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1.
Adv Med Sci ; 69(2): 349-355, 2024 Jul 24.
Article in English | MEDLINE | ID: mdl-39059468

ABSTRACT

PURPOSE: The excessive fructose intake including high-fructose corn syrup (HFCS) may be responsible for increase of obesity occurrence. This study was designed to find potential differences in duodenal fructose transporters on mRNA and protein levels between obese and normal weight children and adolescents. MATERIALS/METHODS: We performed a cross-sectional study on a group of 106 hospitalized patients aged 12 to 18. Glucose transporter 2 (GLUT2) and glucose transporter 5 (GLUT5) mRNA as well as protein levels (ELISA and Western blot methods) were assessed in duodenal mucosa biopsies of the patients categorized as obese or normal weight. Additionally, the expression of the aforementioned transporters was analyzed in patients based on the presence of insulin resistance (IR) and metabolic syndrome (MS). RESULTS: In children with obesity, increased duodenal protein levels of GLUT5 (Relative protein GLUT5 expression/ACTB) (0.027 â€‹± â€‹0.009 vs. 0.011 â€‹± â€‹0.006, p â€‹< â€‹0.05) but not GLUT2 as compared with the normal weight group, were revealed. No significant differences in duodenal relative GLUT2 and GLUT5 genes expression between the studied groups were found. There was no relationship between the presence of IR or MS and intestinal mRNA GLUT2 and GLUT5 as well as GLUT2 protein expression. CONCLUSION: The upregulation of the duodenal GLUT5 may contribute to obesity occurrence in children and adolescents.

2.
BMC Pediatr ; 20(1): 294, 2020 06 16.
Article in English | MEDLINE | ID: mdl-32546231

ABSTRACT

BACKGROUND: Fibroblast growth factor 19 (FGF19), fibroblast growth factor 21 (FGF21) and Klotho are regulators of energy homeostasis. However, in the pediatric population, the relationships between obesity, metabolic disorders and the aforementioned factors have not been clearly investigated. We analyzed the role of FGF19, FGF21 and Klotho protein in children with normal body weight as well as in overweight and obese subjects and explored their associations with insulin resistance (IR) and metabolic syndrome (MS) and its components. METHODS: This was a cross-sectional study conducted in a group of hospitalized children and adolescents. Laboratory investigations included serum analysis of FGF19, FGF21, and Klotho with ELISA kits as well as the analysis of the lipid profile and ALT serum concentrations. Moreover, each subject underwent an oral glucose tolerance test (OGTT) with fasting insulinemia measurement to detect glucose tolerance abnormalities and calculate the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) index. Furthermore, the clinical analysis included blood pressure measurement, body fat percentage estimation and assessment of the prevalence of MS and its components. RESULTS: The study was conducted with 174 children/adolescents aged 6-17 years with normal body weight (N = 48), obesity (N = 92) and overweight (N = 34). Klotho concentration was significantly higher in the obese children [median 168.6 pg/ml (90.2 to 375.9)]) than in the overweight [131.3 pg/ml (78.0 to 313.0)] and normal-body-weight subjects [116.6 pg/ml (38.5 to 163.9)] (p = 0.0334) and was also significantly higher in insulin-resistant children than in insulin-sensitive children [185.3 pg/ml (102.1 to 398.2) vs 132.6 pg/ml (63.9 to 275.6), p = 0.0283]. FGF21 was elevated in patients with MS compared to the FGF21 levels in other subjects [136.2 pg/ml (86.5 to 239.9) vs 82.6 pg/ml (41.8 to 152.4), p = 0.0286]. The multivariable model showed that FGF19 was an independent predictor of IR after adjusting for pubertal stage and BMI Z-score. CONCLUSIONS: Klotho levels were associated with body weight status in children and adolescents. Moreover, Klotho, FGF19 and FGF21 concentrations correlated with IR status and/or components of MS.


Subject(s)
Fibroblast Growth Factors , Ideal Body Weight , Insulin Resistance , Adolescent , Body Mass Index , Body Weight , Child , Cross-Sectional Studies , Glucuronidase , Humans , Klotho Proteins , Obesity
3.
Arch Med Sci ; 15(6): 1425-1432, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31749870

ABSTRACT

INTRODUCTION: Folate is required for fetal, placental and maternal tissue growth during pregnancy. A decline in maternal circulating folate concentrations and an increase in total homocysteine (a non-specific indicator of folate deficiency) have been observed with the progression of pregnancy. However, the role of folate in the third trimester of pregnancy is not clear and folate status in late pregnancy has not so far been widely analyzed. The main aim of this retrospective cross-sectional study was to determine the folate concentrations in amniotic fluid and in maternal and umbilical cord blood serum derived during delivery. MATERIAL AND METHODS: This study was conducted on 175 pregnant Polish women (white/Caucasian) aged between 17 and 42 years. Only pregnancies without birth defects were included in this study. Amniotic fluid, maternal serum, and umbilical cord blood samples were collected during vaginal delivery or cesarean section. Folate concentration was determined using a microbiological assay. RESULTS: Strong correlations were observed between the concentrations of folate in amniotic fluid and maternal serum (rho = 0.67, p < 0.001) and amniotic fluid and cord blood serum (rho = 0.49, p < 0.001) and between maternal serum and cord blood serum (rho = 0.67, p < 0.001). Folate concentrations in amniotic fluid were significantly associated with maternal age (rho = 0.19, p < 0.05). Pre-pregnancy body mass index and maternal weight/neonatal birth weight ratio were independent predictors of folate concentrations in maternal serum (ß = 0.33, p < 0.05; ß = -0.19, p < 0.05) and amniotic fluid (ß = 0.28, p < 0.05; ß = -0.19, p < 0.05) in late pregnancy. CONCLUSIONS: Folate concentrations in amniotic fluid are associated with maternal and neonatal folate status peripartum in healthy women.

4.
Nutrients ; 11(2)2019 Feb 03.
Article in English | MEDLINE | ID: mdl-30717440

ABSTRACT

Congenital birth defects may result in a critical condition affecting the baby, including severe fetal/neonatal handicap and mortality. Several studies have shown that genetic, nutritional, and environmental factors may have an impact on fetal development and neonatal health. The relevance of essential and toxic elements on fetal development has not yet been fully investigated, and the results of recent research indicate that these elements may be crucial in the assessment of the risk of malformations in neonates. We determined the association between essential and toxic elements and the level of folate in maternal serum (MS) and amniotic fluid (AF), along with neonatal abnormalities. A total of 258 pregnant Polish women in the age group of 17⁻42 years participated in this study. AF and MS were collected during vaginal delivery or during cesarean section. An inductively coupled plasma mass spectrometry technique was used to determine the levels of various elements in AF and MS. The results of this exploratory study indicate that the levels of essential and toxic elements are associated with fetal and newborn anatomical abnormalities and growth disorders.


Subject(s)
Amniotic Fluid/metabolism , Congenital Abnormalities/metabolism , Fetal Development , Folic Acid/metabolism , Growth Disorders/metabolism , Minerals/metabolism , Trace Elements/metabolism , Adolescent , Adult , Congenital Abnormalities/blood , Congenital Abnormalities/etiology , Female , Growth Disorders/blood , Growth Disorders/etiology , Humans , Infant, Newborn , Minerals/blood , Pregnancy , Trace Elements/blood , Young Adult
5.
J Trace Elem Med Biol ; 52: 136-142, 2019 Mar.
Article in English | MEDLINE | ID: mdl-30732874

ABSTRACT

The aim of the study was to determine the correlations between body mass index (BMI) values before pregnancy and the concentrations of selected elements (Mg, Co, Cu, Zn, Sr, Cd, Ba, Pb, U, Ca, Cr, Al, Mn, V, Fe) in blood serum and amniotic fluid (AF) in pregnant women. Elemental analysis of serum and amniotic fluid in 225 Polish women (Caucasian/white) showed a relationship between the concentration of minerals in the above-mentioned samples and the pre-pregnancy BMI. Analysis of blood serum was performed by using ICP-MS and it demonstrated that iron concentration was significantly lower in overweight and obese women. Being underweight in pregnant women was associated with a significantly lower concentration of magnesium and cobalt in the blood serum. Both underweight and overweight women were associated with significantly lower concentrations of calcium and strontium in the blood serum. The concentration of cobalt was significantly higher in underweight women. The concentration of lead in the blood serum of overweight and obese women was significantly higher than in other groups. Analysis of the AF showed that the concentration of copper was significantly lower in overweight and obese women, and the concentration of manganese and vanadium significantly higher than in other groups of women. A deficiency in essential minerals and an excess of heavy metals in women may be associated with abnormal body weight and this is important in the etiopathogenesis of pregnancy and fetal development disorders.


Subject(s)
Amniotic Fluid/chemistry , Body Mass Index , Minerals/analysis , Adolescent , Adult , Female , Humans , Pregnancy , Young Adult
6.
Biol Trace Elem Res ; 189(1): 45-54, 2019 May.
Article in English | MEDLINE | ID: mdl-30097982

ABSTRACT

The objective of this study was to determine the concentration and the reference ranges of essential and toxic elements in amniotic fluid (AF) and maternal serum (MS) at birth. This study was conducted among 175 healthy pregnant Caucasian European women aged 18-42. AF and maternal blood samples were collected during delivery. An inductively coupled plasma mass spectrometry (ICP-MS) technique was used to determine the levels of Mg, Co, Cu, Zn, Sr, Cd, Ba, Pb, U, Ca, Cr, Al, Mn, V, Fe, As, Se and Sb in AF and MS. The range of reference values was calculated for all analyzed elements in the serum and AF. The mean concentrations of elements, except Pb, were generally higher in MS than in AF. Multiple regression analysis showed that the maternal/newborn body mass (MBM/NBM) ratio was a strong negative predictor (among maternal age and gravidity) of Mg concentration in amniotic fluid. In the serum, MBN/NBM ratio was a strong positive predictor of Cu concentration. Moreover, regression analysis showed that maternal age was an independent positive predictor of the Se level in maternal serum. The reference value ranges of 18 essential and toxic elements were established in AF and MS among a population of healthy pregnant Polish women at delivery. The level of Mg, Co, Cu, Ca and Se in AF and MS can be determined by maternal age and MBM/NBM ratio. These results can be useful in counseling individuals with pregnancies affected by exposure to one of the parameters under investigation.


Subject(s)
Amniotic Fluid/chemistry , Trace Elements/analysis , Trace Elements/blood , Adolescent , Adult , Female , Humans , Infant, Newborn , Male , Multivariate Analysis , Pregnancy , Regression Analysis , Young Adult
7.
Arch Gynecol Obstet ; 297(6): 1433-1440, 2018 06.
Article in English | MEDLINE | ID: mdl-29541858

ABSTRACT

PURPOSE: To evaluate the dietary intake of pregnant women and their nutritional status of Ca, Mg, Fe, Zn, and Cu, as the nutritional status of pregnant women is an important factor for the proper progression of a pregnancy and the development and health of the foetus. METHODS: The study was conducted on 108 pregnant women ages 18-42, at 6-32 weeks of gestation. We used a questionnaire and a 24-h recall nutrition interview. Hair samples were taken for testing and the level of each mineral was assessed using atomic absorption spectrometry. The results were analysed using the Dietetyk and Statistica 10 software. RESULTS: Low levels of Fe, Zn, Ca, Mg, vitamin D, and folic acid intake were seen in the pregnant women, with the use of dietary supplements significantly increasing their intake of Fe, Zn, and folic acid. The concentration of zinc and magnesium in the women's hair was shown to be affected by their age and, in the case of magnesium, by the week of pregnancy. CONCLUSIONS: It was observed that the diet of pregnant women is characterised by low levels of Fe, Zn, Ca, Mg, vitamin D, and folic acid. Dietary supplementation with vitamins and minerals significantly increases the daily Fe and folic acid intake in pregnant women. The concentration of Zn and Mg in hair depends on the age of pregnant women and Mg level in the hair of women decreases during pregnancy.


Subject(s)
Diet , Dietary Supplements , Folic Acid/administration & dosage , Minerals/administration & dosage , Pregnancy Complications/prevention & control , Pregnant Women , Vitamin D/administration & dosage , Vitamins/administration & dosage , Adolescent , Adult , Female , Humans , Magnesium/administration & dosage , Micronutrients/administration & dosage , Nutritional Status , Pregnancy , Young Adult , Zinc/administration & dosage
8.
Oxid Med Cell Longev ; 2018: 3919106, 2018.
Article in English | MEDLINE | ID: mdl-30622667

ABSTRACT

Preterm birth is defined as delivery before 37 completed weeks of pregnancy, and it is the leading cause of neonatal morbidity and mortality. Oxidative stress is recognized as an important factor in the pathogenesis of premature labor. We conducted this analysis to investigate the safety of administration of the tocolytic drug Atosiban-a reversible, competitive antagonist of the oxytocin receptor in the treatment of preterm birth and its impact on the level of oxidative stress in pregnant women after 48 hours of tocolytic treatment. This prospective study was conducted between March 2016 and August 2017 at the Obstetric Clinic of the Polish Mother's Memorial Hospital Research Institute. Total oxidant status (TOS), total antioxidant status (TAS), and oxidative stress index (OSI) values as well as 3-nitrotyrosine, carbonyl, and thiol group levels were measured using an ELISA test in serum and plasma of 56 pregnant women before and after 48 hours of continuous administration of Atosiban. We found that TAS levels decreased almost twice after the 48-hour drug administration (0.936 ± 0.360 mmol/L vs. 0.582 ± 0.305 mmol/L, P < 0.001) while TOS increased from 18.217 ± 16.093 µmol/L to 30.442 ± 30.578 µmol/L (P < 0.001). We also found a significant increase in OSI index-almost a threefold increase from 0.022 ± 0.022 to 0.075 ± 0.085, P < 0.001. In addition, statistically significant differences in the level of carbonyl groups were found. It increased from 65.358 ± 31.332 µmol/L to 97.982 ± 38.047 µmol/L (P < 0.001), which indicates increased oxidation of plasma proteins. Furthermore, patients who gave birth prematurely had higher levels of TOS after a 48-hour drug administration than the second group with labor after 37 weeks of pregnancy (42.803 ± 34.683 µmol/L vs. 25.792 ± 27.821 µmol/L, P < 0.031). The obtained results clearly indicate that pregnant women during tocolytic treatment with Atosiban are in a state of increased oxidative stress and occurrence of preterm birth can be associated with this phenomenon. This trial is registered with NCT03570294.


Subject(s)
Hormone Antagonists/adverse effects , Oxidative Stress/physiology , Premature Birth/drug therapy , Vasotocin/analogs & derivatives , Adult , Female , Hormone Antagonists/pharmacology , Hormone Antagonists/therapeutic use , Humans , Infant, Newborn , Retrospective Studies , Vasotocin/adverse effects , Vasotocin/pharmacology , Vasotocin/therapeutic use
9.
Biol Trace Elem Res ; 182(2): 217-223, 2018 Apr.
Article in English | MEDLINE | ID: mdl-28762093

ABSTRACT

The mineral levels in maternal serum change during pregnancy and may be correlated with those of newborn cord blood. The aim of this study was to evaluate the concentrations of calcium (Ca), magnesium (Mg), zinc (Zn), iron (Fe), and copper (Cu) in maternal blood before and after delivery and in umbilical cord vein and artery serum. The study was carried out in 64 Caucasian pregnant women who delivered in a district hospital in Greater Poland region, aged 28.1 ± 5.4 years, with a mean gestational age of 39.2 ± 1.3 weeks. Blood samples were taken from women 2-8 h before delivery and immediately after childbirth. The umbilical cord artery and vein blood of newborns was obtained immediately after childbirth. The levels of minerals in serum were determined by flame atomic absorption spectrometry. A significant drop in the concentrations of Mg (17.71 ± 1.51 vs 17.07 ± 1.61 µg/ml; p < 0.007), Fe (1.08 ± 0.46 vs 0.82 ± 0.35 µg/ml; p < 0.0004), and Zn (0.63 ± 0.17 vs 0.46 ± 0.16; p < 0.0001) in maternal serum was found after delivery. Moreover, higher levels of Ca, Fe, and Zn and lower levels of Cu were observed in the umbilical vein (Ca: 102.80 ± 7.80 µg/ml; p < 0.0001, Fe: 1.96 ± 0.43 µg/ml; p < 0.0001, Zn: 0.65 ± 0.16 µg/ml; p < 0.0001, Cu: 0.36 ± 0.09 µg/ml; p < 0.0001) and in the umbilical artery cord blood (Ca: 98.07 ± 8.18 µg/ml; p < 0.0001, Fe: 1.63 ± 0.30 µg/ml; p < 0.0001, Zn: 0.65 ± 0.15 µg/ml; p < 0.0001, and Cu: 0.36 ± 0.10 µg/ml; p < 0.0001) compared to the maternal serum (Ca: 85.05 ± 10.76 µg/ml, Fe: 0.82 ± 0.35 µg/ml, Zn: 0.46 ± 0.16 µg/ml, and Cu: 1.90 ± 0.35 µg/ml). Fe levels in the cord artery serum negatively correlated with blood loss during delivery (R = -0.48; p = 0.01), while the Ca concentration in the maternal serum after birth decreased with the age of the women (R = -0.25; p = 0.03). In conclusion, it seems that the process of birth alters the mineral levels in pregnant women's blood. Moreover, it was found that blood loss and the age of the mother are associated with mineral concentrations in the maternal serum and cord artery blood.


Subject(s)
Fetal Blood/chemistry , Minerals/blood , Postpartum Period/blood , Trace Elements/blood , Adult , Calcium/blood , Copper/blood , Female , Gestational Age , Humans , Infant, Newborn , Iron/blood , Magnesium/blood , Maternal Age , Poland , Pregnancy , Young Adult , Zinc/blood
10.
Ginekol Pol ; 88(9): 509-514, 2017.
Article in English | MEDLINE | ID: mdl-29057438

ABSTRACT

The aim of this study was to review the role of selected trace elements in pregnancy and fetal development. Citations related to the role of iron (Fe), zinc (Zn), manganese (Mn), copper (Cu) and selenium (Se) during pregnancy were searched in PubMed, Medline, Web of Science, using keywords and MeSH terms. Inadequate supply of trace elements can cause abnormalities of fetal development and predispose a child to disorders later on in life. Trace elements are the key elements of complex enzymes responsible for the modulation of the antioxidant defense system of the organism. It has been suggested that there is a correlation between reduced levels of trace elements essential for antioxidant function in the body of pregnant women, and an increased risk of developing preeclampsia. Trace elements are components of numerous regulatory enzymes and hormones essential to the division and differentiation of fetal cells and their further development. Mineral deficiencies in pregnant women can cause birth defects of the central nervous system, and growth disorders. Future research should be directed to explain the interaction between trace elements, and establish the optimum levels of macro and micronutrients supplementation, as well as determine the reference values for trace elements in the maternal serum, umbilical cord blood and amniotic fluid.


Subject(s)
Trace Elements/blood , Trace Elements/deficiency , Congenital Abnormalities/blood , Female , Fetal Development , Fetal Growth Retardation/blood , Humans , Pre-Eclampsia/blood , Pregnancy/blood
11.
Birth Defects Res ; 109(4): 251-253, 2017 Mar 01.
Article in English | MEDLINE | ID: mdl-28398665

ABSTRACT

BACKGROUND: The Matthew-Wood syndrome is associated with mutations of the STRA6 gene. It combines a pulmonary agenesis/hypoplasia; microphthalmia/anophthalmia; congenital cardiac, digestive, and urogenital malformations; and diaphragmatic defects. CASE: A 23-year-old nulliparous woman was referred to our center after a fetal ultrasound examination at 26 weeks of pregnancy revealed an abnormal head shape, a heart malformation, multiple cysts in both kidneys, and dilated ureters. A male baby (46, XY; 3600g; Apgar score 1) was delivered at 38 weeks of gestation and died 1 hr later due to respiratory failure. The diagnosis of Matthew-Wood syndrome was suspected given the association of bilateral anophthalmia, agenesis of the left lung, and heart and kidney defects. It was confirmed by the identification of two deleterious mutations of the STRA6 gene. RESULTS: The child was a compound heterozygote for two previously reported mutations, a paternally inherited missense mutation (c.878C>T [p.Pro293Leu] and a maternally inherited frameshift mutation (c.50_52delACTinsCC [p. Asp17Alafs*55]), producing a premature stop codon. CONCLUSION: The diagnosis of Matthew-Wood syndrome should be considered in all fetuses with microphthalmia/anophthalmia. It requires an extensive ultrasound/MRI examination of the lung, heart, and diaphragm. Birth Defects Research 109:251-253, 2017. © 2017 Wiley Periodicals, Inc.


Subject(s)
Abnormalities, Multiple/genetics , Anophthalmos/genetics , Frameshift Mutation , Lung Diseases/genetics , Membrane Proteins/genetics , Microphthalmos/genetics , Mutation, Missense , Respiratory Insufficiency/genetics , Abnormalities, Multiple/diagnosis , Abnormalities, Multiple/pathology , Anophthalmos/diagnosis , Anophthalmos/pathology , Fatal Outcome , Female , Gene Expression , Humans , Infant , Inheritance Patterns , Lung/abnormalities , Lung/pathology , Lung Diseases/diagnosis , Lung Diseases/pathology , Male , Microphthalmos/diagnosis , Microphthalmos/pathology , Pregnancy , Respiratory Insufficiency/diagnosis , Respiratory Insufficiency/pathology
12.
PLoS One ; 12(1): e0169420, 2017.
Article in English | MEDLINE | ID: mdl-28046022

ABSTRACT

Intracellular Toll-like receptor 3 (TLR3) recognizes viral double-stranded RNA (dsRNA) and activates antiviral immune responses through the production of type I interferons (IFNs) and inflammatory cytokines. This receptor binds to dsRNA molecules produced during human cytomegalovirus (HCMV) replication. TLR7 senses viral single-stranded RNA (ssRNA) in endosomes, and it can interact with endogenous RNAs. We determined the genotype distribution of single-nucleotide polymorphisms (SNPs) within the TLR3 and TLR7 genes in children with HCMV infection and the relationship between TLR polymorphisms and viral infection. We genotyped 59 children with symptomatic HCMV infection and 78 healthy individuals for SNPs in the TLR3 (rs3775290, c.1377C>T, F459F; rs3775291, c.1234C>T, L412F; rs3775296, c.-7C>A) and TLR7 (rs179008, c.32A>T, Q11L; rs5741880, c.3+1716G>T) genes. SNP genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and capillary electrophoresis. The HCMV DNA load was quantified by real-time PCR. We found an increased frequency of the heterozygous genotype TLR3 L412F in children with HCMV infection compared with uninfected cases. In individuals with a mutation present in at least one allele of the L412F SNP, an increased risk of HCMV disease was found, and this result remained highly significant after Bonferroni's correction for multiple testing (Pc < 0.001). The heterozygous genotype of this SNP was associated with the increased risk of HCMV disease in an adjusted model that included the HCMV DNA copy number in whole blood and urine (P < 0.001 and P = 0.008, respectively). Moreover, those with a heterozygous genotype of rs3775296 showed an increased relative risk of HCMV infection (P = 0.042), but this association did not reach statistical significance after correction for multiple testing. In contrast, the rs3775290 SNP of TLR3 and TLR7 SNPs were not related to viral infection. A moderate linkage disequilibrium (LD) was observed between the SNPs rs3775291 and rs3775296 (r2 = 0.514). We suggest that the L412F polymorphism in the TLR3 gene could be a genetic risk factor for the development of HCMV disease.


Subject(s)
Cytomegalovirus Infections/genetics , Polymorphism, Single Nucleotide , Toll-Like Receptor 3/genetics , Alleles , Antiviral Agents , Case-Control Studies , Child , Child, Preschool , Cytomegalovirus , DNA, Viral/blood , DNA, Viral/urine , Endosomes/metabolism , Female , Gene Dosage , Genetic Predisposition to Disease , Genotype , Haplotypes , Heterozygote , Humans , Infant , Linkage Disequilibrium , Male , Models, Statistical , Polymorphism, Restriction Fragment Length , Toll-Like Receptor 7/genetics
13.
PLoS One ; 11(4): e0154100, 2016.
Article in English | MEDLINE | ID: mdl-27105145

ABSTRACT

Toll-like receptor 9 (TLR9) recognizes non-methylated viral CpG-containing DNA and serves as a pattern recognition receptor that signals the presence of human cytomegalovirus (HCMV). Here, we present the genotype distribution of single-nucleotide polymorphisms (SNPs) of the TLR9 gene in infants and the relationship between TLR9 polymorphisms and HCMV infection. Four polymorphisms (-1237T/C, rs5743836; -1486T/C, rs187084; 1174G/A, rs352139; and 2848C/T, rs352140) in the TLR9 gene were genotyped in 72 infants with symptomatic HCMV infection and 70 healthy individuals. SNP genotyping was performed by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Digested fragments were separated and identified by capillary electrophoresis. The HCMV DNA copy number was measured by a quantitative real-time PCR assay. We found an increased frequency of heterozygous genotypes TLR9 -1486T/C and 2848C/T in infants with HCMV infection compared with uninfected cases. Heterozygous variants of these two SNPs increased the risk of HCMV disease in children (P = 0.044 and P = 0.029, respectively). In infants with a mutation present in at least one allele of -1486T/C and 2848C/T SNPs, a trend towards increased risk of cytomegaly was confirmed after Bonferroni's correction for multiple testing (Pc = 0.063). The rs352139 GG genotype showed a significantly reduced relative risk for HCMV infection (Pc = 0.006). In contrast, the -1237T/C SNP was not related to viral infection. We found no evidence for linkage disequilibrium with the four examined TLR9 SNPs. The findings suggest that the TLR9 -1486T/C and 2848C/T polymorphisms could be a genetic risk factor for the development of HCMV disease.


Subject(s)
Cytomegalovirus Infections/genetics , Genetic Predisposition to Disease/genetics , Polymorphism, Single Nucleotide , Toll-Like Receptor 9/genetics , Alleles , Cytomegalovirus/genetics , Cytomegalovirus/physiology , Cytomegalovirus Infections/virology , DNA, Viral/genetics , Female , Gene Dosage , Gene Frequency , Genotype , Host-Pathogen Interactions , Humans , Infant , Logistic Models , Male , Odds Ratio , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length , Risk Factors
14.
J Med Virol ; 87(10): 1737-48, 2015 Oct.
Article in English | MEDLINE | ID: mdl-25926093

ABSTRACT

Cytomegalovirus (CMV) is the most common cause of congenital infection. This pathogen exhibits extensive genetic variability in the genes that encode structural envelope glycoproteins, regulatory proteins, and proteins that contribute to immune evasion. However, the role of specific viral strains in the outcome of congenital CMV infection is unclear. Variation in the UL55 gene encoding glycoprotein B (gB), the UL144 gene encoding TNF α-like receptor, and the US28 gene encoding ß-chemokine receptor was determined in 60 newborn infants with congenital CMV infection and 90 infants with postnatal or undefined CMV infection. CMV polymorphisms were studied in relation to disease outcome and viral load. Genotyping was performed by a sequencing analysis of PCR-amplified fragments, and the viral load was measured by quantitative real-time PCR. The results demonstrated that (1) the UL55 and US28 genotype distributions were similar among the group of congenital and postnatal CMV infection; (2) the UL144 B1 genotype was more prevalent in congenital than in postnatal infection and was detected in 70% of newborns with asymptomatic congenital infection; and (3) none of the examined genotype was significantly linked with symptomatic CMV infection. No relationship was observed between genotype and viral load. The results revealed that UL55, UL144, and US28 polymorphisms are not associated with the outcome of CMV infection in infants, but the presence of UL144 B1 genotype might be virological marker of asymptomatic infection at birth.


Subject(s)
Cytomegalovirus Infections/congenital , Cytomegalovirus Infections/virology , Cytomegalovirus/genetics , Membrane Glycoproteins/genetics , Receptors, Chemokine/genetics , Viral Proteins/genetics , Amino Acid Sequence , Asymptomatic Infections/epidemiology , Biomarkers/blood , Biomarkers/cerebrospinal fluid , Biomarkers/chemistry , Biomarkers/urine , Cytomegalovirus Infections/epidemiology , Genotype , Humans , Infant , Infant, Newborn , Membrane Glycoproteins/blood , Membrane Glycoproteins/cerebrospinal fluid , Membrane Glycoproteins/urine , Phylogeny , Polymorphism, Genetic , Real-Time Polymerase Chain Reaction , Receptors, Chemokine/blood , Sequence Alignment , Sequence Analysis , Time Factors , Viral Envelope Proteins , Viral Load , Viral Proteins/blood , Viral Proteins/cerebrospinal fluid , Viral Proteins/urine
15.
PLoS One ; 10(4): e0122831, 2015.
Article in English | MEDLINE | ID: mdl-25844529

ABSTRACT

BACKGROUND: Some single nucleotide polymorphisms (SNP), located in Toll-like receptor (TLR) genes, were reported to be associated with human cytomegalovirus (HCMV) infections. The study was aimed to assess the correlation of SNPs at TLR4 and TLR9 genes with the occurrence of congenital cytomegaly, based on available samples. METHODS: Reported case-control study included both HCMV infected and non-infected fetuses and newborns. The specimens were classified to the molecular analyses, based on serological features of the recent infection and HCMV DNAemia in body fluids. TLR SNPs were studied, using multiplex nested PCR-RFLP assay, and determined genotypes were confirmed by sequencing. Hardy-Weinberg equilibrium was assessed for the identified genotypes. The linkage disequilibrium was also estimated for TLR4 SNPs. A relationship between the status of TLR genotypes and congenital cytomegaly development was estimated, using a logistic regression model. RESULTS: Hardy Weinberg equilibrium was observed for almost all SNPs, both infected and non-infected patients, with exception of TLR4 896 A>G polymorphism in the control group (P≤0.050). TLR4 896 A>G and 1196 C>T SNPs were found in linkage disequilibrium in both study groups (P≤0.050). The CC genotype at TLR4 1196 SNP and the GA variant at TLR9 2848 G>A SNP were significantly associated with HCMV infection (P≤0.050). The risk of congenital cytomegaly was higher in heterozygotes at TLR9 SNP than in the carriers of other genotypic variants at the reported locus (OR 4.81; P≤0.050). The GC haplotype at TLR4 SNPs and GCA variants at TLR4 and TLR9 SNPs were significantly associated with HCMV infection (P≤0.0001). The ACA variants were more frequent among fetuses and neonates with symptomatic, rather than asymptomatic cytomegaly (P≤0.0001). CONCLUSIONS: TLR4 and TLR9 polymorphisms may contribute to the development of congenital infection with HCMV in fetuses and neonates. The TLR9 2848 GA heterozygotic status possibly predisposes to HCMV infection, increasing the risk of congenital cytomegaly development.


Subject(s)
Cytomegalovirus Infections/congenital , Cytomegalovirus Infections/genetics , Polymorphism, Single Nucleotide , Toll-Like Receptor 4/genetics , Toll-Like Receptor 9/genetics , Case-Control Studies , Fetus/abnormalities , Fetus/virology , Genetic Predisposition to Disease , Humans , Infant, Newborn , Linkage Disequilibrium , Retrospective Studies
16.
Ginekol Pol ; 85(9): 708-12, 2014 Sep.
Article in English | MEDLINE | ID: mdl-25322545

ABSTRACT

Primary fetal chylothorax is an uncommon complication, associated with high perinatal morbidity and mortality. In our report, we describe two cases of fetal bilateral primary chylothorax successfully treated with pleuro-amniotic shunting. In both cases, ultrasound scans showed bilateral, hypoechoic fluid in the pleural space without any associated structural malformations and features of infection and aneuploidy Laboratory analysis of pleural fluids revealed 79% and 92% of lymphocytes, respectively confirming chylothorax in both fetuses. In the first case, pleuro-amniotic shunts were successfully inserted at 31 weeks and 6 days of gestation. Ultrasound scan after two weeks showed expansion of the left lung and lack of fluid in both pleural cavities. At 39 weeks of gestation, a 2660 g baby boy was delivered by cesarean section (Apgar score: 9). The child did not require surgical intervention and was discharged home on day 16 of life. In the second case, the insertion of shunts (at 24 weeks and 6 days of gestation) also significantly reduced the amount of the fluid in the pleural cavities, but one shunt had to be surgically removed after birth. At 30 weeks and 2 days of gestation, a cesarean section was performed due to maternal cholestasis. A female weighing 1400 g was delivered (Apgar score: 7). The chest X-ray revealed only a small amount of fluid in the left pleural cavity The infant was discharged on postnatal day 26, in good condition and with body weight of 2150 g. Pleuro-amniotic shunt insertion is a method of choice in the treatment of confirmed primary fetal chylothorax.


Subject(s)
Amnion/surgery , Chylothorax/congenital , Chylothorax/surgery , Fetal Diseases/surgery , Fetal Therapies/methods , Anastomosis, Surgical , Female , Fetal Therapies/instrumentation , Humans , Infant, Newborn , Male , Pleural Effusion/etiology , Pleural Effusion/surgery , Pregnancy , Pregnancy Outcome , Prenatal Care/methods , Treatment Outcome
17.
Ginekol Pol ; 84(12): 1005-11, 2013 Dec.
Article in Polish | MEDLINE | ID: mdl-24505947

ABSTRACT

UNLABELLED: Congenital cytomegaly is caused by intrauterine mother-to-fetus HCMV transmission and constitutes the most common vertical infection. OBJECTIVES: The aim of the study was to analyze the viremia level in maternal blood and its influence on the course and duration of pregnancy as well as newborn condition. MATERIAL AND METHODS: The material included blood samples collected from 117 pregnant women with serological features of HCMV infection and from 29 neonates hospitalized at DFMMG in Lodz between 1999 and 2009. The presence of HCMV DNA in the maternal and fetal blood was tested using real-time PCR. RESULTS: Prevalence of maternal viremia was observed to increase the risk of viremia in neonates, as compared to children born to mothers with no viremia. However; lack of HCMV DNA in maternal blood does not exclude fetal infection in utero. Newborn condition assessed by Apgar scores was significantly lower in the group of infants born to mothers with serological features of acute cytomegaly (p < 0.05). CONCLUSION: The assessment of viremia level in maternal blood can be helpful in assessing the risk of intrauterine infection in the fetus as well as in predicting the neonatal outcome of newborn.


Subject(s)
Cytomegalovirus Infections/transmission , Fetal Blood/virology , Infectious Disease Transmission, Vertical/statistics & numerical data , Pregnancy Complications, Infectious/virology , Prenatal Exposure Delayed Effects/epidemiology , Viremia/transmission , Adolescent , Adult , Cytomegalovirus , Cytomegalovirus Infections/epidemiology , Female , Humans , Incidence , Infant, Newborn , Male , Poland/epidemiology , Predictive Value of Tests , Pregnancy , Pregnancy Complications, Infectious/epidemiology , Prenatal Diagnosis , Risk Factors , Viremia/epidemiology , Young Adult
18.
Ginekol Pol ; 83(5): 337-41, 2012 May.
Article in Polish | MEDLINE | ID: mdl-22708329

ABSTRACT

OBJECTIVES: Human cytomegalovirus is a common etiological agent of infections and is the most common cause of intrauterine infections. Due to the scale and importance of infections during pregnancy in this study we investigated the incidence of specific IgG and IgM antibodies directed against HCMV in population of Polish pregnant women. MATERIAL AND METHODS: The retrospective study included 1332 pregnant women who were hospitalized at the DFMMG in Lodz between 1999 and 2009. In this group, 117 women had serological features of acute cytomegalovirus infections (study group) and 51 women were seronegative for IgG, IgM and IgA antibodies (control group). HCMV infections in pregnant women were diagnosed by serological assays (IgG, IgM, IgA, IgG avidity) and clinical symptoms. RESULTS: Seroprevalence of CMV IgG was estimated to be 76.7% (n=985). Anti-HCMV immunoglobulin M antibodies were detected in 13% of pregnant women (n=179). CONCLUSIONS: There was no significant correlation between the prevalence of IgG and IgM antibodies and factors such as maternal age, parity a number of births, place of residence and marital status.


Subject(s)
Antibodies, Viral/blood , Cytomegalovirus Infections/diagnosis , Cytomegalovirus Infections/epidemiology , Pregnancy Complications, Infectious/diagnosis , Pregnancy Complications, Infectious/epidemiology , Adult , Cytomegalovirus/immunology , Female , Humans , Immunoglobulin A/blood , Immunoglobulin G/blood , Immunoglobulin M/blood , Incidence , Luminescent Measurements , Poland/epidemiology , Pregnancy , Retrospective Studies , Risk Factors , Seroepidemiologic Studies , Young Adult
19.
Mol Immunol ; 48(15-16): 2203-6, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21722964

ABSTRACT

Cytomegalovirus (CMV) is the leading cause of congenital infections among neonates. About 10% of newborns with such an infection have clinical symptoms at birth and about 1% of infected fetuses die due to developmental malformations. Mannan-binding lectin (MBL) is considered to be an important factor in innate immunity. Its deficiency is believed to predispose to various (including viral) infections. The aim of this study was to investigate the possible role of MBL2 gene polymorphisms in prenatal and perinatal CMV infections. The frequencies of MBL2 gene exon 1 mutations as well as MBL deficiency-associated variants (LXPA/O+O/O) among newborns with confirmed cytomegalovirus infection were not significantly lower than among non-infected individuals. The distribution of MBL2 haplotypes was similar between the groups studied. These data suggest MBL does not have a major influence on susceptibility to prenatal or perinatal CMV infections.


Subject(s)
Cytomegalovirus Infections/genetics , Genetic Predisposition to Disease/genetics , Mannose-Binding Lectin/genetics , Pregnancy Complications, Infectious/genetics , Female , Genotype , Humans , Infant, Newborn , Mannose-Binding Lectin/deficiency , Mutation , Polymorphism, Single Nucleotide , Pregnancy , Reverse Transcriptase Polymerase Chain Reaction
20.
Tumori ; 95(3): 352-6, 2009.
Article in English | MEDLINE | ID: mdl-19688976

ABSTRACT

AIMS AND BACKGROUND: The increased expression of galectin-1 on the mRNA and protein level observed in malignant thyroid tumors in comparison with benign lesions suggests that this protein may be associated with malignant transformation of thyroid epithelium. Extracellular and membrane glycoproteins are the main known ligands for this galactose-binding lectin. However, immunofluorescence studies have shown that galectin-1 is found predominantly in the intracellular compartment. The aim of this study was to examine intracellular carbohydrate ligands of galectin-1 in the thyroid, with particular attention to potential differences in their expression levels between benign and malignant lesions. METHODS: Identification of cytosolic and nuclear glycoproteins binding galectin-1 was performed by affinoblotting after separation of proteins in 8% polyacrylamide slab gels and electrotransfer onto Immobilon-P membranes. For semiquantitative analysis of glycoproteins binding galectin-1, an enzyme-linked lectino-solid-phase assay (ELLSA) was used. RESULTS: The predominant cytosolic glycoproteins binding galectin-1 had molecular masses of 50, 55, 59, 64, 85-87, 100, and 133 kDa and nuclear glycoprotein had a molecular mass of 75 kDa. There were no evident differences in glycoprotein patterns between benign and malignant thyroid lesions. The results obtained by ELLSA did not show any significant differences in lectin binding by cytosolic and nuclear proteins of thyroid lesions either. CONCLUSIONS: On the basis of these results it is tempting to suggest that interactions between galectin-1 and intracellular glycoconjugates are not critical for malignant transformation in the thyroid gland.


Subject(s)
Cell Transformation, Neoplastic/metabolism , Galectin 1/metabolism , Glycoproteins/metabolism , Thyroid Neoplasms/metabolism , Adolescent , Adult , Aged , Aged, 80 and over , Child , Female , Gene Expression Regulation, Neoplastic , Humans , Immunoenzyme Techniques , Male , Middle Aged , Thyroid Diseases/metabolism , Thyroid Neoplasms/pathology
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