黄素在丙酮﹕甲醇(v : v)为1 : 1的混合溶剂中进行重结晶,得到叶黄素晶体,纯度为97.2%.

  8. Down-regulation of messenger ribonucleic acid encoding an importer of sulfoconjugated steroids during human chorionic gonadotropin-induced follicular luteinization in vivo.

    Science.gov (United States)

    Brown, Kristy A; Bouchard, Nadine; Lussier, Jacques G; Sirois, Jean

    2007-01-01

    Members of the organic anion transporting polypeptide (SLCO/OATP) superfamily are capable of importing anionic compounds across the lipid bilayer in a sodium-independent manner. Member 2B1 has been shown to transport few substrates, two of which are dihydroepiandrosterone-3-sulfate (DHEA-S) and estrone-3-sulfate. Steroid sulfatase (STS) catalyses the hydrolysis of these steroids into their unconjugated counterparts. The objective of this study was to investigate the regulation of SLCO2B1 and STS mRNAs during human chorionic gonadotropin (hCG)-induced ovulation/luteinization. The equine SLCO2B1 cDNA was cloned and shown to encode a 709-amino acid protein (OATP2B1) that is highly conserved when compared to mammalian orthologs. RT-PCR/Southern blot analyses were performed to study the regulation of SLCO2B1 and STS transcripts in equine preovulatory follicles isolated between 0 and 39h after hCG treatment. Results showed high levels of SLCO2B1 mRNA expression before hCG, with a marked decrease observed in follicles obtained 24-39h post-hCG (Pimport sulfoconjugated DHEA and estrogens, and that STS can remove the sulfonate moiety from these steroids, their down-regulation in luteinizing preovulatory follicles may provide an additional biochemical basis for the decrease in ovarian 17beta-estradiol biosynthesis after the LH surge.

  9. Overall skin tone and skin-lightening-improving effects with oral supplementation of lutein and zeaxanthin isomers: a double-blind, placebo-controlled clinical trial

    Science.gov (United States)

    Juturu, Vijaya; Bowman, James P; Deshpande, Jayant

    2016-01-01

    Purpose Carotenoids, especially lutein and zeaxanthin isomers (L/Zi), filter blue light and protect skin from environmental factors including high-energy sources. These carotenoids may be able to block the formation of melanin pathways, decrease cytokines, and increase antioxidants. Subjects and methods This is a randomized, double-blind, placebo-controlled clinical trial over a 12-week supplementation period. Fifty healthy people (50 healthy subjects were recruited and 46 subjects completed the study) (males and females, age: 18–45 years) with mild-to-moderate dry skin were included in this study. Skin type of the subjects was classified as Fitzpatrick skin type II–IV scale. Subjects were administered with either an oral dietary supplement containing 10 mg lutein (L) and 2 mg zeaxanthin isomers (Zi) (L/Zi: RR-zeaxanthin and RS (meso)-zeaxanthin) or a placebo daily for 12 weeks. The minimal erythemal dose and skin lightening (L*) were measured via the Chromameter®. The individual typological angle was calculated. Subjective assessments were also recorded. Results Overall skin tone was significantly improved in the L/Zi group compared to placebo (Pskin conditions. PMID:27785083

  10. Differential responsiveness of luteinized human granulosa cells to gonadotropins and insulin-like growth factor I for induction of aromatase activity

    International Nuclear Information System (INIS)

    The objective of this study was to examine the in vitro responsiveness of cultured luteinized human granulosa cells over time to insulin-like growth factor 1 (IGF-1), human follicle-stimulating hormone (FSH), and human chorionic gonadotropin (hCG) for the induction of aromatase activity. Granulosa cells were retrieved from preovulatory follicles in patients undergoing in vitro fertilization. Cells were cultured for a period of 72 hours or 10 days. The ability of hCG, human FSH, and/or IGF-I to induce aromatase activity was assayed by the stereospecific release of tritium from [1B-3H]androstenedione. Short-term cultures (72 hours) demonstrated a marked rise in aromatase activity in response to human FSH and IGF-I, whereas a smaller response to hCG was observed. In contrast, 10-day cultures demonstrated responsiveness predominantly to hCG rather than human FSH for the induction of aromatase activity with no remarkable effect of IGF-I. Luteinized human granulosa cells undergo a transformation from an initial human FSH and IGF-I responsive state to an hCG responsive state in long-term cultures

  11. Equine Chorionic Gonadotropin and Human Chorionic Gonadotropin Stimulation Increase the Number of Luteinized Follicles and the Progesterone Level Compared with Cabergoline Stimulation in Anoestrus Bitches.

    Science.gov (United States)

    Jurczak, A; Domosławska, A; Bukowska, B; Janowski, T

    2016-08-01

    In this study, ovarian morphologies and blood progesterone concentrations following oestrous induction in bitches were examined. Fifty-three clinically healthy anoestrus bitches received cabergoline at a daily dose of 5 μg/kg of body weight per os for 21 days (group I) or subcutaneous equine chorionic gonadotropin at a dose of 20 IU/kg of body weight for five consecutive days with an additional 500 IU s.c. per bitch of human chorionic gonadotropin on the last day of treatment (group II). Twenty bitches that spontaneously displayed oestrous signs were left untreated and served as controls (group III). The induced oestrous rates and ovulation rates in groups I and II were 60.0% vs 64.3% and 86.7% vs 83.3%, respectively. Morphological assessments of the ovarian structures after ovariohysterectomy revealed an increase in the number of luteinized follicles and cysts in group II compared with the two other groups (p similar in all groups. In accordance with the above-mentioned alteration, the progesterone concentration in the gonadotropin group (II) was increased (p similar and typical of normally cycling bitches. In conclusion, gonadotropin treatment is associated with an increased progesterone level during the periovulatory period that probably originates from luteinized follicles, whereas cabergoline treatment induces cycles with both physiological progesterone concentrations and ovarian morphologies. PMID:27321641

  12. Expression of 17beta- and 3beta-hydroxysteroid dehydrogenases and steroidogenic acute regulatory protein in non-luteinizing bovine granulosa cells in vitro.

    Science.gov (United States)

    Sahmi, M; Nicola, E S; Silva, J M; Price, C A

    2004-08-31

    Granulosa cells of small follicles differentiate in vitro in serum-free medium, resulting in increased estradiol secretion and abundance of mRNA encoding cytochrome P450aromatase (P450arom). We tested the hypothesis that differentiation in vitro also involves increased expression of 3beta- and 17beta-hydroxysteroid dehydrogenases (HSD) in the absence of steroidogenic acute regulatory protein (StAR) expression, as has been observed in vivo. Granulosa cells from small (basal layer of the membrana granulosa) did not affect steroidogenesis. We conclude that under the present cell culture system granulosa cells do not luteinize, and show expression of key steroidogenic enzymes in patterns similar to those occurring in differentiating follicles in vivo. Further, the data suggest that 17beta-HSD may be as important as P450arom in regulating estradiol secretion, and that 3beta-HSD is more important than P450scc as a regulator of progesterone secretion in non-luteinizing granulosa cells. PMID:15279910

  13. Lutein and zeaxanthin in the diet and serum and their relation to age-related maculopathy in the third national health and nutrition examination survey.

    Science.gov (United States)

    Mares-Perlman, J A; Fisher, A I; Klein, R; Palta, M; Block, G; Millen, A E; Wright, J D

    2001-03-01

    Relations of the carotenoids lutein and zeaxanthin in the diet and serum to photographic evidence of early and late age-related maculopathy (ARM) among persons over age 40 years (n = 8,222) were examined. Inverse relations of these carotenoids in the diet or serum to any form of ARM were not observed overall. There was a direct relation of dietary levels to one type of early ARM (soft drusen). However, relations differed by age and race. In the youngest age groups who were at risk for developing early (ages 40-59 years) or late (ages 60-79 years) ARM, higher levels of lutein and zeaxanthin in the diet were related to lower odds for pigmentary abnormalities, one sign of early ARM (odds ratio among persons in high vs. low quintiles = 0.1, 95 percent confidence interval: 0.1, 0.3) and of late ARM (odds ratio = 0.1, 95 percent confidence interval: 0.0, 0.9) after adjustment for age, gender, alcohol use, hypertension, smoking, and body mass index. Relations of these carotenoids to ARM may be influenced by age and race and require further evaluation in separate populations and in prospective studies. PMID:11226974

  14. Python bindings for libcloudph++

    OpenAIRE

    Jarecka, Dorota; Arabas, Sylwester; Del Vento, Davide

    2015-01-01

    This technical note introduces the Python bindings for libcloudph++. The libcloudph++ is a C++ library of algorithms for representing atmospheric cloud microphysics in numerical models. The bindings expose the complete functionality of the library to the Python users. The bindings are implemented using the Boost.Python C++ library and use NumPy arrays. This note includes listings with Python scripts exemplifying the use of selected library components. An example solution for using the Python ...

  15. DNS & Bind Cookbook

    CERN Document Server

    Liu, Cricket

    2011-01-01

    The DNS & BIND Cookbook presents solutions to the many problems faced by network administrators responsible for a name server. Following O'Reilly's popular problem-and-solution cookbook format, this title is an indispensable companion to DNS & BIND, 4th Edition, the definitive guide to the critical task of name server administration. The cookbook contains dozens of code recipes showing solutions to everyday problems, ranging from simple questions, like, "How do I get BIND?" to more advanced topics like providing name service for IPv6 addresses. It's full of BIND configuration files that yo

  16. Python bindings for libcloudph++

    CERN Document Server

    Jarecka, Dorota; Del Vento, Davide

    2015-01-01

    This technical note introduces the Python bindings for libcloudph++. The libcloudph++ is a C++ library of algorithms for representing atmospheric cloud microphysics in numerical models. The bindings expose the complete functionality of the library to the Python users. The bindings are implemented using the Boost.Python C++ library and use NumPy arrays. This note includes listings with Python scripts exemplifying the use of selected library components. An example solution for using the Python bindings to access libcloudph++ from Fortran is presented.

  17. LH (Luteinizing Hormone) Test

    Science.gov (United States)

    ... reason for the delayed puberty. Some of the causes for delayed puberty can include: Failure of the ovaries or testicles Hormone deficiency Turner syndrome Klinefelter syndrome Chronic infections Cancer Eating disorder (anorexia nervosa) ^ Back to top Is there anything ...

  18. The acid-labile subunit of human ternary insulin-like growth factor binding protein complex in serum

    DEFF Research Database (Denmark)

    Juul, A; Møller, S; Mosfeldt-Laursen, E;

    1998-01-01

    Circulating insulin-like growth factor-I (IGF-I) is predominantly bound in the trimeric complex comprised of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS). Circulating concentrations of IGF-I, IGFBP-3 and ALS are believed to reflect the GH secretory status, but the clinical use of...

  19. Foot-and-mouth disease virus non-structural protein 3A inhibits the interferon-β signaling pathway

    OpenAIRE

    Dan Li; Caoqi Lei; Zhisheng Xu; Fan Yang; Huanan Liu; Zixiang Zhu; Shu Li; Xiangtao Liu; Hongbing Shu; Haixue Zheng

    2016-01-01

    Foot-and-mouth disease virus (FMDV) is the etiological agent of FMD, which affects cloven-hoofed animals. The pathophysiology of FMDV has not been fully understood and the evasion of host innate immune system is still unclear. Here, the FMDV non-structural protein 3A was identified as a negative regulator of virus-triggered IFN-β signaling pathway. Overexpression of the FMDV 3A inhibited Sendai virus-triggered activation of IRF3 and the expressions of RIG-I/MDA5. Transient transfection and co...

  20. A case of familial central precocious puberty caused by a novel mutation in the makorin RING finger protein 3 gene

    OpenAIRE

    Grandone, Anna; Cantelmi, Grazia; Cirillo, Grazia; Marzuillo, Pierluigi; Luongo, Caterina; Miraglia del Giudice, Emanuele; Perrone, Laura

    2015-01-01

    Background Central precocious puberty (CPP) is often familial but its genetic cause is largely unknown. Very recently, the makorin RING finger protein 3 (MKRN3) gene, located on chromosome 15 in the Prader-Willi syndrome (PWS)-associated region (15q11-q13), has been found mutated in 5 families with familial precocious puberty. The MKRN3 is a maternal imprinted gene and the phenotype is expressed only when the MKRN3 mutations are localized on the allele inherited from the father. The function ...

  1. Melanin-binding radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Packer, S; Fairchild, R G; Watts, K P; Greenberg, D; Hannon, S J

    1980-01-01

    The scope of this paper is limited to an analysis of the factors that are important to the relationship of radiopharmaceuticals to melanin. While the authors do not attempt to deal with differences between melanin-binding vs. melanoma-binding, a notable variance is assumed. (PSB)

  2. DNS BIND Server Configuration

    Directory of Open Access Journals (Sweden)

    Radu MARSANU

    2011-01-01

    Full Text Available After a brief presentation of the DNS and BIND standard for Unix platforms, the paper presents an application which has a principal objective, the configuring of the DNS BIND 9 server. The general objectives of the application are presented, follow by the description of the details of designing the program.

  3. Overnight Levels of Luteinizing Hormone, Follicle-Stimulating Hormone and Growth Hormone before and during Gonadotropin-Releasing Hormone Analogue Treatment in Short Boys Born Small for Gestational Age

    NARCIS (Netherlands)

    van der Kaay, Danielle C. M.; de Jong, Frank H.; Rose, Susan R.; Odink, Roelof J. H.; Bakker-van Waarde, Willie M.; Sulkers, Eric J.; Hokken-Koelega, Anita C. S.

    2009-01-01

    Aims: To evaluate if 3 months of gonadotropin-releasing hormone analogue (GnRHa) treatment results in sufficient suppression of pubertal luteinizing hormone (LH) and follicle-stimulating hormone (FSH) profile patterns in short pubertal small for gestational age (SGA) boys. To compare growth hormone

  4. Overnight levels of luteinizing hormone, follicle-stimulating hormone and growth hormone before and during gonadotropin-releasing hormone analogue treatment in short boys born small for gestational age

    NARCIS (Netherlands)

    D.C.M. van der Kaay (Danielle); F.H. de Jong (Frank); S.R. Rose (Susan); R.J.H. Odink (Roelof); W.M. Bakker-Van Waarde (Willie); E.J. Sulkers (Eric); A.C.S. Hokken-Koelega (Anita)

    2009-01-01

    textabstractAims: To evaluate if 3 months of gonadotropin-releasing hormone analogue (GnRHa) treatment results in sufficient suppression of pubertal luteinizing hormone (LH) and follicle-stimulating hormone (FSH) profile patterns in short pubertal small for gestational age (SGA) boys. To compare gro

  5. Partial Sequence Analysis of Merozoite Surface Proteine-3α Gene in Plasmodium vivax Isolates from Malarious Areas of Iran

    Directory of Open Access Journals (Sweden)

    H Mirhendi

    2008-12-01

    Full Text Available Background: Approximately 85-90% of malaria infections in Iran are attributed to Plasmodium vivax, while little is known about the genetic of the parasite and its strain types in this region. This study was designed and performed for describing genetic characteristics of Plasmodium vivax population of Iran based on the merozoite surface protein-3α gene sequence. Methods: Through a descriptive study we analyzed partial P. vivax merozoite surface protein-3α gene sequences from 17 clinical P. vivax isolates collected from malarious areas of Iran. Genomic DNA was extracted by Q1Aamp® DNA blood mini kit, amplified through nested PCR for a partial nucleotide sequence of PvMSP-3 gene in P. vivax. PCR-amplified products were sequenced with an ABI Prism Perkin-Elmer 310 sequencer machine and the data were analyzed with clustal W software. Results: Analysis of PvMSP-3 gene sequences demonstrated extensive polymorphisms, but the sequence identity between isolates of same types was relatively high. We identified specific insertions and deletions for the types A, B and C variants of P. vivax in our isolates. In phylogenetic comparison of geographically separated isolates, there was not a significant geo­graphical branching of the parasite populations. Conclusion: The highly polymorphic nature of isolates suggests that more investigations of the PvMSP-3 gene are needed to explore its vaccine potential.

  6. Expression of inhibin α, matrix metalloproteinase-2 and tissue inhibitors of metalloproteinase-1 in luteinized granulosa cells: comparison between women with and without endometriosis

    Institute of Scientific and Technical Information of China (English)

    Tan Rong-rong; Liu Li-peng; Pu Dan-hua; Cui Yu-gui; Jiang Shi-Wen; Liu Jia-yin; Wu Jie

    2012-01-01

    Objective: To assess the differences in expression of inhibin α,MMP-2 and TIMP-1 in luteinized granulosa cells from women with and without endometriosis undergoing in vitro fertilization (IVF),and determine whether inhibin α,MMP-2 and TIMP-1 expressions correlate with the follicle development in patients with endometriosis.Methods: Thirty six infertile patients with stage Ⅲ and Ⅳ endometriosis patients (group A) and 35 tubal infertile and/or male factor patients (group B) attending to the clinic of Jiangsu Provincial Hospital Human Reproductive Center during May 2011 and December 2011 were included in this prospective study.The patients with the number of mature oocyte ≤ 4 were considered as poor responders.According to this,the two groups were further divided into four subgroups: A1 group (23 endometriosis patients with normal response),A2 group (13 endometriosis patients with poor response),B1 group (23 controls with normal response) and B2 group (12 controls with poor response).Fasting blood samples were collected on the first day of ovarian stimulation and on the day of hCG administration,and follicle fluid were collected on the day of oocytes retrieved.The concentrations of follicle stimulating hormone (FSH),Luteinizing hormone (LH) and estradiol (E2) were measured by ECILA.Granulosa was collected from follicle fluid by Percoll method,and Stepone real-time polymerase chain reaction (PCR) was used to analysis the expression level of inhibin α,MMP-2 and TIMP-1.Results: The expression of inhibin α in endometriosis group and poor responders in control group were significantly lower than those of the normal responders in control group,in which the alternation of inhibin α expression was not correlated to the variables of follicle development.Moreover,MMP-2 levels were lower and TIMP-1 levels were higher in both endometriosis and tubal/male infertility poor responders compared to normal ovarian responders.Interestingly,the correlation between MMP-2 or

  7. 叶黄素与阿尔茨海默病相关性的研究现状与进展%Advances in the researches of lutein and alzheimer's disease

    Institute of Scientific and Technical Information of China (English)

    徐贤荣; 林晓明

    2015-01-01

    Lutein, a kind of oxycarotenoid, can pass the blood brain barrier and preferentially accumulate in the human brain, which is the most abundant carotenoid in human brain. Evidence from multiple studies suggested that lutein was closely related to age-related cognitive decline and risk of Alzheimer's disease(AD) in human. Dietary, plasma and brain concentrations of lutein were negatively associated with age-related cognitive decline. Lutein concentrations in plasma and brain were significantly lower in AD patients than those of health control. In human brain, lutein was the sole carotenoid which consistently associated with a range of cognitive function measures. In elderly women, lutein supplement can improve the cognitive function. In this article, we systematically reviewed the literature on the role of lutein in age-related cognitive decline and alzheimer's disease and its possible mechanisms. It may prove some benefit information for the advanced research and prevention of AD.%叶黄素是含氧的类胡萝卜素,能通过血脑屏障,被脑组织优先摄取,是人脑中含量最高的类胡萝卜素。机体叶黄素水平与年龄相关性认知功能减退和阿尔茨海默病的发生密切相关。膳食叶黄素摄入量、血清叶黄素浓度及大脑中叶黄素含量与认知功能下降程度呈负相关;在阿尔茨海默病患者中,血清和大脑中叶黄素水平显著降低;叶黄素为人脑中唯一与所有认知功能指标持续相关的类胡萝卜素;补充适宜剂量的叶黄素能改善老年女性的认知功能。本文对近年来叶黄素与年龄相关性认知功能减退、阿尔茨海默病的相关性以及作用的机制进行了系统阐述。

  8. Radioimmunological determination of the level of luteinizing hormone in the serum in the case of various gonadal disturbances and other endocrine diseases

    International Nuclear Information System (INIS)

    The purpose of this work was to determine radioimmunologically the level of luteinizing hormone (LH) in the serum in the case of various gonadal disturbances and other endocrine diseases with the aid of the double antibody method, and to compare the results within different diagnosis groups to each other and to compare these results with those found in the published literature. It was tested whether and with which accuracy the radioimmunological determination of LH in the serum can contribute to the diagnosis of pituitary gonad diseases and whether in the case of endocrine diseases the accompanying disturbances of the gonadotropin secretion which primarily do not affect the hypothalamo - hypophyso - gonadal circuit are demonstrable. The study results for the diagnosis groups primary and secondary hypogonadism of various genesis, gynacomastia, impotentia coeundi, primary and secondary ovarial insufficiency, hirsutism and adiposity were presented and discussed. (orig.)

  9. Reactive oxygen species and transcript analysis upon excess light treatment in wild-type Arabidopsis thaliana vs a photosensitive mutant lacking zeaxanthin and lutein

    Directory of Open Access Journals (Sweden)

    Roncaglia Enrica

    2011-04-01

    Full Text Available Abstract Background Reactive oxygen species (ROS are unavoidable by-products of oxygenic photosynthesis, causing progressive oxidative damage and ultimately cell death. Despite their destructive activity they are also signalling molecules, priming the acclimatory response to stress stimuli. Results To investigate this role further, we exposed wild type Arabidopsis thaliana plants and the double mutant npq1lut2 to excess light. The mutant does not produce the xanthophylls lutein and zeaxanthin, whose key roles include ROS scavenging and prevention of ROS synthesis. Biochemical analysis revealed that singlet oxygen (1O2 accumulated to higher levels in the mutant while other ROS were unaffected, allowing to define the transcriptomic signature of the acclimatory response mediated by 1O2 which is enhanced by the lack of these xanthophylls species. The group of genes differentially regulated in npq1lut2 is enriched in sequences encoding chloroplast proteins involved in cell protection against the damaging effect of ROS. Among the early fine-tuned components, are proteins involved in tetrapyrrole biosynthesis, chlorophyll catabolism, protein import, folding and turnover, synthesis and membrane insertion of photosynthetic subunits. Up to now, the flu mutant was the only biological system adopted to define the regulation of gene expression by 1O2. In this work, we propose the use of mutants accumulating 1O2 by mechanisms different from those activated in flu to better identify ROS signalling. Conclusions We propose that the lack of zeaxanthin and lutein leads to 1O2 accumulation and this represents a signalling pathway in the early stages of stress acclimation, beside the response to ADP/ATP ratio and to the redox state of both plastoquinone pool. Chloroplasts respond to 1O2 accumulation by undergoing a significant change in composition and function towards a fast acclimatory response. The physiological implications of this signalling specificity are

  10. Assessment of lutein and zeaxanthin status and dietary markers as predictors of the contrast threshold in 2 age groups of men and women.

    Science.gov (United States)

    Estévez-Santiago, Rocío; Olmedilla-Alonso, Begoña; Beltrán-de-Miguel, Beatriz

    2016-07-01

    Lutein and zeaxanthin (L + Z) status is associated with the macular pigment (MP). The relationship between MP and visual function is controversial. We hypothesized that, within the framework of nutrition, visual function was related to MP and nutritional and/or/dietary factors influencing it. A cross-sectional study was performed in 108 volunteers divided into 2 age groups (20-35 years; 45-65 years), each 27 women and 27 men, to assess the relationship between MP optical density (MPOD) and contrast threshold (CT), considering the influence of L + Z and, fruit and vegetable (F + V) intake. MPOD, L + Z in serum and dietary intake were determined using heterochromatic flicker photometry, high-performance liquid chromatography and 3-day food records, respectively. CT was measured with the CGT-1000 Contrast Glaretester at 6 stimulus sizes, with and without glare. Spearman correlation coefficient and a generalized linear model were used for the statistical study. MPOD and CT were higher and lower, respectively in younger than in elder individuals (P V intake (correlation coefficients and P values ranging from -.265 to -.176 and from .000 to .010, respectively). As predictors of CT in the total sample, MPOD, F + V (every 100 g/d) and sex were identified (β coefficients ranged from -0.01 to -1.86; from 0.01 to 0.08 and from 0.01 to 0.40, respectively). CT revealed age-specific nutritional predictors: MPOD and serum lutein in the 45- to 65-year group, and F + V intake in the 20- to 35-year group. PMID:27262538

  11. Sexual maturation, serum steroid concentrations, and mRNA expression of IGF-1, luteinizing and progesterone hormone receptors and survivin gene in Japanese quail hens.

    Science.gov (United States)

    Shit, N; Sastry, K V H; Singh, R P; Pandey, N K; Mohan, J

    2014-03-15

    In avian species, sexual maturation represents the evidence of start laying, which is a consequence of the development of ovarian follicles. These follicles are the functional reproductive unit whose maturation and viability critically depends on endocrine, paracrine, and autocrine factors beyond the signals from the central nervous system. The present study was undertaken to investigate the correlation of sexual maturity with tissue growth, mRNA expression of certain genes, and serum steroid concentrations in Japanese quail hens. To carry out the present study, a total of forty Japanese quail hens (5 weeks) were housed individually under uniform husbandry condition with ad libitum quail layer ration and water at 14-hour photo schedule. On sixth week onwards, four birds were sacrificed at each time on 1, 3, 7, 10, 13, 16, 19, 22, 25, and 28 days. Serum was extracted aseptically to analyze the gonadal steroid hormones (estrogen and progesterone) and corticosterone to investigate the liaison with sexual maturation of the species. Expression analyses of four genes i.e., insulin-like growth factor-1, luteinizing hormone receptor, progesterone receptor, and survivin were carried out in the three largest ovarian yellow follicles. A significant (P < 0.05) increase in body weight gain and oviduct weight was recorded during the phase of sexual maturation. Smaller follicles revealed higher insulin-like growth factor-1 and survivin gene expression, whereas the reverse result was manifested in both the luteinizing and progesterone hormone receptors. In biochemical study, the gonadal steroids (estrogen and progesterone) were recorded higher at the first half of the experiment when a gradual decrease in corticosterone concentration was confirmed from the very beginning of this study. This result substantiated that sexual maturation in Japanese quail may be completed by the time of 8 weeks after its birth in support of the analyzed information studied in the current investigation

  12. 高效液相色谱法测定保健食品中的叶黄素%The determination of lutein in health food by HPLC

    Institute of Scientific and Technical Information of China (English)

    党亚敏; 李建平; 张明月; 渠志华; 夏义平; 马永民

    2011-01-01

    目的:建立测定保健食品中叶黄素含量的方法.方法:采用无水乙醇对试样进行提取,纯甲醇体系作为流动相,ODS C18柱,高效液相色谱(HPLC)进行分离检测.结果:方法的检出限为0.1 μg/g,线性范围在0.3 μg/ml~6.2 μg/ml之间,RSD为5.9%,平均回收率为92%~105%.结论:该方法具有简便、快速、可靠、容易推广等优点,适用于液体、片剂、粉剂、胶囊、软胶囊样品的测定.%Objective: To establish a method for the determination of lutein in health foods. Methods: The samples were extracted by alcohol, eluted with methanol on an ODS C18 column by HPLC. Results: The detection limit of the method is 0.1 μg/g, the linear range is 0.3 μg/ml -6.2 μg/ml, and the RSD is 5.9%. The average recovery is 92% - 105%. Conclusion : The method is simple, fast and reliable. It will provide a reliable analysis method for detecting the concentration of lutein in health foods, including liquid, tablet, powder, capsule and soft capsule samples.

  13. Representation of protein 3D structures in spherical (ρ, ϕ, θ) coordinates and two of its potential applications.

    Science.gov (United States)

    Reyes, Vicente M

    2011-09-01

    Three-dimensional objects can be represented using cartesian, spherical or cylindrical coordinate systems, among many others. Currently all protein 3D structures in the PDB are in cartesian coordinates. We wanted to explore the possibility that protein 3D structures, especially the globular type (spheroproteins), when represented in spherical coordinates might find useful novel applications. A Fortran program was written to transform protein 3D structure files in cartesian coordinates (x,y,z) to spherical coordinates (ρ, ϕ, θ), with the centroid of the protein molecule as origin. We present here two applications, namely, (1) separation of the protein outer layer (OL) from the inner core (IC); and (2) identifying protrusions and invaginations on the protein surface. In the first application, ϕ and θ were partitioned into suitable intervals and the point with maximum ρ in each such 'ϕ-θ bin' was determined. A suitable cutoff value for ρ is adopted, and for each ϕ-θ bin, all points with ρ values less than the cutoff are considered part of the IC, and those with ρ values equal to or greater than the cutoff are considered part of the OL. We show that this separation procedure is successful as it gives rise to an OL that is significantly more enriched in hydrophilic amino acid residues, and an IC that is significantly more enriched in hydrophobic amino acid residues, as expected. In the second application, the point with maximum ρ in each ϕ-θ bin are sequestered and their frequency distribution constructed (i.e., maximum ρ's sorted from lowest to highest, collected into 1.50Å-intervals, and the frequency in each interval plotted). We show in such plots that invaginations on the protein surface give rise to subpeaks or shoulders on the lagging side of the main peak, while protrusions give rise to similar subpeaks or shoulders, but on the leading side of the main peak. We used the dataset of Laskowski et al. (1996) to demonstrate both applications.

  14. SHBG (Sex Hormone Binding Globulin)

    Science.gov (United States)

    ... as: Testosterone-estrogen Binding Globulin; TeBG Formal name: Sex Hormone Binding Globulin Related tests: Testosterone , Free Testosterone, ... I should know? How is it used? The sex hormone binding globulin (SHBG) test may be used ...

  15. 叶黄素强化食用油缓解视疲劳效果研究%The Relieving Effect of Lutein-enriching Oil on Asthenopia

    Institute of Scientific and Technical Information of China (English)

    黄增霞; 潘丽军; 张曼

    2011-01-01

    [目的]研究叶黄素强化食用油对视疲劳的缓解效果.[方法]将叶黄素单体添加入食用油中制成叶黄素强化食用油,将50只SD大鼠随机分为正常组、模型组及叶黄素高、中、低剂量组,定期测定各组大鼠体重及血糖值,试验结束后测定各组大鼠晶状体生化指标.[结果]与正常组比较,模型组大鼠血糖明显升高(P<0.01),而体重及SOD、CAT、GSH、GR活性分别降低了21.4%、43.2%、44.1%、36.0%和18.0%,MDA含量升高了73.4%,GSH含量减少了29.7%;较之模型组,高、中、低剂量叶黄素组大鼠血糖无明显改变,体重有所增加,SOD活性分别提高了40.3%、33.9%和9.7%,CAT活性分别提高了56.4%、45.1%和8.8%,GSH-PX活性分别提高了34.0%、10.6%和1.4%,GR活性分别提高了11.1%、4.2%和3.2%,MDA含量分别降低了23.9%、14.9%和7.6%,GSH含量分别增加了20.8%、17.3%和4.7%.[结论]叶黄素强化食用油能够有效提高眼晶体的总抗氧化能力,对视疲劳具有缓解作用.%[Objective] The paper aimed to study the relieving effect of lutein-enriching oil on asthenopia. [ Method ] Lutein monomer was added into edible oil to make lutein-enriching oil. 50 SD rats were distributed to five groups randomly,including normal control group,model group and high,medium,low dose groups of lutein. Body weight,blood sugar,maleie dialdehyde (MDA) content, superoxide dismutase (SOD) activity and catalase( CAT) activity in the lens were measured. After the experiment,biochemical indicators of rats' lentil of each group were measured. [ Result] In comparison with normal control group,the blood sugar in the model group raised significantly(P<0.01) .however the body weight,SOD activity and CAT activity decreased by 21.4% ,43.2% and 44. 1% ,MDA content increased by 73.4%. Compared with the model group,the , blood sugar in the high,middle and low dose groups of lutein changed solely,the body weight

  16. Plasma Levels of Monocyte Chemotactic Protein 3 and Beta-Nerve Growth Factor Increase with Amnestic Mild Cognitive Impairment

    Institute of Scientific and Technical Information of China (English)

    Kang Soo Lee; Ji Hyung Chung; Kyung Hye Lee; Min-Jeong Shin; Byoung Hoon Oh; Soo Hyung Lee; Chang Hyung Hong

    2009-01-01

    A number of studies have investigated peripheral inflammatory indices, including plasma cytokines and related molecules according to subtypes of dementia, but not in mild cognitive impairment (MCI). In this study, we used multiplex cytokine assay to assess the plasma levels of 22 cytokines in patients with MCI subtyped as amnestic and non-amnestic, according to cognitive features. When comparing the levels of plasma growth factors, chemokines and cytokines, plasma levels of monocyte chemotactic protein 3 (MCP-3), and beta-nerve growth factor (β-NGF) in these two groups, they were found to be significantly higher in amnestic MCI patients than in non-amnestic MCI patients, after adjusting for age and gender. This suggests that plasma MCP-3 and β-NGF may be useful in differentiating subtypes of MCI. Cellular & Molecular Immunology.

  17. GNL3L Inhibits Estrogen Receptor-Related Protein Activities by Competing for Coactivator Binding

    OpenAIRE

    Yasumoto, Hiroaki; Meng, Lingjun; Lin, Tao; Zhu, Qubo; Tsai, Robert Y.L.

    2007-01-01

    Guanine-nucleotide binding protein 3-like (GNL3L) is the closest homologue of a stem cell-enriched factor nucleostemin in vertebrates. They share the same yeast orthologue, Grn1p, but only GNL3L can rescue the growth-deficient phenotype in Grn1p-null yeasts. To determine the unique function of GNL3L, we identified estrogen receptor-related protein-γ (ERRγ) as a GNL3L-specific binding protein. GNL3L and ERRγ are coexpressed in the eye, kidney and muscle, and co-reside in the nucleoplasm. The i...

  18. Molecular determinants of the interaction between coxsackievirus protein 3A and guanine nucleotide exchange factor GBF1.

    NARCIS (Netherlands)

    Wessels, E.; Duijsings, D.; Lanke, K.H.W.; Melchers, W.J.G.; Jackson, C.L.; Kuppeveld, F.J.M. van

    2007-01-01

    The 3A protein of coxsackievirus B3 (CVB3), a small membrane protein that forms homodimers, inhibits endoplasmic reticulum-to-Golgi complex transport. Recently, we described the underlying mechanism by showing that the CVB3 3A protein binds to and inhibits the function of GBF1, a guanine nucleotide

  19. EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on the substantiation of health claims related to lutein and maintenance of normal vision (ID 1603, 1604, further assessment) pursuant to Article 13(1) of Regulation (EC) No 1924/2006

    DEFF Research Database (Denmark)

    Tetens, Inge

    Following a request from the European Commission, the Panel on Dietetic Products, Nutrition and Allergies was asked to provide a scientific opinion on a list of health claims pursuant to Article 13 of Regulation (EC) No 1924/2006 in the framework of further assessment related to lutein and mainte......Following a request from the European Commission, the Panel on Dietetic Products, Nutrition and Allergies was asked to provide a scientific opinion on a list of health claims pursuant to Article 13 of Regulation (EC) No 1924/2006 in the framework of further assessment related to lutein...... into account that one human intervention study in healthy subjects did not show an effect of lutein on visual acuity or glare sensitivity, that the results of this study were inconsistent as regards contrast sensitivity, and that the evidence provided for a mechanism by which lutein could exert the claimed...

  20. Cellulose binding domain proteins

    Energy Technology Data Exchange (ETDEWEB)

    Shoseyov, Oded (Karmey Yosef, IL); Shpiegl, Itai (Rehovot, IL); Goldstein, Marc (Davis, CA); Doi, Roy (Davis, CA)

    1998-01-01

    A cellulose binding domain (CBD) having a high affinity for crystalline cellulose and chitin is disclosed, along with methods for the molecular cloning and recombinant production thereof. Fusion products comprising the CBD and a second protein are likewise described. A wide range of applications are contemplated for both the CBD and the fusion products, including drug delivery, affinity separations, and diagnostic techniques.

  1. Sequential memory: Binding dynamics

    Science.gov (United States)

    Afraimovich, Valentin; Gong, Xue; Rabinovich, Mikhail

    2015-10-01

    Temporal order memories are critical for everyday animal and human functioning. Experiments and our own experience show that the binding or association of various features of an event together and the maintaining of multimodality events in sequential order are the key components of any sequential memories—episodic, semantic, working, etc. We study a robustness of binding sequential dynamics based on our previously introduced model in the form of generalized Lotka-Volterra equations. In the phase space of the model, there exists a multi-dimensional binding heteroclinic network consisting of saddle equilibrium points and heteroclinic trajectories joining them. We prove here the robustness of the binding sequential dynamics, i.e., the feasibility phenomenon for coupled heteroclinic networks: for each collection of successive heteroclinic trajectories inside the unified networks, there is an open set of initial points such that the trajectory going through each of them follows the prescribed collection staying in a small neighborhood of it. We show also that the symbolic complexity function of the system restricted to this neighborhood is a polynomial of degree L - 1, where L is the number of modalities.

  2. Lectin binding in meningiomas.

    Science.gov (United States)

    Kleinert, R; Radner, H

    1987-01-01

    Forty-two meningiomas of different morphological sub-type were examined to determine their pattern of binding to 11 different lectins which characterize cell surface components such as carbohydrate residues. Histiocytic and xanthoma cells within meningiomas could be demonstrated with six different lectins: wheat germ agglutinin (WGA), peanut agglutinin (PNA) Bauhinia purpurea agglutinin (BPA), Helix pomatia agglutinin (HPA), Vicia fava agglutinin (VFA) and Soyabean agglutinin (SBA). Vascular elements including endothelial cells and intimal cells, bound Ulex europaeus agglutinin type 1 (UEA 1), WGA and HPA. The fibrous stroma in fibrous and fibroblastic meningiomas bound PNA, Laburnum alpinum agglutinin (LAA) and SBA. Tumour cells in meningotheliomatous meningiomas and some areas of anaplastic meningiomas bound Concanavalin A, PNA, LAA and VFA whereas tumour cells in fibrous and fibroblastic meningiomas bound BPA, LAA and VFA. Lectin binding has proved to be of value in detecting histiocytic and xanthoma cells together with vascular elements within meningiomas. In addition, the different lectin binding patterns allow different histological sub-types of meningioma to be distinguished although the biological significance of the binding patterns is unclear. PMID:3658105

  3. Foot-and-mouth disease virus non-structural protein 3A inhibits the interferon-β signaling pathway.

    Science.gov (United States)

    Li, Dan; Lei, Caoqi; Xu, Zhisheng; Yang, Fan; Liu, Huanan; Zhu, Zixiang; Li, Shu; Liu, Xiangtao; Shu, Hongbing; Zheng, Haixue

    2016-01-01

    Foot-and-mouth disease virus (FMDV) is the etiological agent of FMD, which affects cloven-hoofed animals. The pathophysiology of FMDV has not been fully understood and the evasion of host innate immune system is still unclear. Here, the FMDV non-structural protein 3A was identified as a negative regulator of virus-triggered IFN-β signaling pathway. Overexpression of the FMDV 3A inhibited Sendai virus-triggered activation of IRF3 and the expressions of RIG-I/MDA5. Transient transfection and co-immunoprecipitation experiments suggested that FMDV 3A interacts with RIG-I, MDA5 and VISA, which is dependent on the N-terminal 51 amino acids of 3A. Furthermore, 3A also inhibited the expressions of RIG-I, MDA5, and VISA by disrupting their mRNA levels. These results demonstrated that 3A inhibits the RLR-mediated IFN-β induction and uncovered a novel mechanism by which the FMDV 3A protein evades the host innate immune system. PMID:26883855

  4. Foot-and-mouth disease virus non-structural protein 3A inhibits the interferon-β signaling pathway

    Science.gov (United States)

    Li, Dan; Lei, Caoqi; Xu, Zhisheng; Yang, Fan; Liu, Huanan; Zhu, Zixiang; Li, Shu; Liu, Xiangtao; Shu, Hongbing; Zheng, Haixue

    2016-01-01

    Foot-and-mouth disease virus (FMDV) is the etiological agent of FMD, which affects cloven-hoofed animals. The pathophysiology of FMDV has not been fully understood and the evasion of host innate immune system is still unclear. Here, the FMDV non-structural protein 3A was identified as a negative regulator of virus-triggered IFN-β signaling pathway. Overexpression of the FMDV 3A inhibited Sendai virus-triggered activation of IRF3 and the expressions of RIG-I/MDA5. Transient transfection and co-immunoprecipitation experiments suggested that FMDV 3A interacts with RIG-I, MDA5 and VISA, which is dependent on the N-terminal 51 amino acids of 3A. Furthermore, 3A also inhibited the expressions of RIG-I, MDA5, and VISA by disrupting their mRNA levels. These results demonstrated that 3A inhibits the RLR-mediated IFN-β induction and uncovered a novel mechanism by which the FMDV 3A protein evades the host innate immune system. PMID:26883855

  5. Cell Transformation and Proteome Alteration in QSG7701 Cells Transfected with Hepatitis C Virus Non-structural Protein 3

    Institute of Scientific and Technical Information of China (English)

    Qiongqiong HE; Deyun FENG; Ruixue CHENG; Zhuchu CHEN; Xuxian XIAO; Zhiqiang XIAO; Cui LI; Bo LI; Pengfei ZHANG; Hui ZHENG

    2007-01-01

    Persistent hepatitis C virus (HCV) infection can cause liver cirrhosis and hepatocellular carcinoma. Non-structural protein 3 (NS3), an important part of HCV, has been implicated in the life cycle of the virus and interacts with host cellular proteins. In this study, we investigated the effect of NS3 protein on cell tranformation and related protein alteration in human hepatocyte QSG7701 cells. The results indicated that stable expression of the NS3 protein in QSG7701 cells induced transformed characters with reduced population doubling time, anchorage-independent growth and tumor development. Fifteen differentially-expressed proteins were separated and identified using 2-D electrophoresis and matrix-assisted laser desorption ionization-time of flight mass spectrometry. Western blot analysis confirmed that the increase of phospho-p44/42 and phospho-p38 proteins was associated with transformed cells. These results supported the view that HCV NS3 protein plays a transforming role and provided some clues to elucidate the carcinogenesis mechanism of HCV-related hepatocellular carcinoma.

  6. Trefoil factor family protein 3 (TFF3) is present in cartilage during endochondral ossification in the developing mouse fetus.

    Science.gov (United States)

    Bijelić, Nikola; Belovari, Tatjana; Baus Lončar, Mirela

    2013-04-01

    Trefoil factor family protein 3 (TFF3) is found in cartilage affected by osteoarthritis and septic arthritis, whereas no TFF3 presence is observed in healthy cartilage. During endochondral ossification, bone tissue replaces degenerating cartilage. There is no data about the role of TFF3 in this process. Our aim was to study the localization of TFF3 in cartilage during endochondral ossification in the mouse fetus. CD1 mouse fetuses, days 14-17, were isolated, fixed, and paraffin embedded. Fetuses were cut into 6μm sections, and processed for immunohistochemical staining with affinity purified polyclonal rabbit anti-TFF3 antibody. TFF3 was present in cartilage chondrocytes undergoing endochondral ossification, particularly in zone of proliferation, hypertrophy and calcification as well as in zone of cartilage degeneration during the monitored fetal period. Resting cartilage showed no presence of TFF3, while during endochondral ossification TFF3 localization showed an analogous pattern to that reported in cartilage affected by osteoarthritis and septic arthritis. Our data indicate that the role of TFF3 in these pathological conditions is similar to its role in the physiological process of endochondral ossification.

  7. Variants of tumor necrosis factor-induced protein 3 gene are associated with left ventricular hypertrophy in hypertensive patients

    Institute of Scientific and Technical Information of China (English)

    XUE Hao; WANG Shu-xia; WANG Xiao-jian; XIN Ying; WANG Hu; SONG Xiao-dong; SUN Kai; WANG Yi-bo; HUI Ru-tai

    2011-01-01

    Background Tumor necrosis factor-induced protein 3 (TNFAIP3) gene has been shown important in cardiac remodeling. The aim of the present study was to investigate whether the variants of TNFAIP3 gene are associated with left ventricular hypertrophy (LVH) in hypertensive patients.Methods Four representatives of all the other single nucleotide polymorphisms (SNPs) in TNFAIP3 gene were tested for association with hypertrophy in two independent hypertensive populations (n=2120 and n=324).Results We found that only the tag SNP (rs5029939) was consistently lower in the hypertensives with cardiac hypertrophy than in those without cardiac hypertrophy in the two study populations, indicating a protective effect on LVH (odds ratio (OR) (95% confidence interval (CI))0.58 (0.358-0.863), P=0.035; OR (95% CI)=0.477 (0.225-0.815), P<0.05,respectively). Multiple regression analyses confirmed that the patients with G allele of rs5029939 had less thickness in inter-ventricular septum, left ventricular posterior wall, relative wall thickness and left ventricular mass index than did those with CC allele in the hypertensive patients in both study populations (all P<0.01).Conclusion These findings indicate that the SNP (rs5029939) in the TNFAIP3 gene may serve as a novel protective genetic marker for the development of LVH in patients with hypertension.

  8. The effects of a lutein-based supplement on objective and subjective measures of retinal and visual function in eyes with age-related maculopathy -- a randomised controlled trial.

    Science.gov (United States)

    Berrow, Emma J; Bartlett, Hannah E; Eperjesi, Frank; Gibson, Jonathan M

    2013-06-01

    Lutein and zeaxanthin are lipid-soluble antioxidants found within the macula region of the retina. Links have been suggested between increased levels of these carotenoids and reduced risk for age-related macular disease (ARMD). Therefore, the effect of lutein-based supplementation on retinal and visual function in people with early stages of ARMD (age-related maculopathy, ARM) was assessed using multifocal electroretinography (mfERG), contrast sensitivity and distance visual acuity. A total of fourteen participants were randomly allocated to either receive a lutein-based oral supplement (treated group) or no supplement (non-treated group). There were eight participants aged between 56 and 81 years (65·50 (SD 9·27) years) in the treated group and six participants aged between 61 and 83 years (69·67 (SD 7·52) years) in the non-treated group. Sample sizes provided 80% power at the 5% significance level. Participants attended for three visits (0, 20 and 40 weeks). At 60 weeks, the treated group attended a fourth visit following 20 weeks of supplement withdrawal. No changes were seen between the treated and non-treated groups during supplementation. Although not clinically significant, mfERG ring 3 N2 latency (P=0·041) and ring 4 P1 latency (P=0·016) increased, and a trend for reduction of mfERG amplitudes was observed in rings 1, 3 and 4 on supplement withdrawal. The statistically significant increase in mfERG latencies and the trend for reduced mfERG amplitudes on withdrawal are encouraging and may suggest a potentially beneficial effect of lutein-based supplementation in ARM-affected eyes. PMID:23084077

  9. Activation of the cAMP-dependent protein kinase signaling pathway by luteinizing hormone in trout theca layers.

    Science.gov (United States)

    Méndez, Eva; Maeland, Mari; Skålhegg, Bjørn S; Planas, Josep V

    2003-07-31

    In the fish ovary, LH is the main factor regulating the production of steroids during the periovulatory period and its effects are believed to be mediated, at least partially, through the cAMP-dependent protein kinase (PKA) signaling pathway. However, there is no direct evidence for the presence of PKA in the fish ovary nor on the regulation of its activity by fish LH. Here, we show the identification of regulatory (R) and catalytic (C) subunits of PKA in trout theca cells by immunoblotting. DEAE-cellulose chromatography of theca cell extracts indicated the presence of PKA type I and II and showed that trout theca cells display PKA-specific phosphotransferase and cAMP-binding activities. Salmon LH (sLH) stimulated PKA activity and increased the levels of immunoreactive RIIalpha, RIIbeta and C subunits in trout theca layers. These observations, coupled with the sLH-dependent decrease in the half-life of the C subunit, as shown by pulse-chase experiments, strongly suggest that sLH activates PKA in trout theca cells. Furthermore, our results suggest that ovarian PKA activity and its regulation by LH has been well conserved from fish to humans. PMID:12890563

  10. Plasma luteinizing hormone and progesterone concentrations in goats with estrous cycles of normal or short duration after prostaglandin F2 alpha administration during diestrus or pregnancy.

    Science.gov (United States)

    Bretzlaff, K N; Weston, P G; Hixon, J E; Ott, R S

    1988-06-01

    Plasma luteinizing hormone (LH) and progesterone concentrations were compared in does experiencing short-duration estrous cycles and in does with estrous cycles of normal duration. The short-duration estrous cycles were observed immediately after induction of abortion in pregnant does by use of prostaglandin (PG) F2 alpha. Intramuscular administration of 5 mg of PGF2 alpha was accomplished in 8 does that were 52 to 63 days into gestation and in 9 cycling does at 7 to 10 days after estrus. In both groups, the mean plasma concentration of progesterone decreased from a luteal phase concentration immediately before to less than 1 ng/ml by 24 hours after PGF2 alpha administration. Of the 8 does that aborted, 6 experienced short-duration estrous cycles, and 4 of these 6 had an LH surge during the time of blood sample collection. The mean time from PGF2 alpha administration to the LH surge was significantly (P less than 0.05) longer in does with short-duration estrous cycles (71 hours) than that in does with estrous cycles of normal duration (58 hours). The mean area under the LH concentration curve was significantly (P less than 0.005) less for does with short-duration estrous cycles. Short-duration estrous cycles were associated with delayed preovulatory LH surges of reduced magnitude. PMID:3165252

  11. Profile of follitropin alpha/lutropin alpha combination for the stimulation of follicular development in women with severe luteinizing hormone and follicle-stimulating hormone deficiency

    Science.gov (United States)

    Rinaldi, Leonardo; Selman, Helmy

    2016-01-01

    A severe gonadotropin deficiency together with chronic estradiol deficiency leading to amenorrhea characterizes patients suffering from hypogonadotropic hypogonadism. Administration of both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) to these patients has been shown to be essential in achieving successful stimulation of follicular development, ovulation, and rescue of fertility. In recent years, the availability of both recombinant FSH (rFSH) and recombinant LH (rLH) has provided a new therapeutic option for the stimulation of follicular growth in hypopituitary–hypogonadotropic women (World Health Organization Group I). In this article, we review the data reported in the literature to highlight the role and the efficacy of using recombinant gonadotropins, rFSH and rLH, in the treatment of women with severe LH/FSH deficiency. Although the studies on this issue are limited and the experiences available in the literature are few due to the small number of such patients, it is clearly evident that the recombinant gonadotropins rFSH and rLH are efficient in treating patients affected by hypogonadotropic hypogonadism. The results observed in the studies reported in this review suggest that recombinant gonadotropins are able to induce proper follicular growth, oocyte maturation, and eventually pregnancy in this group of women. Moreover, the clinical use of recombinant gonadotropins in this type of patients has given more insight into some endocrinological aspects of ovarian function that have not yet been fully understood. PMID:27307766

  12. Interleukin 1α inhibits prostaglandin E2 release to suppress pulsatile release of luteinizing hormone but not follicle-stimulating hormone

    International Nuclear Information System (INIS)

    Interleukin 1α (IL-1α), a powerful endogenous pyrogen released from monocytes and macrophages by bacterial endotoxin, stimulates corticotropin, prolactin, and somatotropin release and inhibits thyrotropin release by hypothalamic action. The authors injected recombinant human IL-1α into the third cerebral ventricle, to study its effect on the pulsatile release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in conscious, freely moving, ovariectomized rats. Intraventricular injection of 0.25 pmol of IL-1α caused an almost immediate reduction of plasma LH concentration. To determine the mechanism of the suppression of LH release, mediobasal hypothalamic fragments were incubated in vitro with IL-1α (10 pM) and the release of LH-releasing hormone (LHRH) and prostaglandin E2 into the medium was measured by RIA in the presence or absence of nonrepinephrine. 1α reduced basal LHRH release and blocked LHRH release induced by nonrepinephrine. In conclusion, IL-1α suppresses LH but not FSH release by an almost complete cessation of pulsatile release of LH in the castrated rat. The mechanism of this effect appears to be by inhibition of prostaglandin E2-mediated release of LHRH

  13. Enhanced Anti-Tumoral Activity of Methotrexate-Human Serum Albumin Conjugated Nanoparticles by Targeting with Luteinizing Hormone-Releasing Hormone (LHRH) Peptide

    Science.gov (United States)

    Taheri, Azade; Dinarvand, Rassoul; Atyabi, Fatemeh; Ahadi, Fatemeh; Nouri, Farank Salman; Ghahremani, Mohammad Hossein; Ostad, Seyed Nasser; Borougeni, Atefeh Taheri; Mansoori, Pooria

    2011-01-01

    Active targeting could increase the efficacy of anticancer drugs. Methotrexate-human serum albumin (MTX-HSA) conjugates, functionalized by luteinizing hormone-releasing hormone (LHRH) as targeting moieties, with the aim of specifically targeting the cancer cells, were prepared. Owing to the high expression of LHRH receptors in many cancer cells as compared to normal cells, LHRH was used as the targeting ligand in this study. LHRH was conjugated to MTX-HSA nanoparticles via a cross-linker. Three types of LHRH targeted nanoparticles with a mean particle size between 120–138 nm were prepared. The cytotoxicity of LHRH targeted and non-targeted nanoparticles were determined on the LHRH positive and negative cell lines. The internalization of the targeted and non-targeted nanoparticles in LHRH receptor positive and negative cells was investigated using flow cytometry analysis and fluorescence microscopy. The cytotoxicity of the LHRH targeted nanoparticles on the LHRH receptor positive cells were significantly more than non-targeted nanoparticles. LHRH targeted nanoparticles were also internalized by LHRH receptor positive cells significantly more than non-targeted nanoparticles. There were no significant differences between the uptake of targeted and non-targeted nanoparticles to the LHRH receptor negative cells. The active targeting procedure using LHRH targeted MTX-HSA nanoparticles could increase the anti-tumoral activity of MTX. PMID:21845098

  14. Enhanced Anti-Tumoral Activity of Methotrexate-Human Serum Albumin Conjugated Nanoparticles by Targeting with Luteinizing Hormone-Releasing Hormone (LHRH Peptide

    Directory of Open Access Journals (Sweden)

    Pooria Mansoori

    2011-07-01

    Full Text Available Active targeting could increase the efficacy of anticancer drugs. Methotrexate-human serum albumin (MTX-HSA conjugates, functionalized by luteinizing hormone-releasing hormone (LHRH as targeting moieties, with the aim of specifically targeting the cancer cells, were prepared. Owing to the high expression of LHRH receptors in many cancer cells as compared to normal cells, LHRH was used as the targeting ligand in this study. LHRH was conjugated to MTX-HSA nanoparticles via a cross-linker. Three types of LHRH targeted nanoparticles with a mean particle size between 120–138 nm were prepared. The cytotoxicity of LHRH targeted and non-targeted nanoparticles were determined on the LHRH positive and negative cell lines. The internalization of the targeted and non-targeted nanoparticles in LHRH receptor positive and negative cells was investigated using flow cytometry analysis and fluorescence microscopy. The cytotoxicity of the LHRH targeted nanoparticles on the LHRH receptor positive cells were significantly more than non-targeted nanoparticles. LHRH targeted nanoparticles were also internalized by LHRH receptor positive cells significantly more than non-targeted nanoparticles. There were no significant differences between the uptake of targeted and non-targeted nanoparticles to the LHRH receptor negative cells. The active targeting procedure using LHRH targeted MTX-HSA nanoparticles could increase the anti-tumoral activity of MTX.

  15. Advanced seasonal reproductive development in a male urban bird is reflected in earlier plasma luteinizing hormone rise but not energetic status.

    Science.gov (United States)

    Davies, Scott; Behbahaninia, Hirbod; Giraudeau, Mathieu; Meddle, Simone L; Waites, Kyle; Deviche, Pierre

    2015-12-01

    Urban animals inhabit an environment considerably different than do their non-urban conspecifics, and to persist urban animals must adjust to these novel environments. The timing of seasonal reproductive development (i.e., growth of gonads and secondary sex organs) is a fundamental determinant of the breeding period and is frequently advanced in urban bird populations. However, the underlying mechanism(s) by which birds adjust the timing of reproductive development to urban areas remain(s) largely unknown. Here, we compared the timing of vernal reproductive development in free-ranging urban and non-urban male Abert's Towhees, Melozone aberti, in Phoenix, Arizona, USA, and tested the non-mutually exclusive hypotheses that earlier reproductive development is due to improved energetic status and/or earlier increase in endocrine activity of the reproductive system. We found that urban birds initiated testicular development earlier than non-urban birds, but this disparity was not associated with differences in body condition, fat stores, or innate immune performance. These results provide no support for the hypothesis that energetic constraints are responsible for delayed reproductive development of non-urban relative to urban male Abert's Towhees. Urban birds did, however, increase their plasma luteinizing hormone, but not plasma testosterone, earlier than non-urban birds. These findings suggest that adjustment to urban areas by Abert's Towhees involves increases in the endocrine activity of the anterior pituitary gland and/or hypothalamus earlier than non-urban towhees.

  16. Luteinizing hormone-releasing hormone targeted poly(methyl vinyl ether maleic acid) nanoparticles for doxorubicin delivery to MCF-7 breast cancer cells.

    Science.gov (United States)

    Varshosaz, Jaleh; Jahanian-Najafabadi, Ali; Ghazzavi, Jila

    2016-08-01

    The purpose of this study was to design a targeted anti-cancer drug delivery system for breast cancer. Therefore, doxorubicin (DOX) loaded poly(methyl vinyl ether maleic acid) nanoparticles (NPs) were prepared by ionic cross-linking method using Zn(2+) ions. To optimise the effect of DOX/polymer ratio, Zn/polymer ratio, and stirrer rate a full factorial design was used and their effects on particle size, zeta potential, loading efficiency (LE, %), and release efficiency in 72 h (RE72, %) were studied. Targeted NPs were prepared by chemical coating of tiptorelin/polyallylamin conjugate on the surface of NPs by using 1-ethyl-3-(3-dimethylaminopropyl) carboiimid HCl as cross-linking agent. Conjugation efficiency was measured by Bradford assay. Conjugated triptorelin and targeted NPs were studied by Fourier-transform infrared spectroscopy (FTIR). The cytotoxicity of DOX loaded in targeted NPs and non-targeted ones were studied on MCF-7 cells which overexpress luteinizing hormone-releasing hormone (LHRH) receptors and SKOV3 cells as negative LHRH receptors using Thiazolyl blue tetrazolium bromide assay. The best results obtained from NPs prepared by DOX/polymer ratio of 5%, Zn/polymer ratio of 50%, and stirrer rate of 960 rpm. FTIR spectrum confirmed successful conjugation of triptorelin to NPs. The conjugation efficiency was about 70%. The targeted NPs showed significantly less IC50 for MCF-7 cells compared to free DOX and non-targeted NPs. PMID:27463791

  17. Interleukin 1. alpha. inhibits prostaglandin E sub 2 release to suppress pulsatile release of luteinizing hormone but not follicle-stimulating hormone

    Energy Technology Data Exchange (ETDEWEB)

    Rettori, V.; McCann, S.M. (Univ. of Texas Southwestern Medical Center, Dallas (United States)); Gimeno, M.F. (CEFYBO, Buenos Aires (Argentina)); Karara, A. (Vanderbilt Univ., Nashville, TN (United States)); Gonzalez, M.C. (Univ. de La Laguno, Tenerife (Spain))

    1991-04-01

    Interleukin 1{alpha} (IL-1{alpha}), a powerful endogenous pyrogen released from monocytes and macrophages by bacterial endotoxin, stimulates corticotropin, prolactin, and somatotropin release and inhibits thyrotropin release by hypothalamic action. The authors injected recombinant human IL-1{alpha} into the third cerebral ventricle, to study its effect on the pulsatile release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in conscious, freely moving, ovariectomized rats. Intraventricular injection of 0.25 pmol of IL-1{alpha} caused an almost immediate reduction of plasma LH concentration. To determine the mechanism of the suppression of LH release, mediobasal hypothalamic fragments were incubated in vitro with IL-1{alpha} (10 pM) and the release of LH-releasing hormone (LHRH) and prostaglandin E{sub 2} into the medium was measured by RIA in the presence or absence of nonrepinephrine. 1{alpha} reduced basal LHRH release and blocked LHRH release induced by nonrepinephrine. In conclusion, IL-1{alpha} suppresses LH but not FSH release by an almost complete cessation of pulsatile release of LH in the castrated rat. The mechanism of this effect appears to be by inhibition of prostaglandin E{sub 2}-mediated release of LHRH.

  18. Diapause-associated protein3 functions as Cu/Zn superoxide dismutase in the Chinese oak silkworm (Antheraea pernyi.

    Directory of Open Access Journals (Sweden)

    Zhenle Bi

    Full Text Available To better understand the molecular mechanism underlying of diapause in Antheraea pernyi (A. pernyi, we cloned a novel diapause-associated protein 3 (DAP3 gene from A. pernyi by reverse transcription-polymerase chain reaction (RT-PCR and studied the biological functions. Sequence analysis revealed that this gene encodes 171 amino acids and has a conserved domain of Copper/Zinc superoxide dismutase (Cu/Zn-SOD. Western blot and qRT-PCR results showed that DAP3 was mainly expressed in the pupal stage, and gradually decreased as diapause development. DAP3 was also expressed in 1st and 5th instar larvae of A. pernyi. In tissues of 5th instar larvae of A. pernyi, DAP3 was mainly expressed in the epidermis, followed by the head, hemolymph and fat body. To identify the SOD activity of DAP3, we constructed a prokaryotic expression vector by inserting the coding region sequence into plasmid pET-28a (+ and obtained the purified rHIS-DAP3 fusion protein by Ni-NTA affinitive column. Importantly, we found the SOD activity of DAP3 fusion protein was approximately 0.6674 U/µg. To further confirm the SOD activity of DAP3 in vivo, we induced the oxidative stress model of pupae by UV irradiation. The results showed that both the mRNA and protein level of DAP3 significantly increased by UV irradiation. Furthermore, the SOD activity of the total lysate of pupae increased significantly at 10 min post UV irradiation and transiently returned to normal level afterwards. These results suggested that DAP3 might be a novel protein with SOD activity getting involved in regulation of diapause in A. pernyi.

  19. Tumor Necrosis Factor-alpha Induced Protein 3 Interacting Protein 1 Gene Polymorphisms and Pustular Psoriasis in Chinese Han Population

    Institute of Scientific and Technical Information of China (English)

    Jian-Wen Han; Yong Wang; Chulu Alateng; Hong-Bin Li; Yun-Hua Bai; Xin-Xiang Lyu; Rina Wu

    2016-01-01

    Background:Psoriasis is a common immune-mediated inflammatory dermatosis.Generalized pustular psoriasis (GPP) is the severe and rare type of psoriasis.The association between tumor necrosis factor-alpha induced protein 3 interacting protein 1 (TNIP1) gene and psoriasis was confirmed in people with multiple ethnicities.This study was to investigate the association between TNIP1 gene polymorphisms and pustular psoriasis in Chinese Han population.Methods:Seventy-three patients with GPP,67 patients with palmoplantar pustulosis (PPP),and 476 healthy controls were collected from Chinese Han population.Six single nucleotide polymorphisms (SNPs) of the TNIP1 gene,namely rs3805435,rs3792798,rs3792797,rs869976,rs17728338,and rs999011 were genotyped by using polymerase chain reaction-ligase detection reaction.Statistical analyses were performed using the PLINK 1.07 package.Allele frequencies and genotyping frequencies for six SNPs were compared by using Chi-square test,odd ratio (OR) (including 95% confidence interval) were calculated.The haplotype analysis was conducted by Haploview software.Results:The frequencies of alleles of five SNPs were significantly different between the GPP group and the control group (P≤ 7.22 × 10-3),especially in the GPP patients without psoriasis vulgaris (PsV).In the haplotype analysis,the most significantly different haplotype was H4:ACGAAC,with 13.1% frequency in the GPP group but only 3.4% in the control group (OR =4.16,P =4.459 × 10-7).However,no significant difference in the allele frequencies was found between the PPP group and control group for each of the six SNPs (P > 0.05).Conclusions:Polymorphisms in TNIP1 are associated with GPP in Chinese Han population.However,no association with PPP was found.These findings suggest that TNIP1 might be a susceptibility gene for GPP.

  20. Tumor Necrosis Factor-alpha Induced Protein 3 Interacting Protein 1 Gene Polymorphisms and Pustular Psoriasis in Chinese Han Population

    Science.gov (United States)

    Han, Jian-Wen; Wang, Yong; Alateng, Chulu; Li, Hong-Bin; Bai, Yun-Hua; Lyu, Xin-Xiang; Wu, Rina

    2016-01-01

    Background: Psoriasis is a common immune-mediated inflammatory dermatosis. Generalized pustular psoriasis (GPP) is the severe and rare type of psoriasis. The association between tumor necrosis factor-alpha induced protein 3 interacting protein 1 (TNIP1) gene and psoriasis was confirmed in people with multiple ethnicities. This study was to investigate the association between TNIP1 gene polymorphisms and pustular psoriasis in Chinese Han population. Methods: Seventy-three patients with GPP, 67 patients with palmoplantar pustulosis (PPP), and 476 healthy controls were collected from Chinese Han population. Six single nucleotide polymorphisms (SNPs) of the TNIP1 gene, namely rs3805435, rs3792798, rs3792797, rs869976, rs17728338, and rs999011 were genotyped by using polymerase chain reaction-ligase detection reaction. Statistical analyses were performed using the PLINK 1.07 package. Allele frequencies and genotyping frequencies for six SNPs were compared by using Chi-square test, odd ratio (OR) (including 95% confidence interval) were calculated. The haplotype analysis was conducted by Haploview software. Results: The frequencies of alleles of five SNPs were significantly different between the GPP group and the control group (P ≤ 7.22 × 10−3), especially in the GPP patients without psoriasis vulgaris (PsV). In the haplotype analysis, the most significantly different haplotype was H4: ACGAAC, with 13.1% frequency in the GPP group but only 3.4% in the control group (OR = 4.16, P = 4.459 × 10−7). However, no significant difference in the allele frequencies was found between the PPP group and control group for each of the six SNPs (P > 0.05). Conclusions: Polymorphisms in TNIP1 are associated with GPP in Chinese Han population. However, no association with PPP was found. These findings suggest that TNIP1 might be a susceptibility gene for GPP. PMID:27364786

  1. Polymorphism of Merozoite Surface Protein-3α Gene of Plasmo-dium vivax in Isolates of Iran

    Directory of Open Access Journals (Sweden)

    M Asmar

    2008-04-01

    Full Text Available Background: The worldwide distribution of P. vivax has expanded significantly and the number of reported cases has been on the rise. Approximately 88% of malaria cases in Iran are caused by Plasmodium vivax, and in order to management of the disease, understanding the population genetic structure of the parasite is necessary for designing and applying drugs and vaccines. Among many potential candidates, merozoite surface protein-3α gene (PvMSP-3α is promising target to develop an effective vaccine. This study was carried out to determine the variation of this gene, as a genetic marker, in Plasmodium vivax isolates in malarious areas of Iran. Methods: Diversity in PvMSP-3α gene was assessed in 85 Plasmodium vivax isolated from four southern and east-southern provinces of the country by PCR/RFLP method. Amplification was performed with two primer pair sets in a nested PCR format and the products were digested by the enzyme HhaI in RFLP method. Results: Based on the size of the PCR products, we observed three biotypes A (about 1900bp, B (about 1400bp and C (about 1100bp of PvMSP-3α gene. Biotype A was predominant. According to RFLP patterns, 10 allelic groups of the gene were observed, that, 7, 2 and 1 groups correspond to the biotype A, B and C, respectively. Mixed genotype and multiple infections were not seen. Conclusion: RFLP method with HhaI enzyme is a useful method for determining the polymorphism of biotype A of PvMSP-3agene.

  2. Principles of a competitive binding assay for the study of the interactions of poorly water-soluble ligands with their soluble binding partners. Application to bilirubin with the use of Sephadex G-10 as a competitive adsorbent.

    Science.gov (United States)

    Meuwissen, J A; Kinnaert, M; Michiels, G; Heirwegh, K P

    1988-01-01

    1. A generally applicable method is described for obtaining experimental data on the interactions between a poorly water-soluble ligand and soluble binding factors, with the use of chemically inert solid adsorbent. The equilibrium distribution of the ligand between the liquid phase containing the soluble binders and the adsorbent must be measured and knowledge of the binding isotherm of the adsorbent is required. Procedures are given for the calculation of the binding parameters. 2. The method has been applied to quantify the interactions of bilirubin with serum and liver cytosol from the rat, Sephadex G-10 serving as the competing adsorbent. Reversible adsorption keeps the concentration of the free ligand low, thereby preventing formation of colloidal bilirubin. The sensitivity of the procedure accommodates the rather high binding affinities by which bilirubin generally interacts with its specific binding proteins. 3. The binding activities of serum and liver cytosol are of comparable magnitude. Binding of bilirubin by rat serum can be described by two independent binding sites, the affinities of which differ by two orders of magnitude. Only the site with the higher affinity appears to be of physiological importance. The major bilirubin-binding sites of rat liver cytosol seem to contribute equally to the overall binding activity of this preparation, provided that GSH is present. PMID:2449176

  3. Interaction of foot-and-mouth disease virus non-structural protein 3A with host protein DCTN3 is important for viral virulence in cattle

    Science.gov (United States)

    Non-structural protein 3A of foot-and-mouth disease virus (FMDV) is a partially conserved protein of 153 amino acids in most FMDVs examined to date. The role of 3A in virus growth and virulence within the natural host is not well understood. Using a yeast two-hybrid approach, we identified cellular ...

  4. Megalin binds and mediates cellular internalization of folate binding protein

    DEFF Research Database (Denmark)

    Birn, Henrik; Zhai, Xiaoyue; Holm, Jan;

    2005-01-01

    Folate is an essential vitamin involved in a number of biological processes. High affinity folate binding proteins (FBPs) exist both as glycosylphosphatidylinositol-linked, membrane associated folate binding proteins and as soluble FBPs in plasma and some secretory fluids such as milk, saliva...... to bind and mediate cellular uptake of FBP. Surface plasmon resonance analysis shows binding of bovine and human milk FBP to immobilized megalin, but not to low density lipoprotein receptor related protein. Binding of (125)I-labeled folate binding protein (FBP) to sections of kidney proximal tubule, known...... to express high levels of megalin, is inhibitable by excess unlabeled FBP and by receptor associated protein, a known inhibitor of binding to megalin. Immortalized rat yolk sac cells, representing an established model for studying megalin-mediated uptake, reveal (125)I-labeled FBP uptake which is inhibited...

  5. Receptor Interacting Protein 3-Mediated Necroptosis Promotes Lipopolysaccharide-Induced Inflammation and Acute Respiratory Distress Syndrome in Mice.

    Directory of Open Access Journals (Sweden)

    Linlin Wang

    Full Text Available Necrosis amplifies inflammation and plays important roles in acute respiratory distress syndrome (ARDS. Necroptosis is a newly identified programmed necrosis that is mediated by receptor interacting protein 3 (RIP3. However, the potential involvement and impact of necroptosis in lipopolysaccharide (LPS-induced ARDS remains unknown. We therefore explored the role and mechanism of RIP3-mediated necroptosis in LPS-induced ARDS. Mice were instilled with increasing doses of LPS intratracheally to induce different degrees of ARDS. Lung tissues were harvested for histological and TUNEL staining and western blot for RIP3, p-RIP3, X-linked inhibitor of apoptosis protein (XIAP, mixed lineage kinase domain-like protein (MLKL, total and cleaved caspases-3/8. Then, wild-type and RIP3 knock-out mice were induced ARDS with 30 mg/kg LPS. Pulmonary cellular necrosis was labeled by the propidium Iodide (PI staining. Levels of TNF-a, Interleukin (IL-1β, IL-6, IL-1α, IL-10 and HMGB1, tissue myeloperoxidase (MPO activity, neutrophil counts and total protein concentration were measured. Results showed that in high dose LPS (30mg/kg and 40mg/kg -induced severe ARDS, RIP3 protein was increased significantly, accompanied by increases of p-RIP3 and MLKL, while in low dose LPS (10mg/kg and 20mg/kg -induced mild ARDS, apoptosis was remarkably increased. In LPS-induced severe ARDS, RIP3 knock-out alleviated the hypothermia symptom, increased survival rate and ameliorated the lung tissue injury RIP3 depletion also attenuated LPS-induced increase in IL-1α/β, IL-6 and HMGB1 release, decreased tissue MPO activity, and reduced neutrophil influx and total protein concentration in BALF in severe ARDS. Further, RIP3 depletion reduced the necrotic cells in the lung and decreased the expression of MLKL, but had no impact on cleaved caspase-3 in LPS-induced ARDS. It is concluded that RIP3-mediated necroptosis is a major mechanism of enhanced inflammation and lung tissue injury in

  6. Forkhead box protein 3 mRNA expression in the peripheral blood of kidney-transplant recipients with acute rejection

    Institute of Scientific and Technical Information of China (English)

    WANG Wei; LI Xiao-bei; YANG Xiao-yong; ZHANG Xiao-dong

    2011-01-01

    Background Regulatory T cells (Tregs) are immunologically and clinically interesting not least because of the important role they play in allograft rejection. Likewise, expression of the transcription factor forkhead box protein 3 (FOXP3), detected in transplant biopsies, is also of interest because of its role in the development of regulatory T cells. In this study, we Investigated the relationship between FoxP3 mRNA expression and acute organ rejection in kidney-transplant recipients.Methods In this prospective study, FoxP3 mRNA expression levels in peripheral blood samples from 10 recipients of living relative-donor kidney transplants were measured before transplantation as well as at the 14th and 90th days post-transplantation. In addition, 46 first-time kidney-transplant recipients participated in a cross-sectional study, with 28 patients classified as having acute organ rejection; whilst the remaining 18 patients had functionally stable allografts. FoxP3 mRNA expression levels in peripheral blood samples were compared between these two different groups.Results Before transplantation mean FoxP3 mRNA levels vs. GADPH mRNA levels (lg(FoxP3 mRNA/GADPH mRNA)) in the 10 recipients were 1.11±0.67. The mean FoxP3 mRNA expression levels measured at 14th and 90th days post-transplantation were significantly higher than before transplantation (1.69±0.38, P=0.03; 1.44±0.21, P=0.04, respectively). Additionally, the mean FoxP3 mRNA levels vs. GADPH mRNA expression levels (lg(FoxP3 mRNA/GADPH mRNA)) were significantly higher in recipients suffering acute rejection compared with those with stable allografts (1.77±0.61 and 1.43±0.27, respectively, P=0.03).Conclusions After kidney transplantation, FoxP3 mRNA levels were found to increase in the peripheral blood of all recipients. Considerably higher FoxP3 mRNA levels were observed in recipients suffering acute rejection. These results suggest that FoxP3 mRNA levels in peripheral blood samples can be used as a diagnostic

  7. Prokaryotic expression and purification of fibronectin leucine rich transmembrane protein 3 C-terminal domain proteins in rats

    Institute of Scientific and Technical Information of China (English)

    Yan Cai; Jing Yang; He Huang; Fang Li; Ganqiu Wu; Jing Yang; Xuegang Luo

    2009-01-01

    BACKGROUND: Studies have suggested that fibronectin leucine-rich transmembrane protein 3 (FLRT3) is related to injury and regeneration of the nervous system. However, the expression and biological characteristics of these proteins remain poorly understood.OBJECTIVE: To obtain FLRT3 C-terminal gene fragments, to effectively express and purify the target proteins.DESIGN, TIME AND SETTING: An observational study of cellular and molecular biology was performed at the laboratory of Histology and Embryology in Xiangya School of Medicine, Central South University between October 2007 and June 2008.MATERIALS: Three Sprague Dawley adult rats were used to extract total RNA from rat brains. The pGEX4T3 and Escherichia coli (E. Coli) JM109 were purchased from Promega. E. Coil BL21 was provided by Novagen.METHODS: FLRT3 protein coding C-terminal DNA fragments, at a length of 786 bp, were amplified using RT-PCR technique from rat total RNA. The amplified products were cloned into the expression vector pGEX4T3. A recombinant expression vector was then constructed and introduced into E. Coli BL21. IsopropyI-D-thiogalactopyranoside was applied to induce expression of recombinant GST fusion proteins, followed by isolation, purification, and renaturation of inclusion bodies that comprised recombinant proteins. Finally, the purified recombinant protein was obtained.MAIN OUTCOME MEASURES: Determination of FLRT3 C-terminal DNA sequence; expression of target proteins was assayed by SDS-PAGE electrophoresis; purified recombinant protein was identified with Western blot methods.RESULTS: FLRT3 protein coding C-terminal DNA fragments, at a length of 786 bp, were successfully harvested through RT-PCR amplification, and were then cloned into the prokaryotic expression vector pGEX4T3. The results of the sequence were consistent with the known gene sequence. SDS-PAGE analysis demonstrated that there was a specific protein band in the recombinant GST fusion proteins at a relative molecular mass

  8. Carboplatin binding to histidine

    Energy Technology Data Exchange (ETDEWEB)

    Tanley, Simon W. M. [University of Manchester, Brunswick Street, Manchester M13 9PL (United Kingdom); Diederichs, Kay [University of Konstanz, D-78457 Konstanz (Germany); Kroon-Batenburg, Loes M. J. [Utrecht University, Padualaan 8, 3584 CH Utrecht (Netherlands); Levy, Colin [University of Manchester, 131 Princess Street, Manchester M1 7DN (United Kingdom); Schreurs, Antoine M. M. [Utrecht University, Padualaan 8, 3584 CH Utrecht (Netherlands); Helliwell, John R., E-mail: john.helliwell@manchester.ac.uk [University of Manchester, Brunswick Street, Manchester M13 9PL (United Kingdom)

    2014-08-29

    An X-ray crystal structure showing the binding of purely carboplatin to histidine in a model protein has finally been obtained. This required extensive crystallization trials and various novel crystal structure analyses. Carboplatin is a second-generation platinum anticancer agent used for the treatment of a variety of cancers. Previous X-ray crystallographic studies of carboplatin binding to histidine (in hen egg-white lysozyme; HEWL) showed the partial conversion of carboplatin to cisplatin owing to the high NaCl concentration used in the crystallization conditions. HEWL co-crystallizations with carboplatin in NaBr conditions have now been carried out to confirm whether carboplatin converts to the bromine form and whether this takes place in a similar way to the partial conversion of carboplatin to cisplatin observed previously in NaCl conditions. Here, it is reported that a partial chemical transformation takes place but to a transplatin form. Thus, to attempt to resolve purely carboplatin binding at histidine, this study utilized co-crystallization of HEWL with carboplatin without NaCl to eliminate the partial chemical conversion of carboplatin. Tetragonal HEWL crystals co-crystallized with carboplatin were successfully obtained in four different conditions, each at a different pH value. The structural results obtained show carboplatin bound to either one or both of the N atoms of His15 of HEWL, and this particular variation was dependent on the concentration of anions in the crystallization mixture and the elapsed time, as well as the pH used. The structural details of the bound carboplatin molecule also differed between them. Overall, the most detailed crystal structure showed the majority of the carboplatin atoms bound to the platinum centre; however, the four-carbon ring structure of the cyclobutanedicarboxylate moiety (CBDC) remained elusive. The potential impact of the results for the administration of carboplatin as an anticancer agent are described.

  9. Effects of mutations in the Arabidopsis Cold Shock Domain Protein 3 (AtCSP3) gene on leaf cell expansion.

    Science.gov (United States)

    Yang, Yongil; Karlson, Dale

    2012-08-01

    The cold shock domain is among the most evolutionarily conserved nucleic acid binding domains from prokaryotes to higher eukaryotes, including plants. Although eukaryotic cold shock domain proteins have been extensively studied as transcriptional and post-transcriptional regulators during various developmental processes, their functional roles in plants remains poorly understood. In this study, AtCSP3 (At2g17870), which is one of four Arabidopsis thaliana c old s hock domain proteins (AtCSPs), was functionally characterized. Quantitative RT-PCR analysis confirmed high expression of AtCSP3 in reproductive and meristematic tissues. A homozygous atcsp3 loss-of-function mutant exhibits an overall reduced seedling size, stunted and orbicular rosette leaves, reduced petiole length, and curled leaf blades. Palisade mesophyll cells are smaller and more circular in atcsp3 leaves. Cell size analysis indicated that the reduced size of the circular mesophyll cells appears to be generated by a reduction of cell length along the leaf-length axis, resulting in an orbicular leaf shape. It was also determined that leaf cell expansion is impaired for lateral leaf development in the atcsp3 loss-of-function mutant, but leaf cell proliferation is not affected. AtCSP3 loss-of-function resulted in a dramatic reduction of LNG1 transcript, a gene that is involved in two-dimensional leaf polarity regulation. Transient subcellular localization of AtCSP3 in onion epidermal cells confirmed a nucleocytoplasmic localization pattern. Collectively, these data suggest that AtCSP3 is functionally linked to the regulation of leaf length by affecting LNG1 transcript accumulation during leaf development. A putative function of AtCSP3 as an RNA binding protein is also discussed in relation to leaf development.

  10. Changes in serum concentrations of growth hormone, insulin, insulin-like growth factor and insulin-like growth factor-binding proteins 1 and 3 and urinary growth hormone excretion during the menstrual cycle

    DEFF Research Database (Denmark)

    Juul, A; Scheike, Thomas Harder; Pedersen, A T;

    1997-01-01

    Few studies exist on the physiological changes in the concentrations of growth hormone (GH), insulin-like growth factors (IGF) and IGF-binding proteins (IGFBP) within the menstrual cycle, and some controversy remains. We therefore decided to study the impact of endogenous sex steroids on the GH......-IGF-IGFBP axis during the ovulatory menstrual cycle in 10 healthy women (aged 18-40 years). Blood sampling and urinary collection was performed every morning at 0800 h for 32 consecutive days. Every second day the subjects were fasted overnight before blood sampling. Follicle stimulating hormone, luteinizing...... hormone (LH), oestradiol, progesterone, IGF-I, IGFBP-3, sex hormone-binding globulin, dihydroepiandrosterone sulphate and GH were determined in all samples, whereas insulin and IGFBP-1 were determined in fasted samples only. Serum IGF-I concentrations showed some fluctuation during the menstrual cycle...

  11. Changes in serum concentrations of growth hormone, insulin, insulin-like growth factor and insulin-like growth factor-binding proteins 1 and 3 and urinary growth hormone excretion during the menstrual cycle

    DEFF Research Database (Denmark)

    Juul, A; Scheike, Thomas Harder; Pedersen, A T;

    1997-01-01

    -IGF-IGFBP axis during the ovulatory menstrual cycle in 10 healthy women (aged 18-40 years). Blood sampling and urinary collection was performed every morning at 0800 h for 32 consecutive days. Every second day the subjects were fasted overnight before blood sampling. Follicle stimulating hormone, luteinizing......Few studies exist on the physiological changes in the concentrations of growth hormone (GH), insulin-like growth factors (IGF) and IGF-binding proteins (IGFBP) within the menstrual cycle, and some controversy remains. We therefore decided to study the impact of endogenous sex steroids on the GH...... hormone (LH), oestradiol, progesterone, IGF-I, IGFBP-3, sex hormone-binding globulin, dihydroepiandrosterone sulphate and GH were determined in all samples, whereas insulin and IGFBP-1 were determined in fasted samples only. Serum IGF-I concentrations showed some fluctuation during the menstrual cycle...

  12. 万寿菊叶黄素的提取与皂化工艺研究%The research on marigold extraction and saponification process about lutein

    Institute of Scientific and Technical Information of China (English)

    张志强; 刘进风; 吕伶俐; 向正华; 边丽霞

    2011-01-01

    试验采用了有机溶剂浸提和氢氧化钾甲醇溶液皂化的方法,研究了万寿菊叶黄素的提取与皂化的工艺条件.试验考察了提取剂种类、提取温度、提取时间、料液比对提取效果的影响,以及皂化液种类、皂化液浓度、皂化液用量、皂化温度、皂化时间、对皂化的影响.通过单因素试验确定的提取和皂化工艺条件为:提取剂为无水乙醇:石油醚(沸程为60℃~90℃)(2:1),料液比为1:100,提取温度45℃,提取时间80min,皂化液浓度20%,皂化液用量0.2mL,皂化温度40℃,皂化时间80min.选用乙醇—石油醚混合溶剂作为提取剂,具有价格便宜、低毒、沸点低、溶剂回收成本较低、生产安全性高等优点.该提取剂用于工业生产中提取叶黄素是可行的.%With the method ot organic solvent extraction and mehtanol solution ot potassium hydroxide saponuication, this research studied the extraction and saponification process conditions of lutein in marigold flower. Research examined the effects of extraction agents types, extraction temperature, extraction time, and ratio of material to liquid on extraction, as well as the effects of saponification solution types, saponification solution concentration, saponification liquid dosage, saponification temperature and saponification time on saponification. On the base of single - factor test, the optimized conditions of extraction and saponification were: extraction agents was ethanol: petroleum ether (boiling range of 60 °C~90°C ) (2:1), expected liquid ratio was 1 : 100, extraction temperature was 45°C, extraction time was 80min, saponification solution concentration was 20% , the amount of saponification solution was 0. 2mL, saponification temperature was 40 "C , saponification time was 80min. The use of ethanol - petroleum ether mixed solvent as extraction agent has the advantages of cheap, low toxicity, low boiling point, low solvent recovery costs, safe production. This

  13. Editing of the Luteinizing Hormone Gene to Sterilize Channel Catfish, Ictalurus punctatus, Using a Modified Zinc Finger Nuclease Technology with Electroporation.

    Science.gov (United States)

    Qin, Zhenkui; Li, Yun; Su, Baofeng; Cheng, Qi; Ye, Zhi; Perera, Dayan A; Fobes, Michael; Shang, Mei; Dunham, Rex A

    2016-04-01

    Channel catfish (Ictalurus punctatus) is the most important freshwater aquaculture species in the USA. Genetically enhanced fish that are sterile could both profit the catfish industry and reduce potential environmental and ecological risks. As the first step to generate sterile channel catfish, three sets of zinc finger nuclease (ZFN) plasmids targeting the luteinizing hormone (LH) gene were designed and electroporated into one-cell embryos, different concentrations were introduced, and the Cel-I assay was conducted to detect mutations. Channel catfish carrying the mutated LH gene were sterile, as confirmed by DNA sequencing and mating experiments. The overall mutation rate was 19.7 % for 66 channel catfish, and the best treatment was ZFN set 1 at the concentration 25 μg/ml. To our knowledge, this is the first instance of gene editing of fish via plasmid introduction instead of mRNA microinjection. The introduction of the ZFN plasmids may have reduced mosaicism, as mutated individuals were gene edited in every tissue evaluated. Apparently, the plasmids were eventually degraded without integration, as they were not detectable in mutated individuals using PCR. Carp pituitary extract failed to induce spawning and restoration of fertility, indicating the need for developing other hormone therapies to achieve reversal of sterility upon demand. This is the first sterilization achieved using ZFN technology in an aquaculture species and the first successful gene editing of channel catfish. Our results will help understand the roles of the LH gene, purposeful sterilization of teleost fishes, and is a step towards control of domestic, hybrid, exotic, invasive, and transgenic fishes. PMID:26846523

  14. Role of hypothalamus nociceptin/orphanin FQ in pre-ovulatory luteinizing hormone surge of estrogen and progesterone-primed, ovariectomized rats

    Institute of Scientific and Technical Information of China (English)

    Xiao-fei AN; Jiang-yi YU; Yi FENG; Bo-ying CHEN; Su-lin ZHANG

    2007-01-01

    Aim: To investigate the role of hypothalamus nociceptin/orphanin FQ (OFQ) and its endogenous receptor, the opioid receptor-likel receptor (ORL1 receptor) in the estrus cycle of female rats. Method: Radioimmunoassay was used to detect the effect of the intracerebroventricular (icv) administration of OFQ and/or the ORL1 receptor antagonist [Nphel]Nociceptin(1-13)NH2 that is, NC13 on luteinizing hormone (LH) levels of estrogen- and progesterone (EBP)-primed, ovariectomized (OVX) rats (EBP-primed OVX rats). RT-PCR, Western blotting, and immunohis- tochemistry techniques were adopted to observe the changes of OFQ and the ORL1 receptor in the pre-optic area (POA) and the medial basal hypothalamus (MBH) of the estrus cycle of female rat. Results: Pre-ovulatory LH surges in EBP-primed, OVX rats were significantly reduced by icv administration of 20 and 200 nmol OFQ (P<0.05), and the effect of 20 nmol OFQ could be abolished by pretreat-ment with 20 nmol NC13. The OFQ mRNA level in the POA on pro-estrus was lowered markedly compared to diestrus and estrus (P<0.05), while the mRNA and protein levels of the ORL1 receptor showed no significant changes in the POA and MBH across the estrus cycle. Meanwhile, the number of OFQ-immunoreac-tive neurons in the medial POA, ventromedial hypothalamus, and the arcuate nucleus on pro-estrus was significantly decreased compared to diestrus and es-trus (P<0.05). Conclusion: The inhibitory effect of OFQ on the LH surge of EBP-primed, OVX rats and its downregulation in POA and MBH on pro-estrus sug-gests that it might play a negative modulatory role in the estrus cycle.

  15. Summer (subarctic) versus winter (subtropic) production affects spinach (Spinacia oleracea L.) leaf bionutrients: vitamins (C, E, Folate, K1, provitamin A), lutein, phenolics, and antioxidants.

    Science.gov (United States)

    Lester, Gene E; Makus, Donald J; Hodges, D Mark; Jifon, John L

    2013-07-24

    Comparison of spinach (Spinacia oleracea L.) cultivars Lazio and Samish grown during the summer solstice in the subarctic versus the winter solstice in the subtropics provided insight into interactions between production environment (light intensity), cultivar, and leaf age/maturity/position affecting bionutrient concentrations of vitamins (C, E, folate, K1, provitamin A), lutein, phenolics, and antioxidants. Growing spinach during the winter solstice in the subtropics resulted in increased leaf dry matter %, oxidized (dehydro) ascorbic acid (AsA), α- and γ-tocopherol, and total phenols but lower reduced (free) AsA, α-carotene, folate, and antioxidant capacity compared to summer solstice-grown spinach in the subarctic. Both cultivars had similar bionutrients, except for higher dehydroAsA, and lower α- and γ-tocopherol in 'Samish' compared to 'Lazio'. For most bionutrients measured, there was a linear, and sometimes quadratic, increase in concentrations from bottom to top canopy leaves. However, total phenolics and antioxidant capacity increased basipetally. The current study has thus demonstrated that dehydroAsA, α-tocopherol, and γ-tocopherol were substantially lower in subarctic compared to subtropical-grown spinach, whereas the opposite relationship was found for antioxidant capacity, α-carotene, and folates (vitamin B9). The observations are consistent with previously reported isolated effects of growth environment on bionutrient status of crops. The current results clearly highlight the effect of production environment (predominantly radiation capture), interacting with genetics and plant phenology to alter the bionutrient status of crops. While reflecting the effects of changing growing conditions, these results also indicate potential alterations in the nutritive value of foods with anticipated shifts in global climatic conditions. PMID:23834651

  16. Summer (subarctic) versus winter (subtropic) production affects spinach (Spinacia oleracea L.) leaf bionutrients: vitamins (C, E, Folate, K1, provitamin A), lutein, phenolics, and antioxidants.

    Science.gov (United States)

    Lester, Gene E; Makus, Donald J; Hodges, D Mark; Jifon, John L

    2013-07-24

    Comparison of spinach (Spinacia oleracea L.) cultivars Lazio and Samish grown during the summer solstice in the subarctic versus the winter solstice in the subtropics provided insight into interactions between production environment (light intensity), cultivar, and leaf age/maturity/position affecting bionutrient concentrations of vitamins (C, E, folate, K1, provitamin A), lutein, phenolics, and antioxidants. Growing spinach during the winter solstice in the subtropics resulted in increased leaf dry matter %, oxidized (dehydro) ascorbic acid (AsA), α- and γ-tocopherol, and total phenols but lower reduced (free) AsA, α-carotene, folate, and antioxidant capacity compared to summer solstice-grown spinach in the subarctic. Both cultivars had similar bionutrients, except for higher dehydroAsA, and lower α- and γ-tocopherol in 'Samish' compared to 'Lazio'. For most bionutrients measured, there was a linear, and sometimes quadratic, increase in concentrations from bottom to top canopy leaves. However, total phenolics and antioxidant capacity increased basipetally. The current study has thus demonstrated that dehydroAsA, α-tocopherol, and γ-tocopherol were substantially lower in subarctic compared to subtropical-grown spinach, whereas the opposite relationship was found for antioxidant capacity, α-carotene, and folates (vitamin B9). The observations are consistent with previously reported isolated effects of growth environment on bionutrient status of crops. The current results clearly highlight the effect of production environment (predominantly radiation capture), interacting with genetics and plant phenology to alter the bionutrient status of crops. While reflecting the effects of changing growing conditions, these results also indicate potential alterations in the nutritive value of foods with anticipated shifts in global climatic conditions.

  17. Non-steroidal antiandrogen monotherapy compared with luteinizing hormone-releasing hormone agonists or surgical castration monotherapy for advanced prostate cancer: a Cochrane systematic review.

    Science.gov (United States)

    Kunath, Frank; Grobe, Henrik R; Rücker, Gerta; Motschall, Edith; Antes, Gerd; Dahm, Philipp; Wullich, Bernd; Meerpohl, Joerg J

    2015-07-01

    To assess the effects of non-steroidal antiandrogen monotherapy compared with luteinizing hormone-releasing hormone agonists or surgical castration monotherapy for treating advanced hormone-sensitive stages of prostate cancer. We searched the Cochrane Prostatic Diseases and Urologic Cancers Group Specialized Register (PROSTATE), the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Web of Science with Conference Proceedings, three trial registries and abstracts from three major conferences to 23 December 2013, together with reference lists, and contacted selected experts in the field and manufacturers. We included randomized controlled trials comparing non-steroidal antiandrogen monotherapy with medical or surgical castration monotherapy for men in advanced hormone-sensitive stages of prostate cancer. Two review authors independently examined full-text reports, identified relevant studies, assessed the eligibility of studies for inclusion, extracted data and assessed risk of bias as well as quality of evidence according to the GRADE working group guidelines. We used Review Manager 5.2 for data synthesis and the fixed-effect model as primary analysis (when heterogeneity was low with I(2) cancer-specific survival and biochemical progression remained unclear. Non-steroidal antiandrogen monotherapy compared with medical or surgical castration monotherapy for advanced prostate cancer is less effective in terms of overall survival, clinical progression, treatment failure and treatment discontinuation resulting from adverse events. Evidence quality was rated as moderate according to GRADE; therefore, further research is likely to have an important impact on results for patients with advanced but non-metastatic prostate cancer treated with non-steroidal antiandrogen monotherapy. PMID:25523493

  18. A luteinizing hormone receptor intronic variant is significantly associated with decreased risk of Alzheimer's disease in males carrying an apolipoprotein E ε4 allele

    Directory of Open Access Journals (Sweden)

    Gleason Carey E

    2008-04-01

    Full Text Available Abstract Genetic and biochemical studies support the apolipoprotein E (APOE ε4 allele as a major risk factor for late-onset Alzheimer's disease (AD, though ~50% of AD patients do not carry the allele. APOE transports cholesterol for luteinizing hormone (LH-regulated steroidogenesis, and both LH and neurosteroids have been implicated in the etiology of AD. Since polymorphisms of LH beta-subunit (LHB and its receptor (LHCGR have not been tested for their association with AD, we scored AD and age-matched control samples for APOE genotype and 14 polymorphisms of LHB and LHCGR. Thirteen gene-gene interactions between the loci of LHB, LHCGR, and APOE were associated with AD. The most strongly supported of these interactions was between an LHCGR intronic polymorphism (rs4073366; lhcgr2 and APOE in males, which was detected using all three interaction analyses: linkage disequilibrium, multi-dimensionality reduction, and logistic regression. While the APOE ε4 allele carried significant risk of AD in males [p = 0.007, odds ratio (OR = 3.08(95%confidence interval: 1.37, 6.91], ε4-positive males carrying 1 or 2 C-alleles at lhcgr2 exhibited significantly decreased risk of AD [OR = 0.06(0.01, 0.38; p = 0.003]. This suggests that the lhcgr2 C-allele or a closely linked locus greatly reduces the risk of AD in males carrying an APOE ε4 allele. The reversal of risk embodied in this interaction powerfully supports the importance of considering the role gene-gene interactions play in the etiology of complex biological diseases and demonstrates the importance of using multiple analytic methods to detect well-supported gene-gene interactions.

  19. Expression of antiapoptosis gene survivin in luteinized ovarian granulosa cells of women undergoing IVF or ICSI and embryo transfer: clinical correlations

    Directory of Open Access Journals (Sweden)

    Varras Michail

    2012-09-01

    Full Text Available Abstract Background The purpose of the study was to determine the incidence of survivin gene expression in human granulosa cells during ovarian stimulation in Greek women with normal FSH levels, undergoing IVF or ICSI and to discover any correlation between levels of gene expression and clinical parameters, efficacy of ovulation or outcomes of assisted reproduction. Methods Twenty nine women underwent ovulation induction for IVF or ICSI and ET with standard GnRH analogue-recombinant FSH protocol. Infertility causes were male and tubal factor. Cumulus–mature oocyte complexes were denuded and the granulosa cells were analyzed for each patient separately using quantitative reverse transcription polymerase chain reaction analysis for survivin gene expression with internal standard the ABL gene. Results The ABL and survivin mRNA were detected in granulosa cells in 93.1%. The expression levels of survivin were significantly lower in normal women (male infertility factor compared to women with tubal infertility factor (p = 0.007. There was no additional statistically significant correlation between levels of survivin expression and estradiol levels or dosage of FSH for ovulation induction or number of dominant follicles aspirated or number of retrieved oocytes or embryo grade or clinical pregnancy rates respectively. Conclusions High levels of survivin mRNA expression in luteinized granulosa cells in cases with tubal infertility seem to protect ovaries from follicular apoptosis. A subpopulation of patients with low levels of survivin mRNA in granulosa cells might benefit with ICSI treatment to bypass possible natural barriers of sperm-oocyte interactions.

  20. Profile of follitropin alpha/lutropin alpha combination for the stimulation of follicular development in women with severe luteinizing hormone and follicle-stimulating hormone deficiency

    Directory of Open Access Journals (Sweden)

    Rinaldi L

    2016-05-01

    Full Text Available Leonardo Rinaldi, Helmy Selman One Day Medical Center, IVF Unit, Rome, Italy Abstract: A severe gonadotropin deficiency together with chronic estradiol deficiency leading to amenorrhea characterizes patients suffering from hypogonadotropic hypogonadism. Administration of both follicle-stimulating hormone (FSH and luteinizing hormone (LH to these patients has been shown to be essential in achieving successful stimulation of follicular development, ovulation, and rescue of fertility. In recent years, the availability of both recombinant FSH (rFSH and recombinant LH (rLH has provided a new therapeutic option for the stimulation of follicular growth in hypopituitary–hypogonadotropic women (World Health Organization Group I. In this article, we review the data reported in the literature to highlight the role and the efficacy of using recombinant gonadotropins, rFSH and rLH, in the treatment of women with severe LH/FSH deficiency. Although the studies on this issue are limited and the experiences available in the literature are few due to the small number of such patients, it is clearly evident that the recombinant gonadotropins rFSH and rLH are efficient in treating patients affected by hypogonadotropic hypogonadism. The results observed in the studies reported in this review suggest that recombinant gonadotropins are able to induce proper follicular growth, oocyte maturation, and eventually pregnancy in this group of women. Moreover, the clinical use of recombinant gonadotropins in this type of patients has given more insight into some endocrinological aspects of ovarian function that have not yet been fully understood. Keywords: follicular growth, gonadotropins, implantation, ovarian stimulation, pregnancy

  1. The effect of dietary monensin on th luteinizing hormone response of prepuberal heifers given a multiple gonadotropin-releasing hormone challenge.

    Science.gov (United States)

    Randel, R D; Rhodes, R C

    1980-10-01

    Ten prepuberal Simmental X Brahman-Hereford heifers (average weight 208 +/- 4 kg) were randomly assigned to receive either 2.7 kg/head/day of ground milo containing 0 mg monensin sodium (C) or 2.7 kg/head/day of ground milo containing 200 mg monensin sodium (M). Both groups of animals (n = 5) received Coastal bermudagrass hay ad libitum throughout the trial. On day 21 of the feeding period all heifers were fitted with jugular cannulas. Immediately after cannulation, the heifers were injected IM with 100 microgram of gonadotropin-releasing hormone (GnRH) and blood was collected every 10 min for 4 hours. Four hours after the first GnRH challenge, a second 100-microgram GnRH injection was administered, and blood samples were collected at 10-min intervals for an additional 5 hours. Serum was stored at -20 C until radioimmunoassayed for luteinizing hormone (LH). The amount of LH released after each GnRH injection was greater in the heifers fed M than in the controls (P less than .05). Peak LH after the first GnRH challenge was greater (P less than .05) in heifers fed M than in controls. The area under th first GnRH induced LH curve tended (P less than .20) to be greater for the M group than for the controls. Peak LH concentration was greater in heifers fed M than in control heifers, as the duration (P less than .05) and area under the second GnRH-induced LH curve. In prepuberal heifers, dietary monensin appears to increase hypophyseal capability of releasing LH after a first and second GnRH challenge. PMID:7007307

  2. A comparison of human chorionic gonadotropin and luteinizing hormone releasing hormone on the induction of spermiation and amplexus in the American toad (Anaxyrus americanus

    Directory of Open Access Journals (Sweden)

    Kouba Andrew J

    2012-08-01

    Full Text Available Abstract Background Captive breeding programs for endangered amphibian species often utilize exogenous hormones for species that are difficult to breed. The purpose of our study was to compare the efficacy of two different hormones at various concentrations on sperm production, quantity and quality over time in order to optimize assisted breeding. Methods Male American toads (Anaxyrus americanus were divided into three separate treatment groups, with animals in each group rotated through different concentrations of luteinizing hormone releasing hormone analog (LHRH; 0.1, 1.0, 4.0 and 32 micrograms/toad, human chorionic gonadotropin (hCG; 50, 100, 200, and 300 IU, or the control over 24 hours. We evaluated the number of males that respond by producing spermic urine, the sperm concentration, percent motility, and quality of forward progression. We also evaluated the effects of hCG and LHRH on reproductive behavior as assessed by amplexus. Data were analyzed using the Generalized Estimating Equations incorporating repeated measures over time and including the main effects of treatment and time, and the treatment by time interaction. Results The hormone hCG was significantly more effective at stimulating spermiation in male Anaxyrus americanus than LHRH and showed a dose-dependent response in the number of animals producing sperm. At the most effective hCG dose (300 IU, 100% of the male toads produced sperm, compared to only 35% for the best LHRH dose tested (4.0 micrograms. In addition to having a greater number of responders (P  Conclusion There is a clear dichotomy between the two hormones’ physiological responses on gamete production and stimulation of amplexus. Understanding how these two hormones influence physiology and reproductive behaviors in amphibians will have direct bearing on establishing similar breeding protocols for endangered species.

  3. The effect of dietary monensin on th luteinizing hormone response of prepuberal heifers given a multiple gonadotropin-releasing hormone challenge.

    Science.gov (United States)

    Randel, R D; Rhodes, R C

    1980-10-01

    Ten prepuberal Simmental X Brahman-Hereford heifers (average weight 208 +/- 4 kg) were randomly assigned to receive either 2.7 kg/head/day of ground milo containing 0 mg monensin sodium (C) or 2.7 kg/head/day of ground milo containing 200 mg monensin sodium (M). Both groups of animals (n = 5) received Coastal bermudagrass hay ad libitum throughout the trial. On day 21 of the feeding period all heifers were fitted with jugular cannulas. Immediately after cannulation, the heifers were injected IM with 100 microgram of gonadotropin-releasing hormone (GnRH) and blood was collected every 10 min for 4 hours. Four hours after the first GnRH challenge, a second 100-microgram GnRH injection was administered, and blood samples were collected at 10-min intervals for an additional 5 hours. Serum was stored at -20 C until radioimmunoassayed for luteinizing hormone (LH). The amount of LH released after each GnRH injection was greater in the heifers fed M than in the controls (P less than .05). Peak LH after the first GnRH challenge was greater (P less than .05) in heifers fed M than in controls. The area under th first GnRH induced LH curve tended (P less than .20) to be greater for the M group than for the controls. Peak LH concentration was greater in heifers fed M than in control heifers, as the duration (P less than .05) and area under the second GnRH-induced LH curve. In prepuberal heifers, dietary monensin appears to increase hypophyseal capability of releasing LH after a first and second GnRH challenge.

  4. The CRH-R₁ receptor mediates luteinizing hormone, prolactin, corticosterone and progesterone secretion induced by restraint stress in estrogen-primed rats.

    Science.gov (United States)

    Traslaviña, Guillermo A Ariza; Franci, Celso Rodrigues

    2011-11-01

    Acute stress has been shown to modify hypothalamus-pituitary-gonadal (HPG) axis activity. Corticotropin-releasing hormone (CRH), the principal regulator of the hypothalamus-pituitary-adrenal (HPA) axis, has been implicated as a mediator of stress-induced effects on the reproductive axis. The role of the specific CRH receptor subtypes in this response is not completely understood. In the current study, we investigated the role of the CRH-R(1) receptor on luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin (PRL), progesterone (P) and corticosterone (CT) secretion in stress-induced responses under the influence of estrogen (E(2)). Estrogen-primed ovariectomized rats (estradiol cypionate, 10 μg sc) received an i.v. administration of antalarmin (0.1 or 1mg/kg), a selective CRH-R(1) antagonist, or vehicle before restraint stress for 40 min. Seven blood samples were collected from two experimental groups (one from 10:00 h to 14:00 h and the other from 10:00 h to 18:00 h). An increase of plasma LH induced by restraint acute-stress was followed by alteration of the secretion pattern in the estrogen-induced afternoon surge. In a similar manner, we observed a suppression of the afternoon surge in plasma FSH, a delay of E(2)-induced PRL secretion, and an increase in plasma P and CT. Antalarmin attenuated stress-induce LH increase, decreased CT and P secretion and blocked the stress effects on PRL secretion. These findings suggest that CRH-R(1) mediates, at least in part, the restraint stress effects on the HPA, PRL, and reproductive axes.

  5. Novel C617Y mutation in the 7th transmembrane segment of luteinizing hormone/choriogonadotropin receptor in a Japanese boy with peripheral precocious puberty.

    Science.gov (United States)

    Nagasaki, Keisuke; Katsumata, Noriyuki; Ogawa, Yohei; Kikuchi, Toru; Uchiyama, Makoto

    2010-01-01

    Testotoxicosis, also known as familial male-limited precocious puberty, is an autosomal dominant form of gonadotropin-independent precocious puberty caused by heterozygous constitutively activating mutations of the LHCGR gene encoding the luteinizing hormone/choriogonadotropin receptor (LH/CGR). The patient is an 8-year-old boy who started to develop pubic hair and penile enlargement at 6 years of age. The patient had elevated serum testosterone levels, but initially exhibited a prepubertal response of gonadotropins to GnRH, which was followed by central activation of the hypothalamo-pituitary-gonadal axis. The father reported having experienced precocious puberty, and is 158 cm tall. There is no history of short stature and precocious puberty in the family except for the father. The LHCGR gene was analyzed by direct DNA sequencing of amplified PCR products from the patient and his parents. The wild-type and mutant LH/CGRs were transiently expressed in COS-1 cells and cAMP levels in the cells were determined with or without hCG stimulation. Genetic analysis revealed a novel C617Y mutation of the LHCGR gene in the patient and his mother, while his father had no mutations. Functional expression study demonstrated around 15% increase in the basal intracellular cAMP level in cells expressing the mutant LH/CGR compared with that in cells expressing the wild-type receptor. We have reported the first missense C617Y mutation located in the 7th transmembrane segment of LH/CGR causing testotoxicosis. The modest phenotype of our patient may be explained, at least in part, by the modest increase in the intracellular cAMP level caused by the C617Y mutation. PMID:21060208

  6. Analytic QCD Binding Potentials

    CERN Document Server

    Fried, H M; Grandou, T; Sheu, Y -M

    2011-01-01

    This paper applies the analytic forms of a recent non-perturbative, manifestly gauge- and Lorentz-invariant description (of the exchange of all possible virtual gluons between quarks ($Q$) and/or anti-quarks ($\\bar{Q}$) in a quenched, eikonal approximation) to extract analytic forms for the binding potentials generating a model $Q$-$\\bar{Q}$ "pion", and a model $QQQ$ "nucleon". Other, more complicated $Q$, $\\bar{Q}$ contributions to such color-singlet states may also be identified analytically. An elementary minimization technique, relevant to the ground states of such bound systems, is adopted to approximate the solutions to a more proper, but far more complicated Schroedinger/Dirac equation; the existence of possible contributions to the pion and nucleon masses due to spin, angular momentum, and "deformation" degrees of freedom is noted but not pursued. Neglecting electromagnetic and weak interactions, this analysis illustrates how the one new parameter making its appearance in this exact, realistic formali...

  7. Effect of different dietary concentrations of brown marine algae (Sargassum dentifebium prepared by different methods on plasma and yolk lipid profiles, yolk total carotene and lutein plus zeaxanthin of laying hens

    Directory of Open Access Journals (Sweden)

    Ahmed A. El-Deek

    2012-10-01

    Full Text Available The effect of different concentrations (0%, 3% and 6% of brown marine algae (BMA, Sargassum dentifebium prepared according to different methods (sun-dried, SBMA; boiled, BBMA; autoclaved, ABMA on plasma and yolk lipid profiles, carotene, and lutein plus zeaxanthin in egg yolks was studied in hens aged from 23 to 42 weeks (30 hens per treatment. We determined the fatty acid profiles in BMA and in the egg yolk of hens fed different levels of BMA prepared according to different methods. In addition, plasma and yolk lipid profiles, yolk total carotene, and lutein plus zeaxanthin were determined at week 42 of age. Plasma and yolk cholesterol were significantly lower in groups fed diets containing either 3% or 6% BMA than in the control group, but high-density lipoprotein (HDL significantly decreased as BMA concentration increased. There was a significant similar decline in yolk triglycerides with inclusion of either 3% or 6% BMA in the laying hen diet. Palmitic acid was the main saturated fatty acid (SFA found in BMA and oleic acid (omega-9 and linoleic acid (omega-6 were the main unsaturated fatty acids (UFA, while there was a significant increase in palmitic acid in egg yolk when BMA was included at 6%. There was a significant increase in oleic acid (omega-9 when feed containing 3% BMA was given compared to the control group, but this decreased with a further increase in BMA. Linoleic acid (omega-6 also significantly decreased with inclusion of either 3% or 6% BMA. There was a significant increase in total carotene and lutein plus zeaxanthin in the laying hen eggs as a result of feeding diets containing 3% and 6% BMA.

  8. Fluorogenic Tagging of Peptide and Protein 3-Nitrotyrosine with 4-(Aminomethyl)-benzenesulfonic Acid for Quantitative Analysis of Protein Tyrosine Nitration

    OpenAIRE

    Sharov, Victor S.; Dremina, Elena S.; Galeva, Nadezhda A.; Gerstenecker, Gary S.; Li, Xiaobao; Dobrowsky, Rick T; Stobaugh, John F.; Schöneich, Christian

    2010-01-01

    Protein 3-nitrotyrosine (3-NT) has been recognized as an important biomarker of nitroxidative stress associated with inflammatory and degenerative diseases, and biological aging. Analysis of protein-bound 3-NT continues to represent a challenge since in vivo it frequently does not accumulate on proteins in amounts detectable by quantitative analytical methods. Here, we describe a novel approach of fluorescent tagging and quantitation of peptide-bound 3-NT residues based on the selective reduc...

  9. Cysteine- rich secretory protein 3 (CRISP3), ERG and PTEN define a molecular subtype of prostate cancer with implication to patients’ prognosis

    OpenAIRE

    Al Bashir, Samir; Alshalalfa, Mohammed; Hegazy, Samar A.; Dolph, Michael; Donnelly, Bryan; Bismar, Tarek A.

    2014-01-01

    Cysteine- rich secretory protein 3 (CRISP3) prognostic significance in prostate cancer (PCA) has generated mixed result. Herein, we investigated and independently validated CRISP3 expression in relation to ERG and PTEN genomic aberrations and clinical outcome. CRISP3 protein expression was examined by immunohistochemistry using a cohort of patients with localized PCA (n = 215) and castration resistant PCA (CRPC) (n = 46). The Memorial Sloan Kettering (MSKCC) and Swedish cohorts were used for ...

  10. Analysis of Polymorphisms in the Merozoite Surface Protein-3a Gene and Two Microsatellite Loci in Sri Lankan Plasmodium vivax: Evidence of Population Substructure in Sri Lanka

    DEFF Research Database (Denmark)

    Schousboe, Mette L; Rajakaruna, Rupika S; Amerasinghe, Priyanie H;

    2011-01-01

    Abstract. The geographical distribution of genetic variation in Plasmodium vivax samples (N = 386) from nine districts across Sri Lanka is described using three markers; the P. vivax merozoite surface protein-3a (Pvmsp-3a) gene, and the two microsatellites m1501 and m3502. At Pvmsp-3a, 11 alleles....... The results show evidence of high genetic diversity and possible population substructure of P. vivax populations in Sri Lanka....

  11. OSBP-related protein 3 (ORP3) coupling with VAMP-associated protein A regulates R-Ras activity.

    Science.gov (United States)

    Weber-Boyvat, Marion; Kentala, Henriikka; Lilja, Johanna; Vihervaara, Terhi; Hanninen, Raisa; Zhou, You; Peränen, Johan; Nyman, Tuula A; Ivaska, Johanna; Olkkonen, Vesa M

    2015-02-15

    ORP3 is an R-Ras interacting oxysterol-binding protein homolog that regulates cell adhesion and is overexpressed in several cancers. We investigated here a novel function of ORP3 dependent on its targeting to both the endoplasmic reticulum (ER) and the plasma membrane (PM). Using biochemical and cell imaging techniques we demonstrate the mechanistic requirements for the subcellular targeting and function of ORP3 in control of R-Ras activity. We show that hyperphosphorylated ORP3 (ORP3-P) selectively interacts with the ER membrane protein VAPA, and ORP3-VAPA complexes are targeted to PM sites via the ORP3 pleckstrin homology (PH) domain. A novel FFAT (two phenylalanines in an acidic tract)-like motif was identified in ORP3; only disruption of both the FFAT-like and canonical FFAT motif abolished the phorbol-12-myristate-13-acetate (PMA) stimulated interaction of ORP3-P with VAPA. Co-expression of ORP3 and VAPA induced R-Ras activation, dependent on the interactions of ORP3 with VAPA and the PM. Consistently, downstream AktS473 phosphorylation and β1-integrin activity were enhanced by ORP3-VAPA. To conclude, phosphorylation of ORP3 controls its association with VAPA. Furthermore, we present evidence that ORP3-VAPA complexes stimulate R-Ras signaling.

  12. Quarkonium Binding and Entropic Force

    CERN Document Server

    Satz, Helmut

    2015-01-01

    A Q-Qbar bound state represents a balance between repulsive kinetic and attractive potential energy. In a hot quark-gluon plasma, the interaction potential experiences medium effects. Color screening modifies the attractive binding force between the quarks, while the increase of entropy with Q-Qbar separation gives rise to a growing repulsion. We study the role of these phenomena for in-medium Q-Qbar binding and dissociation. It is found that the relevant potential for Q-Qbar binding is the free energy F; with increasing Q-Qbar separation, further binding through the internal energy U is compensated by repulsive entropic effects.

  13. Multidrug Resistance-Associated Protein 3 Plays an Important Role in Protection against Acute Toxicity of Diclofenac.

    Science.gov (United States)

    Scialis, Renato J; Csanaky, Iván L; Goedken, Michael J; Manautou, José E

    2015-07-01

    Diclofenac (DCF) is a nonsteroidal anti-inflammatory drug commonly prescribed to reduce pain in acute and chronic inflammatory diseases. One of the main DCF metabolites is a reactive diclofenac acyl glucuronide (DCF-AG) that covalently binds to biologic targets and may contribute to adverse drug reactions arising from DCF use. Cellular efflux of DCF-AG is partially mediated by multidrug resistance-associated proteins (Mrp). The importance of Mrp2 during DCF-induced toxicity has been established, yet the role of Mrp3 remains largely unexplored. In the present work, Mrp3-null (KO) mice were used to study the toxicokinetics and toxicodynamics of DCF and its metabolites. DCF-AG plasma concentrations were 90% lower in KO mice than in wild-type (WT) mice, indicating that Mrp3 mediates DCF-AG basolateral efflux. In contrast, there were no differences in DCF-AG biliary excretion between WT and KO, suggesting that only DCF-AG basolateral efflux is compromised by Mrp3 deletion. Susceptibility to toxicity was also evaluated after a single high DCF dose. No signs of injury were detected in livers and kidneys; however, ulcers were found in the small intestines. Furthermore, the observed intestinal injuries were consistently more severe in KO compared with WT. DCF covalent adducts were observed in liver and small intestines; however, staining intensity did not correlate with the severity of injuries, implying that tissues respond differently to covalent modification. Overall, the data provide strong evidence that (1) in vivo Mrp3 plays an important role in DCF-AG disposition and (2) compromised Mrp3 function can enhance injury in the gastrointestinal tract after DCF treatment.

  14. Alcohol Binding to the Odorant Binding Protein LUSH: Multiple Factors Affecting Binding Affinities

    OpenAIRE

    Ader, Lauren; Jones, David N. M.; Lin, Hai

    2010-01-01

    Density function theory (DFT) calculations have been carried out to investigate the binding of alcohols to the odorant binding protein LUSH from Drosophila melanogaster. LUSH is one of the few proteins known to bind to ethanol at physiologically relevant concentrations and where high-resolution structural information is available for the protein bound to alcohol at these concentrations. The structures of the LUSH–alcohol complexes identify a set of specific hydrogen-bonding interactions as cr...

  15. Binding Energy and Enzymatic Catalysis.

    Science.gov (United States)

    Hansen, David E.; Raines, Ronald T.

    1990-01-01

    Discussed is the fundamental role that the favorable free energy of binding of the rate-determining transition state plays in catalysis. The principle that all of the catalytic factors discussed are realized by the use of this binding energy is reviewed. (CW)

  16. Role of endogenous opiates in the expression of negative feedback actions of androgen and estrogen on pulsatile properties of luteinizing hormone secretion in man.

    Science.gov (United States)

    Veldhuis, J D; Rogol, A D; Samojlik, E; Ertel, N H

    1984-07-01

    We have tested the participation of endogenous opiate pathways in the negative feedback actions of gonadal steroids on pulsatile properties of luteinizing (LH) hormone release in normal men. To this end, sex steroid hormones were infused intravenously at dosages that under steady state conditions selectively suppressed either the frequency or the amplitude of the pulsatile LH signal. The properties of pulsatile LH secretion were assessed quantitatively by computerized analysis of LH series derived from serial blood sampling over 12 h of observation. When the pure (nonaromatizable) androgen, 5-alpha-dihydrotestosterone, was infused continuously for 108 h at the blood production rate of testosterone, we were able to achieve selective inhibition of LH pulse frequency akin to that observed in experimental animals after low-dosage androgen replacement. Under these conditions, serum concentrations of testosterone and estradiol-17 beta did not change significantly, but serum 5 alpha-dihydrotestosterone concentrations increased approximately two- to threefold, with a corresponding increase in levels of its major metabolite, 5 alpha-androstan-3 alpha, 17 beta-diol. In separate experiments, the infusion of estradiol-17 beta at its blood production rate over a 4.5-d interval selectively suppressed LH pulse amplitude without influencing LH pulse frequency. Estrogen infusion increased serum estradiol-17 beta levels approximately twofold without significantly altering blood androgen concentrations. We then used these schedules of selective androgen or estrogen infusion to investigate the participation of endogenous opiates in the individual inhibitory feedback actions of pure androgen or estrogen on pulsatile LH release by administering a potent and specific opiate-receptor antagonist, naltrexone, during the infusions. Our observations indicate that, despite the continuous infusion of a dosage of 5 alpha-dihydrotestosterone that significantly suppresses LH pulse frequency, co

  17. Lutropin alpha, recombinant human luteinizing hormone, for the stimulation of follicular development in profoundly LH-deficient hypogonadotropic hypogonadal women: a review

    Directory of Open Access Journals (Sweden)

    Bernd Th Krause

    2009-06-01

    Full Text Available Bernd Th Krause1, Ralf Ohlinger2, Annette Haase31Center for Endocrinology and Reproductive Medicine, MVZ Uhlandstr, Berlin, Germany; 2Ernst-Moritz-Arndt-University, Department of Gynecology and Obstetrics, Greifswald, Germany; 3Uhlandstr. 162, 10719 BerlinAbstract: Hypogonadotropic hypogonadism is defined as a medical condition with low or undetectable gonadotropin secretion, associated with a complete arrest of follicular growth and very low estradiol. The main cause can be traced back to an irregular or absent hypothalamic GnRH secretion, whereas only a minority suffers from a pituitary disorder. The choice of treatment to reverse this situation is a pulsatile GnRH application or a direct ovarian stimulation using gonadotropin injections. The goal is to achieve a proper ovarian function in these cases for a short time to allow ovulation and chance of pregnancy. Since the pulsatile GnRH treatment lost its former importance, several gonadotropins are in use to stimulate follicular growth, such as urine-derived human menopausal gonadotropin, highly purified follicle stimulating hormone (FSH or recombinant FSH, all with different success. The introduction of recombinant luteinizing hormone (LH and FSH provided an opportunity to investigate the distinct influences of LH and FSH alone and in combination on follicular growth in monofollicular ovulation induction cycles, and additionally on oocyte maturation, fertilization competence of the oocyte and embryo quality in downregulated IVF patients. Whereas FSH was known to be indispensable for normal follicular growth, the role of LH remained questionable. Downregulated IVF patients with this short-term gonadotropin depletion displayed no advance in stimulation success with the use of recombinant LH. Patients with hypogonadotropic hypogonadism undergoing monofollicular stimulation for ovulation induction showed clearly a specific role and need for both hormones in normal follicular growth. Therefore, a

  18. Variation in levels of serum inhibin B, testosterone, estradiol, luteinizing hormone, follicle-stimulating hormone, and sex hormone-binding globulin in monthly samples from healthy men during a 17-month period

    DEFF Research Database (Denmark)

    Andersson, Anna-Maria; Carlsen, Elisabeth; Petersen, Jørgen Holm;

    2003-01-01

    seasonal variation was observed in LH and testosterone levels, but not in the levels of the other hormones. The seasonal variation in testosterone levels could be explained by the variation in LH levels. The seasonal variation in LH levels seemed to be related to the mean air temperature during the month...

  19. Effect of feeding duration of diets containing corn distillers dried grains with solubles on productive performance, egg quality, and lutein and zeaxanthin concentrations of egg yolk in laying hens.

    Science.gov (United States)

    Shin, H S; Kim, J W; Kim, J H; Lee, D G; Lee, S; Kil, D Y

    2016-10-01

    This experiment was conducted to investigate the effect of feeding duration of diets containing corn distillers dried grains with solubles (DDGS) on productive performance, egg quality, and lutein and zeaxanthin concentrations of egg yolk in laying hens. A total of 300 57-week-old Hy-Line Brown laying hens were randomly assigned to one of 5 treatment groups (feeding duration) with 6 replicates consisting of 5 consecutive cages with 2 hens per cage. Diets were formulated to contain either 0% (the control diet) or 20% DDGS. Experimental diets were fed to hens for 12 wk. The feeding duration of diets containing 20% DDGS was 0, 3, 6, 9, or 12 wk before the conclusion of the experiment. Feeding the diet containing 20% DDGS for 3, 6, or 9 wk followed feeding the control diet for 9, 6, or 3 wk, respectively. The data for productive performance were summarized for 12 wk of the feeding trial. Results indicated that increasing feeding duration of diets containing 20% DDGS had no effects on productive performance of laying hens, but increased egg yolk color (linear, P hens has no adverse effects on productive performance. Increasing the feeding duration of diets containing 20% DDGS improves egg yolk coloration with a concomitant increase in lutein and zeaxanthin concentrations of egg yolks in laying hens. PMID:27081198

  20. Effect of feeding duration of diets containing corn distillers dried grains with solubles on productive performance, egg quality, and lutein and zeaxanthin concentrations of egg yolk in laying hens.

    Science.gov (United States)

    Shin, H S; Kim, J W; Kim, J H; Lee, D G; Lee, S; Kil, D Y

    2016-10-01

    This experiment was conducted to investigate the effect of feeding duration of diets containing corn distillers dried grains with solubles (DDGS) on productive performance, egg quality, and lutein and zeaxanthin concentrations of egg yolk in laying hens. A total of 300 57-week-old Hy-Line Brown laying hens were randomly assigned to one of 5 treatment groups (feeding duration) with 6 replicates consisting of 5 consecutive cages with 2 hens per cage. Diets were formulated to contain either 0% (the control diet) or 20% DDGS. Experimental diets were fed to hens for 12 wk. The feeding duration of diets containing 20% DDGS was 0, 3, 6, 9, or 12 wk before the conclusion of the experiment. Feeding the diet containing 20% DDGS for 3, 6, or 9 wk followed feeding the control diet for 9, 6, or 3 wk, respectively. The data for productive performance were summarized for 12 wk of the feeding trial. Results indicated that increasing feeding duration of diets containing 20% DDGS had no effects on productive performance of laying hens, but increased egg yolk color (linear, P hens has no adverse effects on productive performance. Increasing the feeding duration of diets containing 20% DDGS improves egg yolk coloration with a concomitant increase in lutein and zeaxanthin concentrations of egg yolks in laying hens.

  1. Cooperative binding: a multiple personality.

    Science.gov (United States)

    Martini, Johannes W R; Diambra, Luis; Habeck, Michael

    2016-06-01

    Cooperative binding has been described in many publications and has been related to or defined by several different properties of the binding behavior of the ligand to the target molecule. In addition to the commonly used Hill coefficient, other characteristics such as a sigmoidal shape of the overall titration curve in a linear plot, a change of ligand affinity of the other binding sites when a site of the target molecule becomes occupied, or complex roots of the binding polynomial have been used to define or to quantify cooperative binding. In this work, we analyze how the different properties are related in the most general model for binding curves based on the grand canonical partition function and present several examples which highlight differences between the cooperativity characterizing properties which are discussed. Our results mainly show that among the presented definitions there are not two which fully coincide. Moreover, this work poses the question whether it can make sense to distinguish between positive and negative cooperativity based on the macroscopic binding isotherm only. This article shall emphasize that scientists who investigate cooperative effects in biological systems could help avoiding misunderstandings by stating clearly which kind of cooperativity they discuss.

  2. [3]tetrahydrotrazodone binding. Association with serotonin binding sites

    International Nuclear Information System (INIS)

    High (17 nM) and low (603 nM) affinity binding sites for [3]tetrahydrotrazodone ([3] THT), a biologically active analogue of trazodone, have been identified in rat brain membranes. The substrate specificity, concentration, and subcellular and regional distributions of these sites suggest that they may represent a component of the serotonin transmitter system. Pharmacological analysis of [3]THT binding, coupled with brain lesion and drug treatment experiments, revealed that, unlike other antidepressants, [3] THT does not attach to either a biogenic amine transporter or serotonin binding sites. Rather, it would appear that [3]THT may be an antagonist ligand for the serotonin binding site. This probe may prove of value in defining the mechanism of action of trazodone and in further characterizing serotonin receptors

  3. Structural studies of sugar binding proteins

    OpenAIRE

    Sooriyaarachchi, Sanjeewani

    2010-01-01

    Binding proteins, which are themselves non-enzymatic, play an important role in enzymatic reactions as well as non-enzymatic processes by providing a binding platform for the specific recognition of particular molecules. For example, periplasmic binding proteins play a vital role in nutrient uptake in Gram-negative bacteria. In the present study, three sugar binding proteins, including two periplasmic binding proteins and a β-glucan binding protein, are described. The glucose/galactose bindin...

  4. TNIP1 reduction of HSPA6 gene expression occurs in promoter regions lacking binding sites for known TNIP1-repressed transcription factors

    OpenAIRE

    Ramirez, Vincent P.; Krueger, Winfried; Aneskievich, Brian J.

    2014-01-01

    TNFα-induced protein 3-interacting protein 1 (TNIP1) represses signaling pathways initiated by specific nuclear and transmembrane receptors. This effect results in reduced activity of distinct transcription factors such as retinoic acid receptors (RAR), peroxisome-proliferator-activated receptors (PPAR), and NFκB. TNIP1-null and TNIP1-knockin defective for ubiquitin-binding mice show increased liver apoptosis, and enlarged spleen and lymph nodes, respectively. To complement current knowledge ...

  5. Luteinizing hormone and follicle-stimulating hormone receptors and their transcribed genes (mRNA) are present in the lower urinary tract of intact male and female dogs.

    Science.gov (United States)

    Ponglowhapan, S; Church, D B; Scaramuzzi, R J; Khalid, M

    2007-01-15

    In dogs, one of the side effects of neutering is the development of urinary incontinence. The relationship between neutering and urinary incontinence caused by acquired urethral sphincter mechanism incompetence (USMI) has been reported. Recently, GnRH analogue treatment that suppresses elevated plasma gonadotrophin concentrations post-spaying has been successfully used in incontinent bitches. These data and the fact that non-gonadal tissues may contain receptors for LH (LHR) and FSH (FSHR) suggest that there might be a functional relationship between gonadotrophins and the lower urinary tract in dogs. This study aimed to investigate the presence of LHR and FSHR in the lower urinary tract of intact male and female dogs. Four regions of the lower urinary tract, i.e. (i) body of the bladder, (ii) neck of the bladder, (iii) proximal urethra and (iv) distal urethra were collected from 10 healthy dogs (5 males and 5 anoestrous females). In situ hybridization and immunohistochemistry were performed to characterise the presence of receptor mRNA and receptor protein. Staining was rated semi-quantitatively, incorporating both the distribution and intensity of specific staining. The distribution of receptor expression in different tissue layers (epithelium, subepithelial stroma and muscle) in each region was statistically analyzed. Luteinizing hormone receptor and FSHR mRNA and protein were present in all four regions and in three tissue layers of males and females. Irrespective of region and layer, female dogs expressed significantly higher expression for LHR mRNA (P<0.001), LHR protein (P<0.05) and FSHR protein (P<0.001). The expression of LHR and FSHR mRNA and protein was not uniform and depended on region, tissue layer and gender. The expression of LHR mRNA was higher in the bladder, compared to the urethra (P<0.05). The FSHR mRNA significantly increased from the bladder to the urethra. Protein expression for LHR and FSHR was highest in the proximal urethra (P<0.05). The

  6. EFSA NDA Panel (EFSA Panel on Dietetic Products, Nutrition and Allergies), 2014. Scientific Opinion on the substantiation of a health claim related to a combination of lutein and zeaxanthin and improved vision under bright light conditions pursuant to Article 13(5) of Regulation (EC) No 1924/2006

    DEFF Research Database (Denmark)

    Tetens, Inge

    EFSA NDA Panel (EFSA Panel on Dietetic Products, Nutrition and Allergies), 2014. Scientific Opinion on the substantiation of a health claim related to a combination of lutein and zeaxanthin and improved vision under bright light conditions pursuant to Article 13(5) of Regulation (EC) No 1924/2006....

  7. 牛类胰岛素生长因子结合蛋白3基因PCR-SSCP分析%PCR-SSCP Analysis on the Insulin-like Growth Factor Binding Protein 3 Gene in Beef

    Institute of Scientific and Technical Information of China (English)

    高雪; 徐秀容; 许尚忠; 任红艳; 张英汉

    2006-01-01

    采用PCR-SSCP技术分析了牛类胰岛素生长因子结合蛋白3(IGFBP3)基因在南阳牛、鲁西牛和中国西门塔尔牛3个牛品种中的遗传多态性.结果表明:IGFBP3的第3外显子不存在遗传多态性;第2外显子在3个牛品种中检测到了AA、AB和BB基因型,而且A等位基因为3个牛群体的优势等位基因,分布较高.3个品种中,中国西门塔尔牛AA基因型频率最高,达到0.6615,而鲁西牛和南阳牛则相对较低,分别为0.4043和0.3095.对第2外显子的多态片段测序分析表明:位于IGFBP3基因第8 069 bp处发生单碱基突变T→C,并导致了苯丙氨酸变为亮氨酸.

  8. Effects of Insulin-Like Growth Factor (IGF)-I/IGF-Binding Protein-3 Treatment on Glucose Metabolism and Fat Distribution in Human Immunodeficiency Virus-Infected Patients with Abdominal Obesity and Insulin Resistance

    OpenAIRE

    Rao, Madhu N.; Mulligan, Kathleen; Tai, Viva; Wen, Michael J.; Dyachenko, Artem; Weinberg, Melissa; Li, Xiaojuan; Lang, Thomas; Grunfeld, Carl; Schwarz, Jean-Marc; Schambelan, Morris

    2010-01-01

    Context: HIV-infected patients on antiretroviral therapy are at increased risk for excess visceral adiposity and insulin resistance. Treatment with GH decreases visceral adiposity but worsens glucose metabolism. IGF-I, which mediates many of the effects of GH, improves insulin sensitivity in HIV-negative individuals.

  9. Transforming growth factor-beta1 stimulates the production of insulin-like growth factor-I and insulin-like growth factor-binding protein-3 in human bone marrow stromal osteoblast progenitors

    DEFF Research Database (Denmark)

    Kveiborg, Marie; Flyvbjerg, Allan; Eriksen, E F;

    2001-01-01

    While transforming growth factor-beta1 (TGF-beta1) regulates proliferation and differentiation of human osteoblast precursor cells, the mechanisms underlying these effects are not known. Several hormones and locally acting growth factors regulate osteoblast functions through changes in the insuli...

  10. Growth hormone (GH) treatment increases serum insulin-like growth factor binding protein-3, bone isoenzyme alkaline phosphatase and forearm bone mineral content in young adults with GH deficiency of childhood onset

    DEFF Research Database (Denmark)

    Juul, A; Pedersen, S A; Sørensen, S;

    1994-01-01

    the effect of GH treatment on a marker of bone formation (bone alkaline phosphatase), hepatic excretory function and distal forearm bone mineral content in GH-deficient adults. Growth hormone was administered subcutaneously in 21 adults (13 males and 8 females) with GH deficiency of childhood onset for 4...... months of GH treatment (p alkaline phosphatase increased significantly from 38.6 to 92.9 U/l during GH therapy in male patients (p ...-derived alkaline phosphatase was unaltered by GH. In the females, the increase in bone alkaline phosphatase did not reach statistical significance (19.1 vs 40.0 U/l, p = 0.06). The GH-induced increase in bone alkaline phosphatase correlated significantly with the increase in serum IGFBP-3 (r = 0.46, p = 0...

  11. Serum insulin-like growth factor (IGF)-I and IGF-binding protein-3 concentrations and prostate cancer risk: results from the European Prospective Investigation into Cancer and Nutrition.

    NARCIS (Netherlands)

    Allen, N.E.; Key, T.J.; Appleby, P.N.; Travis, R.C.; Roddam, A.W.; Rinaldi, S.; Egevad, L.; Rohrmann, S.; Linseisen, J.; Pischon, T.; Boeing, H.; Johnsen, N.F.; Tjonneland, A.; Gronbaek, H.; Overvad, K.; Kiemeney, L.A.L.M.; Bueno-De-Mesquita, H.B.; Bingham, S.; Khaw, K.T.; Tumino, R.; Berrino, F.; Mattiello, A.; Sacerdote, C.; Palli, D.; Quiros, J.R.; Ardanaz, E.; Navarro, C.; Larranaga, N.; Gonzalez, C.; Sanchez, M.J.; Trichopoulou, A.; Travezea, C.; Trichopoulos, D.; Jenab, M.; Ferrari, P.; Riboli, E.; Kaaks, R.

    2007-01-01

    BACKGROUND: Some studies suggest that elevated serum insulin-like growth factor (IGF)-I concentrations are associated with an increased risk of prostate cancer and, in particular, with an increased risk of advanced-stage prostate cancer. METHODS: We analyzed the association between prediagnostic ser

  12. Growth hormone (GH) provocative retesting of 108 young adults with childhood-onset GH deficiency and the diagnostic value of insulin-like growth factor I (IGF-I) and IGF-binding protein-3

    DEFF Research Database (Denmark)

    Juul, A; Kastrup, K W; Pedersen, S A;

    1997-01-01

    .e. 45% of patients treated with GH during childhood because of isolated GHD had a normal GH response when retested in adulthood. Multiple regression analysis revealed that peak GH levels were dependent on the degree of hypopituitarism, body mass index, and duration of disease. IGF-I levels were below -2...... significantly dependent on peak GH levels and the number of other pituitary axes affected. In this analysis, duration of disease was significantly associated with both IGF-I and IGFBP-3, whereas body mass index was significantly associated with IGFBP-3, but not with IGF-I. We conclude that IGF-I and IGFBP-3...... determinations predict the outcome of a GH provocative test in adults suspected of GHD and believe that IGF-I as well as IGFBP-3 serum concentrations are valuable diagnostic parameters in the evaluation of GHD in adults with childhood-onset disease. We suggest that children who have been treated with GH should...

  13. Synergistic effects of 1,25-Dihydroxyvitamin D3 and TGF-beta1 on the production of insulin-like growth factor binding protein 3 in human bone marrow stromal cell cultures

    DEFF Research Database (Denmark)

    Kveiborg, Marie; Flyvbjerg, Allan; Kassem, M

    2002-01-01

    1,25-Dihydroxyvitamin D3 (calcitriol), transforming growth factor-beta (TGF-beta), and insulin-like growth factors (IGFs) are all important bone regulatory factors known to affect proliferation and differentiation of human bone-forming cells (osteoblasts). We have previously shown that TGF-beta1...... actions on components of the IGF-system. We report that co-treatment with TGF-beta1 and calcitriol resulted in a synergistic increase in IGFBP-3 production, thereby suggesting that the effects of these factors on hMS osteoblast differentiation may involve the observed increase in IGFBP-3....

  14. 口服叶黄素治疗低龄单眼弱视儿童的疗效观察%The effect of oral lutein treatment in young children with unilateral amblyopia

    Institute of Scientific and Technical Information of China (English)

    张大卫

    2016-01-01

    目的:观察综合治疗联合口服叶黄素对轻、中度单眼弱视低龄儿童的临床疗效。方法将轻、中度单眼弱视患儿随机分为两组。实验组除进行综合治疗外,同时口服叶黄素;对照组只进行配戴眼镜、健眼单眼遮盖及弱视眼精细目力训练的综合治疗。结果治疗后1个月,实验组视力提高的有效率为36.36%,高于对照组的30.43%,但差异无显著性(χ2=0.178,=0.673)。治疗后6个月视力变化比较,实验组有效率81.82%,高于对照组的64.95%,但差异无显著性(χ2=1.585,=0.208)。结论综合治疗联合口服叶黄素对轻、中度单眼弱视低龄儿童更为有效。%Objective To observe the effect of complex treatment combined with oral lutein in young children with mild and moderate unilateral amblyopia. Methods Young children with unilateral amblyopia were divided into two groups randomly, complex treatment combined with oral lutein in experimental group and complex treatment in control group which included wearing glasses, healthy eye cover and fine eyesight training for amblyopic eye. Results Effective rate of VA(visual acuity)improvement in the experimental group was 36.36%, higher than 30.43%of the control group after one month treat-ment, but there was no significant difference (χ2=0.178, =0.673).After six months treatment, VA improvement rate in the experimental group was 81.82%, higher than 64.95%of the control group, but there was no significant difference (χ2=1.585,=0.208). Conclusions Complex treatment combined with oral lutein was more effetive than complex treatment in young children with mild and moderateunilateral amblyopia.

  15. Temporal lobe epilepsy causes selective changes in mu opioid and nociceptin receptor binding and functional coupling to G-proteins in human temporal neocortex.

    Science.gov (United States)

    Rocha, Luisa; Orozco-Suarez, Sandra; Alonso-Vanegas, Mario; Villeda-Hernandez, Juana; Gaona, Andres; Páldy, Eszter; Benyhe, Sandor; Borsodi, Anna

    2009-09-01

    There is no information concerning signal transduction mechanisms downstream of the opioid/nociceptin receptors in the human epileptic brain. The aim of this work was to evaluate the level of G-proteins activation mediated by DAMGO (a mu receptor selective peptide) and nociceptin, and the binding to mu and nociceptin (NOP) receptors and adenylyl cyclase (AC) in neocortex of patients with pharmacoresistant temporal lobe epilepsy. Patients with temporal lobe epilepsy associated with mesial sclerosis (MTLE) or secondary to tumor or vascular lesion showed enhanced [3H]DAMGO and [3H]forskolin binding, lower DAMGO-stimulated [35S]GTPgammaS binding and no significant changes in nociceptin-stimulated G-protein. [3H]Nociceptin binding was lower in patients with MTLE. Age of seizure onset correlated positively with [3H]DAMGO binding and DAMGO-stimulated [35S]GTPgammaS binding, whereas epilepsy duration correlated negatively with [3H]DAMGO and [3H]nociceptin binding, and positively with [3H]forskolin binding. In conclusion, our present data obtained from neocortex of epileptic patients provide strong evidence that a) temporal lobe epilepsy is associated with alterations in mu opioid and NOP receptor binding and signal transduction mechanisms downstream of these receptors, and b) clinical aspects may play an important role on these receptor changes.

  16. 中西医结合治疗黄素化不破裂卵泡综合症的研究近况%Research recent situation on luteinized unraptured follicle syndrome with ITCWM

    Institute of Scientific and Technical Information of China (English)

    钟紫英; 李林

    2010-01-01

    @@ 一些发育正常的成熟的卵泡不破裂而原位黄素化称为黄素化不破裂卵泡综合征(Luteinized unraptured follicle syn-drone,LUFS)、卵泡未排出而出现泡膜细胞和颗粒细胞发生原位黄素化,形成黄体并分泌孕激素,致使效应器官发生一系列类似排卵周期的改变--BBT呈双相,但其高温相呈阶梯式缓慢上升,且不稳定,由于其持续性不排卵或排卵异常,从而成为不孕症的主要原因之一.

  17. Probing protein phosphatase substrate binding

    DEFF Research Database (Denmark)

    Højlys-Larsen, Kim B.; Sørensen, Kasper Kildegaard; Jensen, Knud Jørgen;

    2012-01-01

    profile of the integrin-linked kinase associated phosphatase (ILKAP), a member of the protein phosphatase 2C (PP2C) family. Phosphatases can potentially dephosphorylate these phosphopeptide substrates but, interestingly, performing the binding studies at 4 °C allowed efficient binding to phosphopeptides...... around the phosphorylated residue are important for the binding affinity of ILKAP. We conclude that solid-phase affinity pull-down of proteins from complex mixtures can be applied in phosphoproteomics and systems biology.......Proteomics and high throughput analysis for systems biology can benefit significantly from solid-phase chemical tools for affinity pull-down of proteins from complex mixtures. Here we report the application of solid-phase synthesis of phosphopeptides for pull-down and analysis of the affinity...

  18. Water binding in legume seeds

    Science.gov (United States)

    Vertucci, C. W.; Leopold, A. C.

    1987-01-01

    The physical status of water in seeds has a pivotal role in determining the physiological reactions that can take place in the dry state. Using water sorption isotherms from cotyledon and axis tissue of five leguminous seeds, the strength of water binding and the numbers of binding sites have been estimated using van't Hoff analyses and the D'Arcy/Watt equation. These parameters of water sorption are calculated for each of the three regions of water binding and for a range of temperatures. Water sorption characteristics are reflective of the chemical composition of the biological materials as well as the temperature at which hydration takes place. Changes in the sorption characteristics with temperature and hydration level may suggest hydration-induced structural changes in cellular components.

  19. Circannual changes in progesterone secretion in intact ewes, luteinizing hormone secretion in ovariectomized estradiol-implanted ewes, and prolactin secretion in three sheep breeds anticipated to differ in seasonality of reproduction.

    Science.gov (United States)

    Goff, Katherine J; Knight, James W; Pelzer, Kevin D; Akers, R Michael; Notter, David R

    2013-05-01

    Changes in progesterone secretion in intact ewes (7 or 9 per breed) and luteinizing hormone secretion in ovariectomized, estradiol-implanted ewes (9 or 10 per breed) were monitored for 12 mo in Suffolk, tropically adapted St. Croix, and OOS ewes. The OOS line is a composite population of 50% Dorset, 25% Rambouillet, and 25% Finnish Landrace breeding that was selected for 10 yr for ability to lamb in October and early November. Ewes were isolated from rams, and blood samples were collected twice weekly. Circulating prolactin concentrations were also determined from blood samples collected near the summer and winter solstice and vernal and autumnal equinox. Intact OOS ewes entered anestrus later, began the subsequent breeding season sooner, and had a shorter seasonal anestrus than Suffolk and St. Croix ewes (P ≤ 0.005). St. Croix ewes did not differ from Suffolk ewes in date of onset or cessation of breeding or duration of anestrus (P ≥ 0.06). Breed differences in duration of luteinizing hormone inhibition in ovariectomized ewes were essentially identical to those observed for duration of anestrous. Prolactin concentrations varied during the year: annual changes were larger in relatively seasonal Suffolk ewes than in tropically-derived St. Croix ewes (P<0.01), and OOS ewes were intermediate to, and tended to differ from (P<0.10), the other two breeds. We conclude that OOS ewes developed by selection for fertility in spring matings had an abbreviated seasonal anestrus that is one of the shortest ever reported for temperate breeds, and that tropical St. Croix sheep did not have a shorter seasonal anestrus than Suffolk sheep under temperate conditions and ram isolation. PMID:23528712

  20. Structural Basis of the High Affinity Interaction between the Alphavirus Nonstructural Protein-3 (nsP3) and the SH3 Domain of Amphiphysin-2.

    Science.gov (United States)

    Tossavainen, Helena; Aitio, Olli; Hellman, Maarit; Saksela, Kalle; Permi, Perttu

    2016-07-29

    We show that a peptide from Chikungunya virus nsP3 protein spanning residues 1728-1744 binds the amphiphysin-2 (BIN1) Src homology-3 (SH3) domain with an unusually high affinity (Kd 24 nm). Our NMR solution complex structure together with isothermal titration calorimetry data on several related viral and cellular peptide ligands reveal that this exceptional affinity originates from interactions between multiple basic residues in the target peptide and the extensive negatively charged binding surface of amphiphysin-2 SH3. Remarkably, these arginines show no fixed conformation in the complex structure, indicating that a transient or fluctuating polyelectrostatic interaction accounts for this affinity. Thus, via optimization of such dynamic electrostatic forces, viral peptides have evolved a superior binding affinity for amphiphysin-2 SH3 compared with typical cellular ligands, such as dynamin, thereby enabling hijacking of amphiphysin-2 SH3-regulated host cell processes by these viruses. Moreover, our data show that the previously described consensus sequence PXRPXR for amphiphysin SH3 ligands is inaccurate and instead define it as an extended Class II binding motif PXXPXRpXR, where additional positive charges between the two constant arginine residues can give rise to extraordinary high SH3 binding affinity.

  1. Endometrial cysteine-rich secretory protein 3 is inhibited by human chorionic gonadotrophin, and is increased in the decidua of tubal ectopic pregnancy

    DEFF Research Database (Denmark)

    Horne, A W; Duncan, W C; King, A E;

    2009-01-01

    gestation-matched women undergoing surgical termination of pregnancy (n = 8), evacuation of uterus for miscarriage (n = 6) and surgery for EP (n = 11) was subjected to quantitative RT-PCR, morphological assessment, immunohistochemistry and western blot analysis. Sera were analysed for progesterone and human...... endometrium from women with ectopic and intrauterine gestations could be used to identify candidate diagnostic biomarkers for EP. The aim of this study was to further investigate the decidual gene with the highest fold increase in EP, cysteine-rich secretory protein-3 (CRISP-3). Decidualized endometrium from...... chorionic gonadotrophin (hCG) levels. Immortalized endometrial epithelial cells were cultured with physiological concentrations of hCG. CRISP-3 mRNA and protein expression were greater in endometrium from ectopic when compared with intrauterine pregnancies (P protein was localized...

  2. Computational Prediction of RNA-Binding Proteins and Binding Sites.

    Science.gov (United States)

    Si, Jingna; Cui, Jing; Cheng, Jin; Wu, Rongling

    2015-01-01

    Proteins and RNA interaction have vital roles in many cellular processes such as protein synthesis, sequence encoding, RNA transfer, and gene regulation at the transcriptional and post-transcriptional levels. Approximately 6%-8% of all proteins are RNA-binding proteins (RBPs). Distinguishing these RBPs or their binding residues is a major aim of structural biology. Previously, a number of experimental methods were developed for the determination of protein-RNA interactions. However, these experimental methods are expensive, time-consuming, and labor-intensive. Alternatively, researchers have developed many computational approaches to predict RBPs and protein-RNA binding sites, by combining various machine learning methods and abundant sequence and/or structural features. There are three kinds of computational approaches, which are prediction from protein sequence, prediction from protein structure, and protein-RNA docking. In this paper, we review all existing studies of predictions of RNA-binding sites and RBPs and complexes, including data sets used in different approaches, sequence and structural features used in several predictors, prediction method classifications, performance comparisons, evaluation methods, and future directions.

  3. Computational Prediction of RNA-Binding Proteins and Binding Sites

    Directory of Open Access Journals (Sweden)

    Jingna Si

    2015-11-01

    Full Text Available Proteins and RNA interaction have vital roles in many cellular processes such as protein synthesis, sequence encoding, RNA transfer, and gene regulation at the transcriptional and post-transcriptional levels. Approximately 6%–8% of all proteins are RNA-binding proteins (RBPs. Distinguishing these RBPs or their binding residues is a major aim of structural biology. Previously, a number of experimental methods were developed for the determination of protein–RNA interactions. However, these experimental methods are expensive, time-consuming, and labor-intensive. Alternatively, researchers have developed many computational approaches to predict RBPs and protein–RNA binding sites, by combining various machine learning methods and abundant sequence and/or structural features. There are three kinds of computational approaches, which are prediction from protein sequence, prediction from protein structure, and protein-RNA docking. In this paper, we review all existing studies of predictions of RNA-binding sites and RBPs and complexes, including data sets used in different approaches, sequence and structural features used in several predictors, prediction method classifications, performance comparisons, evaluation methods, and future directions.

  4. Skyrmions with low binding energies

    Directory of Open Access Journals (Sweden)

    Mike Gillard

    2015-06-01

    Full Text Available Nuclear binding energies are investigated in two variants of the Skyrme model: the first replaces the usual Skyrme term with a term that is sixth order in derivatives, and the second includes a potential that is quartic in the pion fields. Solitons in the first model are shown to deviate significantly from ansätze previously assumed in the literature. The binding energies obtained in both models are lower than those obtained from the standard Skyrme model, and those obtained in the second model are close to the experimental values.

  5. Skyrmions with low binding energies

    Energy Technology Data Exchange (ETDEWEB)

    Gillard, Mike, E-mail: m.n.gillard@leeds.ac.uk; Harland, Derek, E-mail: d.g.harland@leeds.ac.uk; Speight, Martin, E-mail: speight@maths.leeds.ac.uk

    2015-06-15

    Nuclear binding energies are investigated in two variants of the Skyrme model: the first replaces the usual Skyrme term with a term that is sixth order in derivatives, and the second includes a potential that is quartic in the pion fields. Solitons in the first model are shown to deviate significantly from ansätze previously assumed in the literature. The binding energies obtained in both models are lower than those obtained from the standard Skyrme model, and those obtained in the second model are close to the experimental values.

  6. Synthetic heparin-binding growth factor analogs

    Science.gov (United States)

    Pena, Louis A.; Zamora, Paul; Lin, Xinhua; Glass, John D.

    2007-01-23

    The invention provides synthetic heparin-binding growth factor analogs having at least one peptide chain that binds a heparin-binding growth factor receptor, covalently bound to a hydrophobic linker, which is in turn covalently bound to a non-signaling peptide that includes a heparin-binding domain. The synthetic heparin-binding growth factor analogs are useful as soluble biologics or as surface coatings for medical devices.

  7. Stretch regulates expression and binding of chymotrypsin-like elastase 1 in the postnatal lung.

    Science.gov (United States)

    Joshi, Rashika; Liu, Sheng; Brown, Montell D; Young, Sarah M; Batie, Matthew; Kofron, J Matthew; Xu, Yan; Weaver, Timmothy E; Apsley, Karen; Varisco, Brian M

    2016-02-01

    Lung stretch is critical for normal lung development and for compensatory lung growth after pneumonectomy (PNX), but the mechanisms by which strain induces matrix remodeling are unclear. Our prior work demonstrated an association of chymotrypsin-like elastase 1 (Cela1) with lung elastin remodeling, and that strain triggered a near-instantaneous elastin-remodeling response. We sought to determine whether stretch regulates Cela1 expression and Cela1 binding to lung elastin. In C57BL/6J mice, Cela1 protein increased 176-fold during lung morphogenesis. Cela1 was covalently bound to serpin peptidase inhibitor, clade A, member 1, resulting in a higher molecular mass in lung homogenate compared to pancreas homogenate. Post-PNX, Cela1 mRNA increased 6-fold, protein 3-fold, and Cela1-positive cells 2-fold. Cela1 was expressed predominantly in alveolar type II cells in the embryonic lung and predominantly in CD90-positive lung fibroblasts postnatally. During compensatory lung growth, Cela1 expression was induced in nonproliferative mesenchymal cells. In ex vivo mouse lung sections, stretch increased Cela1 binding to lung tissue by 46%. Competitive inhibition with soluble elastin completely abrogated this increase. Areas of stretch-induced elastase activity and Cela1 binding colocalized. The stretch-dependent expression and binding kinetics of Cela1 indicate an important role in stretch-dependent remodeling of the peripheral lung during development and regeneration. PMID:26443822

  8. Crystal structure of TDRD3 and methyl-arginine binding characterization of TDRD3, SMN and SPF30.

    Directory of Open Access Journals (Sweden)

    Ke Liu

    Full Text Available SMN (Survival motor neuron protein was characterized as a dimethyl-arginine binding protein over ten years ago. TDRD3 (Tudor domain-containing protein 3 and SPF30 (Splicing factor 30 kDa were found to bind to various methyl-arginine proteins including Sm proteins as well later on. Recently, TDRD3 was shown to be a transcriptional coactivator, and its transcriptional activity is dependent on its ability to bind arginine-methylated histone marks. In this study, we systematically characterized the binding specificity and affinity of the Tudor domains of these three proteins quantitatively. Our results show that TDRD3 preferentially recognizes asymmetrical dimethylated arginine mark, and SMN is a very promiscuous effector molecule, which recognizes different arginine containing sequence motifs and preferentially binds symmetrical dimethylated arginine. SPF30 is the weakest methyl-arginine binder, which only binds the GAR motif sequences in our library. In addition, we also reported high-resolution crystal structures of the Tudor domain of TDRD3 in complex with two small molecules, which occupy the aromatic cage of TDRD3.

  9. Effect of ovulation monitoring with blood estradiol, progestogen, and luteinizing hormone combined with transvaginal ultrasonography, urine luteinizing hormone peak on opportunity of intrauterine insemination%血E2、P、LH联合阴道B超、尿LH峰监测排卵对IUI手术时机的影响

    Institute of Scientific and Technical Information of China (English)

    韦冰; 邹琳; 许丽华

    2012-01-01

    Objective: To analyze the clinical data of patients receiving intrauterine insemination (IUI) , explore the effect of ovulation monitoring with blood estradiol, progestogen, and luteinizing hormone (LH) combined with transvaginal ultrasonography, urine LH peak on opportunity of IUI. Methods; A total of 89 couples (190 cycles) who received IUI treatment because of infertility in the hospital from January 2009 to December 2011 were selected, and the patients entering into cycles were randomly divided into group A ( monitoring follicular development with transvaginal ultrasonography plus urine LH peak) and group B (monitoring follicular development with transvaginal ultrasonography plus urine LH peak plus blood estradiol, progestogen, and LH) , the clinical pregnancy rates in the two groups were compared. Results; The clinical pregnancy rate in group B was statistically significantly higher than that in group A ( P < 0. 05 ) . Conclusion: The value of ovulation monitoring with blood estradiol, progestogen, and LH combined with transvaginal ultrasonography, urine LH peak during the course of IUI for predicting the opportunity of IUI was superior to that of transvaginal ultrasonography combined with urine LH peak only.%目的:分析夫精宫腔内人工授精(Intrauterine insemination,IUI)患者的临床资料,探讨IUI过程中血雌二醇(E2)、孕酮(P)、黄体生成素(LH)联合阴超以及尿LH峰监测排卵对IUI手术时机的影响.方法:选择2009年1月~2011月12月因不孕在广东医学院附属医院生殖医学中心进行IUI治疗的夫妇89对共190个周期,将进入周期的患者随机分为阴道彩超+尿LH峰监测卵泡发育组(A组)和阴道彩超+尿LH峰+血E2、P、LH监测卵泡发育组(B组),比较两组临床妊娠率的差异.结果:B组临床妊娠率高于A组,差异有统计学意义(P<0.05).结论:IUI过程中血E2、P、LH联合阴超、尿LH峰监测排卵对IUI手术时机的判断优于仅阴超+尿LH峰监测排卵.

  10. Sex hormone binding globulin phenotypes

    DEFF Research Database (Denmark)

    Cornelisse, M M; Bennett, Patrick; Christiansen, M;

    1994-01-01

    Human sex hormone binding globulin (SHBG) is encoded by a normal and a variant allele. The resulting SHBG phenotypes (the homozygous normal SHBG, the heterozygous SHBG and the homozygous variant SHBG phenotype) can be distinguished by their electrophoretic patterns. We developed a novel detection...

  11. BINDING ISOTHERMS SURFACTANT-PROTEINS

    OpenAIRE

    Elena Irina Moater; Cristiana Radulescu; Ionica Ionita

    2011-01-01

    The interactions between surfactants and proteins shows some similarities with interactions between surfactants and polymers, but the hydrophobic amphoteric nature of proteins and their secondary and tertiary structure components make them different from conventional polymer systems. Many studies from the past about surfactant - proteins bonding used the dialysis techniques. Other techniques used to determine the binding isotherm, included ultrafiltration, ultracentrifugation, potentiometry, ...

  12. Cellulose binding domain fusion proteins

    Energy Technology Data Exchange (ETDEWEB)

    Shoseyov, Oded (Karmey Yosef, IL); Shpiegl, Itai (Rehovot, IL); Goldstein, Marc A. (Davis, CA); Doi, Roy H. (Davis, CA)

    1998-01-01

    A cellulose binding domain (CBD) having a high affinity for crystalline cellulose and chitin is disclosed, along with methods for the molecular cloning and recombinant production thereof. Fusion products comprising the CBD and a second protein are likewise described. A wide range of applications are contemplated for both the CBD and the fusion products, including drug delivery, affinity separations, and diagnostic techniques.

  13. Transference of lutein during cheese making, color stability, and sensory acceptance of prato cheese Transferência de luteína na fabricação de queijo prato, estabilidade da cor e aceitação sensorial

    Directory of Open Access Journals (Sweden)

    Mirian Tiaki Kaneiwa Kubo

    2013-02-01

    Full Text Available The consumption of lutein is associated with the prevention and reduction of age-related macular degeneration. Its incorporation into Prato cheese as a yellowish food coloring is a valid alternative to increase the daily intake of this compound. However, part of the lutein added may be lost in the whey during the cheese making, or it can be degraded by light during storage, resulting in color changes reducing the sensory acceptance of the cheese. The objectives of this study were to determine the transference of the lutein (dye, added to the milk, in the whey, and cheese, to evaluate the effect of the lutein addition, light exposure, and storage time on the cheese color, and to verify the sensory acceptance of Prato cheese with addition of lutein. The lutein recovery of cheese was 95.25%. Color saturation (chrome increased during storage time resulting in a cheese with more intense color, but there were no changes in the hue of the cheese. Adjusting the amount of lutein added to Prato cheese may lead to greater acceptance. The high recovery of lutein in the cheese and the fact that the hue remained unchanged during storage under light showed that the incorporation of lutein into Prato cheese is feasible from a technical point of view.A ingestão de luteína está associada à prevenção e redução da degeneração macular relacionada à idade e a sua adição em queijo Prato, como corante de tom amarelado, é uma alternativa válida para aumentar a ingestão diária desse composto. Entretanto, parte da luteína adicionada pode ser perdida no soro durante a fabricação do queijo e também, ser degradada pela ação da luz durante armazenamento, resultando em mudanças na cor dos queijos, diminuindo a aceitação sensorial. O objetivo do trabalho foi determinar a transferência do corante luteína, adicionado ao leite, no soro e queijo, avaliar o efeito da adição de luteína, exposição à luz e tempo de armazenamento na cor do queijo e

  14. Protein binding assay for hyaluronate

    Energy Technology Data Exchange (ETDEWEB)

    Lacy, B.E.; Underhill, C.B.

    1986-11-01

    A relatively quick and simple assay for hyaluronate was developed using the specific binding protein, hyaluronectin. The hyaluronectin was obtained by homogenizing the brains of Sprague-Dawley rats, and then centrifuging the homogenate. The resulting supernatant was used as a source of crude hyaluronectin. In the binding assay, the hyaluronectin was mixed with (/sup 3/H)hyaluronate, followed by an equal volume of saturated (NH/sub 4/)/sub 2/SO/sub 4/, which precipitated the hyaluronectin and any (/sup 3/H)hyaluronate associated with it, but left free (/sup 3/H)hyaluronate in solution. The mixture was then centrifuged, and the amount of bound (/sup 3/H)hyaluronate in the precipitate was determined. Using this assay, the authors found that hyaluronectin specifically bound hyaluronate, since other glycosaminoglycans failed to compete for the binding protein. In addition, the interaction between hyaluronectin and hyaluronate was of relatively high affinity, and the size of the hyaluronate did not appear to substantially alter the amount of binding. To determine the amount of hyaluronate in an unknown sample, they used a competition assay in which the binding of a set amount of (/sup 3/H)hyaluronate was blocked by the addition of unlabeled hyaluronate. By comparing the degree of competition of the unknown samples with that of known amounts of hyaluronate, it was possible to determine the amount of hyaluronate in the unknowns. They have found that this method is sensitive to 1 ..mu..g or less of hyaluronate, and is unaffected by the presence of proteins.

  15. Fast renal trapping of porcine luteinizing hormone (pLH) shown by 123I-scintigraphic imaging in rats explains its short circulatory half-life.

    OpenAIRE

    Locatelli Alain; Magallon Thierry; Leroux Hervé; Lecompte François; Bernard Serge; Klett Danièle; Lepape Alain; Combarnous Yves

    2003-01-01

    Abstract Background Sugar moieties of gonadotropins play no primary role in receptor binding but they strongly affect their circulatory half-life and consequently their in vivo biopotencies. In order to relate more precisely hepatic trapping of these glycoproteic hormones with their circulatory half-life, we undertook a comparative study of the distribution and elimination of porcine LH (pLH) and equine CG (eCG) which exhibit respectively a short and a long half-life. This was done first by f...

  16. Antimicrobial Peptide-Lipid Binding Interactions and Binding Selectivity

    OpenAIRE

    Lad, Mitaben D.; Birembaut, Fabrice; Clifton, Luke A.; Frazier, Richard A.; Webster, John R. P.; Green, Rebecca J.

    2007-01-01

    Surface pressure measurements, external reflection-Fourier transform infrared spectroscopy, and neutron reflectivity have been used to investigate the lipid-binding behavior of three antimicrobial peptides: melittin, magainin II, and cecropin P1. As expected, all three cationic peptides were shown to interact more strongly with the anionic lipid, 1,2 dihexadecanoyl-sn-glycerol-3-(phosphor-rac-(1-glycerol)) (DPPG), compared to the zwitterionic lipid, 1,2 dihexadecanoyl-sn-glycerol-3-phosphocho...

  17. Characteristics of human erythrocyte insulin binding sites.

    OpenAIRE

    Okada, Yoshio

    1981-01-01

    Insulin and human erythrocyte cell membrane interactions were studied with respect to binding and dissociation. The per cent of specific binding of 125I-labeled insulin to erythrocytes was directly proportional to the cell concentration. The optimum pH for binding was 8.1. The initial binding rate was directly proportional to, and the steady state insulin binding was reversely proportional to, the incubation temperature. The per cent of specific binding of 125I-labeled insulin was 12.10 +/- 1...

  18. Fluorogenic Tagging of Peptide and Protein 3-Nitrotyrosine with 4-(Aminomethyl)-benzenesulfonic Acid for Quantitative Analysis of Protein Tyrosine Nitration.

    Science.gov (United States)

    Sharov, Victor S; Dremina, Elena S; Galeva, Nadezhda A; Gerstenecker, Gary S; Li, Xiaobao; Dobrowsky, Rick T; Stobaugh, John F; Schöneich, Christian

    2010-01-01

    Protein 3-nitrotyrosine (3-NT) has been recognized as an important biomarker of nitroxidative stress associated with inflammatory and degenerative diseases, and biological aging. Analysis of protein-bound 3-NT continues to represent a challenge since in vivo it frequently does not accumulate on proteins in amounts detectable by quantitative analytical methods. Here, we describe a novel approach of fluorescent tagging and quantitation of peptide-bound 3-NT residues based on the selective reduction to 3-AT followed by reaction with 4-(amino-methyl)benzenesulfonic acid (ABS) in the presence of K(3)Fe(CN)(6) to form a highly fluorescent 2-phenylbenzoxazole product. Synthetic 3-NT peptide (0.005-1 μM) upon reduction with 10 mM sodium dithionite and tagging with 2 mM ABS and 5 μM K(3)Fe(CN)(6) in 0.1 M Na(2)HPO(4) buffer (pH 9.0) was converted with yields >95% to a single fluorescent product incorporating two ABS molecules per 3-NT residue, with fluorescence excitation and emission maxima at 360 ± 2 and 490 ± 2 nm, respectively, and a quantum yield of 0.77 ± 0.08, based on reverse-phase LC with UV and fluorescence detection, fluorescence spectroscopy and LC-MS-MS analysis. This protocol was successfully tested for quantitative analysis of in vitro Tyr nitration in a model protein, rabbit muscle phosphorylase b, and in a complex mixture of proteins from C2C12 cultured cells exposed to peroxynitrite, with a detection limit of ca. 1 pmol 3-NT by fluorescence spectrometry, and an apparent LOD of 12 and 40 pmol for nitropeptides alone or in the presence of 100 μg digested cell proteins, respectively. LC-MS-MS analysis of ABS tagged peptides revealed that the fluorescent derivatives undergo efficient backbone fragmentations, allowing for sequence-specific characterization of protein Tyr nitration in proteomic studies. Fluorogenic tagging with ABS also can be instrumental for detection and visualization of protein 3-NT in LC and gel-based protein separations. PMID

  19. Dissection of the Critical Binding Determinants of Cellular Retinoic Acid Binding Protein II by Mutagenesis and Fluorescence Binding Assay

    OpenAIRE

    Vasileiou, Chrysoula; Lee, Kin Sing Stephen; Crist, Rachael M.; Vaezeslami, Soheila; Goins, Sarah M.; Geiger, James H.; Borhan, Babak

    2009-01-01

    The binding of retinoic acid to mutants of Cellular Retinoic Acid Binding Protein II (CRABPII) was evaluated to better understand the importance of the direct protein/ligand interactions. The important role of Arg111 for the correct structure and function of the protein was verified and other residues that directly affect retinoic acid binding have been identified. Furthermore, retinoic acid binding to CRABPII mutants that lack all previously identified interacting amino acids was rescued by ...

  20. Human plasminogen binding protein tetranectin

    DEFF Research Database (Denmark)

    Kastrup, J S; Rasmussen, H; Nielsen, B B;

    1997-01-01

    The recombinant human plasminogen binding protein tetranectin (TN) and the C-type lectin CRD of this protein (TN3) have been crystallized. TN3 crystallizes in the tetragonal space group P4(2)2(1)2 with cell dimensions a = b = 64.0, c = 75.7 A and with one molecule per asymmetric unit. The crystals...... to at least 2.5 A. A full data set has been collected to 3.0 A. The asymmetric unit contains one monomer of TN. Molecular replacement solutions for TN3 and TN have been obtained using the structure of the C-type lectin CRD of rat mannose-binding protein as search model. The rhombohedral space group indicates...

  1. Binding effects and nuclear shadowing

    OpenAIRE

    Indumathi, D.; Wei ZHU

    1996-01-01

    The effects of nuclear binding on nuclear structure functions have so far been studied mainly at fixed target experiments, and there is currently much interest in obtaining a clearer understanding of this phenomenon. We use an existing dynamical model of nuclear structure functions, that gives good agreement with current data, to study this effect in a kinematical regime (low $x$, high $Q^2$) that can possibly be probed by an upgrade of {\\sc hera} at {\\sc desy} into a nuclear accelerator.

  2. Calcium binding by dietary fibre

    International Nuclear Information System (INIS)

    Dietary fibre from plants low in phytate bound calcium in proportion to its uronic-acid content. This binding by the non-cellulosic fraction of fibre reduces the availability of calcium for small-intestinal absorption, but the colonic microbial digestion of uronic acids liberates the calcium. Thus the ability to maintain calcium balance on high-fibre diets may depend on the adaptive capacity on the colon for calcium. (author)

  3. Material Binding Peptides for Nanotechnology

    Directory of Open Access Journals (Sweden)

    Urartu Ozgur Safak Seker

    2011-02-01

    Full Text Available Remarkable progress has been made to date in the discovery of material binding peptides and their utilization in nanotechnology, which has brought new challenges and opportunities. Nowadays phage display is a versatile tool, important for the selection of ligands for proteins and peptides. This combinatorial approach has also been adapted over the past decade to select material-specific peptides. Screening and selection of such phage displayed material binding peptides has attracted great interest, in particular because of their use in nanotechnology. Phage display selected peptides are either synthesized independently or expressed on phage coat protein. Selected phage particles are subsequently utilized in the synthesis of nanoparticles, in the assembly of nanostructures on inorganic surfaces, and oriented protein immobilization as fusion partners of proteins. In this paper, we present an overview on the research conducted on this area. In this review we not only focus on the selection process, but also on molecular binding characterization and utilization of peptides as molecular linkers, molecular assemblers and material synthesizers.

  4. Anion binding in biological systems

    Science.gov (United States)

    Feiters, Martin C.; Meyer-Klaucke, Wolfram; Kostenko, Alexander V.; Soldatov, Alexander V.; Leblanc, Catherine; Michel, Gurvan; Potin, Philippe; Küpper, Frithjof C.; Hollenstein, Kaspar; Locher, Kaspar P.; Bevers, Loes E.; Hagedoorn, Peter-Leon; Hagen, Wilfred R.

    2009-11-01

    We compare aspects of biological X-ray absorption spectroscopy (XAS) studies of cations and anions, and report on some examples of anion binding in biological systems. Brown algae such as Laminaria digitata (oarweed) are effective accumulators of I from seawater, with tissue concentrations exceeding 50 mM, and the vanadate-containing enzyme haloperoxidase is implicated in halide accumulation. We have studied the chemical state of iodine and its biological role in Laminaria at the I K edge, and bromoperoxidase from Ascophyllum nodosum (knotted wrack) at the Br K edge. Mo is essential for many forms of life; W only for certain archaea, such as Archaeoglobus fulgidus and the hyperthermophilic archaeon Pyrococcus furiosus, and some bacteria. The metals are bound and transported as their oxo-anions, molybdate and tungstate, which are similar in size. The transport protein WtpA from P. furiosus binds tungstate more strongly than molybdate, and is related in sequence to Archaeoglobus fulgidus ModA, of which a crystal structure is known. We have measured A. fulgidus ModA with tungstate at the W L3 (2p3/2) edge, and compared the results with the refined crystal structure. XAS studies of anion binding are feasible even if only weak interactions are present, are biologically relevant, and give new insights in the spectroscopy.

  5. Anion binding in biological systems

    Energy Technology Data Exchange (ETDEWEB)

    Feiters, Martin C [Department of Organic Chemistry, Institute for Molecules and Materials, Faculty of Science, Radboud University Nijmegen, Heyendaalseweg 135, 6525 AJ Nijmegen (Netherlands); Meyer-Klaucke, Wolfram [EMBL Hamburg Outstation at DESY, Notkestrasse 85, D-22607 Hamburg (Germany); Kostenko, Alexander V; Soldatov, Alexander V [Faculty of Physics, Southern Federal University, Sorge 5, Rostov-na-Donu, 344090 (Russian Federation); Leblanc, Catherine; Michel, Gurvan; Potin, Philippe [Centre National de la Recherche Scientifique and Universite Pierre et Marie Curie Paris-VI, Station Biologique de Roscoff, Place Georges Teissier, BP 74, F-29682 Roscoff cedex, Bretagne (France); Kuepper, Frithjof C [Scottish Association for Marine Science, Dunstaffnage Marine Laboratory, Oban, Argyll PA37 1QA, Scotland (United Kingdom); Hollenstein, Kaspar; Locher, Kaspar P [Institute of Molecular Biology and Biophysics, ETH Zuerich, Schafmattstrasse 20, Zuerich, 8093 (Switzerland); Bevers, Loes E; Hagedoorn, Peter-Leon; Hagen, Wilfred R, E-mail: m.feiters@science.ru.n [Department of Biotechnology, Delft University of Technology, Julianalaan 67, 2628 BC Delft (Netherlands)

    2009-11-15

    We compare aspects of biological X-ray absorption spectroscopy (XAS) studies of cations and anions, and report on some examples of anion binding in biological systems. Brown algae such as Laminaria digitata (oarweed) are effective accumulators of I from seawater, with tissue concentrations exceeding 50 mM, and the vanadate-containing enzyme haloperoxidase is implicated in halide accumulation. We have studied the chemical state of iodine and its biological role in Laminaria at the I K edge, and bromoperoxidase from Ascophyllum nodosum (knotted wrack) at the Br K edge. Mo is essential for many forms of life; W only for certain archaea, such as Archaeoglobus fulgidus and the hyperthermophilic archaeon Pyrococcus furiosus, and some bacteria. The metals are bound and transported as their oxo-anions, molybdate and tungstate, which are similar in size. The transport protein WtpA from P. furiosus binds tungstate more strongly than molybdate, and is related in sequence to Archaeoglobus fulgidus ModA, of which a crystal structure is known. We have measured A. fulgidus ModA with tungstate at the W L{sub 3} (2p{sub 3/2}) edge, and compared the results with the refined crystal structure. XAS studies of anion binding are feasible even if only weak interactions are present, are biologically relevant, and give new insights in the spectroscopy.

  6. Depletion of hepatoma-derived growth factor-related protein-3 induces apoptotic sensitization of radioresistant A549 cells via reactive oxygen species-dependent p53 activation

    International Nuclear Information System (INIS)

    Highlights: •HRP-3 is a radiation- and anticancer drug-responsive protein in A549 cells. •Depletion of HRP-3 induces apoptosis of radio- and chemoresistant A549 cells. •Depletion of HRP-3 promotes ROS generation via inhibition of the Nrf2/HO-1 pathway. •Depletion of HRP-3 enhances ROS-dependent p53 activation and PUMA expression. -- Abstract: Biomarkers based on functional signaling have the potential to provide greater insight into the pathogenesis of cancer and may offer additional targets for anticancer therapeutics. Here, we identified hepatoma-derived growth factor-related protein-3 (HRP-3) as a radioresistance-related gene and characterized the molecular mechanism by which its encoded protein regulates the radio- and chemoresistant phenotype of lung cancer-derived A549 cells. Knockdown of HRP-3 promoted apoptosis of A549 cells and potentiated the apoptosis-inducing action of radio- and chemotherapy. This increase in apoptosis was associated with a substantial generation of reactive oxygen species (ROS) that was attributable to inhibition of the Nrf2/HO-1 antioxidant pathway and resulted in enhanced ROS-dependent p53 activation and p53-dependent expression of PUMA (p53 upregulated modulator of apoptosis). Therefore, the HRP-3/Nrf2/HO-1/ROS/p53/PUMA cascade is an essential feature of the A549 cell phenotype and a potential radiotherapy target, extending the range of targets in multimodal therapies against lung cancer

  7. Enhanced Expression of T-Cell Immunoglobulin and Mucin Domain Protein 3 in Endothelial Cells Facilitates Intracellular Killing of Rickettsia heilongjiangensis.

    Science.gov (United States)

    Yang, Xiaomei; Jiao, Jun; Han, Gencheng; Gong, Wenping; Wang, Pengcheng; Xiong, Xiaolu; Wen, Bohai

    2016-01-01

    Rickettsia heilongjiangensis is the pathogen of Far eastern spotted fever, and T-cell immunoglobulin and mucin domain protein 3 (Tim-3) is expressed in human vascular endothelial cells, the major target cells of rickettsiae. In the present study, we investigated the effects of altered Tim-3 expression in vivo in mice and in vitro in human endothelial cells, on day 3 after R. heilongjiangensis infection. Compared with corresponding controls, rickettsial burdens both in vivo and in vitro were significantly higher with blocked Tim-3 signaling or silenced Tim-3 and significantly lower with overexpressed Tim-3. Additionally, the expression of inducible nitric oxide synthase and interferon γ in endothelial cells with blocked Tim-3 signaling or silenced Tim-3 was significantly lower, while the expression of inducible nitric oxide synthase, interferon γ, and tumor necrosis factor α in transgenic mice with Tim-3 overexpression was significantly higher. These results reveal that enhanced Tim-3 expression facilitates intracellular rickettsial killing in a nitric oxide-dependent manner in endothelial cells during the early phase of rickettsial infection.

  8. Depletion of hepatoma-derived growth factor-related protein-3 induces apoptotic sensitization of radioresistant A549 cells via reactive oxygen species-dependent p53 activation

    Energy Technology Data Exchange (ETDEWEB)

    Yun, Hong Shik; Hong, Eun-Hee [Division of Radiation Cancer Biology, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Department of Chemistry, College of Natural Sciences, Hanyang University, Seoul 133-791 (Korea, Republic of); Lee, Su-Jae [Department of Chemistry, College of Natural Sciences, Hanyang University, Seoul 133-791 (Korea, Republic of); Baek, Jeong-Hwa [Division of Radiation Cancer Biology, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746 (Korea, Republic of); Lee, Chang-Woo [Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746 (Korea, Republic of); Yim, Ji-Hye; Um, Hong-Duck [Division of Radiation Cancer Biology, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Hwang, Sang-Gu, E-mail: sgh63@kcch.re.kr [Division of Radiation Cancer Biology, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of)

    2013-09-27

    Highlights: •HRP-3 is a radiation- and anticancer drug-responsive protein in A549 cells. •Depletion of HRP-3 induces apoptosis of radio- and chemoresistant A549 cells. •Depletion of HRP-3 promotes ROS generation via inhibition of the Nrf2/HO-1 pathway. •Depletion of HRP-3 enhances ROS-dependent p53 activation and PUMA expression. -- Abstract: Biomarkers based on functional signaling have the potential to provide greater insight into the pathogenesis of cancer and may offer additional targets for anticancer therapeutics. Here, we identified hepatoma-derived growth factor-related protein-3 (HRP-3) as a radioresistance-related gene and characterized the molecular mechanism by which its encoded protein regulates the radio- and chemoresistant phenotype of lung cancer-derived A549 cells. Knockdown of HRP-3 promoted apoptosis of A549 cells and potentiated the apoptosis-inducing action of radio- and chemotherapy. This increase in apoptosis was associated with a substantial generation of reactive oxygen species (ROS) that was attributable to inhibition of the Nrf2/HO-1 antioxidant pathway and resulted in enhanced ROS-dependent p53 activation and p53-dependent expression of PUMA (p53 upregulated modulator of apoptosis). Therefore, the HRP-3/Nrf2/HO-1/ROS/p53/PUMA cascade is an essential feature of the A549 cell phenotype and a potential radiotherapy target, extending the range of targets in multimodal therapies against lung cancer.

  9. The Expression of Interleukin-17, Interferon-gamma, and Macrophage Inflammatory Protein-3 Alpha mRNA in Patients with Psoriasis Vulgaris

    Institute of Scientific and Technical Information of China (English)

    李家文; 李东升; 谭志建

    2004-01-01

    Summary: To investigate the role of Interleukin-17 (IL-17), Interferon-gamma (IFN-γ), and macrophage inflammatory protein-3 alpha (MIP-3α) in the pathogenesis of psoriasis, reverse transcriptase-polymerase chain reaction (RT-PCR) was used to semi-quantitatively analyze the mRNA expression of IL 17, IFN-γ, and MIP-3α in 31 psoriatic lesions and 16 normal skin tissues. The results showed that the mRNA of the three cytokines was present in all specimens. And the expression level of IL-17 mRNA in skin lesions was 1. 1416±0. 0591, which was significantly higher than that in normal controls (0. 8788±0. 0344, P<0. 001). The expression levels of IFN-γ mRNA were 1.1142±0. 0561 and 0. 9050±0. 0263, respectively, with significant difference(P<0. 001). And the expression levels of MIP-3α mRNA in psoriatic lesions was 1. 1397 ± 0. 0521, which was markedly higher than that in normal controls (0. 8681±0. 0308, P<0. 001). These findings indicate that up regulated expression of IL-17, IFN-γ, and MIP-3α might be involved in the pathogenesis of psoriasis.

  10. Soluble M3 proteins of murine gammaherpesviruses 68 and 72 expressed in Escherichia coli: analysis of chemokine-binding properties.

    Science.gov (United States)

    Matúšková, R; Pančík, P; Štibrániová, I; Belvončíková, P; Režuchová, I; Kúdelová, M

    2015-12-01

    M3 protein of murine gammaherpesvirus 68 (MHV-68) was identified as a viral chemokine-binding protein 3 (vCKBP-3) capable to bind a broad spectrum of chemokines and their receptors. During both acute and latent infection MHV-68 M3 protein provides a selective advantage for the virus by inhibiting the antiviral and inflammatory response. A unique mutation Asp307Gly was identified in the M3 protein of murine gammaherpesvirus 72 (MHV-72), localized near chemokine-binding domain. Study on chemokine-binding properties of MHV-72 M3 protein purified from medium of infected cells implied reduced binding to some chemokines when compared to MHV-68 M3 protein. It was suggested that the mutation in the M3 protein might be involved in the attenuation of immune response to infection with MHV-72. Recently, Escherichia coli cells were used to prepare native recombinant M3 proteins of murine gammaherpesviruses 68 and 72 (Pančík et al., 2013). In this study, we assessed the chemokine-binding properties of three M3 proteins prepared in E. coli Rosetta-gami 2 (DE3) cells, the full length M3 protein of both MHV-68 and MHV-72 and MHV-68 M3 protein truncated in the signal sequence (the first 24 aa). They all displayed binding activity to human chemokines CCL5 (RANTES), CXCL8 (IL-8), and CCL3 (MIP-1α). The truncated MHV-68 M3 protein had more than twenty times reduced binding activity to CCL5, but only about five and three times reduced binding to CXCL8 and CCL3 when compared to its full length counterpart. Binding of the full length MHV-72 M3 protein to all chemokines was reduced when compared to MHV-68 M3 protein. Its binding to CCL5 and CCL3 was reduced over ten and seven times. However, its binding to CXCL8 was only slightly reduced (64.8 vs 91.8%). These data implied the significance of the signal sequence and also of a single mutation (at aa 307) for efficient M3 protein binding to some chemokines.

  11. A conformational analysis of mouse Nalp3 domain structures by molecular dynamics simulations, and binding site analysis.

    Science.gov (United States)

    Sahoo, Bikash R; Maharana, Jitendra; Bhoi, Gopal K; Lenka, Santosh K; Patra, Mahesh C; Dikhit, Manas R; Dubey, Praveen K; Pradhan, Sukanta K; Behera, Bijay K

    2014-05-01

    Scrutinizing various nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) genes in higher eukaryotes is very important for understanding the intriguing mechanism of the host defense against pathogens. The nucleotide-binding domain (NACHT), leucine-rich repeat (LRR), and pyrin domains (PYD)-containing protein 3 (Nalp3), is an intracellular innate immune receptor and is associated with several immune system related disorders. Despite Nalp3's protective role during a pathogenic invasion, the molecular features and structural organization of this crucial protein is poorly understood. Using comparative modeling and molecular dynamics simulations, we have studied the structural architecture of Nalp3 domains, and characterized the dynamic and energetic parameters of adenosine triphosphate (ATP) binding in NACHT, and pathogen-derived ligands muramyl dipeptide (MDP) and imidazoquinoline with LRR domains. The results suggested that walker A, B and extended walker B motifs were the key ATP binding regions in NACHT that mediate self-oligomerization. The analysis of the binding sites of MDP and imidazoquinoline revealed LRR 7-9 to be the most energetically favored site for imidazoquinoline interaction. However, the binding free energy calculations using the Molecular Mechanics/Poisson-Boltzmann Surface Area (MM/PBSA) method indicated that MDP is incompatible for activating the Nalp3 molecule in its monomeric form, and suggest its complex interaction with NOD2 or other NLRs accounts for MDP recognition. The high binding affinity of ATP with NACHT was correlated to the experimental data for human NLRs. Our binding site prediction for imidazoquinoline in LRR warrants further investigation via in vivo models. This is the first study that provides ligand recognition in mouse Nalp3 and its spatial structural arrangements. PMID:24595807

  12. Probing the pigment binding sites in LHCII with resonance Raman spectroscopy: The effect of mutations at S123.

    Science.gov (United States)

    Kish, Elizabeth; Wang, Ke; Llansola-Portoles, Manuel J; Ilioaia, Cristian; Pascal, Andrew A; Robert, Bruno; Yang, Chunhong

    2016-09-01

    Resonance Raman spectroscopy was used to evaluate the structure of light-harvesting chlorophyll (Chl) a/b complexes of photosystem II (LHCII), reconstituted from wild-type (WT) and mutant apoproteins over-expressed in Escherichia coli. The point mutations involved residue S123, exchanged for either P (S123P) or G (S123G). In all reconstituted proteins, lutein 2 displayed a distorted conformation, as it does in purified LHCII trimers. Reconstituted WT and S123G also exhibited a conformation of bound neoxanthin (Nx) molecules identical to the native protein, while the S123P mutation was found to induce a change in Nx conformation. This structural change of neoxanthin is accompanied by a blue shift of the absorption of this carotenoid molecule. The interactions assumed by (and thus the structure of the binding sites of) the bound Chls b were found identical in all the reconstituted proteins, and only marginally perturbed as compared to purified LHCII. The interactions assumed by bound Chls a were also identical in purified LHCII and the reconstituted WT. However, the keto carbonyl group of one Chl a, originally free-from-interactions in WT LHCII, becomes involved in a strong H-bond with its environment in LHCII reconstituted from the S123P apoprotein. As the absorption in the Qy region of this protein is identical to that of the LHCII reconstituted from the WT apoprotein, we conclude that the interaction state of the keto carbonyl of Chl a does not play a significant role in tuning the binding site energy of these molecules.

  13. Solute-vacancy binding in aluminum

    International Nuclear Information System (INIS)

    Previous efforts to understand solute-vacancy binding in aluminum alloys have been hampered by a scarcity of reliable, quantitative experimental measurements. Here, we report a large database of solute-vacancy binding energies determined from first-principles density functional calculations. The calculated binding energies agree well with accurate measurements where available, and provide an accurate predictor of solute-vacancy binding in other systems. We find: (i) some common solutes in commercial Al alloys (e.g., Cu and Mg) possess either very weak (Cu), or even repulsive (Mg), binding energies. Hence, we assert that some previously reported large binding energies for these solutes are erroneous. (ii) Large binding energies are found for Sn, Cd and In, confirming the proposed mechanism for the reduced natural aging in Al-Cu alloys containing microalloying additions of these solutes. (iii) In addition, we predict that similar reduction in natural aging should occur with additions of Si, Ge and Au. (iv) Even larger binding energies are found for other solutes (e.g., Pb, Bi, Sr, Ba), but these solutes possess essentially no solubility in Al. (v) We have explored the physical effects controlling solute-vacancy binding in Al. We find that there is a strong correlation between binding energy and solute size, with larger solute atoms possessing a stronger binding with vacancies. (vi) Most transition-metal 3d solutes do not bind strongly with vacancies, and some are even energetically strongly repelled from vacancies, particularly for the early 3d solutes, Ti and V

  14. Erythropoietin binding protein from mammalian serum

    Energy Technology Data Exchange (ETDEWEB)

    Clemons, G.K.

    1997-04-29

    Purified mammalian erythropoietin binding-protein is disclosed, and its isolation, identification, characterization, purification, and immunoassay are described. The erythropoietin binding protein can be used for regulation of erythropoiesis by regulating levels and half-life of erythropoietin. A diagnostic kit for determination of level of erythropoietin binding protein is also described. 11 figs.

  15. Erythropoietin binding protein from mammalian serum

    Energy Technology Data Exchange (ETDEWEB)

    Clemons, Gisela K. (Berkeley, CA)

    1997-01-01

    Purified mammalian erythropoietin binding-protein is disclosed, and its isolation, identification, characterization, purification, and immunoassay are described. The erythropoietin binding protein can be used for regulation of erythropoiesis by regulating levels and half-life of erythropoietin. A diagnostic kit for determination of level of erythropoietin binding protein is also described.

  16. Proteomic analysis of egg white heparin-binding proteins: towards the identification of natural antibacterial molecules.

    Science.gov (United States)

    Guyot, Nicolas; Labas, Valérie; Harichaux, Grégoire; Chessé, Magali; Poirier, Jean-Claude; Nys, Yves; Réhault-Godbert, Sophie

    2016-01-01

    The chicken egg resists most environmental microbes suggesting that it potentially contains efficient antimicrobial molecules. Considering that some heparin-binding proteins in mammals are antibacterial, we investigated the presence and the antimicrobial activity of heparin-binding proteins from chicken egg white. Mass spectrometry analysis of the proteins recovered after heparin-affinity chromatography, revealed 20 proteins, including known antimicrobial proteins (avidin, lysozyme, TENP, ovalbumin-related protein X and avian bêta-defensin 11). The antibacterial activity of three new egg candidates (vitelline membrane outer layer protein 1, beta-microseminoprotein-like (LOC101750704) and pleiotrophin) was demonstrated against Listeria monocytogenes and/or Salmonella enterica Enteritidis. We showed that all these molecules share the property to inhibit bacterial growth through their heparin-binding domains. However, vitelline membrane outer layer 1 has additional specific structural features that can contribute to its antimicrobial potential. Moreover, we identified potential supplementary effectors of innate immunity including mucin 5B, E-selectin ligand 1, whey acidic protein 3, peptidyl prolyl isomerase B and retinoic acid receptor responder protein 2. These data support the concept of using heparin affinity combined to mass spectrometry to obtain an overview of the various effectors of innate immunity composing biological milieus, and to identify novel antimicrobial candidates of interest in the race for alternatives to antibiotics. PMID:27294500

  17. Synthetic heparin-binding factor analogs

    Science.gov (United States)

    Pena, Louis A.; Zamora, Paul O.; Lin, Xinhua; Glass, John D.

    2010-04-20

    The invention provides synthetic heparin-binding growth factor analogs having at least one peptide chain, and preferably two peptide chains branched from a dipeptide branch moiety composed of two trifunctional amino acid residues, which peptide chain or chains bind a heparin-binding growth factor receptor and are covalently bound to a non-signaling peptide that includes a heparin-binding domain, preferably by a linker, which may be a hydrophobic linker. The synthetic heparin-binding growth factor analogs are useful as pharmaceutical agents, soluble biologics or as surface coatings for medical devices.

  18. Serum concentrations of free and total insulin-like growth factor-I, IGF binding proteins -1 and -3 and IGFBP-3 protease activity in boys with normal or precocious puberty

    DEFF Research Database (Denmark)

    Juul, A; Flyvbjerg, Allan; Frystyk, Jan;

    1996-01-01

    Circulating IGF-I and IGF binding protein-3 (IGFBP-3) levels both increase in puberty where growth velocity is high. The amount of free IGF-I is dependent on the IGF-I level and on the concentrations of the specific IGFBPs. Furthermore, IGFBP-3 proteolysis regulates the bioavailability of IGF......-I. However, the concentration of free IGF-I and possible IGFBP-3 proteolytic activity in puberty has not previously been studied....

  19. Drug binding properties of neonatal albumin

    DEFF Research Database (Denmark)

    Brodersen, R; Honoré, B

    1989-01-01

    Neonatal and adult albumin was isolated by gel chromatography on Sephacryl S-300, from adult and umbilical cord serum, respectively. Binding of monoacetyl-diamino-diphenyl sulfone, warfarin, sulfamethizole, and diazepam was studied by means of equilibrium dialysis and the binding data were analyzed...... by the method of several acceptable fitted curves. It was found that the binding affinity to neonatal albumin is less than to adult albumin for monoacetyl-diamino-diphenyl sulfone and warfarin. Sulfamethizole binding to the neonatal protein is similarly reduced when more than one molecule of the drug...... is bound per albumin molecule, and binding of the first sulfamethizole molecule is possibly reduced as well. Diazepam binds with equal affinity to the fetal and adult proteins. Among the two main albumin drug-binding functions, for warfarin and diazepam, the former is thus compromised in the newborn...

  20. Malaria immunoepidemiology in low transmission: correlation of infecting genotype and immune response to domains of Plasmodium falciparum merozoite surface protein 3.

    Science.gov (United States)

    Jordan, Stephen J; Oliveira, Ana L; Hernandez, Jean N; Oster, Robert A; Chattopadhyay, Debasish; Branch, OraLee H; Rayner, Julian C

    2011-05-01

    Malaria caused by Plasmodium falciparum is a major cause of global infant mortality, and no effective vaccine currently exists. Multiple potential vaccine targets have been identified, and immunoepidemiology studies have played a major part in assessing those candidates. When such studies are carried out in high-transmission settings, individuals are often superinfected with complex mixtures of genetically distinct P. falciparum types, making it impossible to directly correlate the genotype of the infecting antigen with the antibody response. In contrast, in regions of low transmission P. falciparum infections are often genetically simple, and direct comparison of infecting genotype and antigen-specific immune responses is possible. As a test of the utility of this approach, responses against several domains and allelic variants of the vaccine candidate P. falciparum merozoite surface protein 3 (PfMSP3) were tested in serum samples collected near Iquitos, Peru. Antibodies recognizing both the conserved C-terminal and the more variable N-terminal domain were identified, but anti-N-terminal responses were more prevalent, of higher titers, and primarily of cytophilic subclasses. Comparing antibody responses to different PfMSP3 variants with the PfMSP3 genotype present at the time of infection showed that anti-N-terminal responses were largely allele class specific, but there was some evidence for responses that cross-reacted across allele classes. Evidence for cross-reactive responses was much stronger when variants within one allele class were tested, which has implications for the rational development of genotype-transcending PfMSP3-based vaccines.

  1. Impaired Lysosomal Integral Membrane Protein 2-dependent Peroxiredoxin 6 Delivery to Lamellar Bodies Accounts for Altered Alveolar Phospholipid Content in Adaptor Protein-3-deficient pearl Mice.

    Science.gov (United States)

    Kook, Seunghyi; Wang, Ping; Young, Lisa R; Schwake, Michael; Saftig, Paul; Weng, Xialian; Meng, Ying; Neculai, Dante; Marks, Michael S; Gonzales, Linda; Beers, Michael F; Guttentag, Susan

    2016-04-15

    The Hermansky Pudlak syndromes (HPS) constitute a family of disorders characterized by oculocutaneous albinism and bleeding diathesis, often associated with lethal lung fibrosis. HPS results from mutations in genes of membrane trafficking complexes that facilitate delivery of cargo to lysosome-related organelles. Among the affected lysosome-related organelles are lamellar bodies (LB) within alveolar type 2 cells (AT2) in which surfactant components are assembled, modified, and stored. AT2 from HPS patients and mouse models of HPS exhibit enlarged LB with increased phospholipid content, but the mechanism underlying these defects is unknown. We now show that AT2 in the pearl mouse model of HPS type 2 lacking the adaptor protein 3 complex (AP-3) fails to accumulate the soluble enzyme peroxiredoxin 6 (PRDX6) in LB. This defect reflects impaired AP-3-dependent trafficking of PRDX6 to LB, because pearl mouse AT2 cells harbor a normal total PRDX6 content. AP-3-dependent targeting of PRDX6 to LB requires the transmembrane protein LIMP-2/SCARB2, a known AP-3-dependent cargo protein that functions as a carrier for lysosomal proteins in other cell types. Depletion of LB PRDX6 in AP-3- or LIMP-2/SCARB2-deficient mice correlates with phospholipid accumulation in lamellar bodies and with defective intraluminal degradation of LB disaturated phosphatidylcholine. Furthermore, AP-3-dependent LB targeting is facilitated by protein/protein interaction between LIMP-2/SCARB2 and PRDX6 in vitro and in vivo Our data provide the first evidence for an AP-3-dependent cargo protein required for the maturation of LB in AT2 and suggest that the loss of PRDX6 activity contributes to the pathogenic changes in LB phospholipid homeostasis found HPS2 patients. PMID:26907692

  2. Cysteine-rich secretory protein 3 plays a role in prostate cancer cell invasion and affects expression of PSA and ANXA1.

    Science.gov (United States)

    Pathak, Bhakti R; Breed, Ananya A; Apte, Snehal; Acharya, Kshitish; Mahale, Smita D

    2016-01-01

    Cysteine-rich secretory protein 3 (CRISP-3) is upregulated in prostate cancer as compared to the normal prostate tissue. Higher expression of CRISP-3 has been linked to poor prognosis and hence it has been thought to act as a prognostic marker for prostate cancer. It is proposed to have a role in innate immunity but its role in prostate cancer is still unknown. In order to understand its function, its expression was stably knocked down in LNCaP cells. CRISP-3 knockdown did not affect cell viability but resulted in reduced invasiveness. Global gene expression changes upon CRISP-3 knockdown were identified by microarray analysis. Microarray data were quantitatively validated by evaluating the expression of seven candidate genes in three independent stable clones. Functional annotation of the differentially expressed genes identified cell adhesion, cell motility, and ion transport to be affected among other biological processes. Prostate-specific antigen (PSA, also known as Kallikrein 3) was the top most downregulated gene whose expression was also validated at protein level. Interestingly, expression of Annexin A1 (ANXA1), a known anti-inflammatory protein, was upregulated upon CRISP-3 knockdown. Re-introduction of CRISP-3 into the knockdown clone reversed the effect on invasiveness and also led to increased PSA expression. These results suggest that overexpression of CRISP-3 in prostate tumor may maintain higher PSA expression and lower ANXA1 expression. Our data also indicate that poor prognosis associated with higher CRISP-3 expression could be due to its role in cell invasion. PMID:26369530

  3. Bcl-2/adenovirus E1B 19 kDa interacting protein-3 knockdown enables growth of breast cancer metastases in the lung, liver, and bone.

    Science.gov (United States)

    Manka, David; Spicer, Zachary; Millhorn, David E

    2005-12-15

    The mouse breast cancer cell lines 4T1, 4T07, and 67NR are highly tumorigenic but vary in metastatic potential: 4T1 widely disseminates, resulting in secondary tumors in the lung, liver, bone, and brain; 4T07 spreads to the lung and liver but is unable to establish metastatic nodules; 67NR is unable to metastasize. The Bcl-2/adenovirus E1B 19 kDa interacting protein-3 (Bnip-3) was recently shown to be absent after hypoxia in pancreatic cancer cell lines whereas its overexpression restored hypoxia-induced cell death. We found that Bnip-3 expression increased after 6 hours of hypoxia in all cell lines tested but was highest in the nonmetastatic 67NR cells and lowest in the highly metastatic 4T1 cells. Hypoxia-induced expression of Bnip-3 in the disseminating but nonmetastatic 4T07 cells was intermediate compared with 4T1 and 67NR cells. Cleaved caspase-3, a key downstream effector of cell death, increased after 6 hours of hypoxia in the 67NR and 4T07 cells by 1.9- and 2.5-fold, respectively. Conversely, cleaved caspase-3 decreased by 45% in the highly metastatic 4T1 cells after hypoxia. Small interfering RNA oligonucleotides targeting endogenous Bnip-3 blocked cell death and increased clonigenic survival after hypoxic challenge in vitro and increased primary tumor size and enabled metastasis to the lung, liver, and sternum of mice inoculated with 4T07 cells in vivo. These data inversely correlate the hypoxia-induced expression of the cell death protein Bnip-3 to metastatic potential and suggest that loss of Bnip-3 expression is critical for malignant and metastatic evasion of hypoxia-induced cell death. PMID:16357180

  4. Eps15 Homology Domain-containing Protein 3 Regulates Cardiac T-type Ca2+ Channel Targeting and Function in the Atria*

    Science.gov (United States)

    Curran, Jerry; Musa, Hassan; Kline, Crystal F.; Makara, Michael A.; Little, Sean C.; Higgins, John D.; Hund, Thomas J.; Band, Hamid; Mohler, Peter J.

    2015-01-01

    Proper trafficking of membrane-bound ion channels and transporters is requisite for normal cardiac function. Endosome-based protein trafficking of membrane-bound ion channels and transporters in the heart is poorly understood, particularly in vivo. In fact, for select cardiac cell types such as atrial myocytes, virtually nothing is known regarding endosomal transport. We previously linked the C-terminal Eps15 homology domain-containing protein 3 (EHD3) with endosome-based protein trafficking in ventricular cardiomyocytes. Here we sought to define the roles and membrane protein targets for EHD3 in atria. We identify the voltage-gated T-type Ca2+ channels (CaV3.1, CaV3.2) as substrates for EHD3-dependent trafficking in atria. Mice selectively lacking EHD3 in heart display reduced expression and targeting of both Cav3.1 and CaV3.2 in the atria. Furthermore, functional experiments identify a significant loss of T-type-mediated Ca2+ current in EHD3-deficient atrial myocytes. Moreover, EHD3 associates with both CaV3.1 and CaV3.2 in co-immunoprecipitation experiments. T-type Ca2+ channel function is critical for proper electrical conduction through the atria. Consistent with these roles, EHD3-deficient mice demonstrate heart rate variability, sinus pause, and atrioventricular conduction block. In summary, our findings identify CaV3.1 and CaV3.2 as substrates for EHD3-dependent protein trafficking in heart, provide in vivo data on endosome-based trafficking pathways in atria, and implicate EHD3 as a key player in the regulation of atrial myocyte excitability and cardiac conduction. PMID:25825486

  5. Lower Circulating C1q/TNF-Related Protein-3 (CTRP3 Levels Are Associated with Obesity: A Cross-Sectional Study.

    Directory of Open Access Journals (Sweden)

    Risa M Wolf

    Full Text Available C1q/TNF-related protein-3 (CTRP3 is a novel adipokine that lowers blood glucose levels, reduces liver triglyceride synthesis, and is protective against hepatic steatosis in diet-induced obese mouse models. We hypothesized that higher circulating serum levels of CTRP3 would be associated with a lean body mass index (BMI and a more favorable metabolic profile in humans. The aim of this study was to investigate CTRP3 levels in lean individuals compared to obese individuals.This was a cross-sectional study of obese (n=44 and lean control patients (n=60. Fasting metabolic parameters were measured in all patients and serum CTRP3 levels were measured by ELISA.BMI of the lean group was 21.9 ± 0.2 kg/m2 and obese group was 45.2 ± 1.1 kg/m2. We found significantly lower circulating levels of CTRP3 in obese individuals (405 ± 8.3 vs. 436 ± 6.7 ng/mL, p=0.004 compared to the lean group. Serum CTRP3 levels were inversely correlated with BMI (p=0.001, and triglycerides (p<0.001, and significantly associated with gender (p<0.01, ethnicity (p=0.05, HDL-cholesterol (p<0.01, and adiponectin (p<0.01. We found BMI (p<0.01, gender (p<0.01, and ethnicity (p<0.05 to be significant predictors of CTRP3 levels when controlling for age in multiple regression analysis.CTRP3 is a beneficial adipokine whose circulating levels are significantly lower in obese individuals. Obesity causes dysregulation in adipokine production, including the down-regulation of CTRP3. Lower CTRP3 levels may contribute to the pathophysiology of metabolic disorders associated with obesity. Optimizing CTRP3 levels through novel therapies may improve obesity and its comorbidities.

  6. Degradation of LIM domain-binding protein three during processing of Spanish dry-cured ham.

    Science.gov (United States)

    Gallego, Marta; Mora, Leticia; Fraser, Paul D; Aristoy, María-Concepción; Toldrá, Fidel

    2014-04-15

    Extensive proteolysis takes place during the processing of dry-cured ham due to the action of muscle peptidases. The aim of this work was to study the degradation of LIM domain binding protein 3 (LDB3), which is located at the Z-lines of the sarcomere, at different times during the Spanish dry-cured ham processing (2, 3.5, 5, 6.5, and 9 months). A total of 107 peptides have been identified by mass spectrometry, most of them generated from the first region of the protein sequence (position 1-90) providing evidence for the complexity and variability of proteolytic reactions throughout the whole process of dry-curing. Methionine oxidation has been observed in several peptides by the end of the process. The potential of some of the identified peptides to be used as biomarkers of dry-cured ham processing has also been considered. PMID:24295685

  7. Infinite sets and double binds.

    Science.gov (United States)

    Arden, M

    1984-01-01

    There have been many attempts to bring psychoanalytical theory up to date. This paper approaches the problem by discussing the work of Gregory Bateson and Ignacio Matte-Blanco, with particular reference to the use made by these authors of Russell's theory of logical types. Bateson's theory of the double bind and Matte-Blanco's bilogic are both based on concepts of logical typing. It is argued that the two theories can be linked by the idea that neurotic symptoms are based on category errors in thinking. Clinical material is presented from the analysis of a middle-aged woman. The intention is to demonstrate that the process of making interpretations can be thought of as revealing errors in thinking. Changes in the patient's inner world are then seen to be the result of clarifying childhood experiences based on category errors. Matte-Blanco's theory of bilogic and infinite experiences is a re-evaluation of the place of the primary process in mental life. It is suggested that a combination of bilogic and double bind theory provides a possibility of reformulating psychoanalytical theory.

  8. In vitro effect of Δ9-tetrahydrocannabinol to stimulate somatostatin release and block that of luteinizing hormone-releasing hormone by suppression of the release of prostaglandin E2

    International Nuclear Information System (INIS)

    Previous in vivo studies have shown that Δ9-tetrahydrocannabinol (THC), the principal active ingredient in marijuana, can suppress both luteinizing hormone (LH) and growth hormone (GH) secretion after its injection into the third ventricle of conscious male rats. The present studies were deigned to determine the mechanism of these effects. Various doses of THC were incubated with either stalk median eminence fragments (MEs) or mediobasal hypothalamic (MBH) fragments in vitro. Although THC (10 nM) did not alter basal release of LH-releasing hormone (LHRH) from MEs in vitro, it completely blocked the stimulatory action of dopamine or nonrepinephrine on LHRH release. The effective doses to block LHRH release were associated with a blockade of synthesis and release of prostaglandin E2 (PGE2) from MBH in vitro. In contrast to the suppressive effect of THC on LHRH release, somatostatin release from MEs was enhanced in a dose-related manner with a minimal effective dose of 1 nM. Since PGE2 suppresses somatostatin release, this enhancement may also be related to the suppressive effect of THC on PGE2 synthesis and release. The authors speculate that these actions are mediated by the recently discovered THC receptors in the tissue. The results indicate that the suppressive effect of THC on LH release is mediated by a blockade of LHRH release, whereas the suppressive effect of the compound on growth hormone release is mediated, at least in part, by a stimulation of somatostatin release

  9. Interrelations between herbage yield, α-tocopherol, β-carotene, lutein, protein, and fiber in non-leguminous forbs, forage legumes, and a grass-clover mixture as affected by harvest date.

    Science.gov (United States)

    Elgersma, Anjo; Søegaard, Karen; Jensen, Søren Krogh

    2015-01-21

    Pastures with diverse botanical composition may enhance animal-derived product quality. A recent study demonstrated high vitamin concentrations and yields in some forb species. The objectives of the present study were to investigate interrelations between herbage yields, vitamin concentrations, protein and fiber contents and analyze the effect of harvest date. We hypothesized that interrelations would be similar across investigated forage species. Four nonleguminous forbs: salad burnet (Sanguisorba minor), caraway (Carum carvi), chicory (Cichorium intybus), and ribwort plantain (Plantago lanceolata), three legumes: yellow sweet clover (Melilotus officinalis), lucerne (Medicago sativa), and birdsfoot trefoil (Lotus corniculatus) and a perennial ryegrass (Lolium perenne)-white clover (Trifolium repens) mixture were sown in a field trial with two replicated and randomized blocks. Forage in 1.5 m × 9 m plots was grown in two consecutive years and cut four times per year (May-October). Analyses of variance were performed. In most herbages, α-tocopherol and β-carotene were positively correlated as were β-carotene and lutein; all vitamins were negatively correlated with fiber content and herbage yield. β-Carotene was positively correlated with protein content. α-Tocopherol and β-carotene contents were generally highest in October and lowest in July. Our results showed similar interrelationships in most investigated species, and we suggest that these species may be mixed when designing novel biodiverse mixtures for particular product quality characteristics. PMID:25573460

  10. 促黄体激素受体突变导致的性器官发育异常%Disorders of sexual development caused by luteinizing hormone receptor mutations

    Institute of Scientific and Technical Information of China (English)

    Wai-Yee CHAN

    2005-01-01

    SUMMARY The Luteinizing hormone/chorionic gonadotropin receptor (LHR) plays a critical role in human male sexual development. Both gain-of-function and loss-of-function mutations of the LHR have been described. Gain-of-function mutations are dominant and cause constitutive activation of the receptor resulting in familial male-limited precocious puberty (FMPP). All activating mutations are single point mutations and are located in the transmembrane domain (TM). TM helix Ⅵ harbors the largest number of activating mutations with the codon of Asp-578 being the hot-spot of mutation. Besides causing abnormal sexual development, constitutively activated LHR may predispose an individual to the development of testicular neoplasia. The anti-thesis of FMPP is Leydig cell hypoplasia (LCH). This is caused by mutations that inactivate the LHR resulting in subnormal male sexual development or male pseudohermaphroditism. Inactivating mutations are recessive. The genetic cause of LCH is variable and there is no mutation hot-spot. Genotype-phenotype correlation can be identified in LCH with the milder form caused by mutated LHR with residual activity and the severe form caused by absence of signal transduction activity of the mutated receptor. Molecular diagnosis of the disorders caused by mutation of the LHR can be achieved by direct sequencing of the LHR gene.

  11. 腹腔注射LHRH-A对黑鲷生长激素及其受体的影响%Effects of Luteinizing Hormone-releasing Hormone Analogue Injection on Growth Hormone and Its Receptor in Black Seabream

    Institute of Scientific and Technical Information of China (English)

    邓利; 林浩然

    2003-01-01

    以海水硬骨鱼类黑鲷为研究对象,腹腔注射溶于生理盐水的促性腺激素,释放激素(gonadotropin-releasing hormone,GnRH)的类似物(analogue of luteinizing hormone- releasing hormone,LHRH-A),对照组注射生理盐水.24 h后注射LHRH-A组黑鲷血清生长激素(growth hormone,GH)水平显著高于对照组(p<0.05),于36 h又恢复到对照组水平.注射LHRH-A组肝脏生长激素受体(growth hormone receptor,GHR)及GHR mRNA均与对照组无显著差异.结果表明,腹腔注射LHRH-A刺激了处于性腺成熟期黑鲷GH的分泌,但对黑鲷肝脏GHR及其基因表达无明显影响.

  12. Differentiation of foot-and-mouth disease virus-infected from vaccinated pigs by enzyme-linked immunosorbent assay using nonstructural protein 3AB as the antigen and application to an eradication program

    DEFF Research Database (Denmark)

    Chung, Wen Bin; Sørensen, Karl Johan; Liao, Pei Chih;

    2002-01-01

    Baculovirus-expressed foot-and-mouth disease virus (FMDV) nonstructural protein 3AB was used as the antigen in an enzyme-linked immunosorbent assay. This assay allowed the differentiation of vaccinated from infected pigs. Serial studies were performed using sera collected from pigs in the field...

  13. Heart-type fatty-acid-binding protein (FABP3 is a lysophosphatidic acid-binding protein in human coronary artery endothelial cells

    Directory of Open Access Journals (Sweden)

    Ryoko Tsukahara

    2014-01-01

    Full Text Available Fatty-acid-binding protein 3, muscle and heart (FABP3, also known as heart-type FABP, is a member of the family of intracellular lipid-binding proteins. It is a small cytoplasmic protein with a molecular mass of about 15 kDa. FABPs are known to be carrier proteins for transporting fatty acids and other lipophilic substances from the cytoplasm to the nucleus, where these lipids are released to a group of nuclear receptors such as peroxisome proliferator-activated receptors (PPARs. In this study, using lysophosphatidic acid (LPA-coated agarose beads, we have identified FABP3 as an LPA carrier protein in human coronary artery endothelial cells (HCAECs. Administration of LPA to HCAECs resulted in a dose-dependent increase in PPARγ activation. Furthermore, the LPA-induced PPARγ activation was abolished when the FABP3 expression was reduced using small interfering RNA (siRNA. We further show that the nuclear fraction of control HCAECs contained a significant amount of exogenously added LPA, whereas FABP3 siRNA-transfected HCAECs had a decreased level of LPA in the nucleus. Taken together, these results suggest that FABP3 governs the transcriptional activities of LPA by targeting them to cognate PPARγ in the nucleus.

  14. Erythropoietin binding sites in human foetal tissues

    Energy Technology Data Exchange (ETDEWEB)

    Pekonen, F.; Rosenloef, K.; Rutanen, E.-M.

    1987-01-01

    Using /sup 125/I labelled recombinant DNA human erythropoietin (EP), we have explored the presence and properties of EP binding sites in foetal human tissues. The EP binding site is present in the foetal liver already during the first trimester of pregnancy. The binding site has a equilibrium association constant of 4.1-6.2 x 10/sup 9/l/mol and is specific for EP. The cross-reactivities of FSH, TSH, hCG, insulin and renin substrate were less than 0.01%. The EP binding capacity of foetal liver was 5.4-16 fmol/mg membrane protein. In foetal lung tissue, a slight EP binding activity was observed, whereas foetal spleen, muscle, brain, thyroid and placental tissues were virtually devoid of EP binding capacity. The same level of binding was reached at 37 deg. C in 1 h and at 4 deg. C in 24 h. The binding was pH-dependent with maximal specific binding at pH 7.7. SDS-PAGE gel electrophoresis analysis of covalently cross-linked /sup 125/I-EP to foetal liver membranes suggested that the EP binding site was composed of two subunits with an apparent mol wt of 41000 and 86000 dalton, respectively.

  15. Binding characteristics of swine erythrocyte insulin receptors

    International Nuclear Information System (INIS)

    Crossbred gilts had 8.8 +/- 1.1% maximum binding of [125I]insulin to insulin receptors on erythrocytes. The number of insulin-binding sites per cell was 137 +/- 19, with a binding affinity ranging from 7.4 X 10(7)M-1 to 11.2 X 10(7)M-1 and mean of 8.8 X 10(7)M-1. Pregnant sows had a significant increase in maximum binding due to an increase in number of receptor sites per cell. Lactating sows fed a high-fiber diet and a low-fiber diet did not develop a significant difference in maximum binding of insulin. Sows fed the low-fiber diet had a significantly higher number of binding sites and a significantly lower binding affinity than did sows fed a high-fiber diet. Receptor-binding affinity was lower in the low-fiber diet group than in cycling gilts, whereas data from sows fed the high-fiber diet did not differ from data for cycling gilts. Data from this study indicated that insulin receptors of swine erythrocytes have binding characteristics similar to those in other species. Pregnancy and diet will alter insulin receptor binding in swine

  16. Erythropoietin binding sites in human foetal tissues

    International Nuclear Information System (INIS)

    Using 125I labelled recombinant DNA human erythropoietin (EP), we have explored the presence and properties of EP binding sites in foetal human tissues. The EP binding site is present in the foetal liver already during the first trimester of pregnancy. The binding site has a equilibrium association constant of 4.1-6.2 x 109l/mol and is specific for EP. The cross-reactivities of FSH, TSH, hCG, insulin and renin substrate were less than 0.01%. The EP binding capacity of foetal liver was 5.4-16 fmol/mg membrane protein. In foetal lung tissue, a slight EP binding activity was observed, whereas foetal spleen, muscle, brain, thyroid and placental tissues were virtually devoid of EP binding capacity. The same level of binding was reached at 37 deg. C in 1 h and at 4 deg. C in 24 h. The binding was pH-dependent with maximal specific binding at pH 7.7. SDS-PAGE gel electrophoresis analysis of covalently cross-linked 125I-EP to foetal liver membranes suggested that the EP binding site was composed of two subunits with an apparent mol wt of 41000 and 86000 dalton, respectively. (author)

  17. Adaptive evolution of transcription factor binding sites

    Directory of Open Access Journals (Sweden)

    Berg Johannes

    2004-10-01

    Full Text Available Abstract Background The regulation of a gene depends on the binding of transcription factors to specific sites located in the regulatory region of the gene. The generation of these binding sites and of cooperativity between them are essential building blocks in the evolution of complex regulatory networks. We study a theoretical model for the sequence evolution of binding sites by point mutations. The approach is based on biophysical models for the binding of transcription factors to DNA. Hence we derive empirically grounded fitness landscapes, which enter a population genetics model including mutations, genetic drift, and selection. Results We show that the selection for factor binding generically leads to specific correlations between nucleotide frequencies at different positions of a binding site. We demonstrate the possibility of rapid adaptive evolution generating a new binding site for a given transcription factor by point mutations. The evolutionary time required is estimated in terms of the neutral (background mutation rate, the selection coefficient, and the effective population size. Conclusions The efficiency of binding site formation is seen to depend on two joint conditions: the binding site motif must be short enough and the promoter region must be long enough. These constraints on promoter architecture are indeed seen in eukaryotic systems. Furthermore, we analyse the adaptive evolution of genetic switches and of signal integration through binding cooperativity between different sites. Experimental tests of this picture involving the statistics of polymorphisms and phylogenies of sites are discussed.

  18. Synthetic LPS-Binding Polymer Nanoparticles

    Science.gov (United States)

    Jiang, Tian

    Lipopolysaccharide (LPS), one of the principal components of most gram-negative bacteria's outer membrane, is a type of contaminant that can be frequently found in recombinant DNA products. Because of its strong and even lethal biological effects, selective LPS removal from bioproducts solution is of particular importance in the pharmaceutical and health care industries. In this thesis, for the first time, a proof-of-concept study on preparing LPS-binding hydrogel-like NPs through facile one-step free-radical polymerization was presented. With the incorporation of various hydrophobic (TBAm), cationic (APM, GUA) monomers and cross-linkers (BIS, PEG), a small library of NPs was constructed. Their FITC-LPS binding behaviors were investigated and compared with those of commercially available LPS-binding products. Moreover, the LPS binding selectivity of the NPs was also explored by studying the NPs-BSA interactions. The results showed that all NPs obtained generally presented higher FITC-LPS binding capacity in lower ionic strength buffer than higher ionic strength. However, unlike commercial poly-lysine cellulose and polymyxin B agarose beads' nearly linear increase of FITC-LPS binding with particle concentration, NPs exhibited serious aggregation and the binding quickly saturated or even decreased at high particle concentration. Among various types of NPs, higher FITC-LPS binding capacity was observed for those containing more hydrophobic monomers (TBAm). However, surprisingly, more cationic NPs with higher content of APM exhibited decreased FITC-LPS binding in high ionic strength conditions. Additionally, when new cationic monomer and cross-linker, GUA and PEG, were applied to replace APM and BIS, the obtained NPs showed improved FITC-LPS binding capacity at low NP concentration. But compared with APM- and BIS-containing NPs, the FITC-LPS binding capacity of GUA- and PEG-containing NPs saturated earlier. To investigate the NPs' binding to proteins, we tested the NPs

  19. Why tight-binding theory?

    Science.gov (United States)

    Harrison, Walter A.

    2002-12-01

    In the context of computational physics other methods are more accurate, but tight-binding theory allows very direct physical interpretation and is simple enough to allow much more realistic treatments beyond the local density approximation. We address several important questions of this last category: How does the gap enhancement from Coulomb correlations vary from material to material? Should the enhanced gap be used for calculating the dielectric constant? For calculating the effective mass in k-dot-p theory? How valid is the scissors approximation? How does one line up bands at an interface? How should we match the envelope function at interfaces in effective-mass theory? Why can the resulting quantum-well states seem to violate the uncertainty principle? How should f-shell electrons be treated when they are intermediate between band-like and core-like? The answers to all of these questions are given and discussed.

  20. DNA binding hydroxyl radical probes

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Vicky J.; Konigsfeld, Katie M.; Aguilera, Joe A. [Department of Radiology, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0610 (United States); Milligan, Jamie R., E-mail: jmilligan@ucsd.edu [Department of Radiology, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0610 (United States)

    2012-01-15

    The hydroxyl radical is the primary mediator of DNA damage by the indirect effect of ionizing radiation. It is a powerful oxidizing agent produced by the radiolysis of water and is responsible for a significant fraction of the DNA damage associated with ionizing radiation. There is therefore an interest in the development of sensitive assays for its detection. The hydroxylation of aromatic groups to produce fluorescent products has been used for this purpose. We have examined four different chromophores, which produce fluorescent products when hydroxylated. Of these, the coumarin system suffers from the fewest disadvantages. We have therefore examined its behavior when linked to a cationic peptide ligand designed to bind strongly to DNA. - Highlights: > Examined four aromatic groups as a means to detect hydroxyl radicals by fluorescence. > Coumarin system suffers from the fewest disadvantages. > Characterized its reactivity when linked to a hexa-arginine peptide.