J Tziotis

Athens State University, Athens, Alabama, United States

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Publications (17)49.29 Total impact

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    ABSTRACT: To measure serial serum concentrations of the angiogenic factors vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and angiogenin (ANG) in the periovulatory and secretory phase of normal menstrual cycles in healthy women and to determine their peaks, which might reflect the stage of their critical angiogenic action. Prospective study. University departments of obstetrics and gynecology. Thirty-three healthy Swedish women with regular menstrual cycles. Serial blood samples were collected from each woman. Luteinizing hormone surge was identified by testing morning urine. Circulating levels of VEGF, bFGF, and ANG. Circulating peak concentrations were determined for VEGF on day 0 and 9 after ovulation, for bFGF on day 1 before ovulation and day 9 after ovulation, and for ANG on day 3 after ovulation. Circulating VEGF increased in a stage-dependent cyclic fashion. Basic FGF peaked during the late proliferative and mid secretory phase. Circulating ANG showed increased expression around the early secretory phase of the cycle.
    Fertility and Sterility 06/2004; 81(5):1322-7. · 4.17 Impact Factor
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    ABSTRACT: Chemokines, a superfamily of polypeptide mediators, are a key component of immune surveillance and are implicated in the initiation of the inflammatory cascade. This study investigated whether serum concentrations of the chemokines regulated upon activation, normal T-cell expressed and presumably secreted (RANTES) and interleukin-8 (IL-8) change in the perinatal period because of the transition from intra- to extrauterine life, and compared determined values in mothers (MS) (n = 30) with those in their fetuses (UC), neonates (day of life 1 [N1] and 4 [N4]), and controls (CS) (n = 20). RANTES serum concentrations were higher in MS than in UC ( p < 0.006), N1 ( p < 0.0001), N4 ( p < 0.0001), and CS ( p < 0.0001). IL-8 serum concentrations in MS and UC, respectively, were significantly lower than in N1 ( p < 0.0002 and p < 0.0007) and N4 ( p < 0.0001 and p < 0.0001). Thus, after birth, neonatal serum concentrations of RANTES decrease, possibly because of elimination of the placenta (probable production site), and neonatal serum concentrations of IL-8 increase, possibly triggered by environmental antigenic stimuli to which the neonate is exposed.
    American Journal of Perinatology 05/2004; 21(4):235-40. · 1.57 Impact Factor
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    ABSTRACT: To determine, during normal pregnancy, maternal serum (MS) and amniotic fluid (AF) concentrations of soluble Fas (sFas), an apoptosis-suppressing molecule that might play a role in the apoptotic process. Soluble Fas levels might explain existing immunotolerance, fetal well being, and rupture of membranes at term. Sixty-six healthy, nonsmoking, pregnant women (mean age 32.6 +/- 4.8 years) with uncomplicated singleton pregnancies (15 in the first trimester, 30 in the second trimester, and 21 at term vaginal delivery) and 20 healthy nonpregnant women (mean age 32.5 +/- 3.8 years) were included in the study. MS and AF sFas concentrations were measured by a sandwich enzyme-linked immunosorbent assay, and parametric tests were used in the statistical analysis.MS and AF sFas concentrations significantly depended on gestational age (P < .0008 and P < .0002, respectively). MS concentrations were significantly lower in the first trimester than those in the second trimester (P <.003), those at term (P < .03), and those in nonpregnant controls (P < .005). AF concentrations decreased significantly at term compared with those in the second trimester (P < .0003). AF sFas concentrations in the second trimester and at term were significantly lower than respective MS concentrations (P < .00001). MS sFas concentrations decreased significantly in the first trimester of pregnancy, possibly affecting semiallograft tolerance. In the second trimester, concentrations return to control levels and remain unchanged until delivery. AF sFas concentrations decrease at term compared with the second trimester, possibly indicating increased apoptosis in preparation for rupture of membranes.
    Journal of the Society for Gynecologic Investigation 04/2003; 10(3):158-60. · 2.26 Impact Factor
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    ABSTRACT: To compare the expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), platelet endothelial cell adhesion molecule-1 (PECAM-1) and E-selectin in placental bed biopsies (endothelium of spiral arteries as well as trophoblastic cells) from normal and pre-eclamptic pregnancies. A prospective study. 1. First Department of Obstetrics and Gynaecology, Alexandra Hospital, University of Athens, Greece. 2. Laboratory of Pathophysiology, Laikon Hospital, University of Athens. Sixteen placental bed biopsies from women with pre-eclampsia were compared with 20 placental bed biopsies from uncomplicated normotensive women. Immunocytochemical staining of the placental bed biopsies for ICAM-1, VCAM-1, PECAM-1 and E-selectin. No statistically significant differences were found in the expression of the adhesion molecules ICAM-1, VCAM-1, PECAM-1 and E-selectin in the endothelium of the spiral arteries and the trophoblastic cells of the placental bed of the two studied groups. Adhesion molecules ICAM-1, VCAM-1, PECAM-1, but not E-selectin, are expressed in the placental bed of normal and pre-eclamptic pregnancies, but there are no differences between the two groups of women. It seems that the above molecules are not likely to be implicated in the aetiology of pre-eclampsia.
    BJOG An International Journal of Obstetrics & Gynaecology 03/2002; 109(2):197-201. · 3.76 Impact Factor
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    Diabetes Care 02/2002; 25(1):240-1. · 7.74 Impact Factor
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    ABSTRACT: In fetal life the rates of proliferation and apoptosis are high. We studied if the rate of apoptosis decreases after birth, by measuring the soluble (s) forms of Fas-Fas ligand and Tumor necrosis factor receptor 1 (TNFR1)-TNF-alpha which attenuate apoptosis. Blood was drawn from the umbilical cord and from a peripheral vein on day 1 and 4 of life in 35 infants and sFas, sFas ligand, sTNFR1 and sTNF-alpha were determined by enzyme immunoassays. Data were analyzed by paired t-test and Pearson's correlation analysis. sFas and sTNF increased significantly from birth to day 4 of life (p=0.033 and p<0.0001 respectively), while sTNFR1 increased significantly from birth to day 1 of life (p<0.0001) followed by a significant decrease on day 4 of life (p<0.0001). The levels of sFas and sTNF-alpha on day 1 correlated with those on day 4 (r=0.677, p<0.0002 and r=0.525, p<0.007 respectively). sFAS ligand was not detectable in any specimen. The increasing concentrations of the soluble molecules, sFas, sTNF-alpha and sTNFR1 might indicate that apoptosis may be downregulated in early postnatal life.
    Acta Obstetricia Et Gynecologica Scandinavica 11/2001; 80(11):994-7. · 1.85 Impact Factor
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    ABSTRACT: Alterations in the NH2-terminal region of the estrogen receptor alpha (ERα) gene expressed in placental bed tissue may be implicated in the development of preeclampsia, the pathogenesis of which involves the spiral arteries. Therefore, mutations and polymorphisms on exons 1 and 2 of the gene encoding ERα were studied. Placental bed biopsies were taken from 20 healthy, normotensive pregnant women and 16 preeclamptic patients. DNA was extracted from the tissue and exon 1 and exon 2 were amplified by PCR prior to denaturing gradient gel electrophoresis analysis or to single stranded conformational polymorphism analysis. In exon 1, a codon 10 polymorphism, either homozygous for the wild type gene, homozygous for the mutant type gene, or heterozygous, was revealed in both patients and healthy individuals. A codon 87 polymorphism, homozygous for the wild type gene, was detected in both groups. No mutations or polymorphisms were found in exon 2. The allele distribution for either codon 10 or 87 between patients and healthy individuals showed no significant differences. In conclusion, genetic alterations in the NH2-terminal region of the ERα molecule are not correlated with preeclampsia.
    Steroids 10/2001; · 2.80 Impact Factor
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    ABSTRACT: To determine the concentration of angiogenic factors (vascular endothelial growth factor [VEGF], basic fibroblast growth factor [bFGF], and angiogenin) in the follicular fluid (FF) and oocyte-cumulus complex culture medium (CM) of women undergoing IVF and to investigate the association of the concentrations with the maturity and fertilization of the oocyte. Prospective study. Academic tertiary-care institution. IVF patients with unexplained or tubal factor infertility. Analysis of VEGF, bFGF, and angiogenin FF and CM concentrations. Oocyte maturity and fertilization and FF and CM angiogenic factor concentrations. VEGF, bFGF, and angiogenin were determined in FF and CM. FF angiogenin concentrations were significantly higher when the oocyte was mature versus immature. CM VEGF concentrations were significantly higher when the oocyte was nonfertilized versus fertilized. Positive correlations were observed between angiogenic factors in CM. VEGF, bFGF, and angiogenin (determined for the first time) are secreted in the FF and CM. Elevated CM VEGF concentrations, probably implying oocyte-cumulus complex hypoxia, are negatively associated with oocyte fertilization. Elevated FF angiogenin concentrations are positively associated with oocyte maturity, possibly indicating angiogenin's biological role beyond neovascularization.
    Fertility and Sterility 08/2001; 76(1):98-101. · 4.17 Impact Factor
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    ABSTRACT: This study investigated whether serum levels of the adhesion molecules VCAM-1, PECAM-1 and L-selectin, all of which have been implicated in normal immune function, change soon after birth. Moreover, the dependence of serum levels of the above-mentioned adhesion molecules on sex and mode of delivery was studied. In healthy neonates, serum levels of L-selectin, PECAM-1, and VCAM-1 do not change during early neonatal life. Thus, significant differences in their serum concentrations soon after birth might imply inflammatory processes or deranged endothelial homeostasis, serving as possible diagnostic markers.
    Biology of the Neonate 08/2000; 78(1):65-7. · 1.90 Impact Factor
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    ABSTRACT: These studies investigated whether serum levels of the angiogenic factors angiogenin, basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF) change soon after birth due to the elimination of the placenta and to diminished angiogenic but increased adaptational demands in extrauterine life. Also investigated was whether serum levels correlate with sex, birth weight, or mode of delivery. Serum from healthy mothers and their healthy full-term infants at birth (umbilical cord, UC), day 1 (N1) and day 4 (N4) postpartum was analyzed by enzyme immunoassays. Angiogenin levels were higher in maternal serum and rose significantly from UC to N1 and N4, possibly because of the elimination of the placenta, which produces an angiogenin inhibitor. bFGF and VEGF maternal levels were lower than fetal and neonatal ones. Although neonatal bFGF levels did not differ from fetal levels, possibly reflecting diminished angiogenesis ex utero, VEGF levels increased in neonatal serum, possibly signifying adaptational demands. Neither factor depended on sex, mode of delivery, or birth weight. Thus, significant differences from normal reference values of the studied factors might reflect ill-defined situations of the placenta and fetus/newborn serving as early diagnostic markers.
    Annals of the New York Academy of Sciences 02/2000; 900:169-73. · 4.38 Impact Factor
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    ABSTRACT: This study investigated serum levels of basic fibroblast growth factor (b FGF), a potent angiogenic factor, during distinct periods of the female life and compared them with corresponding levels in age-matched males. Healthy females (n = 59) and males (n = 53) were included in the study, divided into six groups: fetuses (cord blood), neonates, children, adults (females in proliferative and secretory phase), pregnant and "elderly" men and women. Serum b FGF levels were measured by an enzyme immunoassay. No statistically significant difference was found between both genders. Blood levels in fetuses and neonates were significantly increased as compared to adults (p = 0.01, p = 0.02, respectively). Restricting the analysis to females, all age groups, but fetuses (p = 0.05), demonstrated no difference when compared to proliferative phase adults. In conclusion, b FGF serum levels do not differ between males and females and are elevated in fetal and neonatal life, when growth and development are enhanced.
    Growth Factors 02/2000; 17(3):215-20. · 2.20 Impact Factor
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    ABSTRACT: To study serum levels of vascular endothelial growth factor (VEGF), a potent angiogenic factor, during distinct periods of the female life span and compare them with corresponding levels of age-matched males. It is hypothesized that VEGF might be increased at periods of enhanced angiogenesis. Venous blood was drawn from healthy females (n = 59) and males (n = 53) divided into six groups: fetuses (cord blood), neonates, children, adults (same females in the proliferative and secretory phases of their menstrual cycle), pregnant, and elderly (postmenopausal). Serum VEGF levels were measured by an enzyme immunoassay. Females showed 49% higher serum VEGF levels than males (t = 2.74, P = .01). Cord and neonatal blood levels were significantly increased compared with those of adults (t = 2.41, P = .02, and t = 5.81, P = .0001, respectively). All female age groups presented higher serum VEGF levels than the group of women in the proliferative phase of the cycle; nevertheless, VEGF levels in the secretory phase did not differ (t = 1.85, P = .07). Serum VEGF levels are higher in females than in males and during life periods characterized by enhanced growth and development, implying increased rates of angiogenesis.
    Journal of the Society for Gynecologic Investigation 01/2000; 7(5):309-12. · 2.26 Impact Factor
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    ABSTRACT: This study investigated whether serum levels of the potent angiogenic factors basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF), which are abundantly produced in utero by the placenta and fetal tissues, change after birth at term, consequent to diminished angiogenic but increased adaptational demands in extrauterine life. Moreover, whether serum levels of the above factors correlate with sex, birth weight, or mode of delivery was also evaluated. One milliliter of blood was drawn from 30 healthy, appropriate for gestational age, full-term infants on d 1 (N1) and 4 (N4) postnatally. In 10 of the above cases maternal and umbilical cord blood samples were also drawn. Serum was analyzed by enzyme immunoassays, using commercial kits. Levels of bFGF and VEGF were significantly lower in maternal serum than in umbilical cord (p = 0.02 and 0.036, respectively) or N1 (p = 0.009 and 0.006, respectively) and N4 serum (p = 0.009 and 0.006, respectively). Levels of bFGF in umbilical cord serum did not differ significantly from those in N1 and N4. In contrast, levels of VEGF rose in N1, differing significantly from levels in umbilical cord serum (p = 0.008). Both factors did not change from N1 to N4. Neither bFGF nor VEGF serum levels depended on sex, mode of delivery, or birth weight. In conclusion, bFGF levels in neonates do not differ from levels in fetuses, possibly reflecting diminished angiogenesis in extrauterine life, which already has started in utero. On the contrary, neonatal levels of VEGF rise significantly after birth, possibly signifying adaptation demands, in addition to angiogenesis, as VEGF is also considered a regulator of normal function.
    Pediatric Research 07/1999; 45(6):877-80. · 2.67 Impact Factor
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    ABSTRACT: This study investigated serum angiogenin levels of the potent angiogenic factor angiogenin, during fetal and neonatal life, childhood, adulthood, pregnancy and postmenopause and compared them with respective levels in age-matched males. Serum angiogenin levels were measured by an enzyme immunoassay in 139 healthy male and female subjects, allocated in the above six groups. Multiple linear regression applied (a) for both genders and (b) only for females showed serum angiogenin levels in adults to differ statistically highly significantly from levels in cord blood (P = 0.0001), neonates (P = 0.0001), children (P = 0.0001), and pregnant women (P = 0.01), but not from "elderly" subjects (P = 0.80). A significant difference existed between levels in the proliferative and secretory phase of the menstrual cycle (P = 0.006). Furthermore, a significant trend for serum angiogenin levels with advancing age groups was noted (P = 0.0001). In conclusion, serum angiogenin levels increase significantly from fetal life to adulthood, possibly implying additional biological functions to that of angiogenesis.
    Growth Factors 02/1999; 17(1):75-9. · 2.20 Impact Factor
  • Pediatric Research - PEDIAT RES. 01/1999; 45(6).
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    ABSTRACT: Diabetes mellitus is characterized by microangiopathy and increased angiogenic response in various organs. Basic fibroblast growth factor (bFGF) as well as vascular endothelial growth factor (VEGF) are both angiogenic and are involved in vascular endothelial cell growth. The purpose of this study was to determine serum levels of bFGF and VEGF, in children and adolescents (youngsters) with type 1 diabetes mellitus, and correlate them with parameters reflecting the severity of the disease. Forty diabetic youngsters without clinical evidence of complications were compared with 30 healthy control subjects (mean age +/- SD, 14.3 +/- 3.6 and 13.8 +/- 3.6 y, respectively). Diabetes duration and metabolic control (expressed by glycosylated Hb) were (mean +/- SD) 6.2 +/- 3.8 y and 9.6 +/- 1.8%, respectively. bFGF and VEGF (pg/mL) were measured in serum samples by enzyme immunoassays, and both were not significantly different between the type 1 diabetes mellitus and the control group (p = 0.952 and p = 0.559, respectively). Restricting the analysis to the type 1 diabetes mellitus group, neither the duration nor the metabolic control of the disease showed any correlation with bFGF and VEGF serum levels, whereas a significantly positive correlation was found between the two examined angiogenic factors both in the diabetic (r = 0.3464, p = 0.025) and the control group (r = 0.4619, p = 0.0013). In conclusion, serum levels of bFGF and VEGF were not found to vary significantly in diabetic youngsters in relation to controls and had no correlation with the duration and metabolic control of the disease. Nevertheless, a positive correlation was found between these two angiogenic factors both in the type 1 diabetes mellitus and the control group.
    Pediatric Research 01/1999; 44(6):873-5. · 2.67 Impact Factor
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    ABSTRACT: Microangiopathy, one of the most important complications of diabetes mellitus in humans, is associated with increased angiogenic response and proliferative lesions in various organs. Angiogenin, a polypeptide with a molecular size of 14 kD, is a potent inducer of vascular growth. This study aimed at investigating whether serum angiogenin levels are elevated in children and adolescents (youngsters) with insulin-dependent diabetes mellitus and whether angiogenin levels are affected by duration and metabolic control of the disease. It is assumed that angiogenin levels reflect the increased angiogenesis associated with microangiopathy, whether clinically evident or not. Forty diabetic youngsters were compared with 30 healthy control subjects (mean age +/- SD, 14.3 +/- 3.6 y and 13.8 +/- 3.6 y, respectively). The patients' disease duration and glycosylated Hb were (mean +/- SD) 6.2 +/- 3.8 y and 9.6 +/- 1.8%, respectively. Angiogenin (ng/mL) was measured in serum samples by an enzyme immunoassay and was found to be significantly higher (mean +/- SE) in patients (353.3 +/- 20.0) than in control subjects (244.7 +/- 9.6) (p = 0.0002). Levels did not vary with age, but were significantly higher in females compared with male subjects (p = 0.01). In the diabetic youngsters no significant differences were noticed with respect to duration or metabolic control of the disease. In conclusion, serum angiogenin levels were found to be increased among diabetic youngsters, irrespective of the duration and metabolic control of the disease, as well as in female subjects, with or without diabetes.
    Pediatric Research 07/1998; 43(6):798-800. · 2.67 Impact Factor